Prevalence of the Pfdhfr and Pfdhps mutations among asymptomatic pregnant women in Southeast Nigeria

Prevalence of the Pfdhfr and Pfdhps mutations among asymptomatic pregnant women in Southeast Nigeria
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DOI:
10.1007/s00436-018-5754-5
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发表时间:
2018-03-01
影响因子:
2
通讯作者:
Meremikwu, Martin
Meremikwu, Martin
中科院分区:
医学3区
文献类型:
--
作者:
Esu, Ekpereonne;Tacoli, Costanza;Meremikwu, Martin

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磺胺多辛-乙胺(SP)是撒哈拉以南非洲大部分地区用于孕期疟疾间歇预防治疗的推荐药物。恶性疟原虫对SP的抗性与dhfr和dhps基因突变有关。这项研究确定了在尼日利亚卡拉巴尔接受产前护理的无症状孕妇中发现的Pfdhfr和Pfdhps基因多态的流行率。2013年10月至2014年11月,在产前护理诊所就诊的无症状孕妇在获得知情同意后进行登记。疟疾诊断测试是使用厚薄涂片进行的。收集干血斑滤纸。用螯合萃取法从滤纸中提取寄生虫DNA。提取后进行套式聚合酶链式反应和限制性内切酶酶切。镜检发现7%(32/459)的受试者感染了恶性疟原虫。对28株恶性疟原虫分离株进行了基因分型。Pfdhfr基因三重突变基本固定,S108N突变为100%,N51I突变为93%,C59R突变为93%,而I164L突变缺失。Pfdhps S436A、A437G、A581G和A613S突变的发生率分别为82.1%(23/28)、96.4%(27/28)、71.4%(20/28)和71.4%(20/28)。K540E突变缺失。Pfdhfr三重突变IRNI的发生率为92.9%(26/28)。在尼日利亚东南部,SP作为IPTp的效力可能受到严重威胁。需要对抗性的SP分子标记进行持续监测,以评估阈值。可能有必要评估预防孕期疟疾的替代预防治疗战略和药物选择。
Sulfadoxine-pyrimethamine (SP) is the recommended drug for intermittent preventive treatment of malaria in pregnancy in most of sub-Saharan Africa. Resistance to SP is related to mutations in the dhfr and dhps gene of Plasmodium falciparum. This study determined the prevalence of Pfdhfr and Pfdhps polymorphisms found in asymptomatic pregnant women attending antenatal care in Calabar, Nigeria. From October 2013 to November 2014, asymptomatic pregnant women attending antenatal care clinics were enrolled after obtaining informed consent. Malaria diagnosis testing was done using thick and thin smears. Dried blood spot filter papers were collected. Parasite DNA was extracted from the filter papers using a chelex extraction. Extraction was followed by nested PCR and restriction enzyme digestion. P. falciparum infection was detected by microscopy in 7% (32/459) participants. Twenty-eight P. falciparum isolates were successfully genotyped. In the Pfdhfr gene, the triple mutation was almost fixed; S108N mutation was (100%), N51I (93%) and C59R mutations (93%), whereas the I164L mutation was absent. The prevalence of Pfdhps S436A, A437G, A581G and A613S mutations was 82.1% (23/28), 96.4% (27/28), 71.4% (20/28) and 71.4% (20/28) respectively. The K540E mutation was absent. The prevalence of the Pfdhfr triple mutation IRNI was 92.9% (26/28). The efficacy of SP as IPTp in Southeast Nigeria may be severely threatened. The continuous monitoring of SP molecular markers of resistance is required to assess thresholds. The evaluation of alternative preventive treatment strategies and drug options for preventing malaria in pregnancy may be necessary.