Professor Marcel Behr

PHOTO: OWEN EGAN

TB or not TB?
That is the question as deadly disease eludes tests


BRONWYN CHESTER | Medicine may have come a long way in the past century, but not when it comes to detecting tuberculosis. While the highly infectious bacterial disease continues to take more lives in the world than any other illness, Professor Marcel Behr, of the Division of Infectious Diseases, has shown that the test developed by German Robert Koch 117 years ago misses 50 per cent of the individuals infected by the disease.

Or, put another way, people who tested negative for TB were 22 per cent as likely to transmit the disease as people who tested positively. Considering that in poor countries three million people die annually of tuberculosis, these figures are significant.

The problem is, as lead author Behr points out in a recent issue of the British medical journal, The Lancet, Koch's test gives a positive result only to those people whose sputum shows under a light microscope 5,000 to 10,000 organisms of Mycobacterium tuberculosis. (Such people are immediately isolated, started on a six-month course of antibiotics and released from hospital after two weeks.)

Yet, it is estimated that only 10 organisms are needed to infect another person.

So, what Behr and his American and Mexican collaborators did was to examine the patterns of transmission among 1,359 culture-positive patients in the San Francisco area, where Behr has just returned from two and a half years as a research fellow of the McLaughlin Foundation of Canada.

Why this number? Because of the 1,574 culture-positive individuals reported in the city, 1,359 had had their isolates DNA-fingerprinted in an ongoing study of the molecular epidemiology of TB in San Francisco.

DNA fingerprints, better known for their ability to link a suspect to a crime scene, allow scientists to match up those groups of people whose TB bore the same DNA, indicating that transmission had occurred among them. The extensive documentation on each patient made it possible to know if transmission had occurred via a smear-negative person.

It should be noted that the status of culture-positive is determined by the only completely accurate way of detecting TB, which is by taking the sputum sample, culturing it for two weeks in a medium favouring bacterial growth, then examining it under the microscope. The reason this method of detection is not widely used is due to the cost and the time involved. What countries can afford, for instance, to quarantine for two weeks a possible TB transmitter when there is a good chance that she or he will be culture-negative?

What the authors recommend is that clinicians dispose of the notion that a smear-negative patient is automatically TB-free. Instead, if there are worrying clinical signs of TB -- such as fever, coughing up blood and weight-loss -- isolation should be continued until there is a response to treatment or the diagnosis of TB is absolutely ruled out.

"This is particularly important in settings where there are significant numbers of immunocompromised individuals," says Behr. He notes that the worst outbreaks of TB in the United States happened in prisons, where there is a significant population of intravenous drug-users and people who are HIV-positive, and in hospitals, where TB patients and immunocompromised patients were kept on the same floors. In the early '90s, for instance, says Behr, TB was rampant in New York City.

In poor countries, where treatment with antibiotics may be inadequate or non-existent, Behr and his co-authors believe that the implications of their study may be more dramatic than in San Francisco.

In Behr's opinion, it is time to develop an inexpensive, easily administered -- meaning not dependent on such expensive items as freezers, incubators and back-up electricity -- test that's more sensitive than the Koch.

Once he has set up his new lab at the Montreal General Hospital, Behr will be conducting a study in Montreal similar to the one in San Francisco, using the bacterial analyses that have been collected here for the past five years.

Montreal, a city famous for its TB clinicians like Norman Bethune, who developed the procedure for collapsing the TB-infected lung in the days before antibiotics, and Armand Frappier, who introduced the French-developed TB vaccine to Canada where it is still routinely administered to native people (though its efficacy is variable in studies, says Behr), is also home to approximately 100 people suffering from the disease, 50 of whom may be infectious at any one time.

Dr. Richard Menzies, director of McGill's Respiratory Epidemiology Unit, says that "we know that transmission goes on here, largely within households." TB here, he says, is found mostly in hospitals and prisons, among the homeless and in certain immigrant groups from Asia and Africa where the disease is common.

However, he says, the careful screening of refugees and the well-organized public health system -- particularly in light of recent outbreaks in the U.S. -- have kept the disease well under control. He warns though that "without continuous effort, we could see a rise."

Given the presence of such tuberculosis researchers as Menzies and Emil Skamene, who studies the response of the body to the TB bacteria in order to understand why the vast majority of people infected by the bacteria don't develop symptoms, Behr is glad to be back home in Montreal. The sunny and snowy (in principle) Montreal winters are also a draw -- Behr skis to work over the mountain when possible.

TB, thought to be as old as the domestication of cattle 10,000 years ago (when it is believed the bovine tuberculosis crossed over to humans) continues to fascinate the 34-year-old researcher.

"TB is like a barometer of the human condition; it follows wars, homelessness, social breakdown and poverty," he says, noting that the disease can reappear in countries in transition, like Russia, where care for the disease is now inadequate due to the economic state of that country.

"Bad or intermittent control of TB is worse than none," he says, noting that recent reports of some strains of the disease becoming resistant to antibiotics is due to the administration of incomplete courses of the drug.

"TB is something that should have gone away. We know what causes it and how to treat it. Yet, while the fire may have been put out, the embers remain."