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尼日利亚东南部无症状孕妇中Pfdhfr和Pfdhps基因突变的流行情况。

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

作者信息

Esu Ekpereonne, Tacoli Costanza, Gai Prabhanjan, Berens-Riha Nicole, Pritsch Michael, Loescher Thomas, Meremikwu Martin

机构信息

Center for International Health (CIH), Ludwig-Maximilians-Universität (LMU), Leopoldstraße 7, 80802, Munich, Germany.

Department of Public Health, College of Medical Sciences, University of Calabar, Calabar, Nigeria.

出版信息

Parasitol Res. 2018 Mar;117(3):801-807. doi: 10.1007/s00436-018-5754-5. Epub 2018 Jan 13.

Abstract

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.

摘要

磺胺多辛-乙胺嘧啶(SP)是撒哈拉以南非洲大部分地区孕期疟疾间歇性预防治疗的推荐药物。对SP的耐药性与恶性疟原虫的二氢叶酸还原酶(dhfr)和二氢蝶酸合成酶(dhps)基因突变有关。本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恶性疟原虫二氢叶酸还原酶(Pfdhfr)和二氢蝶酸合成酶(Pfdhps)多态性的流行情况。2013年10月至2014年11月,在获得知情同意后,招募了在产前护理诊所就诊的无症状孕妇。使用厚涂片和薄涂片进行疟疾诊断检测。收集干血斑滤纸。使用螯合树脂提取法从滤纸中提取寄生虫DNA。提取后进行巢式聚合酶链反应(PCR)和限制性内切酶消化。通过显微镜检查在7%(32/459)的参与者中检测到恶性疟原虫感染。成功对28株恶性疟原虫分离株进行了基因分型。在Pfdhfr基因中,三重突变几乎固定;S108N突变率为(100%),N51I为(93%),C59R突变为(93%),而I164L突变不存在。Pfdhps S436A、A437G、A581G和A613S突变的流行率分别为82.1%(23/28)、96.4%(27/28)、71.4%(20/28)和71.4%(20/28)。K540E突变不存在。Pfdhfr三重突变IRNI的流行率为92.9%(26/28)。SP作为尼日利亚东南部孕期间歇性预防治疗药物(IPTp)的疗效可能受到严重威胁。需要持续监测SP耐药分子标记以评估阈值。可能有必要评估预防孕期疟疾的替代预防治疗策略和药物选择。

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