11

Florida Heart CPR*
Tuberculosis
2 hours
Objectives
By the end of the course, students will be able to:
A. Define TB and understand the current status of the disease in the American population
B. Demonstrate knowledge about how TB is transmitted and prevented
C. Understand how to treat and diagnosis TB

Tuberculosis (TB), a chronic bacterial infection, causes more deaths

worldwide than any other infectious disease. TB is spread through the air

and usually infects the lungs, although other organs are sometimes involved.

Some 1.7 billion people - one-third of the world's population - are infected

with the predominant TB organism, Mycobacterium tuberculosis.

Most people infected with M. tuberculosis never develop active TB.

However, in people with weakened immune systems, especially those

infected with the human immunodeficiency virus (HIV, the cause of AIDS),

TB organisms may overcome the body's defenses, multiply, and cause

active disease. Each year, 8 million people worldwide develop active TB and 3 million die.

TB on the Rise in the United States.

In the United States, TB has re-emerged as a serious public health problem. In 1993, a total of 25,287 active TB cases, in all 50 states and the District of Columbia, were reported to the Centers for Disease Control and Prevention (CDC), an increase

of 14 percent since 1985. Thanks largely to improved public health control measures, this number decreased to 22,860 in 1995. In addition to those with active TB, however, an estimated 15 million people in the United States have latent TB infections and may develop active TB at some time in their lives. Minorities are affected disproportionately by TB: 54 percent of active TB cases in 1995 were among African-American and Hispanic people, with an additional 17.5 percent found in

Asians. In some sectors of U.S. society, TB rates now surpass those in the world's poorest countries. Among African-American men in New York City aged 35 to 44, for example, 315 out of 100,000 had active TB in 1993, many times the national

average of 9.8 cases per 100,000 people.

Drug Resistance a Concern

With appropriate antibiotic therapy, TB usually can be cured. In recent years, however, drug-resistant cases of TB have increased dramatically. Drug resistance results when patients fail to take their medicine consistently for the six to 12 months necessary to destroy all vestiges of M. tuberculosis. In some U.S. cities, more than 50

percent of patients - often homeless people, drug addicts, and others caught in poverty - fail to complete their prescribed course of TB therapy. One reason for this lack of compliance is that TB patients may feel better after only two to four weeks of

treatment and stop taking their TB drugs, some of which have unpleasant side effects.

Resistance also may develop when patients are treated with too few drugs or with inadequate doses. Particularly alarming is the increase in the number of people

with multi-drug-resistant TB (MDR-TB), caused by M. tuberculosis strains resistant to two or more drugs. Even with treatment, the death rate for MDR-TB patients is 40 to 60 percent, the same as for TB patients who receive no treatment.

For people co infected with HIV and MDR-TB, the death rate may be as high as 80 percent. The time from diagnosis to death for some patients with MDR-TB and HIV may be only months as they are sometimes left with no treatment options.

Of all culture-positive TB cases in New York State in 1995, at least 13 percent were resistant to one or more antibiotic drugs. This figure is similar to that seen in an earlier national survey. At least 39 states reported drug-resistant cases of TB in 1995. In

addition, CDC received numerous reports of outbreaks of MDR-TB in hospitals and prisons. During these outbreaks, MDR-TB has sometimes spread to hospital patients, health care workers, prisoners, and prison guards.

What Caused TB's Resurgence?

During the 19th century, TB claimed more lives in the United States than any other disease. Improvements in nutrition, housing, sanitation, and medical care in the first half of the 20th century dramatically reduced the number of cases and deaths.

TB's decline hastened in the 1940s and 1950s with the introduction of the first effective antibiotic therapies for TB. By 1985, the number of cases had fallen to 22,201 in the United States, the lowest figure recorded in modern U.S. history.

