1. Flaviviruses
1
Friday, June 18, 2010

2. Flaviviridae
• >68 viruses
• small
• spherical
• enveloped
• SS RNA
• cross-related
2
Friday, June 18, 2010

3. Flaviviruses
• Yellow Fever virus
• Dengue viruses
• St. Louis encephalitis virus
• Japanese encephalitis virus
• West Nile virus
• Murray Valley encephalitis virus, tick-borne
encephalitis viruses and others
3
Friday, June 18, 2010

4. Yellow Fever
• vector: Aedes aegypti
• Latin America, Caribbean, Africa
• inapparent to severe infection (jaundice, hemorrhage,
albuminuria)
• hepatic necrosis, Councilman and Torres bodies
• Dx: cell culture, serology, PCR, immunohistochemistry
• supportive treatment
• live attenuated 17D vaccine
4
Friday, June 18, 2010

5. Dengue Fever/Dengue
Hemorrhagic Fever
Friday, June 18, 2010

6. Dengue Virus
• Causes dengue
and dengue
hemorrhagic fever
• Transmitted by
mosquitoes
• Has 4 serotypes
(DEN-1, 2, 3, 4)
Friday, June 18, 2010

7. Aedes aegypti
• Dengue transmitted by
infected female
mosquito
• Primarily a daytime
feeder
• Lives around human
habitation
• Lays eggs and produces
larvae preferentially in
artificial containers with
clean stagnant water
Friday, June 18, 2010

8. Dengue Clinical Presentations
• Undifferentiated fever – may be
the most common presentation*
• Classic dengue fever
• Dengue hemorrhagic fever
• Dengue shock syndrome
*DS Burke, et al. A prospective study of dengue infections
in Bangkok. Am J Trop Med Hyg 1988; 38:172-80.
Friday, June 18, 2010

9. Spectrum of Dengue
Illness
Undifferentiated Dengue Fever Dengue Hemorrhagic
illness Fever
Classic
Dengue Dengue
Shock
Syndrome
Friday, June 18, 2010

10. Clinical Characteristics
of Dengue Fever
• Fever
• Headache
• Muscle and joint pain
• Nausea/vomiting
• Rash
• Hemorrhagic manifestations
Friday, June 18, 2010

11. Hemorrhagic Manifestations
of Dengue
• Skin hemorrhages:
petechiae, purpura,
ecchymoses
• Gum bleeding
• Nose bleeding
• Gastro-intestinal bleeding:
hematemesis, melena,
hematochezia
• Hematuria
• Increased menstrual flow
Friday, June 18, 2010

12. Tourniquet Test
• Inflate blood pressure
cuff to a point midway
between systolic and
diastolic pressure for 5
minutes
• Positive test: 20 or
more petechiae per 1
inch2 (6.25 cm2)
Pan American Health Organization: Dengue and Dengue
Hemorrhagic Fever: Guidelines for Prevention and
Control. PAHO: Washington, D.C., 1994: 12.
Friday, June 18, 2010

13. Clinical Case Definition for
Dengue Hemorrhagic Fever
4 Necessary Criteria:
• Fever, or recent history of acute fever
• Hemorrhagic manifestations
• Low platelet count (100,000/mm3 or less)
• Objective evidence of “leaky capillaries:”
– elevated hematocrit (20% or more over baseline)
– low albumin
– pleural or other effusions
Friday, June 18, 2010

14. Vaughn DW, Green S, Kalayanarooj S, et al. Dengue in the early febrile
CENTERS FOR DISEASE CONTROL
phase: viremia and antibody responses. J Infect Dis 1997; 176:322-30. AND PREVENTION
Friday, June 18, 2010

15. Dengue Hemorrhagic Fever
T Lack of
appettite
40
C Vomiting
Headache Fall in platelets
39 Abdominal pain Increased
hematocrit
Muscle/joint
pain
38 hemorrhagic
manifestations; Shock
+torniquet test
37
Rash
Flushing
36 rash
Day 1 2 3 4 5 6 7
Friday, June 18, 2010

