Prior parasitic worm infections may complicate TB therapy

Tuberculosis (TB) is a major threat to global health, taking the lives of more than a million people worldwide each year. Its greatest impact is often in the most impoverished places on earth, where patients frequently suffer from multiple chronic illnesses at the same time. In such situations, the question of whether each individual illness might make concurrent illnesses more difficult to treat becomes a critical issue both for specific patients and for general public health. New research led by Padmini Salgame, Ph.D., professor and director of the Graduate Medical Research Program at the University of Medicine and Dentistry (UMDNJ)-New Jersey Medical School, has established such a connection between tuberculosis and infection by parasitic worms, a frequent occurrence in much of the world. The study, by a team that also worked in collaboration with William C. Gause, Ph.D., professor and senior associate dean of research at New Jersey Medical School, appears in the Journal of Experimental Medicine.

Finding the molecular switches that control the body's natural defenses against Mycobacterium tuberculosis (Mtb), the causative agent of TB, is central to developing new treatments to control this important disease. In the current study, the researchers report that parasitic worm infections thwart the body's natural defense against Mtb. Macrophages, large white blood cells that attack foreign objects in the body and form a first line of defense against infection, appear to have a reduced capacity to destroy these bacteria when mice are infected with a lung dwelling parasite prior to Mtb infection.

The team probed further to unravel the mechanisms behind the observed findings. They successfully identified an alternatively activated state of macrophages, due to the prior parasite infection, as the reason for the apparent reduction in the body's ability to fight Mtb. These findings are highly significant as they suggest that these parasites may be a risk factor for the progression from infection to the development of TB disease, particularly given that co-infections occur in people in regions of the world that are co-endemic for these parasites and TB. It also raises the possibility that prior parasite infection may be one explanation why vaccines against TB show such variability in effectiveness, and suggests that unique approaches to therapy may be warranted in patients who present with histories of parasitic worm infections in addition to TB.