Marlon M.

Maramion, MD, DPSP

 BACTERIAL DISEASES PATHOGEN
Septic Shock Gram Negative & some Gram
Pericarditis Positive
Streptococcus pyogenes
Rheumatic Fever Grp A beta-hemolyric
Leptospirosis Streptococci
Leptospira interrogans
Tularemia Francisella tularensis
Brucellosis Brucella spp
Anthrax Bacillus anthracis
Gangrene Clostridium perfringens
Cat-scratch disease Bartonella henselae
Plague Yersenia pestis
Endocarditis a. Subacute Streptococci
b. Acute Staphylococcus aureus
 BACTERIAL DISEASES PATHOGEN
Relapsing fever Borrelia spp
Lyme disease Borrelia burgdorferi
Ehrlichiosis Ehlichia spp
Epidemic typhus Rickettsia prowazekii
Endemic murine typhus Rickettsia typhi
Rocky Mountain spotted fever Rickettsia rickettsii
 VIRAL DISEASES PATHOGEN
AIDS HIV
Dengue fever Arbovirus (Dengue fever virus)
Cytomegalovirus Cytomegalovirus (CMV)
Burkitt’s lymphoma Epstein-Barr virus (EBV)
Infectious mononucleosis EBV
Myocarditis Coxsackievirus A & B
Yellow fever Arbovirus(Yellow fever virus)
Viral hemorrhagic fevers Filovirus, Arenavirus
(Marburg, Ebola, Lassa)
Hantavirus pulmonary syndrome Sin Nombre hantavirus
 PROTOZOAN DISEASES PATHOGEN
American trypanosomiasis Trypanosoma cruzi
(Chagas’)
Toxoplasmosis Toxoplasma gondii
Malaria Plasmodium spp
Leishmaniasis Leishmania spp
Babesiosis Babesia microti
HELMINTHIC DISEASES PATHOGEN
Schistosomiasis Schistosoma spp
Swimmer’s Itch Schistosome larvae of animals
Isolation of bacteria from peripheral blood
Sources
1. physical introduction (trauma)
2. focus of infection
Outcomes
1. transient & inconsequential
2. establishment of distant foci of infection
- meningitis, osteomyelitis, syphilis,
endocarditis
3. progression to sepsis
Systemic disease triggered by infection
characterized by hemodynamic abnormalities
and organ failure
Hypotension
Mechanism
- activation of host cells leading to release of
mediators activation of complement and
coagulation systems
Outcomes
1. circulatory collapse ( septic shock)
2. disseminated intravascular coagulation (DIC)
3. multiple organ failure
Gram Positive Bacteria
Staphylococcus aureus
Coagulase- negative staphylococci*
S. epidermidis
S. haemolyticus
S. lugdunensis
Enterococcal spp
Viridans streptococci
S. mutans
S. milleri
S. sanguis
Streptococcus pneumoniae•

* More common in nosocomial infections

• More common in community- acquired infections
Gram Negative Bacteria
Escherichia coli
Klebsiella spp*
Proteus spp
Pseudomonas spp*
Haemophilus influenzae•
Anaerobes*
Bacteroides spp
Fungi
Candida spp

* More common in nosocomial infections

• More common in community- acquired infections
Etiology
Enterobacteriaceae & Pseudomonaceae
1. Escherichia coli (35%)
2. Klebsiella, Enterobacter, Proteus & Serratia
(38%)
3. Pseudomonas (12%)
Origin
- GIT
- GUT
- Skin
Predisposing Factors
1. Surgery (abdominal, genitourinary)
2. Urinary tract manipulation (catheterization)
3. Underlying diseases that compromise
defenses
4. Large blood loss from trauma or surgery
5. Ischemia of intestinal wall
Pathogenesis
- Endotoxin (LPS) release
- Macrophage activation
- Release of cytokines (IL-1, TNFα, IL-8)
- Activation of complement & coagulation
systems

