{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T17:36:12Z","timestamp":1785260172413,"version":"3.55.0"},"reference-count":36,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,9,7]]},"abstract":"<jats:p>A gap in the leptospirosis field remains the lack of well-characterized sample collections that allow for comparison of new methods to standard ones. In the context of a flood-related outbreak of leptospirosis evaluated in Anuradhapura, Sri Lanka, a specimen bank was obtained with detailed metadata accompanied by gold standard diagnostic test results. Blood samples collected on admission and 14 days later from suspected cases of leptospirosis were tested using microscopic agglutination test (MAT) (17 serovars), an in-house enzyme-linked immunosorbent assay (ELISA) using a locally obtained strain of <jats:italic>Leptospira kirschneri<\/jats:italic> as sonicated antigen, a commercially available ELISA based on sonicated <jats:italic>Leptospira biflexa<\/jats:italic>, and a quantitative polymerase chain reaction (qPCR) assay targeting the pathogenic <jats:italic>Leptospira<\/jats:italic>-specific 16S rRNA gene. Of 62 patients presenting within the first 2 days of illness, 31 had confirmed leptospirosis based either on paired-sample MAT or qPCR. During the acute phase, qPCR was most sensitive, detecting 74% of definitively diagnosed cases; immunoglobulin G (IgG) ELISA (in-house), IgG ELISA (commercial), and MAT had sensitivities of 35.5%, 12.0%, and 22.6%, respectively, in detecting definitively diagnosed cases using acute phase serum. Of 40 patients with paired sera, 10 were qPCR positive. Of these, five samples were negative by paired-sample MAT. Of the 11 MAT-positive samples, only five were detected using qPCR confirming that both tests are needed for maximal sensitivity. Regional leptospiral serovar-specific IgG ELISA was superior to MAT. Knowing the regionally dominant serovars improves serological sensitivity in the analysis of acute specimens by ELISA, but qPCR was most sensitive in this patient population.<\/jats:p>","DOI":"10.4269\/ajtmh.16-0033","type":"journal-article","created":{"date-parts":[[2016,7,12]],"date-time":"2016-07-12T06:25:38Z","timestamp":1468304738000},"page":"531-536","source":"Crossref","is-referenced-by-count":32,"title":["Redefining Gold Standard Testing for Diagnosing Leptospirosis: Further Evidence from a Well-Characterized, Flood-Related Outbreak in Sri Lanka"],"prefix":"10.4269","volume":"95","author":[{"given":"Suneth B.","family":"Agampodi","sequence":"first","affiliation":[{"name":"1Department of Community Medicine, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Sri Lanka."},{"name":"2Tropical Disease Research Unit (TDRU), Rajarata University of Sri Lanka, Sri Lanka."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niroshan J.","family":"Dahanayaka","sequence":"additional","affiliation":[{"name":"2Tropical Disease Research Unit (TDRU), Rajarata University of Sri Lanka, Sri Lanka."},{"name":"3Department of Medicine, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Sri Lanka."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"N\u00f6ckler","sequence":"additional","affiliation":[{"name":"4Federal Institute for Risk Assessment, Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayer-Scholl","family":"Anne","sequence":"additional","affiliation":[{"name":"4Federal Institute for Risk Assessment, Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M.","family":"Vinetz","sequence":"additional","affiliation":[{"name":"5Division of Infectious Diseases, Department of Medicine, University of California, San Diego, California."