• Opportunistic fungi typically induce infections in immunocompromised hosts but not in immunocompetent ones.
• These fungi are referred to as opportunistic fungi because they become pathogens in individuals with compromised immunity by taking advantage of the host’s weakened state.
• In recent years, a growing number of exotic and uncommon fungi have been connected with opportunistic infections.
• However, Candida albicans, Aspergillus spp., Penicillium marneffei, and different Zygomycetes are responsible for the majority of opportunistic infections.

Candidiasis

• Candida species are the most frequent fungi that cause human disease.
• These species are real opportunistic infections that obtain access to the circulation and deep tissues by taking advantage of the host’s weakened condition.
• The genus Candida has over a hundred species, of which only a few are pathogenic to humans. In immunocompromised hosts, C. albicans and occasionally other species cause candidiasis, a serious infection.

Properties

• C. albicans is a yeast that is ovoid or spherical with a single bud.
• It is a natural component of the gastrointestinal, genitourinary, and respiratory mucous membrane flora. It generates pseudohyphae in culture and tissue. Pseudohyphae are yeast filaments that mimic hyphae morphologically, but are not actual hyphae. On Sabouraud’s dextrose agar and bacterial culture media, Candida thrives readily. C. albicans develops smooth, creamy-white colonies with a yeasty aroma (Color Photo 64).
• It can be distinguished from other Candida species based on its carbohydrate fermentation reaction and distinctive growth characteristics.
• At 25 degrees Celsius, only Candida albicans develops chlamydospores on cornmeal agar.

Pathogenesis and Immunity 

Candida spp. are typically present as part of the normal flora on the oral cavity, gastrointestinal system, and vaginal mucosa. Candida exhibits colonisation at these sites in over 80% of healthy individuals. However, the organism is rarely seen on the surface of normal human skin, with the exception of the groyne and other intertriginous areas.

Pathogenesis of Candida infection

• Candida acquires entry to systemic circulation from the oropharynx of the gastrointestinal tract under certain situations.
• The initial step in the development of Candidal infection is colonisation of the mucocutaneous surface.
• The fungus invades human tissue through a variety of methods. When the skin or mucosa is compromised, the organism gains access to the bloodstream.
• Massive colonisation with enormous numbers of Candida allows the organism to enter the bloodstream directly and cause illness.
• Candida can spread to numerous organs in immunocompromised hosts, including the lung, spleen, liver, heart, and brain.
• Candida can generate inflammation of the eye, causing endophthalmitis, and in 10–30% of people with a widespread infection, it can also affect the skin.
• Lack of host defences plays an important role in the development of Candida infection.

Host immunity

• In healthy adults, both cell-mediated and humoral antibodies provide protection against Candida. However, cell-mediated immunity (CMI) is the most crucial.
• Despite having normal or increased levels of humoral antibodies, a change in CMI can induce widespread superficial candidiasis.
• The humoral antibodies appear to serve a little function in disease prevention.
• Healthy adults are protected from Candida by their antibodies.

Clinical Syndromes 

Candida causes a diverse array of clinical conditions, including:

• Cutaneous candidiasis: Candida species in immunocompetent hosts can infect any warm, moist, and exposed portion of the body. It causes nail, rectum, and other skin fold infections.
• Mucocutaneous candidiasis: Mucocutaneous candidiasis (thrush, perianal illness, etc.) is the most prevalent manifestation of candidiasis, however it typically does not result in mortality. Candida species can induce severe oropharyngeal and esophageal candidiasis in patients with advanced HIV-associated immunodeficiency, leading to poor food intake, malnutrition, and early death. Additionally, these patients are typically resistant to antifungal treatments.
• Chronic mucocutaneous candidiasis: Chronic mucocutaneous candidiasis is a diverse collection of clinical symptoms. This disease is characterised by a superficial, chronic Candida infection of the skin, nails, and oropharynx that is resistant to treatment. However, these patients exhibit no signs of widespread candidiasis.
• Systemic candidiasis: Endocarditis, gastrointestinal tract candidiasis, respiratory tract candidiasis, genitourinary candidiasis, and hepatosplenic candidiasis are examples of systemic candidiasis. Candidaemia and disseminated candidiasis may be symptoms of systemic candidiasis. Oral thrush and Candida esophagitis are more prevalent in AIDS patients, however candidemia and disseminated candidosis are not. Candida endophthalmitis and Candida infection of the central nervous system (CNS) are further consequences of Candida infection.
• Disseminated candidiasis: Disseminated candidiasis is a growing concern for patients with severe hematologic malignancies who are treated with immunosuppressive medicines for an extended period of time. In these individuals, severe neutropenia is the most critical risk factor for life-threatening Candida infections. In this illness, Candida typically spreads via the bloodstream and affects numerous organs, including the lungs, spleen, kidney, liver, heart, and brain. However, widespread candidiasis is seldom a significant issue for AIDS patients. In such patients, the primary concern is a severe infection of the oropharynx and upper gastrointestinal tract. The development of these problems in previously healthy persons who are not undergoing a broad-spectrum antibiotic regimen should raise a high suspicion of HIV infection. 

