Salute Vivamus 2023 | Central Philippine University | College of Medicine

Medicine II: S01L28

Introduction to Infectious Diseases

Dr. Juan Ismael G. Sumagaysay |11-10-2021 | WF | 10:00-12:00; 7:30-:30 AM

OUTLINE → Increased antibiotic use

→ Increased risk of infection by killing the normal flora
I. Introduction B. Physical Examination
A. Understanding the C. Diagnostic Testing RESURGENCE OF DISEASES IN RECENT TIMES
Microbiota D. Laboratory Diagnosis
• Factor: migration from area of high incidence of disease to
II. Epidemiologic Triangle of the Disease
areas of low incidence
A. Host Pathogen E. Treatment
• Tuberculosis
Interactions IV. Immunization
B. Host Factor Principles and Vaccine • Cholera
Interactions Use • Rheumatic fever
C. Immune Response A. Immunization • West Nile virus encephalitis in New York
III. Approach to the B. Immune Response
Patient With an V. Vaccination RECENTLY EMERGING NEWER DISEASE
Infectious Disease VI. References PATHOGENS
A. History VII. Appendices • Ebola virus
• Human metapneumovirus
I. INTRODUCTION • Anaplasma phagocytophila
• Retroviruses (HIV)
• Infectious disease remains a major cause of death and • Helicobacter pylori
debility around the world. • Zika virus infection
• Broad, composes of different disciplines
• Microorganisms: direct cause of infection MEDICAL CARE FACTORS THAT MAY INCREASE
• Multi-system involvement: outmost (skin) to innermost (bone) INFECTION RISK
• Topmost diseases • Hospitalization
→ Tuberculosis → Prone to develop hospital acquired infection
→ Diarrhea → Increases hospitalization, increases risk
• Second leading cause of death worldwide • Breaching the skin or mucosal membranes
• Introduction of foreign bodies
ETIOLOGIC AGENT CHRONIC DISEASE → Implant
• Peptic ulcer disease → Valve
Helicobacter pylori • Alteration of natural flora (antibiotic use)
• Gastric carcinoma
Human papillomavirus Cervical cancer → Chemotherapy
Hepatitis B and C viruses Liver cancer → Increased antibiotic use
Table 1. Chronic diseases directly/indirectly caused by infectious microbes (book). o Increased risk of infection by killing the normal flora
• Treatment of immunosuppressive drugs
A. UNDERSTANDING THE MICROBIOTA (BOOK) → Important especially in fungal and immunocompromised
patients
• ~50 trillion bacteria colonize healthy humans normally
• Reservoirs of microbes B. HOST FACTOR INTERACTIONS
→ Gastrointestinal tract: major
→ Female genital tract • Geography: dengue and malaria are common in the tropics
→ Oral cavity • Environment
→ Nasopharynx • Behavior
• Majority of infections are caused by organisms that are part of
the normal microbiota SPECIFIC FACTORS THAT INFLUENCE LIKELIHOOD
→ S. aureus OF INFECTIONS
→ S. pneumoniae • Age: extremes
→ P. aeruginosa • Immunization history: common in children
• Prior illness
II. EPIDEMIOLOGIC TRIANGLE • Level of nutrition
→ Malnourished: prone to disease
A. HOST PATHOGEN INTERACTIONS → More nourished: prone to dengue
• Pregnancy: prone to disease
• Antibiotic resistance occurs at an alarming rate. • Coexisting illnesses
→ Microbes developed the ability to elude the best → Diabetes
antimicrobials and developed new survival strategies. → COPD
• There is resurgence of diseases long thought to be eradicated. → Hepatitis
• Infectious diseases do not often occur in isolation → Renal problem
→ Contaminated water respiratory droplets

MD-3 | Med2 | S01L28 | CPU College of Medicine | Salute Vivamus 2023 1|7
• Emotional state • Leptospira spp.
→ Emotionally stressed Unpurified water • Parasites
→ Lack of sleep • Enteric bacteria
→ Always starving • Vibrio spp.
• Norovirus
Raw seafood
C. THE IMMUNE RESPONSE • Helminths
• Protozoa
INNATE IMMUNITY Table 2. Dietary habits that provide insight into possible exposure to microorganisms.

