Tuberculosis

Definition

Tuberculosis (TB) is a chronic, contagious infectious disease that most often affects the lungs but can also affect other parts of the body. It is caused most often by the tubercle bacillus (Mycobacterium tuberculosis) but may also be caused by various other strains of mycobacteria. Tuberculosis is curable and preventable. However, it is potentially fatal and ranks beside HIV as the leading cause of death worldwide. Tuberculosis was commonly called consumption until well into the twentieth century.

History

Tuberculosis caused widespread public health problems in the nineteenth and early twentieth centuries. In 1815, TB was responsible for one in four deaths in England (considered the peak of fatalities in Europe at that time), and it caused one in six deaths in France in 1918. In 1882, the German microbiologist and physician Heinrich Hermann Robert Koch (1843–1910) isolated the tubercle bacillus (species name Mycobacterium tuberculosis) that causes the disease. The tubercle bacillus is transmitted when an infected person coughs or sneezes and another person inhales the infected droplets. The disease is not spread through kissing or other physical contact. Tuberculosis spread widely in Europe as the result of the Industrial Revolution in the late nineteenth century when many people moved to towns and into crowded, unsanitary conditions. The disease became widespread somewhat later in the United States.

Before antibiotics were introduced in the mid1900s, the only means of controlling the spread of TB was to isolate patients in sanatoriums or hospitals limited to patients with TB. This practice continues in some countries. This pattern of treatment was adopted not only to prevent the disease from spreading but to separate the study of tuberculosis from mainstream medicine. Entire organizations were formed to study not only the disease as it affected individual patients, but also its impact on society. At the beginning of the twentieth century, more than 80% of the population in the United States was infected with TB before age 20, and tuberculosis was the single most common cause of death. By 1938, more than 700 specialized TB facilities existed in the United States.




Estimated TB incidence rates, 2016





Estimated TB incidence rates, 2016
SOURCE: World Health Organization

The boundaries and names shown on the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotten and dashed lines on maps represent approximate border lines for which there may not yet be full agreement.

The number of reported TB cases in the United States peaked in 1993 and has since declined. New multidrug-resistant strains of TB (MDR-TB) have become a major public health concern in the United States and virtually all countries regularly surveyed by the World Health Organization (WHO). In the early 2000s, health officials worldwide joined in an effort to prevent drug-resistant forms of the disease from becoming widespread.

Between 2002 and 2008, the CDC reported that 27 outbreaks of TB involving 398 patients occurred in the United States. Twenty-four of the 27 outbreaks involved U.S.-born individuals. In 2016, there were 9,272 TB cases in the United States. The WHO reported in 2007 that 13.7 million chronic, active cases of TB were present around the world.

Approximately 10.4 million new cases were reported in 2016, and 1.7 million deaths were associated with TB, mostly within developing countries. Over 95% of TB deaths occur in low-and middle-income countries, believed due primarily to higher rates of HIV infection and the corresponding development of AIDS. About 40% of the world's reported cases of TB are in India and China, and about 24% of cases are in Africa. TB is the leading cause of death for people living with HIV, causing nearly one out of four deaths. However, the WHO reports that case numbers among HIV patients are decreasing slowly each year.

Description

Tuberculosis is a deadly infectious disease with high rates of morbidity and mortality comparable only to HIV/AIDS. The disease primarily affects the lungs although other areas of the body may be affected as well, including the kidneys, spine, bones or brain.

The Mycobacterium tuberculosis) or tubercle bacillus that causes TB is spread from one individual to another when tiny droplets sprayed into the air by coughs and sneezes of an infected person are inhaled by someone nearby. Although TB incidence had decreased in the middle of the twentieth century, the increase in TB infection that occurred in conjunction with the AIDS epidemic in the 1980s resulted in many strains of causal organisms developing resistance to the antibiotics used to treat the disease. Improved control programs were credited with decreasing incidence again in the 1990s, but then resistance of the TB-causing organisms to treatment created a new challenge. Researchers expanded their efforts to design medication regimens that would eradicate the TB infection and also prevent development of antibiotic resistance, called multi-drug-resistance tuberculosis (MDR-TB). MDR-TB is TB caused by bacteria that resist treatment with two of the powerful anti-TB medications used in modern treatment regimens, isoniazid and rifampin.

