The impact of BCG non-vaccination on TBM severity in a TBM-endemic setting, Cape Town : a case-controlled study
Date
2023-03
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Publisher
Stellenbosch : Stellenbosch University
Abstract
ENGLISH SUMMARY: Introduction: BCG (Bacille Calmette-Guérin) is a live-attenuated vaccine that is routinely administered at birth to all infants in the Western Cape Province of South Africa, consistent with World Health Organization (WHO) guidelines. The protective effects of BCG against tuberculous meningitis (TBM) and miliary tuberculosis (TB) was highlighted following a global BCG vaccine supply shortage in 2015 which resulted in a marked increase in the number of TBM cases in children under the age of 2 years at our institution. It is not known whether the BCG shortage also impacted on TBM disease severity. Objective: The study aimed to describe the clinical, cerebrospinal fluid (CSF) and radiological parameters in children diagnosed with TBM, with and without BCG vaccination, during two time periods: 1985-2015 and 2019-2020 at Tygerberg Hospital in Cape Town, South Africa. Design: A retrospective (1985-2015) and prospective (2019-2020) hospital-based observational cohort study. Results: 518 children with TBM were included in the study. Of the 480 consecutive TBM children in the retrospective study, 183/480 (38%) were not BCG-vaccinated, while in the prospective study of 38 consecutive TBM children, 18/38 (47%) did not receive the BCG vaccine. In the prospective group, unvaccinated TBM patients were younger (median 24.0 months, interquartile range (IQR) 12.5-36.0) compared to those who were vaccinated, median 27.5 months, IQR 19.0-48.0, however when comparing means statistical significance was not obtained; p=0.12. Age of onset was higher in the retrospective group, median 32.0 months, IQR 19.0-59.0. in both studies, non-BCG vaccination was associated with increased TBM disease severity i.e. advanced TBM stage (odds ratio (OR) 2.50: 95% confidence interval (CI) 1.53-4.10; p<0.01), depressed level of consciousness, GCS<15 (OR 2.45: 95% CI 1.50-4.01; p<0.01) and cranial nerve palsy (OR 1.65: 95% CI 1.10-2.47; p<0.01) in the retrospective study, and hemiparesis (OR 6.07: 95% CI 1.49-24.76; p<0.01) and extraneural mycobacteriological confirmation as evidence of disseminated TB (OR 6.14: 95% CI 1.10-32.21; p=0.03) in the prospective study. Furthermore, in the retrospective study BCG vaccination was associated with raised intracranial pressure, but with a weaker significance value (OR 0.62: 95% CI 0.39-0.99; p=0.04) Conclusion: In the prospective group, BCG non-vaccination was associated with hemiparesis and extraneural mycobacteriological confirmation. Retrospectively, BCG non-vaccination was associated with advanced stage TBM, depressed level of consciousness and cranial nerve palsy. The global BCG shortage in 2015 has contributed to an increase in TBM severity in the ensuing 4 years as demonstrated by the prospective association with hemiparesis.
AFRIKAANSE OPSOMMING: Geen opsomming beskikbaar.
AFRIKAANSE OPSOMMING: Geen opsomming beskikbaar.
Description
Thesis (MMed)--Stellenbosch University, 2023.