ANTHRAX

GROUP 1
UV-GCM
TOPICS
• EPIDEMIOLOGY
• PATHOPHYSIOLOGY
• CLINICAL MANIFESTATION
• LABORATORIES AND DIAGNOSIS
• THERAPEUTICS/MGT
Epidemiology

• Anthrax is common in the Middle East, the

Indian subcontinent, Africa, Asia, and Latin
America. It is endemic in Africa and Asia
despite vaccination programs.
Epidemiology
• Sporadic outbreaks have occurred as a result of
both agricultural and military disruptions

• Human anthrax often is associated with

agricultural or industrial workers who come in
contact with infected animal tissue.
Epidemiology

• There is no racial, sexual, or age predilection

for anthrax

• disease most often affects young and middle-

aged adult
PATHOPHYSIOLOGY
• Bacillus anthracis readily form spores when they
dry—an environmental condition unfavorable for
growth.
• Spores resist destruction and can remain viable in
soil, wool, and animal hair and hides for
decades.
• Spores germinate and begin multiplying rapidly
when they enter an environment rich in amino
acids and glucose (eg, tissue, blood).
 PATHOPHYSIOLOGY:
HUMAN INFECTION VIA,

• Cutaneous infection is usually acquired by

contact with infected animals or spore-
contaminated animal products or, rarely, from
contaminated heroin in injection drug users.
• Open wounds or abrasions increase susceptibility,
but infection may occur when skin is intact. Skin
infection may be transmitted from person to person
by direct contact or fomites.
 PATHOPHYSIOLOGY:
HUMAN INFECTION VIA,

• Gastrointestinal (including oropharyngeal) infection

may occur after ingestion of inadequately cooked meat
containing the vegetative forms of the organism, usually
when a break in the pharyngeal or intestinal mucosa
facilitates invasion.
• Ingested anthrax spores can cause lesions from the oral cavity
to the cecum. Released toxin causes hemorrhagic necrotic
ulcers and mesenteric lymphadenitis, which may lead to
intestinal hemorrhage, obstruction, or perforation.
 PATHOPHYSIOLOGY:
HUMAN INFECTION VIA,

• Pulmonary infection (inhalation anthrax),

caused by inhaling spores, is almost always
due to occupational exposure to
contaminated animal products (eg, hides) and
is often fatal.
DIAGNOSTICS
 DIAGNOSTICS
• Skin testing. A sample of fluid from a
suspicious lesion on your skin or a small tissue
sample (biopsy) may be tested in a lab for
signs of cutaneous anthrax.
• Blood tests. You may have a small amount of
blood drawn that's checked in a lab for
anthrax bacteria.
DIAGNOSTICS

• Chest X-ray or computerized

tomography (CT) scan. Your doctor may
request a chest X-ray or CT scan to help
diagnose inhalation anthrax.
• confirm if the patient has mediastinal widening or
pleural effusion, which are X-ray findings typically
seen in patients with inhalation anthrax.
DIAGNOSTICS
• Stool testing. To diagnose gastrointestinal anthrax,
your doctor may check a sample of your stool for
anthrax bacteria.
• Spinal tap (lumbar puncture). In this test, your
doctor inserts a needle into your spinal canal and
withdraws a small amount of fluid. A spinal tap is
usually done only to confirm a diagnosis of anthrax
meningitis.
Manifestation
Cutaneous anthrax symptoms
• A group of small blisters or bumps that may itch
• Swelling can occur around the sore
• A painless skin sore (ulcer) with a black center that
appears after the small blisters or bumps
• Most often the sore will be on the face, neck, arms, or
hands
Inhalation anthrax symptoms
• Fever and chills
• Chest Discomfort
• Shortness of breath
• Confusion or dizziness
• Cough
• Nausea, vomiting, or stomach pains
• Headache
• Sweats (often drenching)
• Extreme tiredness
• Body aches
Gastrointestinal anthrax
• Fever and chills
• Swelling of neck or neck glands
• Sore throat
• Painful swallowing
• Hoarseness
• Nausea and vomiting, especially bloody vomiting
• Diarrhea or bloody diarrhea
• Headache
• Flushing (red face) and red eyes
• Stomach pain
• Fainting
• Swelling of abdomen (stomach)
Injection anthrax symptoms
• Fever and chills
• A group of small blisters or bumps that may itch,
appearing where the drug was injected
• A painless skin sore with a black center that
appears after the blisters or bumps
• Swelling around the sore
• Abscesses deep under the skin or in the muscle
where the drug was injected
THERAPEUTICS and MANAGEMENT
 THERAPEUTICS and MANAGEMENT

• antibiotics and antitoxin is initiated early,

Anthrax can be successfully treated.
• Until sensitivity results are known, suspected
cases are best managed with a combination of
broadly active agents:
 THERAPEUTICS and MANAGEMENT
• Postexposure:
• Ciprofloxacin, 500 mg, PO bid × 60 d or
• Doxycycline, 100 mg PO bid × 60 d or
• Amoxicillin, 500 mg PO q8h × 60 d, likely to be effective if
strain is penicillin sensitive.

• Active disease:
• Ciprofloxacin, 400 mg IV q12h or doxycycline, 100 mg IV q12h
plus
• Clindamycin, 900 mg IV q8h and/or rifampin, 300 mg IV
q12h; switch to PO when stable × 60 d total plus

• Antitoxin Raxibacumab, 40 mg/kg IV over

• 2.25 h; diphenhydramine to reduce reaction
 THERAPEUTICS and MANAGEMENT
• Prophylaxis

• Anthrax vaccine adsorbed Recombinant protective antigen

vaccines are under study Raxibacumab when alternative
therapies are not available or appropriate.

• Although the current recommendation for postexposure

prophylaxis is 60 days of antibiotics, immunization with
anthrax vaccine if available could also be included.
 THERAPEUTICS and MANAGEMENT
• Prophylaxis
• Given the potential for B. anthracis to be engineered to
express penicillin resistance, the empirical regimen of
choice in this setting is either ciprofloxacin or doxycycline.
In settings where these approaches are not available or
appropriate, one can administer the antitoxin monoclonal
antibody raxibacumab.
Inhalational Anthrax Treatment Protocol*†
CATEGORY INITIAL THERAPY (IV)
Adults Ciprofloxacin, 400 mg every 12
hours* or Doxycycline, 100 mg
every 12 hours and ne or two
additional antimicrobials
Children Ciprofloxacin, 10 to 15 mg per
kg every 12 hours or
Doxycycline: >8 years and
>45 kg: 100 mg every 12
hours; >8 years and ≤45 kg:
2.2 mg per kg every 12 hours;
≤8 years: 2.2 mg per kg every
12 hours; and One or two
additional antimicrobials
Pregnant women Same for nonpregnant adults
(the high death rate from
infection outweighs the risk
posed by the antimicrobial
agent)
Immunocompromised Same for
persons nonimmunocompromised
persons and children
DURATION
IV treatment initially ; switch to oral
antimicrobial therapy when clinically
appropriate: Ciprofloxacin, 500 mg
orally twice daily or Doxycycline, 100
mg orally twice daily Continue for 60
days (IV and oral combined).
IV treatment initially; switch to
oral antimicrobial therapy when
clinically
appropriate: Ciprofloxacin, 10 to
15 mg per kg orally every 12
hours or Doxycycline: >8 years
and >45 kg: 100 mg orally twice
daily; >8 years and ≤45 kg: 2.2
mg per kg orally twice daily; ≤8
years: 2.2 mg per kg orally twice
daily Continue for 60 days (IV
and oral combined).
IV treatment initially; switch to
oral antimicrobial therapy when
clinically appropriate†: oral
therapy regimens are same for
nonpregnant adults.
Same for
nonimmunocompromised persons
and children
Cutaneous Anthrax Treatment Protocol*
CATEGORY INITIAL THERAPY (ORAL)† DURATION
Adults Ciprofloxacin, 500 mg twice daily 60 days

or
Doxycycline, 100 mg twice daily

Children Ciprofloxacin, 10 to 15 mg per kg every 12 60 days

hours (not to exceed 1 g per day)

or
Doxycycline§: >8 years and >45 kg: 100
mg every 12 hours; >8 years and <=45 kg:
2.2 mg per kg every 12 hours; <=8 years:
2.2 mg per kg every 12 hours

