Candida Organisms Research Articles

ROLE OF DENTINAL CARIOUS LESIONS IN THE PATHOGENESIS OF ORAL CANDIDIASIS IN HIV INFECTION

The authors describe a clinicopathologic study that evaluated whether dentinal carious lesions are colonized by candidal organisms--and if so, whether there is a relationship between dentinal carious lesion colonization and clinical oral candidiasis, or OC, in HIV infection. Using light microscopy, the authors examined 30 extracted teeth with dentinal carious lesions from people in each of two groups: 30 consecutively treated HIV-positive patients and 30 consecutively treated HIV-negative patients. OC was diagnosed only in HIV-positive patients (40 percent). The dentinal carious lesion pattern in both groups was similar in occlusal, root and proximal caries. Candidal colonization of carious dentinal tubules was more frequent in HIV-positive subjects than it was in HIV-negative subjects. This research shows that it may be important to restore dentinal caries in HIV-infected patients to remove a protected niche for candidal organisms.

Identification of clinically important ascomycetous yeasts based on nucleotide divergence in the 5' end of the large-subunit (26S) ribosomal DNA gene.

Clinically important species of Candida and related organisms were compared for extent of nucleotide divergence in the 5' end of the large-subunit (26S) ribosomal DNA (rDNA) gene. This rDNA region is sufficiently variable to allow reliable separation of all known clinically significant yeast species. Of the 204 described species examined, 21 appeared to be synonyms of previously described organisms. Phylogenetic relationships among the species are presented.

Granulocyte colony-stimulating factor administered in vivo augments neutrophil-mediated activity against opportunistic fungal pathogens.

Granulocyte colony-stimulating factor (G-CSF) not only increases neutrophil (polymorphonuclear leukocyte, PMNL) production but also modulates PMNL biologic function. To assess the ability of G-CSF administered in vivo to enhance PMNL activity against opportunistic fungal pathogens, the antifungal activity of PMNL obtained from normal human volunteers before and after G-CSF administration was compared. In vivo, G-CSF significantly enhanced PMNL-mediated killing of Aspergillus fumigatus and Rhizopus arrhizus by 4-fold and 15-fold, respectively (P < .05). In contrast, PMNL-mediated killing of Candida albicans was unaffected by G-CSF. The ability of aqueous fungal extracts to induce the PMNL respiratory burst was evaluated by luminol-enhanced chemiluminescence. G-CSF in vivo primed PMNL for sustained chemiluminescence in response to extracts of Candida, Aspergillus, and Rhizopus organisms. These data demonstrate that G-CSF in vivo augments antifungal activities of PMNL, thereby implicating a possible therapeutic role for G-CSF as a biologic response-modifying agent during opportunistic fungal infection.

Efficiency of PAPNET in detecting infectious organisms in cervicovaginal smears.

To evaluate the effectiveness of the PAPNET system in identifying microbial organisms. Two hundred forty-nine previously screened cervicovaginal smears with a diagnosis of an infectious agent were rescreened by PAPNET system. The images were reviewed on a high-resolution monitor and the presence or absence of coccobacilli, trichomonads, and Candida and herpes organisms was noted. Of 99 cervicovaginal smears with excessive coccobacilli, 16 were missed by PAPNET (percentage of accuracy, 84). Only 60% of Candida organisms (33 of 55) and 77% of trichomonads (42 of 54) were identified by PAPNET. Herpesvirus was diagnosed correctly on PAPNET in 24 of 41 cases. Two or more infectious agents were present in 14 cases, 5 of which were correctly identified by PAPNET. The accuracy of PAPNET in identifying infectious organism when measured against manual screening was 70%, with a high false negative rate (30%). The PAPNET system identifies coccobacilli, trichomonads and Candida organisms in decreasing order of frequency, missing a high percentage of Candida organisms and trichomonads (40% and 33%, respectively), the most common causative agents in female genital tract infections.

Candida albicans cell walls contain the fluorescent cross-linking amino acid dityrosine.

