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Journal of Oral and Maxillofacial Pathology Vol. 18 Supplement 1 September 2014 81

REVIEW ARTICLE

Oral candidiasis: An overview

Arun Singh, Renuka Verma1, Aditi Murari2, Ashutosh Agrawal2
Departments of Oral Pathology and Microbiology, Kothiwal Dental College and Research Center, Moradabad, 1Career Post Graduate Institute of
Dental Sciences and Hospital, Lucknow, 2Institute of Dental Sciences, Bareilly, Uttar Pradesh, India

Address for correspondence: ABSTRACT

Dr. Ashutosh Agrawal, Candida is the shortened name used to describe a class of fungi that includes more
Department of Oral Pathology and Microbiology, than 150 species of yeast. In healthy individuals, Candida exists harmlessly
Institute of Dental Sciences,
in mucus membranes such as your ears, eyes, gastrointestinal tract, mouth,
Bareilly - 243 006, Uttar Pradesh, India.
nose, reproductive organs, sinuses, skin, stool and vagina, etc. It is known
E-mail: [email protected]
as your “beneficial flora” and has a useful purpose in the body. When an
Received: 07-01-2013 imbalance in the normal flora occurs, it causes an overgrowth of Candida
Accepted: 25-06-2014 albicans. The term is Candidiasis or Thrush. This is a fungal infection (Mycosis)
of any of the Candida species, of which Candida albicans is the most common.
When this happens, it can create a widespread havoc to our overall health
and well-being of our body.
Key words: Candida albicans, fungi, yeast, mitosporic fungi, oral
thrush, mycosis

INTRODUCTION • Chronic
• Erythematous
Fungi are free-living, eukaryotic organisms that exist as • Pseudomembranous
yeasts (round fungi), moulds (filamentous fungi), or a • Hyperplastic
combination of these two (dimorphic fungi). Oral candidiasis • Nodular
is one of the common fungal infection, affecting the oral • Plaque-like
mucosa. These lesions are caused by the yeast Candida • Candida-associated lesions
albicans. Candida albicans are one of the components of • Angular cheilitis
normal oral microflora and around 30% to 50% people carry • Denture stomatitis
this organism. Rate of carriage increases with age of the • Median rhomboid glossitis
patient. Candida albicans are recovered from 60% of dentate • Keratinized primary lesions superinfected with Candida
patient’s mouth over the age of 60 years. There are many • Leukoplakia
types of Candida species, which are seen in the oral cavity. • Lichen planus
[1,2] Species of oral Candida are: C. albicans, C. glabrata, C. • Lupus erythematosus.
guillermondii, C. krusei, C. parapsilosis, C. pseudotropicalis,
C. stellatoidea, C. tropicalis.[3] Secondary oral candidoses (Group II)

Proposed revised classification of Oral Oral manifestations of Systemic mucocutaneous.

Candidosis[4] Primary oral candidosis (Group I)
Candidosis (due to diseases such as thymic aplasia and
• Acute candidosis endocrinopathy syndrome).
• Pseudomembranous
• Erythematous RISK FACTORS

Pathogen
Access this article online
Quick Response Code:
Website: Candida is a fungus and was first isolated in 1844 from the
www.jomfp.in sputum of a tuberculosis patient. [5] Like other fungi, they are
non-photosynthetic, eukaryotic organisms with a cell wall
DOI: that lies external to the plasma membrane. There is a nuclear
10.4103/0973-029X.141325 pore complex within the nuclear membrane. The plasma
membrane contains large quantities of sterols, usually
ergosterol. Apart
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Oral candidiasis Singh, et al. 82

