Fungal Infections

Published on 06/06/2015 by admin

Last modified 22/04/2025

Print this page

This article have been viewed 3138 times

98 Fungal Infections

Fungi are one of the four major groups of infectious organisms, along with viruses, bacteria, and parasites. They are divided into two morphologic forms, yeasts and molds. Yeasts are unicellular organisms, usually round or oval in shape, that reproduce by budding. In contrast, molds are multicellular organisms composed of hyphae, or tubular structures that grow by extension or branching. Fungi that grow as yeast and mold forms are termed dimorphic fungi. Molds also grow by spore formation. In addition to morphologic characteristics, biochemical and molecular assays of fungi are used in laboratory diagnosis to help identify genus and species.

The extent of disease caused by fungal exposure is related to a number of factors, including fungal virulence, inoculum size, and most importantly, the host immune system. The majority of clinically significant fungal infections occur in patients whose defense against infection is either compromised or immature. Dermatophytic infections are an exception and occur in healthy children. Examples of host defense compromise include breaches to the normal skin defenses, such as burns or central catheters, children with decreased neutrophil number (chemotherapy) or function (chronic granulomatous disease), and defects in T-cell functioning (severe combined immunodeficiency or HIV/AIDS). Premature infants comprise another group with increased risk of fungal infections, especially those weighing less than 1000 g because of immature immune function and the complexity of their care, often requiring medical devices.

This chapter discusses the three most clinically significant fungi in childhood—Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans. Each section contains a brief description of the pathogen, clinical manifestations in the immune competent and immune compromised host, diagnosis, and treatment. Finally, there is a discussion of common dermatophytic infections.

Candida Albicans

Candida spp. are yeasts that are ubiquitous in the environment. C. albicans, the most common species causing disease in children, is a dimorphic fungus that can be grown in both yeast and hyphal forms, which aids its ability to survive in varied environments, including host tissues. Other species isolated from children include Candida tropicalis, Candida parapsilosis, Candida glabrata, Candida krusei, and Candida guilliermondii. Nearly 60% of individuals can be colonized with C. albicans without symptoms, most commonly in the vaginal and gastrointestinal (GI) tracts. Pregnancy, a state of relative immune compromise, increases the vaginal colonization rate from less than 20% to greater than 30%. Approximately 10% of full-term infants become colonized in the GI and respiratory tracts in the first 5 days of life. The incidence of colonization of infants weighing less than 1500 g can be as high as 30%. Newborn infants can acquire the organism during passage through the birth canal or postnatally. Some forms of locally invasive candidiasis can be found in immune competent children, including vulvovaginitis, laryngeal candidiasis, and chronic draining otitis externa, but usually in the presence of systemic antibiotics. Systemic candidiasis is limited to immune compromised children, including those who are premature.

Clinical Manifestations and Management

Oral candidiasis, also known as oral thrush, is a candidal infection of the oral-pharyngeal mucosa (Figure 98-1). It can affect up to 2% to 5% of otherwise healthy newborn infants and present as early as 7 to 10 days of life. In immunocompetent children, it is most common in infants and presents as adherent white plaques on the buccal or gingival mucosa. Removal of these plaques can result in localized bleeding. It can present with no symptoms or with increased fussiness and decreased feeding. Oral thrush is uncommon in children older than 12 months except after antibiotic use. Without recent antibiotic use, one may consider a primary immunodeficiency, diabetes mellitus, or HIV infection. Pseudomembranous candidiasis can be diagnosed clinically or by the identification of yeast cells and pseudohyphae by Gram stain or potassium hydroxide prep. Thrush can be treated with nystatin applied directly to the oral mucosa for 7 to 10 days. Thrush caused by antibiotic use generally resolves as the offending agent is discontinued. Bottle nipples and pacifiers should be sterilized as well to prevent reinfection.

Figure 98-1 Pseudomembranous candidiasis of the palate.

Candidal diaper dermatitis is characterized as beefy red plaques with satellite papules and pustules. It can affect the entire diaper area with a predilection for skin folds unlike other forms of diaper dermatitis. The treatment is with topical nystatin, clotrimazole, or miconazole.

Vulvovaginitis is a locally invasive candidal infection seen most often in postpubertal women and can affect up to 75% of women at some point during their lifetime. Risk factors for presentation at a younger age include systemic antibiotic use, diaper use, diabetes, and immune deficiency. Vulvovaginitis presents as a non-odorous white discharge, classically described as “cottage cheese,” from the vagina with associated dysuria, vulvar burning, and pruritus. First-line therapy is generally topical therapy as in diaper dermatitis or systemic fluconazole for recurrent or refractory cases.

Candidal infections in the immunocompromised host can vary from superficial mucocutaneous infections to life-threatening systemic infections. The most serious fungal infection is disseminated candidiasis, in which the organism spreads hematogenously to tissues throughout the body, including the eyes, kidney, bones, meninges, lungs, spleen, or heart valves. Mortality can be as high as 47%. Risk factors include exposure to broad-spectrum antibiotics, central venous catheters, parenteral nutrition, renal replacement therapy in the intensive care unit, neutropenia, immunosuppression, and prosthetic devices. Candida spp. are the fourth leading cause of nosocomial bloodstream infections. Diagnosis requires culturing Candida spp. from blood or other sterile body fluids. Recommended treatment of systemic candidiasis includes lipid formulation amphotericin B, caspofungin, or fluconazole with the duration of therapy determined by the extent of disease and response to therapy. Fluconazole may be added for better penetration into the central nervous system. Prophylactic antifungal medication is recommended in two groups of patients—bone marrow transplant recipients and solid organ transplant recipients because of their prolonged neutropenia and immunosuppression.

