Research article

Rectal artemisinins for malaria: a review of efficacy and safety from individual patient data in clinical studies

Melba Gomes¹ , Isabela Ribeiro^1,7 , Marian Warsame^2,3,6 , Harin Karunajeewa⁴ and Max Petzold^2,5

¹UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases, World Health Organization, 20 Avenue Appia, Geneva 27, Switzerland

²Division of International Health (IHCAR), Karolinska Institutet, Stockholm, Sweden

³Rectal Artesunate Study Team, National Institute for Medical Research (NIMR), Dar es Salaam, Tanzania

⁴University of Western Australia, Crawley, Western Australia and Papua New Guinea Institute of Medical Research, Goroka EHP 441, Papua New Guinea

⁵Nordic School of Public Health, Göteborg, Sweden

⁶Global Malaria Programme, World Health Organization, 20 Avenue Appia, Geneva 27, Switzerland

⁷Drugs for Neglected Diseases – DNDi, Regional Office – Latin America, Rua Santa Luzia 651/11° andar, 20030-041 – Rio de Janeiro, Brasil

author email corresponding author email

BMC Infectious Diseases 2008, 8:39doi:10.1186/1471-2334-8-39

Published:	28 March 2008

Abstract

Background

Rectal administration of artemisinin derivatives has potential for early treatment for severe malaria in remote settings where injectable antimalarial therapy may not be feasible. Preparations available include artesunate, artemisinin, artemether and dihydroartemisinin. However each may have different pharmacokinetic properties and more information is needed to determine optimal dose and comparative efficacy with each another and with conventional parenteral treatments for severe malaria.

Methods

Individual patient data from 1167 patients in 15 clinical trials of rectal artemisinin derivative therapy (artesunate, artemisinin and artemether) were pooled in order to compare the rapidity of clearance of Plasmodium falciparum parasitaemia and the incidence of reported adverse events with each treatment. Data from patients who received comparator treatment (parenteral artemisinin derivative or quinine) were also included. Primary endpoints included percentage reductions in parasitaemia at 12 and 24 hours. A parasite reduction of >90% at 24 hours was defined as parasitological success.

Results

Artemisinin and artesunate treatment cleared parasites more rapidly than parenteral quinine during the first 24 hours of treatment. A single higher dose of rectal artesunate treatment was five times more likely to achieve >90% parasite reductions at 24 hours than were multiple lower doses of rectal artesunate, or a single lower dose administration of rectal artemether.

Conclusion

Artemisinin and artesunate suppositories rapidly eliminate parasites and appear to be safe. There are less data on artemether and dihydroartemisinin suppositories. The more rapid parasite clearance of single high-dose regimens suggests that achieving immediate high drug concentrations may be the optimal strategy.