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Treatment for oral candidiasis in warfarin users may be complicated by drug-drug interactions (DDIs) between warfarin and topically applied antimycotics. However, current knowledge of these putative DDIs is merely based on case series. We therefore performed a cohort cross-over study with the objective to evaluate the potential DDIs between warfarin and miconazole oral gel or nystatin oral solution. The cohort consisted of individuals using warfarin in the period of 1998-2012 (n ≈ 7400). We collected data on cohort members' measurements of the international normalized ratio (INR) from a clinical database, and obtained information on their use of topically applied miconazole and nystatin from a regional prescription register. Potential DDIs were assessed by comparing INR values before and after initiation of an antimycotic drug. Among 17 warfarin users exposed to miconazole oral gel, the mean INR increased from 2.5 (95% CI: 2.1-2.8) to 3.8 (95% CI: 2.8-4.8) after exposure, corresponding to a mean INR increase of 1.4 (95% CI: 0.3-2.4). Among 30 warfarin users exposed to nystatin oral solution, the mean INR was 2.7 (95% CI: 2.3-3.1) before and 2.5 (95% CI: 2.2-2.9) after exposure. In conclusion, we found evidence supporting a clinically relevant drug-drug interaction between warfarin and miconazole oral gel. In contrast, we did not find any indication of an interaction between warfarin and nystatin oral solution. Nystatin rather than miconazole should be preferred when treating warfarin users for oral candidiasis., (© 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Purpose: Systemic immune activation has been recently linked to chronic inflammatory disorders of the oral cavity, particularly to periodontitis. The purpose of this study was to determine whether treatment of a fungus-induced oral inflammation, namely denture-related stomatitis (DRS), can affect the activation of the systemic immune response., Materials and Methods: Peripheral blood from patients with denture-related stomatitis caused by Candida albicans infection (n = 15) was collected at three time points: before treatment with nystatin, at the end of therapy and 2 months after finishing therapy. Activation of T cells and monocytes was assessed by flow cytometry., Results: The percentages of peripheral lymphocytes, T cells and their subpopulations, as well as monocytes were similar before, immediately following and two months after nystatin treatment. Cells expressing early activation marker CD69 and RANTES C-C chemokine receptor type 5 significantly increased immediately after treatment and returned to baseline levels after two months. Th17 cells, which have been implicated in the pathogenesis of DRS, remained unchanged. Central memory CD4+ subset and intermediate subset of monocytes were lower after therapy and this effect was sustained for two months., Conclusion: Treatment of denture-related stomatitis does not seem to affect the general state of the cellular components of the immune system. The results suggest a potential proinflammatory effect of the antifungal agent, nystatin. Although transient and not intense, this effect might be of particular clinical importance, because of relationships between inflammation and certain diseases. Further studies are required to clarify this aspect.

Background: Because of the inherent immunosuppression of cancer patients opportunistic infections by Candida spp, occur frequently. This study aimed to identify Candida species in the oral mucosa of 59 patients with orogastric cancer (OGC) and to analyze the immunological phenotype of these patients., Methods: The yeasts were identified by MALDI-TOF mass spectrometry (MS). For all isolates, we performed phospholipases and proteinases assays, in vitro adherence to buccal epithelial cells (BEC), minimum inhibitory concentration of antifungal drugs and determined the cytokine profile by Cytometric Bead Array flow citometry assay., Results: C. albicans was the most prevalent species in OGC patients (51.6 %) and control group (66.7 %). Candida spp. strains isolated from OGC patients exhibited better adherence to BEC (p = 0.05) than did the control group. Phospholipases production by Candida strains from OGC patients was lower (51.6 %) than in the control group (61.9 %). Proteinases were detected in 41.9 % and 4.8 % of the yeasts from OGC patients and control group, respectively. Significant differences were found in the serum of OGC patients compared to the control group for IL-2, IL-10, TNF-α, IFN-γ and IL-17., Conclusions: The results of this work suggest increased virulence of yeasts isolated from OGC patients and, that this may interfere with the immune phenotype.

The genus Candida is both the commensal microbe and the opportunistic pathogen, containing approximately 200 species inhabiting in oral cavity of 53 % of the general population. Candida species can cause the diseases from local mucosal infections to systemic mycoses, even life-threatening infections in immunocompromised individuals. The timely differentiation of Candida species is important for the guidance of clinical medication. Four common Candida species in Chinese population (Candida albicans, Candida tropicalis, Candida glabrata, Candida krusei) were chosen as the targets to develop the rapid screening method in this work. Combined with amplification by asymmetric PCR, this parallel fluorescence polarization (FP) immunoassay is carried out in homogeneous solution phase. The limit of detection of the assay was shown to be 50 copies/mL in blood samples. The evaluation in multicenter manner showed excellent reproducibility and stability. The comparison between DNA sequencing and the FP immunoassay indicated that there was no significant difference between these methods. This molecular strategy-based method is simple, rapid, and feasible for identifying common Candida species and thereby holding great potential in the application of clinical laboratories.

