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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Efficacy of artesunate plus amodiaquine versus that of artemether- lumefantrine for the treatment of uncomplicated childhood Plasmodium falciparum malaria in Zanzibar, Tanzania
Clinical Infectious Diseases, Volume 41, No. 8, Year 2005
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Description
Background. This is the first clinical trial comparing the efficacy of artesunate plus amodiaquine (ASAQ) and artemether-lumefantrine (AL)-the major artemisinin-based combination therapy (ACT) candidates for treatment of malaria in Africa-that involved an extended, 42-day follow-up period, polymerase chain reaction-adjusted parasitological cure rates (PCR APCRs), and systematic analyses of genetic markers related to quinoline resistance. Methods. A total of 408 children with uncomplicated Plasmodium falciparum malaria in Zanzibar, Tanzania, were enrolled. Children who were 6-8 months of age and/or who weighed 6-8 kg were assigned to receive ASAQ for 3 days. Children who were 9-59 months of age and who weighted ≥9 kg were randomly assigned to receive either ASAQ or AL for 3 days in standard doses. Intention-to-treat analyses were performed. Results. Age- and weight-adjusted PCR-APCRs by follow-up day 42 were 91% (188 of 206 patients) in the ASAQ group and 94% (185 of 197 patients) in the AL group (odds ratio [OR] for the likelihood of cure, 2.07; 95% confidence interval [CI], 0.84-5.10; P = .115). A total of 5 and 7 recrudescences occurred after day 28 in the ASAQ and AL groups, respectively. On the assumption that 10 malaria episodes with uncertain PCR results were recrudescences, PCR-APCRs decreased to 88% in the ASAQ group and to 92% in the AL group. Unadjusted cure rates by day 42 were 56% (116 of 206 patients) in the ASAQ group versus 77% (151 of 197 patients) in the AL group (OR, 2.55; 95% CI, 1.66-3.91; P < .001). Rates of reinfection by day 42 were 36% (65 of 181 patients) in the ASAQ arm versus 17% (31 of 182 patients) in the AL arm (OR, 0.37; 95% CI, 0.22-0.60; P < .001). A significant selection of P. falciparum multidrug resistance gene 1 allele 86N was found in isolates associated with reinfection after AL treatment, compared with isolates at baseline (2.2-fold increase; P < .001). Conclusions. Both treatments were highly efficacious, but AL provided stronger prevention against reinfection. The high proportion of recrudescences found after day 28 and the genetic selection by the long-acting partner drug underlines the importance of long follow-up periods in clinical trials. A long follow-up duration and performance of PCR genotyping should be implemented in programmatic surveillance of antimalarial drugs. © 2005 by the Infectious Diseases Society of America. All rights reserved.
Authors & Co-Authors
Mårtensson, Andreas A.
Sweden, Stockholm
Karolinska Universitetssjukhuset
Sweden, Katrineholm
Kullbergska Hospital
Strömberg, Johan
Sweden, Stockholm
Karolinska Universitetssjukhuset
Sisowath, Christin
Sweden, Stockholm
Karolinska Universitetssjukhuset
Msellem, Mwinyi I.
Tanzania, Mkokotoni
Ministry of Health Zanzibar
Gil, Jose Pedro
Sweden, Stockholm
Karolinska Universitetssjukhuset
Montgomery, Scott M.
Sweden, Stockholm
Karolinska Universitetssjukhuset
Sweden, Orebro
Universitetssjukhuset Örebro
Olliaro, Piero L.
Switzerland, Geneva
Organisation Mondiale de la Santé
Ali, Abdullah Suleiman
Tanzania, Mkokotoni
Ministry of Health Zanzibar
Bjǒrkman, Anders B.
Sweden, Stockholm
Karolinska Universitetssjukhuset
Statistics
Citations: 218
Authors: 9
Affiliations: 5
Identifiers
Doi:
10.1086/444460
ISSN:
10584838
Research Areas
Genetics And Genomics
Infectious Diseases
Maternal And Child Health
Study Design
Cohort Study
Case-Control Study
Study Locations
Tanzania