3. Candida
Candida – anamorph (asexual form)
Teleomorphs of several genera demonstrated for
different species of Candida
Teleomorph genera:
Clavispora
Debaromyces
Issatchenkia
Kluyveromyces
Pichia
Yarrowia
4. Habitat
Ubiquitous yeast
Found on many plants
Normal flora of GI tract of mammals and
mucocutaneous membranes of humans
Present in all areas of human GI tract
Common species in GI tract
C. albicans
C. tropicalis
C. parapsilosis
C. glabrata
5. Major pathogenic species
C. albicans
C. glabrata
C. krusei and its teleomorph Issatchenkia
orientalis
C. kefyr and its teleomorph Kluyveromyces
marxianus
C. guilliermondii and its teleomorph Pichia
guilliermondii
C. parapsilosis
C. tropicalis
C. lusitaniae and its teleomorph Clavispora
lusitaniae
6. Morphology
Polymorphic yeast, i.e., yeast cells, hyphae and
pseudohyphae are produced
Ability to assume various forms may be related to the
pathogenicity
Yeast form:
10-12 microns in diameter
gram positive
grows overnight on most bacterial and fungal media
pseudohyphae may be formed from budding
yeast cells that remain attached to each other.
Spores may be formed on the pseudomycelium,
called chlamydospores and can be used to identify
different species of Candida.
9. Morphology
On Glucose Peptone Agar (GPA) after 3 days at
25oC
Diameter 2-3mm
White to cream colored
Smooth or umbonate
May become wrinkled after further incubation
Dull to glistening
On corn meal agar: intraspecies variation
10. Candida albicans
On corn meal agar
after 3 days of
incubation:
produce true mycelia
and pseudomycelia,
grape like cluster of
blastoconidia at the
septa and
chlamydoconidia at
the ends of hyphae or
their short lateral
branches
12. Epidemiology of C. albicans
Habitat
human commensal
major reservoir- GI tract
can invade into bloodstream from GI tract afgter
damaging GI mucosa
Source of infection
Endogeneous:
primarily
can spread hematogenously into various organs
Exogenous:
introduction into the body through medical devices,
catheters
important in the development of deep-seated and
systemic infections
13. Epidemiology of C. albicans
Transmission: Person to person transmission
not predominant
In case of oral thrush, from mother with
vaginal candidiasis to newborn, during birth
sexual transmission from females with
vaginitis to their sexual partners
Risk factor
Prolonged therapy with broad spectrum
antibiotics
14. Clinical significance
Disease: Candidiasis
Clinical manifestations may be acute, sub acute,
chronic or episodic
Can cause various forms of infections, ranging
from superficial manifestations involving skin,
nails and mucosal surfaces, to deep-seated
infections involving various internal organs to
disseminated disease
Diseases sub-divided into 2 large groups:
Mucocutaneous candidiasis
Deep-seated candidiasis
16. Cutaneous candidiasis
1. Candidal intertrigo (Intertriginous candidiasis)
Most common form
Organisms colonize skin folds, particularly in
moist and macerated sites (axilla, groin, inter and
sub mammary folds, umbilicus)
Form erythrematous lesions with vesicles
(elevation of skin with clear fluid) and pustules
(elevation of skin with purulent fluid) in
combination with pruritis (severe itching)
17. Cutaneous candidiasis (contd.)
2. Erosio interdigitalis
Skin folds between the fingers become
macerated and itchy
Associated with excessive exposure to moisture
Common in dishwashers, barlenders, fruit
cannery workers
3. Perianal rash (Diaper candidiasis)
Involves infants wearing nappies
Rashes seen in perianal area and on the buttocks
Infection may be secondary to pre-existing
inflammatory condition
18. Cutaneous candidiasis (contd.)
4. Chronic mucocutaneous candidiasis
Relatively rare condition
Most severe clinical form of superficial candidiasis
Cause: C. albicans
Characterised by the presence of persistent
lesions, with high rate of recurrence, starting in
early childhood and persisting throughout the
individual’s lifetime
Lesions at various skin site, not limited to skin
folds
Warty lesions termed as candida granuloma
19. Nail infections
(Paronychia and Onychia)
Agent: C. albicans (major), C.
