Modelling the impact of artemisinin combination therapy and long-acting treatments on malaria transmission intensity
Author(s)
Okell, LC
Drakeley, CJ
Bousema, T
Whitty, CJ
Ghani, AC
Type
Journal Article
Abstract
BACKGROUND: Artemisinin derivatives used in recently introduced combination therapies (ACTs) for Plasmodium falciparum malaria significantly lower patient infectiousness and have the potential to reduce population-level transmission of the parasite. With the increased interest in malaria elimination, understanding the impact on transmission of ACT and other antimalarial drugs with different pharmacodynamics becomes a key issue. This study estimates the reduction in transmission that may be achieved by introducing different types of treatment for symptomatic P. falciparum malaria in endemic areas. METHODS AND FINDINGS: We developed a mathematical model to predict the potential impact on transmission outcomes of introducing ACT as first-line treatment for uncomplicated malaria in six areas of varying transmission intensity in Tanzania. We also estimated the impact that could be achieved by antimalarials with different efficacy, prophylactic time, and gametocytocidal effects. Rates of treatment, asymptomatic infection, and symptomatic infection in the six study areas were estimated using the model together with data from a cross-sectional survey of 5,667 individuals conducted prior to policy change from sulfadoxine-pyrimethamine to ACT. The effects of ACT and other drug types on gametocytaemia and infectiousness to mosquitoes were independently estimated from clinical trial data. Predicted percentage reductions in prevalence of infection and incidence of clinical episodes achieved by ACT were highest in the areas with low initial transmission. A 53% reduction in prevalence of infection was seen if 100% of current treatment was switched to ACT in the area where baseline slide-prevalence of parasitaemia was lowest (3.7%), compared to an 11% reduction in the highest-transmission setting (baseline slide prevalence = 57.1%). Estimated percentage reductions in incidence of clinical episodes were similar. The absolute size of the public health impact, however, was greater in the highest-transmission area, with 54 clinical episodes per 100 persons per year averted compared to five per 100 persons per year in the lowest-transmission area. High coverage was important. Reducing presumptive treatment through improved diagnosis substantially reduced the number of treatment courses required per clinical episode averted in the lower-transmission settings although there was some loss of overall impact on transmission. An efficacious antimalarial regimen with no specific gametocytocidal properties but a long prophylactic time was estimated to be more effective at reducing transmission than a short-acting ACT in the highest-transmission setting. CONCLUSIONS: Our results suggest that ACTs have the potential for transmission reductions approaching those achieved by insecticide-treated nets in lower-transmission settings. ACT partner drugs and nonartemisinin regimens with longer prophylactic times could result in a larger impact in higher-transmission settings, although their long term benefit must be evaluated in relation to the risk of development of parasite resistance.
Date Issued
2008
Citation
PLoS Med, 2008, 5 (11), pp.e226-e226
ISSN
1549-1676
Start Page
e226
End Page
e226
Journal / Book Title
PLoS Med
Volume
5
Issue
11
Copyright Statement
© 2008 Okell et al. This is
an open-access article distributed
under the terms of the Creative
Commons Attribution License, which
permits unrestricted use,
distribution, and reproduction in any
medium, provided the original
author and source are credited.
an open-access article distributed
under the terms of the Creative
Commons Attribution License, which
permits unrestricted use,
distribution, and reproduction in any
medium, provided the original
author and source are credited.
Sponsor
Medical Research Council (MRC)
Identifier
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19067479
Grant Number
G0600719B
Subjects
Adolescent Adult Animals Anti-Infective Agents/pharmacokinetics/*therapeutic use Artemisinins/pharmacokinetics/*therapeutic use Child Child, Preschool Drug Therapy, Combination Female Humans Infant Infant, Newborn Malaria, Falciparum/*drug therapy/epidemiology/parasitology/*transmission Male Middle Aged Models, Theoretical Tanzania/epidemiology Young Adult
Notes
Nov 25 Modelling the impact of artemisinin combination therapy and long-acting treatments on malaria transmission intensity Okell, Lucy C Drakeley, Chris J Bousema, Teun Whitty, Christopher J M Ghani, Azra C Medical Research Council/United Kingdom Wellcome Trust/United Kingdom Research Support, Non-U.S. Gov't United States PLoS medicine PLoS Med. 2008 Nov 25;5(11):e226; discussion e226. eng