When Mimi collapses and dies of "consumption" in Puccini's opera La Boheme and when Camille dies coughing up blood in Alexander Dumas' novel Camille, tuberculosis seems a romantic, if tragic, way to go. But in real life, tuberculosis (TB) lacks the romance: it is painful and it is serious. TB is an infectious disease that can harm the lungs, bones, skin, and various organs of those who are sick. Today, around the world, some 2 to 3 million people die of TB each year.

In the United States, TB was pretty much under control for several decades. New antibiotics killed the bacteria that caused the disease -- their Latin name is Mycobacterium tuberculosis -- and a vaccine was developed that seemed to protect healthy people from the disease. From 1953 through the 1960s, 1970s, and early 1980s, there were always fewer new cases each year than in the previous year (1).

The TB story was a continuing success story -- 84,000 new cases in 1953 and just over 22,000 new cases in 1984 (2).

Then, in 1986, the disease escaped control. And, since then, there are more new cases every year than in the previous year.

Doctors have found that many of the new cases are harder to treat than TB cases of the past. The bacteria are not readily responding to antibiotics that once successfully stopped this disease. In a disturbing number of patients (14% of those recently evaluated), the TB bacteria are not killed by several different antibiotic drugs. Such bacteria are called multi-drug resistant (MDR) bacteria.

How do TB bacteria develop antibiotic resistance? All sorts of random, spontaneous, genetic mutations occur in them as they grow and divide. By chance, some of these mutations alter the bacteria so that they can no longer be killed by a given antibiotic.

The treatment strategy that is typically used for people with TB is one that was designed to outsmart mutating bacteria. TB patients take several different antibiotics, either at the same time or in series. The chance that the bacteria will develop resistance to several different antibiotics is much much less than the likelihood that they will develop resistance to a single antibiotic.

Despite this multi-drug approach, the TB bacteria are becoming multi-drug resistant. Medical researchers have found that many TB patients simply do not take their medicine in the right dose or for the right length of time. (This is known as "noncompliance" and is as old a problem for the practice of medicine as is disease. Noncompliance can occur when patients do not understand the value of the treatment, cannot afford to buy medicine, believe that feeling better means being cured and on their own make the decision to stop taking medicine, etc.) In the absence of a full course of antibiotic therapy, the bacteria are not effectively "beaten back" by antibiotics.

TB has always been a disease that is associated with crowded, unhealthy living conditions, with prisons, and with homelessness. It is not caused by these conditions but, in them, the bacteria are easily passed from person to person. The spread of TB in this new outbreak has occurred in close association with the spread of AIDS: more than 90% of patients recently identified as having MDR TB also had AIDS infections.

Unlike AIDS, which is a relatively new and little understood disease, tuberculosis is old and well characterized. More than 100 years ago, Robert Koch, the famous microbiologist who studied many disease-causing bacteria, made the definitive association of Mycobacterium tuberculosis and the disease tuberculosis. In the last century, scientists have discovered much about the bacteria, their actions in the body, their life cycle, and their transmission from person to person. Koch used TB bacteria to formulate "Koch's postulates," his systematic series of steps required for proving that an organism is the cause of a disease. The "fulfillment" of Koch's postulates is still a requirement for associating an infectious agent with a disease.

TB has been around for a long time. A thousand-year-old mummified skeleton of a Peruvian woman contained signs of TB (3). Scientists were able to identify the TB bacteria in the mummy's lymph node, because they found pieces of the bacteria's genetic material DNA there; her lungs also had telltale signs of the disease.

The new problems with TB are stimulating discussions among medical policymakers about whether the TB vaccine works well enough and should be used more widely in this country to protect people who are at risk of contracting the disease. Since the vaccine was developed and first used in 1921, some three billion doses have been given throughout the world. [The vaccine is called BCG for the bacterium or bacille (its French name) that causes the disease, and C and G for the two scientists (Calmette and Guerin) who developed it.] How effective this standard vaccine will be against mutating organisms remains to be seen.

1. Many of the data and concepts discussed in this story are based on two reports and an editorial in the Journal of the American Medical Association, March 2, 1994.
2. These data and other facts are from Morbidity and Mortality Weekly Reports 1993, 42(RR7):1.
3. Washington Post, March 15, 1994, A15. Data cited are from an article published in Proceedings of the National Academy of Science, March 15, 1994.

This article was originally posted on the NIH electronic bulletin board EDNET on 3/15/94.