Recurrent tuberculosis and its risk factors: adequately treated patients are still at high risk

Recurrent tuberculosis (TB) poses significant threats, including drug resistance, to TB control programs. However, recurrence and its causes, particularly in the era of epidemic human immunodeficiency virus (HIV), have not been well described. We systematically searched published material for studies reporting on recurrent TB following completion of standard treatment regimens to provide data on the issue. A total of 32 studies were reviewed. Among controlled trials, the overall recurrence rates (per 100,000 person-years) were respectively 3,010 (95%CI 2,230-3,970) and 2,290 (95%CI 1,730-2,940) at 6 and 12 months after treatment completion. Recurrence rates were higher among observational studies compared to controlled trials and in countries with high versus low background TB incidence. TB recurrence (%) was higher among HIV-infected (6.7, 95%CI 5.9-7.6) than non-HIV-infected individuals (3.3, 95%CI 2.8-3.9). Factors independently associated with recurrence in the literature included residual cavitation, greater area of involved lung tissue, positive sputum culture at 2 months of treatment and HIV infection. Among those with HIV infection, recurrent TB was associated with a low initial CD(4) count and receiving less than 37 weeks of anti-tuberculosis treatment. We argue that adequately treated patients are still at high risk for recurrent disease and should be considered in case-finding strategies. Moreover, those with multiple risk factors may benefit from modification of standard treatment.