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36 Pediatric oral thrush

Payam Behzadi1, Elham Behzadi2, Reza Ranjbar1
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 studii clinice
Pediatric oral thrush
Payam Abstract
Behzadi1,
Candidiasis is a wide spread opportunistic fungal
Elham infectious disease which involves different parts
Behzadi2, of human body. Based on anatomic location,
Reza Ranjbar1 there are several kinds of candidiasis caused by
1. Molecular Biology
opportunistic dimorphic fungus of Candida. Oral
Research Center, candidiasis as a common fungal mouth infection
Baqiyatallah University is divided into two groups of acute and chronic
of Medical Sciences,
Tehran, Iran forms. Acute Pseudomembranous Candidiasis
2. Microbiology (thrush), Acute Erythematous Candidiasis (AEC),
Department,
Faculty of Basic Sciences, Chronic Erythematous Candidiasis (CEC), and
Islamic Azad University, Chronic Hyperplastic Candidiasis (CHC) are four
Shahr-e-Qods branch, types of oropharyngeal candidiasis. Age and risks
Tehran, Iran
factors are two important variables that change
Correspondence:
Dr. Reza Ranjbar
the incidence rate of candidiasis. Thrush is the
e-mail: ranjbarre@ most common pediatric oral candidiasis. Parental
gmail.com consciousness, appropriate diet, proper hygiene,
There is no conflict accurate diagnosis, well management and definitive
of interest for the authors. treatment are required to prevent, to control and
to treat pediatric fungal infection of thrush.
Keywords: oral candidiasis, thrush, candida
albicans, infectious disease, children
Introduction
The human oral cavity contains a vast diversity of
microorganisms including yeasts and bacteria(1). There
are several yeast species found among mouth microbial
normal flora; but a huge number of isolates belongs to
Candida species(2,3).
The fungal genus of Candida is regarded as one of the
most important opportunistic pathogenic yeast-like or-
ganism through human pathogens. The large genus of
Candida comprises more than 200 species which some
of them like Candida albicans are recognized as medically
important pathogenic yeast(2,4-10).
The Candida spp. are ubiquitous yeast-like organisms
which are colonized in different animal reservoirs; but the
most of them are not able to grow at 37°C. C. albicans is
the most frequent yeast which is isolated from the oral
cavity of more than 80% of healthy people.
Any alternation in mouth environmental factors may
lead to appearance of pathogenic state of Candida. The
most frequent predisposing factor for candidiasis (Candida
infection) is correlated with host immunodeficiency. The
occurrence of candidiasis in predisposed patients is risky,
because of high rate of their mortality(4,10).
Candidiasis is a wide spectrum of infections which in-
cludes almost the whole anatomic localizations of human
body. Although systemic candidiasis (Candidiosis) is rare,
its appearance may lead to death(3,6,11).
In recent decade, a significant increase of candidiasis is
observed which involves all age groups and genders.
In this mini-review article we try to show the importance
of oral thrush among children.
36
Rezumat
Candidoza este o boală infecţioasă fungică ce
implică afectează diferite părţi ale corpului uman.
În funcţie de localizarea anatomică, există diferite
tipuri de candidoză, provocată de fungi dismorfici
oportunişti de tipul Candida. Candidoza orală este
infecţie fungică comună, localizată la nivel bucal şi
împărţită în două tipuri de forme - acută şi cronică.
Candidoza acută pseudomembranoasă (afte), candidoza
eritematoasă acută, candidoza eritematoasă cronică
şi candidoza hiperplazică cronică reprezintă patru
tipuri distincte de candidoză orofaringiană. Vârsta
şi factorii de risc sunt două variabile importante în
modificarea ratei de incidenţă a cazurilor de candidoză.
Aftele sunt cel mai răspândit tip de candidoză orală
pediatrică. Modul de creştere a copilului, dieta
adecvată, normele de igienă, diagnosticul précis,
managementul tratamentului sunt considerente
care ajută la prevenirea, controlul şi tratamentul
infecţiilor pediatrice ce cauzează afte.
Cuvinte-cheie: candidoză orală, candida
albicans, boală infecţioasă, copii
Oral candidiasis
Because of appearance of white patches and lesions
which can be observed with naked eyes, oral thrush as
well as other surface located candidiasis is known over
the millennia. There are several reports from Greek and
Persian (Ancient Persia) physicians(2,4).
Oral candidiasis is an opportunistic and the most
frequent fungal infection which particularly is appeared
in early and later life of human.
The involved species in human oral candidiasis are C.
albicans (the most one), C. glabrata, C. tropicalis, C. pse-
udotropicalis, C. krusei, C. stellatoidea, and C. dubliniensis.
According to recorded reports, C.albicans is isolated from
50% of oral candidiasis clinical samples(4,10,12-16).
