Association of asymptomatic oral candidal carriage, oral candidiasis and CD4 lymphocyte count in HIV-positive patients in China

OBJECTIVES: To compare the prevalence of asymptomatic oral candidal carriage in healthy volunteers with human immunodeficiency virus (HIV)-positive patients in China, as well as to investigate the relationship between CD4+ lymphocyte count and oral candidal colonization or oral candidiasis. METHODS: Oral candidal carriage and oral candidiasis were investigated in 101 patients with HIV-infection seen at Youan Hospital, Beijing, China. Two hundred and seventeen healthy volunteers were involved as a control. Culture from saliva was used to test for the presence of oral Candida. CD4+ lymphocyte count was measured by flow cytometry. All data were analyzed statistically by SAS. RESULTS: Asymptomatic oral candidal carriage rate (28.6%) in HIV-positive group was similar to that in the healthy group (18.0%; P = 0.07). No significant difference in CD4+ lymphocyte count was found between oral Candida carriers and non-carriers among HIV-positive subjects (P = 0.89). However, the frequency of oral candidiasis increased with the decrease in CD4+ lymphocyte count (P < 0.0001), and pseudomembranous candidiasis was predominant in HIV-positive patients with CD4+ <200 cells microl(-1) (66.7%). CONCLUSIONS: In HIV-positive subjects, asymptomatic oral candidal colonization is not related to CD4+ lymphocyte count of blood, and the carriage rate is similar to that in the healthy population. Oral candidiasis is more likely to be observed in HIV-positive patients who have a low CD4+ lymphocyte count.     

Oral colonization of Candida species in perinatally HIV-infected children in northern Thailand

Human immunodeficiency virus (HIV) infection remains a serious problem in northern Thailand. A high prevalence of perinatally HIV-infected children with oral candidiasis has been observed in the region. The objective of this study was to determine oral colonization of Candida spp. in children with perinatal HIV infection. Samples were collected by oral rinse or oral swab from 40 HIV-infected children and from 15 HIV-negative children as a control group. Yeasts recovered in culture were identified and quantified. The mean ages of HIV-infected children and HIV-negative children were 5.5 years (SD = 3.5) and 2.9 years (SD = 2.0) respectively. Eighteen HIV-infected children (45%) had clinical symptoms of oral candidiasis while none of the HIV-negative children had any such symptoms. By culture technique, yeasts were isolated from 28/40 (70%) of the HIV-infected children and 6/15 (40%) of the HIV-negative children. C. albicans was the most common species recovered from HIV-infected and HIV-negative children. Statistically, HIV infection was significantly associated with Candida spp. detection (P-value = 0.04). In contrast, the association between HIV infection and asymptomatic oral carriage of Candida spp. was not significant (P-value = 0.74). These findings demonstrate that oral colonization of Candida spp. is prevalent in HIV-infected children and suggest that prevention and treatment of oral candidiasis is needed for these children.     

Candidal carriage in the oral cavity of human immunodeficiency virus-infected subjects

OBJECTIVES. We sought to assess asymptomatic oral carriage of Candida species and relative density in human immunodeficiency virus-infected (HIV+) subjects, as well as to determine whether yeast carriage is associated with CD4+ cell count, HIV-1 RNA quantity, gender, route of HIV transmission, antiretroviral therapy, or smoking. STUDY DESIGN. A cross-sectional analysis of oral rinses from HIV+ and healthy subjects was undertaken. Oral candidal carriage and relative species were investigated in 42 HIV+ and 41 healthy individuals, all of whom were seen at the Palermo University Department of Oral Sciences, Italy. Data were managed and analyzed by means of the computer software package StatView 5.0.1. RESULTS. Carriage rate was 61.9% and 29.3% (P =.003) among HIV+ and healthy subjects, respectively. Similarly, density carriage in the HIV+ group was found to be significantly higher than in the control group (P = .0002). Among HIV+ subjects, Candida carriage was significantly associated with smoking, whereas density was not. Oral candidal carriage and relative density were not significantly associated with the other 4 parameters evaluated. Candida albicans was the most frequently recovered species. CONCLUSIONS. Asymptomatic candidal carriage and relative density were found to be significantly higher in the oral cavity of HIV+ subjects-but not associated with CD4+ counts or HIV-1 RNA quantities.     