from a few exceptions, the macroscopic and microscopic cultural syndrome, immunosuppressive conditions such as HIV
characteristics of the different candida species are similar. They infection, malignancies such as leukemia and nutritional
can metabolize glucose under both aerobic and anaerobic deficiencies – vitamin B deficiencies have been particularly
conditions. Temperature influences their growth with higher implicated.[14]
temperatures such as 37°C that are present in their potential
host, promoting the growth of pseudohyphae. They have been LABORATORY DIAGNOSIS OF ORAL
isolated from animals and environmental sources. They require
environmental sources of fixed carbon for their growth. CANDIDIASIS Specimen collection[15]
Filamentous growth and apical extension of the filament and
formation of lateral branches are seen with hyphae and mycelium The specimen should be collected from an active lesion; old
and single cell division is associated with yeasts. [6] Several ‘burned out’ lesions often do not contain viable organisms.
studies have demonstrated that infection with candida is
associated with certain pathogenic variables. Adhesion of candida Collect the specimen under aseptic conditions.
to epithelial cell walls, an important step in initiation of infection,
is promoted by certain fungal cell wall components such as Collect sufficient specimen.
mannose, C3d receptors, mannoprotein and saccharins.[7-9] Other
factors implicated are germ tube formation, presence of mycelia, Use sterile collection devices and containers
persistence within epithelial cells, endotoxins, induction of tumor
necrosis factor and proteinases.[10-12] Phenotypic switching which Label the specimen appropriately; all clinical specimens
is the ability of certain strains of C. albicans to change between should be considered as potential biohazards and should
different morphologic phenotypes has also been implicated.[13] be handled with care using universal precautions.

The specimen should be kept moist or in a transport

Host medium and stored in a refrigerator at 4ºC. Due to variety
of clinical forms of oral candidiasis, a number of different
Local factors types of specimens may be submitted to the laboratory.[16]
Impaired salivary gland function can predispose to oral
candidiasis. Antimicrobial proteins in the saliva such as Smear
lactoferrin, sialoperoxidase, lysozyme, histidine-rich Smears are taken from the infected oral mucosa, rhagades
polypeptides and specific anti-candida antibodies, interact with and the fitting side of the denture, preferably with wooden
the oral mucosa and prevent overgrowth of candida. [14] Drugs spatulas. Smears were fixed immediately in ether/alcohol 1:1
such as inhaled steroids have been shown to increase the risk of or with spray fix. Dry preparations may be examined by Gram
oral candidiasis by possibly suppressing cellular immunity and stain method and periodic acid Schiff (PAS) method. [16]
phagocytosis. The local mucosal immunity reverts to normal on
discontinuation of the inhaled steroids. Dentures predispose to Swabs
infection with candida in as many as 65% of elderly people Swabs are seeded on Sabouraud’s agar (25ºC or room
wearing full upper dentures. Wearing of dentures produces a temperature), on blood agar (35ºC), on Pagano-Levin medium
microenvironment conducive to the growth of candida with low (35ºC) or on Littmann’s substrate (25ºC). Incubation at
oxygen, low pH and an anaerobic environment. This may be due 25ºC is done to ensure recovery of species growing badly at
to enhanced adherence of Candida sp. to acrylic, reduced saliva 35ºC. Sabouraud’s dextrose agar is frequently used as a
flow under the surfaces of the denture fittings, improperly fitted primary culture medium. Since mixed yeast infections are
dentures, or poor oral hygiene. [14] Other factors are oral seen in the oral cavity more frequently than previously
cancer/leukoplakia and a high carbohydrate diet. Growth of thought, particularly in immunocompromised or debilitated
candida in saliva is enhanced by the presence of glucose and its patients, Pagano-Levin agar or Littmann’s substrate, are
adherence to oral epithelial cells is enhanced by a high useful supplements, because they enable distinction of yeasts
carbohydrate diet.[14] on the basis of difference in colony color.[16]

Systemic factors Biopsy

Extremes of life predispose to infection because of reduced Biopsy specimen should in addition be sent for
immunity. Drugs such as broad spectrum antibiotics alter the histopathological examination when chronic hyperplastic
local oral flora creating a suitable environment for candida to candidosis is suspected.[16]
proliferate. Immunosuppressive drugs such as the
antineoplastic agents have been shown in several studies to Imprint culture technique
predispose to oral candidiasis by altering the oral flora, Sterile, square (2.2 × 2.5 cm), plastic foam pads are dipped in
disrupting the mucosal surface and altering the character of peptone water and placed on the restricted area under study for
the saliva. Other factors are smoking, diabetes, Cushing’s 30-60 seconds. Thereafter the pad is placed directly on
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Oral candidiasis Singh, et al. 83

