Elucidating the role of hyposalivation and autoimmunity in oral candidiasis.

INTRODUCTION: Oral candidiasis (OC) is a potential oral complication in Sjögren's syndrome (SS). Some studies indicate that the low stimulated salivary flow and not low unstimulated salivary flow is associated with OC in SS, while others report that the underlying autoimmune disorders contribute to OC, based solely on correlation coefficients. Given the conflicting and limited existing evidence, we purposed to ascertain the role of both salivary gland dysfunction (hyposalivation based on unstimulated and stimulated flow rates) and autoimmunity (SS, other autoimmune disorders) in OC among those with SS, other salivary gland dysfunction, and non-salivary gland dysfunction controls (NSGD). METHODS: A nested case-control study was designed within a larger NIH/NIDCR cohort. Descriptive analyses, nonparametric tests, comparative analyses, and multivariate logistic regression analyses were undertaken. RESULTS: Data on 1526 subjects (701 SS, 247 ISS, 355 Sicca, and 223 NSGD) were obtained from the source cohort of 2046 and analyzed for this study. The median whole unstimulated salivary flow rate (WUS, ml 15 min-1 ) was lower in SS (0.8, interquartile range (IQR) 1.8) compared to ISS (5.5, IQR: 5.2, P < 0.001) and NSGD (3.8, IQR: 3.8, P < 0.001) but comparable with that of Sicca (1.0, IQR: 1.5, P = 0.777) participants. The median total stimulated salivary flow rate (TSS, ml 15 min-1 ) was lowest in SS (7.0, IQR: 12.4, P < 0.001) compared to other groups. Of the 45 OC cases in this cohort, 71.1% (n = 32) were from the SS group. The prevalence of OC was highest in the SS group (4.6%, P = 0.008). SS group had twice the risk of OC than NSGD (OR = 2.2, 95%CI: 1.1-4.2, P = 0.02) and Sicca (OR = 2.2, 95% CI: 1.0-4.8, P = 0.03), adjusting for confounders; hyposalivation [WUS (OR = 5.1, 95%CI: 2.5-10.4, P < 0.001), TSS (OR = 1.9, 95%CI: 1.0-3.5, P = 0.04)], history of other autoimmune disorders (OR = 4.4, 95%CI: 1.7-11.3, P = 0.002), medications for extraglandular manifestations (OR = 2.3, 95%CI: 1.1-4.9, P = 0.03), and diabetes mellitus (4.2, 95%CI: 1.2-15.2, P = 0.02) were independent predictors of OC; females had a lower risk than males (OR = 0.29, 95%CI: 0.13-0.67, P = 0.004). Age, race, anti-SSA/SSB autoantibodies, focus score, other medications, anxiety, fatigue, cigarette smoking, alcohol, and caffeine use were not associated with oral candidiasis. CONCLUSION: Salivary gland dysfunction (hyposalivation with WUS being a stronger predictor than TSS) and autoimmunity (SS, other autoimmune disorders, medications, i.e., DMARDS) are both independent predictors of OC. Diabetes mellitus is an independent predictor of OC among those with salivary gland dysfunction. Our findings suggest that these independent predictors should be considered in the prevention and management of OC in this population.

Effects of salivary protein flow and indigenous microorganisms on initial colonization of Candida albicans in an in vivo model.

BACKGROUND: Candida albicans is a dimorphic fungus that is part of the commensal microbial flora of the oral cavity. When the host immune defenses are impaired or when the normal microbial flora is disturbed, C. albicans triggers recurrent infections of the oral mucosa and tongue. Recently, we produced NOD/SCID.e2f1-/- mice that show hyposalivation, decrease of salivary protein flow, lack IgA and IgG in saliva, and have decreased NK cells. Our objective was to characterize C. albicans infection and biofilm formation in mice. METHODS: NOD/SCID.e2f1-/- mice were used as an animal model for C. albicans infection. C. albicans yeast and hyphal forms solutions were introduced in the oral cavity after disinfection by Chlorhexidine. RESULTS: The numbers of C. albicans colonized and decreased in a time-dependent manner in NOD/SCID.e2f1+/+ after inoculation. However, the colonization levels were higher in NOD/SCID.e2f1+/+ than NOD/SCID.e2f1-/- mice. In the mice fed 1% sucrose water before inoculation, C. albicans sample was highly contaminated by indigenous microorganisms in the oral cavity; and was not in the mice fed no sucrose water. The colonization of C. albicans was not influenced by the contamination of indigenous microorganisms. The hyphal form of C. albicans restricted the restoration of indigenous microorganisms. The decreased saliva in NOD/SCID.e2f1-/- did not increase the colonization of C. albicans in comparison to NOD/SCID.e2f1+/+ mice. We suggest that the receptor in saliva to C. albicans may not be sufficiently provided in the oral cavity of NOD/SCID.e2f1-/- mice. CONCLUSION: The saliva protein flow may be very important for C. albicans initial colonization, where the indigenous microorganisms do not affect colonization in the oral cavity.

