Adverse Drug Reactions Resulting From the Use of Chiral Medicines Amoxicillin, Amoxicillin-Clavulanic Acid, and Ceftriaxone: A Mixed Prospective-Retrospective Cohort Study.

The use of chiral medicines (possessing center(s) of asymmetric carbon) may cause adverse drug reactions (ADRs). The safety assurance of these medicines is critical. We aimed to evaluate registered and commonly used anti-infective chiral medicines circulating in the Tanzanian market to establish their safety profile to protect public health. A mixed prospective-retrospective cohort study was conducted to assess the safety profile of amoxicillin, amoxicillin-clavulanic acid and ceftriaxone injection. ADRs causality assessment was conducted by using World Health Organization (WHO)-Algorithm criteria. Data were collected from 7 tertiary hospitals: Muhimbili National Hospital (MNH), Kilimanjaro Christian Medical Centre (KCMC), Bugando Medical Centre (BMC), Ligula Referral-Regional Hospital (LRRH), Kitete Referral-Regional Hospital (KRRH), Dodoma Referral-Regional Hospital (DRRH), and Mbeya Zonal-Referral Hospital (MZRH). Data were supplemented by those recorded in the WHO-Vigiflow/VigiLyze database within the same monitoring period. Data were analyzed using STATA version-15. The results were considered statistically significant when P < .05. A total of 2522 patients were enrolled in hospitals: MNH (499), KCMC (407), BMC (396), LRRH (387), KRRH (345), DRRH (249), and MZRH (239). Among those, 1197 (47.5%) were treated with ceftriaxone, 585 (23.2%) amoxicillin and 740(29.3%) amoxicillin-clavulanic acid. Out of those, 102 (4.5%) experienced adverse events (AEs), 49 (48%) were due to ceftriaxone, 37 (36.3%) amoxicillin-clavulanic acid and 16 (15.7%) amoxicillin (P-value .012). A total of 443 participants from the enrolled and WHO-Vigiflow/VigiLyze database were experienced with ADRs. The ADRs affected mainly gastro-intestinal system 234 (53%), skin and subcutaneous tissue 85 (19%), nervous system 49 (11%), respiratory thoracic 22 (5%), and general disorders 18(4%). In this study, approximately 90% of reported AEs were ADRs possible-related to the monitored medicines, with few plausible and certain. Ceftriaxone injection caused more ADRs. Amoxicillin-clavulanic acid was associated with more ADRs than amoxicillin alone. The safety profile of these medicines is still maintained; however, comprehensive monitoring of ADRs is recommended to improve patient safety and enhance overall treatment outcomes.

Effectiveness of a structured stimulated spontaneous safety monitoring of medicines reporting program in strengthening pharmacovigilance system in Tanzania.

Under-reporting of adverse drug events (ADEs) is a challenge facing developing countries including Tanzania. Given the high magnitude of under-reporting, it was necessary to develop and assess the effectiveness of a 'structured stimulated spontaneous safety monitoring' (SSSSM) reporting program of ADEs which aimed at strengthening pharmacovigilance system in Tanzania. A quasi-experimental design and data mining technique were used to assess the effect of intervention after the introduction of program in seven tertiary hospitals. ADEs reports were collected from a single group and compared for 18 months before (July 2017 to December, 2018) and after the program (January 2019 to June 2020). Out of 16,557 ADEs reports, 98.6% (16,332) were reported after intervention and 0.1% (23) death related to adverse drug reactions (ADRs) were reported. Reports increased from 20 to 11,637 after intervention in Dar es salaam, 49 to 316 in Kilimanjaro and 17 to 77 in Mbeya. The population-based reporting ratio per 1,000,000 inhabitants increased from 2 reports per million inhabitants in 2018 to 85 reports in 2019. The SSSSM program can increase the reporting rate of ADEs and was useful in detecting signals from all types of medicines. This was first effective developed spontaneous program to monitor medicine safety in Tanzania.

Mortality and associated factors among adult patients on tuberculosis treatment in Tanzania: A retrospective cohort study.

INTRODUCTION: Tuberculosis (TB) is the global leading cause of death from an infectious agent. Tanzania is among the 30 high TB burden countries with a mortality rate of 47 per 100,000 population and a case fatality of 4%. This study assessed mortality rate, survival probabilities, and factors associated with death among adult TB patients on TB treatment in Tanzania. METHODS: A retrospective cohort study was conducted utilizing case-based national TB program data of adult (≥15 years) TB cases enrolled on TB treatment from January 2017 to December 2017. We determined survival probabilities using the Kaplan-Meier estimator and a Cox proportional hazard model was used to identify independent risk factors of TB mortality. Hazard ratios and their respective 95% confidence intervals were reported. RESULTS: Of 53,753 adult TB patients, 1927 (3.6%) died during TB treatment and the crude mortality rate was 6.31 per 1000 person-months. Male accounted for 33,297 (61.9%) of the study population and the median (interquartile range [IQR]) age was 40 (30-53) years. More than half 1027 (56.7%) of deaths occurred in first two months of treatment. Overall survival probabilities were 96%, and 92% at 6th and 12th month respectively. The independent risk factors for TB mortality among TB patients included: advanced age ≥ 45 years (adjusted hazard ratio (aHR) = 1.74, 95% confidence interval (CI) = 1.45-2.08); receiving service at the hospital level (aHR = 1.22, 95% CI = 1.09-1.36); TB/HIV co-infection (aHR = 2.51, 95% CI = 2.26-2.79); facility-based direct observed therapy (DOT) option (aHR = 2.23, 95% CI = 1.95-2.72); having bacteriological unconfirmed TB results (aHR = 1.58, 95% CI = 1.42-1.76); and other referral type (aHR = 1.44, 95% CI = 1.16-1.78). CONCLUSION: Advanced age, TB/HIV co-infection, bacteriological unconfirmed TB results, other referral types, receiving service at facility-based DOT option and obtaining service at the hospital level were significant contributors to TB death in Tanzania. Appropriate targeted intervention to improve TB referral systems, improve diagnostic capacity in the primary health facilities, minimize delay and misdiagnosis of TB patients might reduce TB mortality.