321. The answer is d. (Levinson, p 295.) Cryptococcus neoformans causes cryptococcosis, especially cryptococcal meningitis. The organisms can be seen in cerebrospinal fluid (CSF) in india ink preparations as an oval budding yeast surrounded by a wide, unstained polysaccharide capsule. Candida albicans, the most important species of Candida, causes thrush and vaginitis, as well as other diseases. It may appear in tissue as a budding yeast or as elongated pseudohyphae (nonseptate). Sporothrix schenckii is a dimorphic fungus which appears as round or cigar-shaped budding yeasts in tissue. It causes a local pustule or ulcer that may become chronic.
322. The answer is a. (Murray, pp 1164, 1300.) Drechslera is a dematia-ceous fungus that had previously been named Helminthosporium. Colonies are fluffy and gray to brownish-black in color. The hyphae are septate and the conidia are multiseptate and elongate. The conidiophores may be twisted.
323. The answer is b. (Levinson, pp 289-293.) Thick-walled spores are characteristic of many fungal infections, including blastomycosis, coccid-ioidomycosis, and histoplasmosis. Observation of these structures in sputum or in tissue should alert the microbiologist to a diagnosis of systemic fungal infection. The presence of encapsulated yeast in clinical specimens may suggest the presence of Cryptococcus.
324. The answer is b. (Levinson, pp 287-288.) Hairs infected with Microsporum canis and M. audouini both fluoresce with a yellow-green color under Wood's light, while Trichophyton rubrum, T. tonsurans, and Epidermo-phyton floccosum do not. But M. audouini is an anthropophilic agent of tinea capitis, whereas M. canis is zoophilic. M. canis is primarily seen in children and is associated with infected cats or dogs.
325. The answer is d. (Levinson, p 295.) Patients with paralysis of their cellular immune system, such as in AIDS, are susceptible to a wide variety of diseases, including infection with Cryptococcus. A brain abscess caused by C. neoformans is not unusual in patients with AIDS. Initial laboratory suspicion is usually aroused by the presence of encapsulated yeast in the CSF. There also could be other microorganisms as well as noninfectious artifacts that superficially resemble yeast. While C. neoformans can be readily cultured, a rapid diagnosis can be made by detecting cryptococcal capsular polysaccharide in CSF or blood. Care must be taken to strictly control the test because rheumatoid factor may cross-react. Once the yeast is isolated, then specific stains as well as panels of assimilatory carbohydrates are available to definitively identify this organism as C. neoformans. The patient may also be infected with Pneumocystis carinii, but not in the central nervous system. P carinii has recently been reclassified as a fungus.
326. The answer is b. (Levinson, p 295.) C. neoformans occurs widely in nature, particularly in soil contaminated with bird droppings. Human infection occurs when inhalation of the organism occurs. Lung infection is often asymptomatic but can result in pneumonia. Meningitis occurs through dissemination, particularly in immunosuppressed patients. India ink preparations of CSF reveal a budding yeast with a wide, unstained capsule in infected persons.
327. The answer is d. (Levinson, pp 287-288.) Eumycotic mycetoma is a slowly progressing disease of the subcutaneous tissues that is caused by a variety of fungi. The term Madura foot has been used to describe the foot lesion. Although several fungi have been isolated in the United States from persons who have mycetoma, Pseudallescheria boydii appears to be one of the most common. Other foot infections that may resemble Madura foot are actinomycotic (bacterial) in nature. These are caused by Nocardia brasiliensis and Actinomadura.
328. The answer is d. (Levinson, p 284.) Granuloma formation occurs in response to infection with many fungi. This cell-mediated immune response is seen in coccidioidomycosis, histoplasmosis, and blastomycosis, as well as in several others.
329. The answer is c. (Howard, pp 600-604.) Cutaneous sporotrichosis, caused by S. schenckii, begins at the site of inoculation, usually on an extremity or the face. The organism often is found on thorns of rose bushes. Ulceration is common and new lesions appear along paths of lym phatic channels. Extracutaneous sporotrichosis is seen primarily in bones and joints. There is no evidence to suggest that any portal of entry besides skin is important.
