Candidiasis

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CANDIDIASIS

Candida albicans is an opportunistic fungal pathogen that is responsible for candidiasis in human hosts.

C. albicans grow in several different morphological forms, ranging from unicellular budding yeast to true hyphae with parallel-side wall .

Candida albicans is a unicellular, oval-shaped diploid fungus (a form of yeast )

Typically, C. albicans live as harmless commensals in the gastrointestinal and genitourinary tract and are found in over 70% of the population. Overgrowth of these organisms, however, will lead to disease

STRUCTURE OF C.ALBICANS

Candidiasis is a fungal infection that can affect areas such as the:

Skin

Genitals

Throat

Mouth

Blood

EPIDEMIOLOGY

Over 75% of women suffer from a C. albicansinfection, usually vulvovaginal candidiasis, in their lifetimes, and 40-50% of them will have additional occurrences(s).

Interestingly, C. albicans are the 4th leading cause for nosocomial infections in patients’ bloodstreams.

This could result in an extremely life-threatening, systemic infection in hospital patients with a mortality rate of 30%

Epidemiology

Several Candida species are commensal and colonize the skin and mucosal surfaces of humans.

Who is at increased risk? Babies with a nappy rash. People with a metabolic disorder, including diabetics. Overweight people. Pregnant women, and women who take high-dose

contraceptive pills, eg Ovran. People who work in wet conditions. People who are HIV-positive or suffer from another type of

immunodeficiency.

There are several types of candidiasis:

If it is in the mouth or throat, it is called oral candidiasis, oropharyngeal candidiasis, or thrush.

If it affects the genital area, it is called a yeast infection. In women, it may be called a vulvovaginalyeast infection.

If yeast infects the skin on a baby's bottom area, it causes a diaper rash.

If the infection enters your bloodstream, it is called invasive candidiasis or candidemia

PATHOGENESIS Candidiasis is caused by the abnormal growth in C.

albicans, which is usually due to an imbalance in the environment.

Usually, this imbalance occurs in a woman’s vagina –this infection less likely to occur for men.

Several events can spark an imbalance. For example, antibiotic use can decrease the amount of lactobacillus bacteria, which decreases the amount of acidic products and the pH of the vagina. Other events are pregnancy, uncontrolled diabetes, impaired immune system, and irritation of the vagina.

C. albicans are able to take advantage of the conditions and outcompete the normal microflora, resulting in candidiasis or a yeast infection

TRANSMITION

Candida albicans is usually transmitted from mother to infant through childbirth, and remains as part of a normal human’s microflora.

The overgrowth of C. albicans leads to symptoms of disease, and it occurs when there are imbalances – for example, changes in the normal acidity of the vagina.

C. albicans infections very rarely spread through sexual intercourse. The typical reservoir for C. albicansis in the normal human microflora, and is not found in animal vectors

Virulence FACTORS C. albicans has several virulence factors which make it

harmful to its host; one of which is its use of cell wall adhesins.

Adhesin proteins promote the binding of the organism to host cells via hydrophobic interactions.

This reduces the level of yeast clearance from the body under normal immune regulation

CONTI… When C. albicans penetrates host mucosal surfaces

following morphogenesis into invasive filaments, the polymorphic growing pattern helps the yeast invade host tissue by secreting various degradative enzymes, including various proteinases, aspartyl proteases, and phospholipases.

phenotypic switching also plays a role in altering the yeast's adherence properties, antigen expression, and tissue affinity. Switching might provide cells with a flexibility that results in the adaptation of the organism to the hostile conditions imposed not only by the host but also by the physician treating the infection

DISEASES AND SYMPTOMS

A candida infection of the skin appears as a clearly defined patch of red, itchy skin, often leaking fluid. Scabs and pustules may be seen around the edge of the rash.

It will usually be found in areas such as the groin, the folds of the buttocks, between the breasts, toes, or fingers, and in the navel.

A vaginal yeast infection may well result in a slow leakage of a thick, white, cheese-like substance. The vagina may itch or burn, especially during urination or sex. Pain or discomfort during intercourse is common.

DISEA… Candidal paronychia is candidiasis of the fingernails.

It often strikes people whose hands are in water a lot. Sometimes it presents as a painful, red, swollen area around the fingernail. In worse cases, the fingernail may separate, revealing a discoloured white or yellow nail bed.

