Comparison of artemether and artemether plus mefloquine in children with malaria and effects on viability of Plasmodium falciparum ex vivo

Objectives: To evaluate the effects of standard parenteral doses of artemet her given over 5 days and to compare these effects with those of a single l oading dose of artemether followed by a single oral dose of mefloquine on P lasmodium falciparum in vivo and on ex vivo parasite viability, and to asse ss the relationships between P. falciparum viability ex vivo and the respon ses in vivo to these regimens in children with severe non-cerebral falcipar um malaria. Methods: 19 children with severe non-cerebral malaria were randomised to re ceive therapeutic doses of intramuscular artemether or a single loading dos e of intramuscular artemether followed by a single oral dose of mefloquine. Parasitaemia quantification and withdrawal of blood for in vitro culture o f P. falciparum were performed before and at specific intervals after drug administration. Therapeutic indices of response were determined by conventi onal methods, i.e time to 50 or 90% reduction of parasitaemia and parasite clearance time. The corresponding viability estimates ex vivo were derived for each treatment regimen and compared with conventional therapeutic indic es. Results: In vivo responses to both therapeutic regimens were similar. Ex vi vo, functional reduction of parasite viability was significant by 8 or 12 h ours after administration of both regimens, with no functionally viable par asites by 24 hours after administration. Indices of therapeutic response we re significantly higher than those derived from the corresponding functiona l viability estimates ex vivo for each drug regimen, and were similar for b oth regimens. Conclusion: A single loading dose of artemether rapidly reduces parasite vi ability ex vivo. A single loading dose of artemether followed by a single o ral dose of mefloquine produced similar effects to those of a 5-day therape utic regimen of artemether. The combination of artemether plus mefloquine m ay be used as an alternative to artemether alone in children with severe no n-cerebral malaria, and may reduce the chances of development of parasite r esistance to both drugs.