• Defensins
• Simple peptides on skin ANIMAL EXPOSURES
• Macrophages • Often vectors of infectious diseases
• Ticks
ADAPTIVE IMMUNITY → Lyme disease
• Cellular immunity → Rocky Mountain spotted fever
→ T lymphocytes → Ehrlichiosis
→ Macrophages • Cats: Bartonella henselae infection
→ Natural killer cells • Reptiles: Salmonella infection
• Rodents: leptospirosis
III. APPROACH TO THE PATIENT WITH AN • Rabbits: tularemia

INFECTIOUS DISEASE TRAVEL HISTORY

• Both international and domestic travel
• Careful history taking
• Kinds of activities and behaviors patient engaged in during
• Careful review of systems travel
• Thorough physical examination → Types of food
→ Sources of water consumed
A. HISTORY (BOOK) → Freshwater swimming
→ Animal exposure
• Paramount in the evaluation
• Whether the patient had necessary immunization prior
• Guides PE and initial diagnostic testing
• Whether patient took necessary prophylactic medications
• Focuses on
→ Exposure history: may identify microorganisms which
patient may have come in contact with
HOST-SPECIFIC FACTORS
• Opportunistic infections affect primarily immunocompromised
→ Host-specific factor: may predispose to the3
patients
development of an infection
→ Pneumocystis jirovecii
HISTORY OF INFECTIONS OR EXPOSURES TO → Aspergillus spp.
→ JC virus
DRUG-RESISTATN MICROBES
• It is of vital importance to determine immune status of patient.
• Drug resistant organisms
• Defects in the immune system may be due to
→ Methicillin-resistant S. aureus
→ Underlying disease
→ Vancomycin-resistant Enterococcus spp.
→ Medication
→ Enteric organisms that produce an extended-spectrum of
o Chemotherapy
beta-lactamase or carbapenemase
o Glucocorticoids
• Drug-resistant microbes
o Monoclonal antibodies
→ During a stain in a hospital, nursing home, or long-term
→ Treatment modality
acute-care facility
o Total body irradiation
• May alter choice of empirical antibiotics o Splenectomy
→ Primary immunodeficiency
SOCIAL HISTORY
• High-risk behaviors B. PHYSICAL EXAMINATION (BOOK)
→ Unsafe sexual behavior
→ IV drug use VITAL SIGNS
• Potential hobby-associated exposures • Temperature
• Occupational exposures → Elevated temperature is often a hallmark of infection.
→ Rectal temperatures more accurately reflect the core body
DIETARY HABITS temperature
o 0.4°C (0.7°F) higher than oral temperatures
FOOD MICROORGANISM o 0.8°C (1.4°F) higher than axillary temperature
Shiga-toxin producing strains of → Fever: ≥38.3°C (≥101°F)
Raw or
→ E.coli • Heart rate
uncooked meat
→ T. gondii → For every 1°C increase in core temperature, the heart rate
• Salmonella typhimurium rises by 15-20 bpm
Unpasteurized
• Listeria monocytogenes → Faget’s sign: lower heart rate than might be expected for
milk
• Mycobacteria bovis a given body temperature
MD-3 | Med2 | S01L28 | CPU College of Medicine | Salute Vivamus 2023 2|7
• Respiratory rate • Can be followed serially over time to monitor disease
• Pulse rate progress/resolution
• Sensitive indicators of inflammation, neither is very specific
LYMPHATICS • ESR >100 nm/h has a 90% predictive value for a serious
• Infections are an important cause of lymphadenopathy. underlying disease
• Evaluation of lymph nodes in multiple regions
→ Popliteal ANALYSIS OF CSF
→ Inguinal • Critical for patient with suspected meningitis or encephalitis
→ Epitrochlear • Opening pressure should always be recorded.
o Palpable epitrochlear nodes are always pathologic. • Fluid should routinely be sent for:
→ Axillary → Cell counts
→ Multiple cervical → Gram’s stain and culture
• Note the following: o Requires >105 bacteria/mL for reliable positivity
→ Location → Determination of glucose and protein levels
→ Size (normal <1cm) • Bacteria antigen tests for CSF are not recommended for
→ Tenderness screening.
→ Consistency (soft, firm, rubbery)
→ Whether nodes are matted (connected and moving CULTURES
together) • Mainstay of infectious disease diagnosis
• Specimens are collected before the administration of
SKIN antimicrobial therapy (blood, urine, sputum, pus from a wound)
• Pay attention to both front and back. • Allows identification of the etiologic agent, determination of the
• Specific rashes are extremely helpful in narrowing the antimicrobial susceptibility profile and isolate typing
diagnosis of an infection.
PATHOGEN SPCIFIC TESTING
FOREIGN BODIES • Serology
• Maintenance of epithelial barriers is one of the most important • Antigen testing
mechanism in protection against infection. • PCR testing
• Hospitalization of patient is often associated with breaches of → Identifies organisms that currently are not cultivable and
barriers due to placement of IV lines, surgical drains, and tubes have unclear relationships to disease
→ Allow microorganisms to localize in sites to which they • Facilitate rapid turnaround that ultimately enhances patient
normally would not have access care

