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Antimicrobial Agents and Chemotherapy, March 2006, p. 968-974, Vol. 50, No. 3
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.3.968-974.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Artesunate Suppositories versus Intramuscular Artemether for Treatment of Severe Malaria in Children in Papua New Guinea

Harin A. Karunajeewa,1 John Reeder,2 Kerry Lorry,2 Elizah Dabod,2,3,{dagger} Juliana Hamzah,1 Madhu Page-Sharp,1 Gregory M. Chiswell,4 Kenneth F. Ilett,1,4 and Timothy M. E. Davis1*

Medicine Unit Fremantle and Pharmacology Unit Nedlands, School of Medicine and Pharmacology, University of Western Australia, Crawley, Australia,1 Papua New Guinea Institute of Medical Research, Madang and Goroka, Papua New Guinea,2 Modilon General Hospital, Madang, Papua New Guinea,3 Clinical Pharmacology and Toxicology, PathWest Laboratory Medicine SCGH, Nedlands, Australia4

Received 30 August 2005/ Returned for modification 4 December 2005/ Accepted 23 December 2005

Drug treatment of severe malaria must be rapidly effective. Suppositories may be valuable for childhood malaria when circumstances prevent oral or parenteral therapy. We compared artesunate suppositories (n = 41; 8 to 16 mg/kg of body weight at 0 and 12 h and then daily) with intramuscular (i.m.) artemether (n = 38; 3.2 mg/kg at 0 h and then 1.6 mg/kg daily) in an open-label, randomized trial with children with severe Plasmodium falciparum malaria in Papua New Guinea (PNG). Parasite density and temperature were measured every 6 h for ≥72 h. Primary endpoints included times to 50% and 90% parasite clearance (PCT50 and PCT90) and the time to per os status. In a subset of 29 patients, plasma levels of artemether, artesunate, and their common active metabolite dihydroartemisinin were measured during the first 12 h. One suppository-treated patient with multiple complications died within 2 h of admission, but the remaining 78 recovered uneventfully. Compared to the artemether-treated children, those receiving artesunate suppositories had a significantly earlier mean PCT50 (9.1 versus 13.8 h; P = 0.008) and PCT90 (15.6 versus 20.4 h; P = 0.011). Mean time to per os status was similar for each group. Plasma concentrations of primary drug plus active metabolite were significantly higher in the artesunate suppository group at 2 h postdose. The earlier initial fall in parasitemia with artesunate is clinically advantageous and mirrors higher initial plasma concentrations of active drug/metabolite. In severely ill children with malaria in PNG, artesunate suppositories were at least as effective as i.m. artemether and may, therefore, be useful in settings where parenteral therapy cannot be given.

* Corresponding author. Mailing address: School of Medicine and Pharmacology, Fremantle Hospital, P.O. Box 480, Fremantle 6959, Western Australia, Australia. Phone: (618) 9431 3229. Fax: (618) 9431 2977. E-mail: tdavis{at}cyllene.uwa.edu.au.

{dagger} Present address: Mugil Health Centre, Mugil, Madang Province, Madang, Papua New Guinea.

Antimicrobial Agents and Chemotherapy, March 2006, p. 968-974, Vol. 50, No. 3
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.3.968-974.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Day, N., Dondorp, A. M. (2007). The Management of Patients with Severe Malaria. Am J Trop Med Hyg 77: 29-35 [Abstract] [Full Text]  
  • Karunajeewa, H. A., Manning, L., Mueller, I., Ilett, K. F., Davis, T. M. E. (2007). Rectal Administration of Artemisinin Derivatives for the Treatment of Malaria. JAMA 297: 2381-2390 [Abstract] [Full Text]  
  • HINTON, R. L., AUWUN, A., PONGUA, G., OA, O., DAVIS, T. M. E., KARUNAJEEWA, H. A., REEDER, J. C. (2007). CAREGIVERS' ACCEPTANCE OF USING ARTESUNATE SUPPOSITORIES FOR TREATING CHILDHOOD MALARIA IN PAPUA NEW GUINEA. Am J Trop Med Hyg 76: 634-640 [Abstract] [Full Text]  


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