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- Title
Flexible and cost-effective genomic surveillance of P. falciparum malaria with targeted nanopore sequencing.
- Authors
de Cesare, Mariateresa; Mwenda, Mulenga; Jeffreys, Anna E.; Chirwa, Jacob; Drakeley, Chris; Schneider, Kammerle; Mambwe, Brenda; Glanz, Karolina; Ntalla, Christina; Carrasquilla, Manuela; Portugal, Silvia; Verity, Robert J.; Bailey, Jeffrey A.; Ghinai, Isaac; Busby, George B.; Hamainza, Busiku; Hawela, Moonga; Bridges, Daniel J.; Hendry, Jason A.
- Abstract
Genomic surveillance of Plasmodium falciparum malaria can provide policy-relevant information about antimalarial drug resistance, diagnostic test failure, and the evolution of vaccine targets. Yet the large and low complexity genome of P. falciparum complicates the development of genomic methods, while resource constraints in malaria endemic regions can limit their deployment. Here, we demonstrate an approach for targeted nanopore sequencing of P. falciparum from dried blood spots (DBS) that enables cost-effective genomic surveillance of malaria in low-resource settings. We release software that facilitates flexible design of amplicon sequencing panels and use this software to design two target panels for P. falciparum. The panels generate 3–4 kbp reads for eight and sixteen targets respectively, covering key drug-resistance associated genes, diagnostic test antigens, polymorphic markers and the vaccine target csp. We validate our approach on mock and field samples, demonstrating robust sequencing coverage, accurate variant calls within coding sequences, the ability to explore P. falciparum within-sample diversity and to detect deletions underlying rapid diagnostic test failure. Genomic surveillance of Plasmodium falciparum could improve monitoring of drug resistance, but implementation has been hampered due to the large and complex genome. Here, de Cesare et al. develop a flexible and cost-effective nanopore sequencing approach to detect drug resistance and diagnostic escape for P. falciparum malaria.
- Subjects
RAPID diagnostic tests; MALARIA; RESOURCE-limited settings; DRUG monitoring; DRUG resistance
- Publication
Nature Communications, 2024, Vol 15, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-45688-z