Common benign and malignant oral mucosal disease.

BACKGROUND: Mucosal diseases of the oral cavity are relatively common, and patients often seek initial assessment from their general practitioner. OBJECTIVE: The aim of this article is to provide an overview of common oral mucosal diseases to help with formulating a differential diagnosis and stratifying the urgency of referral. DISCUSSION: Pathological mucosal conditions of the oral cavity and jaws commonly present as a mucosal ulcer or a white, red or pigmented lesion. In this review, the authors outline the most common conditions organised according to their clinical presentation and describe their typical appearance and management.

Cellular and molecular mechanisms of resistance to oral Candida albicans infections.

Oral candidiasis is a significant health problem in terms of both morbidity and economic outlay. Infections are predominantly caused by the commensal C. albicans, and affect immunocompromised individuals, including HIV-positive and AIDS patients, organ transplant recipients and chemotherapy patients. The molecular and cellular immune mechanisms involved in protection from and responses to oral candidiasis are overlapping, but distinct from those associated with other manifestations of the disease, including systemic, vaginal and gastric candidiasis. In oral candidiasis, clinical observations and experimental mouse models suggest a critical role for cell-mediated immunity. In mice, CD4+ T-cells and the p40 subunit of interleukins 12 and 23 are strict prerequisites for resistance; however abrogation of IFN-gamma does not confer susceptibility. Here, we discuss this apparent inconsistency, and review the experimental evidence that clarifies which immune pathways are specifically involved in resistance and responses to candidiasis of the oral cavity. We also highlight deficiencies in the literature, particularly concerning the putative roles of some relatively new elements in immunobiology: interleukin-23, interleukin-17 and T helper (Th)17 cells.

[Mycological examination and the taste disorder test for the tongues of diabetes mellitus patients].

The mycological examination by the cotton swab method and the taste disorder test using the filter-paper method were taken for the tongues of diabetes mellitus (DM) patients. Candida albicans was isolated from 29 out of 81 patients. The mean serum HbA1c level of patients with C. albicans was significantly higher than that of patients without it. DM patients demonstrated significantly higher incidences of taste disorders than healthy controls, but there was no relationship between C. albicans of the tongue and taste disorders. The taste disorders tended to occur in the DM patients who had nerve complications. The results suggested the taste disorder test using the filter-paper methods contributes to easy detection of the nerve complications in DM patients.

Murine model of concurrent oral and vaginal Candida albicans colonization to study epithelial host-pathogen interactions.

We report the creation of a new low-estrogen murine model of concurrent oral and vaginal C. albicans colonization that resembles human candidal carriage at both mucosal sites. Weekly estrogen administration of 5 microg intramuscular and subcutaneously was optimal for enhancement of oral colonization and was essential for vaginal colonization. In BALB/c mice, a number of C. albicans clinical isolates (n=3) colonized both oral and/or vaginal sites, but only strain 529L colonized 100% of mice persistently for over 5 weeks. Laboratory strains SC5314 and NCPF 3153 did not colonize the model; however, NCPF 3156 showed vaginal colonization up to week 5. Prior passaging through mice enhanced subsequent colonization of SC5314. Intranasal immunization with a C. albicans virulence antigen (secreted aspartyl proteinase 2) significantly reduced or abolished the fungal burden orally and vaginally by week 2 and 7. Our concurrent model of mucosal colonization reduces the numbers of experimental mice by half, can be used to assess potential vaccine candidates, and permits the detailed analysis of host-fungal interactions during the natural state of Candida colonization.

