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Reviewing Fungal Infections

by Dr. Jaclynn Moskow

Candida auris fungi, emerging multidrug resistant fungus, agent of fungal infection
Candida auris, an emerging multidrug-resistant fungus

 

Fungi are similar in many ways to bacteria – both have a cell nucleus and complex cell walls. Unlike bacteria, species of fungi include both single-celled organisms (yeasts) and multicellular forms (molds). Molds resemble plants and often consist of filaments, spores, root structures, etc. Fungal infections (mycoses) include candidiasis, dermatophytosis, blastomycosis, coccidioidomycosis, histoplasmosis, cryptococcosis, paracoccidioidomycosis, aspergillosis, zygomycosis, and pneumocystosis.

 

Candidiasis

Candidiasis refers to infections caused by yeasts of the genus Candida. Candida is the most common cause of fungal infections worldwide; and is part of the normal flora of the mouth, GI tract, vagina, and skin. Candidiasis occurs when an imbalance in the amount of Candida in these areas results in signs and symptoms of inflammation, or when Candida colonizes parts of the body in which it is not normally present. All forms of candidiasis are more common in individuals who are immunocompromised. 

Vulvovaginal candidiasis fungal infection, commonly referred to as a “yeast infection,” is estimated to affect 70-75% of women at least once during their lifetimes (1). Symptoms may include itching, burning, soreness, redness, swelling, pain during intercourse or urination, and a thick, white discharge that is usually odorless and may resemble cottage cheese. Factors that predispose to vulvovaginal candidiasis include the use of antibiotics, douches, and other vaginal products, diabetes, hormonal changes such as those seen with pregnancy and menopause, contraceptives, immune deficiency, including HIV / AIDS, and certain genetic factors. A variety of topical and systemic azole agents can be used for treatment.

Oropharyngeal candidiasis commonly referred to as “thrush,” occurs from Candida overgrowth on the lining of the mouth, tongue, gums, tonsils, and lips. The condition may cause visible white or yellow patches, soreness, an unpleasant taste, and occasionally a “cotton-like sensation.” It is much more common in infants and toddlers than in adults. Predisposing factors in adults include smoking, dentures, antibiotic and corticosteroid use, and hormonal changes. 80-90% of HIV patients will experience oropharyngeal candidiasis (2). Proper dental hygiene may help protect against oropharyngeal candidiasis. Various azole mouthwashes, gels, and lozenges can be used for treatment, as well as oral antifungal medications.

Common sites of cutaneous candidiasis include the axilla (armpit), the area under the breast, the groin region, the intergluteal cleft, and on the hands and feet. Candida is a common cause of “diaper rash.”

Invasive candidiasis (“deep candidiasis”) occurs when Candida affects the bloodstream, heart, brain, eyes, bones, or other organs. It may occur in patients that are immunocompromised, or as a result of fungal infection introduced by vascular lines, prosthetic cardiac valves, and urinary catheters. Systemic symptoms may result, including fever, chills, pain, hypotension, and neurological deficits. The condition can be fatal. One strain, in particular, Candida auris, poses a threat in hospitals, as it is often multidrug-resistant and difficult to identify using standard laboratory methods (3).

 

Dermatophytosis

Dermatophytosis (“tinea”) is a fungal infection of keratinized tissue, including the skin, hair, and nails. Fungal causes include Ascomycota, Euascomycetes, Onygenales: Epidermophyton, Microsporum, Trichophyton, Trichosporon spp., and Arthroderma (4). Dermatophytosis is contracted by contact with infected humans or animals, or contact with contaminated objects, flooring, or soil.

Trichophyton mentagrophytes - an agent of fungal infection
Fungus Trichophyton mentagrophytes

 

The nomenclature of these conditions derives from the body region that is affected. For example, Tinea manuum is a dermatophyte infection of the hands, while Tinea barbae is an infection of the beard or mustache. Tinea pedis affects the feet, Tinea unguium the nails, Tinea cruris the groin, Tinea corporis the trunk, Tinea capitis the scalp, and Tinea faciei the non-bearded area of the face. 

Tinea corporis is commonly referred to as “ringworm.” It presents as a red, annular, scaly patch, often with central clearing. The condition is usually pruritic and is very common – especially among children. High rates are seen in Africa, India, and urban areas of the Americas (5). A common source of adult infection is through handling puppies and kittens. A wide variety of creams, ointments, gels, and sprays are available for treatment.

