Risk factors for pulmonary tuberculosis recurrence, relapse and reinfection: a systematic review and meta-analysis.

BACKGROUND: The rate of pulmonary tuberculosis (TB) recurrence is substantial. Identifying risk factors can support the development of prevention strategies. METHODS: We retrieved studies published between 1 January 1980 and 31 December 2022 that assessed factors associated with undifferentiated TB recurrence, relapse or reinfection. For factors reported in at least four studies, we performed random-effects meta-analysis to estimate a pooled relative risk (RR). We assessed heterogeneity, risk of publication bias and certainty of evidence. RESULTS: We included 85 studies in the review; 81 documented risk factors for undifferentiated recurrence, 17 for relapse and 10 for reinfection. The scope for meta-analyses was limited given the wide variety of factors studied, inconsistency in control for confounding and the fact that only few studies employed molecular genotyping. Factors that significantly contributed to moderately or strongly increased pooled risk and scored at least moderate certainty of evidence were: for undifferentiated recurrence, multidrug resistance (MDR) (RR 3.49; 95% CI 1.86 to 6.53) and fixed-dose combination TB drugs (RR 2.29; 95% CI 1.10 to 4.75) in the previous episode; for relapse, none; and for reinfection, HIV infection (RR 4.65; 95% CI 1.71 to 12.65). Low adherence to treatment increased the pooled risk of recurrence 3.3-fold (95% CI 2.37 to 4.62), but the certainty of evidence was weak. CONCLUSION: This review emphasises the need for standardising methods for TB recurrence research. Actively pursuing MDR prevention, facilitating retention in treatment and providing integrated care for patients with HIV could curb recurrence rates. The use of fixed-dose combinations of TB drugs under field conditions merits further attention. PROSPERO REGISTRATION NUMBER: CRD42018077867.

Lung cancer occurrence after an episode of tuberculosis: a systematic review and meta-analysis.

INTRODUCTION: People with tuberculosis experience long-term health effects beyond cure, including chronic respiratory diseases. We investigated whether tuberculosis is a risk factor for subsequent lung cancer. METHODS: We searched PubMed, Scopus, Cochrane, Latin American and Caribbean Health Sciences Literature and the Scientific Electronic Library Online for cohort and case-control studies providing effect estimates for the association between tuberculosis and subsequent lung cancer. We pooled estimates through random-effects meta-analysis. The study was registered in PROSPERO (CDR42020178362). RESULTS: Out of 6240 records, we included 29 cohort and 44 case-control studies. Pooled estimates adjusted for age and smoking (assessed quantitatively) were hazard ratio (HR) 1.51 (95% CI 1.30-1.76, I2=81%; five studies) and OR 1.74 (95% CI 1.42-2.13, I2=59%; 19 studies). The occurrence of lung cancer was increased for 2 years after tuberculosis diagnosis (HR 5.01, 95% CI 3.64-6.89; two studies), but decreased thereafter. Most studies were retrospective, had moderate to high risk of bias, and did not control for passive smoking, environmental exposure and socioeconomic status. Heterogeneity was high. CONCLUSION: We document an association between tuberculosis and lung cancer occurrence, particularly in, but not limited to, the first 2 years after tuberculosis diagnosis. Some cancer cases may have been present at the time of tuberculosis diagnosis and therefore causality cannot be ascertained. Prospective studies controlling for key confounding factors are needed to identify which tuberculosis patients are at the highest risk, as well as cost-effective approaches to mitigate such risk.