Tuberculosis (TB) is an acute or chronic bacterial infection found most commonly in the lungs. The infection is spread like a cold, mainly through airborne droplets breathed into the air by a person infected with TB. The bacteria causes formation of small tissue masses called tubercles. In the lungs these tubercles produce breathing impairment, coughing and release of sputum. TB may recur after long periods of inactivity (latency) if not treated adequately. Many variations of TB exist and are distinguished by the area of the body affected, degree of severity and affected population. This disease today is considered curable and preventable. It is very rare in the United States but is on an upsurge.
Tuberculosis most commonly affects the lungs, producing breathing difficulties. It may also affect the kidneys, bones, lymph nodes, and membranes surrounding the brain. In some cases, it can spread throughout the body. In the initial stages patients may experience fever, loss of appetite, weight loss, weakness, and sometimes a dry cough.
In the later stages of lung involvement, blood may appear in the sputum. Bleeding in the lungs may occur if an artery or tubercle (small tissue mass produced by the infection) ruptures. The patient can die of this infection if left untreated.
Tuberculosis is a bacterial infection usually caused by either Mycobacterium tuberculosis or Mycobacterium bovis. The Mycobacterium tuberculosis is the most common source of infection and is spread by airborne droplets breathed or coughed into the air by a person infected with active TB. In the past the disorder was caused in most cases by Mycobacterium bovis, a bacteria which was passed to humans through dairy products. Today, dairy and cattle are carefully inspected and tested for this type of TB, and infected products are not sold to the public in the United States. However, in less developed countries the TB infection is still passed to humans through dairy products.
The entire sequencing of the tuberculosis bacterium genome (genetic blueprint) has been fully documented.
In 1944, the Public Health Service launched a TB control program when the yearly number of cases in the United States averaged 126,000. In 1985, the number of cases had dropped to 22,201. However, health officials warn that TB is still a serious health problem, due in part to the rise of AIDS cases and the lowered resistance of AIDS patients to the TB infection. There are still approximately 2,000 deaths annually from TB in the United States, which is more than from all other infectious diseases excluding pneumonia and influenza.
In 1999, more than 17,000 new cases of TB were diagnosed in the United States.
Areas with the highest incidence of AIDS victims such as New York City, California, Florida, and Texas are also the areas with the highest incidence of TB. TB may prove to be the first “opportunistic infection” related to AIDS with potential threat to the general public. An opportunistic infection is one that takes hold because the patient’s immune system is weakened. (For more information on these disorders, choose “AIDS” and “Opportunistic Infection” as your search terms in the Rare Disease Database, and also see the AIDS Update area of NORD Services.) Recently, the southeast area of the United States and states bordering Mexico reported the highest Tuberculosis (TB) cases. Additionally, the recent influx of Southeast Asians, who have a high incidence of TB, now constitutes three to five percent of new cases in the U.S.
Worldwide, TB is a major health problem with as many as four million new cases and three million deaths each year. The impact of TB is felt most by older and poorer people. Cases usually occur in individuals who were infected years ago, particularly the elderly. Many of these people grew up in the first decades of the century when eighty percent of the population had been infected (though not necessarily afflicted with an active case of TB) by the time they were thirty. The Centers for Disease Control (CDC) in Atlanta, GA currently estimates that ten million people worldwide have been infected by the tubercle bacillus, carrying a small but lifelong risk of developing active TB.
There were 1,200 American children diagnosed with TB during 1984, leading to the conclusion that TB is still being spread by people with active infections. Every year, thousands more children are apparently infected, but do not get the active disease, adding to the pool of those at risk of developing active TB in the future.
Since 1984 the incidence of TB has been on the rise, especially in the elderly. The elderly are susceptible to TB in two different ways: dormant germs from old infections becoming active again and new exposure at a time of life when immune defense is lower than in youth. In 1991, 25,709 cases were reported, a 9.4 percent increase over the number of cases diagnosed in 1989. Cases in children are also increasing.
Other persons with suppressed immune systems, such as AIDS patients and persons taking drugs to suppress the body’s immune response to transplants, are also at increased risk from exposure to TB.
