Opportunistic Fungi PDF

OPPORTUNISTIC MYCOSES Opportunistic fungi fail to induce disease in most immunocompetent persons but can do so in those with impaired host defenses. There are five genera of medically important fungi: 1. Candida, 2. Cryptococcus, 3. Aspergillus, 4. Mucor, and 5. Rhizopus CANDIDA...

OPPORTUNISTIC MYCOSES Opportunistic fungi fail to induce disease in most immunocompetent persons but can do so in those with impaired host defenses. There are five genera of medically important fungi: 1. Candida, 2. Cryptococcus, 3. Aspergillus, 4. Mucor, and 5. Rhizopus CANDIDA Diseases Candida albicans, the most important species of Candida, causes thrush, vaginitis, esophagitis, diaper rash, and chronic mucocutaneous candidiasis. It also causes disseminated infections such as right-sided endocarditis (especially in intravenous drug users), bloodstream infections (candidemia), and endophthalmitis. Infections related to indwelling intravenous and urinary catheters are also important. Candida glabrata is the second most common cause of disseminated candidal infections and is more drug resistant than C. albicans. Properties - Candida albicans is an oval yeast with a single bud. It is part of the normal flora of mucous membranes of the upper respiratory, gastrointestinal, and female genital tracts. - In tissues it appears most often as yeasts or as pseudohyphae. Pseudohyphae are elongated yeasts that visually resemble hyphae but are not true hyphae. - True hyphae are also formed when C. albicans invades tissues. - Carbohydrate fermentation reactions can be used to differentiate it from other species (e.g., Candida tropicalis, Candida parapsilosis, Candida krusei, and C. glabrata) that cause human infections. - Candida dubliniensis is closely related to C. albicans. It also causes opportunistic infections in immunocompromised patients, especially AIDS patients. Both species form chlamydospores but C. albicans grows at 42°C whereas C. dubliniensis does not. Transmission - As a member of the normal flora, C. albicans is already present on the skin and mucous membranes. In addition to the skin, C. albicans is found throughout the GI tract (especially the mouth and esophagus) and in the vagina. - Thrush in the newborn is the result of passage through a birth canal heavily colonized by the organism. - The presence of C. albicans on the skin predisposes to infections involving instruments that penetrate the skin, such as needles (intravenous drug use) and indwelling catheters. It is often found in the urine of patients with indwelling urinary (Foley) catheters. Pathogenesis & Clinical Findings - The first line of defense against Candida infections is intact skin and mucous membranes. - The second line is cell mediated immunity, especially Th-1 cells producing gamma-interferon that activates efficient killing by macrophages. Neutrophils are also important as evidenced by the finding that neutropenia predisposes to disseminated Candida infections. - When local or systemic host defenses are impaired, disease may result. Overgrowth of C. albicans in the mouth produces white patches called thrush. Thrush is a pseudomembrane. - Vaginitis with itching and discharge is favored by high pH, diabetes, or use of antibiotics. Antibiotics suppress the normal flora Lactobacillus, which keep the pH low. As a result, the pH rises, which favors the growth of Candida. - Skin invasion occurs in warm, moist areas, which become red and weeping. Fingers and nails become involved when repeatedly immersed in water; persons employed as dishwashers in restaurants are commonly affected. Thickening or loss of the nail can occur. - Diaper rash in infants occurs when wet diapers are not changed promptly. - In immunosuppressed individuals, Candida may disseminate to many organs or cause chronic mucocutaneous candidiasis (CMC). CMC is a prolonged infection of the skin, oral and genital mucosa, and nails that occurs in  individuals deficient in T-cell immunity. Patients with mutations in the gene encoding interleukin-17 (IL-17) and the receptor for IL-17 are predisposed to Candidiasis. - After organ transplantation, patients receiving immunosuppressive drugs to prevent rejection are predisposed to invasive Candida infections. Intravenous drug abuse, indwelling intravenous catheters, and