ASTHMA
August 15, 2000

Tuberculosis: The Comeback Bug

Tuberculosis, the ancient killer, once known as the "White Plague," was, at least in wealthy, medically advanced countries, on its way to extinction, thanks to antibiotics.

In the rest of the world, the story was different. In 1990, the World Health Organization (WHO) estimated that approximately 1.7 billion people were infected with the tubercle bacillus, the bacteria that causes tuberculosis. The vast majority of the eight million active cases are in developing countries. 2.9 million people die from tuberculosis each year.

And, even in the United States, tuberculosis has made a comeback. This is due in part to the spread of AIDS, a disease which weakens the immune system and makes its victims much more vulnerable to tuberculosis and other opportunistic infections. Current estimates hold that 15 million Americans are infected with tuberculosis.

History
Though the tubercle bacillus that causes the disease was only identified by scientists in 1882, tuberculosis has been killing human beings for thousands of years, if not longer. Today, it remains the number one cause of death in developing countries. Early records from the United States show that tuberculosis accounted for 300 deaths per 100,000 of population in 1786, when statistics were first gathered in Massachusetts. Thereafter, the disease seems to have spread, accounting for 1,600 deaths per 100,000 by 1800.

Introduced to North America via white Europeans, tuberculosis spread slowly from New England to the Midwest, Southwest and West. For this reason, African Americans and Native Americans experienced epidemics later in the 19th century. By the end of the 19th century, the disease had peaked and mortality fell to 113 deaths per 100,000 by the year 1920, yet it still was the second most common cause of death.

The number of tuberculosis cases in the United States declined steadily between 1920 and 1985, when the rate of newly reported cases hit a low of 9 deaths per 100,000. In the 1980s, however, tuberculosis made a startling comeback, as AIDS arrived and new, drug-resistant forms of the disease emerged. Nearly a decade passed before the number of new cases once more began to decline.

What Causes T.B.?
A pair of closely related mycobacteria, M. bovis and M. tuberculosis, have enjoyed a long relationship with man. Archeological evidence suggests that the disease began in cattle and was transmitted to man at the time of the domestication of these animals, approximately ten thousand years ago. Examination of Egyptian mummies reveals frequent signs of Pott's disease (tuberculosis of the spine). A variant of the original M. bovis strain, M. tuberculosis, is better adapted for establishing a parasitic relationship with man. Unlike M. bovis, which is contracted by humans through contact with infected animals, M. tuberculosis is contagious from person to person.

Throughout antiquity and the Middle Ages, tuberculosis gradually developed into a disease primarily of the lungs, although it does on occasion affect other organs. With its attraction for young victims and its long debilitating course, tuberculosis has played a unique role in literature and the arts — from Puccini's opera, La Boheme, to the works of Chekhov, Goethe, Dostoevsky, Keats, and Poe — as well as in the evolution of medicine.

How Tuberculosis Is Diagnosed
In the United States, the primary method for diagnosing tuberculosis is tuberculin skin testing — the skin is punctured or injected with tuberculin antigen and then tested for a reaction. When appropriate, this is followed up by analysis of the sputum, chest x-ray and a test called bronchoscopy, where the physician inserts a fiberoptic tube into the lungs to look for signs of the disease. There is a vaccine, called BCG, which is made from a modified form of M. bovis and which is reported to be 50% effective. Rarely used in the U.S., it is a major form of prevention in many countries.

Because the tuberculin antigen test can be unreliable and because symptoms can be difficult to read, however, it is not always easy to diagnose a case of active tuberculosis. One study from the 1970s found that 50 percent of tuberculosis sufferers admitted to the hospital were initially misdiagnosed.

How Tuberculosis Attacks the Body
The tubercle bacilli are inhaled and settle in the lower lungs. The body's immune system attempts to contain the infection, which progresses over a period of three to four weeks. Meanwhile, tubercle bacilli spread through the blood and the lymph system, invading virtually every organ in the body. They thrive in areas with high levels of oxygen saturation, in particular the upper lobes of the lungs, the brain, the vertebrae, the kidneys and the long bones. Often, the body's immune system successfully eradicates the original lower lung infection with very few noticeable symptoms. Unfortunately, the T.B. bacilli can survive, remaining dormant until something weakens the immune system and the disease is "reactivated." In fact, 90 percent of adult, non-HIV tuberculosis cases are not primary infections but are reactivated.

