Properties

 C. albicans is ovoid or spherical yeast with a single bud.

 It forms the part of the normal flora of the mucous membrane

of the gastrointestinal, genitourinary, and respiratory tract. It produces pseudohyphae in the cultures

and in tissues. Pseudohyphae are elongated yeast that may resemble hyphae morphologically, but

are really not true hyphae.

Candida grows readily on Sabouraud’s dextrose agar and on bacteriological culture media. C.

albicans produces creamy white, smooth colonies with a yeasty odor .

 It can be differentiated from other Candida species bycarbohydrate fermentation reaction

and by characteristicgrowth properties.

 Only C. albicans produces chlamydospores on cornmeal agar culture at 25°C.

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Pathogenesis and Immunity

Candida spp. are usually present as part of normal flora on

healthy mucosal surface of the oral cavity, gastrointestinal

tract, and vagina. Candida shows colonization at these sites in

more than 80% of healthy people. The organism, however, is

rarely present on the surface of normal human skin, except

occasionally from certain intertriginous area, such as the groin.

 Pathogenesis of Candida infection

Under certain conditions, Candida gains access to systemic circulation from the oropharynx of the

gastrointestinal tract. Colonization of the mucocutaneous surface is the first stage in the

pathogenesis of Candidal infection. The fungus causes invasion in human tissue through different

routes. Disruption of the skin or mucosa allows the organism access to the blood stream. Massive

colonization with large numbers of Candida

also permits the organism to pass directly into the blood stream, causing the infection. In

immunocompromised hosts, Candida may disseminate to many organs, such as lung, spleen, liver,

heart, and brain. Candida

may induce inflammation of the eye, causing endophthalmitis and also may involve skin in 10–30%

of patients with disseminated infection. Deficiency in host defence mechanisms plays a significant

role in development of Candida infection.

 Host immunity

Both cell-mediated and humoral antibodies confer protection

against Candida in healthy adults. Cell-mediated immunity (CMI) is, however, most important.

Alteration in CMI may cause extensive superficial candidiasis, despite having normal or elevated

humoral antibodies. The humoral antibodies appear to play minimal role in protection against the

disease. Humoral antibodies confer protection against Candida in healthy adults.

 Clinical Syndromes

Candida causes a wide spectrum of clinical illnesses as follows:

Cutaneous candidiasis: Candida species in immunocompetent

host can cause infection of any warm and moist part of the body exposed to environment. It causes

infection of the nail, rectum, and other skin folds.

Mucocutaneous candidiasis: Mucocutaneous candidiasis (thrush, perianal disease, etc.) is the most

common manifestation of candidiasis, but usually does not cause any mortality.

In patients with advanced immunodeficiency due to HIV infection, Candida species can cause severe

oropharyngeal and esophageal candidiasis that result in poor intake of food, leading

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to malnutrition, wasting, and early death. These patients are also usually resistant to treatment with

antifungal therapy.

Systemic candidiasis: These include endocarditis, gastrointestinal tract candidiasis, respiratory tract

candidiasis, genitourinary candidiasis, and hepatosplenic candidiasis. Systemic candidiasis may be

candidemia and disseminated candidiasis. In patients with AIDS, oral thrush and Candida

esophagitis are more common but not candidemia and disseminated candidiasis. Candida

endophthalmitis and central nervous infection (CNS) infection due to Candida species are

other complications of Candida infection.

Disseminated candidiasis: This is increasingly becoming a problem in patients with serious

hematologic malignancies that are treated with immunosuppressive drugs for over a

long period of time. Severe neutropenia in these patients is the most important predisposing

condition for life-threatening infection caused by Candida. In this condition, Candida usually

spreads through the circulation and involves many organs, such as lungs, spleen, kidney, liver, heart,

and brain. However, disseminated candidiasis is not a major problem in patients with AIDS. In such

patients, serious infection of the oropharynx and the upper gastrointestinal tract is the

Laboratory Diagnosis

o Specimens

These include exudates or tissues for microscopy obtained from skin or nails examined by

microscope for demonstration of pseudohyphae or budding yeast cells of Candida.

o Microscopy

Gram-stained smear of the exudates or tissue shows Gram positive,oval, budding yeast and

pseudohyphae . Since Candida is found as a part of normal flora on normal skin or mucosa, only the

presence of large numbers of Candida is of significance. Demonstration of pseudohyphae

indicates infection, and tissue invasion is of more diagnostic value.

o Culture

Culture on Sabouraud’s dextrose agar (SDA) produces typical

creamy white, smooth colonies. Different Candida species are identified by their growth

characteristics, sugar fermentation,

and assimilation tests. Germ tube is a rapid method for identification

of C. albicans and Candida dubliniensis. This test depends

on the ability of C. albicans to produce germ tube within 2 hours

when incubated in human serum at 37°C. This phenomenon is

called Reynold–Braude phenomenon (Figure 4-4).

