Dr. Grace John-Stewart, a professor of global health, epidemiology, medicine, and pediatrics at the University of Washington, was recently awarded an $828,368 grant from the National Institutes of Health and the US Department of Health and Human Services. The grant is titled “The effect of HIV exposure and infection on immunity to TB in children”.

“This study will help us to understand whether HIV exposure or infection modifies the way infants respond to the BCG vaccine and how this, in turn, could affect their susceptibility to TB infection.”
These are the words of John-Stewart, who serves as the Director of the UW Global Center for the Integrated Health of Women, Adolescents, and Children (Global WACh). John-Stewart was recently named co-principal investigator on the grant along with Dr. Cheryl Day. Co-investigators include Sylvia LaCourse, Dalton Wamalwa, and Elizabeth Maleche-Obimbo.

The grant aims to determine the effect of HIV exposure on infants who received the Bacillus Calmette-Guérin (BCG) vaccination, which is commonly used to prevent tuberculosis (TB). Led by John-Stewart, this research is designed to make tangible improvements to pre-existing treatments.

“It is possible that in utero exposure to HIV or antiretroviral therapy (ART) alters the way children respond to the BCG vaccine,” John-Stewart said. “By understanding whether and how HIV exposure modifies BCG immune responses, it may be possible to improve vaccines or protection of HIV-exposed infants.”

“Previous studies have noted that infants who are born to a mother with HIV are much more likely to get TB infection and disease. This could be because of immune susceptibility or exposure.”
While evidence exists that HIV-exposed children carry a higher risk of contracting TB, few studies have actually delved into the ways that HIV-related conditions lead to TB in children. 

“Several research groups have noted that HIV-exposed uninfected (HEU) infants have worse health outcomes than children who are not exposed to HIV - including poorer growth, higher mortality and more infectious diseases,” John-Stewart explained. “It is critical to optimize the outcomes of this growing population of children.” 

Not only is pediatric TB amplified by HIV infection, the disease follows a much more aggressive course in children than it does in adults. Recent data suggests that the BCG vaccine creates “trained immunity”, an immune response that is not honed in on any specific disorder or disease.
“We have done studies to examine how HIV gets transmitted to infants, how to prevent transmission, and how to scale up prevention of mother-to-child HIV transmission (PMTCT),” John-Stewart noted.
“Globally, PMTCT has been a success story with dramatic declines in the number of HIV infected children. Now, most children born to mothers living with HIV infection will be uninfected, and it is important to optimize the health of these children."