Pagano-Levin or Sabouraud’s agar, left in situ for the first 8 pouch for incubation. The O Yeast-I dent system is based
hours of 48 hours incubation at 37ºC. Then, the candidal on the use of chromogenic substances to measure enzyme
density at each site is determined by a Gallenkamp colony activities. Ricult-N dip slide technique is similar to, but of
counter and expressed as colony forming units per mm 2 (CFU higher sensitivity than MC system.[21]
mm-2 ).[16,17] Thus, it yields yeasts per unit mucosal surface. It
is useful for quantitative assessment of yeast growth in Histological identification
different areas of the oral mucosa and is thus useful in
localizing the site of infection and estimating the candidal Demonstration of fungi in biopsy specimens may require
load on a specific area (Budtz-Jorgensen, 1978, Olsen and several serial sections to be cut.[16] Fungi can be easily
Stenderup A, 1990).[16,18] demonstrated and studied in tissue sections with special
stains. The routinely used Hematoxylin and Eosin stain
Impression culture technique poorly stains Candida species. The specific fungal stains such
Taking maxillary and mandibular alginate impressions, as PAS stain, Grocott-Gomori’s methenamine silver (GMS)
transporting them to the laboratory and casting in 6% and Gridley stains are widely used for demonstrating fungi in
fortified agar with incorporated Sabouraud’s dextrose the tissues, which are colored intensely with these stains. [17]
broth. The agar models are then incubated in a wide
necked, sterile, screw-topped jar for 48-72 hours at 37ºC Physiological tests
and the CFU of yeasts estimated.[19]
The main physiological tests used in definitive
Saliva identification of Candida species involve determination of
This simple technique involves requesting the patient to their ability to assimilate and ferment individual carbon
expectorate 2 ml of mixed unstimulated saliva into a sterile, and nitrogen sources.[17,22]
universal container, which is then vibrated for 30 seconds on
a bench vibrator for optimal disaggregation. The number of The assimilation reactions and fermentation reactions of
Candida expressed as CFU/ml of saliva is estimated by Candida species are tabulated in Tables 1 and 2.
counting the resultant growth on Sabouraud’s agar using
either the spiral plating or Miles and Misra surface viable Phenotypic methods[22,23]
counting technique. Patients who display clinical signs of oral
candidiasis usually have more than 400 CFU/mL.[19] Serotyping
Serotyping is limited to the two serotypes (A and B), a fact
Oral rinse technique that makes it inadequate as an epidemiologic tool. It has
It was first described by Mckendrik, Wilson and Main recently been shown that there can be wide discrepancies in
(1967) and later modified by Samaranayake et al. (1968).[20] the results obtained with different methods of serotyping,

Paper Points Table 2: Fermentation reactions

An absorbable sterile point is inserted to the depth of the Candida species Glucose Maltose Sucrose Lactose
pocket and kept there for 10 sec and then the points are C. albicans AG AG − −
transferred to a 2 ml vial containing Moller’s VMGA III C. tropicalis AG AG AG −
transport medium, (which also facilitates survival of C. kefyer AG AG AG −
facultative and anaerobic bacteria).[16] C. guilliermondii AG − AG −
C. parapsilosis AG − − −
Commercial identification kits C. krusei AG − − −
The Microstix-candida (MC) system consists of a plastic strip C. glabrata AG − − −
to which is affixed a dry culture area (10 mm × 10 mm) of +: Positive reaction, −: Negative reaction, A: Acid production, G:
modified Nickerson medium (Nickerson, 1953) and a plastic Gas production

Table 1: Assimilation reactions

Candida species Glu Mal Suc Lac Cel Gal Tre Raff Mel Xyl Ino Dul
C. albicans + + + + + + + − − + − −
C. tropicalis + + + − + + + − − + − −
C. kefyer + − + + + + − + − + − −
C. parapsilosis + + + − − + + − − + − −
C. guilliermondii + + + − + + + + + + − +
C. krusei + − − − − − − − − + − −
Glu: Glucose, Mal: Maltose, Suc: Sucrose, Lac: Lactose, Cel: Cellobiose, Gal: Galactose, Tre: Trehalose, Raf: Raffinose, Mel: Melibiose, Xyl: Xylose,
Ino: Inositol, Dul: Dulcitol, +: Positive reaction, −: Negative reaction

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Oral candidiasis Singh, et al. 84

