2022

Epidemiology, Infectious
Diseases, Medical Parasitology
and Tropical Medicine
SUMMARY V2 – NOW WITH STATE EXAM TOPICS

IVO

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Contents
1. Epidemiology - definition, goals, tasks and methods, relation to other disciplines, modern development. ........... 5
2. Parasitism and infectious process - the biological basis of the epidemic process. Characteristics .......................... 6
3. Epidemic process - definition, elements, epidemic focus, forms ............................................................................. 7
4. Source of infection: human - animal, sick - forms, contagious period, epidemiological significance. Carrier of
infection - types, durability, significance .......................................................................................................................... 8
5. Mechanisms of transmission of the infection - biological relation, types, phases, transmission factors. The
roads of infection spreading. Classification of communicable diseases ........................................................................... 9
6. Factors of infection transmission: water, food products, environmental objects, soil, air, live vectors................ 10
7. Population susceptibility - non-specific and specific factors, immunological structure of the population............ 12
8. Immunoprophylaxis. Types of vaccines. Application method. Side reactions after vaccination. Medical
contraindications for the application of vaccines. Organization of immunizations in the Republic of Bulgaria - levels of
immunization coverage................................................................................................................................................... 13
9. Social Factor - Impact on the epidemic process. .................................................................................................... 18
10. Natural factor - impact on the epidemic process. Natural - focal infections...................................................... 19
11. Forms of epidemic process - sporadic, epidemics (types), pandemics, epidemic outbreak. ............................. 20
12. Epidemiological study - purpose, stages, mode of conduct, epidemiological analysis. ..................................... 21
13. General preventative and basic control measures in the epidemic focus - to the patient, the contact persons
and the environment. ..................................................................................................................................................... 24
14. Epidemiological control and surveillance of infectious diseases. ....................................................................... 25
15. Health-care associated infections (HCAI). Organizing and conducting of epidemiological surveillance and
control in the Republic of Bulgaria. ................................................................................................................................ 26
16. Problems of the liquidation of the infectious diseases ....................................................................................... 30
17. Disinfection and sterilization. ............................................................................................................................. 31
18. Disinsection - definition, methods, tools. Epidemiological significance. ............................................................ 34
19. Deratisation - definition, methods, tools. Epidemiological significance............................................................. 36
20. Bioterrorism. Diseases subject to international health regulation. .................................................................... 39
21. Emerging and re-emerging diseases - definitions, classification, epidemiological features and control. .......... 41
22. Infection, infectious process, infectious disease. ............................................................................................... 43
23. Diagnostic approach to infectious diseases, general syndromes, clinical epidemiological, microbiological,
virological investigations................................................................................................................................................. 45
24. Symptomatic therapy, diet and regime of the infectious patient ...................................................................... 47
25. Pathogenic treatment in infectious diseases ...................................................................................................... 48
26. Etiological treatment in infectious diseases ....................................................................................................... 49
27. Typhoid fever and paratyphoid fever A and B .................................................................................................... 51
28. Food poisoning by Salmonella, conditionally pathogenic intestinal bacteria, staphylococci and other. ........... 53
29. Botulism. ............................................................................................................................................................. 55
30. Bacterial dysentery/ Shigellosis/ Bakterielle Ruhr .............................................................................................. 57
31. Campylobacter enterocolitis ............................................................................................................................... 58

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32. Esherichia coli enteritis/ Diarrheagenic E. coli .................................................................................................... 59
33. Yersiniosis............................................................................................................................................................ 62
34. Cholera ................................................................................................................................................................ 63
35. Brucellosis ........................................................................................................................................................... 64
36. Leptospirosis ....................................................................................................................................................... 65
37. Viral hepatitis A and E ......................................................................................................................................... 66
38. Viral hepatitis B ................................................................................................................................................... 68
39. Viral hepatitis C and D ......................................................................................................................................... 71
40. Enterovirus infections. Poliomyelitis................................................................................................................... 74
41. Coxsackie and ECHO viral infections ................................................................................................................... 76
42. Influenza and parainfluenza ................................................................................................................................ 78
43. Acute respiratory diseases .................................................................................................................................. 81
44. Legionnaire's Disease .......................................................................................................................................... 86
45. Scarlet fever and other Infections cause by Streptococci................................................................................... 88
46. Diphtheria/ Echter Krupp .................................................................................................................................... 92
47. Measles/ Rubeola/ Masern ................................................................................................................................. 94
48. Rubella (German measles). Exanthema subitum, Erythema infectiosum .......................................................... 96
49. Chicken pox/ Windpocken ................................................................................................................................ 100
50. Infectious mononucleosis. Infectious lymphocytosis ....................................................................................... 104
51. Pertussis (Whooping cough) and parapertussis ............................................................................................... 105
52. Mumps .............................................................................................................................................................. 107
53. Epidemic meningitis and other forms of meningococcal infection .................................................................. 108
54. Plague ................................................................................................................................................................ 111
55. Tularemia .......................................................................................................................................................... 112
56. Epidemic (louse-borne) and endemic (murine) typhus/ Fleckenfieber ............................................................ 113
57. Q-fever .............................................................................................................................................................. 115
58. Mediterranean Spotted fever/ Boutonneuse Fever ......................................................................................... 116
59. Typhus recurrence/ Borrelia recurrentis/ Relapsing fever ............................................................................... 117
60. Lyme disease/ Borreliosis.................................................................................................................................. 118
61. Arboviral encephalitis ....................................................................................................................................... 120
62. Viral hemorrhagic fever /Crimean-Congo fever and Hemorrhagic fever with renal syndrome/ ..................... 122
63. Yellow fever....................................................................................................................................................... 126
64. Dengue fever. Zika Fever .................................................................................................................................. 128
65. Sandfly fever/ Pappataci fever/ 3 Days fever ................................................................................................... 130
66. Ornithosis (Psittakosis, parrot fever) ................................................................................................................ 131
67. Anthrax .............................................................................................................................................................. 132
68. Tetanus.............................................................................................................................................................. 134
69. Sodoku (Rat-bite fever) ..................................................................................................................................... 136

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70. Felinosis (Cat-scratch disease) .......................................................................................................................... 137
71. Foot and mouth disease (Aphthe epizooticae) ................................................................................................. 138
72. Rabies ................................................................................................................................................................ 139
73. AIDS ................................................................................................................................................................... 141
74. Sepsis................................................................................................................................................................. 146
75. Fever of unknown origin (FUO) ......................................................................................................................... 149
76. Malaria .............................................................................................................................................................. 151
77. Toxoplasmosis ................................................................................................................................................... 155
78. Leishmanioses ................................................................................................................................................... 157
79. Urogenital trichomoniasis ................................................................................................................................. 159
80. Amebisasis......................................................................................................................................................... 160
81. Lambliosis/ Giardiasis, blastocystosis, cryptosporidiosis .................................................................................. 162
82. Enterobiosis/ Oxyuriasis.................................................................................................................................... 164
83. Ascaridosis......................................................................................................................................................... 165
84. Toxocarosis........................................................................................................................................................ 166
85. Trichocephalosis/ Trichuriasis ........................................................................................................................... 167
86. Taeniases, Cysticercosis .................................................................................................................................... 168
87. Hymenolepidosis ............................................................................................................................................... 170
88. Trichinellosis...................................................................................................................................................... 171
89. Echinococcosis. ................................................................................................................................................. 172
STATE EXAM STUFF ....................................................................................................................................................... 174
1. Infection, Infectious Process, Host – Pathogen Interactions. .............................................................................. 174
2. Infectious Disease – definitions, periods, clinical forms. ...................................................................................... 174
3. Clinical Syndromes ................................................................................................................................................ 174
5. Infections in Immunocompromised Host. HIV/AIDS............................................................................................. 174
9. Infections in Pregnancy. ............................................................................................................................................ 176
20. Acute Infectious Diarrhoeal Diseases – Etiology and Pathogenesis. ................................................................ 178
27. Viral Gastroenteritis .......................................................................................................................................... 180
28. Diagnosis, Differential Diagnosis and Treatment of Acute Gastroenteritis. ..................................................... 181
34. Mycoplasma and Chlamydia infections. ................................................................................................................ 182
37. Varicella – Zoster Virus – Infections. Differential Diagnosis in Patient with Vesicullous Exanthema. Smallpox.
Vaccinia ......................................................................................................................................................................... 182
39. Epstein – Barr V. Infection Incl. Mononucleosis Infectiosa. Infections due to Other Human Herpesviruses,
incl. Cytomegalovirus ................................................................................................................................................... 183
40. Scarlet Fever and Other Infections cause by Streptococci. /STSS, Phagedaena, Erysipelas/........................... 186
42. Diphtheria. Throat Alterations in Infectious Diseases -Differential Diagnosis. .............................................. 187
44. Oedema Cerebri and Meningitis in Acutely Ill Infected Patient. Differential Diagnosis in Meningitis. .................. 188
47. Differential Diagnosis of Icterus in Acutely Ill Infected Patient ........................................................................ 188

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52. Glanders and Melioidosis .................................................................................................................................. 189
53. Rickettsioses. Typhus exanthematicus. Tick Born Typhus. .............................................................................. 190
55. Erlichioses. ........................................................................................................................................................ 191
58. Bartonella Infections, Incl. Cat-Scratch Disease. .............................................................................................. 192
65. Disorders in Haemostasis and Haemorrhagic Syndrome in Infectology. .......................................................... 193
66. Miscellaneous Infections /Sodoku, Aphthe epizootizae, Actinomicosis, Nocardiosis/ ................................... 194
67. Infectious Diseases Common for both Temperate and Tropical Climate. ........................................................ 195
69. Organization of the Control of Tropical Diseases. Sanitary Border Protection. Health Advice for International
Travel Medicine............................................................................................................................................................. 196

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1. Epidemiology - definition, goals, tasks and methods, relation to other
disciplines, modern development.
 Epidemiology is the study (scientific, systematic, and data-driven) of the distribution (frequency, pattern) and
determinants (causes, risk factors) of health-related states and events (not just diseases) in specified populations
(neighborhood, school, city, state, country, global)
 Classical epidemiology: the study of determinants and distribution of disease in populations
 Clinical epidemiology is defined as the study and application of principles of epidemiology to improve the
detection, and treatment of disease in patients as well as making changes to allow prevention
 Descriptive epidemiological studies investigate individual characteristics, places, and/or the time of events in
relation to an outcome.
 Analytical epidemiological studies seek to determine the influence of an exposure on an outcome and can be
further divided into experimental (e.g., randomized control studies) and observational (e.g., cohort or case-
control studies) types
 Source of infection
o Source (origin) of infection is the human organism– diseased or as carrier, and for a group of diseases
(zoonoses) it is an animal
o Object which is the site of natural habitation and multiplication of pathogenic organisms, from where they can
infect healthy people
o a source of infection is the root of the infection human or zoonotic (from animals) from where the host gets
the infection. Or everything can be a source of infection and how and where the pathogen got into them
o An object is designed as the source of infection
 one in which the agent of infection lives and propagates
 it can be man or animal from which the infectious agent is secreted into the outer environment and from
there to individuals.
 In certain circumstances →the outer milieu can be the source of infection where the agent lives as a
saprophyte (lives on dead matter e.g. botulism and legionella)
 Mechanisms of transmission of the infection
o The mechanism of transmission includes a sum of biologic adaptations and conditions of the microorganisms,
when passing from diseased organism to healthy one.
o The mechanism of transmission of an infection is the way how an infection can occur in an individual through
different entries into a body or living organism
o Mechanism of transmission of an infection is the process by which an organism (host) proceeds to pass on a
microorganism to another uninfected organism. It consists of 3 phases.
 five main tasks of epidemiology in public health practice:
o public health surveillance,
o field investigation,
o analytic studies,
o evaluation,
o linkages

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2. Parasitism and infectious process - the biological basis of the epidemic
process. Characteristics
 three forms of symbiotic relationships that can occur at an anatomical level:
o 1. Mutualism: In mutualism, both the microorganism and the body work together. It is the normal flora of
intestine, which find auspicious conditions for its growth.
o 2. Commensalism: In commensalism, either the body or the microorganism benefits, while the other is not
affected by the interaction. It is typical for the normal flora of human’s body.
o 3. Parasitism: In parasitism, one organism benefits at the expense of the other.
 Parasitism refers to an association in which one organism benefits at the expence of the other (many of known
infectious diseases). Host provides total environment for Shigella spp. They feed on intestinal mucosa, causing
ulcers and dysentery.
o Saprophytes are microorganisms that use dead or decaying organic material (soil and water microorganisms).
They are free-living and play an important role in the degradation of organic materials in nature.
o Parasites are microbes that can establish themselves and multiply in hosts. They may be either commensals or
pathogens (from Greek pathos, suffering; and gen, produce, i.e. disease producing).
o Pathogens may be:
 Obligatory, which benefit at any circumstances from the host (V. cholerae, B. anthracis, M. tuberculosis).
 Facultative, which cause diseases in certain circumstances (when host resistance is lowered: Candida spp.
staphylococci on skin etc.)
 five main groups of pathogens are:
o Bacteria – Salmonella, Shigella, V. cholerae, Clostridium botulinum et tetani, etc.
o Viruses – influenza, AIDS, chickenpox, hepatitis, etc.
o Protozoa – Plasmodium spp., Entamoeba spp., Giardia lamblia, etc.
o Fungi – Candida albicans, Aspergillus flavus, Pneumocystis carinii, etc.
o Helminths (worms and flukes) – Taenia solium, Taenia saginata, Schistosoma spp., Fasciola spp., Ascaris, etc.
 Pathogenecity is generally determined sign of microbial species that shows their ability to cause damage. The
degree (level) of pathogenecity as a quantitative individual sign is called virulence.
o Dosis lethalis minima (DLM) = minimum infecting dose (MID) – the minimum number of bacteria, required to
produce clinical evidence of infection in a susceptible animal under standard conditions.
o Dosis lethalis media (LD 50 ) = minimum lethal dose (MLD) – the minimum number of bacteria, required to kill
50 percent of susceptible animals, tested under standard conditions.

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3. Epidemic process - definition, elements, epidemic focus, forms
 Epidemic process – a complex specific process of disseminating the causative agents of infectious diseases in
human society (human population) that is manifested externally as a continuous chain of sequential interrelated
infectious processes on a particular territory. This is the main form of existence of pathogenic microorganisms
and their survival as a biological species.
 The continuity of the epidemic chain is the most characteristic feature of the epidemic process and also a
determinative factor for its interruption and liquidation.
 Several conditions are required for the emergence of an epidemic process: the presence of its constituent parts
or links:
o source of infection;
o mechanism of transmission of the infection;
o susceptible population.
 The three links which are functionally interrelated are the “elementary cell” containing the major features of a
particular epidemic process. It emerges among people within a particular territory or in the epidemic focus
 Epidemic focus: The inhabited territory of the source of infection and the environment within which it is
capable, at definite conditions, to transmit the infection to the susceptible individuals
 The main active forces of the epidemic process are an aggregate of the interaction of its three links through the
impact of social conditions and the factors of the natural environment .
 The leading role for the dissemination of the infectious diseases in the society as well as for their prevention and
liquidation belongs to social conditions .
 Obligatory conditions for the appearance, spread and sustaining of the epidemic process:
o Source of infection
o Mechanism of contraction
o Susceptibility of the population
 epidemiologic triad or triangle: external agent, a susceptible host, and an environment that brings the host and
agent together
o disease results from the interaction between the agent and the susceptible host in an environment that
supports transmission of the agent from a source to that host

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4. Source of infection: human - animal, sick - forms, contagious period,
epidemiological significance. Carrier of infection - types, durability,
significance
 Anthroponosis – diseases where the only source of infection is infected man (diseased or carrier of infection)
 Zoonoses – diseases which are common for man and animals, with a common source of infection. In zoonoses,
the main form of existence of pathogenic microorganisms is the epizootic process (their dissemination among
the animal population). The epidemic process in thee diseases depends on the epizootic process – people are
infected by animals which have diseased or are carriers of the infection
 Sapronoses: Diseases cause by conditionally pathogenic microorganisms, at reduced defensive strength of the
organisms and penetration of the microorganisms through unusual (additional) portals of entry.
 Periods of progression of the infectious disease incubation; initial, which can be preceded by a prodromal stage;
peak, or period of full development of the disease; reconvalescent; residual – in certain cases. The
epidemiological importance of the separate periods depends on the infectious disease group – respiratory,
intestinal, blood, mucocutaneous infection.
 Clinical forms of the course of an infectious disease of certain epidemiological significance. Acute clinical forms
 Typical course: mild, moderate, severe
 Atypical course:
o severe – fulminant, foudroyant, of limited epidemiological significance;
o mild – of great epidemiological significance – undiagnosed, efficacious antiepidemic measures are nor
performed in due time;
o abortive – beginning with typical signs but are suddenly terminated by prompt recovery;
o ambulatory – mild, atypical, the disease is endured “on foot”;
o subclinical – “not obvious” or inapparent – with less manifected clinical signs;
o asymptomatic – there are data for infection, without apparent clinical signs, but paraclinical and
microbiological data prove the presence of an infectious process.
 Chronic forms – continuous or periodical but prolonged elimination of the causative agent from the
macroorganism.
 Latent forms – continuous presence of the causative agent in the macroorganism but with its periodic activation
at certain conditions and prerequisites. Such patients ensure a sustained maintenance of the epidemic process.
 Carrier state – a form of the infectious process in which the health state of the macroorganism is not apparently
affected but there is a possibility of eliminating the pathogenic microorganism from within the macroorganism.
o Types of carriers of infection acute (up to 3 months) healthy (passive) chronic (over 3 months) carriers of
infection temporarily active convalescent (active) chronic continuous periodic
 Reservoirs of infection: Animals which maintain the infection in nature. A man can become infected from these
animals in various circumstances:
o everyday contact with animals;
o breeding animals;
o use of foodstuffs of animal origin or water contaminated by animals;
o injured skin while hunting, butchering, flaying, processing meat, meat products, poultry, fish;
o processing products of animal origin – fur, wool, bristle, hooves;
o animal biting;
o through arthropods – live carriers of infectious diseases.

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5. Mechanisms of transmission of the infection - biological relation, types,
phases, transmission factors. The roads of infection spreading.
Classification of communicable diseases
 mechanism of transmission includes a sum of biologic adaptations and conditions of the microorganisms, when
passing from diseased organism to healthy one
o Phase 1 - discharge of the pathogen from the affected organism
 determined by physiological (breathing, salivation, urination, defecation, desquamation of epithelial cells)
and pathological (coughing, sneezing, vomiting, diarrhea, pus-production, blood- sucking etc.) processes in
the affected organism.
o Phase 2 - survival in the environment for a specific period of time
 The transfer in the pathogen in the environment is of great practical importance.
 It is related to specific biotic and non-biotic elements of that environment (air, water, soil, nutrients, parasitic
or non-parasitic animal carriers, intermediate and additional hosts)
o Phase 3 – penetration in the organism of the next host – infection of the healthy
 Realized in two major modes:
 1. Infiltration of the pathogen through the cavity organs with direct connection with the environment .
 2. Infiltration through skin and mucosa with or without infraction of it’s integrity.
 This chain of reactions is regular for all infections but may vary greatly in details, depending on:
o 1. Qualitative characteristics of physiological and pathological processes in the diseased organism.
o 2. Biological characteristics of the pathogen.
o 3. Particular environmental conditions
 infectious diseases can be rationally classified according to specific localization of infectious agent in the
organism, corresponding mechanism of transmission and biological properties of causative agent
o intestinal infections
o respiratory infections
o blood infections
o infections of external covers
 Direct Transmission – Person to person
o Immediate transfer pf the pathogen or agent from a host/reservoir to a susceptible host
o Can occur through direct physical contact or direct personal contact such as touching contaminated hands,
kissing, sex
 Indirect transmission: Pathogens or agents are transferred or carried by some intermediate item or organism,
means or process to a susceptible host
o Vertical Transmission: Transplacental, Perinatal, Postnatal
 Horizontal Transmission
o Air-droplets mechanism
o Fecal-oral mechanism
o Blood-transmission mechanism
o External covers mechanism
o Sexual transmission mechanism
o Parenteral (artificial) mechanism
o Infections with multiple transmitting mechanism
 Based on the mode of transmission of the infectious agent, communicable diseases can be classified as:
o Waterborne diseases: transmitted by ingestion of contaminated water.
o Foodborne diseases: transmitted by the ingestion of contaminated food.
o Airborne diseases: transmitted through the air.
o Vector-borne diseases: transmitted by vectors, such as mosquitoes and flies.

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6. Factors of infection transmission: water, food products, environmental
objects, soil, air, live vectors.
 Contemporary classification of the transmitting factors
o Alive factors – mosquitoes, fleas, lice, ticks, flies etc.
o Non-alive factors – air, water, food, soil, objects etc.
o Biologic fluids – blood, milk, saliva, sperm, sweat, tears, cervical, vaginal and anal secretions, amniotic fluids,
menstrual blood, pus and other pathologic secretions.
o Biologic products – donor blood, donor plasma, immunoglobulins, plasma vaccines and serums, donor milk,
donor sperm etc.
o Biologic transplants – tissues, organs
o Medical instruments and equipment
o Other factors
 Elements of the environment assuring the transmission of the infectious agent from one (infected) organism to
the other (uninfected)
 Mode (way, path) for transmitting infections: The unity of factors in the specific location for the specific period
of time in the specific direction.
o 1. Short (airborne infections)
o 2. Long (intestinal infections)
o 3. Multifactoral
 AIR as a transmitting infections factor
o Air-droplets mechanism (Air-born route)
 Easy to realize
 In the air the pathogens are present covered with mucus and necrotized epithelial cells (bacterial aerosol)
 The contraction depends mainly on the distance (1,5 – 2 meters at most)
 With increasing the distance from the source the possibility of infection decreases
 At maximum density droplets remain in the air for about 20 minutes
 At specific conditions (humidity and airflow), dispersion of the droplets can spread up to 20 meters
 In the air the droplets can reside up to 2 hours and more
 600 times easier then fecal-oral route
o Air-dust mechanism
 For forming of bacterial dust the pathogens require resistance in dried condition.
 Such are the pathogens of variola, tuberculosis, tularemia, anthrax, Q-fever etc.
 Food products
o Fecal-oral mechanism (Food-born infections, intestinal route)
 Entering point is the mouth
 Through pharynx and stomach pathogens reach the intestines where usually is the specific localization
 The natural exiting path is via defecation
 Food and water are the common factors of this mechanism.
 In nowadays only violent infraction of the sanitary regulations of water-supply, can cause fecal pollution of
tap-water
 Multitude of factors with secondary and unspecific factors with lesser and in some cases irrelevant role in
disease distribution.
 Relay of factors where two or more factors are linked (chains of factors).
 The form of transition is more active when there are more specific factors and shorter chains
 WATER as a transmitting infections factor
o Always investigate for the actual source of infection (human or animal)
 environmental objects
o Polymer-associated infections

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  Polymers are included in artificial joint implants, pacemakers, eye lenses, breast and other implants.
 The risk of polymer-associated infections is high because of the small number of microorganisms (10³)
required for the onset of these infections
o Direct contact mechanism (external covers mechanism)
 Entering points are the external covers of the body – skin, mucosa, hairs etc.
 Some pathogens can penetrate through intact skin.
 Some pathogen infect injured skin (wound infections)
 If there are factors those are objects of the environment strictly specified for that type of transmission.
 Blood-borne mechanism
o Entering and exit points are associated with the blood.
o The specific localization of the pathogen is in the blood and in natural conditions the transmission is via
ectoparasites (bloodsucking insects).
o The factors are living organism (vectors) specified in transmitting infections.
o One vector species can serve as a carrier for multitude of diseases –Anopheles spp.– all types of malaria –
Phlebotomus spp.- leishmaniosis, sand fly fever
o One disease can be carried from different vectors (usually from the same family or species)
o Condition for the transmission of blood-borne infections are the biological an ecological specifics of the
vectors: • endemicity • epizooty • seasonality
o Only epidemic typhus and relapsing typhus are affected by the social conditions in the human population
(vector - louse)
 Sexual transmission mechanism
o The specific localization of the pathogens is the genitourinary system.
o The transmission is during sexual contact in all of it’s aspects ( oral, anal etc.)
o Other then classical STD with this mechanism are transmitted: mycoplasmas, HSV, HBV, HDV, HCV, HIV
 Vertical mechanism
o specific localizations of the pathogens are mother’s blood and birth canal, placenta, umbilical cord, amniotic
fluids, cervical and vaginal secretions etc.
 Transplacental transmission – pathogens crossing the placental barrier
 Perinatal transmission – in the delivery process
 Postnatal transmission – by breastfeeding, contact with body fluids of the mother
o Classical: rubella, measles, toxoplasmosis, listeriosis
o And: HBV-hepatitis (the replication of the virus starts in the first embryonic hepatocytes), HCV-hepatitis, HDV-
hepatitis, HIV infection, the slow form of lymphocytic horiomeningitis etc.
 Infections with multiple transmitting mechanism
o specific localization of the pathogen is in several systems or body fluids (multiple localization) - the contagion is
shed trough different exit points and can be contracted in different entrance points
 Parenteral (artificial) mechanism
o The specific localization of the pathogen is in the patients blood.
o The transmission takes place in blood manipulation, blood-transfusion, plasma- transfusion, laboratory work,
intravenous drug use etc.
o HBV-hepatitis, HCV- hepatitis, HDV- hepatitis, HIV infection, toxoplasmosis, malaria, leishmaniosis
o With the recognition of this new artificial mechanism in the contemporary situation a new groups of factors
transmitting infections were differentiated:
 BIOLOGIC PRODUCTS
 MEDICAL INSTRUMENTS

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7. Population susceptibility - non-specific and specific factors,
immunological structure of the population.
 Immunization status
 Malnutrition and obesity
 Age pyramid structure
 Food (raw meat consumption, raw milk)

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8. Immunoprophylaxis. Types of vaccines. Application method. Side
reactions after vaccination. Medical contraindications for the application
of vaccines. Organization of immunizations in the Republic of Bulgaria -
levels of immunization coverage.
 Vaccine
o A product (e.g., dead or weakened organism) that provides immunity from a disease
o May be administered through injection, orally, or nasally
 Vaccination: administration of a vaccine that induces an active immune reaction in form of cellular and/or
humoral response, providing immunity against a pathogen
 Immunization
o The process by which a person becomes protected from a disease
o Vaccines and recovering from some infections cause immunization.
 Aims of routine immunization
o Herd immunity: Once a certain percentage of the population has received immunization, non-vaccinated
individuals (e.g., children too young to receive vaccination) will also be protected.
 Mass vaccination: Vaccination of a large number of people in the shortest possible time after the outbreak of
an epidemic, with the goal of herd immunity.
o Eradication of disease
 High immunization rates over prolonged periods of time can achieve eradication of certain diseases.
 To date, only two diseases have been eradicated by human efforts: smallpox (1980) and rinderpest (2011).
o Lower incidence and associated risks: The Haemophilus influenzae type b (Hib) vaccine has decreased the
number of cases of invasive Hib disease (e.g., pneumonia, bacteremia, meningitis, epiglottitis, infectious
arthritis) in children younger than 5 by more than 99%
 Passive immunization
o Mechanism of action
 Injection of preformed antibodies induces a rapid humoral response against a specific pathogen
 Provides only temporary protection, as antibodies have a half-life of ∼ 3 weeks and their titers decrease over
time.
o Examples
 Antitoxins
 Humanized monoclonal antibodies
 Maternal immunoglobulins that are transmitted via breast milk (IgA) or cross the placenta (IgG) to provide
passive immunity
o Indications
 Acute, post-exposure elimination of a pathogen
 Viruses: rubella, rabies, hepatitis B
 Toxins: tetanus, botulinum, diphteria
 Rhesus incompatibility prevention
o Application: Vaccines are available for intramuscular as well as for intravenous injection
o Combination
 Simultaneous vaccination: ≥ 1 vaccine administered on the same day, but in different syringes and at
different anatomical locations
 Two different passive vaccines may be administered simultaneously.
 An inactivated active and a passive vaccine may be administered simultaneously (e.g., in acute hepatitis A,
hepatitis B, rabies, or tetanus infection).
 After administration of a passive vaccine against a specific pathogen, a live vaccine against the same
pathogen should not be administered for at least 3 months.

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 Active immunization
o General information
 In active immunity, the body's immune system reacts to the presence of antigens by producing antibodies.
 In general, a combination of different active vaccinations is possible.
 Slow onset, but immunity usually lasts for years or even a lifetime.
 Besides vaccines and toxoids, natural infections lead to active immunization as well.

Types of vaccines
 monovalent vaccine contains a single strain of a single antigen (e.g. Measles vaccine), polyvalent vaccine
contains two or more strains/serotypes of the same antigen (e.g. pneumococcal vaccine)
 Live attenuated vaccines: Modified functioning virus or bacterium that can replicate in the patient's body but
does not cause disease, e.g. MMR, Varicella, Yellow fever
 Inactivated vaccines
o Whole vaccines
 Whole inactivated or dead pathogens (using chemicals or heat) that are unable to replicate
 Surface epitopes remain unchanged, since they are important for triggering an adequate immune response.
 Cause a weaker immune response, but are considered to be safer than live vaccines
 E.g. Polio (Salk; inactivated vaccine), Hepatitis A, Rabies
o Fractional vaccines
 Protein-based (subunit and toxoid vaccines)
 Subunit
o Inactive antigenic subunits of pathogens that provoke the most effective immune response
o Weaker immune response and more expensive
o But lower risk of adverse reactions
o E.g. Hepatitis B (using the HBsAg), Influenza, Pertussis (acellular vaccine)
 Toxoid
o Toxoids are bacterial toxins in which the toxicity has been inactivated while immunogenicity is maintained
through intact receptor binding sites.
o Immune system reacts to exposure with production of antibodies against bacterial toxins → protective
immunization
o E.g. Diphtheria (C. diphtheria), Tetanus (Clostridium tetani)
 Polysaccharide-based
 Bacterial cell wall polysaccharide
 Conjugate polysaccharide vaccine is linked to a protein E.g., conjugation of Hib polysaccharide to tetanus
toxoid. By attaching a weak antigen to a strong antigen, a more intense immune response to the weak
antigen is induced
 E.g. Meningococcal vaccine (conjugate vaccine; various strains of Neisseria meningitidis); Haemophilus
influenzae serotype b (conjugate vaccine), Pneumococcal PCV13 (conjugate vaccine)
 mRNA?

Application method
 Usually injected into the deltoid muscle
(alternatively, e.g., in infants, injected into
the vastus lateralis muscle)
o Live attenuated vaccines: Oral vaccine or
subcutaneous/intramuscular injection in
children > 12 months
o Second dose usually recommended to
“catch” non-responders (not as a boost)

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 First dose does not provide protective immunity
 Multiple doses required
 Periodic “boosts” necessary to ensure sufficiently high antibody titers
 Inactivated vaccines may generally be combined with other vaccines without any time interval in between

Adverse effects of immunization

 Common adverse effects
o Affects ∼ 1/3
o Usually begin within the first 48–72 hours after administration and last 1–2 days
o Symptoms
 Local swelling, redness, and pain at the injection site
 Low-grade fever, Headaches, Tiredness, Flu-like symptoms
o Live attenuated vaccine: can cause mild form of the disease, usually appearing within 1–3 weeks of
administration: usually caused by replication of the attenuated vaccine strain
 Rare adverse effects
o Serious allergic reaction (generally < 1 per million doses)
o Live attenuated vaccine: attenuated course of the disease following immunization (e.g., vaccine-related
measles)
o Vaccine injury (∼ 1/1,000,000): permanent injury from a vaccination or a vaccine-related complication (e.g.,
encephalopathy, seizures, brachial neuritis)

Contraindications for vaccination

 General contraindications
o Previous life-threatening adverse reaction related to vaccination: e.g. anaphylaxis
o Severe allergies to components of a vaccine: e.g., egg white in some live vaccines (e.g., yellow fever)
o Acute illness, such as infection with fever > 38.5°C
 Live vaccinations are not recommended for
o Pregnant individuals
o Immunodeficient individuals
 Special contraindications
o Rotavirus vaccine: severe combined immunodeficiency (SCID), history of intussusception, uncorrected GI tract
malformation (e.g., Meckel's diverticulum)
o Tetanus: development of Guillain-Barré syndrome within 6 weeks after a previous dose of tetanus toxoid-
containing vaccine
o Pertussis-containing vaccines: known anaphylactic reactions, encephalopathy within 7 days following previous
vaccination, progressive or unstable neurologic disorder (e.g., coma, uncontrolled seizures, or progressive
encephalopathy)
 Precautions: fever > 40.5°C (> 105°F), shock-like state within 48 hours following the previous vaccination,
seizure within 3 days following previous vaccination, inconsolable crying > 3 hours following the previous
vaccination
 False contraindications - one of the primary reasons for under-vaccination in children worldwide
o Low-grade fever
o Current or recent mild illness (e.g., rhinorrhea, otitis media, mild diarrhea)
o Current or recent antibiotic therapy (exception is oral live typhoid vaccine)
o Current or recent low-dose and/or short-term steroid use (i.e., < 2mg/kg/d or < 20mg/kg, < 14 days)
o Previous mild or moderate location reaction (e.g., swelling, redness, soreness) following any vaccination
o Preterm infants: should be immunized according to chronological age, not by gestational age (exception is
Hepatitis B vaccine, which should be delayed for infants weighing < 2 kg)
o Adjustment according to weight: no dose adjustment is needed

15
Schedule Bulgaria
2. Administration after 48 hours from birth.
3. Only after negative Montoux test
4. Booster dose after negative Montoux test
5. Not earlier than 12 months after the 3rd dose
6. Subsequent Td booster every 10 years
7. Administration within 24 hours after birth.
8. When using a monovalent vacine, doses are administered at
1 and 6 months
9. When using a combination vaccine (e.g. hexavalent vaccine),
doses are administered at 2, 3 and 4 months
10. Not earlier than 6 months after the previous dose
11. PCV13 is given starting from 50 years. The scheme is
completed with PPSV23 in 65 years and older
12. Girls-only vaccination offered. HPV vaccination is free of
charge but voluntary and not included in the National
Immunisation schedule
13. Annual vaccination. Recommended but not free of charge.
 Mandatory vaccine

https://vaccine-schedule.ecdc.europa.eu/
check here for updates
obligatory planned immunizations and boosters are performed
by:
1. doctor serving newborns in hospital for inpatient care;
2. GP.
3. Immunization office of RHI and NCIPD

16
17
9. Social Factor - Impact on the epidemic process.
 socioeconomic factors such as crowding, sanitation, and the availability of health services

18
10. Natural factor - impact on the epidemic process. Natural - focal
infections.
 Environment refers to extrinsic factors that affect the agent and the opportunity for exposure. Environmental
factors include physical factors such as geology and climate, biologic factors such as insects that transmit the
agent
 elements of the environment (objects, water, foodstuffs, insects, arthropods, etc.) which take part in the single-
point or sequential transmission of the pathogenic microorganisms from the source of infection to the
susceptible organism.
 Types of factors:
o biotic and abiotic
 Abiotic factors refer to non-living physical and chemical elements in the ecosystem. Abiotic resources are
usually obtained from the lithosphere, atmosphere, and hydrosphere. Examples of abiotic factors are water,
air, soil, sunlight, and minerals
 Biotic factors are living or once-living organisms in the ecosystem. These are obtained from the biosphere and
are capable of reproduction. Examples of biotic factors are animals, birds, plants, fungi, and other similar
organisms.
o intermediate and final;
o primary (major) and secondary.
 naturally occurring variations in temperature and rainfall
 Deforestation disrupts natural habitats of animals, and can force animals, searching for food, into closer contact
with humans
 Climate extremes, whether involving excessive rainfall or drought, can likewise displace animal species and bring
them into closer contact with human settlements, or increase vector breeding sites
 adoption of modern consumer habits in urban areas where discarded household appliances, tyres, plastic food
containers and jars have created abundant artificial mosquito breeding sites
 large amounts of stagnant water, created by ineffective irrigation schemes, provided mosquito breeding sites
that permitted the re-emergence of malaria

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 11. Forms of epidemic process - sporadic, epidemics (types), pandemics,
epidemic outbreak.
Endemic Epidemic Pandemic
Definition A disease is endemic when it affects A disease that affects individuals at A disease that affects a wide
individuals at a relatively constant rate an unusually fast rate within a geographic area, such as
within a specific population in a given specific population in a given multiple countries or
region. region continents
Time Unlimited Limited Limited
Area Limited Limited Unlimited
Examples Malaria in Africa Ebola fever in West Africa (2014) Spanish flu (1918/19)
Yellow fever in parts of South America Seasonal influenza COVID-19 (coronavirus
and Africa disease 2019)
Possible  Spread of disease vectors and  Infectivity of a pathogen:  Global trade and travel
factors pathogen reservoirs increased ability to multiply in  Increased infectivity of a
 Geographical conditions a host pathogen (e.g., antigenic
 Climate  Living conditions (e.g., living in shift)
 Living conditions (e.g., sewage crowded areas)
systems, housing, work)  Spread/introduction of the
pathogen to a new
geographical area
 Sporadic refers to a disease that occurs infrequently and irregularly
 Hyperendemic refers to persistent, high levels of disease occurrence

Epidemic Patterns
 can be classified according to their manner of spread through a population
 common-source outbreak is one in which a group of persons are all exposed to an infectious agent or a toxin
from the same source
o point-source outbreak: group is exposed over a relatively brief period, so that everyone who becomes ill does
so within one incubation period
o continuous common-source outbreak: range of exposures and range of incubation periods tend to flatten and
widen the peaks of the epidemic curve
o intermittent common-source outbreak: has a pattern reflecting the intermittent nature of the exposure
 propagated outbreak: results from transmission from one person to another
o transmission is by direct person-to-person contact, as with syphilis, may also be vehicleborne (e.g.,
transmission of hepatitis B or HIV by sharing needles) or vectorborne (e.g., transmission of yellow fever by
mosquitoes)
o cases occur over more than one incubation period
 mixed outbreak: have features of both common-source epidemics and propagated epidemics
o pattern of a common-source outbreak followed by secondary person-to-person spread
 Other: neither common-source in its usual sense nor propagated from person to person
o zoonotic or vectorborne disease may result from sufficient prevalence of infection in host species, sufficient
presence of vectors, and sufficient human-vector interaction

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12. Epidemiological study - purpose, stages, mode of conduct,
epidemiological analysis.
 Purposes of epidemiological study
o To determine the nature and extent of the epidemic process in time and space (territory) and define the
borders of epidemic focus
o To determine the origin of the epidemic process - the source of infection, factors and routes of transmission of
infection and Immunity of population.
o to develop and implement a integrated anti-epidemic measures to quickly eradicate the epidemic focus.
o To conduct preventive measures to avoid the occurrence of new outbreaks by: sanitary measures
(disinfection), current and final disinfection, pestcontrol, specific immunoprophylaxis.
 Stage I: Primary survey of focus.
o Performed mostly by GP hospital, MC, laboratories.:
 medical specialists register and report all cases to the RHI
 They do research,
 They make a diagnosis
 Stage II – Epidemiological surveillance of the focus – performed by RHI
o Deepening of the epidemiological study for locating the source of infection.
o Full investigation of all contacts in the defined limits of the focus.
o Determination of the mechanism of transmission.
o Defining the factors and roads.
 Stage III- anti-epidemic measures. Conducted by RHI
o vs. source: isolation, samples, notification, treatment, correct patient discharge, dispanserisation
 Early detection and diagnosis of disease etiology.
 Registration book for registration of communicable diseases;
 Notification with quickly notice in RHI
 Isolation of patients;
 Specific treatments;
 Correct hospital discharge –Clinical strong and negative microbiological testing, depending on the infection.
 Under certain infections has long monitoring – dispanserisation.
 The transport and hospitalization of the patient must be special transport should be made mandatory
disinfection of the vehicle.
o vs. contacts: detection, medical examination, samples, prophylaxis
 To contact people – Medical monitoring for a maximum period of incubation, according to the infection.
 Clinical monitoring – daily temperature measuring . Quarantine of contact with sick especially dangerous
infections are isolated in isolator.
 No visit permitted at the time of isolation
o vs. environment: disinfection\sterilization, pest control
 Stage ІV – Overall analysis of the result of epidemiological research and elimination of the focus. Placement of
epidemiological diagnose и evaluation of efficiency of the conducted activities – conducted by RHI.
o Analysis of factors determining the characteristics of quantitative and qualitative indicators of the epidemic
process
o Formation of the final epidemiological diagnosis
o Develop recommendations for optimization of preventive and anti-epidemic work.
o Develop a forecast of the epidemiological situation
o Epidemiological analysis is one of the main methods of epidemiology for E. process and to assess the
effectiveness of anti-epidemic and preventive measures in the fight against communicable diseases.

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 Major areas of epidemiological study include disease causation, transmission, outbreak investigation, disease
surveillance, environmental epidemiology, forensic epidemiology, occupational epidemiology, screening,
biomonitoring, and comparisons of treatment effects such as in clinical trials.
 Epidemiologists rely on other scientific disciplines like biology to better understand disease processes, statistics
to make efficient use of the data and draw appropriate conclusions, social sciences to better understand
proximate and distal causes.
 Observational studies have two components, descriptive and analytical.
o Descriptive observations pertain to the "who, what, where and when of health-related state occurrence".
However, analytical observations deal more with the ‘how’ of a health-related event.
o It is important to collect as much information as possible about each event in order to inspect a large number
of possible risk factors. The events may be collected from varied methods of epidemiological study or from
censuses or hospital records.
 Type of research to practical application of epidemiological methods (observation, analysis and experiment) to
clarify the nature, extent and origin of a particular epidemic process, part of it or the individual epidemic focus to
administration and control of the necessary anti- epidemic measures for its eradication and preventive measures
to avoid their occurrence again.
 Epidemiological diagnosis - "Assessment of the epidemiological situation and its causes in a given territory."
o result of multi-faceted activities of physicians, a characteristic feature of which is the analytic and synthetic
thought.
 Objectives of epidemic investigations
o 1.Define magnitude of epidemic (time, person, place) (When, Whom, Where).
o 2.Determine factors responsible for epidemic (Why).
o 3.Identify cause, sources of infection and modes of transmission (How).
o 4.Implement control and preventive measures at commence of epidemic
 method of epidemiological investigation
o Study of epidemic focus – an infectious patient or carrier, their contact people and their surrounding external
environment.
o Epidemic focus – the place where the source of infection is or has been, and the adjacent territory, within the
range of which he can spread under specific circumstances the pathogens
 main task of an epidemiological study/investigation
o o find the characteristics of an epidemic outbreak – his character, place, time, extent, manner of occurrence
 Types of epidemiological analysis
o Current or operational. Performed during the epidemiological study.
o Periodical. Perform every month three months, six months and a year.
o Retrospective. Performed for a shorter or longer passing time in order to forecast the epidemic process,
prospective planning of anti-epidemic and preventive measures and evaluating their effectiveness
 1 Stage of epidemiological analysis
st

o Statistical processing and analysis of the data from study of epidemic outbreaks.
o qualitative signs
 the ratio between the number of diseased and the number of outbreaks.
 Focal morbidity. In its calculation does not include the first bo linen, probably contracted out of the hearth.
 Average duration of the outbreak.
 Seasonality
o quantitative signs
 Morbidity, number of individuals in a population with a disease at a specific point in time: MB =
(diseased)/(population) × 100
 Mortality: MR = (deaths)/(population) × 100

22
  Lethality, Percentage of cases (patients with a specific condition) that result in death within a specific time
interval: CFR = (number of deaths from a specific condition)/(number of cases with the same specific
condition) × 100
 Distribution of the sick and infection carriers: age; sex; profession; heaviness of clinical course
 Second Stage Study of basic epidemiological links
o Sources of infection and modes of transmission of infection with specific descriptions in the various outbreaks.
o Determination of the mechanism of transmission.
 Third stage. Analysis of anti-epidemic events in terms of their effectiveness
o Sources of infection:
 early diagnosis
 location and means of detection (active, passive);
 hospitalization;
 search for the contact;
 dispensary of morbidity
o Mechanism of transmission of infection efficiency measures for interruption:
 assessment of focal disinfection and insect control;
 Increasing immunity of the population
 Epidemiological study or investigation may continue days, months and years (enzootic foci of plague).

23
13. General preventative and basic control measures in the epidemic focus
- to the patient, the contact persons and the environment.
 vs. source: isolation, samples, notification, treatment, correct patient discharge, dispanserisation
o Early detection and diagnosis of disease etiology.
o Registration book for registration of communicable diseases;
o Notification with quickly notice in RHI
o Isolation of patients;
o Specific treatments;
o Correct hospital discharge –Clinical strong and negative microbiological testing, depending on the infection.
o Under certain infections has long monitoring – dispanserisation.
o The transport and hospitalization of the patient must be special transport should be made mandatory
disinfection of the vehicle.
 vs. contacts: detection, medical examination, samples, prophylaxis
o To contact people – Medical monitoring for a maximum period of incubation, according to the infection.
o Clinical monitoring – daily temperature measuring . Quarantine of contact with sick especially dangerous
infections are isolated in isolator.
o No visit permitted at the time of isolation
 vs. environment: disinfection\sterilization, pest control

24
14. Epidemiological control and surveillance of infectious diseases.
 ‘Close observation of individuals suspected of incubating serious infectious diseases in order to detect initial
symptoms of disease in time to institute treatment and isolation’
 Epidemiologic surveillance – system of methods for etiological and clinical diagnosis and enforcement of
complex measures leading to accomplishment of certain epidemiological goal. The whole structure and
functional system adopted by health care services as a policy is known as epidemiologic surveillance.
 Uses of Surveillance
o I) Identify the disease trend so that planning of preventive and control programs can be adjusted to meet the
new situation.
o 2) Identify investigate and help the control of outbreaks or epidemics.
o 3) Identify the population at risk for certain disease or death.
o 4) Identify new emerging disease.
o 5) Evaluation of preventive and control measures of the disease under study
 Tools for Control of Communicable Diseases
o Isolation, treatment, vaccination, prophylaxis, disinfection, quarantine, surveillance
 Steps in setting up surveillance
o 1. Understand the problem: Public Health importance, feasibility
o 2. Identify opportunities for prevention & control
 interventions
 target audience
o 3. Set objectives: Specific, Measurable, Acceptable and Action oriented, Realistic, Time related
o 4. Specify attributes to meet objectives
o 5. Design
 case definitions & indicators
 data needed
 data sources
 data transfer
o 6. Translate information into action
 analyse
 interpret
 disseminate
o 7. Evaluate surveillance system

25
 15. Health-care associated infections (HCAI). Organizing and conducting of
epidemiological surveillance and control in the Republic of Bulgaria.
 Nosocomial infections are defined as infections acquired after hospitalization that occur > 48 hours after
admission.
 At admission, these infections are not present or incubating.
 Risk factors
o Age > 70 years
o Lengthy hospital stays → ↑ risk of infection
 Medical staff (e.g., insufficient disinfection of hands, clothing)
 Contact surfaces (e.g., equipment, furniture)
 Indoor air (e.g., via contaminated by droplets from infected patients, staff, procedures like bronchoscopy)
o Iatrogenic: caused by treatment or a diagnostic procedure
 Foreign bodies (e.g., catheters, intravenous catheters, endotracheal tubes) and invasive instruments
 Conditions which require a high amount of interventional procedures (e.g., shock, major trauma, acute renal
failure, coma)
 Mechanical ventilation
o Prior antibiotic use
o Metabolic diseases (especially diabetes mellitus)
o Immunosuppression
 Surgical site infection
o Definition: infection arising within 30 days of a surgical procedure at the the site of surgical intervention
o Epidemiology
 15–20% of all healthcare-associated infections
 Most common nosocomial infection among patients undergoing surgery
 Incidence: ∼ 5% of all surgical wounds
o Etiology
 Causative pathogens
 During the first 4 days (uncommon)
o Group A streptococci (GAS)
o C. perfringens → necrotizing fasciitis
 After 4 days: SSI due to bacteria in the skin, genital tract, or gastrointestinal tract (e.g., S. aureus)
 > 30 days: SSI due to indolent organisms (e.g., coagulase-negative staphylococci)
 Risk factors
 Patient-related: Corticosteroid therapy, Malnutrition, Obesity, Diabetes mellitus, Advanced age
 Surgical site related: Large incision, Degree of wound contamination
Type of surgical wound Definition Incidence of SSI
 All of the following:
o Noninflamed operative wound
Clean o The respiratory, alimentary, genital, and urinary tracts have not been entered during  1.5%
surgery.
o Wound is closed primarily with or without a drain
 Noninflamed operative wound
Clean-contaminated  8%
 The respiratory, alimentary, genital, and/or urinary tracts have been entered.
 Fresh, open, accidental wounds
Contaminated  Inflamed operative wound without purulent drainage  15%
 Clean or clean-contaminated wounds with a break in sterile technique during surgery
Dirty or infected  Old traumatic wounds
 40%
wounds  Inflamed operative wound with purulent drainage

26
 Incisional SSI
Type of SSI Organ/space SSI
Superficial incisional SSI Deep incisional SSI
 SSI involving any part of the body that is
 SSI involving only the skin
 SSI involving fascia and muscle deeper than the fascia or muscle layers,
Definition and subcutaneous tissue
layers at the site of the incision and was opened or manipulated during
of the incision
surgery
 Purulent discharge from deep
 Purulent discharge from
within the incision  Postoperative fever
the incision
 Postoperative fever  Purulent discharge from a drain placed
Clinical  In some cases,
 Tenderness at the incision within the organ or space, or an abscess
postoperative fever
features  Wound dehiscence  Additional signs will be present
 Tenderness, erythema,
 Necrotizing fasciitis: cloudy gray depending on the site of infection (e.g.,
warm, and/or localized
discharge, possible crepitus of osteomyelitis).
swelling
tissue surrounding the wound
o Diagnostics
 Leukocytosis
 Incisional SSI: wound swab for Gram stain and wound culture
 Organ/space SSI: imaging (e.g., CT, MRI)
o Surgical therapy
 Suture removal, incision and drainage, regular dressings, and daily wound inspection
 Debridement is indicated when there is devitalized tissue.
 Delayed closure once the wound is no longer infected
o Empirical antibiotic therapy
 Indications: Erythema and induration extending > 5 cm from the wound edge; Fever > 38.5° C; Heart rate >
110/min; WBC count > 12,000 cells/mm3
 Antibiotic of choice
 SSI in a clean wound over the trunk, head and neck, or limb:
o Low risk of MRSA: cefazolin
o High risk of MRSA, or individuals allergic to beta-lactams: vancomycin, daptomycin, or linezolid
 SSI in a clean-contaminated wound, or in a clean wound over the perineal region: cephalosporin and
metronidazole, levofloxacin and metronidazole, or carbapenem
 If group A streptococci or C. perfringens is suspected: penicillin and clindamycin
o Targeted antibiotic therapy may be initiated once results of the bacterial culture are available.
 Hospital-acquired pneumonia (HAP): nosocomial pneumonia, with onset > 48 hours after admission
o Ventilator-associated pneumonia (VAP): pneumonia occurring in patients who are on mechanical ventilation
breathing machines in hospitals (typically in the intensive care unit)
o Most common pathogens: S. aureus, P. aeruginosa
 Catheter-associated urinary tract infection (CAUTI)
o Caused by indwelling urinary catheters
o Most common cause of nosocomial urinary tract infection: Occurs when catheters remain in the urethra for an
extended period of time, nursing home residents, and patients with neurologic dysfunction. The risk of
infection can be reduced by proper, aseptic catheter placement and intermittent catheterization.
o Most common pathogen: E. coli
 Bloodstream infections
o Catheter-related bloodstream infection (CRBSI) is a bloodstream infection attributed to an intravascular
catheter.
o Risk factors: Immunosuppression, Bone marrow transplant, Burn, Catheter type: central venous catheters
 Sites of insertion: femoral and inguinal catheter insertion sites have high risk for infection while the
subclavian site carry less risk

27
 o Etiology: the most common pathogens are: Coagulase-negative staphylococci, S. aureus, Enterococci, Candida
species
o Clinical features
 Fever
 Hemodynamic instability
 Swelling, pain, redness, and purulence at catheter insertion sites
 Altered mental status
o Diagnosis
 Approach: Catheter-related blood stream infection should be suspected in patients presenting with septic
features 48 hours after insertion of the catheter.
 Blood culture: samples should be collected prior to initiation of antibiotics
o Treatment
 Short-term catheters should be removed from patients with catheter related blood stream infection that is
caused by the following pathogens: Gram-negative bacilli, S. aureus, Enterococci, Fungi, Mycobacteria
 Long-term catheters should be removed in the following cases:
 Severe sepsis; Suppurative thrombophlebitis; Endocarditis; Persistent bloodstream infection despite > 72
hours of antimicrobial therapy
 Infections caused by the following pathogens: S. aureus, P. aeruginosa, Fungi, Mycobacteria
o Start empiric treatment
 Gram-positive pathogens: Vancomycin is recommended in an institution with high rate of MRSA infection.
 Pseudomonas aeruginosa should be covered with agents such as imipenem, ceftazidime, cefepime, OR
piperacillin-tazobactam
 Candida species  Individuals at risk should be treated with echinocandin.