Manifestations
Fever, ↑sleep, anorexia, ↑Acute phase proteins,
Neutrophilia, Hemodynamic effects (shock)
Septic Shock
Common features
Fever, shock, hypotension, increase
heart rate, acid-base problems,
thrombosis and bleeding
 The physiologic effects are due to
activation of macrophages resulting in the
release of cytokines (TNF, ILs), activation
of complement and coagulation cascade
Death may occur from multiple organ
failure
Hypotension
1. LPS & other bacterial products
activation of coagulation & complement
(bradykinin & C5a- potent vasodilators)
2. IL-2 (increased vascular permeability)- from
lymphocytes activated by IL-1 & TNF-α
3. PAF, Histamine, NO (vasodilators)- from
activated macrophages & PMNs
DISSEMINATED INTRAVASCULAR COAGULATION
(DIC)
A disastrous complication of sepsis
Common features
Clotting in numerous blood vessels
Bleeding due to depletion of coagulation
factors
Can occur with septicemia or with any pathogen
but usually due to Gram-negative bacterial sepsis
Disseminated Intravascular Coagulation
1. increased expression of cell-adhesion
molecules (CAM) in endothelial cells by IL-1 &
TNF-α
2. endothelial cell damage by cytokines,
proteases & oxygen radicals from activated
phagocytes
3. PAF (most potent platelet agggregator)- from
activated phagocytes
4. diminished synthesis of tissue factor pathway
inhibitor (TFPI)- binding of enndotoxin to
endothelial cells
Neisseria meningitidis

Gram (-) diplococci

Kidney bean-shaped
Capsulated
Piliated

Virulence Factors
- Endotoxin- 10x potent than other endotoxins
- IgA protease
 - high fever, chills, nausea & vomiting,
malaise
- petechial hemorrhagic skin lesions
- DIC
- ischemic necrosis of skin & internal
organs
- Waterhouse- Friderichsen syndrome
- hypotension & shock
85% mortality rate
Etiology
Coagulase-negative staphylococci
S. epidermidis
S. Haemolyticus
S. saprophyticus
S. lugdunensis
Staphylococcus aureus
Streptococcus pneumoniae
Viridans streptococci
S. mutans
S. milleri
S. sanguis
Pathogenesis
- EXOTOXINS bind to MHC-II molecules of
macrophages
- presentation to T lymphocytes
- lymphokine activation of numerous T cells
and macrophages
- release of cytokines from activated
macrophages and lymphocytes (same with G-
septic shock)
TSST-1 – directly toxic to endothelial cells
Peptidoglycan & capsule polysaccharide (S.
pneumoniae)- activate macrophages,
coagulation and complement systems
Staphylococcus aureus- most common

Coagulase negative Staphylococci

S. epidermidis
S. saphrophyticus
S. haemolyticus
S. lugdunensis
Staphylococcus aureus

Origin
- cutaneous abscess/furuncle
- minor skin trauma
Outcome
- establishment of infection at distant site
(osteomyelitis, brain abscess)
- Septic Shock- from Toxic Shock Syndrome
Toxin1 (TSST1)
Staphylococcus epidermidis & Staphylococcus
saprophyticus

Origin
- contaminated catheters, cannulae, shunts, IV
drug abuse paraphernalia
Outcome
- transient bacteremia
- prosthetic valve endocarditis
Sepsis- clinical
Culture & isolation- confirmation &
determination of specific etiology
Factors influencing successful recovery of
bacteria from blood:
1. Attention to proper technique in blood
collection
- avoid misdiagnosis as a result of skin flora
contamination
a. venipuncture site should be thoroughly
sterilized
b. drawing of blood from two different sites
Factors influencing successful recovery of
bacteria from blood:
2. Multiple samples should be taken
- 3 blood samples taken over a 24-hr period-
99% recovery of bacteria
- 1 blood sample- 80%
3. Blood should be drawn prior to start of
antimicrobial therapy
-For those who have received antibiotics: 4 to
5 cultures in a span of two days
4. Volume of blood is directly related to yield
(10ml)
Bacteremia
1. Antimicrobial therapy
- based on results of susceptibility tests
- start with broad-spectrum antibiotics before
culture results are available, choice is based on:
a. focus of infection
b. age & condition of patient
c. source of infection (hospital vs
community
acquired)
2. Surgical excision, debribement, draining of
identified foci of infection
SEPSIS
1. Antimicrobial therapy
2. Supportive measures
- fluid replacement
- inotropic agents
3. Administration of inflammatory mediators
antagonists (still under study)
4. Surgical excision of necrotic tissues
Streptococcus pyogenes
- Respiratory tract & Skin
pathogen
o Gram (+) cocci in pairs or long
chains
o β hemolytic more virulent
(strains with capsule)
o Facultative anaerobe
o Produces Streptolysin O
and DNAse B
Virulence Biologic effect
Factor
capsule antiphagocytic