Several clinical and laboratory isolates of Candida albicans have a natural blue surface fluorescence when cultured and observed with sensitive optics. The localization and color of the fluorescence are similar to those of the natural fluorescence of sporulated Saccharomyces cerevisiae which is caused by the generation and surface deposition of the cross-linking amino acid dityrosine. In S. cerevisiae, dityrosine production results from the direct action of at least two genes and is responsible for resistance of the ascospores to lytic enzymes and physicochemical trauma. Among the criteria for the identification of dityrosine is pH sensitivity of the fluorescence intensity and a highly characteristic shift of the fluorescence excitation maximum with a change in pH. Video microscopy of whole Candida organisms revealed the characteristic dityrosine intensity maximum at pH approximately 10 and the intensity minimum at pH approximately 2. Separation of an acid hydrolysate of Candida cell walls by reverse-phase high-performance liquid chromatography revealed a fluorescence peak that coelutes with the reagent dityrosine. At pH approximately 10, this peak has a fluorescence excitation maximum of 320 to 325 nm, while at pH approximately 2, the excitation maximum is 285 to 290 nm. This excitation maximum shift and the observed emission maximum of approximately 410 nm are characteristic of dityrosine. Two separate strains of C. albicans were injected intraperitoneally into mice and harvested at 24 h. Blue surface fluorescence was observed, suggesting that dityrosine generation occurs in vivo as well as in vitro. This is the first report of the presence of dityrosine in a human fungal pathogen.

A comparison of susceptibility to five antifungal agents of yeast cultures from burn patients

Patients with significant degrees of immunocompromise, such as cancer, AIDS and large burns, who have received significant amounts of antibiotics, may develop infections with yeast organisms. Over a 3-year period, all patients with positive fungal blood cultures and most wounds of patients with large burns considered to be at risk of yeast infection were selected and tested for their susceptibility to five antifungal agents, amphotericin B, ketoconazole, miconazole, diflucan, and 5-fluorocytosine. In all, 244 specimens of yeast were tested: 142 Candida albicans, 52 Candida parapsilosis, 26 Candida tropicalis and 13 Trichosporon beigelii. A limited number of other isolates of Candida (12) were also encountered. All Candida organisms were sensitive to amphotericin B. There was wide variation in regard to the susceptibility to the other four agents with C. albicans and C. tropicalis being largely resistant to miconazole and ketoconazole. T. beigelii was recovered in 13 patients. One-half of these organisms was resistant to amphotericin B. Awareness of variations in species and susceptibility are helpful in the selection of appropriate therapeutic antifungal agents.

Specific immunohistochemical identification of Candida albicans in paraffin-embedded tissue with a new monoclonal antibody (1B12).

In invasive candidiasis, the identification of Candida organisms in tissue samples or in normally sterile fluids is essential for an accurate diagnosis. Species identification is an important clue for the source of infection and in epidemiological studies. In this article, the authors have tested the value of a new monoclonal antibody (1B12) to detect C albicans in culture by immunofluorescence, and in tissue samples by immunohistochemistry. MAb 1B12 was found to specifically recognize C albicans, does not cross-react with other Candida species or other structurally similar fungi, and is very sensitive and specific in paraffin-embedded tissue, having no reactivity in normal human tissues or necrotic areas. Therefore, MAb may be a valuable tool in the evaluation of fungal infections in paraffin-embedded tissue, particularly when Candida species identification is needed.

Mice immunized by primary vaginal Candida albicans infection develop acquired vaginal mucosal immunity.

