马里两个村庄中恶性疟原虫感染的复杂性以及与寄生虫清除时间差异相关的基因变异

Complexity of Plasmodium falciparum infection and genetic variations associated with differences in parasite clearance time in two Malian villages.

作者信息

Sissoko Sekou, Kone Aminatou, Dara Antoine, Oboh Mary Aigbiremo, Fofana Bakary, Sangare Cheick O, Dembele Demba, Haidara Aboubecrine Sedhigh, Diallo Nouhoum, Toure Sekou, Haidara Kadidia, Sanogo Kassim, Doumbo Ogobara K, Ouattar Amed, Amambua-Ngwa Alfred, Djimde Abdoulaye A

机构信息

Malaria Research and Training Center, Faculty of Pharmacy, University of Sciences, Techniques and Technologies of Bamako.

Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical.

出版信息

Res Sq. 2023 Jun 26:rs.3.rs-3083860. doi: 10.21203/rs.3.rs-3083860/v1.

DOI:10.21203/rs.3.rs-3083860/v1

PMID:37461533

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10350111/

Abstract

BACKGROUND

Effective approaches to fight against malaria include disease prevention, an early diagnosis of malaria cases, and rapid management of confirmed cases by treatment with effective antimalarials. Artemisinin-based combination therapies are first-line treatments for uncomplicated malaria in endemic areas. However, cases of resistance to artemisinin have already been described in South-East Asia resulting in prolonged parasite clearance time after treatment. In Mali, though mutations in the K13 gene associated with delayed clearance in Asia are absent, a significant difference in parasite clearance time following treatment with artesunate was observed between two malaria endemic sites, Bougoula-Hameau and Faladje. Hypothetically, differences in complexity of infections may be accounted for this difference. Hence, the aims of this study were to assess the complexity of infection (COI) and genetic diversity of parasites during malaria treatment in Bougoula-Hameau and Faladje in Mali.

METHODS

Thirty (30) patients per village were randomly selected from 221 patients enrolled in a prospective artesunate monotherapy study conducted in Faladje and Bougoula-Hameau in 2016. All parasitemic blood samples of patients from enrollment to last positive slide were retained to assess malaria parasite COI and polymorphisms. DNA were extracted with a Qiagen kit and and encoding gene were amplified by nested PCR and sequenced using the Illumina platform. The parasite clearance time (PCT) was determined using the parasite clearance estimator of Worldwide Antimarial Resistance Network (WWARN). Data were analyzed with R.

RESULTS

The median number of genetically distinct parasite clones was similar at enrollment, 7 (IQR of 5-9) in Faladje and 6 (IQR of 4-10) in Bougoula-Hameau (p-value = 0.1). On the first day after treatment initiation, the COI was higher in Faladje (6; CI:4-8) than in Bougoula-Hameau (4; CI:4-6) with a p-value =0. 02. Overall, COI was high with higher PCT. Finally, there was a low genetic diversity between Faladje and Bougoula-Hameau.

CONCLUSION

This study demonstrated that the difference in PCT observed between the two villages could be due to differences in the complexity of infection of these two villages.

摘要

背景

抗击疟疾的有效方法包括疾病预防、疟疾病例的早期诊断以及通过使用有效的抗疟药物对确诊病例进行快速治疗。以青蒿素为基础的联合疗法是疟疾流行地区非复杂性疟疾的一线治疗方法。然而，东南亚已经出现了对青蒿素耐药的病例，导致治疗后寄生虫清除时间延长。在马里，虽然不存在与亚洲延迟清除相关的K13基因突变，但在两个疟疾流行地区布古拉-哈莫和法拉杰，观察到青蒿琥酯治疗后寄生虫清除时间存在显著差异。从理论上讲，感染复杂性的差异可能是造成这种差异的原因。因此，本研究的目的是评估马里布古拉-哈莫和法拉杰疟疾治疗期间的感染复杂性（COI）和寄生虫的遗传多样性。

方法

从2016年在法拉杰和布古拉-哈莫进行的一项前瞻性青蒿琥酯单药治疗研究中登记的221名患者中，每个村庄随机选取30名患者。保留患者从入组到最后一次阳性涂片的所有寄生虫血症血样，以评估疟原虫COI和多态性。使用Qiagen试剂盒提取DNA，通过巢式PCR扩增编码基因，并使用Illumina平台进行测序。使用全球抗疟耐药网络（WWARN）的寄生虫清除估计器确定寄生虫清除时间（PCT）。数据用R软件进行分析。

结果

入组时，遗传上不同的寄生虫克隆的中位数在法拉杰为7（四分位间距为5-9），在布古拉-哈莫为6（四分位间距为4-10），两者相似（p值=0.1）。在开始治疗后的第一天，法拉杰的COI（6；置信区间：4-8）高于布古拉-哈莫（4；置信区间：4-6），p值=0.02。总体而言，COI较高，PCT也较高。最后，法拉杰和布古拉-哈莫之间的遗传多样性较低。