Serious adverse drug reactions at two children's hospitals in South Africa.

BACKGROUND: The high HIV prevalence in South Africa may potentially be shaping the local adverse drug reaction (ADR) burden. We aimed to describe the prevalence and characteristics of serious ADRs at admission, and during admission, to two South African children's hospitals. METHODS: We reviewed the folders of children admitted over sequential 30-day periods in 2015 to the medical wards and intensive care units of each hospital. We identified potential ADRs using a trigger tool developed for this study. A multidisciplinary team assessed ADR causality, type, seriousness, and preventability through consensus discussion. We used multivariate logistic regression to explore associations with serious ADRs. RESULTS: Among 1050 patients (median age 11 months, 56% male, 2.8% HIV-infected) with 1106 admissions we found 40 serious ADRs (3.8 per 100 drug-exposed admissions), including 9/40 (23%) preventable serious ADRs, and 8/40 (20%) fatal or near-fatal serious ADRs. Antibacterials, corticosteroids, psycholeptics, immunosuppressants, and antivirals were the most commonly implicated drug classes. Preterm neonates and children in middle childhood (6 to 11 years) were at increased risk of serious ADRs compared to infants (under 1 year) and term neonates: adjusted odds ratio (aOR) 5.97 (95% confidence interval 1.30 to 27.3) and aOR 3.63 (1.24 to 10.6) respectively. Other risk factors for serious ADRs were HIV infection (aOR 3.87 (1.14 to 13.2) versus HIV-negative) and increasing drug count (aOR 1.08 (1.04 to 1.12) per additional drug). CONCLUSIONS: Serious ADR prevalence in our survey was similar to the prevalence found elsewhere. In our setting, serious ADRs were associated with HIV-infection and the antiviral drug class was one of the most commonly implicated. Similar to other sub-Saharan African studies, a large proportion of serious ADRs were fatal or near-fatal. Many serious ADRs were preventable.

Serious adverse drug reactions in sub-Saharan Africa in the era of antiretroviral treatment: A systematic review.

We aimed to summarize and describe the burden of serious adverse drug reactions (ADRs) in sub-Saharan Africa (SSA) in the era of antiretroviral therapy. We searched Medline, CINAHL, Africa-Wide Information, Scopus, and Web of Science, without language restriction up to March 2021. We hand-searched reference lists, conference abstracts, and dissertation databases. We included studies reporting proportions of admissions attributed to ADRs, admissions prolonged by ADRs, or in-hospital deaths attributed to ADRs. Two reviewers independently screened the studies, reviewed the study quality using a previously published tool, and extracted the data. We tested for heterogeneity using I2 -statistics and summarized the study results using medians and interquartile ranges. Subgroup analyses summarized the results by study quality, setting, methodology, and population. From 1005 unique references identified, we included 15 studies. Median study quality was 7/10; heterogeneity was very high. Median [IQR] proportion of admissions attributed to ADRs was 4.8% [1.5% to 7.0%] (14 studies) and 6.4% [4.0% to 8.4%] in nine active surveillance studies in adults. Two pediatric studies reported the proportion of admissions prolonged by ADRs (0.29% and 0.99%). Three studies reported the proportion of in-hospital deaths attributed to ADRs (2.5%, 13%, and 16%). Antiretroviral and antituberculosis drugs were often implicated in serious ADRs. Evidence of the burden of serious ADRs in SSA is patchy and heterogeneous. A few high-quality studies suggest that the burden is considerable, and that it reflects the regional impact of the HIV pandemic. Further characterization of this burden is required, ideally in studies of standardized methodology.

Adult medical emergency unit presentations due to adverse drug reactions in a setting of high HIV prevalence.

INTRODUCTION: South Africa has the world's largest antiretroviral treatment programme, which may contribute to the adverse drug reaction (ADR) burden. We aimed to determine the proportion of adult non-trauma emergency unit (EU) presentations attributable to ADRs and to characterise ADR-related EU presentations, stratified according to HIV status, to determine the contribution of drugs used in management of HIV and its complications to ADR-related EU presentations, and identify factors associated with ADR-related EU presentation. METHODS: We conducted a retrospective folder review on a random 1.7% sample of presentations over a 12-month period in 2014/2015 to the EUs of two hospitals in Cape Town, South Africa. We identified potential ADRs with the help of a trigger tool. A multidisciplinary panel assessed potential ADRs for causality, severity, and preventability. RESULTS: We included 1010 EU presentations and assessed 80/1010 (7.9%) as ADR-related, including 20/239 (8.4%) presentations among HIV-positive attendees. Among HIV-positive EU attendees with ADRs 17/20 (85%) were admitted, versus 22/60 (37%) of HIV-negative/unknown EU attendees. Only 5/21 (24%) ADRs in HIV-positive EU attendees were preventable, versus 24/63 (38%) in HIV-negative/unknown EU attendees. On multivariate analysis, only increasing drug count was associated with ADR-related EU presentation (adjusted odds ratio 1.10 per additional drug, 95% confidence interval 1.03 to 1.18), adjusted for age, sex, HIV status, comorbidity, and hospital. CONCLUSIONS: ADRs caused a significant proportion of EU presentations, similar to findings from other resource-limited settings. The spectrum of ADR manifestations in our EUs reflects South Africa's colliding epidemics of infectious and non-communicable diseases. ADRs among HIV-positive EU attendees were more severe and less likely to be preventable.