Fungal, or mycotic, infections are normally superficial, but a few fungi can cause serious systemic disease, usually entering through the respiratory tract in the form of spores. Disease manifestation depends on the degree and type of immune response elicited by the host. Fungi are common and harmless inhabitants of skin and mucous membranes under normal conditions (e.g., Candida albicans). In immunocompromised hosts, Candida spp. and other fungi become opportunistic agents that take advantage of the host’s weakened resistance. Manifestations of fungal disease may range from unnoticed respiratory episodes to rapid, fatal dissemination of a violent hypersensitivity reaction.

Survival mechanisms of fungi that successfully invade the body are similar to bacterial characteristics and include the following: (1) presence of an antiphagocytic capsule; (2) resistance to digestion within macrophages; and (3) destruction of phagocytes (e.g., neutrophils). Some types of yeast activate complement through the alternative pathway, but it is unknown whether this activation has any effect on the microorganism’s survival.

Fungal infections are increasing worldwide for a variety of reasons, including the use of immunosuppressive drugs and the development of diseases that result in an immunocompromised host (e.g., acquired immune deficiency syndrome [AIDS]). Serologic tests often play an important role in the diagnosis of these fungal infections (Table 1).

Table1. Testing Methods for Fungal Disease

Several species of fungi are associated with respiratory dis ease in human beings. These diseases are acquired by inhaling spores from exogenous reservoirs, including dust, bird drop pings, and soil.

Histoplasmosis

Histoplasma capsulatum can be found in soil contaminated with chicken, bird, or bat excreta. Spore-laden dust is the source of histoplasmosis, caused by inhalation.

Histoplasmosis can be difficult to diagnose and can range from asymptomatic to chronic pulmonary disease. In addition, a disseminated form manifesting hepatosplenomegaly with diffuse lymphadenopathy is usually present in varying degrees of severity because of the propensity of the fungus to invade the cells of the mononuclear phagocyte system. Disseminated disease is characterized by fever, anemia, leukopenia, weight loss, and lassitude.

Definitive diagnosis requires isolation in culture and microscopic identification of the fungus, as well as serologic evidence. If an immunodiffusion technique is used, H and M bands appearing together indicate active infection. If only an M band is present, it indicates early infection, chronic infection, or a recent reactive skin test. An H band appears later than the M band and disappears earlier. Disappearance of an H band suggests regression of the infection.

Delayed hypersensitivity skin testing is confirmed by a rise in complement-fixing antibodies to Histoplasma antigens. Titers of 8 and 16 (dilutions of 1:8 and 1:16) are highly suggestive of infection. A titer of 32 or higher usually indicates active infection. A rising titer indicates progressive infection; a decreasing titer suggests regression. Some disseminated infections are non-reactive in complement fixation (CF) tests. In addition, recent skin tests in individuals with prior exposure to Histoplasma capsulatum will produce a rise in the CF titer in 17% to 20% of patients. Cross-reactions in the CF test occur in patients with aspergillosis, blastomycosis, or coccidioidomycosis, but the titers are usually lower. Several follow-up serum samples should be tested at 2- to 3-week intervals.

Aspergillosis

Another opportunistic mycotic infection occurring in human beings is aspergillosis, which can be allergic, invasive, or disseminating, depending on pathologic findings in the host. Aspergillosis is usually secondary to another disease. Allergic bronchopulmonary aspergillosis is characterized by allergic reactions to the toxins and endotoxins of Aspergillus spp.

Species identification of aspergillosis can be made microscopically. Serologically, skin reactions and immunodiffusion are useful tools for identification, especially if the culture is negative.

Immunodiffusion antibody test with reference antisera and known antigen is a frequently used test for the identification of Aspergillus spp. in almost all clinical types of aspergillosis. Precipitin formation by immunodiffusion is useful for identifying patients with pulmonary eosinophilia, severe allergic aspergillosis, and aspergillomas. The presence of one or more precipitin bands suggests active infection. The precipitin bands correlate with CF titers. In this test, the greater the number of bands, the higher is the titer. In general, immunodiffusion measures IgG and a positive result may suggest past infection. The test is positive in about 90% of sera from patients with aspergilloma and 50% to 70% of patients with allergic bronchopulmonary aspergillosis. A negative test does not exclude aspergillosis.

In addition, the enzyme immunoassay (EIA) can be used to detect IgE and IgG antibodies. ImmunoCAP is a newer method used to detect Aspergillus niger IgE in serum.

Enzyme immunoassay is used to detect Aspergillus galactomannan antigen in serum. Negative results do not exclude the diagnosis of invasive aspergillosis. A single positive test result should be confirmed by testing a separate serum specimen. Many agents (e.g., antibiotics, food) can cross-react with the assay. The false-positive rate is higher in children than in adults. If invasive aspergillosis is suspected in high-risk patients, serial sampling is recommended.

Hypersensitivity testing is characterized by immediate and delayed-type hypersensitivity reactions as a result of the presence of Aspergillus-specific immunoglobulin. IgE titers are greatly increased in allergic bronchopulmonary aspergillosis.

