CBER Presentation
Enhancing US Blood Availability by Testing for Plasmodium spp. Infection
FDA Workshop on Testing for Malarial Infections in Blood Donors
July 12, 2006
David A. Leiby, PhD
Transmissible Diseases Department
American Red Cross
and
Department of Microbiology and Tropical Medicine
George Washington University
Malaria Deferrals: 2000-2005
| Deferral | n | %* | Lost Donations** |
|---|---|---|---|
| Type 1 | 25,303 | 0.1 | 42,797 |
| Type 2 | 241,503 | 0.96 | 412,520 |
| Type 3 | 494 | 0.002 | 834 |
| Totals | 267,300 | 1.07 | 456,151 |
* total donations = 25,036,751
** lost donations = n x donation rate (~ 1.7)
Donors Lost to Malaria Deferrals
Travelers' Health
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Outbreak Notice
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Released: June 16, 2006
"Malaria" Deferred Donor Study
- are deferred donors infected?
- type of deferral associated with infection?
- effectiveness of EIA assay?
- specificity/sensitivity
- usefulness of PCR/RT-PCR follow-up?
- interventions?
- testing alone
- testing of subset:
- at donation or months later
- permanent deferral for subset
- status quo
Study Approach
- serologic testing of donors by Newmarket EIA
- ~3,000 non-deferred donors from GC&P
- determine EIA background
- "malaria" deferred donors from GC&P and PJ
- supplemental testing of seropositives
- IFA by CDC
- PCR and RT-PCR
- ability to identify species
- risk factor questionnaire
- malaria deferred donors
- positive, non-deferred donors
Challenges
- obtaining sufficient numbers of deferred donors
- specific type of deferred donors
- EIA:
- biased towards only two species, albeit most important
- PCR/RT-PCR:
- parasitemia may have cleared
- sampling/concentration issues
- accuracy of questionnaire
EIA Testing of Non-Deferred Donors
n 3,229IR 21 (0.65%)
RR 11 (0.34%)
11 RR Donors
Supplemental Testing
| EIA Reactivity |
IFA + | PCR + | ||
| n | 1:64 | 1:16 | ||
| Negative | 10 | 1* | 2 | 0 |
| RR | 11 | 2 | 8 | 0 |
* positive for P. ovale
Implications
- significant number of donors with past malaria exposure
- not captured by travel history
- long term antibody titers
Plasmodium spp. Antibody Persistence
Implications
- significant number of donors with past malaria exposure
- not captured by travel history
- long term antibody titers
- semi-immune?
- relationship to transfusion-transmission
- infectious status unclear
- caveat: few transmission cases
Approaches for Enhancing Availability
- "had malaria"
- primary core of blood safety issue
- permanent deferral
- easy to manage
- done in many countries
- precedent with babesiosis
- test
- defer those with persistent titers for defined period
- accept those with baseline titers
- "residence"
- secondary core of blood safety issue
- relationship to "had malaria" group
- limited deferral
- difficult to manage
- questions have specificity/sensitivity issues
- test
- those with measurable titers entered in "had malaria" group
- accept those with baseline titers
- "travel"
- core of blood availability issue
- limited deferral
- questions have specificity/sensitivity issues
- "Princess and the Pea" phenomena
- test
- those with measurable titers entered in "had malaria" group
- accept those with baseline titers
Conclusions
- unique opportunity to address "malaria" issues
- realign the blood availability/safety dynamic
- foster additional research:
- immigration and donor demographic issues
- retention and re-entry of deferred donors
- rate of infectivity in "travel" deferred donors
- significance of long-term Ab titers
- declining rate of transfusion-transmission
- stimulate test development
Acknowledgments
- ARC Holland Laboratory
- Megan Nguyen
- Melanie Proctor
- Ed Notari
- ARC Greater Chesapeake & Potomac
- Joan Gibble
- Tami Goff
- et al.
- CDC
- Marianna Wilson