Marfin New modes 4th03

West Nile virus: New modes of transmission: 

West Nile virus: New modes of transmission Division of Vector-Borne Infectious Diseases Centers for Disease Control and Prevention Fort Collins, Colorado

Epidemic WNME, United States, 2002: 

Epidemic WNME, United States, 2002 Western hemisphere’s largest arboviral ME epidemic 2,741 WNME cases 1,267 WNF / unspecified 263 deaths 39 states & D.C. Largest WNME epidemic EVER Spread to Pacific coast New clinical syndromes Acute flaccid paralysis (“West Nile polio”) Five new transmission modes * As of 2/5/2003 4008 illnesses*

WN virus infections associated with:: 

WN virus infections associated with: Transplantation (TPX) Transfusion (TFX) Breastfeeding Transplacental transmission Occupational exposure

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VECTOR List-server

New modes of transmission: 

New modes of transmission Review previous flavi- and WN virus transmission in animals or humans Example of one transmission event Summary of reported cases Recommendations / comments Future surveillance recommendations

TPX-associated WN virus infection: 

TPX-associated WN virus infection

Previous reports flavivirus transmission: 

Previous reports flavivirus transmission Except for HCV and HGV, NO well-documented reports of flavivirus transmission via TPX Nov ‘94: Puerto Rico dengue outbreak – 6 yr old with probable transmission due to bone marrow TPX (Rigau et al AJTMH 2001)

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WN virus infection in organ donor and four organ recipients, August 2002 Organ donor Blood components 63 donors Crash victim 36 hours

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WN virus infection in organ donor and four organ recipients, August 2002 WNV PCR-neg WNV IgM-neg Organ Donor Blood components 63 donors Organ Donor 36 hours WNV PCR-pos WNV culture-pos WNV IgM-neg

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WN virus infection in organ donor and four organ recipients, August 2002 WNV PCR-neg WNV IgM-neg Organ Donor Blood components 63 donors Organ Donor 36 hours WNV PCR-pos WNV culture-pos WNV IgM-neg F/U: 1 seroconverting donor; Retrieved, stored plasma – WNV PCR-positive

TPX-associated WN virus infection: 

TPX-associated WN virus infection TPX-associated transmission confirmed High attack rate: 4/4 organ recipients ill 3/4 develop encephalitis Large viral load, immunosuppressive drugs Unusual clinical findings: Symptoms 7-17 days post-TPX Minimal CSF pleocytosis observed Organ donor’s infection from infectious blood unit

TPX-associated WN virus infection: 

TPX-associated WN virus infection Prevention? Exclude viremic organ donors Limited exclusion tools: Donor illness? Young infected persons often asymptomatic Serology? Antibodies develop after viremia NAAT blood prior to organ procurement? Virus in kidneys, lungs, spleen, and CNS without viremia At a minimum: Report persons who develop WN viral illness within 4 weeks of receiving organ/tissue Assist in retrieval of other potentially infectious tissues

TFX-associated WN virus infection: 

TFX-associated WN virus infection

Previous reports: 

Previous reports Except for HCV and HGV, NO well-documented reports of other flavivirus transmission via TFX

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TFX-associated WN viral infection Patients A (liver transplant) and B (post-partum) 9/2 9/5 Illness onset CSF IgM + 8/20 PATIENT A (39 donors) RBCs transfused 9/3 9/13 Illness onset PATIENT B (2 donors) 9/18 CSF IgM + Platelets transfused

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TFX-associated WN viral infection Patients A (liver transplant) and B (post-partum) 9/2 9/5 Illness onset CSF IgM + 8/20 8/15 10/7 8/17 Serum IgM + DONOR PATIENT A (39 donors) RBCs transfused 9/3 9/13 Illness onset PATIENT B (2 donors) 9/18 CSF IgM + DONOR Illness onset (fever, rash) Platelets transfused Donation

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TFX-associated WN viral infection Patients A (liver transplant) and B (post-partum) 9/2 9/5 Illness onset CSF IgM + 8/20 8/15 10/7 8/17 Serum IgM + DONOR PATIENT A (39 donors) RBCs transfused 9/3 9/13 Illness onset PATIENT B (2 donors) 9/18 CSF IgM + DONOR Illness onset (fever, rash) Platelets transfused Donation Stored tubing segment – PCR-positive (Lab 1) Retrieved plasma – PCR-equivocal (Lab 1) Retrieved plasma – PCR-positive (Lab 2)

TFX-associated WN virus infection: 

