Curable, preventable, but still a killer; TB

Curable, preventable, but still a killer; TB – tuberculosis; includes related articles

Annabel Hecht

Curable, Preventable, but Still a Killer

To many people in the United States, tuberculosis is an almost forgotten disease, one that is read about, but seldom encountered. But it wasn’t too long ago when 126,000 cases of TB were being reported every year. That was the case in 1944 when the U.S. Public Health Service launched its tuberculosis control program.

A little more than four decades later, in 1985, the number of cases had dropped to 22,201.

While this may seem to be a dramatic improvement, health authorities warn that tuberculosis is still a serious public health problem in the United States. Deaths from tuberculosis–about 2,000 annually–outnumber those for all other infectious diseases reported to the U.S. Centers for Disease Control (CDC). Only pneumonia and influenza, which are not required to be reported, take a greater toll. Worldwide, tuberculosis is a major problem, with as many as 4 million new cases and 3 million deaths every year.

Tuberculosis in humans is caused by two species of rod-shaped bacteria that are called mycobacteria. M. tuberculosis primarily causes pulmonary (lung) tuberculosis, the most prevalent form of the disease. M. bovis causes bovine tuberculosis, a disease of cattle that can be transmitted to humans through cow’s milk, resulting in both pulmonary tuberculosis and disease of other body sites such as the cervical (neck) lymph nodes and the spine. Pasteurization of milk and testing of dairy herds for infected cows has virtually eliminated bovine tuberculosis in the United States.

Pulmonary tuberculosis is spread via contaminated droplets that are coughed, sneezed or otherwise put into the air by a person with active TB. Inhaled by a susceptible individual, the smallest droplets end up in the alveoli, minute air sacs in the lungs located at the tips of the bronchial tree. The bacteria (also called tubercle bacilli) may also infect the kidneys, bones, lymph nodes, and membranes surrounding the brain (meninges), or they may be spread throughout the body.

During the first stage of infection, white blood cells called phagocytes attack and may destroy any bacilli that have gotten into the lung. Those bacilli that escape this defense may continue to grow.

About two to 10 weeks after infection, the individual develops a hypersensitivity to the tubercle bacillus or its proteins, known as tuberculins. This heightened sensitivity persists for a very long time, and a small amount of the tuberculins subsequently injected into the skin will produce a hard, red, raised spot at the injection site. This is the basis for the skin test used to detect exposure to M. tuberculosis.

The response of sensitive lymphocytes (white blood cells) to tuberculin results in the activation of another type of white blood cell, called a macrophage, which engulfs and attempts to destroy the bacilli. The affected tissue becomes infiltrated with macrophages and layers of other cells to form the characteristic tubercle that gives the disease its name.

After this initial tubercle has healed, the lesion becomes calcified, in effect “walling off” the bacilli. There they may remain dormant for months, years or a lifetime.

If healing is imperfect or if the person’s immune capability is lowered the bacilli may multiply more rapidly than the body’s defenses can cope, the bacilli spill out, become engulfed by new macrophages, and start new tubercles in the lungs or throughout the body. In the process, macrophages and other tissue and blood cells that are killed form a soft, caseous (cheese-like) mass that eventually becomes liquified and is discharged into nearby air passages, leaving a cavity in the lung. As the disease becomes extensive and more cavities form, lung function is impaired. Blood in the sputum is usually from ulceration of the lining of the bronchi. Massive hemorrhage can occur if a pulmonary artery in a tuberculous cavity ruptures. In advanced cases, death may occur from loss of blood or obstruction of airflow.

Most persons exposed to the bacilli do not develop TB. In those people who do develop active TB, the disease may spread rapidly and produce a high fever. (This acute form of TB was once called “galloping consumption.”) Or it may become a chronic, slowly progressive disease with low fever, weakness, and loss of weight. If left untreated, many patients eventually die of the disease.

The impact of tuberculosis is felt most by older and poorer people.

Cases usually occur in individuals who were infected years ago, particularly the eldely. Many of these people grew up in the first decades of the century when 80 percent of the population had been infected (though not necessarily afflicted with an active case of the disease) by the time they were 30. By CDC estimates, currently 10 million people in this country are infected by the tubercle bacillus, carrying a small but lifelong risk of developing active TB.

Although most newly diagnosed tuberculosis patients in the United States are adults infected long afo, there were 1,200 new cases of tuberculosis in children in 1984. This means that TB is still being passed on by people with active infections. Also, evey year thousands more children are infected, but do not get the disease, adding to the pool of those at risk of TB in the future.

By all rights, this disease–once the nation’s leading cause of death–should have been eliminated. That was the hope some 40 years ago when the first effective anti-TB drug, streptomycin, was introduced. The number of cases has been going down steadily, but slowly–about 5 percent to 6 percent annually. At that rate, elimination of the disease could not be expected until after the year 2100, according to CDC Director James O, Mason, M.D. “This is unacceptable for a disease which today is considered curable and preventable,” he told a 1985 national conference on tuberculosis research in Pittsfield, Mass.

Even more disturbing is that this decline in the number of cases seems to have come to a virtual halt. The number of reported cases in 1985 was only 54 less than that in the previous year.

TB experts believe the slowdown is related in part to the increasing occurrence of tuberculosis among patients with AIDS (acquired immunodeficiency syndrome). Their suspicions are based on the fact that patients with other disorders that affect the immune system–as AIDS does–also have an increased risk of developing active TB.

