Incidence of early nausea and neurological adverse events in pediatric patients with Plasmodium falciparum malaria treated with mefloquine may be reduced when dosages are split over successive days and co-administered with artesunate, according to study findings.
“The Drugs for Neglected Diseases initiative (DNDi), in partnership with the TDR (the Special Programme for Research and Training in Tropical Diseases) consortium, has collaborated with industry and academia for the development of two fixed dose [artesunate-based combination therapy (ACTs)],” Sodiomon B. Sirima, MD, PhD, head of Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso, and colleagues wrote. “This partnership formed the FACT (fixed-dose artesunate-based combination therapy) project consortium, which is a model needs-driven initiative aiming to increase availability and reliable supply of fixed-dose ACTs of required quality.”
Sirima and colleagues developed a randomized, non-inferiority phase 4 trial comparing artesunate-mefloquine and artemether-lumefantrine fixed-dose combinations in children aged 6 to 59 months infected with P. falciparum malaria in six treatment sites in Burkina Faso, Kenya and Tanzania. The trial included 945 children who were randomly assigned to receive 3 days’ treatment of either 25 mg artesunate and 55 mg mefloquine (n = 473) tablets once daily or 20 mg artemether and 120 mg lumefantrine (n = 472) twice daily.
The primary outcome of PCR-corrected rate of adequate clinical and parasitological response (ACPR) was evaluated at 63 days in the per-protocol population. The researchers assessed for early vomiting, parasitemia, fever and neurological and psychiatric adverse events.
Artesunate-mefloquine was associated with less neurological adverse events, less early vomiting and no detectable psychiatric adverse events. At 72 hours after treatment start, less than 6% of all participants experienced fever and none experienced parasitemia. The PCR-corrected ACPR rate at day 63 was 90.9% (370 participants) in the artesunate-mefloquine group and 89.7% (365 participants) in the artemether-lumefantrine group (treatment difference, 1.23%; 95% CI, –2.84 to 5.29). There were no other significant differences between the two groups.
“Our data are derived from a large trial, optimally designed for testing an ACT, such as artesunate-mefloquine, with a slowly cleared active component,” the researchers wrote. “We believe our results support the deployment of fixed-dose artesunate-mefloquine in young children in Africa. Our findings should have important implications for health policy in sub-Saharan Africa.” – by Kate Sherrer
Disclosure: Sirima reports no relevant financial disclosures. Please see the full study for a list of all researchers’ financial disclosures.