Structure of epidemiological surveillance

 Epidemiological surveillance in BG takes place at the following levels
o Peripheral level - the sources of epidemiological information – GP, hospital, MC, dispensaries, laboratories,
DM,
o Regional level: 28 RHI Regional health inspections
o Central level - organize, plan, supervise and coordinate the overall supervisory actions. Includes:
 MH
 Chief State Health Inspector
 National Center of Infectious and Parasitic Diseases (NCIPD)
 Epidemiological surveillance requires daily monitoring of all aspects of epidemic process.
 In this connection it is necessary:
o early detection and diagnosis of infectious diseases;
o registration and reporting of infectious diseases;
o epidemiological study;
o processing epidemiological information;
o Epidemiological analysis;
o assess the quality and effectiveness of epidemiological control
 List of infectious and parasitic diseases, which are subject to mandatory registration, notification and reporting
o Basically everything on the syllabus plus Creutzfeld-Jakob, Syphilis, Chlamydia
 medical specialists who have detected infectious diseases notify the RHI within 24 hours, by quickly notice.
 GPs, medical specialists of medical institutions, health clinics and schools, kindergartens and RHI register
infectious diseases in a book of communicable diseases

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Nur falls sie nachfragen wie
es in Deutschland ist

29
16. Problems of the liquidation of the infectious diseases
 Elimination - Reduction to zero of the incidence of a specified disease in a defined geographical area as a result
of deliberate efforts
 Eradication - Permanent reduction to zero of the worldwide incidence of infection caused by a specific agent as
a result of deliberate efforts
 Liquidation - process of liquefying an agent in order to wash it out from the preferred area
 Control: The reduction of disease incidence, prevalence, morbidity or mortality to a locally acceptable level as a
result of deliberate efforts; continued intervention measures are required to maintain the reduction. Example:
diarrhoeal diseases.
 Elimination of disease: Reduction to zero of the incidence of a specified disease in a defined geographical area
as a result of deliberate efforts; continued intervention measures are required. Example: neonatal tetanus.
 Elimination of infections: Reduction to zero of the incidence of infection caused by a specific agent in a defined
geographical area as a result of deliberate efforts; continued measures to prevent reestablishment of
transmission are required. Example: measles, poliomyelitis.
 Eradication: Permanent reduction to zero of the worldwide incidence of infection caused by a specific agent as a
result of deliberate efforts; intervention measures are no longer needed. Example: smallpox.
 Extinction: The specific infectious agent no longer exists in nature or in the laboratory. Example: none.
 Principal Indicators of Eradicability
o Humans are essential for the life-cycle of the agent, which has no other vertebrate reservoir and does not
amplify in the environment(anthroponosis)
o An effective intervention is available to interrupt transmission of the agent
o Practical diagnostic tools with sufficient sensitivity and specificity are available to detect levels of infection that
can lead to transmission
o Additional conditions
 The infectious process occurs exclusively with clinical manifestations (high contagious index) without carriers.
 The disease is transmitted only through the natural mechanism and only marginally in other (artificial) roads.
 Absence of biologically evolutionary relationships, revealing a distant relation to other similar parasites.
 Eradicable diseases usually need to meet the following criteria:
o it’s an infectious disease
o humans are the major host of for the disease,
o effective vaccines or treatments are available for the disease,
o there is political and financial support for the eradication efforts
o When a disease stops circulating in a region, it’s considered eliminated in that region.
 Criteria evidencing achievement of the eradication
o Absence of transmission of infection for a two to three years.
o Absence of transmission of infection after stopping of administration of the main means for infection control.
o Demonstration in tests disappearance of the specific agent.
 Proved through laboratory tests that will not adapt closely related parasite that can cause new disease.
 Proved through epidemiological surveillance that no imports of infection.
 Final effects
o The direct effects of eradication are that no morbidity or mortality due to that disease will ever again occur.
o Control programmes can cease.
o The consequent effects are those that impact positively and negatively on the entire health care system.
o Control and elimination can apply to noninfectious diseases

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 17. Disinfection and sterilization.
 High level disinfection - a process in which destroy vegetative forms of bacteria, including, Mycobacterium
tuberculosis, fungi, viruses, incl. enteroviruses
and some spores.. High-level disinfection
traditionally is defined as complete elimination
of all microorganisms in or on an instrument,
except for small numbers of bacterial spores.
 Moderate disinfection - a process in which
destroy vegetative forms of bacteria, including
mycobacteria, fungi, viruses, but does not affect
bacterial spores.
 Low-level disinfection - a process in which
destroy vegetative forms of bacteria other than
Mycobacterium tuberculosis.

Disinfectants and antiseptics

 Disinfection a process that eliminates many or all pathogenic microorganisms, except bacterial spores
 disinfectants are used on nonliving surfaces, whereas antiseptics are used on living tissue
Agent Mechanism of action Active against Sporicidal
Alcohols (e.g., isopropyl alcohol and  Causes membrane damage and denaturation of
ethyl alcohol) proteins
 At low concentrations: leakage of intracellular
components due to cell membrane disruption  Bacteria
Bisbiguanides (e.g., chlorhexidine)
 At high concentrations: cause precipitation of  Enveloped
 No
intracellular proteins and nucleic acids viruses
 At low concentrations: inactivates essential  Fungi
Phenol (e.g., orthophenylphenol
enzymes and induces leakage of metabolites
and ortho-benzyl-para-
 At high concentrations: disrupts cell wall and
chlorophenol)
precipitates cell proteins
Iodine and iodophors
 Yes (with prolonged
(e.g., povidone-iodine  Halogenation of RNA, DNA, and proteins
contact time)
Halogen- and poloxamer-iodine)
releasing Chlorine-releasing  Yes (e.g., effective
agents  Highly active oxidizing agents that denature
agents (e.g., sodium against highly
proteins and nucleic acids and disrupt oxidative
hypochlorite and  Bacteria resistant spores of
phosphorylation
chlorine dioxide)  Viruses Clostridium species)
 An oxidant that produces hydroxyl free radicals  Fungi  Yes (only at higher
Hydrogen peroxide (•OH), which damage essential cell components, concentrations and
including lipids, proteins, and DNA longer contact times)
 Microbicidal effect is mediated by alkylation of
Aldehydes (e.g., glutaraldehyde) sulfhydryl, hydroxyl, carboxyl, and amino groups  Yes
of RNA, DNA, and proteins.
 Bacteria (not
 Induces inactivation of energy-producing mycobacteria)
Quaternary ammonium compounds
enzymes, denaturation of essential cell proteins,  Enveloped  No
(e.g., benzalkonium chloride)
and disruption of the cell membrane viruses
 Fungi
 Skin and/or mucous membrane disinfection
o Commonly used agents: alcohols (e.g., ethanol), biguanides, phenols

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 o Mechanism of action: protein denaturation
o Advantage: rapid onset of action and well tolerated
o Disadvantages
 Ineffective against bacterial spores and nonenveloped viruses
 Decrease in antiseptic/disinfecting efficacy after contact with proteins (e.g., blood)
o Alternative: iodine preparations
 Surface disinfection
o Commonly used agents: aldehyde, halogens, ammonium compounds, oxidants (e.g., hydrogen peroxide)
o Mechanism of action: denaturation of various structures (proteins, nucleic acids, cell nuclei)
o Advantage: high efficacy also against spores and nonenveloped viruses, minimal decrease in
antiseptic/disinfecting efficacy after contact with proteins (e.g., blood)
o Disadvantage: poorly tolerated
o Alternative
 Quaternary ammonium compounds
 Disadvantage
 Ineffective against gram-negative bacteria, mycobacteria, and mycoplasma
 Decreased efficacy after contact with proteins
 Physical methods of disinfection
o Flaming: Inoculation loop or Wire, the tip of Forceps and spatulas are held in a bunsen flame till they are red
hot.
o Incineration is a waste treatment process that involves the combustion of organic substances contained in
waste materials. This is an excellent method of destroying materials such as contaminated cloth, animal
carcasses and pathological materials, hospital waste
o Pasteurization - Process of killing of pathogens in the milk but does not sterilize it
 Milk is heated at 63°C for 30 mins (HOLDER METHOD)
 At 72°C for 15-20 Sec. Rapid cooling to 13°C (FLASH PROCESS)
o INSPISSATOR: Sterilizes by heating at 80-85°C for half an hour for 3 successive days. Inspissator for use in the
preparation of TB culture medium
o Boiling

Sterilization
 Definition: the process of destroying all microbial life, including spores, on a surface or in a fluid.
 Aim
o Medical equipment that has come into contact with sterile tissue or fluids must also be sterilized.
o Heat-stable equipment is sterilized mainly using steam (autoclave).
o Heat- and moisture-sensitive equipment (plastics, electrical devices, and corrosion-susceptible metal alloys)
require low-temperature sterilization using, e.g., ethylene oxide, hydrogen peroxide gas plasma, peracetic acid
 Sterilization techniques for heat-stable equipment
o Steam sterilization (autoclave)
 Exposing equipment to direct steam at a certain temperature and pressure for a specified period of time
 Mechanism of action: irreversible coagulation and denaturation of enzymes and structural proteins
 Active against bacteria, fungi, viruses, and spores
 Treated at > 121°C: typically uses 134°C for 3 minutes or 121°C for 15 min
 Prions are not destroyed by standard autoclaving. They must be sterilized at 121–132°C for 60 min (not a
standardized method).
o Dry air sterilization
 Exposing equipment to dry heat, which gets absorbed by the external layer and transferred inward to the
interior layer by a process called conduction
 Denatures and oxidizes proteins and other cell components

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  Commonly uses 170°C for 60 min, 160°C for 120 min, and 150°C for 150 min
 Sterilization techniques for heat- and moisture-sensitive equipment
o Ethylene oxide gas sterilization
 Ethylene oxide: flammable and explosive gas
 The sterilization process includes preconditioning and humidification, gas introduction, exposure, evacuation,
and air washes.
 Mechanism of action: alkylation of protein, DNA, and RNA
 Microbicidal against all microorganisms, with limited sporicidal effect due to spores resistance.
 Disadvantages: lengthy cycle time, costly, and hazardous
o Hydrogen peroxide gas plasma sterilization
 Hydrogen peroxide diffusion and gas plasma generation → formation of free radicals → damage enzymes,
nucleic acid, and disrupt cellular metabolism
 Active against bacteria (including mycobacteria), yeasts, fungi, viruses, and bacterial spores
 Radiation Sterilization
o NON –IONISING e.g UV
 Electromagnetic rays with longer wavelength
 Absorbed as heat
 Can be considered as hot air sterilisation
 Used in rapid mass sterilisation of prepacked Syringes and catheters
o IONISING RADIATIONS - X- rays, gamma rays & cosmic rays
 High penetrative power
 No appreciable increase in the temperature – COLD STERILISATION
 Sterilise plastics Syringes, catheters, grease fabrics metal foils

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18. Disinsection - definition, methods, tools. Epidemiological significance.
 means the procedure whereby health measures are taken to control or kill the insect vectors of human diseases
Or - method for destroying harmful arthropods (insects and mites)
 Insects can be present in luggage, cargo, containers, transportation, goods and mail parcels
 Preventive - different hygiene and sanitary measures (communal and personal hygiene Hydro - draining of
swamps and other water bodies with stagnant water, wavy patterns)
 Destructive measures destroy the insects, thus interrupting the mechanism of transmission of infection
 biological method involves the use of another living organism to kill a pest
o Uses natural enemies of harmful arthropods -vermin and predators, pathogens, genetic manipulation for
reduce the populations.
o This method is the most environmentally friendly, but through it the desired effect is achieved relatively slowly
o To destroy any mosquito larvae using Gambusia fish (Gambusia affinis)  They are eating with mosquito larvae
 It can be used in rice paddies
 Mechanical method
o includes various methods of cleaning - tapping, brushing, vacuuming, laundry and more. Manual extermination
(baton) used against flies, mosquitoes, cockroaches and others
o Flycatchers of sticky paper used against flying insects. They are covered in a substance that attracts insects, but
are actually very sticky or poisonous
 the sticky mixture may be prepared from 2 parts of rosin and 1 part of castor oil; The ingredients are not
toxic; Used tapes subsequently burned
 Physical method: apply high temperature in various forms – burning, dry heat, boiling, steaming under pressure
 Chemical methods
o most common method of pest control is the use of pesticides—chemicals that either kill pests or inhibit their
development
o often classified according to the pest they are intended to control
o Pesticides also include chemosterilants and growth regulators, which are used to interfere with the normal
reproduction or development of the pest
o Substances extermination arthropods are called insecticides (in ticks - acaricide)
o funds that destroy the larvae of arthropods are called larvotsides and their eggs – ovоcides
o funds that attract insects – attractants or repel – repellents
o Forms of application of insecticides
 Powders - used inert filler (talc or kaolin), and 5 - 10% of insecticide. They are carried pollination of premises,
clothes, etc.
 Granules - plastic or other particles impregnated with insecticide, the content can reach 50%. They have
extended residual effect.
 Solutions - contain up to 5% insecticide and a solvent
 Emulsions - are composed of two liquids in which the middle phase and do not dissolve in each other.
 Aerosols -
 Other forms of application of insecticides - varnishes, paints, shampoos, soaps, bands, food baits, etc
o classified according to their chemical composition in several groups:
 Phosphorus insecticides - In intoxication as an antidote atropine are used.
 Pyrethrins – plant alkaloid extracted from chrysanthemum holding fast effect, as lotion and shampoo for
head lice. Their synthetic analogues are called piretroides
 Carbamate insecticides.
 Chlorinated organic insecticides. – against lice, cockroaches, fleas, bedbugs
 Other insecticides
 Benzyl benzoate
 Sulphur preparations - against lice
 Distillation products

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  Oil, gasoline, naphthalene, xylene.
 Chemosterilants to achieve sterility in insects.
 Repellents and attractants.
 Repellents are substances that repel insects from the treated surfaces with them and protect against bites.
 Attractants are substances that attract insects.
 Was added to the insecticide bait.
 Such action are ammonia, 2% formalin, 0.75% of butyl acetate (in flies), caproic acid, pheromones, certain
essential oils, sugar solutions and the like
o Storage of insecticides
 separate room
 in dry place,
 away from children.
 In no case it is poured into plastic containers
o following requirements must be observed when handling insecticides:
 Do not smoke, drink or eat after working with insecticides hands and face should be washed thoroughly with
soap and water
 with preparations should not operate people who suffer from diseases of the respiratory system,
gastrointestinal tract, skin diseases and disorders of the nervous system.
 The use of special protective clothing, a hat from waterproof material, mouth mask and rubber gloves is
required.
 Dragging for ticks: one basis is grasped lane and drag along the ground and collect other ticks after pest control

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19. Deratisation - definition, methods, tools. Epidemiological significance.
 Definition: destruction of epidemiological significant rodents
 Rodents (ORDER Rodentia) cause huge damages
o to farms by eating or contamination and makes obsolete large amounts of FOOD, FEED,
o buildings, cables, irrigation, equipment and household items
 In years beneficial to them, under suitable climatic and dietary factors, they increased enormously and become a
menace to the crops and stocks in storage.
 Distribution
o Rodents are eurytopic animals.
o They inhabit steppes, fields, meadows, and forest margins.
o From the equator to the north, with a large ecological plasticity, high reproductive and migratory activity
o A synanthrope (from the Greek σύν syn, "together with" + ἄνθρωπος anthropos, "man") is a member of a
species of wild animal or plant that lives near, and benefits from, an association with human beings and the
somewhat artificial habitats that people create around themselves
 Three basic group
o Synanthropic - GREAT ECONOMIC AND HEALTH IMPORTANCE IN SETTLEMENTS
 Gray(Brown) rat [R. norvegicus]
 Black rat [R.ratus ratus vatus]
 house mouse (Mus. Musculus)
o Exananthropic - Year round inhabit natural biotopes, including the natural foci of infectious diseases
 wood mouse (Apodemus sylvaticus)
 Yellow necked wood mouse / Apodemus flavicolis /
 Bank vole (Myodes glareolus; formerly Clethrionomys glareolus)
 harvest mouse (Micromys minutus)
 muskrat (Ondatra zibethicus)
o Hemisynantropic - Economic and epidemiological importance
 striped field mouse (Apodemus agrarius)
 Voles(a high number group) [Wühlmäuse]
 Sours (Reservoir) of infection by many diseases: plague, tularemia, leptospirosis, brucellosis, salmonellosis, Q
fever, hemorrhagic fevers, rat typhus, infestations(parasitic diseases) etc.
 HIGH REPRODUCTION
o THE LARGE NUMBER OF PROGENY - REACHES 18 IN ONE BIRTH
o SHORT PREGNANCY (20-30 DAYS)
o EARLY SEXUAL MATURATION - FROM 20 DAYS IN VOLES 3 MONTHS TO RATS.
o SYNANTROPIC SPECIES PRACTICAL BREED ALL YEAR ROUND, WHILE THOSE INHABITING NATURAL FOCI BIRTH
2-5 TIMES A YEAR.
 MOST RODENTS ARE HERBIVOROUS
o ~ IN PREFERENCE TO CEREALS (GRANIVORES)
o ~ GREEN VEGETATIVE MASS (HERBIVORUS)
o ~ NO PREFERRED FOOD - SUBSTITUTE WITH OTHER FOOD SOURCES – POLYPHAGIA (EURYFAGI) AS ALL
SYNANTROPIC SPECIES
 Mice consume about 3g of food and the Rats 20-40g per day
o Most species are nocturnal(night) activity, stronger occurred at dusk and dawn CERTAIN hibernate (dormice,
ground squirrel)
o Synantropic rodents - ACTIVE year round.
o WINTER food stocks pile forest and field mouse, mole rat
 Methods and tools for exterminating
o SANITARY - PREVENTIVE MEASURES

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  Windows of basements and ground floors MUST be glazed or closed with wire mesh with openings no more
than 1cm 2
 All storage, kitchens, ovens and other similar objects must be built with cement or other rat impervious
flooring
 When refurbishing catering, warehouses, apartments, particular attention is paid to the filling of all
unnecessary holes, cracks - plastering, patching cemented of riddled barriers, replacement of wire mesh,
mounting the safety bars of channels for ventilation, heating and other facilities.
o Prophylactic deratization is directed toward depriving rodents of food, drink, and places for building burrows
and nests
 Keep stockpile food and goods on racks in height and distance from the floor and the wall, not less than 50
cm.
 Food products can be stored in freezer and containers with tight lids.
 Food waste must be collected in metal pails with lids and regularly destroyed or transported.
 Strict compliance with the sanitary requirement is necessary to slaughterhouses, grain and commodity
storage, livestock farms, farmyards, port areas and shops
o EXTERMINATORY MEASURES - EVERY deratisation begins with research:
 Size of objects for DERATTISATION, Sanitary and technical state, Type and relative number of rodents, Food
sources, Shelters (nests), Possibility of elimination
o Mechanical (physical) method
 APPLICATION OF DIFFERENT TYPES OF TRAPS
 Bait PIECES OF CHEESE, shpek salami, bread cubes fried with onions and oil.
 Trap charging OPPORTUNITY NIGHT, along the walls, canals, sewers, garbage pits and other suitable places
where normally walk rodents.
 Covered with materials(masked) - being deceived research sense of rodents - "REACTION TO NEW OBJECT" -
neophobia.
 Traps used only thoroughly cleaned 1 TRAP EVERY 30m2
o CHEMICAL METHODS - BASED ON THE USE OF CHEMICAL AGENTS (RODENTICIDES)
 food products – bait
 liquids - water, milk, broth
 by dusting in places where walking rodents - frequently along the wall
 flooded with poisonous gases (fumigants)
 INJECTION poisoned FOAM in the hole
 TYPE RODENTICIDES
 FAST ACTING (acute): ZINC phosphide, Rodanex – Crimidin, Veronex- sedatives, BROMETALIN
 Slow-acting (cumulative) RODENTICIDES - Anticoagulants I and II generation. Currently they are essential in
deratisating practice
o 1: zoocumarin’ tomorin, racumin, cumatox, ratron. - RELATIVELY low toxicity, it is repeated ingestion of
sublethal doses(6-20 days)  possibility of resistance
o 2. Bromadiolon, flocumafen(Storm), brodifacum, difenacum. - Designed for rodent, resistant to
anticoagulants I-st GENERATION
 GAS RODENTICIDES: methyl bromide, Chloropicrin, CO and C02, cyclone
 No toxic preparations
o Glue- tiles, boards, paperboards
o Consists pellets maize, wheat flour and molasses – enteral disfunction
 Biological methods - Patronize natural enemies of rodents: weasels, cats, snakes, owls,cials
 Deratisation of different type objects
o Entire settlement – stages:
 STUDY - through questionnaires, traps, signals (request) of citizens.

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  Stage of ubiquitous deratisation – charge of poison in any facility where indications or has the presence of
rodents.
 Particular attention is paid to technical deserted shed, attic, basement and food storages.
 Stage of maintenance - periodic replacement and supplementing baits in permanent TOXIC POINTS
 periodic deratisation of sewer is minnimum 2 times per year - spring and autumn
 Every 3 months - landfill wastes
 Transport objects, farms – systematic all year
o Deratisation in natural foci (FIELD DERATTISATION)
 Performed by: epidemic INDICATIONS; epizootic INDICATIONS; IF sudden increase in the number of rodents
in certain areas
 First cut down the grass!
 Deratisators lined up in the form of "SANITARY paddle" a distance of 4 - 5 m to 10 m from each other
depending on the nature on the field. Every deratisator process certain STRIP (Lane)  Dosage - 1 tablespoon
per hole (Toxic bait 300-2000 g. /ha, Pulver 2000 g./ha)
 Protection: Wearing work clothes, rubber gloves, respirator, MASK of mouth and nose, protecting glasses to
the eyes by working with powders
 First aid
o Mandatory termination of contact with preparations
o Removing the contaminated work clothing
o Thorough cleaning of contaminated areas of the skin and mucousa
o Vit. K - antidote for poisoning with anticoagulant rodenticides
o COPPER SULPHATE - Antidote for poisoning with zinc phosphid.
o Luminal (pentobarbital sodium) – Antidote vs. RODANEKS (KRIMIDIN), ETC
o Add. vitamin B6, Active carbon. Atropine
 The most effective means of limiting rodent damage is rodent-proof construction.
o New buildings should be designed and built to prevent rodent entry.
o Rodent-proofing is a good investment.

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20. Bioterrorism. Diseases subject to international health regulation.
Bioterrorism
 terrorism involving the intentional release or dissemination of biological agents. These agents are bacteria,
viruses, insects, fungi or toxins, and may be in a naturally occurring or a human-modified form, in much the same
way as in biological warfare
 WHO definitions:
o biological agent is a “micro-organism (or a toxin derived from it) which causes disease in personnel, plants, or
animals or causes the deterioration of materiel”
o biological warfare “is the use of biological agents to cause the loss of people and livestock, as well as damage
to plants and materials”
o biological defense “includes the established methods, plans and procedures and implemented measures of
defense against biological attacks”
 EU Action Plan on biological and toxin weapons, complementary to the EU Joint Action in support of the BTWC
 CDC Category A
o can be easily disseminated or transmitted from person to person;
o result in high mortality rates and have the potential for major public health impact;
o might cause public panic and social disruption; and
o require special action for public health preparedness.
o Agents/Diseases
 Anthrax (Bacillus anthracis)
 Botulism (Clostridium botulinum toxin)
 Plague (Yersinia pestis)
 Smallpox (variola major)
 Tularemia (Francisella tularensis)
 Viral hemorrhagic fevers, including
 Filoviruses (Ebola, Marburg)
 Arenaviruses (Lassa, Machupo)
 CDC Category B
o are moderately easy to disseminate;
o result in moderate morbidity rates and low mortality rates; and
o require specific enhancements of CDC’s diagnostic capacity and enhanced disease surveillance.
o Agents/Diseases
 Brucellosis (Brucella species)
 Epsilon toxin of Clostridium perfringens
 Food safety threats (Salmonella species, Escherichia coli O157:H7, Shigella)
 Glanders (Burkholderia mallei)
 Melioidosis (Burkholderia pseudomallei)
 Psittacosis (Chlamydia psittaci)
 Q fever (Coxiella burnetii)
 Ricin toxin from Ricinus communis (castor beans)
 Staphylococcal enterotoxin B
 Typhus fever (Rickettsia prowazekii)
 Viral encephalitis (alphaviruses, such as eastern equine encephalitis, Venezuelan equine encephalitis, and
western equine encephalitis])
 Water safety threats (Vibrio cholerae, Cryptosporidium parvum)
 CDC Category C
o emerging pathogens that could be engineered for mass dissemination in the future because of
 availability;
 ease of production and dissemination; and

39
  potential for high morbidity and mortality rates and major health impact.
o Agents: Emerging infectious diseases such as Nipah virus and hantavirus

Diseases subject to international health regulation

 An event involving the following diseases, because they have demonstrated the ability to cause serious public
health impact and to spread rapidly internationally :
o Cholera
o Pneumonic plague
o Yellow fever
o Viral haemorrhagic fevers (Ebola, Lassa, Marburg)
o West Nile fever
o Other diseases that are of special national or regional concern, e.g. dengue fever, Rift Valley fever, and
meningococcal disease
 A case of the following diseases is unusual or unexpected and may have serious public health impact, and thus
shall be notified:
o Smallpox
o Poliomyelitis due to wild-type poliovirus
o Human influenza caused by a new subtype
o Severe acute respiratory syndrome (SARS)
 Any event of potential international public health concern, including those of unknown causes or sources and
those involving other events or diseases than those above

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21. Emerging and re-emerging diseases - definitions, classification,
epidemiological features and control.
 Emerging infectious diseases are diseases that
o have not occurred in humans before (this type of emergence is difficult to establish and is probably rare)
o have occurred previously but affected only small numbers of people in isolated places (AIDS and Ebola
hemorrhagic fever are examples)
o have occurred throughout human history but have only recently been recognized as distinct diseases due to an
infectious agent (Lyme disease and gastric ulcers are examples)
 Re-emerging infectious diseases are diseases that once were major health problems globally or in a particular
country, and then declined dramatically, but are again becoming health problems for a significant proportion of
the population (malaria and tuberculosis are examples). Many specialists in infectious diseases include re-
emerging diseases as a subcategory of emerging diseases

 Factors influencing emergence and re-emergence-

o AGENT
 Evolution of pathogenic infectious agents (microbial adaptation & change)
 Development of resistance to drugs
 Resistance of vectors to pesticides
o Host factors contributing to emergence are
 Mass migration of people
 Migration of labor population from rural to urban areas in unhygienic squatter settlements
 International travel as a result of trade and tourism contributing to global dispersion of disease agents,
disease reservoirs and vectors
 Changes in lifestyle
 Declining immunity of as a result of HIV infection, which make him vulnerable to a host of infections

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o ENVIRONMENT
 Environmental sanitation characterized by unsafe water supply , improper disposal of solid and liquid waste,
poor hygienic practices and congested living conditions all contribute to emergence of infection.
 Climatic changes resulting from global warming inducing increased surface water evaporation , greater
rainfall changes in the direction of bird migration and changes in the habitat of disease vectors are also
contributory factors.
o Weakened public health infrastructure: decreased investment in public health; competing priorities for
development, and suboptimal access to healthcare and sanitation
o Failure of safety procedures/regulations: bushmeat instead of butchered and controlled meat
o Population shifts including rapid increase and uncontrolled urbanization
o Anthropogenic activities or climate change: disruption of natural habitats of animals, and forces animals,
searching for food, into closer contact with human
o Public health consequences of civil disturbance, human displacement, and natural disasters
o Human behaviour
 Occupation: anything to do with animals (vets, farmers, butchers, etc.), health care workers
 Mistrust and misinformation: anti-vaxxers
o Deliberate use to cause terror and harm
o Antimicrobial drug resistance— susceptibility of infectious organisms to anti-infective drugs
 Use of anti-infective drugs in human health: over- or under-prescribing of antibiotics by health workers,
excessive demand for antibiotics by the general population, or the use of substandard drugs with inferior
anti-infective drug content, have had a remarkable impact on the selection and survival of resistant microbes,
rapidly increasing levels of microbial resistance
 Use of anti-infective drugs in animal husbandry and
agriculture

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22. Infection, infectious process, infectious disease.
 Infection - entry and multiplication of a microorganism or parasite in the body of a host.
 Infectious process is the process of overcoming host barriers, multiplication of microorganisms and damage of
the host
 Infectious disease - infection + signs and symptoms.
 Contamination - presence of a living agent on the exterior of the body or on an article of clothing.
 Colonization is different form infection since it does not involve damage of the host. It means presence of
microorganisms at a site of the body and does not necessarily lead to tissue damage, signs and symptoms of a
disease.
 Reservoir - the normal habitat where the agent lives and multiplies. It is where the agent propagates itself in
nature. A dead-end host or temporary resting place of the agent is not a reservoir.
 Carrier - a person or animal that harbor an infectious agent yet manifest no discernible signs of infection.
 Kinds of infections:
o Manifested infection – with typical clinical features
o asymptomatic /subclinical/ infection – without clinical and laboratory sign of infection but with molecular and
pathophysiological changes;
o A persistent infection occurs after a microorganism has been dormant in the host, sometimes for years. For
example EBV infection, salmonella typhi infection.
o An exogenous infection results from environmental pathogens;
o An endogenous infection results from the host's normal flora (for instance, Escherichia coli displaced from the
colon, which may cause urinary tract infection).
o Acute infection is used to refer to microbe living inside a host for a limited period of time, typically less than
three months. If the microbe lives in a host between three and six month, we are talking about sub acute
infection or if the period is longer than six month, it is chronic infection
o Mixed infection is an infection by two and more infectious agents like Chickenpox and scarlet fever.
o Coinfection is the simultaneous infection of a host by multiple pathogen species. For example the coinfection
of liver cells with Hepatitis B virus and Hepatitis D virus.
o Secondary infection is an infection by a microorganism that follows an initial infection by another kind of
organism like Flu and Staphylococcus, Rickettsia and salmonella
o Superinfection is an infection following a previous infection, especially when caused by microorganisms that
are resistant or have become resistant to the antibiotics used earlier. For example, an individual superinfected
with two separate strains of HIV may contract a strain that is resistant to antiretroviral treatment.
o Reinfection is a second infection that follows recovery from a previous infection by the same causative agent.
o A relapse is a recurrence of the clinical features before the normalization of fever . For example, malaria often
exhibit peaks of activity and sometimes long periods of dormancy.
o A recidive is a recurrence of the clinical features after seemingly recovery.
 STEPS IN THE INFECTIOUS PROCESS:
o Entry of the pathogen into the body with or without (+/) attachment to the skin or mucous membranes
o Local multiplication and spread of the pathogen on the surface of the skin or mucous membranes with or
without (+/-) local invasion of tissues
o Systemic spread and multiplication of the pathogen into deeper body tissues and blood.
o Exit of the pathogen from the host
 Portals of infection include the
o Respiratory tract (upper and lower)
o Conjunctiva (lining of the eyes and eyelids)
o Urogenital tract
o Gastrointestinal tract (upper and lower)
o Placenta (mother to child transmission)
o Skin (broken and unbroken skin)

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 pathogen damages the host because of:
o (1) invasion and multiplication in tissues (locally or systemically)
o (2) toxin production,
o (3) immunopathology, or
o (4) a combination of the above
 There are six characteristics of infectious diseases:
o ID are caused by specific agents
o The specific agent enters the body trough specific entrance
o ID are characterize by periodicity and cyclic recurrence
o Infectious pathologies are usually qualified as contagious diseases
(also called communicable diseases) due to their potential of
transmission from one person or species to another
o ID leads to specific immunity after recovery.
o ???
 Phases of Infectious Disease
o Incubation period – time between infection and the appearance of
signs and symptoms.
o Prodromal phase – mild, nonspecific symptoms that signal onset of
some diseases.
o Clinical phase – a person experiences typical signs and symptoms of
disease.
o Decline phase - subsidence of symptoms.
o Recovery phase – symptoms have disappeared, tissues heal, and the body regains strength.
 Immunity: includes all factors that alter the likelihood of infection and disease once the agent is encountered
o Physical barriers: skin, mucosa, mucus sheaths, respiratory tract cilia, cough and gag reflex
o Chemical barriers: acidity of stomach and vagina, enzymes in saliva and GI tract, lipids, interferons, and other
miscellaneous biologically active substances
o Cellular and physiologic barriers: macrophages, polymorphs, reticular endothelial cells, NK cells, inflammation,
fever.
 Immunization is the act of acquiring immunity. It can be acquired passively (e.g., maternal transfer, therapeutic
transfer) or actively (e.g., natural exposure, vaccination)

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23. Diagnostic approach to infectious diseases, general syndromes, clinical
epidemiological, microbiological, virological investigations.
 History
o an exposure history that may identify microorganisms with which the patient may have come into contact
 Social history: any high-risk behaviors (e.g., unsafe sexual behaviors, IV drug use), potential hobby-associated
exposures (e.g., avid gardening, with possible Sporothrix schenckii exposure), or occupational exposures (e.g.,
increased risk for M. tuberculosis exposure in funeral service workers)
 Dietary habits: Shiga toxin–producing strains of Escherichia coli and Toxoplasma gondii are associated with
the consumption of raw or undercooked meat; Salmonella typhimurium, Listeria monocytogenes, and
Mycobacterium bovis with unpasteurized milk; Leptospira species, parasites, and enteric bacteria with
unpurified water; and Vibrio species, norovirus, helminths, and protozoa with raw seafood
 Animal exposure: including contact with their own pets, visits to petting zoos, or random encounters (e.g.,
home rodent infestation)
 Travel history: international and domestic; what kinds of activities and behaviors the patient engaged in
during travel (e.g., the types of food and sources of water consumed, freshwater swimming, animal
exposures) and whether the patient had the necessary immunizations and/or took the necessary prophylactic
medications prior to travel
o host-specific factors that may predispose to the development of an infection: determine the immune status of
the patient; underlying disease (e.g., malignancy, HIV infection, malnutrition), a medication (e.g.,
chemotherapy, glucocorticoids, monoclonal antibodies to components of the immune system), a treatment
modality (e.g., total body irradiation, splenectomy), or a primary immunodeficiency
 Physical examination
o Temperature: fever  core temperature ≥38.3°C, For every 1°C
increase in core temperature, the heart rate typically rises by 15–
20 beats/min.  some infections are associated with relative
bradycardia (Faget’s sign), where patients have a lower heart rate than might be
expected for a given body temperature
o Lymphatics: localized vs generalized lymphadenopathy
o Skin: rashes, ulcer, bite marks
o Foreign bodies: iv’s, drainage, tubes
 Diagnostic testing
o White Blood Cell (WBC) Count
 bacteria are associated with an increase in polymorphonuclear
neutrophils, often with elevated levels of earlier developmental
forms such as bands
 viruses are associated with an increase in lymphocytes
 certain parasites are associated with an increase in eosinophils
o Inflammatory markers: ESR and CRP
o Analysis of Cerebrospinal Fluid (CSF): uspected meningitis or
encephalitis; opening pressure, cell counts, Gram’s stain and culture, and determination of glucose and protein
levels
o Radiology
 microbiological, virological investigations
o culture of infected tissue (e.g., surgical specimens) or fluid (e.g., blood, urine, sputum, pus from a wound)
 allows identification of the etiologic agent(s), determination of the anti-microbial susceptibility profile, and—
when there is concern about an outbreak—isolate typing
o Direct examination
 Light microscopy
 Staining: Gram, acid-fast, iodine

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  Dark-field and Fluorescence Microscopy
o Pathogen-Specific Testing
 ELISA is an enzyme immunoassay that employs enzyme-labeled immunoreactants and an immunoadsorbent
to determine the presence and concentration of certain proteins (e.g., tumor markers, viral proteins, drugs,
antibodies) in serum
 Polymerase chain reaction (PCR) is a technique that allows amplification of specific chromosome segments by
producing more than a billion copies. This makes testing of very small sequences of DNA that could not
otherwise be studied possible.
 Antibody Detection (Serology)
 Antigen Detection

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24. Symptomatic therapy, diet and regime of the infectious patient
 Symptomatic treatment, supportive care, or supportive therapy is any medical therapy of a disease that only
affects its symptoms, not the underlying cause
 usually aimed at reducing the signs and symptoms for the comfort and well-being of the patient, but it also may
be useful in reducing organic consequences and sequelae of these signs and symptoms of the disease
 Analgesics, to reduce pain
 Anti-inflammatory agents, for inflammation caused by arthritis
 Antitussives, for cough
 Antihistaminics (also known as antihistamines), for allergy
 Antipyretics, for fever
 Bed rest
o in the cases of sepsis, chickenpox, mumps, hemorrhagic fevers
o aims: peace of harmed organs, less waste of energy, soon recovery, lack of complications
o cares for the teeth, skin – cleaning every day, prevention of ,,decubitus’’ – by massages, changes in the position
in the bed, special bandages
o cares for passing and defecation – it has to be regularly; if is need urinary catheter could be used or some drugs
for overcoming of constipation
o prophylaxis of hypostatic pneumonia – deep breathing, massages of the thorax and spine, changes the position
in the bed
 Diet: alimentary regimen that includes foods with specific qualitative and quantitative composition, energy value
and culinary cultivation which main aim is treatment
o diet has to be consistent with the present infectious disease and its organ complications
o diet has to be consistent with the present clinical form of infectious diseases and has to be changed when the
patient’s conditions is changed
o diet has to answer to patient’s energy needs
o the food that is included in the present diet has to be mechanical, termic and chemical spare, to be delicious,
with good appearance, and consistent with the patient’s taste
o there are different dietary regimen for diarrheal infections, acute viral hepatitis, acute kidney failure and
hemorrhagic fevers
o Rehydration i.v or oral
 Home made Oral Rehydration Salts (ORS) Recipe
 Six (6) level teaspoons of Sugar
 Half (1/2) level teaspoon of Salt
 One Litre of clean drinking or boiled water and then cooled
o Food several smaller meals per day (Bananas, Rice, Toast, Noodles)

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25. Pathogenic treatment in infectious diseases
 Pathogenical treatment - these are group of medication used as anti edema treatment (to prevent or treat brain
edema - corticosteroids and osmotic diuretics), rehydration therapy ( IV fluids), hepatoprotectors and so on.
Some of these medications are the only option for treatment, especially when there is no etiological treatment.
This is very important!
 Treatment of:
o Dehydration
 Severe hypovolemia
 Children: rapid infusion of 20 mL/kg of isotonic saline → reassess → repeat as needed
 Adults: rapid infusion of isotonic crystalloid (e.g. Ringer) → reassess → repeat as needed
 Moderate hypovolemia
 Children: consider oral hydration therapy or 10 mL/kg of isotonic saline → reassess → repeat as needed
o Cerebral edema: excess accumulation of fluid within the brain parenchyma as a result of damage to the blood-
brain barrier and/or the blood-CSF barrier
 Head of bed elevation (∼ 30°)
 Sedation and analgesia: combinations of benzodiazepines, opioid analgesics, and dexmedetomidine
 IV mannitol: osmotically driving water from inside the brain tissue into the intravascular space, which is then
diuresed by the kidneys
o Acute respiratory and/or circulatory insufficiency
o Acute renal insufficiency
o Acute hepatic insufficiency
o Allergic conditions
 Antihistamines may be given for pruritus or urticaria in Viral infections (e.g., rotavirus and rhinovirus)
 If anaphylaxis is likely (see diagnostic criteria for anaphylaxis), start initial treatment immediately:
 Remove inciting allergen (if possible)
 Administer epinephrine IM 1:1,000 (1 mg/mL) into the anterolateral thigh
 Jarisch-Herxheimer reaction: acute, transient, systemic reaction to bacterial endotoxins and pyrogens that
are released after initiation of antibiotic therapy
 Commonly seen during treatment of infections with spirochetes (Borrelia, Leptospira), also e.g., brucellosis,
Q fever, bartonellosis
 Treatment: NSAIDs for symptomatic treatment; May consider meptazinol
 Dexamethasone or prednisone has been used as an adjunctive treatment
 Treatment of:
o Fever
o Pain
o Vomitus: Ondansetron, Metoclopramide, Prochlorperazine
o Seizures
 short-acting anticonvulsants with a rapid onset of action (e.g., lorazepam or diazepam) should be given,
followed by a long-acting agent, such as phenytoin.
 If these maneuvers fail to terminate the seizure, the patient should be intubated, mechanically ventilated,
and treated with phenobarbital.

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26. Etiological treatment in infectious diseases
 Etiological treatment - It is called like this because this is the treatment against the etiology (causative agent -
bacteria, virus, fungi et.). So, this means antibiotics, antiviral meds, antifungal (antimicotic), medications used
against the immune system (heterologous and homologous Serums or so called serotherapy - anti diphtheria,
anti anthrax serums and so on).
 Basic principles of antimicrobial treatment:
o It has to start as soon as possible
o The chosen drug has to be consistent with the diagnosis or with the most probable agent that is connected
with such symptoms, with the present clinical form of the infectious disease, or with the antibiogram if the last
exist
o The dose of the antibiotic has to be appropriative for the present disease, its clinical form
o The duration of antimicrobial therapy is dependent of the present disease and the patient’s condition
o Changing of the antibiotic with another is not recommended before three days of its use
o Antibiotic combination is indicated in the cases of severe infections, unclear cases
o The using of antibiotics have to be consistent with their pharmacokinetic
o There is not indication for using antibiotics in viral infections
o Every one antibiotic manifests adverse reactions and because of this patients have to be keep a sharp

 Antifungal Drugs
o Amphotericin B –Aspergillus, Histoplasma, Candida, Cryptococcus, Coccidioides, Blastomyces, Sporothrix, etc.
o Nystatin - Candidiasis
o Flucytosine – Candida, Cryptococcus, Aspergillus
o Natamycin – 5% ophthalmic suspension (keratitis)
o Antifungal Imidazoles – Clotrimazole, Fluconazole, Intraconazole, Voriconazole, Ketoconazole
 Antiviral Chemotherapy
o Amantadine – Influenza A - Prophylaxis
o Rimantadine (~Amantadin)
o Neuraminidase inhibitors – zanamivir, oseltamivir (Influenza A and B and Avian Influenza)
o Acyclovir – HSV-, HZV- infections
o Famciclovir
o Valacyclovir
o Foscarnet (inhibits viral DNA – polymerase of CMV, HSV, HZV).
o Cidofovir (nucleotide analog) – Herpes Group Viruses
o Ganciclovir – CMV
o Antiretroviral Drugs

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 o Human Interferons
 Treatment with Antitoxic Drugs
o Mechanism of action – Equine Antitoxins or human immune globulins are given to neutralize circulating toxins
o Adverse Reactions – Allergy. Dessensibilization
o Clinical Use of:
 Antitoxins - Tetanus, Botulismus, Gas Gangrene, Diphtheria, Anthrax
 Specific immune globulins – Hepatitis B, Rabies, Hemorrhagic Fever, etc.
 Immunomodulators
o naturally occurring cytokines - colony-stimulating factors (CSFs), interferons (IFNs), interleukins (ILs),
chemokines, and thymic hormones
o monoclonal antibodies and receptor antagonists that block proinflammatory cytokines
o immunoglobulins, used either as replacement therapy in immunoglobulin-deficient individuals or as true
immunomodulators to upregulate or downregulate the immune response
o Glucocorticosteroids
o synthetic compounds with immunomodulatory activity, such as pentoxifylline imiquimod, and thalidomide
o anti-coagulant proteins with associated anti-inflammatory properties, such as recombinant activated protein C
(APC), which represents the first agent to be approved by the U.S

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27. Typhoid fever and paratyphoid fever A and B
 Most prevalent in resource-limited regions with poor sanitation in East and Southeast Asia, Africa, and Central
and South America
 Pathogen
o Salmonella enterica serotype Typhi: typhoid fever
 Gram-negative rod; Facultative anaerobe with peritrichous flagella
 Produces hydrogen sulfide (H2S - Hydrogen sulfide) on TSI - Triple sugar iron agar
 Oxidase-negative, Cannot ferment lactose
o Salmonella enterica serotype Paratyphi: paratyphoid fever
 Salmonella enterica serotype Paratyphi A
 Salmonella enterica serotype Paratyphi B
 Salmonella enterica serotype Paratyphi C
 Salmonella enterica serotype Choleraesuis
 Reservoir
o Salmonella enterica serotype Typhi: humans
o Other Salmonella species: humans and animals
 Transmission: fecal-oral
o Direct: person-to-person contact; asymptomatic carriers frequently involved (e.g., the pathogen may be
transferred from contaminated stool via handshake to the next person)
o Indirect: contaminated food and water (e.g., if drinking water and sewage systems are not properly separated
or a carrier prepares food)
 Lifecycle
o Oral uptake of pathogen: A relatively large number of organisms (∼ 105) is needed to cause infection (high
infective dose), unlike, e.g., in Shigella infection, where as few as ∼ 10 organisms suffice to infect the host.
o Migration into the Peyer patches of the distal ileum: If the pathogen manages to reach the distal ileum, it
migrates via M cells through the epithelium and into the Peyer patches.
o Infection of macrophages → nonspecific symptoms
o Spread from macrophages to the bloodstream → septicemia → systemic disease
o Migration back to intestine → excretion in feces
 Incubation period: 5–30 days (most commonly 7–14 days)
 Clinical features
o If left untreated, three different disease stages, each lasting a week, classically occur.
o After 3 weeks of disease: slow regression of symptoms; patients may become chronic Salmonella carriers
o Week 1
 Body temperature rises gradually; Relative bradycardia
 Constipation or diarrhea; Headache
o Week 2
 Persistent fever, but no chills; mostly unresponsive to antipyretics
 Rose-colored spots: a small, speckled, rose-colored exanthem that appears on the lower chest and abdomen
(most commonly around the navel) in approx. 30% of affected individuals
 Typhoid tongue: greyish/yellowish-coated tongue with red edges
 Nonspecific abdominal pain and headache
 Yellow-green diarrhea, comparable to pea soup (caused by purulent, bloody necrosis of the Peyer patches),
or obstipation and bowel obstruction (as a result of swollen Peyer patches in the ileum)
 Neurological symptoms (delirium, coma) - toxins may cross the blood-brain barrier, leading to confusion and
drowsiness.
o Week 3 - Clinical features of week 2 + Additional possible complications include:
 Gastrointestinal ulceration with bleeding and perforation
 Hepatosplenomegaly

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  In rare cases: sepsis, meningitis, myocarditis, and renal failure
 Diagnostics
o Laboratory tests
 Anemia
 Leukopenia (adults) or leukocytosis (leukocytosis)
 Absolute eosinopenia
 Relative lymphocytosis
 Abnormal liver function tests
o Pathogen detection
 Blood cultures: Bacteremia is detectable starting in week 1 of the disease.
 Stool cultures
 Bone marrow cultures
 Serology (Widal test)
 Treatment
o First-line treatment: fluoroquinolones (e.g., ciprofloxacin 500 mg p.o. 1-0-1 oder 400 mg i.v. 1-(1)-1 für 14
Tage)
o Azithromycin, if resistance to fluoroquinolones is suspected (e.g., in patients with infection acquired from
certain regions, such as South Asia)
o Third-generation cephalosporins (e.g., ceftriaxone 2 g i.v. 1-0-0 für 14 Tage) are preferred for severe infection.
o Antibiotics prolong the duration of fecal excretion of bacteria.
 Chronic Salmonella carriage
o Definition: positive stool cultures 12 months after overcoming the disease
o Incidence: 2–5% of patients become chronic carriers (S. typhi colonizes the gallbladder)
o Clinical features: typically asymptomatic
o Treatment: fluoroquinolones (e.g., ciprofloxacin) administered for at least 1 month
o Complication: increased risk for gallbladder cancer
 Prevention
o Food and water safety
o Vaccination
 Indication: The WHO recommends typhoid fever vaccination to those traveling to high-risk areas (East and
Southeast Asia, South and Central America, Africa).
 Administration: A parenteral, inactivated vaccine and an oral, live vaccine are available for active
immunization, and both provide similar levels of protection.
 Inactivated vaccine: one intramuscular injection containing Vi polysaccharide (part of S. typhi capsule),
ideally administered at least 10 days before traveling
 Live-attenuated vaccine: oral ingestion of capsules containing live attenuated S. typhi; ideally administered
at least 10 days before traveling
Overcoming an infection with S. typhi or S. paratyphi does not confer lifelong immunity. Vaccination is not entirely
protective.

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28. Food poisoning by Salmonella, conditionally pathogenic intestinal
bacteria, staphylococci and other.
Salmonellosis (Salmonella gastroenteritis)
 Pathogen: Salmonella enterica serotype Enteritidis, Salmonella enterica serotype Typhimurium
o Gram-negative bacteria, obligate pathogen
o Produces hydrogen sulfide, Does not ferment lactose
o 2nd most common pathogen responsible for bacterial foodborne gastroenteritis
 Transmission: foodborne (poultry, raw eggs, and milk)
 Incubation period: 0–3 days
 Clinical features
o Duration: 3–7 days
o Fever (usually resolves within 2 days), chills, headaches, myalgia
o Severe vomiting and inflammatory (watery-bloody) diarrhea
 Treatment (antibiotic therapy in severe cases)
o Fluoroquinolones (e.g., ciprofloxacin 500 mg p.o. 1-0-1 oder 400 mg i.v. 1-0-1 für 5–7 Tage)
o Alternative: TMP-SMX or cephalosporins (e.g., ceftriaxone 2 g i.v. 1-0-0 für 5 Tage), depending on the
antimicrobial susceptibility test
o Antibiotic treatment prolongs fecal excretion of the pathogen; only indicated for systemic manifestations or
diarrhea > 9/day
 Complications: (especially in immunocompromised patients, e.g., HIV)
o Bacteremia, Reactive arthritis
o Systemic disease: osteomyelitis, meningitis, myocarditis

Staphylococcal food poisoning

 Pathogen: Staphylococcus aureus
o Gram-positive bacterium
o Some strains produce heat-stable enterotoxins that cause staphylococcal food poisoning.
o While Staphylococcus aureus is destroyed by cooking, the heat-stable enterotoxins are not.
o Bacteria proliferate in inadequately refrigerated food (canned meats, mayonnaise/potato salad, custards).
 Transmission: ingestion of preformed toxins in contaminated food
 Incubation period: 1– 8 hours
 Clinical features
o Typically involves a short latency period; resolution of symptoms after 24–48 hours
o Nausea, vomiting, abdominal discomfort, diarrhea
 Treatment
o Supportive
o Antibiotics are unnecessary (Since it is the preformed enterotoxins and not the bacterium that cause
symptoms, antibiotics have no effect)

Bacillus cereus infection

 Pathogen: Bacillus cereus, a heat-stable, spore-forming gram-positive rod that produces two different
enterotoxins
 Transmission
o The bacteria grows in heated food that cools down too slowly or is improperly refrigerated.
o Reheated rice is a common source of infection: Spores survive the cooking process and germinate when rice is
kept warm, which results in enterotoxin formation
 Incubation period and clinical findings
o Enterotoxin I (a preformed cereulide) causes the emetic form: 30 minutes to 6 hours after ingestion, nausea
and vomiting begin.

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 o Enterotoxin II causes the diarrheal form: 6–15 hours after ingestion, watery diarrhea and abdominal pain
begin, typically lasting for 24–48 hours.
 Treatment: supportive, as antibiotics are not effective against toxins

Overview of pathogens predominantly causing watery diarrhea

Pathogen Foods/transmission Incubation period Treatment
Staphylococcus
 Inadequately refrigerated food  1–8 hours  Supportive
aureus
 Germination of spores in heavily
Clostridium contaminated food that is left standing at <
perfringens  Supportive; usually resolves in
60°C for too long → vegetative bacteria
24 hours
(Heat-labile  The foods most likely to have been  6–24 hours
 Antibiotics are not
enterotoxins cause colonized include:
recommended.
the symptoms.) o Reheated meat dishes
o Undercooked meat and raw legumes
 Immunocompetent patients:
Listeria  Soft cheese, deli meats, unpasteurized milk, ampicillin
 1–2 days
monocytogenes coleslaw, hot dogs  Immunocompromised patients:
ampicillin + gentamicin
Intestinal  6–8 weeks
 Larvae in undercooked pork/beef, raw
 Asymptomatic  Praziquantel, niclosamide
tapeworms freshwater fish
for years

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29. Botulism.
 Pathogen: Clostridium botulinum
o Gram-positive rod, Spore-forming, Obligate anaerobe, Produces heat-labile neurotoxin
o Botulinum toxin: protease that cleaves SNARE proteins and prevents fusion of transmitter-containing vesicles
with the presynaptic membrane → inhibition of acetylcholine release from the presynaptic axon terminals
o lethal dose is estimated at 30 ng for adults when ingested orally
 Clinical features
o Neurological symptoms
 Descending paralysis
 Peripheral flaccid muscle paralysis that descends caudally (typically begins in frequently used muscles)
 Pupils: accommodation paralysis, mydriasis, diplopia
 Pharynx: dysarthria, dysphagia
 Autonomic nervous system: xerostomia (dryness of the mouth)
 Floppy baby syndrome in infants
o Gastrointestinal symptoms
 Gastrointestinal discomfort, nausea, and vomiting, later followed by constipation
 Only present in 30% of cases of foodborne botulism; absent in wound botulism
 Constipation is often the first symptom of infant botulism.
 Diagnostics: Rapidly identify botulinum toxin in samples from serum, vomit, gastric acid, stool, or suspicious
food
 Treatment
o Secure airways
o Specific treatment depends on type

Foodborne botulism
 Etiology
o Ingestion of preformed botulinum toxin via contaminated foods
 The anaerobic spores survive in poorly pasteurized canned foods (e.g., vegetables with soil contact, meat,
home-fermented tofu)
 Germination of the spores produces dangerous toxins (botulinum toxins = enterotoxins A-F) and gas →
bulging cans
 Incubation period: 12–36 hours
 Specific treatment
o Horse-derived heptavalent botulism antitoxin
o Eradication of toxin through bowel emptying (induced by medication)
 Prevention
o Sterilize food through autoclaving (121°C for a minimum of 15 minutes, or at 134°C for a minimum of 3 min)
o Food should be boiled twice before being canned to kill spores that may have germinated after the first
round of boiling.

