Infection control and latent tuberculosis infection in health care workers in Indonesia

Background: Health care workers (HCWs) and health care students (HCSs), especially in low and middle-income countries (LMICs) are particularly vulnerable to being infected with Mycobacterium tuberculosis. The extent of latent TB infection (LTBI) among HCWs and HCSs in LMICs, and in Indonesia, is currently unknown, as is the degree of implementation of infection control measures in Indonesian health settings. Objective: This thesis aimed to: 1) describe the prevalence and incidence of LTBI in HCWs in LMICs and to identify associated risk factors, 2) assess the implementation of TB infection control measures in primary health centres (PHCs) in Bandung, Indonesia, 3) estimate the prevalence of LTBI measured by tuberculin skin test (TST) and identify factors associated with LTBI in HCWs in a tertiary referral hospital, and 4) estimate the prevalence of LTBI by interferon-gamma release assays (IGRA) and TST, the one-year test conversion rates, and identify associated risk factors in HCSs. Methods and results: In a systematic review of 85 studies published from 2005 to 2017 the prevalence of LTBI in HCWs using TST ranged from 8-98% (mean 49%), and for HCSs from 1-74% (mean 32%). Using IGRA, the prevalence in HCWs ranged from 9-86% (mean 39%), and in HCSs from 10-44% (mean 24%). HCWs from countries with an annual TB incidence of >300/100,000 had the highest prevalence of test positivity. The annual incidence of LTBI ranged from 1-38% (mean 17%) in HCWs, and 3-8% (mean 5%) in HCSs, when estimated from serial TST, and from 10-30% (mean 18%) and 8% (one study), when estimated with IGRA in HCWs and HCSs respectively. Occupational factors associated with LTBI in HCWs were those that involved more direct contact with a TB patient or prolonged exposure. Only 15 studies reported any TB infection control measures. A cross sectional study assessing the implementation of TB infection control practices was conducted in 24 selected PHCs in Bandung, Indonesia. The evaluation of four key areas showed that TB infection control measures were generally not implemented. The median number of TB infection control measures implemented was 21 of 41 assessed. PHCs with laboratory facilities and high TB case numbers were more likely to implement TB infection control measures compared to other PHCs. A cross-sectional study examining the prevalence of LTBI measured by TST was conducted in 395 HCWs working in one public tertiary referral hospital in Bandung. The prevalence of positive TST was 75.1% (95% confidence interval 69.4-80.0%). The risk of TST positivity increased with increasing work years and was high across the hospital, suggesting that hospital wide measures are needed to counter the risk. A cohort study was conducted in HCSs entering their clinical training programme. At baseline, the prevalence of a positive IGRA was 18.5% (n=379), and of a positive TST was 32.7% (n=272). At one-year follow up, the risk of M. tuberculosis infection according to IGRA conversion was 8.9% (n=293) and according to TST was 35.4% (n=180). Discordance between the tests increased from baseline to follow-up. Neither the difference in conversion rates or the increasing discordance were fully explained by boosting of the TST. In the multivariate analysis, medical students (adjusted relative risk (ARR) 5.15, P=0.002), and participation in sputum collection or bronchoscopy procedures (ARR 2.74, P=0.008) were positively associated with IGRA conversion. For one-year TST conversion, increasing age was the only significant factor (ARR 1.22, P=0.017). Conclusion: The prevalence and incidence of LTBI in HCWs in LMICs continue to be high, especially in high TB incidence countries. In Bandung, TB infection control measures in PHCs were generally not well implemented and the prevalence and incidence of LTBI in HCWs and HCSs were high and predominantly associated with occupational exposures. Exposure to M. tuberculosis appears to be high across the tertiary hospital. Our study highlights the importance of strengthening effective TB infection control measures to reduce TB transmission in health care facilities. HCWs and HCSs with LTBI might benefit from receiving LTBI treatment. Bacille Calmette-Guerin re-vaccination or a novel vaccine might confer additional protection for M. tuberculosis uninfected HCWs and HCSs. Together with improved infection control measures, this strategy is worthy of further investigation