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Section 10. Pulmonary Disorders
Chapter 76. Pulmonary Infections
Topics:    Pneumonia | Tuberculosis | Influenza

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Tuberculosis

An infectious disease caused by Mycobacterium tuberculosis.

In the USA, the number of reported cases of tuberculosis (TB) has declined since 1992. However, the number of cases among foreign-born persons residing in the USA is steadily rising, particularly in adults > 45. The elderly are especially at risk of infection; 20 to 30% of newly diagnosed cases of TB occur in persons >= 65. Elderly residents of long-term care facilities are at increased risk of reactivation of latent infection and are susceptible to new infection. About 90% of TB cases in the elderly are due to reactivation of a primary infection.

About 75% of all cases of TB in the elderly occur in the respiratory tract. Common extrapulmonary sites include the bones and joints, particularly the spine, and the genitourinary tract. Miliary TB, a form of disseminated TB, is also relatively common in the elderly.

Pathogenesis

Primary TB infection (ie, no previous exposure to M. tuberculosis) is acquired by inhaling droplet nuclei of viable organisms. Tubercle bacilli may evade the host immune mechanisms in the upper lung zones, brain and meninges, bone, and kidneys, often remaining dormant as long as the host immune system remains intact. Factors such as poor nutrition, homelessness, imprisonment, alcoholism or drug addiction, and immune dysfunction caused by disease, drugs, or aging can reactivate dormant bacilli. In the elderly, reactivation is often caused by diseases common to this age group (eg, diabetes mellitus, malignancies, chronic renal failure), poor nutrition, and the use of immunosuppressants, especially corticosteroids. The major component of the immune system affected by aging is T-lymphocyte-mediated responses, although this component may not be entirely responsible for the increased susceptibility of the elderly to TB.

Some infected persons eventually eliminate the viable tubercle bacilli and revert to negative tuberculin reactor status. These persons have no lasting immunity and are thus susceptible to reinfection.

Persons who have contained the primary infection and who remain asymptomatic with a positive tuberculin skin test are described as having TB infection; those who have symptoms of infection are said to have TB disease. Persistent TB infection without disease occurs in 30 to 50% of cases. Some elderly persons who were previously infected with M. tuberculosis lose their cellular immune reactivity (as indicated by a negative tuberculin skin test) to the organism. Consequently, they are at risk of reinfection with M. tuberculosis.

Symptoms and Signs

Pulmonary TB typically produces respiratory and systemic symptoms of cough, excessive sputum production, hemoptysis, fever, anorexia, weight loss, night sweats, and fatigue, although these symptoms are less common in the elderly.

Miliary TB may occur in elderly patients in either of two forms. The elderly are more likely to present with the nonreactive form, which is an overwhelming tuberculous infection consisting of numerous small caseous lesions with large numbers of replicating bacilli, sparse neutrophil infiltrate, and no granulomatous reaction. Clinical features include acute onset of fever, weight loss, hepatosplenomegaly, and, occasionally, fever of undetermined origin. The chronic hematogenous form consists of repeated episodes of low-grade M. tuberculosis bacillemia, with a slowly progressive protracted illness associated with low-grade fever without localizing symptoms or signs. Radiographic changes of miliary mottling may not be present.

Tuberculous meningitis in the elderly produces clinical features similar to those seen in younger persons, ie, headache, fever, weakness, and confusion. In addition, elderly patients may present with unexplained dementia or obtundation.

Tuberculous spinal infection may cause paravertebral abscesses. Presenting symptoms are pain over the involved vertebrae, fever, weight loss, and constitutional symptoms; in advanced cases, neurologic deficits or sinus tracts may develop.

Tuberculous arthritis can involve large weight-bearing joints, such as the hips, but in the elderly, other peripheral joints, such as the knees, wrists, ankles, and metatarsophalangeal joints, may be involved as well. Degenerative joint disease, common in the elderly, may make the diagnosis more difficult.

Genitourinary TB may involve any part of the genitourinary tract, including the kidneys, ureters, bladder, prostate, epididymis, and seminal vesicles. About 20 to 33% of patients with kidney involvement are asymptomatic. Symptoms, when present, include flank pain, dysuria, and gross hematuria. Abnormal urinary sediment, especially sterile pyuria and hematuria, is a common finding. Rarely, genitourinary TB involves the genitals, and the patient may present with a scrotal or pelvic mass or draining sinus and no systemic symptoms.

Other sites that may be affected by TB include the lymph nodes, pleura, liver, gallbladder, small intestine, large intestine, pericardium, middle ear, and carpal tunnel, although virtually any organ may be infected with M. tuberculosis.

Diagnosis

TB in the elderly often is difficult to diagnose because of nonspecific symptoms and clinical presentations that are often remote from the disease site. TB should be considered in the differential diagnosis in elderly persons who present with the clinical manifestations described above that involve specific organ systems, as well as in elderly persons with a mild decline in their health status, functional capacity, or state of well-being. Because chest x-rays may be atypical, some authorities recommend that any elderly person who requires hospitalization for pneumonia have at least one sputum culture for TB.

