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

Abstract

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 length-for-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 V t (−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.

Pulmonary Function Outcomes after Tuberculosis treatment in Children: A Systematic Review and Meta-analysis

“…Only one included study performed non-spirometry PFTs, they instead reported association coefficients between childhood PTB occurring between one to four years of age with measurements taken at the age of five, as presented in appendix VI. 25…”

“…22 A total of 567 children with history of PTB were included; median number of children in studies was 68 (range: 42-305). [21][22][23][24][25] Key characteristics were reported in Table 1, and details of quality scores shown in appendix IV. One study performed non-spirometry PFTs after early-life TB, 25 thus excluded from meta-analyses.…”

“…22 GeneXpert MTB/RIF® was used to rule out active infection pre-spirometry. 21 26 Only one study reported completion of treatment regimen for drug-susceptible TB according to national guidelines, modified for drug-resistance; 25 other studies [21][22][23][24] did not report treatment regimen details.…”

“…The time between treatment completion to PFTs ranged between 6 to 24 months in the three most recent studies; [23][24][25] two earlier studies 21 22 did not specify this duration. Three studies [21][22][23] reported performing spirometry according to American Thoracic Society/European Respiratory Society 2005 standards, 27 and one 24 according to the 2019 update.…”

Pediatric Post-TB Lung Disease: Ready for Prime Time?

“…In this issue of the Journal , Martinez and colleagues (pp. 1080–1088 ) offer a breath of fresh air as they begin to fill the unacceptable pediatric PTLD evidence gap ( 14 ). This unique analysis leverages data provided by the Drakenstein birth cohort study in South Africa that is composed of 1,068 mother-infant pairs living in a high TB and HIV–burden, economically disadvantaged community.…”