C. DIAGNOSTIC TESTING (BOOK) RADIOLOGY

• Allows evaluation for lymphadenopathy in regions that are:
• Must be directed toward establishing an etiologic diagnosis. → Not externally accessible
• Shortest possible time, lowest possible cost, least possible → Assessment of internal organs for evidence of infection
discomfort to the patient → Facilitation of image-guided percutaneous sampling of
• Specimens must be appropriate and handled carefully. → deep spaces
• CT scan, MRI, Ultrasound, Nuclear medicine
WBC COUNT
• Elevations in the WBC count are associated with infection, D. LABORATORY DIAGNOSIS OF INFECTIOUS
though many viral infections are associated with leukopenia. DISEASES
• Important to assess WBC differential count
→ Different classes of microbes are associated with various • Requires demonstration, either direct or indirect, of viral,
leukocyte types. bacterial, mycotic, or parasitic agents in tissues, fluids, or
→ Bacteria: increase in polymorphonuclear neutrophils excreta of the host
→ Viruses: increase in lymphocytes
→ Certain parasites: increase in eosinophils DETECTION METHODS

INFLAMMATORY MARKERS DETECTION

DEFINITION AND EXAMPLE
METHOD
ERYTHROCYTE • Material that can be reproducibly
C-REACTIVE PROTEIN differentiated from other
SEDIMENTATION RATE
(CRP) substances present in the same
(ESR) Biologic signals
physical environment
Indirect measurement of Direct measurement of the • Structural components of bacteria,
the acute-phase response acute-phase response fungi etc.
• Trained eye of the technologist
Changes rapidly
• Sensitive electronic instruments
Changes slowly • Daily measurements can Detection system
→ Immunofluorescence
be useful
Table 3. Inflammatory markers of the body.
→ Chemiluminescence

