Global WACh

February 7, 2019

New R01 grant to discover immune mechanism responses in HIV and TB co-infected children in Kenya

Dr. Grace John-Stewart, MD, PhD

Dr. Cheryl Day, PhD









Principal Investigators, Drs. Grace John-Stewart (Global WACh Director; Professor, Global Health, Epidemiology, Medicine, and Pediatrics) and Cheryl Day (Assistant Professor, Emory University School of Medicine, Microbiology and Immunology) received a NIH/NIAID R01 award that supports research to discover changes in immune mechanisms and markers of the Mycobacterium tuberculosis (Mtb), the pathogenic bacteria that causes tuberculosis (TB), in children exposed to or infected with HIV.  As the number of TB cases rise in parallel to the HIV/AIDS pandemic in developing countries, there is an urgent need to understand the complex biological interaction between Mtb and HIV, particularly children with immune systems weakened by HIV.  The World Health Organization estimates that there are over one million new cases of TB and 239,000 TB-related deaths every year.

Evidence shows that HIV-exposed or infected children have an increased risk of getting TB, but very few studies have explored the immune system’s recognition and response to HIV-related TB infections.  Some research suggests that early exposure to maternal HIV and antiretroviral treatment (ART) taken by the mother while her baby is in utero, may influence the baby’s immunity to Mtb.  In high TB-burden areas, it is standard practice to give the bacille Calmette-Guérin (BCG) vaccine, an inexpensive and safe vaccine, to newborns for protection against TB.  These early exposures may play an important role in “training” the immune mechanism in the way it identifies Mtb and determines how to respond and appears to alter responses to other infections.

In a new study titled, “The effect of HIV exposure and infection on immunity to TB in children”, Drs. John-Stewart, Day, and their research team will explore and describe how HIV and ART influence the body’s innate (the general defense mechanism that works quickly to destroy foreign pathogens) and adaptive (targeted defense against specific pathogens previously encountered) immune responses to Mtb.  The study team includes UW co-investigators, Drs. Sylvia LaCourse (Acting Assistant Professor, Medicine), Jennifer Slyker (Assistant Professor, Global Health; Adjunct Assistant Professor, Epidemiology), Barbra Richardson (Research Professor, Biostatistics; Adjunct Research Professor, Global Health), and Kenneth Tapia (Biostatistician, CFAR).  Collaborators from the University of Nairobi, Department of Paediatrics and Child Health Drs. Dalton Wamalwa (Associate Professor) and Elizabeth Maleche-Obimbo (Professor) add their clinical expertise in pediatric HIV and TB diagnosis and care to the team.

The team will examine specimens from three cohorts of infants and children from Kenya—HIV-infected, HIV-exposed uninfected, and HIV-unexposed—collected from two ongoing Global WACh studies to conduct their study aims.  The study will contribute an understanding of how HIV-exposure, infection, and ART modify TB immune responses.  Their findings will be important for developing vaccines or other approaches to prevent TB in HIV-exposed and infected children.  We look forward to sharing updates as the study progresses.