Abstract

The study aims to describe the clustering characteristics of Mycobacterium tuberculosis (M.tb) strains circulating in eastern China and determine the ratio of relapse and reinfection in recurrent patients. We recruited sputum smear-positive pulmonary tuberculosis cases from five cities of Jiangsu Province, China, during August 2013 and December 2015. Patients were followed for the treatment outcomes and recurrence based on a cohort design. M.tb strains were isolated and genotyped using the 12-locus MIRU-VNTR. The Beijing family was identified by the extended Region of Difference (RD) analysis. The Hunter-Gaston Discriminatory Index (HGDI) was used to judge the resolution ability of MIRU-VNTR. The odds ratio (OR) together with 95% confidence interval (CI) were used to estimate the strength of association. We performed a cluster analysis on 2098 M.tb isolates and classified them into 545 genotypes and five categories (I, 0.19%; II, 0.43%; III, 3.34%; IV, 77.46%; V, 18.59%). After adjusting for potential confounders, the Beijing family genotype (OR = 118.63, 95% CI: 79.61–176.79, P = 0.001) was significantly related to the dominant strain infections. Patients infected with non-dominant strains had a higher risk of the pulmonary cavity (OR = 1.39, 95% CI: 1.01–1.91, P = 0.046). Among 37 paired recurrent cases, 22 (59.46%) were determined as endogenous reactivation, and 15 (40.54%) were exogenous reinfection. The type of M.tb strains prevalent in Jiangsu Province is relatively single. Beijing family strains infection is dominant in local tuberculosis cases. Endogenous reactivation appears to be a major cause of recurrent tuberculosis in Eastern China. This finding emphasizes the importance of case follow-up and monitoring after the completion of antituberculosis treatment.

Highlights

  • Tuberculosis (TB) is a common chronic infectious and consumptive disease that damages the organs of the whole body

  • Because TB recurrence is usually associated with drug resistance, it is reasonable to distinguish the types of TB recurrence and to understand the mechanism of endogenous reactivation and exogenous reinfection

  • Incomplete retention of primary and recurrent isolates, and samples with failed DNA extraction, 37 pairs of recurrent cases were used for mycobacterial interspersed repetitive units (MIRU)-variable number of tandem repeats (VNTR) genotyping comparison (Figure 1)

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Summary

Introduction

Tuberculosis (TB) is a common chronic infectious and consumptive disease that damages the organs of the whole body. Recurrence of TB can be due to either relapse of an initial infection or exogenous reinfection with new Mycobacterium tuberculosis (M.tb) strains [3]. The causes of such two types of recurrence are different [4]. Poor treatment adherence [5], positive sputum smear, pulmonary cavity [6], drug resistance [7], old age [8], or Beijing family M.tb strains [9] are the risk factors of endogenous reactivation, while human immunodeficiency virus (HIV) infection [10] and diabetes [11] can increase the risk of exogenous reinfection. Because TB recurrence is usually associated with drug resistance, it is reasonable to distinguish the types of TB recurrence and to understand the mechanism of endogenous reactivation and exogenous reinfection

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