Tuberculosis in the US

In developed countries, such as the United States, many people think tuberculosis (TB) is a disease of the past. TB, however, is still a leading killer of young adults worldwide. Some 2 billion people-one-third of the world's population-are thought to be infected with TB bacteria, Mycobacterium tuberculosis.

TB is a chronic bacterial infection. It is spread through the air and usually infects the lungs, although other organs and parts of the body can be involved as well. Most people who are infected with M. tuberculosis harbor the bacterium without symptoms (have latent TB), but some will develop active TB disease. According to World Health Organization (WHO) estimates, each year, 8 million people worldwide develop active TB and nearly 2 million die.

One in 10 people who are infected with M. tuberculosis may develop active TB at some time in their lives. The risk of developing active disease is greatest in the first year after infection, but active disease often does not occur until many years later.

TB in the United States

In 2004, the Centers for Disease Control and Prevention (CDC) reported 14,511 cases of active TB. While the overall rate of new TB cases continues to decline in the United States since national reporting began in 1953, the decrease in TB cases in 2003 (2.3 percent) and 2004 (3.3 percent) were the smallest since 1993, according to CDC. In addition to those with active TB, an estimated 10 to 15 million people in the United States have latent TB.

Minorities are affected disproportionately by TB, which occurs among foreign-born individuals nearly nine times as frequently as among people born in the United States. This is partially because they were often exposed to M. tuberculosis in their country of origin before moving to the United States. In 2004, a very high percentage of Asians (95 percent) and Hispanics (75 percent) who were born outside the United States were reported to have TB.

What caused TB cases to increase the United States?

Cases of TB dropped rapidly in the 1940s and 1950s when the first effective antibiotic treatments for TB were introduced. In 1985, however, the decline ended and the number of active TB cases in the United States began to rise again. Several factors, often interrelated, were behind TB's resurgence.

The HIV/AIDS epidemic- People with HIV are particularly vulnerable to moving from infection with M. tuberculosis to active TB and are also more likely to develop active TB when they are first infected with TB bacteria.

People from many nationalities live in the United States- Increased numbers of foreign-born nationals come from places where many cases of TB occur, such as Africa, Asia, and Latin America. TB cases among foreign-born nationals now living in the United States account for more than half of the U.S. total.

Increased poverty, injection drug use, and homelessness-TB transmission is rampant in crowded shelters and prisons where people weakened by poor nutrition, drug addiction, and alcoholism are exposed to M. tuberculosis.

Failure of patients to take all prescribed antibiotics against TB-TB patients who do not complete TB drug treatment can stay infectious for longer periods of time and therefore can spread TB to more people. In addition, treatment failures may result in M. tuberculosis strains that are resistant to one or more of the standard medicines given to TB patients, making the disease much more difficult to treat.

Increased numbers of residents in long-term care facilities such as nursing homes-Many elderly people whose general health has declined develop active TB from TB infection they had much earlier in life. Other elderly people, especially those with weak immune systems, become newly infected with M. tuberculosis and can develop active TB rapidly.

TRANSMISSION

TB is primarily an airborne disease. The bacteria are spread from person to person in tiny microscopic droplets when a TB sufferer coughs, sneezes, speaks, sings, or laughs. Only people with active TB can spread the disease to others. People with TB who have been treated with the correct drugs for at least 2 weeks, however, are no longer contagious and do not spread the bacteria to others.

DIAGNOSIS

To identify those who may have been exposed to M. tuberculosis, health care providers typically inject a substance called tuberculin under the skin of the forearm. If a red welt forms around the injection site within 72 hours, the person may have been infected. This doesn't necessarily mean he or she has active disease. People who may test positive on the tuberculin test include

Most people with previous exposure to M. tuberculosis

Some people exposed to bacteria related to M. tuberculosis

Some people born outside the United States who were vaccinated with the TB vaccine (see TB vaccine below) used in other countries

If people have an obvious reaction to the skin test, other tests can help to show if they have active TB. In making a diagnosis, doctors rely on symptoms and other physical signs, the person's history of exposure to TB, and X-rays that may show evidence of M. tuberculosis infection.

The health care provider also will take sputum and other samples to see if the TB bacteria will grow in the lab. If bacteria are growing, this positive culture confirms the diagnosis of TB. Because M. tuberculosis grows very slowly, it can take 4 weeks to confirm the diagnosis. An additional 2 to 3 weeks usually are needed to determine which antibiotics to use to treat the disease.

What happens when someone gets infected with M. tuberculosis?

Between 2 to 8 weeks after being infected with M. tuberculosis, a person's immune system responds to the TB germ by walling off infected cells. From then on the body maintains a standoff with the infection, sometimes for years. Most people undergo complete healing of their initial infection, and the bacteria eventually die off. A positive TB skin test, and old scars on a chest X-ray, may provide the only evidence of the infection.

If, however, the body's resistance is low because of aging, infections such as HIV, malnutrition, or other reasons, the bacteria may break out of hiding and cause active TB.

SYMPTOMS

Early symptoms of active TB can include weight loss, fever, night sweats, and loss of appetite. Symptoms may be vague, however, and go unnoticed by the affected person. For some, the disease either goes into remission (halts) or becomes chronic and more debilitating with cough, chest pain, and bloody sputum.

Symptoms of TB involving areas other than the lungs vary, depending upon the organ or area affected.

TREATMENT

With appropriate antibiotic treatment, TB can be cured in most people.

