Evaluating malaria elimination strategies in military forces in Cambodia: a cluster-randomized clinical trial comparing monthly prophylaxis with focused screening and treatment

BackgroundIdentifying effective malaria elimination strategies for remote forested regions in Southeast Asia is challenging given limited resources. In this study, two malaria elimination strategies were evaluated in partnership with the Royal Cambodian Armed Forces - monthly malaria prophylaxis (MMP) and focused screening and treatment (FSAT). MethodsEight primarily military clusters (1,050 volunteers total) along the Cambodian-Thai border were randomized to 3 months of MMP or FSAT with monthly malaria testing by RDT, PCR, and microscopy for six months. Clusters were sub-randomized to permethrin treated (ITU) or sham water-treated clothing (sITU). Volunteers in MMP clusters were given three full monthly dihydroartemisinin-piperaquine (DP) treatment courses with 12 weekly 22.5mg primaquine. Volunteers in FSAT clusters were treated with appropriate first-line antimalarials if malaria-positive by microscopy or PCR. ResultsPf positivity in MMP clusters was reduced by 90% (10% at enrollment to 1% at 6 months; absolute risk reduction (ARR) 9%) at 6 months. However, 32% of Pf cases treated with DP as MMP at baseline recrudesced, requiring rescue treatment at 1 month with artesunate-mefloquine. Pf positivity in FSAT clusters declined 66% over 6 months (7.6% to 2.7%; ARR 4.9%). MMP reduced Pv positivity from 9% to 0% at 3 months, but Pv rebounded to 6.7% at 6 months. FSAT failed to significantly reduce Pv positivity during the study. The 22.5mg weekly primaquine MMP regimen was safe, even for the 15% of volunteers with G6PD-deficiency. Those wearing ITU had additional Pv parasitemia reductions compared to sITU in the FSAT but not MMP groups. PCR was more sensitive than microscopy and RDT for detecting both species. ConclusionsMMP was safe, and superior to FSAT to reduce Pf and Pv, suggesting greater utility to achieve malaria elimination in Cambodia. Low dose (22.5mg) weekly primaquine was a safe adjunct in this setting, even for those with G6PD-deficiency. Permethrin-treated clothing further reduced Pv parasitemia for FSAT but not MMP. MMP may be more easily scaled to eliminate malaria. The military may provide substantial support for regional elimination efforts.