Background: Candidia esophagitis (CE) is an AIDS-defining condition, usually occurring in individuals with low CD4 counts of <200 cells/µL. Endoscopy is a valuable definitive diagnostic method for CE but may not be indicated for asymptomatic patients or for those with high CD4 counts or without oral candidiasis. This study assessed such patients to clarify the factors associated with CE and its severity on endoscopy in the highly active antiretroviral therapy (HAART) era., Methodology Principal Findings: A total of 733 HIV-infected patients who underwent upper gastrointestinal (GI) endoscopy were analyzed. Sexual behavior, CD4(+) count, HIV-RNA viral load (VL), history of HAART, GI symptoms, GI diseases, and oral candidiasis were assessed. Endoscopic severity of CE was classified as mild (Kodsi's grade I/II) or severe (grade III/IV). Of the 733 subjects, 62 (8.46%) were diagnosed with CE (mild, n = 33; severe, n = 29). Of them, 56.5% (35/62) had no GI symptoms, 30.6% (19/62) had CD4 + ≥200 cells/μL, and 55.3% (21/38) had no oral candidiasis. Univariate analysis found lower CD4+ counts, higher HIV VL, and no history of HAART to be significantly associated with CE. With lower CD4(+) counts and higher HIV VL, CE occurrence increased significantly (P<0.01 for trend in odds). Multivariate analysis showed low CD4+ counts and high HIV VL to be independently associated with CE. Of the severe CE patients, 55.2% (16/29) had no GI symptoms and 44.4% (8/18) had no oral candidiasis. Median CD4(+) counts in severe cases were significantly lower than in mild cases (27 vs. 80; P = 0.04)., Conclusions: Low CD4+ counts and high HIV VL were found to be factors associated with CE, and advanced immunosuppression was associated with the development of severity. Endoscopy is useful as it can detect CE, even severe CE, in patients without GI symptoms, those with high CD4 counts, and those without oral candidiasis.

Vitamin D has a potential role in preventing HIV-related complications, based on its extensive involvement in immune and metabolic function, including preventing osteoporosis and premature cardiovascular disease. However, this association has not been examined in large studies or in resource-limited settings. Vitamin D levels were assessed in 884 HIV-infected pregnant women at enrollment in a trial of multivitamin supplementation (excluding vitamin D) in Tanzania. Information on HIV related complications was recorded during follow-up (median, 70 months). Proportional hazards models and generalized estimating equations were used to assess the relationship of vitamin D status with these outcomes. Women with low vitamin D status (serum 25-hydroxyvitamin D<32 ng/mL) had 43% higher risk of reaching a body mass index (BMI) less than 18 kg/m(2) during the first 2 years of follow-up, compared to women with adequate vitamin D levels (hazard ratio [HR]: 1.43; 95% confidence intervals: [1.03-1.99]). The relationship between continuous vitamin D levels and risk of BMI less than 18 kg/m(2) during follow-up was inverse and linear (p=0.03). Women with low vitamin D levels had significantly higher incidence of acute upper respiratory infections (HR: 1.27 [1.04-1.54]) and thrush (HR: 2.74 [1.29-5.83]) diagnosed during the first 2 years of follow-up. Low vitamin D status was a significant risk factor for wasting and HIV-related complications such as thrush during follow-up in this prospective cohort in Tanzania. If these protective associations are confirmed in randomized trials, vitamin D supplementation could represent a simple and inexpensive method to improve health and quality of life of HIV-infected patients, particularly in resource-limited settings.

Human Immunodeficiency Virus (HIV)-related oral lesions can be used as markers of the immune status. The present cross-sectional study was conducted to identify the oral manifestations in HIV-infected individuals and their association with reduced Cluster of Differentiation 4 (CD4) count. The study population included known HIV-positive patients. A detailed case history of 399 HIV-positive patients was obtained and general examination was carried out. Diagnosis of oral lesions was done based on presumptive criteria of EEC Clearinghouse, 1993. The CD4 count was determined in 369 patients and correlated with oral manifestations. The prevalence of oral lesions was found to be 76.70% (n = 306). Oral candidiasis (157 (39.3%)) was the most common oral lesion associated with HIV infection. Amongst various forms of oral candidiasis, erythematous candidiasis (122 (39.3%)) outnumbered the other forms. The mean CD4 count of patients with oral lesions (207 cells/mm(3)) was less than in patients without oral lesions (291 cells/mm(3)) (P = 0.002). Oral candidiasis was found to be significantly correlated to a reduced CD4 cell count below 200 cells/mm(3) (P = 0.000; Odds ratio = 3.1; 95% Confidence interval 1.9-4.9) with good sensitivity, best specificity and positive predictive value. Oral manifestations may be used as an alternative to CD4 count at field-based settings to diagnose the immune compromised status of HIV-infected individuals.

In vivo expression of the developmentally regulated Candida albicans hyphal wall protein 1 (HWP1) gene was analysed in human subjects who were culture positive for C. albicans and had oral symptoms (n=40) or were asymptomatic (n=29), or had vaginal symptoms (n=40) or were asymptomatic (n=29). HWP1 mRNA was present regardless of symptoms, implicating hyphal and possibly pseudohyphal forms in mucosal carriage as well as disease. As expected, in control subjects without oral symptoms (n=10) and without vaginal symptoms (n=10) who were culture negative in oral and vaginal samples, HWP1 mRNA was not detected. However, exposure to Hwp1 in healthy culture-negative controls, as well as in oral candidiasis and asymptomatic mucosal infections, was shown by the existence of local salivary and systemic adaptive antibody responses to Hwp1. The results are consistent with a role for Hwp1 in gastrointestinal colonization as well as in mucosal symptomatic and asymptomatic infections. Overall, Hwp1 and hyphal growth forms appear to be important factors in benign and invasive interactions of C. albicans with human hosts.

