Threats to Blood Safety Posed by Emerging Protozoan Pathogens

1
Chagas Disease From Research to Implementation
David A. Leiby, Ph.D.
Transmissible Diseases Department American Red
Cross and Department of Microbiology and Tropical
Medicine George Washington University
2
Trypanosoma cruzi

• small flagellated parasite
• endemic to the Americas, but primarily Latin
  America
• infections generally asymptomatic and life-long
  with few treatment options
• transmission
• vectorial
• congenital
• organ transplant
• blood transfusion

3
T. cruzi Life-Cycle
CDC
4
Vectorial/Natural Transmission

• triatomine bugs
• reduviids, kissing bugs, vinchucas
• parasites passed in feces
• enter through bite wound or mucosal surface

CDC
5
Congenital Transmission
Leiby et al., Transfusion 199939 310-315
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Chagas Disease After Organ Transplantation

• 2001 initial U.S. case
• single cadaveric donor
• 3 recipients
• kidney/pancreas, kidney liver
• all culture positive
• one death due to acute Chagasic myocarditis
• 2006 two recent cases in LA
• cardiac transplants

Zayas et al., MMWR 200251 210-212 Mascola et
al., MMWR 200655 798-800
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U.S./Canadian Transfusion Cases
1987 California - Mexican donor 1989 New
York City - Bolivian donor Manitoba -
Paraguayan donor 1993 Houston - unknown
donor 1999 Miami - Chilean donor 2000 Manito
ba - German/Paraguayan donor 2002 Rhode Island
Bolivian donor
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Immigration and Demographics
9
Los Angeles Seroprevalence Studies
Total no. donations 1,104,030 Yes to risk
question 78,736 (7.1) Number
tested 77,967 EIA repeat reactive
329 Confirmed by RIPA
147 (0.2) Seropositivity rate 1
in 7,500
Leiby et al., Transfusion 200242 549-555
10
Los Angeles Seroprevalence 1996-98
Leiby et al., Transfusion 200242 549-555
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Changing Donor Demographics Enhanced Minority
Recruitment Efforts Greater Number of At-Risk
Donors More Seropositive Donors Greater Risk of
Transfusion-Transmission
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Nationwide Risk in U.S.
15.0 million donations/year 9.4 million
donors 234,735 at-risk donors 375 seropositive
donors 600 seropositive donations/year 702
potentially infectious components/year
(1/1.6)
(2.5)
(1/625)
(1.6)
(1.17)
15
ARC IND Prevalence Study 8/28/06-1/28/07

• All sites SoCal Arizona NoCal
• Donors 189,828 127,053 26,601 36,174
• Tested 148,969 95,662 23,981 29,326
• RR 63 (12365) 50 (11913)
  4 (15995) 9 (13258)
• Confirmed 32 (14655) 25 (13827)
  2 (111,990) 5 (15865)
• Refusals 40,859 31,391 2620 6848
  (21.5) (24.7)
  (9.8) (18.9)
• 40,859 refusals/detection rate of 14655 9
  undetected donors!

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T. cruzi Reactive Donors by State of Residence
(01/29/07 04/10/07)
1
4
1
2
2
7
5
3
9
5
3
2
7
2
5
1
12
4
1
5
4
2
3
3
6
2
34
1
1
11
3
1
3
8
1
1
PR
8
4
5
2
2
3
54
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Test Performance

• Clinical trial (8/28/06-1/28/07)
• PPV 32 pos/63 RR51 pos in 2 states
• RR rate 63/148,969 0.042
• Prevalence 32/148,969 14655
• Specificity 148,906 test neg/148,90631 false
  pos99.979
• Nationwide screening (1/29/07-3/20/07)
• PPV 27 confd pos/125 RR tested 21.6 pos
  in 10 states
• 18 of 27 confd pos from 2 states (S CA, FL)
• RR rate 185 (152 ARC 33 BSI/1,112,644
  donations 0.016
• Projected prevalence based on 21.6 PPV128,000
• Specificity (ARC) first week 124,934 test
  neg/124,93428 false pos99.978 (6 pos)

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Other Testing Results/Procedures

• IND study
• Follow up of 26 donors 13 of 32 confirmed pos
• 1/13 PCR positive 0 to date hemoculture positive
• Sample handling??
• IVD testing pending
• Special Protocol for PCR and hemoculture
• Increase sensitivity by having regions initiate
  processes
• Pooling EDTA whole blood samples in
  guanidine/EDTA solnPCR (lyses cells and
  stabilizes kinetoplasts containing mutliple
  copies of DNA) store at 2-8C
• Pooling heparinized whole blood samples,
  centrifuge/removal of plasma (Ab) mix buffy coat
  and red cells with LIT media store at 2-8C
• 6 regions with confd pos (including S FL) agree
  to date

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Cumulative Parasitemia Testing
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Lookback Results

• 31 confirmed positive donors during IND
• 16 repeat donors (allogeneic/directed)
• 137 prior donations 148 components
• Of 148 components
• 6 whole blood (destroyed)
• 3 platelets (2 destroyed, 1 transfused)
• 69 red cells (7 destroyed, 32 transfused, 30
  pending)
• 70 plasma (11 destroyed, 2 transfused, 56 frac, 1
  pending)
• Of 1, 32 and 2 transfused components
• 1 platelet recipient deceased 11 days post
  transfusion
• 32 red cell recipients 11 living, 14 deceased,
  7 unknown
• 10 recipients tested (transfused 7-36 days) all
  ELISA/RIPA neg
• 2 plasma recipients deceased

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Summary

• Chagas testing implemented across ARC system
• acceptable test performance to date
• coverage by other blood agencies varies
• confirmed positives widely distributed
• data supports nationwide testing
• follow-up studies initiated
• April 26 BPAC Meeting
• review of issues related to implementation
• alternative testing approaches?
• eventual testing mandate?