Lipoteichoic Binds to epithelial cells

acid
M protein Adhesin; mediates internalization by host cells;
degrades complement C3b

F protein Mediates adherence to epithelial cells and

internalization
Pyrogenic Mediate pyrogenecity; enhancement of delayed HPS
proteins and susceptibility to endotoxin; cytotoxicity;
mitogenicity for T cells; suppression of B cells;
production of scarlatiniform rash
Virulence Biologic effect
factor

Streptolysin S Lyses leukocytes; platelets and erythrocytes;

stimulates release of lysosomal enzymes; non
immunogenic
Streptolysin O Lyses leukocytes; platelets and erythrocytes;
stimulates release of lysossomal enzymes,
immunogenic
Streptokinase Lyses blood clots; facilitates spread of bacteria
in tissues
(used in the treatment of acute MI)
DNAse Depolymerizes cell-free DNA in purulent material

C5a peptidase Degrades complement C5a

- Acute, immune mediated disease (Type 2)
- Multisystem involvement
- Common in children 5-15 years old
- Manifestations develop 2-3 weeks after
Streptococcal Pharyngitis
- Genetic susceptibility (only a minority of
infected patients develop RF)
Antibodies against
M protein of Strep
Clinical manifestations
1. fever
2. migratory polyarthritis
3. Carditis
- murmur & cardiomegaly
- tachycardia, arrhythmia
- progressive worsening with every
recurrence
4. Subcutaneous nodules
5. Sydenham chorea
6. Erythema marginatum
Diagnosis
JONES CRITERIA
Major criteria
 migratory polyarthritis;
 carditis;
Diagnosis:
a. 2 major
 Sydenham chorea;
b. 1 major & 2 minor
 Subcutaneous nodules; and
 erythema marginatum.
Minor criteria
 fever
 Polyarthralgia in the absence of polyarthritis as a major
criterion;
 prolonged PR interval on the electrocardiogram
 Acute phase reactants (leukocytosis, raised erythrocyte
sedimentation rate, and elevated C-reactive protein),
 evidence of a preceding streptococcal infection (elevated or
rising antistreptolysin titre, isolation of streptococci from
throat swab culture, and positive streptozyme test)
PROGNOSIS
- Generally good (only 1% die from fulminant
RF)
- After initial attack, vulnerability to reactivation
of the disease with subsequent pharyngeal
infections is increased
- Most important consequence: Rheumatic
Heart Disease
- chronic valvular deformities (mitral
stenosis-
most common)
TREATMENT
1. Treatment of streptococcal infection that led
to the disease
- Penicillin
2. Anti-inflammatory drugs
a. NSAIDs
b. Corticosteroids
3. Supportive (CHF)
PRIMARY & SECONDARY PREVENTIONS
Primary Prophylaxis
- Treatment of Pharyngitis to prevent initial attack
of RF
-DOC: Penicillin, Erythromycin
Secondary Prophylaxis
- Prevention of subsequent streptococcal infection
in patients who already had RF
- Prevention for the long term consequence of
recurrent RF
- Penicillin (oral/IM) up to 18th birthday or after 5
years from most recent attack
Leptospira interrogans
Tightly coiled, thin, flexible spirochetes, 6-
20 micra in length and 0.1 micron in
diameter, one or both ends are hooked
Ultrastructure
 Leptospira consists of a helicoidal protoplasmic
cylinder, 2 axial filaments, and an outer
envelope
Microaerophilic
Oxidase (+)
Catalase (+)
Leptospira interrogans
Antigenic structure
Outer envelope contains large amounts of
lipopolysaccharide (LPS) of antigenic structure
that is variable from one strain to another
Among the pathogenic strains there are about
19 serogroups
Mechanism of virulence is uncertain; these are
the findings
 Complement activation
 Production of hemolysins and endotoxins
 Probably cell-mediated immune response
Zoonotic disease
 Host reservoirs include wild mammals and
domestic animals, with high prevalence in
rodents
Major mode of transmission between
animals and humans
 Direct contact with urine infected with virulent
Leptospira from an animal with leptospiruria
(URINE)
Leptospira enter the body through break in
the skin and mucous membranes
Dissemination: enters bloodstream
(spirochetemia) & spreads to variety of organs
& tissues
1. Hepatic involvement
- elevated liver enzymes
- hyperbilirubinemia, jaundice
2. Vascular involvement
- diffuse vascular injury hypovolemic
shock
- petechial hemorrhage, conjunctival
suffusion
- DIC
3. Renal involvement
1. Subclinical (Asymptomatic) Disease
- positivity to antibodies, no sign/symptom
- thru serological survey of veterinarians
2. Anicteric Leptospirosis
Initial stage (IP=7-12 days)
- non specific flu-like symptoms
Secondary stage (duration: few days up to 1
month)
- serum positivity for antibody & immune
complex
- severe headache, N & V, myalgia
- splenomegaly, hepatomegaly, meningitis
3. Icteric Leptospirosis (Weil’s Syndrome)
- most severe form of the disease
- disseminated endothelial damage &
vasculitis
- impaired renal & hepatic fxn, internal
hemorrhages, meningitis, cardiovascular
collapse & shock
- hepatomegaly (25%)
Laboratory Diagnosis
1. Culture & Isolation
- blood, CSF, urine
- growth may take up to 6 weeks
- materials from culture examined under dark
field microscopy
2. Serologic testing
- antibody peaks in 4 weeks
Treatment
2.Penicillin- DOC
3.Tetracycline- for Penicillin sensitive
- Disease primary to hervibores
Bacillus anthracis
Gram positive bacillus
Obligate aerobe
Spore-forming
Encapsulated
Non motile
Bacillus anthracis
Antigenic Structure
1. Capsule polypeptide
- (D-glutamic acid)
- poorly immunogenic
- stimulates antibody formation but not
protective
2. Polysaccharide somatic antigen
3. Complex protein toxin
Bacillus anthracis
Virulence Factors
1. Polypeptide capsule
2. Exotoxin
- responsible for the development of lethal
effects
- 3 components
a. Protective antigen
- binds to cell receptor
Exert synergistic effect
b. Edema factor
- adenylate cyclase activity
c. Lethal factor
Pathogenesis
1. Cutaneous Route
- through small abrasions or cuts
- local multiplication
2. Inhalation
- local & hilar node multiplication
- hemorrhagic necrosis
3. Ingestion
- ingestion of infected meat
- invasion & ulceration of GIT mucosa
Possibility of bloodstream invasion & toxemia
from 3 areas
Clinical Disease
1. Cutaneous Anthrax
- IP: 2-5 days
- small painless papules to vesicles which
rupture then develop black eschar
2. Pulmonary Anthrax (wool sorter’s disease)
- influenza-like which develops to severe fatal
pneumonia
3. Gastrointestinal Anthrax
- N & V, hemorrhagic diarrhea, shock, death
Bacteremia, Meningitis, Toxemia
Diagnosis
Specimen: pustule, sputum, blood
Presumptive diagnosis:
- gram stain & fluorescent-antibody stain
Penicillin containing medium
- String of pearls reaction
Treatment
DOC: Penicillin, alternative: Tetracycline or
Erythromycin
- large IV dose
- time of diagnosis is critical esp for Pulmonary
& GIT anthrax
Clostridium perfringens
Requires ischemia & necrosis
- nutrient & anaerobic environment

