{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T12:17:25Z","timestamp":1788956245970,"version":"build-2803163510"},"reference-count":41,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background\/Objectives: Oral candidiasis is frequently encountered in pediatric populations, particularly in infants and toddlers, where the development of immunity and inconsistent oral hygiene contribute to disease susceptibility. While topical antifungal agents remain the standard of care, treatment challenges persist, especially regarding adherence and recurrence. Aloe vera, recognized for its antimicrobial, anti-inflammatory, and mucosal healing properties, may offer therapeutic benefits when used in conjunction with standard regimens. This study aimed to evaluate the adjunctive effect of topical Aloe vera gel, when added to standard antifungal therapy, on reducing fungal load and improving treatment adherence in children with moderate oral candidiasis. Methods: A prospective controlled study was conducted among 54 children diagnosed with moderate oral candidiasis. Participants were randomly assigned to receive either standard topical nystatin or nystatin in conjunction with Aloe vera gel over a 7 day treatment duration. Fungal load was assessed using colony-forming units (CFU) counts from oral swabs collected at baseline and day 7, analyzed via ANCOVA. Additional parameters included treatment adherence, compared using an independent t-test, and clinical recurrence at a 14-day post-treatment follow-up, assessed through logistic regression. Results: Baseline characteristics were similar across groups. By day 7, children in the Aloe vera group exhibited a greater reduction in fungal load compared to those receiving standard therapy alone. Adherence was significantly higher in the aloe group (92.73% vs. 89.21%; p &lt; 0.0001). Regression analysis identified both baseline fungal burden and adherence as factors associated with an increased risk of recurrence. Conclusions: The addition of Aloe vera gel to standard therapy may support a more effective fungal clearance and improved treatment adherence in children with moderate oral candidiasis, suggesting its potential as a complementary treatment option. Given the single-center design, short follow-up, and underpowered recurrence analysis, these findings should be considered preliminary, pending confirmation in larger studies with symptom-anchored endpoints.<\/jats:p>","DOI":"10.3390\/children12111426","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T01:14:02Z","timestamp":1761182042000},"page":"1426","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Aloe vera Adjunctive Therapy for Pediatric Oral Candidiasis: A Prospective Controlled Study on Microbial Clearance and Treatment Adherence"],"prefix":"10.3390","volume":"12","author":[{"given":"Alexandru-Emilian","family":"Flondor","sequence":"first","affiliation":[{"name":"Faculty of Dental Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7779-8987","authenticated-orcid":false,"given":"Irina-Georgeta","family":"Sufaru","sequence":"additional","affiliation":[{"name":"Faculty of Dental Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5092-5234","authenticated-orcid":false,"given":"Maria-Alexandra","family":"Martu","sequence":"additional","affiliation":[{"name":"Faculty of Dental Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasilica","family":"Toma","sequence":"additional","affiliation":[{"name":"Faculty of Dental Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan-Lucian","family":"Burlea","sequence":"additional","affiliation":[{"name":"Faculty of Dental Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioana","family":"Martu","sequence":"additional","affiliation":[{"name":"Faculty of Dental Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kakoschke, S.C., Fleschutz, S., Ruff, E., Dichtl, K., Groeger, M., Schoen, C., Otto, S., and Kakoschke, T.K. (2025). Pediatric Candida Manifestations in the Orofacial Region: A Retrospective Analysis of Different Forms, Risk Factors and Species Distribution. J. Fungi, 