Tuberculosis as a cause or comorbidity of childhood pneumonia in tuberculosis-endemic areas: a systematic review.

Pneumonia is a major cause of morbidity and mortality in infants and children worldwide, with most cases occurring in tuberculosis-endemic settings. Studies have emphasised the potential importance of Mycobacterium tuberculosis in acute severe pneumonia in children as a primary cause or underlying comorbidity, further emphasised by the changing aetiological range with rollout of bacterial conjugate vaccines in high mortality settings. We systematically reviewed clinical and autopsy studies done in tuberculosis-endemic settings that enrolled at least 100 children aged younger than 5 years with severe pneumonia, and that prospectively included a diagnostic approach to tuberculosis in all study participants. We noted substantial heterogeneity between studies in terms of study population and diagnostic methods. Of the 3644 patients who had culture of respiratory specimens for M tuberculosis undertaken, 275 (7·5%) were culture positive, and an acute presentation was common. Inpatient case-fatality rate for pneumonia associated with tuberculosis ranged from 4% to 21% in the four clinical studies that reported pathogen-related outcomes. Prospective studies are needed in high tuberculosis-burden settings to address whether tuberculosis is a cause or comorbidity of childhood acute severe pneumonia.