Porth's Essentials of Pathophysiology, 4e

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Respiratory Tract Infections, Neoplasms, and Childhood Disorders

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requires that a health care worker physically observe the person’s ingestion of the medications, also improves adherence to the program. 16 The primary drugs used are isoniazid (INH), etham- butol, pyrazinamide, and rifampin. In addition to per- sons with active tuberculosis, persons who have had contact with cases of active tuberculosis and who are at risk for development of an active form of the disease are treated. 35–38 Prophylactic treatment is also used for persons who have latent tuberculosis infection but do not have active disease. These persons are considered to harbor a small number of microorganisms and usually are treated with INH. 34 Persons with drug-resistant M. tuberculosis infection require careful supervision and more extensive drug regimens. 36–38 Drug susceptibility tests are used to guide treatment. Tuberculosis in persons with concomitant HIV infection requires management by experts in both tuberculosis and HIV. Fungal Infections Although most fungal infections are asymptomatic, they can be severe or even fatal in persons who have experienced a heavy exposure, have underlying immune deficiencies, or develop progressive disease that is not recognized or treated. The host’s cell-mediated immune response is paramount in controlling such infections; thus, immunocompromised persons, particularly those with HIV infection, are particularly prone to develop- ment of severe or fatal infection. Pathologic fungi generally induce a delayed cell-medi- ated hypersensitivity response to their chemical constit- uents (see Chapter 15). Cellular immunity is mediated by antigen-specific T lymphocytes and cytokine-acti- vated macrophages that assume fungicidal properties. The primary pulmonary lesions consist of aggregates of macrophages stuffed with organisms, with similar lesions developing in the lymph nodes that drain the area. These lesions develop into granulomas complete with giant cells and may develop central necrosis and calcification resembling that of primary tuberculosis. Types of Infections Fungi are classified as yeasts and molds. Yeasts are round and grow by budding. Molds form tubular struc- tures called hyphae and grow by branching and form- ing spores (see Chapter 14). Some fungi are dimorphic, meaning that they grow as yeasts at body temperatures and as molds at room temperatures. A simple classification of mycoses (diseases caused by fungi) divides them into superficial, cutaneous, sub- cutaneous, or deep (systemic) mycoses. The superficial, cutaneous, or subcutaneous mycoses cause disease of the skin, hair, and nails. Deep fungal infections may produce pulmonary and systemic infections and are sometimes fatal. They are caused by virulent fungi that live freely, typically in soil or decaying organic matter and frequently in specific geographic regions. The most

common of these are the dimorphic fungi, Histoplasma capsulatum , Coccidioides immitis , and Blastomyces dermatitidis . 39,40 These fungi form infectious spores, which enter the body through the respiratory system. Most people who become infected with these fungi develop only minor symptoms or none at all—only a small minority develop serious disease. Each of the dimorphic fungi has a typical geographic distribution. H. capsulatum, which is the etiologic agent in histoplasmosis , is endemic along the major river val- leys of the central and eastern United States (i.e., Ohio, Missouri, Mississippi river valleys), eastern Canada, Mexico, Central and South America, Africa, and south- east Asia. 40,41 The organism grows in areas that have been enriched with bird excreta: old chicken houses, pigeon lofts, barns, and trees where birds roost. The infection is acquired by inhaling the fungal spores that are released when the dirt or dust from the infected areas is disturbed. C. immitis, which causes coccidioidomyco- sis , is most prevalent in the southwestern United States, principally in California, Arizona, and Texas; Mexico; and Central and South America. 40,42 Because of its prev- alence in the San Joaquin Valley, the disease is some- times referred to as San Joaquin fever or valley fever. C. immitis lives in soil, and events that disturb soil, such as dust storms and digging during construction, have been associated with increased incidence of the disease. B. capsulatum, the agent causing blastomycosis , is most commonly found in the south-central and northwestern United States and Canada. 40,43 Clinical Features Depending on the host’s resistance and immunocompe- tence, the diseases usually take one of three forms: (1) an acute primary disease, (2) a chronic (cavitary) pulmo- nary disease, or (3) a disseminated infection. The lesions of fungal infections consist of epithelioid cell granuloma- tous containing aggregates of macrophages with engulfed microorganisms. Similar nodules develop in the regional lymph nodes. There is a striking similarity to the primary lesions of tuberculosis. The clinical manifestations often consist of a mild, self-limited flulike syndrome. In the vulnerable host, chronic cavitary lesions develop, with a predilection for the upper lobe of the lung, resembling the secondary form of tuberculosis. The most common manifestations are productive cough, fever, night sweats, and weight loss. Disseminated dis- ease most often develops as an acute and fulminating infection in the very old or the very young or in per- sons with compromised immune function. Although the macrophages of the reticuloendothelial system can remove the fungi from the bloodstream, they are unable to destroy them. Characteristically, this form of the dis- ease presents with a high fever, generalized lymph node enlargement, hepatosplenomegaly, muscle wasting, ane- mia, leukopenia, and thrombocytopenia. There may be hoarseness, ulcerations of the mouth and tongue, nausea, vomiting, diarrhea, and abdominal pain. Often, menin- gitis becomes a dominant feature of the disease. Persons with blastomycosis may experience cutaneous infections