Tuberculosis

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By Medifit Education

TUBERCULOSIS

Tuberculosis 3

TUBERCULOSIS DEFINITION

Tuberculosis (TB) is a potentially serious infectious disease that mainly affects your lungs. The bacteria that cause tuberculosis are spread from one person to another through tiny droplets released into the air via coughs and sneezes.

Once rare in developed countries, tuberculosis infections began increasing in 1985, partly because of the emergence of HIV, the virus that causes AIDS. HIV weakens a person’s immune system so it can’t fight the TB germs. In the United States, because of stronger control programs, tuberculosis began to decrease again in 1993, but remains a concern.

Many strains of tuberculosis resist the drugs most used to treat the disease. People with active tuberculosis must take several types of medications for many months to eradicate the infection and prevent development of antibiotic resistance.

 

TUBERCULOSIS CAUSES

The Mycobacterium tuberculosis bacterium causes TB. It is spread through the air when a person with TB (whose lungs are affected) coughs, sneezes, spits, laughs or talks.

TB is contagious, but it is not easy to catch. The chances of catching TB from someone you live or work with are much higher than from a stranger. Most people with active TB who have received appropriate treatment for at least two weeks are no longer contagious.

Since antibiotics began to be used to fight TB, some strains have become resistant to drugs. Multidrug-resistant TB (MDR-TB) arises when an antibiotic fails to kill all of the bacteria that it targets, with the surviving bacteria developing resistance to that antibiotic and often others at the same time.

MDR-TB is treatable and curable only with the use of very specific anti-TB drugs, which are often limited or not readily available. In 2012, around 450,000 people developed MDR-TB.

 

TUBERCULOSIS PATHOPHYSIOLOGY

Infection with M tuberculosis results most commonly through exposure of the lungs or mucous membranes to infected aerosols. Droplets in these aerosols are 1-5 μm in diameter; in a person with active pulmonary TB, a single cough can generate 3000 infective droplets, with as few as 10 bacilli needed to initiate infection.

When inhaled, droplet nuclei are deposited within the terminal airspaces of the lung. The organisms grow for 2-12 weeks, until they reach 1000-10,000 in number, which is sufficient to elicit a cellular immune response that can be detected by a reaction to the tuberculin skin test.

Mycobacteria are highly antigenic, and they promote a vigorous, nonspecific immune response. Their antigenicity is due to multiple cell wall constituents, including glycoproteins, phospholipids, and wax D, which activate Langerhans cells, lymphocytes, and polymorphonuclear leukocytes

When a person is infected with M tuberculosis, the infection can take 1 of a variety of paths, most of which do not lead to actual TB. The infection may be cleared by the host immune system or suppressed into an inactive form called latent tuberculosis infection (LTBI), with resistant hosts controlling mycobacterial growth at distant foci before the development of active disease. Patients with LTBI cannot spread TB.

The lungs are the most common site for the development of TB; 85% of patients with TB present with pulmonary complaints. Extrapulmonary TB can occur as part of a primary or late, generalized infection. An extrapulmonary location may also serve as a reactivation site; extrapulmonary reactivation may coexist with pulmonary reactivation.

The most common sites of extrapulmonary disease are as follows (the pathology of these lesions is similar to that of pulmonary lesions):

  • Mediastinal, retroperitoneal, and cervical (scrofula) lymph nodes – The most common site of tuberculous lymphadenitis (scrofula) is in the neck, along the sternocleidomastoid muscle; it is usually unilateral and causes little or no pain; advanced cases of tuberculous lymphadenitis may suppurate and form a draining sinus
  • Vertebral bodies
  • Adrenals
  • Meninges
  • GI tract

Infected end organs typically have high regional oxygen tension (as in the kidneys, bones, meninges, eyes, and choroids, and in the apices of the lungs). The principal cause of tissue destruction from M tuberculosis infection is related to the organism’s ability to incite intense host immune reactions to antigenic cell wall proteins.

Uveitis caused by TB is the local inflammatory manifestation of a previously acquired primary systemic tubercular infection. There is some debate with regard to whether molecular mimicry, as well as a nonspecific response to noninfectious tubercular antigens, provides a mechanism for active ocular inflammation in the absence of bacterial replication.

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TB lesions

The typical TB lesion is an epithelioid granuloma with central caseation necrosis. The most common site of the primary lesion is within alveolar macrophages in subpleural regions of the lung. Bacilli proliferate locally and spread through the lymphatics to a hilar node, forming the Ghon complex.

Early tubercles are spherical, 0.5- to 3-mm nodules with 3 or 4 cellular zones demonstrating the following features:

  • A central caseation necrosis
  • An inner cellular zone of epithelioid macrophages and Langhans giant cells admixed with lymphocytes
  • An outer cellular zone of lymphocytes, plasma cells, and immature macrophages
  • A rim of fibrosis (in healing lesions)

Initial lesions may heal and the infection become latent before symptomatic disease occurs. Smaller tubercles may resolve completely. Fibrosis occurs when hydrolytic enzymes dissolve tubercles and larger lesions are surrounded by a fibrous capsule. Such fibrocaseous nodules usually contain viable mycobacteria and are potential lifelong foci for reactivation or cavitation. Some nodules calcify or ossify and are seen easily on chest radiographs.

Tissues within areas of caseation necrosis have high levels of fatty acids, low pH, and low oxygen tension, all of which inhibit growth of the tubercle bacillus.