parapsilosis, C.
guilliermondii
Characterised by prominent
swelling, redness, pain
Paronychia: infection of nail
folds (fold of skin supporting nail
at its base)
Onychia: infection of nails
Affected nails become
discolored, eroded,
brittle,detached from nail bed
and painful
21. Oral candidiasis
Most frequent
Major agent: C. albicans
Others: C. glabrata, C. guilliermondii, C.
parapsilosis, C. tropicalis
Several different clinical forms
Acute pseudomembranous candidiasis (oral thrush)
Acute atrophic candidiasis
Chronic atrophic candidiasis
Chronic hyperplastic candidiasis
Angular chelitis
22. Oral candidiasis
1. Oral thrush
Characterised by white-grey lesions on the gums,
tongue,or oral mucosa, can appear as single
lesion or as confluent large plaques
Lesions covering large area may be painful and
disturb food intake
May spread to the oesophageal mucosa, and
cause dysphagia
Generally occurs in AIDS patient, cancer patient,
debilitated individuals, elderly people and in
infants of the mothers with vaginal candidiasis
23. Oral candidiasis
2. Acute atrophic candidiasis
Characterised by painful, erythematous mucosa,
particularly on the tongue
May cause loss of tongue paillae, affecting food
intake.
3. Chronic atrophic candidiasis
Known as denture stomatitis
Occur in elder individuals wearing dentures
Characterised by erythema and/or oedema of the
mucosa under the dentures
Not painful
24. Oral candidiasis
4. Chronic hyperplastic candidiasis
Also known as candida leucoplakia
Rarer condition
Characterised by white plaques, can appear on
various sites of oral mucosa
Can’t be removed like pseudomembranous form
May transform into a malignant state
5. Angular cheilitis
Characterised by erythema and fissures at the folds of
the corners of the mouth
May be associated with denture stomatitis or oral
thrush
25. Vaginal candidiasis
Common infection in females of reproductive age
group, primarily during the fecund period
Prevalence : 5-20%
Prevalence increases in particular groups like
pregnant or diabetic women, using oral
contraceptives (hormonal effect) and after
antibiotic treatment
Cause: C. albicans, C. glabrata, C. tropicalis
Imporatant feature: recurrence of infection
Transmission: sexual transmission to male
partners
26. Vaginal candidiasis (Contd.)
Syndrome:
Complaints of vulvovaginal pruritis and discharge
(thick curd like or thin)
Erythema of the vulvovaginal mucosa and also of
perianal area
Lesions on the mucosal surface are basically
adherent plaques
May cause pain and discomfort during sexual
intercourse
27. Deep-seated candidiasis
Infection of visceral organs and possibly to
multiple organs or disseminated disease
Includes
Candidiasis of GI tract
Candidiasis of respiratory system
Candidiasis of CNS
Candidiasis of renal and urinary system
Candidiasis of cardiovascular system
Hematogenous disseminated disease
Ocular infection and a variety of other specific
manifestations
28. Deep-seated candidiasis
Candidiasis of GI tract
Oesophagitis
Painful dysphagia and
chest pain
White patches on
oesophageal mucosa as
in oral candidiasis
May be associated with
oral candidiasis
10-30% of AIDS patients
with oral candidiasis may
also have candidal
29. Deep-seated candidiasis
Candidiasis of GI tract
Gastrointestinal candidiasis
Though being normal flora of GI tract, clinical
involvement of mucosal surfaces of the stomach
and/or intestine with mucosal white plaques and
ulcerations are found
Plays an important role in the pathogenesis of
disseminated candidiasis
30. Deep-seated candidiasis
Candidiasis of respiratory system
Involves lungs
Bronchopneumonia originates from
hematogenous spread of the fungus as a part of
a disseminated infection or from introduction of
pathogen into the lungs
CNS candidiasis
C. albicans- cause
Risk group- AIDS patients and pre-term infants
Seen as part of disseminated candidiasis,
involving meninges, abscess formation in brain
tissues
31. Deep-seated candidiasis
Candidiasis of cardiovascular system
Cause: C. albicans, C. parapsilosis, C. tropicalis
Cause clinical manifestations in various organs of
the cardiovascular system: pericardium,
myocardium and endocardium (common)
Endocarditis:
primarily seen in IV drug users and in individuals
with impaired heart valves.
