Malaria Research Lab, Infectious Diseases Unit, Department of Medicine, Karolinska University Hospital/Karolinska Institutet, Retziusväg 10, Stockholm, Sweden.
Malar J. 2011 Jan 28;10:18. doi: 10.1186/1475-2875-10-18.
Scarce data are available on Plasmodium falciparum anti-malarial drug resistance in Pakistan. The aim of this study was, therefore, to determine the prevalence of P. falciparum resistance associated polymorphisms in field isolates from southern Pakistan.
Blood samples from 244 patients with blood-slide confirmed P. falciparum mono-infections were collected between 2005-2007. Single nucleotide polymorphisms in the P. falciparum chloroquine resistance transporter (pfcrt K76T), multi drug resistance (pfmdr1 N86Y), dihydrofolate reductase (pfdhfr A16V, N51I, C59R, S108N, I164L) and dihydropteroate synthetase (pfdhps A436S, G437A and E540K) genes and pfmdr1 gene copy numbers were determined using PCR based methods.
The prevalence of pfcrt 76T and pfmdr1 86Y was 93% and 57%, respectively. The prevalence of pfdhfr double mutations 59R + 108N/51R + 108N was 92%. The pfdhfr triple mutation (51I, 59R, 108N) occurred in 3% of samples. The pfdhfr (51I, 59R, 108N) and pfdhps (437G, 540E) quintuple mutation was found in one isolate. Pfdhps 437G was observed in 51% and 540E in 1% of the isolates. One isolate had two pfmdr1 copies and carried the pfmdr1 86Y and pfcrt 76T alleles.
The results indicate high prevalence of in vivo resistance to chloroquine, whereas high grade resistance to sulphadoxine-pyrimethamine does not appear to be widespread among P. falciparum in southern Pakistan.
关于巴基斯坦恶性疟原虫抗疟药物耐药性的数据十分有限。因此，本研究旨在确定来自巴基斯坦南部地区现场分离株中恶性疟原虫耐药相关突变的流行率。
2005-2007 年间，采集了 244 例经血片证实的恶性疟原虫单一感染患者的血样。采用 PCR 方法检测恶性疟原虫氯喹耐药转运蛋白（pfcrt K76T）、多药耐药基因（pfmdr1 N86Y）、二氢叶酸还原酶（pfdhfr A16V、N51I、C59R、S108N、I164L）和二氢蝶酸合成酶（pfdhps A436S、G437A 和 E540K）基因中的单核苷酸多态性和 pfmdr1 基因拷贝数。
pfcrt 76T 和 pfmdr1 86Y 的流行率分别为 93%和 57%。pfdhfr 双突变 59R + 108N/51R + 108N 的流行率为 92%。pfdhfr 三突变（51I、59R、108N）发生在 3%的样本中。pfdhfr（51I、59R、108N）和 pfdhps（437G、540E）五突变在 1 个分离株中发现。pfdhps 437G 在 51%的分离株中观察到，540E 在 1%的分离株中观察到。1 个分离株有两个 pfmdr1 拷贝，携带 pfmdr1 86Y 和 pfcrt 76T 等位基因。
结果表明，体内对氯喹的耐药性流行率很高，而对磺胺多辛-乙胺嘧啶的高级耐药性在巴基斯坦南部的恶性疟原虫中似乎并不普遍。
