Volume 95, Issue 3
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



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 as sonicated antigen, a commercially available ELISA based on sonicated , and a quantitative polymerase chain reaction (qPCR) assay targeting the pathogenic -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.


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  1. Abela-Ridder B, Bertherat E, Durski K, , 2013. Global Burden of Human Leptospirosis and Cross-Sectoral Interventions for its Prevention and Control Prince Mahidol Award Conference, October 15–17, 2009. Bangkok, Thailand: Prince Mahidol Award Conference.
  2. Abela-Ridder B, Sikkema R, Hartskeerl RA, , 2010. Estimating the burden of human leptospirosis. Int J Antimicrob Agents 36 (Suppl 1): S5S7.[Crossref]
  3. Costa F, Hagan JE, Calcagno J, Kane M, Torgerson P, Martinez-Silveira MS, Stein C, Abela-Ridder B, Ko AI, , 2015. Global morbidity and mortality of leptospirosis: a systematic review. PLoS Negl Trop Dis 9: e0003898.[Crossref]
  4. Torgerson PR, Hagan JE, Costa F, Calcagno J, Kane M, Martinez-Silveira MS, Goris MG, Stein C, Ko AI, Abela-Ridder B, , 2015. Global burden of leptospirosis: estimated in terms of disability adjusted life years. PLoS Negl Trop Dis 9: e0004122.[Crossref]
  5. Pappas G, Papadimitriou P, Siozopoulou V, Christou L, Akritidis N, , 2008. The globalization of leptospirosis: worldwide incidence trends. Int J Infect Dis 12: 351357.[Crossref]
  6. Bandara M, Ananda M, Wickramage K, Berger E, Agampodi S, , 2014. Globalization of leptospirosis through travel and migration. Global Health 10: 61.[Crossref]
  7. Haake DA, Levett PN, , 2015. Leptospirosis in humans. Curr Top Microbiol Immunol 387: 6597.
  8. Picardeau M, Bertherat E, Jancloes M, Skouloudis AN, Durski K, Hartskeerl RA, , 2014. Rapid tests for diagnosis of leptospirosis: current tools and emerging technologies. Diagn Microbiol Infect Dis 78: 18.[Crossref]
  9. Hartskeerl RA, Smythe LD, , 2015. The role of leptospirosis reference laboratories. Curr Top Microbiol Immunol 387: 273288.
  10. Limmathurotsakul D, Turner EL, Wuthiekanun V, Thaipadungpanit J, Suputtamongkol Y, Chierakul W, Smythe LD, Day NP, Cooper B, Peacock SJ, , 2012. Fool's gold: why imperfect reference tests are undermining the evaluation of novel diagnostics: a reevaluation of 5 diagnostic tests for leptospirosis. Clin Infect Dis 55: 322331.[Crossref]
  11. Agampodi SB, Matthias MA, Moreno AC, Vinetz JM, , 2012. Utility of quantitative polymerase chain reaction in leptospirosis diagnosis: association of level of leptospiremia and clinical manifestations in Sri Lanka. Clin Infect Dis 54: 12491255.[Crossref]
  12. Agampodi S, Peacock SJ, Thevanesam V, , 2009. The potential emergence of leptospirosis in Sri Lanka. Lancet Infect Dis 9: 524526.[Crossref]
  13. Agampodi SB, Dahanayaka NJ, Bandaranayaka AK, Perera M, Priyankara S, Weerawansa P, Matthias MA, Vinetz JM, , 2014. Regional differences of leptospirosis in Sri Lanka: observations from a flood-associated outbreak in 2011. PLoS Negl Trop Dis 8: e2626.[Crossref]
  14. Agampodi SB, Karunarathna D, Jayathilala N, Rathnayaka H, Agampodi TC, Karunanayaka L, , 2014. Outbreak of leptospirosis after white-water rafting: sign of a shift from rural to recreational leptospirosis in Sri Lanka? Epidemiol Infect 142: 843846.[Crossref]
  15. Agampodi SB, Peacock SJ, Thevanesam V, Nugegoda DB, Smythe L, Thaipadungpanit J, Craig SB, Burns MA, Dohnt M, Boonsilp S, Senaratne T, Kumara A, Palihawadana P, Perera S, Vinetz JM, , 2011. Leptospirosis outbreak in Sri Lanka in 2008: lessons for assessing the global burden of disease. Am J Trop Med Hyg 85: 471478.[Crossref]
  16. Gamage CD, Amarasekera J, Palihawadana P, Samaraweera S, Mendis D, Janakan N, Lee RB, Obayashi Y, Tamashiro H, , 2012. Analysis of hospital-based sentinel surveillance data on leptospirosis in Sri Lanka, 2005–2008. Jpn J Infect Dis 65: 157161.
  17. Koizumi N, Gamage CD, Muto M, Kularatne SA, Budagoda BD, Rajapakse RP, Tamashiro H, Watanabe H, , 2009. Serological and genetic analysis of leptospirosis in patients with acute febrile illness in Kandy, Sri Lanka. Jpn J Infect Dis 62: 474475.
