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

在刚果民主共和国,以孕妇为哨兵人群开展疟疾基因组监测:一项基于人群的研究

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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.

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