330. The answer is c. (Levinson, p 287.) The dermatophytes (see figure presented in the question) are a group of fungi that infect only superficial keratinized tissue (skin, hair, nails). They form hyphae and arthroconidia on the skin; in culture, they develop colonies and conidia. Tinea pedis, or athlete's foot, is the most common dermatophytosis. Several topical anti-fungal agents, such as undecylenic acid, salicylic acid, and ammoniated mercury, may be useful in treatment. For serious infection, systemic use of griseofulvin is effective.
331. The answer is c. (Levinson, pp 243—295.) C. albicans is the most important species of Candida and causes thrush, vaginitis, skin and nail infections, and other infections. It is part of the normal flora of skin, mouth, GI tract, and vagina. It appears in tissues as an oval budding yeast or elongated pseudohyphae. It grows well on laboratory media and is identified by germ-tube formation. A vaccine is not available and serologic and skin tests have little value.
332. The answer is b. (Howard, pp 616-617.) C. albicans is part of the normal flora of the gastrointestinal tract, mouth, and genital surfaces. Notwithstanding, C. albicans causes severe disease particularly in those patients with compromised immunity. It is generally thought that when C. albicans is unable to adhere to mucosa it is nonpathogenic and that production of germ tubes or hyphae plays a major role in colonization and infection of the mucosal epithelial cells by allowing direct penetration of these cells with specific hydrolytic enzymes. While other mutations such as temperature intolerance, metabolic alterations, and structural substitutions may affect the ability of Candida to survive, these changes would not affect adherence.
333. The answer is a. (Murray, pp 1217-1225.) While all fungi such as Candida and Cryptococcus are potentially serious in a bone marrow transplant unit (BMTU), the most frequent cause of fungal infection and death is Aspergillus. Aspergilli are ubiquitous in the environment. There are instances of multiple infections in new units that have not been monitored prior to opening or in units adjacent to construction projects. Strict precautions should be taken to exclude dust and debris from the BMTU area during construction, but in any event the environment should be monitored for airborne microorganisms, especially Aspergillus, prior to opening the unit.
334. The answer is d. (Levinson, pp 290-291.) Histoplasma capsulatum is a dimorphic fungus that forms two types of spores: tuberculate macro-conidia and microconidia. Inhalation of the microconidia transmits infection. Inhaled spores (microconidia) are engulfed by macrophages and develop into yeast forms. Most infections remain asymptomatic; small granulomatous foci heal by calcification. However, pneumonia can occur. The heterophile antibody test is useful for early diagnosis of infectious mononucleosis. The figure below illustrates the oval budding yeasts.
335. The answer is b. (Levinson, pp 289-290.) Coccidioides immitis is a dimorphic fungus endemic in the southwestern United States. Arthro-spores found in the soil are inhaled and infect the lungs, forming large, thick-walled spherules filled with endospores. A cell-mediated immune response results in asymptomatic infection in most people. Dissemination can occur in immunocompromised persons. A delayed hypersensitivity, manifest as red nodules (erythema nodosum) on extensor surfaces such as the shins, is an indicator of good prognosis. A rising titer of complement-fixing (CF) antibodies indicates dissemination; a decrease in titer correlates with a response to therapy. The figure below illustrates the spherules filled with endospheres.
336. The answer is a. (Levinson, pp 293-295.) C. albicans and Candida tropicalis are opportunistic fungi, and as part of the normal flora are not transmitted by inhalation. C. immitis is a dimorphic fungus and inhalation of the spores transmits the infection. Sprothrix is also a dimorphic fungus but its portal of entry is cutaneous. Trychophyton is a dermatophyte and one of the causes of athlete's foot.
337. The answer is c. (Levinson, pp 295-296.) Aspergillus is an opportunistic pathogen that can invade wounds, burns, abraded skin, cornea, and outer ear. However, in immunocompromised patients, infection of the wound site is not common. Aspergillus does not cause urinary tract infection. In immunocompromised persons, invasive disease occurs. Blood vessel invasion can result in thrombosis and infarction. In pulmonary cavities (due to tuberculosis), "fungus ball" formation can occur, which can be seen on x-ray. Infection of the bronchi can result in allergic bronchopulmonary aspergillosis, characterized by asthmatic symptoms. Thrush is caused by C. albicans. Rashes are not usually seen with Aspergillus infection.
