Genomic malaria surveillance of antenatal care users detects reduced transmission following elimination interventions in Mozambique

Brokhattingen, Nanna; Matambisso, Glória; da Silva, Clemente; Neubauer Vickers, Eric; Pujol, Arnau; Mbeve, Henriques; Cisteró, Pau; Maculuve, Sónia; Cuna, Boaventura; Melembe, Cardoso; Ndimande, Nelo; Palmer, Brian; García-Ulloa, Manuel; Munguambe, Humberto; Montaña-Lopez, Júlia; Nhamussua, Lidia; Simone, Wilson; Chidimatembue, Arlindo; Galatas, Beatriz; Guinovart, Caterina; Rovira-Vallbona, Eduard; Saúte, Francisco; Aide, Pedro; Aranda-Díaz, Andrés; Greenhouse, Bryan; Macete, Eusébio; Mayor, Alfredo

doi:10.1038/s41467-024-46535-x

Cited by 8 publications

References 36 publications

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

Onyamboko,

Wasakul,

Bakomba

et al. 2024

Preprint

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Genomic surveillance is a valuable tool for detecting changes in the drug susceptibility of malaria parasites, allowing early modification of treatment strategies. However, implementation can be costly and problematic to set up in fragile and high-burden countries, especially when targeting cohorts of children. To address these challenges, we investigated whether in the Democratic Republic of Congo pregnant women attending antenatal care (ANC) services could act as a surrogate sentinel population. Between 2021 and 2023, we conducted a study in Kinshasa, targeting 4,001 pregnant women attending ANCs, and 2,794 children living in the same area. 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 mutations prevalence. Parasite populations sampled from the two cohorts exhibited highly similar allele frequencies at all tested loci, including drug resistance markers potentially under selection. Pregnant women did not have higher frequencies of sulphadoxine-pyrimethamine resistant haplotypes, which undermine preventive treatments, than children, and we did not find any kelch13 mutation at significant frequency. Although parasite densities were lower in adults, the complexity of infection was similar to that in children. There was no evidence of Plasmodium vivax infections in the study. A cohort of pregnant women produces highly similar results to those from children, allowing the implementation of simple and efficient genomic surveillance systems integrated into routine ANC activities, while benefitting women with diagnosis and treatment. ClinicalTrials.gov Identifier:NCT05072613.

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

Onyamboko,

Wasakul,

Bakomba

et al. 2024

Preprint

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Sensitive and modular amplicon sequencing ofPlasmodium falciparumdiversity and resistance for research and public health

Aranda-Díaz,

Vickers,

Murie

et al. 2024

Preprint

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Targeted amplicon sequencing is a powerful and efficient tool to interrogate theP.falciparumgenome and generate actionable data from infections to complement traditional malaria epidemiology. For maximum impact, genomic tools should be multi-purpose, robust, sensitive and reproducible. We developed, characterized, and implemented MAD4HatTeR, an amplicon sequencing panel based on Multiplex Amplicons for Drug, Diagnostic, Diversity, and Differentiation Haplotypes using Targeted Resequencing, along with a bioinformatic pipeline for data analysis. MAD4HatTeR targets 165 highly diverse loci, focusing on multiallelic microhaplotypes; key markers for drug and diagnostic resistance, including duplications and deletions; andcspand potential vaccine targets. In addition, it can detect non-falciparumPlasmodiumspecies. We used laboratory control and field sample data to demonstrate the high sensitivity and robustness of the panel. The successful implementation of this method in five laboratories, including three in malaria-endemic African countries, showcases its feasibility in generating reproducible data across laboratories. Finally, we introduce an analytical approach to detect gene duplications and deletions from amplicon sequencing data. MAD4HatTeR is thus a powerful research tool and a robust resource for malaria public health surveillance and control.

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Plasmodium falciparummolecular surveillance to inform the Mozambican National Malaria Control Programme strategy: protocol

da Silva,

Matambisso,

Boene

et al. 2024

BMJ Open

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IntroductionMalaria molecular surveillance has the potential to generate information on biological threats that compromise the effectiveness of antimalarial interventions. This study aims to streamline surveillance activities to inform the new strategic plan of the Mozambican National Malaria Control Programme (2023–2030) for malaria control and elimination.Methods and analysesThis prospective genomic surveillance study aims to generatePlasmodium falciparumgenetic data to monitor diagnostic failures due topfhrp2/3deletions and molecular markers of antimalarial drug resistance, to characterise transmission sources and to inform the implementation of new antimalarial approaches to be introduced in Mozambique (chemoprevention and child malaria vaccination). The study, to be conducted between 2024 and 2026, will use three sampling schemes: a multicluster probabilistic health facility survey in the 10 provinces of the country to detectpfhrp2/3deletions and markers of antimalarial drug resistance; dense sampling of all clinical cases in representative districts in the south targeted for elimination to characterise malaria importation and identify sources of transmission; and testing of pregnant women for malaria at their first antenatal care visit to assess malaria burden and molecular trends. Using a multiplex amplicon-based sequencing approach, the study will target microhaplotypes informative of genomic diversity and relatedness, as well as key drug resistance-associated genes,pfhrp2/3deletion and malaria vaccine targets. Key genomic information will be visualised in a dashboard integrated into the District Health Information System V.2-based Malaria Information Storage System for programmatic use.Ethics and disseminationThe protocol was reviewed and approved by the national ethics committee of Mozambique (Comité Nacional de Bioética para Saúde, Ref: 680/CNBS/23). Project results will be presented to all stakeholders using study-specific brochures and published in open-access journals.Trial registration numberNCT06529237.

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Genomic malaria surveillance of antenatal care users detects reduced transmission following elimination interventions in Mozambique

Cited by 8 publications

References 36 publications

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

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

Sensitive and modular amplicon sequencing ofPlasmodium falciparumdiversity and resistance for research and public health

Plasmodium falciparummolecular surveillance to inform the Mozambican National Malaria Control Programme strategy: protocol

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