• Access to dental care-parents' and caregivers' views on dental treatment services for people with disabilities.

      Prabhu, Neeta T; Nunn, June H; Evans, D J; Girdler, N M; Department of Pediatric Dentistry, Westmead Hospital, Sydney, Australia. neetaprabhu@hotmail.com (2010-03)
      The goal of this study was to elicit the views of patients or parents/caregivers of patients with disabilities regarding access to dental care. A questionnaire was generated both from interviews with patients/parents/caregivers already treated under sedation or general anesthesia as well as by use of the Delphi technique with other stakeholders. One hundred thirteen patients from across six community dental clinics and one dental hospital were included. Approximately, 38% of the subjects used a general dental practitioner and 35% used the community dental service for their dental care, with only 27% using the hospital dental services. Overall waiting time for an appointment at the secondary care setting was longer than for the primary care clinics. There was a high rate of parent/caregiver satisfaction with dental services and only five patients reported any difficulty with travel and access to clinics. This study highlights the need for a greater investment in education and training to improve skills in the primary dental care sector.
    • Alcohol-related cancers and genetic susceptibility in Europe: the ARCAGE project: study samples and data collection.

      Lagiou, Pagona; Georgila, Christina; Minaki, Ploumitsa; Ahrens, Wolfgang; Pohlabeln, Hermann; Benhamou, Simone; Bouchardy, Christine; Slamova, Alena; Schejbalova, Miriam; Merletti, Franco; et al. (2009-02)
      Cancers of the upper aerodigestive tract (UADT) include those of the oral cavity, pharynx (other than nasopharynx), larynx, and esophagus. Tobacco smoking and consumption of alcoholic beverages are established causes of UADT cancers, whereas reduced intake of vegetables and fruits are likely causes. The role of genetic predisposition and possible interactions of genetic with exogenous factors, however, have not been adequately studied. Moreover, the role of pattern of smoking and drinking, as well as the exact nature of the implicated dietary variables, has not been clarified. To address these issues, the International Agency for Research on Cancer initiated in 2002 the alcohol-related cancers and genetic susceptibility (ARCAGE) in Europe project, with the participation of 15 centers in 11 European countries. Information and biological data from a total of 2304 cases and 2227 controls have been collected and will be used in a series of analyses. A total of 166 single nucleotide polymorphisms of 76 genes are being studied for genetic associations with UADT cancers. We report here the methodology of the ARCAGE project, main demographic and lifestyle characteristics of the cases and controls, as well as the distribution of cases by histology and subsite. About 80% of cases were males and fewer than 20% of all cases occurred before the age of 50 years. Overall, the most common subsite was larynx, followed by oral cavity, oropharynx, esophagus and hypopharynx. Close to 90% of UADT cancers were squamous cell carcinomas. A clear preponderance of smokers and alcohol drinkers among UADT cases compared with controls was observed.
    • The association between change in body mass index and upper aerodigestive tract cancers in the ARCAGE project: multicenter case-control study.

      Park, Sungshim Lani; Lee, Yuan-Chin Amy; Marron, Manuela; Agudo, Antonio; Ahrens, Wolfgang; Barzan, Luigi; Bencko, Vladimir; Benhamou, Simone; Bouchardy, Christine; Canova, Cristina; et al. (2011-03-15)
      Previous studies reported an inverse relationship between body mass index (BMI) and upper aerodigestive tract (UADT) cancers. Examining change in BMI over time may clarify these previous observations. We used data from 2,048 cases and 2,173 hospital- and population-based controls from ten European countries (alcohol-related cancers and genetic susceptibility in Europe study) to investigate the relationship with BMI and adult change in BMI on UADT cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for associations between BMI at three time intervals and BMI change on UADT cancer development, adjusting for center, age, sex, education, fruit and vegetable intake, smoking and alcohol consumption. We found an inverse relationship between UADT cancers and BMI at time of interview and 2 years before interview. No association was found with BMI at 30 years of age. Regarding BMI change between age 30 and 2 years before interview, BMI decrease (BMI change <-5%) vs. BMI stability (-5% ≤ BMI change <5%) showed no overall association with UADT cancers (OR = 1.15; 95% CI = 0.89, 1.49). An increase in BMI (BMI change ≥+5%) was inversely associated with UADT cancers (OR = 0.74; 95% CI = 0.62, 0.89). BMI gain remained inversely associated across all subsites except for esophageal cancer. When stratified by smoking or by drinking, association with BMI gain was detected only in drinkers and smokers. In conclusion, BMI gain is inversely associated with UADT cancers. These findings may be influenced by smoking and/or drinking behaviors and/or the development of preclinical UADT cancers and should be corroborated in studies of a prospective nature.
    • An audit comparing the discrepancies between a verbal enquiry, a written history, and an electronic medical history questionnaire: a suggested medical history/social history form for clinical practice.

