Introducing the Microorganism
Candida albicans is a human microbiome member. It is opportunistic in nature and exists as a non- harmful resident of the genitourinary tract in 70% and of oral cavity in 75% of humans. It has shown opportunistic behaviour leading to infections in case of individuals whose immune system is compromised (immunocompromised). C. albicans is mainly responsible for 2 types of infection: superficial candidiasis like vulvovaginal or oral infections and systemic life-threatening infections. C. albicans has been observed to cause vulvovaginal candidiasis in approximately 75% of women.
C. albicans is an obligate and diploid organism possessing 8 pairs of chromosomes, which range from 0.95 to 3.5Mb in size. It shows a diploid morphology and grows both as filamentous fungus like ellipsoid elongated cells with presence of pseudo hyphae and budding yeast. The hyphae formation is promoted by a high pH in environment, starvation, presence of serum or N-acetylglucosamine, CO2, and physiological temperatures. A number of features possessed by Candida genes are rarely found in fungi. A complex repeat referred to as an MRS has a tendency to reoccur in almost every chromosome and is a frequent chromosomal translocation site. It also shows an exceptional level of heterozygosity in the genome (Enfert and Hube, n.d.).
Pathogenesis of C. albicans
A variety of fitness attributes and virulence factors are involved in the ability of C albicans to cause infection. Fitness attributes of Candida albicans are: metabolic flexibility, rapid adaptation ability to changes in environmental pH, robust stress response machineries, and powerful nutrition acquisition system The transition between the hyphal and yeast growth forms have been observed to be important for pathogenicity.
Hyphal form has shown more invasiveness than the yeast forms. The yeast form is believed to have a role in dissemination of the organism. Mutants with the hyphae forming inability are usually attenuated in virulence. Hyphae formation has been linked to expression of virulence factor genes, which do not have any involvement in formation of hyphae. Such proteins are: hyphal wall protein Hwp1, secreted aspartic proteases Sap4, Sap5 and Sap6, agglutinin-like sequence protein Als3, and hypha-associated proteins Ece1 and Hyr1.
Adhesion and Invasion
C. albicans contains a specialised protein set (adhesins) responsible for adherence to other Candida cells, host cells, and other abiotic surfaces like GPI-linked proteins (Hwp1, ALSEap1, Iff4 and Ecm33), cell-surface associated proteases (Sap9 and Sap10), and the non-covalent wall-associated proteins (Mp65, a putative β-glucanase, and Phr1, a β-1,3 glucanosyl transferase) surface protein Int1. Agglutinin like sequence (ALS) proteins are one of the main studied adhesins in C. albicans. ALS gene is involved in coding glycosylphosphatidylinositol (GPI)-linked cell surface glycoproteins. ALS3 gene expression has been found to be upregulated in oral epithelial cells infection in vitro and vaginal infection.
Hwp1 covalently links C. albicans to host cells by acting as a substrate for mammalian transglutinases. Hwp1 mutants (hwp1Δ/Δ) have shown reduced adhesion to buccal epithelial cells and reduced virulence in mouse models.
C. albicans makes use of two mechanisms for entry into host cells: active penetration and induced endocytosis.
Induced endocytosis. They express invasions on cell surface which bind to the host ligands (E cadherin and N cadherin on epithelial and endothelial cells respectively) leading to entry of fungal cell into host cell by engulfment. So far two invasins have been identified viz, ALS3 and Ssa1.
Active Penetration. This process requires a viable hyphae. Factors influencing this route of invasion are still unclear with physical and adhesive forces believed to be crucial. Saps (secreted aspartic proteases) have shown an active contribution in this mechanism.
Formation of Biofilm. Catheters, dentures, and mucosal cell surfaces are some of the common substrates for biofilm formation by this organism. The biofilm formation is sequential beginning with substrate adherence followed by proliferation, hyphal cell formation, extracellular material accumulation, and lastly, yeast cell dispersion from the complex. Transcription factors involved in biofilm formation are Efg1, Bcr1, and Tec1. Other biofilm formation regulators are Rob1, Ndt 80, and Brg1.
Virulence factors
Ability to overcome flushing action of salivary flow; adherence of Candida to human epithelial cells by weak and reversible interactions involving hydrophobic and electrostatic forces (ALS and HWP1 encode glycoproteins that promote candida adherence); and increased virulence factors expression and reduced antimicrobial susceptibility leads to biofilm formation on biomaterials, dentures, and medical devices. C. albicans generates true hyphae which are distinct from pseudohyphae as true hyphae do not have constrictions at yeast or hyphal junctions. Leads to greater resistance to phagocytosis, enhances adherence, ability to invade epithelial layers, and enhanced virulence gene expression (Willimas, & lewis, nd).
Types of Candidiasis
Oral Candidiasis. Generally comprises of 4 primary oral forms of infections:
Oral thrush. White, creamy lesions on surface of oral mucosa. Affects newborns with an immature immune system.
