Low prevalence of oral mucosal lesions in HIV-1 seropositive African women

In Nairobi (Kenya) 334 women prostitutes of whom 80.5% were HIV-1 positive, were examined for oral mucosal lesions; 15.6% of seropositive, and 4.6% of seronegative, women had oral mucosal lesions, predominantly oral candidiasis. In the seropositives, 8.6% had erythematous, 1.1% had hyperplastic candidiasis, and 0.4% had hairly leukoplakia as the only oral lesions; 0.4% had a combination of erythematous and hyperplastic candidiasis, and 1.5% had combinations of pseudomembranous and erythematous candidiasis in the presence of hairly leukoplakia. Of the 211 seropositive women for whom we knew the first date on which a positive serologic test was obtained, the likelihood of developing an oral mucosal lesion was found to be dependent on the duration of seropositivity. The low incidence of oral mucosal lesions in this population may be due to the relatively recent acquisition of HIV-1 infection.     

Gender differences in human immunodeficiency virus-related oral lesions: an Italian study

OBJECTIVE: The purpose of this study was to investigate the relationship between oral lesions and gender, age, CD4(+) cell count, human immunodeficiency virus-1 (HIV-1) viral load, antiretroviral therapy, and route of transmission in a group of HIV-infected (HIV+) persons from the Mediterranean region. STUDY DESIGN: The participants in this study were HIV+ adults who sought dental care between January 1999 and June 1999 in the Department of Oral Medicine (University of Palermo, Italy). RESULTS: One hundred thirty-six HIV+ adults came in for an initial oral examination. Their mean age was 35.2 years (SD +/- 7.97), and 33% were women. Their mean CD4(+) cell count was 325.3 x 10(6) /L (SD +/- 225.8), and their HIV-1 viral load was 39,168.3 copies/mL (SD +/- 144,256.1). Oral lesions were found in 47% of the study group, as well as in 56.5% of women (n = 46) versus 45.5% of men (n = 90; P =.05). Oral candidiasis was the most common disease; it is significantly associated with women (P =.004), CD4(+) cell count (P =.005), and HIV-1 viral load (P =.0003). No significant relationships were found between any types of oral lesions and age, antiretroviral therapy, or route of transmission (P >.2). CONCLUSION: The prevalence of HIV-related oral lesions was significantly higher in women than in men, especially for oral candidiasis, the most common lesion observed related to immune status and HIV-1 viral load.     

Epidemiology, clinical features and prognostic value of HIV-1 related oral lesions

Between February 1987 and February 1990, we studied 737 antibody anti HIV-1 positive (AbHIV+) subjects referred to the Infectious Diseases Institute of the University of Turin (Italy) in order to evaluate types, prevalences, relations with clinical stages, distributions in risk-groups and prognostic significances of HIV-1 related oral lesions. The study evidenced the high prevalence of oral lesions, especially mycoses, in the investigated population: 40.3% of the patients showed, in fact, HIV-1 related oral lesions. The 37 months follow-up of 55 AbHIV+ with oral hairy leukoplakia (HL) and 101 patients with oral candidiasis (OC), demonstrated that the probability of developing AIDS in patient with HL was 0.381 at 15, 0.635 at 25 and 0.824 at 37 months. In the patients with OC the probability was 0.294 at 15 months, 0.524 at 25 and 0.781 at 37 months.     

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.     

Oral diseases, mycology and periodontal microbiology of HIV-1-infected women

HIV-1 infection is increasing more rapidly among heterosexual women. Relatively limited information is available on HIV-related oral pathoses in these individuals. To gain insight into the type and occurrence of oral lesions in this population, 25 HIV-1 infected women including asymptomatic, symptomatic and AIDS patients were examined clinically and sampled for detection of oral yeast and characterization of their subgingival microbial flora. Sixty percent of the subjects were African-American, with 80% infected via heterosexual contact. Oral candidiasis was the most common nonperiodontal oral lesion, observed in 44% of the patients. Oral yeast was cultured from all women with candidiasis and 76% of the total subjects. Oral hairy leukoplakia was clinically diagnosed in 16% of the subjects. Clinically mild to moderate gingivitis and periodontitis were observed in 84% and 52% of the patients, respectively. Candidiasis and the presence of cultivable yeast were observed in patients with low, intermediate, and high CD4⁺ T lymphocyte numbers. Plaque samples were collected from each subject and enumerated by predominant cultivable methods, selective media and microscopy. No differences were detected in the microflora associated with seropositive women with existing periodontitis relative to those without periodontitis or to seronegative women with periodontitis. Candidiasis was the most notable oral clinical manifestation in the HIV-1-infected women and may be a useful clinical indicator of early immune dysfunction mediated by HIV-1.     

