NET, IAS, State-SET (KSET, WBSET, MPSET, etc.), GATE, CUET, Olympiads etc.: Tuberculosis

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Tuberculosis (TB) is an infectious disease caused by the bacterium, Mycobacterium tuberculosi. TB most commonly affects the lungs but can involve almost any organ of the body. There is also a group of organisms referred to as atypical tuberculosis. These involve other types of bacteria of Mycobacterium family. At times, these bacteria can cause an infection that sometimes appears as typical tuberculosis. These “atypical” mycobacteria are: M. Kansasii that may produce similar clinical and pathologic symptoms of disease. M. Avium-intracellulare (MAI) seen in persons with AIDS and is not primarily a pulmonary pathogen but occurs mostly in organs of the mononuclear phagocyte system.

Tuberculosis outside the lungs can appear in the following kinds:

  • Skeletal Tuberculosis: Tuberculous osteomyelitis, known as Pott՚s disease, involves mainly the thoracic and lumbar vertebrae followed by knee and hip. There is extensive necrosis and bony destruction with compressed fractures with kyphosis and extension to soft tissues.
  • Genital Tract Tuberculosis: Tuberculous salpingitis and endometritis result from infection of the fallopian tube that leads to granulomatous salpingitis, which can drain into the endometrial cavity and cause a granulomatous endometritis with irregular menstrual bleeding and infertility. In the male, tuberculosis involves prostate and epididymis leading to infertility.
  • Urinary Tract Tuberculosis: WBC՚s appear in urine but a negative routine bacterial culture may suggest the diagnosis of renal tuberculosis. Progressive destruction of renal parenchyma occurs if not treated. Drainage to the ureters can lead to inflammation and ureteral stricture.
  • CNS Tuberculosis: A meningeal spread can occur and the cerebrospinal fluid typically shows a high protein, low glucose, and lymphocytosis. The base of the brain is often involved, so that various cranial nerves may be affected. Rarely, a solitary granuloma, or “tuberculoma” may form and manifest with seizures.
  • Gastrointestinal Tuberculosis: This is uncommon today because routine pasteurization of milk has eliminated Mycobacterium bovis infections. However, M. Tuberculosi coughed up in sputum may be swallowed through contamination. The classic lesions are circumferential ulcerations with stricture of the small intestine, with ileo-caecal involvement.
  • Adrenal Tuberculosis: Spread of tuberculosis to adrenals is usually bilateral, so that both adrenals are markedly enlarged. Destruction of cortex leads to Addison՚s disease.
  • Scrofula: Tuberculous lymphadenitis of the cervical nodes is caused by Mycobacterium scrofulaceum and may produce a mass of firm, matted nodes just under the mandible.
  • There can be chronic draining fistulous tracts to overlying skin. This complication may appear in children.
  • Cardiac Tuberculosis: The pericardium is the usual site for tubercular infection of heart. The result is a granulomatous pericarditis that can be hemorrhagic. There can be fibrosis with calcification, leading to a constrictive pericarditis.

History

Robert Koch isolated the tubercular bacillus in 1882 and established TB as an infectious disease. In the 19th century, due to the absence of antibiotics, patients were isolated in sanatoria and given treatment. Attempts were made to remove the infectious tissue by surgery called thoracoplasty. Till the first half of 20th century, no effective treatment was available. Streptomycin, the first antibiotic to fight TB, was introduced in 1946, and isoniazid (Laniazid, Nydrazid) became available in 1952.

M tuberculosis is a rod-shaped, slow-growing bacterium. Its cell wall has high acidic content, which makes it hydrophobic, resistant to oral fluids. The cell wall absorbs a certain dye and maintains a red color, hence the name acid-fast bacilli.

Infection Mode

A person can become infected with tuberculosis bacteria through inhalation of droplets containing bacillus from the air. The bacteria get into the air when someone with tuberculosis lung infection coughs, sneezes or spits. TB is not transmitted by just touching the clothes or shaking the hands of someone who is infected. Tuberculosis is spread primarily from person to person by breathing infected air especially in closed rooms. TB caused by Mycobacterium bovis, however, is transmitted by drinking unpasteurized milk. Earlier this bacterium was a major cause of TB in children, but rarely causes TB now since most milk is pasteurized.

Pathology

When the inhaled tuberculosis bacteria enter the lungs, they can multiply and cause pneumonia. The local lymph nodes associated with the lungs may also become involved with the infection and usually become enlarged. The infection can also spread to other parts of the body. The body՚s immune system in healthy people can fight the infection and stop the bacteria from spreading. If the body is able to form scar tissue (fibrosis) around the TB bacteria, then the infection is contained in an inactive state. Such an individual typically has no symptoms and cannot spread TB to other people. The scar tissue and lymph nodes may eventually harden due to the process of calcification of the scars. However, if the body՚s immune system is weakened, the TB bacteria can break through the scar tissue. The breakthrough of bacteria can result in recurrence of the pneumonia and a spread of TB to other parts of the body. It may take many months from the time the infection initially gets into the lungs until symptoms develop. The usual symptoms that occur with an active TB infection are a generalized tiredness or weakness, weight loss, fever, and night sweats. If the infection in the lung worsens, then further symptoms can include coughing, chest pain, coughing up of sputum or blood, and shortness of breath. If the infection spreads beyond the lungs, the symptoms will depend upon the organs involved.

