The Association Between Chronic Oral Candidiasis and Early Childhood Caries: Results of a Clinical-Laboratory Study

Introduction

Oral health in early childhood is a cornerstone of overall physical development, social skill formation, and quality of life [1-3]. Among numerous pathologies in this domain, two hold particular clinical and epidemiological significance for preschoolers: early childhood caries (ECC) and oral candidiasis [4, 5]. Traditionally viewed within different paradigms (dental and pediatric), modern evidence suggests these conditions may be closely linked by shared pathogenic pathways. Their combined influence creates a vicious cycle, exacerbating the course of each condition and posing a complex therapeutic challenge that requires a multidisciplinary approach.

Oral candidiasis, or candidal stomatitis, is an infectious lesion of the oral mucosa caused by opportunistic yeast-like fungi of the genus Candida (predominantly C. albicans) [6-8]. Epidemiological data in the Russian Federation indicate a consistently high prevalence of this pathology among young children. It accounts for 30% to 45% of all infectious-inflammatory diseases of the oral cavity in children under 3 years of age. The average national incidence rate among children aged 0-6 years is 5-7 cases per 1000 children of the corresponding age, with notable regional variability. In regions with warm, humid climates and high population density, this rate can increase by 15-20%. Children in their first year of life are the most vulnerable; however, chronic and recurrent forms, which are of greatest interest for studying long-term consequences, are also actively diagnosed in the preschool period.

Infection occurs both endogenously against a background of dysbiosis and exogenously: vertically (during childbirth from a mother with urogenital candidiasis) or via contact-household routes [9-12]. The classic acute pseudomembranous form ("thrush") with characteristic curd-like plaques is well-known. However, atypical, attenuated, and chronic forms are increasingly encountered in practice: angular cheilitis (perlèche), atrophic candidiasis (manifesting as painful erythema), and hyperplastic candidiasis with dense plaques [13, 14]. It is precisely these forms that often remain undiagnosed, perpetuating a constant inflammatory process.

The high-risk group for developing chronic oral candidiasis comprises children with factors disrupting immune homeostasis or microbial balance: those born prematurely or with perinatal pathology; receiving long-term antibacterial or inhaled corticosteroid therapy; with nutritional disorders, hypovitaminosis (especially of B vitamins and iron), endocrinopathies (e.g., diabetes mellitus); and those with congenital or acquired immunodeficiencies [15-18]. A key unifying risk factor for both studied diseases is a high-carbohydrate diet. Frequent consumption of readily fermentable sugars not only directly stimulates cariogenic microflora but also serves as a powerful trophic factor for the growth, adhesion, and pathogenicity of Candida spp [19, 20].

The consequences of chronic fungal infection extend beyond local discomfort. The prolonged persistence of Candida sustains chronic inflammation, impairs the mucosal barrier function, and, most importantly in the context of caries pathogenesis, can radically alter the ecosystem of dental plaque [21, 22]. Modern research has revealed that C. albicans exhibits high adhesiveness to enamel hydroxyapatite, can actively ferment sugars producing organic acids (lactic, acetic), and synthesize extracellular polysaccharides that strengthen the biofilm matrix [23, 24]. Furthermore, fungi demonstrate high tolerance to acidic environments, allowing them not only to survive but also to actively participate in establishing a low pH within dental plaque [25]. A model of synergy emerges where C. albicans and classic cariogenic bacteria (e.g., Streptococcus mutans) mutually enhance each other's pathogenicity, creating a more aggressive and resilient biofilm [26, 27].

Early childhood caries, defined as the presence of one or more decayed, filled, or missing (due to caries) teeth in a child under 71 months of age, remains one of the most common chronic diseases of childhood [28, 29]. Its etiology is multifactorial, yet the central role belongs to the microbial factor under specific dietary conditions. The hypothesis regarding the involvement of fungal microflora in cariogenesis is gaining increasing support in vitro; however, clinical studies, particularly those focused on preschoolers and chronic forms of candidiasis, are scarce and contradictory. Most research is centered on acute manifestations in infants, overlooking the potentially more significant, in terms of long-term dental consequences, chronic persistence of the fungus [30-32]. A visual representation of this complex interrelationship is presented in Figure 1, integrating key risk factors and pathogenic pathways.