Biotypes of oral Candida albicans isolates in human immunodeficiency virus-infected patients from diverse geographic locations

Oral Candida albicans isolates from HIV-infected individuals in Hong Kong, Australia, Germany and England were characterised using a biotyping system based on enzyme profiles, carbohydrate assimilation patterns and boric acid resistance of the yeasts. A total of 44 biotypes were found amongst the 117 oral C. albicans isolates examined. The major biotype AIR accounted for 17.9% of all isolates while the second commonest biotype was A1S (11.1% of isolates). Whereas these two biotypes were isolated from all the regions studied, there were a number of other biotypes unique to individual countries. The data indicate that there are many different sub-strains of oral C. albicans in HIV-infected patients, some of which are globally prevalent. However, further work is required to ascertain the diversity of oral C. albicans biotypes, if any, in health and disease.     

Yeast species and biotypes associated with oral leukoplakia and lichen planus

Of 36 patients, 17 had oral leukoplakia, including homogeneous and nonhomogeneous types, and 19 had reticular lesions of oral lichen planus. A sample of yeast flora in each patient was taken from the pathologic lesion as well as from normal-appearing mucosa. The isolated yeasts were identified according to species level, and identification was extended beyond the species level for one species, Candida albicans, to reveal the biotype by means of the Odds and Abbott procedure comprising tests for acid and salt tolerance, proteinase production, resistance to 5-fluorocytosine and safranine, and assimilation of urea, sorbose, and citrate. Yeasts were present in the lesions of 82% of leukoplakia patients, compared to 37% of lichen planus patients, a frequency of yeasts corresponding to that in healthy adults. C. albicans was the dominating species in lesions of both diseases, constituting 82% of all yeasts in the leukoplakia lesions. In addition, the following species were identified: Candida tropicalis, Candida pintolopesii, Torulopsis glabrata, and Saccharomyces cerevisiae. Eighteen biotypes of C. albicans were encountered, the most frequently occurring biotypes being 355 and 177. Differences between C. albicans biotypes isolated from pathologic and normal mucosa were encountered in five of eleven leukoplakia patients and in one of three lichen planus patients. This indicates that the oral cavity comprises several ecologic niches for yeasts. As nonhomogeneous leukoplakias are more likely to develop into carcinoma than are homogeneous leukoplakias, it is interesting to note that the C. albicans biotypes isolated from nodular lesions (one type of nonhomogeneous leukoplakia)--biotypes 145, 175, and 575--rarely occur.(ABSTRACT TRUNCATED AT 250 WORDS)     

Biotypes of oral Candida albicans isolated from AIDS patients and HIV-free subjects in Thailand

This study was conducted to examine biotypes and antifungal susceptibility patterns of oral Candida albicans isolated from HIV-infected patients, HIV-free patients with candidiasis and healthy subjects. All isolates were biotyped using a typing system based on enzyme profiles, carbohydrate assimilation patterns and boric acid resistance. Thirty-eight biotypes were found amongst 218 oral C. albicans isolates. The major biotype found was A1S, which accounted for 32.6% of all isolates, and this biotype was the most common in all groups. There was a greater variety of biotypes of C. albicans in the HIV-infected group than in the other groups; however, there was no statistically significant difference between the groups. The minimum inhibitory concentrations (MICs) of a total of 118 isolates were determined for amphotericin B and for ketoconazole using the National Committee for Clinical Laboratory Standards (NCCLS) broth macrodilution method and the E-test. When the antifungal susceptibility patterns among the groups were compared, a statistically significant difference was found only with amphotericin B. The median MIC of amphotericin B in the HIV-infected group was higher than in the healthy group (P=0.013, NCCLS method; P=0.002, E-test). However, this difference in sensitivity was not restricted to any sub-type investigated. Our results showed that the biotype patterns of C. albicans isolates that colonize HIV-infected patients are similar to those of HIV-free subjects, and there is no relationship between antifungal susceptibility patterns and the biotypes.     

