Adherence to tuberculosis (TB) treatment is challenging because of many factors. The World Health Organization has recommended the use of digital adherence monitoring technologies in its End TB Strategy. However, evidence on improving adherence is limited. EvriMED is a real-time medication-monitoring device which was found to be feasible and acceptable in a few studies in Asia. In Tanzania, however, there may be challenges in implementing evriMED due to stigmatization, network and power access, accuracy, and cost effectiveness, which may have implications for treatment outcome. We propose a pragmatic cluster randomized trial to investigate the effectiveness of evriMED with reminder cues and tailored feedback on adherence to TB treatment in Kilimanjaro, Tanzania. We will create clusters in Kilimanjaro based on level of health care facility. Clusters will be randomized in an intervention arm, where evriMED will be implemented, or a control arm, where standard practice directly observed treatment will be followed. TB patients in intervention clusters will take their medication from the evriMED pillbox and receive tailored feedback. We will use the ‘Stages of Change’ model, which assumes that a person has to go through the stages of pre-contemplation, contemplation, preparation, action, and evaluation to change behavior for tailored feedback on adherence reports from the device. If the intervention shows a significant effect on adherence and the devices are accepted, accurate, and sustainable, the intervention can be scaled up within the National Tuberculosis Programmes. Pan African Clinical Trials Registry, PACTR201811755733759 . Registered on 8 November 2018.

Background: New drug classes and regimens have shortened the treatment duration for drug-resistant tuberculosis, but adverse events (AEs) and organ toxicity remain unacceptably common. N-acetylcysteine (NAC) has demonstrated potential in reducing kidney and liver toxicity in other clinical settings, but efficacy in drug-resistant tuberculosis treatment has not been rigorously evaluated. Method: A randomized controlled trial was conducted at Kibong’oto Infectious Diseases Hospital in Tanzania to assess the efficacy of NAC in reducing AEs in patients undergoing rifampin-resistant pulmonary tuberculosis treatment. Participants received an all-oral standardized rifampin-resistant regimen alone, with NAC 900 mg daily, or NAC 900 mg twice daily for 6 months. AEs, severe AEs, and renal and liver toxicity were monitored monthly and classified according to the Risk, Injury, Failure, Loss, and End-stage kidney disease criteria and National Cancer Institute Common Terminology Criteria for Adverse Events. Incident ratios and Kaplan–Meier curves were employed to compare group event occurrences. Results: A total of 66 patients (mean age 47 ± 12 years; 80% male) were randomized into three groups of 22. One hundred and fifty-eight AEs were recorded: 52 (33%) in the standard treatment group, 55 (35%) in the NAC 900 mg daily group, and 51 (32%) in the NAC 900 mg twice-daily group (p > 0.99). Severe AEs were observed in four patients in the standard group, two in the NAC 900 mg daily group, and three in the NAC 900 mg twice-daily group. Renal toxicity was more prevalent in the standard treatment group compared to those that received NAC (45% vs. 23%; p = 0.058), with a shorter onset of time to toxicity (χ² = 3.199; p = 0.074). Liver injury events were rare across all groups. Conclusion: Among Tanzanian adults receiving rifampin-resistant tuberculosis treatment, NAC did not significantly reduce overall AEs but demonstrated important trends in reducing renal toxicity.

Introduction Under-reporting of adverse drug reactions is a major challenge in Tanzania. It is important to educate the health care providers about pharmacovigilance in order to improve the reporting rate. Objectives: We conducted a study with the objective of evaluating the impact of an educational intervention based on the knowledge on pharmacovigilance among healthcare providers in Tanzania. Methods: A pharmacovigilance e-blended learning method was used. Pre and post-test, courses were the basic concepts in Pharmacovigilance and the safety of Anti-Tuberculosis Drugs. Descriptive analyses were run to determine the proportions of the correct and wrong answers for pre and post training. Results A total of 118 (72%) completed the pre-and post-test for both the first and the second courses. There was an increase in the correct answers in the post-test to every question. The median score of pre-intervention for knowledge about basic pharmacovigilance increased from 5 (range 4–7) in pre-test to 8 (range 7–9) in post-test. The median score for anti-TB drug safety issues monitoring and management increased from 4 (range 4–6) in pre-test to 7 (range 7–9) in post-test. Conclusion The findings of this study showed that knowledge scores and correct answers were increased following an educational intervention among HCP.

