Prospective Clinical Trial Assessing Species-Specific Efficacy of Artemether-Lumefantrine for the Treatment of Plasmodium malariae, Plasmodium ovale, and Mixed Plasmodium Malaria in Gabon

Abstract

Treatment recommendations for <i>Plasmodium malariae</i> and <i>Plasmodium ovale</i> malaria are largely based on anecdotal evidence. The aim of this prospective study, conducted in Gabon, was to systematically assess the efficacy and safety of artemether-lumefantrine for the treatment of patients with uncomplicated <i>P. malariae</i> or <i>P. ovale</i> species monoinfections or mixed <i>Plasmodium</i> infections. Patients with microscopically confirmed <i>P. malariae</i>, <i>P. ovale</i>, or mixed-species malaria with at least one of these two <i>Plasmodium</i> species were treated with an oral, fixed-dose combination of artemether-lumefantrine for 3 consecutive days. The primary endpoints were per-protocol PCR-corrected adequate clinical and parasitological response (ACPR) on days 28 and 42. Tolerability and safety were recorded throughout the follow-up period. Seventy-two participants (42 male and 30 female) were enrolled; 62.5% of them had PCR-corrected mixed <i>Plasmodium</i> infections. Per protocol, PCR-corrected ACPR rates were 96.6% (95% confidence interval [CI], 91.9 to 100) on day 28 and 94.2% (95% CI, 87.7 to 100) on day 42. Considering <i>Plasmodium</i> species independently from their coinfecting species, day 42 ACPR rates were 95.5% (95% CI, 89.0 to 100) for <i>P. falciparum</i>, 100% (exact CI, 84.6 to 100) for <i>P. malariae</i>, 100% (exact CI, 76.8 to 100) for <i>P. ovale curtisi</i>, and 90.9% (95% CI, 70.7 to 100) for <i>P. ovale wallikeri</i> Study drug-related adverse events were generally mild or moderate. In conclusion, this clinical trial demonstrated satisfying antimalarial activity of artemether-lumefantrine against <i>P. ovale</i><i>wallikeri</i>, <i>P. ovale curtisi</i>, <i>P. malariae</i>, and mixed <i>Plasmodium</i> infections, with per-protocol efficacies of 90% to 100% and without evident tolerability or safety concerns. (This trial was registered in the clinical study database ClinicalTrials.gov under the identifier NCT02528279.).