Family exposure to TB puts kids at high risk

"Tuberculosis is something that's been perplexing people for thousands of years," says Leonardo Martinez. "In particular, there are a lot of knowledge gaps in our understanding of pediatric TB." (Credit: Getty Images)

When a family member has tuberculosis, children have a surprisingly high risk of developing the disease, according to a new study.

The findings come from the largest modern study to assess tuberculosis (TB) risk among children closely exposed to the disease. TB kills more people than any other infectious disease worldwide, including 205,000 children per year, according to the World Health Organization.

Yet estimates of children’s risk following exposure remain based on data from studies in the 1940s.

“We found that the risk of developing TB disease was really, really high among exposed children, especially those younger than five with the TB infection,” says Leonardo Martinez, a postdoctoral scholar at Stanford University and lead author of the paper in The Lancet.

About 19% of one- to five-year-olds infected with the TB bacteria developed the disease—very different from the rates estimated from historical data. In general, the study shows that, for some age groups, modern rates are lower than estimates for rates in the 1940s, whereas for children and teens, the modern rates are significantly higher.

In the 1940s, the elements contributing to TB risk different greatly from today. HIV infection, now a major TB risk factor, was unknown. Malnutrition, another big risk factor, was much more common. Modern tools for diagnosis, antibiotics, and drug-resistant strains of the disease did not exist.

“We felt a sense of urgency around updating data to reflect the current pediatric TB epidemic,” Martinez says. “So many factors relating to the disease have changed, and there was a significant need for new data.”

TB around the world

The Mycobacterium tuberculosis bacteria causes TB. About a quarter of the world’s population has contracted it, with most transmission occurring in close quarters, such as between family members.

The disease occurs in all regions of the world, and in all age groups, but eight countries account for two-thirds of the world’s TB burden, according to the World Health Organization. These countries are India, China, Indonesia, the Philippines, Pakistan, Nigeria, Bangladesh, and South Africa.

The immune system walls off the microbes in most infected people, keeping them healthy. But some infected individuals develop the active form of the disease, with symptoms such as a bloody cough, chest pain, fever, weakness, and loss of appetite. The researchers focused on investigating how often children catch TB from an infected family member and go on to develop the active disease.

Martinez and colleagues compiled information on TB risk in children from researchers around the world, pooling data from 46 smaller studies conducted since 1998 in 34 countries.

The data tracked 137,647 children, starting when a family member or other close contact received an active TB diagnosis. Researchers followed each child for an average of four years. In addition to tracking TB cases, the researchers also evaluated several other factors, including the effect of medications given to children and other family members to try to prevent the bacteria from spreading.

In the study, 1,299 children received an active TB diagnosis within 90 days of their initial evaluation. Another 999 cases of the active disease were diagnosed during the follow-up period.

Historical data had shown that children younger than 1 infected with the bacteria had about a 20% chance of developing active TB. The historical data indicated that the risk of developing the active disease dropped to about 10% for TB-infected children ages 1-2, and to 5% for those ages 3-5.

In contrast, the new data show that the risk of developing the active disease is 19% among infected children as old as 5. Among children ages 5-19, the risk of developing an active form of the disease after an infection is 8-12%, also higher than historical estimates.

Children with HIV have a higher likelihood of developing active TB than those without HIV, the study shows, mirroring a trend observed in adults.

‘We’re not catching them soon enough’

Preventive medications given to healthy children were quite effective if given before children became ill with TB, reducing the development of active TB disease among TB-infected children 91%. In many cases, however, children developed TB symptoms before they received any preventive medications.

“We can only give preventive therapy to children who have not progressed to full-blown TB disease,” Martinez says. “Since children who are exposed to TB develop the disease so quickly, it is difficult for health care providers to find these children in time to provide the preventive treatment. We’re not catching them soon enough.”

Martinez and colleagues say they hope the findings will help public health experts better focus their TB prevention efforts, especially in identifying TB cases faster to better prevent their spread to children.

“Tuberculosis is something that’s been perplexing people for thousands of years,” Martinez says. “In particular, there are a lot of knowledge gaps in our understanding of pediatric TB. If we don’t dedicate attention to it, it will continue to be the No. 1 killer among infectious diseases.”

Additional coauthors are from Boston University and the Pediatric TB Contact Studies Consortium. The National Institutes of Health funded the work.

Source: Stanford University