Tinea pedis is commonly referred to as “athlete’s foot”; and is the most common form of dermatophytosis in adults (6). The condition can cause itching, stinging, and burning of the feet – often with redness, blisters, and peeling. Tinea pedis is often acquired from wet floor surfaces such as showers, locker rooms, and pool areas. Wearing foot protection in these areas can help prevent transmission. 

The same fungal species that cause Tinea pedis can also cause Tinea cruris, commonly known as “jock itch.” Tinea cruris presents as a red, pruritic, and often annular rash in the crease of the groin. The condition may spread to the upper thigh in a “half-moon” shape. The condition can be acquired by sharing contaminated towels or clothing. Both Tinea pedis and Tinea cruris usually respond well to topical antifungals.

 

Endemic Mycoses

Endemic mycoses refer to a diverse group of fungal infections found in distinct geographical regions. They can cause significant morbidity and mortality in immunocompromised individuals, and may also affect healthy people. 

Blastomycosis is caused by the fungus Blastomyces. It mainly affects people living in regions of the United States and Canada surrounding the Ohio and Mississippi River valleys and the Great Lakes (7). Blastomycosis is acquired through inhalation of spores, often after participating in activities that disturb the soil. Symptoms are “flu-like” and may include fever, fatigue, muscle aches, night sweats, and cough. A chronic disease may affect the lungs, skin, bones, joints, genitourinary tract, or central nervous system. Amphotericin B is the treatment of choice.

Coccidioidomycosis (“Valley Fever”) is caused by Coccidioides immitis and Coccidioides posadasii. The condition is found in the Southwestern United States and parts of Mexico and Central and South America. Like blastomycosis, coccidioidomycosis follows the inhalation of spores from the soil. Symptoms are similar to coccidioidomycosis and are flu-like. A rash on the upper body or legs is commonly encountered. Most people with coccidioidomycosis improve without treatment, but fluconazole and similar antifungals can be used (8).

Fungus Coccidioides immitis, saprophytic stage, 3D illustration showing fungal arthroconidia. Pathogenic fungi that reside in soil and can cause fungal infection Coccidioidomycosis, or Valley fever
Coccidioides immitis, an agent of fungal infection Coccidioidomycosis (aka Valley fever), saprophytic stage.

 

Histoplasmosis, caused by Histoplasma, is acquired by inhaling spores – usually from soil containing bird- or bat-droppings.  The condition is found in the Ohio and Mississippi River valleys and parts of Central and South America, Africa, Asia, and Australia (9).  Histoplasmosis is also characterized by a flu-like illness and is usually self-limiting. 

Cryptococcosis is caused by various species of Cryptococcus, yeasts that are found in the soil and on certain trees. Cryptococcus gattii is found in California, Oregon, Washington, Canada, Australia, Papua New Guinea, and South America (10). Cryptococcus neoformans is found in all countries. Cryptococcus is often associated with pneumonia or meningitis. The current global incidence is estimated at 1 million cases per year, with 50% mortality (11). Most of these cases occur in individuals with HIV / AIDS. Treatment consists of Amphotericin B and Flucytosine, followed by Fluconazole.

Paracoccidioidomycosis is caused by Paracoccidioides, found in parts of Central and South America (12). It can cause lesions in the mouth and throat, rash, lymphadenopathy, fever, cough, and hepatosplenomegaly. Talaromycosis, formally known as sporotrichosis, is an endemic mycosis caused by Talaromyces marneffei and other species. The condition is found in Southeast Asia, Southern China, and Eastern India (13). Clinical manifestations include fever, cough, lymphadenopathy, hepatosplenomegaly, diarrhea, and abdominal pain.

 

Mold Infections

Most people inhale mold spores every day without becoming ill, but occasionally severe disease can result. Infection by Aspergillus (aspergillosis) may present as an allergic reaction. The fungus can also cause infection of the sinuses and lungs. Formation of “fungal ball” (aspergillomas) may occur in patients with pre-existing lung diseases. Aspergillus can also infect the eyes, skin, cardiac valves, brain, gastrointestinal tract, and genitourinary tract. Treatment options include Voriconazole, Amphotericin B, and Isavuconazole (14).

Aspergillus (mold) under the microscopic view. Aspergillus is an agent of fungal infection.
Aspergillus spp. under a microscope

 

Zygomycosis (“mucormycosis”) is caused by a group of molds called Mucormycetes. This fungal infection is commonly associated with hyperglycemia, metabolic (diabetic, uremic) acidosis, corticosteroid therapy, and neutropenia, transplantation, heroin injection, and administration of deferoxamine (15). Common sites of infection include the paranasal sinuses and contiguous structures, cranial nerves, cerebral arteries, lungs, and skin. Treatment may include intravenous Amphotericin B, followed by oral Posaconazole or Isavuconazole.