      Carey, Barbara; Stassen, Leo; Dublin Dental School and Hospital, Lincoln Place, Dublin 2. (2011-04)
      In everyday practice, dentists are confronted with an increasing number of patients with complex medical problems. There is divergence of opinion among dentists regarding how to obtain a thorough medical/social history.
    • Characteristics of patients with orofacial granulomatosis.

      McCartan, B E; Healy, C M; McCreary, C E; Flint, S R; Rogers, S; Toner, M E; School of Medicine, Royal College of Surgeons in Ireland, Dublin School of Dental Science, Trinity College Dublin, Ireland. (2011-10)
      Orofacial granulomatosis has mostly been described in reports of very small numbers of cases. Few large case groups have been described. The aim of this study was to describe the demographics, symptoms, clinical features and laboratory findings in a large cohort of cases.
    • Demographics of implant placement and complications of a patient subgroup in a dental hospital population.

      Brennan, Maire; Houston, Frank; O'Sullivan, Michael; O'Connell, Brian; Department of Restorative Dentistry, University Dental School and Hospital, Wilton, Cork. (2011-03-14)
      Little has been reported about the demographics of implant placement in the Irish population and the complications that occur. This is important in terms of service planning and providing patient information.
    • Diet and the risk of head and neck cancer: a pooled analysis in the INHANCE consortium.

      Chuang, Shu-Chun; Jenab, Mazda; Heck, Julia E; Bosetti, Cristina; Talamini, Renato; Matsuo, Keitaro; Castellsague, Xavier; Franceschi, Silvia; Herrero, Rolando; Winn, Deborah M; et al. (2012-01)
      We investigated the association between diet and head and neck cancer (HNC) risk using data from the International Head and Neck Cancer Epidemiology (INHANCE) consortium. The INHANCE pooled data included 22 case-control studies with 14,520 cases and 22,737 controls. Center-specific quartiles among the controls were used for food groups, and frequencies per week were used for single food items. A dietary pattern score combining high fruit and vegetable intake and low red meat intake was created. Odds ratios (OR) and 95% confidence intervals (CI) for the dietary items on the risk of HNC were estimated with a two-stage random-effects logistic regression model. An inverse association was observed for higher-frequency intake of fruit (4th vs. 1st quartile OR = 0.52, 95% CI = 0.43-0.62, p (trend) < 0.01) and vegetables (OR = 0.66, 95% CI = 0.49-0.90, p (trend) = 0.01). Intake of red meat (OR = 1.40, 95% CI = 1.13-1.74, p (trend) = 0.13) and processed meat (OR = 1.37, 95% CI = 1.14-1.65, p (trend) < 0.01) was positively associated with HNC risk. Higher dietary pattern scores, reflecting high fruit/vegetable and low red meat intake, were associated with reduced HNC risk (per score increment OR = 0.90, 95% CI = 0.84-0.97).
    • Eastern Health Board Regional Orthodontic Service: an initial audit.

      Dowling, P A; Fitzpatrick, P J; Garvey, M T; McNamara, C M; Department of Public and Child Dental Health, Dublin Dental Hospital. (1997)
      This initial audit of 600 recently assessed Eastern Health Board orthodontic patients suggests that a large number of them (47 per cent) requires referral for routine restorative and preventive dental care. Closer links are needed with general dental practitioners and community dental surgeons to resolve these needs. The trend for a high referral of females and Class 11 Division 1 malocclusion type correlated well with studies in other countries.
    • The effect of skeletal pattern on determining articulator settings for prosthodontic rehabilitation: an in vivo study.

