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These genetic deletions reduce detection by the most widely used rapid diagnostic tests, prompting three countries to switch to alternative diagnostics. However, manufacturing of alternative rapid diagnostic tests has not been scaled up and there are no World Health Organization-prequalified combination tests that use\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    lactate dehydrogenase. The continuing spread of\n                    <jats:italic>pfhrp2<\/jats:italic>\n                    and\/or\n                    <jats:italic>pfhrp3<\/jats:italic>\n                    (\n                    <jats:italic>pfhrp2\/3<\/jats:italic>\n                    ) deletions threatens malaria control, creating an emerging public health crisis. Here we use mathematical modeling informed by current\n                    <jats:italic>pfhrp2\/3<\/jats:italic>\n                    deletion prevalence and a literature review to assess the global risk of\n                    <jats:italic>pfhrp2<\/jats:italic>\n                    <jats:italic>\/3<\/jats:italic>\n                    deletions. We identify ten priority countries for surveillance and predict that the primary spread in Africa will move southward from the Horn of Africa through East Africa within 20\u2009years. Despite variation in modeled timelines due to uncertainty in model parameters, four countries yet to switch rapid diagnostic tests are consistently classified as high risk under a range of model assumptions. This updated model offers refined predictions to guide\n                    <jats:italic>pfhrp2<\/jats:italic>\n                    \/\n                    <jats:italic>3<\/jats:italic>\n                    policy and prioritize future surveillance efforts and innovation.\n                  <\/jats:p>","DOI":"10.1038\/s41591-025-03974-3","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T09:04:24Z","timestamp":1759741464000},"page":"3372-3379","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Global risk of selection and spread of Plasmodium falciparum histidine-rich protein 2 and 3 gene deletions"],"prefix":"10.1038","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2374-0741","authenticated-orcid":false,"given":"Oliver J.","family":"Watson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thu Nguyen-Anh","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8757-483X","authenticated-orcid":false,"given":"Robert J.","family":"Zupko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2565-701X","authenticated-orcid":false,"given":"Tasmin","family":"Symons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Thomson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodoor","family":"Visser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Rumisha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4202-9680","authenticated-orcid":false,"given":"Paulina A.","family":"Dzianach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Hathaway","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9737-8100","authenticated-orcid":false,"given":"Isaac","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0591-0850","authenticated-orcid":false,"given":"Jonathan J.","family":"Juliano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6899-8204","authenticated-orcid":false,"given":"Jeffrey A.","family":"Bailey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4291-7899","authenticated-orcid":false,"given":"Hannah","family":"Slater","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7202-6873","authenticated-orcid":false,"given":"Lucy","family":"Okell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Gething","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0007-4910","authenticated-orcid":false,"given":"Azra","family":"Ghani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0830-9630","authenticated-orcid":false,"given":"Maciej F.","family":"Boni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4465-9830","authenticated-orcid":false,"given":"Jonathan B.","family":"Parr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2758-4822","authenticated-orcid":false,"given":"Jane","family":"Cunningham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,6]]},"reference":[{"key":"3974_CR1","unstructured":"World Malaria Report 2022 (World Health Organization, 2022)."},{"key":"3974_CR2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-13-283","volume":"13","author":"Q Cheng","year":"2014","unstructured":"Cheng, Q. et al. 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J.B.P. reports research support from the WHO related to\n                      pfhrp2\/3\n                      deletion molecular surveillance and, outside the scope of this paper, research support from Gilead Sciences, nonfinancial support from Abbott Laboratories and consulting fees for Zymeron Corporation. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}