Drug resistance and vaccine target surveillance of Plasmodium falciparum using nanopore sequencing in Ghana.
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Abstract
Malaria results in over 600,000 deaths annually, with the highest burden of deaths in young children living in sub-Saharan Africa. Molecular surveillance can provide important information for malaria control policies, including detection of antimalarial drug resistance. However, genome sequencing capacity in malaria-endemic countries is limited. We designed and implemented an end-to-end workflow to detect Plasmodium falciparum antimalarial resistance markers and diversity in the vaccine target circumsporozoite protein (csp) using nanopore sequencing in Ghana. We analysed 196 clinical samples and showed that our method is rapid, robust, accurate and straightforward to implement. Importantly, our method could be applied to dried blood spot samples, which are readily collected in endemic settings. We report that P. falciparum parasites in Ghana are mostly susceptible to chloroquine, with persistent sulfadoxine-pyrimethamine resistance and no evidence of artemisinin resistance. Multiple single nucleotide polymorphisms were identified in csp, but their significance is uncertain. Our study demonstrates the feasibility of nanopore sequencing for malaria genomic surveillance in endemic countries.
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Acknowledgements: We thank L. Elton, M. Dorman, A. Kovalenko and I. Goodfellow for advice and suggestions on nanopore sequencing; O. Seret and F. Lasalle for contributions to creating the nano-rave analysis pipeline; the staff at LEKMA Hospital, Accra, and the Navrongo Health Research Centre, Navrongo, for contributing to malaria sample collection; M. Awogbo, K. Anuwe, E. Asobayire, B. Afari, I. Nyaaba and C. Aforbiko for helping with the recruitment of patients; and the patients and their guardians for participating in the study. This work was supported by the Wellcome Trust (220540) and Human Heredity and Health in Africa (H3Africa) grant H3A/18/002. W.L.H. was supported by an NIHR Clinical Lectureship at Cambridge University. H3Africa is managed by the Science for Africa Foundation (SFA Foundation) in partnership with Wellcome, NIH and AfSHG. The views expressed herein are those of the author(s) and not necessarily those of the Wellcome Trust, NIHR, UK government or SFA Foundation and partners.
Funder: Wellcome Trust (Wellcome); doi: https://doi.org/10.13039/100004440
Funder: DH | National Institute for Health Research (NIHR); doi: https://doi.org/10.13039/501100000272
Funder: Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation); doi: https://doi.org/10.13039/100000865
Funder: Human Heredity and Health in Africa (H3Africa) grant H3A/18/002. H3Africa is managed by the Science for Africa Foundation (SFA Foundation) in partnership with Wellcome, NIH and AfSHG.
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2058-5276