Pregnant women Ciprofloxacin, 500 mg twice daily 60 days

or
Doxycycline, 100 mg twice daily

Immunocompromise Same for nonimmunocompromised 60 days

d persons persons and children
Group 2
 Epidemiology
Relatively rare but associated with high
morbidity
primarily affects newborns and children
 Pathogenesis

S. aureus-mediated production of
exfoliative toxin
The syndrome is a generalized
exanthematous disease consisting of
cutaneous tenderness and widespread
superficial blistering and denudation
Exfoliative toxins (A and B)
Attaches to Desmoglein 1 (cell adhesion molecule)
loss of cell–cell adhesion
epidermolysis takes place usually between the
stratum spinosum and granulosum
Results in a very thinwalled, flaccid blister that is
easily disrupted, exhibiting a positive Nikolsky sign
 faint, orange–red
macular exanthem or
uniform erythema
sparing mucosal
surfaces
concomitant cutaneous tenderness is usually present at
this early stage
Within 1–2 days the rash progresses from an
exanthematous scarlatiniform to a blistering eruption
Very superficial tissue paperlike wrinkling of the epidermis
(characteristic)
progresses to large flaccid bullae in flexural and
periorificial surfaces.
A positive Nikolsky sign can be elicited by stroking the
skin which results in a superficial blister
 acantholysis in the
GRANULAR layer and
subcorneal cleft formation in
early lesions
intact viable epidermis
with shedding of the stratum
corneum in the desquamative
stage
 TEN VS. SSS

In contrast to TEN, SSSS never has mucosal

erosions.
Tzanck smear shows acantholytic cells in SSSS
but not in TEN
use of frozen sections rapidly differentiate the
superficial subgranular acantholysis in SSSS
versus the characteristic full-thickness
epidermal necrosis and dermal–epidermal
separation seen in TEN
 Treatment

requires hospitalization
intravenous antistaphylococcal antibiotics
supportive skin care
management of potential fluid and electrolyte
abnormalities
Neonates benefit from incubators to maintain
body temperature and humidity
use of nonadherent dressings (petrolatum-
impregnated gauze)
Antibiotic mupirocin ointment (Adjunct)
Bubonic Plague
Group 3
Epidemiology
 Plague
 also named Black Death caused three great
pandemics that killed an estimated 100 million
people In Egypt and Byzantium in the sixth
century

 one quarter of Europe’s population in the

fourteenth and fifteenth century

 tens of millions in India, Myanmar, and China at

the beginning of the twentieth century.
 Most cases are now found in Africa

 organism is Endemic in many parts of the world,

including nations in the former Soviet Union, the
Americas, and Asia.

 Wild rodents in the rural western United States

are infected with Y. pestis and are the source of
10-15 human cases every year
PATHOPHYSIOLOGY
• Replication of Y. pestis in a regional lymph node results in the local
swelling of the lymph node and periglandular region known as a
bubo.
• On histology, the node is found to be hemorrhagic or necrotic, with
thrombosed blood vessels, and the lymphoid cells and normal
architecture are replaced by large numbers of bacteria and fibrin
• Periglandular tissues are inflamed and also contain large numbers
of bacteria in a serosanguineous, gelatinous exudate.

• Continued spread through the lymphatic vessels to contiguous

lymph nodes produces secondorder primary buboes.
• Infection is initially contained in the infected regional lymph nodes,
although transient bacteremia can be detected.

• As the infection progresses, spread via efferent lymphatics to the

thoracic duct produces high-grade bacteremia.
• Hematogenous spread to the spleen, liver, and secondary buboes
follows, with subsequent uncontrolled septicemia, endotoxic
shock, and disseminated intravascular coagulation leading to
death.

• In some patients, this septicemic phase occurs without obvious

prior bubo development or lung disease (septicemic plague).
• Hematogenous spread to the lungs results in secondary plague
pneumonia.
• bacteria initially more prominent in the interstitium than in the air
spaces.

• Hematogenous spread to other organs, including the meninges.

 Clinical Manifestations
  Bubonic Plague

Incubation Period: 2-6 days

Onset: Sudden
–Characterized by fever (>38C), malaise, myalgia,
dizziness and increasing pain due to progressive
lymphadenitis in the regional nodes near the fleabite or
other inoculation site.
• Lymphadenitis - tense, tender swelling (bubo), boggy with an
underlying hard core
  Bubonic Plague

Generally, there is ONE painful and erythematous

bubo with surrounding periganglionic edema
Bubo - commonly inguinal but can be crural, axillary,
cervical or submaxillary (depending on the site of
the bite)
Children - most likely to present with cervical or
axillary buboes
  Bubonic Plague

Without treatment, Y.pestis dissemination occurs

and cause pneumonia (secondary pneumonic
plague) and meningitis.
– Secondary Pneumonic Plague
• source of person-to-person transmission of respiratory
infection by productive cough, with the consequent
development of primary plague pneumonia
  Bubonic Plague

Appropriate treatment results in fever resolution

within 2-5 days, but buboes may remain enlarged for
>1 week after initial treatment and can become
fluctuant
  Primary Septicemic Plague

Minority (10-25%) of infections with Y.pestis

Gram (-) septicemia (hypotension, shock) without
preceding lymphadenopathy
occurs in all age group, but persons >40 years of age
are at elevated risk
  Pneumonic Plague
results from inhalation of infectious bacteria in
droplets expelled from another person or animal
with primary or secondary plague pneumonia
short incubation period (ave. from 2-3 days, range 1-7
days)
characterized by sudden onset of fever, headache,
myalgia, weakness, n/v and dizziness
  Pneumonic Plague
Respiratory Signs
–cough
–dyspnea
–chest pain
–sputum production with hemoptysis
Typically arise after 24 hours
• Progression of initial segmental pneumonitis to lobar
pneumonia and then to bilateral lung involvement
may occur
  Pneumonic Plague

