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. 2012 Aug 28:11:296.
doi: 10.1186/1475-2875-11-296.

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

Saowanit Vijaykadga  1 , Alisa P Alker, Wichai Satimai, John R MacArthur, Steven R Meshnick, Chansuda Wongsrichanalai
Affiliations

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

Saowanit Vijaykadga et al. Malar J. .

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.

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Figures

Figure 1
Figure 1
The provinces where in vivo efficacy studies took place in Thailand between 1997–2007.
Figure 2
Figure 2
28-day treatment failure over time in Thailand 1997–2007. Chanthaburi and Trat are in the east, the rest of the sites are in the west.
Figure 3
Figure 3
Day-2 and day-3 parasitaemia over time in Thailand 1997–2007. Chanthaburi and Trat are in the east, the rest of the sites are in the west.
Figure 4
Figure 4
Extrapolated positive predictive values (PPVs) and negative predictive values (NPVs). Based on the relationship between day-2 parasitaemia and 28-day treatment failure.
Figure 5
Figure 5
The percentage of subjects who were parasitaemic and the 28-day treatment failure.
See this image and copyright information in PMC

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