Characteristics of dual species Candida biofilms on denture acrylic surfaces.

UNLABELLED: Biofilms contribute to the pathogenesis of oral candidiasis, some 15% of which may be due to dual Candida species. Despite extensive studies on monospecies biofilms (MSB) on denture acrylic surfaces, few have investigated the characteristics of dual species Candida biofilms (DSB). OBJECTIVES: To examine interactions of DSB of Candida albicans and Candida krusei on denture acrylic surfaces. METHODS: Two isolates each of C. albicans (Ca) and C. krusei (Ck), with high (Ca(h), Ck(h)) and low (Ca(l), Ck(l)) biofilm-forming ability were used. The biofilms were developed on acrylic surfaces aerobically at 37 degrees C in yeast nitrogen base (YNB) medium, and growth quantified by colony-forming unit (CFU) assay. We determined: (i) the population profiles of DSB comprising each pair of Candida species, of a total of four combination pairs, after 12 h, (ii) the effect of a constant concentration of Ca(h) (10(7)cells/ml) on varying concentrations of Ck(h) (10(3)-10(7)cells/ml) on DSB development and (iii) the effect of saliva on the growth of DSB. RESULTS: (i) DSB exhibited a lower cell population after 9 or 12 h in comparison to MSB (P<0.05), (ii) C. albicans (10(7)cells/ml) co-cultured with varying initial concentrations of C. krusei was inhibited at high concentrations of the latter (10(6)-10(7)cells/ml) (P<0.05) and (iii) only the MSB development of C. krusei was affected by saliva (P<0.05). CONCLUSION: Our data suggest that the competitive interactions of fungal species are likely to be important in biofilm formation on acrylic surfaces and human saliva may further modulate this process.

Hyphal invasion of Candida albicans inhibits the expression of human beta-defensins in experimental oral candidiasis.

Oral epithelium reacts to microbial challenges by eliciting a defensive response that includes the production of antimicrobial peptides. This study investigated the expression of human beta-defensins-1, 2, and 3 in reconstituted human oral epithelia during experimental oral infections with six different Candida species, and a wild-type C. albicans isolate and five of its mutants. The expression of defensins was induced after 12 hours infection with the wild-type C. albicans, but this response was not seen for the noninvasive hyphal mutants nor the secreted aspartyl proteinase mutants. Furthermore, defensin expression was not detected after 48 hours in epithelia infected with either C. albicans wild-type isolate or its invasive hyphal and proteinase mutants. Most of the non-albicans Candida were capable of inducing the expression of defensins in epithelia after 24 or 48 hours of infection. These Candida-host interaction patterns suggest that the oral epithelia possess mechanisms for sensing the early invasion of C. albicans through recognition of the presence of hyphae and proteinases of Candida and respond to the insult by producing antimicrobial peptides. This hyphal-invasion-dependent inhibition of defensin expression in oral epithelium that undermines the host surveillance system represents a hitherto undescribed novel pathogenic mechanism of C. albicans.

Infection of human oral epithelia with Candida species induces cytokine expression correlated to the degree of virulence.

A defined and balanced immunomodulatory response is crucial for the protection of mucosal surfaces being in contact with pathogenic microorganisms. This study examined the local host response mechanisms of epithelial cells in experimental Candida albicans, C. tropicalis, and C. glabrata infections by measuring the expression of cytokines at the mRNA and protein level. During the course of infection with active but not with heat-killed C. albicans stimulation of the gene expression levels for interleukin-1alpha, interleukin-1beta, tumor necrosis factor, Exodus-2, P-selectin ligand, granulocyte-monocyte colony-stimulating factor, and interleukin-8 was observed by standard and quantitative reverse transcription-polymerase chain reaction. This cytokine pattern may favor a chemotactic and a T helper 1 response. Initial moderate or weak upregulation of these cytokine genes by reverse transcription-polymerase chain reaction was also observed in epithelial infection with the less virulent species C. tropicalis and C. glabrata. Heat-killed C. albicans failed to induce an epithelial immune response. At the protein level, expression of interleukin-8 protein was strongly enhanced during the course of C. albicans infection, whereas lower levels were seen with C. tropicalis and C. glabrata. The different expression patterns of cytokines were associated with differences in virulence of the Candida strains. This study's data, therefore, show a correlation between the virulence potential of pathogenic fungi, possibly mediated by specific virulence factors (such as proteinases), and the secretion of epithelial cytokines and chemokines, which may initiate in vivo a protective T helper 1 immunologic response and contribute to the recruitment of activated leukocytes and lymphocytes to the site of mucosal infection.

