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TUBERCULOSIS
(TB) is an infectious disease caused by Mycobacterium tuberculosis. It usually involves the lungs, but it also occurs in the larynx. kidneys. bones, adrenal glands, lymph nodes, and meninges and can disseminated throughout the TB is the world’s second most common cause of death from infectious disease. after HIV/AIDS. An estimated 2 billion people (one third of the world’s population) are infected the M. tuberculosis bacteria- There are an estimated 8 to 9 million cases a year, and approximately 2 million people die annually— The highest incidence is seen in the developing countries of Africa and Asia, with a recent increase seen in the former Soviet Union 21 Although a decline has been seen in TB rates in the United States, over 14,000 new cases of TB year are still being reported. Despite the decline in TB nati0Wåide, rates have increased in certain states and high rates continue to reported in certain populations (e.g., foreign-born persons, ethnic minorities [see Cultural and Ethnic Health Disparities Box]). Targeted interventions for these at-risk populations and efforts toward a worldwide attack against TB are needed. The major factors that have contributed to the resurgence of TB have been (1) high rates of TB among patients with HIV infection and (2) the emergence of multidrug-resistant (MDR) strains of M. tuberculosis. Once a strain of M. tuberculosis develops resistance to isoniazid and rifampin, it is defined as multidrug-resistant tuberculosis (MDR-TB). MDR-TB developed because patients had poor compliance with drug therapy, leading to treatment failure; were lost to follow-up treatment; or were placed on drug regimens to which their infections were no longer susceptible. TB is seen disproportionately in the poor, the underserved, and minorities. Individuals at risk for TB include homeless persons, residents of inner-city neighborhoods, foreign-born persons, older adults those in institutions (long-term care facilities, prisons), injection drug users, persons at poverty level, and those with poor access to health care. Immunosuppression from any etiology (e.g.,
HIV infection, malignancy) increases the risk of TB infection. The prevalence of TB is high in areas of the United States where there is a large population of Native Americans, such as Arizona and New Mexico. Higher TB rates are found in non-Hispanic whites in seven south eastern states of the Unites States compared with the rest of the country. In the United States, African Americans have TB rates 8 times higher than non-Hispanic whites. Health care workers with increased exposure to TB are considered at high risk.
Etiology and Pathophysiology
M. tuberculosis is a gram-positive, acid-fast bacillus that is usually spread from person to person via airborne droplets. These droplets are produced when the infected individual with pulmonary or laryngeal TB coughs, sneezes, speaks, or sings. Brief exposure to a few tubercle bacilli rarely causes an infection. Rather, TB is more commonly spread by repeated close contact (within 6 inches of the person's mouth) with the infected person. TB is not highly infectious, and transmission usually requires close, frequent, or prolonged exposure. The disease cannot be spread by hands, books, glasses, or dishes. The very small droplet nuclei, 1 to 5 11m in size, contain M. tuberculosis. Because they are so small in size, the particles remain airborne for minutes to hours. Once inhaled, these small nuclei lodge in alveoli in the small distal airways of the lung. M. tuberculosis replicates slowly and spreads via the lymphatic system. The organisms find favourable environments for growth primarily in the upper lobes of the lungs, kidneys, epiphyses of the bone, cerebral cortex, and adrenal glands. Cellular immunity limits further multiplication and spread of the infection. After the cellular immune system is activated, a characteristic tissue granuloma, formed from alveolar macrophages, contains the bacteria and prevents further replication. At this point the person has TB infection, which can be detected by using the tuberculin skin test. (It may take 2 to 10 weeks for the infected person to develop a positive reaction to the tuberculin skin test.) The granuloma is usually not viable and, as a result, the infection remains contained and active disease may never occur.21 Persons who are infected with M. tuberculosis, but who do not have TB disease, cannot spread the infection to other people.
advanced cases. Sometimes TB has more acute, sudden manifestations; the patient has high fever, chills, generalized flu-like symptoms, pleuritic pain, and a productive cough. examination and chest x-ray findings. Classic signs such as fever, cough, and weight loss may be attributed to Pneumocystis jiroveci pneumonia (PCP) or other HIV- associated opportunistic diseases. Clinical manifestations of respiratory problems in patients with HIV must be carefully investigated to determine the cause.
Complications
Miliary TB. Large numbers of organisms can invade the bloodstream and spread to all body organs. This hematogenous disseminated spread with involvement of many organs simultaneously is called miliary TB. It can occur as a result of primary disease or reactivation of latent infection. 21 The patient may be either acutely ill with fever, dyspnea, and cyanosis or chronically ill with systemic manifestations of weight loss, fever, and gastrointestinal (GI) disturbance. Hepatomegaly, splenomegaly, and generalized lymphadenopathy may be present. Pleural Effusion and Empyema. Pleural TB can result from either primary disease or reactivation of latent infection. A pleural effusion is caused by the bacteria in the pleural space triggering an inflammatory reaction and a pleural exudate of proteinrich fluid. Empyema is less common than effusion but may occur from large numbers of tubercular organisms in the pleural space. Tuberculosis Pneumonia. Acute pneumonia may result when large amounts of tubercle bacilli are discharged from granulomas into the lung or lymph nodes. The clinical manifestations are similar to those of bacterial pneumonia, including chills, fever, productive cough, pleuritic pain, and leukocytosis.