It has been postulated that systemic cell-mediated immunity (CMI) is an important host defense mechanism against Candida infections of the vagina. However, in an estrogen-dependent murine model of experimental vaginal candidiasis, we recently showed that systemic Candida-specific Th1-type CMI induced by immunization with Candida culture filtrate antigen had no effect on vaginal Candida population levels during the course of a vaginal infection. In the present study, mice given a second vaginal inoculation in the presence of peripheral Candida-specific Th1-type CMI induced by prior vaginal infection had anamnestic-type increased delayed-type hypersensitivity (DTH) responses, concomitant with significantly fewer Candida organisms in the vagina than in primary-infected mice. In addition, organisms in secondary-infected mice were fragmented and superficial penetration into the epithelium was reduced. The systemic presence of Candida-specific T suppressor (Ts) cells that significantly suppressed the infection-derived anamnestic DTH reactivity did not abrogate the protective effect in the vagina. Additional experiments showed that vaginally immunized mice were not protected from gastrointestinal or systemic candidiasis and, in contrast to mice with a second vaginal infection, did not demonstrate anamnestic DTH reactivity. These results suggest that a moderate level of local protection against a Candida vaginal infection can be achieved by vaginal immunization but that the protective role of acquired peripheral Candida-specific Th1-type reactivity at the vaginal mucosa appears to be limited.

Candida Organisms In Dental Plaque From Aids Patients

Candida Organisms In Dental Plaque From Aids Patients

Infections due to resistant Candida species in patients with cancer who are receiving chemotherapy.

The apparent increase in the prevalence of candidal infections among patients with cancer and the changes in the spectrum of Candida pathogens infecting these patients are associated with a number of factors. Selection of less-susceptible organisms occurs because antibacterial and antifungal agents alter microbial flora, and the use of these agents can lead to mutations that confer antibiotic resistance to initially susceptible organisms. Candida organisms that are resistant to polyenes and azoles have been increasingly isolated from specimens from oncology patients, and outbreaks of infections due to these less-susceptible organisms have been reported in several centers. Antifungal resistance has largely been observed among non-albicans Candida species, especially Candida parapsilosis, Candida lusitaniae, and Candida krusei. However, there also has been an increase in the isolation of resistant Candida albicans, the more prevalent and more virulent species of Candida, from specimens from other patients. Isolation of resistant C. albicans from oncology patients has been rare, although the potential for further problems exists. These observations emphasize the importance of the selective pressure exerted by antifungal agents on the microbiological flora of patients and the influence of these agents on the prevalence and spectrum of fungal pathogens in clinical settings.

Review: microbiology of the gastrostomy tube.

This review summarizes what is presently known about microbial colonization of silicone gastrostomy feeding tubes and their deterioration. Feeding tubes are frequently colonized by fungal and bacterial organisms. Candida organisms seem to originate from the oral cavity from where they colonize the stomach and the gastrostomy tubes. It appears that many microorganisms are able to metabolize certain polymer additives, and although this is well described for polyvinyl chloride, it is not for silicone elastomers. However, clinical evidence for a role of microorganisms in the deterioration of silicone feeding tubes is very strong. The clinical significance of gastrointestinal tract seeding from gastrostomy tubes, which act as incubators, is not fully understood and deserves further study. Likewise, deterioration of feeding tubes must be investigated systematically to address the safety and economical issues it presents.

Candida infection with aneurysm formation in the juxtarenal aorta

We report a case of an elderly patient with diabetes with calcific aortic atherosclerosis in whom a juxtarenal aortic aneurysm developed after Candida fungemia. Our approach included extraanatomic reconstruction of the lower extremities, hepatorenal arterial bypass of the right kidney, retroperitoneal excision of the infected aortic segment, intravenous administration of amphotericin B after operation, and lifetime suppression of Candida organisms with oral antifungal therapy.

Immunoglobulin A (IgA), IgA1, and IgA2 antibodies to Candida albicans in whole and parotid saliva in human immunodeficiency virus infection and AIDS.

