1. West Nile Virus Michigan - 2002 Mary Grace Stobierski, DVM,MPH,DACVPM Michigan Dept. Community Health

2. West Nile Virus 2002, A Season of Surprises Largest arbovirus meningoencephalitis outbreak epidemic ever documented in western hemisphere Largest arbovirus meningoencephalitis outbreak epidemic ever documented in western hemisphere Largest WNME epidemic ever documented Largest WNME epidemic ever documented Geographic spread to the Pacific Coast Geographic spread to the Pacific Coast Clinical syndromes (Acute Flaccid Paralysis, was not Guillian-Barre syndrome) Clinical syndromes (Acute Flaccid Paralysis, was not Guillian-Barre syndrome) New modes of transmission New modes of transmission

3. Novel Modes of West Nile Virus Transmission, 2002 Transplanted organs Transplanted organs Transfused blood Transfused blood Breast milk Breast milk Percutaneous, occupational exposure Percutaneous, occupational exposure Prenatal transmission Prenatal transmission

4. Any WNV Activity Reported - 2002

5. Human Cases

6. WNV Hotline Calls* 2002 (operated by MDCH staff) 1/888/668-0869 * >35,000 calls in Aug & Sept

7. Michigan Department of Community Health Announces Probable Human Cases of West Nile Virus August 16, 2002 Michigan Department of Community Health Chief Medical Executive, David R. Johnson M.D., today announced two probable human cases of West Nile virus. Laboratory samples have been sent to the Centers for Disease Control and Prevention for confirmatory testing. The first case involves an 82 year-old male from Southeast Michigan who was hospitalized and has been released in good condition. The second involves a 63 year-old male from Southeast Michigan who is currently hospitalized and appears to be improving. “We are encouraged that both of these gentlemen appear to be recovering and we will continue to work with health care providers throughout Michigan to quickly identify any other potential human cases,” said Dr. Johnson. “The most important thing a person can do to protect themselves from West Nile virus is to follow the common-sense precautions to minimize exposure to mosquitoes.”

9. Onset Date of Symptoms Among Human West Nile Virus Cases in Michigan for 2002 Data from 614 of the 644Total Cases

10. WNV Human cases Michigan 2002* 644 cases 51 deaths *(Total Cases/Deaths) (Includes probable and confirmed cases, all clinical syndromes)

11. Michigan WNV Case Statistics: All Cases All Cases Age range: 9mo-95yrs Ave Age: 57.6 % Female: 45 % Male: 55 Deaths Age range: 24-95 yrs Ave Age: 74.5 % Female: 41 % Male: 59

12. West Nile Virus Case Summary Total Laboratory Positive Cases: 644 West Nile Meningo-encephalitis cases: 559 (87%) Age range:.75-95 yrs Average age: 57.8 yrs West Nile Fever cases: 57 (9%) Age range: 3-80 yrs Average Age: 47.7 yrs Unknown cases: 28 (4%) Deaths: 51 (9%) Age range: 24-95 yrs Average age: 74.5 yrs

13. 2002 Cases by Agegroup - 2002 N=639 cases

14. Additional Arboviruses in 2002 St. Louis Encephalitis: 3 cases St. Louis Encephalitis: 3 cases Eastern Equine Encephalitis: 6 cases Eastern Equine Encephalitis: 6 cases LaCrosse Encephalitis: 11 cases LaCrosse Encephalitis: 11 cases Powassan virus: 1 case (Emmet Co.) Powassan virus: 1 case (Emmet Co.) (tick borne encephalitis) (tick borne encephalitis) First time ever documented case in First time ever documented case in Michigan! Michigan!

15. Additional Arbovirus Cases Michigan, 2002CountySLEEEELACPOWClare1 Eaton1 Emmet1 Genesee3 Huron1 Kent1 Macomb21 Manistee1 Oakland12 Ottawa1 PresqueIsle1 Wayne22

16. Comprehensive Website www.michigan.gov/westnilevirus

17. The Transfusion Saga Begins in Michigan

18. August 2002

19. West Nile Virus Infection in an Organ Donor and Four Transplant Recipients (GA & FL) August 2002 Organ Donor WNV PCR – IgM – Organ Donor WNV PCR + Culture + IgM – Kidney recipient WNME (fatal) Kidney recipient WNME Liver recipient WNF Heart recipient WNME Blood components from 63 donors

20. Transfusion-associated West Nile virus infection Background Potential transmission - Transient viremia - Most infections asymptomaticPotential transmission - Transient viremia - Most infections asymptomatic “Small but not zero” risk - No chronic carriers - No cases reported in prior years or from endemic countries“Small but not zero” risk - No chronic carriers - No cases reported in prior years or from endemic countries Estimated risk: 1.8-2.7/10,000 donations in 1999 Queens (NYC) epidemicEstimated risk: 1.8-2.7/10,000 donations in 1999 Queens (NYC) epidemic