FLORENCE B. SEIBERT (1897–1991)

American biochemist Florence Barbara Seibert was born on October 6, 1897, in Easton, Pennsylvania, the second of three children. She was the daughter of George Peter Seibert, a rug manufacturer and merchant, and Barbara (Memmert) Seibert. At the age of three years Florence contracted polio. Despite her resultant handicaps, she completed high school, with the help of her highly supportive parents, and entered Goucher College in Baltimore, where she studied chemistry and zoology. She graduated in 1918 and then worked under the direction of one of her chemistry teachers, Jessie E. Minor, at the Chemistry Laboratory of the Hammersley Paper Mill in Garfield, New Jersey. She and her professor, having responded to the call for women to fill positions vacated by men fighting in World War I (1914–1918), coauthored scientific papers on the chemistry of cellulose and wood pulps.

A biochemist who received her doctoral degree (PhD) from Yale University in 1923, Seibert is best known for her research in the biochemistry of tuberculosis. She developed the protein substance used for the tuberculosis skin test. The substance was adopted as the standard in 1941 by the United States and a year later by the World Health Organization. In addition, in the early 1920s, Seibert discovered that bacteria in the distilled water used to make the protein solutions caused the sudden fevers that sometimes occurred during intravenous injections. She invented a distillation apparatus that prevented contamination. This research had great practical significance later when intravenous blood transfusions became widely used in surgery. Seibert authored or coauthored more than 100 scientific papers. Her later research involved the study of bacteria associated with certain cancers. Her many honors include five honorary degrees, the Garvan Gold Medal of the American Chemical Society (1942), the John Elliot Memorial Award of the American Association of Blood Banks (1962), and induction into the National Women's Hall of Fame in Seneca Falls, New York (1990). She died on August 23, 1991.

To fight TB effectively, doctors also must distinguish between latent TB and active TB. In latent TB, the individual is positive for the tubercle bacillus, which is harbored in the body in an inactive state without causing symptoms. Treatment of latent TB is still important so that the disease does not become active and the spread of TB can be controlled. In active TB, symptoms appear and the disease can spread to others; the disease can become active during the first few weeks of infection or years later.

Risk factors

Individuals at heightened risk of contracting TB include adults aged 65 years and older, immunocompromised individuals, people with chronic disease, people with substance abuse issues who use injectable drugs, and members of certain ethnic minorities (African Americans, Hispanics, Native Americans, Asians, and Pacific Islanders). Smokers are at higher than average risk; over 20% of TB cases worldwide are attributable to using tobacco products. Health workers who are exposed to people with a high risk of TB are themselves at higher risk.

People already infected with the tuberculin bacillus have a 10% lifetime risk of becoming ill with active TB. Persons with compromised immune systems, such as people living with HIV, those with malnutrition or diabetes, and transplant patients who are taking immunosuppressive drugs to prevent organ rejection or individuals who take immunosuppressive drugs for autoimmune diseases. The WHO reports that people infected with HIV and the tuberculin bacillus are 21 to 34 times more likely to become sick with active TB than people without those infections.

RACIAL AND ETHNIC GROUPS. Higher rates of TB are found in the non-white population in the United States, but research has shown that this is related to the socioeconomic status of these groups rather than to race-related biological factors. Individuals of lower socioeconomic status tend to live in more crowded conditions that encourage infection with M. tuberculosis and have less access to healthcare than those with higher income. The most common countries of origin for foreign-born persons in the United States with active TB are Mexico, the Philippines, Vietnam, India, and China.

