In vivoefficacy of artemether-lumefantrine against uncomplicated Plasmodium falciparummalaria in Central Ethiopia

Hwang Jimee, Alemayehu, Hoos David, Melaku Zenebe, Tekleyohannes, Teshi Takele, Birhanu, Demeke Leykun, Gobena Kedir, Kassa Moges, Jima Daddi, Reithinger Richard, Nettey Henry, Green Michael, Malone, Kachur, Filler Scott

Description

In vivo efficacy assessments of the first-line treatments for Plasmodium falciparum malaria are essential for ensuring effective case management. In Ethiopia, artemether-lumefantrine (AL) has been the first-line treatment for uncomplicated P. falciparum malaria since 2004. Methods Between October and November 2009, we conducted a 42-day, single arm, open label study of AL for P. falciparum in individuals >6 months of age at two sites in Oromia State, Ethiopia. Eligible patients who had documented P. falciparum mono-infection were enrolled and followed according to the standard 2009 World Health Organization in vivo drug efficacy monitoring protocol. The primary and secondary endpoints were PCR uncorrected and corrected cure rates, as measured by adequate clinical and parasitological response on days 28 and 42, respectively. Results Of 4426 patients tested, 120 with confirmed falciparum malaria were enrolled and treated with AL. Follow-up was completed for 112 patients at day 28 and 104 patients at day 42. There was one late parasitological failure, which was classified as undetermined after genotyping. Uncorrected cure rates at both day 28 and 42 for the per protocol analysis were 99.1% (95% CI 95.1-100.0); corrected cure rates at both day 28 and 42 were 100.0%. Uncorrected cure rates at day 28 and 42 for the intention to treat analysis were 93.3% (95% CI 87.2-97.1) and 86.6% (95% CI 79.1-92.1), respectively, while the corrected cure rates at day 28 and 42 were 94.1% (95% CI 88.2-97.6) and 87.3% (95% CI 79.9-92.7), respectively. Using survival analysis, the unadjusted cure rate was 99.1% and 100.0% adjusted by genotyping for day 28 and 42, respectively. Eight P. falciparum patients (6.7%) presented with Plasmodium vivax infection during follow-up and were excluded from the per protocol analysis. Only one patient had persistent parasitaemia at day 3. No serious adverse events were reported, with cough and nausea/vomiting being the most common adverse events. Conclusions AL remains a highly effective and well-tolerated treatment for uncomplicated falciparum malaria in the study setting after several years of universal access to AL. A high rate of parasitaemia with P. vivax possibly from relapse or new infection was observed. Trial Registration NCT01052584

Informations

• Publié par: biomed
• Publié le: 01 janvier 2011
• Nombre de lectures: 16
• Langue: English

Extrait

Hwanget al.Malaria Journal2011,10:209 http://www.malariajournal.com/content/10/1/209

R E S E A R C HOpen Access In vivoefficacy of artemetherlumefantrine against uncomplicatedPlasmodium falciparum malaria in Central Ethiopia 1,2*†3†3 34 3 Jimee Hwang, Bereket H Alemayehu, David Hoos , Zenebe Melaku , Samuel G Tekleyohannes , Takele Teshi 3 35 67 8 , Sintayehu G Birhanu , Leykun Demeke , Kedir Gobena , Moges Kassa , Daddi Jima , Richard Reithinger , 1 19 110 Henry Nettey , Michael Green , Joseph L Malone , S Patrick Kachurand Scott Filler

Abstract Background:In vivoefficacy assessments of the firstline treatments forPlasmodium falciparummalaria are essential for ensuring effective case management. In Ethiopia, artemetherlumefantrine (AL) has been the firstline treatment for uncomplicatedP. falciparummalaria since 2004. Methods:Between October and November 2009, we conducted a 42day, single arm, open label study of AL forP. falciparumin individuals >6 months of age at two sites in Oromia State, Ethiopia. Eligible patients who had documentedP. falciparummonoinfection were enrolled and followed according to the standard 2009 World Health Organizationin vivodrug efficacy monitoring protocol. The primary and secondary endpoints were PCR uncorrected and corrected cure rates, as measured by adequate clinical and parasitological response on days 28 and 42, respectively. Results:Of 4426 patients tested, 120 with confirmed falciparum malaria were enrolled and treated with AL. Follow up was completed for 112 patients at day 28 and 104 patients at day 42. There was one late parasitological failure, which was classified as undetermined after genotyping. Uncorrected cure rates at both day 28 and 42 for the per protocol analysis were 99.1% (95% CI 95.1100.0); corrected cure rates at both day 28 and 42 were 100.0%. Uncorrected cure rates at day 28 and 42 for the intention to treat analysis were 93.3% (95% CI 87.297.1) and 86.6% (95% CI 79.192.1), respectively, while the corrected cure rates at day 28 and 42 were 94.1% (95% CI 88.297.6) and 87.3% (95% CI 79.992.7), respectively. Using survival analysis, the unadjusted cure rate was 99.1% and 100.0% adjusted by genotyping for day 28 and 42, respectively. EightP. falciparumpatients (6.7%) presented with Plasmodium vivaxinfection during followup and were excluded from the per protocol analysis. Only one patient had persistent parasitaemia at day 3. No serious adverse events were reported, with cough and nausea/vomiting being the most common adverse events. Conclusions:AL remains a highly effective and welltolerated treatment for uncomplicated falciparum malaria in the study setting after several years of universal access to AL. A high rate of parasitaemia withP. vivaxpossibly from relapse or new infection was observed. Trial Registration:NCT01052584

* Correspondence: [e-mail] †Contributed equally 1 U.S. Centers for Disease Control and Prevention, Atlanta, GA, USA Full list of author information is available at the end of the article

© 2011 Hwang et al; licensee 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.