Human immunodeficiency virus (HIV)-infected individuals are predisposed to recurrent oral candidiasis, and, although it has been assumed that this is because of deficient mucosal immune responses, this has not been properly established. The present study aimed to compare the concentrations and secretion rates of immunoglobulin A (IgA) and IgA subclass antibodies to Candida albicans in whole and parotid saliva samples from HIV-infected patients, AIDS patients, and control subjects. Levels of IgA antibody to Candida species in whole saliva were higher in the HIV group than in the controls and were highest in the AIDS group (P < 0.05). In parotid saliva, the mean antibody levels were significantly greater in HIV-positive patients than in controls (P < 0.05) but fell to lower levels in the AIDS group. The secretion rates of Candida antibodies in parotid saliva were reduced in AIDS patients compared with HIV patients. The specific activities of the IgA antibodies and both subclasses were significantly higher in the HIV and AIDS patients than in the controls in both whole and parotid saliva (P < 0.05). Antibody levels were significantly correlated with the numbers of Candida organisms isolated from saliva (P < 0.05). These results suggest clear differences in salivary antibody profiles among HIV-infected. AIDS, and control subjects and are indicative of a response to antigenic challenge by infecting Candida species. No obvious defect in the mucosal immune response in the HIV or AIDS groups that might account for the increased prevalence of candidiasis was apparent.

Aerosolized amphotericin B-liposomes for treatment of systemic Candida infections in mice

Mice lethally infected with Candida albicans were exposed to small-particle aerosols containing amphotericin B-liposomes. The drug, when administered twice daily for 2 h (0.58 mg/kg of body weight per day) on days 1, 2, and 3 postinoculation, significantly reduced the numbers of Candida organisms in the kidneys. Aerosol treatment increased the survival time of mice given 2 2-h treatments once a week for 4 weeks. A twice-weekly, 2-h small-particle aerosol administration of amphotericin B-liposomes for 1, 2, or 3 weeks significantly increased both the mean time of survival and percent survival.

Candida infections in children with HIV disease

The most common fungal infection found in children infected with HIV is from the candida organ ism. This article describes the epidemiology and pathogenesis of the organism. The clinical course of the infection along with the nursing intervention is presented. A brief case presentation illus trates the psychosocial and cultural implications for care.

Nonculture methods for diagnosis of disseminated candidiasis.

Two of the nonculture approaches to the diagnosis of DC, enzymatic-fluorometric determination of serum D-arabinitol and detection of marker antigens in antigenemia (enolase and CWMP), have been commercialized and have shown promise in limited clinical trials. These approaches are not new but are the culmination of efforts made over 10 or more years. Clearly, further fine-tuning of both metabolite and antigen detection is needed to simplify the methods and to improve their sensitivity and specificity so that they will be valuable in guiding clinical treatment decisions. An alternative approach, detection of DC by DNA amplification methods such as PCR, is a special case of a compelling technology and one that is capable of standardization across microbial genera. The availability of simplified PCR diagnostic methods for DC remains a tantalizing prospect. Nevertheless, the development of methods to release DNA from very small numbers of Candida organisms in the blood in a form that is sufficiently free of inhibitors of PCR will require further intensive effort. The maturation of these converging laboratory approaches to nonculture diagnosis of DC leads to more optimism about the eventual use of these methods in clinical laboratories.

Neonatal sepsis and meningitis in Mallorca, Spain, 1977-1991.

In a retrospective study at Son Dureta Hospital (Palma de Mallorca, Mallorca, Spain) of the period 1977-1991, 334 cases of culture-proven sepsis and/or meningitis in neonates born at the facility were identified. Overall, there was an incidence rate of 4.9 cases per 1,000 live births. The case-fatality rate was 7.5%. Infection was more frequent in infants of low birth weight, with the exception of infants with meningitis and infections due to group B Streptococcus and Listeria species. The patterns of predominance among bacterial pathogens that were isolated changed during the period studied. From 1977 to 1984, Klebsiella pneumoniae was the most frequent such isolate, but this frequency declined in the following years. Group B Streptococcus organisms and Staphylococcus epidermidis replaced K. pneumoniae as the predominant pathogens in early- and Staphylococcus epidermidis replaced K. pneumoniae as the predominant pathogens in early- and late-onset infections, respectively. The frequency with which other pathogens were isolated did not vary significantly during the study period. Invasive infection caused by Candida organisms was found in two patients. The incidence of infection due to group B streptococci has increased in the last few years (to 2.4 cases per 1,000 live births in 1991) and has become a significant problem that requires a thorough epidemiological evaluation.

