A prospective birth cohort study conducted in South Africa found that children who grow up in a setting where tuberculosis (TB) transmission is common have a high risk of TB infection and disease, with up to 10% developing the disease by age 10, researchers reported yesterday in The Lancet Child & Adolescent Health.
Although 1.2 million children globally develop TB disease every year, and roughly 200,000 die from it, few studies have investigated the risk of developing TB during childhood, particularly in high-burden countries like South Africa. Approximately 15% to 20% of all TB cases in South Africa, which has one of the highest TB incidence rates in the world, are likely to occur in children.
To assess the risk, researchers from the Boston University School of Public Health (BUSPH), the University of Cape Town, and the University of Sao Paulo followed 1,137 women and their 1,143 children who were living near Cape Town from 2012 through 2023 and were enrolled in the Drakenstein Child Health Study, a cohort study of children born in a setting with high TB and HIV burdens. A previous study of this cohort found high rates of tuberculin skin test conversion (presumptive evidence of TB infection) and TB disease in the first 5 years of life.
For this study, the researchers extended their work to examine the children through the first 10 years of life. They tested the children for Mycobacterium tuberculosis infection and TB disease using tuberculin skin tests at 6 months and 12 months of age, then annually in children with a negative test.
"To the best of our knowledge, this is the first birth cohort study to prospectively investigate M tuberculosis infection and tuberculosis disease in the first decade of life in an area with a high tuberculosis burden," the study authors wrote.
An urgent health problem
Over the follow-up period, the annual risk of tuberculin skin test conversion was 6.6 per 100 person-years, ranging from 4.4 to 9.3, with the greatest annual risk occurring at 1 year (9.3%) and 8 years (8.9%). The cumulative hazard of tuberculin skin test conversion was 36% at age 8 years, and the cumulative hazard of TB disease was 10% at age 10.
"These results are striking and show that children in these communities in South Africa are at extraordinarily high risk," study co-senior author Leonardo Martinez, PhD, MPH, assistant professor of epidemiology at BUSPH, said in a university press release. "It’s clearly an urgent health problem with both short and long-term impacts on these children and their families."
Among the risk factors associated with tuberculin skin test conversion were household cigarette smoke exposure (adjusted hazard ratio [aHR], 1.7; 95% confidence interval [CI], 1.2 to 2.5), households with more than five people (aHR, 1.3; 95% CI, 1.1 to 1.7), and known exposure to an individual with TB (aHR, 1.2; 95% CI, 1.0 to 1.6).
These results are striking and show that children in these communities in South Africa are at extraordinarily high risk.
Preventive treatment was associated with a reduction in TB disease among children who had tuberculin skin test conversion (aHR, 0.23; 95% CI, 0.12 to 0.47). However, most cases of TB disease (78 of 98; 79%) occurred among children who had tuberculin skin test conversion but were not administered preventive treatment.
"This highlights an important challenge in tuberculosis programmes where provision of preventive treatment is of low priority," the authors write.
Martinez and his colleagues say children who develop TB disease are at risk for poor outcomes in young adulthood and later life and that follow-up on this cohort to understand their long-term health trajectories is an important next step. They also call for a multipronged approach to decrease pediatric TB in high-burden settings that combines preventive treatment for children at risk, active case finding, and reduction of community TB transmission.
