Next-Generation Sequencing Analysis of Pathogenic Leptospira: A Way Forward for Understanding Infectious Disease Dynamics in Low/Middle-Income, Disease-Endemic Settings

Suneth B. Agampodi Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut;
Department of Community Medicine, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura, Sri Lanka

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Joseph M. Vinetz Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut;

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ABSTRACT

In the current genomic era, knowledge of diversity of Leptospira, the spirochetal agents of leptospirosis, is changing rapidly. Next-generation sequencing has decreased in price and increased in scale, with the potential to democratize large-scale analysis of pathogens in resource-limited, low/middle-income (LMIC) regions. Consequently, the molecular classification of Leptospira, a pathogen disproportionately affecting LMIC countries, has changed dramatically over the last decade. Leptospira classification and molecular understandings of pathogen diversity have rapidly evolved, now most precisely based on core genome analysis supplemented by new insights provided by culture-independent methods directly using body fluids such as blood and urine. In places where leptospirosis disease burden is highest, genomic technologies have not been available, and serology-based methods remain the mainstay of leptospiral classification. Understanding the epidemiology, pathogenesis, and ultimately new approaches to treating and preventing leptospirosis requires detailed knowledge of regionally circulating Leptospira in highly endemic settings. Next-generation sequencing–based, culture-independent typing overcomes the limitation of culture isolation of Leptospira from clinical samples, with promise of providing public health-actionable information applicable to leptospirosis-endemic LMIC settings.

Author Notes

Address correspondence to Suneth B. Agampodi, Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, Yale University, Winchester Bldg., 25 York St., Rm. 428, New Haven, CT 06510. E-mails: suneth.agampodi@yale.edu or sunethagampodi@yahoo.com

Financial support: This work was supported by U.S. Public Health Service, National Institute of Allergy and Infectious Diseases of the National Institutes of Health, through grant number U19AI115658.

Authors’ addresses: Suneth B. Agampodi, Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, and Department of Community Medicine, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura, Sri Lanka, E-mails: suneth.agampodi@yale.edu or sunethagampodi@yahoo.com. Joseph M. Vinetz, Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, E-mail: joseph.vinetz@yale.edu.

  • 1.

    Vincent AT et al. 2019. Revisiting the taxonomy and evolution of pathogenicity of the genus Leptospira through the prism of genomics. PLoS Negl Trop Dis 13: e0007270.

  • 2.

    Fouts DE et al. 2016. What makes a bacterial species pathogenic? Comparative genomic analysis of the genus Leptospira. PLoS Negl Trop Dis 10: e0004403.

  • 3.

    Thibeaux R, Iraola G, Ferres I, Bierque E, Girault D, Soupe-Gilbert ME, Picardeau M, Goarant C, 2018. Deciphering the unexplored Leptospira diversity from soils uncovers genomic evolution to virulence. Microb Genom 4: e000144.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Guglielmini J, Bourhy P, Schiettekatte O, Zinini F, Brisse S, Picardeau M, 2019. Genus-wide Leptospira core genome multilocus sequence typing for strain taxonomy and global surveillance. PLoS Negl Trop Dis 13: e0007374.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Casanovas-Massana A et al. 2020. Leptospira yasudae sp. nov. and Leptospira stimsonii sp. nov., two new species of the pathogenic group isolated from environmental sources. Int J Syst Evol Microbiol 70, 14501456.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Wolff JW, Broom JC, 1954. The genus Leptospira Noguchi, 1917; problems of classification and a suggested system based on antigenic analysis. Doc Med Geogr Trop 6: 7895.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Kalambaheti T, Bulach DM, Rajakumar K, Adler B, 1999. Genetic organization of the lipopolysaccharide O-antigen biosynthetic locus of Leptospira borgpetersenii serovar Hardjobovis. Microb Pathog 27: 105117.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Levett PN, 2015. Systematics of leptospiraceae. Curr Top Microbiol Immunol 387: 1120.

