A Systematic Review of Clinical, Epidemiological and Demographic Predictors of Tuberculosis in Children with Pneumonia

Background: Tuberculosis (TB) can present as acute, severe pneumonia in children, but features which distinguish TB from other causes of pneumonia are not well understood. We conducted a systematic review to determine the prevalence and to explore clinical and demographic predictors of TB in children presenting with pneumonia over three decades.

Methods: We searched for peer-reviewed, English language studies published between 1990 and 2020 that included children aged between 1 month and 17 years with pneumonia and prospectively evaluated for TB. There were 895 abstracts and titles screened, and 72 full text articles assessed for eligibility.

Results: Thirteen clinical studies, two autopsy studies and one systematic review were included in analyses. Majority of studies were from Africa (12/15) and included children less than five years age. Prevalence of bacteriologically confirmed TB in children with pneumonia ranged from 0.2% to 14.8% (median = 3.7%, interquartile range (IQR) = 5.95) and remained stable over the three decades. TB may be more likely in children with pneumonia if they have a history of close TB contact, HIV infection, malnutrition, age less than one year or failure to respond to empirical antibiotics. However, these features have limited discriminatory value as TB commonly presents as acute severe pneumonia - with a short duration of cough, and clinical and radiographic features indistinguishable from other causes of pneumonia. Approximately half of patients with TB respond to initial empirical antibiotics, presumably due to bacterial co-infection, and follow-up may be critical to detect and treat TB.

Conclusion: TB should be considered as a potential cause or comorbidity in all children presenting with pneumonia in high burden settings. Clinicians should be alert to the presence of known risk factors for TB and bacteriological confirmation sought whenever possible. Quality data regarding clinical predictors of TB in childhood pneumonia are lacking. Further, prospective research is needed to better understand predictors and prevalence of TB in childhood pneumonia, particularly in TB endemic settings outside of Africa and in older children. Children of all ages with pneumonia should be included in research on improved, point-of-care TB diagnostics to support early case detection and treatment.