338. The answer is a. (Levinson, pp 289-290.) In patients with coccidioidomycosis, a positive skin test to coccidioidin appears 2 to 21 days after the appearance of disease symptoms and may persist for 20 years without reex-posure to the fungus. A decrease in intensity of the skin response often occurs in clinically healthy people who move away from endemic areas. A negative skin test frequently is associated with disseminated disease. Complement-fixing (CF) immunoglobulin G (IgG) antibodies, which may not appear at all in mild disease, rise to a high titer in disseminated disease, a poor prognostic sign. For this reason, a persistent or rising CF titer combined with clinical symptoms indicates present or imminent dissemination. Rarely is the CF titer negative. Most persons infected with C. immitis are immune to reinfection.
339-342. The answers are 339-d, 340-a, 341-c, 342-b. (Levinson, pp 293-297.) Fungi that cause opportunistic infections are diverse, and most of them are represented in this group of questions. Infection occurs primarily in the compromised host with underlying diseases such as lymphoma, leukemia, and diabetes. Unfortunately, most of the opportunistic fungi that cause infection are commonly seen in the laboratory as contaminants.
Candidiasis is the most frequent opportunistic infection. While C. albi-cans is most commonly isolated, other species such as C. tropicalis and Toru-lopsis glabrata are also seen. The yeasts may be identified biochemically, but C. albicans is distinctive in that it produces germ tubes and chlamydospores.
Zygomycosis, a term referring to infection by members of the class Zygomycetes, is caused by Rhizopus, Mucor, and Absidia primarily Other Zygomycetes such as Basidiobolus and Cunninghamella are rarely encountered. The lack of septate hyphae on a direct smear may be the initial hint of zygomycosis. However, not uncommonly, the occasional hypha of Mucor will have a septa. The genera cannot be differentiated on a direct patient specimen. The organism must be isolated and slide cultures performed to observe the characteristic morphology of these filamentous fungi.
Rhizopus species have sporangia that arise from a stolon, while Mucor species do not. Mucor species have collarettes; Rhizopus species do not.
Aspergillosis, caused by a number of species of Aspergillus, is characterized in direct smear by septate hyphae, dichotomously branched. A. flavus and A. fumigatus are often seen as saprophytes in the laboratory but also account for the major species isolated from patients with aspergillosis. Differentiation of species, as with the Zygomycetes, is dependent upon isolation of the fungus and precise morphological examination.
343-347. The answers are 343-c, 344-e, 345-d, 346-b, 347-a.
(Howard, pp 543—560.) The classification of fungi is complicated because one pathogenic fungus (holomorph) may have two names—that of the anamorph (asexual form) and that of the teleomorph (sexual form). For example, the teleomorph of Histoplasma capsulatum is Ajellomyces capsulata. It is also interesting to note that the teleomorph (Ajellomyces) of two distinct genera, Blastomyces and Histoplasma, is the same. Similarly the dermato-phyte Microsporum gypseum is the anamorph of two distinctly different sexual forms—Nannizzia gypsea and N. incurvata—and the teleomorph of Trichophyton mentagrophytes is Arthroderma van breuseghemii. The commonly known pathogenic fungus Cryptococcus neoformans has as its teleomorph Filobasidiella neoformans, a name that to date has little clinical meaning.
For those fungi in which no sexual stage has been found, the term fungi imperfecti serves as a convenient repository of asexual forms. In clinical practice, to avoid confusion, the name of the asexual stage is routinely reported.
348-352. The answers are 348-b, 349-c, 350-a, 351-e, 352-d.
(Levinson, pp 287, 289-290, 288, 292.) Microscopic examination of fungal isolates is essential to the identification of the organism. Macroscopically, the colonies of Epidermophyton have a yellowish appearance. This fungus invades skin and nails but never hair. On microscopic examination, clavate or paddle-shaped macroconidia are evident with rounded ends and smooth walls. Microconidia are absent.