Secondary Pneumonic Plague

–consequence of bacteremia occuring in 10 to 15 % of pt
–Bilateral alveolar infiltrates are seen on chest X-ray, and
diffuse interstitial pneumonitis with scanty sputum
production is typical
  Meningitis

uncommon
presentation with headache and fever typically occurs
>1 week after the onset of bubonic or septicemic
plague and may be associated with suboptimal
antimicrobial therapy and cervical or axillary buboes
  Pharyngitis
can follow consumption of contaminated meat from
an animal dyinhg of plague or contact with persons
or animals with pneumonic plague.
resemble tonsilitis, with peritonsillar abscess and
cervical lymphadenopathy.
Assymptomatic pharyngeal carriage of Y.pestis can
also occur in close contact s of patients with
pneumonic plague
Laboratories and
diagnostics
 Laboratory testing is required in order to diagnose and confirm plague.
Confirmation is through the identification of Y. Pestis culture from a patient.
Confirmation can be done by examining serum taken during the early and late stages
of infection.to check for Y. Pestis antigen and rapid dipstick tests .
Samples are.
• Buboes: swollen lymph nodes ,a fluid sample can be taken from them with a needle
• Blood
• Lungs
Therapeutics &
Management
A 10-day course of antimicrobial therapy is recommended.
Streptomycin has historically been the parenteral treatment of
choice for plague and is approved for this indication by the
FDA

In 2012, the FDA approved levofloxacin for prophylaxis and

treatment of plague (including septicemic and pneumonic
disease), making it the first antibiotic approved for a new
indication under a regulatory approach based on animal
studies alone, known as the Animal Rule.
Tetracyclines are also effective and can be given by mouth but
are
not recommended for children under the age of 7 years
because of tooth discoloration

Doxycycline
is the tetracycline of choice; at an oral dosage of 100 mg twice daily,
this drug was as effective as IM gentamicin (2.5 mg/kg twice daily) in
a trial in Tanzania.
INFLUENZA
GROUP 4
 INFLUENZA
• Respiratory illness accompanied by systemic
symptoms of:
– Fever
– Malaise
– Myalgia
 ETIOLOGIC AGENT
• 3 VIRUSES OCCUR IN HUMAN:
– INFLUENZA VIRUS A
– INFLUENZA VIRUS B • Irregularly circular
• 80-120 nm in diameter
– INFLUENZA VIRUS C • Lipid envelope and prominent spikes

– 2 surface glycoproteins:
• Hemagglutinin (H)
– Viral attachment protein binding to sialic acid receptors on the cells that line the superficial
epithelium of the respiratory tract.
– Neuraminidase
»Cleaves the virus from the cell membrane
•Facilitates its release from the cell and prevent self aggregation of viruses.
 EPIDEMIOLOGY
• Causes outbreaks during cooler months.
• Typical outbreak begins
– Early winter
– Last 4-5 weeks
– Largely spread by small and large particle droplet.
The SEVERITY of an epidemic depends on the:

• TRANSMISSIBILITY and VIRULENCE of the viral strain

• SUSCEPTIBILITY of the population
• ADAPTATION of the virus human host
• DEGREE OF ANTIGENIC match to the recommended
vaccine
PATHOGENESIS
 CLINICAL
MANIFESTATION

RHINORRHEA SORE THROAT CONJUNCTIVITIS COUGH

WHAT DISTINGUISHES INLUFENZA FROM OTHER RESPIRATORY
ILLNESS?

THE DEGREE OF:

FEVER FATIGUE MYALGIA MALAISE

 LABORATOY AND DIAGNOSIS

• Nasopharygeal specimens
– samples are most effectively collected with a flocked swab that is
inserted 1–2 inches into the nose (following the course of the
inferior meatus), twirled, placed in viral transport medium
– transported on ice to the laboratory as promptly as possible.
– sample collection early in the course of illness ideally within 48 h of
the onset of symptoms
• PCR-based molecular probe
– most useful clinical approach
– amplifies specific segments of the influenza genome
– most sensitive and specific method
– provides opportunities to identify the strain with some specificity
• Mild leukopenia
• white blood cell count above 15,000/μL
suggests a secondary bacterial component in
influenzal pneumonia.
 PROPHYLAXIS
• VACCINES
 TREATMENT

• Influenza A and B viruses consists

of NEURAMINIDASE INHIBITORS
– most effective in patients whose
influenza illness is recognized
early and confirmed by rapid
antigen detection or on the
basis of clinical and
epidemiologic evidence.
– Recommended for complicated
influenza infections in
hospitalized patients
– risk of development of
resistance
The available neuraminidase inhibitors are
• Oral oseltamivir
– Most widely used.
– orally absorbed drug that is converted to its active
component, oseltamivir carboxylate (LIVER)
– preferred for treatment of pregnant women and is
approved for children ≥1 year of age
• Nasal-spray zanamivir
– relative contraindications : ASTHMA AND COPD
• Intravenous peramivir and zanamivir
– indicated in severely ill patients.
GROUP 5
 CHOLERA

• Rapidly dehydrating diarrheal disease that can lead

to death
• Caused by Vibrio cholerae
– serogroups O1 and O139 have been assumed with
epidemics)
• Humans -only known hosts
• Persist in environment
– formation of a biofilm and ability to enter a viable but
nonculturable state
 CHOLERA
• MOT: Consumption of contaminated water and
ingestion of undercooked shellfish
• Profuse rice-water stools – contain high
concentrations of V. cholerae (up to 108/gm of
stool)
• Most cases: mild and inapparent
• Cholera gravis – most severe form , purging
rates of 500-1,000 mL/hr
 Pathogenesis
Virulence factors:
• Cholera Toxin
 potent protein enterotoxin elaborated by the organism in the small
intestine.
• Toxin-Coregulated Pilus (TCP),
 survive and multiply in (colonize) the small intestine.
 For bacaterial colonization
Regulator:
• ToxR
 modulates the expression of genes coding for virulence factors in
response to environmental signals via a cascade of regulatory
proteins.
• Quorum sensing
– bacterial responses to the density of the bacterial population
 MOT:
Consumption of contaminated water
and ingestion of undercooked shellfish

Bacterial invasion in the small bowel  cholera

toxin production (Activation of A1 subunit)

A1 subunit irreversibly transfers ADP-ribose from

nicotinamide adenine dinucleotide to its specific target
protein upregulation of Adenylate Cyclase

Adenylate Cyclase intracellular accumulation of

high levels of cyclic AMP.
cyclic AMP inhibits the absorptive sodium
transport system in villus cells and activates the
secretory chloride transport system in crypt cells

accumulation of sodium chloride

in the intestinal lumen.

volume of that fluid exceeds the capacity of the

rest of the gut to resorb it watery
diarrhea
Wasted fluid and electrolytes not
replaced  shock (due to profound
dehydration) and acidosis (due to loss
of bicarbonate)
 Risk for Severe Disease:

• Persons with blood group O

• Decreased gastric acidity
• Malnutrition
• Immunocompromised state, and
• Absence at local intestinal immunity (prior
exposure by infection or vaccination)
 Signs and symptoms
• Non billous gray, slighty cloudy fluid with flecks of mucus, no
blood and somewhat fishy, inoffensive odor. “rice water”
• Thirst
• Postural hypotension
• Weakness
• Tachycardia
• Decrease skin turgor
• Oliguria
• Sunken fontanelles
• Somnolence and coma
 Laboratories
• Bacteriological Confirmation

• Confirmation in 10 to 20 stool samples are

sufficient

• Rapid test or Cary Blair Medium, Filter Paper

 Outbreak
• For confirmation of the Outbreak stool samples should be
collected from up to 10 to 20 previously untreated cases who
meet the following criteria:
– Onset of illness less than four days before sampling
– Currently having watery diarrhea
– Have not received antibiotic treatment for this illness
 Collection of specimen

• Stool should be collected either by:

– Collecting a swab from a freshly passed stool specimen

– Swab of the rectal contents

 Management
I. Rehydration
-essential component of treatment,
-to replenish the water and electrolytes lost through diarrhea and
vomiting.

