Journal Article

Efficacy of Artesunate Plus Amodiaquine versus That of Artemether-Lumefantrine for the Treatment of Uncomplicated Childhood <i>Plasmodium falciparum</i> Malaria in Zanzibar, Tanzania

Andreas Mårtensson, Johan Strömberg, Christin Sisowath, Mwinyi I. Msellem, J. Pedro Gil, Scott M. Montgomery, Piero Olliaro, Abdullah S. Ali and Anders Björkman

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 41, issue 8, pages 1079-1086
Published in print October 2005 | ISSN: 1058-4838
Published online October 2005 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/444460
Efficacy of Artesunate Plus Amodiaquine versus That of Artemether-Lumefantrine for the Treatment of Uncomplicated Childhood Plasmodium falciparum Malaria in Zanzibar, Tanzania

More Like This

Show all results sharing these subjects:

  • Infectious Diseases
  • Immunology
  • Public Health and Epidemiology
  • Microbiology

GO

Show Summary Details

Preview

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.

Journal Article.  4543 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.