Fungus

Candida albicans

Brought to you by :- Hind Hamed Abed Collage of Medicine ,University of Baghdad

Candida Culture

Contents
Introduction Mycology Basics Disease capabilities Pathogenesis Laboratory diagnosis Drug therapy Research

Introduction:-

It is the most common fungal pathogen worldwide -It considered the 4th leading causes of nosocomial infections, &cause 40% mortality -It also made significant mortality and morbidity in low birth-weight infants & affect 75% women, 45% experience recurrence. It account more than > 10 million visits/year - classified as a STD by CDC - cancer and HIV-AIDs patients. - most commonly manifested in patients with leukemia or HIV-AIDs infections. Oral candidiasis is often a clue to acute primary infection. - increasing resistance to drug therapies due to antibiotics and antifungals.

www.ken.coar.org

www.arboretum.harvard.edu
www.bio.umass.edu
Mycology Basics
Kingdom: Fungi More than 10 million species, but only ~400 human disease. Sexual Groups Ascomycota Basidiomycota Zygomycota Chytridia Fungi Imperfection Very few species are in a commensally relationship with humans - includes Candida albicans and Malasezia furfur Diseases caused by fungi are usually accidental Endogenous and Exogenous Sources Increasing problem due to antibacterial & immunosuppressive agents Molecular mechanisms of pathogenesis not well-defined

The 5 main groups

Classification of Fungi. Fungi are classified based on their ability to reproduce sexually, asexually, by a combination of both. The different reproductive structures places them in the appropriate category. (Baron, 1996)

Penicillium chrysogenum www.doctorfungus.org

Fungal Characteristics
Plant-like lacking chlorophyll Cell wall chitinous matrix Free-living saprobes and heterotrophy needs Carbon source and Nitrogen source Yeasts or Molds or both Success of an infection Accidental Overcoming host barriers Presiding in host with immunological defects

•Candida is a yeast like fungus which inhabits almost all humans.•Most common cause of opportunistic mycoses worldwide.•The genusCandida includes around 154 species.•6 are most frequently isolated in human infections.•Candida albicans is the most abundant & pathogenic.•C. tropicalis; C. glabrata; C. parapsilosis; C.kusei; & C. lusitaniae,causative human infective agents.•Geotrichum is yeast found worldwide in soil, water, air & sewage. A coloniser of human intestinal tract. Candida


Candida•It lives in the moist dark mucous membranes which line the mouth, vagina and intestinal tract.•Ordinarily it exists only in small colonies. Prevented from growing too rapidly by the human host’s immune system, and by competition from other microorganisms in and on the body’s mucous membranes.•When this delicate balance is upset, candida can grow rapidly and aggressively, causing many unpleasant symptoms.

Figure 1. Typical Yeast

Figure 2. Typical mould
Yeast Characteristics solitary, unicellular reproduction via budding rounded shape moist & mucoid colonies
Mould Characteristics filamentous hyphae hyphal formation tips may be rounded (conidia/spores)


Different strains of Saccharomyces are used in brewing and baking (right) Candida albicans, also a unicellular yeast, causes Candidiasis (thrush) infections in humans.

Saccharomyces sp.

Sporangia and Spores of the Penicillium sp. Fungal hyphae with fruiting structure (r). Similar fungi are the skin-inhabiting dermatophytes of the Epidermophyton and Microspores groups

Fungi-yeasts: Candida albicans

Yeast Bud Formation
Stages of bud growth and yeast cell cycle (Baron et. Al., 1996)
Hyphal Formation
Polarized hyphal formation (Baron et. Al., 1996)

Pathogenesis

Host Recognition Adhesions Enzymes Hydrolysis: Phosphoplipases, Lipases, Proteinases 4.Morphogenesis Yeast form to Filamentous hyphae/pseudohyphae 5.Phenotypic Switching

Figure 1. skin equivalent before infection

Figure 2. Infection with pathogenic clinical isolate of C. albicans. After 48 h the yeast penetrates the skin equivalent and destroys the tissue
Figure 3. Infection with non-pathogenic C. albicans. This strain is not able to penetrate into the tissue and thus behaves as a virulent as shown in the mouse model of systemic infection.
Virulence assay of different C. albicans strains using the skin equivalent (AST 2000)
(Fraunhofer, 2002)

MORPHOGENESIS

Figure 2. Morphogenic forms of Candida albicans http://cbr-rbc.nrc-cnrc.gc.ca/thomaslab/candida/caindex.html
Figure 1. Morphogenesis. Morphogenesis in C. albicans is a pivotal virulence factor that allows rapid multiplication and subsequent dissemination in host tissue. (www.kent.ac.uk)


•Candida albicans can disturb the immune system at different levels.•It is a polyantigenic organism, containing at least 30 different antigens.•It cross-reacts with baker’s yeast and brewer’s yeast.•It can induce production of autoantibodies and endocrinopathy.•It produces IgA proteases.•It contains glycoproteins which stimulate the mast cells to release histamine and prostaglandin. How Does It Cause Disease ?


