The Malaria Transfusion Risk (MATRix) Study

PROJECT SUMMARY
Globally, malaria (Plasmodium spp.) is the leading parasitic threat to humans and a major cause of morbidity
and mortality. Despite longstanding recognition that Plasmodium species are transfusion transmissible, the
burden and risk of transfusion-transmitted malaria (TTM) has not been well characterized and evidence-based
policy to safeguard against TTM has not been determined. The advent of novel, molecular assays for blood
donor screening could transform the existing approaches for TTM. We hypothesize that Blood donor screening
for malaria using highly sensitive molecular assays in Uganda and other endemic countries will prevent a
substantial proportion of transfusion-transmitted infections but will be cost-prohibitive and operationally
unfeasible given associated donor loss. In contrast, molecular screening of blood donors in the US, will be
cost-favorable when applied to those deferred for travel to endemic countries. To test this hypothesis, we will
conduct the Malaria Transfusion Risk (MATRix) study to Aim 1) Evaluate donor prevalence of parasitemia and
lab-based screening approaches to address TTM; Aim 2) Quantify the risk of TTM and identify demographic
factors for TTM in a highly endemic country; and Aim 3) Compare the cost-effectiveness of different strategies
to mitigate TTM to inform donor policies. The MATRix study will capitalize on a US Dept. of Defense-funded
clinical trial that is underway in Uganda to evaluate (a) the feasibility of implementation of pathogen reduction
technology (PRT) and (b) its impact on transfusion-transmitted infections following whole blood transfusions.
The trial will soon begin collecting blood samples and demographic information from 3,500 donors and 2,000
transfusion recipients; recipients will be evaluated before- and after (days 2, 7, 28) transfusion. To address the
MATRix study aims, we will use clinical data and archived samples from the PRT trial to (1a) compare
performance characteristics of nested PCR, transcription-mediated amplification, antigen testing, microscopy
and antibody testing, to detect Plasmodium spp. in Ugandan blood donors (n=3500) and (1b) describe the
prevalence of Plasmodium seroreactivity and parasitemia by demographic and donor status. (2) Lab testing
and clinical assessment of donor recipient pairs from the PRT trial control arm will enable quantification of
incidence and clinical severity of TTM in recipients of blood from donors in Aim 1 (n=1000). We describe the
risk of TTM by demographic, level of parasitemia and recipient clinical characteristics. Finally, a Markov-based
decision analytic model will be used to evaluate TTM mitigation strategies drawing on input data from Aims 1
and 2, previous publication and/or local expert opinion to (3a) assess the cost-effectiveness of donor screening
for TTM in Uganda by test modality and extent of implementation, while accounting for donor loss. It will also
(3b) compare the cost-effectiveness of donor testing vs. risk-based deferral in the US. This study would guide
global policy on TTM. It would also provide key insight into relative performance of the individual testing
modalities for malaria, while offering insight into transmission dynamics and infectivity of TTM.

Grant Number: 5K23HL151826-05
NIH Institute/Center: NIH
Principal Investigator: Evan Bloch