Oral replenishment is preferred, with intravenous replenishment

reserved for the rehydration of patients with severe dehydration or
who eliminate more than 10-20 ml/kg/h.
DEHYDRATION STATUS TREATMENT

MILD Oral rehydration at home.

Practical Advice
• Liquids should be administered in small amounts frequently
• For children more than 14 yrs old and adults ; ensure at least 2
liters per day and one glass per bowel movement

MODERATE Oral rehydration salts and close clinical monitoring especially children
under 18 months of age.

SEVERE INTRAVENOUS REHYDRATION

• ABSENCE OR WEAK RADIAL PULSES indicates a life threatening
emergency. 2 or more lines should be installed. LACTATED RINGER
is the solution of choice.
ORAL REHYDRATION
I. Zinc Supplements
-reduces the duration and severity of
diarrhea in children.

For children <6 months : 10mg/daily x 10 days

Children 6 months-5yrs old : 20mg/daily x 10
days
I. Antibiotic
for prompt eradication of vibrio, diminish the duration of diarrhea
and decrease the fluid loss.

Tetracycline
– effective treatment for cholera 2,3
– superior to furazolidone 8, chloramphenicol 9 and sulfaguanidine 9
in reducing cholera morbidity.
• Erythromycin
– Effective for cholera treatment, and appropriate for children and
pregnant women.
Diphtheria

Group 6
Overview
Nasopharyngeal and skin infection
Corynebacterium diphtheriae
Toxigenic strains causes systemic toxicity,
myocarditis, and polyneuropathy, associated
with the formation of pseudomembranes in
the pharynx during respiratory diphtheria.
Nontoxigenic strains commonly cause
cutaneous disease.
 Epidemiology

Temperate regions, respiratory diphtheria occurs

year-round but is most common during winter
months.
Transmitted via the aerosol route, usually during
close contact with an infected person.
The incubation period for respiratory diphtheria
is 2–5 days
Diisease onset has occurred as late as 10 days
after exposure.
The disease primarily affected children and
nonimmune young adults.
The development of diphtheria antitoxin in
1898 by von Behring and of the diphtheria
toxoid vaccine in 1924 by Ramon led to the
near-elimination of diphtheria in Western
countries.
Risk Factors

Older age

Lack of vaccination

Alcoholism

Socioeconomic status

Crowded living conditions

Native American Ethnic Background

Cutaneous diphtheria is usually a secondary
infection that follows a primary skin lesion
due to trauma, allergy, or autoimmunity.
Isolates lack the tox gene and thus do not
express diphtheria toxin.
In tropical latitudes, cutaneous diphtheria is
more common than respiratory diphtheria.
 Pathogenesis
Diphtheria toxin produced by tox+ strains of C. diphtheriae is the
primary virulence factor. Has a 50% lethal dose of ~100 ng/kg of body
weight.

The toxin is produced in the pseudomembranous lesion and is taken up

in the bloodstream, from which it is distributed to all organ systems in
the body.

Individuals with a diphtheria antitoxin titer of >0.01 U/mL are at low risk
of disease.
Characteristic pathologic findings of
diphtheria include mucosal ulcers with a
pseudomembranous coating composed of an
inner band of fibrin and a luminal band of
neutrophils.
 Clinical Manifestations

Respiratory
Cutaneous
Others
 Respiratory Diphtheria

The clinical diagnosis of diphtheria is based on the constellation of

sore throat; adherent tonsillar, pharyngeal, or nasal
pseudomembranous lesions; and low-grade fever.

In addition, diagnosis requires the isolation of C. diphtheriae or

histopathologic isolation of compatible gram-positive organisms.

Carriers are defined as individuals who have positive cultures for C.

diphtheriae and who either are asymptomatic or have symptoms
but lack pseudomembranes.
The systemic manifestations include weakness as a result of
neurotoxicity and cardiac arrhythmias or congestive heart failure
due to myocarditis.
Most commonly, the pseudomembranous lesion is located in the
tonsillopharyngeal region.
Large pseudomembranes are associated with severe disease and
a poor prognosis.
A few patients develop massive swelling of the tonsils and
present with “bullneck” diphtheria, which results from edema of
the submandibular and paratracheal region and is further
characterized by foul breath, thick speech, and stridorous
breathing.
-Bates' Guide to Physical Examination and History Taking 11th Edition
 Cutaneous Diphtheria

Punched-out ulcerative lesions with

necrotic sloughing or
pseudomembrane formation
Commonly occurs on the lower and
upper extremities, head, and trunk.
 Other Clinical
Manifestations
C. diphtheriae causes rare cases of
endocarditis and septic arthritis
Most often in patients with preexisting risk
factors, such as abnormal cardiac valves,
injection drug use, or cirrhosis.
 Complications

Airway obstruction
Polyneuropathy
Myocarditis- Most common cause of
death
Others: pneumonia, renal failure,
encephalitis, cerebral infarction,
pulmonary embolism, and serum
sickness from antitoxin therapy
 Diagnosis

Based on clinical signs and symptoms plus

laboratory confirmation.
The presence of a pseudomembrane should
prompt strong consideration of diphtheria.
Once a clinical diagnosis of diphtheria is
made, diphtheria antitoxin should be
obtained and administered as rapidly as
possible.
Laboratory diagnosis of diphtheria is based
either on
Cultivation from the site of infection
Demonstration of local lesions with characteristic
histopathology
Corynebacterium pseudodiphtheriticum, a
nontoxigenic organism, is a common
component of the normal throat flora and
does not pose a significant risk.
A diagnosis of cutaneous diphtheria requires
laboratory confirmation since the lesions are not
characteristic and are indistinguishable from
other dermatoses.
Diphtheritic ulcers occasionally—but not
consistently—have a punched-out appearance
The laboratory medium: Löffler’s or Tinsdale’s
selective medium in addition to nonselective
medium such as blood agar.
 Treatment

Dipththeria anti-toxin
Anti-microbial therapy
Other strategies
 Diphtheria Antitoxin

Diphtheria antitoxin, a horse antiserum,

is effective in reducing the extent of local
disease as well as the risk of
complications of myocarditis and
neuropathy.
Diphtheria antitoxin cannot neutralize
cell-bound toxin, prompt initiation is
important.
The current protocol for the use of diphtheria
antitoxin involves a test dose to rule out
immediate hypersensitivity.
Human monoclonal antibody with the
potential to provide a safer alternative to
equine antitoxin therapy is being developed.
 Antimicrobials