It has been reported that poor glycaemic control predisposes to oral candidal infection in diabetic patients. For instance, the carriage of Candida species and the density of candidal growth in the oral cavity is frequently claimed to be increased in patients with diabetes mellitus. However, the validity of these observations remains controversial. Hence, we review and discuss here the clinical data in the literature on the relationship between diabetes and oral candidal carriage and infection, and possible mechanisms associated with its pathogenicity.

Therapeutic activity against oral candidiasis of orally administered bovine lactoferrin (LF), a multifunctional milk protein, was shown in a previous report using an immunosuppressed murine model. In the present study, the influence of orally administered LF on immune responses relevant to this therapeutic effect was examined. Because mice were immunosuppressed with prednisolone 1 day before and 3 days after the infection with Candida, the numbers of peripheral blood leukocytes (PBL) and cervical lymph node (CLN) cells were reduced. LF feeding prevented the reduction in the numbers of PBL on day 1 and CLN cells on days 1, 5 and 6 in the Candida-infected mice. The number of CLN cells of individual mice on days 5 and 6 was inversely correlated with the Candida c.f.u. in the oral cavity. Increased production of IFN-gamma and TNF-alpha by CLN cells stimulated with heat-killed Candida albicans on day 6 was observed in LF-treated mice compared with non-treated mice. Concanavalin A (ConA)-stimulated CLN cells from LF-treated mice also showed a significant increase in the production of IFN-gamma and IL12 on day 5 and a tendency for increased production of IFN-gamma and TNF-alpha on day 6. The levels of cytokine production by ConA-stimulated CLN cells on day 6 were inversely correlated with the Candida c.f.u. in the oral cavity. In conclusion, the alleviation of oral candidiasis by LF feeding in this model may correlate with the enhancement of the number of leukocytes and their cytokine responses in regional lymph nodes against Candida infection.

The prevalence of Candida species with and without denture-related stomatitis were evaluated in 167 Jordanian patients. The study revealed that 47 (28%) of the patients with denture-related stomatitis were colonized with Candida species (clinical group). Candida albicans was responsible for most cases of denture-related stomatitis (72%), and it was the only species capable of secreting aspartic proteinases. The study also indicated that candidal colonization was not influenced by predisposing haematological deficiencies, as both the clinical and control patient groups showed comparable haematological parameters and the differences were not significant (P > 0.05). All Candida species isolates were 100% susceptible to amphotericin B, while these isolates were less susceptible (25-75%) to fluconazole.

Chronic hyperplastic candidosis/candidiasis (CHC; syn. candidal leukoplakia) is a variant of oral candidosis that typically presents as a white patch on the commissures of the oral mucosa. The major etiologic agent of the disease is the oral fungal pathogen Candida predominantly belonging to Candida albicans, although other systemic co-factors, such as vitamin deficiency and generalized immune suppression, may play a contributory role. Clinically, the lesions are symptomless and regress after appropriate antifungal therapy and correction of underlying nutritional or other deficiencies. If the lesions are untreated, a minor proportion may demonstrate dysplasia and develop into carcinomas. This review outlines the demographic features, etiopathogenesis, immunological features, histopathology, and the role of Candida in the disease process. In the final part of the review, newer molecular biological aspects of the disease are considered together with the management protocols that are currently available, and directions for future research.

Buccal and digestive tract opportunistic infections occur frequently in patients infected by HIV. In this study, we measured lysozyme (Lz), lactoferrin (Lf), total IgA (T-IgA), and secretory IgA (S-IgA) levels to investigate nonspecific secretory immunity in HIV-infected patients with oral candidiasis. Serum, saliva, and stool samples were analyzed by time-resolved immunofluorometric assay for Lz and Lf levels and by enzyme-linked immunosorbent assay for T-IgA and S-IgA levels. Mean salivary Lf and T-IgA levels (66.50 mg/L and 0.10 g/L, respectively) and mean fecal Lf, T-IgA, and S-IgA outputs (0.87, 54.0, and 43.6 mg/d, respectively) were significantly higher in HIV-infected patients with oropharyngeal candidiasis than in HIV-infected patients without oropharyngeal candidiasis and healthy subjects. There was a modification in the molecular form rate, with a high increase in S-IgA and monomeric IgA transudation from the plasmatic compartment into salivary and digestive fluids and an increase in salivary Lf local synthesis by polymorphonuclear neutrophils. HIV infection appears to be associated with dysregulation of some of the nonspecific immune factors at the mucosal surface. Despite high saliva concentrations and high intestinal output, innate immunity was not able to stop yeast expansion in HIV-infected patients.

Objective: To identify prognostic factors for the clinical effectiveness of fluconazole in HIV-1-infected patients with oropharyngeal candidiasis., Design and Setting: The study was designed as a prospective, open label, non-comparative, dose escalating, single centre trial., Patients and Methods: Thirty-four HIV-1-infected patients with oropharyngeal Candida infection were treated with 50 or 100mg fluconazoleday(-1), depending on the clinical manifestation (erythematous or pseudomembranous). The dose was doubled weekly until clinical cure. The predictive value of potential prognostic factors for the duration of treatment and cumulative fluconazole dose until cure was studied: exposure to fluconazole, previous use of fluconazole, the use of antiretroviral drugs, the CD4(+) cell count, erythematous or pseudomembranous appearance, the minimum inhibitory concentration (MIC) for fluconazole of the isolated Candida strain, and xerostomia., Results: Twenty-eight patients (with 30 episodes of oropharyngeal candidiasis) were evaluated. Twenty-five episodes were cured within 1-week of treatment, the remaining five episodes were cured within 2 weeks. No predictive value for any of the studied factors on the duration of fluconazole treatment or the cumulative fluconazole dose until cure was demonstrated., Conclusion: Because of the high susceptibility to fluconazole and the positive clinical outcome, the variation in outcome measurements was too modest to establish a significant relationship between any of the investigated potentially prognostic factors and the cumulative fluconazole dose and the duration of treatment to reach cure. On the other hand it can be concluded, that fluconazole is very effective in patients with advanced HIV infection and low CD4(+) cell counts, even if they are not using antiretroviral agents.

