Definition
Tuberculosis (abbreviated as TB for tubercle bacillus or Tuberculosis) is a common and deadly infectious disease caused by mycobacteria, mainly Mycobacterium tuberculosis. Tuberculosis most commonly attacks the lungs (as pulmonary TB) but can also affect the central nervous system, the lymphatic system, the circulatory system, the genitourinary system, bones, joints and even the skin. Other mycobacteria such as Mycobacterium bovis, Mycobacterium africanum, Mycobacterium canetti, and Mycobacterium microti can also cause tuberculosis, but these species do not usually infect healthy adults.
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.
Incubation Period
Infection to the primary lesion or significant tuberculin reaction is about four to twelve weeks.
Signs and Sypmtoms
? A cough lasting three or more weeks that may produce discolored or bloody sputum
? Unintended weight loss
? Fatigue
? Slight fever
? Night sweats
? Chills
? Loss of appetite
? Pain with breathing or coughing (pleurisy)
Pathophysiology
Tuberculosis is spread by airborne droplet nuclei, which are 1-5 µm particles containing 1 to 400 bacilli each. They are expelled in the air with coughing, sneezing, singing, laughing, talking etc and remain suspended in the air for many hours. They can be inhaled and subsequently entrapped in the distal airways and alveoli. There, bacilli are ingested by local macrophages, multiply within the cells, and within 2 weeks are transported through the lymphatics to establish secondary sites (lymphohematogenous spread). The development of an immune response, heralded by a delayed-type hypersensitivity reaction over the next 4 weeks leads to granuloma formation, with subsequent decrease in the number of bacilli. Some of them remain viable or ‘dormant’ for many years. This stage is called latent TB infection (LTBI), which is generally an asymptomatic, radiologically undetected process in humans. Sometimes a primary complex (Ghon complex) can be seen radiographically, mostly in the lower and middle lobes, and comprises the primary lesion, hilar lymphadenopathy plus/minus a lymphangitic track. Later on, the primary lesion tends to become calcified, and can be identified on the chest radiographs for decades. Most commonly, a positive tuberculin test remains the only proof of LTBI, and therefore does not signify active disease.
Under certain conditions of immature or disregulated immunity, alveolar macrophages and the subsequent biologic cascade could fail in limiting the mycobacterial proliferation, leading to primary progressive tuberculosis (mostly in children less than 5 years old, HIV positive or profoundly immunosuppressed individuals). Factors known to influence this unfavorable course are: patients’ age, nutritional status, host immunity, and bacterial infective load.
After inhalation, the pathogenic bacilli start to replicate slowly and continuously and lead to development of a cellular immunity in about 4-6 weeks. T lymphocytes and local (pulmonary and lymphatic node) macrophages represent key-players in limiting further spread of the bacilli in the host’s organism. This can be seen at the pathological level, where the bacilli are in the center of necrotizing (caseating) and non-necrotizing (non-caseating) granulomas, surrounded by lymphocytes and macrophages. The infected macrophages release interleukin 12, and 18, which stimulate CD4-positive T lymphocytes to secrete IFN-? (interferon-gamma), which, in turn, activate the macrophage phagocytosis of M. tuberculosis and the release of TNF-? (tumor necrosis factor-alpha). TNF-? has an important role in the granuloma formation, and the control of infection. Genetic defects illustrated by different polymorphisms of the following genes: NRAMP-1 (natural resistance-associated macrophage protein-1), vitamin D receptors, and interleukin-1 have also been shown to be involved in TB pathogenesis.10 It is often difficult to differentiate between genetic predisposition and overwhelming bacteriological load, as often seen in countries with high prevalence of TB. HIV co-infection is the greatest risk factor for progression to active disease in adults. The ‘partnership’ between HIV and TB has augmented the deadly potentials of each disease. Other risk factors are: diabetes mellitus, renal failure, co-existent malignancies, malnutrition, silicosis, immunosuppressive therapies (including steroids and anti-TNF drugs), and TNF-? receptor, TNF-? receptor, or IL-12 ß1 receptor defects
Diagnosis
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 og 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.
One important new advance in the diagnosis of TB is the use of molecular techniques to speed the diagnostic process as well as improve its accuracy. As of late 2005, four molecular techniques are increasingly used in laboratories around the world. They include polymerase chain reaction to detect 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 drugresistant strains of mycobacteria.
TB is diagnosed by a consideration of the following:
• clinical presentation
• tuberculin skin test using the Mantoux procedure
• radiographic examination, sometimes including CT scans
• bacteriology, direct staining and culture of sputum or other specimens for the presence of M. tuberculosis
• molecular amplification (PCR) and gene probes assist in rapid diagnosis.
Laboratory Test
Because of difficulties with the Tuberculin skin test, many laboratory methods of diagnosis are emerging. These tests have been reviewed in detail.
Adenosine deaminase
In 2007, a systematic review of adenosine deaminase by the NHS Health Technology Assessment Programme concluded “There is no evidence to support the use of ADA tests for the diagnosis of pulmonary TB. However, there is considerable evidence to support their use in pleural fluid samples for diagnosis of pleural TB, where sensitivity was very high, and to a slightly lesser extent for TB meningitis. In both pleural TB and TB meningitis, ADA tests had higher sensitivity than any other tests.”[
Nucleic acid amplification tests (NAAT)
This is a heterogeneous group of tests that use the polymerase chain reaction (PCR) technique to detect mycobacterial nucleic acid. These test vary in which nucleic acid sequence they detect and vary in their accuracy. The two most common commercially available tests are the amplified mycobacterium tuberculosis direct test (MTD, Gen-Probe) and Amplicor (Roche Diagnostics). In 2007, a systematic review of NAAT by the NHS Health Technology Assessment Programme concluded that "NAAT test accuracy to be far superior when applied to respiratory samples as opposed to other specimens. Although the results were not statistically significant, the AMTD test appears to perform better than other currently available commercial tests."
