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; G Narendran; Sujatha Narayanan; Srikanth P Tripathy; Uma Devi Ranganathan; Shailendra Sawleshwarkar; Ben J Marais; Vitali Sintchenko

doi:10.1016/j.ijid.2021.03.020

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

Int J Infect Dis. 2021 Dec:113 Suppl 1:S43-S47. doi: 10.1016/j.ijid.2021.03.020. Epub 2021 Mar 16.

Affiliations

¹ ICMR-National Institute for Research in Tuberculosis, Chennai, Tamil Nadu, India.
² Centre for Infectious Diseases and Microbiology - Public Health, Westmead Hospital, Sydney, New South Wales, Australia. Electronic address: nathan.bachmann@sydney.edu.au.
³ Centre for Infectious Diseases and Microbiology - Public Health, Westmead Hospital, Sydney, New South Wales, Australia.
⁴ Centre for Infectious Diseases and Microbiology - Public Health, Westmead Hospital, Sydney, New South Wales, Australia; Sydney Medical School, Faculty of Medicine and Health, University of Sydney, New South Wales, Australia.
⁵ Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, New South Wales, Australia; Sydney Medical School, Faculty of Medicine and Health, University of Sydney, New South Wales, Australia.
⁶ Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, New South Wales, Australia.
⁷ Centre for Infectious Diseases and Microbiology - Public Health, Westmead Hospital, Sydney, New South Wales, Australia; Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, New South Wales, Australia; Sydney Medical School, Faculty of Medicine and Health, University of Sydney, New South Wales, Australia.

PMID: 33741489
DOI: 10.1016/j.ijid.2021.03.020

Abstract

Introduction: 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. We compared Mycobacterial Interspersed Repeat Unit (MIRU) typing and spoligotyping with whole genome sequencing (WGS) to differentiate between relapse and reinfection in patients (HIV-positive and HIV-negative) with TB recurrence. We also assessed the value of WGS to track acquired drug resistance in those with relapse after successful treatment.

Method: Forty-one paired M. tuberculosis isolates collected from 20 HIV-positive and 21 HIV-negative patients were subjected to WGS in addition to spoligotyping and MIRU typing. Phylogenetic and Single Nucleotide Substitution (SNP) clustering analyses were performed to determine whether recurrences were due to relapse or re-infection.

Results: 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 reinfection (P = 0.0001). New drug resistance mutations were acquired in 5/24 cases (20.8%) that experienced relapse.

Conclusions: WGS provided increased resolution, but differentiation between relapse and reinfection was broadly consistent with MIRU and spoligotyping. The high contribution of reinfection among HIV infected patients experiencing TB recurrence warrants further study to explore risk factors for TB exposure.

Keywords: Antimicrobial resistance; HIV; Mycobacterium tuberculosis; Single nucleotide polymorphism; co-infection; genome sequencing; recurrence.

MeSH terms

Coinfection* / epidemiology
HIV Infections* / complications
HIV Infections* / epidemiology
Humans
Phylogeny
Reinfection
Tuberculosis* / diagnosis
Tuberculosis* / drug therapy
Tuberculosis* / epidemiology
Whole Genome Sequencing