HIV感染者口腔念珠菌负荷及生物型研究

目的调查人类免疫缺陷病毒（human immunodeficiency virus，HIV）感染者口腔中念珠菌负荷状况、生物分型及与口腔念珠菌病临床表现的关系。方法采取漱口法对64例HIV感染者和42名健康对照者进行口腔念珠菌的定量分离培养，并综合利用革兰染色、厚壁孢子生成实验、CHROMagar显色培养和API 20C AUX酵母菌鉴定系统对分离株进行生物型鉴定。结果64例HIV感染者中，52例中可分离出念珠菌74株，阳性分离率为81．3％，而42名健康对照者口腔念珠菌阳性分离率仅为16．7％（P〈0．001）。通过对74株念珠菌的生物型进行鉴定，发现有39株白色念珠菌，15株热带念珠菌及其他6个生物型20株。健康对照组中，分离出5株白色念珠菌和其他裂2株。结论HIV感染者口腔念珠菌感染率明显增加，其口腔念珠菌的检出率和负荷量亦明显增加，白色念珠菌和热带念珠菌为其主要分离菌；与健康对照组相比，HIV感染者的口腔念珠菌分离株生物类型旱现多样化。     

Oral Candida infection and colonization in solid organ transplant recipients

Introduction:  Oral Candida carriage and infection have been reported to be associated with a greater risk for systemic infection in transplant recipients; however, a systematic analysis of the oral Candida titers and species has not been previously conducted. The objectives of this study were to determine the prevalence of oropharyngeal candidiasis, the oral carrier status, Candida titers and species in this population.
Methods:  Ninety kidney and heart transplant subjects and 72 age-matched healthy controls were included. Swabs from the oral mucosa and a standardized amount of unstimulated saliva were plated on Chromagar™ Candida , and colony-forming units per millilitre were calculated. Initial speciation was based on colony color and was confirmed by standard germ tube, biotyping, or polymerase chain reaction assays.
Results:  Infection with C. albicans was detected in seven transplant subjects and none of the controls. The transplant group had significantly higher oral Candida titers than the control group. There were no statistically significant relationships between the dose or type of immunosuppressants and oral Candida titers or infection. A significantly higher percentage of transplant subjects were colonized by more than one species, compared with control subjects. The most frequent species combination in transplant subjects was C. albicans and C. glabrata . C. glabrata was isolated from 13.5% of transplant carriers and none of the controls.
Conclusions:  Increased oral Candida infection and carriage titers were found in the transplant population. Although the majority of transplant patients were colonized by C. albicans , C. glabrata appears to emerge as the second most prevalent species.     

HIV感染者及艾滋病患者口腔白色念珠菌毒性的体外研究

目的从白色念珠菌本身毒性变化的角度探讨人类免疫缺陷病毒(HIV)感染者易感染口腔念珠菌病的原因。方法通过体外试验从天冬氨酸蛋白酶活性、对颊黏膜上皮细胞的黏附性两方面比较HIV阳性与阴性宿主口腔内白色念珠菌的致病能力。结果在天冬氨酸蛋白酶活性和黏附性方面,HIV阳性口腔念珠菌病致病菌的毒性显著低于HIV阴性口腔念珠菌病致病菌(P<0.01);寄生菌间差异无统计学意义;HIV阳性宿主中,口腔念珠菌病致病菌与寄生菌间差异无统计学意义;而HIV阴性宿主中,口腔念珠菌病致病菌毒性显著高于寄生菌(P<0.01)。结论HIV感染者口腔念珠菌病与某些占主导优势的高毒性菌株无关,而HIV阴性的普通宿主则可能与其选择毒性更强的菌株有关。     

