Large-scale Artemisinin–Piperaquine Mass Drug Administration With or Without Primaquine Dramatically Reduces Malaria in a Highly Endemic Region of Africa

Background: Mass drug administration (MDA), with or without low-dose primaquine (PMQLD), is being considered for malaria elimination programs. The potential of PMQLD to block malaria transmission by mosquitoes must be balanced against liabilities of its use. Methods: Artemisinin-piperaquine (AP), with or without PMQLD, was administered in 3 monthly rounds across Anjouan Island, Union of Comoros. Plasmodium falciparum malaria rates, mortality, parasitemias, adverse events, and PfK13 Kelch-propeller gene polymorphisms were evaluated. Results: Coverage of 85 to 93% of the Anjouan population was achieved with AP plus PMQLD (AP+PMQLD) in 2 districts (population 97164) and with AP alone in 5 districts (224471). Between the months of April-September in both 2012 and 2013, average monthly malaria hospital rates per 100000 people fell from 310.8 to 2.06 in the AP+PMQLD population (ratio 2.06/310.8 = 0.66%; 95% CI: 0.02%, 3.62%; P = .00007) and from 412.1 to 2.60 in the AP population (ratio 0.63%; 95% CI: 0.11%, 1.93%; P < .00001). Effectiveness of AP+PMQLD was 0.9908 (95% CI: 0.9053, 0.9991), while effectiveness of AP alone was 0.9913 (95% CI: 0.9657, 0.9978). Both regimens were well tolerated, without severe adverse events. Analysis of 52 malaria samples after MDA showed no evidence for selection of PfK13 Kelch-propeller mutations. Conclusions: Steep reductions of malaria cases were achieved by 3 monthly rounds of either AP+PMQLD or AP alone, suggesting potential for highly successful MDA without PMQLD in epidemiological settings such as those on Anjouan. A major challenge is to sustain and expand the public health benefits of malaria reductions by MDA.