MD-3 | Med2 | S01L28 | CPU College of Medicine | Salute Vivamus 2023 3|7
 • Culture of bacterium on an agar FACTORS THAT CAN GIVE RISE TO INCREASE IN
plate VACCINE-PREVENTABLE DISEASE
Amplification
• PCR • Low rates of immunization that result in an accumulation of
• Enzyme immunoassays susceptible people
• Microscopy • Changes in the infectious agent that permit it to escape
• Staining vaccine-induced protection
→ Gram’s stain • Waning of vaccine-induces immunity
→ Acid fast stain • Point-source introductions of large inoculate
Direct Detection → Fluorochrome stain
→ Immunofluorescent stain APPROACHES TO IMMUNIZATION AND
• Macroscopic Ag Detection VACCINATION
→ Latex agglutination assays • Vaccine: attenuated or live microorganisms/antigenic portions
→ Enzyme immunoassays • Toxoid: modified bacterial toxin
• Specimen collection and transport • Immune globulin: antibody containing protein
• Isolation of bacterial pathogens • Antitoxin: antibody derived from serum of animals
• culture agar
Culture • Isolation of viral agents A. IMMUNIZATION
→ Cultured cell for cytopathic
effect ACTIVE IMMUNIZATION
→ Immunofluorescent detection • Given as toxoids promoting production of antibodies directly
of viral Ag • Will take some time for the body to produce its own antibody
Table 4. Detection methods used and their specific examples.
• Live, attenuated: long-lasting immunity
• Inactivated: multiple doses or periodic boosters
IDENTIFICATION METHODS
• Classic Phenotyping PASSIVE IMMUNIZATION
• Gas-Liquid Chromatography • Given as immunoglobulin
• Nucleic Acid Probes
• Human tetanus immunoglobulin
• Transplacental transfer of maternal antibodies
SUSCEPTIBILITY TESTING • Generally used to provide temporary immunity
• Paper disk method
• Treatment of certain diseases associated with toxins
• Broth tube method
• Minimum inhibitory concentration (MIC) TARGET POPULATIONS AND TIMING OF
IMMUNIZATION
DETECTION OF PATHOGENIC AGENTS BY
• Individual’s responsiveness to vaccines
SEROLOGIC METHODS • Demographic features of the populations at risk
• IgM antibodies
• Duration and character of the immunologic response
• IgG antibodies
B. IMMUNE RESPONSE
E. TREATMENT
PRIMARY RESPONSE
• Requires broad knowledge of medicine
• Measurable circulating antibodies do not appear for 7-10 days
• Careful clinical judgment
• Characterized by early appearing IgM antibodies
• “Primum non nocere:” do no harm
• Obtain relevant samples for culture prior to administration of
SECONDARY RESPONSE
antibiotics.
• Elicited by second exposure to the same antigen
• General maxim for antibiotic treatment
• Usually occur within 4-5 days
→ Use a regimen with as narrow a spectrum as possible
• Characterized by marked proliferation of IgG antibody
→ Empirical regimens are necessarily somewhat broad
• Hypersensitivity reaction
• Herd immunity
IV. IMMUNIZATION PRINCIPLES AND
VACCINE USE C. VACCINATION

• Vaccination is ranked as one of the greatest public health ROUTRE OF ADMINISTRATION

achievements of the 20th century.
• Universal immunization has invariably remained an unattained
goal.
• Vaccination: administration of vaccine
→ Polio: only disease that is totally eradicated
• Immunization: process of inducing or providing immunity
• Determines the rapidity and nature of the immune responses to
vaccines
• Orally, intranasally, intradermally, subcutaneously, or
intramuscularly
• Must be administered by the licensed route to ensure
immunogenicity and safety

CONSTITUENTS OF VACCINES
• Preservatives, stabilizers, antibiotics
• Adjuvants: enhance immune response

MD-3 | Med2 | S01L28 | CPU College of Medicine | Salute Vivamus 2023 4|7
• Suspending fluids

USE OF VACCINES IN SPECIAL CIRCUMSTANCES

• Influenza pandemic preparedness
• Breast feeding
→ Neither killed nor live vaccine affect the safety of breast
feeding for either mother or infant.
• Pregnancy
→ Routine immunization should be avoided
→ Tetanus and diphtheria toxoid can be safely given
→ MMR,varicella should be withheld
o Has teratogenic effects, especially in the first trimester
• Occupational exposure
→ Workers: Hepatitis B
→ Healthcare givers
o Rubella
o Measles
o Varicella
• Immunocompromised persons (HIV+,
hematologic/generalized malignancy)
→ Should be immunized in the same manner as individuals
with normal immune system
→ Live attenuated vaccines are contraindicated
o May lead to disseminated infection with the vaccine virus

V. REFERENCES
• Dr. Sumagaysay’s PowerPoint Presentation
• Harrison’s Principles of Internal Medicine, 20th Edition, pp.
859-866

