Plasmodium falciparum isolates in India exhibit a progressive increase in mutations associated with sulfadoxine-pyrimethamine resistance
Plasmodium falciparum isolates in India exhibit a progressive increase in mutations associated with sulfadoxine-pyrimethamine resistance
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DOI：
10.1128/aac.48.3.879-889.2004
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发表时间：
2004-03-01
影响因子：
4.9
通讯作者：
Sharma, YD
中科院分区：
文献类型：
--
作者：
Ahmed, A;Bararia, D;Sharma, YD
磺胺多辛联合乙胺嘧啶(SP)是治疗单纯性抗氯喹恶性疟的二线药物。对SP的抗性是由于寄生虫的二氢叶酸还原酶(DHFR)和二氢翼酸合成酶(DHPS)基因的某些点突变所致。我们已经分析了来自印度不同地区的312个恶性疟原虫野外分离株的这些突变，以评估药物压力的影响。DHFR基因的突变率高于DHPS基因的突变率，尽管后者有更多的等位基因突变。具有双DHFR突变和单DHPS突变的分离株的数量有一个时间性的上升，导致在5年的时间里，DHFR和DHPS结合的基因座突变总数增加。在这5年中，具有药物敏感基因的菌株数量显著减少，而具有耐药基因(双DHFR突变和单一DHPS突变)的菌株数量显著增加。然而，这两种酶的每个基因都有三个突变的菌株数量(总共有六个突变)仍然非常低，这与该国SP治疗失败率非常低不谋而合。突变率存在地区偏见，来自东北部地区(阿萨姆邦)的分离物表现出比其他地区的分离物更高的突变率和更复杂的基因类型。结论是，尽管在印度将SP作为二线治疗药物，但与SP耐药性相关的突变仍在逐步增加。
The combination of sulfadoxine-pyrimethamine (SP) is used as a second line of therapy for the treatment of uncomplicated chloroquine-resistant Plasmodium falciparum malaria. Resistance to SP arises due to certain point mutations in the genes for the dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) enzymes of the parasite. We have analyzed these mutations in 312 field isolates of P. falciparum collected from different parts of India to assess the effects of drug pressure. The rate of mutation in the gene for DHFR was found to be higher than that in the gene for DHPS, although the latter had mutations in more alleles. There was a temporal rise in the number of isolates with double dhfr mutations and single dhps mutations, resulting in an increased total number of mutations in the loci for DHFR and DHPS combined over a 5-year period. During these 5 years, the number of isolates with drug-sensitive genotypes decreased and the number of isolates with drug-resistant genotypes (double DHFR mutations and a single DHPS mutation) increased significantly. The number of isolates with the triple mutations in each of the genes for the two enzymes (for a total of six mutations), however, remained very low, coinciding with the very low rate of SP treatment failure in the country. There was a regional bias in the mutation rate, as isolates from the northeastern region (the state of Assam) showed higher rates of mutation and more complex genotypes than isolates from the other regions. It was concluded that even though SP is prescribed as a second line of treatment in India, the mutations associated with SP resistance continue to be progressively increasing.