Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link

Disclaimer: Early release articles are not considered as final versions. Any changes will be reflected in the online version in the month the article is officially released.

Volume 32, Number 7—July 2026

Research

Clinical Predictors of Fatal Outcomes from Human Leptospirosis, Thailand, 2015–2024

Umaporn Limothai, Nathan E. Stone, Sasipha Tachaboon, Janejira Dinhuzen, Jason W. Sahl, Theerapon Sukmark, Chayomon Dokpong, David M. Wagner, David A Haake, and Nattachai SrisawatComments to Author 
Author affiliation: Chulalongkorn University Faculty of Medicine, Center of Excellence in Critical Care Nephrology, Bangkok, Thailand (U. Limothai, S. Tachaboon, J. Dinhuzen, N. Srisawat); King Chulalongkorn Memorial Hospital–Thai Red Cross Society, Excellence Center for Critical Care Nephrology, Bangkok (U. Limothai, S. Tachaboon, J. Dinhuzen, N. Srisawat); Northern Arizona University Pathogen and Microbiome Institute, Flagstaff, Arizona, USA (N.E. Stone, J.W. Sahl, D.M. Wagner); Thungsong Hospital, Nakhon Si Thammarat, Thailand (T. Sukmark); Khukhan Hospital, Sisaket, Thailand (C. Dokpong); Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, USA (D.A. Haake); University of California David Geffen School of Medicine, Los Angeles (D.A. Haake); University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA (N. Srisawat); Royal Society of Thailand Academy of Science Bangkok (N. Srisawat)

Main Article

Figure 2

Phylogenetic analysis of Leptospira interrogans from AmpSeq (27) and isolate genome data, Thailand, 2015–2024. Maximum-likelihood phylogenetic tree was generated for high breadth of coverage AmpSeq samples (>25 loci amplified with >10× coverage) by using 59 variable sites across a 1,813-nt core genome of 57 L. interrogans AmpSeq samples, 13 L. interrogans isolates, and 21 publicly available L. interrogans reference genomes. The tree was rooted with L. kirschneri. Five isolate or AmpSeq pairs demonstrate the phylogenetic concordance between methods. A major clade corresponding to CG272 contained most of the clinical samples, including those from several patients with fatal cases, whereas the remaining samples fell into other non-CG272 lineages. A bootstrap value of 98 supports placement in the CG272 clade. CG272 and non-CG272 lineages are color-coded in gold and black. Bold font indicates sequences generated during this study. Scale bar represents nucleotide substitutions per site. AmpSeq, amplicon sequencing; CG272, clonal group 272.

Figure 2. Phylogenetic analysis of Leptospira interrogans from AmpSeq (27) and isolate genome data, Thailand, 2015–2024. Maximum-likelihood phylogenetic tree was generated for high breadth of coverage AmpSeq samples (>25 loci amplified with >10× coverage) by using 59 variable sites across a 1,813-nt core genome of 57 L. interrogans AmpSeq samples, 13 L. interrogans isolates, and 21 publicly available L. interrogans reference genomes. The tree was rooted with L. kirschneri. Five isolate or AmpSeq pairs demonstrate the phylogenetic concordance between methods. A major clade corresponding to CG272 contained most of the clinical samples, including those from several patients with fatal cases, whereas the remaining samples fell into other non-CG272 lineages. A bootstrap value of 98 supports placement in the CG272 clade. CG272 and non-CG272 lineages are color-coded in gold and black. Bold font indicates sequences generated during this study. Scale bar represents nucleotide substitutions per site. AmpSeq, amplicon sequencing; CG272, clonal group 272.

