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Historical prespective

B. Lagenbeck in 1839 in Germany was the first to demonstrate that a yeast-like fungus existed in the human oral infection "thrush." He also found that a fungus was able to cause thrush.

The genera Candida, species albicans was described by botanist Christine Marie Berkhout. She described the fungus in her doctoral thesis, at the University of Utrecht in 1923. Over the years the classification of the genera and species has evolved. Obsolete names for this genus include Mycotorula and Torulopsis. The species has also been known in the past as Monilia albicans and Oidium albicans. The current classification is nomen conservandum, which means the name is authorized for use by the International Botanical Congress (IBC).

The full current taxonomic classification is available at Candida albicans.

The genus Candida includes about 150 different species. However, only a few of those are known to cause human infections. C. albicans is the most significant pathogenic (=disease-causing) species. Other Candida species causing diseases in humans include C. tropicalis, C. glabrata, C. krusei, C. parapsilosis, C. dubliniensis, and C. lusitaniae.

Classification:

Candidiasis can be classified according to the site of infection into:

Localoized mucocutaneous:

• Oropharyngeal candidiasis
• Esophageal candidiasis
• Candida vulvovaginitis
• Chronic mucocutaneous candidiasis.

Invasive Candidiasis:

More serious and usually presenting in an immunocompromised host.

• Candidaemia
• Candida endophthalmitis
• Candida endocarditis
• Candida osteoarticular disease

Pathophysiology:

Candida is a normal commensal of skin and mucous membranes. A competent immune system and an intact regenerating healthy skin prevent the virulence of Candida.

The main virulence factors that mediate the infection: (2)

1. Secreting molecules that mediate adherence into host cells
2. Production of hydrolases which has a lytic effect on tissues and facilitate the invasion by the bacteria.
3. Polymorphism: Candida has the ability to grow either as pseudohyphae (elongated elipsoid form) or in a yeast form (rounded to oval budding form. While the role of #polymorphism is not clearly understood in the virulence of Candida, it’s noted that species capable of producing the most severe form of the disease has this ability.
4. Biofilm production: which means the ability to form a thick layer of the organism on the mucosal surfaces or even on catheters and dentures.

Patients was candida vulvovaginitis were found to have decreased levels of mannose binding lectins (MBL) . Further investigations revealed that 2 genetic mutations in genes responsible for MBL and IL4 production increase the host susceotibility of getting recurrent candidal vulvovaginitis.(3)

Risk factors:

Any condition that compromises cell mediated immunity, worsens the general status of the patient or provide a favorable medium for candida to form biofilms put the patient at increased risk for having candidiasis.(4)

Conditions that compromises cell mediated immunity:

• T cell deficiencies as in DiGeorge syndrome, Wiscot-Aldrich syndrome and ataxia-telengictasia.
• Bone marrow transplant
• Leukaemias
• Corticosteroids use or immunosuppresive drugs.

Conditions that worsens the general condition:

• Malignancies
• Recent chemotherapy
• Trauma
• Recent surgery
• Prolonged hospitalization
• Broad spectrum antibiotics
• Renal failure
• Haemodialysis (especially if prolonged)

Dentures that provide a favorable media for forming biofilms:

• Prolonged central venous catheters insertion
• Prolonged foley’s catheter insertion
• Prolonged mechanical ventilation

Clinical manifaestations:

Oropharyngeal candidiasis:(5), (6)

Many cases are asymptomatic (mild disease or poor general condition) Dysphagia or odynphagia Difficulty tasting food feeling of mouth fullness and discomfort

Candida esophagitis:(7)

Candida esophagitis usually comes late in the course of AIDS (or any immunodeficiency) (8), so patient has the symptoms and signs of the underlying disease. Odynophagia Weight loss due to decreased food intake.

Candida vulvovaginitis:

Symptoms of vulvovaginitis caused by Candida species are indistinguishable and include the following:

• Pruritus is the most significant symptom
• Change in the amount and the color of vaginal discharge: It is characterized by a thick, white "cottage cheese-like" vaginal discharge
• Pain on urination (dysuria)
• Pain on sexual intercourse (dyspareunia)
• Vulvovaginal soreness
• Symptoms aggravate a week before the menses.

Chronic mucocutaneous candidiasis (CMCC): (9)

CMCC is a syndrome characterized by chronic or recurrent superficial candida infection in the skin and mucous membranes in association with endocrinal and autoimmune deficiencies. (10) Characterized by inability of T cells to react to candidal antigens. Presents with: Recurrent or chronic candidal infections. Infection is usually superficial though invasive candidiasis is encountered especially in new born.(11) Enocrinopathies as hypoparathyroidism and adrenal insufficiency may accompany chronic candidiasis.

Invasive candidiasis:

Candidaemia: (12) mimics the presentation of sepsis:

• Fever: in patient who is known immunodeficient, fevers are usually high and spiking.
• A capillary leak syndrome can develop with severe swelling, edema, and third spacing of fluids.
• General symptoms can include flu like symptoms as well as shaking chills or rigors.(13)
• If the respiratory system is the primary source for sepsis then sore throat, productive cough, and pleuritic chest pain may be present.

Candida osteoarticular disease: invasion of bones usually presents after weks to months after candidaemia. Fever is not present in all patients Loss of function, pain and tenderness are the main presenting symptoms.

Candida endophthalmitis: Candida endophthalmitis presents in severly immunocompromised patients but most common risk factor is IV drug abuse.

Fever: is not present consistently in all patients except associated candiaemia is present. Red eye. Floaters and decreased visual acuity: but markedly decreased vision is not present till very late in the course of the disease. Eye pain