Flavivirus

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Flavivirus

  1. 1. Flaviviruses 1 Friday, June 18, 2010
  2. 2. Flaviviridae • >68 viruses • small • spherical • enveloped • SS RNA • cross-related 2 Friday, June 18, 2010
  3. 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. 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. 5. Dengue Fever/Dengue Hemorrhagic Fever Friday, June 18, 2010
  6. 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. 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. 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. 9. Spectrum of Dengue Illness Undifferentiated Dengue Fever Dengue Hemorrhagic illness Fever Classic Dengue Dengue Shock Syndrome Friday, June 18, 2010
  10. 10. Clinical Characteristics of Dengue Fever • Fever • Headache • Muscle and joint pain • Nausea/vomiting • Rash • Hemorrhagic manifestations Friday, June 18, 2010
  11. 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. 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. 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. 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. 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. 16. Friday, June 18, 2010
  17. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 27. Prevention: • Public education • Vector control • vaccine in development Friday, June 18, 2010
  28. 28. St. Louis encephalitis Murray Valley encephalitis West Nile Fever 28 Friday, June 18, 2010
  29. 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. 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. 31 Friday, June 18, 2010
  32. 32. THANK YOU! 31 Friday, June 18, 2010

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