In 1985, however, the decline ended and the number of active TB cases in the United States began to rise again. Several forces, often interrelated, were behind TB's resurgence: The HIV/AIDS epidemic. People with HIV are particularly vulnerable to reactivation of latent TB infections, as well as to disease caused by new TB infections. TB transmission occurs most frequently in crowded environments such as hospitals, prisons, and shelters where HIV-infected individuals make up a growing proportion of the population. Increased numbers of immigrants from countries with many cases of TB, many of whom live in crowded housing.

Because of language and economic difficulties, many immigrants have limited access to health care and may not receive treatment. 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.

People in poor health, especially those infected with HIV, also are prone to deactivation of latent TB infections. Poor compliance with treatment regimens, especially among disadvantaged groups. Some of these people may remain contagious while others develop and pass on resistant strains of M. tuberculosis that are difficult to treat. Increased numbers of residents in long-term care facilities such as nursing homes. Immune function declines with age, and as patients live longer, many suffer recurrences of latent infections often acquired in early adulthood. As a result, other elderly people, especially those with weak immune systems, become newly infected with TB.

The TB Organism

TB is caused by repeated exposure to airborne droplets contaminated with M. tuberculosis, a rod-shaped bacterium. The TB bacterium also is known as the tubercle bacillus. (A small fraction of cases are caused by related bacteria, M. africanum and M. bovis.) M. tuberculosis, like other mycobacteria, has an unusual cell wall, a waxy coat comprised of fatty molecules whose structure and function are not well known. This cell wall appears to allow M. tuberculosis to survive in its preferred environment: inside immune cells called macrophages, which ordinarily degrade pathogens with enzymes. The coat of M. tuberculosis also renders it impermeable to many common drugs. Biologists call M. tuberculosis and other mycobacteria "acid fast" bacteria because their fatty cell walls prevent the cells from being decolorized by acid solutions after staining during diagnostic tests. Several factors make M. tuberculosis a difficult organism to study in the laboratory, hampering TB research. The bacteria

multiply very slowly, only once every 24 hours, and take a month to form a colony. By comparison, other bacteria such as E. coli form colonies within eight hours. TB bacilli tend to form clumps, which makes working with them and counting them difficult. Most daunting, M. tuberculosis, a dangerous, airborne organism, can

be studied only in laboratories that have specialized safety equipment.

Transmission

TB is primarily an airborne disease. The disease is not likely to

be transmitted through personal items belonging to those with

TB, such as clothing, bedding, or other items they have touched.

Adequate ventilation is the most important measure to prevent the transmission of TB.

Because most infected people expel relatively few bacilli,

transmission of TB usually occurs only after prolonged exposure

to someone with active TB. On average, people have a 50

percent chance of becoming infected with TB if they spend eight

hours a day for six months or 24 hours a day for two months

working or living with someone with active TB, researchers have estimated.

People are most likely to be contagious when their sputum

contains bacilli, when they cough frequently and when the extent

of their lung disease, as revealed by a chest x-ray, is great. TB

is spread from person to person in microscopic droplets -

droplet nuclei - expelled from the lungs when a TB sufferer

coughs, sneezes, speaks, sings, or laughs. Only people with

active disease are contagious.

Droplet nuclei are tiny and may remain in the air for prolonged

periods, ready to be inhaled. They are small enough to bypass

the natural defenses of upper respiratory passages, such as

hairs in the nose or the hair like cilia in the bronchial tubes.

Infection begins when the bacilli reach the tiny air sacs of the

lungs known as alveoli, where they multiply within macrophages.

People who have been treated with appropriate drugs for at

least two weeks usually are not infectious.

Infection

The site of initial infection is usually the alveoli - the balloon like

sacs at the ends of the small air passages in the lungs known as

bronchioles. In the alveoli, white blood cells called macrophages

ingest the inhaled M. tuberculosis bacilli.

Some of the bacilli may be killed immediately; others may

multiply within the macrophages. Infrequently, but especially in

HIV-infected people and in children, the bacilli spread to other

sites in the body. This dissemination sometimes results in

life-threatening meningitis and other problems.

