Malaria transmission after artemether-lumefantrine and dihydroartemisinin-piperaquine: a randomized trial

Patrick Sawa, Seif A. Shekalaghe, Chris J. Drakeley, Colin J. Sutherland, Collins K. Mweresa, Amrish Y. Baidjoe, Alphaxard Manjurano, Reginald A. Kavishe, Khalid B. Beshir, Rahma U. Yussuf, Sabah A. Omar, Cornelus C. Hermsen, Lucy Okell, Henk D.F.H. Schallig, Robert W. Sauerwein, Rachel L. Hallett and Teun Bousema
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Background. Artemisinin-combination therapy (ACT) reduces malaria transmission potential compared to non-ACT treatment; it is unclear whether this effect differs between ACTs.

Methods. 298 children (6 m-10y) with uncomplicated falciparum malaria were randomized to artemether-lumefantrine (AL, n=153) or dihydroartemisinin-piperaquine (DP, n=145) in Mbita, western Kenya. Gametocyte carriage was determined by molecular methods at days 0, 1, 2, 3, 7, 14, 28 and 42. Infectiousness to mosquitoes was determined by mosquito feeding assays on day 7.

Results. The cumulative risk of recurrent parasitemia on day 42 after initiation of treatment, unadjusted by PCR, was 20.7% (95% CI 14.4-28.2) for AL compared to 3.7% (95% CI 1.2 -8.5) for DP, P<.001. The mean duration of gametocyte carriage was 5.5 days (95% confidence interval 3.6-8.5) for AL and 15.3 days (95% CI 9.7-24.2) for DP (P=.001). The proportion of mosquitoes that became infected after feeding on blood from AL treated children was 1.88% (43/2293) compared to 3.50% (83/2371) for DP (P = .06); oocyst burden was lower after AL (P=.005).

Conclusions. While DP is associated with a longer prophylactic time after treatment, gametocyte carriage and malaria transmission to mosquitoes are lower after AL.