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Whole-genome sequencing differentiates relapse from re-infection in TB

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BACKGROUND: Distinguishing TB relapse from re-infection is important from a clinical perspective to document transmission patterns. We investigated isolates from patients classified as relapse to understand if these were true relapses or re-infections. We also investigated shifts in drug susceptibility patterns to distinguish acquired drug resistance from re-infection with resistant strains.

METHODS: Isolates from pulmonary TB patients from 2009 to 2017 were analysed using whole-genome sequencing (WGS).

RESULTS: Of 11 patients reported as relapses, WGS results indicated that 4 were true relapses (single nucleotide polymorphism difference ≤5), 3 were re-infections with new strains, 3 were both relapse and re-infection and 1 was a suspected relapse who was later categorised as treatment failure based on sequencing. Of the 9 patients who went from a fully susceptible to a resistant profile, WGS showed that none had acquired drug resistance; 6 were re-infected with new resistant strains, 1 was probably infected by at least two different genotype strains and 2 were phenotypically misclassified.

CONCLUSIONS: WGS was shown to distinguish between relapse and re-infection in an unbiased way. The use of WGS minimises the risk of false classification of treatment failure instead of re-infection. Furthermore, our study showed that strains without major genetic differences can cause re-infection.

Keywords: drug resistance; re-infection; relapse; tuberculosis; whole-genome sequencing

Document Type: Research Article

Affiliations: 1: The Republican Research and Practical Centre for Pulmonology and Tuberculosis, Minsk, Belarus 2: Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden 3: WHO Country Office in Belarus, Minsk, Belarus 4: Latvian Centre of Infectious Diseases Laboratory, National Microbiology Reference Laboratory, Riga East University Hospital, Riga, Latvia 5: Joint Infectious Diseases Programme, WHO Regional Office for Europe, Copenhagen, Denmark

Publication date: December 1, 2021

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  • The International Journal of Tuberculosis and Lung Disease (IJTLD) is for clinical research and epidemiological studies on lung health, including articles on TB, TB-HIV and respiratory diseases such as COVID-19, asthma, COPD, child lung health and the hazards of tobacco and air pollution. Individuals and institutes can subscribe to the IJTLD online or in print – simply email us at [email protected] for details.

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