How Tuberculosis Test Is Done: Tuberculosis Complete

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Tuberculosis

DEFINITION

Tuberculosis (TB) is a chronic, potentially fatal, and contagious disease that most often affects the lungs; however, it can also affect other parts of the body. It is caused by a bacterium or tubercle bacillus, Mycobacterium tuberculosis.How Tuberculosis Test Is Done

DESCRIPTION

Overview

Tuberculosis was a common disease known as consumption until the late twentieth century. In 1882, when the microbiologist Robert Koch discovered the tubercle bacillus that causes the disease, TB caused one of every seven mortalities in Europe.

The tubercle bacillus is transmitted when an infected person coughs or sneezes, and another person breathes in the infected droplets.

The disease usually is not spread through kissing or other physical contacts.

Before antibiotics were discovered in the 1940s, the only means of controlling the spread of TB was to isolate patients in sanatoriums or hospitals limited to patients with TB.

The effect of this pattern of procedure was to split the research of tuberculosis from mainstream medical science.

Whole organizations were set up to study the disease as it affected individual patients and its impact on society.

In the first days of the 20th century, over 80 percent of the United States community was affected by TB before age 20, and tuberculosis was the single most common cause of death.

By 1938, there were more than 700 specialized TB facilities in the United States.

Tuberculosis spread widely in Europe due to the Industrial Revolution in the late nineteenth century, when many people moved to towns where they lived in crowded, unsanitary conditions.

The illness became widespread somewhat later in the United States. At the start of the 1940s, with the discovery of streptomycin, the first antibiotic effective against M. tuberculosis, the infection began to be contained for the first time.

Although more effective anti-tuberculosis drugs had been developed to reduce the number of TB cases, reports of operative TB cases in the United States began to increase in the mid-1980s.

This upsurge resulted from over-crowding and non-sanitary conditions in the poverty-stricken areas of Big cities, correctional institutions, and homeless shelters.

Contaminated visitors and immigrants to the United States also contributed to the resurgence of TB. An additional factor was the AIDS epidemic.

Individuals with HIV/AIDS are much more likely to develop tuberculosis because of their weakened immune systems.

DEMOGRAPHICS

The number of reported TB cases in the United States peaked in 1993 and has since declined.

However, new multidrug-resistant strains of TB (MDR-TB) have become a significant public health concern.

In the mid2000s, health officials worldwide joined to prevent a drug-resistant form of the disease from becoming widespread.

Centers for Disease Control and Prevention claims 8,920 cases of TB in the United States in 2019.

Around the globe, there were 10 million cases of TB in 2018 and 1.5 million deaths from TB. Also, in 2018, 1.1 million children developed TB, and 205,000 died from it.

In addition to individuals with HIV/AIDS, other people who take drugs that suppress the immune system (e.g., transplant patients) are also at higher risk of becoming infected, as are people who have silicosis, a lung disease.

Individuals who are alcoholics, intravenous drug abusers, and the homeless are also at increased risk of contracting tuberculosis.

CAUSES AND SYMPTOMS

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 inhale this fine mist. Tuberculosis is not, however, highly infectious compared to some other infectious diseases.

As a rule, near, frequent, or prolonged contact is required to spread the disease. Most people do not develop TB even when exposed to a person with active.

An infected mother’s embryo can contract TB by inhaling or swallowing the bacilli in the amniotic fluid.

Unlike various other infections, TB is not passed on by contact with an infected individual’s clothing, bed linens, dishes, or cooking utensils.

Progression

Once a person inhales M. tuberculosis, one of the following can happen:

  • The person’s immune system can kill the bacteria; no TB infection results and the person is not contagious.
  • The bacteria can become dormant and never grow; no TB symptoms are seen, and the person is not contagious.
  • The bacteria can become dormant for a period, then begin to grow; TB symptoms appear a long time after infection. The person is not contagious during the dormant period, then becomes contagious when symptoms appear.
  • The bacteria multiples immediately; active TB symptoms appear, and the person is contagious.

At least nine out of ten people infected with M. tuberculosis do not develop TB symptoms, and their chest x-rays remain negative.

