Whole-genome sequencing differentiates relapse from re-infection in TB
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: 01 December 2021
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