      Canning, Tom; O'Connell, Brian C; Houston, Frank; O'Sullivan, Michael; Dublin Dental School and Hospital, Trinity College, Dublin, Ireland. (2011-01)
      During extensive prosthodontic treatment, the use of an accurately adjusted articulator is recommended to simulate mandibular movements. This clinical study was undertaken to assess any possible effect of the underlying skeletal pattern on programming articulator settings.
    • Emergence of hospital- and community-associated panton-valentine leukocidin-positive methicillin-resistant Staphylococcus aureus genotype ST772-MRSA-V in Ireland and detailed investigation of an ST772-MRSA-V cluster in a neonatal intensive care unit.

      Brennan, Gráinne I; Shore, Anna C; Corcoran, Suzanne; Tecklenborg, Sarah; Coleman, David C; O'Connell, Brian; National MRSA Reference Laboratory, St. James’s Hospital, Dublin, Ireland. gbrennan@stjames.ie (2012-03)
      Sequence type 22 (ST22) methicillin-resistant Staphylococcus aureus (MRSA) harboring staphylococcal cassette chromosome mec (SCCmec) IV (ST22-MRSA-IV) has predominated in Irish hospitals since the late 1990s. Six distinct clones of community-associated MRSA (CA-MRSA) have also been identified in Ireland. A new strain of CA-MRSA, ST772-MRSA-V, has recently emerged and become widespread in India and has spread into hospitals. In the present study, highly similar MRSA isolates were recovered from seven colonized neonates in a neonatal intensive care unit (NICU) in a maternity hospital in Ireland during 2010 and 2011, two colonized NICU staff, one of their colonized children, and a NICU environmental site. The isolates exhibited multiantibiotic resistance, spa type t657, and were assigned to ST772-MRSA-V by DNA microarray profiling. All isolates encoded resistance to macrolides [msr(A) and mpb(BM)] and aminoglycosides (aacA-aphD and aphA3) and harbored the Panton-Valentine leukocidin toxin genes (lukF-PV and lukS-PV), enterotoxin genes (sea, sec, sel, and egc), and one of the immune evasion complex genes (scn). One of the NICU staff colonized by ST772-MRSA-V was identified as the probable index case, based on recent travel to India. Seven additional hospital and CA-ST772-MRSA-V isolates recovered from skin and soft tissue infections in Ireland between 2009 and 2011 exhibiting highly similar phenotypic and genotypic characteristics to the NICU isolates were also identified. The clinical details of four of these patients revealed connections with India through ethnic background or travel. Our study indicates that hospital-acquired and CA-ST772-MRSA-V is currently emerging in Ireland and may have been imported from India on several occasions.
    • Functional surgery of the temporomandibular joint with conscious sedation for "closed lock" using eminectomy as a treatment: a case series.

      Stassen, Leo F; O'Halloran, Michael; Dublin Dental School and Hospital, Lincoln Place, Dublin 2, Ireland. (2011-06)
      The purpose of this case series study was to evaluate the advantages and disadvantages of using local anesthesia and conscious sedation (CS) rather than general anesthesia (GA) for performing functional surgery on patients suffering from temporomandibular joint (TMJ) closed lock, using the eminectomy procedure. Performing this procedure using CS allows functional assessment of the TMJ meniscus at the time of surgery. The objectives of this study were to determine if this surgery is possible under CS, to determine the benefits of being able to see the meniscus in action, and to investigate the patients' acceptability for this form of anesthesia.
    • Genetic associations of 115 polymorphisms with cancers of the upper aerodigestive tract across 10 European countries: the ARCAGE project.

