Mortality in children diagnosed with tuberculosis: a systematic review and meta-analysis

Abstract

Background Case fatality ratios among children with tuberculosis disease are poorly understood, particularly among HIV-infected cases and those not receiving tuberculosis treatment. Methods We carried out a systematic review of the published literature to identify studies of population-representative samples of pediatric (<15 years old) tuberculosis cases. We used random effects meta-analysis to produce pooled estimates of case fatality ratios. We stratified our analyses by whether or not children received tuberculosis treatment, age (0–4 years, 5–14 years), and HIV status. Findings We identified 31 papers comprising 35 datasets representing 82,436 children with tuberculosis disease, of whom 9,273 died. Among children with tuberculosis from the pretreatment era, the pooled case fatality ratio was 21.9% (95% confidence interval [CI]: 18.1%, 26.4%). The pooled case fatality ratio was significantly higher among children aged 0–4 years (43.6%; 95% CI: 36.8%, 50.6%) than among children aged 5–14 years (14.9%; 95% CI: 11.5%, 19.1%). In recent studies where the majority of children had tuberculosis treatment, the pooled case fatality ratio was 0.9% (95% CI: 0.5%, 1.6%). USA surveillance data suggest a substantially higher case fatality ratio among HIV-infected children receiving TB treatment, compared with HIV-uninfected children, especially without antiretroviral treatment. Interpretation Without adequate treatment, children with tuberculosis disease, especially those under five years of age, are at high risk of death. HIV-infected children have an increased mortality risk, even when receiving tuberculosis treatment. Funding US National Institutes of Health, Janssen Global Public Health