Serum immunoglobulin G (IgG) and IgA, and salivary IgA antibodies to a mycobacterial stress protein (mSP65) were determined in human immunodeficiency virus (HIV)-positive patients, acquired immunodeficiency syndrome (AIDS) patients and HIV-negative controls with or without oral candidiasis. Serum IgG antibodies were elevated in patients with HIV infection and AIDS and especially in subjects with candidiasis compared with controls (P < 0.02, P < 0.005). This was not apparent with serum IgA. In the absence of candidiasis, salivary IgA antibodies were elevated in HIV-positive patients compared with AIDS (P < 0.005) patients and healthy controls (P = 0.001). The relative avidity of serum IgG antibodies to mSP65 in controls with candidiasis was lower than healthy controls (P < 0.0001). In saliva there was a decrease in the relative avidity of IgA antibodies in AIDS patients with candidiasis compared with HIV patients (P < 0.03). In patients without candidiasis, the relative avidity was higher in HIV patients than healthy controls (P = 0.02). The results suggest that HIV infection leads to raised serum and salivary antibodies to heat shock proteins. Concurrent Candida infection may modify both the titer and relative avidity differently for serum and saliva.

Candida is a common opportunistic pathogen in HIV infection and is regarded a signal infection for progression to AIDS. Cytokine imbalances between Th1/Th2 groups have been described in both candida and HIV infections. A study was undertaken to assess the role of candida in furthering immunosuppression in HIV infection based on cytokine levels and CD4 cell counts. 30 Indian subjects were enrolled; 10 HIV positive patients with and 10 without mucosal candidiasis and 10 age matched controls. Th1 cytokines; interleukin (IL) 2, IL 12 and interferon (IFN) gamma, Th2 cytokines; IL 4, IL 6, IL 10 and tumor necrosis factor (TNF) alpha with CD 4 cell counts were estimated using ELISA in all subjects. CD4 cell counts were reduced in both patient groups as compared to controls; significantly more in patients with both HIV and candida infections. There was a decrease in Th1 cytokine levels in all patients; lower levels of Th1 cytokines were seen in patients with both infections. Among the Th2 cytokines, there was a significant increase in the levels of IL 6, IL 10 and TNF alpha in both patient groups; IL 10 and TNF alpha values were significantly raised in patients with dual HIV and candida infections as compared to the other patients. There was no difference in IL 4 values across the subject groups. A positive correlation between CD4 cell counts and Th1 cytokine levels and a negative correlation with Th2 cytokines were noted; these were stronger in patients with both HIV and candidiasis. Thus, there was a Th1/Th2 cytokine imbalance with CD4 cell count reduction in all HIV infected patients, which was more pronounced in patients with both infections. It can be concluded that, owing to the depressed CD4 cell count and Th1 response and increased Th2 cytokines in patients with both candidiasis and HIV as compared to patients with only HIV candidiasis may have a synergistic immunosuppressive effect with HIV in patients with dual infections.

Objective: The measurement of HIV viral load as a predictor of disease progression has revolutionized the medical management of HIV patients. In this study, oral diseases as measured by DMFT (decayed, missing and filled teeth), periodontal assessment and oral Candidacolonization, were related to HIV viral load. Also correlated was HIV status assessments, including CD4+ count, a history of intravenous drug abuse (IVDA) and the use of protease inhibitor drugs., Materials and Methods: Oral and periodontal examination, dental radiographs, and tongue swab for fungal culture was accomplished over a 2-month period on 39 HIV positive patients attending the University of Maryland Dental School. Twenty-eight (71. 8%) of these patients had a history of IVDA. Viral load was measured by a quantitative RT-PCR., Results: Among the patients with high viral load (>10 000 copies ml-1), 92.3% were found to have a history of IVDA. Also, patients with high viral load demonstrated average CD4+ counts of 136 mm-3 while moderate viral load (400-10 000 copies ml-1) corresponded to average counts of 271 mm-3. Periodontal pocket depths (PPD) of >5 mm at a minimum of two oral sites were found in 76.9% of the patients with high viral load. Among the high viral load patients, 69.2% had DMFT >20, 69.2% were culture positive for Candida and 81.5% of patients on protease inhibitors demonstrated moderate or low viral loads., Conclusion: These data demonstrated that elevated viral load levels correlate well with oral disease prevalence in this predominantly IVDA population of HIV-infected dental patients.

