Prevalence and factors associated with reported adverse-events among patients on multi-drug-resistant tuberculosis treatment in two referral hospitals in Uganda.

BACKGROUND: Multi-drug-resistant tuberculosis (MDR-TB) treatment involves toxic drugs that cause adverse events (AEs), which are life-threatening and may lead to death if not well managed. In Uganda, the prevalence of MDR-TB is increasingly high, and about 95% of the patients are on treatment. However, little is known about the prevalence of AEs among patients on MDR-TB medicines. We therefore estimated the prevalence of reported adverse events (AEs) of MDR-TB drugs and factors associated with AEs in two health facilities in Uganda. METHODS: A retrospective cohort study of MDR-TB was conducted among patients enrolled at Mulago National Referral and Mbarara Regional Referral hospitals in Uganda. Medical records of MDR-TB patients enrolled between January 2015 and December 2020 were reviewed. Data on AEs, which were defined as irritative reactions to MDR-TB drugs, were extracted and analyzed. To describe reported AEs, descriptive statistics were computed. A modified Poisson regression analysis was used to determine factors associated with reported AEs. RESULTS: Overall, 369 (43.1%) of 856 patients had AEs, and 145 (17%) of 856 had more than one. Joint pain (244/369, or 66%), hearing loss (75/369, or 20%), and vomiting (58/369, or 16%) were the most frequently reported effects. Patients started on the 24-month regimen (adj. PR = 1.4, 95%; 1.07, 1.76) and individualized regimens (adj. PR = 1.5, 95%; 1.11, 1.93) were more likely to suffer from AEs. Lack of transport for clinical monitoring (adj. PR = 1.9, 95%; 1.21, 3.11); alcohol consumption (adj. PR = 1.2, 95%; 1.05, 1.43); and receipt of directly observed therapy from peripheral health facilities (adj. PR = 1.6, 95%; 1.10, 2.41) were significantly associated with experiencing AEs. However, patients who received food supplies (adj. PR = 0.61, 95%; 0.51, 0.71) were less likely to suffer from AEs. CONCLUSION: The frequency of adverse events reported by MDR-TB patients is considerably high, with joint pain being the most common. Interventions such as the provision of food supplies, transportation, and consistent counseling on alcohol consumption to patients at initiation treatment facilities may contribute to a reduction in the rate of occurrence of AEs.

Treatment outcomes of drug resistant tuberculosis patients with multiple poor prognostic indicators in Uganda: A countrywide 5-year retrospective study.

BACKGROUND: Comorbid conditions and adverse drug events are associated with poor treatment outcomes among patients with drug resistant tuberculosis (DR - TB). This study aimed at determining the treatment outcomes of DR - TB patients with poor prognostic indicators in Uganda. METHODS: We reviewed treatment records of DR - TB patients from 16 treatment sites in Uganda. Eligible patients had confirmed DR - TB, a treatment outcome in 2014-2019 and at least one of 15 pre-defined poor prognostic indicators at treatment initiation or during therapy. The pre-defined poor prognostic indicators were HIV co-infection, diabetes, heart failure, malignancy, psychiatric illness/symptoms, severe anaemia, alcohol use, cigarette smoking, low body mass index, elevated creatinine, hepatic dysfunction, hearing loss, resistance to fluoroquinolones and/or second-line aminoglycosides, previous exposure to second-line drugs (SLDs), and pregnancy. Tuberculosis treatment outcomes were treatment success, mortality, loss to follow up, and treatment failure as defined by the World Health Organisation. We used logistic and cox proportional hazards regression analysis to determine predictors of treatment success and mortality, respectively. RESULTS: Of 1122 DR - TB patients, 709 (63.2%) were male and the median (interquartile range, IQR) age was 36.0 (28.0-45.0) years. A total of 925 (82.4%) had ≥2 poor prognostic indicators. Treatment success and mortality occurred among 806 (71.8%) and 207 (18.4%) patients whereas treatment loss-to-follow-up and failure were observed among 96 (8.6%) and 13 (1.2%) patients, respectively. Mild (OR: 0.57, 95% CI 0.39-0.84, p = 0.004), moderate (OR: 0.18, 95% CI 0.12-0.26, p < 0.001) and severe anaemia (OR: 0.09, 95% CI 0.05-0.17, p < 0.001) and previous exposure to SLDs (OR: 0.19, 95% CI 0.08-0.48, p < 0.001) predicted lower odds of treatment success while the number of poor prognostic indicators (HR: 1.62, 95% CI 1.30-2.01, p < 0.001), for every additional poor prognostic indicator) predicted mortality. CONCLUSION: Among DR - TB patients with multiple poor prognostic indicators, mortality was the most frequent unsuccessful outcomes. Every additional poor prognostic indicator increased the risk of mortality while anaemia and previous exposure to SLDs were associated with lower odds of treatment success. The management of anaemia among DR - TB patients needs to be evaluated by prospective studies. DR - TB programs should also optimise DR - TB treatment the first time it is initiated.