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Infantile diarrhoea and malnutrition associated with Candida in a developing community.

The association of infantile diarrhoea with the occurrence of Candida species and their different morphological cell forms (pseudohyphae and/or blastospores) in faeces was studied in children of 0-15 months in a developing community (Lahore, Pakistan) where malnutrition is prevalent. Stool samples from 119 patients admitted to the Diarrhoea Treatment Unit, Department of Pediatrics, King Edward Medical College, and 46 healthy children were investigated for yeasts, bacteria, viruses and parasites. Salmonella and enteropathogenic Escherichia coli were seen in 13 (11%) each of the cases while Candida was the most frequent micro-organism, grown in cultures from 38 (32%) of the diarrhoea cases. C. tropicalis dominated (19%) over C. albicans (6%) and C. parapsilosis (3%). However, in a great number of cases (23, equals 19%), Candida did not grow in cultures but blastospores and/or pseudohyphae were seen on microscopical examination. Other Candida species and yeasts were relatively more common in the control group. Candida albicans, C. tropicalis and C. parapsilosis were the only identified agents in 23 of the cases (19%). The characteristic clinical findings in children with Candida as the only identified pathogen were malnutrition (69%), age less than 8 months (90%), and microscopically identified pseudohyphae in faecal smears (71%).

Bacterial Infections↗

Epidemiological study of Candida spp. colonization in cardiovascular surgical patients.

Candida infections involve multiple risk factors. Among the independent risk factors identified, the degree of colonization of Candida spp. allows the prediction of subsequent severe candidosis in surgical patients. The aim of this study was to assess among 13 selected variables, those that would best predict the perioperative variation of the colonization index (CI) of Candida spp. in cardiovascular surgical patients. The colonization index took into account the number of sites colonized and the density of growth. The results showed that 56.8% of our patients were colonized perioperatively. A total of 116 isolates were identified and Candida albicans accounted for 76.7% of the strains. Among the patients who developed post-surgical Candida infections, 57.1% had an increase of the CI early after the operation. By univariate analysis, three factors were significantly associated with an increase of the CI in patients after surgery; sex (female), the duration of central intravascular catheterization and the length of stay in the surgical intensive care unit (SICU). Epidemiological data could help predict those patients who are at risk of developing Candida infections.

Aged↗

Topical application of a corticosteroid destabilizes the host-parasite relationship in an experimental model of the oral carrier state of Candida albicans.

Using an experimental model in the mouse we have shown that both local and central lines of defense, involving CD4+ T cells, participate in a dynamic interaction to maintain a long-term carrier state of Candida albicans in the oral cavity. We have tested the impact of a predisposing factor to oral candidiasis in the form of a topical application of a corticosteroid (Topsyn gel) to the oral mucosa for 75 mice twice a day for a 20-day period. Very rapidly after the treatment was initiated, i.e. on day 4, the residual population of Candida increased up to 40-fold and by day 21, the population was 400-fold that of the carrier state. The resident population of intraepithelial CD4+ T cells in the oral mucosa virtually disappeared during the treatment. A topical corticosteroid application also resulted in a massive depletion of T cells in the lymph nodes and in the transient abrogation of the DTH reaction to Candida antigens. On cessation of treatment, normal levels of both Candida and intraepithelial CD4+ T cells were also quickly restored. These results suggest that resistance to superficial invasion by Candida is linked to the presence of an oral mucosal line of defense and that topical application of corticosteroids may dramatically shift the host-parasite relationship in favor of Candida.

Administration, Topical↗

Local anticandidal immune responses in a rat model of vaginal infection by and protection against Candida albicans.