Aspergillus Fumigatus

Aspergillus is a mycelial fungus, ubiquitous in the environment found in the soil and on decaying plants. A. fumigatus is the most common species isolated clinically, followed by Aspergillus flavus. Exposure occurs commonly by inhalation of conidia (spores); however inhalation of contaminated aerosols and direct inoculation of skin also occur. Some estimate that most people inhale hundreds of A. fumigatus conidia per day. Once inhaled Aspergillus can colonize the upper and lower respiratory tract. In an immune competent host, macrophages and neutrophils prevent the development of invasive disease. Immunocompromised children are at risk for invasive respiratory disease and for hematogenous dissemination. Invasive aspergillosis in an otherwise healthy child with no known risk factors should prompt an evaluation for chronic granulomatous disease. Aspergillus-related diseases may be hypersensitivity (IgE) mediated, saprophytic (noninvasive), or invasive (Figure 98-2).

Figure 98-2 Aspergillosis.

Clinical Presentation and Management

Cryptococcus Neoformans

Cryptococcus is an encapsulated yeast. C. neoformans is the most common form worldwide. It is found in temperate climates in soil contaminated by certain bird droppings. It may also be found on some fruits and vegetables and carried on cockroaches. It grows best at 37 degrees Celsius. Humans come in contact by inhalation of fungal spores.

Clinical Presentation and Management

Pneumonia is the most common form of cryptococcosus and may be asymptomatic in up to one third of immune competent hosts. Symptoms may include fever, pleuritic chest pain, and constitutional symptoms. Chest radiograph may show diffuse interstitial infiltrates and hilar lymphadenopathy (Figure 98-3). Dissemination following pulmonary disease is uncommon except where there is a deficiency in cell mediated immunity—HIV, leukemia, SLE, congenital immunodeficiency, chronic cutaneous candidiasis. HIV infection is the most common immune compromised state for Cryptococcal infection. In addition, Cryptococcus is an AIDS defining infection in HIV patients.

Figure 98-3 Cryptococcus.

Subacute or chronic meningitis is the most common manifestation of disseminated Cryptococcus and may present only as behavioral change or may present with fever and headache (see Figure 98-3). Signs of increased intracranial pressure are also common and may be life threatening. Focal neurologic signs are present in less than 10%. Classically diagnosis was made by staining CSH with India Ink where encapsulated yeast may be visualized. More recently diagnosis is enhanced by latex agglutination testing for cryptococcal antigen. Treatment of Cryptococcus depends on the status of the host and on the site of infection. Asymptomatic, immune competent hosts may be watched closely or treated with fluconazole daily for 3-12 months. Those with symptomatic or disseminated disease are treated initially with amphotericin B and fluconazole for 2-10 weeks depending on clinical response, then with single therapy with fluconazole for 6-12 months. Children with HIV who complete initial therapy for Cryptococcus should remain on lifelong suppressive therapy with fluconazole.

Common Tinea Infections

Tinea is a superficial infection of the hair, skin, or nails caused by dermatophytic fungi. They invade the stratum corneum layer of the skin and feed on keratin within the skin. There are three genera of dermatophytes that cause infection—Trichophyton, Epidermophyton, and Microsporum—and about 28 species within those genera. Specific organisms tend to cause disease in different body sites. The specific condition is often named by the body site involved.

Tinea Capitis

Tinea capitis is a dermatophyte infection of the scalp and hair shafts. It is most common in kids younger than 10 with peak occurrence at 3-7 years. The predominant organism casing disease is Trichophyton tonsurans in the United States. Infection is spread by infective spores. In addition to direct person-to-person contact, infective spores have been cultured from hairbrushes, clothing, and other inanimate objects. Asymptomatic carries are common and can also perpetuate disease.

Tinea capitis may present in many ways including diffuse scaling, diffuse pustule formation, patchy hair loss, black dot (well-demarcated areas of hair loss with short broken hairs), or with kerion formation (an inflammatory lesion with edematous, boggy swelling). Posterior cervical and suboccipital lymphadenopathy is also common. Topical treatment is not effective as topical medicines do not effectively penetrate the hair shaft. First-line systemic therapy includes griseofulvin for at least 8 weeks. Absorption is improved if taken with fatty foods.

Tinea Corporis (Ringworm)

Tinea corporis is a dermatophyte infection of the glabrous (smooth and hairless) skin. The lesion is typically well demarcated, circular, and slightly erythematous, with a scaly, pustular, or vesicular border and is often pruritic (Figure 98-4). The main causative agents include Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans, Microsporum canis, and Epidermophyton floccosum. Treatment of tinea corporis is topical with medication applied to the skin at least 2 cm beyond the border of the lesion once or twice daily (depending on the antifungal) for 2 weeks. Persistence of the lesion after 4 weeks of therapy indicates treatment failure and may require systemic therapy. Common topical antifungal therapy for tinea corporis includes miconazole, clotrimazole, terbinafine, ketoconazole, and econazole.