•It assimilates all sugars except lactose.•It depresses the activity of lactase.•Dietary carbohydrates are fungal growth promoters and associated with increased adherence of Candida species to mucosal epithelial cells.•Release of toxic fungal metabolites. How Does It Cause Disease ?

Candida albicans -Antibodies

Candida –Risk Factors of Infection Examples
Factor
Pregnancy, age (elderly & infants) Diet high in sweets, fruit juices, alcohol
Physiological
Infection, burn wounds.
Trauma
Neutropenia, cellular immunodeficiency (leukaemia, lymphoma, AIDS, aplastic anaemia
Haematological
Diabetes mellitus, Addison’s disease, hypoparathyroidism Endocrinological
Chemotherapeutics, corticosteroids, oral contraceptives, antibiotics catheters, surgery
Iatrogenic
Intravenous drugs, malnutrition, malabsorption, Chronic Stress
Others


Diseases by C. albicans
Thrush :it is a white yeast infection of mouth &tongue most common in infant. Esophagitis Cutaneous Candidiasis Genital Yeast Infections Deep Candidiasis

Thrush is commonly seen in infants. It is not considered abnormal in infants unless it lasts longer than a couple of weeks. Candida can also cause yeast infections in the vagina. People who have diabetes and had high blood sugar levels are more likely to get thrush in the mouth (oral thrush), because the extra sugar in your saliva acts like food for Candida. Taking high doses of antibiotics or taking antibiotics for a long time also increases the risk of oral thrush. Antibiotics kill some of the healthy bacteria that help keep Candida from growing too much. People with poorly fitting dentures are also more likely to get thrush.

Oral thrush Note multiple white plaques on lips, gingivae, tongue, and palate

Oral candidiasis (thrush)…common in immunocompromised hosts,such as those with HIV infection.

Candidiasis

Candida in culture
Pseudohyphae and budding cells in specimens
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Figure 1. Angular chelitis (www.emed.com)

Figure 2. Oral Thrush, atrophic (www.mycolog.com)
Figure 3. Oral Thrush, pseudomembranous (www.emed.com)
Oropharyngeal Thrush * Pseudo membranous * Atrophic * Angular chelitis Risk Factors HIV


Symptoms Thrush appears as whitish, velvety lesions in the mouth and on the tongue. Underneath the whitish material, there is red tissue that may bleed easily. The lesions can slowly increase in number and size.

Candida Esophagitis

Candidiasis, cutaneous - around the mouth
This child has a large rash caused by Candidiasis, affecting the skin around the mouth. There are also other lesions that aren't connected to the large lesion, called "satellite lesions".

Vulvovaginal Candidiasis

Secondary infection
Secondary infection occurs during or after treatment of a primary infection because the normal bacterial flora is destroyed, allowing yeast to flourish.


•It is generally known that about 50% of the medical evaluations of out-patient polysymptomatic patients fail to elucidate a specific causative disease.•The symptom patterns often suggest the possibility of a systemic disease process involving multiple body systems.•The patient may complain of chronic fatigue, poor concentration, impaired memory, respiratory tract symptoms, GI distress, pains in muscles and joints, skin problems, recurrent infections, urogenital problems etc.•Usually diagnosis is ‘stress’, ‘psychosomatic symptoms’ or an assurance ‘there is nothing physically wrong’. Candidiasis

Candidiasis -Symptoms

•Nasal congestion•Nasal itching•Dry mouth or throat•Rash or blisters in mouth•Sore throat•Laryngitis, loss of voice•Cough or bronchitis•Pain or tightness in chest•Bad breath •Indigestion or heartburn•Abdominal pain•Constipation / diarrhoea•Mucus in stools•Rectal itching•Bloated, belching, gas•Food sensitivity/intolerance•Chronic rashes or itching•Numbness, burning


•Foot, hair or body odour•Muscle aches•Muscle weakness/paralysis•Pain and/or swelling joints•Vaginal burning, discharge•Rash or blisters in mouth•Sore throat•Laryngitis, loss of voice•Cough or bronchitis Candidiasis -Symptoms
•Pain or tightness in chest•Bad breath•Indigestion or heartburn•Abdominal pain•Constipation / diarrhoea•Mucus in stools•Rectal itching•Bloated, belching, gas

•Food sensitivity/intolerance•Chronic rashes or itching•Numbness, burning•Foot, hair or body odour•Muscle aches•Muscle weakness/paralysis•Pain and/or swelling joints •Vaginal burning, discharge•Loss of sexual desire•Urinary frequency or urgency•Burning on urination•Cold hands or feet and / or chilliness Candidiasis -Symptoms

Deep Candidiasis

Figure 1. Four forms of invasive candidiasis (www.doctorfungus.org)


Onchomycosis Nail infections are much more difficult to cure and can last a lifetime without proper treatment

hematogenous seeding Spread to the eye Can cause blindness

Laboratory diagnosis
�� Diagnosis based ondirect exam ofscrapings, culture onselective media�� Examine for fungalhyphae andcharacteristic asexualspores – macroconidia�� Culture – colonies alsoCharacteristic

