Extending malaria prevention to older children cut infection sharply in Burkina Faso trial

Seasonal malaria chemoprevention has, since WHO first recommended it, been aimed at the youngest children — those under five who bear the heaviest burden of severe disease. A cluster-randomised trial published in The Lancet Infectious Diseases on July 29 tested two ways of doing more: supervising each dose, and widening the age net to older children [s1].

The stakes are set by a rising global tally. WHO's malaria fact sheet records an estimated 282 million cases and 610,000 deaths across 80 countries in 2024, with the WHO African Region carrying about 95% of cases (265 million) and 95% of deaths (579,000) [s2]. Children under five years of age remain among those at highest risk of severe disease and death, which is why chemoprevention has been aimed at them first [s2].

The trial's design

The study ran in Saponé, Burkina Faso, and randomised clusters of three compounds to one of three groups: programmatic chemoprevention in children younger than five; the same, but delivered by directly observed treatment in the under-fives (DOTu5); and directly observed treatment extended to children younger than 10 (DOTu10) [s1]. The trial covered 61 programmatic clusters and 62 in each of the two supervised-delivery groups [s1]. Every targeted child received four cycles of sulfadoxine- pyrimethamine plus amodiaquine [s1].

Between July 13 and August 29, 2023, the trial enrolled 3,467 participants of all ages, including 980 who were targeted by chemoprevention — 236 in the programmatic group, 231 in DOTu5, and 513 in DOTu10 [s1]. The primary endpoint was Plasmodium falciparum parasite prevalence at the end of the transmission season in the age groups targeted by chemoprevention, compared between groups [s1].

Supervision alone changed little; extending the age range changed a lot

The first comparison — whether watching a child swallow each dose beat routine programmatic delivery — came out flat. Among children younger than five, parasite prevalence at season's end was 24.9% (52 of 209) in the programmatic group and 19.7% (40 of 203) in the DOTu5 group, a difference that did not reach significance (rate ratio 0.84, 95% CI 0.55–1.30; p=0.4419) [s1].

The second comparison was decisive. Among children aged five to nine, parasite prevalence was 28.1% (63 of 224) in the DOTu10 group, which treated them, against 47.1% (98 of 208) in the DOTu5 group, which did not — a rate ratio of 0.56 (95% CI 0.43–0.74; p<0.0001) [s1]. Extending chemoprevention to older children cut their parasite carriage by close to half.

Clinical disease followed the same pattern. In children younger than five, the incidence of clinical malaria was lower in the DOTu5 group than in the programmatic group (protective efficacy 0.57, 95% CI 0.29–0.74; p=0.0009) [s1]. In children aged five to nine, clinical incidence was lower in the DOTu10 group than in the DOTu5 group (protective efficacy 0.72, 95% CI 0.54–0.83; p<0.001) [s1].

Adherence, measured in the blood

The trial did not rely on a caregiver's word that a course had been completed. It scored adherence from drug plasma concentrations after the fourth cycle, and the gap between the adherent and the non-adherent was stark: clinical incidence after the fourth cycle was far lower in children scored as adherent than in those scored as non-adherent (incidence rate ratio 0.21, 95% CI 0.09–0.51; p=0.0006) [s1].

That finding sits in tension with the flat result on supervised delivery. Directly observed treatment did not, on its own, beat programmatic delivery in the under-fives — yet biologically confirmed adherence was strongly protective. The implication is that observing a single dose is not the same as securing a completed, absorbed course, and that the programmatic approach was already achieving reasonable adherence in the youngest children.

What it means, and what it costs

The authors' read is measured. The findings support extending the chemoprevention age range to older children, but they flag that the logistical and financial barriers to doing so need to be examined [s1]. Older children are more numerous and were, in this trial, the group where the extra doses delivered the clearest benefit — DOTu10 alone accounted for 513 of the 980 targeted participants [s1].

There is a background reason to weigh the benefit against the cost carefully. Sulfadoxine-pyrimethamine plus amodiaquine is the backbone of seasonal chemoprevention, and every additional child-course is also additional drug pressure in a region where WHO is tracking antimalarial resistance. The trial does not adjudicate that trade-off; it establishes that, on efficacy alone, the older children have the most to gain.

The trial was registered as NCT05878366 and funded by the Gates Foundation [s1].

This article is informational and is not medical advice.