On the basis of clinical demonstrations, there are four
types of oral candidiasis including Acute Pseudomem-
branous Candidiasis (APC), Acute Erythematous Candi-
diasis (AEC), Chronic Erythematous Candidiasis (CEC),
and Chronic Hyperplastic Candidiasis (CHC) (candidal
leukoplakia (CL))(10,17-22).
Clinical demonstrations of oral candidiasis
As mentioned above, each type of oral candidiasis is intro-
duced by a series of clinical signs and symptoms as below:
Acute pseudomembranous candidiasis (thrush)
APC often occurs in infants with immature immuno-
regulatory system regarding to loss of colonization of
microflora on their gastro-intestinal tracts. In addition,
the infection can be revealed in children and young adults
who are involved with nutritional limitation, immunosup-
pression, acquired immunodeficiency syndrome (AIDS),
leukemia, cancers, diabetes, and lymphoma(10,14,23-25).
Anul X • Nr. 34 (2/2014)

APC is distinguished by superficial lesions covered by
easily removable milk-curd-like white plaques. The easily
removable white plaques are a significant diagnostic fea-
ture which may lead to distinguish APC from the other
types of oral candidiasis. White patches are seen on the
surface of mucosal tissues of oral cavity, tongue, palate
and oropharynx.
In direct microscopic studies through the clinical sam-
ples, fungal elements of yeast and filamentous forms are
observed among epithelial cells(2,6,14,25).
Acute erythematous candidiasis
AEC is another type of oral candidiasis with painful
lesions and red mouth which repeatedly happens in broad-
spectrum antibiotic consumers, because of significant
decrease of the mouth bacterial normal flora populati-
ons and providing a suitable situation for overgrowth
of Candida species(2,10,18,19,25). The lesions are most on the
dorsal surface of the tongue, palate and buccal mucosa.
Mostly, the normal condition will be back after cessation
of antibiotic consumption(4,6,25).
Chronic erythematous candidiasis
CEC is known as denture-related candidiasis. It often
is seen in adults but may occur in children with poor oral
hygiene and AIDS(6,10,25,26).
pediatru
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Chronic hyperplastic candidiasis
CHC and CL are the same infections; however, they are
different from the aspect of age range in patients. CHC is
occurred in adults and CL in children(21). There are some
debatable reports about the correlation between CHC or
CL and malignant transformation(10,21). Smoking in adults
is an important predisposing factor for prevalence of CHC,
while immune defects are the most important risk factor
in children(21). The white plaques are not removable as easy
as in APC and frequently occur on the internal surfaces
of both cheeks(25).
The most common predisposing factors
As previous studies show, thrush (oral persistent can-
didiasis) is the most common fungal infection among the
HIV-positive pediatric populations. In addition to immune
system defects in children, anemia, antiretroviral drugs,
broad-spectrum antibiotics, genetic, hospitalization, head
and neck radiotherapy, diabetes, and malnutrition are
frequent predisposing factors which may lead to severe
oral candidiasis. In other words, persistent childhood
thrush is considered as a multifactorial fungal infecti-
on in which, pediatric individuals experience enormous
morbidities with low level quality life. Furthermore, the

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Bibliografie:
*ESPGHAN = Societatea Europeană de Gastroenterologie, Hepatologie și Nutriţie Pediatrică//GPGE =
Societatea Germană de Gastroenterologie și Nutriţie Pediatrică
1. Sandhu J Pediatr Gastreoenterol Nutr 2001; 33: S36-39
2. Guarino et al. J Pediatr Gastreoenterol Nutr 2001; 33: S2-12
3. Pleścik-Lech et al. Acta Paediatrica 2012; 101: e458-e464
studii clinice
progression of HIV increases the severity of persistent
thrush which may lead to mortality(4,14,21,22,27-35).
Extensive and severe oral and oropharyngeal candidi-
asis are clear indicators for progressive status of HIV in
patients with AIDS(2).
It is important to know that, the high colonization of
Candida in oral cavity of children supports the phenome-
non of dental decay(36).
Candida pathogenicity and virulence
factors
The process of evolution can be observed in life cycle
of dimorphic fungus of Candida and particularly in
C. albicans. The morphologic transformations switch
from single-celled yeast to pseudo-hypha and true
hypha(4-6,37).
In balanced environmental conditions of oral cavity,
the commensal yeast-like Candida spp. float through the
saliva and weak attachments of Candida yeasts are broken
by flow of saliva(10).
Saliva in healthy individuals is composed of different
antimicrobial agents including lactoferrin, lysozyme,
peroxidase, histidine-rich polypeptides and anti-candida
antibodies which inhibit the overgrowth of Candida po-
pulations. Therefore, any malfunction of salivary glands
may lead to oral candidiasis(14,15,38).
Investigations show that hydrophobic status on the
surface of Candida yeast cells and attachments between
the yeast cells and host mucosal tissue receptors are
recognized as pathogenic potentials which may lead to
adhesion, colonization and formation of biofilm in oral
cavity(6,10,39-42).