Oral thrush causes curd-like white patches inside the mouth, on the tongue and palate and around the lips. It may also cause cracked, red, moist areas of skin at the corners of the mouth. Thrush patches may or may not be painful.

DIAGNOSIS The diagnosis is most commonly made on the basis of

the skin's appearance and occasionally a skin scrape sample is taken to confirm the clinical findings

For oral thrush, a suspension of antifungal medication can be swished in the mouth and swallowed.

vaginal mucosa are examined under the microscope; a potassium hydroxide smear, Gram stain, or methylene blue is useful for direct demonstration of fungal cells

DIAGNOSIS Diagnosis of a yeast infection is done either via microscopic

examination or culturing. For identification by light microscopy, a scraping or swab of the affected area is placed on a microscope slide. A single drop of 10% potassium hydroxide (KOH) solution is then added to the specimen. The KOH dissolves the skin cells, but leaves the Candida cells intact, permitting visualization of pseudohyphae and budding yeast cells typical of many Candida species.

For the culturing method, a sterile swab is rubbed on the infected skin surface. The swab is then streaked on a culture medium. The culture is incubated at 37 °C for several days, to allow development of yeast or bacterial colonies. The characteristics (such as morphology and colour) of the colonies may allow initial diagnosis of the organism causing disease symptoms.

Treatment For infection of the skin, you can get an antifungal

cream or powder or prescription of antifungal drug.

For vaginal yeast infections, treatment consists of antifungal medications that are administered directly into the vagina as tablets, creams, ointments, or suppositories, or administered by mouth (e.g., fluconazole).

TREATMENT Cutaneous candidiasis — This skin infection can be

effectively treated with a variety of antifungal powders and creams. The affected area must be kept clean and dry and protected from chafing.

Deep candidiasis — This infection is usually treated with intravenous fluconazole. People with very low white blood cell counts may need an alternative intravenous anti-fungal drug, such as caspofungin or micafungin

MECHANISM OF ACTION OF DRUG

•Amphotericin B binds with ergosterol, a component of fungal cell membranes, forming a transmembrane channel that leads to monovalent ion (K+, Na+, H+ and Cl−) leakage, which is the primary effect leading to fungal cell death.

• fluconazole inhibits the fungal cytochrome P450 enzyme 14α-demethylase. This inhibition prevents the conversion of lanosterol to ergosterol, an essential component of the fungal cytoplasmic membrane, and subsequent accumulation of 14α-methyl sterols.

• Fluconazole is primarily fungistatic; however, it may be fungicidal against certain organisms in a dose-dependent manner, specifically Cryptococcus.

CLOTRIMAZOLE

Clotrimazole works to kill individual Candida or fungal cells by altering the permeability of the fungal cell wall.

It binds to phospholipids in the cell membrane and inhibits the biosynthesis of ergosterol and other sterols required for cell membrane production. This leads to the cell's death via loss of intracellular elements

KETACONAZOLE interferes with the fungal synthesis of ergosterol, a

constituent of fungal cell membranes, as well as certain enzymes.

As with all azole antifungal agents, ketoconazoleworks principally by inhibiting the enzyme cytochrome P450 14-alpha-demethylase (P45014DM).

This enzyme participates in the sterol biosynthesis pathway that leads from lanosterol to ergosterol. Lower doses of fluconazole and itraconazole are required to kill fungi compared to ketoconazole, as they have been found to have a greater affinity for fungal cell membranes.

Disrupt fungal cell membrane

Polyenes – amphotericin, Nystatin

Azoles

Imidazole – Ketoconazole, Miconazole, Clotrimazole

Triazole – Fluconazole, Itraconazole

Allylamines - Terbinafin

Echinocandins - Capsofungin

Inhibit mitosis - Gresiofulvin

Inhibit DNA synthesis - Flucytosine

Miscellaneous

Tolnaftate

Cyclopirox

Mechanism of action of Antifungal agents

PREVENTION In general, you can prevent most Candida infections by

keeping your skin clean and dry, by using antibiotics only as your doctor directs, and by following a healthy lifestyle, including proper nutrition.

People with diabetes should try to keep their blood sugar under tight control.

If you have HIV or another cause of recurrent episodes of thrush, then antifungal drugs such as clotrimazole(Lotrimin, Mycelex) can help to minimize flare-ups

THANK YOU…