Malaria Risk for Transfusions and Possible Testing for Blood Donors in the U.S.

Malaria – a parasitic disease caused by Plasmodia (five species can infect humans) is a worldwide public health issue, causing 249 million cases and 608,000 deaths worldwide in 2022. The United States (U.S.) eradicated malaria in the 1950s and it is no longer endemic in the U.S. Most cases of malaria in the U.S. would be considered imported – either U.S. residents traveling to malarial risk areas who get bitten by mosquitoes or current U.S. residents who previously lived in malarial endemic countries and suffered from clinical or subclinical malaria (referred to as partial immunity) and continue to carry the parasite in their blood. While predominantly transmitted by mosquito bites, because the parasite resides in the human red cells it has the potential to be transmitted by transfusion. 

The Food and Drug Administration (FDA) recognizes malaria as a relevant transfusion transmitted infection (RTTI), and blood donors are required to be screened and are asked questions about a history of travel to malaria-endemic countries, as well as residence in countries outside the U.S. The questions are complicated to administer, and errors do happen either from the blood center staff missing something during questioning or donors forgetting to disclose relevant information.

In the last 21 years (2000 to 2021), 13 cases of transfusion-transmitted malaria have been reported in the U.S., a rate of 0.59 cases per year on average. Twelve of these were donated by individuals who previously resided in malarial-endemic countries (sub–Saharan Africa). The details could not be obtained in the one remaining case. In seven of these cases, the donors were screened appropriately and qualified as donors but were previously residents of malaria endemic countries. In four cases, the information was either not disclosed by donors or missed by staff, and in two cases, no determination could be made about where the error occurred. The FDA understands very well that the donor screening process is less than perfect and fails to defer donors with asymptomatic malaria. On the flip side, the current donor screening process defers 1-3% of donors for malaria risk and most of these travel-related deferrals do not have the same risk of transmitting malaria by transfusion. No transfusion-transmitted malaria in the last three decades has been caused by travelers visiting malarial risk areas.

In March 2024, the FDA licensed the first test for blood donor malaria testing. Currently, only one manufacturer has obtained licensure. It is a nucleic acid amplification test (NAT) performed on an individual donor whole blood sample. 

Most blood donor tests are performed on each donor at each donation. The FDA recognizes that performing malaria testing in this fashion will not add significantly to blood safety and selective testing would be better suited for this process. The Blood Product Advisory Committee (BPAC) is a committee that the FDA asks for advice before they publish an official guidance for the blood industry. The BPAC meeting was held on May 9, 2024, and the FDA asked for an opinion on performing selective testing in four situations: First, should donors with history of malaria be tested at each donation? Second, should donors who are previous residents of malaria-endemic countries be tested for each donation? Thirdly, should donors who have traveled to malaria risk areas in the last three months with no other residence history be tested for each donation? Lastly, though it is rare, should donors who are donating in an area with a locally acquired malaria outbreak in the U.S. (the last one was 10 cases in multiple states in 2023 and was short lived) be tested, even if there was one case, and continue universal testing for three months?

The FDA received comments from the blood center industry; BPAC also allows public members a short time to comment. The blood center industry had many reservations and made them known. Testing by this manufacturer requires blood to be drawn in a special test tube, the current deferral process works well, and testing should not be mandated by the FDA. Universal testing of donors when there is only one locally acquired case and continuing for three months is excessive, and mandating testing when only one manufacturer has a licensed test is not a good practice. In addition, false positive results leading to unnecessary one year deferral is a concern. These were the most common comments.

The Malaria Testing Guidance is on the “to be published this year” list for the FDA but what the FDA will decide after receiving advice from BPAC and industry experts is unknown.