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2016 年至 2020 年间从尼日利亚输入的恶性疟原虫分离株的耐药基因分子流行病学:完全耐药等位基因的持续出现。

Molecular Epidemiology of Drug Resistance Genes in Plasmodium falciparum Isolates Imported from Nigeria between 2016 and 2020: Continued Emergence of Fully Resistant - Alleles.

机构信息

Zhejiang Provincial Center for Disease Control and Prevention, Zhejiang, People's Republic of China.

出版信息

Microbiol Spectr. 2022 Oct 26;10(5):e0052822. doi: 10.1128/spectrum.00528-22. Epub 2022 Sep 15.

Abstract

Malaria poses public health threats worldwide. Nigeria accounted for the highest numbers of cases (26.8%) and deaths (31.9%) among countries where malaria is endemic in 2020. Currently, monitoring molecular markers in imported malaria cases provides an efficient means to screen for emerging drug resistance in countries where malaria is endemic, particularly in those where field surveillance is challenging. Here, we investigated 165 Plasmodium falciparum infections imported from Nigeria to Zhejiang Province, China, between 2016 and 2020. Multiple molecular markers in , , , , and were detected. The prevalences and patterns of mutations were analyzed. Polymorphism of was limited to 5 of 156 (3.21%) isolates. The wild-type CVMNK allele of became predominant (65.36%) compared with the triple mutation CVIET. A low frequency (4.73%) of double mutations (N86Y and Y184F) in was observed. The dominant haplotypes of and were DI (92.41%) and ISKAA (36.84%), respectively. The newly discovered mutant I431V was identified in 21.71% of isolates. A "fully resistant" combination of , IRN-GE, was found in eight (5.67%) samples, which was hardly seen in Nigeria. The current study demonstrated a high frequency of wild-type . Limited polymorphism of but a high prevalence of and mutations was illustrated. Our data so far serve as comprehensive surveillance of molecular markers of the , , , , and genes. Based on our findings, it has become crucial to evaluate the impact of the emerging fully resistant type of - as well as its combination with I431V on the efficacy of sulfadoxine-pyrimethamine (SP) in Nigeria. Monitoring the current resistance to antimalarial drugs is critical to enable timely action to prevent its spread and limit its impact. The high prevalence of wild-type found in our study is an optimistic signal to reevaluate chloroquine (CQ) sensitivity in Nigeria, which is cost-effective and once played a crucial role in the fight against malaria. Based on the continued emergence of fully resistant - alleles illustrated in the current investigation, actions are needed in Nigeria, such as national systemic surveillance to monitor their updated epidemiology as well as assessments of their influence on SP efficacy to minimize any public health impact. These findings urge a response to the threat of drug resistance to facilitate appropriate drug policies in the study area.

摘要

疟疾对全球公共卫生构成威胁。在 2020 年疟疾流行的国家中,尼日利亚的疟疾病例(26.8%)和死亡人数(31.9%)均居首位。目前,监测输入性疟疾病例中的分子标记物为在疟疾流行的国家中筛查新出现的耐药性提供了一种有效的手段,特别是在现场监测具有挑战性的国家。在这里,我们调查了 2016 年至 2020 年间从尼日利亚输入到中国浙江省的 165 例恶性疟原虫感染。检测到 、 、 、 和 中的多个分子标记物。分析了突变的流行率和模式。 的多态性仅限于 156 个分离株中的 5 个(3.21%)。与三重突变 CVIET 相比, 野生型 CVMNK 等位基因成为主要(65.36%)。 在 中观察到双突变(N86Y 和 Y184F)的低频(4.73%)。 和 的主要单倍型分别为 DI(92.41%)和 ISKAA(36.84%)。在 21.71%的分离株中发现了新发现的突变 I431V。在 8 份(5.67%)样本中发现了 “完全耐药”的 、IRN-GE 组合,在尼日利亚几乎未见。目前的研究表明 野生型的高频率 。 但 多态性有限, 和 突变的流行率很高。我们迄今为止的数据为 、 、 、 和 基因的分子标记物的全面监测提供了依据。基于我们的发现,评估新型完全耐药型 - 及其与 I431V 的组合对尼日利亚磺胺多辛-乙胺嘧啶(SP)疗效的影响变得至关重要。监测抗疟药物的当前耐药性对于及时采取行动防止其传播和限制其影响至关重要。我们的研究发现野生型 高流行率是重新评估尼日利亚氯喹(CQ)敏感性的一个乐观信号,氯喹具有成本效益,在抗击疟疾方面曾发挥关键作用。基于当前研究中显示的新型完全耐药 - 等位基因的持续出现,尼日利亚需要采取行动,例如进行全国系统监测,以监测其最新的流行病学,并评估其对 SP 疗效的影响,以尽量减少任何对公共卫生的影响。这些发现促使对耐药性威胁做出反应,以促进在研究地区制定适当的药物政策。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fc8/9604097/f0d8e253f1bf/spectrum.00528-22-f001.jpg

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