Oral Candida in β-thalassemia Major and Healthy Population and Their Fluconazole Susceptibility Pattern

Sazan Moffaq Abdulaziz^1, and Aso Ako Muhammad¹

¹Department of Basic Science, College of Dentistry, Hawler Medical University, Erbil, Iraq

Cite this paper:
Sazan Moffaq Abdulaziz and Aso Ako Muhammad. Oral Candida in β-thalassemia Major and Healthy Population and Their Fluconazole Susceptibility Pattern. International Journal of Dental Sciences and Research. 2014; 2(2):27-31. doi: 10.12691/ijdsr-2-2-1

Abstract

Objective: Candida constitutes the main yeast flora in the oral cavity. Different species are known with C. albicans being the principal one. In healthy individuals, the balance among the oral microbial flora is maintained. However, this equilibrium might be altered in certain diseases resulting in the predominance of yeast flora over other microorganisms and behave as pathogens. Thalassemias constitute a large group of immunocompromised patients in our country with multiple hematological, immunological and endocrine disorders making them susceptible to local and systemic opportunistic yeast infections. Fluconazole is a globally used antifungal antibiotic especially in treating recurrent infections in immunocompromised patients. Little is known about the oral yeast carriage in the healthy individuals and thalassemic patients in our population, and their susceptibility pattern to fluconazole. This study has been done to assess the frequency of oral Candida carriage in a group of β-thalassemia major patients and sex and age-matched healthy controls, and to evaluate the susceptibility pattern of the isolates to fluconazole. Place of study: Microbiology Laboratory at College of dentistry/Hawler Medical University, Erbil, Iraq. Methodology: Two hundred subjects were included in the present study, 100 patients with β-thalassemia major (38 females &62 males) aged 4-26 years and 100 apparently healthy subjects age and sex-matched with thalassemic patients. Oral swab specimens were collected from each individual subject, cultured on sabouraud dextrose agar plates and incubated at 37^oC for 48-72 hours. Identification of Candida species was based on colony morphology, germ tube test, biochemical reaction using API Candida system and growth characteristics on CHROMagar Candida. The disc diffusion method was applied to test sensitivity of the isolated strains to various concentrations of fluconazole. Results: All the subjects included in this study harbored only C. albicans in their oral cavities, with higher carriage rate observed among thalassemic patients (20%) than healthy controls (7%). Candida albicans was recovered much frequently from healthy children (57%) and adolescent thalassemias (65%) than other age groups within each study group. However the statistical analysis showed no significant correlation between age and oral C. albicans carriage rate (χ² p-value > 0.05). Healthy females showed higher carrier rate than males, meanwhile C. albicans was equally distributed between male and female thalassemic patients. Susceptibility of C. albicans isolates to a 25 μg/ml fluconazole showed that out of the 27 C. albicans isolates, 23 were resistant to fluconazole. The resistant albicans strains showed high resistance rate (>128 μg/ml) within both groups. Whereas the response of sensitive strains to fluconazole was variable ranged from >16 μg/ml in healthy subjects to 4 - >16 μg/ml in thalasemias. Conclusion: C. albicans was the only isolated species from the oral cavity of thalassemic patients and healthy subjects. However the carrier rate was higher among thalassemias than healthy controls. Most of the isolated strains were resistant to fluconazole. Further studies are required to assess the sensitivity of oral Candida isolates to other antifungal drugs.

Keywords:
β-thalassemia major disk diffusion Candida fluconazole

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References:

[1]	Kleinegger CL, Lockhart SR, Vargas K, Soll DR (1996). Frequency, intensity, species, and strains of oral Candida vary as a function of host age. J Clin Microbiol, 34(9): 2246-2254.
[2]	Qi QG, Hu T, Zhou XD (2005). Frequency, species and molecular characterization of oral Candida in hosts of different age in China. J Oral Pathol Med, 34(6): 352-356.
[3]	Samaranayake LP, Cheung LK, Samaranayake YH (2002). Mycotic infections of the oral cavity. Dermatologic Therapy, 15: 252-70.
[4]	Soll DR (2002). Candida commensalisms and virulence: the evolution of phenotypic plasticity. Acta tropica. 81: 101-10.
[5]	Bartholomew GA, Rodu B, Bell DS (1987). Oral candidiasis in patients with diabetes mellitus: a thorough analysis. Diabetes Care, 10(5): 607-12.
[6]	Boerlin P, Boerlin-Petzold F, Goudet J, Durussel C, Pagani JL, Chave JPand, Bille J (1996). Typing Candida albicans oral isolates from human immunodeficiency virus-infected patients by multilocus enzyme electrophoresis and DNA fingerprinting. J. Clin. Microbiol, 34(5):1235-48.
[7]	Davies AN, Brailsford S, Broadley K, Beighton D (2002). Oral yeast carriage in patients with advanced cancer. Oral Microbiol Immunol, 17: 79-84.
[8]	Abu-Elteen KH, Hamad MA, Salah SA (2006). Prevalence of oral Candida infections in diabetic patients. Bahrain Medical Bulletin, 28(1): 1-8.
[9]	Alberth M, Majoros L, Kovalecs G, Borbas E, Szeged I, Marton IJ, Kiss C (2006). Significance of oral candidiasis infections in children with cancer. Pathology Oncology Research, 12(4): 237-41.
[10]	Honig GR. Hemoglobin disorders. In: Behrman RE, Kliegman RM,Jenson HB, editors. Nelson Textbook of Pediatrics. 16th ed. Philadelphia: WB Saunders; 2000. p.1478-88.
[11]	White TC, Marr KA, Bowden RA (1998). Clinical, cellular and molecular factors that contribute to antifungal drug resistance. Clin. Micobiol. Rev., 11: 382-402.
[12]	Samaranayake L (2012). Essential microbiology for dentistry. 4th ed. Edinburgh: Churchill Livingstone-Elsevier. P. 184-91.
[13]	Hoffman, HL and Pfaller MA (2001). In vitro antifungal susceptibility testing. Pharmacotherapy, 21: 111s-23s.
[14]	Kirkpatrick WR, Turner TM, Fothergill AW, McCathy DI, Redding SW, Michael GR, Patterson TF (1996). Fluconazole disc diffusion susceptibility testing of Candida species. J Clin Microbiol, 36(11): 3429-3432.
[15]	Ruhnke M, Schmidt-Westhausen A, Engelmann E, Trautmann M (1996). Comparative evaluation of three antifungal susceptibility test methods for Candida albicans isolates and correlation with response to fluconazole therapy. J Clin Microbiol,34: 3208-3211.
[16]	Cronvall G and Carlsson I (2001). Fluconazole and voriconazole multidisc testing of Candida species for disc test calibration and MIC estimation. J Clin Microbiol, 39(4): 1422-1428.
[17]	Xu J and Mitchell TG (2002). Geographical differences in human oral yeast flora. CID, 36: 221-224.
[18]	Nneka UG and Ebele OM (2005). The occurance of oral thrush yeasts among school children in Onitsha Urban, Anambra State, Nigeria. J Med Sci, 5(3): 177-180.
[19]	Gravina HG, de Morán EG, Zambrano O, Chourio ML, de Valero SR, Robertis S, Mesa L (2007). Oral candidiasis in children and adolescents with cancer. Identificaion of Candida spp. Med Oral Patol Oral Cir Bucal, 12(6): E419-E423.
[20]	Martins ACM, Maluf MLF, Svidzinski TIS (2011). Prevalence of yeast species in the oral cavity and its relationship to dental caries. Maringá, 33(1): 107-112.
[21]	Selim HS, Hammouda A, Sadek NA, Ahmed MA, Al-Kadassy AM (2006). Fungal infection among patients with some hematopoietic disorders. J Egypt Public Health Assoc, 81(5 & 6): 321-36.
[22]	Hazza'a AM, Darwazeh AMG, Museedi OSM (2009). Oral candida flora in a group of Jordanian patients with β-thalassemia major. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 109(2): 252-256.
