Jacques Grosset, MD
M. tuberculosis still infects over 1.7 billion people, causes disease in over 8 million people every year, and kills more than 2 million people every year. Since the beginning of my professional life I have been involved in research to improve the control of tuberculosis, mainly by improving treatment of tuberculosis and preventing the development of drug resistance.
Tuberculosis was a leading cause of death in industrialized countries when I started my medical studies. Despite the tremendous progress made during the past half-century,
During the past 45 years, I have participated in the development of nearly all new drug regimens used for tuberculosis and a number of other mycobacterial diseases, namely leprosy, M. avium complex infection in HIV-infected persons, and M. ulcerans infection (Buruli ulcer). Using the murine experimental model, I directed the development of an antibiotic regimen that led to the first clinical that demonstrated the efficacy of this treatment for Buruli ulcer. I also participated in the design and evaluation of this trial. At present, my primary involvement is in the use of the mouse model to investigate the efficacy of new drugs and new drug combinations in human diseases caused by mycobacteria for improving both the efficacy of treatment and the implementation of Directly Observed Therapy (DOT) with the main following objectives:
1. Shorten the duration of therapy
2. Increase the interval between dosing by using drugs with long half lives and/or slow release preparations
Any investigator involved in the study of antituberculous chemotherapy must grapple with 2 phenomena unique to the pathogenesis and treatment of tuberculosis. The first is a propensity for the initial infection to evolve under the pressure of host immunity into a paucibacillary latent state which may reactivate into clinical disease at a later point in time.
The second is a capacity for persistence of a small bacillary population in a state of unresponsiveness to antimicrobials to which they are genotypically susceptible. The mechanisms by which the bacteria transition to and survive in the latent and persistent states are unknown. Therefore, the identification of bacterial factors involved in both states would be extremely beneficial for both the preventive and the curative therapy of tuberculosis. The genomics revolution has provided the tools and techniques necessary to begin to identify those bacterial factors regulating the adaptive response. My collaboration with Dr. William Bishai, a recognized expert in the field of mycobacterial genetics and pathogenesis, offers a unique opportunity to address these crucial issues.