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

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  • 1 Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut;
  • 2 Department of Community Medicine, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura, Sri Lanka

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 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-mail: suneth.agampodi@yale.edu

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-mail: suneth.agampodi@yale.edu. 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.

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