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U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

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Issue Summary - FDA Workshop on Testing for Malarial Infections in Blood Donors

July 12, 2006

Issue Summary

Issue

FDA seeks public discussion of scientific developments that might support donor testing for malarial infections as part of pre-donation testing or as follow-up testing to permit a reduced deferral period for donors deferred for risk of malaria.

Background

Transfusion-transmitted malaria (TTM) is a public health concern in the USA and around the world. In the USA, all four species of human Plasmodium (Plasmodium falciparum, P. vivax, P. malariae, and P. ovale) have caused TTM. Currently, in the USA, no laboratory test is approved to screen donors for malarial infections. TTM is prevented by deferring donors with a history of malarial infection, or travel to or residence in malaria-endemic countries or regions. Each year, more than 28 million US residents visit parts of world where malaria is transmitted, affecting their eligibility to donate blood.

During the four decades before 2000, the rate of TTM remained stable at 0.25 cases per million units of blood collected [1]. However, in more recent years (1995-2005), the rate of TTM has declined to approximately 0.07 cases per million blood units collected. Nonetheless, incidents of TTM continue to occur; the most recent case of TTM was reported in 2005. Major factors responsible for the declining incidence of TTM are increased awareness among blood donors and screeners and careful implementation of existing deferral policies. While current donor deferral polices have been effective in reducing the incidence of TTM, this approach leads to a sizable loss of otherwise suitable donors. Approximately 150,000 donors are deferred each year due to a perceived risk of malaria exposure.

Donor deferral policies

USA: Under the current policy in the USA, individuals who have had malaria are deferred for three years after becoming asymptomatic. Travelers from non-endemic countries with no previous history of malaria are deferred for a one-year period after departing from an endemic area. Prior residents of malaria endemic countries are deferred for a three-year period after each departure from an endemic country [2].

Europe and Australia: Several European countries and Australia now test deferred at-malaria-risk donors; for donors without malarial antibodies the deferral period otherwise prescribed is shortened. The test in use detects antibodies to only 2 out of 4 human Plasmodium species, P. falciparum and P. vivax by enzyme-linked immunosorbent assay (EIA). According to donor deferral guidelines in the UK, individuals with a diagnosis of malaria or a history of prior residence in endemic countries are deferred indefinitely from blood donation; all other prospective donors are deferred for one year after each return from an endemic area [3]. However, following the introduction of malaria antibody test, at-risk donors having no antibodies detected by EIA at least six months after the last potential exposure or symptom of malaria are allowed to renter. In France, travelers are allowed to donate if found negative for malarial antibody at least four months after return from an endemic area.

Donor testing to improve blood safety from TTM

In principle, direct detection of malaria parasites in blood would be the most appropriate method to reduce the risk of TTM while minimizing the loss of otherwise suitable donors. Demonstrations of malaria parasites by microscopy in a blood film or by nucleic acid detection tests (NAT) are the most convincing methods to detect a current infection. Although these methods offer sufficient sensitivity to detect a single malaria parasite in a few microliters of blood, a challenge remains to detect the small number of malaria parasites that might be present in a unit of blood. It is documented that as few as 10 P. vivax parasites in blood can transmit virulent infection in humans [4]. However, when the level of parasitemia is low, a small test sample of blood taken from an infected unit may not be informative. Development of methods to concentrate malaria parasites from a large volume of blood for subsequent detection by a sensitive NAT may help to resolve this issue. Such technologies are under development but are not yet available and feasible in the donor screening setting.

Donor testing to reduce the deferral period

It is estimated that each year approximately 150, 000 blood donors are deferred due to a perceived risk of malaria exposure. A validated antibody detection test could identify donors who had experienced an acute infection or who carry low-grade parasitemia without clinical symptoms. Absence of detectable malarial antibodies in travelers and prior residents of endemic countries, tested after a prescribed window period had passed, would be a strong indicator that the prospective donor is free of infection with malaria parasites. Antibody-negative individuals could be allowed to donate blood after a shortened deferral period. The window period before reentry is based on ability of a test to detect the earliest appearance of antibodies after infection with malaria parasites. Hence, there is a need to develop sensitivity assays for the early detection of antibodies after exposure to malaria parasites.

Topics for Discussion at the Workshop: Based on the above mentioned issues, the scientific merits of the following topics will be discussed.

 

  1. Malaria in the USA and the main sources of malaria risk to the blood supply
  2. Risks and benefits of screening donors for malaria infections in lieu of risk-based deferrals
  3. Available and emerging technologies to test blood donors for malarial infections
  4. Potential effects of donor testing for malarial infections on the safety and availability of the blood supply under the following scenarios:

     

     

    1. Universal malaria antibody testing of all blood donors
    2. Testing for donors who are deferred based on a history of possible malaria exposure or had experienced clinical malaria in order to accelerate reentry.

 

References

  1. Mungai, M., Tegtmeier, G., Chamberland, M., Parise, M. Transfusion-transmitted malaria in the United States from 1963 through 1999. New England Journal of Medicine 2001; 344:1973-1978.
  2. FDA Memorandum. Recommendations for deferral of donors for malaria risk. July 26, 1994.
  3. Current UK donor selection guidelines: http://www.transfusionguidelines.org.uk/index.asp?Selected=M&Publication=WB&Section=1&topicid=2203.
  4. Boyd MF and Kitchen SF. An attempt to hyperimmunize convalescents from vivax malaria. American Journal of Tropical Medicine and Hygiene 1943; 23: 209.