In vitro antimalarial drug susceptibility in Thai border areas from 1998-2003

Abstract

Background: The Thai-Myanmar and Thai-Cambodia borders have been historically linked with the emergence and spread of Plasmodium falciparum parasites resistant to antimalarial drugs. Indeed, the areas are often described as harbouring multi-drug resistant parasites. These areas of Thailand have experienced significant changes in antimalarial drug exposure patterns over the past decade. This study describes the in vitro antimalarial susceptibility patterns of 95 laboratory-adapted P. falciparum isolates, collected between 1998 and 2003.

Methods: Ninety five P. falciparum isolates were collected from five sites in Thailand between 1998 and 2003. After laboratory adaptation to in vitro culture, the susceptibility of these parasites to a range of established antimalarial drugs (chloroquine [CQ], mefloquine [MQ], quinine [QN] and dihydroartemisinin [DHA]) was determined by the isotopic microtest.

Results: Mefloquine (MQ) sensitivity remained poorest in areas previously described as MQ-resistant areas. Sensitivity to MQ of parasites from this area was significantly lower than those from areas reported to harbour moderate (p = 0.002) of low level MQ resistance (p = 000001). Importantly for all drugs tested, there was a considerable range in absolute parasite sensitivities. There was a weak, but statistically positive correlation between parasite sensitivity to CQ and sensitivity to both QN and MQ and a positive correlation between MQ and QN. In terms of geographical distribution, parasites from the Thai-Cambodia were tended to be less sensitive to all drugs tested compared to the Thai-Myanmar border. Parasite sensitivity to all drugs was stable over the 6-year collection period with the exception of QN.

Conclusion: This study highlights the high degree of variability in parasite drug sensitivity in Thailand. There were geographical differences in the pattern of resistance which might reflect differences in drug usage in each area. In contrast to many other studies there were weak, but statistically significant positive, correlations between sensitivity to CQ and sensitivity to MQ and QN. Over the six years of sample collection, parasite sensitivity appears to have stabilized to these drugs in these sites.

Figure 1

Map of Thailand showing the sampling sites: Tak, Kanchanaburi, Ratchaburi, Ranong and Chantaburi provinces.

Figure 2

The scatter plot between the IC₅₀ (nM) and the mefloquine resistance areas and the border regions. A represents the chloroquine data, B the quinine data and C the mefloquine data. (a) is the geometric mean 50% inhibitory concentration in vitro with the 95% CI and (b) is the median.

Figure 3

The scatter diagram and the regression line representing the relationship between IC₅₀ (nM) values of CQ, QN and MQ.