Humoral (antibody [Ab]) and cellular Candida-specific immune responses in the vaginas of pseudoestrus rats were investigated during three successive infections by Candida albicans. After the first, protective infection, Abs against mannan and aspartyl proteinase antigens were present in the vaginal fluid, and their titers clearly increased during the two subsequent, rapidly healing infections. In all animals, about 65 and 10% of vaginal lymphocytes (VL) were CD3(+) (T cells) and CD3(-) CD5(+) (B cells), respectively. Two-thirds of the CD3(+) T cells expressed the alpha/beta and one-third expressed the gamma/delta T-cell receptor (TCR). This proportion slightly fluctuated during the three rounds of C. albicans infection, but no significant differences between infected and noninfected rats were found. More relevant were the changes in the CD4(+)/CD8(+) T-cell ratio, particularly for cells bearing the CD25 (interleukin-2 receptor alpha) marker. In fact, a progressively increased number of both CD4(+) alpha/beta TCR and CD4(+) CD25(+) VL was observed after the second and third Candida challenges, reversing the high initial CD8(+) cell number of controls (estrogenized but uninfected rats). The CD3(-) CD5(+) cells also almost doubled from the first to the third infection. Analysis of the cytokines secreted in the vaginal fluid of Candida-infected rats showed high levels of interleukin 12 (IL-12) during the first infection, followed by progressively increasing amounts of IL-2 and gamma interferon during the subsequent infections. No IL-4 or IL-5 was ever detected. During the third infection, VL with in vitro proliferative activity in response to an immunodominant mannoprotein antigen of C. albicans were present in the vaginal tissue. No response to this antigen by mitogen-responsive blood, lymph node, and spleen cells was found. In summary, the presence of protective Ab and T helper type 1 cytokines in the vaginal fluids, the in vitro proliferation of vaginal lymphocytes in response to Candida antigenic stimulation, and the increased number of activated CD4(+) cells and some special B lymphocytes after C. albicans challenge constitute good evidence for induction of locally expressed Candida-specific Ab and cellular responses which are potentially involved in anticandidal protection at the vaginal level.

Animals↗

Comparative evaluation of the Candida agglutinin test, precipitin test, and germ tube dispersion test in the diagnosis of candidiasis.

Normal sera and sera from burned patients were examined for Candida agglutinin titers, precipitin titers, and the ability to disperse germ tubes of Candida albicans in an attempt to determine whether germ tube dispersion is correlated with Candida infection as animal models have indicated. Other investigators have reported that immunoglobulin G antibody to Candida interferes with a serum clumping factor resulting in germ tube dispersion. Germ tube dispersion in sera from burned patients with varying degrees of Candida infection is significantly greater than that found in uninfected controls. In addition, the germ tube dispersion test indicated the presence of Candida infection in several patients who had clinical evidence of infection but no detectable agglutinins or precipitins.

Agglutination Tests↗

Faecal candida and diarrhoea.

BACKGROUND: Candida species are frequently isolated from stools of children with diarrhoea but are not proven enteropathogens. It is hypothesised that faecal candida causes diarrhoea. AIMS: To determine the prevalence of faecal candida in childhood diarrhoea and the relation between faecal yeasts and diarrhoea. METHODS: Comparison of clinical and laboratory data, including quantitative stool culture for yeasts from 107 children hospitalised with diarrhoea and 67 age matched controls without diarrhoea. RESULTS: Yeast species, predominantly candida, were identified in the stools of 43 children (39%) with diarrhoea and 26 (36%) without diarrhoea. The concentration of candida was positively associated with recent antibiotic use (p = 0.03) and with the presence of another enteric pathogen (p < 0.005), but not with patient age, nutritional status, or duration of diarrhoea. CONCLUSION: Candida species do not cause childhood diarrhoea in well nourished children.

Anti-Bacterial Agents↗

Effect of inhaled NG-nitro-L-arginine methyl ester on Candida-induced acute lung injury.

STUDY OBJECTIVES: Nitric oxide (NO) and peroxynitrite play a crucial role in acute lung injury (ALI). Whether NO synthase (NOS) inhibition is beneficial in the treatment of lung injury remains controversial. The objective of this study was to test the hypothesis that local inhibition of NOS in the lung reduces lung injury. DESIGN: We developed a model of Candida-induced ALI in the mouse by IV injection of Candida albicans. To evaluate the effect of NOS inhibitor, mice were pretreated by inhalation of saline solution or N(G)-nitro-L-arginine methyl ester (L-NAME) before induction of Candida-induced ALI. MEASUREMENTS AND RESULTS: After inhalation of 1 mM aerosolized L-NAME, nitrite-nitrate concentrations in BAL fluid (BALF) were significantly lower at 24 h and 48 h than those in mice treated with C albicans alone. Tumor necrosis factor-alpha, interleukin-1beta, and macrophage inflammatory protein-2 concentrations in lung homogenates, measured by enzyme-linked immunosorbent assay, and neutrophil counts in BALF were decreased by inhalation of L-NAME (n = 6 per group). Immunohistochemical analysis of inducible NOS (iNOS) and nitrotyrosine, a major product of protein nitration by peroxynitrite, revealed that alveolar macrophages and alveolar epithelial cells were positive for both substances in Candida-induced ALI. Inhalation of L-NAME markedly suppressed iNOS protein expression and nitrotyrosine production. Histologic evidence of lung injury decreased and survival improved after inhalation of L-NAME. CONCLUSIONS: We conclude that NO might play a crucial role in the pathogenesis of Candida-induced ALI, and such injury might be reduced by local inhibition of NOS. Our findings suggest that inhalation of L-NAME is beneficial in the treatment of Candida-induced ALI.