Sentinels and signposts: The epidemiology and significance of the oral manifestations of HIV disease

A large number of studies attest to the frequency of oral disease in those with HIV infection. Most show that hairy leukoplakia and pseudomembranous candidiasis are the commonest lesions in those with HIV infection and AIDS, with higher prevalence and incidence rates correlating with falling CD4 counts and disease progression. HIV-infected individuals with oral candidiasis or hairy leukoplakia progress to AIDS more rapidly than matched controls without these lesions. Oral candidiasis and hairy leukoplakia increase with time since seroconversion. On the other hand, parotid enlargement in children appears to be associated with slower progression to AIDS. As a consequence of these and other observations, oral lesions are widely included in natural history studies, staging and classification schemes for HIV infection. In addition to their role in the diagnosis of HIV infection and as indicators of the progression of HIV disease, oral lesions are used as clinical correlates of CD4 counts and as criteria for entry into clinical trials.     

Oral manifestations of HIV infection and their management. I. More common lesions

Oral lesions are common at all stages of HIV infection. This first of two articles reviews the clinical features and pathogenesis of common oral manifestations of HIV disease (candidiasis, hairy leukoplakia, Kaposi's sarcoma, and HIV-related periodontal disease) and considers current treatment measures.     

The role of yeasts in oral cancer by means of endogenous nitrosation

Oral leukoplakias, particularly non-homogeneous types, are often invaded by yeasts, with Candida albicans being the dominant species. The more advanced precancerous leukoplakia lesions yield more rarely occurring biotypes of C. albicans, suggesting a causal role for these biotypes in the malignant transformation. N-nitroso-benzylmethylamine (NBMA) is a compound able to induce carcinoma of the esophagus and the oral cavity in the rat. The catalytic potential of yeasts, isolated from leukoplakia lesions and from normal mucosa, to produce NBMA from the precursors N-benzyl-methylamine and nitrite was assessed at pH 6.8. The yeast strains differed in nitrosation potential, ranking from 0 to 1.2 micrograms NBMA/10(6) cells. C. albicans strains of the more rarely occurring biotypes showed the highest nitrosation potential, whereas C. tropicalis, C. parapsilosis, and Torulopsis glabrata were ranked lower. Strains with high nitrosation potential were generally isolated from lesions with more advanced precancerous changes. Thus, further evidence is provided supporting the hypothesis that yeasts play a causal role in oral cancer by means of endogenous nitrosamine production.     

Asymptomatic oral Candida albicans carriage in HIV-infection: frequency and predisposing factors

Many studies have focused on the epidemiology and pathogenesis of oral candidiasis in HIV infection. Little is known on the incidence and predisposing factors of asymptomatic oral Candida carriage in this setting, obviously an important issue in view of prophylaxis. To address this question. 261 consecutive HIV-infected individuals without clinical evidence of candidiasis were investigated. C. albicans was isolated from cultured oral cavity swabs of 63 subjects (24%). Colonization was significantly more frequent in IV drug users. CDC groups IV. and in subjects with lymphocytopenia. CD4+ cell depletion, or elevated beta-2 microglobulin. These data further suggest that oral candidiasis occurs in HIV infection as a result of C. albicans overgrowth and raise the question of primary antifungal prophylaxis in subjects with low CD4 counts and asymptomatic oral Candida carriage.     

