Immune Mediated Paradoxical Reaction In Hiv Negative Childhood Cns Tuberculosis:a Longitudinal Observational Study

Introduction: This study estimates the prevalence and pattern of immune-mediated paradoxical reaction (PR) in childhood CNS TB. Methods: Consecutive children(6months-14 years) with newly diagnosed HIV-negative CNS TB registered between 2020-2022 were enrolled. Clinical evaluation, CSF and contrast enhanced CT head or brain MRI was performed at baseline. All participants received 4-drug anti-tubercular therapy(ATT) alongwith oral dexamethasone. Repeat neuroimaging was performed if clinical worsening occurred or at 8+2 weeks follow up. PR was defined as worsening of pre-existing tuberculous lesions or appearance of new lesions in patients whose clinical symptoms initially improved with ATT. Functional outcome was assessed at 6-months using pediatric cerebral performance scale(PCPC). Results: Sixty-eight children with newly diagnosed CNS TB were screened, 57 HIV-negative participants were enrolled. Mean age was 8.2 +- 4.2 years; 44% males; BMRC stage 2: 42% and stage 1 and 3 29% each. On follow up 4(7%) expired, 3(5%) had rifampicin resistance and 19(33.33%) developed PR. Seventeen (29.82%) participants developed PR within 3 months while two had late occurrence. Median time of appearance of PR was 3.5 weeks(range 2-7 weeks). Nine(47%) had infarcts, 7(37%) tuberculoma and spinal arachnoiditis each, 5(26%) optochiasmatic arachnoiditis and basal exudates each. On multivariate analysis, BMRC grade 2 and 3 were independent predictors of PR. Functional outcome of children with PR was poor, mean PCPC score was (2.89±1.19) compared to non-paradoxical group (1.22±0.61; p=0.001) at 6-months. Conclusion: A third of children with HIV-negative CNS tuberculosis may develop PR within the initial three months. PR may worsen functional outcome in TB.