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Measurement of adherence, drug concentrations and the effectiveness of artemether-lumefantrine, chlorproguanil-dapsone or sulphadoxine-pyrimethamine in the treatment of uncomplicated malaria in Malawi

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Bell, David J., Wootton, D., Mukaka, Mavuto, Montgomery, Jacqui, Kayange, N., Chimpeni, P., Hughes, D. A., Molyneux, Malcolm E, Ward, Stephen ORCID: https://orcid.org/0000-0003-2331-3192, Winstanley, P. A. and Lalloo, David ORCID: https://orcid.org/0000-0001-7680-2200 (2009) 'Measurement of adherence, drug concentrations and the effectiveness of artemether-lumefantrine, chlorproguanil-dapsone or sulphadoxine-pyrimethamine in the treatment of uncomplicated malaria in Malawi'. Malaria Journal, Vol 8, p. 11.

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Abstract

Background: Sulphadoxine-pyrimethamine (SP) is the only single dose therapy for uncomplicated malaria, but there is widespread resistance. At the time of this study, artemether-lumefantrine (AL) and chlorproguanil-dapsone (CPD), both multi-dose regimes, were considered possible alternatives to SP in Malawi. The aim of this study was to investigate the impact of poor adherence on the effectiveness of AL and CPD. Methods: Children >= 12 months and adults with uncomplicated malaria were randomized to receive AL, CPD or SP. Adherence was measured using a questionnaire and electronic monitoring devices, MEMS (TM), pill bottles that recorded the date and time of opening. Day-7 plasma dapsone or lumefantrine concentrations were measured to examine their relationship with adherence and clinical response. Results: 841 patients were recruited. The day-28 adequate clinical and parasitological response (ACPR) rates, using intention to treat analysis (missing data treated as failure), were AL 85.2%, CPD 63.7% and SP 50%. ACPR rates for AL were higher than CPD or SP on days 28 and 42 (p <= 0.002 for all comparisons). CPD was more effective than SP on day-28 (p = 0.01), but not day-42. Very high adherence was reported using the questionnaire, 100% for AL treated patients and 99.2% for the CPD group. Only three CPD participants admitted missing any doses. 164/181 (90.6%) of CPD treated patients took all their doses out of the MEMS T container and they were more likely to have a day-28 ACPR than those who did not take all their medication out of the container, p = 0.024. Only 7/87 (8%) AL treated patients did not take all of their doses out of their MEMS (TM) container and none had treatment failure. Median day-7 dapsone concentrations were higher in CPD treated patients with ACPR than in treatment failures, p = 0.012. There were no differences in day-7 dapsone or lumefantrine concentrations between those who took all their doses from the MEMS (TM) container and those who did not. A day-7 lumefantrine concentration reported to be predictive of AL treatment failure in Thailand was not useful in this population; only one of 16 participants with a concentration below this threshold (175 ng/ml) had treatment failure. Conclusion: This study provides reassurance of the effectiveness of AL, even with unsupervised dosing, as it is rolled out across sub-Saharan Africa. Self-reported adherence appears to be an unreliable measure of adherence in this population.

Item Type: Article
Additional Information: The electronic version of this article is the complete one and can be found online at: http://www.malariajournal.com/content/8/1/204. BIOMED CENTRAL LTD
Uncontrolled Keywords: PLASMODIUM-FALCIPARUM MALARIA RANDOMIZED-TRIAL ARTESUNATE EFFICACY THERAPY UGANDA
Subjects: WB Practice of Medicine > Therapeutics > WB 340 Drug Administration
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
QV Pharmacology > QV 38 Drug action.
Faculty: Department: Groups (2002 - 2012) > Clinical Group
Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI): https://doi.org/10.1186/1475-2875-8-204
Depositing User: Users 43 not found.
Date Deposited: 20 Apr 2010 09:28
Last Modified: 06 Feb 2018 12:59
URI: http://archive.lstmed.ac.uk/id/eprint/231

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