These people have what is called a latent TB infection. However, they are not infectious; they do form a pool of infected individuals who may get sick later and then transmit TB to other people.

It is the belief that more than 90% of cases of active tuberculosis come from this pool. It is unreasonable to predict which individuals with latent TB infections will develop active TB.

An estimated 5–10% of infected people who go untreated will get sick within 12–24 months of being infected.

Some heal initially, but after years or decades, they develop active tuberculosis either in the lungs or elsewhere in the body.

A formerly infected person gets sick again after a later exposure to the tubercle bacillus on rare occasions.

Pulmonary tuberculosis 

Pulmonary tuberculosis is a sort of TB that affects the lungs.

Its leading symptoms are easily confused with those of other diseases. At first, an infected person may feel vaguely unwell or develop a cough associated with smoking or a cold.

A low amount of greenish or yellow sputum may be coughed up when the person gets up in the morning.

In time, more sputum, usually streaked with blood, is produced. People who have pulmonary TB do not get a high fever, but they often have a low-grade one.

The individual frequently loses interest in food and can lose weight. Chest ache is occasionally present.

If the infection lets air escape from the lungs in the chest cavity (pneumothorax) or fluid amass in the pleural region (pleural effusion), the sick person may have trouble breathing.

If an adolescent develops a pleural effusion, the chance of tubercular infection is very high.

Before the development of effective TB drugs, many patients became chronically ill with severe lung symptoms.

This disease process caused them to lose weight and develop a wasted appearance, hence the name consumption.

This outcome is uncommon today because of modern treatment methods.

Extrapulmonary tuberculosis

Although the lungs are the initial site of damage caused by tuberculosis, further organs and tissues inside the body can be affected.

The usual evolution is for the disease to spread from the lungs to locations outside the lungs (extrapulmonary sites).

In occasional instances, nonetheless, the initial sign of illness shows outside the lungs.

The plenty tissues or organs which tuberculosis can consist of:

  • Bones: TB is most likely to infiltrate the spine and the ends of the long bones. Kids are specifically prone to contract spinal tuberculosis. If not handled, the spinal segments (vertebrae) can crumble and cause dullness in one or both legs.
  • Kidneys: As well as the bones, the kidneys are the most standard site of extrapulmonary TB. There may be few symptoms even after part of a kidney is destroyed. TB also can disperse to the bladder. In men, it can advance to the prostatic gland and near systems.
  • Female procreative organs: The ovaries in women may be infected, and TB may move from them to the peritoneum (the membrane covering the intestinal cavity).
  • Abdominal cavity: Tubercular peritonitis may cause pain ranging from stomach cramps’ vague discomfort to intense pain that may mimic appendicitis symptoms.
  • Joints: Tubercular infection of joints causes arthritis that very often influences the hips and also knees. The wrist, hand, and elbow joints also can become painful and inflamed.
  • Meninges: The meninges are the tissues that cover the brain and the spinal cord. The meninges’ TB bacillus infection causes tubercular meningitis, a universal syndrome in young kids but is specifically dangerous in the elderly. Patients develop headaches, become drowsy, and eventually become comatose. Permanent brain damage usually occurs unless prompt treatment is given. Some patients with tubercular meningitis create a tumor-like brain lump labeled a tuberculoma that may inflict stroke-like syndrome.
  • Skin, abdominals, adrenal glands, and blood vessels: All these body parts can be spread to M. tuberculosis. Contamination of the wall of the body’s main artery (aorta) can cause it to rupture with catastrophic results. Tubercular pericarditis occurs when the membrane surrounding the heart (pericardium) is infected and fills up with fluid that conflicts with the heart’s power to pump blood.
  • Miliary tuberculosis: Miliary TB is a deadly condition occurring when huge numbers of tubercle bacilli disperse all over the body. Large numbers of tiny tubercular lesions develop that cause marked weakness, weight loss, severe anemia, and gradual body waste.

Multidrug-resistant tuberculosis (MDR-TB)

There is increasing concern about strains of M. tuberculosis that are resistant to the TB drugs that have brought the disease under control in the past.

