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寄生虫遗传多样性反映了南非林波波省热点地区威姆比地区持续存在的残留疟疾传播。

Parasite genetic diversity reflects continued residual malaria transmission in Vhembe District, a hotspot in the Limpopo Province of South Africa.

机构信息

Malaria Parasite Molecular Laboratory, Department of Biochemistry, Genetics and Microbiology, Institute for Sustainable Malaria Control, University of Pretoria, Private Bag X20, Hatfield, 0028, Pretoria, South Africa.

Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.

出版信息

Malar J. 2021 Feb 16;20(1):96. doi: 10.1186/s12936-021-03635-z.

Abstract

BACKGROUND

South Africa aims to eliminate malaria transmission by 2023. However, despite sustained vector control efforts and case management interventions, the Vhembe District remains a malaria transmission hotspot. To better understand Plasmodium falciparum transmission dynamics in the area, this study characterized the genetic diversity of parasites circulating within the Vhembe District.

METHODS

A total of 1153 falciparum-positive rapid diagnostic tests (RDTs) were randomly collected from seven clinics within the district, over three consecutive years (2016, 2017 and 2018) during the wet and dry malaria transmission seasons. Using 26 neutral microsatellite markers, differences in genetic diversity were described using a multiparameter scale of multiplicity of infection (MOI), inbreeding metric (Fws), number of unique alleles (A), expected heterozygosity (He), multilocus linkage disequilibrium (LD) and genetic differentiation, and were associated with temporal and geospatial variances.

RESULTS

A total of 747 (65%) samples were successfully genotyped. Moderate to high genetic diversity (mean He = 0.74 ± 0.03) was observed in the parasite population. This was ascribed to high allelic richness (mean A = 12.2 ± 1.2). The majority of samples (99%) had unique multi-locus genotypes, indicating high genetic diversity in the sample set. Complex infections were observed in 66% of samples (mean MOI = 2.13 ± 0.04), with 33% of infections showing high within-host diversity as described by the Fws metric. Low, but significant LD (standardised index of association, ISA = 0.08, P < 0.001) was observed that indicates recombination of distinct clones. Limited impact of temporal (F range - 0.00005 to 0.0003) and spatial (F = - 0.028 to 0.023) variation on genetic diversity existed during the sampling timeframe and study sites respectively.

CONCLUSIONS

Consistent with the Vhembe District's classification as a 'high' transmission setting within South Africa, P. falciparum diversity in the area was moderate to high and complex. This study showed that genetic diversity within the parasite population reflects the continued residual transmission observed in the Vhembe District. This data can be used as a reference point for the assessment of the effectiveness of on-going interventions over time, the identification of imported cases and/or outbreaks, as well as monitoring for the potential spread of anti-malarial drug resistance.

摘要

背景

南非计划在 2023 年消除疟疾传播。然而,尽管持续进行病媒控制工作和病例管理干预,韦林德拉地区仍然是疟疾传播的热点地区。为了更好地了解该地区间日疟原虫的传播动态,本研究对韦林德拉地区循环寄生虫的遗传多样性进行了特征描述。

方法

在连续三年(2016 年、2017 年和 2018 年)的湿季和干季疟疾传播季节,从该地区的七个诊所中随机收集了 1153 份间日疟原虫阳性快速诊断检测(RDT)。使用 26 个中性微卫星标记,通过多重感染(MOI)、近亲繁殖度量(Fws)、独特等位基因数(A)、预期杂合度(He)、多位点连锁不平衡(LD)和遗传分化等多参数尺度来描述遗传多样性,并将其与时间和地理空间方差相关联。

结果

共有 747 个(65%)样本成功进行了基因分型。寄生虫种群中观察到中等至高度遗传多样性(平均 He=0.74±0.03)。这归因于高等位基因丰富度(平均 A=12.2±1.2)。大多数样本(99%)具有独特的多基因座基因型,表明样本集中遗传多样性高。在 66%的样本中观察到复杂感染(平均 MOI=2.13±0.04),33%的感染显示出由 Fws 度量描述的高宿主内多样性。观察到低度但显著的 LD(标准化关联指数,ISA=0.08,P<0.001),表明不同克隆之间发生了重组。在采样时间框架内,遗传多样性受时间(F 范围-0.00005 至 0.0003)和空间(F=-0.028 至 0.023)变化的影响有限。

结论

与韦林德拉地区在南非被归类为“高”传播地区一致,该地区间日疟原虫的多样性为中等至高且复杂。本研究表明,寄生虫种群内的遗传多样性反映了在韦林德拉地区持续观察到的残留传播。该数据可作为评估随着时间推移进行中的干预措施的有效性、鉴定输入病例和/或暴发以及监测抗疟药物耐药性潜在传播的参考点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee68/7885214/1346e6894ef7/12936_2021_3635_Fig1_HTML.jpg

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