The possible influence of the menstrual cycle on the adherence of Candida albicans to human buccal epithelial cells in vitro.

Although the influence of the menstrual cycle on both vaginal candidosis and Candida albicans adherence to vaginal epithelial cells in vitro has been shown to be significant, similar studies have not been made on oral candidosis and adherence to buccal epithelial cells. The aim of this study was therefore to use an in vitro adherence assay to investigate the possible influence of the menstrual cycle on the adherence of C. albicans to buccal epithelial cells. Epithelial cells were collected from a single, healthy, female volunteer on days 5, 15, 22 and 28 of six menstrual cycles. Adherence of C. albicans was significantly higher to buccal epithelial cells collected on day 5 of the menstrual cycle when compared with days 15, 22 and 28, both in terms of the percentage of buccal epithelial cells with adherent C. albicans and the number of C. albicans adhering per 200 buccal epithelial cells in four out of six menstrual cycles (p < 0.001). This result indicates that hormonal influences should be considered when buccal epithelial cells are used in vitro to assess candidal adherence and may implicate hormonal factors in the aetiology of oral candidosis.

Biofilm formation of Candida albicans is variably affected by saliva and dietary sugars.

The pathogenesis of both superficial and systemic candidiasis is closely dictated by properties of the yeast biofilms. Despite extensive investigations on bacterial biofilms, the characteristics of candidal biofilms, and various factors affecting this process remain to be determined. Therefore we examined the effect of human whole saliva and dietary sugars, glucose and galactose on the adhesion and biofilm formation of Candida albicans. Biofilms of C. albicans isolate 192 887 g were developed on polystyrene, flat-bottomed 96-well microtiter plates and monitored using ATP bioluminescence and tetrazolium (XTT) reduction assays as well as the conventional colony forming unit (CFU) evaluation. Our data showed that both the ATP and the XTT assays strongly correlated with the CFU assay (ATP versus CFU: r = 0.994, P = 0.006; XTT versus CFU: r = 0.985, P = 0.015). Compared with a glucose-supplemented (100 mM) medium, galactose containing (500 mM) medium generated consistently lower levels of both candidal adhesion and biofilm formation (all P < 0.05), but a higher pace of biofilm development over time (96 h). Whist the presence of an immobilised saliva coating had little effect on either the candidal adhesion or biofilm formation, the addition of saliva to the incubation medium quantitatively affected biofilm formation especially on day 3 and 4, without any significant effect on yeast adhesion. To conclude, biofilm formation of C. albicans within the oral milieu appears to be modulated to varying extents by dietary and salivary factors and, further investigations are required to elucidate these complex interactions.

Delayed eruption of permanent teeth in hyperimmunoglobulinemia E recurrent infection syndrome.

OBJECTIVE: To determine the incidence of abnormal tooth eruption in patients with hyperimmunoglobulinemia E (hyper-IgE) syndrome. STUDY DESIGN: This study evaluated 34 individuals with hyper-IgE syndrome (age range, 2-40 years). A comprehensive dental history and a head and neck evaluation were performed on all patients. Dental age was assessed in patients younger than 17 years by 2 methods: (1) clinical assessment of tooth eruption and (2) a radiographic method. Relationships between the chronologic age, dental developmental age, and age at tooth eruption were determined. Other oral or dental anomalies were recorded. RESULTS: Of patients older than 7 years, 75% reported problems with permanent tooth eruption, as evidenced by retained primary teeth or the need for elective extractions of primary teeth to allow eruption of permanent teeth. None of the patients experienced problems with eruption of primary teeth. Eruption of the first and second permanent molars also occurred on time. Dental maturity scores were established for 14 patients 17 years of age or younger. In each case, the difference between chronologic age and the estimated dental developmental age was less than 12 months; however, we found a significant discrepancy between the chronologic age and the mean age of tooth eruption in 80% of these patients when using a particular set of standardized values. Persistence of Hertwig's epithelial root sheath was observed on histologic examination. Chronic multifocal oral candidiasis was a consistent feature in patients with hyper-IgE recurrent infection syndrome. Other oral anomalies were also noted. CONCLUSION: We confirmed that a disorder of tooth eruption is part of the hyper-IgE syndrome. This problem occurs because of delayed primary tooth exfoliation rather than a developmental delay in the formation of the permanent dentition. The persistence of Hertwig's epithelial root sheath is unusual and may be associated with the lack of resorption of the primary teeth. Dentists should be aware of this feature of hyper-IgE syndrome because timely intervention will allow normal eruption to occur.