MDR-TB is TB that fails to respond to at least two drugs (isoniazid [INH] and rifampin [RIF]) routinely used to treat TB.

A rare form of MDR-TB, known as extensively drug-resistant TB (XDR-TB), also exists. This strain is resistant to INH, RIF, fluoroquinolone, and one of three injectable second-line drugs (amikacin, kanamycin, or capreomycin).

The CDC has developed a particular group of experts to work with physicians with MDR-TB and XDR-TB patients.

There is concern that these could spread widely and cause a public health crisis. When alternate drug therapy fails, lung surgery is the preferred treatment option.

Diseases similar to tuberculosis

There are numerous forms of mycobacteria other than M. tuberculosis, the tubercle bacillus.

Certain cause infections that may closely resemble tuberculosis, but they usually do so only when an infected person’s immune system is defective.

This occurs, for example, in some people who have HIV/AIDS. The most common mycobacteria that infect HIV/AIDS patients are a group known as Mycobacterium avium complex (MAC).

Individuals infected by MAC are not contagious, but they may develop a severe lung infection that is highly immune to antibiotics. MAC infections usually start with the patient coughing up mucus.

The condition progresses slowly, but eventually, blood is brought up in the sputum, and the patient has trouble breathing.

In HIV/AIDS patients, MAC disease can spread throughout the body, with anemia, diarrhea, and stomach pain as common symptoms.

Frequently these patients die unless their immune system can be fortified. Other mycobacteria thrive in swimming pools and can provoke skin infections.

A couple of them infect wounds and artificial body parts such as breast implants or mechanical heart valves.

DIAGNOSIS 

How Tuberculosis Test Is Done

The standard screening test for tuberculosis is the tuberculin skin test. This test detects the presence of infection, not active TB.

Tuberculin is a concentrate prepared from cultures of M. tuberculosis. It contains proteins belonging to the bacillus (antigens) to which an infected person has been sensitized.

When tuberculin is injected into an infected person’s skin, the space around the injection gets hard, swollen, and red for one to three days.

Skin tests use purified protein derivative (PPD), which has a regular chemical structure and is a good measure of tubercular infection. 

The PPD trial is also called the Mantoux test. The Mantoux PPD skin test is not 100% accurate; it can produce false-positive and false-negative results.

A few people who have a skin reaction are not infected (false positive), and some who do not react are infected (false negative).

HOWEVER, the PPD test is a practical screening test and is required in most states for children to enter school.

Besides, anyone who has suspicious findings on a chest x-ray or any condition that makes a diagnosis of TB more likely should have a PPD test, as should people who are in close contact with a TB patient;

those who come from a country where TB is common; all healthcare personnel; and people living or working in institutions such as prisons.

To verify the test results, the physician will do a chest x-ray and obtain a sputum sample or a tissue sample (biopsy).

Three to five sputum samples must be taken early in the morning. Culturing M. tuberculosis is beneficial for diagnosis since the bacillus has particular distinctive traits.

Contrary to many other types of bacteria, mycobacteria can retain certain dyes even when exposed to acid. This acid-fast property is a distinctive nature of the tubercle bacillus.

Body fluids other than sputum can be used for a TB culture. If TB has infested the brain or spinal line, culturing a spinal fluid specimen will make the diagnosis.

If TB of the kidneys is suspected due to pus or blood present in the urine, the urine culture can unravel tubercular infection.

Infection of the ovaries in females can be exposed by inserting a laparoscope inside the area.

Specimens also may be taken from the liver or bone marrow to detect the tubercle bacillus.

For most people, a simple skin test is adequate to screen for TB. However, new advances in the diagnosis of TB use molecular techniques to speed the diagnostic process and improve its accuracy.

Molecular testing is being used more frequently in laboratories around the world.

Molecular tests include a polymerase chain reaction to expose mycobacterial DNA in patient specimens; nucleic acid probes to identify mycobacteria in culture;

restriction fragment length polymorphism analysis to compare different strains of TB for epidemiological studies;

and genetic-based susceptibility testing to identify drug-resistant strains of mycobacteria.

