Diagnosis of fungal infections

Definition

The approach to the diagnosis of a fungal infection depends on the complexity of the infection and on the health status of the infected person. Noninvasive infections can usually be diagnosed based on a physical examination. Invasive or systemic infections require laboratory tests to confirm the diagnosis.

Noninvasive Infections

Noninvasive infections include superficial and cutaneous infections. Superficial infections affect hair, nails, and the surface layer of the skin. Cutaneous infections affect living cells of the inner layers of the skin and mucous membranes. The location, appearance, and other distinctive signs and symptoms of an infection are used to obtain a diagnosis. Through diagnosis, one needs to distinguish between fungal infections (and similar infections caused by bacteria) and noninfectious inflammatory skin disorders, such as contact dermatitis and psoriasis. Some fungal infections, such as athlete’s foot (tinea pedis) and jock itch (tinea cruris), are identified by where they occur. Common signs and symptoms of noninvasive fungal infections include characteristic itchy, red, scaly, and peeling areas of skin; brittle, thickened, or deformed nails (tinea unguium); brittle hair (tinea capitis); and vaginal itching and discharge (vaginal candidiasis).

The presence of pathogenic fungi is confirmed by studying a sample of infected matter under a light microscope. Typical samples, depending on the site of infection, are skin scrapings, nail or hair clippings, vaginal discharge, and sputum. Spores and yeasts that cause noninvasive infections are relatively large microorganisms that will be apparent on standard magnification. Staining enhances the image. A KOH preparation (a 10 percent potassium hydroxide solution) dissolves nonfungal components and distinguishes the rigid walls and other morphologic characteristics of fungi. A calcofluor white stain is more sensitive than a KOH prep. It binds to fungi and illuminates them under ultraviolet light. Both staining methods are easy to perform and provide rapid results. However, neither identifies specific fungi.

Invasive and Systemic Infections

Invasive (subcutaneous) and systemic infections can cause a variety of symptoms, depending on the part of the body affected. Lung infections may cause flu-like symptoms such as coughing, fever, muscle ache, headache, and rash. Blood infections (sepsis) may cause chills, fever, nausea, and rapid heartbeat. Central nervous system infections (meningitis) may cause severe, persistent headache, stiff neck, and sensitivity to light. Systemic infections may cause night sweating, chest pain, weight loss, and enlarged lymph nodes. These symptoms are nonspecific to fungal infections.

As for superficial infections, obtaining a fungal stain is usually the first step in confirming fungal involvement. Some invasive fungal pathogens (for example, those that cause histoplasmosis) are too small or too few (for example, those that cause cryptococcosis) to be observed under light microscopy. For all invasive and systemic infections, it is essential to isolate the specific pathogen to confirm the diagnosis and to direct treatment.

To identify the specific pathogen, fungi obtained by sampling are grown in a culture media that inhibits bacterial growth while encouraging fungal growth. Depending on the location of the presenting symptoms, samples are taken from the blood, the lungs, a tissue biopsy, or cerebrospinal fluid. Care must be taken to avoid contamination. For example, when Aspergillosis species are suspected, it may be necessary to perform a biopsy of lung tissue, lung aspiration, or bronchoalveolar lavage to avoid contamination.

The most commonly used medium for culturing fungi is Sabouraud agar or Sabouraud dextrose agar (SDA). Most bacteria associated with human infections do not grow or grow poorly in this medium. Because many fungi are slow-growing, it may take several weeks to obtain sufficient fungi to confirm a diagnosis.

As a follow-up to a culture, a susceptibility test can help in selecting the most effective antifungal or antifungals for addressing specific infections. Antigen or antibody testing of blood, cerebrospinal, or other body fluids may be ordered, especially if the infection is systemic or at risk of becoming so. Antigen testing detects proteins associated with a specific fungus for which a test has been developed. Effective antigen tests have been developed for the detection of the pathogens causing histoplasmosis and coccidioidomycosis. Antibody testing detects the immune response to specific fungi. Antibody testing is not effective for detecting aspergillosis, as healthy persons also have antibodies against Aspergillus.