16. Friday, June 18, 2010

17. Clinical Case Definition for
Dengue Shock Syndrome
• 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
Friday, June 18, 2010

18. Clinical Evaluation in Dengue
Fever
• Blood pressure
• Evidence of bleeding in skin or other sites
• Hydration status
• Evidence of increased vascular
permeability-- pleural effusions, ascites
• Tourniquet test
Friday, June 18, 2010

19. Warning Signs for Dengue Shock
Alarm Signals:
• Severe abdominal pain
• Prolonged vomiting
Four Criteria for DHF: • Abrupt change from
• Fever fever to hypothermia
• Hemorrhagic manifestations •Change in level of
• Excessive capillary consciousness
permeability (irritability or somnolence)
• ≤ 100,000/mm3 platelets
Initial Warning Signals:
• Disappearance of fever When Patients Develop
• Drop in platelets DSS:
• Increase in hematocrit • 3 to 6 days after onset of
symptoms
CDC
Friday, June 18, 2010

20. Differential Diagnosis of
Dengue
• Influenza • Leptospirosis
• Measles • Meningococcemia
• Rubella • Rickettsial infections
• Malaria • Bacterial sepsis
• Other viral
• Typhoid fever
hemorrhagic fevers
Friday, June 18, 2010

21. Laboratory Tests
in Dengue Fever
• Clinical laboratory tests
– CBC--WBC, platelets, hematocrit
– Albumin
– Liver function tests
– Urine--check for microscopic hematuria
• Dengue-specific tests
– Virus isolation
– Serology
Friday, June 18, 2010

22. Laboratory Methods for
Dengue Diagnosis
• Virus isolation to determine serotype of
the infecting virus
• IgM ELISA test for serologic diagnosis
Friday, June 18, 2010

23. Temperature, Virus Positivity
and Anti-Dengue IgM , by
Fever Day
Temperature (degrees Celsius)
100 300
Dengue IgM (EIA units)
39.5
Percent Virus Positive
80
39.0 225
38.5 60
150
38.0 40
37.5 20 75
37.0
0 0
-4 -3 -2 -1 0 1 2 3 4 5 6
Fever Day
Mean Max. Temperature Virus Dengue IgM
Adapted from Figure 1 in Vaughn et al.,
J Infect Dis, 1997; 176:322-30.
Friday, June 18, 2010

24. Management
• No hemorrhagic manifestations and patient
is well-hydrated: home treatment
• Hemorrhagic manifestations or hydration
borderline: consider hospitalization
• Warning signs (even without profound
shock) or DSS: hospitalize
Friday, June 18, 2010

25. Management of Dengue Fever
• Fluids
• Antipyretics (avoid
aspirin and non-steroidal
anti-inflammatory drugs)
• Monitor blood pressure,
hematocrit, platelet
count, level of
consciousness, intake &
output
• Blood products only
when needed
Friday, June 18, 2010

26. Mosquito Barriers
• Only needed until fever subsides, to
prevent Aedes aegypti mosquitoes from
biting patients and acquiring virus
• Keep patient in screened sickroom or
under a mosquito net
Friday, June 18, 2010

27. Prevention:
• Public education
• Vector control
• vaccine in development
Friday, June 18, 2010

28. St. Louis encephalitis
Murray Valley encephalitis
West Nile Fever
28
Friday, June 18, 2010

29. Japanese encephalitis virus
• single serotype, 5 genotypes based on E
protein
• Asia, including SEA
• cycle: birds - Culex mosquitoes - swine
• humans, horses
29
Friday, June 18, 2010

30. Japanese encephalitis
• 99% subclinical
• lethargy, behavioral changes, motor
abnormalities
• Dx: CSF analysis, EEG, IgM ELISA, NT, HI,
CF, PCR
• Rx: supportive
• Prevention: inactivated vaccine (3 yr
protection)
30
Friday, June 18, 2010

31. 31
Friday, June 18, 2010

32. THANK YOU!
31
Friday, June 18, 2010