LIFESTYLE FACTORS. The high risk of TB in AIDS patients extends to those infected by HIV who have not yet developed clinical signs of AIDS but whose immune systems are weakened by the virus. People who take drugs to suppress immune system activity (e.g., transplant patients, people with autoimmune diseases) are also at higher risk of becoming infected. People who have silicosis, a lung disease, are at increased risk. Risk is also higher in individuals who abuse alcohol, for intravenous drug abusers, and for the homeless.

Demographics

About 80% of populations in Asia and Africa test positive for TB, whereas fewer than 10% are positive at any given time in the United States. In 2016, 9,272 new cases of TB were reported in the United States, accounting for about 2.9 cases per 100,000 and representing a decrease of nearly 3.6% from 2015, the lowest case count on record as of 2018. Many individuals who are positive for TB belong to immigrant groups that come from countries where TB infection is common. U.S. states with large immigrant populations such as California, New York, Texas, and Florida account for almost half of all active TB cases.

The WHO estimates that almost two billion individuals, about one-fourth of the global population, is infected with M. tuberculosis. In 2016, 10.4 million individuals developed active TB and 1.7 million died of the disease. Among individuals who have HIV/AIDS infections, the rates of TB infection and death are much higher. The greatest number of active TB infections per capita is found in sub-Saharan Africa where AIDS is epidemic. About one-third of infections occur in Southeast Asia. Although the rate per capita of active TB is declining worldwide, the absolute number of cases is increasing in many areas because of high population growth.

Causes and symptoms

The causes and symptoms of tuberculosis vary according to the way TB is transmitted into the body and how it progresses once inside. As TB develops, two common diseases can result: pulmonary tuberculosis and extrapulmonary tuberculosis. In addition, MDR TB has become a major concern in the world. Many other diseases resemble tuberculosis.

Transmission

Tuberculosis spreads by droplet infection. When a person infected with M. tuberculosis exhales, coughs, or sneezes, tiny droplets of fluid containing tubercle bacilli are released into the air. People in close physical contact with the infected person are likely to inhale this fine mist. Tuberculosis is not highly contagious compared to some other infectious diseases. Close, frequent, or prolonged contact is needed to spread the disease. Most people do not develop TB even when exposed to a person with active TB. Unlike many other infections, TB is not passed on by contact with an infected individual's clothing, bed linens, dishes, or cooking utensils. The disease is not spread through kissing or other physical contact. 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.

Progression

Once a person inhales the tubercle bacillus M. tuberculosis, one of four situations can occur:

Pulmonary tuberculosis

Pulmonary TB affects the lungs. Its initial symptoms are easily confused with those of other diseases and must be differentiated so that appropriate treatment can be determined. An infected person may initially feel vaguely unwell or develop a cough that could be 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 that is streaked with blood may be produced. People who have pulmonary TB do not develop a high fever, but low-grade fever is common. Individuals may lose 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), these individuals may have difficulty breathing. In young adults who develop pleural effusion, tubercular infection is highly likely to be the cause.

Before effective TB drugs were developed, many patients became chronically ill with increasingly severe lung symptoms. They could lose a great deal of weight and develop a wasted appearance, hence the name consumption. This outcome is uncommon in countries and areas where modern treatment methods are available.

Extrapulmonary tuberculosis

Although the lungs are the major site of damage caused by tuberculosis, other organs and tissues may be affected. The most typical progression is for the disease to spread from the lungs to locations outside the lungs (extrapulmonary sites). Occasionally, the first sign of disease may appear outside the lungs. The tissues or organs that TB may affect include:

Multi drug-resistant tuberculosis (MDR TB) Diseases similar to tuberculosis

Many forms of mycobacteria exist other than M. tuberculosis, the tubercle bacillus. Some cause infections that may closely resemble tuberculosis, but this happens primarily among individuals with a compromised immune system such as in HIV-positive individuals. The most common mycobacteria that infect patients with HIV/AIDS are 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 will appear in the sputum, and the patient will have trouble breathing. In HIV/AIDS patients, MAC disease can spread throughout the body, accompanied by anemia, diarrhea, and stomach pain. Mortality is high in such patients unless their immune systems function can be restored. Other mycobacteria grow in swimming pools and may cause skin infection. Some infect wounds and implanted synthetic body parts such as breast implants or mechanical heart valves.

