New approaches to vaccines against tuberculosis: where we stand and where we want to go. Introductory remarks to the symposium.

Abstract

The discovery of the tubercle bacillus, Mycobacterium tuberculosis, by Robert Koch in 1882, was a great moment in the history of medical research. The description of the bacterium was the ¢rst step in overcoming one of the most devastating epidemics, that of tuberculosis. In 1907 the `Robert Koch Foundation to Fight Tuberculosis' was founded and Robert Koch was the ¢rst scientist to receive a grant from the foundation for his research activities. In his speech of thanks to one of the patrons he made the following comments (in German):The general public is already convinced that tuberculosis is an avertable disease and people have learned to avoid infection better than was previously the case. Since the public awareness of this fact, the mortality rate of tuberculosis has been greatly reduced in all civilised countries and the indications that this disease will be completely wiped out are increasing. This is the moment to take up arms on all fronts. Unfortunately, these words still hold true 90 years later. Among infectious diseases, tuberculosis is responsible for the greatest number of deaths. Each year 54 million people are infected with M. tuberculosis, 7 million develop clinical diseases and 3 million people die of tuberculosis. BCG is currently the only available vaccine against tuberculosis and is widely administered within the WHO Expanded Programme for Immunization. It is generally accepted that the BCG vaccine can prevent death from disseminated tuberculosis in children, but its e¤cacy in preventing pulmonary tuberculosis in adults is extremely doubtful (trials of e¤cacy ranging from 0% in India to 77% in UK). Due to this insu¤cient e¤cacy and because the vaccine interferes with skin test screening, thwarting a discrimination between a BCG vaccination and an infection of M. tuberculosis, the BCG vaccination is not recommended for general use in many countries. The tool which has been adopted by the WHO as the main strategy for the global control of tuberculosis, but which requires that drug therapy be carefully supervised to assure compliance, is the `Directly Observed Treatment Short-course' (DOTS). Unfortunately this chemotherapy is relatively expensive, has signi¢cant side eiects, and a cure requires more than six months of DOTS. In areas of the world