{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:52:48Z","timestamp":1792806768226,"version":"4.5.0"},"reference-count":44,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technology, and Innovation (MinCiencias) of Colombia","id":[{"id":"https:\/\/ror.org\/03fd5ne08","id-type":"ROR","asserted-by":"crossref"}]},{"name":"University of Cordoba (Colombia)","id":[{"id":"https:\/\/ror.org\/04nmbd607","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TropicalMed"],"abstract":"<jats:p>Background\/Objectives: Leptospirosis is a zoonotic disease that is widely distributed around the world and presents symptoms similar to other febrile illnesses in tropical regions, which complicates clinical diagnosis. This study aimed to evaluate the performance and agreement between serological diagnostic tests for detecting both acute and convalescent human leptospirosis, using the micro agglutination test (MAT) as a reference in an endemic region of the Colombian Caribbean. Methods: A prospective descriptive study was conducted on 275 participants with suspected leptospirosis. Paired serum samples were obtained, and an epidemiological survey was conducted. Using the MAT as the gold standard, we calculated positive and negative predictive values, sensitivity, specificity, and kappa index. A Bayesian latent class model was also used to compare the diagnostic tests. Results: In 223 paired serum samples, the sensitivity values for various stages of the disease ranged between 10.8% to 54.1% in the acute and 6.1% to 66.7% during the convalescent phase compared to the MAT. According to the Bayesian model, sensitivity was 9.5% to 75.3% in the acute phase and 5.7% to 85.3% in the convalescent phase. The Kappa value, an indicator of agreement, was moderate for the IgM ELISA in the acute phase (0.553) and substantial in the convalescent phase (0.692). Conclusions: The MAT was the best confirmatory test in both acute and convalescent phases of leptospirosis. Despite the high specificity of ELISA, 21.62% of participants identified as negative by IgM-ELISA in both phases were subsequently confirmed as positive by the MAT. It is necessary to re-evaluate diagnostic guidelines that do not employ the MAT for confirmation and to enhance the diagnostic and clinical identification of leptospirosis within healthcare institutions and public health laboratories while providing a rapid and reliable test for its implementation.<\/jats:p>","DOI":"10.3390\/tropicalmed9110283","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T03:57:04Z","timestamp":1732075024000},"page":"283","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Evaluation of Serological Tests for Different Disease Stages of Leptospirosis Infection in Humans"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0295-4647","authenticated-orcid":false,"given":"Virginia","family":"Rodr\u00edguez-Rodriguez","sequence":"first","affiliation":[{"name":"Grupo de Investigaciones Microbiol\u00f3gicas y Biom\u00e9dicas de C\u00f3rdoba (GIMBIC), Universidad de C\u00f3rdoba, C\u00f3rdoba 230002, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3899-156X","authenticated-orcid":false,"given":"Ana","family":"Castro","sequence":"additional","affiliation":[{"name":"Grupo de Investigaciones Microbiol\u00f3gicas y Biom\u00e9dicas de C\u00f3rdoba (GIMBIC), Universidad de C\u00f3rdoba, C\u00f3rdoba 230002, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Soto-Florez","sequence":"additional","affiliation":[{"name":"Grupo de Investigaciones Microbiol\u00f3gicas y Biom\u00e9dicas de C\u00f3rdoba (GIMBIC), Universidad de C\u00f3rdoba, C\u00f3rdoba 230002, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Urango-Gallego","sequence":"additional","affiliation":[{"name":"Grupo de Investigaciones Microbiol\u00f3gicas y Biom\u00e9dicas de C\u00f3rdoba (GIMBIC), Universidad de C\u00f3rdoba, C\u00f3rdoba 230002, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Calder\u00f3n-Rangel","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biol\u00f3gicas del Tr\u00f3pico (IIBT), Universidad de C\u00f3rdoba, C\u00f3rdoba 230002, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0002-776X","authenticated-orcid":false,"given":"Piedad","family":"Agudelo-Fl\u00f3rez","sequence":"additional","affiliation":[{"name":"Ciencias de la Vida y la Salud, Escuela de Graduados, Universidad