Resistogram typing • A and B immunofluorescence

Resistograms do not correlate with pathogenic potential • Nonspecific Candida Antigens
and even though improvements have been made in the • Latex agglutination
method growth end-points often present problems because • Immunobloting
of inoculum size, interpretation and reproducibility. • Cell Wall Components
• Cell Wall Mannoprotein (CWMP)
Yeast ‘Killer Toxin’ typing • b-(1,3)-D-glucan
These authors initially used nine killer strains, developing • Candida Enolase Antigen testing.
a triplet code to distinguish between 100 strains of C.
albicans and found 25 killer- sensitive types. This method Immunodiagnosis[17]
was expanded by using 30 killer strains and three The use of specific antibodies labeled with fluorescent stain
antifungal agents, which appeared to discriminate between permits causative organisms to be diagnosed accurately within
sufficient numbers of strains of C. albicans. minutes. However, the preparation of specific antisera and
purified polyclonal or monoclonal antibodies entails a much more
Morphotyping extensive technical outlay, so the application of these reagents
This method has been used in a study of the morphotypes need only be considered when a very precise diagnosis is of
of 446 strains of C. albicans isolated from various clinical therapeutic consequence (Olsen and Stenderup, 1990). The
specimens. usefulness of antibody testing in the diagnosis of oral candidosis
when other simpler, sensitive and reliable techniques are
Biotyping available is questionable (Silverman et al., 1990).
Williamson (1987) has proposed a simpler method. This
system comprised three tests, the APIZYM system, the MANAGEMENT[4]
API 20C system and a plate test for resistance to boric
acid. This system was found to distinguish a possible 234 Assessment of predisposing factor plays a crucial role in
biotypes, of which 33 were found among the 1430 isolates the management of candidal infection. Mostly the infection
of C. albicans taken from oral, genital and skin sites. is simply and effectively treated with topical application of
antifungal ointments. However in chronic mucocutaneous
Protein typing candidiasis with immunosuppression, topical agents may
Non-lethal mutations of proteins during the yeast cell not be effective. In such instances systemic administration
cycle yield proteins of differing physical properties of medications is required [Tables 3 and 4].[4]
between strains, which may be distinguishable by one or
two dimensional gel electrophoresis. These methods have CONCLUSION
been used to separate C. albicans at the subspecies level.
Yeast-free diets, or people, are both impossible to come by. They
Genetic methods can only be totally avoided in the diet by eating solely fresh dairy,
meat, fish and peeled fresh fruits and vegetables. From a practical
The earliest molecular methods used for fingerprinting C. standpoint, this is neither feasible nor necessary. Total elimination of
albicans strains were karyotyping, restriction yeast from the body is also neither feasible nor desirable, considering
endonuclease analysis (REA) and restriction fragment that yeasts are beneficial to the body
length polymorphism (RFLP). In arbitrarily primed
Table 3: Topical antifungal medications[4]
polymerase chain reaction (AP-PCR) analysis (synonym:
randomly amplified polymorphic DNA (RAPD) analysis), Dosage form/strength Indication
the genomic DNA is used as a template and amplified at a Miconazole cream 2% (OTC) Angular cheilitis
low annealing temperature with use of a single short Clotrimazole cream 1% (OTC) Angular cheilitis
primer (9 to 10 bases) of an arbitrary sequence.[22] Ketoconazole cream 2% (Prescription) Angular cheilitis
Nystatin ointment 100,000 units/gram Angular cheilitis
Serological tests[23] (prescription)
Nystatin topical powder 100,000 units/gram Denture stomatitis
Serological tests for invasive candidiasis (prescription)
• Detection of antibodies Nystatin oral suspension 100,000 units/gram Intraoral candidiasis
• Slide agglutination (prescription)
• Immunodiffusion Betamethasone dipropionate clotrimazole
• Phytohemagglutination cream (prescription)
• Coelectosynersis Clotrimazole troches 10 mg (prescription) Intraoral candidiasis
• Immunoprecipitation Amphotericin B 100 mg/ml (prescription) Intraoral candidiasis

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Oral candidiasis Singh, et al. 85