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.

Fungal load and candidiasis in Sjögren's syndrome.

OBJECTIVE: We sought to investigate the prevalence of Candida carriage and the relationships between salivary flow rates and oral Candida load in patients with Sjögren's syndrome (SS). METHODS: The oral Candida load of patients with SS was evaluated by culturing oral rinse (swish and spit) samples. Culture, Gram stain, and wet-mount test results were reported. RESULTS: One hundred three patients (96 women) met European criteria for SS (91 with primary SS and 12 with secondary SS). The mean age (95% confidence interval) was 55 years (range, 51-57 years). Oral rinse cultures were positive in 77% of subjects. The total stimulated salivary flow rate was inversely correlated with oral Candida load (r = -0.47; P

Acquired immune deficiency syndrome: review.

PIP: Acquired immunodeficiency syndrome (AIDS) is reviewed for dental practitioners, with an emphasis on oral findings; the clinical course, diagnosis, reporting, treatment, prognosis, transmission, and epidemiology are also covered. HIV infection has an incubation period that may be associated with glandular fever, a prodrome called AIDS-Related Complex (ARC) characterized by lymphadenopathy, low fever, weight loss, night sweats, diarrhea, oral candidosis, nonproductive cough and recurrent infections. AIDS is characterized by opportunistic infections. Over 50% present with pneumocystis carinii pneumonia, 21% with Kaposi's sarcoma, and 6% have both. The AIDS virus causes direct neurological symptoms in some cases. Oral candidosis (thrush) in a young male without a local cause such as xerostomia or immune suppression is strongly suggestive of AIDS. Other oral manifestations are severe herpes simplex, varicella-zoster, Epstein-Barr virus, cytomegalovirus, venereal warts, aphthous ulceration, mycobacterial oral ulcers, oral histoplasmosis, sinusitis and osteomyelitis of the jaw. Hairy leukoplakia, usually seen on the lateral border of the tongue, is probably caused by Epstein-Barr virus. Kaposi's sarcoma, an endothelial cell tumor, is characteristic of AIDS, and in 50% of patients is oral or perioral. Cervical lymph node enlargement will be seen in those with ARC as well as AIDS. No guidelines have been issued by the Department of Health and Social Security for dental surgeons in the UK for reporting AIDS cases. Although HIV virions have been isolated from saliva, there are no known incidents of transmission via saliva. HIV is less likely to be transmitted by needle stick injuries than, for example hepatitis B (25% risk), especially if the blood is from a carrier rather than a full blown AIDS case.^ieng

Oral candidosis.

Oral candidosis is the most common opportunistic fungal infection encountered in dentistry. Normally a benign inhabitant of mucous membranes, the fungal organism, Candida albicans, may present serious, even life-threatening infection in specific patient populations. As an opportunistic organism, Candida albicans is extremely responsive to any process resulting in immunosuppression. The clinical manifestations of oral candidosis are variable, occasionally complicating the clinical diagnosis and management. Treatment is often initially rendered based on a provisional clinical diagnosis and supplemented with adjunctive laboratory tests. Specific therapeutic intervention should be tailored to the individual patient, based on the current health status of the patient and the clinical presentation and severity of the infection.

Clinical profile and risk factors for oral candidosis in sick newborns.