Diagnosis

The standard screening test to detect the presence of the TB bacterium is the tuberculin skin test. The test does not differentiate between latent and active TB. Tuberculin is an extract prepared from cultures of M. tuberculosis. It contains proteins (antigens) belonging to the bacillus to which an infected person has been sensitized. When tuberculin is injected under the skin of an infected person, the area around the injection becomes hard, swollen, and red within one to three days.

Skin tests use a substance called purified protein derivative (PPD) that has a standard chemical composition that is a reliable measure of the presence of tubercular infection. However, the PPD test, also called the Mantoux test, is not 100% accurate; it can produce false positive and false negative results. In other words, not all individuals who have a skin reaction are infected (false positive), and some who do not react are in fact infected (false negative). Repeat testing is usually performed. The PPD test is still a highly useful screening test and is required in most states for children wanting to enter school. In addition, anyone who has suspicious findings on a chest x ray or any condition that makes TB more likely is advised to have a PPD test. People who are in close contact with a TB patient, those who come from a country where TB is common, all healthcare personnel, and persons living or working in institutions such as prisons are advised to undergo a PPD test each year.




An Indian patient suffering from tuberculosis, admitted under treatment in Government tuberculosis hospital, two days after World tuberculosis day in Allahabad on March 26,2016.





An Indian patient suffering from tuberculosis, admitted under treatment in Government tuberculosis hospital, two days after World tuberculosis day in Allahabad on March 26,2016. A recent WHO global TB report has ranked India with having the highest number of Tuberculosis (TB) cases in the world.
(Sipa via AP Images)

To confirm PPD test results and make a definitive diagnosis of TB, a chest x ray may be done and a sample of sputum or a tissue sample (biopsy) may be cultured. Three to five sputum samples are taken early in the morning and planted in culture media. The use of culture to identify M. tuberculosis is especially helpful for diagnosis by laboratory methods because the tubercle bacillus, unlike many other types of bacteria, are acid-fast, retaining certain stains even when exposed to acid.

Body fluids other than sputum also can be cultured. If TB has invaded the brain or spinal cord, spinal fluid culture may help to confirm the diagnosis. If TB of the kidneys is suspected because of pus or blood in the urine, urine culture may reveal a tubercular infection. Infection of the ovaries can be detected by inserting a lighted fiberoptic tube (laparoscope) into the pelvic area through the vaginal opening to obtain tissue for culture. Biopsy may also be done on tissue samples taken from the liver or bone marrow to detect the tubercle bacillus.

Treatment

Treatment for tuberculosis includes supportive care, drug therapy, and sometimes surgery.

Supportive care

Conventional treatment of TB has been historically supportive. Patients were kept in isolation, encouraged to rest, and fed well. If these measures failed, the lung was collapsed surgically so that it could rest and heal. Surgical procedures are still used when necessary, but modern medicine relies on antibiotic drug therapy as first-line treatment and maintenance. Relying on effective combinations of drugs to help avoid antibiotic resistance, TB patients are typically treated at home rather than hospitalized.

