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Whole genome sequencing based differentiation between re-infection and relapse in Indian patients with tuberculosis recurrence, with and without HIV co-infection

Sivakumar Shanmugam, Nathan L Bachmann, Elena Martinez, Ranjeeta Menon, Gopalan Narendran, Sujantha Narayanan, Srikanth Tripathy, K R Uma Devi, Shailendra Sawleshwarkar, Ben Marais, Vitali Sintchenko
doi: https://doi.org/10.1101/2020.07.29.227926
Sivakumar Shanmugam
1National Institute for Research in Tuberculosis, Chennai, Tamil Nadu, India
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Nathan L Bachmann
2Centre for Infectious Diseases and Microbiology – Public Health, Westmead Hospital, Sydney, New South Wales, Australia
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  • For correspondence: nathan.bachmann@sydney.edu.au
Elena Martinez
2Centre for Infectious Diseases and Microbiology – Public Health, Westmead Hospital, Sydney, New South Wales, Australia
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Ranjeeta Menon
2Centre for Infectious Diseases and Microbiology – Public Health, Westmead Hospital, Sydney, New South Wales, Australia
4Sydney Medical School, Faculty of Medicine and Health, University of Sydney, New South Wales, Australia
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Gopalan Narendran
1National Institute for Research in Tuberculosis, Chennai, Tamil Nadu, India
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Sujantha Narayanan
1National Institute for Research in Tuberculosis, Chennai, Tamil Nadu, India
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Srikanth Tripathy
1National Institute for Research in Tuberculosis, Chennai, Tamil Nadu, India
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K R Uma Devi
1National Institute for Research in Tuberculosis, Chennai, Tamil Nadu, India
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Shailendra Sawleshwarkar
3Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, New South Wales, Australia
4Sydney Medical School, Faculty of Medicine and Health, University of Sydney, New South Wales, Australia
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Ben Marais
3Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, New South Wales, Australia
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Vitali Sintchenko
2Centre for Infectious Diseases and Microbiology – Public Health, Westmead Hospital, Sydney, New South Wales, Australia
3Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, New South Wales, Australia
4Sydney Medical School, Faculty of Medicine and Health, University of Sydney, New South Wales, Australia
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Abstract

Differentiation between relapse and reinfection in cases with tuberculosis (TB) recurrence has important implications for public health, especially in patients with human immunodeficiency virus (HIV) co-infection. Forty-one paired M. tuberculosis isolates collected from 20 HIV-positive and 21 HIV-negative patients, who experienced TB recurrence after previous successful treatment, were subjected to whole genome sequencing (WGS) in addition to spoligotyping and mycobacterial interspersed repeat unit (MIRU) typing. Comparison of M. tuberculosis genomes indicated that 95% of TB recurrences in the HIV-negative cohort were due to relapse, while the majority of TB recurrences (75%) in the HIV-positive cohort was due to re-infection (P=0.0001). Drug resistance conferring mutations were documented in four pairs (9%) of isolates associated with relapse. The high contribution of re-infection to TB among HIV patients warrants further study to explore risk factors for TB exposure in the community.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted July 30, 2020.
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Whole genome sequencing based differentiation between re-infection and relapse in Indian patients with tuberculosis recurrence, with and without HIV co-infection
Sivakumar Shanmugam, Nathan L Bachmann, Elena Martinez, Ranjeeta Menon, Gopalan Narendran, Sujantha Narayanan, Srikanth Tripathy, K R Uma Devi, Shailendra Sawleshwarkar, Ben Marais, Vitali Sintchenko
bioRxiv 2020.07.29.227926; doi: https://doi.org/10.1101/2020.07.29.227926
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Whole genome sequencing based differentiation between re-infection and relapse in Indian patients with tuberculosis recurrence, with and without HIV co-infection
Sivakumar Shanmugam, Nathan L Bachmann, Elena Martinez, Ranjeeta Menon, Gopalan Narendran, Sujantha Narayanan, Srikanth Tripathy, K R Uma Devi, Shailendra Sawleshwarkar, Ben Marais, Vitali Sintchenko
bioRxiv 2020.07.29.227926; doi: https://doi.org/10.1101/2020.07.29.227926

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