Infant botulism
 Etiology: ingestion of spores
o Spores may be present in honey, juice, and contaminated soil.
o Germination of the spores in intestinal tract → synthesis of botulinum toxin
 Incubation period: days to 4 weeks
 Clinical features: Infants may present with floppy baby syndrome (generalized decrease in muscle tone
(hypotonia))
o Ptosis (drooping or falling of a body part)
o Floppy movements

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 o General weakness
o Poor feeding (weak sucking)
 Specific treatment: IV human botulism immune globulin (BIG-IV) (sensitivity test first!)
 Prevention: Avoid exposure of < 1-year-old infants to potentially contaminated material (e.g., raw honey, dust,
soil)

Wound botulism
 Etiology: germinating spores in contaminated wounds (most common among IV drug users)
 Incubation period: 10 days (ranges from 4–14 days)
 Specific treatment
o Administration of horse-derived botulism antitoxin
o Surgical debridement
o Antibiotics are only used to treat secondary bacterial infections.
 Prevention
o Government-sponsored sterile needle and syringe programs
o Avoidance of IV drug use
o Seek medical attention for infected wounds.

Left image: physiological neuromuscular transmission at the motor end plate

- Action potential reaches the motor end plate → SNARE protein complex facilitates the fusion of vesicles containing
acetylcholine (ACh) with the prejunctional membrane → release of ACh into the synaptic cleft → reversible binding
of ACh with ACh receptors on the postjunctional membrane → opening of the ion channels of ACh receptors →
depolarization of the muscle.
- Acetylcholinesterase present on the postjunctional membrane breaks down ACh and releases it into the
neuromuscular junction cleft → choline is taken up by the choline transporter on the prejunctional membrane and
recycled in ACh synthesis.

Right image: cleavage of SNARE proteins by botulinum toxin

- Botulinum toxin is endocytosed by cholinergic axon terminals (depicted in the left image)
- The light chain of botulinum toxin released into the prejunctional neuron cleaves the SNARE protein complex →
failure of fusion of vesicles containing ACh with the presynaptic membrane → ACh is not released into the
neuromuscular junction → neural impulse is not transmitted to the muscle → flaccid paralysis of the muscle.

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30. Bacterial dysentery/ Shigellosis/ Bakterielle Ruhr
 Pathogens: Shigella dysenteriae, Shigella flexneri, Shigella sonnei
o Gram-negative rods
o Produce Shiga toxin (enterotoxin) and endotoxin
o Invade M cells via pinocytosis and travel from cell to cell via actin filaments (no hematogenous spread)
 Transmission
o Fecal-oral (especially a concern in areas with poor sanitation)
o Oral-anal sexual contact
o Foodborne (unpasteurized milk products and raw, unwashed vegetables)
o Contaminated water
 Incubation period: 0–2 days
 Infectivity: highly contagious; very low infective dose required (10 or more bacteria)
 Clinical features
o Duration: 2–7 days
o High fever
o Tenesmus (distressing and persistent but ineffectual urge to empty the rectum or bladder), abdominal cramps
o Profuse inflammatory, mucoid-bloody diarrhea
 Treatment: in severe cases, antibiotic therapy with fluoroquinolones (Ciprofloxacin 500 mg p.o. 1-0-1 oder 400
mg i.v. 1-0-1 für 3–5 Tage) or 3rd generation cephalosporins (Ceftriaxon 2 g i.v. 1-0-0 für 5 Tage)
 Complications
o Hemolytic uremic syndrome: microthrombi occlude the arterioles and capillaries, which results in
microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury
o Intestinal complications (e.g., toxic megacolon, colonic perforation, intestinal obstruction, proctitis, rectal
prolapse)
o Febrile seizures
o Reactive arthritis
 Prevention: no vaccine available

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31. Campylobacter enterocolitis
 Pathogen
o Campylobacter jejuni, Campylobacter coli
o Curved, gram-negative, oxidase-positive rods with polar flagella
o Optimal growth temperature: 37–42°C
o Most common pathogen responsible for foodborne gastroenteritis in the US
o Highly contagious: low infective dose required (> 500 pathogens)
 Transmission
o Fecal-oral
o Foodborne (undercooked meat and unpasteurized milk) and contaminated water
o Direct contact with infected animals (cats, dogs, pigs) or animal products
 Incubation period: 2–4 days
 Clinical features
o Duration: up to a week
o High fever, aches, dizziness
o Inflammatory (bloody) diarrhea, especially in children
o Severe abdominal pain may present as pseudoappendicitis or colitis
 Diagnostics: stool sample culture
 Treatment: (in severe cases) macrolides (e.g., erythromycin or azithromycin 500 mg p.o. 1-0-0 für 3 Tage oder 1g
einmalig)
 Complications (more common and severe in HIV-positive patients)
o Guillain-Barré syndrome
o Reactive arthritis
o Acute abdomen: cholecystitis, pancreatitis
o Bacteremia

58
32. Esherichia coli enteritis/ Diarrheagenic E. coli
 Pathogen: Escherichia coli (E. coli)
o Gram-negative, rod-shaped, indole-positive, and flagellated
o Various pathogenic strains of E. coli include:
 Enterohemorrhagic E. coli (EHEC)
 Enterotoxigenic E. coli (ETEC)
 Enteropathogenic E. coli (EPEC)
 Enteroinvasive E. coli (EIEC)
o Some strains are an essential component of the bacterial gut flora and even have a protective effect against
enteropathogens
 Transmission: fecal-oral
o Contaminated food (e.g., raw meat products, vegetables, fruits) and water
o Person-to-person
 Diagnostic steps
o Culture and/or PCR from stool samples
o Differential media (based on E.coli lactose fermenting properties)
 MacConkey agar: pink colonies
 Eosin-methylene blue agar: colonies with a metallic green sheen
 General guidelines for treating E. coli infections
o Supportive therapy
 Rehydration and electrolyte replenishment (e.g., oral rehydration salts or solutions; IV fluids)
 Clear liquids, easy-to-digest foods
 The patient should return to a normal diet as soon as tolerated
o Antibiotic therapy for E. coli: Although some indications exist, antibiotic therapy is generally not recommended
and is strongly contraindicated in EHEC.
 Considered only in cases of severe and/or persistent diarrhea, bloody diarrhea, fever with heavy general
symptoms, immunosuppression
 First-line agents in adults: fluoroquinolones (e.g., ciprofloxacin, norfloxacin, levofloxacin, and moxifloxacin)
 Alternative (drug of choice in children and pregnant women): azithromycin

Enterohemorrhagic Escherichia coli (EHEC)

 Pathogen: enterohemorrhagic E. coli (EHEC)
o Produces Shiga-like toxin (verotoxin) that causes bloody diarrhea and, possibly, HUS
o O157:H7 is the strain most commonly associated with HUS worldwide.
 Transmission: fecal-oral
o Contaminated food (associated with industrial food production in developed countries)
 Raw beef and milk
 Raw vegetables (fresh spinach and raw bean sprouts)
o Contact with contaminated stool
o At-risk groups: infants/toddlers and the elderly
 Pathophysiology
o EHEC bacteria are infected by bacteriophages that integrate their genes into the bacteria's genome; these
genes then code for toxins (verotoxin/Shiga toxin 1 and 2).
o Adhesion to receptors of gut cells→ Shiga-like toxin secretion → cleavage of adenine from the rRNA →
inactivation of the 60S subunit → protein synthesis inhibition → cell death → necrosis and inflammation of the
GI mucosa → watery-bloody diarrhea with mucus (otherwise known as dysentery)
 Incubation period: 2–10 days
 Clinical features
o Bloody diarrhea, dehydration, and abdominal tenderness

59
 o Little to no fever
o Hemolytic uremic syndrome (decreased urine output, petechiae, and neurologic manifestations).
 Diagnosis
o Stool samples should be tested for EHEC:
 In all cases of community-acquired diarrhea
 In possible HUS/ Thrombotic thrombocytopenic purpura
o Culture for O157:H7 on sorbitol MacConkey agar
o Check for non-O157 EHEC by detection of Shiga toxins (via enzyme immunoassay) or Shiga toxin-encoding
genes (via polymerase chain reaction)
 Treatment
o Monitor for possible development of HUS (condition in which microthrombi occlude the arterioles and
capillaries, which results in microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury.
Predominantly affects children and most commonly occurs following dysentery due to Shiga toxin-producing
enterohemorrhagic Escherichia coli (EHEC), typically serotype O157:H7.)
o Avoid antiperistaltic agents (e.g., diphenoxylate/atropine) since they increase the risk of systemic
complications.
o Antibiotic therapy is contraindicated (Antibiotics eradicate the bacteria, which can lead to an increased release
of toxins that exacerbate the course of the disease.)

Enterotoxigenic Escherichia coli (ETEC)

 Epidemiology
o Enterotoxigenic E. coli (ETEC) is the most common pathogen causing traveler's diarrhea.
o A major cause of diarrhea among children in developing countries
o Very common while traveling in Asian, African, and Latin American countries
 Pathophysiology
o ETEC produces two types of enterotoxins:
 Heat-labile enterotoxin (AB toxin; two-component protein, similar to cholera toxin): activation of adenylate
cyclase → ↑ cAMP levels → ↑ chloride secretion → water efflux into the intestinal lumen → secretory
diarrhea
 Heat-stable enterotoxin: activation of guanylate cyclase → ↑ cGMP levels → ↓ NaCl reabsorption → water
efflux into the intestinal lumen → secretory diarrhea
o No invasion of the intestinal mucosa and no inflammation
 Clinical presentation: Symptoms last 3–4 days.
o Watery diarrhea, Abdominal cramping; Nausea, possibly vomiting
o Fever, Decreased appetite
 Treatment
o Antibiotics may shorten the duration of symptoms (Azithromycin 1 g Einmaldosis oder 500 mg 1-0-0 für 3 Tage)
o Bismuth subsalicylate compounds may decrease the frequency of bowel movements.
 Prevention
o Practice good food and water safety.
o Prophylactic antibiotics are not recommended for most travelers.
o Prophylaxis may be considered for pregnant women and immunocompromised patients.

Enteropathogenic Escherichia coli (EPEC)

 Pathogen: Enteropathogenic E. coli (EPEC) leads to infantile diarrhea.
 Epidemiology
o Adults are less susceptible to EPEC infection.
o A common cause of diarrhea in children < 5 years old, especially in developing countries
o After rotavirus infections, EPEC is one of the leading causes of death in children in developing countries.
 Pathophysiology
o EPEC blocks absorption by attaching to the apical surfaces of the intestinal epithelium, causing the villi to
flatten.
o No toxin production is involved.

60
 Clinical presentation
o 10–20 watery bowel movements per day for about 2 weeks
o Vomiting
o Low-grade fever
 Treatment
o In cases of persistent diarrhea (e.g., loose stools for > 2 weeks) antibiotics may be used (Aufgrund
zunehmender Resistenzen wird eine antibiotische Therapie bei Nachweis von EPEC in aktuellen Leitlinien nicht
empfohlen)

Enteroinvasive Escherichia coli (EIEC)

 Pathogen: enteroinvasive E. coli (EIEC)
 Pathophysiology: invasion of gut epithelium → inflammation and necrosis
 Clinical presentation
o Watery to bloody diarrhea, possibly with mucus (dysentery)
o Fever, chills, malaise
o Abdominal cramps
o Possibly vomiting
o Symptoms similar to shigellosis

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33. Yersiniosis
 Pathogen: Yersinia enterocolitica, Yersinia pseudotuberculosis
o Gram-negative, rod-shaped, pleomorphic bacterium; obligate pathogen
 Transmission
o Foodborne (e.g., raw/undercooked pork, unpasteurized milk products)
o Contaminated water
o Direct/indirect contact with infected animal (e.g., dogs, pigs, rodents, and their feces)
 Incubation period: 4–6 days
 Clinical features
o Duration: 1–46 days
o Low-grade fever, vomiting
o Inflammatory diarrhea (may be bloody in severe cases)
o Pseudoappendicitis → mesenteric lymphadenitis, particularly in the ileum, with typical signs of appendicitis
 Diagnosis: direct pathogen detection in culture or cold enrichment
 Treatment: in severe cases, antibiotic therapy with fluoroquinolones (Ciprofloxacin 500 mg p.o. 1-0-1 oder 400
mg i.v. 1-0-1 für 5–7 Tage bei Enterokolitis, 7–14 Tage bei Bakteriämie) or 3rd generation cephalosporins
(Ceftriaxon 2 g i.v. 1-0-0 für 7–14 Tage) (depends on susceptibility to the drug)
 Complications: particularly in patients with HLA-B27
o Reactive arthritis
o Erythema nodosum
o Acute abdomen: appendicitis, bowel perforation, toxic megacolon, cholangitis
o Bacteremia

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34. Cholera
 Pathogen: Vibrio cholerae (Serogroups O1 and O139)
o Rare in developed countries; Southeast Asia, South America, West and central Africa
o Gram-negative, oxidase positive, curved bacterium with a single polar flagellum → produces cholera toxin
 Cholera toxin stimulates adenylate cyclase via activation of Gs → increased cyclic AMP → increased ion
secretion (mainly chloride)
 Transmission
o Fecal-oral
o Undercooked seafood or contaminated water (e.g., non-segregated drinking water and sewage systems)
 Incubation period: 0–2 days
 Infectivity: Acid-labile (grows well in an alkaline medium) → High infective dose required (over 108 pathogens)
 Clinical features
o Low-grade fever, vomiting
o Profuse 'rice-water' stools: The cholera enterotoxin activates adenylate cyclase. As a result, cAMP is increased,
which leads to the hypersecretion of water into the intestinal lumina. The stool is of almost liquid consistency
and resembles water with a white turbid color. Hence the name “rice-water” stools. They may occur up to 20–
30 times per day.
 Diagnosis: dipstick (rapid test; initial test) and stool culture (confirmatory)
 Treatment
o Urgent fluid replacement: Oral rehydration therapy, escalate to i.V. if necessary
o Antibiotic therapy in severe cases: doxycycline (500 mg 1-0-1 p.o., 3 Tage) OR Ciprofloxacin (500 mg 1-0-1 p.o.,
3 Tage); alternatively, Azithromycin (20 mg/kgKG p.o. einmalig, Maximaldosis 1 g) in children
 Complications
o Severe dehydration
o Pneumonia may occur in children
 Prevention
o Impfstoffart: Cholera-Totimpfstoff; Inaktiviertes Vibrio cholerae und rekombinantes Toxin,
Ganzpartikelimpfstoff
 Reiseimpfung
 Bei hohem Expositionsrisiko in Endemiegebieten insb. bei längeren Aufenthalten ohne gesicherte
medizinische Versorgung
 Bei erhöhtem Risiko schwerer Verläufe einer Cholera im Rahmen von best. Grunderkrankungen
 Grundimmunisierung
 Bei Kindern 2–6 Jahre: 3 Impfdosen im Abstand von jeweils 1–6 Wochen
 Bei Kindern >6 Jahre und Erwachsenen: 2 Impfdosen im Abstand von jeweils 1–6 Wochen
 Auffrischungsimpfung
 Bei Kindern im Alter 2–6 Jahre: 1 Impfdosis nach 6 Monaten
 Bei Kindern >6 Jahre und Erwachsenen: 1 Impfdosis nach 2 Jahren
o Sick or suspected individual should be isolated in a hospital suitable special regime
 Disinfection of linen and articles used by the patient is required
 Terminal cleaning of hospital rooms and equipment is required
o Patients Discharge from hospital: after clinical recovery and 3 negative results of bacteriological study that
began 24h after completion of antibiotic treatment
o Dispensarization (complex preventive and curative services) for 1 year.
o Contact persons: observed for 5 days, Immunization not indicated
 from Ist order(level) –isolation and urgent prevention with antibiotics (tetracycline)
 II order(level) - medical observation for five days and tested for vibriones
o Tighter control over water and nutrition of the population

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35. Brucellosis
 Pathogen: Brucella spp. are facultative intracellular, gram-negative, aerobic, coccobacilli.
o Brucella melitensis: mainly affects sheep, goats, and camels → Malta fever
o Brucella abortus: mainly affects cattle, but also bison, deer, and elk → Bang disease
o Rare causes of disease in humans
 Brucella suis: mainly affects (feral and domestic) pigs and reindeer, but also cattle and bison
 Brucella canis: affects dogs
 Transmission
o Contaminated food, esp. raw dairy products/meat
o Contact with infected animals (Inhalation)
 Area: Mediterranean, Africa, Asia
 Risk factors: occupational or recreational exposure to infected animals and animal products (e.g., farmers,
veterinarians, hunters, slaughterhouse workers, laboratory personnel)
 Pathophysiology: Brucella spp. survive and replicate within macrophages of the reticuloendothelial system →
formation of non-caseating granulomas
 Incubation period: 1–3 weeks
 Clinical features
o Flu-like symptoms; Night sweats (wet hay smell); High, potentially undulant fever
o Painful lymphadenopathy
o Localized infection
 Migratory Arthralgias, low back pain → osteoarticular infection (e.g., osteomyelitis, spondylitis)
 Epididymal and testicular tenderness, flank pain → genitourinary infection (e.g., epididymo-orchitis,
pyelonephritis)
 Murmurs, friction rubs, tachycardia → cardiac infection (e.g., endocarditis, myocarditis)
o Symptoms might return after afebrile period
 Diagnostics
o Laboratory studies: may show anemia, neutropenia, mild elevation of liver enzymes
o Serology: serum agglutination, ELISA
o Confirmatory test
 Blood culture
 Lymph node or bone marrow biopsy specimen and culture: noncaseating granulomas
 Rose Bengal test: rapid agglutination assay
 Pedro Pons’ sign: destructive appearance at the anterosuperior angle of the vertebra accompanied by
osteosclerosis and osteophytes, which are characteristic radiological findings of brucellar spondylitis
 Treatment
o First-line therapy: doxycycline (100 mg p.o. 2×/Tag für 6 Wochen) PLUS rifampicin (600 mg p.o. 1×/Tag für 6
Wochen)
o Second-line therapy: doxycycline PLUS streptomycin (15 mg/kgKG i.m. 1×/Tag für 2–3 Wochen)

64
36. Leptospirosis
 Leptospirosis is the most common zoonotic disease worldwide and is most common in the tropics
 Pathogen: Leptospira(especially L. interrogans), a genus of gram-negative spirochete with hook-shaped ends
 Route of infection
o Contact with soil, food, and/or water contaminated with the urine of infected animals (most commonly
rodents, cattle, pigs, horses, dogs) → entry of Leptospira through skin/mucous membrane lesions
o Occupational groups at risk: Farmers, sewer workers, Water sports enthusiasts (e.g., surfers) may also be
affected
 Incubation time: 2–30 days
 Clinical features
o Mild (anicteric) leptospirosis: due to bacteremia.
 High fever, headache; Diarrhea, vomiting
 Conjunctival suffusion: bilateral diffuse reddening of the
conjunctivae without exudates ↑
 Photophobia; Rash
 Myalgias (especially in the calves and lower back)
 Possibly aseptic meningitis → worsening headache and photophobia
o Severe leptospirosis (Weil disease, icterohemorrhagic leptospirosis): due to systemic spread and multiorgan
involvement
 Fever; Hepatitis → hepatomegaly, jaundice, acute liver failure
 Acute kidney injury (interstitial nephritis, acute tubular necrosis) → oliguria, hematuria
 Anemia, azotemia;
 Hemorrhagic diathesis: Purpura; Pulmonary hemorrhage → hemoptysis
 Cardiac abnormalities (e.g. myocarditis, pericarditis, arrhythmia, conductivity impairment)
 Diagnostics
o Dark-field microscopy of urine or blood samples (the thin Leptospira spirochetes cannot be visualized by light
microscopy)
o Serological tests
 Four-fold rise in the level of IgM titers within one month of the onset of symptoms
 Microscopic agglutination test (MAT)
o PCR: detect leptospiral DNA in bodily fluids
o Culture
o Complete blood count: Leukocytosis (neutrophilic); Can show thrombocytopenia and anemia in Weil disease
o Kidney function tests: elevated BUN in Weil disease; Liver function tests: ↑ AST/ALT
 Treatment
o For mild leptospirosis: aminopenicillins (ampicillin, amoxicillin), doxycycline (100 mg p.o. 2×/d 7 Tage)
o For severe leptospirosis
 IV penicillin G (drug of choice) (1,5 Mio. IE i.v. 4×/d 7 Tage), 3rd generation cephalosporins (e.g., ceftriaxone)
 Supportive therapy for multiorgan failure

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37. Viral hepatitis A and E
Hepatitis A
 Area: very common in tropical and subtropical regions
 Pathogen: hepatitis A virus; family of Picornaviridae and the genus Hepatoviridae
o Small (27 nm in diameter), non-enveloped virus with single-stranded, positive-sense RNA
o Resistant to denaturation by gastric acid, heat, and chemicals, and can remain viable for months in fresh and
saltwater
o Humans are the only reservoir for the hepatitis A virus
o not cytopathic in itself; research suggests that liver damage is caused by cellular immunity (especially CD8+ T
cells)
 Route of transmission: fecal-oral
o Contaminated water and food (e.g., raw shellfish)
o Risk groups: nursing home residents, international travelers, prison inmates, men who have sex with men, IV
drug users.
 Infectious period: 2 weeks before to 1 week after the onset of the illness
 Incubation period: 2–6 weeks
 Clinical features: in children is typically asymptomatic, risk of symptomatic disease increases with age
o Prodromal phase: 1–2 weeks
 Right upper quadrant pain, tender hepatomegaly
 Fever, malaise; Anorexia, nausea, vomiting
o Icteric phase: ∼ 2 weeks
 Jaundice, Dark urine and pale stools, Pruritus
o Resolution of symptoms
 Diagnostics
o Laboratory findings
 ↑ Serum transaminases (AST, ALT) - AST/ALT ratio is usually < 1, If > 1 acute liver failure (fulminant hepatitis)
should be suspected
 Mixed hyperbilirubinemia; Possibly ↑ ALP, ↑ γ-GT
 Atypical lymphocytosis; Urine analysis: ↑ urine bilirubin, ↑ urobilinogen
o Confirmatory test
 ↑ Anti-HAV IgM: active infection
 Anti-HAV IgM antibody levels begin to increase 1 week after the onset of symptoms and peak at around 4
weeks, after which they decrease again.
 Anti-HAV IgM can be found in serum 3–6 months after infection.
 ↑ Anti-HAV IgG: past infection or vaccination
 HAV RNA can be detected by PCR in stool and serum samples.
o Liver biopsy (not normally
necessary)
 Periportal inflammation
(monocyte infiltration),
Hepatocyte swelling,
Ballooning degeneration
 Bridging necrosis,
Councilman bodies
(apoptotic hepatocytes)
 Treatment: Disease is self-
limiting; only supportive care
is required

66
 Prevention
o Routine active immunization is now recommended for all children over 12 months consisting of a first IM dose
of hepatitis A vaccine followed by a booster dose after 6 months
o post-exposure prophylaxis: for all previously unvaccinated individuals who have been exposed to a
serologically confirmed case of HAV infection
 Healthy individuals aged 1–40 years: active immunization with hepatitis A vaccine
 Infants, individuals older than 40 years, patients with chronic liver disease and/or immunosuppression:
passive immunization with anti-HAV immunoglobulins
o The measures in epidemic outbreak is early diagnosis, Reporting with quickly notice of RHI and isolation of
patients in the infectious ward. disinfection in outbreaks of infection. Exclude from childcare, school or work
for at least one week after the onset of illness or jaundice and until they are well.
 Toilet hygiene, no food preparation by infected, lifelong ban on blood donations
 contact persons are subject to medical monitoring for 45 days and are given a double test for urobilinogen
and bilirubin and serum transaminases every 15 to 20 days

Hepatitis E
 Pathogen: hepatitis E virus (HEV)
o family of Hepeviridae and the genus Orthohepeviridae, is a small (34 nm in diameter), non-enveloped virus
with single-stranded, positive-sense RNA.
o HEV genotypes 1 and 2 are found only in humans, but genotypes 3 and 4 are zoonotic diseases with reservoirs
in both humans and animals (e.g., pigs, monkeys, and dogs)
 Epidemiology: An important cause of endemic viral hepatitis in developing countries and equatorial regions
(e.g., India, western and northern Africa, Middle East, and Mexico)
 Route of transmission: fecal-oral (especially via contaminated water, food, or sources)
 Pathophysiology: The degree of hepatic injury is usually mild and the patient may present with clinical features
of acute hepatitis.
 Incubation period: 2–8 weeks
 Clinical features: similar to those of hepatitis A
o In the majority of cases, the disease is self-limiting with complete recovery.
o Fulminant hepatitis in pregnant women (high risk of mortality for both mother and fetus)
o Affected individuals do not become carriers nor do they develop chronic hepatitis (unlike in hepatitis B and
hepatitis C).
 Diagnostics
o Laboratory findings are the same as in hepatitis A.
o Confirmatory test
 Anti-HEV IgM: active infection
 Anti-HEV IgG: past infection
 HEV RNA can be detected by PCR in stool and serum samples during the prodromal phase and up to 3 months
after the onset of symptoms.
o Liver biopsy (not normally necessary): patchy necrosis
 Treatment: supportive care
 Prevention: no vaccine available (one in China)
o maintaining hygienic practices;
o avoiding consumption of water and ice of unknown purity.

A fulminant course is relatively common in pregnant women with HEV infection (occurring in up to 20% of cases) and
is life-threatening for both the mother and fetus.

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38. Viral hepatitis B
 Area: High prevalence in Asia, Africa, and the Amazon basin
 Pathogen: Hepatitis B virus (HBV: DNA virus, hepadnavirus)
 Transmission
o Sexual
o Parenteral
 Needlestick injury; Contaminated instruments and shared needles; Contaminated blood products
o Perinatal
 High-risk groups
o IV drug users
o Individuals whose close contacts have chronic HBV infection; Infants of HBV-positive mothers
o Professions with exposure to human blood and/or seminal/vaginal fluids
o Individuals with multiple sex partners or sex partners of HBV-positive people (MSM)
o Patients undergoing hemodialysis; organ or blood transfusion recipients
o Hepatitis C virus (HCV) or HIV-positive individuals
 Pathophysiology
o Acute infection
 Hepatocytes infected by the hepatitis B virus express viral peptides on their surfaces (HBcAg and HBeAg)→
lymphocytes recognize HBV-derived peptides and become activated (CD8+ cytotoxic T cells) → lymphocytes
attack liver cells (cellular immune response) → hepatic inflammation with destruction of hepatocytes
o Chronic: clearance of the virus fails
 Persistent hepatic inflammation with necrosis, mitosis, and regeneration processes → cirrhosis, cellular
dysplasia → HCC
 Integration of HBV DNA into the host genome → altered expression of endogenous genes, chromosomal
instability → HCC
 Incubation period: 1–6 months
 Clinical Features
o Acute infection: acquired in the past 6 months
 Serum sickness-like syndrome can develop during the prodromal (preicteric) period: rash, polyarthritis, fever
 Subclinical hepatitis (70% of cases)
 Symptomatic hepatitis (30% of cases)
 Fever, skin rash, arthralgias, myalgias, fatigue
 Nausea
 Jaundice; Right upper quadrant pain
 Symptoms usually resolve after 1–3 months
 Fulminant hepatitis (∼ 0.5% of cases)
 Most adults will clear infection
o Chronic infection: Infections persisting >6 months with detection of HBsAg and possibly symptoms of liver
damage
 Most patients are inactive, non-contagious carriers.
 Potential reactivation of chronic inactive hepatitis: may be asymptomatic, imitate acute hepatitis, or result in
hepatic failure
 Cirrhosis, stigmata of chronic liver disease (25% of cases)
 Extrahepatic manifestations (10–20% of cases)
 Polyarteritis nodosa
 Membranous glomerulonephritis

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 Diagnostics
HBV antigen/DNA Description Corresponding antibodies
 Anti-HBs
 Hepatitis B  Protein on the surface of o Indicates immunity to HBV due to
 HBsAg surface HBV; first evidence of vaccination or resolved infection
antigen infection o Usually appears 1–3 months after
infection.
 Anti-HBc
o Anti-HBC IgM indicates recent infection
 Hepatitis B
 HBcAg  Protein of the nucleocapsid with HBV (≤ 6 months)
core antigen
o Anti-HBc IgG indicates resolved or chronic
infections
 Hepatitis B  Protein secreted by the virus
 Anti-HBe
 HBeAg envelope that indicates viral
o Indicates long-term clearance of HBV
antigen replication and infectivity
 HBV DNA  DNA of HBV

Anti- Anti-
HBsAg HbeAg Anti-HBc HBV DNA Transaminases
HBs HBe
Acute infection ↑ ∅ ↑ ∅ ↑ IgM ∅–↑ ↑ (ALT > AST)
↑ IgM first,
“Window period” ∅ ∅ ∅ ∅–↑ ∅–↑ ↑ (ALT > AST)
then IgG
Resolved prior infection ∅ ↑ ∅ ↑ ↑ IgG ∅ ∅
Active chronic HBV DNA
Virus persistence ↑ ∅ ↑ ∅ ↑ IgG Normal or ↑
infection >2000 IU/mL
(chronic infection)
↑ HBsAg > 6 months
Inactive chronic HBV DNA
↑ ∅ ∅ ↑ ↑ IgG Normal
infection ≤2000 IU/mL
Vaccination ∅ ↑ ∅ ∅ ∅ ∅ ∅
Window period: In the process of immune clearance, when HBsAg is disappearing and anti‑HBs is not yet detectable,
anti‑HBc IgM and anti-HBe is the only marker to diagnose an acute HBV infection.
 Testing algorithm
o Screening: HBsAg (detectable 1–5 months after infection) and anti HBc IgM
o If HBsAg is positive → measure HBeAg and HBV DNA
o Seroconversion of HBsAg to anti HBs indicates acute hepatitis resolution.

69
The main serological feature of chronic HBV infection is the persistence of HBV DNA and the antigens HBsAg and HBeAg despite
resolution of acute infection. Transaminase levels may be normal or increased and fluctuate between periods of active and
inactive chronic infection.
 Additional Tests
o Laboratory studies
 Transaminases (AST, ALT)
 Acute hepatitis: ↑ with AST/ALT ratio of < 1 (> 1 in fulminant infection)
 Chronic hepatitis: variable values (usually < 100 U/L; in active infection > 100 U/L) with AST/ALT ratio of ≥1
 ↑ γ-GT, bilirubin, GLDH, and/or AP
 In cirrhosis: ↓ albumin, CHE
o Abdominal ultrasound
 Acute hepatitis
 ↑ Brightness of portal vein radicle walls
 ↓ Echogenicity of the liver
 Chronic hepatitis
 ↓ Brightness and number of portal vein radicle walls
 ↑ Liver echogenicity
o Liver biopsy: Piecemeal necrosis, Ground glass hepatocytes
o Test of common coinfections (e.g., hepatitis C/D, syphilis, HIV)
 Treatment
o Acute: supportive care
o Chronic
 Antiviral treatment: patients with evidence of liver inflammation (ALT ≥ 2 times upper limit) or cirrhosis
 Nucleoside/nucleotide analogs: indicated for patients with both decompensated and compensated liver
disease and nonresponders to interferon treatment; Tenofovir is commonly the drug of choice, Entecavir
 Pegylated interferon alfa (PEG-IFN-a): especially in younger patients with compensated liver disease
 Liver transplantation: In cases of end-stage liver disease due to HBV; In cases of fulminant hepatic failure
(emergent transplantation)
 Prevention
o Vaccination: 1st dose 24hrs after birth, 2nd dose 1-2 months, 3rd dose 6 months
o Pre-exposure vaccination: recommended for all unvaccinated individuals
o Post-exposure prophylaxis (PEP) for hepatitis B: medical surveillance for 180 days
 Documented vaccine responder with HBsIgG ≥ 10 mIU/mL: no intervention needed
 Documented non-responder: Administer two doses of hepatitis B immune globulin (HBIG) separated by 1
month
 Unvaccinated individuals or incompletely vaccinated: simultaneous administration of hepatitis B immune
globulin (HBIG) and hepatitis B vaccine (see also perinatal hepatitis B) and completion of original vaccination
series

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39. Viral hepatitis C and D
Hepatitis C
 Area: Africa, Middle East, East Asia, Former Soviet Union
 Pathogen: Hepacivirus C (Hepatitis C virus): RNA virus of the Hepacivirus genus and Flaviviridae family
o The risk of chronic infection is multifactorial and depends on the host's ability to clear the pathogen through
activation of multiple innate immunity pathways against the viral envelope
 Flawed proofreading capability of RNA-dependent RNA polymerase (no 3'-5' exonuclease activity)
introduces mutations into genes encoding viral glycoprotein envelope and enabling novel antigen
production.
 Rapid replication rate produces many antigenically unique viral envelopes.
 Infection persists because the production rate of new mutant virions exceeds the production rate of host
antibodies.
o There are six genotypes (plus subtypes 1a, 1b, …): In Germany, the main ones are genotype 1 (62%) and
genotype 3 (27%)
o Reinfection with another HCV genotype is possible
 Transmission
o Parenteral
 Needle sharing among IV drug users; Needlestick injury (e.g., health care workers)
 Blood transfusion, Dialysis
o Organ transplantation
o Sexual: rare (in contrast to HBV and HIV)
o Perinatal (vertical)
 Incubation period: 2 weeks to 6 months
 Clinical features
o Acute course: Asymptomatic in 80% of cases
 Symptomatic
 Malaise, fever, myalgias, arthralgias
 RUQ pain, tender hepatomegaly
 Nausea, vomiting, diarrhea
 Jaundice, possibly pruritus
o Chronic course: Seen especially in asymptomatic individuals (up to 85%), as the disease may go undiagnosed
and treatment may be delayed or never initiated (carrier state)
 Findings often mild, nonspecific (e.g., fatigue)
 Liver cirrhosis (up to 25% of cases) within 20 years of infection
 Extrahepatic features (common)
 Hematological
o Mixed cryoglobulinemia (low C4, red macules and or purpura), Lymphoma (especially B-cell non-Hodgkin
lymphoma)
o Immune thrombocytopenic purpura, Autoimmune hemolytic anemia, Monoclonal gammopathies
 Renal
o Membranoproliferative glomerulonephritis (more common)
o Membranous glomerulonephritis
 Rheumatological: Polyarteritis nodosa, Sjogren syndrome
 Dermatological: Porphyria cutanea tarda, Lichen planus
 Endocrine: Diabetes mellitus, Autoimmune thyroiditis (may lead to hypothyroidism)
 Vascular: leukocytoclastic vasculitis
 Others: sialadenitis

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 Diagnostics
o Detection of antibodies
 EIA/ELISA: standard immunoassay tests for anti-HCV antibodies (positive in cases of acute, chronic, and
previous HCV infection)
 PCR for HCV RNA if antibodies are positive.
 If positive PCR: active HCV infection (may be acute or chronic)
 If negative PCR: no active infection, but prior infection
 Determines HCV genotype and virus titer assists in treatment planning and monitoring
o Liver function tests
 ↑ Transaminases with AST/ALT ratio: Ratio < 1: acute hepatitis, Ratio ≥ 1: chronic hepatitis
 ↓ Total protein/albumin, coagulation (particularly ↑ prothrombin time), ↓ cholinesterase
 Cholestasis parameters: ↑ γ-GT, ↑ alkaline phosphatase, ↑ bilirubin
o Inflammation markers: leukocytosis, ↑ ferritin
o Liver biopsy indications: If diagnosis is inconclusive, For evaluating fibrosis in patients with chronic hepatitis C
o Ultrasound: detection of cirrhosis and neoplasia, e.g., HCC
o Rule out coinfections: HIV, hepatitis A virus (HAV), hepatitis B virus (HBV) serology necessary

HCV RNA is continuously detectable throughout chronic hepatitis C infection, with levels peaking at approx. 6 weeks
and lower spikes occurring episodically thereafter. Transaminase levels follow the pattern of HCV RNA with a slight
delay of approx. 1 week. Antibody production begins at 2 months after infection and plateaus at approx. 4 months,
thus not corresponding to HCV RNA and transaminase levels.

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 Treatment
o Avoid hepatotoxic drugs (e.g., acetaminophen) and alcohol use.
o Acute hepatitis C - Treatment goal: prevent transition to chronic infection
 Antiviral therapy: The same regimens as for chronic HCV infection
 Monitoring for 12–16 weeks is recommended before initiation.
o Treatment should be started if HCV is not cleared.
o No treatment is necessary if HCV is cleared.
 Monitoring: regular monitoring of HCV RNA every 4–8 weeks for 6–12 months
o Chronic: Complete cure approx. 95%, especially in patients without liver cirrhosis
 Regimen chosen based on viral genotype (the most important predictive factor for response to therapy),
viral load, history of antiviral treatment, and degree of liver fibrosis
 Combination of two direct-acting antivirals (DAAs): Antivirals target and inhibit HCV-encoded proteins that
are essential for the HCV replication cycle.
 Ledipasvir PLUS sofosbuvir (± Ribavirin) for 8–12 weeks (genotypes 1, 4, 5, and 6)
 Sofosbuvir PLUS velpatasvir for 12 weeks (all 6 genotypes)
 Interferon PLUS ribavirin 16-24 weeks: still used as a last resort in cases of treatment failure, all genotypes
o Endstage liver failure  Surgery: liver transplantation
o contact persons are monitored by GPs for a period of 120 days

Hepatitis D virus infection

 Epidemiology: 5% of all chronically infected HBV patients are carriers of the hepatitis D(elta) virus
o Endemic in Africa and South America
 Pathogen: Hepatitis D virus (HDV)
o Incomplete viral particle resembling a viroid; Defective single-stranded RNA virus
o Utilizes the HBsAg coat of HBV for propagation
 Transmission: sexual, parenteral, perinatal (only possible in combination with HBV - HDV requires HBsAg for
replication)
 incubation period is 21-45 days but may be shorter in cases of superinfection
 Course - dependent on the hepatitis B status
o Coinfection: more severe acute hepatitis, but 90% rate of convalescence
o Superinfection of a chronic HBsAg carrier: ↑ risk of liver cirrhosis  In rare cases, fulminant hepatitis

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40. Enterovirus infections. Poliomyelitis
Enterovirus
genus of positive-sense single-stranded RNA viruses, including poliovirus, Coxsackie A and B, and rhinovirus. These
viruses are spread via the fecal-oral route and can cause several different infectious diseases
see TOPICS 41 and 43
Poliomyelitis/ Poliomyelitis epidemica anterior acuta/ Kinderlähmung
 Area: still endemic in Afghanistan, Nigeria, and Pakistan
 Pathogen: Poliovirus is an RNA virus in the family Picornaviridae, genus enterovirus, and has three serotypes.
o Poliovirus type 1 causes most paralytic manifestations of poliomyelitis; Humans are the only hosts
 Transmission route
o Fecal-oral route: absorption of poliovirus in the intestinal tract
o Rarely, droplet transmission may occur during epidemics
o The virus replicates in the gastrointestinal tract (oropharynx and small intestine) following oral ingestion →
enters the bloodstream → potential invasion of the grey matter of the spinal cord (particularly the lower motor
neurons of the anterior horn) → myelitis
o The polimyelitis virus primarily affects certain brain structures:
 cells in the anterior horns of the spinal cord
 large pyramidal cells of gyrus precentralis
 nuclei of the brainstem
 subcortical nuclei of the cerebellum
 less frequently - hypothalamus and others
 Incubation time: 7–14 days
 Clinical features: >72% of infections asymptomatic
o Poliomyelitis without CNS involvement (abortive poliomyelitis)
 Nonspecific symptoms: gastroenteritis, fever, nausea, sore throat, myalgia, and headaches for 1–3 days
 Complete recovery without complications or transition to poliomyelitis with CNS involvement
o Nonparalytic poliomyelitis: aseptic meningitic form
 Begins several days following abortive poliomyelitis (often temporary, symptom-free interval)
 Fever, neck stiffness, headache, vomiting, muscle pain
 Neck muscle weakness (head drop sign: head falls back when placed in a supine position)
 No paresis
o Paralytic poliomyelitis
 Occurs 2–3 days following the meningitic form after a brief symptom-free interval
 Fever, malaise, headache, nausea; Severe back, neck, and muscle pain
 Asymmetric flaccid paralysis worsens over hours to days
 Most commonly affects the leg muscles, although the arms, abdomen, trunk, thorax, and eyes may be
affected ; Paralysis is usually more severe in proximal muscles than in distal muscles.
 Ascending paralysis with diaphragmatic involvement → respiratory failure
 Bulbar form with brain stem involvement (rare): damage to the cerebral or autonomic nerve centers
(cranial nerves and respiratory center) → central respiratory paralysis
 Diminished deep tendon reflexes; Muscle atrophy, Hypotonia, Fasciculations
 Diagnostics
o The best diagnostic test is PCR amplification of poliovirus RNA from CSF.
o Poliovirus RNA can also be isolated from stool or oropharynx (throat swab).
o CSF will show:
 High protein levels; Normal glucose levels
 Pleocytosis with either neutrophils (early infection) or lymphocytes (late infection)
 Treatment: Pain relief, Mechanical ventilation if needed, Close monitoring of blood pressure and respiratory
function

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 Prevention
o The inactivated poliovirus vaccine (IPV) is recommended for childhood immunization in the US and most high-
income countries
o live attenuated oral poliovirus vaccine (OPV) is used for childhood immunization in resource-limited countries
 Post-polio syndrome (PPS)
o Most frequent complication observed following poliovirus infection (up to 40% of survivors)
o Occurs decades after infection
o Manifests with progressive muscle weakness and pain, even in areas that were not affected by the initial
infection

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41. Coxsackie and ECHO viral infections
Coxsackie virus infections
 Pathogen: coxsackie virus Single stranded RNA virus
o Genus: enterovirus, Family: picornaviridae
o Over 20 serotypes, divided into group A and group B coxsackie viruses
 Route of transmission: Airborne droplets, Fecal oral route
 Coxsackie A
o Conjunctivitis
o Herpangina
 Herpes-like oral lesions: multiple 1-mm vesicles located on the posterior
oropharynx and tonsils; pharyngeal and tonsillar redness; Fibrin-covered
ulcerations appear in later stages
 Sore throat and high fever; May occur as a component of hand, foot, and
mouth disease
o Respiratory form: Acute onset, fever for 3-5 days, headache, muscle aches and
mild catarrhal manifestations (rhinopharyngitis, tracheitis, laryngitis), rhinitis, dry irritable cough.
 Coxsackie B
o Myocarditis/ Meningoencephalomyocarditis in newborns
 Source of infection are the mother (intrauterine or during delivery) and the service staff /carriers/
 IP: 1-7 days. The illness is expressed with drowsiness, denial of food. The temperature rises, newborns
become loosely, dyspnea, cyanosis or tachycardia may occur. On auscultation - deaf cardiac tones, on
percussion - enlarged heart measurements. ECG - evidence of myocardial damage. In pericarditis there is
pericardial friction and a typical X-ray image. Cardiac decompensation occurs rapidly.
 Exitus due to severe cardiovascular weakness - lethality up to 75%. In children and adults myocarditis is
relatively favorable.
 CBC and the CSF are as described in serous meningitis, but with less pronounced lymphomonocytosis.
o Pericarditis
o Dilated cardiomyopathy
o Pleurodynia (Bornholm disease)
 Characteristics: highly contagious
 Clinical features
 Flu like symptoms
 Sudden thoracic and upper abdominal pain caused by irritation of the pleura and muscles
 Diagnosis - Clinical
 Viral culture or PCR (throat or stool sample), serological testing
 Creatine kinase may be elevated
 Treatment: symptomatic
 Prognosis: self limiting
 Coxsackie A and B
o Viral meningitis, encephalitis
o Pneumonia
o “Summer flu”/ Little disease
 Acute onset, short-term rise in temperature, headache, moderate muscle pain, abdominal pain, vomiting.
 Objectively: facial hyperemia, conjunctival irritation, red mucous membranes of the oral cavity, pharynx,
soft palate and tonsils
o Hand, foot, and mouth disease/ Vesicular stomatitis with skin manifestations
 Highly contagious, pathogen: Enterovirus 71
 Clinical features
 General symptoms: fever, malaise

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 Anorexia, oral pain
Skin/mucosa
o Maculopapular and partially vesicular rash on the hands and
feet (can also involve the buttocks)
o Oral ulcers
 Diagnosis: clinical
 Treatment: symptomatic
 Prognosis: almost always self limiting

Echovirus (enteric, cytopathic, human, orphan viruses) + Coxsackie A and/or B

 Serous meningitis: Coxsackie A and ECHO
o affects mostly the age 1-7-14 years and young people and has marked spring-
summer seasonality
o acute illness, with a fever (39/40C), severe headache in the frontal, temporal and rarely occipital area
o Well-expressed meningial irritation: /+/ nuchial rigrdity and Kernig sign and less frequently (+/-) of Brudzinsky and the
tripod sign. In the first days, transient cerebrovascular manifestations / paralysis of the cranial nerves, pyramidal damages
- elevated tendon and superficial reflexes to clonus, transient ataxia, and tremor) are observed in the early days. In
children at an early age, the disease can begin with epileptiform seizures (generalized or equivalent), and in older children
and adults, with varying transient changes in consciousness /obtundation, sopor, rarely coma/.
o Facial hyperemia, erythema of the conjunctiva and sclera, rarely herpes of the lips and nose, manifestations of autonomic
nervous system- skin dryness, tachycardia, elevated BP, upper respiratory tract catarrh
o LP, the CSF is clear, is leaked under elevated pressure with moderate lymphomonuclear cytosis. In the early days,
segmented nucleotide pleocytosis can also be observed, which rapidly changes to lymphomonuclear. Proteins are normal,
mildly or moderately elevated.
o CBC is not typical - normocytosis, less frequently leukopenia or moderate leukocytosis with lympho- monocytosis in DBC
and normal or slightly increased ESR
 Encephalitis or meningoencephalitis
o start sharply, with fever, headache, vomiting and mental changes /drowsiness, looseness, less often with
psychomotor agitation /. They are also associated with focal neurologic symptoms /paresis and paralysis of the
cranial nerves, hyperkinesias, epileptiform seizures and others/ depending on the localization of the process
 Aseptic meningitis syndrome: Rash,Sore throat, Muscle pain, Sign of meningeal irritation CSF (PMN
pleocytosis,High protein,Normal glucose)
 Conjunctivitis
 Myocarditis
 Hepatitis
 Severe neonatal diarrhea
 Enteroviral /ECHO/ exanthema - Boston disease
o sporadic cases and epidemic outbreaks reported in children under the age of 10 and young people during the
spring-summer season
o manifested with acute onset, fever /38-39C/, headache, myalgia, sometimes abdominal pain and vomiting
o may also begin with catarrhal manifestations from the upper respiratory tract
o After 1-2 days from the onset of the disease, a pink-red macular or maculopapular Scarlet fever-like rash
appears on the face, body, legs. On the mucous membrane of the soft palate there may be spotted exanthem
or vesicles, which later pass into aphthous
 Poliomyelitis-like /paralytic/ form
o begin suddenly, with a rise in temperature, restlessness, respiratory and cardiovascular disorders, coma,
paralysis of breathing, and fatal outcome /hours to 1-2 days/. Some patients may have bulbar and spinal
paralysis, which may end up fatally. Some patients develop mono-, bi-, tri- and quadriplegia, as with polio, but
with better prognosis and quicker recovery

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42. Influenza and parainfluenza
 Distribution: Influenza viruses have a worldwide distribution.
 Seasonal pattern: Most infections occur during the fall and winter
 Pathogen: Influenza virus A and B (and rarely influenza C)
o RNA viruses of the family orthomyxoviruses, Enveloped virus with a helical capsid
o Single-stranded, negative-stranded, segmented (8 segments), Replication in cell nucleus
o Influenza A: The term “influenza” typically refers to influenza A infections (occurs in nature in pigs, horses,
birds and man). Viruses are classified into various subtypes based on glycoproteins of the viral envelope.
 Hemagglutinin (H): H1, H2, H3, and H5 most relevant
 Neuraminidase (N): N1, N2, and N7 most relevant
o Influenza B/C (less common): significantly milder course
 No evidence of genetic shift in influenza B → risk of epidemics is much lower
 two lineages: B/Yamagata and B/Victoria
 Transmission: directly via respiratory droplets (sneezing or coughing) or indirectly through contact with
contaminated surfaces
 Replication cycle
o Influenza viruses bind to the respiratory tract epithelium.
o Viral hemagglutinin (H) binds sialic acid residues (neuraminic acid derivatives) on the host cell membrane →
virus fusion with the membrane → entry into the cell
o The virus replicates in the nucleus of the cell.
o The new virus particles travel to the cell membrane → formation of a membrane bud around the virus particles
(budding)
o Viral neuraminidase (N) cleaves the neuraminic acid → virions exit the cell
o Host cell dies → cellular breakdown triggers a strong immune response
 Genetic mutations
o Antigenic shift
 Two subtypes of viruses (e.g., human and swine influenza) infect the same cell and exchange genetic
segments (reassortment) to create new subtypes (e.g., H3N1 → H2N1).
 Occurs in particular when human pathogenic and animal pathogenic influenza viruses exchange genetic
information
 Causes pandemics (limited to a specific time period)
o Antigenic drift
 Minor changes in antigenic structure (hemagglutinin and/or neuraminidase) via random point mutation
 Does not alter the subtype (e.g., H5N1 or “avian flu”).
 Causes epidemics (limited to a specific population or region)
 Incubation period: a few hours to several days
 Clinical features: asymptomatic or mild in 75% of cases
o Sudden onset of high fever, chills, headache, arthralgia, myalgia, fatigue, and malaise  “flu-like symptoms”
o Patients often develop acute bronchitis with a cough that is usually dry but may produce small amounts of
clear or blood-tinged sputum.
o Hypotension and bradycardia are common (especially among women and older patients)
 Diagnostics
o Blood tests: Normal or slightly elevated inflammatory markers; Relative lymphocytosis
o Rapid antigen test
 Used for early diagnosis; Detection of various influenza A/B antigens via nasal or pharyngeal swabs
 High specificity, limited sensitivity
o Serological testing (e.g., via complement fixation)
 Used to diagnose an infection after it has resolved (not relevant in acute illness)
 Infection is likely if serum antibody titers increase 4-fold within 1–2 weeks after acute illness

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 Treatment
o Supportive therapy
 Rehydration
 Antipyretics and analgesia (e.g., acetaminophen) to decrease fever
 Antitussives (e.g., dextromethorphan) to relieve dry cough.
o Antiviral therapy
 Patients with severe disease or patients at risk of developing complications (see “Complications” below)
 Sometimes considered if there is a high suspicion of early disease (e.g., prodromal symptoms and recent
exposure)
 Should be initiated as soon as possible (within the first 48 hours)
 Neuraminidase inhibitors: inhibit the release of viruses from the host cell.
 Inhalative zanamivir 10 mg 1-0-1 5 Tage
 Oral oseltamivir 75 mg p.o. 1-0-1 5 Tage >13 yrs. and adults
 IV Peramivir
 Complications
o High-risk groups for complications
 Elderly individuals ≥ 65 years of age; Children < 5 years of age, especially < 2 years of age
 Pregnant women (and women up to two weeks after giving birth)
 Individuals with chronic medical conditions (e.g., asthma, heart disease, diabetes mellitus,
immunocompromise); Nursing home residents
o Primary influenza pneumonia
 Hemorrhagic pneumonia with poor prognosis (less common than secondary bacterial bronchitis/pneumonia)
 May progress to acute respiratory distress syndrome (ARDS) with respiratory/multiorgan failure
o Secondary bacterial bronchitis/pneumonia
 After flu symptoms have improved, patients suddenly become febrile again and develop a productive cough
with large amounts of purulent (sometimes bloody) sputum.
 most frequently Streptococcus pneumoniae, but also other typical pneumonia pathogens such as S. aureus
and Haemophilus influenzae
 Prevention
o Influenza vaccine
 Annual flu shot for all persons aged 6 months and older every flu season as soon as the vaccine becomes
available
 The trivalent vaccine protects against two influenza A viruses (currently a H1N1 and a H3N2 subtype) and one
influenza B virus.
 In addition to these types, the quadrivalent vaccine protects against a second influenza B virus.
o Hygiene
 Hand hygiene
 Wash hands with soap and water before and after each patient contact
 Alternatively, use an alcohol-based hand rub
 Avoid contact with infected individuals and stay home when sick
 Adhere to standard precautions
 Surface cleaning with alcohol- or aldehyde-based agents
 Face mask; Gloves and gown for contact with potentially infectious material
o Antiviral medications may be considered in patients with exposure to an infected person under certain
circumstances (e.g., high risk of complications, contraindications for the vaccine, and influenza outbreaks in
nursing homes).