  18. Dahanayaka NJ, Agampodi SB, Bandaranayaka AK, Priyankara S, Vinetz JM, , 2014. Hantavirus infection mimicking leptospirosis: how long are we going to rely on clinical suspicion? J Infect Dev Ctries 8: 10721075.[Crossref]
  19. Epidemiological Unit, 2005. Leptospirosis. Surveillance Case Definitions for Notifiable Diseases in Sri Lanka. Colombo: Epidemiology Unit, Ministry of Health, 1920.
  20. Agampodi SB, Nugegoda DB, Thevanesam V, , 2010. Determinants of leptospirosis in Sri Lanka: study protocol. BMC Infect Dis 10: 332.[Crossref]
  21. Greiner M, Pfeiffer D, Smith RD, , 2000. Principles and practical application of the receiver-operating characteristic analysis for diagnostic tests. Prev Vet Med 45: 2341.[Crossref]
  22. World Organization for Animal Health, 2008. Leptospirosis. Manual for Diagnostic Tests and Vaccines for Terrestrial Animal. Paris, France: World Organization for Animal Health, 251264.
  23. Levett PN, , 2001. Leptospirosis. Clin Microbiol Rev 14: 296327.[Crossref]
  24. Ganoza CA, Matthias MA, Saito M, Cespedes M, Gotuzzo E, Vinetz JM, , 2010. Asymptomatic renal colonization of humans in the Peruvian Amazon by Leptospira . PLoS Negl Trop Dis 4: e612.[Crossref]
  25. Swoboda P, Fuehrer HP, Ley B, Starzengruber P, Ley-Thriemer K, Jung M, Matt J, Fally MA, Mueller MK, Reismann JA, Haque R, Khan WA, Noedl H, , 2014. Evidence of a major reservoir of non-malarial febrile diseases in malaria-endemic regions of Bangladesh. Am J Trop Med Hyg 90: 377382.[Crossref]
  26. Valarezo-Sevilla D, Sarzosa-Teran V, , 2014. Leptospirosis: case-series report in a prison of the coast in Ecuador [in Spanish]. Rev Esp Sanid Penit 16: 2023.[Crossref]
  27. Perez Rodriguez NM, Galloway R, Blau DM, Traxler R, Bhatnagar J, Zaki SR, Rivera A, Torres JV, Noyd D, Santiago-Albizu XE, Rivera Garcia B, Tomashek KM, Bower WA, Sharp TM, , 2014. Case series of fatal Leptospira spp./dengue virus co-infections-Puerto Rico, 2010–2012. Am J Trop Med Hyg 91: 760765.[Crossref]
  28. LaRocque RC, Breiman RF, Ari MD, Morey RE, Janan FA, Hayes JM, Hossain MA, Brooks WA, Levett PN, , 2005. Leptospirosis during dengue outbreak, Bangladesh. Emerg Infect Dis 11: 766769.[Crossref]
  29. Karande S, Gandhi D, Kulkarni M, Bharadwaj R, Pol S, Thakare J, De A, , 2005. Concurrent outbreak of leptospirosis and dengue in Mumbai, India, 2002. J Trop Pediatr 51: 174181.[Crossref]
  30. Sunil-Chandra NP, Clement J, Maes P, De Silva HJ, Van Esbroeck M, Van Ranst M, , 2015. Concomitant leptospirosis-hantavirus co-infection in acute patients hospitalized in Sri Lanka: implications for a potentially worldwide underestimated problem—Erratum. Epidemiol Infect 143: 2029.[Crossref]
  31. Clement J, Maes P, Muthusethupathi M, Nainan G, van Ranst M, , 2006. First evidence of fatal hantavirus nephropathy in India, mimicking leptospirosis. Nephrol Dial Transplant 21: 826827.[Crossref]
  32. Santos VM, Rocha de Sa DA, Turra TZ, Ferreira Borges NM, Nascimento UM, Damasceno EA, , 2009. Hantavirus pulmonary syndrome in Brasilia periphery: a diagnostic challenge. J Infect Dev Ctries 3: 639643.
  33. Ramyasree A, Kalawat U, Rani ND, Chaudhury A, , 2015. Seroprevalence of scrub typhus at a tertiary care hospital in Andhra Pradesh. Indian J Med Microbiol 33: 6872.[Crossref]
  34. Nachega JB, Bottieau E, Zech F, Van Gompel A, , 2007. Travel-acquired scrub typhus: emphasis on the differential diagnosis, treatment, and prevention strategies. J Travel Med 14: 352355.[Crossref]
  35. Agampodi SB, Thevanesam V, Senaratne T, , 2014. Validity of a commercially available IgM ELISA test for diagnosing acute leptospirosis in high endemic districts of Sri Lanka. Sri Lankan J Infect Dis 4: 8389.
  36. Levett PN, Branch SL, , 2002. Evaluation of two enzyme-linked immunosorbent assay methods for detection of immunoglobulin M antibodies in acute leptospirosis. Am J Trop Med Hyg 66: 745748.

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  • Received : 11 Jan 2016
  • Accepted : 24 Feb 2016

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