Background: New drug classes and regimens have shortened the treatment duration for drug-resistant tuberculosis, but adverse events (AEs) and organ toxicity remain unacceptably common. N-acetylcysteine (NAC) has demonstrated potential in reducing kidney and liver toxicity in other clinical settings, but efficacy in drug-resistant tuberculosis treatment has not been rigorously evaluated. Method: A randomized controlled trial (PACTR202007736854169) was conducted at Kibong’oto Infectious Disease Hospital in Tanzania to assess the efficacy of NAC in reducing AEs in patients undergoing rifampin-resistant pulmonary tuberculosis treatment. Participants received an all-oral standardized rifampin-resistant regimen alone, with NAC 900 mg daily, or NAC 900 mg twice daily for 6 months. AEs, severe AEs, and renal and liver toxicity were monitored monthly and classified according to the Risk, Injury, Failure, Loss, and End-stage kidney disease criteria and National Cancer Institute Common Terminology Criteria for Adverse Events. Incident ratios and Kaplan-Meier curves were employed to compare group event occurrences. Results: 66 patients (mean age 47±12 years; 80% male) were randomized into three groups of 22. One hundred and fifty-eight AEs were recorded: 52 (33%) in the standard treatment group, 55 (35%) in the NAC 900 mg daily group, and 51 (32%) in the NAC 900 mg twice daily group (p>0.99). Severe AEs were observed in 4 patients in the standard group, 2 in the NAC 900 mg daily group, and 3 in the NAC 900 mg twice daily group. Renal toxicity was more prevalent in the standard treatment group (45% vs. 23%; p=0.058), with a shorter onset of time to toxicity ( χ 2 = 3.199; p=0.074). Liver injury events were rare across all groups. Conclusion: Among Tanzanian adults receiving rifampin-resistant tuberculosis treatment, NAC did not significantly reduce overall AEs but demonstrated important trends in reducing renal toxicity.

INTRODUCTION Tuberculosis (TB) remains a major cause of morbidity and mortality, especially in sub-Saharan Africa. We qualitatively evaluated the implementation of an Evidence-Based Multiple Focus Integrated Intensified TB Screening package (EXIT-TB) in the East African region, aimed at increasing TB case detection and number of patients receiving care. OBJECTIVE We present the accounts of participants from Tanzania, Kenya, Uganda, and Ethiopia regarding the implementation of EXIT-TB, and suggestions for scaling up. METHODS A qualitative descriptive design was used to gather insights from purposefully selected healthcare workers, community health workers, and other stakeholders. A total of 27, 13, 14, and 19 in-depth interviews were conducted in Tanzania, Kenya, Uganda, and Ethiopia respectively. Data were transcribed and translated simultaneously and then thematically analysed. RESULTS The EXIT-TB project was described to contribute to increased TB case detection, improved detection of Multidrug-resistant TB patients, reduced delays and waiting time for diagnosis, raised the index of TB suspicion, and improved decision-making among HCWs. The attributes of TB case detection were: (i) free X-ray screening services; (ii) integrating TB case-finding activities in other clinics such as Reproductive and Child Health clinics (RCH), and diabetic clinics; (iii), engagement of CHWs, policymakers, and ministry level program managers; (iv) enhanced community awareness and linkage of clients; (v) cooperation between HCWs and CHWs, (vi) improved screening infrastructure, (vii) the adoption of the new simplified screening criteria and (viii) training of implementers. The supply-side challenges encountered ranged from disorganized care, limited space, the COVID-19 pandemic, inadequate human resources, inadequate knowledge and expertise, stock out of supplies, delayed maintenance of equipment, to absence of X-ray and GeneXpert machines in some facilities. The demand side challenges ranged from delayed care seeking, inadequate awareness, negative beliefs, fears towards screening, to financial challenges. Suggestions for scaling up ranged from improving service delivery, access to diagnostic equipment and supplies, and infrastructure, to addressing client fears and stigma. CONCLUSION The EXIT-TB package appears to have contributed towards increasing TB case detection and reducing delays in TB treatment in the study settings. Addressing the challenges identified is needed to maximize the impact of the EXIT-TB intervention.

Introduction: Plasma is the standard biological fluid used in pharmacokinetic (PK) studies and therapeutic drug monitoring (TDM) of pyrazinamide, a key antituberculosis (TB) drug. This study described the PK of pyrazinamide in saliva and investigated whether saliva could serve as an alternative matrix for pyrazinamide PK evaluations. Methods: Fifteen adult Tanzanian TB patients in the intensive treatment phase participated in a descriptive PK study. Time-matched saliva (stimulated using a Salivette^® with citric acid) and plasma samples were collected at multiple intervals up to 24 h after drug intake. Pyrazinamide concentrations were measured using validated HPLC methods, exposure measures were assessed, and predictive performance for salivary concentrations was determined. Results: Salivary exposure to pyrazinamide (AUC_0–24h: 230 h·mg/L; C_max: 28.6 mg/L) was lower than plasma exposure (AUC_0–24h: 377 h·mg/L; C_max: 36.4 mg/L, p < 0.001), but T_max was similar (median 2.0 h, p = 0.893). A saliva/plasma ratio of 0.59 was assessed, and a reciprocal conversion factor of 1.68 allowed for reasonably accurate (bias 5.8%) but imprecise (imprecision 24.3%) plasma concentration predictions from saliva. Use of a conversion factor of 1.49, based on more stable saliva/plasma concentration ratios for samples between 2 and 6 h post-dose, resulted in a bias of 0.74% and imprecision of 17.7% for predicting plasma concentrations from salivary concentrations in the 2–6 h interval. Conclusions: The exposure to pyrazinamide in saliva is relatively high. Salivary measurement of pyrazinamide can be used as a semi-quantitative predictor of pyrazinamide plasma concentrations.