The prevalence and risk factors for tuberculosis among healthcare workers in Yogyakarta, Indonesia.

Healthcare workers (HCWs) are at risk of contracting TB, particularly when in high tuberculosis (TB) burden settings. Routine surveillance data and evidence are limited on the burden of TB amongst HCWs in Indonesia. We aimed to measure the prevalence of TB infection (TBI) and disease among HCWs in four healthcare facilities in Yogyakarta province in Indonesia, and explore risk factors for TBI. A cross-sectional TB screening study targeted all HCWs from four pre-selected facilities (1 hospital, 3 primary care) in Yogyakarta, Indonesia. Voluntary screening included symptom assessment, Chest X-ray (CXR), Xpert MTB/RIF (if indicated) and tuberculin skin test (TST). Analyses were descriptive and included multivariable logistic regression. Of 792 HCWs, 681 consented (86%) to the screening; 59% (n = 401) were female, 62% were medical staff (n = 421), 77% worked in the one participating hospital (n = 524), and the median time working in the health sector was 13 years (IQR: 6-25 years). Nearly half had provided services for people with TB (46%, n = 316) and 9% reported ever having TB (n = 60). Among participants with presumptive TB (15%, n = 99/662), none were diagnosed microbiologically or clinically with active TB disease. TBI was detected in 25% (95% CI: 22-30; n = 112/441) of eligible HCWs with a TST result. A significant association was found between TB infection and being male (adjusted Odds Ratio (aOR) 2.02 (95%CI: 1.29-3.17)), currently working in the participating hospital compared to primary care (aOR 3.15 (95%CI: 1.75-5.66)), and older age (1.05 OR increase per year of life between 19-73 years (95%CI: 1.02-1.06)). This study supports prioritisation of HCWs as a high-risk group for TB infection and disease, and the need for comprehensive prevention and control programs in Indonesia. Further, it identifies characteristics of HCWs in Yogyakarta at higher risk of TBI, who could be prioritised in screening programs if universal coverage of prevention and control measures cannot be achieved.

TB-PRACTECAL: study protocol for a randomised, controlled, open-label, phase II-III trial to evaluate the safety and efficacy of regimens containing bedaquiline and pretomanid for the treatment of adult patients with pulmonary multidrug-resistant tuberculosis.

BACKGROUND: Globally rifampicin-resistant tuberculosis disease affects around 460,000 people each year. Currently recommended regimens are 9-24 months duration, have poor efficacy and carry significant toxicity. A shorter, less toxic and more efficacious regimen would improve outcomes for people with rifampicin-resistant tuberculosis. METHODS: TB-PRACTECAL is an open-label, randomised, controlled, phase II/III non-inferiority trial evaluating the safety and efficacy of 24-week regimens containing bedaquiline and pretomanid to treat rifampicin-resistant tuberculosis. Conducted in Uzbekistan, South Africa and Belarus, patients aged 15 and above with rifampicin-resistant pulmonary tuberculosis and requiring a new course of therapy were eligible for inclusion irrespective of HIV status. In the first stage, equivalent to a phase IIB trial, patients were randomly assigned one of four regimens, stratified by site. Investigational regimens include oral bedaquiline, pretomanid and linezolid. Additionally, two of the regimens also included moxifloxacin (arm 1) and clofazimine (arm 2) respectively. Treatment was administered under direct observation for 24 weeks in investigational arms and 36 to 96 weeks in the standard of care arm. The second stage of the study was equivalent to a phase III trial, investigating the safety and efficacy of the most promising regimen/s. The primary outcome was the percentage of unfavourable outcomes at 72 weeks post-randomisation. This was a composite of early treatment discontinuation, treatment failure, recurrence, lost-to-follow-up and death. The study is being conducted in accordance with ICH-GCP and full ethical approval was obtained from Médecins sans Frontières ethical review board, London School of Hygiene and Tropical Medicine ethical review board as well as ERBs and regulatory authorities at each site. DISCUSSION: TB-PRACTECAL is an ambitious trial using adaptive design to accelerate regimen assessment and bring novel treatments that are effective and safe to patients quicker. The trial took a patient-centred approach, adapting to best practice guidelines throughout recruitment. The implementation faced significant challenges from the COVID-19 pandemic. The trial was terminated early for efficacy on the advice of the DSMB and will report on data collected up to the end of recruitment and, additionally, the planned final analysis at 72 weeks after the end of recruitment. TRIAL REGISTRATION: Clinicaltrials.gov NCT02589782. Registered on 28 October 2015.