Recurrent tuberculosis is an important indicator of the effectiveness of tuberculosis control and can occur by relapse or exogenous reinfection. We conducted a retrospective cohort study on all bacteriologically confirmed tuberculosis cases that were successfully treated between 2000 and 2012 in Shanghai, an urban area with a high number but a low prevalence rate of tuberculosis cases and a low prevalence of HIV infection. Genotyping the Mycobacterium tuberculosis from clinical isolates was used to distinguish between relapse and reinfection. In total, 5.3% (710/13,417) of successfully treated cases had a recurrence, a rate of 7.55 (95% CI 7.01–8.13) episodes per 1000 person-years, more than 18 times the rate of tuberculosis in the general population. Patients who were male, age 30–59, retreatment cases, had cavitation, diabetes, drug-resistant or multidrug-resistant tuberculosis in their initial episode of tuberculosis, were at high risk for a recurrence. Among 141 recurrent cases that had paired isolates, 59 (41.8%) had different genotypes, indicating reinfection with a different strain. Patients who completed treatment were still at high risk of another episode of tuberculosis and exogenous reinfection contributed a significant proportion of the recurrent tuberculosis cases. Targeted control strategies are needed to prevent new tuberculosis infections in this setting.

BackgroundFluoroquinolones (FQs) are the most important second-line anti-tuberculosis (anti-TB) drugs, primarily used for the treatment of multidrug- or rifampicin-resistant TB (MDR/RR-TB). However, FQs are also commonly used to treat other bacterial infections. There are few published data on the rates of FQ resistance among rifampicin-susceptible TB.MethodsWe used whole-genome sequencing (WGS) to determine the prevalence of FQ resistance among rifampicin-susceptible TB in a rural district of Shanghai. This was a population-based retrospective study of all culture-positive pulmonary TB patients diagnosed in the Chongming district of Shanghai, China during 2009–2018.ResultsThe rate of FQ resistance was 8.4% (29/345) among TB, 6.2% (20/324) among rifampicin-susceptible TB, and 42.9% (9/21) among MDR/RR-TB. Transmission of FQ-resistant strains was defined as strains differing within 12 single-nucleotide polymorphisms (SNPs) based on WGS. Among the rifampicin-susceptible TB, 20% (4/20) of FQ resistance was caused by the transmission of FQ-resistant strains and 45% (9/20) of FQ resistance was identified as hetero-resistance.ConclusionsThe prevalence of FQ resistance in rifampicin-susceptible TB was higher than expected in Shanghai. Both the transmission and the selection of drug-resistant strains drive the emergence of FQ resistance in rifampicin-susceptible TB isolates. Therefore, the WGS-based surveillance system for TB should be urgently established and the clinical awareness of the rational use of FQs for respiratory infections should be enhanced to prevent the premature occurrence of FQ resistance.

No abstract