hyperalimentation also predispose to disseminated candidiasis, especially right-sided endocarditis and endophthalmitis (infection within the eye). - Candida esophagitis, often accompanied by involvement of the stomach and small intestine, is seen in patients with leukemia and lymphoma. Subcutaneous nodules are often seen in neutropenic patients with disseminated disease. Candida albicans is the most common species to cause disseminated disease but C. tropicalis and C. parapsilosis are important pathogens also. Laboratory Diagnosis - In exudates or tissues, budding yeasts and pseudohyphae appear gram-positive and can be visualized by using calcofluor-white staining. In culture, typical yeast colonies are formed that resemble large staphylococcal colonies. Candida albicans forms germ tubes in serum at 37°C, whereas most other species of pathogenic Candida species do not. - Chlamydospores are typically formed by C. albicans but not by most other species of Candida. Note that C. dubliniensis also forms chlamydospores but will not grow at 42°C whereas C. albicans will. Serologic testing is rarely helpful. A laboratory test that can identify C. albicans and four other - Candida species in blood cultures in 3 to 5 hours instead of the usual several days was approved in 2014. The test uses magnetic resonance technology to detect the presence of yeast DNA and then to identify the species. - Skin tests with Candida antigens are uniformly positive in immunocompetent adults and are used as an indicator that the person can mount a cellular immune response. A person who does not respond to Candida antigens in the skin test is presumed to have deficient cell-mediated immunity. Such a person is anergic, and other skin tests cannot be interpreted. Thus, if a person has a negative Candida skin test, a negative purified protein derivative (PPD) skin test for tuberculosis could be a false-negative result. Treatment & Prevention - Thrush – fluconazole or Itraconazole or voriconazole. Certain candidal infections (e.g., thrush) can be prevented by oral clotrimazole troches, buccal miconazole tablets, or nystatin “swish and swallow.” - Esophageal Candidiasis - An echinocandin, such as caspofungin or micafungin - Skin infections - Topical antifungal drugs (e.g., clotrimazole or nystatin). - Candida vaginitis - Topical (intravaginal) azole drugs, such as clotrimazole or miconazole, or with oral fluconazole. - Chronic mucocutaneous candidiasis can be controlled by fluconazole or itraconazole. - Strains of C. albicans resistant to azole drugs have emerged in patients with acquired immunodeficiency syndrome (AIDS) receiving long-term prophylaxis with fluconazole. - Most isolates of C. glabrata are resistant to fluconazole and voriconaziole. An echinocandin such as caspofungin or amphoptericin B should be used. CRYPTOCOCCUS Disease a. Cryptococcus neoformans causes cryptococcosis, especially cryptococcal meningitis. Cryptococcosis is the most common, life-threatening invasive fungal disease worldwide. It is especially important in AIDS patients. b. Another species, Cryptococcus gattii, causes human disease less frequently than C. neoformans. Properties - Cryptococcus neoformans is an oval, budding yeast surrounded by a wide polysaccharide capsule. - It is not dimorphic. - Forms a narrow-based bud, whereas the yeast form of Blastomyces dermatitidis forms a broad-based bud. Transmission a. Cryptococcus neoformans occurs widely in nature and grows abundantly in soil containing bird (especially pigeon) droppings. The birds are not infected. b. Cryptococcus gattii is more capable of causing disease in an immunocompetent person than C. neoformans. Cryptococcus gattii is more likely to cause cryptococcomas (granulomas), especially in the brain, than C. neoformans. Laboratory Diagnosis - In spinal fluid mixed with India ink, the yeast cell is seen microscopically surrounded by a wide, unstained capsule. - Appearance of the organism in Gram stain is unreliable, but stains such as periodic acid–Schiff (PAS stain), methenamine silver, and mucicarmine will allow the organism to be visualized. - The organism can be cultured from spinal fluid and other specimens. The colonies are highly mucoid—a reflection of the large amount of capsular polysaccharide. - Serologic tests can be done