CES, Medell\u00edn 050021, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3466-7466","authenticated-orcid":false,"given":"Fernando","family":"Monroy","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ 86001, USA"},{"name":"Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ 86011, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,20]]},"reference":[{"key":"ref_1","first-page":"65","article-title":"Leptospirosis in humans","volume":"387","author":"Haake","year":"2015","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1111\/zph.12317","article-title":"Seroprevalence and risk factors for Leptospira seropositivity in beef cattle, sheep and deer farmers in New Zealand","volume":"64","author":"Sanhueza","year":"2017","journal-title":"Zoonoses Public Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.revmed.2018.12.003","article-title":"Mise au point sur la leptospirose Update on leptospirosis","volume":"40","author":"Epelboin","year":"2019","journal-title":"Rev. Med. Int."},{"key":"ref_4","first-page":"148","article-title":"Leptospirosis","volume":"67","author":"Phillips","year":"2019","journal-title":"Curr. Top."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"E11829","DOI":"10.1016\/j.heliyon.2022.e11829","article-title":"Evaluating immunochromatographic test kits for diagnosis of acute human leptospirosis: A systematic review","volume":"8","author":"Clemente","year":"2022","journal-title":"Helyon"},{"key":"ref_6","first-page":"156","article-title":"Prevalencia de anticuerpos anti-Leptospira spp. en personas con exposici\u00f3n laboral en el departamento del Tolima","volume":"34","year":"2016","journal-title":"Rev. Fac. Nac. Salud P\u00fablica"},{"key":"ref_7","first-page":"150","article-title":"Incidence and underreporting of leptospirosis comparing three diagnostic methods in the endemic region of Urab\u00e1, Colombia","volume":"39","author":"Ochoa","year":"2019","journal-title":"Biomedica"},{"key":"ref_8","unstructured":"World Health Organization (2024, October 03). Human Leptospirosis: Guidance for Diagnosis, Surveillance and Control. Malta. Available online: https:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/42667\/WHO_CDS_CSR_EPH_2002.23.pdf?sequence=1&isAllowed=y."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"416","DOI":"10.4103\/0255-0857.158570","article-title":"An evaluation of dark field microscopy, culture and commercial serological kits in the diagnosis of leptospirosis","volume":"33","author":"Bhatia","year":"2015","journal-title":"Indian J. Med. Microbiol."},{"key":"ref_10","first-page":"199","article-title":"Leptospirosis Diagnosis: Competancy of various laboratory Tests","volume":"8","author":"Budihal","year":"2014","journal-title":"J. Clin. Diagn. Rest."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.jmii.2013.03.001","article-title":"Laboratory diagnosis of leptospirosis: A challenge","volume":"46","author":"Musso","year":"2013","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Samrot, A.V., Sean, T.C., Bhavya, K.S., Sahithya, C.S., Chan-Drasekaran, S., Palanisamy, R., Robinson, E.R., Subbiah, S.K., and Mok, P.L. (2021). Leptospiral infection, pathogenesis and Its diagnosis-A Review. Pathogens, 10.","DOI":"10.3390\/pathogens10020145"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"531","DOI":"10.4269\/ajtmh.16-0033","article-title":"Redefining gold standard testing for diagnosing Leptospirosis: Further evidence from a well-characterized, flood related outbreak in Sri Lanka","volume":"95","author":"Agampodi","year":"2016","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Jayasundara, D., Gamage, C., Senavirathna, I., Warnasekara, J., Matthias, M.A., Vinetz, J.M., and Agampodi, S. (2021). Optimizing the microscopic agglutination test (MAT) panel for the diagnosis of Leptospirosis in a low resource, hyper-endemic setting with varied microgeographic variation in reactivity. PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0009565"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Eugene, E.J., Handunnetti, S.M., Wickramasinghe, S.A., Kalugalage, T.L., Rodrigo, C., Wickremesinghe, H., Dikmadugoda, N., Somaratne, P., de Silva, H.J., and Rajapakse, S. (2015). Evaluation of two immunodiagnostic tests for early rapid diagnosis of Leptospirosis in Sri Lanka: A preliminary study. BMC Infect. Dis., 