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Global risk of selection and spread of Plasmodium falciparum histidine-rich protein 2 and 3 gene deletions [preprint]

Title: Global risk of selection and spread of Plasmodium falciparum histidine-rich protein 2 and 3 gene deletions [preprint]
Authors: Watson, Oliver J; Tran, Thu Nguyen-Anh; Zupko, Robert J; Symons, Tasmin; Thomson, Rebecca; Visser, Theodoor; Rumisha, Susan; Dzianach, Paulina A; Hathaway, Nicholas; Kim, Isaac; Juliano, Jonathan J; Bailey, Jeffrey A; Slater, Hannah; Okell, Lucy; Gething, Peter; Ghani, Azra; Boni, Maciej F; Parr, Jonathan B; Cunningham, Jane
Contributors: Medicine
Publication Year: 2026
Collection: University of Massachusetts, Medical School: eScholarship@UMMS
Subject Terms: Infectious Diseases (except HIV/AIDS); pfhrp2-deleted parasites
Description: This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review. ; In the thirteen years since the first report of -deleted parasites in 2010, the World Health Organization (WHO) has found that 40 of 47 countries surveyed worldwide have reported gene deletions. Due to a high prevalence of deletions causing false-negative HRP2 RDTs, in the last five years, Eritrea, Djibouti and Ethiopia have switched or started switching to using alternative RDTs, that target pan-specific-pLDH or specific-pLDH alone of in combination with HRP2. However, manufacturing of alternative RDTs has not been brought to scale and there are no WHO prequalified combination tests that use Pf-pLDH instead of HRP2 for detection. For these reasons, the continued spread of deletions represents a growing public health crisis that threatens efforts to control and eliminate malaria. National malaria control programmes, their implementing partners and test developers desperately seek deletion data that can inform their immediate and future resource allocation. In response, we use a mathematical modelling approach to evaluate the global risk posed by deletions and explore scenarios for how deletions will continue to spread in Africa. We incorporate current best estimates of the prevalence of deletions and conduct a literature review to estimate model parameters known to impact the selection of deletions for each malaria endemic country. We identify 20 countries worldwide to prioritise for surveillance and future deployment of alternative RDT, based on quickly selecting for deletions once established. In scenarios designed to explore the continued spread of deletions in Africa, we identify 10 high threat countries that are most at risk of deletions both spreading to and subsequently being rapidly selected for. If HRP2-based RDTs continue to be relied on for malaria case management, we predict that the major route for deletions to spread is south out from the current hotspot in the Horn of Africa, moving ...
Document Type: report
Language: unknown
Relation: medRxiv; https://doi.org/10.1101/2023.10.21.23297352; https://hdl.handle.net/20.500.14038/55130
DOI: 10.1101/2023.10.21.23297352
Availability: https://doi.org/10.1101/2023.10.21.23297352; https://hdl.handle.net/20.500.14038/55130
Rights: The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license. ; http://creativecommons.org/licenses/by-nd/4.0/
Accession Number: edsbas.13579C3D
Database: BASE