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This disease has been called the most important mosquito-transmitted viral disease in terms of morbidity and mortality.
Second only to malaria as mosquito-transmitted disease affecting humans
An estimated 2.5 billion people live in areas at risk fo
DENGUE
HOW MANY SEROTYPES DOES DENGUE HAVE AND WHAT TYPE OF VIRUSES ARE THEY?
The dengue viruses, of which four serotypes are known (DV-1, -2, -3, and -4), are the most widespread arthropod-borne viruses (arboviruses).

This disease involves the only known arboviruses that have fully adapted to the human host and lost the need of an enzootic cycle for maintenance.

DENGUE
THIS MENTALITY IS APPLIED TO DENGUE FEVER LEADING TO LACK OF RECOGNITION OF CASES.
"crisis mentality" with emphasis on emergency control methods in response to epidemics rather than on developing programs to prevent epidemic transmission.
This approach has been particularly detrimental to dengue control because, in most countries, surveillance is (just as in the U.S.) passive
TYPICAL LOCATION DENGUE IS FOUND.
MAINLY EQUATORIAL. LOTS OF RAINFALL/HUMIDITY!
WHAT IS THE VECTOR FOR DENGUE?
The most common epidemic vector of dengue in the world is the Aedes aegypti mosquito. It can be identified by the white bands or scale patterns on its legs and thorax. Bites early morning, early evening
WHAT ARE THE THREE CLINICAL OUTCOMES FOR DENGUE VIRUS?
Undifferentiated fever
Classic dengue fever
Dengue hemorrhagic fever or DHF
Dengue shock syndrome, or DSS.




SYMPTOMS FOR DENGUE?
Incubation period – 4 to 7 (max 3 to 14)days
Viremia – starts just before the onset of symptoms; lasts for about 5 days
Symptomatic – 3 to 10 days (average 5 days)
So clinical illness lasts longer than viremia
CFR FOR DENGUE?
30% WITHOUT TREATMENT
WHAT ARE THE 4 CRITERIA FOR DHF?
Hemorrhagic manifestations
Low platelet count (100,000/mm3 or less)
Objective evidence of “leaky capillaries:”



CLUES FOR DHF?
1ST CLUE = WBC COUNT DROPS
2ND CLUE = PLATELETS DROP
WHAT IS THE MOST CRITICAL PHASE?
WHEN THE FEVER SUBSIDES: CAN EITHER RECOVER OR CAN GO INTO SHOCK (DSS)
TESTS FOR DENGUE?
BLOOD IN STOOL
POSITIVE TOURNIQUET TEST
PLEURAL EFFUSION INDEX (LARGER IS WORSE)

DELAYED CAPILLARY REFILL = MAIN INDICATOR (NORMAL = 2 SECS, DELAYED = >2)
DSS CLINICAL DEFINITION CRITERIA?
4 criteria for DHF + Evidence of circulatory failure manifested indirectly by all of the following: Rapid and weak pulse Narrow pulse pressure (< 20 mm Hg) OR hypotension for age Cold, clammy skin and altered mental status
IS THERE CROSS PROTECTION BETWEEN DENGUE SEROTYPES?
No cross protection between different serotypes
A population could experience a dengue-1 epidemic one year, followed by a dengue-2 epidemic the next year.
Most primary infections cause a debilitating, but nonfatal, form of illness.
Some patients, particularly children, experience a more severe and occasionally fatal form of the disease, called DHF and the most severe form, DSS.




WHAT IS ADE?
There is a higher risk for DHF in secondary infections.
There is also higher risk in locations with two or more serotypes circulating simultaneously at high levels—this is called hyperendemic transmission.

The most widely accepted hypothesis for the increased risk of DHF in secondary infections is called antibody-dependent enhancement.

ADE is the process in which certain strains of dengue virus, complexed with non-neutralizing antibodies, can enter a greater proportion of cells of the mononuclear lineage, thus increasing virus production






WHAT IS THE WORST TYPE OF DENGUE INFECTION?
2ND INFECTION WITH DEN-2
WHAT ARE THE RISK LEVELS OF DENGUE SEROTYPES IN ORDER?
DEN-2, 3, 4, 1
WHAT ARE TESTS USED TO DETECT DENGUE?
Routine
CBC: WBC, platelets, hematocrit (serial hematocrits for hemoconcentration)
Albumin
Liver function tests
Urine: check for microscopic hematuria
Dengue-specific tests
Virus isolation to determine serotype
Serology -ELISA, Immune chromatography
(acute phase and convalescent phase sera
DENGUE TREATMENTS?
Fluids
Rest
Antipyretics - avoid aspirin and non-steroidal anti-inflammatory drugs (Platelets!)
Monitor blood pressure, hematocrit, platelet count, level of consciousness




DENGUE MISCONCEPTIONS
DHF is a pediatric disease
All age groups are involved in the Americas

Dengue + bleeding = DHF
Need 4 WHO criteria, capillary permeability

DHF kills only by hemorrhage
Patient dies as a result of shock

Poor management turns dengue into DHF
Poorly managed dengue can be more severe, but DHF is a distinct condition, which even well-treated patients may develop

