Malaria recrudescence after artemether-lumefantrine treatment in travellers- a hospital-based observational study and literature review

IntroductionArtemether-lumefantrine (AL) is an effective drug combination that is used to treat uncomplicated falciparum malaria worldwide including travellers. Although this treatment is regarded as highly effective, recrudescence of falciparum malaria may occur in the weeks after treatment with AL. The occurrence of recrudescence and its potential (risk) factors in travellers remain poorly investigated.MethodsThis retrospective cohort study included falciparum malaria cases treated with AL at a tertiary referral hospital in the Netherlands, between January 1, 2010, and July 1, 2024. The primary outcome was the proportion of recrudescence cases among falciparum malaria cases who completed treatment with AL. Recrudescence was defined as a negative microscopy result for Plasmodium falciparum at least once after AL treatment, followed by a subsequent positive result without intercurrent travel to malaria-endemic areas. Secondary outcomes included the proportion of recrudescence cases that experienced secondary treatment failures (recrudescence after retreatment with AL or other malaria therapies) and factors associated with recrudescence. In addition to our cohort study, we performed a literature review on studies reporting on falciparum recrudescence cases after AL treatment among travellers.ResultsOf 391 falciparum malaria cases identified, 270 were treated with AL and thus included in this study. Among these, eight (3%; 95% confidence interval [CI]: 1-6%) recrudescence cases were identified. Diarrhoea was a risk factor for recrudescence in our cohort (unadjusted OR 4.9 95%; CI: 1.14-21.06). In the literature, 19 studies reported on 61 recrudescence cases amongst a total of 1,770 malaria cases (3%). No secondary treatment failures occurred in recrudescence cases treated with AL from our cohort or the literature (0/19), whereas secondary treatment with atovaquone-proguanil failed in 2/28 (7%) of cases.InterpretationRecrudescence after AL treatment is rare among travellers, and was associated with diarrhoea, which might cause malabsorption. When recrudescence occurs, retreatment with AL is effective.