Lost genes may be causing TB vaccine's failure
The tuberculosis vaccine may no longer work. McGill and Stanford researchers have discovered that the bacteria used to make the vaccine have jettisoned some of their genes.
According to Health Canada and the U.S. Centers for Disease Control, every year more than 22,000 North Americans develop tuberculosis. In poorer countries of the world, tuberculosis is responsible for 3 million deaths annually. "The Mycobacterium tuberculosis bacillus is the most deadly pathogen on earth. Responsible for the death of one European out of four, at the beginning of the twentieth century, it still accounts for the greatest number of deaths from a single organism," says Dr Marcel Behr, of the McGill University Health Centres Division of Infectious Diseases and Medical Microbiology, who will publish in the February 5, 1999, issue of The Lancet the results of a 6-year epidemiologic study he led in San Francisco on tuberculosis transmission.
Every year, an estimated 8 million cases of tuberculosis occur globally, but in most parts of the world, the diagnosis is made based on a test that is over a century old: examining through the microscope smears of sputum from patients. Unfortunately, only about one-half of tuberculosis patients have sufficient numbers of bacteria in their sputum for the diagnosis to be made by this technique.The threshold for detecting bacteria on light microscopy is about 5,000 -10,000 bacilli/ml., much greater than the number needed to infect another person, estimated at fewer than ten organisms.The study Dr Behr conducted with colleagues at Stanford University and the University of California in San Francisco used DNA-fingerprinting of bacteria to track the spread of tuberculosis, in order to determine whether examining sputum from patients under the microscope is able to detect those patients most likely to infect others.
The most reliable way to diagnose tuberculosis is to culture the sputum in a medium favourable to the growth of the bacilli and this can take up to two weeks. It is commonly assumed that patients who test negative under the microscope but who will later prove culture-positive are unlikely to transmit tuberculosis to others. Therefore, these cases are generally not isolated during hospitalization, and are largely left untreated in countries that do not have the resources to perform cultures.
Dr Behr and his team showed that "in San Francisco, the acid-fast bacilli smear identifies the most infectious patients, but patients with smear-negative culture-positive tuberculosis appear responsible for about one sixth of tuberculosis transmission."
"These findings from San Francisco call for improved and inexpensive new methods of diagnosing tuberculosis" said Dr Behr, who concluded his Lancet article with the following statement: "The overall impact of transmission from smear-negative patients on the epidemiology of tuberculosis in countries where such patients are usually not identified is an important research priority."
Dr Marcel Behr graduated in medicine from Queens University. He was trained in Internal Medicine, Infectious Diseases and Microbiology at McGill University from which he obtained an M.Sc in Epidemiology and Biostatistics. He pursued post-doctoral training at Stanford University with the support of the McLaughlin Foundation of Canada. Dr Behr is currently Assistant professor of Medicine at McGill and Assistant Physician at the MUHC.
NOTE: Dr Behr will be in Seattle until February 12. He can be reached at 206- 674-6677.