Other molds that can cause allergies and infections in humans include Stachybotrys chartarum, Alternaria alternata, Lomentospora prolificans, Scedosporium apiospermum, Cladosporium, and Penicillium.

Pneumocystis jirovecii, an agent of Pneymocystis pneumonia
Pneumocystis jirovecii, an agent of Pneumocystis pneumonia fungal infection

Pneumocystis pneumonia

Pneumocystis pneumonia (PCP) is caused by the fungus Pneumocystis jirovecii.  Until recent years, the organism had been classified as a protozoan parasite. Pneumocystis pneumonia usually occurs in individuals with severe immune suppression, including HIV / AIDS.  Presenting symptoms include shortness of breath, fever, and a nonproductive cough. Extrapulmonary infection is rare but can occur. Treatment options include Sulfamethoxazole / Trimethoprim, Pentamidine, Dapsone + Trimethoprim, Atovaquone, or Primaquine + Clindamycin (16).

 

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References

(1) Sobel JD. Vulvovaginal candidosis. Lancet. 2007 Jun 9;369(9577):1961-71. doi: 10.1016/S0140-6736(07)60917-9.

(2) Patil S, Majumdar B, Sarode SC, Sarode GS, Awan KH. Oropharyngeal Candidosis in HIV-Infected Patients-An Update. Front Microbiol. 2018 May 15;9:980. doi: 10.3389/fmicb.2018.00980.

(3) “General Information about Candida auris”, Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Foodborne, Waterborne, and Environmental Diseases (DFWED), 2019. [Online]. Available: https://www.cdc.gov/fungal/candida-auris/candida-auris-qanda.html

(4)”Dermatophytosis”, GIDEON Informatics, Inc, 2021. [Online]. Available: https://app.gideononline.com/explore/diseases/dermatophytosis-10600

(5) M. Handler, “What is the global incidence of tinea capitis (scalp ringworm)?”, Medscape.com, 2020. [Online]. Available: https://www.medscape.com/answers/1091351-36134/what-is-the-global-incidence-of-tinea-capitis-scalp-ringworm

(6) Ilkit M, Durdu M. Tinea pedis: the etiology and global epidemiology of a common fungal infection. Crit Rev Microbiol. 2015;41(3):374-88. doi: 10.3109/1040841X.2013.856853.

(7) “Blastomycosis”, Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Foodborne, Waterborne, and Environmental Diseases (DFWED), 2020. [Online]. Available: https://www.cdc.gov/fungal/diseases/blastomycosis/index.html

(8) “Treatment for Valley Fever (Coccidioidomycosis)”, Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Foodborne, Waterborne, and Environmental Diseases (DFWED), 2019. [Online]. Available: https://www.cdc.gov/fungal/diseases/coccidioidomycosis/treatment.html

(9) “Histoplasmosis”, Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Foodborne, Waterborne, and Environmental Diseases (DFWED), 2020. [Online]. Available: https://www.cdc.gov/fungal/diseases/histoplasmosis/index.html

(10) “C. gattii Infection Statistics”, Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Foodborne, Waterborne, and Environmental Diseases (DFWED), 2020. [Online]. Available: https://www.cdc.gov/fungal/diseases/cryptococcosis-gattii/statistics.html

(11)”Cryptococcosis worldwide distribution”, GIDEON Informatics, Inc, 2021. [Online]. Available: https://app.gideononline.com/explore/diseases/cryptococcosis-10530/worldwide

(12) “Paracoccidioidomycosis”, Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Foodborne, Waterborne, and Environmental Diseases (DFWED), 2020. [Online]. Available: https://www.cdc.gov/fungal/diseases/other/paracoccidioidomycosis.html

(13) “Talaromycosis (formerly Penicilliosis)”, Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Foodborne, Waterborne, and Environmental Diseases (DFWED), 2020. [Online]. Available: https://www.cdc.gov/fungal/diseases/other/talaromycosis.html

(14) “Aspergillosis”, GIDEON Informatics, Inc, 2021. [Online]. Available: https://app.gideononline.com/explore/diseases/aspergillosis-10140

(15) “Zygomycosis”, GIDEON Informatics, Inc, 2021. [Online]. Available: https://app.gideononline.com/explore/diseases/zygomycosis-12670

(16) “Pneumocystis pneumonia”, GIDEON Informatics, Inc, 2021. [Online]. Available: https://app.gideononline.com/explore/diseases/pneumocystis-pneumonia-11850

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