Can malaria rapid diagnostic tests be used to detect simian malaria?

Background: The increasing recognition of zoonotic malaria, particularly from Plasmodium species infecting non-human primates (NHP), poses significant diagnostic challenges. Performance of human malaria Rapid Diagnostic Tests (RDTs) has not been evaluated in simian malaria.

Methods: A total of 131 blood samples from NHP hosts with confirmed malaria were analyzed using 14 different commercially available RDTs, detecting the antigens P. falciparum HRP2 (PfHRP2) and either Plasmodium Lactate-dehydrogenase (pLDH) or aldolase. Thirty samples from macaque monkeys without malaria served as controls. Subgroup analysis assessed RDT sensitivity in samples with parasite densities above the conventional cut-off of >200 parasites/μL. Quantitative PCR (qPCR) was used as reference standard.

Results: Observed Plasmodium species and geometric mean parasite genome equivalents in the blood samples from monkeys with malaria were P. cynomolgi (73.2 parasites/μL), P. inui (272.8 parasites/μL), and P. coatneyi (158.4 parasites/μL. Overall RDT sensitivity ranged from 34.2 to 94.3% across RDT brands and was higher in samples with parasite densities exceeding 200 parasites/μL, reaching >90% sensitivity for the detection of for P. cynomolgi, P. inui, or P. coatneyi in the best-performing RDT. False positive test results were not observed in the control samples from monkeys without malaria, but in those with malaria, a PfHRP2 positive test result was observed in 1% to 17% of the RDTs. Overall, the performance of pLDH-based tests was similar to aldolase-based tests. Observed test sensitivity was highest for the detection of P. inui infections.

Conclusions: The performance of RDTs in detecting simian malaria varies according to RDT brand, infecting Plasmodium species, and parasite density. Most RDT brands show good performance to detect simian Plasmodium species when parasite density exceeds 200 parasites/µL.