Mycoses

Candida albicans

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.
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)

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

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
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 hosts immune system, and by competition from other microorganisms in and on the bodys mucous membranes.
When this delicate balance is upset, candida can grow rapidly and aggressively, causing many unpleasant symptoms.
Mould CharacteristicsYeast Characteristicsfilamentous hyphaesolitary, unicellularhyphal formationreproduction via buddingtips may be roundedrounded shape(conidia/spores) moist & mucoid colonies 


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




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

Pathogenesis

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

Virulence assay of different C. albicans strains using



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.

MORPHOGENESIS

Morphogenesis in
C. albicans is a pivotal
virulence factor that allows
rapid multiplication and
subsequent dissemination
in host tissue.

(www.kent.ac.uk)




How Does It Cause Disease ?
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 bakers yeast and brewers 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.
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.
Candida albicans -Antibodies





Examples Factor Pregnancy, age (elderly & infants)

Diet high in sweets, fruit juices, alcohol PhysiologicalInfection, burn wounds.TraumaNeutropenia, cellular immunodeficiency (leukaemia, lymphoma, AIDS, aplastic anaemia Haematological Diabetes mellitus, Addisons disease, hypoparathyroidism Endocrinological Chemotherapeutics, corticosteroids, oral contraceptives, antibiotics catheters, surgeryIatrogenic Intravenous drugs, malnutrition, malabsorption, Chronic Stress OthersCandida Risk Factors of Infection

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  HYPERLINK "http://www.nlm.nih.gov/medlineplus/ency/article/001214.htm" 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




Candidiasis



Oropharyngeal Thrush

* Pseudo membranous
 * Atrophic
* Angular chelitis
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".


Secondary infection

Candidiasis
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 -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


Candidiasis -Symptoms
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
Pain or tightness in chest
Bad breath
Indigestion or heartburn
Abdominal pain
Constipation / diarrhoea
Mucus in stools
Rectal itching
Bloated, belching, gas
Candidiasis -Symptoms
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


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




Candidemia

hematogenous seeding
Spread to the eye Can cause blindness

Laboratory diagnosis

�� Diagnosis based on direct exam of
scrapings, culture on selective media
�� Examine for fungal hyphae and
characteristic asexual
spores – macroconidia
�� Culture – colonies also
Characteristic


Diagnosis
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 .

Candida Culture (Mixed)

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.
-Ketoglutarate toxic metabolic interference.
All are related central energy pathway, may lead to blocks, -autism, Alzheimers.

Deep Candidasis

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) Plant Tannins Volatile Oils (enteric-coated)
Astragalus Anise
Barberry, Oregon Grape Oregano
Citrus Seed Extract Rosemary
GrapeFruit Seed Extract Sage
Hydrastis(Golden Seal) Thyme
Olive Leaf
Tebebuia(Pau dArco)
Current Drug Therapies
antifungal drugs:
Amphotericin B (Fungizone)
Clotrimazole (Mycelex)
Fluconazole (Diflucan)
Itraconazole (Sporanox)
Ketoconazole (Nizoral)
Nystatin (Mycostatin)


References
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.
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Kauffman CA. Candidiasis. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 359.
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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


Thank You
HIND HAMED ABED








Figure 1. Morphogenesis

Figure 2. Morphogenic forms of Candida albicans
 HYPERLINK "http://cbr-rbc.nrc-cnrc.gc.ca/thomaslab/" http://cbr-rbc.nrc-cnrc.gc.ca/thomaslab/
candida/caindex.html

the skin equivalent (AST 2000)

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


Vulvovaginal Candidiasis

Brought to you By:-

Hind Hamed Abed
Cokkage of Medicine, University of Baghdad