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2795","reference":[{"key":"ref1","article-title":"Global Burden of Human Leptospirosis and Cross-Sectoral Interventions for its Prevention and Control Prince Mahidol Award Conference","author":"Abela-Ridder","year":"2013"},{"issue":"(Suppl 1)","key":"ref2","series-title":"Int J Antimicrob Agents","first-page":"S5","article-title":"Estimating the burden of human leptospirosis","volume":"36","author":"Abela-Ridder","year":"2010"},{"key":"ref3","series-title":"PLoS Negl Trop Dis","first-page":"e0003898","article-title":"Global morbidity and mortality of leptospirosis: a systematic review","volume":"9","author":"Costa","year":"2015"},{"key":"ref4","series-title":"PLoS Negl Trop Dis","first-page":"e0004122","article-title":"Global burden of leptospirosis: estimated in terms of disability adjusted life years","volume":"9","author":"Torgerson","year":"2015"},{"key":"ref5","series-title":"Int J Infect Dis","first-page":"351","article-title":"The globalization of leptospirosis: worldwide incidence trends","volume":"12","author":"Pappas","year":"2008"},{"key":"ref6","series-title":"Global Health","first-page":"61","article-title":"Globalization of leptospirosis through travel and migration","volume":"10","author":"Bandara","year":"2014"},{"key":"ref7","series-title":"Curr Top Microbiol Immunol","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/978-3-662-45059-8_5","article-title":"Leptospirosis in humans","volume":"387","author":"Haake","year":"2015"},{"key":"ref8","series-title":"Diagn Microbiol Infect Dis","first-page":"1","article-title":"Rapid tests for diagnosis of leptospirosis: current tools and emerging technologies","volume":"78","author":"Picardeau","year":"2014"},{"key":"ref9","series-title":"Curr Top Microbiol Immunol","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/978-3-662-45059-8_11","article-title":"The role of leptospirosis reference laboratories","volume":"387","author":"Hartskeerl","year":"2015"},{"key":"ref10","series-title":"Clin Infect Dis","first-page":"322","article-title":"Fool's 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"},{"key":"ref11","series-title":"Clin Infect Dis","first-page":"1249","article-title":"Utility of quantitative polymerase chain reaction in leptospirosis diagnosis: association of level of leptospiremia and clinical manifestations in Sri Lanka","volume":"54","author":"Agampodi","year":"2012"},{"key":"ref12","series-title":"Lancet Infect Dis","first-page":"524","article-title":"The potential emergence of leptospirosis in Sri Lanka","volume":"9","author":"Agampodi","year":"2009"},{"key":"ref13","series-title":"PLoS Negl Trop Dis","first-page":"e2626","article-title":"Regional differences of leptospirosis in Sri Lanka: observations from a flood-associated outbreak in 2011","volume":"8","author":"Agampodi","year":"2014"},{"key":"ref14","series-title":"Epidemiol Infect","first-page":"843","article-title":"Outbreak of leptospirosis after white-water rafting: sign of a shift from rural to recreational leptospirosis in Sri Lanka?","volume":"142","author":"Agampodi","year":"2014"},{"key":"ref15","series-title":"Am J Trop Med Hyg","first-page":"471","article-title":"Leptospirosis outbreak in Sri Lanka in 2008: lessons for assessing the global burden of disease","volume":"85","author":"Agampodi","year":"2011"},{"key":"ref16","series-title":"Jpn J Infect Dis","first-page":"157","article-title":"Analysis of hospital-based sentinel surveillance data on leptospirosis in Sri Lanka, 2005\u20132008","volume":"65","author":"Gamage","year":"2012"},{"key":"ref17","series-title":"Jpn J Infect Dis","first-page":"474","article-title":"Serological and genetic analysis of leptospirosis in patients with acute febrile illness in Kandy, Sri Lanka","volume":"62","author":"Koizumi","year":"2009"},{"key":"ref18","series-title":"J Infect Dev Ctries","first-page":"1072","article-title":"Hantavirus infection mimicking leptospirosis: how long are we going to rely on clinical suspicion?","volume":"8","author":"Dahanayaka","year":"2014"},{"key":"ref19","series-title":"Leptospirosis. Surveillance Case Definitions for Notifiable Diseases in Sri Lanka","first-page":"19","author":"Epidemiological Unit","year":"2005"},{"key":"ref20","series-title":"BMC Infect Dis","first-page":"332","article-title":"Determinants of leptospirosis in Sri Lanka: study protocol","volume":"10","author":"Agampodi","year":"2010"},{"key":"ref21","series-title":"Prev Vet Med","first-page":"23","article-title":"Principles and practical application of the receiver-operating characteristic analysis for diagnostic tests","volume":"45","author":"Greiner","year":"2000"},{"key":"ref22","series-title":"Leptospirosis. Manual