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Parainfluenza
 four viruses in this group and each one causes different symptoms and illnesses (HPIV)
o Type 1 causes an acute croup /laryngotracheobronchitis/
o Type 2 is associated with croup and mild upper respiratory tract infections and occasionally with acute lower
respiratory disease
o Type 3 is the major cause of severe lower respiratory disease in infants and young children; often causes
bronchiolitis, pneumonia and croup in those under 1 year
o Type 4 is usually associated with mild forms of upper respiratory tract infections
 ways in which the patient can become infected with an HPIV: through droplet or close contact with someone
who is already infected or through hand-to-eye, hand-to-nose, or hand-to-mouth transmission, either from
contaminated surfaces or from direct personal contact such as a hand-shake
 Incubation period: 2-7 days
 Diagnostics
o Isolation and detection of the virus in cell culture
o Detection of viral antigens directly within bodily respiratory tract secretions using immunofluorescence,
enzyme immunoassays or fluroimmunoassays
o Polymerase chain reaction (PCR)
o Because of the similarity in terms of the antigenic profile between the viruses, hemagglutination assay (HA) or
hemadsorption inhibition (HAdI) processes are often used. Both complement fixation, neutralisation and
enzyme linked immunosorbent assays – ELISA, can also be used to aid in the process of distinguishing between
viral serotypes
 Treatment
o Ribavirin is one medication which has shown good potential for the treatment of hPIV-3 given recent in-vitro
tests (in-vivo tests show mixed results).
o Furthermore, antibiotics may be used if a secondary bacterial infection develops. Corticosteroid treatment and
nebulizers and also a first line choice against croup if breathing difficulties ensue.
o No vaccines currently exist

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43. Acute respiratory diseases
Adenovirus infections
 non-enveloped viruses with double-stranded DNA
 almost 100 different serotypes, 47 of which affecting humans and subdivided into six groups
 transmitted by direct contact, fecal-oral transmission, and occasionally waterborne transmission
o adenovirus serotype 36 (Adv36), have been shown to cause obesity in animals, and are associated with human
obesity
 Incubation period: 4-7 days
 Signs and Symptoms
o Febrile respiratory disease – The illness can include symptoms of pharyngitis, rhinitis, cough, and swollen
lymph nodes
o Adenovirus causes bronchiolitis, croup, or viral pneumonia. Adenovirus can also produce a dry, harsh cough
that can resemble whooping cough (pertussis)
o Gastroenteritis with watery diarrhea, vomiting, headache, fever, and abdominal cramps
o Genitourinary infections: Adenoviruses are known to cause a condition called hemorrhagic cystitis, which is
characterized by blood in the urine
o Eye infections:
o Pinkeye (conjunctivitis) is a mild inflammation of the conjunctiva. Symptoms include red eyes, discharge,
tearing, and the feeling that there is something in the eye
o Pharyngoconjunctival fever occurs when adenovirus affects both the lining of the eye and the respiratory
tract. Symptoms include very red eyes and a severe sore throat, sometimes accompanied by low-grade fever,
rhinitis, and swollen lymph nodes
o Keratoconjunctivitis is a more severe infection that involves both the conjunctiva and cornea in both eyes. This
type of adenoviral infection is extremely contagious and occurs most often in older kids and young adults,
causing red eyes, photophobia, blurry vision, tearing, and pain
 Diagnosis
o Antigen detection, PCR, virus isolation and serology can be used to identify adenovirus infections
o Adenovirus typing is usually accomplished by hemagglutination-inhibition and/or neutralization with type-
specific antisera. Since adenovirus can be excreted for prolonged periods, the presence of virus does not
necessarily mean it is associated with disease
 Treatment
o Most infections are mild and require no therapy or only symptomatic treatment. Because there is no virus-
specific therapy, serious adenovirus illness can be managed only by treating symptoms and complications of
the infection
o There is a vaccine, but availability is limited

Rhinoviruses
 More than 110 serotypes, Very high incidence
 Transmission occurs by airborne and smear infections
 Attaches to ICAM-1 receptors (CD54) on respiratory epithelial cells
 Acid labile (inactivated by gastric acid): proliferation is limited to local portals of entry (nasopharyngeal
epithelium, not GI tract)
 major cause for mild upper respiratory tract infections in all age group, especially in older children and adults
 incubation period is 2-4 days followed by rhinorrhea, sneezing, cough, sore throat and headache; nasal
congestion, sneezing, rhinorrhea, and post-nasal drip
 diagnosis only by clinical presentation
 There is no specific treatment

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Reovirus infection
 caused by a virus from the Reovirdae family. It contains RNA
 Infection in humans is usually asymptomatic or produces only mild symptoms
 The source of infection is ill person via respiratory or fecal-oral route
 The disease has two forms of clinical presentation:
o Rhinitis
o Acute gastroenteritis, predominantly in young children

Rotavirus infection(Rotavirus gastroenteritis)

 Pathogen: Rotavirus is a nonenveloped, segmented, double-stranded RNA reovirus.
 Transmission: fecal-oral route (e.g., by contact with hands, objects, food, water contaminated with the virus)
 Pathophysiology: Mucosal damage and villous atrophy in the gastrointestinal tract impair absorption of sodium
and loss potassium → nonbloody, watery diarrhea
 Clinical features
o Incubation period: 1–3 days
o Fever, malaise; Abdominal pain
o Vomiting and watery diarrhea
 Can be severe: > 10 loose, watery stools within 24 hours
 Usually lasts 3–7 days
o Mild to severe dehydration
 Diagnostics: Antigen detection in stool via enzyme immunoassay (EIA): a highly sensitive test that can be
performed quickly and easily
 Treatment: Supportive - Oral rehydration, IV fluids in patients with severe dehydration
 Prevention: Rotavirus vaccination (a live attenuated vaccine) is recommended for all infants unless there is a
contraindication.

RSV infection
 RSV belongs to the genus Pneumovirus in the family Paramyxoviridae
 It is an enveloped virus of 120–300 nm diameter
 The helical, single-stranded, positive-sense RNA genome codes for at least 10 polypeptides including F, G and Sh
envelope-associated glycoproteins
o The F (fusion) protein is associated with penetration of the virus into cells, and its spread from cell to cell.
o The larger G protein is responsible for initial attachment of the virus to host cells
 Bronchiolitis
o Primarily affects children < 2 years; Peak incidence: 2–6 months of age; Common during winter months
o Etiology Most common: respiratory syncytial virus (RSV)
o Clinical features
 Initially presents with upper respiratory tract symptoms (e.g., rhinorrhea), fever, and cough
 Respiratory distress (usually occurs in infants)
 Tachypnea, Prolonged expiration, Nasal flaring, Intercostal retractions, Cyanosis
 Poor feeding in breastfed infants
 Auscultatory findings: wheezing, crackles
o Diagnostics - clinical diagnosis
 Nasopharyngeal aspirate test for RSV
 Chest x-ray: hyperinflation of the lungs, interstitial infiltrates, atelectasis
o Treatment
 Supportive treatment: Adequate hydration, Relief of nasal congestion/obstruction, Monitoring
 Pharmacologic treatment
 Bronchodilators, epinephrine, and corticosteroids have historically been part of the treatment for
bronchiolitis, but recent guidelines recommend using such therapies mainly in severe cases.

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  Ribavirin: currently not recommended for routine treatment of bronchiolitis; may be considered in
immunocompromised patients

Severe acute respiratory syndrome (SARS)

 viral respiratory illness, worldwide outbreak in 2003
 Pathogen: SARS-CoV, +ssRNA, Linear Coronaviridae
 Epidemiology
o Area: China, including Hong Kong; spread worldwide
o Intermediate host and reservoir: horseshoe bats (genus Rhinolophus), palm civets?
o Transmission: person to person and could be acquired from face-to-face contact, suggesting droplet spread;
airborne, fomites
o Incubation period: usually two to seven days, 95 percent of patients will develop symptoms within 10 days
 Clinical manifestations
o prodrome, 3-7 days, and is characterized by fever (>38ºC) malaise, headache, and myalgias
o respiratory phase typically begins with a nonproductive cough. Dyspnea may follow and may progress to
respiratory failure, with progressive pulmonary infiltrates on chest radiograph, necessitating mechanical
ventilation
o diarrhea (20 percent) and chest pain or pleurisy (22 percent)
 Diagnostics
o ↓total lymphocytes, ↑ lactate dehydrogenase (LDH),↑alanine aminotransferase
o Imaging
 CXR: patterns ranged from normal to diffuse interstitial infiltrates characteristic of acute respiratory distress
syndrome. Bilateral peripheral infiltrates were common, usually in the middle or lower lung zones
 CT: parenchymal abnormalities in patients with apparently normal chest radiographs. Infiltrates are usually
ground glass in character and peripheral in location
o RT-PCR assays: respiratory, stool, and serum or plasma samples
o Serum antibody, usually measured by enzyme-linked immunosorbent assay, is the most sensitive of available
tests; mean time to seroconversion was 19-20 days
 Treatment
o No specific treatment is recommended except for meticulous supportive care
o no antiviral agents have been found to provide benefit for treating SARS
o Lopinavir-ritonavir may have some activity against the virus in vitro, but its clinical efficacy has not been
established
o Remdesivir (GS-5734), has activity against the SARS and MERS coronaviruses

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COVID-19 (Coronavirus disease 2019) This data is from May 2021, so it probably needs to be updated in the future!
 acute infectious respiratory disease caused by infection with the coronavirus subtype SARS-CoV-2, first detected
in Wuhan, China, in December 2019
o WHO declared COVID-19 outbreak a Public Health Emergency of International Concern on January 30, 2020.
o WHO classified COVID-19 as a pandemic on March 11, 2020.
 Basic reproduction number (R0): ∼ 2–4
 Demographics: ♂ = ♀, Affects people of all ages
 Fatality rate: ∼ 0.5–3%; Greatly increases > 60 years of age, and for individuals > 80 years reaching ∼ 15%
 Pathogen: SARS-CoV-2 - enveloped, nonsegmented, positive-sense, ssRNA virus
o L-type evolved from the S-type and is somewhat more contagious and aggressive.
o S-type was the original type transmitted to humans from the animal host and is less contagious and aggressive.
 Transmission: mainly person-to-person
 Incubation period: 2–14 days, usually ∼ 5 days
 Duration of infectiousness
o It is estimated that infected individuals:
 Become infectious 2.5 days before the onset of symptoms
 Cease to be infectious 8 days after the onset of symptoms.
o The period of greatest infectiousness is at the beginning of symptoms.
 Clinical features
o Often asymptomatic Children are more likely to be asymptomatic
o Trio of fever, cough, and dyspnea: only present in ∼ 15%
o Most common: Fever (often not initially!), Fatigue, Dry cough
o Common
 Shortness of breath; Loss of smell and/or taste; Loss of appetite
 Myalgia; Oral problems: xerostomia, ulcers, “COVID tongue”
 Clinical course
o Typically starts with mild symptoms that may progress to more severe after about 5–7 days.
o Mild (∼ 80%)
 Uncomplicated course without dyspnea
 Lasts 1–2 weeks
o Severe (∼ 15%)
 Develops ∼ 5–7 days after symptom onset
 Indicates the disease has progressed to pneumonia
 Signs include dyspnea and hypoxia
 Lasts 3–6 weeks
o Critical disease (∼ 5%)
 Signs of severe pneumonia (respiratory failure), acute respiratory distress syndrome (ARDS), coagulopathy,
shock, and possibly multiple organ dysfunction syndrome (MODS)
 Lasts 3–6 weeks
 Infection control and preventive measures
o Hand hygiene
o Respiratory hygiene and cough etiquette
o Avoid exposure, social distancing
o Masks
o Quarantine: separation of a person or group of people who were exposed to the virus but are not yet
symptomatic
o Isolation: separation of a person or group of people who are infected or reasonably believed to be infected
with SARS-CoV-2

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 o Discontinuation of isolation
 For patients with symptomatic COVID-19:
 10 days after the onset of symptoms AND
 No fever for at least 24 hours without antipyretics AND
 Respiratory symptoms have improved
 For patients with asymptomatic COVID-19: 10 days have passed without illness since the date of the positive
COVID-19 test
 Diagnostics
o Quantitative reverse transcription PCR (RT-qPCR)
o Antigen testing
o Serological studies: Rapid IgM-IgG antibody tests, ELISA
 Management
o Asymptomatic and mild: no effective antiviral treatment; management consists of supportive self-care at home
(home care) and isolation in accordance with health department regulations
o Severe and critical: O2, ICU;Recommended therapies may include remdesivir, dexamethasone, empiric
antibiotic therapy, and/or anticoagulation
 Vaccination
o Pfizer-BioNtech COVID-19 vaccine: mRNA, 2 doses administered 3 weeks apart
o Moderna COVID-19 vaccine: mRNA, 2 doses administered 1 month apart
o Janssen COVID-19 vaccine (Johnson & Johnson vaccine): Viral vector, Single dose
o AstraZeneca: Viral vector, 2 doses administered 4–12 weeks apart
o Sputnik V vaccine: Viral vector, 2 doses administered 21 days apart

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44. Legionnaire's Disease
 Frequency: occurs rarely in infants, almost solely in adults (of any age) and typically in outbreaks
 High-risk groups
o Elderly individuals; Individuals with chronic diseases (e.g., COPD, emphysema, diabetes, CKD)
o Immunocompromised individuals; Smokers
 Causative organism: Legionella pneumophila (gram-negative, obligate aerobic, facultative intracellular rod)
 Path of infection
o Inhalation of contaminated aerosols
 Cold and hot water systems (e.g., those found in hotels, hospitals, and retirement homes)
 Whirlpools/hot tubs, swimming pools, showers
 Air-conditioning systems with contaminated condensed water
o Person-to-person transmission is uncommon
 Incubation period: 2–10 days
 Clinical features
o Fever, chills, headache
o Severe pneumonia
 Unilateral lobar pneumonia
 Atypical pneumonia: dry cough which can become productive, shortness of breath, bilateral crackles
o Relative bradycardia (uncommon)
o Diarrhea
o Neurological features, especially confusion, agitation, and stupor
o Failure to respond to beta-lactam monotherapy
o Pontiac fever
 Incubation period: 1–3 days
 Mild, self-limiting course of legionellosis without pneumonia.
 Flu-like symptoms (e.g. fever, headache, and muscle ache)
o Lochgoilhead fever: similar to Pontiac fever, caused by Legionella micdadei
 Diagnostics
o Blood
 Hyponatremia (serum sodium < 130 mEq/L) and hypophosphatemia are common.
 Aminotransferases and creatinine may be elevated.
 Possible thrombocytopenia and leukocytosis
o Urine
 Legionella urinary antigen test: most important diagnostic tool; rapid test, but only detects serogroup 1
 Hematuria and proteinuria are common.
o Respiratory secretions
 Gram stain of respiratory secretions shows many neutrophils but, usually, no organisms.
 Visualization of Legionella requires silver stain.
 Legionella culture: slow; requires buffered (iron and cysteine) charcoal yeast extract agar (results after 3–5
days)
o PCR: high sensitivity, high specificity
o Serology: A four-fold rise in antibody titer confirms legionellosis. However, the antibody titers have low
specificity and sensitivity, and seroconversion can take up to 12 weeks. Therefore, more rapid tests, such as the
urinary antigen test or PCR, are more often used.
o Imaging
 Chest x-ray: Diffuse reticular opacities are commonly seen (especially in atypical pneumonia).
 Chest CT
 Bilateral or unilateral consolidative changes and/or ground-glass opacities
 Air bronchograms may also be seen

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 Treatment
o If legionellosis is verified:
 Drug of choice: fluoroquinolones (preferably levofloxacin - 500 mg i.v. als Kurzinfusion 1-0-1 über mindestens
60 Min.; Oralisierung im Therapieverlauf bei gutem Ansprechen möglich; alternatively moxifloxacin) for 7–10
days
 Initial parenteral treatment is recommended for all patients to avoid possibly poor gastrointestinal
absorption
 Second-line treatment: macrolides (e.g., erythromycin or azithromycin) for 3 weeks (IV at first, later orally)
o If patients are unresponsive to monotherapy, consider adding rifampin or tigecycline (laut RKI nicht mehr
empfohlen)
 Prevention
o avoiding water temperatures between 20 °C and 45 °C and conditions that favor the growth of legionella
bacteria and other microorganisms;
o avoiding water stagnation which may encourage the growth of biofilm;
o avoiding the use of materials that harbor bacteria and other microorganisms, or provide nutrients for microbial
growth.
o controlling the release of water spray;
o maintaining the cleanliness of the system and water in it;
o using water treatment techniques;
o taking action to ensure the correct and safe operation and maintenance of the water system.

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45. Scarlet fever and other Infections cause by Streptococci
Scarlet fever/ Scharlach
 Pathogen
o Group A β hemolytic streptococci (Streptococcus pyogenes) produce erythrogenic exotoxin A, B, or C
o Previous infection does not rule out additional episodes of the disease, as there are several different types of
scarlet fever toxin.
 Route of transmission: aerosol
 Peak incidence: 5–15 years (although it may affect individuals of any age)
o Generally occurs in association with streptococcal cases of tonsillopharyngitis
 Incubation period: 2–5 days
 Clinical features:
o Initial phase (acute tonsillitis)
 Fever; Malaise, headache, chills, and
myalgias
 Tonsillopharyngitis
 Sore throat and difficulty swallowing;
White coating on the tongue
(strawberry tongue)
 Enlarged cervical lymph nodes
 Gastrointestinal symptoms (possible in young children)
 Abdominal pain, Nausea and vomiting
o Exanthem phase - Scarlet‑colored maculopapular
exanthem (rash) appears 12–48 hours after onset of fever.
 Presentation
 Fine, erythematous, sandpaper like texture; Blanches with pressure
 Nonblanching petechiae are often additionally present; May be pruritic
 Pastia lines
o A key sign of scarlet fever: linear, petechial appearance
o Most pronounced in the groin, underarm, and elbow creases (i.e., flexural areas)
 Location: Begins on the neck, Disseminates to the trunk and extremities
 Duration: ∼ 7 days
o Tonsillopharyngitis
 Pharyngeal erythema, possibly with tonsillar exudates
 Raspberry tongue: bright red tongue color with papillary hyperplasia, which is revealed once the white
coating has sloughed off
 Typical red, flushed appearance of the cheeks with perioral pallor (Triangle Filatov)
o Desquamation phase
 Appears 7–10 days after resolution of rash
 Skin desquamation: desquamation of the skin in flakes
 Affects face, trunk, hands, fingers, and toes
 Diagnostics - primarily a clinical diagnosis that should be confirmed with additional testing.
o Pathogen detection: Throat culture, Rapid antigen detection testing (rapid strep test)
o Blood and urine studies
 Complete blood cell (CBC) count shows leukocytosis with a left shift and possibly eosinophilia over the course
of the disease.
 Urinalysis and liver function tests may indicate complications of scarlet fever
 ↑ Inflammatory markers: CRP, ESR
o Other tests
 During the course of disease: elevated antistreptolysin O (ASO) and anti deoxyribonuclease B (ADB) titers

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  Positive tourniquet test (Rumpel-Leede capillary fragility test
 Treatment
o Indication: All cases of scarlet fever should be treated with antibiotics, both to prevent complications and to
prevent transmission.
o Drug of choice: oral penicillin V
 3-14 years: 100.000 IE/kgKG p.o. verteilt auf 3 Einzeldosen/Tag über 7 Tage, Tagesmaximaldosis 2 Mio. IE/Tag
 >15 and adults: 0,8–1 Mio. IE p.o. 1-1-1 über 7 Tage, Tagesmaximaldosis 3 Mio. IE/Tag
o Alternative antibiotics
 In patients allergic to penicillin: macrolides
 In cases of recurrence due to antibiotic resistance: cephalosporins
o After 24 hours of antibiotic treatment, the patient is no longer infectious and may return to daycare or school
 anti-epidemic measures
o Isolation of patients at home or hospital for 10 days.
o if there are long-term complications of scarlet fever such as kidney disease, rheumatic heart disease and
arthritis is necessary observation (dispensary) for 3 months
o Contact persons Quarantine 7 days at a single contact - 10 days in constant contact.
o All contact with angina treated with penicillin 10 days.
 Complications
o Scarlet fever is considered one of the nonsuppurative (i.e., non-pus forming) complications of streptococcal
tonsillopharyngitis. Other complications of GAS infection may also occur during or following scarlet fever,
especially in patients who did not receive antibiotic treatment.
o Suppurative (i.e., pus-forming)
 Cervical lymphadenitis
 Retropharyngeal or peritonsillar abscess
 Otitis media, Sinusitis, Mastoiditis
o Nonsuppurative
 Poststreptococcal glomerulonephritis
 Acute rheumatic fever (rare)
 Sydenham chorea: nvoluntary, irregular, non-repetitive movements of the limbs, neck, head, and/or face
 Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS)
 rare disorder that is characterized by sudden onset or exacerbation of obsessive-compulsive disorder (OCD)
and/or a tic disorder following infection with S. pyogenes

Ludwig angina/ Angina Ludovici

 Mixed infection (Viridans streptococci and anaerobes)
 Usually arising from an infected mandibular molar, an infection of the
upper airways, or acute lingual tonsillitis
 Predisposing factors: diabetes mellitus, alcohol use disorder, and other
immunocompromising conditions
 Clinical features
o Submandibular space infection (Rapidly spreading bilateral cellulitis of
the sublingual and submandibular space without lymphadenopathy. An abscess may develop)
o Fever, mouth pain, stiff neck, difficulty swallowing, trismus
o Airway obstruction may occur!

Nonpurulent skin and soft tissue infections

 Erysipelas: superficial skin infection involving the upper dermis
 Cellulitis: local infection of the deep dermis and subcutaneous tissue

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 Clinical features
o Local signs: erythema, edema, warmth, tenderness
 Specific to erysipelas: raised, sharply demarcated lesion
 Specific to cellulitis: poorly defined lesion with induration
o Cutaneous lymphatic edema (historically referred to as “peau d'orange”)
o Common locations: lower limbs, face
o Possible additional features
 Lymphangitis: red streaks radiating from the skin lesion and following the direction of the lymphatic vessels
 Lymphadenitis: swollen, tender, regional lymph nodes
 Bullae, Purulent exudate
o Systemic symptoms (in moderate/severe infections): fever, chills, confusion, nausea, headache, muscle and
joint pain
 Pathophysiology
o Entry is commonly via a minor skin injury (E.g., rhagades, athlete's foot, ulcers, blisters, insect bites); erysipelas
can consequently spread via superficial lymphatic vessels.
o May also be secondary to a systemic infection
 Etiology
o Beta-hemolytic streptococci: mostly group A Streptococcus (S. pyogenes)
o Less common pathogens for cellulitis: S. aureus
 Diagnostics - usually clinical
o Laboratory studies
 CBC: possible leukocytosis
 BMP: signs of underlying conditions that are risk factors for infections (e.g., diabetes mellitus, chronic kidney
disease)
 Inflammatory markers (e.g., CRP, procalcitonin): may be elevated
o Soft tissue ultrasound: ypoechoic strands (signs of edema) between subcutaneous fat tissue
 Treatment
o Mild infection - Oral therapy with one of the following: Penicillin VK, Cephalexin, Dicloxacillin, Clindamycin
o Moderate infection - Intravenous therapy with one of the following: Penicillin, Ceftriaxone, Cefazolin,
Clindamycin
o Severe infection - Rule out necrotizing infections (consider surgical exploration and samples for cultures)
 Intravenous combination therapy: Vancomycin PLUS one of the following: Piperacillin/tazobactam;
Meropenem

Impetigo
 Age
o Primarily affects children (especially between 2–6 years of age)
o Impetigo is highly contagious and can cause epidemics in preschools or schools
 Prevalence: high in resource-limited countries
 Pathogens: superficial bacterial skin infection
o Staphylococcus aureus: ∼ 80% of cases
 Causes both bullous impetigo and nonbullous impetigo
 S. aureus strains that produce exfoliative toxins A and B are responsible for bullous impetigo. [3][4]
o Streptococcus pyogenes (GAS): ∼ 10% of cases: causes nonbullous impetigo only
o S. aureus and GAS coinfection: ∼ 10% of cases
 Predisposing factors
o Warm and humid climate; crowded, unsanitary living conditions; Poor personal hygiene
o Medical conditions: Atopic dermatitis and other skin conditions; Diabetes mellitus; Immunodeficiency (e.g.,
HIV, post-organ transplantation, systemic corticosteroids)

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  Route of infection
o Primary impetigo: bacterial infection of previously healthy skin
o Secondary impetigo (impetiginization): secondary infection of pre-existing skin lesions (e.g., scabies, insect
bites, abrasions, eczema)
 Clinical features
o Rare manifestation: ecthyma - Ulcerative impetigo that extends into the dermis; Manifests as a coin-sized,
superficial ulcer with a punched-out appearance
Nonbullous impetigo Bullous impetigo
Epidemiology ∼ 70% of cases ∼ 30% of cases
Lesions  Papules, which turn into small vesicles surrounded  Vesicles that grow to form large,
by erythema and/or pustules flaccid bullae, which go on to
o Vesicles and pustules can rupture rupture and form thin, brown crusts
o Oozing secretion that dries forms honey-colored  Positive Nikolsky sign (lateral
crusts that heal without scarring traction causes sloughing of the skin)
 May be pruritic (especially pustules) but is rarely
painful
 Negative Nikolsky sign
Distribution pattern  Face (most common), especially around the nose Trunk and upper extremities
and mouth
 Extremities
Other findings Regional lymphadenopathy Systemic signs (e.g., fever, malaise,
weakness) in severe cases
 Diagnostics
o Generally diagnosed based on clinical presentation
o Microbiological culture
 Assists with detection of the causative pathogen
 Indications: inconclusive diagnosis, recurrence despite treatment
 Treatment
o General: wound cleansing with antibacterial washes (e.g.,
chlorhexidine)
o Mild nonbullous impetigo (single lesions or small areas affected):
topical antibiotics (mupirocin, retapamulin)
o Bullous impetigo, ecthyma, or severe nonbullous impetigo
(widespread dispersion, numerous lesions, and/or fever)
 First-line treatment: first generation cephalosporins (e.g.,
cephalexin) or dicloxacillin
 Alternative: amoxicillin-clavulanate, macrolides
 If MRSA infection is confirmed or suspected: clindamycin,
trimethoprim-sulfamethoxazole, doxycycline

Erythema marginatum – in Rheumatic fever

 centrifugally expanding pink or light red rash with a well-defined outer border and central clearing.
 Painless and nonpruritic
 Location: The trunk and limbs are affected; the face is spared. May rapidly appear and disappear at different
locations

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46. Diphtheria/ Echter Krupp
 Pathogen: Corynebacterium diphtheriae
o A gram-positive, non-sporulating, club-shaped bacillus
o Contains metachromatic granules (volutin granules; stain red with a blue dye)
 Route of infection
o Droplet transmission
o Less commonly through direct or indirect contact with open lesions
 Infectious period: variable
o Without antibiotic therapy, the organism may be shed for 2–4 weeks. Certain chronic carriers may shed C.
diphtheriae for more than 6 months
o antibiotic therapy stops the shedding of C. diphtheriae within 48 hours
 Pathophysiology
o C. diphtheriae colonizes the mucous membrane of the respiratory tract (respiratory diphtheria) and, less
commonly, pre-existing skin lesions (cutaneous diphtheria)
o C. diphtheriae has both toxigenic and non-toxigenic strains; toxigenic strains contain a beta-prophage gene
(tox), which encodes for the exotoxin diphtheria toxin:
 General characteristics: a heat-labile protein with a molecular weight of 62,000 kDa made of A and B
fragments
 Mechanism of action: the A fragment enters cells and catalyzes the transfer of ADP-ribosylation of the
elongation factor-2 (EF-2) → inhibition of EF-2 → arrested protein translation and synthesis → cell death and
necrosis (lethal dose is 0.1 μg/kg)
 Local effects of the toxin: destruction of the respiratory epithelium with a subsequent inflammatory response
 Deposition of necrotic epithelium embedded within fibrinosuppurative inflammatory exudate
(pseudomembrane) over the pharynx, tonsils, and/or larynx
 Enlargement of the cervical lymph nodes and edema of the soft tissue of the neck → bull neck appearance,
airway obstruction
 Systemic effects of the toxin (result of the systemic absorption of the toxin, doesn’t enter bloodstream)
 Fatty changes and focal necrosis of the myocardium and less commonly, the liver,
kidney, and adrenal glands
 Nerve demyelination
 Respiratory diphtheria
o Incubation period: 2–5 days
o Prodromal symptoms: fever, malaise, and sore throat. 4–5 days after the onset of
prodromal symptoms, symptoms due to the local and systemic effects of the toxin
occur
o Local features
 Anterior nasal diphtheria: bloody rhinorrhea
 Tonsillar and pharyngeal diphtheria
 A grayish-white pseudomembrane over the posterior pharyngeal wall, and/or tonsils
 Any attempt to scrape off the pseudomembrane exposes the underlying capillaries
and results in heavy bleeding.
 Bull neck due to cervical lymphadenopathy and swelling of the soft tissue of the neck
→ airway obstruction (laryngeal edema and/or pseudomembranous covering over
the laryngeal folds)
 Foul mouth odor
 Laryngeal diphtheria: difficulty breathing, inspiratory stridor, croup barking cough
o Systemic features (due to dissemination of toxin)
 Cardiac: Myocarditis, Arrhythmias; Rarely, endocarditis
 Reversible polyneuropathy; Acute tubular necrosis; Adrenal insufficiency; Septic arthritis

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 Cutaneous diphtheria
o Cutaneous diphtheria is the result of direct inoculation of C. diphtheriae into the skin (e.g., skin abrasions) or
pre-existing skin lesions.
o Usually seen in tropical regions, where it is more common than respiratory diphtheria
o Patients present with scaly erythematous rash, impetigo, or deep, punched-out ulcers
o Cutaneous diphtheria does not result in systemic effects
 Diagnostics
o Cultures of pharyngeal swabs: used to confirm the diagnosis
 Microscopic examination of pharyngeal swabs or culture isolates reveals multiple C. diphtheriae clustered in
angular arrangements.
 Culture media of choice
 Cystine-tellurite agar: C. diphtheriae appear as black colonies.
 Loffler medium: shows metachromatic granules
o Other tests: used to identify whether the strain is toxigenic once the culture reveals C. diphtheriae
 Elek test
 An immunoprecipitation test in which C. diphtheriae are grown in an agar culture that is embedded with an
antitoxin-impregnated filter paper  Positive if the strain is toxicogenic
 Polymerase chain reaction: to identify the tox gene
o Test for myocarditis: Conduct multiple ECGs (QT prolongation, ST-T wave changes, and/or first-degree AV
block) and serial measurement of cardiac markers
 Treatment
o The patient should be isolated as soon as diphtheria is suspected.
o Antibiotic therapy: IM injections of penicillin G (≤10 kg: 300,000 IU/day; >10 kg: 600,000 IU/day) or oral/IV
erythromycin (40 mg/kg/day) for 14 days
o Immediate administration of diphtheria antitoxin: The antitoxin can only neutralize the unbound toxin and
should therefore be administered early in the course of the disease (hypersensitivity testing should be
performed before initiating therapy)
 Laryngeal/pharyngeal diphtheria lasting < 48 hours: 20,000–40,000 units IV over 60 minutes
 Nasopharyngeal diphtheria: 40,000–60,000 units IV over 60 minutes
 Bull neck or diphtheria lasting > 3 days: 80,000–120,000 units IV over 60 minutes
o Airway support
o discharge from the hospital after 2 negative results in 2 days, three days after treatment.
 Prevention
o Pre-exposure prophylaxis
 Toxoid vaccine
 There are four vaccines available in the US: DTaP, Tdap, DT, and Td
o Post-exposure prophylaxis
 Post-exposure prophylaxis is indicated for close personal contacts and caretakers of a patient with diphtheria.
 Erythromycin (500 mg 1-1-1-1 7–10 days) or a single dose of benzathine penicillin (< 6 years: 600,000 units
IM; ≥ 6 years: 1,200,000 units IM)
 Complete immunization schedule if vaccinations are not up-to-date
 Contact - Medical surveillance 7 days

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47. Measles/ Rubeola/ Masern
 Distribution: Measles typically occurs in regions with low vaccination rates and in resource-limited countries
 Peak incidence: < 12 months of age
 Infectivity: ∼ 90%; Highly contagious 4 days before and up to 4 days after the onset of exanthem
 Pathogen: measles virus (MV), an RNA virus of the Morbillivirus genus belonging to the Paramyxoviridae family
 Route of transmission: direct contact with or inhalation of virus-containing droplets
 Incubation period: ~2 weeks after infection
 Clinical features
o Prodromal stage (catarrhal stage):
Duration: ∼ 4–7 days
 Coryza, cough, and conjunctivitis
 Fever
 Koplik spots
 Pathognomonic enanthem of the buccal mucosa
 Tiny white or bluish-gray spots on an irregular
erythematous background that resemble grains of sand
o Exanthem stage: Duration: ∼ 7 days (develops 1–2 days after
enanthem)
 High fever, malaise
 Generalized lymphadenopathy
 Erythematous maculopapular, blanching,
partially confluent exanthem
 Begins behind the ears along the hairline
 Disseminates to the rest of the body towards the feet (palm and sole involvement is rare)
 Fades after ∼ 5 days of onset, leaving a brown discoloration and desquamation in severely affected areas
o cough may persist for another week and may be the last remaining symptom
 Diagnostics
o CBC: ↓ leukocytes, ↓ platelets
o Serology
 Gold standard: detection of Measles-specific IgM antibodies
 IgG antibodies
o Identification of pathogen: direct virus detection via reverse-transcriptase polymerase chain reaction (RT-PCR)
possible
o Biopsy: affected lymph nodes show paracortical hyperplasia and Warthin-Finkeldey cells (multinucleated giant
cells formed by lymphocytic fusion).
 Treatment
o Symptomatic treatment
o Vitamin A supplementation reduces morbidity and mortality (especially in malnurished children)
 Subacute sclerosing panencephalitis (SSPE)
o Definition: a lethal, generalized, demyelinating inflammation of the brain caused by persistent measles virus
infection
o Epidemiology
 Primarily affects males between 8 and 11 years of age
 Usually develops ≥ 7 years after measles infection
o Clinical presentation: characterized by four clinical stages
 Stage I: dementia, personality changes
 Stage II: epilepsy, myoclonus, autonomic dysfunction
 Stage III: decerebration, spasticity, extrapyramidal symptoms
 Stage IV: vegetative state, autonomic failure

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 o Diagnosis
 Electroencephalography
 Paroxysmal delta waves (very slow, 1–3/sec)
 Periodic sharp and slow wave complexes
 Cerebrospinal fluid: ↑ anti-measles IgG
o Prognosis: SSPE leads to death within 1–3 years of diagnosis)
 Prevention
o Primary immunization: Every infant, Adults born after 1957 with unknown immunization or incomplete status
 Live vaccination with attenuated virus in combination with mumps and rubella (MMR) vaccine and possibly
varicella (MMRV) vaccine: First dose between 12 and 15 months; second dose between 4 and 6 years or at
least 28 days after the first dose
o Postexposure prophylaxis (PEP): negative or indeterminate serology
 Active immunizationfor immunocompetent individuals after direct exposure
 Passive immunization for chronically ill and immunocompromised individuals
o Control measure
 Isolation for 5 days after onset of rash.
 Immunization of contacts within `3 days of exposure. If vaccine is contraindicated, immunoglobulin should be
given within 3- 4 days of exposure.
 contact children under 7 years of age non-immunized and have not received gamma globulin -observed for
21 days
 not carried out disinfection only aerationand wet cleaning

Number Other names for the disease Etiology(ies)

First disease Rubeola, Measles, Hard measles, 14-day measles, Morbilli Measles virus
Second disease Scarlet Fever, Scarlatina Streptococcus pyogenes
Third disease Rubella, German measles, 3-day measles Rubella virus
Some say the disease does not exist. Others believe it
Filatow-Dukes' Disease, Staphylococcal Scalded Skin Syndrome,
Fourth disease is due to Staphylococcus aureus strains that make
Ritter's disease
epidermolytic (exfoliative) toxin
Fifth disease Erythema infectiosum Erythrovirus (Parvovirus) B19
Exanthem subitum, Roseola infantum, "Sudden Rash", rose rash
Sixth disease Human Herpes Virus 6B or Human Herpes Virus 7
of infants, 3-day fever

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48. Rubella (German measles). Exanthema subitum, Erythema infectiosum
Rubella (German measles)/ Röteln
 Pathogen: Rubella virus, an RNA virus of the family Togaviridae; Humans are the only hosts.
 Route of transmission: Airborne droplets or transplacental
 Infectivity: 7 days prior to and 7 days following the appearance of an exanthem; Low infectivity and virulence
 Clinical features: asymptomatic in ∼ 50% of cases; Young children have a far milder course than older children
and adults
o Prodromal phase
 Incubation period: 2–3 weeks after infection
 Duration: 1–5 days
 Findings
 Post-auricular and suboccipital lymphadenopathy and occasionally splenomegaly
 Mild and nonspecific symptoms such as low-grade fever, mild sore throat, conjunctivitis, headache, and
aching joints
 Forchheimer sign: enanthem of the soft palate
o Exanthem phase
 Duration: lasts 2–3 days
 Findings
 Fine, nonconfluent, pink
maculopapular rash: size between
measles (large) and scarlet fever (small).
 Begins at the head, primarily behind the ears, extends
to the trunk and extremities, sparing palms and soles
 Rash may be itchy in adults; Polyarthritis: 70% of
teenagers and adult females present with
polyarthritis
 Diagnostics: clinical diagnosis, laboratory confirmation is
necessary for certain patient groups to assess the risk of complications
o CBC: leukocytopenia with relative lymphocytosis and increased plasma cells
o Confirmatory test: serology; Detection of IgM antibodies; ≥ 4-fold increase in IgG titer
 Treatment: symptomatic
o Severe pruritis: antihistamines
o Severe polyarthritis: rest and nonsteroidal anti-inflammatory drugs
 Complications
o Thrombocytopenic purpura
o Rubella during pregnancy (TORCH infection): congenital rubella syndrome
 Classic triad of defects is sensorineural hearing loss, cataracts, and cardiac defects
o Rare: rubella encephalitis, bronchitis, otitis, myocarditis, pericarditis
 Prevention
o Immunization: Live attenuated virus that is administered in combination with the measles and mumps vaccine
 First dose: 12–15 months of age
 Second dose: 4–6 years of age or at least 28 days following the first dose.
o Patients with rubella infection should be isolated for 7 days after the onset of the rash
o Precautions regarding droplet transmission should be taken.
 Control measures
o Rubella is a notifiable disease  Cases should be reported within 24 hours
o Isolation for 5 days after onset of rash.
o contact persons are monitored 21 days; contact pregnant in the first three months of pregnancy are tested
serological.

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Exanthema subitum/ Roseola infantum/ Sixth Disease/ Dreitagefieber
 Peak incidence: 6 months to 2 years
 Pathogen: HHV-6 (and in rare cases HHV-7); Humans are the sole hosts.
 Route of transmission: droplet infection (e.g., saliva)
 Incubation period: 5–15 days
 Clinical features
o Febrile phase: Duration 3–5 days
 Fever
 Abrupt onset of high fever, in some cases > 40ºC
 Febrile seizures are a potential complication of roseola (see “Complications” below).
 Cervical, postauricular, and/or occipital lymphadenopathy
 Inflamed tympanic membranes
 Nagayama spots: papular enanthem on the uvula and soft palate
 Other possible symptoms:
 Mild upper and lower respiratory symptoms
(pharyngitis, cough, etc.)
 Vomiting and/or diarrhea
 Conjunctivitis and edema of the eyelid
o Exanthem phase: Duration 1–3 days
 Characteristic presentation: subsequent sudden
decrease in temperature and development of a
patchy, maculopapular exanthem
 Rose-pink in color; blanches upon pressure
 Nonpruritic (in contrast to the drug allergy rash)
 Originates on the trunk; sometimes spreads to
the face and extremities
 Diagnostics: clinical diagnosis
o Laboratory tests are rarely necessary, may be useful in immunocompromised patients or those with atypical
presentations
 Antibody testing: HHV-6 IgM detection is possible.
 Viral DNA testing: pathogen DNA detection via PCR (possible detection using blood, urine, cerebrospinal fluid,
or saliva samples)
 Symptomatic treatment (e.g., fluids and possibly acetaminophen to reduce fever)
 Complications
o Febrile seizures (in up to 15% of cases), usually without sequelae
o Meningoencephalitis (very rare)
 Prognosis
o Very good prognosis; self-limiting disease
o The virus persists lifelong in its host, and reactivation of latent virus or reinfection may occur later in life
(especially if individuals become immunocompromised)

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Erythema infectiosum/ Fifth Disease/ Ringelröteln
 Peak incidence: 5–15 years
 Pathogen: Human parvovirus B19 (the smallest of the DNA viruses)
o Single‑stranded DNA virus (linear), Nonenveloped
o Humans are the only reservoir for parvovirus B19
 Route of transmission: aerosol, rarely: Hematogenous, Transplacental; Only contagious before onset of rash
 Pathophysiology
o Parvovirus B19 binds to the P antigen (globoside) on erythroid progenitor cells → cellular invasion → viral DNA
enters the nucleus of erythroid cells → viral DNA replication → cytotoxicity → clinical manifestations +
transient cessation of erythropoiesis
o Parvovirus B19 can also bind to and infect endothelial cells via the P antigen, potentially causing cardiovascular
complications.
 Incubation period: 4–14 days
 Clinical features
o Mild cold like symptoms
o Exanthem (25% of cases): 2–5 days
following the onset of cold like symptoms
 Initial diffuse redness of the face with perioral sparing
(slapped cheek rash)
 Spread of exanthem to the extremities and trunk
 Initially confluent and maculopapular; adopts a lace
like, reticular appearance over time as it clears.
 Associated with mild pruritus (in ∼ 50% of cases)
 Fades after ∼ 7–10 days; can be recurrent over
several weeks (becoming more pronounced after
exposure to sunlight or heat)
 Third phase with rash that varies with
exposure to sun or heat and resolves spontaneously after several weeks.
o Parvovirus B19-associated arthritis: affects < 10% of children and up to 60% of adults (♀ > ♂)
 Arthralgia with symmetrical, nondestructive polyarthritis, particularly in the joints of the fingers, hand, knee,
and ankle; Usually resolves after 3–4 weeks
 In some cases, persistent arthritis may develop
 Diagnostics
o immunocompetent children: clinical diagnosis (i.e., slapped-cheek or lace-like appearance of rash)
o Immunocompetent adults: Lab tests only if the diagnosis is unclear
 IgM antibody: Appears within ∼ 10 days of initial exposure, indicating acute illness; Remains positive for 2–3
months
 IgG antibody: Appears approx. 2 weeks following infection; Remains positive for life
o Patients with transient aplastic crisis and immunocompromised patients
 CBC with reticulocytes: ↓ Reticulocytes (0–1%)
 ↓ Hemoglobin below patient's baseline by ≥ 2 g/dL (aplastic crisis) or (< 8 g/dL) (severe anemia as in pure
red cell aplasia)
 Initial diagnostic test: viral DNA testing (PCR of blood or bone marrow)
 Adjunctive diagnostic test: serologic antibody testing (in immunocompetent adults)
 Treatment
o Treatment is not necessary in most cases, as the disease is often self-limited
o Analgesics and nonsteroidal anti‑inflammatory drugs (NSAIDs)
o Short course of low‑dose prednisone for parvovirus B19‑associated arthritis

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 Complications
o Transient aplastic crisis in patients with chronic hemolytic diseases (e.g., sickle cell disease, hereditary
spherocytosis, thalassemia, pyruvate kinase deficiency, autoimmune hemolytic anemia)
 Pathophysiology: parvovirus B19 infection of stem cells
 Treatment: blood transfusions if anemia is symptomatic
o Chronic pure red cell aplasia in immunocompromised patients
 Pathophysiology: parvovirus B19 infection of proerythroblasts
 Treatment: blood transfusions for severe anemia; intravenous immunoglobulin (IVIG) against parvovirus B19
o Hydrops fetalis, fetal death, and miscarriage (parvovirus B19 is a TORCH infection)
 Most often asymptomatic but some infections result in aplastic anemia and fetal hydrops. Less common
features include hepatosplenomegaly, blueberry muffin rash, as well radiolucent metaphyseal lesions.
Intrauterine demise occurs in ~ 10% of cases, most often during the 1st or 2nd trimester.
o Hepatitis, myocarditis, and aseptic meningitis/encephalitis (rare)

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49. Chicken pox/ Windpocken
 Pathogen: varicella-zoster virus (VZV), a human herpesvirus type 3 (HHV-3)
 Transmission: Airborne droplets; Direct skin contact with VZV-infected vesicle fluid; Transplacental
 Infectivity
o Highly contagious
o 2 days before and up to 5 days after the onset of exanthem (or until all the pustules have formed crusts)
 Latency: can become latent after primary infection and reside inside Dorsal root ganglia, Trigeminal ganglia
 Incubation period: 2 weeks (10–21 days)
 Clinical features
o Prodromes
 1–2 days prior to the onset of exanthem
 Presents with constitutional symptoms
(e.g., fever, malaise)
 More common with primary infection in
adults (less typical in children, in which rash
is often the first sign of infection)
o Exanthem phase (Duration: ∼ 6 days)
 Widespread rash starting on the trunk, spreading to the
face, scalp, and extremities
 Simultaneous occurrence of various stages of rash
(pseudopolymorphism): erythematous macules →
papules → vesicles filled with a clear fluid on an
erythematous base → eruption of vesicles → crusted
papules → hypopigmentation of healed lesions
 Severe pruritus; Fever, headache, and muscle or joint pain
 Diagnostics
o Clinical diagnosis is made on the basis of the characteristic rash, although further tests may be necessary in
atypical or complicated cases (e.g., older or immunosuppressed patients and pregnant women).
o Best initial test: Tzanck smear
 Smear of vesicle fluid shows multinucleated giant epithelial cells with eosinophilic intranuclear Cowdry A
inclusion bodies.
 Not specific for VZV (also seen in HSV infections).
o Best confirmatory test: PCR
 Material: vesicle fluid
 Amniotic fluid, chorionic villi, or fetal blood may be used in suspected fetal infection.
 CSF for encephalitis
o Other tests
 Viral culture
 Serology: IgG detection with enzyme-linked immunosorbent assay (ELISA) (to determine exposure and
immunity)
 Treatment
o Pruritus: topical applications (e.g., calamine lotion or pramoxine gel) and, in more severe cases, oral
antihistamines (e.g., cetirizine)
o Antiviral therapy
 Indication
 Immunosuppressed individuals; Primary infection in adults and in unvaccinated adolescents ≥ 13 years
 Individuals on long-term salicylate therapy (e.g., aspirin)
 Administration: within 24 hours of onset of rash

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  Drug of choice: acyclovir (10–15 mg/kgKG i.v. 1-1-1, Tagesmaximaldosis 2,5 g, 7–10 Tage) (or also:
valacyclovir, famciclovir)
 Complications
o Skin
 Bacterial superinfection (including impetigo, phlegmon, necrotizing fascitis), which often leads to scarring and
is managed with antibiotics e.g. Cefuroxim 20–30 mg/kgKG p.o. verteilt auf 2 Einzeldosen pro Tag, 5–10 Tage)
 Reactivation of latent VZV results in shingles (herpes zoster); Scarring
o Central nervous system
 Acute cerebellar ataxia (∼ 0.1% of cases): good prognosis, mainly self-limiting after several weeks
 Encephalitis (very rare): cramps, coma, poor prognosis
o Lungs: Pneumonia (viral or bacterial) - Rare in children, more frequent in adults; most common complication in
pregnant women
o Fetus (chickenpox during pregnancy): Congenital varicella syndrome
o Severe forms:
 Varicella haemorrhagica
 Varicella necrotica
 Fulminant and hyperoxic varicella
 Varicella bullosa
 Prognosis
o In healthy children, chickenpox infection generally has a benign course and heals without any consequences.
o Residual scarring may occur because of excessive scratching or bacterial superinfection.
o Immunosuppressed individuals are at a greater risk of the disease taking a generalized or even fatal course.
 Prevention
o Chickenpox immunization
 Vaccine: live, attenuated vaccine
 Primary immunization
 two doses of the vaccine: first dose at 12–15 months of age; second dose at 4–6 years of age (may be given
earlier, but must be at least three months after the first dose); A combined measles, mumps, rubella,
varicella (MMRV) vaccine is available.
 Catch-up vaccination: two doses of varicella vaccine recommended for all children without evidence of
immunity between the ages of 7–18
o Postexposure prophylaxis of chickenpox
 Active immunization (live, attenuated vaccine): within 5 days following exposure
 Indications: > 12 months of age, asymptomatic, non-immune and immunocompetent patient following
exposure
 Passive immunization (varicella-zoster immune globulin): within 10 days following exposure (ideally 4 days)
 Indications:
o Pregnant women with no evidence of immunity; Immunosuppressed individuals with no evidence of
immunity
o Newborn infants, if the mother was infected 5 days before or up to 2 days after birth; Premature babies
 Anti-epidemic measures
o Isolating the patient at home, or if he is hospitalized, he stops visiting nursery, garden, school, work until all
rashes are covered with crusts (an average of 10 days from the onset of the disease)

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Shingles/ Herpes zoster/ Gürtelrose
 dermatomal rash with painful blistering that is caused by the reactivation of the varicella-zoster virus (VZV)
 Prevalence: increasing among adults, especially >60
 Sex: ♀ > ♂
 Etiology
o Causative pathogen: Varicella-zoster virus (VZV)
o Transmission: via respiratory droplets and direct contact with VZV-infected vesicular fluid, causing chickenpox
in those infected
o Risk factors for VZV reactivation: Reactivation typically occurs in immunocompromized individuals.
 Decline in immune function with advancing age
 Malignancy, HIV infection, Immunosuppressive therapy, Malnutrition, Chronic stress
 Pathophysiology
o Primary infection (chickenpox): respiratory transmission → VZV inoculates the lymphoid tissue of the
nasopharynx and, subsequently, regional lymphoid tissue → viremia and chickenpox → recovery from
chickenpox, but virus remains dormant in dorsal root ganglia (unless reactivated → recurrent infection)
o Reactivation (shingles): VZV reactivated, often many years after the primary infection (e.g., especially in
immunocompromised individuals) → virus replicates in the dorsal root ganglia → travels through peripheral
sensory nerves to the skin → shingles (less contagious than primary infection)
 Clinical features
o Main symptoms: dermatomal distribution, typically affecting 1–3 dermatomes on one side of the body (most
commonly affects the cervical, trigeminal, thoracic, and lumbar dermatomes)
 Pain
 The most frequent symptom and may precede the rash
 Usually described as “burning”, “throbbing”, or “stabbing”
 Allodynia (sensation of pain triggered by a stimulus that is not ordinarily considered painful) may occur.
 Erythematous maculopapular rash that quickly evolves into vesicular lesions
 Vesicles are initially clear.
 Pustulation and rupture typically occur after 3 or 4 days.
 Crusting and involution typically occurs between day 7 and 10.
 Lesions may become necrotic, generalized, or may not be present at all
o Additional symptoms
 Fever, headache, and fatigue; Paresthesia; Itching; Motor deficits (rare)
 Children: usually milder course and lower risk of complications
o Disseminated herpes zoster: > 20 extradermatomal lesions, involvement of ≥ 3 dermatomes, and/or visceral
organ involvement  Pneumonia, Hepatitis, Meningoencephalitis, Acute retinal necrosis
o Herpes zoster ophthalmicus: reactivation of VZV in the ophthalmic division of the trigeminal nerve
o Herpes zoster oticus: reactivation of VZV in the geniculate ganglion, affecting the seventh (facial) and eighth
(vestibulocochlear) cranial nerves (also known as
Ramsay Hunt syndrome)
 Diagnostics - Clinical presentation is usually
sufficient for a diagnosis
o PCR of VZV DNA
o Serologic assay of VZV (IgM and IgG): can
be used to identify active or passive
immunity and diagnose primary VZV
infection

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 Treatment
o Antiviral therapy
 For immunocompetent patients, choose one of the following: Acyclovir, Valacyclovir, Famciclovir
 Immunocompromised patients and/or those with disseminated zoster: IV acyclovir
o Supportive care
 Anti-inflammatory and analgesic therapy
 Consider an adjuvant corticosteroid taper in patients with CNS complications (e.g., Bell palsy or vasculopathy)
and/or severe pain
 Complications
o Postherpetic neuralgia: chronic neuropathic pain persisting for at least three months in the area previously
affected by the rash
 Risk factors: Age > 50 years, Severe infection, Ocular involvement, Immunosuppression
 Clinical features
 Pain (including allodynia, paresthesias, dysesthesias) in the same dermatome as the rash
 Duration of symptoms > 3 months but can persist for years
 Treatment
 One of the following tricyclic antidepressants: Amitriptyline, Nortriptyline
 One of the following anticonvulsants: Pregabalin, Gabapentin
 Topical treatments: Topical capsaicin patch or capsaicin cream, Lidocaine patch
 2nd line: Opioids: Morphine, Oxycodone, Tramadol
o Herpes zoster encephalitis
 Risk factors: Immunosuppression, More than one prior episode of herpes zoster infection, Herpes zoster with
cranial nerve involvement, Disseminated herpes zoster infection
 Clinical features
 Usually manifests as acute or subacute delirium within days of vesicular eruption
 Focal neurologic deficits
 Possible additional features: Headache, fever, meningismus; Ataxia; Seizures
 Diagnostics
 CSF analysis: Mononuclear pleocytosis, PCR positive for VZV DNA
 MRI brain may show: Plaque-like lesions in white matter; Signs of demyelination; Late findings: hemorrhagic
infarcts or ischemia
 Treatment
 Acyclovir
 Corticosteroids (e.g., prednisolone)

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50. Infectious mononucleosis. Infectious lymphocytosis
Infectious mononucleosis/ Kissing disease/ Pfeiffer-Drüsenfieber
 General: Approx. 90–95% of adults are EBV-seropositive worldwide
 Peak incidence (of symptomatic disease): 15–24 years of age
 Pathogen: Epstein-Barr virus (EBV), also called human herpesvirus 4 (HHV-4)
 Transmission: Infectious mononucleosis is highly contagious and spreads via bodily secretions, especially saliva
o EBV infects B lymphocytes in mucosal epithelium (e.g., oropharynx, cervix) via the CD21 receptor → infected B
lymphocytes induce a humoral (B-cell) as well as a cellular (T-cell) immune response → an increased
concentration of atypical lymphocytes in the bloodstream, which are CD8+ cytotoxic T cells that fight infected B
lymphocytes
 Incubation period: ∼ 6 weeks
 Clinical features
o Clinical course
 Symptoms typically occur in adolescents and young adults and last for 2–4 weeks.
 Young children are often asymptomatic.
o Symptoms
 Splenomegaly, fever, fatigue, malaise (potentially life-threatening splenic rupture)
 Pharyngitis and/or tonsillitis (reddened, enlarged tonsils covered in pus), palatal
petechiae
 Bilateral cervical lymphadenopathy (especially posterior) that may become
generalized and can, in severe cases, lead to airway obstruction
 Abdominal pain; Possibly hepatomegaly and jaundice
 Maculopapular rash (similar to measles): The rash is caused by the infection itself in about 5% of cases but is
most commonly associated with the administration of aminopenicillin (e.g., ampicillin, amoxicillin)
 Diagnostic: Clinical suspicion of IM is confirmed via antibody testing
o Monospot test
 Detects heterophile antibodies produced in response to EBV infection using RBCs from sheep or horses
 Positive test: cross-reaction between heterophile antibodies and sheep/horse RBCs → agglutination
 Negative test: no heterophile antibodies present → no cross-reaction → no agglutination
 Specificity of ∼ 100%, sensitivity of 85%
o Laboratory analysis: elevated LDH and liver transaminases
o Peripheral smear: lymphocytosis with > 10% atypical lymphocytes (in some cases, up to 90%)
o Serology: indicated if IM is suspected but monospot testing is negative
 Anti-viral capsid antigen antibodies (anti-VCA)
 Anti-VCA IgM: appears early and vanishes ∼ 3 months after infection
 Anti-VCA IgG: appears after 2–4 weeks and persists for life
 Anti-EBV nuclear antigen-antibody (anti-EBNA-1) IgG
 Treatment
o Avoid physical activity that may trigger splenic rupture (e.g., contact sports) for at least 3 weeks after the onset
of symptoms.
o Fluids (IV administration if necessary)
o Analgesics/antipyretics (e.g., acetaminophen): Avoid aspirin, as viral infections like IM in combination with
aspirin use can cause Reye syndrome in children.
o Steroids are not recommended for routine use but may be considered in complicated cases.