for both antibody and antigen. In infected spinal fluid, capsular antigen can be detected by the latex particle agglutination test. This test is called the cryptococcal antigen test, often abbreviated as “crag.” Treatment & Prevention - Combined treatment with amphotericin B and flucytosine. - Liposomal amphotericin B should be used in patients with preexisting kidney damage. - Fluconazole is used in AIDS patients for long-term suppression of cryptococcal meningitis. - Cryptococcus gattii is less responsive to antifungal drugs than is C. neoformans. ASPERGILLUS Disease Aspergillus species, especially Aspergillus fumigatus, cause infections of the skin, eyes, ears, and other organs; “fungus ball” in the lungs; and allergic bronchopulmonary aspergillosis. Properties - Aspergillus species exist only as molds; they are not dimorphic. - They have septate hyphae that form V-shaped (dichotomous) branches. - The walls are parallel, in contrast to Mucor and Rhizopus walls, which are irregular. - The conidia of Aspergillus form radiating chains, in contrast to those of Mucor and Rhizopus, which are enclosed within a sporangium. Transmission They grow on decaying vegetation, producing chains of conidia. Transmission is by airborne conidia. Pathogenesis & Clinical Findings - Aspergillus fumigatus can colonize and later invade abraded skin, wounds, burns, the cornea, the external ear, or paranasal sinuses. - It is the most common cause of fungal sinusitis. - In immunocompromised persons, especially those with neutropenia, it can invade the lungs producing hemoptysis and the brain causing an abscess. - Neutropenic patients are also predisposed to intravenous catheter infections caused by this organism. - Aspergilli are well-known for their ability to grow in cavities within the lungs, especially cavities caused by tuberculosis. Within the cavities, they produce an aspergilloma (fungus ball), which can be seen on chest X-ray as a radiopaque structure that changes its position when the patient is moved from an erect to a supine position. - Aspergillus flavus growing on cereals or nuts produces aflatoxins that may be carcinogenic or acutely toxic. Laboratory Diagnosis - Biopsy specimens show septate, branching hyphae invading tissue. Cultures show colonies with characteristic radiating chains of conidia. - However, positive cultures do not prove disease because colonization is common. In persons with invasive aspergillosis, there may be high titers of galactomannan antigen in serum. - Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to the presence of Aspergillus in the bronchi. Patients with ABPA have asthmatic symptoms and a high IgE titer against Aspergillus antigens with brownish bronchial plugs containing hyphae, prominent eosinophilia. IgG precipitins are also present. Treatment & Prevention - Voriconazole is the drug of choice for invasive aspergillosis. - Liposomal amphotericin B, posaconazole, and caspofungin are alternative drugs. - A fungus ball growing in a sinus or in a pulmonary cavity can be surgically removed. - Patients with ABPA can be treated with corticosteroids and antifungal agents, such as itraconazole. MUCOR & RHIZOPUS - Mucormycosis (zygomycosis, phycomycosis) is a disease caused by saprophytic molds (e.g., Mucor, Rhizopus, and Absidia) found widely in the environment. - They are not dimorphic. - These organisms are transmitted by airborne asexual spores and invade tissues of patients with reduced host defenses. They proliferate in the walls of blood vessels, particularly of the paranasal sinuses, lungs, or gut, and cause infarction and necrosis of tissue distal to the blocked vessel. - Patients with diabetic ketoacidosis, burns, bone marrow transplants, or leukemia are particularly susceptible. Diabetic patients are particularly susceptible to rhinocerebral mucormycosis, in which mold spores in the sinuses germinate to form hyphae that invade blood vessels that supply the brain. - One species, Rhizopus oryzae, causes about 60% of cases of mucormycosis. In biopsy specimens, organisms are seen microscopically as nonseptate hyphae with broad, irregular walls and branches that form right angles. - Cultures show colonies with spores contained within a sporangium. - These organisms are difficult to culture because they are a single, very