Background: The pharynx is one of the open spaces where fungi can settle easily. The purpose of the investigation was to estimate an overall prevalence of fungal colonization and some parameters of humoral and cell immunity., Methods: The study consisted of 167 patients, from whom swabs of the posterior and lateral part of the pharynx were taken for mycological examinations, during which tests based on morphological and biochemical (zymogram, auxanogram) characteristics were used. In all cases, the leukocyte count, overall protein level, and protein individual fractions were determined. Also determined were the levels of IgA, IgM and IgG immunoglobulin in blood serum, and IgA immunoglobulin (S-IgA) in saliva. At the same time, blastic transformation test and rosette tests: E (ER) to determine lymphocytes T count, as well as EA (EAR) and EAC (EACR) to detect lymphocytes B, were performed., Results: Fungal infection was found in 2/3 of patients. Fungi were classified as belonging to six species of Candida, which are considered to be important etiological factors of mycoses; the most common fungus was Candida albicans (in 86 cases). All cases of candidosis showed a decreased count of lymphocytes T, with their function deficient, and most of them a low S-IgA level in saliva (over three times lower than the norm) and high mean values for sedimentation rate., Conclusions: In patients in our study the IgA level in serum remained within normal limits, yet the ratio fo this fraction to other immunoglobulins deviated from that in healthy individuals.

The aims of this study were to assess types and prevalence of HIV-related oral lesions and to correlate these lesions to the main laboratory parameters such as CD4+ cell count and plasma HIV-RNA. The study population consisted of 104 consecutive HIV+ patients living in Sicily (M=67, 64.4%; F=37, 35.6%; median age=35 years). CD4+ cell count and viral load were measured within 24 h of oral examination. Data were managed and analysed by Epi-Info 6.0. HIV-related oral lesions, as classified by the EC-Clearinghouse, were diagnosed in 35.6% of patients: these were of the Strongly Associated (SA) type in 22.1%, the Less Common Associated (LCA) type in 12.5%, and the Lesions Seen in HIV Infection (LS) type in 3.8%. CD4+ cell counts <200 x 10(6)/l were significantly associated only with SA lesions (P=0.03); median values of CD4+ cell count were also significantly correlated (P=0.02). Viral load, expressed both by median values of copies/ml (P=0.0001) and log10 copies/ml (P=0.0003), was significantly associated only with SA lesions. Treatment failure was significantly correlated to SA lesions (P=0.04). Besides the confirmed correlation with CD4 depletion, the strong association with a high level of viral load could make SA oral lesions a useful tool for identifying progression of HIV infection and could be of value in monitoring antiretroviral therapy.

The objective of this study was to determine the relationships between saliva protein concentrations, oral mucosal lesions, and systemic parameters in HIV positive patients and controls. Twenty-three control volunteers and 58 HIV-antibody positive patients received a complete oral examination and medical evaluation. In saliva and serum samples, protein concentrations were recorded by a nephelometric method. The systemic parameters assessed were CD4+ cell count, CDC stages and antiretroviral therapy. Oral mucosal lesion prevalence was higher among subjects with lower CD4+ counts. Considering the protein profile, correlations were recorded between saliva and serum protein concentration for IgA, haptoglobin and alpha1-proteinase inhibitor. Using assays of immune and non-immune saliva defence factors, we found that the evolution of cellular immuno-suppression during HIV infection was correlated to oral mucosal disease, showing a relationship between local and general systems.

Serum IFN-gamma levels were studied in adult patients with chronic oral candidosis, associated with Candida albicans infection. In the group of patients, mean serum IFN-gamma levels (2.74+/-465 pg ml(-1)) were significantly lower than in healthy individuals (9.80+/-1.68 pg ml(-1)). In analysis of the C. albicans strains isolated from lesions in the patients, their ability was estimated to secrete proteinases. Serum IFN-gamma levels failed to correlate with infections induced by proteinase-producing C. albicans. The results allowed us to conclude that Candida infection may be associated with an insufficient IFN-gamma response of the host, which seems to result in chronic conversion of candidosis. Proteolytic activity of C. albicans strains in vitro is not related to virulence of the strains.

Oral fluids are convenient alternatives to blood sampling for evaluating significant metabolic components. Two forms of oral fluids, oral mucosal transudates (OMT) and saliva, were collected and compared for content of soluble products of immune activation. The data confirm that OMT and saliva represent distinct body fluids. The concentrations, outputs, and analyte/protein ratios of beta-2-microglobulin (beta2M), soluble tumor necrosis factor alpha receptor II (sTNFalphaRII), and neopterin were measured. Both the OMT and the saliva of most of the individuals in the control healthy populations had measurable levels of all three activation markers. When the immune system is activated, as in human immunodeficiency virus (HIV) infection, the levels of beta2M and sTNFalphaRII are increased in both OMT and saliva compared to those in a healthy control population. OMT levels correlated better with levels in serum than did saliva and appear to reflect systemic immune activation in HIV infection. Because acquisition of oral fluids is noninvasive and easily repeatable, measurement of beta2M and/or sTNFalphaRII content in OMT could be useful in the assessment of disease activity in patients with HIV infection or chronic inflammatory diseases.

The present study involves the analysis of some saliva components (SC) and serum components in patients with oral candidosis topically treated with Ketoconazole 2% (K) or Nystatin 100,000 IU (N). Twenty-four male and female patients, age range 39-82 years, were included in the study. A double-blind study was undertaken in which the patients were divided into 2 treatment groups. These groups were compared with a control group (CG) of 16 healthy patients, both male and female, age-matched with the treated groups. The parameters evaluated were oral mucous membrane lesion index (MLI), CFU of Candida, saliva flow rate, protein-bound Fe (Fe-prot), Fe-prot binding capacity (Fe-prot cap), IgAs, peroxidase activity (PA), hypothiocyanite and thiocyanite. The values of Candida CFU and MLI were significantly reduced in patients treated with K and N. The pre-treatment values of SC as compared to the CG revealed a reduction in Fe-prot and Fe-prot cap. These parameters reach values similar to control towards the end of the treatment. The PA was significantly higher in candidosis patients and fell to control values with treatment. The other SC and serum components did not exhibit significant differences with the CG. Patients with oral candidosis treated locally exhibit not only an improvement in clinical manifestations but also a return to control values of altered SC.