15.","DOI":"10.1186\/s12879-015-1080-z"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Behera, S.K., Sabarinath, T., Ganesh, B., Mishra, P.K.K., Niloofa, R., Senthilkumar, K., Verma, M.R., Hota, A., Chandrasekar, S., and Deneke, Y. (2022). Diagnosis of human Leptospirosis: Comparison of microscopic agglutination test with recombinant LigA\/B antigen-based in-house IgM Dot ELISA dipstick test and latex agglutination test using Bayesian latent class model and MAT as gold standard. Diagnostics, 12.","DOI":"10.3390\/diagnostics12061455"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1099\/jmm.0.45735-0","article-title":"Percutaneous exposure resulting in laboratory-acquired Leptospirosis-a case report","volume":"53","author":"Sugunan","year":"2004","journal-title":"J. Med. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1099\/00222615-11-4-387","article-title":"The antibodies involved in the human immune response to leptospiral infection","volume":"11","author":"Alder","year":"1978","journal-title":"J. Med. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1023\/A:1015509105668","article-title":"Persistence of anti-leptospiral IgM, IgG and agglutinating antibodies in patients presenting with acute febrile illness in Barbados 1979\u20131989","volume":"17","author":"Cumberland","year":"2001","journal-title":"Eur. J. Epidemiol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Brachman, P., and Abrutyn, E. (2009). Leptospirosis. Bacterial Infections of Humans: Epidemiology and Control, Springer.","DOI":"10.1007\/978-0-387-09843-2"},{"key":"ref_21","unstructured":"Faine, S. (1982). Guidelines for the Control of Leptospirosis, World Health Organization."},{"key":"ref_22","first-page":"24","article-title":"Diagn\u00f3stico de Leptospirosis mediante la PCR en pacientes con s\u00edndrome febril icterohemorr\u00e1gico","volume":"28","author":"Cardona","year":"2008","journal-title":"Rev. Soc. Ven. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1128\/JCM.40.4.1464-1469.2002","article-title":"Evaluation of eight rapid screening tests for acute leptospirosis in Hawaii","volume":"40","author":"Effler","year":"2002","journal-title":"J. Clin. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1093\/cid\/cis403","article-title":"Fool\u2019s gold: Why imperfect reference tests are undermining the evaluation of novel diagnostics: A reevaluation of 5 diagnostic tests for leptospirosis","volume":"55","author":"Limmathurotsakul","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Valente, M., Bramugy, J., Keddie, S.H., Hopkins, H., Bassat, Q., Baerenbold, O., Bradley, J., Falconer, J., Keogh, R.H., and Newton, P.N. (2024). Diagnosis of human leptospirosis: Systematic review and meta-analysis of the diagnostic accuracy of the Leptospira microscopic agglutination test, PCR targeting Lfb1, and IgM ELISA to Leptospira Faine serovar Hurstbridge. BMC Infect. Dis., 24.","DOI":"10.1186\/s12879-023-08935-0"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Speybroeck, N., Praet, N., Claes, F., Van Hong, N., Torres, K., Mao, S., Van den, E.P., Thi Thinh, T., Gamboa, D., and Sochantha, T. (2011). True versus apparent malaria infection prevalence: The contribution of a Bayesian approach. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016705"},{"key":"ref_27","unstructured":"Ministerio de Salud, Rep\u00fablica de Colombia (2024, October 03). Normas Cient\u00edficas, T\u00e9cnicas y Administrativas en Salud. Resoluci\u00f3n 008430. Available online: https:\/\/urosario.edu.co\/Escuela-Medicina\/Investigacion\/Documentos-de-interes\/Files\/resolucion_008430_1993.pdf."},{"key":"ref_28","unstructured":"Instituto Nacional de Salud (2024, October 03). Gu\u00eda para la Vigilancia por Laboratorio del Leptospira spp., Available online: https:\/\/www.ins.gov.co\/buscador-eventos\/Informacin%20de%20laboratorio\/Gu%C3%ADa%20para%20la%20vigilancia%20por%20laboratorio%20de%20Leptospira%20spp.pdf."