Procaine penicillin G
600,000 U IM q12h
Children: 12,500-25,000 U/kg IM q12h (until
the patient can swallow comfortably);
Then oral penicillin V, 125–250 mg qid to
complete a 14-day course •
Erythromycin
500 mg IV q6h
For children: 40–50 mg/kg per day IV
in 2-4 divided doses (until the patient can swallow
comfortably);
Then 500 mg PO qid to complete a 14-day course
Penicillin was associated with a more rapid
resolution of fever and a lower rate of bacterial
resistance than erythromycin; however, relapses
were more common.
Erythromycin therapy targets protein synthesis
and thus offers the presumed benefit of stopping
toxin synthesis more quickly than a cell wall–
active β-lactam agent.
Alternative therapeutic agents for patients who
are allergic to penicillin or cannot take
erythromycin include rifampin and clindamycin.
Eradication of C. diphtheriae should be
documented after antimicrobial therapy is
complete.
A repeat throat culture 2 weeks later is
recommended.
For patients in whom the organism is not
eradicated after a 14-day course of erythromycin
or penicillin, an additional 10-day course
followed by repeat culture is recommended.
 Other Strategies

Suspected cases should be hospitalized in respiratory isolation rooms

Close monitoring of cardiac and respiratory function, to assess the
possibility of myocarditis.
In patients with extensive pseudomembranes, an anesthesiology or
ENT consultation is recommended because of the possible need for
tracheostomy or intubation.
 Prognosis

Mortality rate for diphtheria (5–10%)

20% among <5 & >40 years old
Fatal pseudomembranous diphtheria typically occurs in patients
with nonprotective antibody titers and in unimmunized
patients.
Risk factors for death include bullneck diphtheria; myocarditis
with ventricular tachycardia; atrial fibrillation; complete
heart block; an age of >60 years or <6 months; alcoholism;
extensive pseudomembrane elongation; and laryngeal, tracheal,
or bronchial involvement.
Another important predictor of fatal outcome
is the interval between the onset of local
disease and the administration of antitoxin.
Cutaneous diphtheria has a low mortality rate
and is rarely associated with myocarditis or
peripheral neuropathy.
 Prevention

Vaccination
Prophylaxis Administration
Vaccination
Currently, DTaP Tdap
diphtheria toxoid
vaccine is
coadministered Tdap is a tetanus toxoid, reduced
with tetanus diphtheria toxoid, and acellular
vaccine (with or pertussis vaccine
without acellular
pertussis).
Full-leveled diphtheria toxoid, tetanus Recommended that all adults (i.e.,
toxoid, and acellular pertussis vaccine persons >19 years old) receive a single
dose of Tdap if they have not received it
previously, regardless of the interval
since the last dose of Td (tetanus and
reduceddose diphtheria toxoids,
adsorbed).

Recommended for children up to the age Recommended for children ≥7 years old
of 6 and for adults.

Adults who have received acellular

DTaP replaced the earlier whole-cell pertussis vaccine should continue to
pertussis vaccine DTP in 1997 receive decennial Td booster
vaccinations.
 Vaccination

Tetanus/diphtheria (Td) vaccine

Adults with an uncertain or incomplete history of primary

vaccination,should receive three doses of Td or Tdap (Td
plus acellular pertussis), then a Td booster every 10 years.

Adults ≤65 years should get Tdap if they have never received
Tdap previously and/or have contact with infants ≤12
months of age to protect against pertussis.

-Bates' Guide to Physical Examination and History Taking 11th

Edition
 Prophylaxis
Administration
Close contacts of diphtheria patients should undergo throat
culture to determine whether they are carriers. After samples
for throat culture are obtained, antimicrobial prophylaxis
should be considered for all contacts, even those whose cultures
are negative. The options are 7–10 days of oral erythromycin or
one dose of IM benzathine penicillin G (1.2 million units for
persons ≥6 years of age or 600,000 units for children <6 years of
age). Contacts of diphtheria patients whose immunization status
is uncertain should receive the appropriate diphtheria toxoid–
containing vaccine. The Tdap vaccine (rather than Td) is now the
booster vaccine of choice for adults who have not recently
received an acellular pertussis–-containing vaccine. Carriers of C.
diphtheriae in the community should be treated and vaccinated
when identified.
 Clostridial Myonecrosis
(Clostridium perfringens)
GROUP 7
 Etiologic Agent
• pleomorphic, rod-shaped, arranged singly or in short
chains
• cells have rounded or sometimes pointed ends
• stain gram-positive in the early stages, may appear to
be gram-negative or gram-variable later in the growth
cycle or in infected tissue specimens
• Most strains are motile by means of peritrichous
flagella
• Nonmotile species include C. perfringens, C. ramosum,
and C. innocuum
• Most species are obligately anaerobic
• Clostridia produce more protein toxins than
any other bacterial genus:
• neurotoxins, enterotoxins, cytotoxins,
collagenases, permeases, necrotizing toxins,
lipases, lecithinases, hemolysins,
proteinases, hyaluronidases, DNases, ADP-
ribosyltransferases, and neuraminidases
• Botulinum and tetanus neurotoxins are the
most potent toxins known
• lethal doses of 0.2–10 ng/kg for humans
 Epidemiology

endospores > commonly found in soil, feces,

sewage, and marine sediments
greatly influenced by the degree and duration of
animal husbandry in a given location
incidence of clostridial gas gangrene is higher in
agricultural regions of Europe than in the Sahara
Desert of Africa
present in intestinal tract of
humans and animals, in the
female genital tract, and on
the oral mucosa
In developing nations, food
poisoning, necrotizing
enterocolitis, and gas
gangrene are common
Gas gangrene commonly
follows knife or gunshot
wounds or vehicular
accidents or develops as a
complication of surgery or
gastrointestinal carcinoma
Vaccination against exotoxins
important in pathogenesis
would be of great benefit in
developing nations
could also be used safely in
at-risk populations such as
the elderly
hyperimmune globulin >
valuable tool for prophylaxis
in victims of acute
traumatic injury or for
attenuation of the spread of
infection in patients with
established gas gangrene
 Pathogenesis

• In traumatic gas gangrene, organisms

are introduced into devitalized tissue
• C. perfringens and C. novyi, trauma
must be sufficient to interrupt the
blood supply and thereby to establish
an optimal anaerobic environment for
growth of these species
• The major C. perfringens
extracellular toxins implicated in gas
gangrene are α toxin and θ toxin
• A lethal hemolysin that has
both phospholipase C and
sphingomyelinase activities,
α toxin has been implicated
as the major virulence factor
of C. perfringens
• The formation of these
aggregates, which occurs
within minutes, is largely
mediated by α toxin’s ability
to activate the platelet
adhesion molecule gpIIb/IIIa
• the implication is that platelet
glycoprotein inhibitors (e.g.,
eptifibatide, abciximab) may be
therapeutic for maintaining tissue
blood flow
• C. perfringens θ toxin
(perfringolysin) is a member of
the thiol-activated cytolysin
family known as cholesterol-
dependent cytolysins, which
includes streptolysin O from
group A Streptococcus,
pneumolysin from Streptococcus
pneumoniae, and several other
toxins
• Cardiovascular collapse and
end-organ failure occur late in
the course of C. perfringens
gas gangrene and are largely
attributable to both direct and
indirect effects of α and θ
toxins
• C. septicum produces three
main toxins—α toxin (lethal,
hemolytic, necrotizing activity),
β toxin (DNase), and γ toxin
(hyaluronidase)— as well as a
protease and a neuraminidase
 Clostridial
Myonecrosis
CLINICAL MANIFESTATIONS
 TRAUMATIC GAS GANGRENE