for Diagnostic Tests and Vaccines for Terrestrial Animal","first-page":"251","author":"World Organization for Animal Health","year":"2008"},{"key":"ref23","series-title":"Clin Microbiol Rev","first-page":"296","article-title":"Leptospirosis","volume":"14","author":"Levett","year":"2001"},{"key":"ref24","series-title":"PLoS Negl Trop Dis","first-page":"e612","article-title":"Asymptomatic renal colonization of humans in the Peruvian Amazon by Leptospira","volume":"4","author":"Ganoza","year":"2010"},{"key":"ref25","series-title":"Am J Trop Med Hyg","first-page":"377","article-title":"Evidence of a major reservoir of non-malarial febrile diseases in malaria-endemic regions of Bangladesh","volume":"90","author":"Swoboda","year":"2014"},{"key":"ref26","series-title":"Rev Esp Sanid Penit","first-page":"20","article-title":"Leptospirosis: case-series report in a prison of the coast in Ecuador [in Spanish]","volume":"16","author":"Valarezo-Sevilla","year":"2014"},{"key":"ref27","series-title":"Am J Trop Med Hyg","first-page":"760","article-title":"Case series of fatal Leptospira spp.\/dengue virus co-infections-Puerto Rico, 2010\u20132012","volume":"91","author":"Perez Rodriguez","year":"2014"},{"key":"ref28","series-title":"Emerg Infect Dis","first-page":"766","article-title":"Leptospirosis during dengue outbreak, Bangladesh","volume":"11","author":"LaRocque","year":"2005"},{"key":"ref29","series-title":"J Trop Pediatr","first-page":"174","article-title":"Concurrent outbreak of leptospirosis and dengue in Mumbai, India, 2002","volume":"51","author":"Karande","year":"2005"},{"key":"ref30","series-title":"Epidemiol Infect","first-page":"2029","article-title":"Concomitant leptospirosis-hantavirus co-infection in acute patients hospitalized in Sri Lanka: implications for a potentially worldwide underestimated problem\u2014Erratum","volume":"143","author":"Sunil-Chandra","year":"2015"},{"key":"ref31","series-title":"Nephrol Dial Transplant","first-page":"826","article-title":"First evidence of fatal hantavirus nephropathy in India, mimicking leptospirosis","volume":"21","author":"Clement","year":"2006"},{"key":"ref32","series-title":"J Infect Dev Ctries","first-page":"639","article-title":"Hantavirus pulmonary syndrome in Brasilia periphery: a diagnostic challenge","volume":"3","author":"Santos","year":"2009"},{"key":"ref33","series-title":"Indian J Med Microbiol","first-page":"68","article-title":"Seroprevalence of scrub typhus at a tertiary care hospital in Andhra Pradesh","volume":"33","author":"Ramyasree","year":"2015"},{"key":"ref34","series-title":"J Travel Med","first-page":"352","article-title":"Travel-acquired scrub typhus: emphasis on the differential diagnosis, treatment, and prevention strategies","volume":"14","author":"Nachega","year":"2007"},{"key":"ref35","series-title":"Sri Lankan J Infect Dis","first-page":"83","article-title":"Validity of a commercially available IgM ELISA test for diagnosing acute leptospirosis in high endemic districts of Sri Lanka","volume":"4","author":"Agampodi","year":"2014"},{"key":"ref36","series-title":"Am J Trop Med Hyg","first-page":"745","article-title":"Evaluation of two enzyme-linked immunosorbent assay methods for detection of immunoglobulin M antibodies in acute leptospirosis","volume":"66","author":"Levett","year":"2002"}],"container-title":["The American Society of Tropical Medicine and Hygiene"],"original-title":[],"link":[{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/95\/3\/article-p531.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/95\/3\/article-p531.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/95\/3\/article-p531.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T21:58:25Z","timestamp":1723067905000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/95\/3\/article-p531.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,9,7]]},"references-count":36,"journal-issue":{"issue":"3"},"URL":"https:\/\/doi.org\/10.4269\/ajtmh.16-0033","relation":{},"ISSN":["0002-9637","1476-1645"],"issn-type":[{"value":"0002-9637","type":"print"},{"value":"1476-1645","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,9,7]]}}}