{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T12:20:35Z","timestamp":1767874835541,"version":"3.49.0"},"posted":{"date-parts":[[2026,1,6]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":38,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,6]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>\n                    Failure of rapid diagnostic tests (RDTs) to detect\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    parasites in peripheral blood of individuals is a major barrier to successful case management and control of malaria in Ethiopia. Characterizing factors contributing to RDT failure is essential if malaria control and elimination strategies are to succeed.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    We consented and enrolled 148 individuals with suspected malaria presenting to health clinics in Mizan Aman, Ethiopia. We administered a clinical questionnaire, diagnosed the presence of malaria parasites via RDT, and collected venous blood. Samples were assayed using molecular methods to detect parasite DNA,\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    species, parasite load, and\n                    <jats:italic>pfhrp2<\/jats:italic>\n                    and\n                    <jats:italic>pfhrp3<\/jats:italic>\n                    gene deletions. RNA-seq libraries and LC-MS proteomics data were generated from all molecularly confirmed\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    -infected individuals.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    We identified 29\/148 (27.9%) individuals as\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    PCR positive with 26\/29 (89.7%) false negative by a P.f\/Pan RDT. RDT+\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    and\n                    <jats:italic>P. vivax<\/jats:italic>\n                    infections had higher parasite densities than RDT- infections. Of the 29\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    infections, 27 (93.1%) had deletions in both\n                    <jats:italic>pfhrp2<\/jats:italic>\n                    and\n                    <jats:italic>pfhrp3<\/jats:italic>\n                    genes, and 22 (75.9%) had negligible\n                    <jats:italic>pfhrp2<\/jats:italic>\n                    transcripts. Ten\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    samples had detectable PfLDH peptides, but no samples had PfHRP2 or PfHRP3 peptides detectable by LC-MS.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>\n                    Our molecular, transcriptomic, and proteomic characterization of\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    infections that fail detection by PfHRP2\/pLDH-based RDTs in Mizan Aman, Ethiopia, revealed a heterogeneous array of factors that could be responsible for the observed RDT failure.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.01.04.25343089","type":"posted-content","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T02:55:17Z","timestamp":1767754517000},"source":"Crossref","is-referenced-by-count":0,"title":["Molecular, Transcriptomic, and Proteomic Characterization of\n                  <i>Plasmodium<\/i>\n                  Infections that Evade Detection by Rapid Diagnostic Tests in Mizan Aman, Ethiopia"],"prefix":"10.64898","author":[{"given":"Maria","family":"Nikulkova","sequence":"first","affiliation":[{"name":"Johns Hopkins Malaria Research Institute, Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States"},{"name":"Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Kessler","sequence":"additional","affiliation":[{"name":"Johns Hopkins 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Research Centre, Jimma University, Jimma, Ethiopia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taye","family":"Teka","sequence":"additional","affiliation":[{"name":"Tropical and Infectious Diseases Research Centre, Jimma University, Jimma, Ethiopia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Tesfaye","sequence":"additional","affiliation":[{"name":"Tropical and Infectious Diseases Research Centre, Jimma University, Jimma, Ethiopia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Biniam","family":"Lukas","sequence":"additional","affiliation":[{"name":"Tropical and Infectious Diseases Research Centre, Jimma University, Jimma, Ethiopia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deje","family":"Lemessa","sequence":"additional","affiliation":[{"name":"Tropical and Infectious Diseases Research Centre, Jimma University, Jimma, 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