Oral lesions in children with perinatally acquired human immunodeficiency virus infection

Fifteen vertically HIV-infected children aged between 2 and 12 years were followed up for 1 year, weekly to monthly, to study the incidence of oral lesions. At the time of first examination, oral candidiasis (OC) was observed in nine children. Seven children presented with the erythematous type only and two with pseudomembranous oral candidiasis. Four cases of cheilitis were seen in association with the erythematous forms of oral candidiasis. One erythematous candidiasis progressed to pseudomembranous form. A second case of erythematous OC, after multiple recurrences in the form of erythematous OC, recurred as pseudomembranous OC. Another case of erythematous OC and one of pseudomembranous OC presented after multiple recurrences as a persistent, adherent pseudomembranous OC. An orofacial herpes-zoster infection, a hairy leukoplakia and a necrotic lingual ulcer were observed as second lesions and in association with oral candidiasis in three children. Erythematous oral candidiasis was the most frequent oral HIV-related lesion, was observed in different stages of HIV-infection, and in some cases progressed to pseudomembranous candidiasis. A different, selectively resistant, Candida clone was isolated in three cases of recurrent candidiasis.     

Efficacy of chlorhexidine gluconate rinse for treatment and prevention of oral candidiasis in HIV-infected children: a pilot study

PURPOSE: We evaluated the effect of chlorhexidine (CHX) 0.12% rinses on the clinical and microbiologic manifestations of oral candidiasis in HIV-infected children. STUDY DESIGN: This was a cross-sectional, clinical intervention study of 38 HIV-positive children. Inclusion in the study was based on oral examination and positive oral culture for Candida. At baseline, subjects with no clinical lesions but who were culture-positive for Candida (N = 9) were placed on preventive therapy of CHX q.d. for 90 days. Subjects with clinical oral candidiasis (N = 9) were placed on therapeutic CHX b.i.d. All 38 subjects received oral exams at monthly intervals. At 90 days oral mucosal samples were again taken for Candida. Colony-forming units (CFU) were determined before and after CHX treatment. RESULTS: Of 18 culture-positive subjects, 12 were included in the CFU analyses. After 3 months of CHX oral rinse therapy, Candida was undetectable in 3 children; another 8 showed an average 2-fold reduction in CFU. In 1 child the number of CFU increased modestly. Overall, the average pre- and posttreatment mean CFU was 6.18 +/- 2.19 and 2.73 +/- 3.15, respectively (P = .009). Five patients with clinical oral candidiasis at baseline, including all 3 who had pseudomembranous candidiasis, were free of signs of disease at the end of the study. CONCLUSIONS: This study suggests that the topical disinfectant CHX may be a promising agent for treating and preventing oral candidiasis in HIV-infected children.     

Oral epithelium-Candida glabrata interactions in vitro

BACKGROUND: Oropharyngeal candidiasis is a common opportunistic infection and Candida glabrata is the second or third most frequently isolated species from oropharyngeal candidiasis lesions, after Candida albicans. The aim of this study was to study the cytokine-inducing and cell-damaging potential of C. glabrata in oral epithelial cells and compare this to C. albicans. METHODS: Oral epithelial cell lines and primary gingival epithelial cells were cocultured with C. glabrata strains GDH2269 and 94-11 or C. albicans strains SC5314 and ATCC28366. Supernatants were analysed for the presence of interleukin-1alpha (IL-1alpha), IL-8 and granulocyte-macrophage colony-stimulating factor (GM-CSF) by enzyme-linked immunosorbent assay. The cytotoxity of different strains was determined using the CytoTox-96 assay. RESULTS: Compared to C. albicans, C. glabrata induced different proinflammatory cytokine responses in oral epithelial cells; a high level of GM-CSF induction was only detected in C. glabrata-infected cells and not in C. albicans-infected cells, regardless of the origin of these cells (cell lines or primary cells) or the strain used. Like C. albicans, C. glabrata induced an IL-1alpha response by oral epithelial cells, but this response was both strain-dependent and epithelial cell origin-dependent. Unlike C. albicans, C. glabrata failed to induce a strong IL-8 response in any of the cell systems studied. Finally, in these studies C. glabrata showed lower cytotoxicity than C. albicans. CONCLUSIONS: C. glabrata is less cytotoxic than C. albicans and induces different proinflammatory cytokine responses in oral epithelial cells.     

Candida species and Candida albicans morphotypes in erythematous candidiasis.

