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With the emergence of\n                      <jats:italic>hrp2\/hrp3<\/jats:italic>\n                      gene deletions, RDTs targeting other antigens such as the essential enzyme Lactate Dehydrogenase (LDH) are needed. The dynamics of LDH relative to HRP2 are currently not well described but are needed to inform the use of next-generation (NG-) LDH and HRP2 RDTs that are designed to address\n                      <jats:italic>hrp2\/hrp3<\/jats:italic>\n                      gene deletions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A longitudinal cohort study conducted in a low transmission setting in Namibia was leveraged to compare HRP2 and LDH decay rates. Passive and active case detection were used to recruit individuals with positive HRP2-RDT results. Study participants were treated and subsequently followed weekly until they received two consecutive HRP2-RDT negative results. Blood specimens were characterized for antigen concentration and parasite density. Antigen decay rates were calculated and used to estimate time to negativity (TTN) of NG-RDTs: two HRP2 and LDH-based RDTs (Rapigen Pf and a WHO prequalified Pf\/Pv RDT) and an LDH-only RDT (Rapigen Pf\/Pv).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In 135 participants, the starting geometric mean concentrations for HRP2 and LDH were 899\u00a0ng\/mL and 344\u00a0ng\/mL respectively. Both antigens followed a biphasic decay rate, with a faster decay rate in the first phase. For current RDTs with an analytical sensitivity of 1\u00a0ng\/mL for HRP2 and 5\u00a0ng\/mL for LDH, TTN was 44 and 4\u00a0days, respectively. With a NG-RDT with LDH analytical sensitivity of 0.37\u00a0ng\/mL, average TTN was 9\u00a0days. Multiple levels of analytical sensitivity were also modeled.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      In the detection of\n                      <jats:italic>P. falciparum<\/jats:italic>\n                      malaria, LDH versus HRP2-based RDTs had a faster TTN due to a combination of lower accumulated antigen concentrations and faster decay rates, even for more sensitive LDH-based RDTs. Detection of LDH versus HRP2 by RDT is more likely to reflect a new or very recent infection. For NG-RDTs that target both antigens, HRP2 is likely to contribute more to the test signal than LDH in recently treated infections unless the infection has\n                      <jats:italic>hrp2\/hrp3<\/jats:italic>\n                      gene deletions. Antigen decay data combined with analytical sensitivity contributes to understanding RDT performance and interpretation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12936-025-05350-5","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T22:30:00Z","timestamp":1743805800000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Estimating malaria antigen dynamics and the time to negativity of next-generation malaria rapid diagnostic tests"],"prefix":"10.1186","volume":"24","author":[{"given":"William","family":"Sheahan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Golden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Barney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smita","family":"Das","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ihn-Kyung","family":"Jang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Ntuku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brooke","family":"Whittemore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucille","family":"Dausab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davis","family":"Mumbengegwi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonzalo J.","family":"Domingo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle S.","family":"Hsiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Slater","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,4]]},"reference":[{"key":"5350_CR1","unstructured":"WHO. 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Written informed consent was obtained from all participating adults and from parents or guardians of children, and minor assent was obtained from minors 12\u201317\u00a0years of age.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors of this manuscript do not note any issue relating to the policies of Malaria Journal, nor do they declare any competing interests for this publication. All coauthors have approved the manuscript for submission and acknowledge that these findings have not been submitted directly for publication anywhere else.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"109"}}