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"159","DOI":"10.2307\/2529310","article-title":"The measurement of observer agreement for categorical data","volume":"33","author":"Landis","year":"1977","journal-title":"Biometrics"},{"key":"ref_30","first-page":"37","article-title":"Leptospirosis: Diagn\u00f3stico serol\u00f3gico","volume":"19","author":"Agudelo","year":"2005","journal-title":"Rev. CES Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"340","DOI":"10.4269\/ajtmh.1995.52.340","article-title":"Evaluation of the immunofluorescent antibody test for the diagnosis of human leptospirosis","volume":"52","author":"Appassakij","year":"1995","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.4269\/ajtmh.20-0818","article-title":"Evaluation of the Panbio Leptospira IgM ELISA among outpatients attending primary care in Southeast Asia","volume":"104","author":"Dhawan","year":"2021","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1128\/JCM.41.2.803-809.2003","article-title":"Evaluation of four commercially available rapid serologic tests for diagnosis of leptospirosis","volume":"41","author":"Bajani","year":"2003","journal-title":"J. Clin. Microbiol."},{"key":"ref_34","first-page":"50","article-title":"Cepario aut\u00f3ctono de leptospiras en la prueba de micro\u2013aglutinaci\u00f3n","volume":"22","author":"Saltaren","year":"2018","journal-title":"Correo Cient\u00edfico M\u00e9dico De Holgu\u00edn"},{"key":"ref_35","first-page":"153","article-title":"Comportamiento de la vigilancia epidemiol\u00f3gica de leptospirosis humana en Colombia, 2007\u20132011","volume":"33","author":"Bello","year":"2013","journal-title":"Biomedica"},{"key":"ref_36","first-page":"DC21","article-title":"To Evaluate the different rapid screening tests for diagnosis of leptospirosis","volume":"9","author":"Panwala","year":"2015","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_37","first-page":"195","article-title":"Laboratory diagnosis of leptospirosis","volume":"51","author":"Ahmad","year":"2005","journal-title":"J. Postgrad. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1111\/j.1365-3156.2006.01727.x","article-title":"Polymerase chain reaction in comparison with serological tests for early diagnosis of human leptospirosis","volume":"11","author":"Spinosa","year":"2006","journal-title":"Trop. Med. Int. Health"},{"key":"ref_39","first-page":"8","article-title":"Polymerase chain reaction: An important tool for early diagnosis of leptospirosis Cases","volume":"10","author":"Mullan","year":"2016","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.mimet.2005.07.015","article-title":"Evaluation of MAT, IgM ELISA and PCR methods for the diagnosis of human leptospirosis","volume":"65","author":"Costa","year":"2006","journal-title":"J. Microbiol. Methods"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Dreyfus, A., Ruf, M.T., Goris, M., Poppert, S., Mayer-Scholl, A., Loosli, N., Bier, N.S., Paris, D.H., Tshokey, T., and Stenos, J. (2022). Comparison of the Serion IgM ELISA and microscopic agglutination test for diagnosis of Leptospira spp. infections in sera from different geographical origins and estimation of Leptospira seroprevalence in the Wiwa indigenous population from Colombia. PLoS Negl. Trop. Dis., 16.","DOI":"10.1371\/journal.pntd.0009876"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"204","DOI":"10.15446\/rsap.v19n2.54235","article-title":"Prevalencia de leptospirosis en Colombia: Revisi\u00f3n sistem\u00e1tica de literatura","volume":"19","author":"Salas","year":"2017","journal-title":"Rev. Salud P\u00fablica"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Philip, N., Affendy, N.B., Masri, S.N., Yuhana, M.Y., Than, L.T.L., Sekawi, Z., and Neela, V.K. (2020). Combined PCR and MAT improves the early diagnosis of the biphasic illness leptospirosis. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0239069"},{"key":"ref_44","first-page":"50","article-title":"Estudio comparativo del diagn\u00f3stico de leptospirosis mediante PCR y MAT en el noroeste de M\u00e9xico","volume":"28","author":"Sandoval","year":"2018","journal-title":"Acta Univ."}],"container-title":["Tropical Medicine and Infectious Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2414-6366\/9\/11\/283\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:35:40Z","timestamp":1760114140000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2414-6366\/9\/11\/283"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,20]]},"references-count":44,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["tropicalmed9110283"],"URL":"https:\/\/doi.org\/10.3390\/tropicalmed9110283","relation":{},"ISSN":["2414-6366"],"issn-type":[{"value":"2414-6366","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,20]]}}}