Fungi are eukaryotic organisms that exist as yeast, molds, or both forms. Yeasts consist of solitary cells that reproduce by budding. Molds occur in filaments, also known as hyphae, which extend by apical elongation. Dimorphic fungi grow as mold in the environment and as yeast cells or spherules (sac-like cells that are the reproductive form of the fungus) in vivo.
Fungal infections are often classified as either
Primary
Opportunistic
Primary infections are able to develop in immunocompetent hosts.
Opportunistic infections are those that develop mainly in immunocompromised hosts.
Fungal infections can be
Local
Systemic
Local fungal infections typically involve the skin (see Fungal Skin Infections), mouth (causing stomatitis), and/or vagina (causing candidal vaginitis) and may occur in normal or immunocompromised hosts.
Systemic fungal infections can affect the skin and organs such as the lungs, eyes, liver, and brain and typically occur in immunocompromised hosts (see Opportunistic fungal infections).
(See also Antifungal Medications.)
Primary fungal infections
Primary fungal infections usually result from inhalation of fungal spores, which can cause a localized pneumonia as the primary manifestation of infection.
In immunocompetent patients, systemic mycoses typically have a chronic course; dissemination is rare, and, if lung lesions develop, they usually progress slowly. Months may elapse before medical attention is sought or a diagnosis is made. Symptoms are rarely intense in such chronic mycoses, but fever, chills, night sweats, anorexia, weight loss, malaise, and depression may occur. Various organs may be infected, causing symptoms and dysfunction.
Primary fungal infections may have a characteristic geographic distribution, which is especially true for the endemic mycoses caused by certain dimorphic fungi. For example,
Coccidioidomycosis: Confined primarily, in the United States, to the southwestern region and Washington state and also to northern Mexico, and Central and South America
Histoplasmosis: Occurring primarily in the eastern and midwestern United States and parts of Central and South America, Africa, Asia, and Australia
Blastomycosis: Confined to North America and Africa
Paracoccidioidomycosis: Confined to South America
However, the latency from transmission to infection varies, and symptoms may develop after travelers have returned from endemic areas.
When fungi disseminate from a primary focus in the lung, the manifestations may be characteristic, as for the following:
Cryptococcosis: Usually, chronic meningitis
Progressive disseminated histoplasmosis: Generalized involvement of the reticuloendothelial system (liver, spleen, bone marrow)
Blastomycosis: Single or multiple skin lesions or involvement of the central nervous system, bone, or prostate
Coccidioidomycosis: Bone and joint infections, skin lesions, and meningitis
Opportunistic fungal infections
Many fungi are opportunists and are usually not pathogenic, except in an immunocompromised host. Causes of immunocompromise include AIDS, azotemia, diabetes mellitus, lymphoma, leukemia, other hematologic cancers, burns, and therapy with corticosteroids, immunosuppressants, or antimetabolites. Patients who spend more than several days in an intensive care unit can become compromised because of medical procedures (eg, central venous catheters, major surgery), underlying disorders, and/or undernutrition.
Examples of opportunistic systemic fungal infections (mycoses) include
Mucormycosis (zygomycosis)
Fusariosis
Systemic mycoses affecting patients who are severely immunocompromised often manifest acutely with rapidly progressive pneumonia, fungemia, or manifestations of extrapulmonary dissemination.
Diagnosis of Fungal Infections
Cultures and stains
Histopathology
Serologic tests (mainly for Aspergillus, Blastomyces, Candida, Coccidioides, Cryptococcus, and Histoplasma)
Molecular diagnostics
If clinicians suspect an acute or a chronic primary fungal infection, they should obtain a detailed travel and residential history to determine whether patients may have been exposed to certain endemic mycoses, even if the exposure was years ago.
Pulmonary fungal infections must be distinguished from tumors and chronic pneumonias caused by nonfungal organisms such as mycobacteria (including Mycobacterium tuberculosis). Specimens are obtained for fungal and mycobacterial culture and histopathology. Sputum samples may be adequate, but occasionally bronchoalveolar lavage, transthoracic needle biopsy, or even surgery may be required to obtain an acceptable specimen.
Fungi that cause primary systemic infections can be recognized by their histopathologic appearance. However, identifying the specific fungus may be difficult and usually requires fungal culture or molecular diagnostics.
The clinical significance of positive sputum cultures may be unclear if they show commensal organisms (eg, Candida albicans) or fungi ubiquitous in the environment (eg, Aspergillus species). Therefore, other evidence (eg, host factors such as immunosuppression, serologic evidence, tissue invasion seen on biopsy, or radiologic findings) may be required to help establish a diagnosis.
Serologic tests may be used to evaluate for many systemic mycoses if culture and histopathology are unavailable or unrevealing, although few provide definitive diagnoses. Particularly useful tests include the following:
Measurement of organism-specific antigens, most notably from Cryptococcus neoformans, Histoplasma capsulatum, and Aspergillus species (occasional cross-reactivity with other fungi has been noted with each of these serologic tests)
Serum (1,3)beta-D-glucan, which is often positive in invasive candidiasis and aspergillosis as well as Pneumocystis jirovecii infections
Complement fixation and immunodiffusion assays for endemic mycoses (histoplasmosis, blastomycosis, coccidioidomycosis)
Most other tests for antifungal antibodies have low sensitivity, specificity, or both and, because measurement of acute and convalescent titers is required, cannot be used to guide initial therapy.
Molecular diagnostics are useful tools for identifying molecular components of certain fungal infections. DNA probes that use culture specimens to identify Histoplasma, Blastomyces, and Coccidioides and polymerase chain reaction or DNA hybridization tests that use blood culture specimens to identify Candida are available. Matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry done on culture specimens also can be done to identify multiple yeasts, including Candida species. T2Candida is a non-culture–based platform that uses magnetic resonance technology to detect Candida DNA directly from whole blood and can be used for the rapid diagnosis of candidemia. Microbial cell-free DNA next-generation sequencing is an emerging technology for the detection of a broad array of fungal and other microbial pathogens from blood.