The continued testing of dairy herds as preventive therapy remains essential to the control of tuberculosis. Since some individuals with tuberculosis do not develop respiratory symptoms (latent tuberculosis), they often go undiagnosed and can potentially spread the disease. A tuberculin skin test, required for school age children in the United States, is also extremely useful in identifying unsuspected cases of TB. Researchers have developed blood tests that can identify latent cases of tuberculosis. These blood tests can be used alone or in combination with the tuberculin skin test.
Vaccination with BCG (a weakened strain of Mycobacterium tuberculosis) is useful in many parts of the world where the incidence of TB is high. However, this vaccine is used rarely in the United States. Antibiotic therapy with careful monitoring by a physician is necessary for cases of active tuberculosis. Hospitalizing or isolating a patient under treatment, as was done in the past, is usually no longer necessary to prevent the spread of TB. Hospitalization may be useful now in some cases for treating disabling symptoms or complications. Ten to fourteen days of antibiotic treatment is usually necessary before patients become noninfectious.
Four drugs commonly used to treat tuberculosis are isoniazid, streptomycin, rifampin, and/or ethambutol. These drugs are used separately or in various combinations. Recently, researchers have identified drug-resistant strains of tuberculosis in various countries around the world.
Surgical treatment of some skin manifestations of TB may be of limited usefulness. Corticosteroid therapy (in conjunction with antibiotics) may be advantageous in some recurrent or very persistent cases, or in some cases that overlap with other diseases.
The Food and Drug Administration (FDA) has given marketing approval for the use of the orphan drug Aminosalicylic Acid (Paser Granules) for the treatment of tuberculosis infections. The drug is produced by:
Jacobus Pharmaceutical Company
37 Cleveland Lane
Princeton, NJ 08540
The drug rifapentine has been approved by the FDA for the treatment of pulmonary tuberculosis. Rifapentine is manufactured by Marion Merrell Dow, Inc.
Researchers are studying the effectiveness of several drugs known as fluoroquinolones (e.g., levoflaxin, gatifloxacin, moxifloxacin) for the treatment of individuals with pulmonary tuberculosis. More research is necessary to determine the long-term safety and effectiveness of these potential treatments for pulmonary tuberculosis.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
For information about clinical trials sponsored by private sources, contact:
As of August 2006, there were 84 clinical trials listed at www.clinicaltrials.gov. As of the same date, the US Food & Drug Administration had designated seven (7) pharmaceuticals as “orphan drugs” approved for the treatment of tuberculosis.
Most recently, in January of 2005, the FDA approved a drug developed by Tibotec, Inc. The address for this company is:
1020 Stony Hill Road
Yardley, PA 19067
An “orphan drug”, approved much earlier (September, 1985) is Rifater, which conists of combined Rifampin, Isoniazid, and Pyrazinamide. Rifater is made by:
Hoechst Marion Roussel
P. O. Box 9627
Mail Station: H3-M2516
Kansas City, MO 64134-0627
In 2004, a “biological” designed to treat active tuberculosis and prepared with heat-killed Mycobacterium to which an immunomodulator is added, was designated as an orphan drug. This product is made by:
16020 Swingley Ridge
Chesterfield, MO 63017
For further details consult the FDA web site at: http://www.fda.gov/orphan/designat/alldes.
Hecht A. Curable, preventable, but still a killer: tuberculosis. FDA Consumer. Dec. 1986-Jan. 1987:7-10.
Johnson JL, Hadad DJ, Boom WH, et al., Early and extended bactericidal activity of levofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis. Int J Tuberc Lung Dis. 2006;10:605-12.
Pablos-Mendez A, Raviglione MC, Laszlo C, et al., Global surveillance for antituberculosis-drug resistance 1994-1997. N Engl J Med. 1998;338:1641-9.
Snider DE, Castro KG. The global threat of drug-resistant tuberculosis. N Engl J Med. 1998;338:1689-90.
Laszlo A, Rahman M, Raviglione M, Bustreo F. Quality assurance programme for drug susceptibility testing of mycobacterium tuberculosis in the WHO/IUATLD supranational laboratory network: first round of proficiency testing. Int J Tuberc Lung Dis. 1997;1:231-8.
Moore M, Onorato IM, McCray E, Castro KG. Trends in drug-resistant tuberculosis in the United States, 1993-1996. JAMA. 1997;278:833-7.
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