21. Investigation of transfusion-associated West Nile virus infection Comprehensive chart review of caseComprehensive chart review of case Determine number & type of components transfused to recipient in 4 weeks before WNV illness onsetDetermine number & type of components transfused to recipient in 4 weeks before WNV illness onset Retrieve “initial donation samples” (retention segments, untransfused product, NAAT tubes) Test for WNV RNA (TaqMan rtPCR) and IgM antibody (ELISA) Donor F/U serum questionnaire & serum sample for WNV IgM antibody testDonor F/U serum questionnaire & serum sample for WNV IgM antibody test F/U questionnaire & WNV IgM antibody testing of “other recipients” who received “suspect” blood product (if indicated)F/U questionnaire & WNV IgM antibody testing of “other recipients” who received “suspect” blood product (if indicated)

22. Case definition: Confirmed transfusion- associated West Nile virus infection Probable/confirmed WNV illness* in blood product recipientProbable/confirmed WNV illness* in blood product recipient Transfusion within 4 weeks of illness onsetTransfusion within 4 weeks of illness onset Evidence of viremia in donor:Evidence of viremia in donor: TaqMan-positive index donation sample(s) AND virus isolation OR TaqMan-positive index donation sample(s) AND seroconversion in donor * CDC. Epidemic/Epizootic West Nile Virus in the United States: Revised Guidelines for Surveillance, Prevention, and Control, April 2001.

23. Transfusion investigations in MI Case # Age Age # Donors Underlying Condition Outcome 14739 Liver transplant Alive 2402ObstetricAlive 3444 Organ donor Fatal 41283LeukemiaAlive 57210CABGFatal 643 Stem Cell Transplant Not WNV 75179LeukemiaFatal 87810MIFatal

24. Transfusion investigations in MI, cont’d Case # Age Age # Donors Underlying Condition Outcome 9768CancerFatal 10808Dementia Not WNV 112617LeukemiaAlive 1269- Blood Donor Alive 13754CABGAlive 14713CancerAlive 157321Co-recipientAlive

25. MI 0001 47 yr, male, Wayne county resident 47 yr, male, Wayne county resident History of cirrhosis, hepatitis B, hepatocellular carcinoma History of cirrhosis, hepatitis B, hepatocellular carcinoma Liver transplant 8/14/02 Liver transplant 8/14/02 Recovered, released 8/24/02 Recovered, released 8/24/02

26. MI 0001 cont’d ER visit 9/3/02, Readmit 9/4/02 ER visit 9/3/02, Readmit 9/4/02  FEVER, H/A, MENTAL STATUS CHANGE CSF 9/5/02 WNV (+) IgM @ MDCH CSF 9/5/02 WNV (+) IgM @ MDCH Recovered, discharged 9/13/02 Recovered, discharged 9/13/02 Received 39 blood components from 8/14/02 through 8/21/02 Received 39 blood components from 8/14/02 through 8/21/02

27. MI 0002 40 yr, female, Macomb county resident 40 yr, female, Macomb county resident Normal delivery, 9/2/02; received 2 transfusions Normal delivery, 9/2/02; received 2 transfusions Discharged 9/4/02 Discharged 9/4/02 Readmitted 9/17/02: fever, headache, confusion/agitation Readmitted 9/17/02: fever, headache, confusion/agitation

28. MI 0002 cont’d CSF 9/18/02 IgM (+) WNV @ MDCH CSF 9/18/02 IgM (+) WNV @ MDCH Infant has been healthy throughout Infant has been healthy throughout Traceback of blood revealed one component in common with liver recipient (MI 0001) Traceback of blood revealed one component in common with liver recipient (MI 0001)

29. MI 0003: LIVER DONOR 44 yr, male, Wayne/Oakland resident 44 yr, male, Wayne/Oakland resident 8/10 -12/02: intracerebral hemorrhage; Declared dead; Organs harvested. 8/10 -12/02: intracerebral hemorrhage; Declared dead; Organs harvested. Autopsy 8/14/02 Autopsy 8/14/02 Liver transplanted into MI resident 8/14/02 Liver transplanted into MI resident 8/14/02 Kidneys transplanted in MD resident 8/14/02 Kidneys transplanted in MD resident 8/14/02

30. MI 0003 cont’d DONOR LAB RESULTS Archived serum (@ time of harvest): IgM negative at CDC – Ft. Collins Archived serum (@ time of harvest): IgM negative at CDC – Ft. Collins Kidney nephrectomized from recipient: IHC negative at CDC – Atlanta Kidney nephrectomized from recipient: IHC negative at CDC – Atlanta Autopsy tissues (inc. Brain, heart, lungs): IHC negative at CDC – Atlanta Autopsy tissues (inc. Brain, heart, lungs): IHC negative at CDC – Atlanta Thus, donor was NOT INFECTED with WNV. Thus, donor was NOT INFECTED with WNV.

