Zhong Daibin, Afrane Yaw, Githeko Andrew, Cui Liwang, Menge David M, Yan Guiyun
Program in Public Health, College of Health Sciences, University of California at Irvine, Irvine, CA 92697, USA.
BMC Infect Dis. 2008 Jul 31;8:105. doi: 10.1186/1471-2334-8-105.
Since the late 1980s a series of malaria epidemics has occurred in western Kenya highlands. Among the possible factors that may contribute to the highland malaria epidemics, parasite resistance to antimalarials has not been well investigated.
Using parasites from highland and lowland areas of western Kenya, we examined key mutations associated with Plasmodium falciparum resistance to sulfadoxine - pyrimethamine and chloroquine, including dihydrofolate reductase (pfdhfr) and dihydropteroate synthetase (pfdhps), chloroquine resistance transporter gene (pfcrt), and multi-drug resistance gene 1 (pfmdr1).
We found that >70% of samples harbored 76T pfcrt mutations and over 80% of samples harbored quintuple mutations (51I/59R/108N pfdhfr and 437G/540E pfdhps) in both highland and lowland samples. Further, we did not detect significant difference in the frequencies of these mutations between symptomatic and asymptomatic malaria volunteers, and between highland and lowland samples.
These findings suggest that drug resistance of malaria parasites in the highlands could be contributed by the mutations and their high frequencies as found in the lowland. The results are discussed in terms of the role of drug resistance as a driving force for malaria outbreaks in the highlands.
自20世纪80年代末以来，肯尼亚西部高地发生了一系列疟疾疫情。在可能导致高地疟疾疫情的因素中，寄生虫对抗疟药物的耐药性尚未得到充分研究。
我们使用来自肯尼亚西部高地和低地的寄生虫，检测了与恶性疟原虫对磺胺多辛-乙胺嘧啶和氯喹耐药性相关的关键突变，包括二氢叶酸还原酶（pfdhfr）、二氢蝶酸合酶（pfdhps）、氯喹耐药转运蛋白基因（pfcrt）和多药耐药基因1（pfmdr1）。
我们发现，在高地和低地样本中，超过70%的样本携带76T pfcrt突变，超过80%的样本携带五重突变（51I/59R/108N pfdhfr和437G/540E pfdhps）。此外，我们未检测到有症状和无症状疟疾志愿者之间以及高地和低地样本之间这些突变频率的显著差异。
这些发现表明，高地疟原虫的耐药性可能是由低地发现的突变及其高频率所致。从耐药性作为高地疟疾暴发驱动力的作用方面对结果进行了讨论。
