Recurrence of tuberculosis among patients following treatment completion in eight provinces of Vietnam: A nested case-control study

Background: Patients completing treatment for tuberculosis (TB) in high-prevalence settings face a risk of developing recurrent disease. This has important consequences for public health, given its association with drug resistance and a poor prognosis. Previous research has implicated individual factors such as smoking, alcohol use, HIV, poor treatment adherence, and drug resistant disease as risk factors for recurrence. However, little is known about how these factors co-act to produce recurrent disease. Furthermore, perhaps factors related to the index disease means higher burden/low resource settings may be more prone to recurrent disease that could be preventable. Methods: We conducted a case-control study nested within a cohort of consecutively enrolled adults who were being treated for smear positive pulmonary TB in 70 randomly selected district clinics in Vietnam. Cases were patients with recurrent TB, identified by follow-up from the parent cohort study. Controls were selected from the cohort by random sampling. Information on demographic, clinical and disease-related characteristics was obtained by interview. Treatment information was extracted from clinic registries. Logistic regression, with stepwise selection, was used to develop a fully adjusted model for the odds of recurrence of TB. Results: We recruited 10,964 patients between October 2010 and July 2013. Median follow-up was 988 days. At the end of follow-up, 505 patients (4.7%) with recurrence were identified as cases and 630 other patients were randomly selected as controls. Predictors of recurrence included multidrug-resistant (MDR)-TB (adjusted odds ratio 79.6; 95% CI: 25.1-252.0), self-reported prior TB therapy (aOR = 2.5; 95% CI: 1.7-3.5), and incomplete adherence (aOR = 1.9; 95% CI 1.1-3.1). Conclusions: Index disease treatment history is a leading determinant of relapse among patients with TB in Vietnam. Further research is required to identify interventions that will reduce the risk of recurrent disease and enhance its early detection within high-risk populations. Keywords: Contact investigation, Tuberculosis, Active tuberculosis, Tuberculosis epidemiology, Relapse, Risk factors, Screenin