11.","DOI":"10.3390\/jof11050363"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"d\u2019Enfert, C., Kaune, A.K., Alaban, L.R., Chakraborty, S., Cole, N., Delavy, M., Kosmala, D., Marsaux, B., Fr\u00f3is-Martins, R., and Morelli, M. (2021). The Impact of the Fungus\u2013Host\u2013Microbiota Interplay upon Candida albicans Infections: Current Knowledge and New Perspectives. FEMS Microbiol. Rev., 45.","DOI":"10.1093\/femsre\/fuaa060"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Talapko, J., Juzba\u0161i\u0107, M., Matijevi\u0107, T., Pustijanac, E., Beki\u0107, S., Kotris, I., and \u0160krlec, I. (2021). Candida albicans-the virulence factors and clinical manifestations of infection. J. Fungi, 7.","DOI":"10.3390\/jof7020079"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Satala, D., Gonzalez-Gonzalez, M., Smolarz, M., Surowiec, M., Kulig, K., Wronowska, E., Zawrotniak, M., Kozik, A., Rapala-Kozik, M., and Karkowska-Kuleta, J. (2022). The role of Candida albicans virulence factors in the formation of multispecies biofilms with bacterial periodontal pathogens. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.765942"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Lu, S.-Y. (2021). Oral Candidosis: Pathophysiology and Best Practice for Diagnosis, Classification, and Successful Management. J. Fungi, 7.","DOI":"10.3390\/jof7070555"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.clindermatol.2016.02.022","article-title":"Oral Candidiasis","volume":"34","author":"Millsop","year":"2016","journal-title":"Clin. Dermatol."},{"key":"ref_7","first-page":"e279","article-title":"Clinical and Microbiological Diagnosis of Oral Candidiasis","volume":"5","year":"2013","journal-title":"J. Clin. Exp. Dent."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Tamai, R., and Kiyoura, Y. (2025). Candida Infections: The Role of Saliva in Oral Health\u2014A Narrative Review. Microorganisms, 13.","DOI":"10.3390\/microorganisms13040717"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Badiu Ti\u0219a, I., Cozma-Petru\u021b, A., Sama\u0219ca, G., Miere, D., Filip, L., Banc, R., M\u00eerza, O., and Iancu, M. (2024). Vitamin D Status among 2\u201318-Year-Old Romanian Pediatric Patients: A Single-Center Study. Nutrients, 16.","DOI":"10.3390\/nu16142266"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Vila, T., Sultan, A.S., Montelongo-Jauregui, D., and Jabra-Rizk, M.A. (2020). Oral Candidiasis: A Disease of Opportunity. J. Fungi, 6.","DOI":"10.3390\/jof6010015"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1179\/2046904714Z.000000000218","article-title":"Severe Acute Malnutrition and Infection","volume":"34","author":"Jones","year":"2014","journal-title":"Paediatr. Int. Child Health"},{"key":"ref_12","first-page":"e172","article-title":"Therapeutic Tools for Oral Candidiasis: Current and New Antifungal Drugs","volume":"24","author":"Sevillano","year":"2019","journal-title":"Med. Oral Patol. Oral Cir. Bucal."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.prosdent.2019.12.025","article-title":"Efficacy of Antifungal Drugs in the Treatment of Oral Candidiasis: A Bayesian Network Meta-Analysis","volume":"125","author":"Fang","year":"2021","journal-title":"J. Prosthet. Dent."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Rai, A., Misra, S.R., Panda, S., Sokolowski, G., Mishra, L., Das, R., and Lapinska, B. (2022). Nystatin Effectiveness in Oral Candidiasis Treatment: A Systematic Review and Meta-Analysis of Clinical Trials. Life, 12.","DOI":"10.3390\/life12111677"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41368-018-0012-3","article-title":"Common Dental Diseases in Children and Malocclusion","volume":"10","author":"Zou","year":"2018","journal-title":"Int. J. Oral Sci."},{"key":"ref_16","first-page":"CD012676","article-title":"Non-Pharmacological Interventions for Managing Dental Anxiety in Children","volume":"2017","author":"Anthonappa","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"104","DOI":"10.4103\/phrev.phrev_8_17","article-title":"Plants\u2019 Natural Products as Alternative Promising Anti-Candida Drugs","volume":"11","author":"Soliman","year":"2017","journal-title":"Pharmacogn. