中美洲洪都拉斯采集的疟原虫恶性疟原虫和间日疟原虫相关耐药基因突变。
Drug resistance associated genetic polymorphisms in Plasmodium falciparum and Plasmodium vivax collected in Honduras, Central America.
机构信息
Malaria Research Laboratory, Infectious Diseases Unit, Department of Medicine, Karolinska University Hospital/Karolinska Institutet, Retzius väg 10, 171 77 Stockholm, Sweden.
出版信息
Malar J. 2011 Dec 19;10:376. doi: 10.1186/1475-2875-10-376.
BACKGROUND
In Honduras, chloroquine and primaquine are recommended and still appear to be effective for treatment of Plasmodium falciparum and Plasmodium vivax malaria. The aim of this study was to determine the proportion of resistance associated genetic polymorphisms in P. falciparum and P. vivax collected in Honduras.
METHODS
Blood samples were collected from patients seeking medical attention at the Hospital Escuela in Tegucigalpa from 2004 to 2006 as well as three regional hospitals, two health centres and one regional laboratory during 2009. Single nucleotide polymorphisms in P. falciparum chloroquine resistance transporter (pfcrt), multidrug resistance 1 (pfmdr1), dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) genes and in P. vivax multidrug resistance 1 (pvmdr1) and dihydrofolate reductase (pvdhfr) genes were detected using PCR based methods.
RESULTS
Thirty seven P. falciparum and 64 P. vivax samples were collected. All P. falciparum infections acquired in Honduras carried pfcrt, pfmdr1, pfdhps and pfdhfr alleles associated with chloroquine, amodiaquine and sulphadoxine-pyrimethamine sensitivity only. One patient with parasites acquired on a Pacific Island had pfcrt 76 T and pfmdr1 86Y alleles. That patient and a patient infected in West Africa had pfdhfr 51I, 59 R and 108 N alleles. Pvmdr1 976 F was found in 7/37 and two copies of pvmdr1 were found in 1/37 samples. Pvdhfr 57 L + 58 R was observed in 2/57 samples.
CONCLUSION
The results indicate that P. falciparum from Honduras remain sensitive to chloroquine and sulphadoxine-pyrimethamine. This suggests that chloroquine and sulphadoxine-pyrimethamine should be efficacious for treatment of uncomplicated P. falciparum malaria, supporting current national treatment guidelines. However, genetic polymorphisms associated with chloroquine and sulphadoxine-pyrimethamine tolerance were detected in local P. vivax and imported P. falciparum infections. Continuous monitoring of the prevalence of drug resistant/tolerant P. falciparum and P. vivax is therefore essential also in Honduras.
背景
在洪都拉斯，氯喹和伯氨喹仍被推荐用于治疗恶性疟原虫和间日疟原虫疟疾，且似乎仍然有效。本研究旨在确定 2004 年至 2006 年期间在特古西加尔巴的埃斯库埃拉医院以及 2009 年期间在 3 家地区医院、2 家卫生中心和 1 家地区实验室就诊的患者中采集的恶性疟原虫和间日疟原虫样本中与耐药相关的遗传多态性的比例。
方法
采用聚合酶链反应（PCR）方法检测恶性疟原虫氯喹耐药转运蛋白（pfcrt）、多药耐药 1 型（pfmdr1）、二氢叶酸还原酶（pfdhfr）和二氢蝶酸合成酶（pfdhps）基因以及间日疟原虫多药耐药 1 型（pvmdr1）和二氢叶酸还原酶（pvdhfr）基因中的单核苷酸多态性。
结果
共采集了 37 株恶性疟原虫和 64 株间日疟原虫样本。所有在洪都拉斯感染的恶性疟原虫均携带与氯喹、阿莫地喹和磺胺多辛-乙胺嘧啶敏感性相关的 pfcrt、pfmdr1、pfdhps 和 pfdhfr 等位基因。1 例在太平洋岛屿感染的患者携带 pfcrt76T 和 pfmdr186Y 等位基因。该患者和 1 例在西非感染的患者携带 pfdhfr51I、59R 和 108N 等位基因。37 例样本中有 7 例发现 pvmdr1976F，37 例样本中有 1 例发现 2 个 pvmdr1 拷贝。在 57 例样本中观察到 pvdhfr57L+58R，在 2 例样本中观察到 pvdhfr57L+58R。
结论
结果表明，来自洪都拉斯的恶性疟原虫对氯喹和磺胺多辛-乙胺嘧啶仍然敏感。这表明氯喹和磺胺多辛-乙胺嘧啶治疗无并发症恶性疟原虫疟疾应是有效的，支持当前的国家治疗指南。然而，在当地的间日疟原虫和输入性恶性疟原虫感染中发现了与氯喹和磺胺多辛-乙胺嘧啶耐受性相关的遗传多态性。因此，在洪都拉斯也必须持续监测抗疟药物敏感/耐药的恶性疟原虫和间日疟原虫的流行情况。
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