Infectious lymphocytosis of childhood is a disease of uncertain cause that is characterized by fever,

lymphadenopathy, occasionally diarrhea, and a lymphocytosis (40-100 × 109/liter) that consists almost exclusively
of small mature lymphocytes. The disease is most common in the pediatric age group, may occur in epidemics, and
is not associated with EBV infection. Incubation period: 14-21 days; fecal-oral or airborne transmission

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51. Pertussis (Whooping cough) and parapertussis
 Typically a childhood disease (particularly children aged < 1 year); however, older patients are increasingly
affected (gradual age-related loss of immunity and failure to obtain booster doses)
 Pathogen: Bordetella pertussis is a gram negative, obligate aerobic coccobacillus.
 Transmission: airborne droplet (through coughing); direct contact with oral or nasal secretions
 Infectivity - Highly virulent
o Without antibiotic treatment: 4–6 weeks; With treatment: ∼ 5 days;
 Incubation period: on average 7–10 days (range 4–21 days)
 Pathophysiology
o Proliferation of Bordetella pertussis on ciliated epithelial cells of the respiratory mucosa → production of
virulence factors (e.g., tracheal cytotoxin) → paralysis of respiratory epithelium cilia and inflammation →
secretion of inflammatory exudate into respiratory tract → compromise of small airways → cough, pneumonia,
cyanosis
o Bordetella pertussis produces pertussis toxin → ADP-ribosylation of the α subunit of Gi protein → inhibition of
Gi protein → adenylate cyclase disinhibition → cAMP accumulation → impaired cell signaling pathways [5]
o Pertussis toxin is responsible for most of the systemic manifestations associated with whooping cough (e.g.
hypoglycemia, lymphocytosis, modulation of host immune response).
o Neither vaccination nor actual infection confers complete or lifelong immunity.
 Stages
o Catarrhal stage (1–2 weeks)
 Nonspecific symptoms similar to an upper respiratory infection (mild cough, watery nasal discharge, rarely
low-grade fever)
 Possibly conjunctivitis
o Paroxysmal stage (2–6 weeks)
 Intense paroxysmal coughing (often occurring at night)
 Followed by a deep and loud inhalation or high-pitched whooping sound
 Accompanied by tongue protrusion, gagging, and struggling for breath
 Possibly accompanied by cyanosis
 Increases in frequency and severity throughout the stage
 Followed by the expulsion of phlegm or posttussive vomiting (risk of dehydration)
 Potential bleeding of the conjunctiva, petechiae, and venous congestion
 Infants (< 6 months) may only develop apnea and not the characteristic cough.
o Convalescent stage (weeks to months)
 Progressive reduction of symptoms
 Coughing attacks may persist over several weeks before resolving
 Diagnostics
o presumptive diagnosis of pertussis may be made based on clinical history and findings
o Blood count: lymphocyte-predominant leukocytosis (50,000–60,000/μL) that corresponds with disease severity
o Pathogen detection (to confirm the diagnosis)
 Culture (gold standard) or PCR: samples from deep nasopharyngeal aspiration or posterior nasopharyngeal
swab; obtained within the first two weeks (catarrhal stage)
 Serology: unsuitable for early diagnosis because antibody detection (IgA, IgG, IgM) first occurs after a period
of 2–4 weeks
 Treatment
o Early initiation of treatment, especially in high-risk patients (e.g., infants), while confirmatory laboratory tests
are pending
o Hospitalization and monitoring: infants < 4 months; severe cases (e.g., respiratory distress, cyanosis, apnea,
inability to feed)
o Oxygen administration with humidification

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 o Increased fluid intake and nutritional support
o If necessary, sedation
o Medical therapy
 Macrolides (e.g., azithromycin (500 mg p.o. Tag 1, 250 mg p.o. Tag 2–5, Dauer 5 Tage), clarithromycin (15
mg/kgKG p.o. verteilt auf 2 Einzeldosen pro Tag, Tagesmaximaldosis 1 g, Dauer 7 Tage), erythromycin)
 In children > 1 month and adults: any macrolide; If macrolides are not tolerated, use trimethroprim-
sulfamethoxazole.
 Infants < 1 month: azithromycin (10 mg/kgKG p.o. in einer Einzeldosis pro Tag, Dauer 5 Tage)
 Early administration may lessen symptoms of the catarrhal stage and early paroxysmal stage.
 Late antibiotic administration has little influence on disease severity but reduces infectivity.
 Prognosis
o In children > 3 months: very good; lengthy convalescence, but full recovery
o In children < 3 months: mortality 1–3%, particularly due to apnea
o Increased risk for complications
 Premature infants
 Children < 6 months
 People with underlying cardiac, pulmonary, neurologic, or neuromuscular disease
 Complications
o Infections: otitis media, pneumonia
o Pulmonary: atelectasis, pneumothorax (Severe bouts of coughing → increased intra-alveolar pressure → air
leaks into tissue layers → subcutaneous emphysema. Emphysema, in turn, can lead to pneumothorax.)
o Neurologic: seizures, encephalopathy with possible permanent damage (caused by hypoxia and apnea
secondary to coughing fits. Other possible etiologies include hypoglycemia and intracranial hemorrhages)
 Prevention
o Immunization
 Children: Routine immunization: DTaP vaccine (diphtheria, tetanus, and pertussis) at 2, 4, 6, and 15–18
months and at 4–6 years
 Booster vaccination: Tdap vaccine
o Single dose at 7–10 years of age if immunization is incomplete
o Single-dose boost at 11–18 years of age, at least 10 years following the last dose
 Adults: One-time dose of Tdap; In particular, pregnant women (27–36 weeks) and people in contact with
newborns should be vaccinated
o Post-exposure prophylaxis
 Choice of antibiotics identical to treatment recommendations
 Administered to household and close contacts of infected people (especially people at risk of developing
complications or close contacts of high-risk individuals)
 Administered regardless of immunization status
 Isolation
 Required for 5 days after initiation of antibiotic therapy
 Without antibiotic treatment: minimum of 3 weeks after the onset of first symptoms
 Control measures
o patient - quarantine clinically rehabilitation – 14 days but not more than 30 days or 20 days from the start of
the convulsive coughs
o Patients parapertussis be quarantined for 14 days
o Contact children up to 7 years: Not ever suffered and unvaccinated. – Medical surveillance 21 days
o Vaccinated children of contact- observed for 7 days

Parapertussis
 Pathogen: Bordetella parapertussis, In 5–20 % of cases of whooping cough, leads to a milder variant

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52. Mumps
 Pathogen: Mumps virus from the Paramyxoviridae family
 Transmission
o Humans are the sole host and the virus is transmitted via airborne droplets.
o Direct contact with contaminated saliva or respiratory secretions
o Contaminated fomites
 Infectivity
o Highly infectious
o Affected individuals are contagious ∼ 7 days before and up to 9 days after disease onset (when the parotid
gland becomes swollen).
 Nasopharyngeal entry → replication of the virus in the mucous membranes and lymph nodes → viremia and
secondary infection of the salivary glands (particularly the parotid gland) → further dissemination possible
(lacrimal, thyroid, and mammary glands, pancreas, testes, ovaries, CNS)
 Incubation period: 16–18 days
 Clinical features
o Prodrome: Duration: 3–4 days; Symptoms: low-grade fever, malaise, headache
o Classic course: inflammation of the salivary glands, particularly parotitis/ Sialadenitis
 Duration of parotitis: at least 2 days (may persist > 10 days)
 Symptoms
 May initially present with local tenderness, pain, and earache
 Unilateral swelling of the salivary gland (lateral cheek and jaw area); During
the course of disease, both salivary glands are usually swollen.
 Redness in the area of the parotid duct; Possible protruding ears
 Chronic courses are rare.
o Subclinical presentation
 Nonspecific or predominantly respiratory symptoms
 Asymptomatic (in 15–20% of cases)
 Diagnostics
o Pathogen detection
 Real-time reverse transcriptase PCR (rRT-PCR) on serum or buccal or oral swab
 Viral culture (e.g., on CSF, urine, or saliva)
o Serology: Positive serum IgM suggests recent infection and confirms the diagnosis.
o Relative lymphocytosis; ↑ CRP, ↑ ESR; ↑ Amylase
 Treatment: usually self-limited with a good prognosis
o Medication for pain and fever (e.g., acetaminophen)
o Bedrest, Adequate fluid intake
o Avoidance of acidic foods and drinks, Ice packs to soothe parotitis
 Primary immunization: a live attenuated vaccine in combination with measles and rubella vaccine (i.e., MMR)
and, if necessary, varicella (MMRV) - first dose at 12–15 months, second dose at 4–6 years
 Complications
o Orchitis – inflammation of testis
 most common complication of mumps in postpubertal male individuals - Swollen and tender affected
testicle(s); primarily unilateral  may lead to atrophy and, in rare cases, hypofertility
o Aseptic meningitis (1–10% of cases): predominantly mild course and usually no permanent sequelae
o Encephalitis (< 1% of cases): Reduced consciousness, seizures; Neurological deficits: cranial nerve palsy,
hemiplegia, sensorineural hearing loss (rare)
o Acute pancreatitis (< 1% of cases)
 Control measures - reportable disease
o Isolation of infected patients up to 9 days after onset of symptoms; contact persons are Monitoring 21 days

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53. Epidemic meningitis and other forms of meningococcal infection
 Neisseria meningitidis (meningococcus)
o G-, Diplococcus, Facultative intracellular, Aerobe
o Several serotypes have been indentified: groups A.B,C,D,X,Y,W135. B are capable of causing major epidemics
o Reservoir
 Nasopharynx: bacteria attach to the nasopharyngeal mucosa, where they can persist for long periods of
time. Hematogenous dissemination may then occur subsequent to mucosal infiltration facilitated by
infection with another pathogen capable of infiltrating the mucosa, e.g., adenovirus
 Humans are the only hosts (most commonly affects individuals living in close vicinity to one another, e.g.,
college students or soldiers)
 Worldwide, the incidence of meningitis caused by N. meningitidis is highest in sub-Saharan Africa,
collectively referred to as the “meningitis belt.”
 Most common age – 6 years old children
 Seasonality – winter - spring
 Pathways of infection: colonize the nasopharynx or the upper airways before entering the CNS
o Portal of entry – nasopharynx. The pathogen multiplies in mucosa and catarrhal inflammation appears →
regional lymph nodes → Blood borne– bacteremia
 skin – specific hemorrhagic-necrotic rash
 penetrates through blood-CSF barrier and reaches the CSF → invades the meninges (pia mater) and
purulent meningitis appears
 later invasion of brain tissue (encephalon) is possible and purulent meningoencephalitis appears
 Pathophysiology
o Endotoxin stimulates the Sympaticus → spasm of the vessels and increased permeability of the cells’
membranes.
o Endotoxin stimulates plexus chorioideus → increased production of cerebrospinal fluid.
o As a result disorders in circulation of CSF appear followed by intra- and extracellular brain edema.
 Meningococcal meningitis
o Is characterized by general intoxication, catarrhal inflammation of the nasopharynx, inflammation of the
cerebral mucous membranes of the brain and spinal cord, severe outcome and high lethality.
o Beginning- sharp, Alone or after meningococcemia.
o Adult - Incubation period: 2-10 (1-4) days
o Starting triad: Fever (39-40°C), Headache, Vomiting
 Altered mental status, Photophobia, Nausea, vomiting, Malaise, Seizures
 Possibly cranial nerve palsies (strabismus, nystagmus, asymmetry of the face, decrease or loss of hearing,
visual disturbances); Pathological reflexes - Babinski, Oppenheim, Gordon
 Myalgia and, possibly, petechial or purpuric rash (especially in children)
 Possibly Waterhouse-Friderichsen syndrome
 Posture of the patient - lying in the lateral position, with the head turned back and the lower limbs
collapsed in the knees and hips
o Signs of meningeal irritation
 Kernig sign: placing the patient in supine position, flexing the thigh at the hip, and subsequently extending
the knee. Considered positive if extension of the knee causes pain and resistance
 Brudzinski sign: forced flexion of the neck elicits an involuntary flexion of the knees and hips
 Diagnostics
o Blood cultures (two sets): obtain before starting antibiotic therapy
o CBC: Normal/↑ WBC count; In severe infections, ↓ WBC count and thrombocytopenia
o BMP: Blood glucose is needed to analyze CSF glucose.
 Common finding: mild electrolyte disturbances (e.g., hyponatremia from SIADH)
 In critically ill patients: possible signs of acute kidney injury

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 o CRP: elevated
o Cerebrospinal fluid analysis
 Cloudy, purulent fluid
 Elevated cell count with significant pleocytosis (leukocyte count > 1000/mm3); ↑ Granulocytes (> 80%)
 ↑↑ opening pressure
 ↑↑ Lactate, ↑ Protein, ↓ Glucose (bacteria consume glucose)
 Positive gram stain and culture  Meningococci: gram-negative diplococci
 Treatment
o Antibiotics: Third-generation cephalosporin (e.g., cefotaxime OR ceftriaxone)
 Prevention
o Meningococcal vaccination (a polysaccharide conjugate vaccine): Consists of the meningococcal conjugate
(MenACWY vaccine) and the meningococcal B vaccine
o Postexposure measures in bacterial meningitis
 Close contact with the index patient in the 7 days before the onset of symptoms
 All household and/or day-care members
 Anyone exposed to secretions, including:
o Healthcare providers
o Travelers: either direct or ≥ 8 hours of contact with people from endemic areas
 Recommended regimen
 Rifampicin
 OR ceftriaxone - Preferred chemoprophylaxis during pregnancy.
 OR ciprofloxacin - Avoid during pregnancy and for patients < 18 years of age
 Medical observation for seven (7) days with bacteriological examination of Oropharyngeal sample for the
presence of meningococcus; Daily medical monitoring thermometry, view of the nasopharynx
 Complications
o In the meningococcal meningitis: the most dangerous is the acute cerebral edema with lowering of the
cerebellar tonsils, squeezing the medulla, and paralysis of the respiratory center and heart.
o Excessive rash and hemorrhagic disorders can lead to dry necrosis of the phalanges of the fingers and ear buds,
as well as in many places on the skin.
o Adrenal apoplexy determines Waterhouse-Friderichsen syndrome.
o Meningococcemia leads to myo-, endo- and pericarditis.
o Deafness, blindness, decrease in intelligence, epileptic seizures, hydrocephalus
 Meningococcal meningoencephalitis
o Changes in the consciousness to coma, psychomotor agitation, clonic-tonic seizures, more frequent paresis,
and cranial nerve involvement.
o Serious prognosis.
 Meningococcsemia /meningococcal sepsis/
o often happens in conjunction with meningococcal meningitis.
o Acute onset, with chills and fever
o General intoxication: headache, dyspnoea, cyanosis, adynamia, tachycardia, hypotension, reduced diuresis,
shock, often meningeal irritation syndrome is absent
o On 1-2 days, a characteristic rash (meningococcal exanthema) appears with haemorrhagic-necrotic character.
o Meningococcal metastasis may occur in the heart, adrenal glands, and joints.
o Severe leukocytosis, extreme neutropenia, thrombocytopenia, increased ESR.
o Discrete CSF Changes.
 Meningococcal nasopharyngitis:
o This form starts acutely and the symptoms are fever, sore throat, cough, rhinitis
o The diagnosis meningococcal nasopharingitis can not be made without microbiologic analyzes and out of
epidemic situation

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 Meningitis levissima /aseptical meningitis/
o This form appears in patients with typical meningitis who were treated with low dose of antibiotics or
antibiotic course was insufficient
o The symptoms are fever about 37.5-38.0° C and mild meningeal symptoms

Waterhouse-Friderichsen syndrome
 Epidemiology: predominantly affects small children and asplenic individuals
 Description: acute primary insufficiency of the adrenal gland most commonly caused by adrenal hemorrhage
o Dangerous complication of a number of diseases but most commonly associated with meningococcal
meningitis
o Rarer causes include DIC, endotoxic shock, and septicemia due to other pathogens (e.g., S. pneumoniae)
 Pathophysiology: coagulopathy triggered by endotoxins, which often leads to hemorrhagic necrosis of the
adrenal glands
 Clinical features
o Fever, Myalgia
o Nonblanching, petechial rash (mostly on trunk and legs); in severe cases, even purpura fulminans with
extensive necrosis of the skin
o Severe malaise, Hypotension
or even shock, Findings of
disseminated intravascular
coagulation
o Findings of acute adrenal gland
failure, Respiratory failure
 Treatment
o Treatment of the underlying
cause
o Parenteral fluid therapy and
management of disorders of
sodium balance
o Coagulopathy treatment
 Prognosis: fatal without
treatment and often fatal even
with treatment, particularly if
associated with meningococcal
infection (> 40% mortality rate)

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54. Plague
 Epidemiology: western US, Asia, Africa, Middle- and South america
 Pathogen: Yersinia pestis
 Reservoir: prairie dogs, squirrels, rodents
 Route of transmission: flea bites (Xenopsilla cheopsis, Pulex irritans) following an outbreak in a host rodent
population (epizootic); most cases are acquired from late spring to early fall
 Incubation period is typically 1–6 days
 Clinical features
o Bubonic plague (most common):
 Sudden onset of fever, headache, myalgias, chills, and painful swollen lymph nodes (buboes, often inguinal)
 May progress to sepsis, pneumonia, and meningitis
o Septicemic plague: signs and symptoms of sepsis, abdominal pain, possible shock, DIC
 Pestis siderans- massive infection which leads to shock and death in 24 h
o Pneumonic plague (possible human transmission via infectious droplets): rapidly progressing pneumonia with
possible respiratory failure and shock
o “Facies pestica” - red face, perioral cyanosis, red conjunctiva; suffering face
o Unstable walking - “like a drunk man” and obnubilation
o Meningeal plague
 Diagnostics
o Culture
o Microscopy with Wayson stain taken from buboes, blood, or sputum show bipolar staining of bacteria
(appearance of “closed safety pin”)
o (WBC) count is generally raised (to 10,000– 20,000/μL) in plague, with neutrophilic leukocytosis and a left shift
(numerous immature neutrophils
 Treatment: Do not delay treatment for diagnosis.
o Isolation with droplet precautions until pneumonic plague is ruled out
o First-line: IV gentamicin OR fluoroquinolones for 10–14 days
o Second-line: doxycycline OR tetracycline
 Prevention
o Postexposure antimicrobial prophylaxis lasting 7 days is recommended following household, hospital, or other
close contact with persons with untreated pneumonic plague.
o Severely ill patients should be isolated in hospital
o People in close contact with very sick pneumonic plague patients may be evaluated and possibly placed under
observation
o Contact persons –
 from 1 line – isolation for six days, monitoring, urgent prevention with AB and / or vaccination with a live
attenuated vaccine,
 2 line – vaccination (live vaccine strain EV76 or killed vaccine strain USP)

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55. Tularemia
 Pathogen: Francisella tularensis (facultative intracellular bacterium)
 Vector
o Ticks (Amblyomma americanum, Dermacentor spp.)
o Deer flies (Chrysops species)
 Reservoir: rodents (e.g., hares, rabbits)
 Transmission without a vector is possible:
o Inhalation of contaminated dust or aerosols
o Ingestion of contaminated food or water
 Distribution: North America, especially USA
 Incubation period: typically 3–5 days (range 1–21 days)
 Clinical features
o Sudden onset High fever, chills, headache, myalgia and arthralgia
o Skin ulcer at the site where F. tularensis enters the body
o Tender regional lymphadenopathy and lymphadenitis
o Localized signs if:
 Ulceroglandular/Glandular Tularemia (75-85% of cases): ulcer is
erythematous, indurated, and nonhealing, with a punched-out appearance
that lasts 1–3 weeks
 Oculoglandular (1% of cases): inflamed conjunctiva is painful, with
numerous yellowish nodules and pinpoint ulcers. Purulent conjunctivitis
with regional lymphadenopathy (preauricular (pathognomic), submandibular, or cervical)
 Oropharyngeal: follows ingestion of contaminated undercooked meat
 acute, exudative, or membranous pharyngitis associated with cervical lymphadenopathy or in ulcerative
intestinal lesions associated with mesenteric lymphadenopathy, diarrhea, abdominal pain, nausea,
vomiting, and gastrointestinal bleeding
 Infected tonsils become enlarged and develop a yellowish-white pseudomembrane
 Pneumonic: nonproductive cough and may have dyspnea or pleuritic chest pain
 Typhoidal
 Fever usually develops without apparent skin lesions or lymphadenopathy
 cervical and mesenteric lymphadenopathy
 associated with a huge inoculum or with a preexisting compromising condition
 High continuous fevers, signs of sepsis, and severe headache are common. The patient may be delirious
and may develop prostration and shock
 Diagnostics
o CBC: Normal or ↑ leukocyte count, thrombocytopenia
o Hyponatremia
o ↑ Serum transaminase levels, creatine phosphokinase
o Myoglobinuria
o Sterile pyuria
o Confirmatory test
 Positive culture (e.g., on charcoal yeast extract agar) from skin lesions and/or lymph node aspirate/biopsy
 OR Serologic test: four-fold increase in F. tularensis specific antibody titers between the acute and
convalescent serum samples
 Treatment: Streptomycin OR Gentamicin OR Doxycycline (not in children)
 Vaccine – only for endemic areas and risk groups /laboratory workers/

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56. Epidemic (louse-borne) and endemic (murine) typhus/ Fleckenfieber
Epidemic typhus
 Definition: an exanthematous typhus fever caused by Rickettsia prowazekii
 Etiology: Rickettsia prowazekii, Obligate intracellular parasite, Gram negative pleomorphic rods
o Transmission: feces of infected body louse (vector); the louse is transmitted by direct contact
o areas that are overcrowded and where people aren’t able to bathe or change clothes regularly
 Epidemiology: extremely rare in the US; occurs in Rwanda, Ethiopia, Asia, and rural parts of South America
 Incubation period: 10-14 days
 Clinical features
o Abrupt onset of fever, severe headache, malaise, myalgia, abdominal
pain, and nausea
o After 4–5 days: maculopapular or petechial rash that spreads from the
trunk to the extremities
o Brill –Zinsser disease/ Recrudescent typhus: relapse in disease, months
or years following their first illness
 Diagnosis
o Serology
o Positive Weil-Felix reaction
 Treatment: doxycycline or tetracycline (or chloramphenicol)
 Prevention
o avoid contact with flying squirrels and their nests
o In each suspected typhus patient should be hospitalized immediately.
 Patients are leaving hospital after at - least 12 days after normalization of body temperature.
 Dispensarization as a clinical and serological surveillance.
o The contact persons are observed and thermometered for 21 days and tested serologically
o The village which was established pediculosis is observed 73 days after the last case of typhus.
o Specific immunization of contact persons or risk groups with 5 types of vaccines - two live and 3 inactivated
 live, attenuated vaccine against R. prowazekii confers protection. However, some patients develop mild
typhus fever, and reversion of the vaccine strain to a pathogenic state has been demonstrated after in vivo
passage of the organisms
o Anti lice: wash using hot water; treat bedding, uniforms, and other clothing with permethrin

Endemic typhus (also known as murine typhus)

 Definition: an exanthematous typhus fever caused by Rickettsia typhi
 Epidemiology: occurs worldwide, mainly in warm coastal regions, southern US
 Pathogen: Rickettsia typhi
 Transmission: via vector (rat and cat fleas)
 Incubation period: 8–16 days
 Clinical features
o Fever, severe headache, malaise
o Maculopapular or petechial rash erupts on the trunk → spread to extremities (palms and soles are spared)
o No eschar (scab at site of flea bite)
o Relative bradycardia
o Brill-Zinsser disease: exacerbated recurrence many years after the primary episode
 Diagnostics
o Indirect immunofluorescence (four-fold rise in antibodies)

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 o Positive Weil-Felix reaction: a diagnostic test for rickettsial infections, whereby suspensions of proteus antigens
(OX 19, OX 2, or OX K) are mixed with a patient's serum
 Agglutination occurs in the serum of patients infected with Rickettsia.
 No longer recommended in routine practice due to low sensitivity and specificity
 Still valuable test in resource-limited areas where indirect immunofluorescence is not available
 Treatment: doxycycline or tetracycline (or chloramphenicol)
o single, 200 mg dose of doxycycline. Treatment is generally continued for 2 or 3 days after defervescence to
avoid relapse of the infection
 Prevention: avoiding contact with infected fleas

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 57. Q-fever
 Definition: a notifiable zoonotic disease with cattle, sheep, and goats as the primary reservoir
 Epidemiology: Worldwide occurrence; 70% of cases occur in men; Peak incidence in April and May
 Pathogen: Coxiella burnetii (gram-negative, intracellular)
o Morphological similarities to Rickettsia
o Can survive in harsh environments in endospore form
 Route of transmission
o Direct infection (no vector transmission)
o Inhalation of spore-containing aerosols from the amniotic fluid or secretions of infected livestock
o Ingestion of raw milk produced by infected animals
 Risk groups: slaughterhouse workers, farmers, shepherds, veterinarians
Acute Q fever Chronic Q fever
Incubation period  2–6 weeks  Months to years
 Often asymptomatic.
 Sudden onset of flu-like symptoms, which last for
1–2 weeks (self-limiting)
o High-grade fever, chills, malaise, myalgia
o Headache, retroorbital pain, photophobia
o Rhinitis, pharyngitis, laryngitis
 Nausea, vomiting, diarrhea
 Atypical pneumonia: generally mild with  Low-grade fever
nonproductive cough and fever  Endocarditis: Q-fever is the most
Clinical features  Hepatitis, possibly hepatomegaly without jaundice common cause of culture-negative
 Rare manifestations: meningoencephalitis, acute endocarditis.
endocarditis associated with antiphospholipid  Culture-negative osteomyelitis
syndrome, and immunosuppression
 Post-Q fever fatigue syndrome: fatigue, headache,
night sweats, arthralgia, myalgia, blurred vision,
fasciculations, painful lymphadenopathy
 Pregnancy: ↑ risk of spontaneous abortion,
intrauterine growth retardation, intrauterine fetal
death, and premature delivery
 Anti-phase II antibody IgG titers ≥ 200 and IgM  Anti-phase I antibody IgG titers > 800
Serology via titers ≥ 50 or persistently high levels of anti-
Immunofluorescence  In cases of negative IFA but high clinical suspicion, phase I antibody 6 months after
perform PCR on serum or tissue samples before completing therapy
assay administering antibiotics.  Antibodies with titers to phase I
Diagnostics (best initial test)  IgM antibody titers to phase II antigens much antigens are much higher than the
higher than titers to phase I antigens titers to phase II antigens.
 ↑ Liver enzymes, leukocytosis, thrombocytopenia
Additional findings  Blood cultures are often negative.
 Chest x-ray: round opacities in patients with
atypical pneumonia
 First-line: doxycycline PLUS
 First-line: doxycycline for 2 weeks hydroxychloroquine for ≥ 18 months
 Second-line: macrolides (e.g., azithromycin)  Second-line: rifampin and
Treatment
 Among pregnant women or children < 8 years with doxycycline/ciprofloxacin
mild disease: trimethoprim-sulfamethoxazole  Valve repair may be required in the
case of endocarditis.
 Avoid consuming unpasteurized milk products
Prevention
 Vaccine for risk groups (vets, farmers, sheep shearers)

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58. Mediterranean Spotted fever/ Boutonneuse Fever
 Aka: Marseilles fever, MSF, Kenya tick typhus, Israeli tick typhus, Astrakhan spotted fever, and Indian tick typhus
 Pathogen: Rickettsia conorii
 Vector: Rhipicephalus sanguineus ticks, July-August
 Area: India, Pakistan, Israel, Russia, Georgia, Bulgaria, Turkey, Ukraine, Ethiopia, Kenya, South Africa, Morocco,
and southern Europe
 Incubation period: ~3-7 days
 Clinical features
o fever, myalgias, and headache characterize the onset
o triad: Fever, rash, and headache
o seminar: intoxication and conjunctival suffusions; primary affect on the place of the tick bite; generalized
maculopapulous rash; hepatosplenomegaly
 red papule appears at the site of the tick bite and progresses to develop into an eschar/ tache noire 
associated with regional lymphadenopathy
 rash most often appears on the fourth day of illness but may be delayed, is maculopapular, and involves the
palms and soles
o in serious cases:
 disseminated vascular infection
 meningoencephalitis
 vascular lesions in kidneys, lungs, gastrointestinal tract, liver, pancreas, heart, spleen, and skin
 multifocal hepatocellular necrosis and granuloma-like lesions
 petechial rash, gastrointestinal symptoms, obtundation, dehydration,
tachypnea, hepatomegaly, leukocytosis, coagulopathy, acute renal failure,
hyperbilirubinemia
o deep venous thrombosis late in the course
 Diagnostics
o ↑ TNF-alpha
o ↑ serum transaminase and creatine kinase levels, possible anemia
o Rash at bite site, 10% purpuric, eschar (tache noire/black spot) 
o immunohistological demonstration of R. conorii in a biopsy of the tache noire or rash, or in circulating
endothelial cells separated from the peripheral blood; isolated in intraperitoneal inoculation in guinea-pigs or
in shell-vial cell culture
o PCR; immunofluorescence
 Treatment: doxycycline 100 mg twice daily for 7 days (just one day also possible)
o Alternative – fluoroquinolones are active against rickettsiae, and ciprofloxacin (200 mg, intravenously every
12h or 750 mg orally every 12 h)
 Prophylaxis:
o Specific – there is no vaccine to protect against R. conorii.
o Non specific: education, personal prevention, cares for dogs.
 Prognosis: death rate among hospitalized patients ranges from 1.4% to 5.6%

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59. Typhus recurrence/ Borrelia recurrentis/ Relapsing fever
 Pathogen: Borrelia spp. that cause relapsing fever (in contrast to B. burgdorferi, which causes Lyme disease),
family Spirochaetaceae

 Associated with poverty, crowding, and poor sanitation (louse-borne); or with camping (tick-borne), particularly
in the Grand Canyon
 Clinical Features: High fever with rigors,
headache, delirium, arthralgias, myalgias,
and hepatosplenomegaly
o sudden onset of fever, punctuated by an
intervening afebrile period, and then
recurrent fevers
o first fever episode ends by a crisis phase,
which lasts for approximately 15 to 30
minutes and consists of rigors, a further
elevation in temperature, and an increase
in pulse and blood pressure
o followed by profuse diaphoresis, falling
temperature, and hypotension, which
usually persist for several hours
 Diagnostics
o identifying the spirochetes on a Giemsa or
Wright blood smear ↓
o Acute and convalescent serologic testing
with indirect fluorescent antibody and
enzyme-linked immunosorbent assay
o Leukocyte count ranges from 3000 to 16,000 cells/mm3
o ↑LDH and CK

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60. Lyme disease/ Borreliosis
 Pathogen
o In the US: Borrelia burgdorferi, an anaerobic, obligate intracellular spirochete bacteria
 Atypical and cystic forms of B. burgdorferi can persist in the body for years.
o In Europe and Asia: B. afzelii and B. garinii
 Rarely B. valaisiana, B. lusitaniae, B. spielmanii, and B. bavariensis infect humans.
 Vector
o Various tick species (only the females bite):
 Ixodes ricinus (castor bean tick) and persulcatus: in Europe (5-35% of ticks infected)
 Ixodes scapularis (deer or black-legged tick) in the northeastern and upper US
 Ixodes pacificus (western black-legged tick) in the northwestern US
o Typically found in forests or fields on tall brush or grass
o The incidence of Lyme disease is highest between April and October (especially from June to August).
o Increased risk of disease for: Outdoor workers (landscapers, farmers, etc.), Outdoor enthusiasts (i.e., hikers,
hunters, etc.) tick bite infection risk 1,5-6% (1,4% for Borreliosis)
 Reservoir hosts: deer, cattle
 Incubation period: 3-35 days
 Clinical features
o Stage I (early localized Lyme disease) 7-14 days after tick bite
 Erythema chronicum migrans (EM)
 Pathognomonic of early Lyme disease, Occurs in 70–80% of infected
individuals
 Usually a slowly expanding red ring around the bite site with central clearing
(“bull’s eye rash”)
 Typically warm, painless; EM is often the only symptom.
 Self-limiting (typically subsides within 3–4 weeks)
 Flu like symptoms: fever, fatigue, malaise, lethargy, headache, myalgias, and
arthralgias
o Stage II (early disseminated Lyme disease) 3-10 weeks after tick bite
 Migratory arthralgia: can progress to Lyme arthritis
 Spreads from one joint to another; Generally in large joints (especially knee or elbow)
 Early neuroborreliosis
 Cranial nerve disorders
o Most commonly peripheral facial nerve palsy; Nocturnal radicular pain, paresthesia, and paresis
 Meningitis that may cause benign intracranial hypertension
 Polyneuropathy (mononeuritis multiplex, asymmetrical); meningopolyneuritis (syndrome of Banwort)
 Lyme carditis
 Risk of cardiac arrhythmias (e.g., AV Block) and rarely myopericarditis; Adams Stokes syndrome
 Cutaneous manifestations
 Multiple erythema migrans lesions
 Primarily in Europe (endemic for Ixodes ricinus): rarely borrelial lymphocytoma
o Violaceous nodule
o Most commonly affected sites: ear lobe, face, mamillae; often appears close to the site of EM lesion
o Localized lymphadenopathy is common; Resolves spontaneously
 Ocular manifestations: including conjunctivitis, retinal vasculitis, optic neuropathy, and uveitis
o Stage III (late Lyme disease) month to years after initial infection
 Chronic Lyme arthritis (10% of cases): common in North America
 Lasts over a year and may be intermittent or persistent; Typically in large joints (especially knee or elbow)
 Late neuroborreliosis manifestations include:

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 
Aseptic (lymphocytic) meningitis; Progressive encephalomyelitis
 Cognitive impairment; Gait abnormality; Bladder dysfunction
 Psychiatric abnormalities (e.g., depression, anxiety, bipolar disorder etc.)
 Peripheral polyneuropathy
 Acrodermatitis chronica atrophicans (ACA, also called Herxheimer’s disease): in Europe and Asia
 Chronic progressive dermatological disease due to infection with Borrelia afzelii that occurs only in Europe
and Asia and most commonly affects women > 40 years of age;
 Manifestation on the extensor side of extremities
 Stages in the course of the disease:
o Edematous stage with inflammatory reaction (livid discoloration)
o Atrophic stage: hairless, sclerotic skin plaques
 Diagnostics
o If stage I Lyme disease is likely (e.g., EM is present), start empiric antibiotics without further testing.
o If symptoms of Lyme disease arise in a patient with possible exposure (especially if recently traveled to an
endemic area), conduct two-step serological testing: 20-22 days after tick bite, if negative retest in 6-8 weeks
 Initial test: enzyme‑linked immunosorbent assay (ELISA); Confirmatory test: Western blot
 Detect IgG and IgM antibodies against Borrelia
o Cerebrospinal fluid testing
 Signs of lymphocytic meningitis, including elevated protein (due to a disrupted blood-brain barrier) and
pleocytosis; Measure intrathecal IgG or IgM antibodies
 Treatment
Therapy in
Stages Presentation General therapy
pregnant/nursing patients
Localized Lyme  Erythema migrans  First-line oral
disease  Flu-like symptoms antibiotics  First-line oral antibiotics
 Isolated CN palsy o Doxycycline (200 o Amoxicillin (500–
 Mild carditis mg p.o. 1×/Tag, 1.000 mg p.o.
 Borrelial lymphocytoma 14 Tage) 3×/Tag, 14 Tage)
 Initial arthralgia/arthritis o Amoxicillin o Cefuroxime axetil
 Acrodermatitis chronica atrophicans o Cefuroxime axetil

Disseminated  Neurological signs (except isolated CN palsy)

Lyme disease o Meningitis  Hospitalize patient
o Polyneuropathy  Intravenous antibiotics
o Ocular manifestations o Drug of choice: ceftriaxone (2 g i.v. 1×/Tag,
o Chronic neuroborreliosis 14–21 Tage)
o Encephalopathy o Cefotaxime
 Severe carditis o Penicillin G
 Recurrent arthritis after oral therapy
o dispensaries are for a period of 2 years; 35 days of medical observation with thermometry at discretion and
testing for IgM antibodies by ELISA
 Post-Lyme disease syndrome (PLDS)
o Description: a somewhat controversial syndrome (the medical community does not agree on its existence)
following successful treatment of Lyme disease that is associated with pain, fatigue, and difficulty
concentrating that lasts > 6 months
o Differential diagnosis: somatoform disorders, unsuccessfully treated chronic Lyme disease
o Treatment: symptomatic treatment with general medical and psychosomatic support
 Prevention - Avoiding exposure is the only effective protection against Lyme disease.
o Wear protective clothing: e.g., long-sleeved shirts, long pants, and light colors.
o Use tick repellent and pesticides; vaccine only for risk groups
o Check body for tick bites, Remove ticks immediately!  Observe the bite site for early detection of EM

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61. Arboviral encephalitis
 Pathogens
o Japanese encephalitis virus (JEV) is a significant cause of encephalitis in Southeast and South Asia.
o West Nile virus (WNV), St. Louis encephalitis (SLE) virus, JEV, Usutu virus (USUV), and tick-borne encephalitis
virus (TBEV) are the major neurotropic members of the genus Flavivirus
 SLE virus is found in the Americas, and USUV is found in Africa and Europe, whereas TBEV occurs from
Western Europe to Russia, Japan, and China.
 WNV: across much of Africa, southern Europe, the Middle East, Asia, Australia (Kunjin subtype), and, more
recently, the Americas
o Flaviviruses are icosahedral, approximately 50 nm in diameter, approximately 11-kb single-stranded, positive-
sense RNA viruses consisting of a lipid envelope covered densely with surface projections consisting of M
(membrane) and E (envelope) glycoproteins. Nonstructural proteins make up the remainder of the genome

 Clinical features
o Japanese Encephalitis Virus: symptomatic <1% of cases
 high fever and altered consciousness, ranging from mild disorientation or a subtle personality change to a
severe state of confusion, delirium, and coma
 Mutism
 Nuchal rigidity
 Cranial nerve palsies resulting in facial paralysis and disconjugate gaze
 improvement can be expected after 1 week with the defervescence of fever. Neurologic function is regained
gradually over several weeks, with further recovery after hospital discharge over intervals of months to
years
o West Nile Virus: most asymptomatic, incubation period 2 to 6 days
 sudden onset of an acute, onspecific, influenza-like illness lasting 3 to 6 days, with high fever and chills,
malaise, headache, backache, arthralgia, myalgia, and retro orbital pain, without overt neurologic signs
 anorexia, nausea, vomiting, diarrhea, cough, and sore throat. flushed face, conjunctival injection, and
generalized lymphadenopathy, maculopapular or pale roseolar rash
 Neurologic disease occurs in less than 1% of infected: febrile prodrome of 1 to 7 days, which may be
biphasic, before developing neurologic symptoms

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  two-thirds of hospitalized patients had encephalitis (with or without signs of meningeal irritation), and
one-third had meningitis
 Acute flaccid paralysis caused by virus infection of the anterior horn of the spinal cord (myelitis)
o St. Louis Encephalitis
 Usually begins with a febrile prodrome of malaise, fever, headache, and myalgias, sometimes with upper
respiratory or abdominal symptoms, that evolves over several days to more than 1 week with progressive
lethargy, periods of confusion, and the onset of tremors, clumsiness, and ataxia
 Altered consciousness, marked by confusion, delirium, or somnolence, is the predominant presenting
feature; generalized motor weakness is more usual than are focal signs
 Tremulousness involving the eyelids, tongue, lips, and extremities is usual, and cerebellar and cranial nerve
signs are common
o Tick-Borne Encephalitis: symptoms of TBE in as many as 1/3 bitten, incubation period: ~8 days
 usually begins with a nonspecific grippe of fever, malaise, headache, nausea, vomiting, and myalgias that
may be accompanied by fasciculation
 Within 1 week, these symptoms resolve spontaneously.
 remission of symptoms 2 to 8 days before high fever, headache, and vomiting resume
 second phase may be limited to a “meningeal form” with aseptic meningitis (commonly in children), or it
may manifest as a “meningoencephalitis form,” a “poliomyelitic form” with poliomyelitis-like flaccid
paralysis, or a “polyradiculoneuritic form” with a Guillain-Barré–like paralysis, which usually resolves
spontaneously
 Altered consciousness, ataxia, tremor, paresthesias, focal signs, and, less often, seizures
 Limb weakness and paralysis usually represent lower motor neuron lesions caused by myelitis or radicular
neuritis; paresis may be transient, or it may evolve to permanent weakness and muscular atrophy
 Sequelae are reported in up to 40% to 60% of patients, most frequently consisting of psychological
disturbances such as asthenia, headache, memory loss and decreased concentration, anxiety, and
emotional lability
 Diagnostics
o real-time RT-PCR
o serologic testing of serum
and, in the case of
neurologic infections, the
CSF

 Treatment
o No specific antiviral therapy for flavivirus encephalitis has been developed
o Supportive care: controlling seizures, providing ventilatory support in respiratory failure, and monitoring and
reducing cerebral edema
 Prevention
o Vaccines against Japanese and Tick Borne encephalitis viruses
o avoidance of risky habitats, wearing protective clothing, using repellents

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62. Viral hemorrhagic fever /Crimean-Congo fever and Hemorrhagic fever
with renal syndrome/
Crimean-Congo fever
 Pathogen: Crimean Congo hemorrhagic fever virus, family Nairoviridae
 Area: Southeastern Europe, Africa, Middle East, Asia
 Transmission
o Tick bites from Ixodid tick reservoir hosts (Hyalomma genus)
o Contact with infected animal or human bodily fluids
 Incubation period: 1-13 days
 Clinical features
o Initial flu-like illness
 Headache, dizziness; Conjunctivitis
 High fever, Lymphadenopathy
 Sore throat, Myalgia, arthralgia
 Rash; Weakness, fatigue, prostration
 Gastrointestinal symptoms (abdominal pain, diarrhea, nausea, vomiting)
o Severe VHF with bleeding diathesis: develops in a variable number of cases, depending on the causative
pathogen
 Diffuse hemorrhage including:
 Bloody diarrhea, hematuria, hematemesis, melena; Mucosal bleeding; Petechiae, ecchymoses
 Hypovolemic shock and multiorgan failure, Sepsis, DIC, Meningoencephalitis
 Diagnostics
o A detailed travel history to endemic regions is essential!; History of exposure to a potential source of infection
(e.g., rodents, mosquitoes, ticks)
o General laboratory studies
 CBC; Electrolytes, BUN/creatinine, liver function tests
 Urinalysis; Coagulation studies
o Confirmatory tests
 Generally performed by specialized reference laboratories
 Serology: IgM and/or rising levels of IgG antibodies detected using enzyme-linked immunosorbent assay
(ELISA) or other diagnostic assays
 Reverse transcription-polymerase chain reaction (RT-PCR); Immunohistochemistry
 Treatment
o Supportive treatment
 Management of fluids and electrolyte balance
 Maintenance of blood pressure and oxygenation
 Analgesics for pain and fever
 Blood products in patients with severe thrombocytopenia, coagulopathy, hemorrhage
o Medical treatment: Ribavirin may be used in some cases
o Fatality rate: up to 80% (10-50%)
 Prevention
o inactivated CCHFV antigen vaccine in Bulgaria
o Avoid contact with blood, body fluids, or tissue from infected reservoirs or humans
o Avoid travel to endemic areas
o Patients are hospitalized in strict isolation/regime as for particularly dangerous infections
o persons who have been in contact with the sick have been observed 15 d.
o prophylaxis with 3-5ml specific immunoglobulin.

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Hemorrhagic fever with renal syndrome (HFRS)
 Pathogen: Hantavirus (Dobrava, Hantaan, Saaremaa and Seoul viruses.)
 Area: Asia, Korea, Russia, Europe; Highest annual incidence in China
 Transmission: Contact with infected rodent reservoir hosts (field mice) or ingestion/inhalation of their urine,
droppings, or saliva  Seasonal peaks of HFRS in spring and fall are due to rodent breeding seasons
 Incubation period: 1-8 weeks
 Clinical features
o Prodromal/febrile phase (∼ 2–7 days upon onset of illness): clinical features of VHF (see above)
o Syndrome-specific features
 HFRS: group of clinical syndromes of acute interstitial nephritis occurring mainly in Europe and Asia
 Signs of renal failure
 Hypotension
 Diagnostics
o CBC: thrombocytopenia, leukocytosis
o BMP: ↑ serum creatinine
o Urinalysis: Proteinuria, Hematuria
o Confirmatory studies
 Serology: IgM and/or rising levels of IgG antibodies (fourfold in one week) detected using enzyme-linked
immunosorbent assay (ELISA) or other diagnostic assays
 Reverse transcription-polymerase chain reaction (RT-PCR)
 Immunohistochemistry
 Treatment
o Supportive care (e.g., ICU admission, early intubation, supplementary oxygen)
o Ribavirin
o Fatality rate: up to 15%

Nephropathia epidemica: mild form of HFRS; Puumala virus type; Area: Europe (common in Germany)

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 Ebolavirus/Marburgvirus
 Marburg hemorrhagic fever and Ebola hemorrhagic fever (HF) are severe and often fatal diseases characterized
by fever, headache, malaise, myalgia, coagulation disorders, and multiorgan failure
o term "hemorrhagic fever" is no longer used to refer to Ebola virus disease because only a small percentage of
Ebola patients actually develop significant hemorrhage, and it usually occurs in the terminal phase of fatal
illness, when the individual is already in shock
 genus Ebolavirus consists of six species: Zaire, Sudan, Bundibugyo, Tai Forest, Reston, and Bombali
 nonsegmented, negative-sense, single-stranded RNA virus, member of the family Filoviridae
 Epidemiology
o Human outbreaks occur sporadically in regions of Central Africa
o initial cases occur as a result of contact with an infected animal (fruit bats)
o Nosocomial transmission has occurred frequently during outbreaks of filovirus HF in endemic areas.
o Incubation period —abrupt onset of symptoms 6 to 12 days after exposure
 Clinical symptoms are nonspecific, but a constellation of symptoms, including fever, headache, malaise, myalgia,
sore throat, vomiting, diarrhea, and, in particular, the appearance of a maculopapular rash, may indicate
infection with a filovirus.
Time post-
Stage of illness symptom Clinical Laboratory
onset
Leukopenia, lymphopenia,
Early febrile Days 1-3 Fever, malaise, fatigue, body aches thrombocytopenia, elevated AST and
ALT
Persistently elevated AST/ALT and
Primary: Epigastric and abdominal pain, nausea, thrombocytopenia
vomiting, diarrhea Elevated BUN and creatinine
Hypokalemia, hypomagnesemia,
Gastrointestinal Days 3-10 Associated: Persistent fever, asthenia, headache, hyponatremia, hypoalbuminemia
conjunctival injection, chest pain, dysphagia, Elevated PT/PTT/INR/fibrin-split
odynophagia, arthralgias, myalgias, hiccups, delirium, products
and rash Leukocytosis (elevated neutrophils
and band cells)
In addition to findings
Diminished consciousness or coma, thready pulse, during gastrointestinal stage:
Shock Days 7-12
oliguria, anuria, tachypnea Elevated lactate
Decreased bicarbonate
Findings may overlap with prior
Gastrointestinal hemorrhage, respiratory failure stages of illness
associated with aggressive fluid resuscitation or lung Decreased hemoglobin and
Day 10 and
Other complications injury, secondary infections, neurocognitive hematocrit observed with
after
abnormalities, seizures, syndrome consistent with gastrointestinal bleeding
menigoencephalitis Hypoxemia observed with
respiratory failure
Resolution of gastrointestinal symptoms, increased Resolution of laboratory
Recovery Days 7-12
oral intake, increased energy abnormalities
Arthralgias, myalgias, abdominal pain, fatigue,
Up to 12
Convalescence persistent neurocognitive abnormalities, uveitis,
months
meningitis, hearing loss

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 Antigen-capture enzyme-linked immunosorbent assay and polymerase chain reaction are the most frequently
used assays to diagnose filovirus infection.
 Treatment
o primarily intensive supportive care, which is directed toward maintaining effective blood volume and
electrolyte balance
o Invasive mechanical ventilation (intubation) patients with progressive respiratory failure
o Ebola-specific therapies
 Atoltivimab, maftivimab, and odesivimab (REGN-EB3): triple-monoclonal antibody (mAb) product, targets
three nonoverlapping epitopes on the Ebola virus surface glycoprotein, providing potent virus neutralization
 Ansuvimab (mAb114) –monoclonal antibody ansuvimab, isolated from a survivor of Ebola virus disease and
neutralizes the virus.
 Prevention
o Barrier nursing procedures include the donning of protective clothing, masks, and eye shields.
o Infected patients and close contacts should be isolated.
o Avoid contact with bush meat and sick animals, particularly nonhuman primates, in endemic regions.
o Vaccine: ebola Recombinant vesicular stomatitis virus–Zaire Ebola virus (rVSV-ZEBOV) vaccine
o Outbreak containment measures:
 Prompt, safe and dignified burials
 Identify close contacts and monitor health for 21 days
 Separation of the healthy and sick to prevent spread
 Good hygiene
 Maintaining a clean environment

Lassa fever
 Pathogen: Lassa virus, family Arenaviridae
 Area: West Africa (e.g., Liberia, Sierra Leone, Guinea)
 Transmission
o Ingestion/inhalation of rodent urine or droppings from reservoir hosts of the virus: the multimammate rat
o Contact with bodily fluids of other infected animals or humans
 Incubation period: 1–21 days
 Clinical features
o Insidious onset: Fever, headache, sore throat, chest and muscle pain, nausea, vomiting, diarrhea; severe:
bleeding
o 1 in 5 cases of Lassa fever develops into severe disease where the virus affects organs such as the liver, spleen
and kidneys
 Diagnostics
o ELISA
o RT-PCR (reverse transcriptase polymerase chain reaction assay)
o Viral isolation by cell culture
 Treatment: maybe ribavirin

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63. Yellow fever
 Yellow fever is endemic in tropical regions of South America and Sub-Saharan Africa; Asia, Europe, North
America, and Australia are free of yellow fever (except for occasional imported cases)
 Pathogen: yellow fever virus
o Genus: 126 lavivirus, type of arbovirus
o Genetics: single-stranded, positive-sense, linear RNA virus
o Appearance: enveloped, icosahedral
 Transmission
o Vectors: mosquitoes (primarily Aedes aegypti – an transmit yellow fever, dengue fever, and Zika virus)
o Main reservoir: primates (human and non-human)
o Different transmission cycles (depending on local circumstances and geography)
 jungle cycle involves infections and transmission between non-human primates (e.g., monkeys).
 intermediate cycle in jungle border regions in which both human and non-human primates are infected and
serve as reservoirs.
 urban cycle begins when the virus is brought to an urban area by an infected human (e.g., working in the
jungle) and involves viral transmission between urban mosquitoes and humans, with humans as reservoir.
 Incubation time: 3–6 days
 Clinical features
o The majority of infected individuals remain asymptomatic.
o In symptomatic patients: classic progression in three stages
 Period of infection (3–4 days)
 Sudden onset of high fever (up to 41°C)
 Headaches, chills, Nausea, vomiting
 Period of remission (up to 2 days): Easing of symptoms and decline in fever
 Period of intoxication (only in ∼ 15% of symptomatic patients)
 Hemorrhage (epistaxis, mucosal bleeding, melena, hematuria, black vomiting)
 Multiorgan dysfunction (e.g., acute kidney and liver failure)
 Abdominal pain, severe jaundice
 Diagnostics
o Laboratory tests
 ↑ ALT/AST begins 2-3 days after symptoms onset
 Leukopenia
 In period of intoxication: Thrombocytopenia, ↑ PTT ; Signs of organ failure (see acute liver failure, acute
renal failure)
o Virus detection: PCR, ELISA
o Liver biopsy
 Used for definitive diagnosis (e.g., postmortem)
 Must not be done while the patient has an active yellow fever infection
 May show Councilman bodies (eosinophilic apoptotic globules)
 Treatment
o Symptomatic treatment, No specific antiviral treatment is available
Avoid NSAIDs that increase the risk of bleeding (e.g., aspirin, ibuprofen, naproxen) in patients with confirmed or
suspected yellow fever infection!
 Vaccination
o recommended for individuals (≥ 9 months age) traveling to areas where yellow fever is endemic
o contraindications: egg protein allergy, age <6 months, nursing mothers
o A single dose of live-attenuated vaccine is sufficient for most patients and provides life-long protection
(administer at least 10 days before travel)

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 Prevention
o Case control: the case should be protected from exposure to mosquitoes for greater than five days after
onset of infection. The case should be cared for in an isolation room or in a screened room with use of a
mosquito net and a suitable spray for mosquitoes if not in hospital.
o Control of contacts: spray inside and around the home of the patient and all houses within a half a kilometer
radius with an effective insecticide. Potential vector breeding sites should be destroyed, emptied or sprayed.
Contacts of the patient who have not previously been immunized should be offered a vaccine.
o Outbreak measures: a single case of indigenous transmission constitutes an outbreak. In the event of an
epidemic of yellow fever in an urban area, all persons living in the area infested with Ae. aegypti should be
offered yellow fever vaccine and a wider mosquito spraying and breeding site elimination program
implemented.

