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An update on dengue and related viral illnesses

An update on dengue and related viral illnesses. Dr Alan Wu Dept of Microbiology, PYNEH 12 Nov 2010. Rift valley fever virus (Bunyavirus). Yellow fever virus (Flavivirus). Junin virus (Arenavirus). Ebola virus (Filovirus). Cohen & Powderly: Infectious Diseases, 3rd ed.

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An update on dengue and related viral illnesses

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  1. An update on dengue and related viral illnesses Dr Alan Wu Dept of Microbiology, PYNEH 12 Nov 2010

  2. Rift valley fever virus (Bunyavirus) Yellow fever virus (Flavivirus) Junin virus (Arenavirus) Ebola virus (Filovirus) Cohen & Powderly: Infectious Diseases, 3rd ed.

  3. Lassa fever virus (Arenavirus) Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 7th ed.

  4. Flaviviridae Dengue fever (1994 – now) ~30-50 cases per year, mostly imported Yellow fever (1997 – now) No cases reported locally so far Togaviridae Chikungunya fever (2009 – now) 1 case reported in 2009 only so far Miscellaneous “Viral haemorrhagic fever” (2008 – now) No case reported locally so far Hantavirus infection (2008 – now) ~1 case reported per year Statutory notifiable haemorrhagic and related viral diseases in HK CHP data, as at Aug 2010

  5. Dengue: an overview Most rapidly spreading mosquito-borne viral disease in the world

  6. Small (50nm), enveloped single stranded +ve strand RNA virus. Flaviridae. 4 serotypes: DEN1-4; no lasting cross-protection with infection by one serotype Distinct genotypes / lineages within each serotype; some associated with more severe diseases (e.g. “Asian genotypes” of DEN-2 and 3)

  7. Dengue: 2009 WHO guidelines for diagnosis, treatment, prevention and control. Available for download from: http://whqlibdoc.who.int/publications/2009/9789241547871_eng.pdf

  8. Dengue: 2009 WHO guidelines for diagnosis, treatment, prevention and control. Available for download from: http://whqlibdoc.who.int/publications/2009/9789241547871_eng.pdf

  9. 1 20 1994 – 2001: 72 cases, no local, 4 DHFs Local cases reported in 2002, 2003 and in 2010 All other cases imported Chuang VW, Wong TY, Leung YH, et al. Review of dengue fever cases in Hong Kong during 1998 to 2005. Hong Kong Med J. 2008 Jun;14(3):170-7.

  10. 2007 2010 Data from CHP, as at Aug 2010.

  11. PCR: Dengue serotype 1 pos Tsuen Wan, Tin Shui Wai, Sham Shui Po. No Epi-link with Ma Wan. DEN-2 pos 6 (7) M:F= 13:3; age 17-60 10 16 (17) from Ma Wan, 3 outside Ma Wan, 1 transfusion related. All recovered. Dept of Health Public Health and Epidemiology Bulletin. Oct 2002

  12. DEN-1 ~48%, DEN-2 ~23% Local cases: DEN-1 & 2 Imported cases: all serotypes Chuang VW, Wong TY, Leung YH, et al. Review of dengue fever cases in Hong Kong during 1998 to 2005. Hong Kong Med J. 2008 Jun;14(3):170-7.

  13. CHP Communicable Diseases Watch vol. 7 no.21 Sept 26 – Oct 9 2010

  14. Aedes albopictus Aedes aegypti Dept of Health Public Health and Epidemiology Bulletin. Oct 2002; Cohen & Powderly: Infectious Diseases, 3rd ed.

  15. Distribution of Aedes aegypti in the Americas (1970 vs 2002) Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 7th ed.

  16. Approximate actual and potential distribution of Aedes aegypti (WHO) 35N to 35S (as north as 45 N during warmer months); uncommon above 1000m Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 7th ed.

  17. Immature stages of A. aegypti found in water-filled habitats, mostly artificial containers associated with human dwellings Adult female mosquitoes spend lifetime in and around human houses Clustering of cases within ~800 m and around rainy seasons A.aegypti (life span 1-4 weeks); bite during dawn and sunset Mosquito/extrinsicincubation period 1-2 weeks Dengue outbreaks also attributed to other Aedes sp. vectors A. albopictus Spreading worldwide, from Asia to Africa, the Americas and Europe; eggs carried in tyres can survive without water for months A. polynesiensis A. scutellaris complex Dengue: vectors and transmission

  18. Introduction of virus into a susceptible population usually by viraemic travellers resulting in epidemic (3-5 days/before end of fever) Epidemic rate >70% Potentially transmissible through needle stick injury, transfusion and even transplantation as suggested by isolated case reports Important cause of “fever of returning travelers” (NEJM 2002) Dengue: further facts on transmission

  19. Transfusion related dengue fever in 2002 HK – first reported case in literature F/76, Hx of HT and bronchiectasis Admitted to hospital in 2002 due to malaise, blood tests confirmed anaemia due to B12 deficiency Patient received blood transfusion on 24 Aug 2002, blood unit was collected from an asymptomatic 17 y.o. Ma Wan resident on 17 July 2002 On day 2 post-transfusion, patient developed low grade fever w/o rash or other symptoms. Treated as UTI, fever down after 3 days. The Ma Wan resident presented to AED on 24 July 2002 with fever and rash. Retrospectively diagnosed in Oct 2002 as a case of dengue Molecular tests on the donated blood product showed PCR +ve for DEN-1 Patient recalled for blood testing on 7 Oct 2002, found dengue IgM +ve, HAI 1:2560, Since incident, BTS intensified donor screening to look for possible symptoms suggestive of dengue fever 2 weeks before or after blood donation. Chuang VW, Wong TY, Leung YH, et al. Review of dengue fever cases in Hong Kong during 1998 to 2005. Hong Kong Med J. 2008 Jun;14(3):170-7.

