Efficacy of a 3-day artesunate-mefloquine combination in the treatment of uncomplicated falciparum malaria in Kanchanaburi province of Thailand

Background: In Kanchanaburi province located on the Thai-Myanmar border, Plasmodium falciparum parasites have developed significant resistance to commonly-used anti-malarials. For use against falciparum malaria, 2-day artesunate-mefloquine combination (MAS2) has recently been replaced by a 3-day artesunate-mefloquine combination (MAS3) that is an artemisinin-based combination therapy regimen recommended by the WHO. Objective: Investigate the efficacy and safety of MAS3 in the treatment of uncomplicated falciparum malaria in patients of Kanchaburi province. Methods: The study was conducted at Bongtee sub-district, Sai Yok district, Kanchanaburi province between June and November 2009. Fifty-one uncomplicated falciparum malaria patients were enrolled. Inclusion, exclusion and study method followed the WHO protocol for assessment and monitoring of antimalarial drug efficacy for the treatment of uncomplicated falciparum malaria. Patients received a MAS3 and were followed for 42 days. Results: All patients clinically recovered, but four patients were again parasitaemic on day 21, (1 patient) 28 (2 patients) and 42 (1 patient), respectively. Molecular analyses suggested that all recurrences were caused by recrudescence. There were no severe adverse events, but complaints of headache, gastrointestinal upset, nausea, and vomiting. Delay in parasite clearance was found. Proportion of parasite clearance on day 1, 2, 3 and 7 were 17.7%, 62.7%, 80.4%, and 100%, respectively. Conclusion: MAS3 is comparable to MAS2, and meet the WHO efficacy criteria for use against falciparum malaria, but the effect on parasite clearance was inferior to that of MAS2. Close monitoring evaluation is required.

Comparison of the OptiMAL rapid test with routine microscopic examination of Giemsa-Stained Thick Blood Film for diagnosis of malaria.

The OptiMAL is a rapid immunodiagnostic test developed by Flow Inc., Portland, Oreg. for diagnosis and differentiation of P. falciparum and non P. falciparum malaria infection. It has been based on detection of circulating parasite lactate dehydrogenase enzyme (pLDH), produced by live Plasmodium parasites. The purpose of this study was to compare the efficacy of the OptiMAL test with routine microscopic examination of Giemsa-Stained Thick Blood Film (routine GS-TBF) for the diagnosis of malaria at a local malaria clinic in a hyperendemic area of Thailand by using a standard GS-TBF (standard GS-TBF) as reference. One hundred and seventy five patients attending the clinic were recruited; 50, 42 and 83 were falciparum malaria, vivax malaria and non-malaria patients, respectively. Compared with the reference, the OptiMAL test had sensitivities of 92 per cent and 97.6 per cent, whereas, the routine GS-TBF had sensitivities of 81.3 per cent and 81 per cent for the detection of P. falciparum and P. vivax, respectively. Both tests showed no false positive resulting in 100 per cent specificities. However, the OptiMAL test was able to detect only 20 per cent of infection with less than 200 parasitaemia/microlitre. It was also shown in our study that the OptiMAL test was advantageous in follow-up of the treatment outcome. No false positive occurred among 40 follow-up cases. The OptiMAL test detected malaria infection more accurately than the routine GS-TBF (p < 0.05) and was simple, easy to perform and rapid. It is an alternative tool for the diagnosis of malaria in a hyperendemic area where experienced microscopists are not available.

Drug resistant malaria on the Thai-Myanmar and Thai-Cambodian borders.

We describe the changing epidemiology of drug resistant malaria in Thailand over the past decade. Factors determining the characteristic patterns of the development and spread of resistance to anti-malarial drugs on the Thai-Cambodian border and the Thai-Myanmar border are explored, namely, population dynamics, drug usage and malaria control measures. The introduction of artesunate-mefloquine combination in selected areas along the two borders in 1995 is believed to be one of the multiple factors responsible for stabilizing the multidrug resistance problems in Thailand today. Other control measures and inter-governmental co-operation must continue to be strengthened in order to limit the spread of drug resistance malaria in the Southeast Asian region.

Investigations of incidence of pretreatment, drug sensitivity in vitro, and plasma levels of pyrimethamine in patients with multidrug resistant falciparum malaria following the three combination regimens of artemether/pyrimethamine.

The study was carried out to investigate the status of in vitro susceptibility of Plasmodium falciparum to pyrimethamine (PYR) in multidrug resistant area of the Thai-Myanmar border, the incidence of unregulated use of the combination of PYR with sulfadoxine (Fansidar) in this area and the relevance of pharmacodynamic and pharmacokinetic factors in determining the treatment outcome from the three combination regimens of ART/PYR (1-, 2- and 3-day regimens), in patients with acute uncomplicated falciparum malaria. The majority of patients had baseline PYR concentrations in the range of 1-100 (50.6%) or 100-500 (34.8%) ng/ml, while concentrations of more than 500 ng/ml were found in only 1.1%. All of the isolates exhibited high grade resistance to PYR with the minimum inhibition concentration (MIC) of as high as 10(-5) M. No association was observed between treatment outcome and the presence of baseline plasma PYR concentrations. In addition, lack of association between plasma concentrations during the acute phase (day-1 and -2) and treatment outcome was found.