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64. Dengue fever. Zika Fever
Dengue
 Distribution: tropical regions worldwide, particularly Asia (e.g., Thailand)
 Most common viral disease affecting tourists in tropical regions
 Pathogen
o Dengue virus (Serotype: DENV 1–5), no cross immunity
o RNA virus of the genus Flavivirus
 Transmission route: Vector-borne: mosquitoes most commonly from the species Aedes aegypti
 Classic dengue fever
o Incubation period: 2–14 days
o Children are usually asymptomatic
o Starts with fever and malaise that lasts ∼ 1 week
o Severe arthralgia and myalgia (often referred to as “break-bone fever”)
o Severe headache and retro-orbital pain
o Maculopapular, measles-like exanthem (typically appears 2–5 days following fever)
o Generalized lymphadenopathy
 Dengue hemorrhagic fever (DHF)
o Occurs in 1–2% of cases
o Generally develops as the initial fever subsides (∼ 1 week after onset)
o Clinical manifestations
 Temperature change: ranges from hypothermia to a second spike in fever
 Abdominal pain, vomiting
 Changes in mental status (e.g., confusion)
 Hemorrhagic manifestations (e.g., petechiae, epistaxis, gingival bleeding)
 Positive capillary fragility test
 Increased vascular permeability → signs of pleural effusion and/or ascites
o Dengue shock syndrome (DSS): DHF + shock
 Diagnostics
o Laboratory tests
 Leukopenia, Thrombocytopenia
 ↑ AST, Hct elevated ≥ 20% of normal values if vascular permeability (in DHF)
o Best test for confirming infection: serology (IgM, IgG)
o Alternatives: PCR, Molecular methods (ELISA): detection of viral antigen
 Treatment
o Symptomatic treatment: Fluid administration to avoid dehydration, Acetaminophen/Paracetamol (no
NSAIDS!)
o Dengue hemorrhagic fever
 Blood transfusions in case of significant internal bleeding (e.g., epistaxis, gastrointestinal bleeding, or
menorrhagia); IV fluids
 Prevention
o Avoid exposure, use of mosquito repellent (mosquito bite prevention)
o A tetravalent attenuated live vaccine (CYD-TDV; Dengvaxia®) has been approved for use in children between
9–16 years of age who live in endemic areas and have a laboratory confirmed prior dengue virus infection.

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Zika fever
 Outbreaks most commonly occur in tropical and subtropical regions; Since 2015, epidemic outbreaks have been
reported in South America (especially Brazil)
 Pathogen: Zika virus
o Genus: 129lavivirus, type of arbovirus
o Positive-sense, single-stranded, enveloped RNA
 Route of transmission
o Vector-borne transmission by the mosquito Aedes aegypti (common)
o Transplacental transmission from the mother to the fetus
o Sexual transmission: men to women even months after initial infection because the virus persists in testicles
 Incubation time: 2–14 days
 Approx. 80% of cases remain asymptomatic
 In symptomatic patients, the manifestations are usually mild and last for 2–7 days
o Low-grade fever
o Flu-like symptoms: headache, arthralgia, myalgia, non-purulent conjunctivitis, malaise
o Maculopapular, pruritic rash (20% of cases)
 Diagnostics
o Possible findings
 ↑ Acute phase reactants (e.g., CRP, ferritin)
 Leukopenia, thrombocytopenia
 ↑ LDH, ↑ γ-GT
o Definitive diagnosis
 During the first 7 days of the infection: PCR detects Zika virus RNA in blood and/or urine samples
 During days 7–28: RT-PCR and/or serology
 After 28 days: serology confirms Zika virus antibodies
 Treatment
o Definitive therapy does not yet exist.
o Treatment is primarily symptomatic with rest, oral/IV fluids, and/or acetaminophen to relieve fever and pain.
 Complications
o Guillain-Barre syndrome: immune-mediated polyneuropathy that typically manifests with ascending flaccid
paralysis 1-2 weeks after certain infections
o During pregnancy
 Congenital infections can result in microcephaly (craniofacial disproportion)
 Other congenital manifestations: spasticity (contractures), hyperreflexia, ocular abnormalities (e.g.,
pigmentary retinal mottling), and sensorineural hearing loss
 Miscarriage in the case of intrauterine transmission
 Prevention
o A vaccine against Zika virus does not exist yet.
o Vector control and safe sexual practices are the most important public health measure in endemic regions.
o Individuals traveling to endemic regions should be told to use insect repellents, mosquito nets, and long-
sleeved clothing

129
65. Sandfly fever/ Pappataci fever/ 3 Days fever
 Pathogen: Phlebovirus, Sicilian, Naples and Toscana viruses
 Transmission: mosquito bite
o Vector: mosquitoes (Phlebotomus papatasi), virtually eliminated in Europe
o Phlebotomus perniciosus, spreads the related but distinct Toscana virus, which appears to be a common
cause of infections in Tuscany and areas of Southern Europe
 Area: Circum-Mediterranean distribution in Southern Europe, Iraq, Iran, Pakistan, Afghanistan and India
 Risk groups: nonimmune adults entering endemic area (often militaries in the past)
 Incubation period: 2-6 days
 Clinical signs: Fever, headache, myalgia, meningitis, flushing of the face and a fast heart rate
o After two days the fever begins to subside and the temperature returns to normal. Fatigue, a slow heart rate
and low blood pressure may persist from few days to several weeks but complete recovery is the rule
o Toscana virus can cause febrile disease, aseptic meningitis, or mild encephalitis
 Diagnosis: virus-specific IgM by ELISA and immunofluorescence assays, PCR
o Marked leukopenia (<4000/µL), consisting of initial lymphopenia, followed by protracted neutropenia, also
occurs in PF
 Treatment: supportive (fluids, analgesics)
 Prevention: Prevention of sandfly bites, and control of sandflies and their breeding grounds with insecticides

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66. Ornithosis (Psittakosis, parrot fever)
 Pathogen: Chlamydophila psittaci
 Transmission
o Airborne (pathogens from feces and/or dander of infected birds)
o Mainly affects individuals in contact with free-ranging birds or pets, or occurs as an occupational disease
 Incubation period: 5–14 days (1-4 weeks)
 Clinical features: Symptoms can vary greatly.
o Acute onset of flu-like symptoms, especially fever
o Atypical pneumonia with non-productive cough
o Headaches
o Arthralgia, myalgia
 Diagnostics
o Culture of respiratory specimens (e.g., sputum, pleural fluid)
o Polymerase chain reaction (PCR) of respiratory specimens
o Serology for Chlamydophila psittaci IgG and IgM with the complement-fixation test (CFT) or micro-
immunofluorescence (MIF); diagnosis requires either of the following:
 Four-fold or greater increase in antibody titer between acute and convalescent sera (I.e., specimens
collected at the beginning of the disease and again 2 weeks later)
 A single IgM antibody titer of 1:16 or higher
 Treatment
o First-line treatment: doxycycline (200 mg p.o. 1-0-1 for 10–21 days)
o Second-line treatment: macrolides (Clarithromycin 500 mg p.o. 1-0-1 für 10–21 Tage)
 Drugs of choice for children and pregnant women
 Alternative: fluoroquinolones (Levofloxacin 500 mg p.o. 1-0-0 für 10–21 Tage)
 Complications
o Respiratory failure
o Myocarditis, endocarditis
o Meningoencephalitis
o Hepatitis

131
 67. Anthrax
 Global distribution: Anthrax is endemic in agricultural regions of the USA, Canada, Central and South America,
southern and eastern Europe, central and southwest Asia, and sub-Saharan Africa
 Pathogen: Bacillus anthracis
o Gram-positive, spore-forming, nonmotile rod
o Edge of colony shows irregular comma-shaped outgrowths on blood agar (also referred to as Medusa head).
o Spores of B. anthracis can remain viable for decades, Soil and mammals (including humans) constitute the
reservoirs for the pathogen
o Anthrax is a zoonotic infection that primarily infects cows, goats, and sheep when they breathe in or ingest
spores in contaminated soil, plants, or water
 Transmission
o Human infection occurs following exposure to B. anthracis or its spores (e.g., inhalation), usually as a result of
contact with infected animals or infected animal products (e.g., wool, hide, meat)
 Local germination of B. anthracis spores and multiplication of bacteria
 Spreading to local/regional lymph nodes
 Bacteremia → systemic spread
o Bioterrorism or biological warfare: exposure to weaponized B. anthracis or its spores.
o Person-to-person transmission is rare, but cases of person-to-person transmission of cutaneous anthrax have
been reported.
 Virulence factors
o Antiphagocytic capsule
 B. anthracis is the only bacterium that is capable of forming a polypeptide capsule;
 Contains poly-D-glutamate
o Anthrax toxin: responsible for the local and systemic manifestations of anthrax; made up of A and B subunits
 The A subunit has 2 components:
 EF (edema factor): binds to calcium and calmodulin and gains adenylate cyclase activity → ↑ cAMP →
cell edema
 LF (lethal factor): a metalloprotease that destroys MAPKK (mitogen-activated protein kinase kinase) →
cell death
 The B subunit (PA; protective antigen) binds to endothelial receptors and facilitates entry of the A subunit
into the host cell.
 Clinical Features
Feature Cutaneous anthrax Inhalation anthrax (Woolsorters’ disease) Gastrointestinal anthrax
Relative  < 1%
 ∼ 95%  ∼ 5%
frequency
Route of entry  Skin contact (cuts, wounds)  Inhalation  Ingestion
Incubation  2–5 days
 Typically 5–7 days  Typically 1–3 days
period
 Skin lesion: painless, pruritic
papule → vesicle → ulcer 1. Prodromal phase (1–6 days):
with surrounding edema → nonspecific, flu-likesymptoms (e.g.,  Nausea, vomiting
painless, necrotic, black fever, malaise)  Abdominal pain
eschar → healing by 2. Fulminant phase  Severe, bloody diarrhea
Clinical granulation → o Substernal chest pain  Hematemesis
features hyperpigmented skin and/or o High-grade fever  Hemorrhagic
scar o Progressive dyspnea; Hypoxia lymphadenitis
 stefanski symptom/ oedema o Shock  Ascites
malignum – eyelid edema o Mediastinal widening due to
 Usually does not progress to hemorrhagic mediastinitis
bacteremia and death.

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 Feature Cutaneous anthrax Inhalation anthrax (Woolsorters’ disease) Gastrointestinal anthrax
 Local/regional lymphadenopathy
 In case of bacteremia: meningitis, septic shock
 Diagnostics
Cutaneous anthrax Inhalation anthrax Gastrointestinal anthrax
 Oral and rectal swabs
 Swab of fluid from the vesicle and/or  Pleural fluid
 Ascitic fluid
Samples to eschar  Swab of respiratory
 Splenic and/or mesenteric lymph node
collect  Full-thickness punch biopsy secretions
biopsy
 Blood, CSF  Blood, CSF
 Blood, CSF
Diagnosis of anthrax infection can be made if either the confirmatory test or at least two of the supportive
microbiologic tests indicate an infection.
 Confirmatory test: microscopic examination and culture
Pathogen
 Supportive tests
detection
o PCR
o Immunohistochemistry
o ELISA in acute-phase serum and convalescent-phase serum
 Leukocytosis, ↑ AST, ALT
Additional
 In inhalational anthrax: x-ray and/or CT chest reveals mediastinal widening, perihilar interstitial pneumonia, and/or
findings
hemorrhagic pleural effusion
 Treatment
Gastrointestinal
Type of treatment Cutaneous anthrax Inhalation anthrax
anthrax
 Oral monotherapy with either a
Without systemic fluoroquinolone (e.g., ciprofloxacin,
- -
spread levofloxacin, or moxifloxacin) or
doxycycline
Antibacterial
 Antitoxin therapy: raxibacumab, obiltoxaximab, or anthrax immunoglobulin
With systemic  Combination of IV antibiotics
spread o Patients without meningitis: ciprofloxacin and linezolid
o Patients with (confirmed or suspected) meningitis: ciprofloxacin, linezolid, and meropenem
 Fluid resuscitation in case of shock
 Systemic glucocorticoids are indicated in the following situations:
General o Meningitis
o Shock that does not respond to fluid resuscitation and vasopressors
Supportive o Severe edema of the head and neck
 Large pleural effusions:
 In case of ascites:
Specific  None chest tube insertion or
ascitic tap
thoracocentesis
o
Discharge from hospital after complete clinical recovery. For pulmonary or intestinal form after two negative
results of culture of sputum or enteric material.
 Lethality
o With antibiotic treatment: < 1% in cutaneous anthrax, ∼ 50% in inhalation anthrax, and ∼ 40% in
gastrointestinal anthrax
o Without antibiotic treatment: ∼ 20% in cutaneous and > 90% in inhalational anthrax
 Prevention
o AVA (anthrax vaccine adsorbed), BioThrax® - 5 doses over 18 months
 Routine pre-exposure prophylaxis is recommended for individuals at a high risk of exposure to anthrax (e.g.,
laboratory workers who work with B. anthracis, veterinarians who work with livestock, certain military
personnel)
 Post-exposure prophylaxis: AVA along with antibiotics (ciprofloxacin or doxycycline) for 8 days
o Screening of farm animals; wash people with antimicrobial soap or formaldehyde, burn cloths
o corpses are wrapped in a bed sheet with 10% chlorine, no autopsy, buried in sealed closed coffin or cremation

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68. Tetanus
 Pathogen: Clostridium tetani: a gram-positive, obligate anaerobic, spore-forming rod
 Route of infection
o Clostridial spores contaminate a wound (e.g., through dirt, saliva, feces).
o Localized ischemia, necrosis, foreign bodies and/or coinfection with other bacteria predispose to infection.
o Wounds with compromised blood supply create anaerobic conditions that are required for the germination
and multiplication of C. tetani.
 Deep, penetrating wounds (e.g., knife, gunshot, animal bites); Open fractures
 Surgical procedures (e.g., bowel, biliary tract, or dental surgery); Burns; Umbilical stump infections
 Pathophysiology: Ubiquitous C. tetani spores contaminate a wound → bacterial reproduction under anaerobic
conditions → production of the neurotoxins tetanospasmin and tetanolysin
o Tetanospasmin: reaches the CNS through retrograde axonal transport
 Toxin binds to receptors of peripheral nerves and is then transported to interneurons (Renshaw cells) in the
CNS via vesicles
 Acts as protease that cleaves synaptobrevin, a SNARE protein → prevention of inhibitory neurotransmitters
(i.e., GABA and glycine) release from Renshaw cells in the spinal cord → uninhibited activation of alpha motor
neurons → muscle spasms, rigidity, and autonomic instability
o Tetanolysin: causes hemolysis and has cardiotoxic effects
 Incubation period: 3–21 days (average: ∼ 10 days)
 Clinical features
o Generalized tetanus: painful muscle spasms and rigidity
 Trismus: lockjaw due to spasms of jaw musculature (commonly the first tetanus-specific symptom)
 Risus sardonicus: sustained facial muscle spasm that causes a characteristic, apparently sardonic grin and
raised eyebrows
 Opisthotonus: backward arching of spine, neck, and head caused by spasms of the back muscles
 Neck stiffness; Abdominal rigidity
o Life-threatening complications
 Laryngospasm and/or respiratory muscles spasms → respiratory failure
 Autonomic dysfunction → circulatory arrest and shock
o Localized tetanus: Patients present with painful muscle contractions in areas surrounding the injury site only
o Cephalic tetanus: In patients with open head or neck injuries; Initially, only affects cranial nerves (especially
flaccid paralysis of n. facialis, CN VI, III, IV, and XII may also occur either alone or in combination), can be mistaken for stroke
 Diagnostics
o clinical diagnosis based on muscle spasms and rigidity associated with an entry point for bacteria and
inadequate immunization;
o Wound culture and serology may confirm the diagnosis but have low sensitivity and specificity.
 Treatment lethality ~25%
o Wound cleaning and debridement; benzodiazepines and/or paralytics for control of muscle spasms
o Antibiotic treatment: Drug of choice: Metronidazole 500 mg i.v. 1-1-1-1, 7–10 days (Alternative: penicillin G)
o Active and passive immunization
 Single IM dose of human tetanus immunoglobulin (HTIG) (Binds tetanus toxin → neutralizes unbound toxins
before they enter the CNS) 3.000–6.000 IE i.m. 1×1
 Tetanus toxoid-containing vaccine (separate site from HTIG)
 Prevention: Tetanus vaccination (diphtheria, tetanus, and acellular pertussis)↓
o Initial immunization recommendations: Сhildren < 7 years of age should receive 5 doses of DtaP
o Booster recommendations
 Children 11–12 years of age: a single dose of Tdap (tetanus, diphtheria, pertussis)
 Adults 19–64 years of age: a single dose of Tdap
 Adults ≥ 19 years of age: Td (tetanus, diphtheria) every 10 years

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Gas gangrene (Clostridial myonecrosis)
 Pathogen
o Clostridium perfringens (> 80% of cases): a gram-positive, obligate anaerobic, spore-forming bacterium
o Less common: C. septicum, C. histolyticum
 Path of infection: wounds with compromised blood supply create an optimal anaerobic environment for the
proliferation of C. perfringens → necrosis that progresses within 24–36 hours
o Septic surgical wounds or procedures (e.g., bowel and biliary tract surgery, septic abortion)
o Deep, penetrating wounds (e.g., knife, gunshot); Open fractures
 Risk groups: Diabetes Mellitus, blood vessel disease, colon cancer, trauma
 Pathophysiology: Ubiquitous C. perfringens spores contaminate a wound → bacterial reproduction under
anaerobic conditions → ↑ secretion of exotoxins, especially C. perfringens alpha-toxin (a phospholipase
lecithinase) → degradation of phospholipids → tissue destruction (myonecrosis), inhibition of leukocyte
function, and gas production → gas separation into healthy tissue → further colonization and more local tissue
destruction → further exacerbation of anaerobic conditions by the development of edema
 Incubation period: hours to days
 Clinical features
o Local signs and symptoms
 Excruciating muscle pain
 Massive edema with skin discoloration that progresses from bronze to red-purple to
black and overlying bullae
 Sweet and foul-smelling or nonodorous discharge produced by anaerobic metabolic
products
 Crepitus: Palpation reveals crackling of the skin due to gas production (skin
emphysema)
 Spreading infection
o Systemic toxicity
 Can progress to systemic infection within a few hours
 Early signs: Fever, Tachycardia, Altered mental status
 Late signs: Shock, Multi-organ failure, Hemolytic anemia, ARDS, Kidney and liver failure
 Diagnostics
o Imaging: Radiography, CT, or MRI typically show a characteristic feathering pattern of the soft tissue ↑
o Laboratory tests
 Gram staining: large, gram-positive rods
 Wound culture: double zone of hemolysis on blood agar (Complete hemolysis can be seen in inner zone,
while incomplete hemolysis can be seen in outer zone.)
 Blood cultures
 PCR or ELISA for detection of toxin in wound material (not widely available)
o Surgical exploration
 Affected muscle does not bleed or contract, and may be pale or discolored red-purple to black.
 Histopathological findings of biopsy
 Myonecrosis and destruction of surrounding degenerative tissue (muscle, skin fat, subcutaneous tissue)
 Presence of pathogens; without inflammatory infiltrate
 Differential: Necrotizing fasciitis, Rhabdomyolysis, Pyomyositis
 Treatment
o Surgical exploration and debridement: If applicable, amputation of the affected extremity may be necessary.
o Antibiotic therapy: penicillin plus clindamycin or tetracycline
o Assessment of compartment pressure if compartment syndrome is suspected
o Hyperbaric oxygenation use is controversial.
o Tetanus toxoid if indicated

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69. Sodoku (Rat-bite fever)
 Pathogen: Spirillum Minus, short, thick, gram-negative, tightly coiled spiral rod measuring 0.2 to 0.5 µm by 3 to 5
µm, Terminal polytrichous flagella
 Area: Asia
 Transmission: rat bites
 Clinical manifestations
o initial bite wound heals promptly but then becomes painful, swollen, and purple approximately 1 to 4 weeks
later  regional lymphangitis and lymphadenitis
o afterwards systemic illness characterized by fever, chills, headache, and malaise
o bite wound progresses to chancre-like ulceration and induration with eschar formation
o During first week of fever, a blotchy violaceous or reddish-brown macular rash erupts over the extremities,
face, scalp, and trunk, and then it fades during subsequent afebrile intervals
o Without specific antibiotic therapy, fevers lasting 3 to 4 days recur at regular intervals between afebrile periods
of 3 to 9 days. Spontaneous cure usually occurs within 1 to 2 months, but in selected instances, fevers have
relapsed for years
o Complications: endocarditis, myocarditis, pleural effusions, hepatitis, splenomegaly, meningitis, epididymitis,
conjunctivitis, and anemia
 Diagnostics
o examination of blood, exudate, or lymph node tissue by using Giemsa stain, Wright stain, or darkfield
microscopy
o No specific serologic test or PCR assay is available
o Leukocytosis with peripheral white blood cell counts in the range of 10,000 to 20,000/mm 3 may be observed,
and up to 50% of patients have false-positive syphilis serologies
 Treatment
o intravenous (IV) penicillin G (400,000–600,000 IU/day or every 12h) or ceftriaxone
 after 5 to 7 days of parenteral therapy, the course can be completed with an additional week of oral penicillin
V or ampicillin, 500 mg every 6 hours
o Oral tetracycline, 500 mg every 6 hours, is preferred for penicillin-allergic patients
o Jarisch-Herxheimer reaction possible: acute systemic reaction to bacterial endotoxins and pyrogens that are
released following initiation of antibiotic treatment; typically flu-like (e.g., fever, chills), accompanied by
tachycardia, tachypnea, hypotension, and, less commonly, reoccurrence of syphilitic exanthema. Usually self-
limiting within 12-24 hours
 Prevention
o wound should be thoroughly cleaned, and tetanus prophylaxis should be administered if warranted by the
patient’s immunization history.
o prophylactic 3-day course of oral penicillin (2 g/day) would seem reasonable, although efficacy is unknown, and
the patient should be advised to report any subsequent symptoms

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70. Felinosis (Cat-scratch disease)
 Definition: a benign, self-limiting infectious disease that is transmitted mainly by cats (via scratching, biting, or
licking)
 Epidemiology: predominantly affects children and adolescents
 Pathogen: Bartonella henselae (gram negative, aerobic bacillus)
 Clinical features
o General: malaise, loss of appetite, fever
o Localized
 One or more 5–10 mm large, erythematous, nontender cutaneous papules or vesicles develop approx. 3–10
days after exposure at the site of inoculation.
 Swollen, tender lymph nodes 7–60 days following exposure
 Develops as primary lesions disappear
 Usually unilateral, occasionally suppurative
 Most commonly involves lymph nodes of axillae, neck, or groin (nearest the site of inoculation)
 Resolves after 2–4 months
o In immunocompromised individuals (e.g., patients with HIV)
 Bacillary angiomatosis (red-purple papules that bleed easily)
 Hepatic peliosis: a benign vascular condition characterized by multiple blood-filled cysts and vascular sinuses
in the liver
 Can be asymptomatic or cause abdominal pain, jaundice, and/or liver failure
 In rare cases, cysts may rupture, causing intraperitoneal hemorrhage
 Bacteremia and endocarditis
 Diagnostics
o Bacterial culture from blood, swabs, or lymph node aspirate
o Antibody testing: ndirect fluorescence assay (IFA) testing and enzyme-linked immunoassay (ELISA)
o Histological study
 Warthin-Starry staining of the involved lymph node may show clusters of rod-shaped bacteria.
 H&E staining of cutaneous lesions may show necrotizing granuloma formation and neutrophilic infiltrate.
 Treatment
o Often spontaneous healing after several weeks
o Mild or moderate cases: azithromycin (5-day course) to decrease lymphadenopathy and the duration of illness
o In the case of persistent and/or disseminated disease (e.g., bacillary angiomatosis): erythromycin OR
doxycycline
o In the case of CNS involvement or endocarditis: rifampicin PLUS either erythromycin OR doxycycline

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71. Foot and mouth disease (Aphthe epizooticae)
 Pathogen: Aphthovirus, family Picornaviridae, seven serotypes (O, A, C, SAT1, SAT2, SAT3, and Asia1)
 Vector: all cloven-hoofed animals (often cows and sheep)
 Transmission: close contact with infected animals, raw milk
o Zoonosis: crosses the species barrier with difficulty and with little effect, commonly serotype type O followed
by type C and rarely A
o No person-to-person spread
 Incubation period: 2-6 days
 Clinical Manifestations: mild and self limiting
o uncomfortable tingling blisters (Aphthe) on the hands but also fever, sore throat, and blisters on the feet and in
the mouth, including the tongue
o blisters dry out  erosions heal in 5-10 days
 Diagnostics
o PCR
o Antibody test
 Prevention: general hygiene when handling animals, veterinarian measures (culling, risk zones)

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72. Rabies
 Found in animal reservoirs in most countries throughout the world
 Pathogen
o Rabies is caused by several different members of the Rhabdoviridae family
 Rabiesvirus (Asia, America, Africa)
 European-Bat-Lyssa-virus 1 (EBLV-1), European-Bat-Lyssa-virus 2 (EBLV-2) (Europe)
o Rhabdoviruses are rod or bullet shaped
o Genus: Lyssavirus; ssRNA
 Transmission
o Most common urban animal reservoir worldwide: dogs, eradicated in Western Europe
o Most common wild animal reservoirs: bats (raccoons, skunks, foxes, doe, badgers: eradicated in Western
Europe)
o Spread through saliva of rabid animal after bite injury; Via aerosols (e.g., bat caves); rare
 Pathophysiology
o Rabies virus binds the ACh receptor of peripheral nerves in the bite wound → migrates retrogradely along the
axonal microtubules (using motor protein dynein) → enters the CNS → infects the brain
 Diencephalon, hippocampus, and brainstem are involved first
 Causes acute, progressive, and fatal encephalitis → encephalitic rabies
 In < 20% of cases, causes ascending flaccid paralysis → paralytic rabies
 Incubation period: 4–12 weeks average (7-15 to 60 days)
 Clinical features
o Prodromal symptoms
 Flu-like symptoms (e.g., fever, malaise)
 Locally: pain, paresthesia, and pruritus near the bite site
o Encephalitic rabies (most common type)
 Hydrophobia (Pathognomonic): Rabies patients experience involuntary, painful pharyngeal muscle spasm
when trying to drink; later on in the disease, the sight of water alone may provoke nausea or vomiting.
 CNS symptoms
 Anxiety, agitation, and combativeness alternating with calm periods
 Confusion and hallucinations; Photophobia; Fasciculations (twitching of muscles); Seizures
 ↑ Muscle tone and reflexes with nuchal rigidity
 Autonomic symptoms: e.g., hypersalivation, hyperhidrosis
 Coma and death within days to weeks of the development of neurological symptoms
 The actual cause of death varies: pituitary failure, prolonged seizures, respiratory failure due to involvement
of the respiratory center in the brainstem; hypotension, cardiac arrhythmia or arrest; pneumothorax,
intravascular thrombosis, or secondary infections.
o Paralytic rabies (< 20% of cases)
 Flaccid paralysis, gradually ascending and spreading from bite wound
 Paraplegia and loss of sphincter tone
 Respiratory failure and death: Paralysis of the muscles necessary for breathing and swallowing (bulbar and
respiratory paralysis)
 Diagnostics
o Laboratory diagnosis: Several tests must be combined, as each individual test has limited sensitivity
 Serum
 Non-immunized patient: rabies antibodies
 Immunized patient: rising serum antibodies over a few days
 CSF: findings characteristic of encephalitis
 Skin: biopsy from the back of the neck
 for RT-PCR and immunofluorescence staining

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 
Saliva: RT-PCR for viral RNA, viral culture
o Postmortem brain tissue autopsy (also in suspected animals): Negri bodies (eosinophilic cytoplasmic inclusion
bodies typically found in the cerebellum and hippocampus)
 Treatment

o Rabies post-exposure prophylaxis


Cleaning and debridement, as with all bite wounds

Tetanus shot and antibiotic prophylaxis may be indicated

Nonimmunized patient: postexposure prophylaxis (passive-active immunization)
 Rabies immunoglobulin is given into the site of the wound by injection (passive immunization) Tollwut-
Immunglobulin (z.B. Berirab®) 20 IE/kgKG, Instillation intramuskulär in und um die Wunde herum,
eventuellen Rest an anderer Körperstelle i.m.
 PLUS inactivated rabies vaccine is given IM on days 0, 3, 7, 14 and 28 (active immunization)
 Prior immunization
 Even patients who have been vaccinated against rabies should be treated after exposure!
 Rabies vaccine IM on days 0 and 3.
 No immunoglobulin
 Check antibody titers on day 14.
o Symptomatic encephalitic or paralytic rabies: Palliative treatment (pain management and sedation)
 Prognosis
o Mortality: Symptomatic rabies is almost always fatal.
o Rabies is preventable following exposure to a rabid animal with adequate PEP
 Prevention: Vaccination
o Inactivated (killed) vaccine
o Indications
 People with frequent occupational contact with potentially rabid animals
 Travelers to regions in which rabies is widespread (especially if PEP may not be readily available)

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73. AIDS
 Incidence
o HIV infection: peak incidence between ages 20 and 30
o AIDS: peak incidence approx. age 45
 Pathogen (human immunodeficiency virus)
o Family: Retroviridae, Genus: Lentivirus
o Species
 HIV-1: most common species worldwide (subtype B predominates in industrialized countries)
 HIV-2: restricted almost completely to West Africa
o Structure: icosahedral with a conical capsid and a spiked envelope
 Incubation period: usually 2–4 weeks (up to 10 months)
 Infectiousness: two peaks (1st peak: within the first months after infection; 2nd peak: during AIDS-stage);
transmission is possible at any point in the course of disease
 Routes of transmission
o Sexual: responsible for ∼ 80% of infections worldwide
 Risk for men who have sex with men (MSM): 0.5% for receptive partner
 Risk for male-to-female sex: 0.1% for female partner, 0.05% for male partner
 Coinfection: genital inflammation (e.g., as a result of coinfection with other pathogens such as HPV or genital
herpes) increases local virus concentration and therefore risk of transmission
o Parenteral transmission: Needle sharing: 0.67% per exposure through needle-sharing contact, Needlestick
injuries: 0.36% per injury
o Vertical transmission: from mother to child
 During childbirth (∼ 5–15%)
 Through breastfeeding after birth (∼ 5–20%)
 Pathophysiology
o Initial infection and HIV replication cycle
 HIV enters the body (e.g., via mucosal lesions or via infection of mucosal/cutaneous immune cells.), then
attaches to the CD4 receptor on target cells with its gp120 glycoprotein (binding)
 Cells that have CD4 receptors: T lymphocytes (e.g., T helper cells), macrophages, monocytes, dendritic cells.
 Viral envelope fuses with host cell, capsid enters the cell.
 For fusion, CD4 receptor and a coreceptor (CCR5 in macrophages, and CCR5 or CXCR4 in T-cells) must be
present.
 Viral entry into macrophages via CCR5 mainly occurs during the early stages of infection, while entry via
CXCR4 occurs in later stages.
 Individuals without CCR5 receptors appear to be resistant to HIV, those patients either have a homozygous
CCR5 mutation (substantial resistance) or a heterozygous CCR5 mutation (slower course).
 A virion's RNA is transcribed into dsDNA by viral reverse transcriptase and then integrated into the host's
DNA by viral integrase.
 Viral DNA is replicated and virions are assembled
 Virion repurposes a portion of the cell's membrane as an envelope and leaves the cell (budding) → cell death
o Progression to chronic immunodeficiency
 HIV infects CD4+ lymphocytes, then reproduces and spreads to other CD4+ lymphocytes near the original site
of infection → infection of CD4+ lymphocytes concentrated in specialized lymphoid tissue (e.g., lymph nodes
or gut-associated lymphatic tissue (GALT)) → explosive growth and dissemination→ acute HIV syndrome with
high viral load
 Window period: The time between infection and detectability of HIV antibodies.
 After the acute stage, viral load decreases and remains at roughly that level for approximately 8–10 years
(clinical latency stage)
 During the clinical latency phase, the virus mainly replicates inside the lymph nodes.

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  Increasing loss of CD4+ lymphocytes (especially T cells) impairs immune function and, thereby, facilitates
opportunistic infections and development of malignancies (AIDS). These secondary diseases are usually the
cause of death in individuals with HIV.
 Increased viral load generally leads to a decreased number of CD4+ lymphocytes and vice versa, but the
relation is not linear.

 Clinical features
o Acute HIV infection
 Also referred to as acute retroviral syndrome (ARS) or described as a mononucleosis-like syndrome.
 Fever, Fatigue, Myalgia and arthralgia, Headache
 Generalized nontender lymphadenopathy, Generalized rash
 Gastrointestinal symptoms (nausea, diarrhea, weight loss)
 Oropharyngeal symptoms (sore throat, ulcerations, painful swallowing)
o Clinical latency and AIDS
 Clinical latency: Infected individuals may still be asymptomatic
 AIDS: development of an AIDS-defining condition or a CD4 cell count of < 200 cells/μL in HIV-infected patients
 Non-AIDS-defining conditions (common when CD4+ count is below 500 cells/mm3)
 Chronic subfebrile temperatures, Persistent generalized lymphadenopathy
 Chronic diarrhea (> 1 month)
 Localized opportunistic infections
o Oral candidiasis: creamy, white patches on the mucous membranes of the mouth that can be scraped off
o Vaginal infections (e.g., yeast, trichomonads)
 Oral hairy leukoplakia: lesions that cannot be scraped off located mainly on the lateral borders of the
tongue; triggered by Epstein-Barr virus
 HPV-related: squamous cell carcinoma of the anus (common in men who have sex with men) or cervix
 Skin manifestations (e.g. molluscum contagiosum, warts, exacerbations of psoriasis, shingles)

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  AIDS-Defining Conditions

Stages
o WHO (World Health Organization) classification
 Primary HIV infection: acute retroviral syndrome or asymptomatic
 Clinical stage 1: persistent generalized lymphadenopathy (PGL) or asymptomatic
 Clinical stage 2: e.g., unexplained moderate weight loss (< 10%), recurrent fungal/viral/bacterial infections
 Clinical stage 3: e.g., unexplained severe weight loss (> 10%), unexplained chronic diarrhea (> 1 month),
unexplained persistent fever (≥ 37.6°C intermittent or constant > 1 month), persistent/severe
fungal/viral/bacterial infections, unexplained anemia (< 8 g/dL) and/or neutropenia (< 500 cells/mm3) and/or
chronic thrombocytopenia (< 50,000/μL) for more than 1 month
 Clinical stage 4: AIDS-defining conditions (e.g., Kaposi sarcoma, Pneumocystis pneumonia)
o CDC classification system for HIV: A3, B3 or C1-C3 is considered to have AIDS
Clinical category A Clinical category B
CD4 cell count category Clinical category C
Asymptomatic, Acute HIV Symptomatic conditions,
(normal cell count: 500-1500 cells/mm3) AIDS-defining conditions
or PGL not A or C
(1) ≥ 500 cells/mm3 A1 B1 C1
(2) 200–499 cells/mm3 A2 B2 C2
(3) < 200 cells/mm3 A3 B3 C3
 Diagnostics
o Screening tests
 Combination antigen/antibody tests (first-choice screening test): Detect both HIV antigen (p24 capsid
protein) and anti-HIV antibodies (IgG antibodies against HIV-1/HIV-2) → a negative result essentially rules out
HIV infection (almost 100% sensitivity)
 Antibody-only tests (HIV serology)
o Confirmatory tests: HIV-1/HIV-2 antibody differentiation immunoassay (first-choice confirmatory test): can
detect both HIV-1 and HIV-2 in ∼ 20 minutes and distinguish between the two types
o CBC: possibly lymphocytopenia
o Liver enzymes: if abnormal, rule out coinfection with hepatitis virus (HCV or HBV)

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 Treatment - combined antiretroviral therapy (cART)
o Nucleoside reverse transcriptase inhibitors (NRTI): Zidovudine (ZDV, formerly AZT), Lamivudine (3TC), Abacavir,
Emtricitabine; Tenofovir (nucleotide analog, also called nucleotide reverse-transcriptase inhibitor; NtRTI)
o Nonnucleoside reverse-transcriptase inhibitors (NNRTI): Nevirapine, Efavirenz, Delavirdine
o HIV protease inhibitors (PI): Indinavir, Ritonavir, Nelfinavir
o Integrase inhibitors (INI): Raltegravir, Dolutegravir, Bictegravir, Elvitegravir
o Entry inhibitors: Enfuvirtide (fusion inhibitor), Maraviroc (CCR5-antagonist)
o Recommended regimens
 3 NRTI (e.g., zidovudine, lamivudine, abacavir) OR
 2 NRTI (e.g., lamivudine PLUS abacavir) PLUS
 1 NNRTI (e.g., efavirenz) OR 1 PI (e.g., lopinavir) OR 1 INI (e.g., raltegravir)
 Germany: Tenofovir-Alafenamid + Emtricitabin PLUS Elvitegravir + Cobicistat OR Raltegravir OR Dolutegravir

 Complications
o Immune reconstitution inflammatory syndrome
 Deterioriation of a preexisting opportunistic infection (e.g., PML, Kaposi sarcoma) within 60 days after
initiation of HAART therapy
 Thought to be caused by the restoration of immune function that results in inflammatory reactions at
previously dormant sites of infection.
o AIDS-defining conditions
 For HIV-infected individuals with CD4 < 200 cells/mm3: Pneumocystis jiroveci prophylaxis – TMP/SMZ
 […] with CD4 < 75 cells/mm3: Mycobacterium avium complex prophylaxis – macrolides
 For HIV-infected individuals with CD4 < 50 cells/mm3: Consider CMV prophylaxis - ganciclovir
 Prognosis
o Untreated, HIV leads to death on average 8–10 years after infection
o The average life expectancy of HIV-infected individuals who receive adequate antiretroviral treatment is
approaching that of noninfected individuals of the same age

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 HIV pre-exposure prophylaxis: Emtricitabine + tenofovir disoproxil fumarate (TDF-FTC) OR Emtricitabine +
tenofovir alafenamide (TAF-FTC); ↓ risk of HIV infection from sexual contact by ∼ 99% and injection drug use by
at least 74% when taken as prescribed
 HIV post-exposure prophylaxis: Tenofovir-emtricitabine + dolutegravir OR Tenofovir-emtricitabine + raltegravir
 Prevention
o Patients positive for HIV are hospitalized for treatment in specialized infectious clinic.
o Therapy is conducted by infectionists trained in this direction.
o All infected shall be communicated to the Ministry of Health and WHO.
o Medical staff must work with masks, gloves, goggles and protective clothing.
o Restrictive measures are not applied to contact persons compared to seropositives.
o In Bulgaria Ministry of Health has developed and implements the HIV / AIDS Prevention and Control Program.
o Across the country in RHI in big cities works KABKIS/ office for anonymous and free AIDS monitoring and
research
o WHO recommends options for prevention of MTCT mother-to-child transmission (PMTCT), which includes
providing ARVs to mothers and infants during pregnancy, labour and the post- natal period, and offering life-
long treatment to HIV-positive pregnant women regardless of their CD4 count.

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74. Sepsis
 Sepsis: a severe, life-threatening condition that results from a dysregulation of the patient's response to an
infection, causing tissue and organ damage and subsequent organ dysfunction
 Septic shock: a sepsis syndrome accompanied by circulatory and metabolic abnormalities that can significantly
increase mortality
o Persistent hypotension: Vasopressors are required to maintain MAP ≥ 65 mm Hg.
o Persistent lactic acidosis: lactate > 2 mmol/L (18 mg/dL) despite adequate fluid resuscitation
 Systemic inflammatory response syndrome (SIRS criteria): a constellation of physiological and immune-
mediated reactions of the body to an infection or noninfectious insult (e.g., an acute inflammatory process or
trauma). At least 2 of the following 4 criteria are required to define SIRS:
o Temperature > 38°C or < 36°C
o Heart rate > 90/min
o Respiratory rate > 20/min or PaCO2 < 32 mm Hg
o White blood cell count > 12,000/mm3 or < 4,000/mm3 or > 10% immature bands
 Sepsis: SIRS criteria PLUS a suspected or confirmed underlying infection
 Severe sepsis: sepsis PLUS dysfunction of at least one organ or system
 Multiple organ dysfunction syndrome (MODS)
o Progressive and potentially reversible failure in the physiologic function of several organs and/or systems
o The more organs that are affected, the greater the mortality risk
 Bacteremia: the presence of bacteria in the bloodstream, confirmed on blood cultures
 Etiology
o Common sources of sepsis:
 Respiratory: pneumonia (most common cause of sepsis)
 Abdominal infections (e.g., intraabdominal abscess)
 Genitourinary: pyelonephritis
 Skin and soft tissue infections
 Implanted devices (e.g., central venous catheter, port-a-cath, urinary catheter, endotracheal tube)
o Pathogens
 Bacterial: gram-negative bacteria (E.coli, E. coli, P. aeruginosa, K. pneumoniae, H. influenzae, Acinetobacter,
Enterobacter); gram-positive bacteria (S. aureus, S. pneumoniae, S. viridans)
 Fungal, viral, or parasitic infection (rare)
o Common risk factors
 Age: < 1 year or > 75 years
 Primary comorbidities (diabetes mellitus, cirrhosis, community acquired pneumonia, bacteremia, alcoholism)
 Immunosuppression (neutropenia, corticosteroid treatment)
 Intensive care or prolonged admission (nosocomial infections)
 Recent antibiotic or corticosteroid treatment
 Invasive medical devices (e.g., endotracheal tubes, intravenous lines, urinary catheters)
 Pathophysiology
o Local activation of inflammatory mediators (complement system, mast cells, macrophages) results in vessel
dilation and further release of proinflammatory cytokines (esp. TNFα, IL-1).
o Generalized endothelial disruption → capillary leak → generalized edema due to a shift of intravascular fluid
and albumin into the surrounding tissue
o Intravascular hypovolemia → excessive triggering of the extrinsic coagulation cascade → disseminated
intravascular coagulation (DIC) and microvascular thrombosis
o Decreased oxygen utilization and tissue ischemia → widespread cellular injury → organ dysfunction (commonly
multisystem)
 Clinical features
o Fever, chills, and diaphoresis

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 o Tachycardia, Tachypnea
o Features of organ dysfunction
 CNS impairment: altered mental status
 Cardiovascular failure: hypotension
 Coagulopathy → disseminated intravascular coagulation → petechiae, purpura
 Liver failure: jaundice
 Kidney failure: oliguria
 Respiratory failure: symptoms of acute respiratory distress syndrome (ARDS)
o Additionally in septic shock
 Hypotension (MAP < 65 mm Hg)
 Initially warm skin and normal capillary refill time (warm shock) → cold cyanotic, pale, or mottled skin with
prolonged capillary refill time (cold shock)
o Features of the primary infection; Generalized edema (capillary leak)
 Diagnostics
o serum lactate and blood cultures (at least two sets)
 Elevated lactate reflects hypoperfusion and is associated with worse outcomes
o CBC: variable findings; Leukocytosis or leukopenia; Thrombocytosis or thrombocytopenia
o CRP, procalcitonin: typically elevated
o BMP and electrolytes
 Renal function: ↑ BUN and ↑ creatinine
 Glucose: hyperglycemia, hypoglycemia
 Electrolyte derangements
o Liver chemistry and synthetic function tests: hyperbilirubinemia, ↑ INR, ↑ ALT, ↑ AST
o Coagulation panel, D dimer: ↑ prothrombin time, ↑ activated partial thromboplastin time, ↓ antithrombin III,
↑ D dimer may be present (see “Disseminated intravascular coagulation”)
o MiBi: Urinalysis and urine culture, Sputum culture, Consider also: CSF, wound secretion, tissue/fluid
o Imaging: CXR (Pneumonia); US, CT, Echo
 Treatment - Hour-1 bundle for sepsis: lactate + cultures + fluids + vasopressors + antibiotics
o Initial resuscitation: rapid crystalloid infusion of 30 mL/kg  Start immediately (within the first hour of
presentation) and complete within 3 hours
o Vasopressors: persistent hypotension during or after fluid resuscitation to maintain Mean arterial pressure ≥ 65
mm Hg (estimated as ⅓ systolic pressure + ⅔ diastolic pressure)
 First-line: norepinephrine (increasing systemic vascular resistance and inotropy)
 Second-line: if MAP persistently low - Add vasopressin (synthetic ADH analog)
o Antibiotic therapy
 Unknown risk factors: Vancomycon PLUS one of the following:
 Broad-spectrum carbapenem: Meropenem, Doripenem
 Extended-range penicillin/B lactamase inhibitor: Piperacillin/tazobactam, Ticarcillin/clavulanate
 Third-generation (or higher) cephalosporin: Cefotaxime, Ceftriaxone, Ceftazidime, Cefepime
 At risk for specific pathogens
 MRSA: Vancomycin
 Resistant gram-negative organisms (e.g., Pseudomonas)
o At least one of the following: A carbapenem (e.g., meropenem), Piperacillin/tazobactam, Cefepime
o Consider the addition of one of the following: Polymyxin B, Colistin, An aminoglycoside (e.g., gentamicin,
amikacin)
 Anaerobes: Consider adding metronidazole
o Source control
 Abscess drainage
 Debridement of infected necrotic tissue (e.g., necrotizing fasciitis)

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  Removal of infected devices
 Operative management of surgical pathologies (e.g., intraabdominal abscess, gastrointestinal perforation,
ischemic bowel, volvulus, cholecystitis, cholangitis)
 Nephrostomy/drain placement in obstructive pyelonephritis/abscess
 Pseudosepsis:
o Pseudosepsis is a common cause of misdiagnosis in hospitalized patients
o The most common causes of pseudosepsis include gastrointestinal hemorrhage, pulmonary embolism, acute
myocardial infarction, acute pancreatitis, diuretic-induced hypovolemia, and relative adrenal insufficiency.
o Patients with pseudosepsis may have fever, chills, leukocytosis, with or without hypotension

SOFA score (≥ 2 points): overall mortality risk ∼ 10%

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75. Fever of unknown origin (FUO)
 Definition: temperature elevation > 38.3°C (101°F) lasting ≥ 3 weeks without a definitive diagnosis despite
thorough clinical investigation
 Classification
o Classical FUO
 Criteria: according to the definition + present at ≥ 3 outpatient visits or ≥ 3 days in hospital
 Causes: infection, autoimmune disease, and malignant neoplasm
o Nosocomial FUO
 Criteria: new temperature elevation > 38.3°C (101°F) in patients who have been admitted to the hospital at
least 24 hours ago present at ≥ 3 days of evaluation
 Causes: surgery, medications, intravascular devices, DVT, pulmonary embolism, Clostridium difficile
enterocolitis, sinusitis
o HIV-associated FUO
 Criteria: according to the definition but lasting > 4 weeks for outpatients and > 3 days for inpatients with
confirmed HIV infection
 Causes: CMV, Pneumocystis pneumonia, Mycobacterium avium-intracellulare, Kaposi sarcoma, and
lymphoma
 Diagnostic approach
o The patient history should be taken and physical examination should be performed several times as the
inflammatory process develops.
o The pattern of fever should be documented and analyzed.
o History should include:
 Contact with animals
 Travel history
 Diet history
 Immunosuppression
 Family history
 Social and sexual history
 Occupational history
 Drugs and medications
o Specific investigations should be guided by physical
findings and clinical suspicion.
o If there are no diagnostic clues, the following tests should
be performed:
 CBC with differential
 ESR and C-reactive protein
 Electrolytes
 Liver function tests
 At least three sequential blood cultures
 Urine culture, Urinalysis
 PPD test
 Chest X-ray
o If there are no findings from the tests above, abdominal and chest CT should be performed.
 Patients with a negative workup generally have a favorable prognosis, with resolution of fever over time.
Infections and cancer account for the majority of cases of FUO!
Severe febrile neutropenia is life-threatening because of an impaired neutrophil-mediated inflammatory response to
bacterial infections. After drawing blood and urine cultures, immediate empiric antibiotic therapy should be
initiated.