MD-3 | Med2 | S01L28 | CPU College of Medicine | Salute Vivamus 2023 5|7
VI. APPENDIX

REPORT MORBIDITY 2001 2002

DISEASE DECREASE %
PERIOD PRIOR MORBIDITY MORBIDITY

Smallpox 1900-1904 48,164 0 0 100

Diphtheria 1920-1922 175,885 2 1 100

Pertussis 1922-1925 147,271 7580 8296 94.6

Tetanus 1922-1926 1314 27 23 98.1

Neonate tet 1972-1985 785 29 1 98.1

Poliovirus 1951-1954 16.316 0 0 100

Measles 1958-1962 503,282 116 37 99.9

Mumps 1968 152, 209 266 328 99.8

Rubella 1966-1968 47,745 23 14 99.9

Congenital Rubella 1969 823 3 3 99.6

Hemophilus
Before 1985 20,000 27 27 99.9
Influenza type B
Table 5. Impact of immunization.

TYPE
YEAR PROTECTIVE ROUTE EFFICACY
VACCINE IMMUNIZING ADVERSE EVENTS
LICENSED AB ADMIN %
AGENT
Diphtheria, D:95 Local reactions,
DT 1949 Toxoid IM
tetanus T:95 Allergy
Inactivated
aP 1991 Not establish IM 80-90 Local reactions
bacterial Antigen
DTaP 1996 Acellular Not establish IM 80-90 No serious reaction
Bacterial Ab to capsular
Hib 1987 IM 90 Local reactions
polysaccharide polysaccharide
Inactivated IV Few
Ab to capsular
Hep B 1981 serum derivative IM 80-95
polysaccharide
Antigen GBS
Influenza 1945 Inactivated virus Neutralizing Ab IM 40-60 GBS
M:95
Neutralizing Acute encephalitis,
MMR 1971 Live virus SC Mu:90
measles Ab mumps, arthralgia
R:95
Pneumococcal Capsular Ab to
1983 IM.SC 60-80 Local reaction
polysaccharide polysaccharide polysaccharide
Polysaccharide-
Pneumo Ab to
2000 protein IM 73-94 None
conjugate polysaccharide
conjugates
No significant
IPV 1967 Inactive virus Neutralizing Ab SC 95
reaction
Varicella 1995 Live virus Neutralizing Ab SC 86-100 Local reaction
Table 6. Routinely recommended vaccines for infants, children and adults.

MD-3 | Med2 | S01L28 | CPU College of Medicine | Salute Vivamus 2023 6|7
 YEAR TYPE OF ROUTE OF ADVERSE
VACCINE INDICATION EFFICACY
LICENSE AGENT ADMINISTRATION EVENTS
Inactive virulent SC-6 doses, annual High risk No serious
Anthrax 1970 90%
bacteria booster exposure effects
Regional
BCG 1950 Living bacteria ID Exposed PDD Controversial adenitis,
disseminate
Mild local
Hep A 1995 Killed virus Ag IM Travelers 94
reaction
Inactive whole Not for public Fever, local
Cholera 1914 SC, IM 50?
Ag use reaction
Bacterial
Military,
Meningococcus 1981 polysaccharide, SC 90 for 2-3 y.0. Rare
travelers
4 types
Lab
Plague 1994 Inactive bacteria IM workworn, 90 Local reaction
foresters
Travelers,
Local reaction,
Rabies 1980 Inactivated virus IM, ID vet’s lab 100
arthritis
workworn
Live attenuated Encephalitis,
Yellow Fever 1978 SC Lab workworn High
virus death
Japanese B
1992 Inactivated virus SC Travelers 80-90 Anaphylaxis
encephalitis
Traveler’s,
Heat or phenol Fever, local
Typhoid 1952 IM contact of 50-70
killed bacteria reaction
carriers
Table 7. Special vaccines for infants, children, and adults.

MD-3 | Med2 | S01L28 | CPU College of Medicine | Salute Vivamus 2023 7|7