Positive tourniquet test = DHF
Tourniquet test is a nonspecific indicator of capillary fragility












DENGUE VACCINE AVAILABLE?
No licensed vaccine yet and probably not for the next 5-10 years
Must be tetravalent
Field testing of an attenuated tetravalent vaccine currently underway





WHERE CAN CARRIONS BE FOUND?
PERU, COLOMBIA, AND ECUADOR
MALARIA AND BARTONELLOSIS HAVE WHAT IN COMMON?
IN RED BLOOD CELLS AND HAVE FEVER/ANEMIA
CLINICAL SYMPTOMS FOR TYPHOID?
Enteritis (acute gastroenteritis)

Enteric fever (prototype is typhoid fever and less severe paratyphoid fever)

Septicemia (particularly S. choleraesuis, S. typhi, and S. paratyphi)

Asymptomatic carriage (gall bladder is the reservoir for Salmonella typhi)
IS TYPHOID CAUSED BY AN INTRACELLULAR BACTERIA?
YES.
1880--Eberth identifies intracellular rod-like organism in mesenteric lymph nodes and spleen
ENTERIC FEVER FACTS
The term enteric fever is a communicable disease, found only in man
includes both typhoid fever caused by S.typhi and paratyphoid fever caused by S.paratyphi A, B and C .
It is an acute generalized infection of the reticulo endothelial system, intestinal lymphoid tissue, and the gall bladder.



TRANSMISSION OF TYPHOID?
USUALLY THROUGH WATER. CAN ALSO BE SPREAD BY INFECTED DAIRY PRODUCTS AND MEAT/POULTRY/EGGS

Humans are the only reservoir
Human to human; feco-oral; water
Infectious dose : 10^3 or 10^ 4 organisms
Increased risk if lower gastric acid
WHAT ANTIGENS ARE INVOLVED WITH TYPHOID FEVER?
Somatic "O" antigens
Basis of serogroups A-E

Flagellar "H" antigens
Phase 1 (stable) and phase 2 (variable); basis of large number of serotypes

Capsular "Vi" antigen (Virulence antigen)
Corresponds to "K" antigen in E. coli,increased pathogenicity
Phage-mediated capsular lysis forms basis of S.typhI phage-typing
CLINICAL SYMPTOMS OF TYPHOID
A. Incubation period - inversely related to inoculum   B. Physical Findings Stepwise increase in fever with abdominal pain and palpable loops of bowel Rose spots--develop in the first week in
TYPHOID CLUES
Fever escalates for Week 1, then sustained
White blood count may be low or normal (TYPICALLY HIGH WITH INFECTION, BUT NOT IN TYPHOID BECAUSE INTRACELLULAR), with bandemia (shift to early neutrophil forms)
GI symptoms – diarrhea rare
Cough may be present
WHAT IS THE MOST EFFECTIVE TEST FOR TYPHOID?
BONE MARROW TEST ESPECIALLY IF ALREADY RECEIVED ANTIBIOTICS
TYPHOID WITHOUT TREATMENT FACTS?
Case fatality rate = 12%
Duration of fever = 3 weeks
Persistent carriage = 1-3 weeks
DRUG TREATMENTS FOR TYPHOID?
CAM = USED TO BE DOC, BUT MANY COMPLICATIONS
AMP = QUICK RESPONSE BUT BAD RASHES
CEFTRIAXONE = NOW DRUG OF CHOICE!!! FOR KIDS AND ADULTS
S.TYPHI CARRIER STATES ARE...
A. Urinary carriage
1. Related to prior urinary tract damage from past or present schistosomal infection
2. Persistently positive urine culture with intermittently positive blood culture during brief febrile periods
3. Hematuria, dysuria, anemia, low grade fever
4. Treatment difficult--symptoms improve on chloramphenicol but relapses common

B. BILIARY CARRIAGE
1. Related to colonization of gallstones or scarred foci in gall bladder; defined as excretion > 6 months
2. Occurs in 3-5% patients with enteric fever
3. Estimated 2000 carriers in U.S.A. in 1978
4. Very high incidence in endemic areas (694/100,000 in Santiago, Chile) related to high incidence of cholelithiasis
5. No antibody response
TYPHOID VACCINES AVAILABLE?
1. Classical Heat-phenol inactivated vaccine
Efficacy 51-76%
Fever, headache, local pain and swelling common
Two-dose regimen at 4 week interval for 1o immunization
No longer manufactured in the United States

2. LIVE ORAL S.TYPHI Ty21a
Attenuated live oral vcaccine
Elicits CMI + antibodies to O and H antigens
53 – 96% efficacy
Oral: 4 doses (one capsule each) taken on alternate days; complete one week before travel
Licensed for adults, children > age 6 years
Protective for 5 years (maybe 7)

3. Vi VACCINE
Available worldwide
Based on capsular polysaccharide antigen: antibodies against Vi antigen
Given IM as single dose IM one week before travel; mild side effects
*Efficacy 64-72%
Duration of protection : 3 years
Booster every 2 years
Approved for patients > 2 years

*Systematic review and meta analyses found a cumulative efficacy of 55% (95% CI, 30%-70%).
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