The density of Candida colonization in mouthwash fluid of 59 HIV-seropositive patients and 21 controls was determined. No significant difference in colony-forming units was found. No correlation was found between the colonizing density of Candida albicans and the CD4 count among the patients. Twenty-seven of the HIV-seropositive patients were followed for almost 3 years. No difference was found between the number of Candida albicans colony-forming units at the first and second time of sampling. Vaccination with HIV IIIB GP 160 vaccine did not have any influence on the prevalence of Candida albicans.

The serum and saliva components of 36 chronic Candidosis patients, both male and female, ages 38-82 who attended the Department of Clinical Stomatology were studied. Total Mucous Lesion Index (TMLI) and salivary flow rate were assessed. The following parameters were evaluated: iron bound protein, unsaturated iron binding capacity, peroxidase activity, protein content, OSCN-, SCN-, IgAs, Candida and St. mutans levels and lactobacilli activity. Candidosis patients exhibited higher Candida CFU values and increased activity of the peroxidase system (p < 0.05) whereas unsaturated iron binding capacity was significantly lower as compared to healthy subjects (p < 0.05). Furthermore, TMLI and Candida CFU values were higher in diseased subjects wearing complete prosthesis as compared to those without complete prosthesis. Diseased subjects with < 1.2 ml/min salivary flow rate exhibited even greater differences with control. This subgroup exhibited a marked reduction in IgAs. The serum components assayed were iron bound protein, unsaturated iron binding capacity, IgG, IgA and IgM. Unsaturated iron binding capacity was significantly lower in the Candidosis group (p = 0.03). Subjects suffering from oral Candidosis display deficiencies in some of their saliva components, evidencing impaired oral defense capacity.

We present the case of a 47-year-old patient who was seen for recurrent opportunistic infections. Immunophenotypic analyses disclosed severe reduction of CD4+ T cells. Repeated Elisa, Western blot and polymerase chain reaction tests for HIV were negative. The low CD4+ T lymphocyte count unaccompanied by increased CD8+ T lymphocytes and hypergammaglobulinemia, along with negativity for HIV infection, suggested the diagnosis of idiopathic CD4+ lymphocytopenia (ICL). The patient's clinical manifestations and laboratory results conformed with the case definition of ICL established in 1992 by the Centers for Disease Control of Atlanta, i.e., CD4+ T cells < 300/mm3 on two occasions and no evidence of HIV infection. In vitro analyses evidenced depressed lymphoproliferative responses to mitogens such as concanavalin A and pokeweed mitogen, while the expression of Fas antigen on peripheral lymphocytes and the percentage of apoptotic cells after propidium iodide staining were increased. Since in vitro concanavalin A stimulation inhibits T cell proliferation and induces apoptosis, these results suggest that the patient's lymphocytes are susceptible, in vivo, to an apoptotic signal.

Although numerous studies of oral manifestations associated with HIV have been reported, only a few refer to the correlation of these lesions with laboratory parameters. In this study we investigated the relationships between the two most common HIV-associated oral lesions, oral candidiasis and hairy leukoplakia, with the stage of the disease, circulating CD4+ cell counts, and the presence of anti-p24 antibodies in serum and stimulated whole saliva in 43 known HIV-1-infected persons. Although oral candidiasis and hairy leukoplakia were exclusively observed in subjects who were classified as Centers for Disease Control and Prevention group IV, only the prevalence of oral candidiasis is strongly associated with circulating CD4+ counts less than 200/mm3 (p < 0.02). The prevalence of oral candidiasis and hairy leukoplakia was significantly related to the absence of anti-p24 antibodies in serum (p < 0.01 and p < 0.01, respectively), but was only statistically significant for hairy leukoplakia in stimulated whole saliva (p < 0.02). The results suggest that oral candidiasis and hairy leukoplakia in correlation with immunologic status as indicated by low circulating CD4+ cell counts and the absence of anti-p24 antibodies in serum and the loss of secretory anti-p24 antibodies in subjects with hairy leukoplakia, may constitute prognostic markers for the progression of HIV-infection to AIDS. Our results also indicate that the absence of anti-p24 antibodies is not only influenced by the low levels of circulating CD4+ cells but probably by the presence of oral candidiasis or hairy leukoplakia as well.

In an open phase-III study 103 HIV-positive patients with oral candidiasis were treated with oral fluconazole 100 mg/day for 7-21 days (mean 12.2 +/- 6.1 days). Ninety per cent of the patients presented with the full clinical picture of AIDS, in 83% CD4-lymphocytes were < 100/mm3. Clinical and mycological (smear and mouth rinsing) examinations were performed at the start of therapy, after weeks 1, 2, and 3, and at the end of therapy. The clinical findings showed fluconazole therapy to have achieved cure in 71% of the patients and improvement in 16%. Therapy failed in 13%. Mycological tests revealed elimination in 57% and reduction in colony counts in 23% of patients. Therapy failure according to mycological criteria was observed in 20% of all subjects. Adverse events were recorded for 26% of all patients. A causal connection with study therapy was considered as "unlikely" in 20 cases, "questionable" in 17 cases, and "likely" in three cases. Premature discontinuation of fluconazole therapy was required in seven patients, in three of them because of adverse events due to fluconazole. Even in patients with advanced HIV infection and consequently severe immunodeficiency, fluconazole is an important improvement of the therapeutic spectrum.