A group of full-denture-wearing patients with erythematous candidiasis was matched by age and sex with a group of healthy, full-denture-wearing persons who served as controls. In the group with erythematous candidiasis, clinical symptoms and signs of the disease were recorded. Denture hygiene and tobacco use were noted in both groups. Epithelial smears and imprint cultures were obtained from both groups from specified sites. Cultures were grown and subjected to species identification and C. albicans strain differentiation by a morphotyping technique. Denture-wearing subjects who smoked tobacco had a significantly greater incidence of erythematous candidiasis than the controls. Five species of Candida were isolated from both groups, with C. albicans as the dominant species. Twenty different morphotypes of C. albicans as well as strains involved in erythematous candidiasis were also isolated from the oral cavities of healthy, full-denture-wearing control subjects.     

High levels of oral yeasts in early HIV-1 infection

Ten human immunodeficiency virus-1 (HIV-1) infected homosexual or bisexual individuals (ages 24-45) with no history of opportunistic infection were examined, by culture, for the presence of yeasts in whole saliva and on oral mucosa. All were HIV-1 antibody-positive men, non-smokers, non-denture wearers, and taking no medication. The mean salivary level of yeast was four logs higher in the HIV-1 infected group compared to a control group of normal, unmedicated, non-smoking men (ages 20-41) who denied any risk behavior for HIV-1 infection. Identification of the yeast in these HIV-1 positive individuals established that Candida albicans was the predominant species found in whole saliva and on buccal mucosa and tongue. Distinct hyphae were observed with only one mucosal sample. No significant correlation was found between whole saliva yeast concentration and the T4/T8 lymphocyte ratios or absolute number of T4 cells. No correlation was observed between oral yeast concentration and anti-C. albicans IgA titers. The high level of oral yeast in these individuals prior to the development of opportunistic infections is consistent with the suggestion that oral defense mechanisms are compromised in individuals following HIV-1 infection.     

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 lesions in Mexican HIV-infected patients

One hundred and twenty-five HIV-infected patients, of whom 49 (39%) were at early stages of the infection (CDC-II & III) and 76 (61%) in CDC IV, were prospectively examined. In 100 (80%) one or more oral mucosal lesions were observed; candidiasis (51%) and hairy leukoplakia (43%) were the commonest. Erythematous candidiasis was more often seen (35%) than the pseudomembranous type (16%), and appeared with the higher values at early than later stages. The prevalence of hairy leukoplakia, oral hyperpigmentation and xerostomia were incremented in groups CDC-IV. Pseudomembranous candidiasis and exfoliative cheilitis increased significantly with severity of disease. Our study demonstrates that oral alterations associated to HIV are a frequent finding, both at early (76%) and late (83%) stages of the infection in Mexican patients.     

Cellular immunity in acquired candidiasis of the palate

abstract — In vitro cellular hypersensitivity and agglutinating antibody to C. albicans was assessed in 180 subjects of whom 55 were patients with Candida -induced denture stomatitis (25 with the generalized simple and 30 with the granular type) whereas 16 had traumainduced lesions in the palatal mucosa. Patients with other candidal manifestations, such as cutaneous candidiasis (5), vaginal candidiasis (3), Candida leukoplakia (1), chronic mucocutaneous candidiasis (2), and appropriate controls were included in the study. Using the leukocyte migration test, cellular hypersensitivity to C. albicans was demonstrated in 76% of the patients with the generalized simple type of denture stomatitis and in most of the patients with vaginal or cutaneous candidiasis. However, only 28% of the patients with the granular type of denture stomatitis and none of those with mucocutaneous candidiasis showed significant inhibition of migration. Upon antifungal therapy of 13 patients, cellular hypersensitivity was restored. The increase of the cellular immune response to C. albicans was most pronounced for the granular type of denture stomatitis. In the infected patients an inverse relationship was demonstrated between cellular hypersensitivity and agglutinating antibody titer to C. albicans . The immediate increase in leukocyte response to C. albicans that was demonstrated after antifungal therapy was taken as indirect evidence that a Candida infection may lead to a suppression of the systemic cellular immune response to C. albicans .