During the two to eight weeks after initial infection in people with

intact immune systems, macrophages present pieces of the

bacilli, displayed on their cell surfaces, to another type of white

blood cell - the T cell. When stimulated, T cells release an

elaborate array of chemical signals. Once this response, called

cell-mediated hypersensitivity, is established, a person's T cells

usually will respond to the tuberculin skin test (PPD test) and

produce a characteristic red welt.

Some of the T-cell signals produce inflammatory reactions;

other signals recruit and activate specialized cells to kill bacilli

and wall-off infected macrophages in tiny, hard grayish capsules known as tubercles.

From then on the body's immune system maintains a standoff

with the infection, sometimes for years. In the tubercles, TB

bacilli may persist within macrophages, but further multiplication

and spread of M. tuberculosis are confined. Most people

undergo complete healing of their initial infection, and the

tubercles calcify and lose their viability. A positive TB skin test,

and in some cases 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 factors, the bacilli

may break out of the tubercles in the alveoli and lead to active disease.

Active Disease

On the average, people infected with M. tuberculosis have a 10

percent chance of developing 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 sometimes does not

occur until many years later.

Active TB usually results from the spread of bacilli from the

alveoli through the bloodstream or lymphatic system to other

sites, usually elsewhere in the lungs or local lymph nodes. In 15

percent of cases, the bacilli cause disease in other regions,

such as the skin, kidneys, bones, or reproductive and urinary systems.

At the new sites, the body's immune defenses kill many bacilli,

but immune cells and local tissue die as well. The dead cells

and tissue form granulomas with the consistency of soft cheese,

where the bacilli survive but do not flourish. The early symptoms

of active TB can include weight loss, fever, night sweats, and

loss of appetite, or they may be vague and go unnoticed by the affected individual.

As more lung tissue is destroyed and the granulomas expand,

cavities in the lungs develop, and sometimes break into larger

airways called bronchi. This allows large numbers of bacilli to

spread when patients cough. As the disease progresses, the

granulomas may liquefy, perhaps as a result of enzymes

secreted by the body's own immune cells. This creates a rich

medium in which the bacilli multiply rapidly and spread, creating

further lesions and the characteristic chest pain, cough, and,

when a blood vessel is eroded, bloody sputum.

Most patients do not suffer shortness of breath until the lungs are

extensively damaged by the formation of cavities. Symptoms of

TB involving areas other than the lungs vary, depending upon the organ affected.

Diagnosing TB

The tuberculin skin test, also known as the Mantoux test, can

identify most people infected with tubercle bacilli six to eight

weeks after initial exposure. A substance called purified protein

derivative (PPD) is injected under the skin of the forearm and

examined about 48 to 72 hours later. If a red welt forms around

the injection site, the person may have been infected with M.

tuberculosis, but doesn't necessarily have active disease. Most

people with previous exposure to TB will test positive on the

tuberculin test, as will some people exposed to related

mycobacteria. An important exception is people with severely

weakened immune systems, such as those with HIV.

If a person has a significant reaction to the tuberculin skin test,

additional methods can determine if the individual has active

TB. This is sometimes difficult because TB can mimic other

diseases, such as pneumonia, lung abscesses, tumors, and

fungal infections, or occur along with them. In making a

diagnosis, doctors rely on symptoms and other physical signs, a

person's history of exposure to TB, and x-rays that may show

evidence of TB infection, usually in the form of cavities or lesions in the lungs.

The physician also will take sputum and other samples, because

a positive bacteriologic culture of M. tuberculosis is essential to

confirm the diagnosis and determine which drugs will work

against the strain of TB the patient carries. Because M.

tuberculosis grows very slowly, the laboratory diagnosis

requires approximately four weeks. An additional two to three

weeks usually are needed to determine the drug susceptibility of

the organism, making treatment decisions difficult.

Advances in Diagnosis

Recently, researchers supported by the National Institute of