TFX-associated WN virus infection 60 investigations, Aug 2002 - Jan 2003 20 confirmed cases 14 infectious unit donors identified 21 on-going investigations 19 no transmission evidence > 2500 samples tested (NAAT & serology) Transmitted in RBCs, plasma, & platelets Virus isolated from one stored plasma unit 5 of 14 infectious donors asymptomatic 7 of 20 confirmed cases asymptomatic

TFX-associated WN virus infection: 

TFX-associated WN virus infection Reduce risk of TFX-associated transmission Defer unsuitable blood donors Report post-donation illnesses that suggest WN virus infection Withdraw & quarantine blood products from ill donors Diagnostics industry developing screening tests Testing strategies and deferral policies TBA Will need to investigate transfusion cases in 2003 to evaluate strategies and policies

Transplacental WN virus transmission: 

Transplacental WN virus transmission

Transplacental flavivirus transmission: 

Transplacental flavivirus transmission Human: Vertical dengue transmission Moderate to severe neonatal dengue Human: Rare neonatal infections in asymptomatic newborns of YEL vaccinees & YF-infected mothers Human: Japanese encephalitis virus Late 70s/early 80s – India 9 cases of infected mothers 4 spontaneous abortions, 4 “normal,” 1 ? Previous SLE outbreaks – no neonatal infections reported Anecdotal report of WN virus in equine aborted fetuses No previous reports of transplacental WN virus infection in humans

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Aug Sep Oct Nov 20 year-old pregnant woman Fever, h/a, blurred vision, leg weakness, hyporeflexia Leaves AMA

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Aug Sep Oct Nov 20 year-old pregnant woman Fever (39.3C) H/A Blurred vision Leg weakness Hyporeflexia Leaves AMA Re-admit; fall due to weakness TORCH- & HIV-negative Flavivirus IgM/IgG (IFA)

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Aug Sep Oct Nov 20 year-old pregnant woman Fever (39.3C) H/A Blurred vision Leg weakness Hyporeflexia Leaves AMA Re-admit; fall due to weakness TORCH- & HIV-negative Flavivirus IgM/IgG (IFA) CSF pleocytosis WNV IgM –CSF/serum Abnormal EMG

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Aug Sep Oct Nov 20 year old pregnant woman Fever (39.3C) H/A Blurred vision Leg weakness Hyporeflexia Leaves AMA Re-admit; fall due to weakness TORCH- & HIV-negative Flavivirus IgM/IgG (IFA) CSF pleocytosis WNV IgM –CSF/serum Abnormal EMG Delivery EGA: 38 weeks

Transplacental flavivirus transmission: 

Transplacental flavivirus transmission Late 2nd trimester infection Prolonged clinical illness (viremia?) in mother Child: Chorioretinitis; bilateral white matter loss in temporal/occipital; temporal lobe cyst Cord & heel-stick blood – WN virus IgM-positive CSF – WN virus IgM-positive TORCH, CMV, & LCMV antibody negative WN, entero-, & HS viruses all PCR negative Placenta/umbilical cord – WN virus PCR positive or equivocal in two labs

Transplacental flavivirus transmission: 

Transplacental flavivirus transmission 1st reported human transplacental transmission of WN virus Infection & structural CNS abnormalities – no proven causality Recommendations: Infection screening: No Illness testing: Yes Personal protection for pregnant woman: Yes Voluntary birth outcome registry

Neonatal outcome among four pregnant woman with WN viral illness: 

Neonatal outcome among four pregnant woman with WN viral illness Four more pending - 1 unborn; 3 born but illness and infection not yet defined Neonatal illness

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Web-based reporting Health care providers report on-line that they care for a pregnant woman with WN virus infection States informed when their providers report Provider contacted; informed of tissues needed for testing

Breastfeeding-associated WN virus infection: 

Breastfeeding-associated WN virus infection

Flavivirus transmission in milk: 

Flavivirus transmission in milk Animal-to-animal: Powassan virus (experimentally) Louping ill virus West Nile virus (experimentally; hamsters) Animal-to-human: Tick-borne encephalitis virus (raw sheep & goat milk/cheese) Primate-to-primate: Kyasanur Forest disease virus (langurs) Human-to-human: Hepatitis C virus

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TFX-associated WN virus infection Patients A (liver transplant) and B (post-partum) 9/2 9/5 Illness onset CSF IgM + 8/20 8/15 10/7 8/17 Serum IgM + DONOR PATIENT A (39 donors) RBCs transfused 9/3 9/13 Illness onset PATIENT B (2 donors) 9/18 CSF IgM + DONOR Illness onset (fever, rash) Platelets transfused Donation