      Canova, Cristina; Hashibe, Mia; Simonato, Lorenzo; Nelis, Mari; Metspalu, Andres; Lagiou, Pagona; Trichopoulos, Dimitrios; Ahrens, Wolfgang; Pigeot, Iris; Merletti, Franco; et al. (2009-04-01)
      Cancers of the upper aerodigestive tract (UADT) include malignant tumors of the oral cavity, pharynx, larynx, and esophagus and account for 6.4% of all new cancers in Europe. In the context of a multicenter case-control study conducted in 14 centers within 10 European countries and comprising 1,511 cases and 1,457 controls (ARCAGE study), 115 single nucleotide polymorphisms (SNP) from 62 a priori-selected genes were studied in relation to UADT cancer. We found 11 SNPs that were statistically associated with UADT cancers overall (5.75 expected). Considering the possibility of false-positive results, we focused on SNPs in CYP2A6, MDM2, tumor necrosis factor (TNF), and gene amplified in squamous cell carcinoma 1 (GASC1), for which low P values for trend (P trend<0.01) were observed in the main effects analyses of UADT cancer overall or by subsite. The rare variant of CYP2A6 -47A>C (rs28399433), a phase I metabolism gene, was associated with reduced UADT cancer risk (P trend=0.01). Three SNPs in the MDM2 gene, involved in cell cycle control, were associated with UADT cancer. MDM2 IVS5+1285A>G (rs3730536) showed a strong codominant effect (P trend=0.007). The rare variants of two SNPs in the TNF gene were associated with a decreased risk; for TNF IVS1+123G>A (rs1800610), the P trend was 0.007. Variants in two SNPs of GASC1 were found to be strongly associated with increased UADT cancer risk (for both, P trend=0.008). This study is the largest genetic epidemiologic study on UADT cancers in Europe. Our analysis points to potentially relevant genes in various pathways.
    • Genioglossus fatigue in obstructive sleep apnea.

      McSharry, David; O'Connor, Ciara; McNicholas, Triona; Langran, Simon; O'Sullivan, Michael; Lowery, Madeleine; McNicholas, Walter T; Sleep Research Laboratory, St. Vincent's University Hospital, Dublin, Ireland. dmcsharry@partners.org (2012-08-15)
      Obstructive sleep apnea (OSA) is a prevalent disorder that may cause cardiovascular disease and fatal traffic accidents but the pathophysiology remains incompletely understood. Increased fatigability of the genioglossus (the principal upper airway dilator muscle) might be important in OSA pathophysiology but the existing literature is uncertain. We hypothesized that the genioglossus in OSA subjects would fatigue more than in controls. In 9 OSA subjects and 9 controls during wakefulness we measured maximum voluntary tongue protrusion force (Tpmax). Using surface electromyography arrays we measured the rate of decline in muscle fiber conduction velocity (MFCV) during an isometric fatiguing contraction at 30% Tpmax. The rate of decline in MFCV provides an objective means of quantifying localized muscle fatigue. Linear regression analysis of individual subject data demonstrated a significantly greater decrease in MFCV in OSA subjects compared to control subjects (29.2 ± 20.8% [mean ± SD] versus 11.2 ± 20.8%; p=0.04). These data support increased fatigability of the genioglossus muscle in OSA subjects which may be important in the pathophysiology of OSA.
    • A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium.

      McKay, James D; Truong, Therese; Gaborieau, Valerie; Chabrier, Amelie; Chuang, Shu-Chun; Byrnes, Graham; Zaridze, David; Shangina, Oxana; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; et al. (2011-03)
      Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p ≤ 5 × 10⁻⁷). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10⁻⁸) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p =2 × 10⁻⁸) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 × 10⁻⁸); rs1229984-ADH1B, p = 7 × 10⁻⁹; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.
    • Life course social mobility and risk of upper aerodigestive tract cancer in men.

      Schmeisser, N; Conway, D I; McKinney, P A; McMahon, A D; Pohlabeln, H; Marron, M; Benhamou, S; Bouchardy, C; Macfarlane, G J; Macfarlane, T V; et al. (2010-03)
      The aim of this study was to explore associations between social mobility and tumours of the upper aero-digestive tract (UADT), focussing on life-course transitions in social prestige (SP) based on occupational history. 1,796 cases diagnosed between 1993 and 2005 in ten European countries were compared with 1585 controls. SP was classified by the Standard International Occupational Prestige Scale (SIOPS) based on job histories. SIOPS was categorised in high (H), medium (M) and low (L). Time weighted average achieved and transitions between SP with nine trajectories: H --> H, H --> M, H --> L, M --> H, M --> M, M --> L, L --> H, L --> M and L --> L were analysed. Odds ratios (ORs) and 95%-confidence intervals [95%-CIs] were estimated with logistic regression models including age, consumption of fruits/vegetables, study centre, smoking and alcohol consumption. The adjusted OR for the lowest versus the highest of three categories (time weighted average of SP) was 1.28 [1.04-1.56]. The distance of SP widened between cases and controls during working life. The downward trajectory H --> L gave an OR of 1.71 [0.75-3.87] as compared to H --> H. Subjects with M --> M and L --> L trajectories ORs were also elevated relative to subjects with H --> H trajectories. The association between SP and UADT is not fully explained by confounding factors. Downward social trajectory during the life course may be an independent risk factor for UADT cancers.
    • Longitudinal genotyping of Candida dubliniensis isolates reveals strain maintenance, microevolution, and the emergence of itraconazole resistance.

