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Open Access Research

Delayed Plasmodium falciparum clearance following artesunate-mefloquine combination therapy in Thailand, 1997–2007

Saowanit Vijaykadga1, Alisa P Alker2, Wichai Satimai1*, John R MacArthur34, Steven R Meshnick5 and Chansuda Wongsrichanalai3

Author Affiliations

1 Bureau of Vector Borne Diseases, Department of Diseases Control, Ministry of Public Health, Nonthaburi, Thailand

2 Division of Infectious Diseases, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA

3 US Agency for International Development Regional Development Mission for Asia (USAID/RDMA), Bangkok, Thailand

4 Malaria Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA

5 Department of Epidemiology, Gilings School of Public Health, University of North Carolina, Chapel Hill, NC, USA

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Malaria Journal 2012, 11:296  doi:10.1186/1475-2875-11-296

Published: 28 August 2012

Abstract

Background

There is concern that artesunate resistance is developing in Southeast Asia. The purpose of this study is to investigate the prevalence of parasitaemia in the few days following treatment with artesunate-mefloquine (AM), which is an indirect measure of decreased artesunate susceptibility.

Methods

This is a retrospective analysis of 31 therapeutic efficacy studies involving 1,327 patients treated with AM conducted by the Thai National Malaria Control Programme from 1997–2007.

Results

The prevalence of patients with parasitaemia on day 2 was higher in the east compared to the west (east: 20%, west: 9%, OR 2.47, 95% CI: 1.77, 3.45). In addition, the prevalence of day-2 parasitaemia increased over time (OR for each year = 1.10, 95% CI: 1.03, 1.19). After controlling for initial parasitaemia and age, year and region remained important determinants of day-2 parasitaemia (OR for region = 3.98, 95%CI 2.63, 6.00; OR for year = 1.28, 95%CI: 1.17, 1.39). The presence of parasitaemia on day 2 and day 3 were specific, but not sensitive predictors of treatment failure.

Discussion

Delayed resolution of parasitaemia after AM treatment increased in eastern Thailand between 1997 and 2007, which may be an early manifestation of decreased artesunate susceptibility. However, clinical and parasitological treatment failure after 28 days (which is related to both mefloquine and artesunate decreased susceptibility) is not changing over time. The presence of parasitaemia on day 2 is a poor indicator of AM 28-day treatment failure.

Keywords:
Malaria; drug resistance; parasite clearance