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

Abstract

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.

Frequency, management and impact of adverse events on treatment outcomes in patients with multidrug resistant tuberculosis in Balochistan, Pakistan

“…As per the guidelines recommendation, patients with resistance to any SLD were prescribed the addition of PAS to their treatment regimen. Given that PAS, both alone and when combined with Eto, is widely acknowledged to induce GI disturbances and hypothyroidism (Ategyeka et al, 2023 ; Bloss et al, 2010 ; Buajordet et al, 2001 ; Furin et al, 2001 ; Lan et al, 2020 ; Sagwa et al, 2014 ; Sonya Shin et al, 2004 ; SS Shin et al, 2007 ; Wrohan et al, 2021 ; Zhang et al, 2017 ), this could potentially account for the observed increase in AEs among patients resistant to any SLD.…”

“…This can result in higher rates of treatment failure and adverse events (AEs) in these patients (Ahmad, Javaid, et al, 2015 ; Ahmad, Ahuja, et al, 2018 ; Lan et al, 2020 ). The AEs experienced during MDR-TB treatment can range from mild discomfort (such as gastrointestinal problems) to permanent disability (such as hearing and vision loss) and life threatening events (such as liver, kidney and heart damage) (Ategyeka et al, 2023 ; Bloss et al, 2010 ; Buajordet et al, 2001 ; Furin et al, 2001 ; Lan et al, 2020 ; Sagwa et al, 2014 ; Sonya Shin et al, 2004 ; SS Shin et al, 2007 ; Wrohan et al, 2021 ; Zhang et al, 2017 ). The management of AEs among MDR-TB patients is difficult for doctors, especially when there are few or no alternative drugs available that are equally effective and safe (Ahmad, Javaid, Sulaiman, et al, 2018 ; Lan et al, 2020 ; Merid et al, 2019 ; Törün et al, 2005 ).…”

Discharge Outcomes of Severely Sick Patients Hospitalized with Multidrug-Resistant Tuberculosis, Comorbidities, and Serious Adverse Events in Kyrgyz Republic, 2020–2022

“…All patients with unfavorable outcomes at hospital discharge had at least one comorbidity (diabetes and HIV) associated with other clinical conditions such as severe anemia, pulmonary complications, cardiovascular disorders, alcohol abuse, and more than 40% also had SAEs. Alcohol abuse is elsewhere associated with a statistically significant higher risk of developing SAEs in hospitalized patients [ 16 ], but also with a higher risk of loss to follow-up after discharge from hospital [ 17 ].…”

“…The frequency of SAEs in our study was associated with 62% of patients treated with individual longer treatment regimens, with a relative risk that was not statistically significant. In the study in the two referral hospitals in Uganda, there was a statistically significant association between developing SAEs and the longer standardized regimens (24 months) and individualized regimens [ 16 ]. Severe anemia was significantly associated with SAEs, which might be related to the use of linezolid as observed in regimens that include this drug [ 19 ].…”

Whole-Genome Sequencing to Predict Mycobacterium tuberculosis Drug Resistance: A Retrospective Observational Study in Eastern China

“…That year, 3.6% of new patients and 18% of retreated patients developed RFP-resistant or multidrug-resistant tuberculosis (MDR-TB), and 450,000 patients developed drug-resistant TB (DR-TB) [ 1 ]. DR-TB, especially MDR-TB, poses many problems during diagnosis and treatment and is one of the main challenges affecting global TB prevention and control [ 2 , 3 , 4 ].…”