Drug therapy

Early and appropriate medication over a sufficient length of time usually provides effective treatment for TB. Three principles govern modern drug treatment of TB:

Drug therapy for TB depends on combination therapy using at least two of five drugs: isoniazid (INH, Laniazid, Nydrazid); rifampin (Rifadin, Rimactane); pyrazinamide (Tebrazid); streptomycin; and ethambutol (Myambutol). The CDC and the American Thoracic Society have developed standard combination regimens for treating TB in an effort to prevent the spread of drug resistant strains. For lung infections in non-immunocompromised people, the disease is usually treated with a regimen of rifampin and isoniazid (INH) for six months, supplemented in the first two months with pyrazinamide and sometimes ethambutol (or streptomycin in young children). Because some strains of the disease are highly drug-resistant, cultures are grown from bacteria in the patient's sputum and tested for sensitivity against a variety of drugs to determine the most effective treatment. Results may suggest that certain alternate medication regimens may be more effective than the current treatment regimen.

Except in cases of MDR-TB, prolonged hospitalization is rarely necessary because most patients are no longer infectious after about two weeks of combination treatment. Follow-up involves monitoring treatment with monthly sputum tests and observing for side effects. Of the five medications, INH is the most frequently used drug for both treatment and prevention. Hospitalization, isolation, and infectious control measures are required for individuals with MDR TB, which is a more serious disease both for the individual and from a public health standpoint. Most states have laws that allow individuals with TB to be hospitalized against their will for noncompliance with treatment.

Surgery

Surgical treatment of TB is an option used only if drugs fail to control the disease. Three different surgical treatments are used for pulmonary TB: pneumothorax, in which air is introduced into the chest to collapse the lung; thoracoplasty, in which one or more ribs are removed; and removal (surgical resection) of a diseased lung, in whole or in part. Resection is usually required in the case of MDR TB. Individuals are able to survive with one healthy lung. Extrapulmonary TB may result in the need for other surgeries.

Public health role and response

Prognosis

Most patients recover from TB if the disease is diagnosed early and given prompt treatment with appropriate medications on a long-term regimen. The relapse rate is less than 4%. The exception is for those with MDR-TB. When TB is multi-drug-resistant, the prognosis depends largely on the ability to surgically remove all infected tissue. The outcome of surgery depends on where and how widespread the infected area is. Miliary TB is still fatal in many cases but is rarely seen in developed countries.

Prevention

The prevention of TB includes general measures, vaccinations, and prophylactic use of isoniazid.

General measures

General measures such as avoiding overcrowded and unsanitary conditions are one aspect of prevention. Hospital emergency rooms and similar locations can be treated with ultraviolet light, which has an antibacterial effect. Regular skin testing is required by some employers and most schools. Children are tested when they enter school and often again when entering college. Screening does not prevent TB but identifies those who are infected and allows early treatment. Such preventive measures are the only way to reduce the likelihood of spreading the disease.

Vaccination

Vaccination is a preventive measure against TB. A vaccine called BCG (Bacillus Calmette-Guérin, named after its French developers) is made from a weakened mycobacterium that infects cattle (bovine vaccine). Vaccination with BCG strengthens the immune system response to M. tuberculosis, to reduce chances of infection if exposed. BCG is used more widely in developing countries than in the United States. The effectiveness of vaccination and of certain vaccines was still being studied as of 2018; it was not clear whether the vaccine's effectiveness depends on the population in which it is used or on variations in its formulation.

MVA85A (modified vaccinia Ankara 85A) was developed by researchers at Oxford University, England, in response to increasing concern about the rise of MDR-TB. This vaccine is intended to work with BCG vaccine to boost its effectiveness and produce a strong immune system response. Clinical trials were ongoing through 2013–2015, evaluating the safety, immunogenicity and effectiveness of MVA85A against M. tuberculosis,. The drug was safe and well tolerated in infants and induced a modest immune response. However, researchers agreed that increased efficacy was needed before the drug could be widely used as TB treatment. As of 2017, the promising drug was still not available. Other vaccines against the TB bacillus were in development as of 2018.

