Candida albicans
Summary
Candida albicans (C. albicans) is a unicellular yeast. Besides its allergenic potential, it is an opportunistic pathogen in immunocompromised individuals. C. albicans has three distinct growing features - yeast, pseudo-hyphae, and true hyphae. The cell wall of the fungus is a complicated, multi-faceted, solid structure made up of mannoproteins, β-glucans, and chitin. C. albicans is thermotolerant and a part of normal human microbiota, found at mucosal sites in healthy individuals. They grow in colonies, which are white in color with smooth and creamy texture. C. albicans can adapt and proliferate in various host environments. Ideal environmental conditions for C. albicans hyphal growth are 37°C temperature, presence of serum, neutral pH, and high CO2. In sensitized individuals, C. albicans can induce or worsen life threatening asthma and skin symptoms and atopic dermatitis. Major allergens identified are Cand a 1 and Cand a 3. Cross reactivity of C. albicans allergenic molecules is reported with molds and yeast.
Epidemiology
Worldwide distribution
Candida species are associated with immediate or delayed-type hypersensitivity (DTH). The former occurs mainly as asthma or AD, while the latter can be used to evaluate cell mediated immunity in a given patient. In 200 Tanzanian children of preschool age, DTH to C. albicans was inversely associated with infectious disease.
Candida spp. is the most important agent causing opportunistic mycoses globally, responsible for 72.8 cases/million/year with 33.9% case/fatality ratio worldwide. C. albicans is also the most common species responsible for invasive candidiasis (66% of all the Candida spp.) throughout the world. In HIV patients, the prevalence of oral candidiasis due to C. albicans correlates with the degree of immunosuppression.
Candida species, especially C. albicans, may cause hospital-acquired bloodstream infections (BSI) with variable frequency worldwide, from 37% in Latin America to 70% in Norway. It is the 4th leading cause of nosocomial BSI in the United States (US), responsible for 8-10% of all hospital-acquired BSIs and considered as the second most common cause of death from such infections in the US.
Risk factors
Sino-nasal polyposis increases the risk of hypersensitivity to C. albicans. On the infectious side, low neutrophil counts, post-surgical breaches in GI tract, use of broad-spectrum antibiotics, corticosteroids, central venous catheters, parenteral nutrition, prolonged ICU stay, invasive ventilation, and Candida spp. colonization at different body sites are risk factors for the development of candidemia.
Route Of Exposure
Main
Inhalation is the primary route of exposure, however it is still controversial whether inhalation of this mold causes allergenicity.
Clinical Relevance
C. albicans, although a normal component of human microbiota, can cause hypersensitivity diseases in healthy individuals due to its ability to activate Th 1, Th 2 and Th17 responses. Candida spp. elicits IgG responses in normal subjects, and type II hypersensitivity reactions in some patients, such as those showing reactions against the mannan-polysaccharide present in Candida cell wall.
Asthma
Mold-sensitized individuals are more predisposed to developing life threatening asthma. A study by Khosravi et al. (2009) extracted the C. albicans antigens and evaluated the specific anti-Candida IgE in the sera of 95 atopic dermatitis (AD), 85 asthmatic patients, and 70 non-atopic individuals (controls). Sensitization to C. albicans was present in 52.6% of AD patients and 54.1% of asthmatic patients versus 4.3% of controls. In AD patients, predominant allergens were found at the 25, 34, and 57 kDa protein bands, only partially overlapping with major allergens 22, 25, and 34 kDa in asthmatic patients. The study indicated that C. albicans may produce various allergenic components, which can lead to allergic reactions and may be important pathogenetically for AD and asthma patients.
Atopic Dermatitis
Fungi are considered to be important allergen sources in individuals with atopic disease. C. albicans colonizing the GI tract can induce or aggravate atopic dermatitis (AD), asthma, and other atopic diseases. Diabetic patients may develop skin candidiasis, while immunocompromised patients are at greater risk for sepsis. Chronic exposure to C. albicans may aggravate AD in atopic and allergic individuals.
A study by Savolainen et al. (1993) evaluated the association between C. albicans exposure and sensitization with AD symptoms among 156 allergic individuals. The results showed a statistically significant association between C. albicans sensitization and AD symptoms in sensitized individuals exposed to C. albicans.
Other diseases
Candida infections can involve skin (intertrigo, wound infections), mucous membranes (oropharyngitis, esophagitis, and vulvovaginitis), and lower urinary tract. C. albicans can cause painful mucosal infections, which includes vaginitis in women or oropharyngeal thrush (in HIV + patients), and also severe life-threatening blood/systemic infections in vulnerable patients.
Mucosal infections: C. albicans can cause thrush, identified as white spots, which underlines the inflammation site, also known as pseudomembranous candidiasis. Common locations comprise vaginal (vulvovaginal candidiasis), oral and pharyngeal (oropharyngeal candidiasis), esophageal, and GI mucosae (gastrointestinal candidiasis).
Systemic infections: Candida spp. are also reported to cause hospital acquired blood stream infections, and the incidence of nosocomial candidiasis may range from 3% to 15% depending on the hospitals. Mortality rate of invasive candidiasis ranges from 40-60%, and may increase above 60% when complicated with septic shock. In immunocompromised individuals, C. albicans can induce systemic infections affecting the cardiovascular system, bones, and brain.
Cross-Reactivity
C. albicans allergenic compounds of molecular weight 18, 24, 26, 34, 38 and 48 kDa have shown cross reactivity with the yeast Pityrosporum orbieular. Allergenic molecules such as Cand a 3, Cand a CyP, and Cand a enolase are cross reactive to fungal spp. from the same phylum.
Aspergillus fumigatus allergen Asp f 12, (a HSP90 protein) shows remarkable homology to the HSP90 heat shock protein of C. albicans, but also to HSP90 from S. cerevisiae, Trypanosoma, housefly, mouse, and Homo sapiens. In inhibition experiments, cross reactivity was observed between the allergen enolase of C. albicans (Cand a enolase), A. alternata, C. herbarum, and A. fumigatus.
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