Also may occur in patients after cardiac surgery
procedures or as a sequelae of anticancer therapy
32. Deep-seated candidiasis
Renal and Urinary tract candidiasis
Lower urinary tract infection:
Frequently seen in association with indwelling
catheters
Source: GI and genital biota
More in women
Also found in diabetic patients
Infection may be mild or severe
No unique symptoms
Clinical feature: formation of fungal masses,
which may cause obstruction and impair normal
urine flow
33. Deep-seated candidiasis
Deep-seated candidiasis
Renal infection
Originate from hematogenous dissemination of
Candida spp or as an ascending UTI
Characterised by microabscess formation,
primarily in the cortex of the kidneys
34. Deep-seated candidiasis
Disseminated candidiasis
Multi-organ infection and possibly candidemia
May include CNS, kidneys, heart, eyes or other organs
or systems
Hepatosplenic candidiasis- a specific clinical
manifestation of disseminated infection
Seen in cancer patients, particularly those with acute
leukaemia, in patients after surgery (GI and cardiac), in
transplant recepients (bone marrow), in preterm infants,
burn patients and drug addicts
Ocular infection- common, typical white (cotton-
like)lesions in the retina
Cutaneous- nodular lesions on the skin
35. Virulence factors
Adherence: biofilm formation, a significant factor in the
pathogenesis affecting the host’s response to infection and
causing difficulty in therapy
Dimorphism:
Specific enzymes that facilitate tissYeast-hyphal morphogenetic
transformation, which facilitate penetration and assist the
microbe to evade the host defense system
Interference with phagocytosis, immune defenses and
complement
Production of specific enzymes that could facilitate tissue
penetration and invasion such as secretory aspartyl proteinases
(SAPs) and phospholipases
Germ tube: adhesin on the surface of tube
Acidic metabolites
Growth rate and undemanding nutrient requirement
36. Laboratory diagnosis of Candida
Depends on the nature of infection, whether
mucocutaneous or deep-seated forms
Mucocutaneous candidiasis
Sample: skin, nail or mucosal surface swabs
Includes 2 steps:
Direct examination of the specimen to demonstrate
fungal presence
Isolation of the fungus and its identification
37. Laboratory diagnosis of Candida
1. Direct examination (wet mount method)
Treat specimen with keratinolytic substance (10-30%
KOH) to facilitate the microscopic examination of the
specimen
Demonstration of fungi enhanced by
the addition of cotton blue or acid Parker’s ink
the use of calcofluor white, a fluorochrome with an
affinity for chitin and glucan which makes a
demonstration of fungal elements with a
fluorescent microscope relatively simple
Gram’s staining for nail and skin specimens-not
generally done
38. Laboratory diagnosis of Candida
Mucosal infections
Vaginal and oral swabs preferably kept in
transport medium before being processed in the
lab
Oral lesion specimen also obtained by scrappings
Both wet mount and fixed mount can be done
Wet mount: unstained slide prepared in saline or
water or stained with lactophenol cotton blue or
calcofluor white
Fixed mount: stained using Gram’s stain, Geimsa
stain or methylene blue
39. Laboratory diagnosis of Candida
Microscopic examination of specimes from
vulvovaginitis or oral candidiasis will reveal the
presence of budding yeast cells, pseudohyphae
and hyphae
Presence of hyphal elements in direct
microscopic examination important (vagina and
mouth normally colonised by Candida spp)
Presence of hyphal elements indicates infection
40. Laboratory diagnosis of Candida
Culture
Isolation of Candida spp
Routine medium: SDA supplemented with
