Efficacy of artesunate-amodiaquine for treating uncomplicated falciparum malaria in sub-Saharan Africa: a multi-centre analysis.

Hdl Handle:
http://hdl.handle.net/10144/98754
Title:
Efficacy of artesunate-amodiaquine for treating uncomplicated falciparum malaria in sub-Saharan Africa: a multi-centre analysis.
Authors:
Zwang, Julien; Olliaro, Piero; Barennes, Hubert; Bonnet, Maryline; Brasseur, Philippe; Bukirwa, Hasifa; Cohuet, Sandra; D'Alessandro, Umberto; Djimdé, Abdulaye; Karema, Corine; Guthmann, Jean-Paul; Hamour, Sally; Ndiaye, Jean-Louis; Mårtensson, Andreas; Rwagacondo, Claude; Sagara, Issaka; Same-Ekobo, Albert; Sirima, Sodiomon B; van den Broek, Ingrid; Yeka, Adoke; Taylor, Walter R J; Dorsey, Grant; Randrianarivelojosia, Milijaona
Journal:
Malaria Journal
Abstract:
BACKGROUND: Artesunate and amodiaquine (AS&AQ) is at present the world's second most widely used artemisinin-based combination therapy (ACT). It was necessary to evaluate the efficacy of ACT, recently adopted by the World Health Organization (WHO) and deployed over 80 countries, in order to make an evidence-based drug policy. METHODS: An individual patient data (IPD) analysis was conducted on efficacy outcomes in 26 clinical studies in sub-Saharan Africa using the WHO protocol with similar primary and secondary endpoints. RESULTS: A total of 11,700 patients (75% under 5 years old), from 33 different sites in 16 countries were followed for 28 days. Loss to follow-up was 4.9% (575/11,700). AS&AQ was given to 5,897 patients. Of these, 82% (4,826/5,897) were included in randomized comparative trials with polymerase chain reaction (PCR) genotyping results and compared to 5,413 patients (half receiving an ACT). AS&AQ and other ACT comparators resulted in rapid clearance of fever and parasitaemia, superior to non-ACT. Using survival analysis on a modified intent-to-treat population, the Day 28 PCR-adjusted efficacy of AS&AQ was greater than 90% (the WHO cut-off) in 11/16 countries. In randomized comparative trials (n = 22), the crude efficacy of AS&AQ was 75.9% (95% CI 74.6-77.1) and the PCR-adjusted efficacy was 93.9% (95% CI 93.2-94.5). The risk (weighted by site) of failure PCR-adjusted of AS&AQ was significantly inferior to non-ACT, superior to dihydroartemisinin-piperaquine (DP, in one Ugandan site), and not different from AS+SP or AL (artemether-lumefantrine). The risk of gametocyte appearance and the carriage rate of AS&AQ was only greater in one Ugandan site compared to AL and DP, and lower compared to non-ACT (p = 0.001, for all comparisons). Anaemia recovery was not different than comparator groups, except in one site in Rwanda where the patients in the DP group had a slower recovery. CONCLUSION: AS&AQ compares well to other treatments and meets the WHO efficacy criteria for use against falciparum malaria in many, but not all, the sub-Saharan African countries where it was studied. Efficacy varies between and within countries. An IPD analysis can inform general and local treatment policies. Ongoing monitoring evaluation is required.
Affiliation:
Shoklo Malaria Research Unit, Mae Sot, Thailand. jul@shoklo-unit.com
Issue Date:
Nov-2009
URI:
http://hdl.handle.net/10144/98754
DOI:
10.1186/1475-2875-8-203
PubMed ID:
19698172
Language:
en
ISSN:
1475-2875
Appears in Collections:
Other Diseases