Administration, Inhalation↗

Candida epiglottitis in immunocompromised patients.

Candida seldom has been reported to be a cause of epiglottitis. The clinical manifestations and management of three patients with Candida epiglottitis complicating their neoplastic disease are described. All patients were granulocytopenic. Candida epiglottitis occurred either as a localized infection, as a source of Candida bronchopneumonia, or as a manifestation of disseminated infection. Candida epiglottitis may be under-diagnosed and should be considered, especially in immunocompromised patients with symptoms of refractory pharyngitis. Treatment of Candida epiglottitis with intravenous amphotericin B is warranted in patients with sustained granulocytopenia. Prompt endotracheal intubation is indicated if the airway patency cannot be maintained.

Adult↗

[Two cases of Candida endocarditis associated with abdominal disease].

Two cases of Candida endocarditis are reported. The first case was of a 63-year-old man who had a positive blood culture for Candida albicans during treatment for liver abscess and early gastric cancer. He was transferred to our department, and aortic and tricuspid regurgitation due to Candida endocarditis was diagnosed. The patient was successfully treated with aortic valve replacement, tricuspid valve plasty and anti-fungal agents. The second case was of a 65-year-old man who complained of fever. Despite a diagnosis of common bile duct cancer and resection of the tumor, the fever persisted. He was transferred to our department and was diagnosed having aortic regurgitation due to Candida endocarditis, complicated by heart failure. Although intense medical therapy including antifungal agents, diuretics, catecholamines and digoxin was initiated, the patient died from multiple embolisms 9 days later. In the treatment of Candida endocarditis, early diagnosis and early decision-making for either surgical or medical therapy is indispensable. Although the prevalence of Candida endocarditis is low, the differentiation of this disease should be taken into account in febrile elderly patients with long-standing therapy with antibiotics.

Aged↗

Evaluation of a latex agglutination test for the identification of Candida species in vaginal discharge.

BACKGROUND: The diagnosis of Candida vulvovaginitis using historical symptoms, pelvic examination findings, and results of traditional in-office laboratory tests is often inaccurate. Although Candida cultures can verify the diagnosis, they are not routinely used. METHODS: We prospectively compared the accuracy of a commercially available, in-office, rapid, latex agglutination test (CandidaSure) for the identification of Candida species with results from Candida culture. RESULTS: The sensitivity of the latex agglutination test was 66 percent and the specificity was 63 percent when compared with Candida culture results in patients with vaginal symptoms. When compared with a microscopic evaluation using potassium hydroxide (KOH), the CandidaSure test had greater sensitivity but a lower specificity. In 74 percent of cases with a positive KOH preparation, yeast forms were present on culture, and little was gained by adding the CandidaSure test in this situation. The addition of the CandidaSure test in those cases with a negative KOH preparation resulted in increased sensitivity but also increased the number of false-positive diagnoses. CONCLUSIONS: The CandidaSure test has greater sensitivity than the KOH preparation, but it is less predictive of a positive culture. Because of this limitation, Candida should be documented by culture for any patient who has recurrent or persistent disease and a negative KOH slide.

Adolescent↗

Inter and intra-specific genetic variability of oral Candida species.

In this report, strains of five different Candida species (Candida albicans, Candida guilliermondii, Candida tropicalis, Candida krusei, and Candida parapsilosis) isolated from healthy human oral cavities as well as their respective type-strains were used in order to establish the genetic diversity existing among the different species and within a certain species, by the analysis of their electrophoretic alloenzyme patterns. These profiles were analyzed for their band positions in the gels, which allowed to group the strains of the same species in species-specific clusters and to treat them as conspecific populations. A total of thirteen enzymatic loci were obtained (ACO, ADH1, ADH2, CAT, G6PDH, GDH, GOT, IDH1, IDH2, LAP, LDH, PER, and SOD). The allelic frequencies (p) and the heterozygosity (h) for all the thirteen loci were determined by diversity index formulas. The GST index is the estimated proportion of genetic diversity that was applied in order to establish inter and intra populational diversity, which, for our results, indicated that 37.75% of total genetic diversity was attributable to differences among the species and the remaining 62.25% was attributable to differences within these populations. An Euclidian distance dendrogram for the different conspecific populations was built, showing that C. guilliermondii grouped first with C. tropicalis and thus formed a expanded cluster with C. albicans. This cluster combined later with another one composed by C. parapsilosis and C. krusei. Comparing our results to the others that were obtained by different molecular techniques, we have observed that the clustering hierarchies follow different paths of organization, varying according to the methodology employed.