      Fleischhacker, M; Pasligh, J; Moran, G; Ruhnke, M; Charitè-Universitätsmedizin Berlin Medizinische Klinik m.S. Onkologie u. Hämatologie, Mol. Biol. Labor, Alte Apotheke, CCM, Charitèplatz 1, 10117 Berlin, Germany. michael.fleischhacker@charite.de (2010-05)
      We investigated the population structure of 208 Candida dubliniensis isolates obtained from 29 patients (25 human immunodeficiency virus [HIV] positive and 4 HIV negative) as part of a longitudinal study. The isolates were identified as C. dubliniensis by arbitrarily primed PCR (AP-PCR) and then genotyped using the Cd25 probe specific for C. dubliniensis. The majority of the isolates (55 of 58) were unique to individual patients, and more than one genotype was recovered from 15 of 29 patients. A total of 21 HIV-positive patients were sampled on more than one occasion (2 to 36 times). Sequential isolates recovered from these patients were all closely related, as demonstrated by hybridization with Cd25 and genotyping by PCR. Six patients were colonized by the same genotype of C. dubliniensis on repeated sampling, while strains exhibiting altered genotypes were recovered from 15 of 21 patients. The majority of these isolates demonstrated minor genetic alterations, i.e., microevolution, while one patient acquired an unrelated strain. The C. dubliniensis strains could not be separated into genetically distinct groups based on patient viral load, CD4 cell count, or oropharyngeal candidosis. However, C. dubliniensis isolates obtained from HIV-positive patients were more closely related than those recovered from HIV-negative patients. Approximately 8% (16 of 194) of isolates exhibited itraconazole resistance. Cross-resistance to fluconazole was only observed in one of these patients. Two patients harboring itraconazole-resistant isolates had not received any previous azole therapy. In conclusion, longitudinal genotyping of C. dubliniensis isolates from HIV-infected patients reveals that isolates from the same patient are generally closely related and may undergo microevolution. In addition, isolates may acquire itraconazole resistance, even in the absence of prior azole therapy.
    • Looking in the mouth for Crohn's disease.

      Rowland, Marion; Fleming, Paddy; Bourke, Billy; UCD School of Medicine & Medical Science, Crumlin, Dublin, Ireland. (2010-02)
      It is widely acknowledged among gastroenterologists that the oral cavity may be involved in Crohn's disease (CD). However, the specific manifestations are poorly appreciated. Although oral aphthous ulceration is probably not diagnostically useful in patients with suspected CD, disease-specific manifestations do occur and are particularly common in children presenting with CD. These manifestations can be subtle, often are subclinical, yet commonly harbor diagnostically useful material (granulomas). Orofacial granulomatosis (OFG) is conventionally used to describe patients with overt oral disease without obvious involvement of the gastrointestinal tract. However, many patients with OFG have subclinical intestinal CD or will progress to develop overt intestinal CD with time. The management of severe oral disease is challenging and lacks a clear evidence base.
    • Maxillary anterior tooth dimensions and proportions in an Irish young adult population.

      Condon, M; Bready, M; Quinn, F; O'Connell, B C; Houston, F J; O'Sullivan, M; Division of Restorative Dentistry and Periodontology, Dublin Dental School and Hospital, Trinity College, Dublin, Ireland. (2011-07)
      This study was undertaken in a young Irish population to determine the dimensions and ratios of the six maxillary anterior teeth. One hundred and nine Irish subjects (age 18-25 inclusive) had irreversible hydrocolloid impressions made of their maxillary dentition poured in type V stone. Clinical crown dimensions were measured with a digital calliper. The stone casts were digitally photographed in a standardised manner enabling calculation of various ratios between the maxillary anterior teeth. Sexual dimorphism existed for various tooth dimensions; most notably canine teeth were in the region of 0·8 mm longer and 0·6 mm wider in males. Central and lateral incisors were found to be 0·5 mm wider in males. It is, therefore, recommended that dimensional tooth guidelines should be given for each of the sexes and not on a population basis. With regard to tooth proportion ratios, no significant differences were found between genders or the left and right sides for any of the measurements or ratios measured. The digitally recorded tooth proportions were similar for both sexes, and the Golden Proportion guidelines could only be applied to the lateral incisor/central incisor widths (0·618). Identified width proportions for the canine/central incisor were 0·58 and for canine/lateral incisor 0·89.
    • Microbiological screening of Irish patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy reveals persistence of Candida albicans strains, gradual reduction in susceptibility to azoles, and incidences of clinical signs of oral candidiasis without culture evidence.

