Abstract
1 min readAbstract Background Seasonal malaria chemoprevention (SMC) using monthly sulfadoxine-pyrimethamine-amodiaquine (SPAQ) is being deployed in East Africa, where antimalarial drug-resistance levels are high. Dihydroartemisinin-piperaquine (DP) is a potential alternative. Methods A prospective 28-day pharmacometric assessment of SMC was conducted in Karamoja, northern Uganda. In 2 villages children received SPAQ and in a third were randomized to DP versus no SMC. The primary outcome was malaria infection defined by capillary blood sample quantitative PCR (qPCR) positivity on day 28, or presentation with fever and slide or rapid test positivity after day 2. Results Baseline qPCR malaria parasitemia prevalence among 1250 enrolled children was 46% (575/1250); Plasmodium falciparum 85%, other malarias (mainly Plasmodium ovale) 25%. Breakthrough parasitemias occurred in 7% (33/496) of DP, 31% (158/504) of SPAQ, and 39% (98/250) of no drug recipients. Clinical malaria (all P falciparum) developed in 17% of no drug (42/250; 1 severe), 8% of SPAQ (38/504; 2 severe), and 2% of DP (13/496) recipients. Adjusted protective efficacies against all malaria parasitemia, P falciparum parasitemia, and clinical malaria for SPAQ were 56% (95% CI, 35%–70%), 46% (11%–68%), and 60% (27%–78%) and for DP were 84% (77%–89%), 86% (75%–92%), and 86% (74%–92%), respectively. Some asymptomatic P falciparum infections were not cleared by SPAQ. All 260 P falciparum isolates genotyped were PfCRT K76 (haplotype CVMNK, marker of 4-aminoquinoline susceptibility); most were quintuple Pfdhfr/dhps mutants (ie, relatively sulfadoxine-pyrimethamine resistant). The chemoprevention drug exposure–response relationship was strong for desethylamodiaquine, but weak for sulfadoxine. Conclusions SPAQ SMC had low clinical and parasitological chemopreventive efficacy in northern Uganda, whereas DP was effective. Clinical Trials Registration NCT05323721.
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