Journal Article↗

[A case report of pulmonary infiltration with eosinophilia syndrome induced by Candida albicans].

A sixty six-year-old female who had been treated for bronchial asthma for about 25 years was admitted to the hospital with complaints of episodes of dyspnea, eosinophilia and infiltrative shadows in the chest X-ray film. An infiltrative shadow appeared to move from the left to the right lung field and finally formed a shadow of atelectasis in the middle field of the right lung. A sputum culture showed only Candida albicans. Allergic and immunologic examination revealed high IgE serum levels with specific IgE against Candida albicans in high titer, and Aspergillus fumigatus in low titer. The precipitating antibody was shown only against Candida antigen. Additionally, the blastogenic response to Candida antigen was high in comparison with other fungal antigens including Aspergillus fumigatus. The clinical features and laboratory findings of this patient were found to satisfy Rosenberg's criteria for allergic bronchopulmonary aspergillosis (ABPA), except for the existence of Candida albicans in place of Aspergillus species as the causative antigen. The pathogenesis of PIE syndrome has been studied and various allergic mechanisms against many antigens reported. In this patient Candida albicans could be playing the crucial role in the formation of PIE syndrome, which might be best described as allergic bronchopulmonary candidiasis (ABPC).

Aged↗

[Study of in vitro activity of caspofungin on non-Candida albicans yeast strains determined by two methods: M27-A2 and EUCAST].

The in vitro activity of caspofungin against 147 non-Candida albicans yeasts isolated from blood culture was studied using two broth microdilution methods: M27-A2 and EUCAST. The minimum concentrations that produced a growth inhibition of > or = 50% and of 100% (MIC2 and MIC0, respectively) and a reduction in the number of viable colonies > or = 99% versus the initial inoculum (MFC) were determined for all strains. Caspofungin demonstrated good activity (MIC2 and MIC0 < or = 2 mg/l for 90% of the strains) against the species studied, including those that are normally resistant or have a high percentage of azole resistance (Candida krusei, Candida glabrata, Candida tropicalis). Nevertheless, the antifungal activity is lower (MFC < or = 2 mg/l in 73.47% of the strains with the M27-A2 method versus 62.59% with EUCAST), particularly for Candida guilliermondii and Candida parapsilosis. The two methods tested demonstrated good correlation for the MIC and lower correlation for the MFC. Essential agreement and concordance (+/- 2 log) between both methods for all strains tested were: 73.47% and 93.20% for MIC2; 74.8% and 91.84% for MIC0; and 57.1% and 74.15% for MFC, respectively. MICs determined by the EUCAST method are one- to three-fold dilutions lower, while the MFC are higher than those obtained by the M27-A2 method.

Antifungal Agents↗

[Candida arthritis: report of two cases].

Candida arthritis is extremely rare. However, there has been a steady increase in the incidence of candida arthritis during the last decade because of increasing candida infections in immunocompromised hosts, drug addicts, premature babies, and those who have received prosthetic joint operations or intraarticular injections of steroids. We report herein two cases of candida arthritis: a 27-year-old man with aplastic anemia and transfusional hemosiderosis, and a 60-year-old man with osteoarthritis who received repeated intra-articular injections of steroids. Definite diagnoses were made after repeated smear examinations of synovial fluids. In the first case, candida arthritis occurred about 2 weeks after an antecedent candidemia. Although the arthritis relapsed once due to inadequate antifungal treatment, it was finally successfully treated with systemic amphotericin B, oral ketoconazole and surgical drainage of the synovial fluid. In the second case, it took several months to make the diagnosis. The patient was also treated with amphotericin B, ketoconazole, and surgery with a satisfactory outcome. We conclude that since candida arthritis is a slow, less destructive joint infection, it can almost always be resolved. Also, late orthopedic complications can be avoided by early diagnosis and prompt treatment, including aggressive antifungal therapy, adequate drainage and necessary surgical intervention.

Adult↗

Validity of the Papanicolaou Smear in the Diagnosis of Candida spp., Trichomonas vaginalis, and Bacterial Vaginosis.