KEY TERMS
Bacillus Calmette-Guérin (BCG)—
A vaccine made from a weakened bovine bacillus similar to the tubercle bacillus in humans. Also called Mantoux-BCG vaccine, BCG vaccination boosts immune system response to the TB bacillus, which helps to prevent TB infection.
Miliary tuberculosis—
A form of TB in which the bacillus spreads throughout the body producing many thousands of tiny tubercular lesions in body tissues. It is often fatal unless treated promptly.
Mycobacteria—
A group of bacteria that includes Mycobacterium tuberculosis, the bacterium that causes tuberculosis and other forms that cause related illnesses.
Pneumothorax—
Air inside the chest cavity that may cause the lung to collapse. It is both a complication of pulmonary tuberculosis and a means of treatment designed to allow an infected lung to rest and heal.
Purified protein derivative (PPD)—
An extract of tubercle bacilli that is injected into the skin to find out whether a person has at present or has ever had tuberculosis.
Sputum—
Secretions produced in the lung and coughed up. A sign of illness, sputum is routinely cultured to identify the tubercle bacillus.
Tuberculoma—
A tumor-like mass in the brain that sometimes develops as a complication of tuberculosis meningitis.
Prophylactic use of isoniazid
QUESTIONS TO ASK YOUR DOCTOR

High-risk groups for whom isoniazid prevention may be justified include:

See also Disease outbreaks ; HIV/AIDS ; Vaccination .

Resources

BOOKS

Grosset, Jaques H., and Richard E. Chaisson, editors. Handbook of Tuberculosis. New York: Adis/Springer, 2017.

Looughheed, Kathryn. Catching Breath: The Making and Unmaking of Tuberculosis. Sydney, Australia: Bloomsbury SigmaScience, 2017.

PERIODICALS

Diel, R., S Niemann, and A. Nienhaus. “Risk of Tuberculosis Transmission Among HealthCare Workers. Heart Failure as an Autonomic Nervous System Dysfunction.” ERJ Open Research 4 (April 2018): doi: 10.1183/23120541.00161-2917..

Lange, C., D. Chesov, J. Heyckendorf, et al. “Drug Resistant Tuberculosis: An Update on Disease Burden, Diagnosis and Treatment.” Respirology (April 2018): doi: 10.1111/resp.133004.

Tameris, M. D., M. Hatherill, B. S. Landry, et al. “Safety and Efficacy of MVA85A, a new Tuberculosis Vaccine, in Infants Previously Vaccinated with BCG: A Randomised Placebo-controlled Phase 2b Trial.” The Lancet 381 (March 2013): 1021–28.

WEBSITES

Centers for Disease Control and Prevention. “Tuberculosis (TB).”) http://www.cdc.gov/tb/default.htm (accessed April 17, 2018).

Mayo Clinic staff. “Tuberculosis: Diagnosis and Treatment.” MayoClinic.org . http://www.mayoclinic.org/diseases-conditions/tuberculosis/diagnosis-treatment/drc-20351256 (accessed April 17, 2018).

World Health Organization Fact Sheets. “Tuberculosis.” http://www.ho.int/tb/publications/factsheets/en/ (accessed April 17, 2018).

ORGANIZATIONS

American Lung Association, 55 West Wacker Dr., Ste. 1150, Chicago, IL, 60601, (800) 586-4872(LUNGUSA), info@lung.org, http://www.lung.org/ .

American Thoracic Society, 25 Broadway, 18th Fl., New York, NY, 10004, (212) 315-8600, Fax: (212) 315-6498, atsinfo@thoracic.org, http://www.thoracic.org .

U.S. Centers for Disease Control and Prevention, 1600 Clifton Rd., Atlanta, GA, 30333, (800) 232-4636, cdcinfo@cdc.gov, http://www.cdc.gov/ .

World Health Organization, Avenue Appia 20, Geneva, Switzerland, 1211 27, 41 22 791-2111, Fax: 41 22 791-3111, http://www.who.int/en/ .

Tish Davidson, AM
Rebecca J. Frey, PhD
Revised by L. Lee Culvert, BB, BS, MBA

  This information is not a tool for self-diagnosis or a substitute for professional care.