Epidemiology

• The Candida species is found globally. Candida species have surpassed Cryptococcus species as the most prevalent fungus affecting the CNS of immunocompromised people worldwide in recent years.
• C. albicans and Candida glabrata are responsible for infecting 70–80% of invasive candidiasis patients.
• Candida tropicalis is a leading cause of candidemia in leukaemia and bone marrow transplant patients.
• Important pathogen related with the use of vascular catheters is Candida parapsilosis.
• Since Candida is already present in the skin and mucous membranes of the host as part of the normal flora, it causes infection in the infected host and is therefore not contagious.

Laboratory Diagnosis 

Specimens

• These comprise exudates or tissues for microscopy taken from the skin or nails and examined under a microscope for the presence of Candida pseudohyphae or yeast cells in the growth phase.

Microscopy

• A Gram-stained smear of the exudates or tissue reveals oval, budding yeast and pseudohyphae that are Gram-positive and oval.
• Candida is part of the normal flora on normal skin and mucosa; therefore, only the presence of Candida in large numbers is significant.
• The presence of pseudohyphae implies an infection, although the diagnostic significance of tissue invasion is greater.

Culture 

• On Sabouraud’s dextrose agar (SDA), characteristic smooth, creamy-white colonies form.
• The growth parameters, sugar fermentation, and absorption tests are used to identify distinct Candida species.
• Germ tube is an efficient method for identifying Candida albicans and Candida dublienii. This test is dependent on C. albicans’ capacity to form germ tubes within two hours when incubated in human serum at 37 degrees Celsius.
• The term for this phenomenon is Reynold–Braude phenomenon. C. albicans produces chlamydospores on cornmeal agar at 25°C, whereas other Candida species do not.
• In addition, CHROM agar enables the presumed identification of many Candida species with the use of colour reaction in specialised medium, consequently displaying distinct colony colours based on the Candida species.
• Biochemical assays, such as AP120C and AP131C, can also be used to distinguish Candida species with greater precision.
• These assays evaluate the assimilation of various sugars in order to identify distinct kinds of fungi.

Nonculture Candida detection tests

• These consist of (a) the Candida mannan assay, (b) the Candida heat-labile-antigen assay, (c) the D-arabinitol assay, (d) the D-inositol assay, and (e) the 1,3-beta-D-glucan assay.
• Beta-Dglucan assay is a broad-spectrum test that identifies Candida in addition to species of Aspergillus, Fusarium, Acremonium, and Saccharomyces.
• This test is based on the premise that beta-D-glucan is a component of the cell wall of these fungi, detectable by its capacity to activate factor G of the horseshoe crab coagulation cascade.
• This test is extremely sensitive and specific.

Immunological tests 

• Due to the presence of anti-Candida antibodies in the sera of both sick and healthy individuals, serological testing for diagnosing candidiasis are not very effective.
• The Candida antigen skin test is a delayed hypersensitivity skin test used as an indicator of CMI functions.
• The skin test is consistently positive in immunocompetent individuals, indicating that the individual has a CMI that is intact.
• The skin test is negative in CMI-deficient patients. This individual is anergic and negative on further skin tests, including the pure protein derivative (PPD) skin test for tuberculosis.

Treatment

• Antifungal medication is the cornerstone of treatment for Candida infections.
• The azoles (fluconazole, triazole, and ketoconazole), nystatin, and amphotericin B are examples of these medications. C. glabrata is innately less susceptible to amphotericin B and other azoles and is growing in importance worldwide (ketoconazole, fluconazole, etc).
• Candida krusei is becoming more prevalent due to its tolerance to numerous antifungal treatments.
• It has innate resistance to fluconazole and ketoconazole. Additionally, it is resistant to all other antifungal drugs, such as itraconazole and amphotericin B. The fact that C. lusitaniae is resistant to amphotericin B, yet vulnerable to azoles and echinocandins, gives it clinical importance.

Prevention and Control

• Antifungal prophylaxis is indicated for patients at high risk of acquiring invasive candidiasis who have invasive candidiasis.
• There is no available vaccination for candidiasis.

References

• Medical Microbiology by Jawertz, 25th Edition
• Microbiology by Prescott 5th Edition
• https://www.cdc.gov/fungal/diseases/candidiasis/index.html#:~:text=Candidiasis%20is%20a%20fungal%20infection,and%20vagina%2C%20without%20causing%20problems.
• https://www.cdc.gov/fungal/diseases/candidiasis/genital/index.html
• https://en.wikipedia.org/wiki/Candidiasis
• https://www.webmd.com/skin-problems-and-treatments/guide/what-is-candidiasis-yeast-infection
• https://emedicine.medscape.com/article/213853-overview
• https://www.ncbi.nlm.nih.gov/books/NBK560624/
• https://rarediseases.org/rare-diseases/candidiasis/
• https://www.mayoclinic.org/diseases-conditions/yeast-infection/symptoms-causes/syc-20378999
• https://www.medicalnewstoday.com/articles/151172
• https://www.ncbi.nlm.nih.gov/books/NBK545282/
• https://www.msdmanuals.com/en-in/professional/dermatologic-disorders/fungal-skin-infections/candidiasis-mucocutaneous
• https://www.msdmanuals.com/en-in/home/skin-disorders/fungal-skin-infections/candidiasis-yeast-infection
• https://www.healthline.com/health/skin/cutaneous-candidiasis
• https://medlineplus.gov/ency/article/000880.htm
• https://academic.oup.com/cid/article/62/4/e1/2462830