Main Article

References
  1. Costa  F, Hagan  JE, Calcagno  J, Kane  M, Torgerson  P, Martinez-Silveira  MS, et al. Global morbidity and mortality of leptospirosis: a systematic review. PLoS Negl Trop Dis. 2015;9:e0003898. DOIPubMedGoogle Scholar
  2. Haake  DA, Levett  PN. Leptospirosis in humans. Curr Top Microbiol Immunol. 2015;387:65–97. DOIPubMedGoogle Scholar
  3. Picardeau  M. Virulence of the zoonotic agent of leptospirosis: still terra incognita? Nat Rev Microbiol. 2017;15:297–307. DOIPubMedGoogle Scholar
  4. Baharom  M, Ahmad  N, Hod  R, Ja’afar  MH, Arsad  FS, Tangang  F, et al. Environmental and occupational factors associated with leptospirosis: a systematic review. Heliyon. 2023;10:e23473.PubMedGoogle Scholar
  5. Muñoz-Zanzi  C, Dreyfus  A, Limothai  U, Foley  W, Srisawat  N, Picardeau  M, et al. Leptospirosis—improving healthcare outcomes for a neglected tropical disease. Open Forum Infect Dis. 2025;12:ofaf035. DOIPubMedGoogle Scholar
  6. Narkkul  U, Thaipadungpanit  J, Srisawat  N, Rudge  JW, Thongdee  M, Pawarana  R, et al. Human, animal, water source interactions and leptospirosis in Thailand. Sci Rep. 2021;11:3215. DOIPubMedGoogle Scholar
  7. Sawangpol  C, Aimyong  N, Phosri  A. Epidemiological changes in the incidence of human leptospirosis in Thailand: findings from the National Disease Surveillance System from 2013 to 2022. Infect Dis Now. 2025;55:105108. DOIPubMedGoogle Scholar
  8. Limothai  U, Lumlertgul  N, Sirivongrangson  P, Kulvichit  W, Tachaboon  S, Dinhuzen  J, et al. The role of leptospiremia and specific immune response in severe leptospirosis. Sci Rep. 2021;11:14630. DOIPubMedGoogle Scholar
  9. Spichler  AS, Vilaça  PJ, Athanazio  DA, Albuquerque  JO, Buzzar  M, Castro  B, et al. Predictors of lethality in severe leptospirosis in urban Brazil. Am J Trop Med Hyg. 2008;79:911–4. DOIPubMedGoogle Scholar
  10. Petakh  P, Rostoka  L, Isevych  V, Kamyshnyi  A. Identifying risk factors and disease severity in leptospirosis: a meta-analysis of clinical predictors. Trop Doct. 2023;53:464–9. DOIPubMedGoogle Scholar
  11. Daher  EF, Soares  DS, Galdino  GS, Macedo  ÊS, Gomes  PEAC, Pires Neto  RDJ, et al. Leptospirosis in the elderly: the role of age as a predictor of poor outcomes in hospitalized patients. Pathog Glob Health. 2019;113:117–23. DOIPubMedGoogle Scholar
  12. Dupont  H, Dupont-Perdrizet  D, Perie  JL, Zehner-Hansen  S, Jarrige  B, Daijardin  JB. Leptospirosis: prognostic factors associated with mortality. Clin Infect Dis. 1997;25:720–4. DOIPubMedGoogle Scholar
  13. Galdino  GS, de Sandes-Freitas  TV, de Andrade  LGM, Adamian  CMC, Meneses  GC, da Silva  GB Junior, et al. Development and validation of a simple machine learning tool to predict mortality in leptospirosis. Sci Rep. 2023;13:4506. DOIPubMedGoogle Scholar
  14. Tubiana  S, Mikulski  M, Becam  J, Lacassin  F, Lefèvre  P, Gourinat  AC, et al. Risk factors and predictors of severe leptospirosis in New Caledonia. PLoS Negl Trop Dis. 2013;7:e1991. DOIPubMedGoogle Scholar
  15. Abgueguen  P, Delbos  V, Blanvillain  J, Chennebault  JM, Cottin  J, Fanello  S, et al. Clinical aspects and prognostic factors of leptospirosis in adults. Retrospective study in France. J Infect. 2008;57:171–8. DOIPubMedGoogle Scholar
  16. Reis  EA, Hagan  JE, Ribeiro  GS, Teixeira-Carvalho  A, Martins-Filho  OA, Montgomery  RR, et al. Cytokine response signatures in disease progression and development of severe clinical outcomes for leptospirosis. PLoS Negl Trop Dis. 2013;7:e2457. DOIPubMedGoogle Scholar
  17. Senavirathna  I, Rathish  D, Agampodi  S. Cytokine response in human leptospirosis with different clinical outcomes: a systematic review. BMC Infect Dis. 2020;20:268. DOIPubMedGoogle Scholar
  18. Boonsilp  S, Thaipadungpanit  J, Amornchai  P, Wuthiekanun  V, Bailey  MS, Holden  MT, et al. A single multilocus sequence typing (MLST) scheme for seven pathogenic Leptospira species. PLoS Negl Trop Dis. 2013;7:e1954. DOIPubMedGoogle Scholar
  19. Thaipadungpanit  J, Wuthiekanun  V, Chierakul  W, Smythe  LD, Petkanchanapong  W, Limpaiboon  R, et al. A dominant clone of Leptospira interrogans associated with an outbreak of human leptospirosis in Thailand. PLoS Negl Trop Dis. 2007;1:e56. DOIPubMedGoogle Scholar