OBJECTIVES: To provide the clinical profile and assess the significance of various risk factors contributing to the occurrence of oral candidosis in newborns. DESIGN: Case-control study. SETTING: Neonatal Intensive Care Unit (NICU). SUBJECTS: Twenty newborns with oral candidosis and an equal number of age and weight matched controls. INTERVENTIONS: All cases of oral candidosis were treated with local application of 1% Clotrimazole. RESULTS: Oral candidosis was documented in 3.2% (20/650) cases in the NICU. Acute pseudomembranous candidosis was the most common presentation. The mean age of onset was 10.5 days. Candida albicans was isolated in 50% cases in addition to C. tropicalis, C. paratropicalis, C. krusei, C. glabrata and C. parapsilosis. On univariate analysis, male sex, birth asphyxia and prolonged antibiotic therapy had a significant correlation with occurence of oral candidosis in neonates. Out of these, birth asphyxia was the only factor significantly associated with oral candidosis (OR 8.09, 95% CI 1.34-48.8, p = 0.0226) on multivariate analysis. CONCLUSIONS: C. albicans was the predominant isolate in this series of oral candidosis. Clinical manifestations were evident in the second week of life and birth asphyxia was the most important associated perinatal event.

PIP: During February-September 1992, all 650 infants admitted to the neonatal intensive care unit of the University College of Medical Sciences and G.T.B. Hospital were screened for oral thrush. A case control study was conducted to determine risk factors for oral candidiasis in newborns. The rate of oral candidiasis in this population was 3.2% (20 cases). The most common pathogen was Candida albicans (50%). All but 1 oral thrush case had acute pseudomembranous candidiasis. 75% of oral thrush cases were asymptomatic. Mean age of onset was 10.4 days (median, 9.5 days). Clotrimazole solution was applied to oral lesions of all oral thrush cases. The multiple logistic regression revealed that birth asphyxia was the only significant factor responsible for oral thrush in newborns (odds ratio = 8.09; p = 0.0226). These findings show that the most important perinatal event associated with oral thrush in newborns was birth asphyxia.

Candidiasis: pathogenesis, clinical characteristics, and treatment.

Candida organisms live on the skin and mucous membranes of up to 75 percent of the population. They can live commensally without causing harm or can change to an aggressive form and invade tissue, causing both acute and chronic disease in the host. Oropharyngeal candidiasis manifests clinically as acute pseudomembranous, acute atrophic, chronic atrophic, chronic hypertrophic/hyperplastic, and angular cheilitis. Systemic infection leading to candidemia can be devastating and cause up to a 60 percent mortality rate in medical or post-surgical intensive care wards. Oral nystatin, clotrimazole, and fluconazole usually provide appropriate therapy; although resistance to medications is increasing, particularly in immunocompromised hosts.

Predictors and prognostic value of oral hairy leukoplakia and oral candidiasis in South African HIV-infected patients.

BACKGROUND: Oral hairy leukoplakia and oral candidiasis diseases (OHL/OC) are common clinical manifestations of HIV/AIDS. Sparse literature exists from resource-limited countries on their incidence and impact on HIV-infected patients. OBJECTIVE: To determine the predictors and prognosis of OHL/OC in HIV-infected patients. METHODS: Patients were drawn from a cohort established in 1992 and prospectively followed until 1997 in the adult HIV clinics, University of Cape Town. Cox hazards regression models were fitted to determine the predictors of OHL/OC, and the association between OHL/OC and progression to AIDS and death. RESULTS: 218 patients presenting with OHL/OC at their initial clinic visit were excluded. 205/772 patients developed OHL/OC (27.8 cases/100 years). White ethnicity (hazard ratio [HR] = 1.73, 95% CI 1.23-2.33), CD4+ count < 200 cells/(L (HR = 2.55, 95% CI 1.89-3.45), total lymphocyte count < 1250 cells/(L (HR = 1.72, 95% CI 1.28-2.31) and WHO stage 3 or 4 (HR = 2.61, 95% CI = 1.93-3.53) where variables predictive of increased hazard to developing OHL/OC. OHL/OC were independently associated with hazard of AIDS (HR = 3.65, 95% CI 1.89-6.69) and death (HR = 2.12, 95% CI 1.47-4.34). CONCLUSIONS: The presence of OHL/OC in HIV-infected patients provides important prognostic information, and can be used as a cost-effective tool for screening patients in therapeutic interventions in resource-limited settings.