C. immitis is a dimorphic fungus endemic in some regions of the southwestern United States and in Latin America. In tissue, the organism exists as a spherule filled with endospores. When grown on solid media, the organism produces barrel-shaped arthroconidia, which stain with lac-tophenol cotton blue.
Phialophora verrucosa is one of the causes of chromoblastomycosis, a chronic localized infection of the skin and subcutaneous tissue. Microscop ically, short or somewhat elongated, flask-shaped, pigmented phialides are seen. The collarettes are vase-shaped and darkly pigmented.
M. canis is a dermatophyte that infects skin and hair but rarely nails. When hair is infected with this organism, it will fluoresce. Microscopic examination of this organism demonstrates rough-walled macroconidia of 8 to 15 cells.
Blastomyces dermatitidis causes a chronic granulomatous disease. The yeast cells are globose or ovoid in shape. The single blastoconidium is attached by a broad base to the parent cell. The following figure illustrates the broad-based budding cells.
353-357. The answers are 353-c, 354-a, 355-a, 356-c, 357-b.
(Levinson, p 287.) Dermatomycoses are cutaneous mycoses caused by three genera of fungi: Microsporum, Trichophyton, and Epidermophyton. These infections are called tinea or ringworm, a misnomer that has persisted from the days when they were thought to be caused by worms or lice.
Tinea capitis (ringworm of the scalp) is due to an infection with M. canis or T. tonsurans. It usually occurs during childhood and heals spontaneously at puberty. Circular areas on the scalp with broken or no hair are characteristic of this disorder.
Tinea corporis (ringworm of the body) is caused by M. canis and T. mentagrophytes. This disorder affects smooth skin and produces circular pruritic areas of redness and scaling. Both tinea cruris (ringworm of the groin, "jock itch") and tinea pedis (ringworm of the feet, athlete's foot) are caused by T rubrum, T. mentagrophytes, or E. floccosum. These common conditions are pruritic and can cause scaling.
Tinea versicolor (pityriasis versicolor) is not a dermatomycotic condition but, rather, a superficial mycosis now thought to be caused by Malassezia furfur The disorder is characterized by chronic but asymptomatic scaling on the trunk, arms, or other parts of the body.
358-362. The answers are 358-e, 359-c, 360-a, 361-b, 362-d.
(Howard, pp 627—629.) Candidiasis, cryptococcosis, zygomycosis, and aspergillosis are among the most common opportunistic fungal infections. These fungi are commonly observed in the environment and are innocuous to people with intact host defenses. However, when host defenses are compromised by immunosuppression (AIDS), cytotoxic drugs, diabetes, or devices that breach the normal host defenses, these usually harmless fungi become potent pathogenic microorganisms.
Lungs are the most common site for infection by Aspergillus. These infections range from allergic bronchopulmonary disease (with increased serum IgE), to fungus balls known as aspergillomas, to life-threatening invasive infections of the lung parenchyma. Typically, the fungus will spread to other organs. Patients with lymphoma, for instance, are highly susceptible to invasive aspergillosis. Death rates of 25% are not uncommon.
C. albicans is a member of the normal human microflora. This yeast causes such relatively mild infections as "jock itch" and diaper rash. Suppression of cellular immunity often results in more serious yeast infections. Oral candidiasis is one of the earliest and most frequent of the opportunis tic infections in patients with AIDS. Diagnosis of invasive candidiasis is difficult, especially when patients are symptomatic and Candida is not recovered from blood specimens. Candidal antibody tests, antigen detection, and metabolite detection have not been successful in differentiating between invasive disease and colonization. The figure presented in question 339 illustrates C. albicans from a skin smear.
Zygomycosis (sometimes called mucormycosis) is caused by a variety of fungi called Zygomycetes. These fungi include Conidiobolus, Rhizopus, and Basidiobolus, which can be differentiated mycologically, but all are characterized by large (6 to 25 mm), irregularly branched, usually nonseptate hyphae. The differentiation of these fungi clinically is a function of the location of the lesion: limbs and trunk, nose, or brain. Basidiobolus lesions are most commonly seen on the arms and legs. Conidiobolus is usually found in the nasal mucosa and nasal sinuses. Rhizopus infection may start in the nasal tissue but spreads rapidly to the eyes and brain.
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