Table 4: Systemic antifungal medications human buccal epithelial cells. Infect Immun 1986;54:189-93.
of oropharyngeal candidiasis[4] 9. Douglas LJ. Surface composition and adhesion of Candida
albicans. Biochem Soc Trans 1985;13:982-4.
Generic name Formulation 10. Sobel JD, Muller G, Buckley HR. Critical role of germ tube
Amphotericin B 100 mg/ml oral suspension formation in the pathogenesis of candidal vaginitis. Infect Immun
Clotrimazole 10 mg troche 1984;44:576-80.
Fluconazole 100 mg tablet 11. Saltarelli CG, Gentile KA, Mancuso SC. Lethality of
10 mg/ml oral suspension candidal strains as influenced by the host. Can J Microbiol
40 mg/ml oral suspension 1975;21:648-54.
Itraconazole 100 mg capsule 12. Smith CB. Candidiasis: Pathogenesis, host resistance, and
10 mg/ml oral suspension predisposing factors. In: Bodey GP and Fainstein V, editors:
Candidiasis. New York: Raven Press; 1985.P. 53-70.
Ketoconazole 200 mg tablet
13. Slutsky B, Buffo J, Soll DR. High frequency switching of colony
Nystatin 100,000 units/ml oral suspension morphology in Candida albicans. Science 1985;230:666-9.
200,000 units/ml pastille 14. Akpan A, Morgan R. Oral candidiasis. Postgrad Med J
500,000 units/ml tablet 2002;78:455-9.
100,000 units/ml vaginal table 15. Epstein JB, Pearsall NN, Truelove EL. Oral candidosis: Effects
of antifungal therapy upon clinical signs and symptoms, salivary
when a proper balance exists. Treatment of candida overgrowth antibody, and mucosal adherence of Candida albicans. Oral Surg
does not seek the eradication of candida from the diet or the Oral Med Oral Pathol 1981;51:32-6.
person, but rather a restoration of the proper and balanced 16. Olsen I, Stenderup A. Clinical – mycologic diagnosis of oral
ecological relationship between man and yeast. yeast infections. Acta Odontol Scand 1990;48:11-8.
17. Silverman Jr S. Laboratory diagnosis of oral candidosis. In:
Samaranayake LP, MacFarlane TW, editors. Oral Candidosis. 1 st
REFERENCES
ed. Cambridge: Butterwort; 1990. p. 213-37.
18. Budtz-Jorgensen E. Clinical aspects of Candida infection in
1. Terezhalmy GT, Huber MA. Oropharyngeal candidiasis:
denture wearers. J Am Dent Assoc 1978;96:474-9.
Etiology, epidemiology, clinical manifestations, diagnosis, and
19. Epstein JB, Pearsall NN, Truelove EL. Quantitative
treatment. Crest Oral-B at dentalcare.com Contin Educ Course relationships between candida albicans in saliva and the clinical
2011;1-16. status of human subjects. J Clin Microbiol 1980;12:475-6.
2. Prasanna KR. Oral candidiasis – A review. Scholarly J Med
20. Samaranayake LP. Nutritional factors and oral candidosis. J
2012;2:6-30.
Oral Pathol 1986;15:61-5.
3. Dangi YS, Soni MS, Namdeo KP. Oral candidiasis: A review.
21. Cutler JE, Friedman L, Milner KC. Biological and chemical
Int J Pharm Pharm Sci 2010;2:36-41.
characteristics of toxic substances from Candida albicans. Infect
4. Parihar S. Oral candidiasis- A review. Webmedcentral Dent
Immun 1972;6:616-27.
2011;2:1-18.
22. Sandven P. Laboratory identification and sensitivity testing of
5. Mandell GL, Bennett JE, Dolin R. Anti-fungal agents.
yeast isolates. Acta Odontal Scand 1990;48:27-36.
Principles and practice of infectious diseases. 4 th ed. New York: 23. McCullough MJ, Ross BC, Reade PC. Candida albicans: A
Churchill Livingstone; 1994. p. 401-10. review of its history, taxonomy, epidemiology, virulence
6. Lehmann PF. Fungal structure and morphology. Med Mycol
attributes, and methods of strain differentiation. Int J Oral
1998;4:57-8.
7. Brassart D, Woltz A, Golliard M, Neeser JR. In-vitro Maxillofac Surg 1996;25:136-44.
inhibition of adhesion of Candida albicans clinical isolates to human
buccal epithelial cells by Fuca1 ®2Galb-bearing complex carbohydrates. How to cite this article: Singh A, Verma R, Murari A, Agrawal A. Oral
Infect Immun 1991;59:1605-13. candidiasis: An overview. J Oral Maxillofac Pathol 2014;18:81-5.
8. Ghannoum MA, Burns GR, Elteen A, Radwan SS. Experimental Source of Support: Nil. Conflict of Interest: None declared.
evidence for the role of lipids in adherence of Candida spp to

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