Gram positive bacillus

Spore-forming
Obligate anaerobe
Clostridium perfringens
Virulence factors
1. Exotoxin (α-toxin)
- hydrolyzes lecithin & sphingomyelin
- cell & mitochondrial membrane disruption
2. Enterotoxin
- associated with food poisoning
Pathogenesis
Exogenous contamination
- deep penetrating wounds
Endogenous contamination
- part of GIT & female genitalia flora (5% of
population)
- secondary to abdominal surgery/trauma
- associated with septic abortion
Manifestations
Myonecrosis
-necrosis, foul smell
- gas formation (bubbles)
- extension along muscle bundles up to the
blood
Suppurative infections
- GIT & GUT
Enteritis necroticans
- acute ulcerative process with gut denudation
Diagnosis
- Culture & Isolation
Treatment
- Antibiotic: Penicillin
- Debridement
- Hyperbaric oxygen exposure
- Black Death
- Zoonotic infection (rodents)
Yersenia pestis
Gram negative coccobacillus
Non motile
Facultative anaerobe
Catalase positive
Grows best at 28°C
Facultative intracellular organism
Yersenia pestis
Virulence factors
1. F-1 glycoprotein (capsule)- antiphagocytic
2. Pla (protease)- activates plasminogen
- bacteremic spread
- inactivates C3b & C5a
3. W/V antigen
- antiphagocytic
- promote intracellular growth
Pathogenesis & Manifestations
- Inoculation (flea bite)
- Proliferation in the lymph
- Enlargement of lymph nodes (buboes), Fever
- Further proliferation- SEPTICEMIC PLAGUE
- vascular injury (dark blue
areas in the skin)
- septic shock
- Entry to the lungs- PNEUMONIC PLAGUE
- 100% death rate (3 days)
- can be spread thru respiratory
Diagnosis
Culture & Isolation
Treatment
Antibiotic therapy:
Streptomycin
Chloramphenicol
Tetracycline
Infection of endocardium
Associated with cardiac abnormalities
 congenital valvular diseases
Pathogenesis
- attachment of blood borne bacteria to heart valves
- multiplication
- covered with platelets & fibrin (shield from
phagocytes & complement)
- sorce of bacteremia
- may become an embolus
Pathology- Vegetations
Common among nondrug-abusers
 Viridans streptococci: S. anginosus, S. sanguis, S.
mutans
 Enterococci
 Staphylococcus aureus
Common among drug-abusers
 Coagulase-negative staphylococci
 Pseudomonas spp

