Is a new tuberculosis vaccine necessary and feasible? A Cuban opinion

Mycobacterium tuberculosis kills more human beings worldwide than any other pathogen. An estimated two billion people are already infected with the bacterium. In 2006, tuberculosis (TB) will kill nearly one million more people than in 1992. In Cuba, TB is not a serious health problem any more and we are striving to eliminate it in the near future. The most widely applied human vaccine in the world is BCG. It is also a safe vaccine except when it is applied to immunocompromised persons. Its protective efficacy is a controversial topic. In spite of this, more than 80 years of experience with this vaccine has demonstrated that BCG is effective, at least in significantly preventing childhood TB, including the meningeal and disseminated forms of the disease, but does not protect against the predominant pulmonary form of the disease in adults, which means that our best TB vaccine now is inadequate; we therefore need a new vaccine. The following facts, apart from the experience with BCG, support discussion about the feasibility of a new and better TB vaccine: Less than 10% of the 2 billion TB infected persons develop active disease. It has been demonstrated that HIV + TB co-infection increases 30 times the risk of contracting active TB and it increases the risk of being killed by the bacterium. Some new vaccine candidates, now under development and evaluation, are showing promising results in preclinical studies, and a few of them have entered clinical trials. There seems to be a consensus that a new TB vaccine will be feasible, but some challenging issues must be positively solved, such as, the lack of universally accepted correlates for protection, improved diagnostics, and final vaccine efficacy evaluation conducted on large phase III clinical trials in underdeveloped countries. The ethical, economical, organizational and scientific questions involved in this global task are enormous, but feasible.