In a more recent before-after observational study, found that use of the MTD test reduce inappropriate tuberculosis therapy. The study found the accuracy of the MTD test as follows:
Overall
• sensitivity 92%
• specificity 99%
Smear positive patients
• sensitivity 99%
• specificity 98%
Smear negative patients
• sensitivity 62%
• specificity 99%
Interferon-? release assays
Interferon-? (interferon-gamma) release assays (IGRAs) are based on the ability of the mycobacterium tuberculosis antigens for early secretory antigen target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) to stimulate host production of interferon-gamma. Because these antigens are not present in non-tuberculous mycobacteria or in BCG vaccine, these tests can distinguish latent tuberculosis infection (LTBI).
The blood tests QuantiFERON-TB Gold and T-SPOT.TB use these antigens to detect people with tuberculosis. Lymphocytes from the patient's blood are cultured with the antigens. These tests are called interferon ? tests and are not equivalent. If the patient has been exposed to tuberculosis before, T lymphocytes produce interferon ? in response. Both tests use ELISA to detect the interferon ? with great sensitivity.[citation needed] The distinction between the tests is that QuantiFERON-TB Gold quantifies the total amount of interferon ? when whole blood is exposed to the antigens, whereas T-SPOT.TB, a type of ELISPOT assay,[9] counts the number of activated T lymphocytes that secrete interferon ?. Guidelines for the use of the FDA approved QuantiFERON-TB Gold were released by the CDC in December 2005.
The enzyme-linked immunospot assay (ELISPOT) is another blood test available in the UK that may replace the skin test for diagnosis
For diagnosing latent TB, two systematic reviews of IGRAs concluded the tests noted excellent specificity for the tests to distinguish latent TB from prior vaccination.
For diagnosing active TB, IGRAs have reduced specificity due to their ability to detect latent TB.
Full blood count
Although a full blood count is never diagnostic, normocytic anemia and lymphopenia are common. Neutrophilia is rarely found. [iron deficiency anemia may develop with isoniazid treatment] Urea and electrolytes are usually normal, although hypocalcemia and hyponatremia are possible in tuberculous meningoencephalitis due to SIADHS. In advanced disease, hypoalbuminemia, hyperproteinemia, and hyperglobulinemia may be present.
Erythrocyte sedimentation rate is usually raised.
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 so that it could “rest” and heal. Today surgical procedures still are used when necessary, but contemporary medicine relies on drug therapy as the mainstay of home care. Given an effective combination of drugs, patients with TB can be treated at home as well as in a sanitorium. Treatment at home does not pose the risk of infecting other household members.
Drug therapy
Most patients with TB can recover if given appropriate medication for a sufficient length of time. Three principles govern modern drug treatment of TB:
Five drugs are most commonly used today to treat tuberculosis: isoniazid (INH, Laniazid, Nydrazid); rifampin (Rifadin, Rimactane); pyrazinamide (Tebrazid); streptomycin; and ethambutol (Myambutol). The first three drugs may be given in the same capsule to minimize the number of pills in the dosage. As of 1998, many patients are given INH and rifampin together for six months, with pyrazinamide added for the first two months. Hospitalization is rarely necessary because many 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
Drugs
• ethambutol is EMB or E,
• isoniazid is INH or H,
• pyrazinamide is PZA or Z,
• rifampicin is RMP or R,
• streptomycin is STM or S
Surgical Management
Surgical treatment of TB may be used if medications are ineffective. 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. It is possible for patients to survive with one healthy lung. Spinal TB may result in a severe deformity that can be corrected surgically.
Prevention
General measures
General measures such as avoidance of overcrowded and unsanitary conditions are also necessary aspects of prevention. Hospital emergency rooms and similar locations can be treated with ultraviolet light, which has an antibacterial effect.
Vaccination
Vaccination is one major 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 infection by M. tuberculosis but it does strengthen the immune system of first-time TB patients. As a result, serious complications are less likely to develop. BCG is used more widely in developing countsies than in the United States. The effectiveness of vaccination is still being studied; it is not clear whether the vaccine’s effectiveness depends on the population in which it is used or on variations in its formulation.
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 six to 12 months to people in high-risk categories. INH appears to be most beneficial to persons under the age of 25. Because INH carries the risk of side-effects (liver inflammation, nerve damage, changes in mood and behavior), it is important to give it only to persons at special risk.
High-risk groups for whom isoniazid prevention may be justified include
Nursing Responsibility
Nurses must be informed and educated about the etiology, transmission, prevention and treatment and the potential risk factors of environmental TB exposure in the workplace. Appropriate precautionary measures, including guidelines and standards of practice for nurses, should be implemented in all health care settings to prevent further spread of the infection. Following the recommendations of the ICN Guidelines for Nurses in the Care and Control of Tuberculosis and Multi-Drug Resistant Tuberculosis, ICN supports:
• Nurse responsibility to engage in continuous risk assessment related to workplace (environmental) risk factors known to increase the potential of TB transmission;
• Employer responsibility to ensure protective equipment (e.g. high filtration masks) and the implementation of guidelines and standards for safe nursing practice;
• Employer responsibility for occupational (environmental) safety (e.g. providing ventilation systems or isolating patients with active TB in negative pressure rooms)
• Education for all nurses about the epidemiology, diagnosis, transmission, preventive measures and post-event alternatives;
• Increased participation of nurses in the development of institutional/organizational strategies that support close monitoring of all TB infected persons as part of the routine health- and nursing care.
