Prevalence of polymorphisms in the dihydrofolate reductase and dihydropteroate synthetase genes of Plasmodium falciparum isolates from southern Mauritania
Prevalence of polymorphisms in the dihydrofolate reductase and dihydropteroate synthetase genes of Plasmodium falciparum isolates from southern Mauritania
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DOI：
10.1046/j.1365-3156.2001.00791.x
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发表时间：
2001-10-01
影响因子：
3.3
通讯作者：
Christophel, EM
中科院分区：
文献类型：
--
作者：
Eberl, KJ;Jelinek, T;Christophel, EM
恶性疟原虫在用乙胺嘧啶/磺胺嘧啶治疗无并发症的疟疾中的耐药性增加在几项研究中与二氢叶酸还原酶（DHFR）和二氢蝶酸合成酶（DHPS）基因中的点突变的发生有关。在这项研究中，这些突变的流行率在毛里塔尼亚东南部的样本中进行了检查，在1998年和1999年，那里的恶性疟爆发严重。本文应用聚合酶链反应（PCR）对386例恶性疟原虫感染者进行了检测，阳性162例，阳性率为41.97%。通过巢式PCR和随后的突变特异性限制性内切酶消化来检查这些分离株的DHFR（密码子16、51、59、108和164）和DHPS（密码子436、437、540、581和613）基因中的点突变。我们发现DHFR基因突变的总体患病率较低（高达18.6%的分离株），但DHPS基因突变的总体患病率较高（高达49.1%的分离株）。因此，预计研究地区可能很快就会出现对抗叶酸药物的耐药性。这项研究证明了简单，相对快速和廉价的分子方法及其在监测方案中的应用的效用。检测引起抗叶酸剂耐药的点突变的流行率可能有助于在非常早期的阶段识别耐药的发展。
The increasing resistance of Plasmodium falciparum in the treatment of uncomplicated malaria with pyrimethamine/sulphadoxine has been associated in several studies with the occurrence of point mutations in the genes of dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS). In this study, the prevalence of these mutations was examined in samples from south-east Mauritania, where atypically strong rainfalls in 1998 and 1999 led to a severe outbreak of falciparum malaria. We analysed 386 samples by polymerase chain reaction (PCR) for infection with P. falciparum, of which 162 (41.97%) were positive. These isolates were examined for point mutations in the genes of DHFR (codons 16, 51, 59, 108 and 164) and DHPS (codons 436, 437, 540, 581 and 613) by nested PCR and subsequent mutation-specific restriction enzyme digest. We found a low overall prevalence of DHFR gene mutations (up to 18.6% of isolates), but a high overall prevalence of DHPS gene mutations (up to 49.1% of isolates). Thus, emerging resistance to antifolate drugs may be expected to develop soon in the investigated area. This study demonstrates the utility of simple, relatively rapid and inexpensive molecular methods and their application in surveillance programmes. Testing for prevalence of point mutations conferring antifolate resistance might help to identify the developing of drug resistance at a very early stage.