Research in context
malaria, sickle cell anaemia
MALARIA, MALARIA, SICKLE CELL ANAEMIA, FALCIPARUM MALARIA

We searched PubMed for articles in English published from database inception until June 30, 2022, using the terms antimalarial AND prophylaxis AND malaria, filtering the search for Clinical Trials, Meta-Analyses, Randomized Controlled Trial, and Humans, and screening for clinical trials and systematic reviews. The search resulted in 104 articles. Of these, 19 described systematic reviews and meta-analyses. Of the remaining 85 describing clinical trials, five were controlled human challenge models; 52 presented intermittent preventive treatment in infants, children, or pregnant women; four assessed seasonal malaria chemoprophylaxis; and 17 investigated the malaria-prophylactic effects of co-trimoxazole or antiretrovirals in people with HIV (n=13), travellers (n=2), or people with sickle cell anaemia (n=2). Of the remaining seven studies, one in Kenyan school children found proguanil to be effective in preventing falciparum malaria. Five trials assessed chemoprophylaxis efficacy in Asian adults, including two placebo-controlled trials of monthly, single-dose naphthoquine–azithromycin in a low-risk setting on the China–Myanmar border that showed more than 90% efficacy in preventing malaria, with a good safety profile and tolerability and follow-up periods of 1 month and 2 months. In Thailand, a trial in men with occupational risk of malaria who received monthly or bimonthly 3-day treatment courses of dihydroartemisinin–piperaquine or placebo found 98% protective efficacy and good tolerability but required close supervision with weekly follow-up. This trial was done during a period of relatively high parasite prevalence. A trial of chloroquine chemoprophylaxis in pregnancy in Thailand found it to be completely effective in preventing 
This study reports the efficacy of antimalarial chemotherapy in a low-transmission setting deliberately designed to be feasible for scale-up for routine use as an elimination intervention. Unlike previous chemoprophylaxis trials, it used low-intensity, monthly follow-up and peer supervision of dosing between follow-up visits as many of the target population spent long periods away from the village. It is the first trial to target forest goers, only recruiting those at highest risk of malaria to maximise efficiency of the intervention. Choice of antimalarials was limited to the relatively short-acting regimen of weekly artemether–lumefantrine; previous trials have used drugs with less frequent dosing and longer half-lives, which might affect adherence. PCR was used to detect parasites, as it has higher sensitivity than microscopy. Despite the low-intensity monitoring, the chemoprophylaxis had high efficacy in preventing malaria, and adherence to the study drug was high. This study provides much-needed evidence for the efficacy, tolerability, and pragmatic implementation of antimalarial chemoprophylaxis in high-risk mobile populations in real-world settings.
This study adds to existing evidence for the efficacy and tolerability of antimalarial chemoprophylaxis in groups at high risk of malaria in low-endemic settings. It demonstrates that chemoprophylaxis is effective to prevent malaria in forest goers and can be safely managed with relatively low-intensity monthly follow-up through close engagement with, and involvement of, the local community. Malaria chemoprophylaxis among high-risk groups such as forest goers could be a valuable additional tool for malaria elimination in the Greater Mekong subregion.