Reduction of transmission from malaria patients by artemisinin combination therapies: a pooled analysis of six randomized trials
Author(s)
Okell, LC
Drakeley, CJ
Ghani, AC
Bousema, T
Sutherland, CJ
Type
Journal Article
Abstract
BACKGROUND: Artemisinin combination therapies (ACT), which are increasingly being introduced for treatment of Plasmodium falciparum malaria, are more effective against sexual stage parasites (gametocytes) than previous first-line antimalarials and therefore have the potential to reduce parasite transmission. The size of this effect is estimated in symptomatic P. falciparum infections. METHODS: Data on 3,174 patients were pooled from six antimalarial trials conducted in The Gambia and Kenya. Multivariable regression was used to investigate the role of ACT versus non-artemisinin antimalarial treatment, treatment failure, presence of pre-treatment gametocytes and submicroscopic gametocytaemia on transmission to mosquitoes and the area under the curve (AUC) of gametocyte density during the 28 days of follow up. RESULTS: ACT treatment was associated with a significant reduction in the probability of being gametocytaemic on the day of transmission experiments (OR 0.20 95% CI 0.16-0.26), transmission to mosquitoes by slide-positive gametocyte carriers (OR mosquito infection 0.49 95% CI 0.33-0.73) and AUC of gametocyte density (ratio of means 0.35 95% CI 0.31-0.41). Parasitological treatment failure did not account for the difference between ACT and non-artemisinin impact. The presence of slide-positive gametocytaemia prior to treatment significantly reduced ACT impact on gametocytaemia (p < 0.001). Taking account of submicroscopic gametocytaemia reduced estimates of ACT impact in a high transmission setting in Kenya, but not in a lower transmission setting in the Gambia. CONCLUSION: Treatment with ACT significantly reduces infectiousness of individual patients with uncomplicated falciparum malaria compared to previous first line treatments. Rapid treatment of cases before gametocytaemia is well developed may enhance the impact of ACT on transmission.
Date Issued
2008
Citation
Malar J, 2008, 7, pp.125-
ISSN
1475-2875
Start Page
125
Journal / Book Title
Malar J
Volume
7
Copyright Statement
© 2008 Okell 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.
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.
Sponsor
Medical Research Council (MRC)
Identifier
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18613962
Grant Number
G0600719B
Subjects
Animals Antimalarials/*therapeutic use Artemisinins/*therapeutic use Child Child, Preschool Culicidae/parasitology Drug Therapy, Combination Gambia Humans Kenya Malaria, Falciparum/*transmission Multivariate Analysis Parasitemia Plasmodium falciparum/*drug effects Randomized Controlled Trials as Topic Regression Analysis Treatment Failure
Notes
Reduction of transmission from malaria patients by artemisinin combination therapies: a pooled analysis of six randomized trials Okell, Lucy C Drakeley, Chris J Ghani, Azra C Bousema, Teun Sutherland, Colin J Medical Research Council/United Kingdom Wellcome Trust/United Kingdom Meta-Analysis Research Support, Non-U.S. Gov't England Malaria journal Malar J. 2008 Jul 9;7:125. eng