TREATMENT

Supportive care

In the past, treatment of TB was primarily supportive. Patients were kept in isolation, encouraged to rest, and fed well.

If these measures failed, the lung was collapsed surgically to “rest” and heal.

As of 2020, surgical procedures still are used when necessary, but contemporary medicine relies on antibiotic therapy as the mainstay of care.

Given an effective combination of drugs, most patients with TB can be treated at home.

Drug therapy

Most patients with TB recover if given appropriate medication for a sufficient length of time. Three principles govern modern drug treatment of TB:

  • Lowering the number of bacilli as quickly as possible: This reduction minimizes the risk of transmitting the disease. When sputum cultures become negative, this goal has been achieved. Conversely, if the sputum remains positive after five to six months, treatment has failed.
  • Preventing drug resistance development: For this reason, at least two different drugs, and routinely up to four, are always given as initial treatment.
  • Long-term treatment: This phase of therapy is intended to prevent relapse.

Four drugs are most commonly used to treat tuberculosis: isoniazid (INH, Laniazid, Nydrazid); rifampin (Rifadin, Rimactane); pyrazinamide (Tebrazid); and ethambutol (Myambutol).

The CDC and the American Thoracic Society have developed standard regimens for treating TB 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 pyrazinamide and sometimes ethambutol (or streptomycin in very young children).

Because some diseases are highly drug-resistant, cultures are grown from the patient’s bacteria and tested with a variety of drugs to determine the most effective treatment. Alternate regimens may be determined to be more appropriate.

Except in MDR-TB cases, prolonged hospitalization is rarely necessary because most patients are no longer infectious after about two weeks of combination treatment.

Follow-up involves monitoring of side effects and monthly sputum tests. Of the five medications, INH is the most frequently used drug for both treatment and prevention.

Hospitalization, isolation, and infection control measures are usually required for individuals with MDRTB, a severe 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 may be used if drugs fail to control the disease.

There are three surgical treatments 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 of a diseased lung, in whole or in part.

Removal is sometimes required in the case of MDR-TB or XDR-TB. Individuals can survive with one healthy lung. Extrapulmonary TB may result in the need for other surgeries.

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 those with resistant TB.

When TB is highly drug-resistant, the prognosis depends largely on adherence to a lengthy regimen featuring any remaining effective antibiotics and on surgery to remove all infected tissue.

The outcome of surgery depends on where and how widespread the infected area is. Miliary tuberculosis is still fatal in many cases, but it is rarely seen in developed countries.

PREVENTION

General measures

General measures such as avoidance of 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 in some jobs and most children when they enter school and often again if or when they enter college.

Although screening does not prevent TB, it allows early treatment of infected people, reducing the likelihood that they will spread 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.

Vaccination with BCG does not prevent all infections by M. tuberculosis, but it does strengthen the immune system response and provide partial protection.

BCG is used more widely in developing countries than in the United States.

In 2007, the first new TB vaccine in more than 90 years was tested in clinical trials in South Africa.

The new vaccine known as MVA85A was developed at Oxford University, England, to increase concern about the rise of MDR-TB.

This vaccine works with the BCG vaccine to increase its effectiveness and produce a powerful immune system response.

In 2007, clinical trials focused on whether the new vaccine actually prevents the disease.

A study of the vaccine in 2013 found that it had no added benefit over the current vaccine; however, the vaccine was still in trials as of 2019.

Prophylactic use of isoniazid

INH can be given for the prevention as well as the treatment of TB. INH is effective when given daily over a period of 6–12 months to people in high-risk categories.

INH appears to be most beneficial to people under the age of 25. Because INH carries the risk of side effects (liver inflammation, nerve damage, changes in mood and behavior) in about one-fifth of people taking the drug, it is important to give it only to people at special risk.

The increase in MDR-TB is also causing some TB experts to reevaluate preventive drug treatment.