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kunyeit, L., Ajesh, K., and Rao, R.P. (2020). Application of Probiotic Yeasts on Candida Species Associated Infection. J. Fungi, 6.","DOI":"10.3390\/jof6040189"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"100436","DOI":"10.1016\/j.phanu.2025.100436","article-title":"Aloe vera and Its Byproducts as Sources of Valuable Bioactive Compounds: Extraction, Biological Activities, and Applications in Various Food Industries","volume":"31","author":"Mensah","year":"2025","journal-title":"PharmaNutrition"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Darzi, S., Paul, K., Leitan, S., Werkmeister, J.A., and Mukherjee, S. (2021). Immunobiology and Application of Aloe vera-Based Scaffolds in Tissue Engineering. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041708"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Figueiredo, L.C., Figueiredo, N.F., da Cruz, D.F., Baccelli, G.T., Sarachini, G.E., Bueno, M.R., Feres, M., and Bueno-Silva, B. (2022). Propolis, Aloe vera, Green Tea, Cranberry, Calendula, Myrrha and Salvia Properties against Periodontal Microorganisms. Microorganisms, 10.","DOI":"10.3390\/microorganisms10112172"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Liao, B., Zhang, C., Shen, J., Chen, D., Wang, J., Chen, X., Zhou, Y., Wei, Y., Shi, Y., and Gou, L. (2025). Aloin Remodels the Cell Wall of Candida albicans to Reduce Its Hyphal Virulence against Oral Candidiasis. Appl. Microbiol. Biotechnol., 109.","DOI":"10.1007\/s00253-025-13411-7"},{"key":"ref_23","first-page":"1934578X241285207","article-title":"A Review on Aloe weloensis: Unveiling Its Phytochemical Composition and Promising Pharmacological Properties in Antioxidant, Antibacterial, and Antimalarial Activities","volume":"19","author":"Mengesha","year":"2024","journal-title":"Nat. Prod. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e122029","DOI":"10.5812\/jjhs-122029","article-title":"Comparison of Effect of Aloe vera Gel and Nystatin on Candida Species: An In Vitro Study","volume":"14","author":"Rezvaninejad","year":"2022","journal-title":"Jundishapur J. Health Sci."},{"key":"ref_25","first-page":"32","article-title":"A Comparative Laboratory Study on the Effectiveness of Aloe vera Extracts and Nystatin in Inhibiting the Growth of Candida albicans","volume":"3","author":"Ahmadi","year":"2025","journal-title":"Contemp. Orofac. Sci."},{"key":"ref_26","first-page":"434","article-title":"Antiplaque, Antifungal Effectiveness of Aloe vera among Intellectually Disabled Adolescents: Pilot Study","volume":"39","author":"Khatri","year":"2017","journal-title":"Pediatr. Dent."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1007\/s00277-022-04934-4","article-title":"Efficacy and Safety of a Colostrum- and Aloe vera-Based Oral Care Protocol to Prevent and Treat Severe Oral Mucositis in Patients Undergoing Hematopoietic Stem Cell Transplantation: A Single-Arm Phase II Study","volume":"101","author":"Guberti","year":"2022","journal-title":"Ann. Hematol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1002\/(SICI)1097-0142(19990515)85:10<2103::AID-CNCR2>3.0.CO;2-0","article-title":"Validation of a New Scoring System for the Assessment of Clinical Trial Research of Oral Mucositis Induced by Radiation or Chemotherapy. Mucositis Study Group","volume":"85","author":"Sonis","year":"1999","journal-title":"Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Flondor, A.-E., Sufaru, I.-G., Martu, I., Burlea, S.-L., Flondor, C., and Toma, V. (2025). Nutritional Deficiencies and Oral Candidiasis in Children from Northeastern Romania: A Cross-Sectional Biochemical Assessment. Nutrients, 17.","DOI":"10.3390\/nu17111815"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6479","DOI":"10.1007\/s00784-022-04716-2","article-title":"Resistance Profiles to Antifungal Agents in Candida albicans Isolated from Human Oral Cavities: Systematic Review and Meta-Analysis","volume":"26","author":"Kessler","year":"2022","journal-title":"Clin. Oral Investig."