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利用伊维菌素治疗前后获得的单个微丝蚴的线粒体基因组测序评估感染强度和遗传多样性。

Assessing Intensity of Infection and Genetic Diversity Using Mitochondrial Genome Sequencing of Single Microfilariae Obtained before and after Ivermectin Treatment.

作者信息

Hedtke Shannon M, Choi Young-Jun, Kode Anusha, Chalasani Gowtam C, Sirwani Neha, Jada Stephen R, Hotterbeekx An, Mandro Michel, Siewe Fodjo Joseph N, Amambo Glory Ngongeh, Abong Raphael A, Wanji Samuel, Kuesel Annette C, Colebunders Robert, Mitreva Makedonka, Grant Warwick N

机构信息

Department of Environment and Genetics, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, VIC 3086, Australia.

Department of Medicine, Washington University in St. Louis and McDonnell Genome Institute, St. Louis, MO 63108, USA.

出版信息

Pathogens. 2023 Jul 24;12(7):971. doi: 10.3390/pathogens12070971.

DOI:10.3390/pathogens12070971
PMID:37513818
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10385737/
Abstract

Onchocerciasis is a neglected tropical disease targeted for elimination using ivermectin mass administration. Ivermectin kills the microfilariae and temporarily arrests microfilariae production by the macrofilariae. We genotyped 436 microfilariae from 10 people each in Ituri, Democratic Republic of the Congo (DRC), and Maridi County, South Sudan, collected before and 4-5 months after ivermectin treatment. Population genetic analyses identified 52 and 103 mitochondrial DNA haplotypes among the microfilariae from DRC and South Sudan, respectively, with few haplotypes shared between people. The percentage of genotype-based correct assignment to person within DRC was ~88% and within South Sudan ~64%. Rarefaction and extrapolation analysis showed that the genetic diversity in DRC, and even more so in South Sudan, was captured incompletely. The results indicate that the per-person adult worm burden is likely higher in South Sudan than DRC. Analyses of haplotype data from a subsample ( = 4) did not discriminate genetically between pre- and post-treatment microfilariae, confirming that post-treatment microfilariae are not the result of new infections. With appropriate sampling, mitochondrial haplotype analysis could help monitor changes in the number of macrofilariae in a population as a result of treatment, identify cases of potential treatment failure, and detect new infections as an indicator of continuing transmission.

摘要

盘尾丝虫病是一种被忽视的热带疾病,目标是通过大规模施用伊维菌素予以消除。伊维菌素可杀死微丝蚴,并暂时阻止成虫产生微丝蚴。我们对来自刚果民主共和国(DRC)伊图里和南苏丹马迪县的10人身上采集的436条微丝蚴进行了基因分型,这些微丝蚴是在伊维菌素治疗前及治疗后4 - 5个月采集的。群体遗传学分析分别在来自刚果民主共和国和南苏丹的微丝蚴中鉴定出52种和103种线粒体DNA单倍型,人与人之间共享的单倍型很少。在刚果民主共和国内,基于基因型正确归属于个人的比例约为88%,在南苏丹约为64%。稀疏化和外推分析表明,刚果民主共和国的遗传多样性,尤其是南苏丹的遗传多样性,并未被完全捕获。结果表明,南苏丹每人的成虫负担可能高于刚果民主共和国。对一个子样本( = 4)的单倍型数据进行分析,未在治疗前和治疗后的微丝蚴之间进行基因区分,证实治疗后的微丝蚴不是新感染的结果。通过适当的采样,线粒体单倍型分析有助于监测治疗后人群中成虫数量的变化,识别潜在治疗失败的病例,并检测新感染情况,作为持续传播的指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f25c/10385737/485a43629fe5/pathogens-12-00971-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f25c/10385737/9718c8d40d30/pathogens-12-00971-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f25c/10385737/b42b542bc280/pathogens-12-00971-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f25c/10385737/151b9ec426e6/pathogens-12-00971-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f25c/10385737/001f7a543eb2/pathogens-12-00971-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f25c/10385737/485a43629fe5/pathogens-12-00971-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f25c/10385737/9718c8d40d30/pathogens-12-00971-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f25c/10385737/b42b542bc280/pathogens-12-00971-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f25c/10385737/151b9ec426e6/pathogens-12-00971-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f25c/10385737/001f7a543eb2/pathogens-12-00971-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f25c/10385737/485a43629fe5/pathogens-12-00971-g005.jpg

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