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With the decline of reported cases, maintaining active surveillance is essential, including for the potential emergence of drug-resistant parasites. We have developed new highly specific diagnostic tools, using the Cas13a-based Specific High-Sensitivity Reporter Enzymatic UnLOCKing (SHERLOCK) technology, for the detection of drug-resistant genotypes that (i) are already circulating, such as the AQP2\/3\n                      <jats:sub>(814)<\/jats:sub>\n                      chimera providing resistance to pentamidine and melarsoprol or (ii) could emerge, such as the\n                      <jats:italic toggle=\"yes\">Tb<\/jats:italic>\n                      CPSF3 (N\n                      <jats:sup>232<\/jats:sup>\n                      H) mutation, associated with acoziborole resistance under laboratory conditions. The\n                      <jats:italic toggle=\"yes\">\n                        AQP2\/3\n                        <jats:sub>(814)<\/jats:sub>\n                      <\/jats:italic>\n                      SHERLOCK assay detected RNA from both cultured parasites and field strains isolated from gHAT patients who relapsed following melarsoprol or pentamidine treatment. The\n                      <jats:italic toggle=\"yes\">\n                        CPSF3\n                        <jats:sub>(SNV)<\/jats:sub>\n                      <\/jats:italic>\n                      SHERLOCK assay discriminated between wild-type\n                      <jats:italic toggle=\"yes\">CPSF3<\/jats:italic>\n                      RNA and\n                      <jats:italic toggle=\"yes\">CPSF3<\/jats:italic>\n                      bearing a single A-C mutation that confers resistance to acoziborole\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      . These SHERLOCK assays are amenable for use as a high-throughput screening method to monitor for drug-resistant-associated mutations in\n                      <jats:italic toggle=\"yes\">Trypanosoma brucei<\/jats:italic>\n                      , providing a new molecular tool for epidemiological surveillance during the gHAT elimination phase.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00933-25","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T13:00:36Z","timestamp":1763470836000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["A CRISPR-based diagnostic tool to survey drug resistance in human African trypanosomiasis"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9397-3914","authenticated-orcid":true,"given":"Elena","family":"P\u00e9rez Ant\u00f3n","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f82e368","id-type":"ROR","asserted-by":"publisher"}],"name":"Trypanosome Molecular Biology Unit, Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, INSERM U1347","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1881-9826","authenticated-orcid":true,"given":"Annick","family":"Dujeancourt-Henry","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f82e368","id-type":"ROR","asserted-by":"publisher"}],"name":"Trypanosome Molecular Biology Unit, Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, INSERM U1347","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0671-8999","authenticated-orcid":true,"given":"Brice","family":"Rotureau","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f82e368","id-type":"ROR","asserted-by":"publisher"}],"name":"Trypanosome Transmission Group, Trypanosome Cell Biology Unit, INSERM U1347, Institut Pasteur, Universit\u00e9 Paris Cit\u00e9","place":["Paris, France"]},{"name":"Parasitology Unit, Institut Pasteur of Guinea","place":["Conakry, Guinea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7191-6890","authenticated-orcid":true,"given":"Lucy","family":"Glover","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f82e368","id-type":"ROR","asserted-by":"publisher"}],"name":"Trypanosome Molecular Biology Unit, Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, INSERM U1347","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"Global report on neglected tropical diseases 2024","author":"WHO","year":"2024","unstructured":"WHO. 2024. 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