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WN virus transmission in human milk Patients B (post-partum) and her child RBCs transfused 9/3 9/13 Illness onset PATIENT B (2 donors) 9/18 CSF IgM + Delivery 9/2 Breastfed child Heel-stick (baby): WNV IgM-negative Breast milk (mother): WNV PCR & IgM positive 9/18 Breast milk (mother): PCR-negative IgM-positive 9/27 Serum (baby): PCR-negative IgM-positive No evidence of illness in baby

Flavivirus transmission in milk: 

Flavivirus transmission in milk 1 of 2 youngest WN virus-infected persons ever; no illness No evidence for transplacental infection Mother not infected at delivery WNME 9 days after WN virus-infected unit Child breast-fed for first 17 days Low titer IgM Ab in human milk Passive transfer of Ab’s inefficient WN virus-specific IgM in infant independent production WN virus genetic material present transiently in milk Attempts to culture WN virus failed

Flavivirus transmission in milk: 

Flavivirus transmission in milk WN viral illnesses in children aged <1 year infrequently reported 1999-2001, no reports 2002, SIX persons < 1 year old with WN virus infection reported (excluded one transplacental infection) Ages: 0, 1, 3, 6, 9 & 11 mos. 1 asymptomatic (breast feeding-associated) 5 WNME cases 1 breastfed but mother without infection 4 not breast fed in month prior to illness

Occupationally-acquired WN virus infection: 

Occupationally-acquired WN virus infection

Occupationally-acquired infection: 

Occupationally-acquired infection Occupational transmission of WN and Kunjin viruses among lab workers reported prior to 1999 Percutaneous injury Aerosol In 2001, suspect case of lab-acquired WN virus infection reported in New York

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Dr. visit aaa WN viral transmission through percutaneous injury of laboratory worker A Illness onset (h/a, chills, sweats, lymphadenopathy) D4 Lab worker A Percutaneous injury – D0 D6 Rash onset a D7 Days relative to injury

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Dr. visit aaa WN viral transmission through percutaneous injury of laboratory worker A Illness onset (h/a, chills, sweats, lymphadenopathy) D4 Lab worker A Percutaneous injury – D0 Serum: WNV IgM- and PCR-negative D6 Rash onset a D7 Serum: WNV IgM-positive IgM P/N 10.3 D17 Days relative to injury Serum: WNV IgM-positive IgM P/N 10.3 WNV neut ab 1:160 D25

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Dr. visit aaa WN viral transmission through percutaneous injury of laboratory worker A Illness onset (h/a, chills, sweats, lymphadenopathy) D4 Lab worker A Percutaneous injury – D0 Serum: WNV IgM- and PCR-negative D6 Rash onset a D7 Serum: WNV IgM-positive IgM P/N 10.3 D17 Days relative to injury Serum: WNV IgM-positive IgM P/N 10.3 WNV neut ab 1:160 D25 Blue jay brain PCR-positive

Occupationally-acquired infection: 

Occupationally-acquired infection In 2002, 2 reported cases of occupationally acquired infection among lab workers Both percutaneous injury Performing necropsy for WN virus surveillance Making reagents Both WN fever Heterologous antibody to closely-related flaviviruses did not protect from illness (ameliorate illness?)

Occupationally-acquired infection: 

Occupationally-acquired infection Anecdotal reports of illness in bird handlers Many people working with samples containing live virus Goal of surveillance Estimate incidence of work-related infections Define specific activities that result in infection so that protective interventions can be engineered Study role of post-exposure treatment

Surveillance changes: 

Surveillance changes Abbreviate ArboNET data fields Add core data fields, questions to determine if following occurred in specified period before illness: Organ transplantation Blood transfusion Birth Breast feeding Work with known infectious material Add field to accommodate these data in local databases Add field to accommodate data in ArboNET software and web-based ArboNET Rewrite XML file format to accept data transfer from states with other systems

References: 

References Anonymous. Laboratory safety for arboviruses and certain other viruses of vertebrates: the Subcommittee on Arbovirus Laboratory Safety of the American Committee on Arthropod-Borne Viruses. Am J Trop Med Hyg 1980;291:359--81. Pike RM. Laboratory-associated infections: summary and analysis of 3,921 cases. Health Lab Sci 1976;13:105--14. Sewell DL. Laboratory-associated infections and biosafety. Clin Microbiol Rev 1995;8:389--405.