Alteration of humoral responses to Candida in HIV infection

The objectives of this preliminary study were to determine the prevalence of oral candidal carriage and infection in a group of HIV-positive individuals and compare the humoral immune responses in serum and saliva in this group with a control group of HIV-negative subjects. Patients were examined clinically with particular reference to the presence of candidal lesions and oral swabs taken to identify carriers. Venous blood and whole saliva were obtained for estimation of total and anti-Candida antibody levels. Pseudomembranous candidiasis was the commonest clinical variant in HIV-positive individuals. Candida albicans was the commonest species isolated in both groups. Increased levels of anti-Candida IgG were found in both serum and saliva of HIV-negative individuals who were either carriers of Candida species or had clinical candidiasis. This was associated with a reciprocal fall in anti-Candida IgA. Similar trends were seen in HIV-positive individuals in association with candidal carriage and infection, although the changes were more marked.     

Candida dubliniensis in radiation-induced oropharyngeal candidiasis

Candida dubliniensis is a recently described species that has been shown to cause oropharyngeal candidiasis in patients with HIV. We present a detailed evaluation of a patient undergoing head and neck radiation for oral cancer who developed oropharyngeal candidiasis from a mixed infection of C dubliniensis and Candida albicans. To our knowledge, this is the first described case of C dubliniensis contributing to oropharyngeal candidiasis in this patient population.     

Prevalence of Candida species in AIDS patients and HIV-free subjects in Thailand

Teanpaisan R, Nittayananta W: Prevalence of Candida species in AIDS patients and HIV-free subjects in Thailand. J Oral Pathol Med 1998; 27: 4–7. © Munksgaard, 1998.
The purpose of this study was to examine the prevalence of Candida species among groups of HIV-infected and HIV-free subjects in Thailand and to ascertain whether particular Candida species were associated with HIV infection. Oral rinse specimens were collected from 45 AIDS patients (CDC stage IV), 74 HIV-free healthy subjects, and 42 HIV-free patients who had clinical candidiasis. Yeasts recovered in culture were identified and quantified. The mean ages of the cohorts were 30.75 ± 8.19 years (AIDS group), 28.50 ± 7.98 (HIV-free healthy group) and 41.83 ± 12.25 years (HIV-free candidiasis group). Yeasts were isolated from 30/45 (66.66%, range 6.6 ± 10²-5.7 × 10⁶ CFU/ml) of the AIDS group, 8/74 (10.81%, range 8.0 × 10¹-3.5 × 10⁴ CFU/ml) of the HIV-free healthy group, and 24/42 (57.14%, range l.0 × 10 10²-1.1 × 10⁵ CFU/ml) of the HIV-free candidiasis group. There were statistically significant differences in the Candida colony counts between the AIDS group without oral candidiasis and the healthy group ( P =0.0078) and between the AIDS group with candidiasis and the HIV-free, oral candidiasis group ( P = 0.0003). Candida albicans was the most common species recovered from AIDS patients (29 out of 30; 96.66%).     

Persistence of oral Candida albicans carriage in healthy Portuguese schoolchildren followed for 3 years

Little is known about carriage of Candida albicans, the predominant pathogenic yeast in oral infection, in children. We cultured buccal mucosal and gingival swabs from 150 Portuguese children to investigate the prevalence of C. albicans at baseline (before dental treatment), post-treatment, and 12, 24, and 36 months post-baseline. The children, aged 8 to 11 years at baseline, had no systemic disease or clinical symptoms of oral candidiasis. At each successive visit, respectively, 47, 32, 21, 27, and 28% of children were C. albicans positive, resulting in an almost 50% reduction in prevalence from baseline to post-treatment (P < 0.0005). Children who carried C. albicans at one visit had 3 to 20 times greater odds of carrying C. albicans at another visit. C. albicans was cultured from 12 children at all time-points and from 10 children at four time-points. Children with oral C. albicans frequently maintained carriage over time, even with regular dental care.     

