Drug resistance profile and clonality of Plasmodium falciparum parasites in Cape Verde: the 2017 malaria outbreak.

Drug resistance profile and clonality of Plasmodium falciparum parasites in Cape Verde: the 2017 malaria outbreak.
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DOI:
10.1186/s12936-021-03708-z
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发表时间:
2021-03-31
期刊:
影响因子:
3
通讯作者:
Nogueira F
Nogueira F
中科院分区:
医学3区
文献类型:
--
作者:
Da Veiga Leal S;Ward D;Campino S;Benavente ED;Ibrahim A;Claret T;Isaías V;Monteiro D;Clark TG;Gonçalves L;Valdez T;da Luz Lima Mendonça M;Silveira H;Nogueira F

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佛得角是一个位于西非海岸外的群岛,目前正处于疟疾控制的消灭前阶段。自2010年以来,每年报告的恶性疟疾病例不到20例,但2017年除外,当时雨季前普拉亚爆发导致423例本土病例。了解循环中恶性疟原虫的遗传多样性对于了解耐药性、潜在的传播网络和感染源,包括寄生虫输入是很重要的。登记对象包括2017年7月至10月期间在佛得角圣地亚哥岛普拉亚市Agostinho Neto医生医院住院的疟疾患者。对登记病例的邻居和家人进行了抗-P抗体检测。恶性疟原虫抗体。采用Sanger测序和实时定量聚合酶链式反应(Real-Time-PCR)技术分析恶性疟原虫耐药相关基因(如pfdhfr、pfdhps、pfmdr1、pfk13、pfcrt)中的SNPs,并生成全基因组测序数据,以研究恶性疟原虫的种群结构。这项研究分析了190份寄生虫样本,其中187份来自本土,3份来自外地感染。疟疾病例分布在普拉亚市各地。没有严重疟疾病例,所有患者在治疗后都有足够的临床和寄生虫学反应。抗P。在接受检测的137名邻居和家庭成员中,没有检测到恶性疟原虫抗体。未检测到pfdhps基因突变。Pfdhfr基因的S108N/N51I/C59R三重突变和pfcrt基因的抗氯喹CVIET单倍型几乎在所有样本中都被检测到。仅在一个样本(R645T、E668K)中发现了pfk13的变异。Pfmdr1单倍型NFD在大多数样本中检出(89.7%)。东南亚地区未检测到与青蒿素联合疗法(ACT)耐受性相关的pfk13基因多态性,但大多数受测样本携带pfmdr1单倍型NFD以及pfcrt和pfdhfr基因中的抗疟疾相关突变。对佛得角寄生虫进行了第一次全基因组测序,结果表明,样本聚集在一起,具有非常高的相似性,并且与西非的其他寄生虫种群接近。网上版载有补充材料,可在10.1186/s12936-021-03708-z查阅。
Cape Verde is an archipelago located off the West African coast and is in a pre-elimination phase of malaria control. Since 2010, fewer than 20 Plasmodium falciparum malaria cases have been reported annually, except in 2017, when an outbreak in Praia before the rainy season led to 423 autochthonous cases. It is important to understand the genetic diversity of circulating P. falciparum to inform on drug resistance, potential transmission networks and sources of infection, including parasite importation. Enrolled subjects involved malaria patients admitted to Dr Agostinho Neto Hospital at Praia city, Santiago island, Cape Verde, between July and October 2017. Neighbours and family members of enrolled cases were assessed for the presence of anti-P. falciparum antibodies. Sanger sequencing and real-time PCR was used to identify SNPs in genes associated with drug resistance (e.g., pfdhfr, pfdhps, pfmdr1, pfk13, pfcrt), and whole genome sequencing data were generated to investigate the population structure of P. falciparum parasites. The study analysed 190 parasite samples, 187 indigenous and 3 from imported infections. Malaria cases were distributed throughout Praia city. There were no cases of severe malaria and all patients had an adequate clinical and parasitological response after treatment. Anti-P. falciparum antibodies were not detected in the 137 neighbours and family members tested. No mutations were detected in pfdhps. The triple mutation S108N/N51I/C59R in pfdhfr and the chloroquine-resistant CVIET haplotype in the pfcrt gene were detected in almost all samples. Variations in pfk13 were identified in only one sample (R645T, E668K). The haplotype NFD for pfmdr1 was detected in the majority of samples (89.7%). Polymorphisms in pfk13 associated with artemisinin-based combination therapy (ACT) tolerance in Southeast Asia were not detected, but the majority of the tested samples carried the pfmdr1 haplotype NFD and anti-malarial-associated mutations in the the pfcrt and pfdhfr genes. The first whole genome sequencing (WGS) was performed for Cape Verdean parasites that showed that the samples cluster together, have a very high level of similarity and are close to other parasites populations from West Africa. The online version contains supplementary material available at 10.1186/s12936-021-03708-z.
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