Objective: To develop a simple clinical staging system based on CD4 count and clinical variables that predicts progression to AIDS in HIV-infected non-AIDS patients., Design: Retrospective cohort study., Setting: A primary care outpatient clinic for HIV-infected patients at a VA Medical Center., Patients: One hundred seventy-six HIV-infected non-AIDS patients seen at the Houston VA Special Medicine Clinic between January 1986 and December 1990 and followed for a mean of 22 months. Fifty-four patients (31%) progressed to AIDS during follow-up., Measurements: The medical records were reviewed, and data corresponding to the initial (baseline) clinic visit and subsequent six-month visits were extracted., Main Results: "Predictive" baseline variables (i.e., those associated with progression to AIDS) were first identified and then examined in Cox proportional hazards modeling. In the final model, CD4 category, oral thrush, and night sweats made significant independent contributions. A three-stage prognostic system was constructed by assigning points to the three variables: CD4 > 500 cells/mm3 = 0; 500 > or = CD4 > or = 200 = 1; CD4 < 200 = 2; presence of oral thrush = 1; presence of night sweats = 1. Stages were assigned as follows: stage I = 0 points, stage II = 1-2 points, and stage III = 3-4 points. The proportions of patients who progressed to AIDS were: stage I, 6/39 (15%); stage II, 31/106 (29%); and stage III, 17/31 (55%)., Conclusions: These results demonstrate that simple, clinically sensible prognostic staging systems that predict progression to AIDS can be constructed using CD4 count and clinical variables.

This study correlates the prevalent oral disease findings in 390 patients seropositive for human immunodeficiency virus type 1 (HIV-1) with their level of staging (Walter Reed) and depletion of peripheral helper T lymphocytes (CD4+). Chronic lymphadenopathy of the head and neck was a common finding (59.2%) that occurred early in staging progression and did not correlate with depression of helper T-cell levels. Of the three prevalent oral disease findings (oral hairy leukoplakia (OHL), candidiasis, necrotizing ulcerative gingivitis [NUG]) only OHL and NUG were significantly correlated with helper T-cell depletion. The occurrence of visually detectable OHL and NUG corresponds to depletion of peripheral helper T-lymphocyte values in a range of 157 to 299 cells/mm3. This range may represent a more accurate value for biologically significant lymphocyte depletion than the Walter Reed value of 400 cells/mm3. The presence of OHL showed a weak statistical correlation with staging progression, indicating deteriorating immunoregulation. No cases of Kaposi's sarcoma or other HIV-1-associated oral diseases were observed in the sample population, regardless of the patient's staging category or peripheral helper T-lymphocyte count.

To determine the interrelation between ABO blood types of denture wearers, denture plaque accumulation, and denture stomatitis, 442 denture wearers were studied using a simplified culture method, which is convenient to use in the dental office. The degree of plaque accumulation and the occurrence of denture stomatitis varied depending on the blood type of the patients. Especially in blood group O compared with other types, both denture plaque accumulation and denture stomatitis were found to be higher or more severe. These results suggest that the ABO blood group is one of the etiologic factors of denture stomatitis and that denture wearers of blood group O are more susceptible to denture stomatitis.

Serum cytokine levels were examined in 18 oral squamous cell carcinoma (SCC), 26 lichen planus (OLP), 20 recurrent aphthous stomatitis (RAS), 8 herpetic gingivostomatitis (HGS), 16 pseudomembrane candidiasis (PMC) and 19 acute bacterial infection (ABI) cases. All SCC and most PMC patients possessed clear serum IL-3. No clear increase of IL-4 was observed in most cases though over 20 pg/ml were found in a few OLP, RAS and ABI. ABI exhibited the highest IL-6, and the cytokine level was lower in RAS, PMC, HGS and OLP in this order. Suppressed IL-6 activity was elevated with improvement of HGS lesion. TNF-alpha increased in 9 OLP, but the levels were below 100 pg/ml in all cases. Most SCC possessed higher GM-CSF activity than the controls. Increase of the cytokine corresponding with improvement of the oral lesion was seen in HGS, but not in OLP. From these results, each serum cytokine seems to reflect a characteristic pathophysiology of individual oral disorder.

A prospective study was undertaken of 22 patients with chronic hyperplastic candidosis and 50 age and sex matched individuals with no evidence of oral mucosal disease. Specifically the relationship between the inherited ability to secrete blood group antigens in saliva and chronic hyperplastic candidosis was investigated. The proportion of non-secretors of blood group antigens was significantly higher in patients with chronic hyperplastic candidosis (68%) compared to the control subjects (38%). The inability to secrete blood group antigens in saliva may therefore be a risk factor in the development of, or persistence of chronic hyperplastic candidosis.

The concentrations of nystatin excreted with faeces during and after oral application of 3 x 150,000 IU/d, either continuously for 14-21 days or every second day were determined in 42 newborns at risk by means of a bioassay (agar diffusion test). Results indicate that nystatin is distributed heterogeneously in the gastrointestinal tract. The excretion occurs discontinuously. 24 to 48 h after beginning of therapy there were effective concentrations of nystatin in the faeces. The daily application of 3 x 150,000 IU nystatin is recommended.

