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– Viral

– Bacterial

– Protozoa

– Ricketsia

– Other• ?Prion

• Non-infectious risks– Transfusion Reaction

– Metabolic

– Cardiac Overload

– Dilutional Coagulopathy

– TAGVHD

– Alloimmunization

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

101102103104 100105106107108

HIV

HCVHBV

Mis-Transfusion

TRALI

TA-GVHD

Under transfusion

Cardiac

Paling Risk Scale for Major Transfusion Hazards

Metabolic risk in neonates

Bacteria

General anesthesia

Sunny Dzik, MD

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 # HCVRate

# HIVRate

UBS

ABC-Roche

AIBC

ARC

US Total

16

23

2

29

70

1:294,926

1:239,630

1:236,937

1:331,828

1:275,830

2

1

0

1

4

1:2,359,409

1:2,581,512

0:473,874

1:9,623,012

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

200,000

Cost-effectiveness ($/YLE)

600,000

400,000

2,000,000

4,000,000

6,000,000

8,000,000

ALTTesting

p24 AgTesting

Anti-HBcTestingfor HIV

MP NATHIV+HCV

SD FPHCVLook-back

RhIg/HDN Prophy-

laxis

CABG(one

vessel)

HTN

Therapy

AnnualMammo-

gram

CardiacTrans-

plantation

Transfusion Safety Interventions

Commonly Accepted Medical Practices

PAD- CABG

MP=>SDNAT

Cost-Effectiveness Comparisons

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

• 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

West Nile Virus: Background and Ecology

The Japanese Encephalitis Serocomplexof the Family Flaviviridae

1999 - 2002 Verified WNV Surveillance Results Reported to ArboNet

731919733266/927 + DC2001

44 + DC

11 + DC

4

States

11,450

63

25

Horses

593814,7903949/262 2002

515430521/22000

16?62/61999

MosquitoPools

BirdsHumans/Fatalities

Year

Date of Symptom Onset, West Nile VirusUnited States, 1999-2001

0

5

10

15

20

25

30

7/7

8/4

9/1

9/29

10/2

711

/24

12/2

3

Week ending

Nu

mb

er

of

ca

se

s

2001

2000

1999

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

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

• 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

COBAS AmpliPrep

COBAS TaqMan (96/48)

Hamilton Pipettor

WNV Human cases and deaths

State Cases Deaths Colorado 2647 61 Nebraska 1942 29 South Dakota 1039 14 Texas 717 37 North Dakota 617 5 Wyoming 375 9 Pennsylvania 237 8 Total 9862 264

+ WNV rate weekly (6/30-9/30)WNV Incidence

0.000%

0.100%

0.200%

0.300%

0.400%

0.500%

0.600%

0.700%

0.800%

1 2 3 4 5 6 7 8 9 10 11 12 13

Week

% P

osi

tive CBBLAN

MBC

Siouxland

SFSV+Avera

1 / 500

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