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Neutropenic fever (Febrile neutropenia)
 Neutropenia: ANC < 500/μL OR expected to decrease to < 500/μL within 48 hours
 Fever: single oral temperature ≥ 38.3°C (101°F) OR ≥ 38°C (100.4°F) for at least 1 hour
 Diagnostics
o Laboratory studies
 CBC with differential, Blood cultures x 2 sets (at least), Culture from any suspected site of infection, Urinalysis
with reflex urine culture
 BMP, LFTs, Serum lactate, Blood glucose, ESR/CRP, Procalcitonin, Type and screen, Coagulation studies (e.g.,
INR, PTT)
o Imaging
 CXR for patients with respiratory symptoms
 Further imaging (e.g., CT) should be guided by history and clinical findings.
 Common bacterial pathogens in neutropenic fever
o G+: Coagulase-negative staphylococci; Staphylococcus aureus, including MRSA; Viridans group streptococci,
Streptococcus pneumoniae, Streptococcus pyogenes
o G-: Escherichia coli, Klebsiella species, Enterobacter species, Pseudomonas aeruginosa, Citrobacter species,
Acinetobacter species, Stenotrophomonas maltophilia
 Treatment

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 76. Malaria
 Distribution
oMost cases of malaria occur in tropical Africa (West and Central Africa).
o Transmission also occurs in other tropical and subtropical regions such as Asia (e.g., India, Thailand, Indonesia),
and Latin America (e.g., Brazil, Colombia)
 Pathogen: Plasmodia, Eukaryotic parasites (belonging to the Sporozoa group)
Different Geographic distribution Fever spikes due to
species of Disease rupture of mature
plasmodium schizonts↓

Plasmodium  Vivax: widespread in tropical and subtropical

vivax areas, range extends into temperate areas,
 Tertian malaria (usually  Every 48
relatively uncommon in Africa
Plasmodium less severe) hours
 Ovale: primarily tropical Africa, especially
ovale western coast
Plasmodium  Quartan malaria (usually  broad, but spotty geographical distribution  Every 72
malariae less severe) hours

Plasmodium  Falciparum malaria (most  widespread, but primarily in tropics and

severe form; also known as subtropics  Irregular
falciparum
malignant tertian malaria)
Plasmodium  Southeast Asia
 Quotidian malaria  Irregular
knowlesi
 Transmission
o Vector: the female Anopheles mosquito, blood transfusion,
needle sharing, organ transplantation, transplacental
o Host: humans
 Partial resistance against malaria
o Carriers of sickle cell mutation
o Individuals with either certain Duffy antigens or no Duffy
antigens are resistant to P. vivax and P. knowlesi
o Other hemoglobinopathies (e.g., beta-thalassemia, HbC, HbS,
HbE, HbF, G6PDD)
o Infection with malaria subsequently leads to the development
of specific Plasmodium antibodies that result in partial
immunity for a limited amount of time (less than a year)
 Life cycle of Plasmodium
o sexual development in humans
 Transmission of Plasmodium sporozoites via Anopheles
mosquito bite → sporozoites travel through the bloodstream
to the liver of the host
 Liver: sporozoites enter hepatocytes → sporozoites multiply
asexually → schizonts are formed containing thousands of
merozoites → release of merozoites into the bloodstream
 Circulatory system (two possible outcomes)
 Merozoites enter erythrocytes → maturation to trophozoites → red cell schizonts are formed containing
thousands of merozoites → release of merozoites into the bloodstream (which causes fever and other
manifestations of malaria) → penetration of erythrocytes recurs
 Merozoites enter erythrocytes → differentiation into gametocytes (male or female)

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 o Sexual development in female Anopheles mosquito
 A mosquito bites an infected human and ingests gametocytes → gametocytes mature within the mosquito
intestines → sporozoites are formed and these migrate to the salivary glands → transmission of sporozoites
to humans via mosquito bite

 Incubation period: 7-30 days

 Clinical features
o Infection → asymptomatic parasitemia → uncomplicated illness → severe malaria → death
 Asymptomatic parasitemia: Especially in endemic regions, cases of asymptomatic plasmodia carriers are
reported
 Tertian and quartan malaria are associated with less severe symptoms, the involvement of fewer organs
(rarely CNS or gastrointestinal symptoms), and a markedly lower risk of severe malaria.
 Following the successful treatment of tertian malaria, dormant P. ovale or P. vivax forms (hypnozoites) may
persist within the liver and cause reinfection (relapse) after months or even years.
o General symptoms
 Flu like symptoms, headache; Diaphoresis (excessive sweating)
 High fever
 Tertian malaria: periodic fever spikes every 48 hrs
 Quartan malaria: periodic fever spikes every 72 hrs
 Falciparum malaria (malignant tertian malaria): irregular fever spikes without a noticeable rhythm
o Organ-specific
 Blood: Thrombocytopenia: increased bleeding risk; Hemolytic anemia: weakness, paleness, dizziness
 Gastrointestinal: Nausea, vomiting; Diarrhea, abdominal pain
 Liver: hepatosplenomegaly, discrete jaundice
o Severe malaria
 Description: potentially fatal manifestation or complication of malaria
 Etiology: most commonly a result of falciparum malaria
 Pathophysiology: infected erythrocytes occlude capillaries, which can lead to severe organ dysfunction
 Manifestations
 Kidneys: flank pain, oliguria, hemoglobinuria, acute kidney injury

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  Cerebral: hallucinations, confusion, impaired consciousness, seizures, or even coma
 Cardiopulmonary: heart failure, pulmonary edema, ARDS, shock
 Hematologic: severe anemia, coagulation disorders
 Metabolic: hypoglycemia, metabolic acidosis
 Hyperparasitemia: > 5% of RBC are infected with plasmodia
o malaria paroxysm comprises three successive stages
 15-to-60 minute cold stage characterized by shivering and a feeling of cold
 2-to-6 hour hot stage, in which there is fever, sometimes reaching 41°C, flushed, dry skin, and often
headache, nausea, and vomiting
 2-to-4 hour sweating stage during which the fever drops rapidly and the patient sweats
 Diagnostics
o CBC
 Hemolytic anemia: ↓ Hb, ↓ haptoglobin, ↑ LDH, ↑
indirect bilirubin, ↑ reticulocytes
 Thrombocytopenia, Possibly leukocytopenia
o Blood smear: confirms suspected cases by visualizing parasites
within RBCs
 Best initial test: thick blood smear
 High sensitivity
 Detects the presence of parasites
 Confirmatory testing: thin blood smear
 Lower sensitivity than thick blood smear, but higher
specificity
 Parasites are visible within red blood cells since the morphology of erythrocytes is preserved
 Allows determination of Plasmodium species
 Schuffner granules (fine, brick-red dots) within the cytoplasm of P. vivax and P. ovale
 Evaluation of negative test results
 If parasite densities are very low, malaria may be initially undetectable.
 If an initial test result is negative, blood smears should be repeated three times every 12–24 hours
 If all three sets are negative, malaria can be ruled out.
o Rapid diagnostic tests (RDTs)
 Determination of specific malaria antigens, e.g., HRP2, pLDH, and aldolase
 Benefits: quick determination of malaria infection in areas lacking high quality malaria microscopy
 All RDT results should be confirmed via microscopy (if available).
o Serological tests
 Not appropriate for acute diagnosis of malaria because antibodies are undetectable for 1–2 weeks after
primary infection
 Positive serological results indicate prior exposure to Plasmodium
 Differential diagnosis: Ebola and other viral hemorrhagic fevers (eg, Dengue hemorrhagic fever, Marburg
hemorrhagic fever), Rickettsial infections (eg, African tick fever, ehrlichiosis), Yellow fever
Treatment Tertian malaria
 Chloroquine OR hydroxychloroquine
Chloroquine-sensitive  PLUS primaquine or tafenoquine: to eradicate
hypnozoites of P. vivax and P. ovale and prevent relapse
P. vivax,  Artemether-lumefantrine OR atovaquone-proguanil
P. ovale  OR quinine PLUS doxycycline OR tetracycline
Chloroquine-resistant  OR mefloquine (if no other options are available)
 PLUS primaquine OR tafenoquine to eradicate
hypnozoites of P. vivax and P. ovale and prevent relapse

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 Treatment Quartan malaria
 Chloroquine or hydroxychloroquine
 OR atemether-lumefantrine OR atovaquone-proguanil
P. malariae, P. knowlesi  OR quinine PLUS doxycycline OR quinine PLUS
tetracycline
 OR quinine PLUS clindamycin OR mefloquine
Severity of disease Region Treatment
 Chloroquine-sensitive  Chloroquine OR hydroxychloroquine
 Artemether-lumefantrine
Uncomplicated  OR atovaquone-proguanil
falciparum malaria  Chloroquine-resistant  OR mefloquine OR quinine PLUS doxycycline
 OR quinine PLUS tetracycline
 OR quinine PLUS clindamycin
 IM or IV artesunate
 Reassess 4 hours after the third dose and if the parasite
density is ≤ 1% on blood smear and the patient tolerates
oral medication, switch to:
Severe falciparum o Oral artemether-lumefantrine (drug of choice)
 All regions o OR atovaquone-proguanil
malaria
o OR quinidine (in the US; quinine elsewhere) PLUS
doxycycline or clindamycin
o Mefloquine (if no other options are available)
 Intensive care and supportive therapy (lowering fever,
avoiding hypoglycemia) are essential.
 Blackwater fever is the syndrome of massive hemolysis (with visible hemoglobinuria) in the setting of severe
malaria, glucose-6-phosphate dehydrogenase deficiency (G6PDd), and quinine treatment. Because malaria is
also associated with hemolysis, the relative roles of quinine and G6PD are unclear
 Prevention
o Mosquito bite prevention: avoid exposure (net, cloths, repellent), mosquito control
o Malaria prophylaxis: initiated before traveling to regions with a high risk of malaria
 Areas with P. falciparum
 If chloroquine-resistant P. falciparum (most malaria endemic regions): atovaquone-proguanil, doxycycline,
mefloquine
 If chloroquine-sensitive P. falciparum: chloroquine
 Areas without P. falciparum (some areas of Central/South America, Mexico, China, South Korea):
primaquine
 cannot prevent infection but instead suppresses the course of the disease and its symptoms by killing the
parasite within the host before it can cause severe disease
o Standby emergency treatment: Depending on the risk, either prophylactic or standby emergency treatment
may be recommended
 Atovaquone-proguanil, Artemether-lumefantrine
 Chloroquine with limitations: there are now many chloroquine-resistant Plasmodium strains with
membrane pumps that lower intracellular chloroquine concentrations

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77. Toxoplasmosis
 Pathogen: Toxoplasma gondii, an obligate intracellular, single-celled protozoan
 Route of transmission
o Oral ingestion: The oocysts are excreted in the feces of cats (final host) and are orally ingested by other
mammals such as humans, hoofed animals, and birds (intermediate hosts). Primary modes of transmission
include the following:
 Cat feces
 Raw or insufficiently cooked meat (most common)
 Unpasteurized milk (especially goat milk)
o Transplacental transmission; Via organ transplantation or blood transfusion (check recipient and donor)
 Incubation time: 3 days to 3 weeks
 Clinical features
o Immunocompetent patients
 Mainly asymptomatic (90% of cases)
 Symptomatic (< 10% of cases): mononucleosis-like symptoms with bilateral cervical adenopathy (but
negative heterophile antibody test)
 Lifelong immunity following infection
o Immunosuppressed patients (e.g., AIDS): primary infection or reactivation in previously infected individuals
 Cerebral toxoplasmosis (the most common neurological AIDS-defining illness)
 Ocular toxoplasmosis
 Cerebral toxoplasmosis
o Description
 Caused by reactivation of T. gondii in immunocompromised individuals
 Most common neurological disorder associated with AIDS (considered an AIDS-defining condition)
o Clinical features (symptomatic usually if CD4 count < 100 cells/μL)
 Fever, Headache, Mental status changes, Seizures, Focal neurological deficits
o Diagnostics
 CT or MRI with contrast: multiple ring-enhancing lesions (brain abscesses) predominantly in the basal
ganglia and/or the subcortical white matter
 Serology: detection of anti-toxoplasma IgG antibodies
 Biopsy: rarely performed due to the risk associated with obtaining a brain specimen
 Toxoplasma tachyzoites and bradyzoites
 Chronic inflammation and necrosis of brain tissue
o Prophylaxis
 Adequate HIV treatment (cART)
 TMP/SMX
 Ocular toxoplasmosis/ Chorioretinitis: Inflammation of the retina and choroid
o Acute toxoplasmosis (current focal infection): yellow-white retinal lesion, marked vitreous reaction,
concomitant vasculitis, defects in the visual field at the site of inflammation
o Previous toxoplasmosis (previous focal infection): formation of scars with white atrophic areas and surrounding
dark, sharply-defined pigmentation
o Recurrent focal infection usually develops at chorioretinal scars.
o Congenital toxoplasmosis is almost always accompanied by the formation of scars of the macula and
corresponding visual impairment.
 Diagnostics
o Serology
 IgM antibody test: positive within first week of acute infection
 IgG antibody test: positive 2 weeks following infection and remains positive for life
o CT/MRI of the brain for suspected cerebral toxoplasmosis

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 Treatment
o Immunocompetent patients usually do not require treatment.
o Medical therapy
 Indications
 Immunosuppression (e.g., HIV)
 Infected pregnant women (for both pre-existing and new infections)
 Severe symptoms in immunocompetent patients
 First choice
 Spiramycin if maternal infection before the 18th week of pregnancy is suspected/confirmed and infection
of the fetus is not suspected/documented
 Combination treatment with pyrimethamine, sulfadiazine, and leucovorin (folinic acid) in all other cases
 Duration: minimum of 4–6 week
 Congenital toxoplasmosis
o Transplacental transmission: First trimester: ∼ 15%, Third trimester: ∼ 70%
o Clinical features
 First trimester
 Increased risk of premature birth and spontaneous abortion
 Classic triad of toxoplasmosis
o Chorioretinitis (a form of posterior uveitis)
o Diffuse intracranial calcifications
o Hydrocephalus
 Possible other nonspecific clinical features
o Petechiae and purpura (blueberry muffin rash), Fever, Jaundice, Hepatosplenomegaly,
o Lymphadenopathy, Pneumonitis, Seizures, Macrocephaly, Thrombocytopenia
 Second or third trimester: subclinical or mild toxoplasmosis
 Sequelae of congenital toxoplasmosis
 Epilepsy, Intellectual disability
 Visual disabilities (chorioretinitis → increased risk of retinal lesions, cataracts, and glaucoma)
 Sensorineural hearing loss
 Prevention: no handling of cat litter box or eating of any foods made from unpasteurised milk in pregnancy

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78. Leishmanioses
 Distribution: endemic in the Mediterranean region, Africa, India, southwest and central Asia, South and Central
America
 Pathogen: Leishmania donovani (protozoan)
o Cutaneous leishmaniasis
 Americas: L. mexicana, L. braziliensis, L. guyanensis, L. panamensis (L. braziliensis, L. guyanensis, L.
panamensis can also cause mucosal leishmaniasis)
 Asia/Africa: L. major, L. tropica. L. aethiopica
o Visceral leishmaniasis: L. donovani, L. infantum, L. chagasi
 Transmission
o Vector: phlebotomine sandflies
o Reservoir: mammals (especially dogs, humans, and rodents)
o Indian VL: Anthroponotic infection humans as reservoir; Mediterranean VL: Zoonotic infection, dogs reservoir

Cutaneous leishmaniasis
 Clinical Features
o Localized cutaneous leishmaniasis
 Incubation period: weeks to months
 Manifestation: solitary or multiple reddish macules/papules around the
sandfly bite that quickly increase in size and develop central ulceration
o Mucosal leishmaniasis
 Some Leishmania subtypes (e.g., L. braziliensis, L. guyanensis, L.
panamensis) cause mucosal leishmaniasis, which can develop months to
years after cutaneous leishmaniasis that was not treated properly
 Manifestation: commonly affects the nasopharynx (mucosal bleeding, nasal blockage)
 Diagnostics: Detection of the pathogen in skin biopsy
o Microscopy: macrophages that contain amastigotes, the intracellular, nonmotile form of Leishmania (appear as
ovoid inclusions)
o PCR
 Treatment manage clinical symptoms  parasite often persists despite the best available treatment.
o Uncomplicated disease (no immunosuppression, small lesions, no mucosal involvement)
 No systemic treatment
 Local treatment (cryotherapy, thermotherapy, or topical paromomycin) for skin lesions that do not heal
spontaneously.
o Complicated disease (mucosal involvement, numerous lesions, immunosuppression)  see visceral below
o Treatment reduces the recurrence rate of cutaneous leishmaniasis, accelerates the healing of lesions, and
reduces the risk of dissemination and incidence of mucosal leishmaniasis

Visceral leishmaniasis
 Incubation period: 2-6 months/ 3 weeks – 18 months
 Clinical features
o Many patients are asymptomatic.
o Kala-azar (Hindi for “black fever,” in reference to the darkening of the skin it can cause in Indian type)
 Usually insidious progression; Flu-like symptoms, spiking fevers; Weight loss
 Lymphadenopathy; Hepatosplenomegaly; Ascites and edema; Pancytopenia
 Possible darkened or gray skin color (especially on the palms and soles)
 Immunosuppression may lead to secondary bacterial infections in advanced disease E.g., pneumonia, otitis
media, sepsis, mucosal infections
 highly fatal without treatment!

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 o Mediterranean
 Risk groups: children (2-5 y.), adults with immunodeficiency (AIDS)
 Leading sympthoms - anemia and pale skin (“old wax”)
 major peripheral lymph node enlargement
 everely enlarged abdomen (organomegaly + ascites) with thin extremities
 Diagnostics
o Laboratory tests
 Hemolytic anemia
 Neutropenia, eosinopenia, thrombocytopenia
o Detection of pathogen
 Microscopy of tissue biopsy (e.g., bone marrow, spleen, lymph nodes, liver) with visualization of macrophages
with amastigotes (Giemsa staining + culture)
 Immunological methods: ELISA, Antigen coated dipsticks test, Direct agglutination test (DAT)
 PCR
 Treatment
o Liposomal Amphotericin B is the preferred monotherapy in Europe, North America, and South America
 3-4 mg/kg KG/Tag an den Tagen 0, 1, 2, 3, 4 und 10
o Other drugs that may be used include:
 Sodium stibogluconate
 Miltefosine: 1,5-2,5 mg/kg KG/Tag p.o. 28 days
 Paromomycin

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79. Urogenital trichomoniasis
 Pathogen: Trichomonas vaginalis
o Anaerobic, motile protozoan with flagella
o Does not encyst and, therefore, does not survive well outside the human body
 Transmission: sexual
 Incubation period: 5-28 days
 Clinical features 70% of infected individuals are asymptomatic
o Foul-smelling, frothy, yellow-green, purulent discharge
o Vulvovaginal pruritus, burning sensation, dyspareunia, dysuria, strawberry cervix (erythematous mucosa with
petechiae)
o In men: mild to severe urethritis, complicated with prostatitis. Discharge (purulent to mucoid in character),
dysuria, and urethral pruritus. Some patients report pain in the urethra, testicular pain, or lower abdominal
pain.
 Diagnostics
o Saline wet mount of vaginal smear: motile trophozoites with multiple flagella
o If wet mount is inconclusive, perform culture/antigen detection test/PCR
o (pH of vaginal discharge > 4.5)
 Treatment
o Oral metronidazole OR tinidazole for the patient and sexual partner(s)
 Metronidazole 1–2 g p.o. als Einmaldosis oder 500 mg p.o. 1-0-1, Dauer 7 Tage
o Check for other sexually transmitted infections

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80. Amebisasis
 Occurence: E. histolytica is very common in tropical and subtropical regions (e.g., Mexico, Southeast Asia, India)
and affects more than 50 million people worldwide. Amebic infection is relatively rare in the US
 Pathogen: Entamoeba histolytica, a protozoan
 Transmission
o Fecal-oral
 Amebic cysts are excreted in stool and can contaminate drinking water or food
 Transmission may also occur through sexual contact.
o Infection typically occurs following travel to endemic regions such as the tropics and subtropics.
 Pathophysiology
o Life cycle: ingestion of mature cysts → excystation in the small intestine → cysts divide into 4 and then 8 →
noninvasive colonization of the colon by trophozoites (may lead to intestinal and extraintestinal disease) →
trophozoites encyst → the cysts are excreted (along with trophozoites) → cysts are reingested by the same
patient or spread to another individual.
o Stages
 Cyst stage: Cysts are very resilient (even against gastric acid) and are able to survive outside the host for
months.
 Vegetative stage: trophozoite formation
 Trophozoites can produce proteolytic enzymes that allow them to invade the intestinal submucosa. They
can then enter the bloodstream where they consume erythrocytes and disseminate to target tissues like the
liver via the portal system.
 Incubation period
o Intestinal amebiasis: 1–4 weeks
o Extraintestinal amebiasis: a few weeks to several years
 Clinical features
o Intestinal amebiasis (Amebic dysentery)
 Loose stools with mucus and bright red blood
 Painful defecation, tenesmus, abdominal pain, cramps, weight loss, and anorexia
 Fever in 10–30% of cases and possible systemic symptoms (e.g., fatigue)
 High risk of recurrence, e.g., through self-inoculation (hand to mouth)
 A chronic form is also possible, which is clinically similar to inflammatory bowel disease.
o Extraintestinal amebiasis
 Mostly acute onset of symptoms; subacute courses are rare
 In 95% of cases: amebic liver abscess, usually a solitary abscess in the right lobe
 Fever in 85–90% of cases (compared to amebic dysentery)
 RUQ pain or pressure sensation; Chest pain, pleuralgia
 Diarrhea precedes only a third of all cases of amebic liver abscesses.
 In 5% of cases: abscesses in other organs (e.g., especially the lungs; in rare cases, the brain), with
accompanying organ-specific symptoms
 Diagnostics
o Intestinal amebiasis
 Stool analysis
 Microscopic identification of cysts or trophozoites in fresh stool (must be warm and analyzed ASAP)
o Trophozoites often contain ingested erythrocytes; Cysts contain up to four nuclei
 The following tests confirm the microscopic findings (important since E. histolytica and Entamoeba dispar
are morphologically identical):
o EIA or coproantigen ELISA; Molecular methods: e.g., PCR
 Stool microscopy is not sensitive, especially in later phases, so at least three stool samples should be
examined before reporting a negative result (wet mount, iodine staining)

160
  Colonoscopy with biopsy: flask-shaped ulcers
o Extraintestinal amebiasis
 Serological antibody detection
 Aspiration of abscesses: shows brown fluid/pus (exudate resembles anchovy paste)
 In amebic hepatic abscess
 Liver function tests: ALP, AST, ALT, bilirubin slightly elevated
 Imaging (US, CT/MRI): shows a solitary lesion, typically in the right lobe of the liver
 Treatment
o Asymptomatic intestinal amebiasis
 No treatment in endemic areas
 In nonendemic areas
 Luminal agents such as paromomycin, diloxanide, or iodoquinol
 Goal: To prevent the development of invasive disease and the shedding of cysts.
o Symptomatic intestinal amebiasis and invasive extraintestinal amebiasis
 Initial treatment with a nitroimidazole derivative such as metronidazole or tinidazole to eradicate invasive
trophozoites
 Followed by a luminal agent (e.g., paromomycin, diloxanide, or iodoquinol) to eradicate intestinal cysts and
prevent relapse
o Aspiration: ultrasound or CT-guided puncture of complicated liver abscesses at risk for perforation
 Indications: Localized in the left lobe, Pyogenic abscess, Multiple abscesses, Failure to respond to
pharmacotherapy
o Surgical drainage: should generally be avoided, but may be indicated for inaccessible abscesses or ruptured
abscesses in combination with peritonitis
 Complications
o Intestinal amebiasis
 Fulminant or necrotizing colitis
 Toxic megacolon → colon rupture
 Ameboma: Annular colonic granulation
leads to a local lesion of the bowel wall.
 Fistula formation (e.g., rectovaginal)
o Extraintestinal amebiasis
 Secondary infection → pyogenic abscess
 Abscess rupture → peritonitis
 Dissemination, possibly resulting in a
brain abscess
 Direct extension to the pericardium or
pleura
 Prevention
o Unpeeled fruits or vegetables should not
be consumed if there is a potential risk of
contamination by Entamoeba histolytica
cysts (e.g., endemic region with low
hygiene standards).
o Even chlorinated water can contain high
concentrations of amebae; therefore,
water should be boiled before use.

161
81. Lambliosis/ Giardiasis, blastocystosis, cryptosporidiosis
Giardiasis
 Pathogen: Giardia lamblia (also known as Giardia intestinalis or duodenalis), a protozoan
 Transmission
o Waterborne: from drinking recreational water (e.g., lakes, rivers, ponds, swimming pools)
 Swallowing cysts in contaminated water → entry of Giardia into the gastrointestinal tract
 Most commonly affects hikers or campers
o Fecal-oral (e.g., through food handlers, people in daycare and nurseries, oral-anal sexual contact): Giardia cysts
are passed into the environment from the feces of infected people and animals (beavers, dogs, cats, rodents)
o Infection is more likely to occur after traveling to endemic regions such as the tropics, subtropics, and North-
American mountain regions
 Life cycle
o Giardia have 2 stages in the life cycle.
 Trophozoite: active form of the pathogen that multiplies, lives within the host's body
 Morphology: long oval shape with two nuclei and four pairs of flagella that resemble a kite
 Cysts: excreted, infectious form of the pathogen, able to survive in moist environments
 Morphology: oval, four nuclei
o Ingestion of cysts → excystation and conversion to trophozoite form → rapid multiplication, adhesion to
intestinal walls → encystation in large bowel → excretion of cysts → possible reinfection
 Mechanism:
o Although several theories exist, it is commonly suspected that infection with Giardia leads to impaired function
and structure of intestinal tissue, resulting in malabsorption and diarrhea.
o IgA deficiencies (e.g., selective IgA deficiency, X-linked agammaglobulinemia, common variable
immunodeficiency) increases susceptibility to giardiasis because of the disruption of gastrointestinal protective
barrier.
 Clinical features
o Diarrhea: foul-smelling, voluminous, frothy,
and fatty stools (stools tend to float and do
not appear bloody)
 May lead to dehydration
o Excessive gas (flatulence, bloating), abdominal
pain, and cramps
o Fatigue, nausea/vomiting, anorexia,
malabsorption
o Can be asymptomatic
 Diagnostics
o Stool analysis: microscopic confirmation of
cysts or multinucleated trophozoites
o Immunoassay: detection of Giardia lamblia
antigens in stool
o Gastroduodenoscopy: confirms trophozoites
in duodenal fluids, but generally not indicated
 Treatment
o Metronidazole 250-500 mg p.o. 2–3×/Tag für
5–7 Tage
o Tinidazole (2g single oral dose)
o Alternatives: nitazoxanide, albendazole, or
mebendazole

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Blastocystosis
 Pathogen: Blastocystis species, taxonomy and pathogenicity uncertain
o Subtypes 1 to 4, and particularly subtype 3, are most frequently found in humans
 Transmission: ingestion of infective cysts, excystation occurs in the large intestine. Cysts then develop into
vacuolar forms and undergo encystation before being excreted in stool
 Reservoir: other primates, mammals, rodents, and birds
 Clinical Features (role of Blastocystis in causing disease remains controversial)
o acute or chronic diarrhea, bloating, flatulence, abdominal cramps, and fatigue
o maybe Irritable bowel syndrome (IBS), refractory
ulcerative colitis, recurrent megacolon, and invasive
colonic disease
o Extraintestinal manifestations: generalized urticaria
and iron-deficiency anemia during pregnancy
 Diagnostics
o PCR
o stool sample microscopy with trichrome stain

Cryptosporidiosis
 Pathogen: Cryptosporidium parasite (e.g. Cryptosporidium parvum – zoonotic, C. hominis - anthroponotic)
 Transmission: ingestion of infected food or water
 Clinical Features
o mild, self-limited diarrhea about a week after infection in immunocompetent patients
o more severe in immunocompromised individuals, causing potentially life-threatening protracted diarrhea
and/or biliary tract infections (e.g., cholangitis, cholecystitis)
 AIDS-defining condition:
Intestinal, for over 1
month; CD4 count (in cells/μL) <100
 Acid-fast cysts in stool
o Antiparasitic therapy (e.g., nitazoxanide) -
Eradication is usually only possible via
restoration of immune function 
cART

163
82. Enterobiosis/ Oxyuriasis
 Pathogen: Enterobius vermicularis (pinworm),
nematodes (male 2-5mm, female 10-12mm)
 Epidemiology
o Most common helminthic infection in Europe
o Primarily affects children 5–10 years of age 
prophylactic treatment in some countries
 Mode of transmission
o Initial infection: fecal-oral
o Reinfection: digital-oral after scratching anal region (Females deposit eggs on the perianal skin, usually at night.
An inflammatory reaction caused by the worms and eggs leads to nocturnal perianal itching. Reinfection occurs
when eggs lodged underneath fingernails are transmitted back to the mouth.)
 Clinical features
o Anal pruritus (especially at night)
o Vulvovaginitis, especially in children (also salpingitis and appendicitis possible)
o Occasionally, symptoms of intestinal infection (i.e., nausea, vomiting, and abdominal pain which may become
severe enough to mimic appendicitis)  indicate a high worm burden
o High worm burden: insomnia, loss of appetite, weight loss, restlessness, irritability, emotional instability,
dysuria, enuresis nocturna, nighttime fears
 Diagnosis
o Tape test: microscopic detection of oval eggs (ova) and/or pinworms on tape that has been pressed against the
perianal region
o Can be an incidental finding on endoscopy
 Treatment: bendazoles OR pyrantel pamoate
o Pyrantelembonat 10 mg/kgKG p.o. als Einzeldosis, Wiederholung nach 2 Wochen,
Tagesmaximaldosis 1 g, bei schwerem Befall 10 mg/kgKG p.o. als Einmaldosis an 3
aufeinanderfolgenden Tagen
o Mebendazol 100 mg p.o. als Einzeldosis, Wiederholung nach 20 Tagen
o During pregnancy: pyrantel pamoate
is the drug of choice
 Should only be administered if
pregnancy is compromised (e.g.,
weight loss, sleeplessness)
 Should not be started until the 3rd
trimester, after which the risk to
fetus is likely to be low.

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83. Ascaridosis
 Pathogen: Ascaris lumbricoides (giant roundworm), nematodes (Adult usually
10–40 cm in length and resemble earthworms.)
 Epidemiology: most common helminth infection worldwide (mainly affects
children in tropical countries with low standards of hygiene)
 Mode of transmission: fecal-oral (infection occurs in the larval state following
the consumption of contaminated food, especially raw vegetables that have been contaminated by human
waste used as a fertilizer)
o Pica – Geophagia: eating of soil (eating disorder)
 Life cycle: Host ingests eggs → Eggs hatch and release larvae → Larvae invade intestinal
walls → Larvae migrate to lungs via portal vein → Larvae migrate into alveoli, trachea
(“tracheal migration”), and larynx → Larvae are expectorated into the mouth and
swallowed back into the intestine → Larvae return to the intestine → Larvae mature into
adult worms, which then lay new eggs
 Clinical features: Most patients are asymptomatic.
o Early symptoms: –16 days after egg ingestion and are caused by migration of larvae
through lungs and systemic eosinophilia (usually transient)
 Dry cough, blood-tinged sputum, wheezing
 Loeffler syndrome: a transient respiratory disorder characterized by accumulation of eosinophils in the lungs
due to certain infections (usually parasites) or allergic reactions to drugs. Symptoms are usually mild and
resolve spontaneously
o Late symptoms (6–8 weeks after egg ingestion and are caused by mature worms in the intestinal tract):
anorexia, abdominal discomfort, nausea, vomiting, and diarrhea
o Additional symptoms due to blockage by adult worms depend on the location of the obstruction:
 Bowel obstruction, especially at ileocecal valve (may lead to intestinal perforation)
 Obstruction of the appendix → features of appendicitis
 Obstruction of biliary and pancreatic ducts → features of cholestasis, pancreatitis
 Diagnosis
o CBC shows eosinophilia.
o Confirmatory test: Stool
samples show the presence of
worms or visible oval eggs with a knobby
appearance under the microscope.
 Treatment
o Treatment of choice:
bendazoles (Mebendazol,
Albendazol)  advise patients
that they will defecate dead worms
o During pregnancy: pyrantel pamoate
o Surgery before medical treatment in
case of obstruction of ducts

165
84. Toxocarosis
 Pathogen: Toxocara canis (dog roundworm), Toxocara mystax/Toxocara cati (cat roundworm); nematodes.
 Mode of transmission: fecal-oral (ingestion of Toxocara eggs from an infected dog or cat feces, e.g., in
contaminated playground sand or garden soil)
o Humans are accidental hosts for Toxocara, i.e., hosts in which the helminth life cycle cannot be completed
 Incubation period: 2–4 weeks
 Clinical features
o Symptoms are caused by migrating larvae rather than adult worms. A mild infection may be asymptomatic
 runny nose, cough, sleeplessness, headaches, behavioral changes, low level eosinophilia
o Visceral toxocariasis (also called visceral larva migrans): caused by larvae migrating through the intestinal wall
into the blood and reaching other organs
 Fever and flu-like symptoms
 Additional symptoms depend on the affected organs
 Liver: hepatomegaly and abdominal pain
 Lungs: Dyspnea, wheezing, cough, pneumonia, asthma-like attacks; Loeffler syndrome
 Skin: rash, urticaria, dermatitis, edemas, conjunctivitis
 Heart: myocarditis
 CNS (also called neural larva migrans): seizures, coma, Meningitis, encephalitis, myelitis, cerebral vasculitis
o In children: epilepsy, cognitive deficits
o In adults: amplified symptoms of insomnia, irritability, behavioral changes, depression, dementia
o Ocular toxocariasis (also called ocular larva migrans): caused by larvae migrating into the eye
 Unilateral impairment or loss of vision and resulting strabismus
 Leukocoria: Abnormal white reflection from the pupil; Granuloma resembling retinoblastoma
 Inflammation, scarring, and possible detachment of the retina
 Diagnosis
o Initial tests
 Complete blood cell (CBC) count: eosinophilia (low grade to hypereosinophilia with leukocytosis)
 ↑ Serum total IgE
 Iron deficiency anemia
o Confirmatory test: ELISA detects IgG antibodies to Toxocara
excretory/secretory antigens, Western Blot - for
conformation
 Treatment
o Etiological: Albendazole (Zentel) - tab 400 mg (10 mg/
kg orally twice a day with meals) for 5-7-10 or 14 days
(individually)
o Antiallergic: for suppressing allergic symptoms, due to
toxo-allergic reactions against the dying larvae

166
85. Trichocephalosis/ Trichuriasis
 Pathogen
o Trichuris trichiura (whipworm)
o Whipworms are nematodes, 2,5-6cm
 Mode of transmission: fecal-oral, soil transmitted
 Life cycle: Host ingests eggs → Eggs hatch and release
larvae in the small intestine → Larvae mature into adult worms in colon → Adult worms lay eggs, which are shed
in feces.
 Clinical features
o Mostly asymptomatic
o Severe cases: chronic colitis and Trichuris-induced dysentery
 abdominal discomfort, pain and distention; loose stools with minimal blood; anemia
o Massive infestations: bloody or mucus-filled diarrhea; tenesmus; rectal prolapse with visible worms
o In children: severe infection causes diarrhea, iron deficiency anemia, growth retardation, rectal prolapse
o Coinfection with other large bowel pathogens (Salmonella typhi, Shigella, E. histolytica, Schistosoma spp.) can
cause exacerbation of symptoms: massive gastrointestinal bleeding; perforation and peritonitis
 Diagnosis
o Microscopic examination of stool for eggs
o Concentration technique can be used for light infections.
 Treatment: mebendazole (500 mg daily or 100 mg twice a day by mouth for 3 to 7 days) OR albendazole (400 mg
for 3 to 7 days)

Barrel-shaped, thick-walled eggs with bipolar hyaline protuberances are

visible, which are characteristic of Trichuris trichiura

167
 86. Taeniases, Cysticercosis
Intestinal taeniasis
Description  An intestinal infection with adult tapeworms 
that causes mainly GI symptoms
 Taenia saginata (beef tapeworm)
Pathogen
 Taenia solium (pork tapeworm)
Mode of  Ingestion of larvae (cysticerci) in raw or
transmission undercooked beef/pork
Life cycle  Eggs hatch in the human intestine → Develop into adult worms → Produce proglottids which can detach from
the tapeworm and are passed in the feces.
 Incubation period - 2,5 - 3 months
 Often asymptomatic
Clinical  Symptoms caused by adult worms in the
intestinal tract: abdominal pain, anorexia,
features
weight loss, nausea, and vomiting
 most common symptom is passage of
proglottids
 Initial test: CBC may show eosinophilia (in
Diagnosis
only ∼ 45% of patients)
 Confirmatory test: stool examination to
detect eggs/proglottids and/or worms
Treatment  Praziquantel (single-dose therapy of
10mg/kg)
 Avoid raw pork and inspect for cysticerci
 Adequately freeze and cook meat to destroy viable cysticerci
Prevention
 Dispose of human feces properly
 Hand washing before meal preparation
168
Cysticercosis
A tissue infection with tapeworm larvae. Symptoms depend
on the infected organ (e.g., muscles, brain, skin).
 Taenia solium (pork tapeworm)
 Fecal-oral: eggs are ingested from contaminated water or
vegetables
 Symptoms caused by cysticerci accumulation in
subcutaneous tissue, muscles, brain, spinal cord, and eyes
o Palpable subcutaneous cysts
o Myalgia
o Neurocysticercosis (cysticerci-containing cysts in the CNS):
increased intracranial pressure, neurological deficits,
seizures
o Ocular cysticercosis: eye pain, loss of visual acuity or
vision in one eye
 Initial test: CBC may show eosinophilia
 Additional testing
o Imaging: cerebral MRI/CT showing multiple, small (< 1 cm)
cystic lesions with a membranous wall and an invaginated
scolex (“dot sign”)
o CT/MRI may also show
 Cysts with an invaginated scolex during earlier stages
 Calcified cyst remnants in later stages
o Lumbar puncture: ↑ protein, ↓ glucose, mononuclear
pleocytosis
 Confirmatory test: serum enzyme-linked immunotransfer
blot (EITB) assay
 Praziquantel
 For neurocysticercosis: albendazole (15 mg/kg/d, orally into
2 daily doses for 7-30 days) PLUS corticosteroids
169
87. Hymenolepidosis
 Pathogen: Hymenolepis nana (dwarf tapeworm), 1,5-5cm length
 Mode of transmission
o Ingestion of eggs from contaminated food or water
o Ingestion of cysticercoids from infected arthropods
 Incubation period - 14-16 days
 Age – mainly affects preschool and school-aged children (4-10 years), due to improper personal hygiene
 Life cycle: Ingestion of eggs → Develop into cysticercoid larvae in the small intestine villus (alternatively
cysticercoids can be consumed from infected arthropods) → Cysticercoids (released upon rupture of the
intestinal villus) develop into an adult worm in the intestinal lumen → Eggs are passed through the stool
 Clinical features
o Mostly asymptomatic
o Severe infection with Hymenolepis nana presents with: Anorexia, abdominal pain, bloody diarrhea
o Chronic infections (moderate to high worm burden for prolonged time)
 + malabsorption syndromes, lactose and saccharose intolerance, decreased vitamin absorption (РР, С, В2) =>
low body mass, disturbance in mental and physical development
o Weakness, headache, hives and other unspecific allergic reactions
 Diagnosis: stool examination for eggs; Laboratory: low grade anemia, +/- mild eosinophilia - 5-15%
 Treatment
o Praziquantel (single-dose therapy of 15-20 mg/kg - repeating (2-3) courses in 10 days intervals)
o Niclosamide or nitazoxanide

170
88. Trichinellosis.
 Pathogen: Trichinella spiralis and other Trichinella spp.; nematodes.
 Mode of transmission
o Consumption of undercooked meat (especially pork; also boar, bear, badger)
containing encysted larvae
o Fecal-oral (rarely)
 Life cycle: Host ingests meat that contains cysts → Larvae invade the small
bowel mucosa → Larvae develop into adult worms → Adult worms release
larvae, which then migrate to muscles, where they encyst
o Predilection for the most metabolically active muscle groups: tongue, diaphragm, masseteric and laryngeal,
extraocular
o In tissues other than skeletal muscle (myocardium, CNS, lungs) the larvae disintegrate and are then
reabsorbed. The destruction of the dying larvae and their exotoxins leads to:
 Early systemic toxo-allergic reactions in 2-3 weeks - (edema, temperature)
 Delayed toxo-allergic inflammation (after 3-4 weeks) – myocarditis, meningoencephalitis, pneumonitis
 Incubation period: 7–30 days [2 - 45 (average 5-20)]
 Clinical features
o Intestinal phase ~1 week after ingestion: abdominal pain, diarrhea, nausea, and vomiting
o Muscle phase ~1 month after ingestion
 Fever - 39-40-41°С - continua or irregular: manifesting symptom in most cases; 2-3 weeks; drop of
temperature marks beginning of muscle aches
 Periorbital edema (starts 1-2 days after fever)
 Myositis: myalgia, muscle swelling, weakness (enhanced by pressure and movement)
 Other symptoms include: rash, splinter hemorrhages, retinal and conjunctival hemorrhages, chemosis
o Late onset: CNS involvement, Toxo-allergic myocarditis, Toxo-allergic or secondary pneumonia
 Diagnosis
o CBC shows eosinophilia (and sometimes leukocytosis) 15-20% (mild) tо 50-80% (hypereosinophilia)
o Confirmatory test: serological detection of antibodies ~4 weeks after ingestion
o ↑ Creatinine kinase, LDH, liver enzymes, IgE
o Rarely muscle biopsy
 Treatment
o Albendazole - tab 400 mg (10 mg/kg orally)
twice a day with meals, 1-st day - 1/3 of the
daily dose, 2-nd day - 2/3 of the daily dose
then the whole dose
o antihistamines for suppressing allergic symptoms,
due to the reactions against the dying larvae
 Complications
o Cardiac: ECG changes (e.g., arrhythmias)
o CNS: meningitis, encephalitis
o Pulmonary: myositis involving respiratory
muscles, pneumonia
 Prevention
o Cook meat
 At 60°С die for 4 minutes, at 76°С die instantly
 Frozen (– 15°С) die after 20 days

171
 89. Echinococcosis.
 Pathogens: Echinococcus tapeworms
o Echinococcus granulosus (dog tapeworm) causes cystic echinococcosis (CE)
o Echinococcus multilocularis (fox tapeworm) causes alveolar echinococcosis (AE)
 Transmission
o Hand-to-mouth
 From the fur of definitive hosts (e.g., petting a dog or cat)
 Contaminated dirt (e.g., dog feces)
o Fecal-contaminated food or water (e.g., wild berries,
mushrooms)
 Hosts
o Definitive hosts: foxes, dogs, and cats
o Intermediate hosts: hoofed animals (e.g., sheep, goats, camels, horses, cattle, and pigs)
o Humans are accidental hosts (e.g., sheep farmers)
 Life cycle: The definitive host consumes hydatid cysts from an intermediate host → adult tapeworms develop
and inhabit the small intestine → tapeworms produce eggs that are shed through stool, contaminating the
ground → eggs are ingested by intermediate hosts → eggs hatch within the intestine and penetrate the
intestinal wall → travel through the bloodstream and lymphatic system → liver or other organs → hydatid cysts
 Clinical features
Features Cystic echinococcosis Alveolar echinococcosis
Incubation time  Up to 50 years  5–10 years
Onset  Usually asymptomatic  Typically nonspecific symptoms
 Hepatic cyst
 Single hepatic cyst (hydatid cyst) o Hepatomegaly → RUQ pain
o Symptoms depend on the location and o Malaise, weight loss, nausea, vomiting
size of the cyst  Cyst that invades and destroys the liver and surrounding
Hepatic o Cyst rupture may cause anaphylactic tissue
reaction o Portal hypertension,
 Hepatomegaly → RUQ pain o Budd-Chiari syndrome
 Malaise, nausea, vomiting o Liver cirrhosis
o May resemble hepatocellular carcinoma
 Primary involvement of other organs is very rare (< 1% of
 Lung involvement in 25% of cases →
cases)
Extrahepatic chest pain, cough, dyspnea, hemoptysis
 Metastasis to other organs (especially lungs, brain, spleen) in
 Involvement of other organs is rare
∼ 13% of cases
 NATURAL COURSE OF INFECTION
o Growth of the cyst to a certain size, persist without noticeable change for many years, might die and calcify
o Spontaneous rupture with complete disappearance of the cysts (spontaneous cure) - very rare
o Spontaneous or traumatic cyst rupture:
 severe anaphylactic reaction =>shock => death
 spillage of germinative elements => secondary multiple echinococcosis - peritoneal or pleural cavity,
pericardium, bile ducts, gastrointestinal tract blood vessels, urinary bladder or ureter
o Microrupture or dying of the cyst leading to bacterial colonization and symptoms of abscess or sepsis.
 Diagnostics
o Laboratory tests (nonspecific; low diagnostic value): mild eosinophilia, leukopenia or thrombocytopenia, liver
function abnormalities
o Serology: positive ELISA antibodies (false negatives are common)

172
 o Imaging
 Ultrasonography
 Cystic echinococcosis: unilocular, anechoic, smooth, well-defined hepatic cyst with or without daughter
cysts
o Possibly daughter cysts and hyperdense internal septa
o Eggshell calcifications within the wall of a hydatid cyst may be visible
 Alveolar echinococcosis: lesions with irregular, poorly defined margins, central necrosis, and irregular
calcifications within the cyst and cyst wall
 CT scan: indicated for further evaluation of cysts, Best test for evaluating extrahepatic cysts
 Alveolar echinococcosis usually not well-defined, but shows infiltration of the liver and surrounding tissue
 Treatment
o Cystic echinococcosis
 Observation: inactive cyst with heterogeneous hypoechoic/hyperechoic contents, or solid, calcified wall
 Medical therapy: may be considered as the sole treatment for cysts < 5 cm
 Drug of choice: albendazole (10-15 mg/kg p.o. twice daily with food for 28 days period)
 Alternative drugs: mebendazole, praziquantel
 Surgery - Indications: > 10 cm, complicated cysts
 Goal: resect the whole cyst to prevent spillage of its content
 Ultrasonography/CT-guided percutaneous drainage
 Commonly conducted using the PAIR (puncture, aspiration, injection, respiration) procedure
 Should only be done in combination with medical therapy (albendazole)
 Follow-up: Because relapse is common, patients should be closely monitored via imaging for up to five years
(Serology testing for the antibody titers evaluation, CBC for eosinophilia, Imaging studies)
o Alveolar echinococcosis
 Curative resection followed by at least 2 years of treatment with albendazole to prevent a potential relapse
 Palliative care if surgery is not possible or unsuccessful; drugs are only parasitostatic, lifelong therapy may
be necessary in some cases.
 Follow-up for at least 10 years
 Prognosis
o Cystic echinococcosis: the long-term outcome depends on organ manifestation
o Alveolar echinococcosis: 90% of patients die within 10 years if left untreated. However, patients who receive
treatment have a life
expectancy only 2–3
years lower than the
general population

173
STATE EXAM STUFF
1. Infection, Infectious Process, Host – Pathogen Interactions.
 Pathogenesis is the method by which a disease can develop.
 This can occur through food-borne intoxication where the causative agent produces toxins in the body (e.g.,
botulism).
 Another route is the colonization of an invading pathogen on the host surface, which allows the pathogen to
increase in numbers and produce toxins that are damaging to the host’s cells (e.g., Vibrio and Corynebacterium).
 Pathogenesis can also occur by pathogens invading and breaching the body’s barrier in order to multiply. They
can also evade antibody detection (e.g., tuberculosis and plague). Finally, organisms can invade tissues within
the body and produce toxins (e.g., Shigella).
 The relationship between a host and pathogen is dynamic. Production of disease occurs through a process of
steps. The first five mechanisms make up a pathogen’s invasiveness (i.e., ability to invade tissues).

2. Infectious Disease – definitions, periods, clinical forms.

 Classification of Infectious Disease
o By duration
 Acute – develops and runs its course quickly.
 Chronic – develops more slowly and is usually less severe, but may persist for a long, indefinite period of
time.
o By burden
 mild
 severe
o By nature:
 Typical
 Atypical – deleted (without a typical symptom or syndrom); abortive (with typical onset and fast extinction
of the symptoms) and fulminant (coming on suddenly with great severity)
o By location
 Local – confined to a specific area of the body.
 Systemic – a generalized illness that infects most of the body with pathogens distributed widely in tissues.
3. Clinical Syndromes
 Syndrome: a group of signs and symptoms that occur together and characterize a particular abnormality or
condition
 Upper respiratory tract
o Sore throat
o Common cold (coryza)
o Sinusitis and otitis media
 Lower respiratory tract
o Epiglottitis
o Laryngotracheobronchitis
o Whooping cough; Acute bronchitis; Acute pneumonias; Chronic chest disease
 Gastrointestinal infection
o Acute diarrhoea with or without vomiting
 Urinary tract infections
 Infections of the central nervous system
o Meningitis; Cerebral infections: Encephalitis, Abscesses
 Skin and soft tissue infections
 Genital tract infections
 Eye infections
 Systemic and general syndromes
o Pyrexia of unknown origin; Endocarditis; Septicaemia; Imported infections; Cryptogenic infections;

5. Infections in Immunocompromised Host. HIV/AIDS.

 Most common types
o Primary (congenital): Fanconi anemia, Selective IgA deficiency, Wiskott-Aldrich syndrome, Ataxia telangiectasia,
DiGeorge syndrome

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 oSecondary: HIV/AIDS, Iatrogenic immune suppression (asplenia, post transplant), cancer
 Clinical findings
o The main symptom of primary immunodeficiency is a pathological susceptibility to infection.
o suspected when recurrent infections are the following: Severe, Complicated, In multiple locations, Resistant to
treatment, Caused by unusual organisms
o often atypical presentations
o Not all immune deficiencies are clinically apparent.
o B-cell deficiencies (decreased number of B cells and/or impaired B-cell function) typically results in recurrent
bacterial infections.
o T-cell deficiencies typically result in recurrent viral and fungal infections.
Defective immune
Bacteria Viruses Fungi/parasites
system component

 Recurrent infections with:  Local candidiasis

o CMV  Cryptococcus infection
↓ T cells  Sepsis
o VZV  Pneumocystis
o EBV pneumonia
o JC virus
 Elevated susceptibility to
encapsulated bacteria
 ↑ Risk of enteroviral
o Streptococcus
infection (may lead to
pneumoniae
encephalitis)
o Group B streptococci  IgA deficiency increases
 Affected individuals have
o Pseudomonas the risk of
↓ B cells an increased susceptibility
aeruginosa gastrointestinal
to viral infections.
o Haemophilus influenza giardiasis
Therefore, live vaccination
type b
against poliovirus is
o Salmonella
contraindicated.
o Neisseria meningitidis
o Escherichia coli
o Klebsiella pneumoniae
 Early complement
deficiencies: ↑
susceptibility to
↓ Complement  N/A  N/A
encapsulated pathogens
 Late complement
deficiencies (C5-C9):
Neisseria
 Staphylococcus
 Systemic candidiasis
 Pseudomonas aeruginosa
↓ Granulocytes  N/A  Mucor
 Nocardia
 Aspergillus
 Serratia
 Burkholderia cepacia
 Lab values
o Leukopenia: WBC count < 4,500/mm3
o Neutropenia: ANC < 500/mcL OR expected to decrease to < 500/mcL within 48 hours
o Lymphopenia: < 25%
o Quantitative serum Ig levels

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 9. Infections in Pregnancy.
Congenital TORCH infections
 TORCH infections: vertically transmitted infections that are capable of significantly influencing fetal and neonatal
morbidity and mortality
o Toxoplasmosis
o Others (e.g., syphilis, varicella, parvovirus B19 infection, listeriosis)
o Rubella
o Cytomegaly (CMV)
o Herpes simplex virus (HSV) infection
 Vertical transmission: an infection acquired directly from the mother that is transmitted to the embryo, fetus, or
newborn through the placenta or birth canal.
Infection Clinical features Diagnosis Treatment Prevention

 T. gondii-specific  Avoidance of uncooked


Classic triad
IgM antibodies meat
o Chorioretinitis (Inflammation
 Sabin-Feldman  Avoidance of handling
of retina and choroid)  Pyrimethamine,
IgG Test cat feces
Toxoplasmosis o Hydrocephalus  PCR for T. gondii
sulfadiazine, and
 Spiramycin: prevention
o Intracranial calcifications folinic acid >16
DNA of fetal toxoplasmosis in
(ring-enhancing lesions) weeks
 Ring-enhancing acute maternal
 Petechiae and purpura
lesions on head toxoplasmosis infection
(blueberry muffin rash)
MRI <16 weeks
 Early congenital syphilis (onset
< 2 years)
o Jaundice and
hepatosplenomegaly
o Lymphadenopathy
o Nasal discharge (sniffles)
o Maculopapular rash (with
desquamation of the palms
and soles)
 VDRL or RPR
o Skeletal abnormalities (e.g.,  Treatment (penicillin G)
Syphilis  Dark-field
osteodystrophy)  Penicillin of mother in early
microscopy
 Late congenital syphilis (onset pregnancy
 PCR
> 2 years)
o Facial abnormalities: Frontal
bossing, rhagades,
Hutchinson triad (saddle
nose, Hutchinson teeth,
mulberry molars)
o Interstitial keratitis
o Sensorineural deafness
o Saber shins
 Spontaneous abortion and
premature birth  Avoidance of
 Meningitis, sepsis unpasteurized dairy
Listeriosis  Vesicular and pustular skin  Ampicillin and
 Bacterial culture products
lesions (granulomatosis gentamicin
 Avoidance of cold deli
infantiseptica) meats

 IUGR, premature birth  Direct  Varicella-zoster  Active immunization of

Varicella zoster  Chorioretinitis, cataract fluorescent immune globulin mother before
virus (VZV)  Encephalitis antigen test (VZIG) pregnancy
 Pneumonia (DFA)  Acyclovir  Passive immunization

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 Infection Clinical features Diagnosis Treatment Prevention

 CNS abnormalities  PCR for VZV DNA  Breastfeeding with VZIG

 Hypoplastic limbs
Parvovirus B19  Aplastic anemia
 Fetal hydrops
 Petechiae and purpura
(blueberry muffin rash)
 Congenital rubella syndrome
(rare in developed countries)
o IUGR
o Sensorineural deafness
Rubella o Cataracts
o Heart defects (e.g., PDA,
pulmonary artery stenosis)
o CNS abnormalities (e.g.,
intellectual disability,
speech defect)
o Hepatitis
 Jaundice, hepatosplenomegaly
 IUGR
 Chorioretinitis
Cytomegaly  Sensorineural deafness
virus (CMV)  Periventricular calcifications 
 Petechiae and purpura
(blueberry muffin rash)
 Microcephaly
 Seizures
 Premature birth, IUGR
 Skin, eyes, and mouth
involvement: vesicular lesions,
Herpes simplex
keratoconjunctivitis
virus (HSV)  Localized CNS involvement:
meningitis
 Disseminated disease: multiple
organ involvement, sepsis
Transplacental transmission occurs following primary infection of a seronegative mother during pregnancy. Maternal
IgM antibodies, which are unable to cross the placenta, form first. Protective IgG antibodies, which are able to cross
the placenta, have not yet been formed, so the infant is not protected from infection via the placenta.
 Serology (IgM
antibodies)
 Frequent hand washing
 PCR for
 Pregnant women with
parvovirus B19
 Intrauterine fetal risk factors for TORCH
DNA
 Serial
blood infection should avoid
transfusion if potentially
ultrasounds to
indicated contaminated
rule out fetal
workplaces (e.g.,
hydrops
schools, pediatric clinics)
 Active immunization of
 Viral culture mother before
 Serology (IgM pregnancy
antibodies)  Supportive care  Second immunization of
 PCR for rubella mother after delivery if
RNA serologic titers remain
negative
 Frequent hand washing
 Pregnant women with
risk factors for TORCH
 Viral culture  Ganciclovir and
infection should avoid
PCR for CMV valganciclovir
potentially
DNA  Supportive care
contaminated
workplaces (e.g.,
schools, pediatric clinics)
 clinical  Cesarean section if
 Acyclovir
 (Viral culture) lesions are present at
 Supportive care
 PCR for HSV DNA delivery

In general, the earlier the TORCH infection occurs during pregnancy, the more severe the complications!

Attenuated live vaccines (measles, mumps, rubella, and varicella) are contraindicated in pregnancy! Conception
should be avoided for at least 3 months after immunization with live vaccines!

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 20. Acute Infectious Diarrhoeal Diseases – Etiology and Pathogenesis.