long cell, and damage to any part of the cell can limit its ability to grow. - Amphotericin B and surgical removal of necrotic infected tissue. Liposomal amphotericin B should be used in patients with preexisting kidney damage. Posaconazole can also be used. PNEUMOCYSTIS - Pneumocystis jiroveci is classified as a yeast on the basis of molecular analysis, but it has many characteristics of a protozoan. In 2002, taxonomists renamed the human species of Pneumocystis as P. jiroveci. P. carinii is used only to describe the rat species of Pneumocystis. Pneumocystis is acquired by inhalation of airborne organisms into the lungs. - An inflammatory exudate composed primarily of plasma cells occurs, oxygen exchange is reduced, and dyspnea occurs. A reduced number of CD 4-postive T lymphocytes, such as occurs in AIDS, predisposes to pneumonia. - Most immunocompetent people have asymptomatic infections. - Chest X-ray shows a “ground glass” pattern. The mortality rate of untreated Pneumocystis pneumonia is approximately 100%. The diagnosis is typically made by finding the cysts of Pneumocystis in bronchial lavage specimens. - Fluorescent antibody stains or tissue stains, such as methenamine silver or Giemsa, are used to identify the organism. PCR-based tests are also used. Serological tests are not useful. - Trimethoprim-sulfamethoxazole or aerosolized pentamidine can be used for prophylaxis in patients with CD4 counts below 200.  SPOROTRICHOSIS (OPPORTUNISTIC INFECTION) - Sporothrix schenckii is a dimorphic fungus. The mold form lives on plants, and the yeast form occurs in human tissue. When spores of the mold are introduced into the skin, typically by a thorn, it causes a local pustule or ulcer with nodules along the draining lymphatics. The lesions are typically painless, and there is little systemic illness. Untreated lesions may wax and wane for years. - In human immunodeficiency virus (HIV)–infected patients with low CD4 counts, disseminated sporotrichosis can occur. - Sporotrichosis occurs most often in gardeners, especially those who prune roses, because they may be stuck by a rose thorn. - In the clinical laboratory, round or cigar-shaped budding yeasts are seen in tissue specimens. - In culture at room temperature, hyphae occur bearing oval conidia in clusters at the tip of slender conidiophores (resembling a daisy). - The drug of choice for skin lesions is itraconazole (Sporanox). It can be prevented by protecting skin when touching plants, moss, and wood. FUNGI OF MINOR IMPORTANCE 1. PENICILLIUM MARNEFFEI is a dimorphic fungus that causes tuberculosis-like disease in AIDS patients, particularly in Southeast Asian countries such as Thailand. It grows as a mold that produces a rose-colored pigment at 25°C but at 37°C grows as a small yeast that resembles Histoplasma capsulatum. Bamboo rats are the only other known hosts. The diagnosis is made either by growing the organism in culture or by using fluorescent antibody staining of affected tissue. The treatment of choice consists of amphotericin B for 2 weeks followed by oral itraconazole for 10 weeks. Relapses can be prevented with prolonged administration of oral itraconazole. 2. PSEUDALLESCHERIA BOYDII is a mold that causes disease primarily in immunocompromised patients. The clinical findings and the microscopic appearance of the septate hyphae in tissue closely resemble those of Aspergillus. In culture, the appearance of the conidia (pear-shaped) and the color of the mycelium (brownish-gray) of P. boydii are different from those of Aspergillus. The drug of choice is either ketoconazole or itraconazole because the response to amphotericin B is poor. Debridement of necrotic tissue is important as well. 3. FUSARIUM SOLANI is a mold that causes disease primarily in neutropenic patients. Fever and skin lesions are the most common clinical features. The organism is similar to Aspergillus in that it is a mold with septate hyphae that tends to invade blood vessels. Blood cultures are often positive in disseminated disease. In culture, banana-shaped conidia are seen. Liposomal amphotericin B is the drug of choice. Indwelling catheters should be removed or replaced. In 2006, an outbreak of Fusarium keratitis (infection of the cornea) occurred in people who used a certain contact lens solution SUMMARY