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

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

Author by Prof. Christiana Sowunmi

Journal/Publisher: Clinical Drug Investigation

Volume/Edition: 21

Language: English

Pages: 33 - 40

Abstract

Objectives

To evaluate the effects of standard parenteral doses of artemether given over 5 days and to compare these effects with those of a single loading dose of artemether followed by a single oral dose of mefloquine on Plasmodium falciparum in vivo and on ex vivo parasite viability, and to assess the relationships between P. falciparum viability ex vivo and the responses in vivo to these regimens in children with severe non-cerebral falciparum malaria.

Methods

19 children with severe non-cerebral malaria were randomised to receive therapeutic doses of intramuscular artemether or a single loading dose of intramuscular artemether followed by a single oral dose of mefloquine. Parasitaemia quantification and withdrawal of blood for in vitro culture of P. falciparum were performed before and at specific intervals after drug administration. Therapeutic indices of response were determined by conventional 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 indices.

Results

In vivo responses to both therapeutic regimens were similar. Ex vivo, functional reduction of parasite viability was significant by 8 or 12 hours after administration of both regimens, with no functionally viable parasites by 24 hours after administration. Indices of therapeutic response were significantly higher than those derived from the corresponding functional viability estimates ex vivo for each drug regimen, and were similar for both regimens.

Conclusion

A single loading dose of artemether rapidly reduces parasite viability ex vivo. A single loading dose of artemether followed by a single oral dose of mefloquine produced similar effects to those of a 5-day therapeutic regimen of artemether. The combination of artemether plus mefloquine may be used as an alternative to artemether alone in children with severe non-cerebral malaria, and may reduce the chances of development of parasite resistance to both drugs.


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