Incidence and Risk Factors of Active Tuberculosis Among Hospitalized Patients with Latent Tuberculosis Infection in China: A Cohort Study

Background: The population with latent tuberculosis infection (LTBI) represents a potential pool of patients with active tuberculosis (ATB). T-SPOT.TB is an important test tool for screening LTBI. Owing to the large population of LTBI patients in China, it is necessary to identify a high-risk group for LTBI and enlarge tuberculosis preventive treatment (TPT) to reduce the incidence of ATB. Methods: Hospitalized patients with positive T-SPOT.TB results were recruited from January 2013 to December 2016. Patients with ATB were excluded. Basic information was collected and the development of ATBs was examined during follow-up. The life-table method was used to calculate cumulative incidence rates. Potential risk factors were analyzed through Cox regression analysis. Results: A total of 1680 patients with LTBI were recruited in the follow-up cohort, and 377 (22.44%) patients dropped out. With a median follow-up time of 81 months [interquartile range (IQR):61– 93], 19 of 1303 patients with LTBI developed ATB. The 1-year incidence of ATB was 614 per 100,000 individuals [95%confidence interval (95% CI):584– 644]. Over 5-year period, the cumulative incidence of ATB was 1496 per 100,000 [95% CI:1430– 1570], and the incidence density was 240 per 100,000 person-years[95% CI:144– 375]. In the Cox regression model, exposure of pulmonary tuberculosis (PTB) [adjusted hazard ratio (aHR)=10.557, 95% CI:2.273– 49.031], maximum daily dosage of glucocorticoids (GCs)≥ 50 mg/d (aHR=2.948, 95% CI:1.122– 7.748), leflunomide (LEF) treatment (aHR=8.572, 95% CI:2.222 − 33.070), anemia (aHR=2.565, 95% CI:1.015– 6.479) and T-SPOT.TB level≥ 300SFCs/10 6 PBMCs (aHR=4.195, 95% CI:1.365– 12.892) were independent risk factors for ATB development in LTBI patients. Conclusion: The incidence of ATB is significantly higher in hospitalized patients with LTBI than in the general population. The exposure history of PTB, maximum daily dosage of GCs≥ 50 mg/day, LEF treatment, anemia, and T-SPOT.TB level≥ 300SFCs/10 6 PBMCs, were the risk factors of tuberculosis reactivation. Hospitalized LTBI patients with the above factors may need TPT. Keywords: latent tuberculosis infection, active tuberculosis, incidence, risk factors