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o Nonculture Candida detection tests

These include (a) Candida mannan assay, (b) Candida heat-labile-antigen assay, (c) D-arabinitol assay,

(d) D-inositol assay, and (e) 1,3-beta-D-glucan assay. Beta-Dglucan assay is a broad-spectrum test

that detects Candida as well as Aspergillus, Fusarium, Acremonium, and Saccharomyces species. This

test depends on the principle that beta-D-glucan is a component of the cell wall of these fungi, which

can be detected by its ability to activate factor G of the horseshoe crab coagulation cascade. This test

is a highly specific and sensitive test.

Treatment

Antifungal therapy forms the mainstay of treatment of the infections caused by Candida. These agents

include azoles ( fluconazole, triazole, ketoconazole), nystatin, and amphotericin is becoming

increasingly important worldwide .

Aspergillosis

A broad spectrum of diseases in humans ranging from direct invasion to hypersensitive reactions are

caused by Aspergillus species. Although more than 100 species have been described, the majority of

human diseases are caused by Aspergillus fumigates and Aspergillus niger, and less frequently by

Aspergillus flavus and Aspergillus clavatus.

Figure(74-2)Candida albicans showing formation of the germ

tube (_400).

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Aspergillus Species

Properties

 Aspergillus species are molds.

 They have septate hyphae that form V-shaped dichotomous branches (Figure 4-5). The

Aspergillus species are identified by (a) their morphological features, (b) the pattern of

conidiophores development, and (c) the color of the conidia.

 The presence of septate hyphae that branch at 45° angles is the typical feature of Aspergillus

species hyphae. The hyphae in tissues are best demonstrated with silver stains. The walls of

the hyphae are more or less parallel, unlike those of Mucor and Rhizopus, which are more or

less irregular.

Pathogenesis and Immunity

Aspergillus species rarely cause infections in immunocompetent individuals. They cause invasive

infections mostly in the patients who are immunocompromised either due to (a) use

of immunosuppressive drugs, (b) underlying lung diseases, or (c) immunodeficiency diseases, such

as HIV. In immunocompromised host, Aspergillus species cause invasion of the blood, thereby

causing infarction, hemorrhage, and necrosis of lung tissues. Aspergillus spp. also produces toxic

metabolites that inhibit macrophage and neutrophil phagocytosis, facilitating

dissemination of the infection.

Aspergillus species unlike Candida species do not form the part of normal flora of humans. They are

ubiquitous in the environment; hence transmission of infection is mostly exogenous.

Clinical Syndromes

In immunocompetent hosts, Aspergillus species may primarily affect the lungs, causing four main

syndromes including (a) allergic bronchopulmonary aspergillosis, (b) chronic necrotizing

aspergillus pneumonia, (c) aspergilloma, and (d) invasive aspergillosis.

Figure( 4-5) Aspergillus species with septate hyphae that form V-shaped

dichotomous branches.

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Allergic bronchopulmonary aspergillosis: It is a hypersensitivity reaction to A. fumigatus organisms,

which have colonized in tracheobronchial tree. This condition occurs often in association with

asthma and cystic fibrosis.

Chronic necrotizing pulmonary aspergillosis: It is a subacute infection seen in patients with some

degree of immunosuppression. The condition occurs in conjunction with alcoholism, underlying

lung disease, or chronic corticosteroid therapy.

Aspergilloma: It is a condition that occurs in a preexisting cavity in the lung parenchyma. This cavity

may have been caused earlier by tuberculosis, sarcoidosis, cystic fibrosis, and

emphysematous bullae. The condition is characterized by the presence of a ball of fungus within the

cavity. The fungus, however, does not invade the cavity. It may cause hemoptysis.

Invasive aspergillosis: It is a rapidly progressive infection in patients who are severely

immunocompromised. The condition is mostly fatal. In immunocompromised host, Aspergillus

organisms cause a disseminated disease, leading to endophthalmitis, endocarditis, and abscesses in

the viscera, such as liver, spleen, kidney, soft tissues, and bone.

Laboratory Diagnosis

Laboratory diagnosis of invasive aspergillosis or chronic necrotizing aspergillus pneumonia depends

on demonstration of Aspergillus in tissue by direct microscopy and culture.