  20. Distribution of Dengue: Eastern hemisphere (CDC, 2010) CDC Health Information for International Travel 2010, 1st ed.

  21. Dengue in the WHO SE Asia Region Indonesia: Jakarta and West Java Thailand: all regions of the country, recent outbreaks in Bangkok Dengue: 2009 WHO guidelines for diagnosis, treatment, prevention and control. Available for download from: http://whqlibdoc.who.int/publications/2009/9789241547871_eng.pdf

  22. Dengue in the WHO Western Pacific Region Dengue: 2009 WHO guidelines for diagnosis, treatment, prevention and control. Available for download from: http://whqlibdoc.who.int/publications/2009/9789241547871_eng.pdf

  23. Dengue in the WHO African Region Dengue: 2009 WHO guidelines for diagnosis, treatment, prevention and control. Available for download from: http://whqlibdoc.who.int/publications/2009/9789241547871_eng.pdf

  24. Dengue in the WHO Eastern Mediterranean Region Dengue: 2009 WHO guidelines for diagnosis, treatment, prevention and control. Available for download from: http://whqlibdoc.who.int/publications/2009/9789241547871_eng.pdf

  25. Distribution of Dengue: Western hemisphere (CDC, 2010) CDC Health Information for International Travel 2010, 1st ed.

  26. Dengue in the Americas Dengue: 2009 WHO guidelines for diagnosis, treatment, prevention and control. Available for download from: http://whqlibdoc.who.int/publications/2009/9789241547871_eng.pdf

  27. Dengue in unexpected areas: North American countries Dengue: 2009 WHO guidelines for diagnosis, treatment, prevention and control. Available for download from: http://whqlibdoc.who.int/publications/2009/9789241547871_eng.pdf

  28. Dengue in other regions Dengue: 2009 WHO guidelines for diagnosis, treatment, prevention and control. Available for download from: http://whqlibdoc.who.int/publications/2009/9789241547871_eng.pdf

  29. 91% from South-East Asian countries Indonesia Thailand The Philippines Vietnam Singapore Malaysia Cambodia Macau The Pacific Islands 7% from South Asia India Pakistan Bangladesh Sri-Lanka Nepal Others (1%) Pitcairn Islands HK: Country of origin for imported cases (N=116) Chuang VW, Wong TY, Leung YH, et al. Review of dengue fever cases in Hong Kong during 1998 to 2005. Hong Kong Med J. 2008 Jun;14(3):170-7.

  30. Incubation period: 3-14 days (usually 4-7 days) Mosquito bite  local LN  viraemia with invasion of lymphocytes, monocytes  cytokine release  fever, malaise Viremia occurs for 4-5 days, usually detectable 6-18hrs before symptom onset, until end of fever Myalgia: perivascular mononuclear cell infiltration  muscle necrosis and elevated CPK Marrow suppression  cytopenia; anti-platelet Ab Skin rash: dermal vasculitis  viral antigen Elevated LFT: necrosis of hepatocytes and accelerated apoptosis CNS invasion: intrathecal IgM; cerebral edema and encephalitis (rare) The virus: what happens after it enters the body

  31. Dengue: 2009 WHO guidelines for diagnosis, treatment, prevention and control. Available for download from: http://whqlibdoc.who.int/publications/2009/9789241547871_eng.pdf

  32. Dengue associated skin rash Diffuse macular rash Appears on day 3-6 after fever onset “Islands” of normal skin surrounded by erythema Cohen & Powderly: Infectious Diseases, 3rd ed.; Keystone: Travel Medicine, 2nd ed.

  33. Patient with severe shock in ICU Haemorrhagic manifestations of DHF Severe complications occur in <1% of cases overall Globally ~500,000 annual cases of DHF SE Asia: DHF = 0.3%, usually in children <15 yr Cohen & Powderly: Infectious Diseases, 3rd ed.

  34. DF and DHF by country and number of cases reported to WHO: 1995-2004 Plotkin: Vaccines, 5th ed.

  35. Webster DP, Farrar J, Rowland-Jones S. Progress towards a dengue vaccine. Lancet Infect Dis. 2009 Nov;9(11):678-87.

  36. Infants between 6-12 months

  37. DHF: classification and pathophysiology Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 7th ed.

  38. 4 cardinal features: 1. Fever 2. Platelet <100 3. Bleeding tendency / positive tourniquet test 4. Plasma leakage (Hct, serous effusions) DSS: DHF + Shock Shock: within 24 hours just after fever subsides Case-fatality 40-50% if untreated (grade III-IV; mainly in children; < 4 yrs or >50 yrs )  1-2% if supported DHF / DSS Criteria too stringent? Many patients do not fulfill criteria for DHF / DSS but clinically has severe disease

  39. New WHO classification

  40. Dengue: 2009 WHO guidelines for diagnosis, treatment, prevention and control. Available for download from: http://whqlibdoc.who.int/publications/2009/9789241547871_eng.pdf

  41. Positive tourniquet test Auerbach: Wilderness Medicine, 5th ed.; Cohen & Powderly: Infectious Diseases, 3rd ed.

  42. No major differences in clinical manifestations between different DEN serotypes DEN-3: More leukopenia and lower lymphocyte count (?) Chuang VW, Wong TY, Leung YH, et al. Review of dengue fever cases in Hong Kong during 1998 to 2005. Hong Kong Med J. 2008 Jun;14(3):170-7.

  43. Dengue: 2009 WHO guidelines for diagnosis, treatment, prevention and control. Available for download from: http://whqlibdoc.who.int/publications/2009/9789241547871_eng.pdf

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