  20. Jolley  KA, Bray  JE, Maiden  MCJ. Open-access bacterial population genomics: BIGSdb software, the PubMLST.org website and their applications. Wellcome Open Res. 2018;3:124. DOIPubMedGoogle Scholar
  21. Grillová  L, Robinson  MT, Chanthongthip  A, Vincent  AT, Nieves  C, Oppelt  J, et al. Genetic diversity of Leptospira isolates in Lao PDR and genome analysis of an outbreak strain. PLoS Negl Trop Dis. 2021;15:e0010076. DOIPubMedGoogle Scholar
  22. World Health Organization (WHO). Human leptospirosis: guidance for diagnosis, surveillance and control. 2003 [cited 2026 Jan 5]. https://www.who.int/publications/i/item/human-leptospirosis-guidance-for-diagnosis-surveillance-and-control
  23. Moreno  R, Rhodes  A, Piquilloud  L, Hernandez  G, Takala  J, Gershengorn  HB, et al. The Sequential Organ Failure Assessment (SOFA) score: has the time come for an update? Crit Care. 2023;27:15. DOIPubMedGoogle Scholar
  24. Singer  M, Deutschman  CS, Seymour  CW, Shankar-Hari  M, Annane  D, Bauer  M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315:801–10. DOIPubMedGoogle Scholar
  25. Vincent  JL, Moreno  R, Takala  J, Willatts  S, De Mendonça  A, Bruining  H, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. Intensive Care Med. 1996;22:707–10. DOIPubMedGoogle Scholar
  26. Stoddard  RA, Gee  JE, Wilkins  PP, McCaustland  K, Hoffmaster  AR. Detection of pathogenic Leptospira spp. through TaqMan polymerase chain reaction targeting the LipL32 gene. Diagn Microbiol Infect Dis. 2009;64:247–55. DOIPubMedGoogle Scholar
  27. Stone  NE, Hamond  C, Clegg  JR, McDonough  RF, Bourgeois  RM, Ballard  R, et al. Host population dynamics influence Leptospira spp. transmission patterns among Rattus norvegicus in Boston, Massachusetts, US. PLoS Negl Trop Dis. 2025;19:e0012966. DOIPubMedGoogle Scholar
  28. Giraud-Gatineau  A, Nieves  C, Harrison  LB, Benaroudj  N, Veyrier  FJ, Picardeau  M. Evolutionary insights into the emergence of virulent Leptospira spirochetes. PLoS Pathog. 2024;20:e1012161. DOIPubMedGoogle Scholar
  29. Al Hariri  YK, Sulaiman  SAS, Khan  AH, Adnan  AS, Al-Ebrahem  SQ. Determinants of prolonged hospitalization and mortality among leptospirosis patients attending tertiary care hospitals in northeastern state in peninsular Malaysia: a cross sectional retrospective analysis. Front Med (Lausanne). 2022;9:887292. DOIPubMedGoogle Scholar
  30. Gancheva  GI. Leptospirosis in elderly patients. Braz J Infect Dis. 2013;17:592–5. DOIPubMedGoogle Scholar
  31. Mikulski  M, Boisier  P, Lacassin  F, Soupé-Gilbert  ME, Mauron  C, Bruyere-Ostells  L, et al. Severity markers in severe leptospirosis: a cohort study. Eur J Clin Microbiol Infect Dis. 2015;34:687–95. DOIPubMedGoogle Scholar
  32. Petakh  P, Nykyforuk  A. Predictors of lethality in severe leptospirosis in Transcarpathian region of Ukraine. Infez Med. 2022;30:272–6.PubMedGoogle Scholar
  33. Agampodi  SB, Matthias  MA, Moreno  AC, Vinetz  JM. Utility of quantitative polymerase chain reaction in leptospirosis diagnosis: association of level of leptospiremia and clinical manifestations in Sri Lanka. Clin Infect Dis. 2012;54:1249–55. DOIPubMedGoogle Scholar
  34. Tubiana  S, Mikulski  M, Becam  J, Lacassin  F, Lefèvre  P, Gourinat  A-C, et al. Risk factors and predictors of severe leptospirosis in New Caledonia. PLoS Negl Trop Dis. 2013;7:e1991. DOIPubMedGoogle Scholar
  35. Hochedez  P, Theodose  R, Olive  C, Bourhy  P, Hurtrel  G, Vignier  N, et al. Factors associated with severe leptospirosis, Martinique, 2010–2013. Emerg Infect Dis. 2015;21:2221–4. DOIPubMedGoogle Scholar
  36. Philip  N, Bahtiar Affendy  N, Ramli  SNA, Arif  M, Raja  P, Nagandran  E, et al. Leptospira interrogans and Leptospira kirschneri are the dominant Leptospira species causing human leptospirosis in Central Malaysia. PLoS Negl Trop Dis. 2020;14:e0008197. DOIPubMedGoogle Scholar
  37. Ravindranathan  AT, Mukundan  A, Puthanpurayil  SNT, Kavuthodi  B, Karunakaran  S, John  R. Molecular and genomic characterization of Leptospira isolates in humans and its relation to disease severity. Indian J Med Microbiol. 2025;56:100910. DOIPubMedGoogle Scholar

Main Article

Page created: April 27, 2026
Page updated: June 05, 2026
Page reviewed: June 05, 2026
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
file_external