Others: Enterobacteriaceae, Yeast spp,

Haemophilus spp
Risk factors
 An artificial (prosthetic) heart valve
 A family history of endocarditis
 Heart valves damaged (scarred) by conditions such as
rheumatic fever
 Congenital heart or heart valve defects
 Mitral valve prolapse with a murmur
 Hypertrophic cardiomyopathy
 Patients who already have some kind of heart problem have
a greater risk
 Children with congenital, rheumatic, or degenerative
heart diseases have a 60-80 per cent risk
 Adults age 15 - 50 with a preexisting heart disease have a
35-60 per cent risk
Manifestations
fever, malaise, fatigue, weight loss, skin
petechiae, embolic infarction of vital
organs, and valve dysfunction with
congestive failure
Diagnosis
1. blood culture
2. Echocardiogram
Treatment
- Antibiotic specific for etiology
 VIRAL DISEASES PATHOGEN
AIDS HIV
Dengue fever Arbovirus (Dengue fever virus)
Cytomegalovirus Cytomegalovirus (CMV)
Burkitt’s lymphoma Epstein-Barr virus (EBV)
Infectious mononucleosis EBV
Myocarditis Coxsackievirus A & B
Yellow fever Arbovirus(Yellow fever virus)
Viral hemorrhagic fevers Filovirus, Arenavirus
(Marburg, Ebola, Lassa)
Hantavirus pulmonary syndrome Sin Nombre hantavirus
Ubiquitous DNA virus
Trophic for B lymphocytes (C3 receptor)
 B cell infection:
- does not cause death
- results in polyclonal proliferation and EBV
antigen expression (some cells become
permanently infected)
- latent infection
Transmission
- respiratory secretions, saliva
- oral contact
- minority of cases: blood transfusion &
 EBV in saliva Infection of oropharyngeal
epithelial cells

Infection of B Pharyngitis
cells

B cell Viral shedding in

Formation of
proliferation saliva
heterophile
antibodies (IgM)

Expression of EBV
early proteins
Enlargement of liver,
spleen, and lymph Atypical
nodes T-cell activation lymphocytes
Atypical lymphocyte: “Downy
cell”
Clinical Disease
1. Infectious Mononucleosis
- pharyngitis, lymphadenopathy, fever,
rash
- heterophile antibody formation
- slow recovery with relapses
2. Burkitt’s Lymphoma
3. Nasopharyngeal Carcinoma
- common in Asia
- Lymphoid malignancy of the jaw
- High prevalence in Africa
- Associated with translocation of c-MYC gene
on chromosome 8 (EBV implicated in the
mutation)
- viral antigens/DNA in tumor tissue
- transformation of cultured B
lymphocytes by EBV in vitro
- high EBV antibody titers in patients with
Burkitt Lymphoma
- induction of lymphoma by EBV in
primates
Diagnosis
1. Lymphocytosis with atypical lymphocytes
2. Decreased CD4/CD8 ratio (increased CD8)
3. Serology
a. (monospot test) detection of heterophile
antibody
b. Epstein-Barr virus specific antibody tests
1. viral capsid antigen (VCA)
IgM- recent infection
IgA- nasopharyngeal CA
2. Early antigens (EA) Antibody- Burkitt
Lymphoma &
Nasopharyngeal Ca
Treatment
- SUPPORTIVE
- Ubiquitous DNA virus
- Associated with wide spectrum of illness
- Target cells:
Neutrophils, monocytes, B cells, epithelial
cells(salivary glands & kidneys)
(possible latent infection)
Pathology:
- cell enlargement
- inclusion bodies
MOT
2.Respiratory route (oral secretions)
3.Sexual transmission
4.Perinatal transmission
5.Congenital transmission
Clinical Disease
1. Infectious mononucleosis
- EBV mononucleosis- like S/Sx
- no heterophile antibody
2. Congenital % Perinatal Infection
- asymptomatic or severe disease
- hepatosplenomegaly, jaundice,
chorioretinitis, petechiae, respiratory distress,
microcephaly
- hearing loss, Low IQ (congenital)
Diagnosis
1. Microscopic examination
- urinary sediment/ kidney biopsy
(+) owl-eye inclusion
2. Culture & isolation
3. Serology (IgM & IgG)

