Content area
Full Text
About the Authors:
Steven C. Derrick
* E-mail: [email protected]
Affiliation: Center for Biologics Evaluation and Research, United States Food and Drug Administration, Bethesda, Maryland, United States of America
Dee Dao
Affiliation: Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, New York, United States of America
Amy Yang
Affiliation: Center for Biologics Evaluation and Research, United States Food and Drug Administration, Bethesda, Maryland, United States of America
Kris Kolibab
Affiliation: Center for Biologics Evaluation and Research, United States Food and Drug Administration, Bethesda, Maryland, United States of America
William R. Jacobs
Affiliation: Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, New York, United States of America
Sheldon L. Morris
Affiliation: Center for Biologics Evaluation and Research, United States Food and Drug Administration, Bethesda, Maryland, United States of America
Introduction
Despite being an ancient disease, TB remains an enormous public health concern in the 21st century. One-third of the world's population is thought to be infected with Mycobacterium tuberculosis and new infections likely occur every second. In 2009, the World Health Organization estimated that there were 14 million active cases of TB, 9.4 million new cases, and 1.7 million deaths due to this disease [1]. A driving force for the resurgent TB epidemic has been the HIV/AIDS pandemic. It has been estimated that approximately 1.5 million individuals are co-infected with TB and HIV and more than 400,000 co-infected persons die each year [2]. Importantly, control of this epidemic has been further confounded by the emergence of multiple drug resistant and extensively drug-resistant M. tuberculosis strains which often limit treatment options and make appropriate medical interventions challenging [3].
The only licensed vaccine against TB, M. bovis BCG, has been given to over 3 billion persons during its eight decades of clinical use. Randomized controlled trials and retrospective case control studies have shown that BCG immunization is effective in reducing cases of severe disseminated tuberculosis (TB meningitis and miliary TB) in children [4], [5]. Surprisingly, recent studies have also suggested that BCG vaccination may also reduce the risk of childhood infection by M. tuberculosis [6]–[8]. However, the effectiveness of BCG vaccine in preventing the most contagious and prevalent form of disease, pulmonary TB, is unclear. BCG-induced protection against TB has been highly variable with protective...