The diagram clearly illustrates how diverse exogenous and endogenous risk factors can lead to the development of chronic oral candidiasis, which, in turn, through a series of interrelated mechanisms (creation of an acidic environment, synergy with bacteria, direct acid production), creates the conditions for the onset and aggressive course of early childhood caries. It is important to note the presence of a feedback loop: formed carious cavities serve as ideal anatomical reservoirs for the persistence and protection of Candida from the action of saliva and antifungal agents, closing the pathological cycle [33].

Thus, the existing scientific basis allows us to hypothesize that chronic oral candidiasis is a significant biological risk factor for the development and progression of ECC in preschool children. However, targeted studies combining thorough dental diagnostics with modern microbiological methods are necessary to confirm this hypothesis at the clinical level.

The present study aimed to assess, based on a comprehensive clinical-laboratory analysis, the relationship between the presence of chronic oral candidiasis and the prevalence and intensity of early childhood caries in preschool children (3-6 years).

Materials and Methods

This study is a prospective comparative clinical-laboratory investigation, jointly organized at the clinical facilities of the Chechen State University named after A.A. Kadyrov and the Saratov State Medical University named after V.I. Razumovsky. The study was conducted from September 2023 to May 2024. Its design was developed for a comprehensive assessment of dental status, dietary patterns, and microbiological indicators in preschool children with chronic oral candidiasis.

Seventy kids, ages three to six, participated in the study and were split into two observation groups. The main group consisted of 35 children with a verified diagnosis of chronic oral candidiasis, confirmed clinically and microbiologically. The control group, comparable in age and sex, consisted of 35 children without clinical signs of oral candidiasis and with no history of the condition. Acute infectious diseases at the time of examination, severe somatic pathologies in the decompensation stage, congenital maxillofacial malformations, systemic antifungal or antibacterial drug use within the previous four weeks, and documented diabetes mellitus were common exclusion criteria for all participants.

Each child underwent a comprehensive examination consisting of three key components. The first stage was a structured questionnaire for parents or legal guardians to assess the child's dietary habits. The questionnaire, developed based on validated surveys, included questions about the frequency and type of consumption of major food groups, with an emphasis on readily fermentable carbohydrates: frequency of sweet beverage consumption (juices, soft drinks), confectionery, sweet baked goods, and the history of nocturnal feeding habits. Responses were coded and analyzed to calculate a total cariogenic dietary index.

The second stage was a detailed dental examination conducted under standard conditions using dental instruments. The condition of hard tooth tissues was assessed using a visual-tactile method under artificial lighting. The number of decayed, filled, and extracted primary teeth was recorded with the calculation of caries intensity indices (DMFT for teeth and DMFS for surfaces). To objectively assess oral hygiene status, the simplified Oral Hygiene Index (OHI-S) by Green-Vermillion was determined by staining six key teeth with fuchsin solution and calculating plaque scores on vestibular and lingual surfaces. Additionally, the presence and location of white spot lesions (enamel demineralization) were assessed.

The third, laboratory stage, involved the diagnosis of oral candidiasis and the quantitative assessment of fungal contamination. Using a sterile spatula, scrapings were taken from the buccal mucosa in the affected area (or from the dorsal surface of the tongue) and from supragingival dental plaque on the approximal surfaces of the first and second primary molars. The obtained material was transported in Amies transport medium. Microbiological investigation included culture on selective chromogenic CHROMagar™ Candida medium with subsequent incubation under aerobic conditions at 37°C for 72 hours. Identification of Candida albicans was based on colony morphology and characteristic color, and semi-quantitative assessment was performed to determine colony-forming unit (CFU/mL) concentration. For all children in the main group and for a portion of the control group with positive growth, additional microscopy of a native preparation with potassium hydroxide was performed to confirm the presence of fungal elements.

