High dose rifampin for 2 months vs standard dose rifampin for 4 months, to treat TB infection: Protocol of a 3-arm randomized trial (2R2).

INTRODUCTION: Tuberculosis preventive treatment (TPT) is an essential component for TB elimination. In order to be successfully implemented on a large scale, TPT needs to be safe, affordable and widely available in all settings. Short TPT regimens, that are less burdensome than longer regimens, to patients and health systems, are needed. Doses of rifampin higher than the standard 10mg/kg/day were tolerated in studies to reduce duration of treatment for tuberculosis disease (TBD). The objective of this trial is to test the safety of high dose rifampin monotherapy to shorten the duration of the currently recommended TPT of 4 months rifampin. METHODS AND ANALYSIS: This is a phase 2b, randomised, controlled, parallel group, superiority, partially-blind trial. Primary outcomes are completion of treatment (as a proxy measure of tolerability) and safety. The two experimental arms comprise 60 days of (i) 20mg/kg/day or (ii) 30mg/kg/day rifampin; the control arm comprises 120 days of 10mg/kg/day rifampin as TPT. Participants are adults and children 10 years or older, eligible for TPT. Completion is the primary outcome, measured by pill count and is defined as taking minimum of 80% of treatment in 120% of allowed time; it will be tested for superiority by logistic regression. Safety outcome comprises proportion of grade 3-5 adverse events and grade 1-2 rash, adjudicated related to study drug, and resulting in permanent drug discontinuation; compared for non-inferiority between each of the two high dose arms and the standard arm, using Poisson regression. A sample size of 1,359 participants will give 80% power to detect a 10% difference in completion rates and a 1% difference in the safety outcome. The study is conducted in Canada, Indonesia and Vietnam. Enrolment is ongoing at all sites. ETHICS AND DISSEMINATION: Approvals from a local research ethics board (REB) have been obtained at all participating sites and by the trial coordinating centre. Approval has been given by drug regulatory agencies in Canada and Indonesia and by Ministry of Health in Vietnam; participants give written informed consent before participation. All data collected are non-nominal. Primary results will be submitted for publication in a peer-reviewed journal when all participants have completed treatment; results of secondary outcomes will be submitted for publication at the end of study; all sites will receive the final data of participants from their sites. TRIAL REGISTRATION: Trial registered in ClinicalTrials.gov (Identifier: NCT03988933). Coordinating center is the study team working at McGill University Health Center-Research Institute (MUHC-RI); sponsor is the MUHC-RI; funding has been granted by Canadian Institute of Health Research (FDN-143350).

Knowledge, attitude and practice of community pharmacy personnel in tuberculosis patient detection: a multicentre cross-sectional study in a high-burden tuberculosis setting.

INTRODUCTION: Control of tuberculosis (TB) is hampered by suboptimal case detection and subsequent delays in treatment, which is worsened by the COVID-19 pandemic. The community pharmacy is reported as the place for first aid medication among patients with TB. We, therefore, analysed knowledge, attitude and practice (KAP) on TB patient detection (TBPD) of community pharmacy personnel, aiming to find innovative strategies to engage community pharmacies in TBPD. METHODS: A multicentre cross-sectional study was performed in four areas of Indonesia's eastern, central and western parts. Pharmacists and pharmacy technicians who worked in community pharmacies were assessed for their characteristics and KAP related to TBPD. Descriptive analysis was used to assess participant characteristics and their KAP, while multivariable regression analyses were used to analyse factors associated with the KAP on TBPD. RESULTS: A total of 1129 participants from 979 pharmacies, comprising pharmacists (56.6%) and pharmacy technicians (43.4%), were included. Most participants knew about TB. However, knowledge related to TB symptoms, populations at risk and medication for TB were still suboptimal. Most participants showed a positive attitude towards TBPD. They believed in their professional role (75.1%), capacity in TB screening (65.4%) and responsibility for TBPD (67.4%). Nevertheless, a lack of TBPD practice was identified in most participants. Several factors significantly associated with performing the TBPD practice (p<0.05), such as TB training experience (p<0.001), provision of a drug consultation service (p<0.001), male gender (p<0.05), a positive attitude towards TBPD (p<0.001), short working hours (p<0.001) and central city location of the pharmacy (p<0.05). CONCLUSIONS: Most participants had good knowledge and attitude, which did not translate into actual TBPD practice. We identified that TB educational programmes are essential in improving the KAP. A comprehensive assessment is needed to develop effective strategies to engage the community pharmacy in TBPD activities.

Treatment Outcomes of Childhood Tuberculous Meningitis in a Real-World Retrospective Cohort, Bandung, Indonesia.

We retrospectively evaluated clinical features and outcomes in children treated for tuberculous meningitis (TBM) at Hasan Sadikin Hospital, Bandung, Indonesia, during 2011-2020. Among 283 patients, 153 (54.1%) were <5 years of age, and 226 (79.9%) had stage II or III TBM. Predictors of in-hospital death (n = 44 [15.5%]) were stage III TBM, hydrocephalus, male sex, low-income parents, seizures at admission, and lack of bacillus Calmette-Guérin vaccination. Predictors of postdischarge death (n = 18 [6.4%]) were hydrocephalus, tuberculoma, and lack of bacillus Calmette-Guérin vaccination. At treatment completion, 91 (32.1%) patients were documented to have survived, of whom 33 (36.3%) had severe neurologic sequelae and 118 (41.7%) had unknown outcomes. Predictors of severe neurologic sequelae were baseline temperature >38°C, stage III TBM, and baseline motor deficit. Despite treatment, childhood TBM in Indonesia causes substantial neurologic sequelae and death, highlighting the importance of improved early diagnosis, better tuberculosis prevention, and optimized TBM management strategies.

Knowledge, attitude, and practice of undergraduate medical students in Indonesia on the COVID-19 prevention.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) caused a global pandemic since March 2020. Undergraduate medical students were encouraged to educate Indonesian society about COVID-19. This study aimed to evaluate the knowledge, attitude, and practice of Indonesian students on COVID-19 prevention. METHODS: An online cross-sectional study was conducted online between August 22 and September 2, 2020, with a minimum sample size of 1,068 subjects. The questionnaire was sent to 86 Faculty of Medicine (FoM) in Indonesia. The questionnaire consisted of knowledge, attitude, and practice section, with the scores above median were considered as sufficient knowledge, positive attitude, and positive practice. Association between knowledge, attitude, and practice, which were dependent variables, with gender, year of study, location of FoM, and source of information, which were independent variables, were tested using Chi-Square Test. Correlation among knowledge, attitude, and practice scores was tested using Spearman Rank Test. RESULTS: Among 1,390 participated students, 51.4, 55.7, and 56.3% had sufficient knowledge, positive attitude, and, positive practice, respectively. There were associations between knowledge and gender (p = 0.005), year of study (p = 0.000), location of FoM (p=0.000), and source of information (p = 0.000); between attitude and gender (p = 0.022), year of study (p = 0.004), and source of information (p = 0.015); and between practice and gender (p = 0.000) and source of information (p = 0.000). There were weak correlations between knowledge and attitude (r = 0.246, p<0.001); and between attitude and practice (r = 0.272, p < 0.001). CONCLUSIONS: Half of Indonesian medical students showed sufficient knowledge, positive attitude, and positive practice on COVID-19 prevention. Hence, improvement towards COVID-19 prevention is required.