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Rajadurai, S.G., Maharajan, M.K., Veettil, S.K., and Gopinath, D. (2021). Comparative Efficacy of Antifungal Agents Used in the Treatment of Oropharyngeal Candidiasis among HIV-Infected Adults: A Systematic Review and Network Meta-Analysis. J. Fungi, 7.","DOI":"10.3390\/jof7080637"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Kirchner, F.R., Littringer, K., Altmeier, S., Tran, V.D.T., Sch\u00f6nherr, F., Lemberg, C., Pagni, M., Sanglard, D., Joller, N., and LeibundGut-Landmann, S. (2019). Persistence of Candida albicans in the Oral Mucosa Induces a Curbed Inflammatory Host Response That Is Independent of Immunosuppression. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00330"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"114969","DOI":"10.1016\/j.addr.2023.114969","article-title":"Reviving the Interest in the Versatile Drug Nystatin: A Multitude of Strategies to Increase Its Potential as an Effective and Safe Antifungal Agent","volume":"199","author":"Sousa","year":"2023","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1080\/24694193.2020.1727065","article-title":"Efficacy of Aloe vera Use for Prevention of Chemotherapy-Induced Oral Mucositis in Children with Acute Lymphoblastic Leukemia: A Randomized Controlled Clinical Trial","volume":"44","author":"Alkhouli","year":"2021","journal-title":"Compr. Child Adolesc. Nurs."},{"key":"ref_35","unstructured":"Chandran, A. (2024). Evaluation of Antifungal Activity of Children\u2019s Toothpaste on Candida albicans Isolated from Children with Early Childhood Caries. J. Indian Soc. Pedod. Prev. Dent., 42."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1002\/cre2.417","article-title":"A Systematic Review on the Effectiveness of Organic Unprocessed Products in Controlling Gingivitis in Patients Undergoing Orthodontic Treatment with Fixed Appliances","volume":"7","author":"Papadopoulou","year":"2021","journal-title":"Clin. Exp. Dent. Res."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Casta\u00f1o, G.P., Rosenau, F., St\u00e4ndker, L., and Firacative, C. (2023). Antimicrobial Peptides: Avant-Garde Antifungal Agents to Fight against Medically Important Candida Species. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15030789"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Anu\u021ba, V., Talianu, M.-T., Dinu-P\u00eervu, C.-E., Ghica, M.V., Prisada, R.M., Albu Kaya, M.G., and Popa, L. (2022). Molecular Mapping of Antifungal Mechanisms Accessing Biomaterials and New Agents to Target Oral Candidiasis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23147520"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Xie, Y., Hua, H., and Zhou, P. (2022). Magnolol as a Potent Antifungal Agent Inhibits Candida albicans Virulence Factors via the PKC and Cek1 MAPK Signaling Pathways. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.935322"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Scribante, A., Gallo, S., Pascadopoli, M., Soleo, R., Di Fonso, F., Politi, L., Venugopal, A., Marya, A., and Butera, A. (2022). Management of periodontal disease with adjunctive therapy with ozone and photobiomodulation (PBM): A randomized clinical trial. Photonics, 9.","DOI":"10.3390\/photonics9030138"},{"key":"ref_41","first-page":"85","article-title":"Effects of probiotics on preventing caries in preschool children: A systematic review and meta-analysis","volume":"47","author":"Meng","year":"2023","journal-title":"J. Clin. Pediatr. Dent."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/12\/11\/1426\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T01:58:33Z","timestamp":1761184713000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/12\/11\/1426"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,22]]},"references-count":41,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["children12111426"],"URL":"https:\/\/doi.org\/10.3390\/children12111426","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,22]]}}}