Tuberculosis: Causes and symptoms

Tuberculosis spreads by droplet infection. This type of transmission means that when a TB patient exhales, coughs, or sneezes, tiny droplets of fluid containing tubercle bacilli are released into the air. This mist, or aerosol as it is often called, can be taken into the nasal passages and lungs of a susceptible person nearby. Tuberculosis is not, however, highly contagious compared to some other infectious diseases. Only about one in three close contacts of a TB patient, and fewer than 15% of more remote contacts, are likely to become infected. As a rule, close, frequent, or prolonged contact is needed to spread the disease. Of course, if a severely infected patient emits huge numbers of bacilli, the chance of transmitting infection is much greater. Unlike many other infections, TB is not passed on by contact with a patient's clothing, bed linens, or dishes and cooking utensils. The most important exception is pregnancy. The fetus of an infected mother may contract TB by inhaling or swallowing the bacilli in the amniotic fluid.

Once inhaled, tubercle bacilli may reach the small breathing sacs in the lungs (the alveoli), where they are taken up by cells called macrophages. The bacilli multiply within these cells and then spread through the lymph vessels to nearby lymph nodes. Sometimes the bacilli move through blood vessels to distant organs. At this point they may either remain alive but inactive (quiescent), or they may cause active disease. Actual tissue damage is not caused directly by the tubercle bacillus, but by the reaction of the person's tissues to its presence. In a matter of weeks the host develops an immune response to the bacillus. Cells attack the bacilli, permit the initial damage to heal, and prevent future disease permanently.

Infection does not always mean disease; in fact, it usually does not. At least nine of ten patients who harbor M. tuberculosis do not develop symptoms or physical evidence of active disease, and their x-rays remain negative. They are not contagious; however, they do form a pool of infected patients who may get sick at a later date and then pass on TB to others. It is thought that more than 90% of cases of active tuberculosis come from this pool. In the United States this group numbers 10 to 15 million persons. Whether or not a particular infected person will become ill is impossible to predict with certainty. An estimated 5% of infected persons get sick within 12–24 months of being infected. Another 5% heal initially but, after years or decades, develop active tuberculosis either in the lungs or elsewhere in the body. This form of the disease is called reactivation TB, or post-primary disease. On rare occasions a previously infected person gets sick again after a later exposure to the tubercle bacillus.

Pulmonary tuberculosis is TB that affects the lungs. Its initial symptoms are easily confused with those of other diseases. An infected person may at first feel vaguely unwell or develop a cough blamed on smoking or a cold. A small amount of greenish or yellow sputum may be coughed up when the person gets up in the morning. In time, more sputum is produced that is streaked with blood. Persons with pulmonary TB do not run a high fever, but they often have a low-grade one. They may wake up in the night drenched with cold sweat when the fever breaks. The patient often loses interest in food and may lose weight. Chest pain is sometimes present. If the infection allows air to escape from the lungs into the chest cavity (pneumothorax) or if fluid collects in the pleural space (pleural effusion), the patient may have difficulty breathing. If a young adult develops a pleural effusion, the chance of tubercular infection being the cause is very high. The TB bacilli may travel from the lungs to lymph nodes in the sides and back of the neck. Infection in these areas can break through the skin and discharge pus. Before the development of effective antibiotics, many patients became chronically ill with increasingly severe lung symptoms. They lost a great deal of weight and developed a wasted appearance. This outcome is uncommon today—at least where modern treatment methods are available.

Although the lungs are the major site of damage caused by tuberculosis, many other organs and tissues in the body may be affected. The usual progression is for the disease to spread from the lungs to locations outside the lungs (extrapulmonary sites). In some cases, however, the first sign of disease appears outside the lungs. The many tissues or organs that tuberculosis may affect include:

• Bones. TB is particularly likely to attack the spine and the ends of the long bones. Children are especially prone to spinal tuberculosis. If not treated, the spinal segments (vertebrae) may collapse and cause paralysis in one or both legs.
• Kidneys. Along with the bones, the kidneys are probably the commonest site of extrapulmonary TB. There may, however, be few symptoms even though part of a kidney is destroyed. TB may spread to the bladder. In men, it may spread to the prostate gland and nearby structures.
• Female reproductive organs. The ovaries in women may be infected; TB can spread from them to the peritoneum, which is the membrane lining the abdominal cavity.
• Abdominal cavity. Tuberculous peritonitis may cause pain ranging from the vague discomfort of stomach cramps to intense pain that may mimic the symptoms of appendicitis.
• Joints. Tubercular infection of joints causes a form of arthritis that most often affects the hips and knees. The wrist, hand, and elbow joints also may become painful and inflamed.
• Meninges. The meninges are tissues that cover the brain and the spinal cord. Infection of the meninges by the TB bacillus causes tuberculous meningitis, a condition that is most common in young children but is especially dangerous in the elderly. Patients develop headaches, become drowsy, and eventually comatose. Permanent brain damage is the rule unless prompt treatment is given. Some patients with tuberculous meningitis develop a tumor-like brain mass called a tuberculoma that can cause stroke-like symptoms.
• Skin, intestines, adrenal glands, and blood vessels. All these parts of the body can be infected by M. tuberculosis. Infection of the wall of the body's main artery (the aorta), can cause it to rupture with catastrophic results. Tuberculous pericarditis occurs when the membrane surrounding the heart (the pericardium) is infected and fills up with fluid that interferes with the heart's ability to pump blood.
• Miliary tuberculosis. Miliary TB is a life-threatening condition that occurs when large numbers of tubercle bacilli spread throughout the body. Huge numbers of tiny tubercular lesions develop that cause marked weakness and weight loss, severe anemia, and gradual wasting of the body.

There are many forms of mycobacteria other than M. tuberculosis, the tubercle bacillus. Some cause infections that may closely resemble tuberculosis, but they usually do so only when an infected person's immune system is defective. People who are HIV-positive are a prime example. The most common mycobacteria that infect AIDS patients are a group known as Mycobacterium avium complex (MAC). People infected by MAC are not contagious, but they may develop a serious lung infection that is highly resistant to antibiotics. MAC infections typically start with the patient coughing up mucus. The infection progresses slowly, but eventually blood is brought up and the patient has trouble breathing. In AIDS patients, MAC disease can spread throughout the body, with anemia, diarrhea, and stomach pain as common features. Often these patients die unless their immune system can be strengthened. Other mycobacteria grow in swimming pools and may cause skin infection. Some of them infect wounds and artificial body parts such as a breast implant or mechanical heart valve.

The diagnosis of TB is made on the basis of laboratory test results. The standard test for tuberculosis—which is the so-called tuberculin skin test—detects the presence of infection, not of active TB. Tuberculin is an extract prepared from cultures of M. tuberculosis. It contains substances belonging to the bacillus (antigens) to which an infected person has been sensitized. When tuberculin is injected into the skin of an infected person, the area around the injection becomes hard, swollen, and red within one to three days. Today skin tests utilize a substance called purified protein derivative (PPD) that has a standard chemical composition and is therefore is a good measure of the presence of tubercular infection. The PPD test is also called the Mantoux test. The Mantoux PPD skin test is not, however, 100% accurate; it can produce false positive as well as false negative results. What these terms mean is that some people who have a skin reaction are not infected (false positive) and that some who do not react are in fact infected (false negative). The PPD test is, however, useful as a screener. Anyone who has suspicious findings on a chest x ray, or any condition that makes TB more likely should have a PPD test. In addition, those in close contact with a TB patient and persons who come from a country where TB is common also should be tested, as should all healthcare personnel and those living in crowded conditions or institutions.

Because the symptoms of TB cover a wide range of severity and affected body parts, diagnosis on the basis of external symptoms is not always possible. Often, the first indication of TB is an abnormal chest x-ray or other test result rather than physical discomfort. On a chest x ray, evidence of the disease appears as numerous white, irregular areas against a dark background, or as enlarged lymph nodes. The upper parts of the lungs are most often affected. A PPD test is always done to show whether the patient has been infected by the tubercle bacillus. To verify the test results, the physician obtains a sample of sputum or a tissue sample (biopsy) for culture. Three to five sputum samples should be taken early in the morning. If necessary, sputum for culture can be produced by spraying salt solution into the windpipe. Culturing M. tuberculosis is useful for diagnosis because the bacillus has certain distinctive characteristics. Unlike many other types of bacteria, mycobacteria can retain certain dyes even when exposed to acid. This so-called acid-fast property is characteristic of the tubercle bacillus.

Body fluids other than sputum can be used for culture. If TB has invaded the brain or spinal cord, culturing a sample of spinal fluid will make the diagnosis. If TB of the kidneys is suspected because of pus or blood in the urine, culture of the urine may reveal tubercular infection. Infection of the ovaries in women can be detected by placing a tube having a light on its end (a laparoscope) into the area. Samples also may be taken from the liver or bone marrow to detect the tubercle bacillus.

— David A. Cramer, MD