Transcript Candida albicans

Candida albicans
Brought to you by :- Hind Hamed Abed
Collage of Medicine ,University of Baghdad
Candida Culture
Contents
1.
Introduction
2. Mycology Basics
3. Disease capabilities
4. Pathogenesis
5. Laboratory diagnosis
6.
7.
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 birthweight 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.
www.ken.coar.org
Sexual Groups
Ascomycota
Basidiomycota
Zygomycota
Chytridia
Fungi Imperfection
Very few species are in a commensally relationship with humans
- includes Candida albicans and Malasezia furfur
www.arboretum.harvard.edu
Diseases caused by fungi are usually accidental
Endogenous and Exogenous Sources
www.bio.umass.edu
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
Penicillium chrysogenum www.doctorfungus.org
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 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.
Yeast Characteristics
Mould Characteristics
solitary, unicellular
filamentous hyphae
reproduction via budding
hyphal formation
rounded shape
tips may be rounded
(conidia/spores)
moist & mucoid colonies
Figure 1. Typical Yeast
Figure 2. Typical mould
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.
© Dennis Kunkel (www.denniskunkel.com)
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
© Dennis Kunkel (www.denniskunkel.com)
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
1. Host Recognition
2. Adhesions
3. Enzymes
Hydrolysis: Phosphoplipases, Lipases, Proteinases
4.Morphogenesis
Yeast form to Filamentous hyphae/pseudohyphae
5.Phenotypic Switching
Virulence assay of different C. albicans strains using the skin equivalent (AST 2000)
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.
(Fraunhofer, 2002)
MORPHOGENESIS
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)
Figure 2. Morphogenic forms of Candida albicans
http://cbr-rbc.nrc-cnrc.gc.ca/thomaslab/candida/caindex.html
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 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.
Candida albicans -Antibodies
Candida –Risk Factors of Infection
Factor
Examples
Physiological
Pregnancy, age (elderly & infants)
Diet high in sweets, fruit juices, alcohol
Trauma
Infection, burn wounds.
Haematological
Neutropenia, cellular immunodeficiency (leukaemia,
lymphoma, AIDS, aplastic anaemia
Endocrinological
Diabetes mellitus, Addison’s disease,
hypoparathyroidism
Iatrogenic
Chemotherapeutics, corticosteroids, oral
contraceptives, antibiotics catheters, surgery
Others
Intravenous drugs, malnutrition, malabsorption,
Chronic Stress
Diseases by C. albicans
Thrush :it is a white yeast infection of mouth
&tongue most common in infant.
Esophagitis .2
Cutaneous Candidiasis .3
Genital Yeast Infections .4
Deep Candidiasis .5
.1
 Thrush is commonly seen in infants. It is not
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


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
http://www.edison.edu/course_material/
Pseudohyphae
and budding cells
in specimens
Oropharyngeal Thrush
* Pseudo membranous
* Atrophic
* Angular chelitis
Figure 1. Angular chelitis
(www.emed.com)
Risk Factors
HIV
Figure 2. Oral Thrush, atrophic
(www.mycolog.com)
Figure 3. Oral Thrush, pseudomembranous
(www.emed.com)
 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
."snoisel etilletas"
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.
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
•Indigestion or heartburn
•Nasal itching
•Abdominal pain
•Dry mouth or throat
•Constipation / diarrhoea
•Rash or blisters in mouth
•Mucus in stools
•Sore throat
•Rectal itching
•Laryngitis, loss of voice
•Bloated, belching, gas
•Cough or bronchitis
•Food sensitivity/intolerance
•Pain or tightness in chest
•Chronic rashes or itching
•Bad breath
•Numbness, burning
Candidiasis -Symptoms
•Foot, hair or body odour
•Pain or tightness in chest
•Muscle aches
•Bad breath
•Muscle weakness/paralysis
•Indigestion or heartburn
•Pain and/or swelling joints
•Abdominal pain
•Vaginal burning, discharge
•Constipation / diarrhoea
•Rash or blisters in mouth
•Mucus in stools
•Sore throat
•Rectal itching
•Laryngitis, loss of voice
•Bloated, belching, gas
•Cough or bronchitis
Candidiasis -Symptoms
•Food sensitivity/intolerance
•Vaginal burning, discharge
•Chronic rashes or itching
•Loss of sexual desire
•Numbness, burning
•Urinary frequency or urgency
•Foot, hair or body odour
•Burning on urination
•Muscle aches
•Cold hands or feet and / or
•Muscle weakness/paralysis
chilliness
•Pain and/or swelling joints
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
1. History, signs and symptoms
2. Visualization of pseudohyphae (mycelia) and/or budding yeast
(conidia) on KOH or saline wet prep
3. Stained with special fungal stain like lacto phenol blue .
4. Stained histology slides :-gomoris methylamine sliver stains
(GMS).
5.Culture :sabourauds glucose agar medium; brain
heart infusion.
6.Serology by CFT &Latex agglutination test &
ELISA.
7.Skin test
8.PCR& Fluorescent Abs Technique .
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.
•ß-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)
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 d’Arco)
•Plant Tannins
Current Drug Therapies
antifungal drugs:
Amphotericin B (Fungizone)
Clotrimazole (Mycelex)
Fluconazole (Diflucan)
Itraconazole (Sporanox)
Ketoconazole (Nizoral)
Nystatin (Mycostatin)
Medical Economics. Drug Topics Red Book. Montvale, NJ: Medical Economics
Co., Inc., 2000.
References
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albicans biofilme. J. Med. Microbiol. 48:671-679.
2. Brown, JP. 2002. Morphogenetic Signaling Pathways in Candida albicans. Washington: ASM
Press: Candida and Candidiasis. pp. 95-106.
3. Calderone, R.A. (ed.). Candida and Candidiasis. Washington: ASM Press; 2002.
4. Calderone R and N.A.R. Gow. 2002. Host recognition by Candida species. Washington: ASM
Press: Candida and Candidiasis. pp. 67-86.
5. 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.
6. Ghannoum, MA. 2000. Potential role of phospholipaes in virulence and fungal pathogenesis.
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Candidiasis. pp. 145-158.
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Diseases. 10(1): 14-19.
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www.webpathology.com
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
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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