Symptoms of the active disease include cough, frequent spitting, bleeding from the lungs, fever, night sweats and weight loss.

Tuberculosis and HIV
Doctors noticed very early on that mycobacterial infections were common in individuals with HIV. HIV sufferers also came down with other, similar infections such as M. avium, a close cousin to tuberculosis that is carried by birds. M. avium presents virtually no danger to a person with a healthy immune system. To someone with HIV, however, it can be fatal.

A resurgence of disease from M. tuberculosis was associated with the AIDS epidemic in many areas of the United States. Between 1980 and 1987, the number of cases of tuberculosis among non-Hispanic blacks in New York City nearly doubled (699 to 1250). In the prison system, there was a more than six-fold rise among inmates infected with tuberculosis, the vast majority of whom were also HIV positive. It is estimated that 10 percent of the 88 million new cases of tuberculosis seen worldwide between 1990 and 1999 and 14 percent of the deaths are attributable to co-infection with HIV.

T.B. and Chemotherapy
Drug therapy, first introduced in the 1940s, is the main treatment for tuberculosis. For active tuberculosis cases, doctors usuall prescribe at least two drugs given concurrently. Two drugs are used because treatment with only one drug can breed resistant strains of M. tuberculosis. Before the discovery of this technique, a majority of patients relapsed following treatment with a single drug.

So-called "first line" drugs, normally given to tuberculosis sufferers for a minimum of six months, include: Isoniazid (INH), rifampin, streptomycin and pyrizinamide (PZA).

Extrapulmonary tuberculosis, or tuberculosis that affects organs other than the lungs, is usually treated with the same regimen as pulmonary tuberculosis. Children receive similar treament but with two exceptions. First, dosages must be adjusted for weight and age. Second, ethambutol, a drug which can damage the optic nerve that controls vision, is usually not given to very young children because of the difficulty of administering eye examinations to young children.

Drug resistance has become more and more of a problem in treating tuberculosis. Patient non-compliance is a major contributing factor in the development of drug-resistant T.B.. When patients fail to take their anti-tuberculosis drugs for the proper length of time to totally eradicate the infection, drug-resistant strains have a better chance of surviving. In many Third World countries and in certain areas of New York City, the prevalence of multi-drug resistant (MDR-TB) organisms may well be greater than 30 percent.

Treatment of TB strains that are resistant to only one agent is accomplished fairly easily by turning to other first line agents. The cure rate for these cases is 90% or higher. When the organism is resistant to more than one agent, however, second line drugs must be used; many of these require much longer courses of treatment to be effective.

In the beginning, MDR-TB was a major problem for those with HIV. While the cure rate for non-HIV patients approached 90 percent, MDR-TB once killed a very high percentage of infected HIV patients in a short period of time. As better treatments have been developed for HIV patients, however, the outlook for those with both HIV and MDR-TB has also improved.

Public Policy and the Law
The return of pulmonary tuberculosis in the U.S. and the emergence of MDR-TB have renewed an old debate on how far public health measures should go to control the new epidemic. To deal with the problem of non-compliance, public health officials launched a program called Directly Observed Therapy (DOT), in which patients are closely monitored to make sure they are taking their medicine. While proposals for across-the-board, mandatory DOT therapy have been widely rejected, a limited DOT program in New York City has led to a documented decline in new cases of tuberculosis.

Several factors have contributed to the return of tuberculosis in the United States. They include HIV infection, homelesness and other changing social conditions, and an increase in immigration from high prevalence areas abroad. All of these issues must be addressed if the epidemic is to be dealt with successfully.

Conclusion
While tuberculosis has been allowed to make a comeback in the U.S., thanks to the emergence of drug resistant strains of the disease and the susceptibility of HIV patients to mycobacterial infections, improvement in the diagnosis and treatment of these diseases, our growing success in treating HIV and a renewed public health effort have put us back on course to control and possibly even eliminate tuberculosis in the U.S. once and for all. By contrast, prospects for the war against tuberculosis in most of the rest of the world are very poor, mainly because of the HIV epidemic.
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