The rate of sputum smear-positive tuberculosis after treatment default in a high-burden setting: a retrospective cohort study

Abstract

Rationale: High rates of recurrent tuberculosis after successful treatment have been reported from different high burden settings in Sub-Saharan Africa. However, little is known about the rate of smear-positive tuberculosis after treatment default. In particular, it is not known whether or not treatment defaulters continue to be or become again smear-positive and thus pose a potential for transmission of infection to others.

Objective: To investigate, in a high tuberculosis burden setting, the rate of re-treatment for smear-positive tuberculosis among cases defaulting from standardized treatment compared to successfully treated cases.

Methods: Retrospective cohort study among smear-positive tuberculosis cases treated between 1996 and 2008 in two urban communities in Cape Town, South Africa. Episodes of re-treatment for smear-positive tuberculosis were ascertained via probabilistic record linkage. Survival analysis and Poisson regression were used to compare the rate of smear-positive tuberculosis after treatment default to that after successful treatment.

Results: A total of 2,136 smear-positive tuberculosis cases were included in the study. After treatment default, the rate of re-treatment for smear-positive tuberculosis was 6.86 (95% confidence interval [CI]: 5.59-8.41) per 100 person-years compared to 2.09 (95% CI: 1.81-2.41) after cure (adjusted Hazard Ratio [aHR]: 3.97; 95% CI: 3.00-5.26). Among defaulters, the rate was inversely associated with treatment duration and sputum conversion prior to defaulting. Smear grade at start of the index treatment episode (Smear3+: aHR 1.61; 95%CI 1.11-2.33) was independently associated with smear-positive tuberculosis re-treatment, regardless of treatment outcome.

Conclusions: In this high-burden setting, there is a high rate of subsequent smear-positive tuberculosis after treatment default. Treatment defaulters are therefore likely to contribute to the pool of infectious source cases in the community. Our findings underscore the importance of preventing treatment default, as a means of successful tuberculosis control in high-burden settings.

Figure 1. Overview of smear-positive tuberculosis cases included in and excluded from the study.

Figure 2. Ascertainment of subsequent episodes of re-treatment via record linkage and manual review for the study.

Figure 3. Kaplan Meier failure estimates of re-treatment for smear-positive tuberculosis by index episode sputum smear grading and treatment outcome.

Figure 4. Kaplan Meier failure estimates of smear-positive re-treatment after treatment default, stratified by smear conversion prior to defaulting (adjusted for time to default).