Distinct clinical outcomes in pediatric tuberculosis: A study utilizing infant macaques exposed to aerosol Mycobacterium tuberculosis

Clinically relevant pediatric animal models are required to advance research and therapies for <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) infections in children. Utilizing infant rhesus macaques exposed to controlled doses of aerosolized <i>Mtb</i> CDC1551, we systematically monitored physical changes and assessed signs of tuberculosis, including physical examinations, clinical blood chemistry, radiography, and histopathology. Our results demonstrated that infant macaques exposed a physiologically relevant, low dose of aerosolized <i>Mtb</i> CDC1551 and exhibited immune control of infection similar to that observed in human infants, while those exposed to a higher dose experienced widespread dissemination, rapid disease progression, and mortality within six weeks after <i>Mtb</i> exposure. These findings suggest that pediatric rhesus macaques exposed to a low dose of <i>Mtb</i> via the aerosol route could serve as a translational model for natural <i>Mtb</i> infection in children, thereby allowing for the recapitulation of the immunopathogenesis and treatment of pediatric tuberculosis in a clinical setting.