In addition, some of the areas with the largest number of TB cases are also the areas with the largest number of AIDS cases (New York City, California, Florida, and Texas). In New York City, matching AIDS and TB case registers has revealed an increasing number of AIDS patients with a history of tuberculosis. In Dade County, Fla., a substantial number of people with AIDS eithe had tuberculosis at the time that AIDS was diagnosed, or had it in the previous 18 months. Thus, tuberculosis may prove to be the first AIDS-related “opportunistic” infection that can be a threat to the general public. (An opportunistic infection is one that takes hold because the patient’s immune system is weakened.)

Two other reasons for the persistence of TB are outbreaks of the disease among the homeless, and the growing number of immigrants and refugees from areas where there is a high prevalence of TB, such as Southeast Asia and Central and South America.

Tuberculosis can be reduced by finding and treating new cases, and giving preventive therapy to those who wee in contact with TB patients and those who have positive reactions to tuberculin skin tests. Unfortunately, control efforts have been hampered by several factors, Dr. Mason told the Pittsfield conference. One of them is that health-care providers just don’t think of tuberculosis as a major problem.

This perception has been fostered by past success in reducing the number of cases and deaths from tuberculosis, Dr. Mason said. Because the disease is less common than in the past, doctors are less likely to consider it as a possible diagnosis. The classic symptoms–cough, loss of appetite, and blood-tinged sputum–often don’t appear in older patients or they may go unrecognized because they are masked by another illness or by the use of drugs such as antibiotics, steroids and anticoagulants (blood-thinning drugs).

Despite the availability of an array of effective drugs to treat tuberculosis, health-care providers are not always up-to-date on the latest recommendations for their best use. And patients often don’t take their medications correctly or stop taking them too soon. Until recently, tuberculosis patients had to take a number of drugs for a year or more. Unfortunately, the price of noncompliance can be the emergence of drug-resistant bacteria and continued transmission of the infection to others.

Today the length of treatment has been reduced in most instances to nine months. The primary drugs used are isoniazid and rifampin, both of which destroy the mycobacteria. During the initial phase of treatment, other drugs may be added: streptomycin, ethambutol or pyrazinamide. TB drugs must be taken in combinations to avoid the emergence of drug-resistant strains of the tubercle bacillus and to increase effectiveness. When a drug-resistant strain is suspected, the initial use of at least three drugs is necessary.

The regimen can be reduced to six months if three drugs–isoniazid, rifampin and pyrazinamide (and perhaps ethambutol if isoniazid-resistance is detected)–are given for two months, followed by an additional four months of isoniazid and rifampin, according to recently published recommendations by CDC and the American Thoracic Society, the medical section of the American Lung Association. Treatment lasting less than six months is not acceptable because of the risk of relapse.

Most patients have no problems with isoniazid and rifampin, although some may develop liver disorders. Ethambutol may cause reversible eye problems such as blurred vision, eye pain, red-green color blindness, or even temporary loss of vision. Streptomycin may permanently damage hearing. Pyrazinamide occasionally causes rash, hepatitis and gastrointestinal disturbances.

TB drugs may also interact with other medications. Isoniazid, for instance, increases the blood concentration of phenytoin, used to treat epilepsy. Rifampin may lessen the expected effects of oral contraceptives, quinidine, corticosteroids, warfarin (a blood thinner), and oral hypoglycemics taken for diabetes. Patients being treated for TB should make sure their doctor knows what other medications they are taking.

While combinations of various drugs can cure active cases of TB, the eradication of tubeculosis from the population rests, in large part, on preventing the disease from developing in those already infected by the tubercle bacillus. The risk of disease is particularly high in infected infants, adolescents and patients on immunosuppressive therapy, such as organ transplant patients. Many years ago, the Public Health Service demonstrated that a year’s treatment with isoniazid was very effective in preventing active TB in infected individuals.

Public health officials recommended that isoniazid preventive therapy can be given to contacts of persons with active disease; people who have recently had a change from a negative to a positive tuberculin skin test; people with previously known tuberculosis, now inactive, who have not had adequate treatment; and other positive tuberculin reactors. This last group includes particularly those with abnormal findings on a chest X-ray or underlying medical conditions such as diabetes, leukemia or Hodgkin’s disease (a form of cancer), and those under 35.

Lately, however, some experts have questioned the application of isoniazid preventive therapy to thos under 35, who may be at greater risk of developing hepatitis from the drug than tuberculosis.

In addition, the inconvenience of long-term drug taking and the lack of motivation on the part of apparently healthy individuals pose problems of compliance with the drug regimen.

Recently, a group of physicians and scientists involved in tuberculosis therapy met in Atlanta, under the auspices of CDC, to consider short-course alternatives to the long-term preventive approach. One suggestion by the group was that a six-month course of rifampin alone or a two-month multiple drug regimen with rifampin and pyrazinamide, with or without isoniazid, may prove as effective as the year-long treatment with isoniazid alone. Rifampin and pyrazinamide are particularly effective in eliminating the tuberculosis bacteria that persist in the bodies of infected individuals.

The group recommended evaluation of the short-course regimen in animals and pilot studies in humans, followed by full-scale human trials here and abroad.

CDC’s Mason sees an end to the transmission of tuberculosis by the year 2000, if more effective use is made of existing diagnostic, treatment and other control measures and new technologies are developed. Many of the tools now used to control tuberculosis–the tuberculin skin test, X-rays, and methods of culturing the bacillus–are adaptations of 19th century discoveries, Mason said.

He also called for more effective drugs that need fewer doses to cure the disease, better ways to monitor and improve patient compliance, a better approach to preventing disease among infected persons, are a reliable, effective vaccine.

“Let us declare total, all-out war against a disease that should only be part of our history,” Mason said.

If the campaign is successful, the disease the 17th century English author John Bunyan called “The captain of all these men of death” can be demoted to the lowest rank of all.

COPYRIGHT 1986 U.S. Government Printing Office

COPYRIGHT 2004 Gale Group