An AFB (acid-fast bacillus) smear and culture may be ordered to rule out tuberculosis or infection caused by nontuberculous mycobacteria. An AFB culture can provide a test result in one to two days, but cultures may take up to eight weeks to grow in the lab and return a result. The AFB culture and smear tests are most commonly performed together. If a fungal mass is suspected, an imaging scan, such as an X-ray of the lungs, may be ordered.

In the first two decades of the twenty-first century, a global increase in invasive fungal infections increased the importance of accurate and timely diagnosis, and several novel testing methods emerged. Polymerase chain reaction (PCR) testing was developed to identify fungal DNA in superficial infections, fungal infections of the eye, and invasive fungal infections. The first U.S. Food and Drug Administration-approved whole blood rapid diagnostic test to detect Candida cells, T2Candida, was developed using a magnetic resonance technique. In three to five hours, results can indicate the presence of the five most common strains of Candida species. Other advances in testing for fungal infections include next-generation sequencing and biosensors, artificial intelligence-based methods, and microfluidic chip technology.

Impact

In immunocompromised persons or in persons with an underlying disease, care must be taken to identify the specific pathogen or pathogens, even with noninvasive infections. Such care applies to all persons who present with an invasive or systemic infection. Knowing what fungal pathogen is causing the infection confirms the diagnosis and is instrumental in directing treatment.

Key Terms: Fungal Infections

• Filamentous fungusA threadlike fungus (mold)
• FungusA nonphotosynthetic, plantlike organism
• HyphaeThin tubes in fungi that secure food and grow, expanding the size of molds and yeasts
• MoldA filamentous fungus that grows by branching and extending
• MyceliumA collection of threadlike fungal strands (hyphae) making up the thallus, or nonreproductive portion, of a fungus
• MycologyThe study of fungi
• MycosisA disease of humans, plants, or animals caused by a fungus; the prefix myco- means "fungus"
• MycotoxinA poison released by fungi
• Pleomorphic fungusA fungus whose morphology changes markedly from one phase of its life cycle to another, or according to changes in environmental conditions
• TineaA medical term for fungal skin diseases, such as ringworm and athlete’s foot, caused by a variety of fungi
• YeastA unicellular fungus that grows by budding off smaller cells from the parent cell; yeasts belong to several different groups of fungi, and some fungi are capable of growing either as a yeast or as a filamentous fungus

Bibliography

Chandrasekar, Pranatharthi. “Diagnostic Challenges and Recent Advances in the Early Management of Invasive Fungal Infections.” European Journal of Haematology, vol. 84, no. 4, 2010, pp. 281–90, doi.org/10.1111/j.1600-0609.2009.01391.x. Accessed 2 Nov. 2024.

Fang, Wenjie, et al. “Diagnosis of Invasive Fungal Infections: Challenges and Recent Developments.” Journal of Biomedical Science, vol. 30, no. 1, 2023, p. 42, doi.org/10.1186/s12929-023-00926-2. Accessed 2 Nov. 2024.

"Fungal Culture Test." MedlinePlus, 7 July 2022, medlineplus.gov/lab-tests/fungal-culture-test. Accessed 2 Nov. 2024.

Gladwin, Mark, and Bill Trattler. Clinical Microbiology Made Ridiculously Simple. 9th ed., MedMaster, 2023.

Howell, S. A. “Dermatopathology and the Diagnosis of Fungal Infections.” British Journal of Biomedical Science, vol. 80, 2023, p. 11314, doi.org/10.3389/bjbs.2023.11314. Accessed 2 Nov. 2024.

Richardson, Malcolm D., and Elizabeth M. Johnson. The Pocket Guide to Fungal Infection. 2nd ed., Blackwell, 2006.

Ryan, Kenneth J., and George Ray. Sherris Medical Microbiology: An Introduction to Infectious Diseases. 7th ed., McGraw-Hill Medical, 2018.

Webster, John, and Roland Weber. Introduction to Fungi. Cambridge UP, 2007.