Statistical analysis of the obtained data was performed using the IBM SPSS Statistics 26.0 software package. Quantitative parameters with a normal distribution are presented as mean ± standard deviation (M ± SD). For comparing mean values between two independent groups, Student's t-test was used; for three or more groups, one-way analysis of variance (ANOVA) with Tukey's post-hoc test was applied. Data with a non-normal distribution are described as median and interquartile range (Me [Q25; Q75]), and the non-parametric Mann-Whitney U test was used for their comparison. Analysis of qualitative characteristics was performed using the chi-square (χ²) test or Fisher's exact test. For multivariate analysis and assessment of the independent contribution of various factors (presence of candidiasis, dietary index, hygiene) to caries intensity, multiple linear regression was used. To assess the strength and direction of relationships between parameters, Spearman's rank correlation coefficient (rs) was calculated. In all analyses, differences were considered statistically significant at a significance level of p < 0.05.

The study was conducted in strict accordance with the ethical principles of the Helsinki Declaration. The study protocol was approved by the local ethics committees of the participating universities. Parents or legal guardians of all participating children were informed about the study's aims and methods and provided voluntary written informed consent.

Results and Discussion

The clinical-laboratory examination was completed for all 70 children included in the study. The groups were comparable in terms of basic demographic indicators. The mean age of children in the main group was 4.7 ± 1.1 years, and in the control group, 4.5 ± 1.2 years (p>0.05). The sex distribution also showed no statistically significant differences: there were 54.3% boys in the main group and 51.4% in the control group (p>0.05).

Questionnaire data, presented in Table 1, revealed significant differences in dietary patterns between the groups. The cariogenic dietary index was significantly higher in the main group (6.8 ± 2.1 points versus 3.9 ± 1.8 points in the control, p<0.001). The most significant differences concerned the frequency of sweet beverage consumption between main meals and the history of nocturnal feeding with sweet products, which was reported for the vast majority of children with chronic candidiasis.

Table 1. Dietary characteristics of children in the compared groups (n=70)

The results of the dental examination, summarized in Table 2, demonstrated a pronounced difference in oral health status. Caries intensity in the main group was 2.8 times higher than in the control group for the DMFT index (6.4 ± 3.1 versus 2.3 ± 1.9, p<0.001) and 3.1 times higher for the DMFS index (11.2 ± 6.5 versus 3.6 ± 3.1, p<0.001). Oral hygiene was also significantly worse in the group of children with candidiasis (OHI-S 2.5 ± 0.7 versus 1.4 ± 0.5, p<0.001).

Table 2. Dental status of children in the compared groups (n=70)

Microbiological data (Table 3) confirmed not only the presence but also a high level of fungal contamination in the children of the main group. Candida albicans was isolated from the mucosa in 100% of children in this group with a mean concentration of 4.2*10⁴ CFU/mL. In the control group, C. albicans carriage was detected in only 22.9% of children, and the concentration was two orders of magnitude lower (1.5*10² CFU/mL). Moreover, fungi were detected in the dental plaque of children in the main group in 88.6% of cases, indicating their integration into the cariogenic biofilm.

Table 3. Results of microbiological investigation (n=70)

A key result of the study was the identified system of strong correlations (Table 4). The closest direct association was observed between the concentration of C. albicans on the mucosa and caries intensity (rs=0.82 for DMFS). A strong correlation was also found between the cariogenic dietary index and fungal concentration (rs=0.78), as well as between poor hygiene and caries intensity (rs=0.74). Multiple regression analysis showed that a high level of C. albicans colonization is an independent predictor of caries intensity even after accounting for the influence of hygiene and diet (β=0.51, p<0.01).

Table 4. Correlation matrix (Spearman's coefficient, rs) of key parameters for the entire sample (n=70)