Recurrent Tuberculosis Disease in Singapore

Abstract

Background: Previously treated (ie, recurrent) tuberculosis (TB) cases account for approximately 7%-8% of incident TB globally and in Singapore. Molecular fingerprinting has enabled the differentiation of these patients into relapsed or reinfection cases.

Methods: Patient demographics, disease characteristics, and treatment information were obtained from the national TB notification registry and TB Control Unit. We performed a retrospective, case-control study to evaluate factors associated with recurrent TB disease in Singapore citizens and permanent residents with culture-positive TB from 2006 to 2013 and who developed a second episode of culture-positive TB up to 2016 using multivariable logistic regression analyses.

Results: Ninety-one cases with culture-positive first and recurrent TB disease episodes were identified. Recurrent TB was associated with age ≥60 years (adjusted odds ratio [aOR], 1.98 [95% confidence interval {CI}, 1.09-3.61), male sex (aOR, 2.29 [95% CI, 1.22-4.51]), having concomitant pulmonary and extrapulmonary TB (aOR, 3.10 [95% CI, 1.59-6.10]) and extrapulmonary TB alone (aOR, 3.82 [95% CI, 1.12-13.31]), and was less likely in non-Malays (aOR, 0.52 [95% CI, .27-.99]). DNA fingerprinting results for both episodes in 49 cases differentiated these into 28 relapsed and 21 reinfection cases. Relapse was associated with having concomitant pulmonary and extrapulmonary TB (aOR, 9.24 [95% CI, 2.50-42.42]) and positive sputum acid-fast bacilli smear (aOR, 3.95 [95% CI, 1.36-13.10]).

Conclusions: Relapse and reinfection contributed to 57% and 43%, respectively, of recurrent TB in Singapore. Our study highlights the underappreciated association of concomitant pulmonary and extrapulmonary TB as a significant risk factor for disease relapse.

Keywords: exogenous reinfection; extrapulmonary; relapse; tuberculosis.

Figure 1.

There were 7478 culture-positive tuberculosis (TB) cases notified from 1 January 2006 to 31 December 2013. Of these, 91 had 2 or more culture-positive TB episodes as of 31 December 2016. Mycobacterial interspersed repetitive unit variable number tandem repeat and spoligotyping results were available for both TB disease episodes in 49 of the 91 (53.8%) cases. Twenty-four cases had identical results and 4 had results that differed by 1 or 2 loci (relapse cases). Twenty-one cases had different DNA fingerprint results for the first and recurrent episodes (reinfection cases). Abbreviations: HIV, human immunodeficiency virus; INH, isoniazid; TB, tuberculosis.