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刚果民主共和国将孕妇作为疟疾基因组监测的哨点人群:一项基于人群的研究。

Pregnant women as a sentinel population for genomic surveillance of malaria in the Democratic Republic of the Congo: a population-based study.

作者信息

Onyamboko Marie, Wasakul Varanya, Bakomba Sarah Benie, Kayembe Daddy Kalala, Nzambiwishe Bejos Kifakiou, Ekombolo Pascal Epe, Badjanga Benjamen Basara, Maindombe Jean-Robert Moke, Ngavuka Jephte Ndundu, Lwadi Brunette Nsunda, Drury Eleanor, Ariani Cristina, Goncalves Sonia, Chamsukhee Vanapol, Waithira Naomi, Verschuuren Tess D, Lee Sue J, Miotto Olivo, Fanello Caterina

机构信息

Kinshasa-Oxford Medical Research Unit, Kinshasa School of Public Health, University of Kinshasa, Kinshasa, Democratic Republic of the Congo.

Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

出版信息

Lancet Glob Health. 2025 Mar;13(3):e479-e487. doi: 10.1016/S2214-109X(24)00497-2.

Abstract

BACKGROUND

Genomic surveillance is a valuable tool for detecting changes in the drug susceptibility of malaria parasites, enabling timely adjustments to treatment strategies. However, implementation can be costly and challenging in high-burden countries, especially when targeting cohorts of children. To address these challenges, we investigated whether in the Democratic Republic of the Congo pregnant women attending antenatal care services could act as an effective sentinel population for children in the same area.

METHODS

This population-based study aimed to target pregnant women in Kinshasa (Democratic Republic of the Congo), regardless of age, trimester of pregnancy, parity, or previous antenatal care centre attendance, and children younger than 14 years living in the same area. Women were invited to participate and enrolled during their routine antenatal care visit. For children, we originally planned to conduct standard school-based surveys, but implementation was affected by the COVID-19 pandemic and subsequent vaccination campaign. Therefore, we adopted an alternative approach, setting up screening posts in existing health centres and, with the support of community health workers, encouraging families to visit the posts at their convenience. The study was done in two areas of Kinshasa, urban (Binza) and semirural (Maluku), where malaria transmission is endemic and perennial. Blood samples from malaria-positive cases were genotyped using an amplicon sequencing platform, to allow comparisons of Plasmodium falciparum genomes between the two cohorts and estimations of drug resistance mutation prevalence. The study is registered with ClinicalTrials.gov, NCT05072613.

FINDINGS

Between Nov 11, 2021, and June 21, 2023, 2794 children and 4001 pregnant women were recruited to the study. Malaria prevalence by rapid diagnostic test was 49·0% (95% CI 47·1-50·8) in children and 19·1% (17·9-20·3) in pregnant women. Parasite populations sampled from the two cohorts showed highly similar allele frequencies at all tested loci, including drug resistance markers potentially under selection. Pregnant women did not have higher frequencies of sulfadoxine-pyrimethamine resistant haplotypes, which undermine preventive treatments, than children and we did not find any kelch13 mutations at significant frequency. Although parasite densities were lower in pregnant women, the complexity of infection was similar to that in children. We found no evidence of Plasmodium vivax infections in the study.

INTERPRETATION

A cohort of pregnant women produced highly similar results for antimalarial drug resistance surveillance as a cohort of children from the same area, through implementation of simple and efficient genomic surveillance systems integrated into routine antenatal care activities, while benefiting women with diagnosis and treatment.

FUNDING

Bill & Melinda Gates Foundation and Wellcome Trust.

摘要

背景

基因组监测是检测疟原虫药物敏感性变化的重要工具,有助于及时调整治疗策略。然而,在高负担国家实施该监测可能成本高昂且具有挑战性,尤其是针对儿童群体时。为应对这些挑战,我们调查了在刚果民主共和国,接受产前保健服务的孕妇是否可作为同一地区儿童的有效监测人群。

方法

这项基于人群的研究旨在针对金沙萨(刚果民主共和国)的孕妇,无论其年龄、妊娠阶段、胎次或之前是否去过产前保健中心,以及居住在同一地区的14岁以下儿童。在孕妇进行常规产前检查时邀请并招募她们。对于儿童,我们原计划进行标准的学校调查,但实施过程受到了新冠疫情及后续疫苗接种活动的影响。因此,我们采用了另一种方法,在现有的健康中心设立筛查点,并在社区卫生工作者的支持下,鼓励家庭在方便时前往筛查点。该研究在金沙萨的两个地区进行,一个是城市地区(宾扎),另一个是半农村地区(马鲁库),这两个地区疟疾传播呈地方性且常年流行。对疟疾病例的血样使用扩增子测序平台进行基因分型,以便比较两个群体间的恶性疟原虫基因组,并估计耐药性突变的流行率。该研究已在ClinicalTrials.gov注册,注册号为NCT05072613。

结果

在2021年11月11日至2023年6月21日期间,共有2794名儿童和4001名孕妇被纳入研究。通过快速诊断检测得出的疟疾患病率在儿童中为49.0%(95%置信区间47.1 - 50.8),在孕妇中为19.1%(17.9 - 20.3)。从两个群体中采集的寄生虫种群在所有测试位点显示出高度相似的等位基因频率,包括可能处于选择状态的耐药性标记。孕妇中对磺胺多辛 - 乙胺嘧啶耐药单倍型的频率并不高于儿童,而这种单倍型会影响预防性治疗效果,并且我们未发现任何显著频率的kelch13突变。虽然孕妇体内的寄生虫密度较低,但其感染的复杂性与儿童相似。在该研究中我们未发现间日疟原虫感染的证据。

解读

通过实施整合到常规产前保健活动中的简单高效基因组监测系统,一组孕妇在抗疟药物耐药性监测方面产生了与来自同一地区的一组儿童高度相似的结果,同时还能使妇女受益于诊断和治疗。

资金来源

比尔及梅琳达·盖茨基金会和惠康信托基金会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d704/11868776/f58c5523fe90/gr1.jpg

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