31. MI 0001 & MI 0002 Found to have one blood component in common Found to have one blood component in common Blood component in common found to be Taqman PCR positive @ CDC Blood component in common found to be Taqman PCR positive @ CDC Donor of blood traced; Wayne county resident; reported symptoms 3 days post-donation Donor of blood traced; Wayne county resident; reported symptoms 3 days post-donation  Fever, rash, myalgia, minor weakness. Recovered 6-7 days later. Blood sample 10/7/02 IgM + at CDC.

32. MI 0002 cont’d Breast milk Breast milk  Sample collected 9/19: Taqman +, IgM +, IgG +; Viral culture - at CDC  Sample collected 9/27: Taqman -, IgM + Infant test results Infant test results  Serum collected 9/27: IgM + (MDCH & CDC)  PKU card: Taqman - (MDCH)

33. MI 0002 cont’d Mother reported infant had little outdoor or other exposure to mosquitoes Mother reported infant had little outdoor or other exposure to mosquitoes Presence of measurable WNV-specific IgM suggests independent IgM production by infant as result of WNV infection via breast milk Presence of measurable WNV-specific IgM suggests independent IgM production by infant as result of WNV infection via breast milk No change in breastfeeding recommendations No change in breastfeeding recommendations

34. MMWR10/4/2002 Transmission Via Breast Feeding

35. MI0004 Case Detail 12 year old, AML 12 year old, AML Had been in isolation at hospital for 65 continuous days Had been in isolation at hospital for 65 continuous days Received 83 blood components Received 83 blood components No mosquito exposure, thus only means of transmission was via blood transfusion No mosquito exposure, thus only means of transmission was via blood transfusion

36. Transfusion Investigations: Michigan Summary 15 Investigations 15 Investigations  Patients: 7 yr – 80 yr  Includes 2 donors (1 organ and 1 blood)  # Blood Components: 2 – 83  5 Fatal  2 Subsequently ruled out as WNV

37. West Nile virus infections in blood transfusion recipients, US Summary 61 possible cases reported to CDC since Aug 28, 2002 61 possible cases reported to CDC since Aug 28, 2002 19 not transfusion-associated WNV 19 not transfusion-associated WNV 21 had inconclusive investigations 21 had inconclusive investigations 21 confirmed cases of transfusion-associated transmission 21 confirmed cases of transfusion-associated transmission  Aged 7-90 years  11 Female; 10 Male  10 were immunocompromised

38. Prevention of Transfusion- Related Infection Current: donor screening Current: donor screening FDA encouraging development of nucleic acid- based screening tests FDA encouraging development of nucleic acid- based screening tests  Will pooled nucleic acid testing have high enough sensitivity?  Can these tests, if developed, be implemented in time for the 2003 season? Retrieval & quarantine of blood products collected during 2002 epidemic period Retrieval & quarantine of blood products collected during 2002 epidemic period

39. Intrauterine WNV Infection New York, August 2002 20 yr old in 27 th week of pregnancy 20 yr old in 27 th week of pregnancy  Fever, H/A, blurred vision, vomiting, abdominal & back pain, severe weakness.  5 weeks later, delivered a live infant; has a number of congenital abnormalities. Mother: serum & CSF IgM + Mother: serum & CSF IgM + Infant: serum & CSF IgM + Infant: serum & CSF IgM +  MMWR Vol.51/No.50

40. Laboratory-Acquired WNV 2 laboratory workers 2 laboratory workers Percutaneous inoculation Percutaneous inoculation Illnesses in both: mild & self-limiting Illnesses in both: mild & self-limiting  Serum IgM (+) in both cases MMWR Vol 51/ No 50 MMWR Vol 51/ No 50

41. West Nile virus, 2002:Emerging issues Emergence in western U.S. Emergence in western U.S. New modes of transmission New modes of transmission  Breast milk  Transplacental  Transfusion / transplantation  Laboratory/occupational Emerging clinical syndromes Emerging clinical syndromes  WN fever  WNME / acute flaccid paralysis  WNME / rhabdomyolysis Long-term outcome studies Long-term outcome studies

42. 2002 SEASON CHALLENGES Coordination between multiple agencies Coordination between multiple agencies Deluge of human case appearances Deluge of human case appearances Rapid communication of results to multiple parties Rapid communication of results to multiple parties New modes of transmission discovered New modes of transmission discovered