Successful treatment of TB depends on close cooperation between patient and health care provider. Treatment usually combines several different antibiotic drugs that are given for at least 6 months, sometimes for as long as 12 months.

Some people with TB do not get better with treatment because their disease is caused by a TB strain that is resistant to one or more of the standard TB drugs. If that happens, their health care providers will prescribe different drugs and increase the length of treatment.

The importance of finishing the TB medicine

People who do not take all the required medications can become sick again and spread TB to others. Additionally, when people do not take all the prescribed medicines or skip times when they are supposed to take them, the TB bacteria evolve to outwit the TB antibiotics. Soon those medicines no longer work against the disease. If this happens, the person now has drug-resistant TB.

Some people have disease that is resistant to two or more drugs. This is called multidrug-resistant TB or MDR-TB. This form of TB is much more difficult to cure.

Treatment for MDR-TB

Treatment for MDR-TB often requires the use of special TB drugs, all of which can produce serious side effects. People with MDR-TB may have to take several antibiotics, at least three to which the bacteria still respond, every day for up to 2 years. Even with this treatment, however, between four and six out of 10 patients with MDR-TB will die, which is the same rate seen with TB patients who are not treated.

PREVENTION

TB is largely a preventable disease, and adequate ventilation is the most important measure to prevent its transmission in the community.

In the United States, health care providers try to identify people infected with M. tuberculosis as early as possible, before they have developed active TB. They will give infected people a medicine called isoniazid (INH) to prevent active disease. This medicine is given every day for 6 to 12 months. INH can cause hepatitis (inflammation of the liver) in a small percentage of people, especially those older than 35 years.

Hospitals and clinics take precautions to prevent the spread of TB, which include using ultraviolet light to sterilize the air, special filters, and special respirators and masks. In hospitals, people with TB are isolated in special rooms with controlled ventilation and airflow until they can no longer spread TB bacteria.

TB vaccine

In those parts of the world where the disease is common, WHO recommends that infants receive a vaccine called BCG (Bacille Calmette Guerin) made from a live weakened bacterium related to M. tuberculosis. BCG vaccine prevents M. tuberculosis from spreading within the body, thus preventing TB from developing.

BCG has its drawbacks, however. It does not protect adults very well against TB. In addition, BCG may interfere with the TB skin test, showing a positive skin test reaction in people who have received the vaccine. In countries where BCG vaccine is used, the ability of the skin test to identify people infected with M. tuberculosis is limited. Because of these limitations, U.S. health experts do not recommend BCG for general use in this country.

TB AND HIV INFECTION

WHO estimates 11.4 million people worldwide are infected with both M. tuberculosis and HIV (human immunodeficiency virus, which causes AIDS [acquired immunodeficiency disease]). The primary cause of death in those infected with body microbes is from TB, not AIDS. In the United States, health experts estimate about two out of ten people who have TB are also infected with HIV.

One of the first signs that a person is infected with HIV may be that he or she suddenly develops TB. This form of TB often occurs in areas outside the lungs, particularly when the person is in the later stages of AIDS.

It is much more likely for people infected with M. tuberculosis and HIV to develop active TB than it is for someone that is only infected with M. tuberculosis. Fortunately, TB disease can be prevented and cured, even in people with HIV infection.

People infected with both MDR-TB and HIV appear to have a more rapid and deadly disease course than do those with MDR-TB only. If no medicines are available, as many as eight out of ten people with both infections may die, often within months of diagnosis.

Diagnosing TB in people with HIV infection is often difficult. They frequently have disease symptoms similar to those of TB and may not react to the standard TB skin test because their immune system does not work properly. X-rays, sputum tests, and physical exams may also fail to show evidence of M. tuberculosis infection with in people infected with HIV.

RESEARCH

The National Institute of Allergy and Infectious Diseases (NIAID) leads TB research at the National Institutes of Health. NIAID supports not only studies to better understand how M. tuberculosis infects and causes disease in humans but also how the human immune system responds to it. This research will help to develop new tools to diagnose TB and to find better vaccines and new medicines against TB. Below are some important advances that have been made in TB research.

Diagnostics

Potential new tests may speed the diagnosis of TB from 4 weeks to 2 days

Differences found in the DNA of M. tuberculosis and the bacterium used in the BCG vaccine may lead to a test to tell the difference between people who really have TB and those who are merely reacting to previous BCG vaccination

Characterization of antibodies and other components of the immune response may potentially identify people who are infected with M. tuberculosis and are at the highest risk of developing active disease

Treatment

Development of promising new drug candidates, some of which are currently being tested in human clinical trials

Evaluation of shorter treatment regimens to make it easier for people to complete drug therapy

Inclusion of antibiotics that are already available for treatment of other infections and have been shown to act on M. tuberculosis may make therapy more potent and easier to tolerate

Vaccines

Three new vaccine candidates are now in clinical trials and several more are being analyzed in animal studies.

Training

NIAID offers an intensive 3-year Infectious Diseases Training Program for physicians to produce investigators in clinical, basic, or translational research. These programs offer exposure to and insight into the science and management of mycobacterial diseases. They will increase the cadre of investigators with medical training to help identify and answer complex questions in the area of host/pathogen interactions in TB and other mycobacterial diseases.

Recognizing that disease knows no borders, NIAID has developed a global TB research agenda. A concerted global effort will require collaborations with sister agencies and other organizations with similar goals such as the Global Alliance for TB Drug Development and the STOP TB initiative, as well as partnerships with governments and scientists from countries where the burden of tuberculosis is greatest.

Source
NIAID