Diagnosis

TB can be diagnosed in several different ways, including chest X-rays, analysis of sputum, and skin tests. The chest x-rays can reveal evidence of active tuberculosis pneumonia or scarring (fibrosis) or hardening (calcification) in the lungs. Examination of the sputum on a slide (smear) under the microscope can show the presence of the tuberculosis bacteria. A sample of the sputum can also be cultured in special incubators so that the tuberculosis bacteria can subsequently be identified.

Several types of skin tests are used to screen for TB, e. g. Tuberculin skin tests that include the Mantoux test, the Tine test, and the PPD (Purified Protein Derivative) test. In each of these tests, a small amount of purified extract from dead tuberculosis bacteria is injected under the skin. If a person is not infected with TB, then no reaction will occur at the site of the injection. If a person is infected with tuberculosis, however, a raised and reddened area will appear around the site of the test injection within 48 to 72 hours after the injection.

If the infection with tuberculosis has occurred recently, the skin test may be negative, because usually it takes 2 to 10 weeks after infection for the skin to test positive. The skin test can also be falsely negative if a person՚s immune system is weakened due to another illness such as AIDS or cancer or he is on medication that can suppress the immune response such as cortisone or anti-cancer drugs.

Treatment

Treatment with antibiotics is recommended to treat as well as to prevent the TB from turning into an active infection in those where it is dormant. The antibiotic used for this purpose is called isoniazid (INH) . If taken for 6 to 12 months, it will prevent the TB from becoming active in the future. In fact, if a person with a positive skin test does not take INH, there is a 5 to 10% lifelong risk that the TB will become active. Taking isoniazid is not advisable (contraindicated) during pregnancy or for those suffering from alcoholism or liver disease. Also, isoniazid can have side effects such as rashes, tiredness or irritableness. Liver damage from isoniazid is rare and typically reverses once the drug is stopped. Very rarely, however, in older people, the liver damage (INH hepatitis) can even be fatal. It is important therefore, for the doctor to monitor a patient՚s liver by periodically carrying out liver function tests during the course of INH therapy.

Active TB is treated with a combination of medications with isoniazid, Rifampicin (Rifadin) , ethambutol (Myambutol) and pyrazinamide. Drugs are often taken for the first two months of therapy to help kill any potentially resistant strains of bacteria. Then the number is usually reduced to two drugs for the remainder of the treatment based on drug sensitivity testing. Streptomycin, a drug that is given by injection, may be used as well, particularly when the disease is extensive. Treatment usually lasts for many months and sometimes for years. Successful treatment of TB is dependent largely on the compliance of the patient.

Drug-resistant TB has become a very serious problem in recent years in certain populations. For example, INH-resistant TB is seen among patients in Southeast Asia. Even more serious problem is the multi-drug resistant TB that has been seen in prison populations. Poor compliance by the inmates is thought to be the main reason for the development of multi-drug resistance.

Surgery on the lungs may be indicated to help cure TB when medication has failed, but in most cases is not required. Treatment with appropriate antibiotics will usually cure the disease. Without treatment, however, tuberculosis can be lethal and hence early diagnosis is important.

Summary

  • Tuberculosis (TB) is an infection primarily of lungs (a pneumonia) , caused by bacteria called Mycobacterium tuberculosis. It is spread usually from person to person by breathing infected air during close contacts.
  • TB can remain in an inactive (dormant) state for years without causing symptoms or spreading to other people.
  • When the immune system of a patient with dormant TB is weakened, the TB can become active and cause infections in the lungs or other parts of the body.
  • The risk factors for acquiring TB include close-contact situations, alcohol and IV drug abuse, and certain diseases (e. g. diabetes, cancer, and HIV) and occupations (e. g. health care workers) .
  • The most common symptoms of TB are fatigue, fever, weight loss, coughing, and night sweats.
  • The diagnosis of TB involves skin tests, chest x-rays, sputum analysis (smear and culture) , and PCR tests to detect the genetic material of the causative bacteria.
  • Inactive tuberculosis may be treated with an antibiotic, isoniazid (INH) , to prevent the TB infection from becoming active.
  • Active TB is treated, usually successfully, with INH in combination with one or more of several drugs, including rifampicin, ethambutol, pyrazinamide, and streptomycin.
  • Drug-resistant TB is a serious, as yet unsolved, public health problem, especially in Southeast Asia and in prison populations.
  • The occurrence of HIV has been responsible for an increased frequency of tuberculosis. Control of HIV in the future, however, should substantially decrease the frequency of TB.