• C. perfringens myonecrosis (gas gangrene) is

one of the most fulminant gram-positive
bacterial infections of humans
• accompanied by bacteremia, hypotension,
and multiorgan failure and is invariably fatal
if untreated.
• is a true emergency and requires immediate
surgical debridement
• The development of gas gangrene requires
an anaerobic environment and
contamination of a wound with spores or
vegetative organisms
 Traumatic gas gangrene:

• Sudden onset of excruciating

pain at affected site
• Rapid developement of foul-
smelling wound containing a
thin serosangineous discharge
& gas bubbles
• Brawning edema & induration
• Cutaneous blisters containing
bluish to maroon-colored fluid
• Liquefied & sloughed tissue
 Spontaneous (nontraumatic) gas
gangrene:

• Confusion ( 1st symptom)

• Abrupt onset of excruciating pain
in the absence of trauma
• Fever
• Rapid progression of tissue
destruction with gas in tissue
• Swelling
• Bullae filled with clear, cloudy,
hemorrhagic or purplish fluid
• Purple hue on surrounding skin
 Systemic findings:
• Tachycardia disproportionate to the degeree
of fever
• Pallor
• Diaphoresis
• Hypotension/shock
• Renal failure/multiorgan failure
• Mental status alteration
Untreated clostridial myonecrosis:

• Disseminated
myonecrosis
• Suppurative
visceral infection
• Septicemia
• Death within
hours
 Laboratory and diagnostics

prompt surgical inspection of the infected site.

Direct examination of a Gram-stained smear of the involved tissues
Characteristic histologic findings in clostridial gas gangrene include
widespread tissue destruction, a paucity of leukocytes in infected tissues in
conjunction with an accumulation of leukocytes in adjacent vessels, and
the presence of gram-positive rods (with or without spores).
CT and MRI are invaluable for determining whether the infection is
localized or is spreading along fascial planes.
When spontaneous gas gangrene is suspected, blood cultured should be
done
Immediate workup: CBC, CMP,
urinalysis, PT, APTT, blood and
wound cultures
blood tests: ABG, lactic acid, and
pre-calcitonin helpful in the
evaluation of sepsis
imaging studies: x-rays, CT scan
of the infected body part, and
ultrasound helpful in identifying
the extent of the infection,
abscess, and gas in the tissues
 Treatment
• Direct examination of a Gram-stained smear of
the involved tissues is of major importance
• Characteristic histologic findings in clostridial gas
gangrene include widespread tissue destruction,
a paucity of leukocytes in infected tissues in
conjunction with an accumulation of leukocytes
in adjacent vessels
• Patients with evidence of clostridial gas gangrene,
thorough emergent surgical debridement is of
extreme importance
• Closure of traumatic wounds or compound
fractures should be delayed for 5–6 days until it is
certain that these sites are free of infection
• C. tertium is
resistant to
penicillin,
cephalosporins, and
clindamycin.
Appropriate
antibiotic therapy
for C. tertium
infection is
vancomycin (1 g
every 12 h IV) or
metronidazole (500
mg every 8 h IV).
 Prognosis
• more favorable when the infection involves an
extremity rather than the trunk or visceral
organs, since debridement of the latter sites is
more difficult
• Gas gangrene is most likely to progress to
shock and death in patients with associated
bacteremia and intravascular hemolysis
 Prevention
• Initial aggressive debridement of devitalised
tissue can reduce the risk of gas gangrene in
contaminated deep wounds.
• Interventions to be avoided: prolonged
application of tourniquets and surgical closure of
traumatic wounds
• hyperimmune globulin would represent a
significant advance for prophylaxis in victims of
acute traumatic injury or for attenuation of the
spread of infection in patients with established
gas gangrene
Tetanus
Epidemiology
Tetanus is a rare disease in the developed
world.
Two cases of neonatal tetanus have occurred
in the United States since 1989.
In 2013, 26 cases of tetanus were reported to
the U.S. national surveillance system.
Epidemiology

Most cases occur in incompletely vaccinated or

unvaccinated individuals. Vaccination status is
known in 50% of cases reported in the United
States between 1972 and 2009; among these
cases, only 16% of patients had had three or
more doses of tetanus.
Epidemiology

 Vaccination status is known in 50% of cases

reported in the United States between 1972
and 2009; among these cases, only 16% of
patients had had three or more doses of
tetanus.
Epidemiology

Persons more than 60 years of age has greater

risk because antibody levels decreases overtime
1/3 of cases in United States are more than 65
years old
High risk groups were people who inject drugs-
heroin (15% cases were reported in 2001-2008)
Epidemiology

There was an outbreak in 2004 in United

Kingdom, report was unclear but are thought
of combination of heroin use and incomplete
vaccination.
Epidemiology

The majority of reported tetanus cases are:

1. Birth associated
2. occurring in low income countries among i
insufficiently vaccinated mothers and their
newborn infants
3. following unhygienic deliveries and
abortions
4. and poor postnatal hygiene and cord care
practice
Epidemiology
Epidemiology
Epidemiology
Pathophysiolo
gy
Pathophysiolo
gy
• Clostridium tetani is an obligate, anaerobic, motile,
gram-positive bacillus.
• It is nonencapsulated and forms spores that are
resistant to heat, desiccation, and disinfectants.
• . They are found in soil, house dust, animal
intestines, and human feces.
• Spores can persist in normal tissue for months to
years.
Pathophysiolo
gy
• To germinate, the spores require specific anaerobic
conditions, such as wounds with low oxidation-
reduction potential (eg, dead or devitalized tissue,
foreign body, active infection).
• Under these conditions, upon germination, they may
release their toxin.
Pathophysiolo
gy
• Infection by C tetani results in a benign appearance
at the portal of entry because of the inability of the
organism to evoke an inflammatory reaction unless
coinfection with other organisms develops.
• When the proper anaerobic conditions are present,
the spores germinate and produce the following 2
toxins:
Pathophysiolo
gy
• Tetanolysin – This substance is a hemolysin with no
recognized pathologic activity.
• Tetanospasmin – This toxin is responsible for the
clinical manifestations of tetanus ; by weight, it is
one of the most potent toxins known, with an
estimated minimum lethal dose of 2.5 ng/kg body
weight
Pathophysiolo
gy
• After the light chain enters the motor neuron, it
travels by retrograde axonal transport from the
contaminated site to the spinal cord in 2-14 days.
• When the toxin reaches the spinal cord, it enters
central inhibitory neurons. The light chain cleaves
the protein synaptobrevin, which is integral to the
binding of neurotransmitter containing vesicles to
the cell membrane.
Pathophysiolo
gy
• As a result, gamma-aminobutyric acid (GABA)-
containing and glycine-containing vesicles are not
released, and there is a loss of inhibitory action on
motor and autonomic neurons. With this loss of
central inhibition, there is autonomic hyperactivity as
well as uncontrolled muscle contractions (spasms) in
response to normal stimuli such as noises or lights.
Pathophysiolo
gy
• Once the toxin becomes fixed to neurons, it cannot
be neutralized with antitoxin. Recovery of nerve
function from tetanus toxins requires sprouting of
new nerve terminals and formation of new synapses.
Pathophysiolo
gy
• Localized tetanus develops when only the nerves
supplying the affected muscle are involved.
• Generalized tetanus develops when the toxin
released at the wound spreads through the
lymphatics and blood to multiple nerve terminals.
The blood-brain barrier prevents direct entry of toxin
to the CNS.
 Clinical
Manifestations
• trismus (lockjaw) • muscle spasm
• Autonomic disturbances
• muscle pain and • Death
stiffness
• back pain
• difficulty swallow
• difficulty in feeding
(neonates)
Clinical Manifestations
Laboratory diagnostics