Pseudomembrane candidiasis: Affects older individuals with immune suppression and nutritional limitation or AIDS.
Acute Erythrematosus candidiasis: Affects after the intake of abroad spectrum antibiotic which lowers the oral bacterial population and allows growth of Candida by removal of competitive microbes. Seen as red lesions on the tongue dorsum and palate.
Chronic erythrematous candidiasis: Atrophic lesions with denture stomatitis and angular cheilitis. Prevalently found in HIV positive individuals and AIDS patients.
Chronic hyperplastic candidiasis: Also known as candida leucoplakia. Smooth or nodular white lesions on surface of oral mucosa that cannot be removed by gentle scraping. Higher prevalence in middle-aged smokers (men). Characteristic feature is oral epithelium penetration by C. albicans hyphae. The hyphae can be detected in biopsy section by Periodic Acid-Schiff (PAS) or other staining methods.
There have been speculations about candida having a role in oral cancer. However, it is yet to be confirmed.
Candida-associated lesions. Secondary form of oral candidiasis.
Angular cheilitis. C albicans in combination with S. aureus form lesions at angles of mouth.
Median Rhomboid Glossitis: Diamond-shaped lesions at posterior midline on dorsum of tongue.
Candida associated denture stomatitis. Denture when not properly cleaned provide ideal environment for Candida growth. Candida adheres to the acrylic acid in denture base material.
Genital/vulvovaginal Candidiasis (VVC)
Genital/vulvovaginal candidiasis (VAC) is also known as “yeast infection.” It occurs when there has been an overgrowth of yeast in the vaginal area. Near 75% of all women suffer from at least one “yeast infection” in their lifetime; hence, the infection is quite common (Centers for Disease Control and Prevention, 2015a).
Candida albicans is present tin the body all the time. However, when the acidity of the vagina changes or there are hormonal imbalances, then Candida can multiply manifold. Under this condition, candidiasis occurs.
Symptoms of Vaginal Candidiasis
Women who suffer from VVC have genital burning, itching, and once in awhile have a cottage cheese-like discharge from the vagina.
Normally 75% of the women suffer from vaginal candidiasis at least once in a life time. Sometimes, men can get the infection too. VVC occurs in people whose immune system is compromised mostly. Other risks conditions for candidiasis to occur in a woman include pregnancy, long-term usage of broad spectrum antibiotics, corticosteroid medicine usage, and diabetes.
What Is Invasive Candidiasis?
When the yeast called Candida causes an infection in the body, invasive candidiasis occurs. Invasive candidiasis is unlike the oral candidiasis or vaginal candidiasis where it is localized to one part of the body. Invasive candidiasis is capable of affecting the heart, eyes, brain, bone s, blood, and other parts of the body.
C. albicans normally lives in the skin and in the gastrointestinal tract. However, under certain conditions, the C. albicans enters the blood stream of patients leading to invasive candidiasis or candidemia. In the USA, the maximum number of hospitalizations due to bloodstream infections is due to invasive candidiasis and often results in high medical spending, poor outcomes, and lengthy hospital stays (Centers for Disease Control and Prevention, 2015b).
Symptoms of Invasive Candidiasis
Invasive candidiasis has common symptoms like fever and chills. These fever and chills conditions do not improve after antibiotic treatments against suspected bacterial infections. Other symptoms develop, if the infection by C. albicans spreads to eyes, heart, bones, and joints.
Who Gets Invasive Candidiasis?
Most of the people who get cnadidiasis include people who have been admitted to hospitals or been in contact with hospital settings such as nursing homes. People who are highly at risk for developing cnadidiasis include those who have had a central venous catheter; People admitted to the ICU, people whose immune system is weak such as those in HIV patients; people who have been on broad spectrum antibiotics, those with low neutrophil counts, and people with a kidney failure or those who have had a surgery in the GI tract, and people with diabetes.
Sources of Invasive Candidiasis
Candida albicans normally lives on the skin and in the GI tract without leading to any problems. However, when the person’s own Candida sp. enters the bloodstream, for example, when an IV catheter is inserted upon surgery, then invasive candididasis cocurs. Medical equipment can become infected with Candida and allow it to enter the blood stream. Hand hygiene is important in the case of candidiasis as health workers may carry the microorganism on their hands.
Treatment for Invasive Candidiasis
Invasive candidiasis is treated depending on the age, severity of infection, patient location, and immune status. Echinocandin can be given through the vein for most of the candidiasis patients. Sometime, the use of fluconazole and amphotericin B is allowed.
How Long Does The Treatment Last?
For invasive candidiasis, treatment should be continuous even after two weeks after the resolution of signs and symptoms. This is to ensure that no Candida yeast is present in the blood stream. Other forms of invasive candidiasis of the bones, blood, eyes, and joints need longer times ot be treated.