Effect of cannabis use on oral candidal carriage

The effects of cigarette smoking on oral candidal carriage and candidosis have been well documented but few similar studies on cannabis smoking have appeared, therefore it was felt that such a study needed to be undertaken. In this investigation, the effect of cannabis smoking combined with methaqualone and tobacco on candidal prevalence, density and candidosis was examined in 55 users. Age and sex matched tobacco-smoking (n = 58) and non-smoking controls (n = 50) were examined similarly. The imprint culture technique was used for harvesting Candida. Results showed an increased prevalence and density of C. albicans in cannabis users while there was no apparent difference in the prevalence of candidiasis. However, two subjects presented with oral multifocal candidiasis.     

Oral candidiasis in HIV infection: predictive value and comparison of findings in injecting drug users and homosexual men

The objectives of this study were to compare the relationship of oral candidiasis to HIV status, cohort and CD4+ lymphocyte values in injecting drug users and homosexual men and to examine its impact on prognosis. An oral examination was added to an ongoing longitudinal study of HIV infection. Data obtained at 6-month intervals included smoking, illicit drug use. medication use. symptoms and medical diagnoses, physical examination findings and laboratory data. In this study HIV+ subjects were much more likely to present with oral candidiasis than were HIV- subjects (OR = 6.3. P < 0.0l), Injecting drug users, regardless of serostatus. were more likely than homosexual men to present with oral candidiasis I OR = 3.0. P =0.00l). In both cohorts oral candidiasis was associated with low CD4+ lymphocyte counts and percent ages, and Kaplan-Meier survival estimates showed that subjects with oral candidiasis had a poorer prognosis than those without candidiasis, even after controlling for CD4+ lymphocyte count.     

Phenotypic and genotypic characterization of oral yeasts from Finland and the United States

A total of 4–22 isolates of oral yeasts per subjects from 48 yeast-positive Finnish and American subjects (25 females and 23 males) were phenotyped and genotyped to determine the frequency of simultaneous oral carriage of multiple yeast taxa. An oral sample from either periodontal pockets, oral mucosa or saliva was obtained. All subjects yielded Candida albicans and 3 subjects an additional yeast species ( Candida krusei, Candida glabrata or Saccharomyces cerevisiae ). The API 20C Aux kit distinguished 9 different carbohydrate assimilation profiles among the C. albicans isolates. Thirty-eight of 46 C. albicans biotype I isolates were categorized in a single numerical profile. PCR analysis, using a random primer OPA-03 and a repetitive primer (GACA)₄, detected 2 major genotypic groups among the C. albicans isolates; 44 subjects showing isolates with a "typical" PCR-profile and 4 subjects isolates with an "atypical" PCR-profile. The "atypical" PCR-profile was similar to that of Candida dubliniensis. All C. albicans isolates assimilated xylose, except 5, including the 4 with an "atypical" PCR-profile. No difference was found in distribution of oral yeast species, and of C. albicans phenotypes and genotypes between Finnish and American subjects. The present PCR method may offer a rapid and easy means of distinguishing oral Candida species.     

Salivary calprotectin levels are raised in patients with oral candidiasis or Sjögren's syndrome but decreased by HIV infection

Calprotectin levels were determined in whole saliva from patients predisposed to oral candidiasis due to HIV infection or Sj?gren's syndrome and from patients with candidiasis associated with various oral disorders (e.g. lichen planus, oral ulceration). Mean calprotectin levels were higher in whole saliva (2 microgram/ml) than in parotid saliva (0.3 microgram/ml). Oral candidiasis was associated with raised whole saliva calprotectin levels in all groups studied. HIV infection was associated with lower levels of salivary calprotectin, in the presence of high or low salivary Candida counts, although CD4+ lymphocyte counts did not significantly correlate with calprotectin concentrations. Calprotectin levels were elevated in saliva from Sj?gren's syndrome patients with oral candidiasis, consistent with mucosal transudation of calprotectin from inflamed mucosa and limited dilution due to decreased salivary flow rates. This study indicates that oral candidiasis is associated with raised calprotectin levels secondary to mucosal inflammation, but that diminution of this candidacidal factor due to HIV infection may be a predisposing factor in the aetiology of oral candidiasis.     