• CBC • Chest Xray

• RBS • ECG
• Creatinine, Potassium
• Wound G/S and C/S
• Urinalysis
Therapeutics and Management

• Clean the wound with soap and water

• Give antitoxin: Human Tetanus
Immunoglobulin (Tetagam P)
250 IU/syringes IM (500 units) within first 24
hours
Therapeutics and Management

• Give Tetanus Toxoid (Tetavax) 0.5

ml/amp, 1 amp IM now, then after 1
month and after 6 months.
note - 3rd dose should be Tdap
Therapeutics and Management

• Start antibiotics:
 Penicillin G 3-4 Mil units IV q 4 hours (18-24 Mil
units per day) or Metronidazole 500 mg IV q6
• For muscle spasms:
 Diazepam 2.5 - 5 mg IV q 6 hours or Diazepam drip: 10
mg in 100 ml D5W infuse in 2 hours q 8 hour (max of
60 mg per day)
Therapeutics and Management

• Supportive therapy:
a. Respiratory support, protection of the airway, IV
hydration.
b. Prevent DVT, decubitus ulcers and GI bleeding
 may give antacids per NGT
c. Pain reliever: Ibuprofen 200 mg tab TID per NGT if
needed
d. Clean wound
GROUP 9
Infectious Mononucleosis

Group 9
 DEFINITION

Epstein-Barr virus (EBV) is the cause of heterophile-

positive infectious mononucleosis (IM)

characterized by fever, sore throat, lymphadenopathy,

and atypical lymphocytosis.

The virus is a member of the family Herpesviridae.

 EPIDEMOLOGY
occur worldwide
most common in early childhood, with
second peak during late adolescence
usually a disease of the young adults. In
lower socioeconomic groups and in areas of
the world with deficient standards of
hygiene.
EBV is spread by contact with oral
secretions
frequently transmitted from asymptomatic adults
to infants and among young adults by transfer of
saliva during kissing
Transmission by less intimate contact is rare
EBV has been transmitted by blood transfusion and
by bone marrow transplantation
More than 90% of asymptomatic seropositive
individuals shed the virus in oropharyngeal
secretions.
PATHOGENESIS
“Type a quote here.”

–Johnny Appleseed
“Type a quote here.”

–Johnny Appleseed
 LABORATORY FINDINGS
The white blood cell count is usually elevated and peaks at 10,000–20,000/μL
during the second or third week of illness.

Lymphocytosis is usually demonstrable, with >10% atypical lymphocytes.

CD8+ cells predominate among the atypical lymphocytes. Low-grade

neutropenia and thrombocytopenia are common during the first month of
illness.

Liver function is abnormal in >90% of cases.

Serum levels of aminotransferases and alkaline phosphatase are usually mildly

elevated.
The serum concentration of bilirubin is elevated in ~40% of cases.
 COMPLICATIONS

When CNS complications develop, they usually do so during the first 2 weeksMeningitis and encephalitis are the most common
neurologic abnormalities, and patients may present with headache, meningismus, or cerebellar ataxia.

Autoimmune hemolytic anemia occurs in ~2% of cases during the first 2 weeks.

The spleen ruptures in <0.5% of cases

Hypertrophy of lymphoid tissue in the tonsils or adenoids can result in upper airway obstruction
 DIAGNOSIS

SEROLOGIC TESTING

The heterophile test is used for the diagnosis of IM in children and adults.

EBV-specific antibody testing is used for patients with suspected acute EBV infection
who lack heterophile antibodies and for patients with atypical infections.

IgM antibody to VCA is most useful for the diagnosis of acute IM because it is present at
elevated titers only during the first 2–3 months of the disease;

in contrast, IgG antibody to VCA is usually not useful for diagnosis of IM but is often
used to assess past exposure to EBV because it persists for life.

Seroconversion to EBNA positivity also is useful for the diagnosis of acute infection with
EBV.
 MANAGEMENT/TREATME
NT
Therapy for IM consists of supportive measures, with rest and analgesia.

Excessive physical activity during the first month should be avoided to

reduce the possibility of splenic rupture, which often necessitates
splenectomy.

Prednisone (40–60 mg/d for 2–3 days, with subsequent tapering of the
dose over 1–2 weeks) has been used for the prevention of airway
obstruction.

Glucocorticoids have also been administered to rare patients with

severe malaise and fever and to patients with severe CNS or cardiac
disease.

.
Acyclovir, at a dosage of 400–800 mg five times daily, has been
effective for the treatment of oral hairy leukoplakia (despite
common relapses).

Antibody to CD20 (rituximab) has been effective in some cases.

Infusions of donor lymphocytes are often effective for stem cell
transplant recipients, although graftversus-host disease can occur.

Infusions of EBV-specific cytotoxic T cells have been used to prevent

EBV lymphoproliferative disease in high-risk settings as well as to treat
the disease.

Interferon α administration, cytotoxic chemotherapy, and radiation

therapy (especially for CNS lesions) also have been used
 PREVENTION

The isolation of patients with IM is unnecessary.

A vaccine directed against the major EBV

glycoprotein reduced the frequency of IM but did
not affect the rate of asymptomatic infection in a
phase 2 trial.
 Crytococcal Meningitis

Group 10
Almendras, Borinaga, Capoy,
Estremos,Kumbagiri, Lajid, Llamera,
Palarpalar, Pasarla, Sandla, Sebalda
Epidemiology

 220,000 new cases worldwide each

year, resulting to 181,000 deaths.
 Most cases are opportunistic infections
that occur among people with HIV/AIDS
despite ART.
 Cryptococcus is now the most common
cause of meningitis.
 Cryptococcal meningitis is one of the
leading causes of death in HIV/AIDS
patients; in sub-Saharan Africa, it may
kill more people each year than
tuberculosis.
PATHOPHYSIOLOGY
 • C.neoformans can cause asymptomatic pulmonary infection, followed by
later development of meningitis
• Following inhalation the spores are transmitted into the alveoli of lungs ad
1 are phagocytosized by alveolar macrophages.

• If confined to the lungs, they cause pneumonia, pulmonary nodules, and

rarely pleural effusion.
2

• The organism disseminates hematogenously and localize In CNS

3
 Clinical Manifestation

• Arthritis
Symptoms include: • Gastroenteritis
• Myocarditis
• Fever • Prostatitis
• Cranial nerve palsies and papilledema
• Nausea are the most common ocular
manifestations seen in patients with
• Vomiting cryptococcal CNS invasion.