The natural cytotoxic activity of lymphocytes isolated from patients with oral candidosis during prosthetic stomatopathy was studied. The natural cytotoxic activity test was carried out in a group of 10 patients before treatment and immediately after effective antimycotic treatment. The material for the tests was venous blood of the patients sampled in volumes of 10-15 ml. The results of the test before and after the treatment were within normal range.

The number of immunocompromised patients has increased during recent years. Most fungal infections in these patients are caused by Candida, Aspergillus, Mucor, and Cryptococcus species. Patients with low granulocyte count are at the highest risk of invasive candidal infection. The commonest type of granulocytopenia is observed in connection with malignant diseases of the hematopoietic system. Cytotoxic treatment and radiotherapy of large-body areas tend to produce a significant decrease in circulating granulocytes. Early diagnosis and adequate treatment of fungal infections are mandatory for a successful outcome. In the oral cavity it is important to differentiate between colonization and invasive infection. The optimal approach to diagnosis is a combination of histology and cultivation of specimens obtained from the same site of suspected infection. Prophylaxis of oral fungal infection in immunocompromised patients is generally aimed at preventing colonization.

To estimate clinical, pathogenic and serological aspects of acute oral candidiasis (AOC) during febril episodes in patients with haematologic malignancies, 23 consecutive patients who developed AOC within 7 days from start of fever were compared with 23 consecutive patients who did not develop AOC. The duration of fever and severe granulocytopenia (less than 0.5 x 10(9)/l) was significantly longer in patients with AOC than in patients without AOC, the median differences between the patients with and without AOC being 4 and 3 days, respectively. Development of AOC could not be correlated to a change in the qualitative composition of the oral microflora. The thrombocyte count was lower in patients with AOC on day 4, whereas no differences were found in leukocyte counts. The prevalences of Candida albicans agglutinin titres greater than or equal to 5 were similar in patients with (24%) and without AOC (33%), and in controls (29%). Seroconversion or a significant increase in the agglutinin titre occurred in 4 patients with AOC and long-lasting fever, who became afebrile after systemic antifungal therapy. It is concluded that AOC is associated with long-lasting fever and decreased bone marrow function as judged by low thrombocyte counts, but not related to specific bacteria in the oral cavity or to an increased occurrence of C. albicans antibodies in the serum.

One of the innate defences against superficial infections by Candida species appears to be the ability of an individual to secrete the water-soluble form of his ABO blood group antigens into body fluids. There was a significantly higher number of non-secretors (48.9%) among 174 patients with either oral or vaginal candida infections compared with the proportion of non-secretors in the local population (26.6%). The protective effect afforded by the secretor gene might be due to the ability of glycocompounds in the body fluids of secretors to inhibit adhesins on the surface of the yeast. In attachment studies, preincubation of blastospores with boiled secretor saliva significantly reduced their ability to bind to epithelial cells. Non-secretor saliva did not reduce the binding and often enhanced the numbers of attached yeasts. Possible host-parasite interactions underlying the susceptibility of non-secretors to candida and other infections are discussed.

A series of 322 patients presenting with non-ulcerative conditions of the oral mucosa was examined for haematological abnormalities. The series was divided into 5 major groups--lichen planus (103 patients), candidiasis (50), leukoplakia (30), stomatitis or glossitis (66), and a miscellaneous group (73). The prevalence of anaemia, and deficiences in iron, folate and vitamin B12 in each group were compared with that found in 100 controls. The prevalence of anaemia in the series as a whole was not significantly increased, but the prevalences of sideropenia (14.0%), folate deficiency (4.7%) and vitamin B12 deficiency (3.1%) were increased as compared with controls. The prevalence of a haematological abnormality was increased in patients with lichen planus (18/103 p less than 0.05), stomatitis (15/66 p less than 0.01) and particularly in patients with Candidiasis (18/50 p less than 0.001). In the stomatitis group, approximately 45% of the male patients were found to have some haematological deficiency compared with less than 20% of the female patients. The increased prevalence of haematological deficiences suggests that patients presenting with non-ulcerative conditions of the oral mucosa (particularly candidiasis and non-specific stomatitis) should be screened haematologically and that, in some patients with candidiasis, haematological deficiencies may predispose towards candidal infection.

Factors associated with oral candidiasis in 51 diabetics were examined. The prevalence of oral yeast infection was 49 (n = 25)%. The association with diabetic control, as measured by fasting blood glucose concentration, urinary glucose concentration, and glycosylated haemoglobin, with the presence of yeast was analysed in the 51 diabetic patients. Glycosylated haemoglobin above 12% was strongly associated with oral yeast infection (odds ratio = 13.00) (p less than 0.001), while fasting blood and urinary glucose concentrations were not. The risk of oral candidiasis among diabetics wearing dentures was significantly higher than among dentate diabetics (odds ratio = 4.78). After controlling for the effect of denture wearing, glycosylated haemoglobin greater than 12% remained highly predictive of oral yeast infection, particularly among diabetics without dentures.

Antibody-dependent cellular cytotoxicity (ADCC) and lymphocyte-induced angiogenesis (LIA) of mononuclear leucocytes (MNC) isolated from the peripheral blood of patients with denture stomatitis mycotic were examined. The obtained results have shown a decrease in ADCC in patients with mycotic infection of oral cavity. Similarly, the ability to induce angiogenesis by MNC isolated from these patients was decreased in comparison with angiogenesis induced by control MNC. After the anti-mycotic treatment, an increase in ADCC and LIA was noted.