The classical molecular Pacritinib Sigma techniques are based on individual examination of SNPs by restriction fragment length polymorphism (RFLP) analysis, allele-specific amplification or DNA sequencing. Unfortunately, these methods are labour-intensive if performed on many SNPs, especially for the analysis of large sample sizes. The analysis of multiple SNPs has been shown to allow a better prediction of the clinical outcome compared to the evaluation of individual SNPs. This argued for a technique facilitating parallel typing of multiple SNPs [9,18-24]. To enable high throughput analysis of several point mutations, a sensitive and rapid SNP typing technique based on DNA microarray was used for the simultaneous assessment of all known resistance-associated SNPs located in genes pfcrt, pfmdr1, pfdhfr, pfdhps and pfATPase6 [25].
Prior to this study, the malaria drug resistance microarray was validated with field studies conducted in different epidemiological and geographical settings, including Papua New Guinea (PNG) [17,24], and Tanzania. The relationship between SNP prevalence in samples collected in the asymptomatic community and the rate of treatment failure derived from clinical in vivo studies was investigated. In PNG, two investigated sites had different rates of treatment failure, which were reflected by different patterns of resistance markers in the corresponding parasite populations [17]. In the frame of that multisite study, the present work reports on an additional field study conducted in 2004 at the north of Guadalcanal province in the SI.
A classical in vivo study was conducted to assess the level of CQ+SP failure among symptomatic P. falciparum malaria patients. In parallel, a cross-sectional survey in the surrounding asymptomatic community allowed the assessment of SNP prevalence. After the completion of this study, the SI Ministry of Health modified the national treatment guidelines for P. falciparum infections. Since 2008, standard first-line treatment for P. falciparum malaria has been changed to the combination of artemether plus lumefantrine. Methods Study area The study was conducted in Tetere area, Guadalcanal Province of SI between November 2004 and May 2005, roughly corresponding to the rainy season. The SI are located northeast of Australia, at a latitude of 8�� South and a longitude of 159�� East.
The drug efficacy in vivo study was conducted at the Lunga clinic, located about 10 km east from Honiara, the capital city of the country. The community-based cross-sectional survey was carried out in 3 villages nearby, which are part of the Lunga clinic catchment area. According to the prevalence of malaria among children aged between Carfilzomib 2 and 9 years, the endemicity of P. falciparum and Plasmodium vivax malaria in that area is considered mesoendemic.