The Long-Term Impact of Early-Life Tuberculosis Disease on Child Health A Prospective Birth Cohort Study

Rationale: There is growing concern that post-tuberculosis disease (TB) sequelae and morbidity are substantial, but no studies have controlled for preexisting factors before disease. Whether children have post-TB morbidity is not well characterized. Objectives: To assess the effect of a TB diagnosis on wheezing episodes, lung function, and anthropometric measurements among children enrolled in a prospective birth cohort study in South Africa. Methods: We prospectively followed children from birth through 5 years for TB using diagnostic tests including chest radiography and repeated induced sputum sample testing with Xpert MTB/RIF and liquid culture. We longitudinally measured health outcomes including growth, wheezing, and lung function up to 5 years. Mixed-effects linear regression models were used to assess growth and lung function after TB. Poisson regression was used to assess risk of subsequent wheezing. Measurements and Main Results: Among 1,068 participants, 96 TB cases occurred (1,228 cases per 100,000 person-years [95% confidence interval (CI), 1,006-1,500]) occurred over 7,815 child-years of follow-up. TB was associated with lower lengthfor-age (-0.40 [95% CI, -0.68 to -0.11]), weight-for-age (-0.30 [95% CI, -0.59 to -0.01]), and body mass index (-0.54 [95% CI, -0.83 to -0.25]) z-scores at 5 years. Children developing TB were consistently more likely to wheeze regardless of the timing of TB. Children with diagnoses of TB between 0 and 1 year of age had reduced time to peak tidal expiratory flow over total expiratory time (-2.35% [95% CI, -4.86% to -0.17%]) and higher fractional exhaled nitric oxide (2.88 ppb [95% CI, 0.57-5.19 ppb]) at 5 years. Children with diagnoses of TB between 1 and 4 years of age had impaired VT (-9.32 ml [95% CI, -14.89 to -3.75 ml]) and time to peak tidal expiratory flow over total expiratory time (-2.73% [95% CI, -5.45% to -0.01%]) at 5 years. Conclusions: Prevention of TB disease in the first few years of life may have substantial long-term benefits through childhood.

Automated summary

This study found that children may experience respiratory difficulties, decreased lung function, and stunted growth after contracting tuberculosis. The results indicated that early TB diagnosis and prevention in childhood could have long-term benefits for their health.