Transcript Black Bugs Blood: West Nile Virus & the Blood Supply

Black Bugs Blood:
West 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
Risks of Transmission
• Infectious Risks
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Viral
Bacterial
Protozoa
Ricketsia
Other
• ?Prion
• Non-infectious risks
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Transfusion Reaction
Metabolic
Cardiac Overload
Dilutional Coagulopathy
TAGVHD
Alloimmunization
Transfusion Safety
• Product Safety
– Donor Recruitment
– Donor history
screening
– Donor Testing
– Manufacturing cGMP
• Transfusion Safety
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Patient blood sample
Med indication for Tx.
Special Tx needs
Select right unit
Issue to floor
administration
monitoring &
evaluation of reaction
108
Paling
Risk 6Scale for
Major4 Transfusion
Hazards
7
5
3
10
10
10
10
10
102 101
HIV
HCV
100
General anesthesia
HBV
Bacteria
Mis-Transfusion
TRALI
TA-GVHD
Cardiac
Metabolic risk in neonates
Sunny Dzik, MD
Under transfusion
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.
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
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.
U.S. NAT Program Yields
Program
#
HCV
Rate
#
HIV
Rate
UBS
16
1:294,926
2
1:2,359,409
ABC-Roche
23
1:239,630
1
1:2,581,512
AIBC
2
1:236,937
0
0:473,874
ARC
29
1:331,828
1
1:9,623,012
US Total
70
1:275,830 4
1:3,759,451
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
Cost/HCV-NAT positive
donation:
• Average HCV-NAT pos. rate in US =
1:276,000 donations
• 13 million donations/yr collected
• 47 window case donations expected @
$104,000,000 total
• Cost/HCV-NAT positive donation detected
= $>2,200,000/donation
Cost/HIV-NAT positive donation:
• Average HIV-NAT pos. rate in US =
1:3,760,000 donations
• 13 million donations/yr collected
• 3.5 window case donations expected @
$104,000,000 total
• Cost/HIV-NAT positive donation detected =
> $28,000,000/donation
Cost-Effectiveness Comparisons
Cost-effectiveness
($/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
RhIg/HDN HTN
Annual Cardiac
CABG
Prophy- Therapy Mammo- Trans(one
gram
plantation
vessel)
laxis
HCV
Lookback
PADCABG
ALT
Anti-HBc MP NAT p24 Ag MP=>SD
Testing
Testing
Testing HIV+HCV
NAT
for HIV
SD FP
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
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
The Japanese Encephalitis Serocomplex
of the Family Flaviviridae
1999 - 2002 Verified WNV Surveillance
Results Reported to ArboNet
Year
States
Humans/
Fatalities
Birds
Mosquito
Pools
Horses
1999
4
62/6
?
16
25
2000
11 + DC
21/2
4305
515
63
2001
27 + DC
66/9
7332
919
731
2002
44 + DC
3949/262
14,790
5938
11,450
Date of Symptom Onset, West Nile Virus
United States, 1999-2001
Number of cases
30
2001
2000
1999
25
20
15
10
5
0
Week ending
Clinical Epidemiology
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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
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%
Summer 2003
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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
More Automated System
Hamilton Pipettor
COBAS TaqMan (96/48)
COBAS AmpliPrep
WNV Human cases and deaths
State
Colorado
Nebraska
South Dakota
Texas
North Dakota
Wyoming
Pennsylvania
Total
Cases
2647
1942
1039
717
617
375
237
9862
Deaths
61
29
14
37
5
9
8
264
+ WNV rate weekly (6/30-9/30)
WNV Incidence
0.800%
0.700%
0.600%
% Positive
0.500%
CBBLAN
MBC
0.400%
Siouxland
SFSV+Avera
0.300%
0.200%
1 / 500
0.100%
0.000%
1
2
3
4
5
6
7
Week
8
9
10
11
12
13
2004 map as of 10/26/04
2004 counties 10/26/04
WNV+ blood donors - 10/26/04
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.
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