Molecular monitoring of Plasmodium falciparum resistance to antimalarial drugs after adoption of sulfadoxine-pyrimethamine plus artesunate as the first line treatment in Iran
Molecular monitoring of Plasmodium falciparum resistance to antimalarial drugs after adoption of sulfadoxine-pyrimethamine plus artesunate as the first line treatment in Iran
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DOI：
10.1016/j.actatropica.2011.09.010
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发表时间：
2012-01-01
期刊：
影响因子：
2.7
通讯作者：
Djadid, Navid Dinparast
中科院分区：
文献类型：
--
作者：
Afsharpad, Mandana;Zakeri, Sedigheh;Djadid, Navid Dinparast
这项调查的主要目的是联合治疗磺胺嘧啶乙胺嘧啶（SP）加青蒿琥酯（AS）是否防止传播的耐药性SP在疟疾流行的伊朗东南部。在伊朗采用SP-AS作为一线治疗后，于2008-2010年期间收集了恶性疟原虫感染的血液样本（n = 170）。采用PCR-RFLP方法分析了恶性疟原虫与SP和CQ耐药相关的4个基因：二氢蝶酸合成酶（pfdhps）、二氢叶酸还原酶（pfdhfr）、氯喹耐药转运蛋白（pfcrt K76 T）和多药耐药细胞（pfmdr 1 N86 Y）。结果显示pfdhfr 51 I、59 R和108 N的检出率分别为4.1%、95.9%和100%，绝大多数患者（95.9%）同时携带59 R和108 N。pfdhps 437 G基因单突变率在SP-AS治疗前为26.9%，但随着SP-AS作为一线治疗，该突变率开始上升，至2008年达到55.5%的高水平（χ 2检验，P < 0.05）。然而，在引入SP-AS三年后，患病率从55.5%（2008年）降至39.1%（2009年），然后降至40.5%（2010年）。携带pfdhfr/pfdhps突变（N51 R59 N105/G（437））的寄生虫频率从2008年的53.3%下降到2009年的39.1%和2010年的38%。此外，在研究地区停止使用CQ治疗恶性疟原虫后，未观察到pfcrt 76 T和pfmdr 1 86 Y突变等位基因频率的显著降低。这可以通过pfcrt 76 T在恶性疟原虫群体中的固定来解释，在该区域没有药物压力的情况下，恶性疟原虫群体需要更多的时间从CQ敏感性恢复。总之，目前的研究结果表明，在伊朗，SP仍然是有效的治疗简单的恶性疟疾作为合作伙伴药物青蒿素联合治疗（ACT）在该地区。(C)2011爱思唯尔有限公司版权所有。
The main objective of this investigation was whether the combination therapy of sulfadoxine pyrimethamine (SP) plus artesunate (AS) protects against the spread of resistance to SP in malaria-endemic south-eastern Iran. Infected blood samples of Plasmodium falciparum (n = 170) were collected during 2008-2010 after the adoption of SP-AS as the first line treatment in Iran. Four different genes of P. falciparum [dihydropteroate synthetase (pfdhps), dihydrofolate reductase (pfdhfr), chloroquine (CQ) resistance transporter (pfcrt K76T) and multidrug resistancel (pfmdr1 N86Y)], associated with SP and CQ resistance were analyzed using PCR-RFLP methods. The result showed 4.1, 95.9 and 100% prevalence of pfdhfr 51I, 59R and 108N, respectively and the majority of patients (95.9%) were found to carry both 59R and 108N. The prevalence of single mutation at pfdhps 437G gene was 26.9% before the adoption of SP-AS, but as SP was used as the first line treatment; this mutation started to increase and reached a high level of 55.5% in 2008 (chi(2) test, P < 0.05). However, three years after the introduction of SP-AS, this prevalence was reduced from 55.5% (in 2008) to 39.1% (in 2009) and then 40.5% (in 2010). The frequency of parasites carrying pfdhfr/pfdhps mutations (N51R59N105/G(437)) decreased from 53.3% in 2008 to 39.1% in 2009 and 38% in 2010. In addition, no significant reduction was seen in the frequency of mutant alleles of pfcrt 76T and pfmdr1 86Y after CQ was discontinued from study areas as a treatment for P. falciparum. This is explained by the fixation of pfcrt 76T in the falciparum populations that need more time to recover from CQ sensitivity in the absence of drug pressure in this region. In conclusion, the present findings suggest that in Iran, SP is still effective for the treatment of uncomplicated falciparum malaria as a partner drug of Artemisinin Combination Therapy (ACT) in this region. (C) 2011 Elsevier B.V. All rights reserved.