Treatment
DOC- Ganciclovir and Foscarnet
Dengue Virus (Flavivirus)

Enveloped, spherical viruses, 40-60nm diameter.

Capsid proteins:
nucleocapsid ('C') and matrix ('M').
Envelope: 1 glycoprotein ('E')
Single-stranded, (+)sense RNA, ~10.5kb.
Four closely related, but antigenically distinct
serotypes (DEN-1, DEN-2, DEN-3, DEN-4)
 maintained in a cycle that involves humans and
the Aedes mosquito
Infection provides lifetime immunity to only that
serotype:
 persons living in endemic areas can have more
than one dengue infection during their lifetime
Flu-like viral disease spread by the bite of
infected mosquitoes
 Aedes aegypti
 Day-biting; short-distance flight
 Breed in discarded tires, flower pots, old oil
drums, and water storage containers close to
human dwellings

Occurs in most tropical and subtropical areas of

the world
Pathogenesis
Target cells: macrophages
- Inoculation
- Multiplication : bite site
regional lymph nodes
reticuloendothelial system
- Viremia
- Release of cytokines from the infected
macrophages
> vascular injury
> complement activation
> abnormal hemostasis
3 Distinct Syndromes
2.Classic Dengue Fever
3.Dengue Hemorrhagic Fever
4.Dengue Shock Syndrome

The time between the bite of a mosquito

carrying dengue virus and the start of
symptoms averages 4 to 6 days, with a
range of 3 to 14 days
Self limiting
Fever phase (3-5 days)
- headache, N & V
- severe myalgia & bone pain (break bone fever)
Rash phase (maculopapular)
- trunk limbs & face
- lymphadenopathy, granulocytopenia,
thrombocytopenia
- minor bleeding: petechiae, epistaxis,
menorrhagia
(+) tourniquet test
- Begins with fever & other S/Sx of Classic
Dengue
- Marked increased vascular permeability
and abnormal homeostasis (diffuse
capillary leak)
- Hemorrhagic diathesis
-associated with hemoconcentration,
thrombocytopenia & DIC
- May progress into Shock
- Marked increase in vascular permeability
- Decreased plasma volume
- Shock
- acidosis, hyperkalemia & death

* 90% of DHF & DSS occur in children with

history of multiple dengue infections
A. Enhancement of viral entry into
macrophages by antibodies:
1. maternal antibody
2. antibody from previous infections
- enhanced phagocytosis & increased viral
replication of the virus in the
macrophages
B. Cross reacting helper T cells
Host Defense
- Antiviral antibody (IgM & IgG)
- Virus- specific Cytotoxic T cells
- helper T cells
Primary Infection
 IgM antibodies appear approximately 5 days after
onset of symptoms and rise for the next 1-3 weeks;
detectable for up to 6 months
 IgG are detectable at approximately 14 days after
onset of symptoms and are maintained for life

Secondary Infection
 Approximately 5% patients do not produce
detectable levels of specific IgM
 IgM titre can be slower to rise in secondary infection
 IgG appears approximately 2 days after symptoms
appear; significantly higher in secondary infection
Epidemiology
- incidence is associated with vector
dispersion
- affects primarily children
- major cause of death in children in
epidemics
(3-10% case fatality rate)
Diagnosis
1. Clinical features: tourniquet test
thrombocytopenia
2. Laboratory test:
serology