The University of Texas Health Science Center at Tyler (UTHSCT) has received a $2.8 million grant from the National Institutes for Health (NIH) for a study of Mycobacterium tuberculosis (Mtb), which infects a third of the world’s population, causing 1.3 million deaths per year, including 100,000 children. Principal investigator on the research is UTHSCT Chair and Professor of Pulmonary Immunology Dr. Raman (Krishna) Vankayalapati. UTHSCT researchers Drs. Karan Singh and Deepak Tripathi are co-investigators on the grant.

“Approximately 90% of infected persons have latent tuberculosis infection (LTBI). They have protective immunity and remain well,” Dr. Vankayalapati said. “But 10% of infected persons develop primary tuberculosis (TB) soon after infection or experience reactivation TB many years later.”

TB is the leading cause of death in HIV-infected persons. More than half a million coinfected people die annually. Children are more susceptible to TB infection due to an immature immune system. HIV infection in children markedly increases their susceptibility to TB.

Dr. Vankayalapati said that to develop an adequate prophylaxis or therapy, it is important to understand immune responses to Mtb. Identifying HIV-positive children with LTBI — who are at greatly increased risk for developing TB — would allow treating only high-risk children, which would facilitate completion of therapy for LTBI and prevent future development of TB.

To identify these children, it is important to pinpoint the nature of the defective immune responses that permit development of active TB in coinfected pediatric patients who are HIV-positive and LTBI-positive.

The NIH-grant-funded study will be performed in India as a part of a RePORT-India consortium. This study will leverage the large Indo-U.S. investment and TB/HIV research consortium of RePORT-India, which has developed cohorts of TB cases and household contacts in India and as paired Indian investigators with U.S. investigators at six sites.

The focus of the research is on identifying immune defects that make children, particularly HIV-positive children, at greatest risk for progression of LTBI to TB. These studies will lay the groundwork for strategies to develop novel anti-tuberculosis vaccines that stimulate strong Natural Killer (NK) cell-mediated immunity in HIV-positive and HIV-negative children with LTBI and reduce the development of TB.