• Altered mental
status
• Headache
 Laboratory Diagnostic

• Ct Scan Brain
• MRI Brain
• India ink test – rapid and relatively sensitive test
• CSF examination (Lumbar puncture) with India ink test – Definitive
Diagnosis
• Cryptococcal Antigen Test (CRAG) – highly sensitive and specific; expensive
• CBC
Therapeutics and Management
Toxoplasmosis gondii
GROUP 11
Ep
Pathogenesi
CLINICAL MANIFESTATIONS
Congenitally Infected Children

• Hydocephalus
• Microcephaly
• Mental Retardation
• Chorioretinitis
 Immunocompetent Patients
• Cervical Lymphadenopathy- most common
• Myalgia
• Sore throat
• Abdominal pain
• Maculopapular rash
• Meningoencephalitis
• Confusion

• Rare Complications: pneumonia, myocarditis,

encephalopathy, pericarditis & polymyositis
Immunocompromised Patients
• Encephalopathy
• Meningoencephalitis
• Mass lesions
• Altered mental status (75%)
• Fever (10-72%)
• Seizures (33%)
• Headache (56%)
• Focal Neurologic Findings (60%)
Laboratory and Diagnostic
• Tissues and Body fluids
• Serology
• Molecular diagnostics
 Tissues and Body
fluids
• No parasites found in mouse’s peritoneal fluid 6-
10days after inoculation  anti Toxoplasma serum
titer 4-6 weeks after inoculation
• Isolation of T. gondii from patient’s body fluids 
acute infection
• Demonstration of tachyzoites in LN  Diagnosis of
acute Toxoplasmosis
 Serology
• Diagnosis of acute infection  detection of the
simultaneous presence of IgG and IgM antibodies
Immunocompetent Adult or Child
• (+) of Lymphadenopathy only  positive IgM titer
 Immunocompromised
Host
• Latent infection with T. gondii  IgG antibody to
toxoplasma
 Congenital
Infection
• Serologic diagnosis is based on the persistence of IgG
antibody or positive IgM titer after the first week of
life.
• Increase IgM beyond first week of life  indicative of
acute infection
 Ocular Toxoplasmosis
• Diagnosis:
– Parasitic antigen – specific polyclonal IgG assay
– Parasite specific PCR
Therapeutics and Management
 Treatment
Toxoplasmosis is either congenital or acquired
Congenitally infected neonates are treated with daily
oral pyrimethamine (1 mg/kg) and sulfadiazine (100
mg/kg) along with folinic acid for 1 year
Prednisone (1 mg/kg per day) may be used for
congenital infection
 Management
Most experts use spiramycin to treat pregnant women who
have acute toxoplasmosis early in pregnancy
Prenal therapy: Spiramycin, due to relative lack of toxicity and
high concentrations achieved in placenta.
Use pyrimethamine/sulfadiazine/folinic acid to treat women
who seroconvert after 18 weeks of pregnancy or in cases of
documented fetal infection
 Primary Prophylaxis
Patients with AIDS should be treated for acute toxoplasmosis; in
immunocompromised patients, toxoplasmosis is rapidly fatal if
untreated.
Despite their toxicity, the drugs used to treat TE were required
for survival prior to cART
AIDS patients who are seropositive for T. gondii and who have a
CD4+ T lymphocyte count of <100/μL should receive prophylaxis
against TE.
 Discontinuing Primary Prophylaxis
Current studies indicate that prophylaxis against TE can be
discontinued in patients who have responded to cART and whose
CD4+ T lymphocyte count has been >200/μL for 3 months
Individuals who have completed initial therapy for TE should receive
treatment indefinitely unless immune reconstitution, with a CD4+ T
cell count of >200/μL, occurs as a consequence of cART
EBOLAVIRUS
Group - 12
 Filoviruses
Highly infectious but not very contagious

Transmission – direct person – to – person (skin

– skin) contact or exposure to infected body
fluids and tissues

WHO Risk Group 4 Pathogen

Family – Filoviridae
Genera:
Cuevavirus
Ebolavirus
Marburgvirus
 Ebolavirus
Pathogenic to Humans Not Pathogenic to Humans
• Bundibugyo virus (BDBV) • Reston virus (RESTV)
• Ebola virus (EBOV)
• Sudan virus (SUDV)
• Tai Forest virus (TAFV)
 Morphology
• RNA genome
– Linear
– Non segmented
– Single stranded
– Negative sense
– Contains 6-7 genes.
 Seven structural proteins
1. Nucleoprotein
2. Polymerase cofactor (VP35)
3. Matrix protein (VP40)
4. Secondary matrix protein (VP24)
5. Glycoprotein (GP1,2)
6. Transcriptional cofactor (VP30)
7. RNA dependent RNA polymerase (L protein)
 Three non structural proteins
1. sGP
2. ssGP
3. Delta peptide
 Epidemiology
Exclusively endemic to equatorial Africa
Endemic in humid rainforests
Hunting or contact with bush meat
Bats – suspected to be hosts for Ebolavirus
 Pathophysiology
DIRECT EXPOSURE TO

SKIN LESIONS

CONTAMINATED BODILY FLUIDS

PARENTERAL INOCULATION
 LOCAL
CELL & TISSUE
MACROPHAGES PATHOGENETIC
TROPISM
HALLMARK OF
GP1,2
FILOVIRUS
SPIKES MONOCYTES INFECTION:
ON
SURFACE PRONOUNCED
SUPRESSION OF
DENDRITIC
CELLS
IMMUNE SYSTEM
 VP35, VP40, VP24
Suppression
of innate
cellular INHIBIT INTERFERON PATHWAY
immune
response

SECRETION OF COPIOUS NUMBERS OF PROGENY

VIRIONS

INFECTS

OTHER MACROPHAGES: OTHER TARGETS:

ALVEOLAR ADRENAL CORTICAL CELLS
PERITONEAL FIBROBLASTS
PLEURAL HEPATOCYTES
KUPFFER CELLS ENDOTHELIAL CELLS
MICROGLIA VARIETIES OF EPITHELIAL CELLS
 OTHER PATHOGENETIC HALLMARKS OF
FILOVIRUS:
SEVERE DISTURBANCE OF CLOTTING SYSTEM
IMPAIREMENT OF VASCULAR INTEGRITY
 CLINICAL MANIFESTATIONS
BIPHASIC SYNDROME:
First Phase – (D5-7) resembles influenza.
Characterized by sudden onset of fever and
chills.
Severe headaches, cough, myalgia, pharyngitis,
arthralgia (larger joints), development of
maculopapular rash.
 Second Phase – (5-7days after disease onset)
involves:
GIT – Abdominal pain with vomiting/diarrhea
Respiratory – chest pain, cough
CNS – confusion, coma, headache
Vascular system – postural hypotension, edema
Hemorrhagic manifestations – subconjunctival
injection, hematemesis, hematuria, melena.
 Diagnostic Manifestations
• Leukopenia w left shift prior to leucocytosis
• Thrombocytopenia
• Increased liver and pancreatic enzymes
• Hypokalemia
• Hypoproteinemia
• Increased creatinine and urea
• Prolonged prothrombin & partial
thromboplastin time
 Differentials for Ebolavirus infection
• Falciparum malaria • Rickettsial infection
• Enterohemorrhagic • Fulminant viral
Ecoli enteritis hepatitis
• Gram negative • Leptospirosis
septicemia • Measles
• Meningococcal • All viral hemorrhagic
septicemia fevers
 Diagnosis
Biosafety Level 4

Acute phase blood/serum is the preferred

diagnostic specimen – contains high titers of
filovirions and filovirion-specific antibody.

Method of choice – reverse-transcription

polymerase chain reaction and antigen capture
ELISA
 Treatment
Supportive treatment

Hyperimmune equine immunoglobulin – Russia

Post exposure vaccination