(B1) Candida and mycotic infections

Oral candidiasis (OC) is the most common mucosal manifestation of HIV infection. This workshop examined OC and other mycoses associated with HIV infection. Historically, blood CD4 cell numbers were the primary prognosticator for the development of OC. However, a study that statistically evaluated the predictive role of HIV viral load vs. CD4 cell counts revealed viral load to be a stronger predictor for OC. The role of biofilms and antifungal resistance in recalcitrant OC is unclear at present. In general, micro-organisms including yeasts in biofilms are more resistant to antifungals than their planktonic counterparts. When the remaining organisms are eliminated, the few resistant organisms may not be problematic, because they are present in low numbers. Unusual exotic mycoses in HIV-infected patients are more common in patients from the developing than the developed world. These infections may be recurrent and recalcitrant to therapy, be present in multiple and uncommon sites, increase with the progression of HIV disease, and may play a role similar to that of the more common mycoses. Typing and subtyping of yeasts are probably not critical to the clinical management of candidiasis caused by Candida albicans and non-albicans strains, including C. dubliniensis, because it is responsive to antifungal therapy. C. glabrata is probably the only exception. The presence of oral thrush in infants younger than 6 months of age is associated with an increased post-natal transmission risk of HIV infection. Thus, perinatal retroviral therapy should be combined with the treatment of oral thrush to prevent the post-natal acquisition of HIV.     

小鼠对口腔念珠菌感染的体液免疫应答

目的建立敏感株和阻抗株小鼠口腔念珠菌感染模型，揭示两种小鼠对口腔念珠菌感染的体液免疫反应。方法雌性BALB／c和CBA／CaH小鼠及白色念珠菌3630用于本研究。1×10^8念珠菌／20μl接种于小鼠的口腔黏膜，建立口腔念珠菌感染模型；SDS—PAGE和Western—Blotting用于检测血清抗体。结果念珠菌敏感株鼠CBA／CaH的口腔感染比阻抗株鼠BALB／c严重（P〈0．05）；CBA／CaH小鼠在口腔免疫后5周产生了IgG1、IgG2a、IgM，而BALB／c小鼠仅产生IgG1。结论念珠菌敏感鼠CBA／CaH的口腔念珠菌感染比念珠菌阻抗鼠BALB／c感染更为严重；抗白色念珠菌抗体IgM可能对宿主的口腔念珠菌感染起保护作用。     

Candida-host interactions in HIV disease: implications for oropharyngeal candidiasis

Oropharyngeal candidiasis (OPC), caused primarily by Candida albicans, is the most common oral infection in HIV(+) persons. Although Th1-type CD4(+) T cells are the predominant host defense mechanism against OPC, CD8(+) T cells and epithelial cells become important when blood CD4(+) T cells are reduced below a protective threshold during progression to AIDS. In an early cross-sectional study, OPC(+) tissue biopsied from HIV(+) persons had an accumulation of activated memory CD8(+) T cells at the oral epithelial-lamina propria interface, with reduced expression of the adhesion molecule E-cadherin, suggesting a protective role for CD8(+) T cells but a dysfunction in the mucosal migration of the cells. In a subsequent 1-year longitudinal study, OPC(-) patients with high oral Candida colonization (indicative of a preclinical OPC condition), had higher numbers of CD8(+) T cells distributed throughout the tissue, with normal E-cadherin expression. In OPC(+) patients, where lack of CD8(+) T cell migration was associated with reduced E-cadherin, subsequent evaluations following successful treatment of infection revealed normal E-cadherin expression and cellular distribution. Regarding epithelial cell responses, intact oral epithelial cells exhibit fungistatic activity via an acid-labile protein moiety. A proteomic analysis revealed that annexin A1 is a strong candidate for the effector moiety. The current hypothesis is that under reduced CD4(+) T cells, HIV(+) persons protected from OPC have CD8(+) T cells that migrate to the site of a preclinical infection under normal expression of E-cadherin, whereas those with OPC have a transient reduction in E-cadherin that prohibits CD8(+) T cells from migrating for effector function. Oral epithelial cells concomitantly function through annexin A1 to keep Candida in a commensal state but can easily be overwhelmed, thereby contributing to susceptibility to OPC.     