antibiotics (chloramphenicol, gentamycin and /or
tetracyclin) to prevent bacterial overgrowth
Other medium: SDA with cycloheximide to prevent
the growth of air-borne molds
Incubation at 28oC or/and at 37oC for 2-3 days
Growth can also be observed at 24 hours and
some species take more than 3 days
41. Laboratory diagnosis of Candida
Identification
Morphological characteristics
SDA: appears smooth, but some species (C. krusei)
from dry, creamy colonies
CHROM agar:
uses chromogenic substances
based on the reaction between specific enzymes of
different species and chromogenic substrates, which
results in the formation of differently colored colonies
rapid presumptive identification of C. albicans, C. krusei
and C. tropicalis
Wet mount or fixed mount can be done to observe the
cellular morphology of isolates
42. Different species of Candida on Chrome
agar
C. albicans, C. glabrate, C. tropicalis, C. krusei
43.
44. Laboratory diagnosis of Candida
Physiological/ Biochemical characterization
characterised by patterns of their use of specific
carbohydrate and nitrogen substances
Serologic identification
Can be identified using specific antisera by slide
agglutination test
Not used as a routine method
45. Laboratory diagnosis of Candida
Deep-seated candidiasis
More difficult than in case of mucocutaneous
forms
Includes
direct microscopy
isolation in culture
immunodiagnosis(presence of antibodies and/or the
presence of microbial antigens in patient’s body
fluid
46. Laboratory diagnosis of Candida
Direct examination
Demonstration of the presence of candidal cells
and/or hyphal forms in clinical samples from
normally sterile sites such as CSF, bronchial
aspirate, sample from bone marrow and other
tissues
Sputum and urine specimens may be
contaminated with normal microbiota
Tissue biopsy can be prepared and stained by
histopathological techniques
47. Laboratory diagnosis of Candida
Culture
Isolation of Candida
Difficult to isolate if the infection is localized in
internal organ
Sample: Blood, CSF, tissue biopsies
Media: SDA with antibiotics
Identification
Similar as with mucocutaneous candidiasis
48. Laboratory diagnosis of Candida
Immunodiagnosis
For deep-seated infection, microscopy and culture
methods not sufficient as in case of mucocutaneous
infection
Based on
Detection of antibody production
Detection of fungal antigens in body fluids and in serum
Antibody detection
Agglutination technique representing anti-mannan
antibodies, can also be found in healthy individuals and
with superficial infections not useful for diagnosis of deep-
seated infection
Antibody detection for the presence of antibodies to
candidal internal antigens released into patient’s body
during invasion
Techniques: gel immunodiffusion, CCIE, ELISA, latex
49. Laboratory diagnosis of Candida
Immunodiagnosis
Antigen detection
Important diagnostic tool, particularly in
immunocompromised patients
Techniques: LA and ELISA
Detection in serum, urine and other body fluids
Antigens: mannan, an undefined glycoprotein, a
47 kDa protein, enolase
50. Treatment
commonly treated with antimycotics; include
topical clotrimazole, topical nystatin, fluconazole, and
topical ketoconazole
Localized infection
Oral candidiasis :topical treatments or oral medication
Candida esophagitis :orally or intravenously; for severe or
azole-resistant esophageal candidiasis, treatment with
amphotericin B may be necessary.
A one-time dose of fluconazole is 90% effective in treating a
vaginal yeast infection.
For vaginal yeast infection in pregnancy,
topical imidazole or triazole antifungals.
Blood infection
intravenous fluconazole or an echinocandin such
as caspofungin may be used.Amphotericin B is another