Other Organ Involvement. Although the lungs are the primary site of TB, other body organs may also be involved. The most serious is involvement of the central nervous system with inflammation of the meninges. Bone (Pott's disease of the spine) and joint tissue may be involved in the infectious disease process. The kidneys, adrenal glands, lymph nodes, and both female and male genital tracts may also be infected.
Diagnostic Studies
TB Skin Test. The intradermal administration of tuberculin as a diagnostic test for tuberculous infection has been used for over 100 years. 21 The tuberculin skin test (TST) (Mantoux test) using purified protein derivative (PPI)) is the best way to diagnose latent M. tuberculosis infection. Induration (not redness) at the injection site 48 to 72 hours after the test means the person has been exposed to TB and has developed antibodies. The reaction occurs 2 to 12 weeks after the initial exposure. The induration is measured and, based on the size of the induration and the population risk, an i nterpretation is made according to diagnostic standards for deter-mining a positive test reaction. 24 If a person has y a positive reaction, he or she should not be tested again since the sensitivity to tuberculin tends to persist throughout life. Guidelines for targeted tuberculin testing emphasize targeting only high-risk groups and discourage testing low-risk individuals. Because the response to TST may be decreased in the immunocompromised patient, smaller induration reactions (25 mm) are considered positive. Two-step testing is recommended for initial testing for health care workers, who get repeated testing, and for individuals who have a decreased response to allergens. In these people, a second TST may cause an accelerated response ("booster effect") that may be misinterpreted as a new conversion. Chest X-Ray. Although the findings on chest X-ray examination are important, it is not possible to make a diagnosis of TB solely on the basis of this examination. This is because other diseases can mimic the x-ray appearance of TB. The chest
Active Disease. In view of the growing prevalence of multidrug resistant TB, the patient with active TB should be managed aggressively. Because of the high number of patients with organisms resistant to isoniazid (INH), four drugs are necessary in the initial phase for the 6-month regimen to be maximally effective. Four drug regimen options have been identified by the CDC for previously untreated TB. In most circumstances, the treatment regimen for patients with previously untreated TB consists of a 2-month initial phase with four-drug therapy (INH, rifampin [Rifadin] pyrazinamide [PZA] and ethambutol). If drug susceptibility test results indicate the bacteria are susceptible to all drugs, ethambutol may be discontinued. If PZA cannot be included in the initial phase (due to liver disease, pregnancy, etc.), option 4 is recommended. Drug Alert - Isoniazid (INH) Alcohol may Increase hepatotoxicity of drug. Instruct patient to avoid drinking alcohol during treatment. Monitor for Signs of liver damage before and while taking drug. Other drugs are primarily used for treatment of resistant strains or if the patient develops toxicity to the primary drugs. The newer rifamycins, rifabutin and rifapentine, should be considered first line in special situations: rifabutin for patients receiving medications that have interactions with rifampin or who have an intolerance to rifampin, and rifapentine with INH in once-weekly dosing for selected patients. 26 Directly observed therapy (DOT) involves providing the anti tuberculous drugs directly to the patient and watching as he or she swallows the medications. It is the preferred strategy for all patients with TB to assure adherence. 26 When DOT is not being used, fixed-dose combination antituberculous drugs may enhance adherence to treatment
recommendations. Combinations of isoniazid and rifampin (Rifamate) and of isoniazid, rifampin, and pyrazinamide (Rifater) are available to simplify therapy. The therapy for persons with HIV follows the same therapy options outlined in Table 28-10 except that alternative regimens that include once weekly INH plus rifapentine continuation dosing in any HIV infected patient and twice-weekly INH plus rifampin or rifabutin should not be used if CD4+ counts are < 100/111. Health care providers must be alert for possible drug interactions between antiretrovirals and rifamycins. Many second-line drugs for treatment of TB carry a greater risk of toxicity and require closer monitoring. Newer drugs for the treatment of TB that have been placed in categories of second-line drugs include the quinolones, such as levofloxacin, moxifloxacin, and gatifloxacin. An important reason for follow-up care in the patient with TB is to ensure adherence to the treatment regimen. Noncompliance is a major factor in the emergence of multidrug resistance and treatment failures. Many individuals do not adhere to the treatment program in spite of understanding the disease process and the value of treatment. DOT is recommended for patients known to be at risk for noncompliance with therapy. DOT is an expensive but essential public health issue. Completing therapy is important because of the danger of reactivation of TB and MDR-TB seen in patients who do not complete the full course of therapy. In many areas, the public health nurse administers DOT at a clinic site. Teaching patients about the side effects of these drugs and when to seek prompt medical attention is critical. The major side effect of isoniazid, rifampin, and pyrazinamide is nonviral hepatitis. Liver function tests should be monitored. Baseline liver function tests are done at the start of treatment. Monthly monitoring of liver function tests is done if baseline tests are abnormal. Latent Tuberculosis Infection. Latent TB infection (LTBI) occurs when an individual becomes infected with M. tuberculosis. Drug therapy can be used to prevent a TB infection from developing into active disease. The indications for treatment of LTBI are presented in Table 28-11. The drug generally used in treatment of LTBI is isoniazid (INH). It is effective and inexpensive and can be administered orally. Isoniazid is usually administered once daily for 6 to 9 months. INH can be given daily or twice