Prevalence of oral Candida carriage in Thai adolescents

Aim: Oral candidiasis is among the most common AIDS‐associated opportunistic infections. Adolescents remain at the highest risk of HIV infection and could suffer from oral candidiasis. However, information on oral Candida carriage in this population is limited. This study aims to evaluate the prevalence of oral Candida in Thai adolescents. Methods: Oral rinse samples from 80 healthy Thais (age: 15–17 years) were collected and analyzed for the prevalence of Candida species using culture‐based and polymerase chain reaction assays. Results: Twenty six adolescents (32.5%) carried Candida in the oral cavity. Candida albicans was detected in 28.75% (23/80). Non‐albicans Candida species were detected in 6.25% (5/80). The majority (92.3%, 24/26) of adolescents with Candida carried a single species. Two carried two species: one with Candida glabrata and Candida albicans, and the other with Candida parapsilosis and Candida albicans. Three adolescents harbored only non‐albicans species, with one carrying Candida tropicalis and two carrying Candida parapsilosis. Candida dubliniensis was not detected in this population. Most adolescents carried Candida at a low level (<500 c.f.u./mL). Conclusions: Oral Candida was present in approximately one‐third of adolescents. Candida albicans was the most prevalent (88.5%), and non‐albicans species were present in 19.2% of those with oral Candida.     

Oral candidal infection as a sign of HIV infection in homosexual men

The oral mucosae of 66 homosexual men were examined clinically and by means of cultivation to determine the presence of Candida infection. In addition, clinically detected mucosal changes were recorded and a biopsy specimen was obtained for the histopathologic classification. A total of forty one subjects (62%) showed clinical evidence of candidiasis. Fourteen (21%) of the sixty-six men were seropositive for human immunodeficiency virus (HIV). A total of thirteen of fourteen (93%) of the seropositive men and twenty-six of fifty-two (50%) of the HIV seronegative men had culture-confirmed oral candidiasis. In the latter group, oral candidiasis was clearly correlated to cigarette smoking. Clinical mucosal changes other than candidiasis were found in forty-five of the sixty-six subjects studied. The most frequent finding was trauma resulting from biting, which was usually localized on the cheek. Leukoplakia was found in twelve of sixty-six subjects, while cauliflower-like condylomas were present in 4 persons. The results emphasize the frequent occurrence of different oral lesions in subjects seropositive for HIV and in those at high risk for HIV infection. Oral examination in search for potential early manifestations of HIV infection in homosexual men is advocated.     

Oral yeast carriage in patients with advanced cancer

The aim of this study was to investigate oral yeast carriage amongst patients with advanced cancer. Oral rinse samples were obtained from 120 subjects. Yeasts were isolated using Sabouraud's dextrose agar and CHROMagar Candida, and were identified using a combination of the API 20 C AUX yeast identification system, species-specific PCR and 26S rDNA gene sequencing. Oral yeast carriage was present in 66% of subjects. The frequency of isolation of individual species was: Candida albicans, 46%; Candida glabrata, 18%; Candida dubliniensis, 5%; others, < 5%. The increasing isolation of non-Candida albicans species is clinically important, since these species are often more resistant to antifungal drugs. Oral yeast carriage was associated with denture wearing (P = 0.006), and low stimulated whole salivary flow rate (P = 0.009). Identification of these risk factors offers new strategies for the prevention of oral candidosis in this group of patients.