Full metadata record

DC FieldValue Language
dc.contributor.authorZwang, Julienen
dc.contributor.authorOlliaro, Pieroen
dc.contributor.authorBarennes, Huberten
dc.contributor.authorBonnet, Marylineen
dc.contributor.authorBrasseur, Philippeen
dc.contributor.authorBukirwa, Hasifaen
dc.contributor.authorCohuet, Sandraen
dc.contributor.authorD'Alessandro, Umbertoen
dc.contributor.authorDjimdé, Abdulayeen
dc.contributor.authorKarema, Corineen
dc.contributor.authorGuthmann, Jean-Paulen
dc.contributor.authorHamour, Sallyen
dc.contributor.authorNdiaye, Jean-Louisen
dc.contributor.authorMårtensson, Andreasen
dc.contributor.authorRwagacondo, Claudeen
dc.contributor.authorSagara, Issakaen
dc.contributor.authorSame-Ekobo, Alberten
dc.contributor.authorSirima, Sodiomon Ben
dc.contributor.authorvan den Broek, Ingriden
dc.contributor.authorYeka, Adokeen
dc.contributor.authorTaylor, Walter R Jen
dc.contributor.authorDorsey, Granten
dc.contributor.authorRandrianarivelojosia, Milijaonaen
dc.date.accessioned2010-05-13T22:21:23Z-
dc.date.available2010-05-13T22:21:23Z-
dc.date.issued2009-11-
dc.identifier.citationEfficacy of artesunate-amodiaquine for treating uncomplicated falciparum malaria in sub-Saharan Africa: a multi-centre analysis. 2009, 8:203 Malar. J.en
dc.identifier.issn1475-2875-
dc.identifier.pmid19698172-
dc.identifier.doi10.1186/1475-2875-8-203-
dc.identifier.urihttp://hdl.handle.net/10144/98754-
dc.description.abstractBACKGROUND: Artesunate and amodiaquine (AS&AQ) is at present the world's second most widely used artemisinin-based combination therapy (ACT). It was necessary to evaluate the efficacy of ACT, recently adopted by the World Health Organization (WHO) and deployed over 80 countries, in order to make an evidence-based drug policy. METHODS: An individual patient data (IPD) analysis was conducted on efficacy outcomes in 26 clinical studies in sub-Saharan Africa using the WHO protocol with similar primary and secondary endpoints. RESULTS: A total of 11,700 patients (75% under 5 years old), from 33 different sites in 16 countries were followed for 28 days. Loss to follow-up was 4.9% (575/11,700). AS&AQ was given to 5,897 patients. Of these, 82% (4,826/5,897) were included in randomized comparative trials with polymerase chain reaction (PCR) genotyping results and compared to 5,413 patients (half receiving an ACT). AS&AQ and other ACT comparators resulted in rapid clearance of fever and parasitaemia, superior to non-ACT. Using survival analysis on a modified intent-to-treat population, the Day 28 PCR-adjusted efficacy of AS&AQ was greater than 90% (the WHO cut-off) in 11/16 countries. In randomized comparative trials (n = 22), the crude efficacy of AS&AQ was 75.9% (95% CI 74.6-77.1) and the PCR-adjusted efficacy was 93.9% (95% CI 93.2-94.5). The risk (weighted by site) of failure PCR-adjusted of AS&AQ was significantly inferior to non-ACT, superior to dihydroartemisinin-piperaquine (DP, in one Ugandan site), and not different from AS+SP or AL (artemether-lumefantrine). The risk of gametocyte appearance and the carriage rate of AS&AQ was only greater in one Ugandan site compared to AL and DP, and lower compared to non-ACT (p = 0.001, for all comparisons). Anaemia recovery was not different than comparator groups, except in one site in Rwanda where the patients in the DP group had a slower recovery. CONCLUSION: AS&AQ compares well to other treatments and meets the WHO efficacy criteria for use against falciparum malaria in many, but not all, the sub-Saharan African countries where it was studied. Efficacy varies between and within countries. An IPD analysis can inform general and local treatment policies. Ongoing monitoring evaluation is required.en
dc.language.isoenen
dc.rightsPublished by BioMed Central, [url]http://www.malariajournal.com/[/url] Archived on this site by Open Access permissionen
dc.subject.meshAdolescenten
dc.subject.meshAdulten
dc.subject.meshAfrica South of the Saharaen
dc.subject.meshAgeden
dc.subject.meshAged, 80 and overen
dc.subject.meshAmodiaquineen
dc.subject.meshAnimalsen
dc.subject.meshAntimalarialsen
dc.subject.meshArtemisininsen
dc.subject.meshChilden
dc.subject.meshChild, Preschoolen
dc.subject.meshDrug Combinationsen
dc.subject.meshFemaleen
dc.subject.meshHumansen
dc.subject.meshInfanten
dc.subject.meshMalaria, Falciparumen
dc.subject.meshMaleen
dc.subject.meshMiddle Ageden
dc.subject.meshPlasmodium falciparumen
dc.subject.meshTreatment Outcomeen
dc.subject.meshYoung Adulten
dc.titleEfficacy of artesunate-amodiaquine for treating uncomplicated falciparum malaria in sub-Saharan Africa: a multi-centre analysis.en
dc.contributor.departmentShoklo Malaria Research Unit, Mae Sot, Thailand. jul@shoklo-unit.comen
dc.identifier.journalMalaria Journalen

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