  • 9.

    Martin L, Pettit A, 1918. Sero-diagnostic de la spirochaetose icterohaemorrhagique. Bull Mem Soc Med Hop Paris 42: 672675.

  • 10.

    Levett PN, 2003. Usefulness of serologic analysis as a predictor of the infecting serovar in patients with severe leptospirosis. Clin Infect Dis 36: 447452.

  • 11.

    Lecour H, Miranda M, Magro C, Rocha A, Goncalves V, 1989. Human leptospirosis–a review of 50 cases. Infection 17: 812.

  • 12.

    Gollop JH, Katz AR, Rudoy RC, Sasaki DM, 1993. Rat-bite leptospirosis. West J Med 159: 7677.

  • 13.

    Torre D, Giola M, Martegani R, Zeroli C, Fiori GP, Ferrario G, Bonetta G, 1994. Aseptic meningitis caused by Leptospira australis. Eur J Clin Microbiol Infect Dis 13: 496497.

  • 14.

    Agampodi SB, Thevanesam V, Wimalarathna H, Senarathna T, Wijedasa MH, 2008. A preliminary study on prevalent serovars of leptospirosis among patients admitted to teaching hospital, Kandy, Sri Lanka. Indian J Med Microbiol 26: 405406.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Rajapakse S et al. 2020. Seroprevalence of leptospirosis in an endemic mixed urban and semi-urban setting-A community-based study in the district of Colombo, Sri Lanka. PLoS Negl Trop Dis 14: e0008309.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Smythe LD et al. 2009. The microscopic agglutination test (MAT) is an unreliable predictor of infecting Leptospira serovar in Thailand. Am J Trop Med Hyg 81: 695697.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Chappel RJ, Goris M, Palmer MF, Hartskeerl RA, 2004. Impact of proficiency testing on results of the microscopic agglutination test for diagnosis of leptospirosis. J Clin Microbiol 42: 54845488.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Perez J, Goarant C, 2010. Rapid Leptospira identification by direct sequencing of the diagnostic PCR products in New Caledonia. BMC Microbiol 10: 325.

  • 19.

    Chiani Y, Jacob P, Varni V, Landolt N, Schmeling MF, Pujato N, Caimi K, Vanasco B, 2016. Isolation and clinical sample typing of human leptospirosis cases in Argentina. Infect Genet Evol 37: 245251.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Philip N et al. 2020. Leptospira interrogans and Leptospira kirschneri are the dominant Leptospira species causing human leptospirosis in Central Malaysia. PLoS Negl Trop Dis 14: e0008197.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    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.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Agampodi SB et al. 2011. Leptospirosis outbreak in Sri Lanka in 2008: lessons for assessing the global burden of disease. Am J Trop Med Hyg 85: 471478.

  • 23.

    Agampodi SB, Moreno AC, Vinetz JM, Matthias MA, 2013. Utility and limitations of direct multi-locus sequence typing on qPCR-positive blood to determine infecting Leptospira strain. Am J Trop Med Hyg 88: 184185.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Weiss S, Menezes A, Woods K, Chanthongthip A, Dittrich S, Opoku-Boateng A, Kimuli M, Chalker V, 2016. An extended multilocus sequence typing (MLST) scheme for rapid direct typing of Leptospira from clinical samples. PLoS Negl Trop Dis 10: e0004996.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Varni V, Chiani Y, Nagel A, Ruybal P, Vanasco NB, Caimi K, 2018. Simplified MLST scheme for direct typing of Leptospira human clinical samples. Pathog Glob Health 112: 203209.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26.

    Schwarze K, Buchanan J, Taylor JC, Wordsworth S, 2018. Are whole-exome and whole-genome sequencing approaches cost-effective? A systematic review of the literature. Genet Med 20: 11221130.

    • PubMed
    • Search Google Scholar
    • Export Citation
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