Tuberculin skin test: The Mantoux method of skin testing with polysorbate-stabilized purified protein derivative (PPD) antigen is the standard screening procedure for TB infection and reflects the delayed-type hypersensitivity response to M. tuberculosis antigen. A positive test result indicates that the person harbors viable organisms, although the test does not distinguish TB infection from TB disease. The dose of 5 tuberculin units is biologically standardized and routinely used for skin testing. The skin is examined 48 to 72 hours after intradermal PPD injection, at which time the diameter of induration is measured. The size of the induration reaction correlates to some extent with the probability of TB; induration of >= 10 mm is significant. A smaller reaction (5 to 10 mm of induration) is suspect in high-risk populations. The bacille Calmette-Guérin vaccine, which may have been administered to some foreign-born elderly persons in childhood, has an unpredictable effect on PPD skin test reactivity, but reactivity to the vaccine often wanes after 10 years.

Because skin-test reactivity to tuberculin wanes with time, a test that produces a negative result in the elderly should be repeated (using the same dose) a week later to detect the booster phenomenon. Most elderly patients with TB disease have positive test results. The higher-strength (250 tuberculin units) PPD test generally should be avoided, and patients with a history of having positive test results should not be retested.

Chest x-ray: Primary TB can involve any lung segment but usually involves the middle or lower lobes as well as the mediastinal or hilar lymph nodes. The usual sites of lung involvement for reactivated TB are the apical and posterior segments of the upper lobes and the superior segments of the lower lobes. However, the lower lung fields and anterior segment of the upper lobes may also be involved. Infiltrates in the elderly may be interstitial, lobar, patchy or cavitary, and bilateral.

Laboratory findings: Clinical specimens taken from suspected sites of TB are initially examined by smear to detect acid-fast bacilli and are subsequently cultured for M. tuberculosis. In the case of possible pulmonary or genitourinary involvement, three consecutive early morning sputum or urine specimens, respectively, are recommended for routine mycobacteriologic studies. Induced-sputum or bronchoscopic specimens may be needed for patients who cannot expectorate sputum. Sterile body fluids and tissues can be inoculated into a liquid medium, which allows growth and detection of M. tuberculosis 7 to 10 days earlier than the solid medium techniques.

On histologic examination, tissue that shows caseous necrosis with granuloma formation with or without acid-fast bacilli also strongly supports the diagnosis.

Polymerase chain reaction testing detects very small numbers of TB, may help increase the sensitivity of diagnosis, and may be used to predict drug resistance before standard results are available. The nucleic acid amplification test uses transcription-mediated amplification to detect M. tuberculosis-complex ribosomal RNA. Serologic tests for detecting antibodies against mycobacterial antigens have not been refined sufficiently for routine clinical use.

Prevention and Treatment

The Centers for Disease Control and Prevention (CDC) has established recommendations for surveillance, control, and reporting of TB in long-term care facilities and acute-care institutions. All new employees and new residents in long-term care facilities should undergo an initial skin test and then annual testing. The two-step PPD screening is recommended as part of the initial comprehensive assessment of all elderly patients. Chest x-rays are recommended for all persons who test tuberculin positive on admission to a long-term care facility to ensure that they do not have pulmonary infiltrates consistent with TB. In addition, the CDC recommends that all persons suspected of having TB have a chest x-ray, regardless of the primary site of infection.

TB infection: High-risk persons of any age who do not have active disease should undergo treatment of TB infection with isoniazid 300 mg/day po for 6 to 12 months. Persons considered to be at high risk are household members and other close contacts of potentially infectious persons; newly infected persons (those who have had a tuberculin skin test conversion within the previous 2 years); persons with positive skin tests and abnormal chest x-rays compatible with previous TB; and persons with positive skin tests and clinical situations favorable to infection, such as silicosis, diabetes, immunosuppression (including that resulting from corticosteroid administration and cancer chemotherapy), HIV-positive serologic findings, hematologic and reticuloendothelial malignancies, end-stage renal disease, and associated conditions characterized by rapid weight loss or chronic malnutrition.

TB disease: Patients with active TB require four antituberculous drugs, usually isoniazid, rifampin, pyrazinamide, and ethambutol. Treatment is given for 2 months, until sensitivity test results are available. All M. tuberculosis isolates should undergo sensitivity testing for resistance. Patients with strains of TB sensitive to isoniazid and rifampin should receive these drugs for an additional 4 months. Isoniazid and rifampin are usually effective because most elderly patients acquired their original strains many decades before, when most TB strains were susceptible to these drugs. A 9-month course of isoniazid and rifampin is also acceptable as an alternative therapy for most elderly patients. Pyridoxine 25 to 50 mg/day po is given to prevent peripheral neuropathy caused by isoniazid use. These recommendations are modified if in vitro sensitivity tests indicate infection with resistant strains.

All patients with TB should remain under observation until adherence with their treatment regimen is established. Treatment monitoring includes obtaining baseline measurements of liver enzyme, bilirubin, and serum creatinine levels; a CBC; and a platelet count or estimate. Serum uric acid concentration should be measured when pyrazinamide is used. Patients should be monitored at least monthly for symptoms suggesting hepatitis (eg, jaundice, fever, anorexia, dark urine), which is more common in the elderly and is a common adverse effect of isoniazid use. Testing liver function with aspartate transaminase is recommended, especially during the first 6 months of treatment, when hepatitis is most likely to occur. If transaminase levels increase >= 5 times higher than the upper limit of normal values, isoniazid should be discontinued. For patients with active disease, sputum should be examined at least monthly until cultures convert to negative. In about 90% of patients, cultures convert within 3 months of initiating the recommended regimens.

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