2. Management of Dengue Fever Dr David Tran 16/09/09

3. Classic clinical dengue fever Incubation period 3 to 14 days (usually 4 to 7 days) Sudden onset of fever with severe headache Retro-orbital pain, fatigue Often associated with myalgia and arthralgia Duration of fever usually 5 to 7 days Sometime maculopapular rash (50% to 66% of cases) Other non specific signs as inflamed pharynx, gastro-intestinal symptoms

4. Classic definition of dengue fever (WHO 1997)

5. Hemorrhagic manifestations / biologic abnormalities Petechiae, purpura Gum bleeding, epistaxis, menorrhagia, gastro- intestinal bleedings (rare) Thrombocytopenia, leukopenia with lymphopenia Mild elevation of hepatic transaminases & LDH

6. Definition of dengue hemorrhagic fever (WHO 1997)

7. Dengue hemorrhagic fever & Dengue shock syndrome Physiopathology: capillary leakage & hemorrhagic manifestations. 4 to 7 days after the onset (at approximately the date of defervescence) Abdominal pain, vomiting, consciousness troubles, hypothermia Marked decrease in platelet count. Mortality: up to 10 or 20%

8. Definition of dengue shock syndrome (WHO 1997)

9. Diagnosis of dengue hemorrhagic fever (triad of symptoms) Hemorrhagic manifestations Platelet count 3 rd day of illness) Evidence of plasma leakage (Hematocrite  pleural effusion, ascites, hypoproteinemia)

10. Lowest platelet count by day of illness in adult dengue hemorrhagic patients

11. Dengue shock syndrome Rapid weak pulse & low blood pressure (BP < 90mmHg) The duration of this shock is short after appropriate volume replacement therapy (Colloid or Cristalloid infusions) Mortality rate is up to 40%

12. Different clinical presentation of dengue fever

13. Serodiagnosis of dengue fever Serology (IgM capture ELISA) Problem: negativity of the test early in the course of the disease > should be performed only 4 to 5 days after the onset of fever. IgM: remain positive for 3 to 6 month IgG: remain positive for life

14. Dengue NS1 antigen testing Early detection of Ag NS1 in blood sample of infected patients > confirm early acute infection Detection of all 4 types of dengue serotypes Result available in 15 min. (BioRad ® chromatographic strip test) High specificity (100%) and positive predictive value

15. Although in some reports, the same efficiency of detection for virus of the 4 serotypes has been described for the Dengue Early ELISA and Strip tests (Dussart et al., 2008), A recent analysis of the performance of these tests in Vietnam suggests a lower sensitivity for DENV-2 compared with DENV-1 and DENV-3.

16. Problem of sensibility of NS1 detection tests (Ramirez, diagnostic microbiology & infectious disease, Sept 2009) These tests in Vietnam suggests a lower sensitivity for DENV-2 compared with DENV-1 and DENV-3. Also, a decreased sensitivity for DENV-4 with the Dengue Early ELISA has been reported in studies from South America (Bessoff et al., 2008; Dussart et al., 2008). A lower sensitivity for DENV-2 has been described in samples from Vietnam (Hang et al., 2009) tested by the PLATELIA ™ systems (ELISA and Strip) and belonging to the Asian genotype 1 (according to the classification of Twiddy et al., 2002).

17. Sensitivity of NS1 Ag detection tests according to the day of illness (Mc Bride, Diagnostic Microbiology & Infectious Diseases, 64 – 2009 – 31,36)

18. Management of dengue virus infected patient Most of cases can be managed on an outpatient basis (antipyretic like paracetamol, bed rest, oral hydratation) Platelet counts and hematocrite determination should be repeated at least every 24 hours Patient with platelet count < 100.000 should be hospitalized (high risk for dengue hemorrhagic & dengue shock syndrome)