History, signs and symptoms Visualization of pseudohyphae (mycelia) and/or budding yeast (conidia) on KOH or saline wet prep Stained with special fungal stain like lacto phenol blue . Stained histology slides :-gomoris methylamine sliver stains (GMS). Culture :sabourauds glucose agar medium; brain heart infusion. Serology by CFT &Latex agglutination test & ELISA. Skin test PCR& Fluorescent Abs Technique .
Diagnosis

Candida Cross-Reactivity byImmunofluorescence

Vulvovaginal Candidiasis - Vulvar component often dominant Diagnosis = symptoms with pseudohyphae On KOH prep - Women are often misdiagnosed as having VVC when they really have - Genital herpes - Contact dermatitis - Lichen planus - Atrophic vaginitis - Recurrent BV - Uncomplicated VVC defined by all 4: - Sporadic - Mild-moderate severity - Likely to be Candida albicans - Non-immunocompromised host


Dysbiosis Markers –Urine•Compounds produced by bacteria, yeast, fungi, & protozoa that may colonise or grow in the small or large intestines.•Dysbiosis involves overgrowth of one or more species leading to increased production of these compounds, that are absorbed & excreted in urine.•When pathogens are distributed throughout the small & large intestine, stool testing is possible. However, it does not reveal the situation in the small intestine.

Dysbiosis Markers –Yeast / Fungal•Their metabolic products appearing in urine, is a strong indicator of intestinal overgrowth.•Treatment with antifungals lowers these compounds.•Arabinitol –known toxicity due to metabolic interference.•Я-Ketoglutarate –toxic metabolic interference.•All are related central energy pathway, may lead to blocks, -autism, Alzheimer’s.


Dietary Treatment of Candida albicans•Eliminate all sugar:–fruit juice–white flour–refined grains•Eat a higher protein, lower carbohydrate, high fiber diet•Avoid fermented foods including alcohol

Botanical Medicines with Anti-Fungal Activity

•Allium (garlic)•Astragalus•Barberry, Oregon Grape•Citrus Seed Extract•GrapeFruit Seed Extract•Hydrastis(Golden Seal)•Olive Leaf•Tebebuia(Pau d’Arco)•Plant Tannins Volatile Oils (enteric-coated)
•Anise•Oregano•Rosemary•Sage•Thyme

Current Drug Therapies

antifungal drugs: Amphotericin B (Fungizone) Clotrimazole (Mycelex) Fluconazole (Diflucan) Itraconazole (Sporanox) Ketoconazole (Nizoral) Nystatin (Mycostatin)



Baillie, GS and LJ Douglas. 1999. Role of dimorphism in the development of Candida albicans biofilme. J. Med. Microbiol. 48:671-679. Brown, JP. 2002. Morphogenetic Signaling Pathways in Candida albicans. Washington: ASM Press: Candida and Candidiasis. pp. 95-106. Calderone, R.A. (ed.). Candida and Candidiasis. Washington: ASM Press; 2002. Calderone R and N.A.R. Gow. 2002. Host recognition by Candida species. Washington: ASM Press: Candida and Candidiasis. pp. 67-86. Cormack, B.P., N. Ghori, and s. Falkow. 1999. An adhesin of the yeast pathogen Candidia glabrata mediating adherence to human epithelial cells. Science 285: 578-582. Ghannoum, MA. 2000. Potential role of phospholipaes in virulence and fungal pathogenesis. Clin Micro Review. 13(1): 122-143. Gow, NAR. 2002. Cell Biology and the Cell Cycle of Candida. ASM Press: Candida and Candidiasis. pp. 145-158. Hawser, SP and LJ Douglas. 1994. Biofilm formation by Candida species on the surface of catheter materials in vitro. Infect. Immuno. 62:915-921. Jabra-Rizk, MA. Et. al. 2004. Fungal Biofilms and Drug Resistance. Emerging Infectious Diseases. 10(1): 14-19. Jarvis, WR. 1995. Epidemiology of nosocomial fungal infections, with emphasis on Candida species. Clin Infec Dis. 20(6): 1526-30. http://www.intelihealth.com/IH/ihtIH/WSIHW000/9339/31092.html http://www.emedicine.com/emerg/topic76.htm http://www.ncbi.nlm.nih.gov www.webpathology.com
References


15. U.S. National Library of Medicine 8600 Rockville Pike, Bethesda, MD 20894 U.S. Department of Health and Human Services National Institutes of Health Page last updated: 15 November 2010 16. Kauffman CA. Candidiasis. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 359.
17. WARREN LEVINSON;BOARD REVIEW OF MED. MICRO.&IMMUN;2008. 18. JAWETZ;MELNICK.MED.MICRO;2004. 19. CRUICK SHANK; BACTERIOLOGY ILLUSTRATED;1976. 20. URL of this page: http://www.nlm.nih.gov/medlineplus/ency/article/000626.htm Thrush is a yeast infection of the mucus membrane lining of the mouth and tongue