[23]	Cheesbrough M (2006). District laboratory practice in tropical countries. 2nd ed. Part 2. Cambridge University Press. UK. pp. 243-244.
[24]	Forbes BA, Sahm DF, Weissfeld AS (2007). Baily and Scott's diagnostic microbiology. 12th ed. Mosby-Elseveier. pp. 702-709.
[25]	Odds FC (1988). Candida and candidosis. 2nd ed. London: Baillière Tindall: p. 68-92.
[26]	Leung WK, Dassanayake RS, Yau JY, Jin LJ, Yam WC, Samaranayake LP (2000). Oral colonization, phenotypic, and genotypic profiles of Candida species in irradiated, dentate, xerostomic nasopharyngeal carcinoma survivors. J Clin Microbiol, 38:2219-26.
[27]	AL-Karaawi Z M, Manfredi M, Waugh ACW, McCullough MJ, Jorge J, Scully C, Porter SR (2002). Molecular characterization of Candida spp. isolated from the oral cavities of patients from diverse clinical settings. Oral Microbiology and Immunology, 17(1): 44-49.
[28]	Sculley C, El-Kabir M, Samaranayake LP (994). Candida and oral candidosis; a review. CROBM, 5(2): 125-157.
[29]	Ananthalakshmi R, Mirali S, Sekar B (2011). Association of asymptomatic oral candidal carriage, oral candidiasis with CD4 lymphocyte count in HIV/AIDS patients- a comparative study. JIADS, 2(1): 6-10.
[30]	Campisi G, Pizzo G, Milici ME, Mancuso S, Margiotta V (2002). Candidal carriage in the oral cavity of HIV infected subjects. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 93(3): 281-286.
[31]	Breuer W, Hershko C, Cabantchik ZI. The importance of non-transferrin bound iron in disorders of iron metabolism. Transfus Sci 2000;23:185-191.
[32]	Rehman M and Lodhi Y. Prospects and future of conservative management of beta thalassaemia major in a developing country. Pak J Med Sci, 2004; 20(2): 105-112
[33]	Porter JB. Pathophysiology of transfusional iron overload: contrasting patterns in thalassemia major and sickle cell disease Hemoglobin 2009;33:S37-S45.
[34]	Skoutelis AT, Lianou E, Papavassiliou T, Karamerou A, Politi K, Bassaris HP (1984). Defective phagocytic and bactericidal function of polymorphonuclear leukocytes in patients with beta- thalassaemia major. J infec, 8, 118-122.
[35]	Vaiopoulos G, Konstantopoulos K, Kittas C, Hatzakis A, Bogdanos K, Mastrovassilopoulos A, Meletis J, Loukopoulos (1995). Histological and functional changes in the salivary glands in thalassaemia major. Haematologia, 27(1): 33-38.
[36]	Tobgi RS, Samaranayake LP, MacFarlane TW. In vitro susceptibility of Candida species to lysozyme. Oral Microbiol Immunol 1988: 3: 35-39.
[37]	Lenander-Lumikari M. Inhibition of Candida albicans by the peroxidase/SCN-/H2O2 system. Oral Microbiol Immunol 1992: 7: 315-320.
[38]	Nikawa H, Samaranayake LP, Tenovuo J, Pang KM, Hamada T. The fungicidal effect of human lactoferrin on Candida albicans and Candida krusei. Arch Oral Biol 1993: 38: 1057-1063.
[39]	Jainkittivong A, Johnson DA, Yeh CK. The relationship between salivary histatin levels and oral yeast carriage. Oral Microbiol Immunol 1998: 13: 181-187.
[40]	Ugun-Can B, Kader T, Akyüs S (2007). Oral candidal carriage in children with and without dental caries. Quintessence International, 38(1): 45-49.
[41]	Moalic E, Gestalin A, Quinio D, Gest PE, Zerilli A, Le Flohic AM (2001). The extent of oral fungal flora in 353 students and possible relationships with dental caries. Caries Research, 35(2): 149-155.
[42]	Weatherall DJ and Clegg JB (2001). The thalassemia syndromes. 4th ed. Blackwell Scientific, Oxford.
[43]	Fothergill AW. Antifungal susceptibility testing: clinical laboratory and standards institute (CLSI) methods. In: Hall GS, editors. Interactions of yeasts, molds, and antifungal agents: how to detect resistance [internet]. Springer. P. 65-74. Available from: http://www.springer.com/978-1-58829-8478.
[44]	Sun J, Qi C, Lafleur MD, Qi QG (2009). Fluconazole susceptibility and genotypic heterogeneity of oral Candida albicans colonies from the patients with cancer receiving chemotherapy in China. Int J Oral Sci, 1(3): 156-162.