Incidence, risk factors and management of paradoxical reaction in central nervous system tuberculosis in the United Kingdom

OBJECTIVES: The aim of this study was to evaluate the incidence, clinical presentation, risk factors, management, and outcomes of paradoxical reaction (PR) in central nervous system tuberculosis (CNS TB) in the United Kingdom. METHODS: We conducted a retrospective cohort study in 20 UK hospitals, including all patients diagnosed with CNS TB between 2017 and 2022, with 12 months follow-up. Clinical, microbiological and imaging data were collected from patient records. RESULTS: 229 adult patients without HIV were included and 19 patients with HIV in a subgroup analysis. 21% (49/229, 95% CI 16.3-27.3%) of patients developed PR which was associated with worse outcomes, including disability, longer hospitalisation, and neurosurgical intervention. Risk factors for PR included Mycobacterium tuberculosis positive cerebrospinal fluid, severe disease, and higher CSF neutrophils. 40% (20/50) of patients with PR received host directed therapy (HDT). CONCLUSIONS: We present, to our knowledge, the largest cohort study of CNS TB from a high resource setting. We found a high incidence of PR associated with worse outcomes and variation in management. Our findings highlight the need for randomised controlled trials of HDT in PR which would most likely be conducted in high burden, low-resource settings, so should ensure sustainable access to HDT.