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

  • close contacts of TB patients, including healthcare workers
  • newly infected patients whose skin test has turned positive in the past two years
  • anyone who is HIV-positive with a positive PPD skin test; isoniazid may be given even if the PPD results are negative when there is a risk of exposure to active tuberculosis
  • intravenous drug users, even if they are negative for HIV
  • people with positive PPD results and evidence of the previous disease on the chest x-ray who have never been treated for TB
  • patients who have an illness or are taking a drug that can suppress the immune system
  • people with positive PPD results who have had intestinal surgery; have diabetes or chronic kidney failure; have any cancer, or are more than 10% below their ideal body weight
  • people from countries with high rates of TB who have positive PPD results
  • people from low-income groups with positive skin test results
  • people with a positive PPD reaction who belong to high-risk ethnic groups (African Americans, Hispanics, Native Americans, Asians, and Pacific Islanders)
  • householders who have lived with someone who has been diagnosed with an active TB infection

PARENTAL CONCERNS

If a child has been infected with TB and is prescribed drug therapy to treat the disease, it is imperative for parents to closely monitor their child to ensure that it is taken as prescribed.

If the medication is not taken frequently enough or is no longer needed, drug-resistant TB can arise.

Parents of a child with TB should be tested for the disease because it is highly contagious.

Resources

BOOKS

Bynum, Helen. Spitting Blood: The History of Tuberculosis. Oxford, UK: Oxford University Press, 2012.

Davies, Peter, Stephen B. Gordon, and Geraint Davies. Clinical Tuberculosis. 5th ed. Boca Raton, FL: CRC Press, 2014.

Murphy, Jim. Invincible Microbe: Tuberculosis and the Never-Ending Search for a Cure. New York: Clarion, 2012.

PERIODICALS

Denkinger, C.M., et al. “Defining the Needs for Next Generation Assays for Tuberculosis.” Journal of Infectious Diseases 211 (April 2015): S29–S38.

Pai, M., and M. Schito. “Tuberculosis Diagnostics in 2015: Landscape, Priorities, Needs, and Prospects.” Journal of Infectious Diseases 211 (April 2015): S21–S28.

Principi, N., and S. Esposito. “The Present and Future of Tuberculosis Vaccinations.” Tuberculosis 95, no. 1 (January 2015): 6–13.

WEBSITES

Batram, Vandana. “Pediatric Tuberculosis.” Medscape.comhttp://emedicine.medscape.com/article/969401-overview (accessed April 1, 2020).

Centers for Disease Control and Prevention. “Tuberculosis (TB).” CDC.govhttp://www.cdc.gov/tb/?404;http://www.cdc.gov:80/tb/faqs/default.htm (accessed April 1, 2020).

Herchline, Thomas. “Tuberculosis (TB).” Medscape.com http://emedicine.medscape.com/article/230802-overview (accessed April 1, 2020).

Steenhuysen, Julie. “MVA85A: Disappointing Results in Key Tuberculosis Vaccine Trial.” Huffington Post. http://www.huffingtonpost.com/2013/02/04/mva85a-tuberculosis-vaccine-trial_n_2614391.html (accessed April 1, 2020).

World Health Organization. “Tuberculosis.” WHO.inthttps://www.who.int/news-room/fact-sheets/detail/tuberculosis (accessed April 1, 2020).

ORGANIZATIONS

American Lung Association, 55 W. Wacker Dr., Suite 1150, Chicago, IL 60601, (800) LUNGUSA (800-586-4872), Fax: (202) 452-1805, http://www.lungusa.org.

American Thoracic Society, 25 Broadway, New York, NY 10004, (212) 315-8600, ATSInfo@Thoracic.org, http://www.thoracic.org.

Centers for Disease Control and Prevention (CDC), 1600 Clifton Rd., Atlanta, GA 30329-4027, (800) CDC-INFO (232-4636); TTY: (888) 232-6348, cdcinfo@cdc.gov, http://www.cdc.gov .

National Heart, Lung, and Blood Institute (NHLBI), PO Box 30105, Bethesda, MD 20824-0105, (301) 592 8573, nhlbiinfo@nhlbi.nih.gov, http://www.nhlbi.nih.gov.

World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland+41 22 791 21 11, http://www.who.int .