Black Bugs Blood: West Nile Virus

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Black Bugs BloodWest Nile Virus the Blood
Supply

• Infectious Transfusion Risks, Screening Blood
  donations for WNV and other icky things
• Jed Gorlin, Memorial Blood Centers Duluth TAM
  11/04

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Risks of Transmission

• Infectious Risks
• Viral
• Bacterial
• Protozoa
• Ricketsia
• Other
• ?Prion

• Non-infectious risks
• Transfusion Reaction
• Metabolic
• Cardiac Overload
• Dilutional Coagulopathy
• TAGVHD
• Alloimmunization

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Transfusion Safety

• Product Safety
• Donor Recruitment
• Donor history screening
• Donor Testing
• Manufacturing cGMP

• Transfusion Safety
• Patient blood sample
• Med indication for Tx.
• Special Tx needs
• Select right unit
• Issue to floor
• administration
• monitoring evaluation of reaction

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Paling Risk Scale for Major Transfusion Hazards
101
102
103
104
100
105
106
107
108
HIV
General anesthesia
HCV
HBV
Bacteria
Mis-Transfusion
TRALI
TA-GVHD
Cardiac
Metabolic risk in neonates
Under transfusion
Sunny Dzik, MD
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Window period risk

• Why is there any residual risk? There is
  potential for transfusion transmission, if donors
  is drawn after acquiring the disease but before
  they make an antibody response.
• Time from infectivity to test reactivity
• Chance of transmission is a function of both
  incidence and length of window period.

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NAT screening (HCV/HIV/HBV)

• Two major testing platforms for HIV/HCV
• Roche-Pools of 24, separate tests for HCV, HIV.
  Advantage automated detection, disadvantage,
  very manual sample prep
• Chiron-Gen Probe (TMA) Multiplex test
• Pools of 16, automated sample prep, manual
  detection. Requires extra round to resolve
  positive samples. More false positives

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MBC Experience

• After testing almost 2,000,000 samples, MBC has
  detected 1 HIV NAT window period case and 5 HCV
  NAT/EIA negative samples.
• Almost 1,000,000 samples were tested for both HCV
  and HIV before a single NAT/EIA - sample was
  found.

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U.S. NAT Program Yields
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What Has NAT Testing Cost the US??

• Assume 13 million blood donations annually
• Assume an average cost/donation of 16
• Cost of HCV/HIV- NAT
  
• 208,000,000/yr or 104M each

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Cost/HCV-NAT positive donation

• Average HCV-NAT pos. rate in US 1276,000
  donations
• 13 million donations/yr collected
• 47 window case donations expected _at_ 104,000,000
  total
• Cost/HCV-NAT positive donation detected
  gt2,200,000/donation

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Cost/HIV-NAT positive donation

• Average HIV-NAT pos. rate in US 13,760,000
  donations
• 13 million donations/yr collected
• 3.5 window case donations expected _at_
  104,000,000 total
• Cost/HIV-NAT positive donation detected gt
  28,000,000/donation

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Cost-Effectiveness Comparisons
Cost-effectiveness


(/YLE)
8,000,000
6,000,000
Transfusion Safety Interventions
4,000,000
2,000,000
600,000
400,000
200,000
Commonly Accepted Medical Practices
ALT Testing
p24 Ag Testing


RhIg/HDN

CABG (one vessel)

HTN

Annual Mammo- gram
Cardiac Trans- plantation
PAD-


SD FP
HCV Look- back

Anti-HBc Testing for HIV
MP NAT HIVHCV



MPgtSD NAT
Prophy-

CABG

Therapy
laxis
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Other Transfusable Parasitic

• Chagas
• Trypanosoma cruzi Endemic Central So. America
• Infected reduviid (kissing) bug falls from
  thatched roof, defecates and inoculates skin
• May be under-recognized cause of heart failure
• Only 7 cases Tx transmission in US/Canada
• Screened for in Brazil and other LA countries
• ARC proposes to implement screening
• MBC to participate in Chagas trial 1/05

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West Nile Virus Background and Ecology
West Nile Virus Background and Ecology

• First isolated in West Nile district, Uganda,
  1937
• Commonly found in humans and birds and other
  vertebrates in Africa, Eastern Europe, West Asia,
  and the Middle East, but has not previously been
  documented in the Western Hemisphere
• Basic transmission cycle involves mosquitoes
  feeding on birds infected with the West Nile
  virus
• Infected mosquitoes then transmit West Nile virus
  to humans and animals when taking a blood meal

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The Japanese Encephalitis Serocomplexof the
Family Flaviviridae
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1999 - 2002 Verified WNV Surveillance Results
Reported to ArboNet
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Date of Symptom Onset, West Nile VirusUnited
States, 1999-2001
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Clinical Epidemiology

• Incubation period 3 - 14 days
• 80 of infections are asymptomatic
• 20 develop West Nile fever
• 1 in 150 develop meningoencephalitis
• Advanced age primary risk factor for severe
  neurological disease and death

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Outcome of West Nile Virus Infection among
Hospitalized Patients

• At discharge (NY and NJ, 2000)
• More than half did not return to functional level
• Only one-third fully ambulatory
• At one year (NYC 1999 patients)
• Fatigue 67, memory loss 50, difficulty walking
  49, muscle weakness 44, depression 38

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Summer 2003

• Implemented WNV NAT screening 7/1/03
• Automated DNA extraction
• Pool size 6-dedicated pooling machines
• TaqMan platform requires lots of room. Total NAT
  laboratory space doubled
• MBC detected 36 WNV blood donors, mostly in
  Nebraska, South Dakota and Iowa

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More Automated System
COBAS TaqMan (96/48)
Hamilton Pipettor
COBAS AmpliPrep
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(No Transcript)
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WNV Human cases and deaths
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WNV rate weekly (6/30-9/30)
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2004 map as of 10/26/04
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2004 counties 10/26/04
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WNV blood donors - 10/26/04
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2004 WNV Transfusion transmission in Arizona

• MMWR Sept 17, 2004 p 842
• In 2003 blood centers interdicted 800 blood
  components via pooled testing. Because of 6 cases
  of transfusion transmission, a policy for single
  donor (SD) testing was implemented for 2004.
• 3 days before switch to SD in Arizona (from TMA
  pool of 16), a 43 yo with severe diabetes was
  transfused following a knee amputation. He
  subsequently developed WNV and died. The units
  were traced and one donor was shown to be WNV by
  SD but not pooled testing.

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Implications

• Despite reduced pool size and plans to implement
  single donor testing, window period cases of WNV
  continue to occur.
• There have been two HIV transmissions despite
  pooled NAT testing
• Both manufacturers are working to create more
  automated systems that facilitate single donor
  testing. These will be more expensive, but will
  allow greater throughput than current manual tests