DENGUE

1. DENGUE Dr. Halesh .L.H. Professor and Head of the department , Microbiology SIMS,Shimoga

3. Virus, Vector and Transmission

4. Causative agent of dengue fever, belongs to family flaviviridae, genus flavivirus. • It is a spherical enveloped virus • Genomic material – single stranded RNA • There are presently 5 serotypes identified Dengue Virus

5. Fifth serotype, identified in 2013, october follows sylvatic cycle,and is found only in Sarawak forest, Malaysia • Each serotype provides specific lifetime immunity, and short-term cross-immunity • All serotypes can cause severe and fatal disease Dengue Virus (cont’d.)

6. Genetic variation within serotypes • Some genetic variants within each serotype appear to be more virulent or have greater epidemic potential Dengue virus

7. The first record of dengue fever is in chinese medical encyclopedia referred as water poison caused by flying insects • Reports of epidemics – 1779-80 • Then until 1940 , epidemics were infrequent • Then there was marked spread of dengue during and after second world war HISTORY

8. The incidence is dramatically increasing • 390 million dengue cases per year • Infections are acquired in urban environment • Rate of dengue has increased 10folds between 1960-2010 HISTORY

9. Replication and Transmissionof Dengue Virus

10. 1. Virus is transmitted to human in mosquito saliva 2. Virus replicates in target organs 3. Virus infects white blood cells and lymphatic tissues Replication and Transmissionof Dengue Virus 4. Virus released and circulates in blood

11. 5. Second mosquito ingests virus with blood 6. Virus replicates in mosquito midgut and other organs, infects salivary glands 7. Virus replicates in salivary glands

12. Aedesaegypti Mosquito

13. Dengue transmitted by infected female mosquito • Primarily a daytime feeder • Lives around human habitation • Lays eggs and produces larvae preferentially in artificial containers Aedesaegypti

15. Clinical Manifestations of Dengue and DHF

16. Undifferentiated fever • Classic dengue fever • Dengue hemorrhagic fever • Dengue shock syndrome Dengue Clinical Syndromes

17. Clinical Characteristicsof Dengue Fever

18. 4 Necessary Criteria: 1.Fever, or recent history of acute fever 2.Hemorrhagic manifestations 3.Low platelet count (100,000/mm3 or less) 4.Objective evidence of “leaky capillaries:” • elevated hematocrit (20% or more over baseline) • low albumin • pleural or other effusions Clinical Case Definition forDengue Hemorrhagic Fever

19. criteria for DHF 1.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 2.Frank shock is direct evidence of circulatory failure Clinical Case Definition for Dengue Shock Syndrome

20. Grade 1 • Fever and nonspecific constitutional symptoms • Positive tourniquet test is only hemorrhagic Manifestation • Grade 2 • Grade 1 manifestations + spontaneous bleeding 4 Grades of DHF

21. Grade 3 • Signs of circulatory failure (rapid/weak pulse, narrow pulse pressure, hypotension, cold/clammy skin) • Grade 4 • Profound shock (undetectable pulse and BP)

22. Abdominal pain - intense and sustained • Persistent vomiting • Abrupt change from fever to hypothermia, with sweating and prostration • Restlessness or somnolence DANGER SIGNS OF DHS

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

24. Encephalopathy • Hepatic damage • Cardiomyopathy • Severe gastrointestinal hemorrhage Unusual Presentationsof Severe Dengue Fever

25. Disease Pathogenesis

26. Higher risk in secondary infections • Higher risk in locations with two or more serotypes circulating simultaneously at high levels (hyperendemic transmission) Risk Factors for DHF

27. Persons who have experienced a dengue infection develop serum antibodies that can neutralize the dengue virus of that same (homologous) serotype Hypothesis on Pathogenesisof DHF

28. 1 1 1 1 1 Homologous Antibodies Form Non-infectious Complexes Dengue 1 virus Neutralizing antibody to Dengue 1 virus Non-neutralizing antibody Complex formed by neutralizing antibody and virus

29. In a subsequent infection, the pre-existing heterologous antibodies form complexes with the new infecting virus serotype, but do not neutralize the new virus Hypothesis on Pathogenesisof DHF

30. 2 2 2 2 2 2 Heterologous Antibodies Form Infectious Complexes Dengue 2 virus Non-neutralizing antibody to Dengue 1 virus Complex formed by non-neutralizing antibody and virus

31. Antibody-dependent enhancement 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 Hypothesis on Pathogenesis of DHF

32. 2 2 2 2 2 2 2 2 2 2 2 2 Heterologous Complexes Enter More Monocytes, Where Virus Replicates Dengue 2 virus Non-neutralizing antibody Complex formed by non-neutralizing antibody and Dengue 2 virus

33. Infected monocytes release vasoactive mediators, resulting in increased vascular permeability & hemorrhagic manifestations that characterize DHF and DSS Hypothesis on Pathogenesisof DHF

34. Virus serotype • DHF risk is greatest for DEN-2, followed by DEN-3, DEN-4 & DEN-1 Viral Risk Factorsfor DHF Pathogenesis

35. Diagnosis

36. Blood pressure • Evidence of bleeding in skin or other sites • Hydration status • Evidence of increased vascular permeability- • pleural effusions, ascites Clinical Evaluation in Dengue Fever

37. Petechiae

38. Laboratory Testsin Dengue Fever

39. Clinical laboratory tests • CBC--WBC, platelets, hematocrit • Albumin • Liver function tests • Urine--check for microscopic hematuria VIRUS SPECIFIC TEST • Virus isolation • Serology Laboratory Testsin Dengue Fever

40. Virus Isolation:Cell Culture

41. Virus Isolation:Mosquito Inoculation

42. Virus Isolation:Fluorescent Antibody Test

43. Treatment

44. No hemorrhagic manifestations and patient is well-hydrated: home treatment • Hemorrhagic manifestations or hydration borderline: outpatient observation center or hospitalization • Warning signs (even without profound shock) or DSS: hospitalize Outpatient Triage

45. Patients treated at home • Instruction regarding danger signs • Consider repeat clinical evaluation • Patients with bleeding manifestations • Serial hematocrits and platelets at least daily until temperature normal for 1 to 2 days Patient Follow-Up

46. All patients • If blood sample taken in first 5 days after onset, need convalescent sample between days 6 - 30 • All hospitalized patients need samples on admission and at discharge or death Patient Follow-Up (cont’d.)

47. Fluids • Rest • Antipyretics (avoid aspirin & NSAIDs) • Monitor blood pressure, hematocrit, platelet count, level of consciousness Treatment of Dengue Fever

48. Only needed until fever subsides, to prevent Aedes aegypti mosquitoes from biting patients and acquiring virus • Keep patient in screened sick room or under a mosquito net Mosquito Barriers

49. Absence of fever for 24 hours (without anti-fever therapy) and return of appetite • Visible improvement in clinical picture • Stable hematocrit • 3 days after recovery from shock • Platelets  50,000 / mm3 • No respiratory distress from pleural effusions / ascites Indications for Hospital Discharge

50. DHF is a pediatric disease • All age groups are involved • DHF is a problem of low income families • All socioeconomic groups are affected More Common Misconceptions about DHF