If the host is unable to arrest the initial infection, the patient develops progressive, primary TB with tuberculous pneumonia in the lower and middle lobes of the lung. Purulent exudates with large numbers of acid-fast bacilli can be found in sputum and tissue. Subserosal granulomas may rupture into the pleural or pericardial spaces and create serous inflammation and effusions.

With the onset of the host immune response, lesions that develop around mycobacterial foci can be either proliferative or exudative. Both types of lesions develop in the same host, since infective dose and local immunity vary from site to site.

Proliferative lesions develop where the bacillary load is small and host cellular immune responses dominate. These tubercles are compact, with activated macrophages admixed, and are surrounded by proliferating lymphocytes, plasma cells, and an outer rim of fibrosis. Intracellular killing of mycobacteria is effective, and the bacillary load remains low.

Exudative lesions predominate when large numbers of bacilli are present and host defenses are weak. These loose aggregates of immature macrophages, neutrophils, fibrin, and caseation necrosis are sites of mycobacterial growth. Without treatment, these lesions progress and infection spreads.

 

TUBERCULOSIS SYMPTOMS

Although your body may harbor the bacteria that cause tuberculosis, your immune system usually can prevent you from becoming sick. For this reason, doctors make a distinction between:

  • Latent TB. In this condition, you have a TB infection, but the bacteria remain in your body in an inactive state and cause no symptoms. Latent TB, also called inactive TB or TB infection, isn’t contagious. It can turn into active TB, so treatment is important for the person with latent TB and to help control the spread of TB in general. An estimated 2 billion people have latent TB.
  • Active TB. This condition makes you sick and can spread to others. It can occur in the first few weeks after infection with the TB bacteria, or it might occur years later.

Signs and symptoms of active TB include:

  • Coughing that lasts three or more weeks
  • Coughing up blood
  • Chest pain, or pain with breathing or coughing
  • Unintentional weight loss
  • Fatigue
  • Fever
  • Night sweats
  • Chills
  • Loss of appetite

Tuberculosis can also affect other parts of your body, including your kidneys, spine or brain. When TB occurs outside your lungs, signs and symptoms vary according to the organs involved. For example, tuberculosis of the spine may give you back pain, and tuberculosis in your kidneys might cause blood in your urine.

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TUBERCULOSIS DIAGNOSIS

To check for TB, a health care provider will use a stethoscope to listen to the lungs and will check for swelling in the lymph nodes. They will also ask about symptoms and medical history as well as assessing a person’s risk of exposure to TB.

The most common diagnostic test for TB is a skin test where a small injection of PPD tuberculin, an extract of the TB bacterium, is made just below the inside forearm.

The injection site should be checked after 2-3 days, and if a hard, red bump has swollen up then it is likely that TB is present.

Unfortunately, the skin test is not 100% accurate and has been known to give incorrect positive and negative readings.

However, there are other tests that are available to diagnose TB. Blood tests, chest X-rays and sputum tests can all be used to test for the presence of TB bacteria, and may be used alongside a skin test.

MDR-TB is more difficult to diagnose than regular TB. It is also difficult to diagnose regular TB in children.

 

TUBERCULOSIS TREATMENT

Medications are the cornerstone of tuberculosis treatment. But treating TB takes much longer than treating other types of bacterial infections.

With tuberculosis, you must take antibiotics for at least six to nine months. The exact drugs and length of treatment depend on your age, overall health, possible drug resistance, the form of TB (latent or active) and the infection’s location in the body.

Recent research suggests that a shorter term of treatment — four months instead of nine — with combined medication may be effective in keeping latent TB from becoming active TB. With the shorter course of treatment, people are more likely to take all their medication and the risk of side effects is lessened. Studies are ongoing.

Most common TB drugs

If you have latent tuberculosis, you may need to take just one type of TB drug. Active tuberculosis, particularly if it’s a drug-resistant strain, will require several drugs at once. The most common medications used to treat tuberculosis include:

  • Isoniazid
  • Rifampin (Rifadin, Rimactane)
  • Ethambutol (Myambutol)
  • Pyrazinamide

If you have drug-resistant TB, a combination of antibiotics called fluoroquinolones and injectable medications, such as amikacin, kanamycin or capreomycin, are generally used for 20 to 30 months. Some types of TB are developing resistance to these medications as well.

A number of new drugs are being looked at as add-on therapy to the current drug-resistant combination treatment including:

  • Bedaquiline
  • Delamanid
  • PA-824
  • Linezolid
  • Sutezolid

Medication side effects

Serious side effects of TB drugs aren’t common but can be dangerous when they do occur. All tuberculosis medications can be highly toxic to your liver. When taking these medications, call your doctor immediately if you experience any of the following:

  • Nausea or vomiting
  • Loss of appetite
  • A yellow color to your skin (jaundice)
  • Dark urine
  • A fever that lasts three or more days and has no obvious cause

Completing treatment is essential

After a few weeks, you won’t be contagious and you may start to feel better. It might be tempting to stop taking your TB drugs. But it is crucial that you finish the full course of therapy and take the medications exactly as prescribed by your doctor. Stopping treatment too soon or skipping doses can allow the bacteria that are still alive to become resistant to those drugs, leading to TB that is much more dangerous and difficult to treat.

To help people stick with their treatment, a program called directly observed therapy (DOT) is recommended. In this approach, a health care worker administers your medication so that you don’t have to remember to take it on your own.

By Medifit Education

www.themedifit.in