Coccidioidomycosis

 Coccidioidomycosis is also known as desert fever, San Joaquin fever, or valley fever. The disease may assume several forms, including primary pulmonary, primary cutaneous, and disseminated. The disease is contracted from inhalation of soil or dust containing the arthrospores of Coccidioides immitis.

Hypersensitivity testing using intradermal injections is useful in screening for C. immitis. It is usually the first immunologic test to be positive in asymptomatic and symptomatic cases. Skin testing does not differentiate between recent and past exposures to C. immitis. A positive skin test should be followed by other serodiagnostic tests. A negative test in a previously positive person can indicate a disseminated infection and a state of anergy.

T he fluorescent antibody (FA) test can be applied directly to clinical specimens. This procedure is invaluable for making a rapid and specific identification of fungal structures. In addition to culturing the organism, serologic tests used to confirm the diagnosis of coccidioidomycosis include the tube precipitin test, immunodiffusion, CF, and latex agglutination. The CF test is the most widely used quantitative serodiagnostic test to identify infection with C. immitis. It is very effective in detecting disseminated disease. The tube precipitin test is positive in more than 90% of primary symptomatic cases.

Immunodiffusion is equivalent to CF; it can be used as a screening test, but the results should be confirmed by CF. Latex agglutination is not usually a recommended method because it lacks specificity, which leads to many false-positive results.

Two antigens have been developed for the serologic identification of circulating antibodies to C. immitis. IgM appears 1 to 3 weeks after infection in 90% of symptomatic patients. IgG develops 3 to 6 months after the onset of symptoms. Titers of 1:2 to 1:4 are presumptive evidence of an early infection and should be repeated in 3 to 4 weeks. Titers of 1:8 to 1:16 are evidence of active infection, particularly when accompanied by a positive immunodiffusion test. Titers higher than 1:16 occur in 90% to 95% of patients with disseminated coccidioidomycosis.

North American Blastomycosis

Blastomycosis is a chronic fungal disease that is usually secondary to pulmonary involvement. Blastomyces dermatitidis causes tumors in the skin or lesions in the lungs, bones, subcutaneous tissues, liver, spleen, and kidneys.

Serologic diagnosis is problematic because of high cross reactivity with antigenic components of the organism. Although immunodiffusion and CF are used, immunodiffusion is considered the better method. CF titers of 8 and 16 are highly suggestive of active infection and titers of 32 or higher are diagnostic. A decreasing titer indicates regression; however, most patients with blastomycosis have negative CF tests.

Sporotrichosis

This chronic, progressive, subcutaneous lymphatic mycosis is caused by Sporothrix schenckii. The disease takes three forms— lymphatic (which is the most common), disseminated, and respiratory. It is characterized by a sporotrichotic chancre at the site of inoculation, followed by the development and formation of subcutaneous nodules along the lymphatics draining the primary lesions. Infection is associated with injuries caused by thorns or splinters. Handlers of peat moss are particularly susceptible to the disease, especially when working in rose gardens.

Laboratory methods of identification include cultures, serologic techniques, and the FA staining technique. Two of the most sensitive tests are yeast cell and latex agglutination. Titers of 80 or higher usually indicate active infection.

Skin testing is also available. Patients with cutaneous infection usually demonstrate negative tests; patients with extracutaneous infections have positive tests.

Cryptococcosis

Cryptococcus neoformans is the etiologic agent of this disease. Infected pigeons are the chief vector. Cryptococcosis is acquired by inhaling the fungus, which grows in culture as yeast. It may initially be asymptomatic or may develop as a symptomatic pulmonary infection. Any organ or tissue of the body may be infected, but localization outside the lungs or brain is relatively uncommon. The disease can be serious in immunocompromised or debilitated patients.

Antigen tests take less time to perform and are more specific than antibody detection. Latex agglutination antigen tests can be performed on serum or cerebrospinal fluid (CSF). Titers of 1:2 suggest infection, although such findings have been found in individuals with no evidence of cryptococcosis. Titers of 1:4 or higher are evidence of an active infection. Higher titers also indicate more severe infections. Positive titers are found in CSF in 95% of patients with involvement of the central nervous system.

The indirect FA test detects antibodies to C. neoformans. It is most valuable when antigen tests are negative and can even be combined with an antigen test to determine a patient’s prognosis. A positive test suggests a present or recent infection.

Complement fixation is the most specific antibody detection test but is very insensitive. Tube agglutination, using serum or CSF that demonstrates a titer of 1:2 or higher, suggests a current or recent infection with C. neoformans.

As cryptococcosis progresses, antigens begin to appear, along with a decrease in antibody production. After treatment, a decrease in antigen titer and reappearance of antibodies indicate a good prognosis.

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مواضيع ذات صلة

Immunologic Manifestations of Viral, Rickettsial, and Mycoplasmal Diseases

The Structure of Antibodies

Myelomas and Monoclonal Antibodies

Telling the Difference Between Foreign and Self

The Basic Adaptive Immune Response

The Immunoglobulin Domain and Variations

Deficiencies of the Immune Response

Hypersensitivity

Cytokines

Complement Deficiencies and Pathogen Evasion

Complement Pathways

T Cells