Candida-specific cell-mediated immunity is demonstrable in mice with experimental vaginal candidiasis

Women with recurrent vulvovaginal candidiasis often demonstrate a down-regulation of cell-mediated immunity (CMI) to Candida albicans detected by a lack of cutaneous delayed-type hypersensitivity (DTH) to Candida antigens. However, the role of systemic CMI as a host defense mechanism against recurrent vulvovaginal candidiasis is not well understood, in part because of the lack of a well-defined murine model of vaginal candidiasis. The present study was undertaken to determine: (i) whether soluble Candida culture filtrate antigens (CaCF) could be used to induce and detect Candida-specific CMI in mice and (ii) whether these antigens would be useful in detecting systemic CMI in mice given an experimental Candida vaginal infection. To this end, mice were immunized subcutaneously with CaCF in complete Freund's adjuvant, and within 7 days they developed Candida-specific DTH reactivity detected by footpad swelling (increase in footpad thickness, 0.36 mm) 24 h after footpad challenge with CaCF. Adoptive transfer studies showed that the DTH responsiveness was elicited by CD4+ DTH T cells. In mice given a vaginal inoculum of C. albicans blastoconidia (5 x 10(5)), footpad challenge with CaCF resulted in positive DTH responses (0.24 mm) as early as 1 week, responses similar to immunization in 2 to 3 weeks (0.33 mm), and sustained low levels of DTH reactivity (0.15 mm) through 10 weeks of vaginal infection. Vaginal lavage cultures revealed that peak vaginal Candida burden occurred 1 week post-vaginal inoculation (10(5) CFU) and declined 16-fold by week 10. These results provide evidence that Candida-specific systemic CMI is generated and can be detected longitudinally in mice with Candida vaginitis by a multiantigen preparation of Candida organisms which both initiates and detects Candida-specific CMI.

Oral Candida in HIV Infection and AIDS: New Perspectives/New Approaches

Oral candidosis has become an increasingly important problem in HIV-infected individuals. At present, the small body of published literature on the characterization of the Candida strains and species found in HIV+ patients is full of confusion and contradictions. Some of these difficulties are the result of the methodological shortcomings of a number of the techniques that have been used. Examples of the problems that may be encountered on primary isolation and subculture are described and the drawbacks associated with the systems used to date for phenotyping Candida are quoted. While molecular characterization techniques would appear to offer a reliable and objective alternative, they too have their strengths and weaknesses. An attempt is made to summarize the progress that has been made recently in the detection and identification of Candida albicans and also the non-albicans species from HIV-infected individuals. What emerges is that the commensal Candida species that inhabit the oral cavities of HIV+ patients are subjected to a number of significant pressures that probably promote the selection of organisms with unusual phenotypes and genotypes. These Candida are more difficult to characterize and behave differently compared to their counterparts in HIV- individuals. It is clear that uncovering the factors that are important for the selection of treatment regimens and will be predictive of outcome will not be easy. Candida organisms are neither as benign nor as simple as once thought.

Changing flora in burn and trauma units: historical perspective--experience in the United States.

Changes in patient management, increased survival rates, and widespread use of antimicrobials have altered the flora that are found to colonize the wounds of patients with burns and trauma-related injuries. Enterococci have emerged as a prominent cause of wound infection and are capable of producing significant morbidity. Staphylococcus aureus, although it remains a common colonizer, has developed resistance to several antimicrobial agents. Recent reports suggest that the incidence of Pseudomonas infections is decreasing, whereas multiple antimicrobial resistance has emerged in a number of other gram-negative organisms that were not heretofore considered major pathogens. Candida organisms appear to be the prominent pathogens among opportunistic yeasts and fungi, and Bacteroides and Clostridium species appear to be the most common causes of infection by anaerobes. Patterns of viral infection in patients with burns and trauma-related injuries have not been investigated in detail. Overall, it appears that rates of infection and associated mortality have decreased in some patient populations; progress in this regard can be attributed to improvements in antimicrobial therapy, would management, and nutrition.