      McManus, Brenda A; McGovern, Eleanor; Moran, Gary P; Healy, Claire M; Nunn, June; Fleming, Pádraig; Costigan, Colm; Sullivan, Derek J; Coleman, David C; Microbiology Research Unit, Division of Oral Biosciences, Dublin Dental University Hospital, University of Dublin, Trinity College Dublin, Dublin 2, Republic of Ireland. (2011-05)
      Patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) are prone to chronic mucocutaneous candidiasis, which is often treated with azoles. The purpose of this study was to characterize the oral Candida populations from 16 Irish APECED patients, who comprise approximately half the total number identified in Ireland, and to examine the effect of intermittent antifungal therapy on the azole susceptibility patterns of Candida isolates. Patients attended between one and four clinical evaluations over a 5-year period, providing oral rinses and/or oral swab samples each time. Candida was recovered from 14/16 patients, and Candida albicans was the only Candida species identified. Interestingly, clinical diagnosis of candidiasis did not correlate with microbiological evidence of Candida infection at 7/22 (32%) clinical assessments. Multilocus sequence typing analysis of C. albicans isolates recovered from the same patients on separate occasions identified the same sequence type each time. Fluconazole resistance was detected in isolates from one patient, and isolates exhibiting a progressive reduction in itraconazole and/or fluconazole susceptibility were identified in a further 3/16 patients, in each case correlating with the upregulation of CDR- and MDR-encoded efflux pumps. Mutations were also identified in the ERG11 and the TAC1 genes of isolates from these four patients; some of these mutations have previously been associated with azole resistance. The findings suggest that alternative Candida treatment options, other than azoles such as chlorhexidine, should be considered in APECED patients and that clinical diagnosis of oral candidiasis should be confirmed by culture prior to the commencement of anti-Candida therapy.
    • Microbiological screening of Irish patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy reveals persistence of Candida albicans strains, gradual reduction in susceptibility to azoles, and incidences of clinical signs of oral candidiasis without culture evidence.

      McManus, Brenda A; McGovern, Eleanor; Moran, Gary P; Healy, Claire M; Nunn, June; Fleming, Pádraig; Costigan, Colm; Sullivan, Derek J; Coleman, David C; Microbiology Research Unit, Division of Oral Biosciences, Dublin Dental University Hospital, University of Dublin, Trinity College Dublin, Dublin 2, Republic of Ireland. (2011-05)
      Patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) are prone to chronic mucocutaneous candidiasis, which is often treated with azoles. The purpose of this study was to characterize the oral Candida populations from 16 Irish APECED patients, who comprise approximately half the total number identified in Ireland, and to examine the effect of intermittent antifungal therapy on the azole susceptibility patterns of Candida isolates. Patients attended between one and four clinical evaluations over a 5-year period, providing oral rinses and/or oral swab samples each time. Candida was recovered from 14/16 patients, and Candida albicans was the only Candida species identified. Interestingly, clinical diagnosis of candidiasis did not correlate with microbiological evidence of Candida infection at 7/22 (32%) clinical assessments. Multilocus sequence typing analysis of C. albicans isolates recovered from the same patients on separate occasions identified the same sequence type each time. Fluconazole resistance was detected in isolates from one patient, and isolates exhibiting a progressive reduction in itraconazole and/or fluconazole susceptibility were identified in a further 3/16 patients, in each case correlating with the upregulation of CDR- and MDR-encoded efflux pumps. Mutations were also identified in the ERG11 and the TAC1 genes of isolates from these four patients; some of these mutations have previously been associated with azole resistance. The findings suggest that alternative Candida treatment options, other than azoles such as chlorhexidine, should be considered in APECED patients and that clinical diagnosis of oral candidiasis should be confirmed by culture prior to the commencement of anti-Candida therapy.