Epidemiology/Outbreaks of Candidiasis
C. albicans is prevalent worldwide. It has been isolated from animals, soil, animals, inanimate objects, foods, and hospitals (Ruhnke, 2006; Edwards, 2009). C. Albicans occurs in both immunosuppressed and immunocompromised people. Risk factors for candidiasis include steroid administration, antibiotic therapy, chemotherapy, administration of immunosuppressants, soild organ and stem cell transplants, disease states such as diabetes, AIDS, lymphoma, and leukaemia as well as in burn and trauma patients. However, with the introduction of HART or highly active retroviral therapy there has been a decrease in incidences of candidiasis in HIV-infected patients.
Transmission from One Host to Another
Most infections are from the self that arise from the person’s own flora, rather than a cross infection occurring. Although rarely occurs, there have been nosocomal transmissions between patients, from the hands of workers in the health care departments, and from inanimate surfaces. Although rare, person-to-person transmission between patients or relatives can occur (Rangel-Frausto et al., 1994).
Therapies for Candidiasis - Drug Susceptibility
Susceptibility of Candidiasis has been shown for amphotericin B, the azoles, flucytosine, combination drug therapies, and echinocandins. Oral and topical azoles such as clotrimazole, butoconazole, econazole lipogel, and triazole can be utilized for vaginal candidiasis. Mucocutaneous candida infections can be treated with itraconazole and fluconazole, which are effective systemic anitfungals. Cutaneous candididasis can be treated with echinocandins and voriconazoe. Caspofungin is used to treat invasive candidiasis and oral candididasis treatred with posaconazole.
Drug Resistance
Repeated use of fluconazole for candidiasis has led to resistance towards the durg. This is even more so pronounced in immune-suppressed people who are taking this drug for prophylaxis. Echincandins resistance has also been reported.
Supportive Therapy - Susceptibility to Disinfectants
Candida albicans strains can be effectively killed by sodium hypochlorite, potassium iodide, and iodine. C. albican strains are also completely killed within 5 minutes by chlorhexidine. However, calcium hydroxide has no effect on candididasis. Isolates of C. albicans are susceptible to 0.5% ecodiol, 70% ethanol, and a combination of 0.5% ecodiol and 1.2% sodium hypochlorite.
Supportive Therapy - Physical Inactivation
UV light is effective in reducing the load of the fungus, but cannot completely kill the yeast.
Survival Outside Host
C. albicans can survive on the palm of hands for 45 minutes and on inanimate surfaces up to 120 days. C. albicans have been isolates from cots, bed sheets, nursery washbasins, and even from distilled water maintained at room temperature.
Diagnosis and Testing of VVC
The symptoms of VVC overlap with many genital infections. However, physical examination alone may be difficult to confirm the VVC presence. Normally, the testing includes collecting a sample of vaginal secretion and observing the sample under the microscope. The observation under the microscope is done to check if there is an abnormal l number of C. albicans. A fungal culture may not help diagnose the condition as C. albicans are present in the body at all times.
Diagnosis and Testing of Invasive Candidiasis
Plate cultures of Candida albicans is normally used to diagnose candidiasis. Also, healthcare providers depend on your symptoms, history, physical examination and lab tests to diagnose invasive candidiasis. Growing Candida in culture, by taken a blood sample and sending it to the laboratory is the commonest way of detecting candidiasis.
Molecular Diagnostic Tests for C. albicans
Molecular diagnostic tests can be used to detect candidiasis in a fast and reliable manner. The PCR technology, especially, appears to be sensitive and precise. The commonly appearing C. albicans infection can be diagnosed this way
During the developmental stages of the disease, the PCR technique can be used as even minute quantities of the fungal DNA can be detected through this method. Contrary to other techniques, PCR is the only technique used to detect Candida spp.. from clinical samples and specimens.
References
Centers for Disease Control and Prevention, 2015a, Genital / vulvovaginal candidiasis (VVC), Available at <http://www.cdc.gov/fungal/diseases/Candidiasis/genital/>(Accessed: 3 May 2016)
Centers for Disease Control and Prevention, 2015b, Invasive Candidiasis, Available at <http://www.cdc.gov/fungal/diseases/candidiasis/invasive/index.html>(Accessed: 3 May 2016)
Edwards, J E, 2009, Candida species. In G. L. Mandell, J. E. Bennett & R. Dolin (Eds.), Mandell, Douglas, and Bennett's Principles and Practices of Infectious Diseases (7th ed., ). USA: (c) Churchill Livingston, New York.
Enfert, C and Hube, B n.d., Candida: Comparative and Functional Genomics. Available at <http://www.horizonpress.com/can> (Accessed: 3 May 2016).
Rangel-Frausto, MS., et al., 1994, An experimental model for study of Candida survival and transmission in human volunteers. European Journal of Clinical Microbiology and Infectious Diseases, vol. 13, 590-595.
Ruhnke, M, 2006, Epidemiology of Candida albicans infections and role of non-Candida albicans yeasts. Current Drug Targets, vol. 7, 495-504.
Williams & Lewis M, nd, Pathogenesis and treatment of oral candidosis, United Kingdom : Cardiff University.
