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In Argentina, dengue has transitioned from a sporadic disease to a recurrent epidemic, now affecting 18 of 23 provinces and exposing gaps in diagnostic capacity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methodology and Principal Findings<\/jats:title>\n                    <jats:p>The DENV genome encodes the non-structural protein 1 (NS1), a key biomarker for early infection detection. Given the limited access to commercially available diagnostic kits within the public health system, we developed a combined ELISA system incorporating Nanobodies designed to target NS1 across all four DENV serotypes as detection antibodies. This system demonstrates excellent discriminative performance (AUC &gt; 0.9), with a diagnostic sensitivity of 93.6% (95% CI: 86.6\u201397.6%) and a specificity of 81.1% (95% CI: 70.3\u201389.3%). The analytical sensitivity showed strong correlation between sera pool dilutions and detected signals, with a limit of detection aligning with reported NS1 concentrations in human samples. While the system exhibits limitations in detecting NS1 from DENV-4, it successfully identified cases in patients five days post-symptom onset who were initially considered epidemiologically negative for dengue infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Our results underscore the urgent need for accessible, high-precision diagnostic tools in regions facing a surge in dengue outbreaks. Additionally, they highlight the necessity of revising current diagnostic algorithms to enhance the detection of late-presenting cases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pntd.0013168","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T17:57:59Z","timestamp":1761933479000},"page":"e0013168","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Engineered Nanobodies for early and accurate diagnosis of dengue virus infection"],"prefix":"10.1371","volume":"19","author":[{"given":"Mar\u00eda Florencia","family":"Pavan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian Miguel","family":"Malnero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Emilia","family":"Mora Alvarado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Camila","family":"Carzoglio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yesica Paredes","family":"Rojas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agostina","family":"Bruno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura Perez","family":"Vidakovics","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Hanke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Castello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald","family":"McInerney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cybele Carina","family":"Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviana","family":"Parre\u00f1o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9393-2004","authenticated-orcid":true,"given":"Lorena Itat\u00ed","family":"Iba\u00f1ez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"issue":"7","key":"pntd.0013168.ref001","doi-asserted-by":"crossref","DOI":"10.1093\/femspd\/ftab043","article-title":"Minireview: Epidemiological impact of arboviral diseases in Latin American countries, arbovirus-vector interactions and control strategies","volume":"79","author":"NA Segura","year":"2021","journal-title":"Pathog Dis"},{"key":"pntd.0013168.ref002","doi-asserted-by":"crossref","first-page":"100452","DOI":"10.1016\/j.onehlt.2022.100452","article-title":"The association between dengue case and climate: A systematic review and meta-analysis","volume":"15","author":"NAMH Abdullah","year":"2022","journal-title":"One Health"},{"issue":"12","key":"pntd.0013168.ref003","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgph.0002598","article-title":"Facing the escalating burden of dengue: Challenges and perspectives","volume":"3","author":"GN Malavige","year":"2023","journal-title":"PLOS Glob Public Health"},{"key":"pntd.0013168.ref004","unstructured":"WHO. 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