Investigation on the cause of recurrent tuberculosis in a rural area in China using whole-genome sequencing: A retrospective cohort study

Recurrent tuberculosis (TB) in China has been studied in urban areas but not in rural settings. We conducted a retrospective cohort study on all successfully treated bacteriologically confirmed TB patients between 2009 and 2020 in Wusheng County, Sichuan Province using whole-genome sequencing (WGS). Isolates differing by ≤ 12 single nucleotide polymorphisms (SNPs) were considered relapse, otherwise were considered exogenous reinfection, and molecular drug susceptibility results were also compared. In total, 4.9% (75/1532) of successfully treated cases had subsequent bouts of TB, with 4 patients having two subsequent bouts, yielding a total of 79 events and a rate of 8.56 (95% CI 6.86-10.67) cases per 1000 person years, 8.9 times higher than in the general population. Most recurrences (74.4%, 58/79) occurred within three years. The risk for recurrent TB was increased for men and patients with drug-resistant isolates. Among the 44 recurrent events with genotyped paired isolates, 39 were classified as relapse and 5 as exogenous reinfection. Ten (25%, 10/40) recurrent patients acquired new resistance during treatment. Recurrent TB in rural Wusheng was mostly relapse and associated with drug resistance, suggesting the need to improve patient management, resistance testing and patient follow-up for at least 3 years after completing treatment.