 The time to onset – For suspected foodborne, illness, the timing of symptom onset following exposure to the
suspect food can be informative. Ingested preformed toxins (eg, those produced by Staphylococcus aureus and
Bacillus cereus) cause illness within hours of exposure, whereas ingested pathogens that subsequently produce
toxin (eg, enterotoxigenic Escherichia coli) or directly damage or invade across the intestinal epithelial cell wall
(eg, Salmonella, Campylobacter, Shigella) usually result in symptoms after approximately 24 hours or longer.
Protozoal pathogens (eg, Cryptosporidium parvum) generally produce enteric illness after an incubation period
of approximately seven days.
 Classification of infectious diarrhea based on pathogenesis:
o Type I: Enterotoxin-related (eg, enterotoxigenic E coli [ETEC]).
o Type II: Inflammatory (eg, C difficile).
o Type III: Invasive (eg, Salmonella spp, Shigella spp, L monocytogenes).
 watery diarrhea: small bowel pathogens predominate
 inflammatory diarrhea (with fever and bloody or mucoid stool): large bowel pathogens predominate
 foodborne infections will typically manifest as a mixture of diarrhea, nausea, vomiting, and abdominal
discomfort. With certain pathogens, vomiting rather than diarrhea may predominate
Mean
Classic/common food
Likely pathogens incubation Other epidemiologic clues
sources
period

 Outbreaks in:
o Restaurants
Shellfish, prepared foods, o Health care facilities
Norovirus 24 to 48 hours
vegetables, fruit o Schools and childcare centers
o Cruise ships
o Military populations
 Antibiotic use
Clostridioides  Hospitalization
Watery diarrhea (formerly N/A N/A  Cancer chemotherapy
Clostridium) difficile*
 Gastric acid suppression
 Inflammatory bowel disease
Clostridium Meat, poultry, gravy,
8 to 16 hours
perfringens home-canned goods

Enterotoxigenic Fecally contaminated food  Travel to resource-limited

1 to 3 days
Escherichia coli or water settings

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 Other enteric viruses
(rotavirus, enteric Fecally contaminated food  Daycare centers
10 to 72 hours  Gastroenteritis in children
adenovirus, or water
astrovirus, sapovirus)  Immunocompromised adults

 Daycare centers
 Swimming pools
Fecally contaminated food
Giardia lamblia 7 to 14 days  Travel, hiking, camping
or water
(particularly when there is
contact with water in which
beavers reside)
 Daycare centers
 Swimming pools and recreational
Cryptosporidium Vegetables, fruit, water sources
2 to 28 days
parvum unpasteurized milk  Animal exposure
 Chronic diarrhea in advanced HIV
infection
Processed/delicatessen  Pregnancy
Listeria 1 day
meats, hot dogs, soft  Immunocompromising condition
monocytogenes (gastroenteritis)
cheese, pâtés, and fruit
 Extremes of age
Cyclospora  Chronic diarrhea in advanced HIV
1 to 11 days Imported berries, herbs
cayetanensis infection
Poultry, eggs, and egg
products, fresh produce,  Animal contact (petting zoos,
Nontyphoidal reptiles, live poultry, other pets)
1 to 3 days meat, fish, unpasteurized
Salmonella
milk or juice, nut butters,  Travel to resource-limited
spices settings

 Travel to resource-limited
Poultry, meat, settings
Campylobacter spp 1 to 3 days
unpasteurized milk
 Animal contact (young puppies
or kittens, occupational contact)
 Daycare centers
 Crowded living conditions
Shigella spp 1 to 3 days Raw vegetables
 Men who have sex with men
Inflammatory  Travel to resource-limited
diarrhea settings
(fever, mucoid or
Ground beef and other
bloody stools)  Daycare centers
Enterohemorrhagic E. meat, fresh produce,
1 to 8 days  Nursing homes
coli unpasteurized milk and
juice  Extremes of age

 Abnormalities of iron-
Pork or pork products, metabolism (eg, cirrhosis,
Yersinia spp 4 to 6 days
untreated water hemochromatosis, thalassemia)
 Blood transfusion
Vibrio
1 to 3 days Raw seafood and shellfish  Cirrhosis
parahemolyticus

Entamoeba Fecally contaminated food  Travel to resource-limited

1 to 3 weeks settings
histolytica or water
 Men who have sex with men

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27. Viral Gastroenteritis
Incubation
Pathogen Transmission Key features
period

 Fecal-oral
 Aerosol  Individuals of all ages are affected.
Norovirus  Fomites  Very young and very elderly patients are at risk for
 1–2 days
 Food, water, or complications and mortality.
environmental  Outbreaks may be seen in semi-closed environments.
contamination

Rotavirus  Primarily occurs in children < 5 years of age (may be fatal)

 1–4 days  Primarily fecal-oral
 Adult infections may be related to travel or an outbreak.

Enteric  Young children are most commonly affected.

 Predominantly
adenovirus  8–10 days  May cause periodic diarrhea that lasts ≥ 10 days
fecal-oral
 May result in outbreaks

 Primarily affects children < 2 years of age and elderly

Astrovirus patients
 1–5 days  Primarily fecal-oral
 Diarrhea and vomiting are usually milder than with
norovirus or rotavirus infections.

 Contact with  Commonly manifests as colitis but may affect any part of
infected body the GI tract
Cytomegalovirus
fluids  Most commonly affects immunocompromised individuals
(CMV)  Not defined
 Transplanted  Endoscopy may reveal severe ulceration.
organs or blood  Antiviral therapy may be indicated (e.g., ganciclovir,
transfusions valganciclovir).

Norovirus infection
 Pathogen: Norovirus is a non‑enveloped RNA calicivirus.
 Transmission
o Fecal oral route through contaminated food or water, person to person contact, via airborne droplets, and
contact with contaminated surfaces
o The virus is highly virulent (Less than 18 viral particles are needed to cause infection)
 Peak incidence: November–March (winter months)
 Community outbreaks (in nursing homes, hospitals, preschools, cruise ships, etc.) are common.
 Incubation period: 12–48 hours
 Clinical features
o Nausea and acute-onset vomiting
o Watery, non-bloody diarrhea; Abdominal cramps
o Fever
o Symptoms resolve after 48–72 hours.
 Viral studies for norovirus: usually performed on whole stool - Reverse transcription-quantitative PCR (RT-qPCR)
 Treatment
o Provide symptomatic treatment as needed: antipyretics, analgesia, antiemetics, and antidiarrheal agents.
o Encourage food as tolerated (continue breastfeeding infants)
o Initiate treatment of dehydration and electrolyte repletion with either IV fluids or oral rehydration therapy.
 Prevention
o patient isolation or cohorting, usage of gloves and gowns upon entering the patient's room, frequent cleaning
of surfaces, and single patient use medical equipment.
o hand hygiene; wash hands with soap and water for at least 20 seconds:
o Avoid preparing food for others until 48 hours after symptoms have resolved.
o Consider a possible outbreak if:
 > 2 linked patients (e.g., travel on the same cruise ship, use of the same community pool) present with
symptoms of gastroenteritis
 Patients present with symptoms within 1–2 days of each other

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Rotavirus infection (Rotavirus gastroenteritis)
 Pathogen: Rotavirus is a nonenveloped, segmented, double-stranded RNA reovirus.
 Transmission: fecal-oral route (e.g., by contact with hands, objects, food, water contaminated with the virus)
o Leading cause of severe diarrhea among infants and children worldwide, although all age groups are
susceptible to infection.
 Pathophysiology: Mucosal damage and villous atrophy in the gastrointestinal tract impair absorption of sodium
and loss of potassium → nonbloody, watery diarrhea
 Incubation period: 1–3 days
 Clinical features
o Fever, malaise; Abdominal pain
o Vomiting and watery diarrhea: Can be severe: > 10 loose, watery stools within 24 hours; Usually lasts 3–7 days
o Mild to severe dehydration: See clinical signs of significant dehydration.
 Antigen detection in stool via enzyme immunoassay (EIA): a highly sensitive test that can be performed quickly
and easily
 Treatment: Supportive - Oral rehydration, IV fluids in patients with severe dehydration
 Prevention: Vaccination
o Rotavirus vaccination (a live attenuated vaccine) is recommended for all infants unless there is a
contraindication
o Dose 1: 2 months of age, Dose 2: 4 months of age, Dose 3: 6 months of age

28. Diagnosis, Differential Diagnosis and Treatment of Acute

Gastroenteritis.
 Gastroenteritis: inflammation of the gastrointestinal tract that usually manifests with acute diarrhea, vomiting,
and/or abdominal pain
 Infectious gastroenteritis: gastroenteritis caused by pathogens; most commonly viruses, but can also be caused
by bacteria, parasites, and fungi
 Mild-to-moderate gastroenteritis
o Abdominal pain with normal abdominal examination
o Mild diarrhea, nausea, and/or vomiting
 Severe gastroenteritis includes:
o Gastrointestinal features: Bloody stools; Severe diarrhea, nausea, and/or vomiting; Severe abdominal cramping
and/or tenderness
o Systemic features: Fever (≥ 38.3°C) or sepsis; Clinical signs of significant dehydration; End-organ damage
o Duration > 1 week
 Diagnostics
o BMP and serum electrolytes: may show AKI or electrolyte abnormalities
o CBC
 Leukocytosis with left shift: may indicate an inflammatory bacterial infection
 Eosinophilia: may indicate a parasitic infection caused by invasive helminths
o Stool analysis (for inflammatory markers): may show leukocytes, occult blood, and/or lactoferrin
o Obtain a stool culture to look for Shigella, Salmonella, Campylobacter, Yersinia, and STEC.
o Clostridioides difficile toxin: Obtain for patients with risk factors for C. difficile infection (CDI), e.g., recent
history of antibiotic use.
 Differential Diagnosis
o Bacterial: Campylobacter enteritis (campylobacteriosis), Salmonellosis (salmonella gastroenteritis), Shigellosis
(bacillary dysentery), Cholera, Yersiniosis, Clostridium perfringens enterocolitis, Noncholera Vibrio infection
o Viral: Norovirus, Rotavirus, Enteric adenovirus, Astrovirus, Cytomegalovirus (CMV)
o Food poisoning, food allergies
o colorectal cancer, irritable bowel syndrome, inflammatory bowel disease, microscopic colitis, malabsorption
syndromes, post-cholecystectomy related diarrhea, medication-induced diarrhea, laxative abuse, and chronic
infections; Mushroom poisoning
o history of travel, hiking, or oral-anal sexual activity should prompt evaluation for protozoa such as Giardia and
cryptosporidium
 Treatment
o usually self-limiting. Supportive therapy may suffice for most patients.

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  Bland diet: e.g., broths, saltine crackers, broiled food, baked food
 Oral rehydration therapy or intravenous fluid therapy: i.e., fluid replacement or fluid resuscitation
 Oral or parenteral electrolyte repletion
 Oral or parenteral antiemetics as needed: e.g., ondansetron (off label) or promethazine
 Consider antimotility drugs (e.g., loperamide) for immunocompetent adult patients with acute watery diarrhea
o Emperic abx: Azithromycin 500mg/d po for 3 days
o Targeted therapy: Once a pathogen has been identified, modify therapy accordingly.
 treatment for C. difficile infection: Metronidazol, Vancomycin or fidaxomicin p.o.
 CMV: Antiviral therapy may be indicated (e.g., ganciclovir, valganciclovir

34. Mycoplasma and Chlamydia infections.

 Gonococcal urethritis (GU): Neisseria gonorrhoeae
 Nongonococcal urethritis (NGU)
o Chlamydia trachomatis (most common)
o Mycoplasma genitalium
o Trichomonas vaginalis
 Risk factors: Unprotected sexual intercourse, Multiple sexual partners, History of other sexually transmitted
infections
 Clinical features
o Dysuria; Burning or itching of the urethral meatus
o Urethral discharge: purulent, cloudy, blood-tinged, or clear
o Initial hematuria
o General symptoms (e.g., fever, chills, or myalgia) are uncommon in urethritis and should raise suspicion for
complications  cystitis, epididymitis, prostatitis, cervicitis, pelvic inflammatory disease, Reactive arthritis
(Reiter triad)
 Diagnostics
o Confirming urethritis: Urine dipstick of first-void urine: positive leukocyte esterase, Pyuria (≥ 5–10 WBC per high
power field)
o Gram stain of urethral swab or discharge: Gram-negative diplococci: GU  Otherwise NGU
o Nucleic acid amplification testing (NAAT) of first-void urine without prior precleaning of the urethra for N.
gonorrhea and C. trachomatis
 Treatment
o Nongonococcal urethritis: single dose azithromycin or doxycycline PO for seven days
o Patients should refrain from sexual activity for 1 week after initiation of therapy.
o All sexual partners from the 2 months prior to diagnosis should be notified, evaluated for urethritis, and offered
empiric treatment.
o Repeat NAAT 3–6 months after completion of therapy.

37. Varicella – Zoster Virus – Infections.

Differential Diagnosis in Patient with
Vesicullous Exanthema. Smallpox.
Vaccinia
 differential diagnosis for HZ includes herpes simplex virus
(zosteriform herpes simplex), impetigo, candidiasis, contact
dermatitis, insect bites, autoimmune blistering disease,
dermatitis herpetiformis, and drug eruptions
Smallpox - eradicated in 1980
 Pathogen: Variola virus
 transmitted by respiratory shedding and is clinically characterized
by fever, rash, headache, backache, and malaise
 lesions on the mucous membranes (enanthem) followed
approximately 24 hours later by the cutaneous rash (exanthem)

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 spread of the exanthem was centrifugal, involving initially the face, followed by proximal extremities, the trunk,
and the distal extremities
o Confluent rash present on face and forearms
o Semi-confluent rash present on the face with discrete rash elsewhere
o Discrete rash on all involved areas with normal skin between pustules

39. Epstein – Barr V. Infection Incl. Mononucleosis Infectiosa. Infections

due to Other Human Herpesviruses, incl. Cytomegalovirus
 Pathogen: cytomegalovirus (CMV, human herpes virus 5, HHV-5)
 Transmission
o Blood transfusions; Sexual transmission; Transplacentaly (highest risk during the first trimester of pregnancy)
o Perinatal transmission (e.g., contact with contaminated blood/vaginal secretions during delivery or
breastfeeding)
o Body fluids (e.g., respiratory droplets, saliva, urine, genital secretions)
o Transplant-transmitted infection (e.g., bone marrow, lungs, kidneys)
 Prevalence of CMV infection in the general population: 40–100%
 Seroprevalence increases with age with more than 90% in individuals > 80 years
 After primary infection resolves, CMV remains latent in mononuclear cells (e.g., myeloid cells). Reactivation can
occur if the patient becomes immunocompromised
 Clinical features
o In immunocompetent patients
 > 90%: asymptomatic course
 < 10%: CMV mononucleosis
 Fever, malaise, myalgia/arthralgia, fatigue, headache
 Less common: sore throat, cervical lymphadenopathy, hepatomegaly, splenomegaly
 Differential diagnosis: infectious mononucleosis caused by EBV (in the case of CMV, heterophile antibody
test would be negative)
o In immunocompromised patients
 CMV mononucleosis
 CMV pneumonia: interstitial pneumonitis
 Clinical findings: fever, nonproductive cough, dyspnea
 CMV retinitis: floaters, photopsia, visual field defects
 Fundoscopy: “pizza-pie” appearance (retinal hemorrhages, fluffy/granular white opacities around retinal
vessels resembling cotton-wool spots, retinal detachment)
 CMV esophagitis and/or CMV colitis
 Most commonly occurs in patients with HIV.
 Manifests with odynophagia, abdominal pain, bloody diarrhea
 Endoscopic examination of the GI tract typically shows linear ulcers
 Adrenal insufficiency
 CMV encephalitis: impaired cognitive function, neurological deficits
 Diagnostics
o CBC: relative lymphocytosis with > 10% atypical lymphocytes and sometimes pancytopenia
o Tissue biopsy: large atypical lymphocytes with intranuclear inclusion bodies that have an owl-eye appearance
o Monospot (heterophile antibody) test: negative
o Serological tests
 Active disease: IgM antibodies, A four-fold increase in the levels of IgG antibodies
 Inactive disease: IgG antibodies in the absence of IgM antibodies
o Direct evidence of viremia: immunosuppressed patients - PCR to detect CMV DNA in bodily fluids
o Fundoscopy: retinal hemorrhages and cotton-wool spots (“pizza-pie” appearance) in CMV retinitis
 Treatment
o In immunocompetent patients: No specific treatment is needed.
o In immunosuppressed patients
 Retinitis, colitis, esophagitis: valganciclovir
 Pneumonia: IV ganciclovir (or IV foscarnet) and IV immunoglobulin (IVIG) therapy
 Encephalitis: IV ganciclovir and IV foscarnet

183
Human
herpes Subtypes Seroprevalence Mode of transmission Characteristics Disease Management
virus

 Herpes labialis (cold sores)

 Herpetic gingivostomatitis
 Eczema herpeticum
Herpes simplex virus 1  Saliva  Herpetic whitlow
HHV-1  ≥ 50% in

(HSV-1)
adults  Respiratory Herpes simplex encephalitis
secretions  HSV keratitis
 HSV conjunctivitis
 HSV esophagitis
 After primary infection,  Erythema multiforme  Antivirals may be indicated
the virus remains
dormant in nerve ganglia
o HHV-1: trigeminal  Genital herpes
o HHV-2: sacral  Eczema herpeticum
HHV-2
Herpes simplex virus 2
 10–20%  Sexual intercourse
o VZV: dorsal root,  Congenital herpes simplex,
(HSV-2) trigeminal neonatal herpes simplex
in adults  Perinatal
 Viral meningitis (more commonly
caused by HSV-2 than by HSV-1)
 Herpetic whitlow

 Primary infection: chickenpox

HHV-3
Varicella zoster virus  Respiratory (varicella)  Vaccinations are widely used
(VZV)  Up to 90% secretions
 Reactivation: shingles (zoster)
to prevent VZV infections in
 Vesicular fluid children.
 Congenital varicella syndrome

 Infectious mononucleosis
(positive monospot test)
 65% in
children,  Saliva  Oncogenic potential: can  Oral hairy leukoplakia  Symptomatic therapy
HHV-4 Epstein-Barr virus (EBV) teens, and  Respiratory immortalize and  Burkitt lymphoma  Avoid physical activity that
young adults secretions (EBV is transform host B cells  Nasopharyngeal carcinoma may trigger splenic rupture
between 6 also called “kissing  Uses CD21 receptor to (especially in adults of Southeast (e.g., contact sports) for at
and 19 years disease.”) cause infection in B cells Asian descent) least 3 weeks
old
 Post-transplant
lymphoproliferative disorder

HHV-5 Cytomegalovirus (CMV)  ∼ 50% in the  Congenital  Large atypical  Cytomegalovirus infection
lymphocytes with  Antivirals may be indicated.
US  Sexual intercourse intranuclear inclusion  CMV mononucleosis (occurs in

184
Human
herpes Subtypes Seroprevalence Mode of transmission Characteristics Disease Management
virus

 Transfusions, bodies that have an owl- immunocompetent individuals)

transplants eye appearance  Congenital CMV infection
 Saliva  Uses integrins to cause
infection
 Urine

HHV-6  Virus spreads early.

 Reactivation of latent
 Roseola infantum (more  Self-limiting condition
 ∼ 90% in the

virus or reinfection may
US
Saliva occur later in life commonly caused by HHV-6 than  Symptomatic treatment to reduce
HHV-7 (especially if individuals HHV-7) fever
become
immunocompromised).

 < 10% in the

US
  Has oncogenic potential
HHV-8
Kaposi's sarcoma- Higher in men
 Sexual  Infects endothelial cells causing
 Treatment of the underlying
associated virus (KSHV) who have sex
intercourse malignant, multifocal, highly
 Kaposi sarcoma disease (e.g., antiretroviral
with men treatment in patients with HIV)
(MSM) and vascularized tumor
HIV-positive
patients

185
40. Scarlet Fever and Other Infections cause by Streptococci. /STSS,
Phagedaena, Erysipelas/
Toxic shock syndrome
 rare toxin-mediated life-threatening acute condition caused by toxin-producing strains of Streptococcus
pyogenes and Staphylococcus aureus
 Age: Invasive Group A Streptococcus infections and subsequent complications are more common in young
children and adults > 65 years of age.
 Risk factors
o Streptococcal TSS
 Invasive: Soft tissue infections (necrotizing fasciitis and myositis), Bacteremia, Postpartum sepsis, Pneumonia
 Noninvasive: Cellulitis, Infected cuts
o Staphylococcal TSS
 Menstrual factors (∼ 50% of cases): High-absorbency tampons, Prolonged placement of tampons, menstrual
cups, and vaginal sponges
 Nonmenstrual: Burn and wound infections, Postpartum or postabortion infections, Postsurgical wound packing
o Recent viral infections: Varicella, Influenza
 Pathophysiology
o Superantigen production: Causative organisms (S. pyogenes and S. aureus) produce superantigens
 Streptococcal pyrogenic exotoxins (SPE)
 Toxic shock syndrome toxin-1 (TSST-1), Staphylococcal enterotoxin (SE)
o Very small amounts of superantigens can rapidly activate excessive numbers of T cells, triggering a massive
release of proinflammatory cytokines, resulting in SIRS
 ↑↑↑ Cytokines → generalized endothelial disruption → capillary leak syndrome → generalized edema →
intravascular hypovolemia → organ dysfunction and disseminated intravascular coagulation (DIC)
 Clinical features
o Streptococcal TSS: variable onset
o Staphylococcal TSS: Menstrual etiology: peak onset on days 3–4 of menstruation; Postsurgical and postpartum
TSS: typically < 48 hours after surgery or delivery
o Prodrome
 Flu-like symptoms: high fever, chills, myalgia, headache, nausea, vomiting, diarrhea
 Dermal rash: more common in menstrual staphylococcal TSS than in nonmenstrual staphylococcal TSS and
streptococcal TSS
 Transient erythematous macular (sunburn-like) rash
 Commonly involves the palms and soles
 Typically desquamates 1–2 weeks after onset
o Shock and end-organ dysfunction
 Early: tachycardia, tachypnea, high fever, altered mental status
 Late
 Hypotension; Delayed capillary refill; Worsening altered mental status; Evidence of organ failure
 Signs of deranged clotting, e.g., purpura fulminans; Mucosal ulceration
 Diagnostics
o Obtain blood cultures and initiate empiric antibiotic therapy for TSS as soon as TSS is suspected.
o Inflammatory markers: ↑ ESR, ↑ CRP
o CBC: Normal or ↑ WBC with significant left shift, Anemia, Thrombocytopenia
o Coagulation screen: ↑ PT, ↑ PTT, ↓ fibrinogen, ↑ fibrin degradation products
o Liver chemistries: ↑ ALT/AST, ↑ total bilirubin, ↓ albumin, ↓ total protein
o TSST-1 assay of S. aureus culture isolate or TSST-1 antibody titers
 Treatment
o Management of source(s) of infection
o Antibiotic therapy: all patients with suspected TSS; preferably initiated within an hour of presentation
 Causative organism unclear: Vancomycin PLUS clindamycin OR linezolid
 Suspected streptococcal TSS: Penicillin G PLUS clindamycin
 Suspected staphylococcal TSS: Vancomycin PLUS clindamycin
o Consider IVIG in patients with streptococcal TSS (e.g., those with hypotension refractory to vasopressors)
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Necrotizing fasciitis, Phagedaena
 rapidly progressive infection resulting in extensive necrosis of superficial and deep fascia and overlying
subcutaneous fat that can develop into a life-threatening condition within hours
 Fournier gangrene: Necrotizing fasciitis of the external genitalia that can spread rapidly to the anterior
abdominal wall and gluteal muscles.
 Pathogen
o Both monomicrobial and polymicrobial causes are common.
 Polymicrobial: wide variety of aerobic and anaerobic pathogens, often of intra-abdominal or genitourinary
origin (E. coli, Bacteroides spp.)
 Monomicrobial: commonly group A Streptococcus (S. pyogenes), Peptostreptococcus spp., S. aureus
 Clinical features
o Systemic symptoms: fever, chills, altered mental status
o Cutaneous findings
 Diffuse erythema (often manifests initially as suspected cellulitis that is not responding to initial antibiotic
therapy)
 Extreme tenderness and pain out of proportion to the area of erythema
 Significant induration of the subcutaneous tissue
 Crepitus: due to the production of methane and CO2 by bacteria
 Purple skin discoloration (skin necrosis, ecchymosis)
 Bullae
 Loss of sensation in the affected area (paresthesias)
 Diagnostics
o Laboratory studies
 CBC: leukocytosis
 BMP: possibly hyperglycemia; renal function may be compromised
 Inflammatory markers (CRP, ESR, procalcitonin): elevated
 CK: elevated
 Assess organ failure and severity.
o Microbiology: Blood cultures (2 sets), Gram stain and cultures from deep tissue
o Imaging: not routinely indicated and should not delay treatment
 CT/MRI with/without IV contrast: Gas in soft tissue
 X-ray: May detect gas in soft tissue, The absence of gas does not rule out NSTI.
 Management
o Surgical exploration with debridement (confirms the diagnosis and the mainstay of treatment)
o Broad-spectrum antibiotic therapy: Meropenem + Linezolid or Piperacillin/Tazobactam + Clindamycin

42. Diphtheria. Throat Alterations in Infectious Diseases -Differential

Diagnosis.
 Infectious mononucleosis – Clinical manifestations of infectious mononucleosis include fever, pharyngitis,
adenopathy, and fatigue. Laboratory findings include atypical lymphocytosis; the diagnosis is established based
on the presence of heterophile antibodies.
 Group A streptococcal tonsillopharyngitis – Clinical manifestations of streptococcal pharyngitis include presence
of tonsillar exudates, tender anterior cervical adenopathy, history of fever, and absence of cough. The diagnosis
is established via a rapid antigen detection test or culture.
 Epiglottitis – Clinical manifestations of epiglottitis include fever, sore throat, dysphagia, drooling, and respiratory
distress. The diagnosis is made by visualization of the epiglottis or demonstration of epiglottal swelling on lateral
neck radiograph.
 Viral pharyngitis – Viral infection is the most common cause of pharyngitis; etiologies include influenza,
rhinovirus, respiratory syncytial virus, herpes simplex virus, human immunodeficiency virus (HIV), and others.
 Vincent’s angina – Vincent’s angina (also called acute necrotizing ulcerative gingivitis) is an infection of the gums
with sudden onset of painful, bleeding gums, blunting of interdental papillae, and an ulcerative necrotic slough
of the gingiva.

187
 Oral candidiasis – Clinical manifestations of oral candidiasis consist of white plaques on the buccal mucosa,
palate, tongue or oropharynx. Patients may have loss of taste and pain with eating or swallowing. The diagnosis
is confirmed by visualization of budding yeast on a Gram stain or potassium hydroxide preparation.
 Corynebacterium ulcerans infection – C. ulcerans is primarily an animal pathogen but has the potential to
elaborate diphtheria toxin and cause an exudative pharyngitis in humans that is indistinguishable from C.
diphtheriae.
 Corynebacterium hemolyticum infection – C. hemolyticum is associated with pharyngitis, sometimes
accompanied by a maculopapular or scarlatiniform rash. Membranous pharyngitis mimicking diphtheria caused
by C. hemolyticum has also been described. Other clinical manifestations include peritonsillar abscess and
endocarditis.

44. Oedema Cerebri and Meningitis in Acutely Ill Infected Patient.

Differential Diagnosis in Meningitis.
Cerebral Edema and Increased Intracranial Pressure
 Vasogenic cerebral edema: increased BBB permeability
 Cytotoxic cerebral edema: swelling of the cellular elements of the brain, most likely through release of toxic
factors from neutrophils, bacteria, or both
 interstitial cerebral edema reflects obstruction of the flow of normal CSF as in hydrocephalus
 Clinical features
o Cushing triad: irregular breathing, widening pulse pressure, and bradycardia
o Reduced levels of consciousness
o Headache; Vomiting; Papilledema; Psychiatric changes
o In infants: macrocephaly, bulging fontanel, sunset sign
o Diplopia
 Treatment
o Head of bed elevation (∼ 30°)
o Hyperosmolar therapy: IV mannitol 20% 0.25–1.0 g/kg IV every 6–8 hours
o Glucocorticoids: e.g., dexamethasone only if elevated ICP is caused by vasogenic edema secondary to CNS
infection or inflammation (e.g., bacterial or tuberculous meningitis)

Differential
 clinical and laboratory findings of bacterial meningitis overlap with those of meningitis caused by viruses,
mycobacteria, fungi, or protozoa
 Viral meningitis – Aseptic (usually viral) meningitis is a less severe disease that is often monitored in the
outpatient setting without antimicrobial therapy, whereas bacterial meningitis is a life-threatening illness that
requires hospital admission. Similar to bacterial meningitis, viral meningitis presents acutely with classic signs
and symptoms of meningitis. Unlike bacterial meningitis, the CSF normally has a lymphocytic pleocytosis, normal
glucose, moderate elevation of protein, and negative-CSF Gram stain and culture. Definitive diagnosis of viral
meningitis is generally made by CSF polymerase chain reaction (PCR), although serologies are typically used for
the diagnosis of meningitis due to arboviruses (eg, West Nile virus).
 TB meningitis – Patients with tuberculous (TB) meningitis may have classic signs and symptoms of meningitis at
presentation, however, it is generally a subacute process. CSF exam typically reveals a lymphocyte predominant
pleocytosis with elevated protein and decreased glucose.
 Fungal meningitis – Several fungal species may cause meningitis including Candida, Cryptococcus, Histoplasma,
Blastomyces, and Coccidioides. Although fungal meningitis may present with classic symptoms of meningitis, it
often is a subacute process in patients with epidemiologic risk factors for fungal disease (eg,
immunocompromise, HIV).

47. Differential Diagnosis of Icterus in Acutely Ill Infected Patient

 Hepatocellular injury is typically characterized by the release of intracellular proteins and small molecules into
the plasma. Thus, in contrast to cholestatic syndromes, the elevations in serum conjugated and unconjugated

188
 bilirubin and bile salts are accompanied by elevations in the serum concentrations of hepatocellular enzymes,
such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT).
 Viruses: Epstein Barr Virus (EBV], Cytomegalovirus (CMV), Herpes Simplex Virus(HSV) and other Herpes Viruses,
Yellow Fever Virus, Dengue Virus
 Bacteria and Mycobacteria: Salmonella enterica serotype typhi, Mycobacterium tuberculosis, Brucella species,
Coxiella bunerii (Q fever), Leptospira and other Spirochetes
 Parasites: Schistosoma species (Schistosomiasis), Plasmodium species (malaria)
 Fungi: Candida species, Histoplasma capsulatum
 Viral hepatitis — Viral hepatitis can present as a predominantly cholestatic syndrome with marked pruritus.
Unless the patient has risk factors for viral hepatitis, it is difficult to distinguish this clinically from other causes of
cholestasis.
 Sepsis and low perfusion states — Bacterial sepsis is very often accompanied by cholestasis. Multiple factors
including hypotension, drugs, and bacterial endotoxins are responsible for the jaundice in these patients. Signs
of cholestasis can also be found in other low perfusion states of the liver (heart failure, hypotension) and
hypoxemia that is not profound enough to produce hepatic necrosis.

52. Glanders and Melioidosis

GLANDERS
 Pathogen: Burkholderia mallei, a Gram negative, non-motile, non-encapsulated and non-spore-forming bacillus
 Distribution: sporadically reported in a number of Asian, African, Middle Eastern, and South American countries
 Hosts: Donkeys, Mules, humans, domestic cats, tigers, lions, leopards
 Transmission
o Zoonotic transmission of B. mallei from solipeds to humans appears to be uncommon, even in cases of
frequent and close contact with infected animals
o direct invasion of abraded or lacerated skin; inhalation with deep lung deposition; and by bacterial invasion of
the nasal, oral, and conjunctival mucous membranes
o Risk groups: veterinarians, veterinary students, farriers (hoof care workers), flayers (hide workers), transport
workers, soldiers, slaughterhouse personnel, farmers, horse fanciers, and stable hands
o ingestion of food or water contaminated via discharges from the respiratory tract or ulcerated skin lesions from
carrier animals
o Carnivores may become infected by eating infected so-called glanderous meat
 Incubation time: acute - 1–14 days, chronic – up to 12 weeks
 Clinical features
o chronic, disseminated, pulmonary, and septicemic
o afternoon to evening low-grade fever, malaise, fatigue, headache, myalgias including backache,
lymphadenopathy, and chest pain
o Localized infections are generally regionally confined and typically characterized by foci of suppuration. The
abscesses can ulcerate and drain for long periods of time
o pulmonary infection typically results in pneumonia, pulmonary abscess, pleuritis, and plural effusion
o Dissemination from local cutaneous or mucosal infection result in septicemia and the colonization of internal
organs such as the spleen, liver, and lungs with the development of abscesses
 Diagnostics
o isolation of the organism and positive identification
o Radiology may reveal abcesses in multiple organs including lungs, liver, and spleen
 Treatment
o 10 days iv:: imipenem, meropenem or ceftazidime with or without trimethoprim-sulfamethoxazole (TMP-SMX)
o 12 weeks to 12 months Oral: TMP-SMX with or without a secondary oral medication of doxycycline
 Prevention
o early detection, testing of suspect clinical cases, screening of apparently healthy equids, and humane
elimination of reactors
o strict animal movement controls, effective quarantine of the facilities and thorough cleaning and disinfection
of the contaminated area where the outbreak occurred

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Melioidosis, also known as Whitmore disease
 Pathogen: Burkholderia pseudomallei, Facultative intracellular gram-negative bacterium
 Distribution: occurs in tropical climates, mainly in Southeast Asia (e.g., Thailand, Malaysia) and Northern
Australia
 Transmission
o Percutaneous inoculation: contact with contaminated soil or water (most common)
o Inhalation, aspiration, or ingestion of contaminated dust or water
o Person-to-person transmission is rare
o Occupational exposure: agricultural work
 Clinical features
o Incubation period: 1–21 days (mean ∼ 9 days)
o Most cases are subclinical or asymptomatic.
o Symptomatic cases can be acute, chronic (> 2 months), or reactivations of latent infection.
o Clinical features depend on the infected organ:
 Acute pulmonary infection (most common): wide range of presentations (mild to severe)
 Localized infection: skin ulcer, nodule, or abscess
 Visceral abscesses: especially in the prostate, spleen, kidney, and liver
 Disseminated infection: occurs in ∼ 55% of cases and has a 20% mortality rate. Manifests with fever and
septic shock.
 Diagnostics
o Laboratory testing
 Culture: mainstay of diagnosis
 Gram stain of sputum or abscess pus
o Imaging
 Chest radiography: may show signs of acute pneumonia
 CT and MRI imaging: to identify abscess formation in multiple organs
 Treatment
o Antimicrobial therapy
 Initial intensive therapy: IV ceftazidime, imipenem, or meropenem for 10–14 days
 Followed by eradication therapy: oral TMP/SMX (plus doxycycline) for 3–6 months
o Adjunct therapy: abscess drainage
 Prevention
o In endemic areas, contact with soil and standing water should be avoided (e.g., agricultural workers should
wear boots).
o Health care and laboratory workers should wear masks, gloves, and gowns to prevent infection.
o No vaccination available

53. Rickettsioses. Typhus exanthematicus. Tick Born Typhus.

 “spotted fever” group of rickettsiae, which contains a large number of species transmitted from rodents, dogs,
and wild animals by ticks:
o R rickettsii, the agent of Rocky Mountain spotted fever, so-called because of the area of its discovery, but now
mainly occurring in the eastern Atlantic states of USA, especially in trekkers and hunters exposed to wild
animal ticks, and with the potential for a severe haemorrhagic illness.
 Pathophysiology: Rickettsia species invade capillary endothelium → inflammation → small vessel vasculitis
 Clinical features
 Incubation period: 4–10 days
 Flu-like symptoms (e.g., fever, headache)
 Blanching maculopapular rash: begins on the wrists and ankles  Spreads to the trunk, palms, and soles;
May become petechial and/or hemorrhagic
 Ankle and/or wrist swelling
 Gastrointestinal symptoms (e.g., nausea, vomiting, abdominal pain)
 Meningitis, focal neurological deficits
 Rapid clinical deterioration with shock and multiorgan dysfunction (e.g., DIC)
190
  Diagnostics: clinical
 CBC: typically normal WBC count, thrombocytopenia
 BMP: ↓ Na, ↓ renal function in severe cases; Mildly ↑ AST and/or ALT; ↑ PT, ↑ INR, ↑ PTT
 PCR: detection of R. rickettsii DNA in a skin biopsy specimen or acute phase whole blood specimen
 immunohistochemical staining of R. rickettsii in a skin biopsy specimen
 Treatment: Doxycycline
 If treated after the first 5 days, symptoms are more severe and often require hospitalization. There is also
a greater risk of long-term consequences of ischemia (e.g., amputations, paralysis, hearing loss,
intellectual disability)
 If not treated early enough, the disease can be fatal.
o R conorii, the cause of tick typhus in the Mediterranean area and in India, which is transmitted by the brown
dog tick Rhipicephalus sanguineus—the tick is brown, the dog not necessarily so.
o R africae, which is found in the African veld, is transmitted in game park areas by ticks living on cattle, hippo,
and rhino
o R japonica, R australis, and a variety of other similar organisms, which are widely distributed in Asia and
Australia, and infect man through various species of animal ticks.
 R tsutsugamushi, recently renamed as a new genus with only one species, Orientia tsutsugamushi, the agent of
scrub typhus, acquired from the bite of larval trombiculid mites living on the waist high Imperata grass growing
in previously cleared jungle around villages and in plantations. The area of risk includes South East Asia, the
Indian subcontinent, Sri Lanka, and other Indian Ocean islands, Papua New Guinea, and North Queensland.

55. Erlichioses.
Anaplasmosis
 Pathogen: Anaplasma phagocytophilum
 Vector
o Deer tick (Ixodes scapularis)
o Western black-legged tick (Ixodes pacificus)
o Ixodes is also the vector for Borrelia burgdorferi and Babesia species, so coinfection is possible.
 Reservoir: deer and mice
 Distribution: same as Borreliosis in Europe, Upper midwestern and northeastern US, Growing number of cases
on the West Coast
 Incubation period: 1–2 weeks
 Clinical features
o Fever and other flu-like symptoms (headache, chills, muscle aches)
o Gastrointestinal symptoms (e.g., nausea, vomiting, abdominal pain)
o Cough
o Typically no rash
 Diagnostics
o Laboratory studies
 CBC: mild anemia, thrombocytopenia, leukopenia
 Mild to moderate ↑ AST and/or ALT
o Peripheral blood smear may show morulae within granulocytes.
o IFA test (gold standard): four-fold increase in IgG-specific antibodies
o PCR: detection of Anaplasma DNA in a whole blood sample
 Treatment: doxycycline 100 mg PO/IV twice daily, 10 days

Ehrlichiosis (only in the USA)

 Pathogens: Ehrlichia chaffeensis, Ehrlichia ewingii, Ehrlichia muris eauclairensis
 Vectors
o Lone star tick (Amblyomma americanum): E. chaffeensis and E. ewingii
o Deer tick (Ixodes scapularis): E. muris eauclairensis
 Distribution: Mainly east of the Rocky Mountains, Also some cases in the Southwest
 Incubation period: 1–2 weeks
191
 Clinical features
o Flu-like symptoms (e.g., fever, myalgia), Gastrointestinal symptoms (e.g., nausea, vomiting, abdominal pain)
o Hepatomegaly
o Rarely, symptoms of meningitis and/or encephalitis (e.g., headache, altered mental status, stiff neck,
neurological deficits)
o Sometimes an erythematous maculopapular or petechial rash: Adults: ∼ 30% of cases, Children: ∼ 60% of cases
 Diagnostics
o Laboratory studies
 CBC: anemia, thrombocytopenia, leukopenia
 Mild to moderate ↑ AST and/or ALT
 BMP: mild to moderate ↓ Na
o Peripheral blood smear (with Wright stain or Giemsa stain): leukocytes with morulae (clustered inclusion
bodies that resemble a mulberry)
o IFA test (gold standard): four-fold increase in IgG-specific antibodies
o PCR: detection of Ehrlichia DNA in a whole blood sample
 Differential diagnosis: Rocky Mountain spotted fever
 Treatment: doxycycline 100 mg PO/IV twice daily, 5-7 days minimum

58. Bartonella Infections, Incl. Cat-Scratch Disease.

Bacillary angiomatosis is a skin condition in immunocompromised patients (especially patients with AIDS and/or CD4
count < 100) characterized by vascular proliferation that results in lesions on the skin and potentially other organs
(e.g., GI tract, respiratory tract). It is caused primarily by Bartonella henselae, which is most commonly transmitted
via cat scratches. Skin manifestations include red papules and nodules that bleed easily. Diagnosis is confirmed on
biopsy. Antibiotics are used to treat bacillary angiomatosis, and patients with HIV should be started on ART.

Trench fever (five-day fever)

 Epidemiology: most commonly affects people who are at risk of body louse infestation (e.g., homeless)
 Etiology: Bartonella quintana
 Transmission: feces of infected body louse (vector)
 Clinical features
o Recurrent fever episodes that last ∼ 5 days
o Nonspecific, flu-like symptoms (malaise, headache, nausea, vomiting)
o Bone pain, splenomegaly, and maculopapular rash of the trunk may occur
 Diagnostics: isolation of Bartonella confirms the diagnosis
o Bartonella is difficult to grow on culture
o Serology testing or PCR are often necessary
 Treatment: doxycycline PLUS gentamicin

Carrion’s disease
 Pathogen: Bartonella bacilliformis
 Vector: sand flies (Lutzomyia spp.), Humans are the only known reservoir
 Area: South American Andean valleys
 Clinical features
o Biphasic, hemolytic fever (“Oroya fever”) with case-fatality rates as high as ~90% in
untreated patients, followed by a chronical phase resulting in angiogenic skin lesions
(“verruga peruana”)
o Oroya fever: fever, hemolytic anemia, pallor, myalgia, headache, anorexia,
tachycardia and hepatomegaly
o verruga peruana: blood-filled nodular hemangioma-like lesions in the skin (abnormal
endothelial cell proliferation)
 Peruvian warts are mostly found on the head and extremities persisting from weeks to months ↑
 Diagnostics
o ↓ Hematocrit, Hemolytic Anemia, ↑ Protein C Reactive
192
 Treatment
o Oroya fever: Amoxicillin plus clavulanic acid, Chloramphenicol ± other antibiotics, Ciprofloxacin ±
Cephalosporin
o verruga peruana: Erythromycin, Azithromycin, Rifampicin

65. Disorders in Haemostasis and Haemorrhagic Syndrome in Infectology.

 Hemorrhagic fever viruses have an affinity for the vascular system, which results in increased vascular
permeability
 The main change in human’s body is DIC syndrome onset which includes hypercoagulation first, hypocoagulation
second and acoagulation finally
 Injured spinal cord by toxins, acidosis, hypoxia, activation of PAF by bacterial toxins or viruses causes
thrombocytopenia and thrombocytopathies
 Hepatic involvement by viral replication goes to changes in coagulation system
 Hemorrhagic form of the course of an infectious disease is defined in the presence of 3 criteria:
o Thrombocytopenia </= 150 G/mm2
o Hemorrhages, in the presence of at least one of the following findings:
 Petechiae, ecchimoses or Purpurа (skin hemorrhages of various stages)
 Positive Tourniquet - Test (as per WHO)
 Bleeding from the mucus, the gastrointestinal tract, injection or other places
 Hemoptoe or melena
o Increased vessel permeability, expressed by at least one of the following criteria:
 Hematocrit > 120% of normal level
 Reduction in hematocrit >/= 20% of exit level after substitution of volume losses with liquids
 Data for plasma loss (e.g. pleural outflow, ascites, hypoproteinemia)
 Caused by arenaviruses (e.g., Lassa, Junin, and Lujo virus), bunyaviruses (Crimean-Congo hemorrhagic fever and
hemorrhagic fever with renal syndrome virus), filoviruses (Ebola and Marburg virus), and flaviviruses (yellow
fever virus and dengue virus)characterized by malaise, fever, vascular permeability, decreased plasma volume,
coagulation abnormalities, and varying degrees of haemorrhage
 Thrombocytopenia, consumption of clotting factors, and increased levels of fibrin
degradation products indicate impairment of the coagulation system
 Virus-infected macrophages synthesize cell-surface tissue factor (TF), triggering the
extrinsic coagulation pathway; proinflammatory cytokines also induce
macrophages to produce TF
 excessive proinflammatory cytokine production and absence of
an adaptive immune response are major factors in Ebola virus
pathogenesis
 Rapid systemic spread is aided by virus-induced
suppression of type I interferon responses
 Endothelial cell activation and injury and activation of
coagulation and fibrinolysis have been reported in
dengue, particularly in severe infections. Abnormalities
that have been described include increased numbers of
circulating endothelial cells, elevated levels of von
Willebrand factor, tissue factor, tissue plasminogen
activator, and platelet activator inhibitor, and an increased
fractional catabolic rate of fibrinogen
 antibody responses to homologous peptides derived from the
DENV E protein cross-reacted with plasminogen; these
antibodies correlated with the occurrence of hemorrhagic signs
(including petechiae) but not with thrombocytopenia or shock

193
66. Miscellaneous Infections /Sodoku, Aphthe epizootizae, Actinomicosis,
Nocardiosis/
Actinomycosis
 Pathogen
o Actinomyces are primarily anaerobic, gram-positive, non-acid fast, branching, rod-shaped bacteria.
o Actinomyces bacteria, particularly Actinomyces israelii, are found in the normal oral flora.
 Predisposing factors
o Cervicofacial actinomycosis (most frequent form of actinomycosis)
 Poor dental hygiene (e.g., dental caries), Oral surgery (e.g., tooth extraction), Maxillofacial trauma
 Local tissue inflammation (e.g., tonsillitis, tumor); Comorbidities (e.g., diabetes)
o Ascending infection from the uterus, associated with intra-uterine contraceptive devices
o Thoracic actinomycosis: History of aspiration, Recent oral infection
 Clinical features
o Cervicofacial actinomycosis
 Slowly progressive mass in the neck and/or face; most commonly in the mandible region
 Usually painless nodular lesions
 Becomes indurated with purulent discharge that contains sulfur granules (macroscopic grains – approx. 1 mm
in diameter – of hard clumps of bacterial filaments, pus, debris, and hyaline. The granules appear yellow
within pus) from fistulae and draining sinus tracts.
 Canaliculitis: affects the lacrimal ducts or mouth, typically in the perimandibular region
o Abdominal and pelvic actinomycosis
 Fever, abdominal discomfort, changes in bowel habits; Possible pathological vaginal bleeding or discharge
o Thoracic actinomycosis
 Cough, chest pain; Possible hemoptysis with yellow granules; Constitutional symptoms: fatigue, weight loss,
malaise
 Diagnostics
o Culture (confirmatory test)
o Microscopy: direct visualization and staining of specimen → accumulations of radially protruding and branching
Actinomyces (conglomerates with a “cauliflower-like” appearance) that are surrounded by numerous
granulocytes
o Inflammatory markers: ↑ CRP, ↑ ESR
o CT scan: assists in the identification of the exact location, extent of pathology, and/or guiding percutaneous
aspiration of pus
 Treatment
o Antibiotics: Penicillin (drug of choice), Alternatives (in the event of penicillin allergy): doxycycline, clindamycin
o Surgical treatment: for extensive or severe disease

Nocardiosis
 Pathogen: Nocardia species (ubiquitous in soil worldwide)
o N. otitidiscaviarum
o N. brasiliensis
o Nocardia asteroides complex
 Transmission: inhalation (most common), ingestion, and inoculation through a skin wound or injury
 Risk factors
o Immunocompromise (e.g., due to HIV infection, organ transplant, glucocorticoid therapy, recent
chemotherapy, diabetes mellitus)
o Advanced age
 Pulmonary nocardiosis
o Course: acute, subacute, or chronic
o Risk group: immunocompromised individuals
o Clinical features
 Constitutional: fever, weight loss, anorexia, night sweats
 Respiratory (recurrent pneumonia): productive cough, dyspnea, pleuritic chest pain

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  Pulmonary nocardiosis symptoms such as fever, chills, and weight loss are often mistaken for tuberculosis
 Cutaneous nocardiosis
o Primary infection
 Superficial cutaneous: cellulitis (pain, swelling, erythema, and warmth), nodules, abscesses, ulceration
 Lymphocutaneous: superficial cutaneous infection, regional lymphadenopathy, and lymphangitis
 Subcutaneous mycetoma: chronic pyogenic lesion of the extremities (usually affecting the feet, back, and
hands) → painless indurated nodule → draining sinus tract
o Cutaneous involvement
 Originates from a disseminated focus or after trauma
 Indiscernible from primary lesions, although features of underlying systemic disease (pneumonia, seizures,
focal deficits) are present
 Disseminated nocardiosis
o Definition: two or more sites of involvement
o Clinical features: generally involves both the lungs and the brain
 Pulmonary findings are prominent.
 Metastatic abscesses may be found almost anywhere but are predominantly located on the lower
extremities.
 CNS features: headache, lethargy, confusion, seizures, sudden onset of neurological deficits
 Diagnostics
o Culture: confirmatory test
o Imaging
 Chest x-ray or CT:Pulmonary nodules (with or without cavitation), Infiltrates (reticulonodular pattern or
diffuse)
 Head CT or MRI: brain abscesses
 Treatment
o Antibiotic therapy: trimethoprim-sulfamethoxazole (drug of choice)
o Alternatives: carbapenems (imipenem or meropenem), third-generation cephalosporins (cefotaxime or
ceftriaxone), and amikacin
o Long-term therapy of at least 6 months is recommended
o Surgical drainage of abscesses and debridement of necrotic tissue

67. Infectious Diseases Common for both Temperate and Tropical Climate.
 tropical climate: climatic zone typically found in the equatorial or tropical zone and characterized by high
temperatures throughout the year (i.e. with no marked ‘winter’ season), generally high humidity, and high
precipitation, although the latter may occur in a distinct rainy season
 temperate climate: mid-latitude climates influenced from time to time by both tropical and polar air masses.
Temperature criteria provide subdivisions into warm, cool, or cold-temperate climates
 Bacterial: Diphtheria (cutaneous form)
 Viral: Hepatitis A and E, Zika fever, Yellow fever, Dengue fever, Crimean-Congo hemorrhagic fever
 Parasitic: Malaria, Amebiasis

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69. Organization of the Control of Tropical Diseases. Sanitary Border
Protection. Health Advice for International Travel Medicine.
Organization of the Control of Tropical Diseases
(1) preventive chemotherapy; (2) case management and rehabilitation; (3) vector and intermediate host control; (4)
veterinary public health; and (5) safe water, sanitation and hygiene

 most realistic goal at present is not eradication but control  lowering morbidity and mortality to tolerable
levels and containing the spread of disease
 International alert systems by the WHO and intergovernmental organizations

Sanitary Border Protection

 with regard to travellers:
o information concerning the traveller’s destination so that the traveller may be contacted;
o information concerning the traveller’s itinerary to ascertain if there was any travel in or near an affected area
or other possible contacts with infection or contamination prior to arrival, as well as review of the traveller’s
health documents if they are required under these Regulations; and/or
o a non-invasive medical examination which is the least intrusive examination that would achieve the public
health objective;
 check vaccinations in endemic areas
o implement quarantine or other health measures for suspect persons;
o implement isolation and treatment where necessary of affected persons;
o implement tracing of contacts of suspect or affected persons;
o refuse entry of suspect and affected persons;
 check import/export of live animals, animal products, plants and plant products
 implement treatment of the baggage, cargo, containers, conveyances, goods, postal parcels or human remains
to remove infection or contamination, including vectors and reservoirs
 seizure and destruction of infected or contaminated or suspect baggage, cargo, containers, conveyances, goods
or postal parcels under controlled conditions if no available treatment or process will otherwise be successful;
and refuse departure or entry
 disinfect, decontaminate, disinsect or derat the conveyance/ship/airplane, as appropriate, or cause these
measures to be carried out under its supervision

Travel medicine
 Exact itinerary, including regions within each country to be visited, dates of travel to assess risk of seasonal
diseases, age, past vaccination and travel history, immune status, underlying illnesses, current medications,
pregnancy status, allergies, purpose of trip, risk exposures (blood, body fluids, adventure or extensive outdoor
exposures), urban versus rural travel, type of accommodations, travelers’ risk tolerance, and financial limitations
that may necessitate prioritization of interventions
 Routine vaccinations that are not up-to-date, including measles-mumps-rubella (MMR), tetanus-diphtheria–
acellular pertussis (Tdap), pneumococcal, varicella zoster virus
 Indicated routine travel vaccines, including hepatitis A, hepatitis B, typhoid, and influenza
 Indicated specialized vaccines, including yellow fever, rabies, polio, meningococcal, cholera, Japanese
encephalitis, and tick-borne encephalitis in certain countries
 PROVIDE MALARIA PREVENTION (IF INDICATED)
o Several equally effective drugs of choice may be indicated, including atovaquone-proguanil, mefloquine, and
doxycycline. Ascertain which drug is best suited to the individual patient and itinerary.
o Educate on personal protection against arthropods
 Educate on personal protection measures for malaria, dengue, chikungunya, Zika virus infection, leishmaniasis,
rickettsial disease, and sleeping sickness
 Educate on appropriate strategies in the following categories (some topics are not applicable to all destinations):
bloodborne and sexually transmitted diseases, safety and crime avoidance, transportation-associated and other
injury prevention, swimming safety, rabies, skin/wound care, and tuberculosis.
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