C. albicans and some other species including C. dublini-
ensis and C. stellatoidea are able to produce true hyphae by
the formation of germ tubes. But C. albicans is the only
species that is able to survive at 45°C. The ability of true
hyphae generation in dimorphic fungus of Candida is an
effective pathogenic factor. True hyphae are resistant to
phagocytosis, are invasive forms of the fungus and have
significant adhesion force. Furthermore, true hyphae
are able to produce and secrete enzymes which facilitate
hyphal growth by easy penetration through the host cells
tissues(4,6,10,43-47).
So, in nutrition rich condition the yeast form of
Candida appears while in the lack of accessible nutriti-
on, the true hyphae are dominant forms of the genus
Candida(4,5,10,43).
How to manage and treat oral candidiasis?
To manage and treat an infectious disease like oral
candidiasis, several data are needed. These essential
data include accurate diagnosis, detection and identifi-
cation of fungal elements, identification of predisposing
factors, medical history of the patients, and antifungal
therapy(4,6,10).
In the first step, the presence of skillful experts is ne-
cessary for achieving an accurate diagnosis, detection
and identification of genus and species of the fungal
elements.
38
In the second step, some of the risks factors such as
malnutrition, low oral hygiene, and long-term consump-
tion of antibiotics are able to be improved respectively
by appropriate food intake, suitable oral hygiene (via
tooth brushing) and stopping the use of antibiotics if
needed. As there is no solution for improving some
of the risks factors including immunosuppression,
AIDS, cancers, and diabetes, consumption of anti-
fungal drugs is proposed. The medical history of each
patient confirms the accuracy of clinical diagnosis,
detection and identification of fungal element and
helps managing and treating the infection in the better
manner(4,6,10,48).
The classification of antifungal drugs is based on their
functional activities consisted of polyenes (destructing
fungal cell membrane), azoles (inhibiting biosynthesis
pathway of ergostrol), echinocandins (inhibiting bi-
osynthesis pathway of β-1,3-D-glucan), antifungal
mutagens (by inducing biosynthesis of wrong RNA and
interfering with DNA replication)(6,10,48).
Polyenes are known as fungicide drugs which interact
with ergostrol in fungal cell membrane and may lead to
creation of pores in cell membrane and collapsing fungal
cell. Because of broad spectrum activity of polyenes,
they are used for treating invasive fungal infections.
Nystatin and amphotericin B are effective polyene
antifungal drugs on Candida with a wide range of ac-
tivities. As the absorption of polyenes in human gut
is limited, their use for oral candidiasis treatment is
topical and are applied in the form of lozenges and/or
suspensions(6,10,14,48).
Azoles are fungistatic antifungal drugs which prevent
the biosynthesis pathway of ergosterol. Fluconazole,
ketoconazole, and itraconazole are the most adminis-
tered azoles for treating oral candidiasis. In contrast to
polyenes, azoles are well absorbed through the human
gut, thus the oral administration of azole antifungal
drugs has no limitation(6,10,14,48).
According to previous studies, fluconazole is a favori-
te choice for treating different types of oral candidiasis
excluding CEC. The high secretion of fluconazole in
patient’s saliva has made it as the first choice of anti-
fungal drug for oral candidiasis treatment. However,
some Candida species are reported as resistant strains
to azoles. Voriconazole and pozoconazole are new gene-
rations of effective azoles applied for oral candidiasis
treatment(6,10,14,48).
Anidulafungin, caspofungin, and micafungin are echi-
nocandin members which have fungicidal effects against
Candida species by preventing biosynthesis pathway
of β-1,3-D-glucan. Big molecular size and intravenous
application of echinocandins make them limited as
antifungal drugs for treating oral candidiasis(6,10,14,48).
Conclusion
Candida infections and in particular, oral candidiasis
are multifactorial infections; however two factors in-
cluding infectious agent (Candida species and strains)
and host conditions are considered as predominant
Anul X • Nr. 34 (2/2014)

subjects. The interaction between fungus and human,
determines the type of fungus-host relationship as
commensalism or parasitism.
Standard and appropriate daily nutritional regime,
proper and suitable oral hygiene, and healthy immune
system are valuable prophylactic strategies and ap-
proaches to prevent oral candidiasis among children.
Thrush (APC) as an acute oral candidiasis has the most
incidence between infants and children. In prophylactic
achievements and prompt managements of pediatric
infectious diseases like oral candidiasis, parents play a
key role for their child/children health care. They are
responsible for pediatric health care considerations.
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pediatru
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In other hand, rapid and accurate clinical diagnoses
relating to children with normal immune system is an
appropriate approach has to be achieved for a definitive
and successful treatment.
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are not yet infected may have a successful prophylactic
role to inhibit oral candidiasis.
Finally, appropriate administered antifungal drugs for
children with AIDS or other immunodeficiency problems
that are infected by Candida spp. may help them to control
and reduce signs and symptoms of oral candidiasis. n
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