Early variations in plasmodium falciparum dynamics in Nigerian children after treatment with two artemisinin-based combinations: implications on delayed parasite clearance

Malaria Journal

Research

Obaro S Michael¹  Titilope Okuboyejo¹  Akintunde Sowunmi¹  Grace O Gbotosho¹  Christian T Happi²  Onikepe A Folarin³  Ayoade MJ Oduola⁴ 

[1] Department of Pharmacology and Therapeutics, University of Ibadan, Ibadan, Nigeria;Department of Pharmacology and Therapeutics, University of Ibadan, Ibadan, Nigeria;Malaria Research Laboratories and Clinics, Institute of Advanced Medical Research and Training (IMRAT), College of medicine, University of Ibadan, Ibadan, Nigeria;Malaria Research Laboratories and Clinics, Institute of Advanced Medical Research and Training (IMRAT), College of medicine, University of Ibadan, Ibadan, Nigeria;Special Programme for Research and Training in Tropical Diseases (WHO/TDR), Geneva, Switzerland;

关键词: Malaria;    Artesunate;    Artemisinin Derivative;    Amodiaquine;    Asexual Parasite;   

DOI  :  10.1186/1475-2875-9-335

 received in 2010-09-16, accepted in 2010-11-22,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundCombination treatments, preferably containing an artemisinin derivative, are recommended to improve efficacy and prevent Plasmodium falciparum drug resistance. Artemether-lumefantrine (AL) and artesunate-amodiaquine (AA) are efficacious regimens that have been widely adopted in sub-Saharan Africa. However, most study designs ignore the effects of these regimens on peripheral parasitaemia in the first 24 hours of therapy. The study protocol was designed to evaluate more closely the early effects and the standard measures of efficacies of these two regimens.MethodsIn an open label, randomized controlled clinical trial, children aged 12 months to 132 months were randomized to receive AL (5-14 kg, one tablet; 15-24 kg, two tablets and 25-34 kg, three tablets twice daily) or artesunate (4 mg/kg daily) plus amodiaquine (10 mg/kg daily) for three days. Peripheral blood smears were made hourly in the first 4 hours, 8 h, 16 h, 24 h, and daily on days 2-7, and on days 7, 14, 21, 28, 35, and 42 for microscopic identification and quantification of Plasmodium falciparum.ResultsA total of 193 children were randomized to receive either AL (97) or AA (96). In children that received both medications, early response of peripheral parasitaemia showed that 42% of children who received AL and 36.7% of those who received AA had an immediate rise in peripheral parasitaemia (0-4 h after treatment) followed by a rapid fall. The rise in parasitaemia was significant and seems to suggest a mobilization of asexual parasites from the deep tissues to the periphery. Days 3, 7, 14, 28, and 42 cure rates in the per protocol (PP) population were > 90% in both groups of children. Both drug combinations were well tolerated with minimal side effects.ConclusionThe study showed the high efficacy of AL and AA in Nigerian children. In addition the study demonstrated the mobilisation of asexual parasites from the deep to the periphery in the early hours of commencing ACT treatment in a subset of patients in both study groups. It is unclear whether the early parasite dynamics discovered in this study play any role in the development of drug resistance and thus it is important to further evaluate this discovery. It may be useful for studies investigating delay in parasite clearance of artemisinin derivatives as a way of monitoring the development of resistance to artemisinin to assess the early effects of the drugs on the parasites.

【 授权许可】

Unknown   
© Michael et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.