OBJECTIVE: To determine the validity of the Papanicolaou smear in the diagnosis of bacterial vaginosis, Trichomonas vaginalis, and Candida spp. MATERIALS AND METHODS: We determined the sensitivity, specificity, positive predictive value, and negative predictive value of Pap smears we performed in 824 symptomatic patients. We compared Pap smear diagnoses with those obtained by standard microscopic examination and Gram stain of the exudate. RESULTS: The sensitivity of the Pap smear for Candida spp. was 31%, 57% for BV, and 51% for T. vaginalis. The specificity for Candida was 98.5%, 94% for BV, and 97% for T. vaginalis. The PPV for Candida was 85%, 70% for BV, and 57%for T. vaginalis. The NPV for Candida was 84%, 90% for BV, and 97% for T. vaginalis. CONCLUSION: The sensitivity of Pap smears for Candida spp., BV, and T. vaginalis is inadequate for screening. Pap smear that are positive for T. vaginalis could be used to complement the diagnosis.

Journal Article↗

Prospective evaluation of blind brushing of the esophagus for Candida esophagitis in patients with human immunodeficiency virus infection.

We prospectively evaluated the diagnostic value of blind brushing of the esophagus via nasogastric tube in 66 patients with human immunodeficiency virus (HIV) infection [acquired immune deficiency syndrome (AIDS) (N = 59), or AIDS-related complex (ARC), (N = 7)] complaining of odynophagia and/or dysphagia. Brushings were obtained between 20 and 35 cm from the incisors. Patients then underwent upper endoscopy with directed brushings and biopsies; esophageal lavage was also done in the first 40 patients. Candida esophagitis was defined as an abnormal appearance of the esophageal mucosa, together with microscopic evidence of pseudohyphae in the endoscopic brushings or invasive candidiasis on biopsy. The presence of oral thrush was also recorded. Candida esophagitis was present in 28 (42%) of the 66 patients. Blind brushings diagnosed candidiasis in 27/28 cases and produced five false positives (sensitivity 96%, specificity 87%). Blind brushing of the esophagus was significantly more sensitive than the presence of oral thrush for the diagnosis of esophageal candidiasis (p = 0.02). Oral thrush was found in only 20/28 cases of Candida esophagitis and in eight patients without Candida (sensitivity 71%, specificity 79%). Esophageal lavage yielded Candida in all cases (sensitivity 100%) but had a poor specificity (64%). We conclude that blind brushing of the esophagus is a rapid, safe, and economical way to diagnose Candida esophagitis in patients with AIDS. This procedure can be performed by primary care physicians with minimal loss of sensitivity and specificity as compared to endoscopy.

Acquired Immunodeficiency Syndrome↗

[A case of candida endocarditis with consecutive measurement of serum mannan and D-arabinitol concentrations].

We encountered a case of an 83-year-old patient with candida endocarditis. He had been diagnosed as having aortic regurgitation with moderately calcified aortic valve 5 years previously, and had received medication. He was admitted to our hospital because of pancreatic cancer. He had high fever from the time of his admission and antibiotics produced no effect. Candida albicans was detected in arterial blood culture. We also detected antibody against Candida albicans, and investigated serum mannan and the D-arabinitol creatinine ratio several times. We performed echo-cardiographic examination and recorded a vegetation at the aortic valve. Rising antibody titers against Candida albicans, mannan antigenemia and an elevated creatinine ratio were also observed. So we concluded that these examinations were also effective in the diagnosis of candida infection. Finally, this patient died of cerebral hemorrhage and was autopsied. Macroscopic findings showed mass-like vegetation involving the aortic valve, and microscopic findings showed candida organisms scattered within the vegetation.

Aged↗

The association between dietary intake and reported history of Candida vulvovaginitis.

The association between dietary intake and the history of Candida vulvovaginitis was evaluated in 166 women who had a history of Candida vulvovaginitis in the past 5 years (cases) and in 207 women without such a history (total population), as well as in 74 women with five or more episodes in the past 5 years and 125 women with no history of Candida vulvovaginitis. Women were interviewed about their demographic data, past medical and sexual history, and their history of vaginal or pelvic infections. An extensive dietary history was taken to determine each woman's usual adult dietary intake. Results indicate associations between total caloric intake, carbohydrates, and fiber and a history of Candida vulvovaginitis. The results were not altered by controlling for age, body mass index, smoking, use of oral contraceptives, and sexual activity variables. These results suggest several dietary constituents may influence susceptibility to Candida vulvovaginitis infections. A follow-up prospective study, using culture confirmation of Candida infection, is needed.

Adult↗