Candida endophthalmitis after heroin abuse

Three cases of ocular candidosis involving heroin abusers have been observed in 1983 in Toulouse department of ophthalmology. These three patients had used iranian brown heroin. Twenty similar cases have been published in these last years. This new pathology can be explained on two reasons. The first is that the drug abusers have some immunity pertubation; however, immunity exploration in these patients does not reveal any immunodeficiency. The second reason, certainly more important, is the method of using heroin. The diagnosis of Candida endophthalmitis of course based on clinical context must be proved by biological tests. Candida albicans is never identified in aqueous humor. For this reason, it seems very interesting to detect anti-candida antibodies in aqueous humor. It has been used as methods of dosage laser Nephelemetry for IgG and immunofluorescence for candidosis antibodies. The criterion used is similar to the toxoplasmosis coefficient established by Desmonts (3). In two cases, this test was the only way that permits us to have certitude of candidosis ocular diagnosis. Otherwise the observations show that anterior chamber punction is more significant when there is an anterior uveitis.     

Serotypes of Candida albicans isolated from HIV positive patients.

Twenty-one HIV-positive patients in different stages of the disease were studied to evaluate candidosis in the oral cavity. All patients in clinical category C were infected with Candida. The most frequently observed clinical forms were pseudomembranous and hypertrophic, in contrast to reports by other authors. Candida albicans was the species isolated in these HIV-positive patients. Alterations of cell-mediated immunity were reflected in the negativity of intradermal test. The predominant serotype of C. albicans in these patients was A, in agreement with what has been found in non-immunosuppressed patients in Venezuela. There was no correlation between the serotype of C. albicans and the clinical forms of candidosis. Based in our results and those of other authors, no conclusions can be drawn concerning a particular serotype as an indicator of immunosuppression.     

Salivary pH and culture determinations in HIV infected and non-HIV infected patients with oral candidosis

The aim of the present study was to determine the salivary pH in HIV (Human Immunodeficiency Virus) positive(+) and negative(-) patients and in a control group, for assessing if variations or changes in pH are related to the development of oral candidosis and the species isolated. The sample comprised 120 patients from the Infectology Unit of the Mexico General Hospital, and from the School of Dentistry, UNAM. Three study groups were performed: with oral candidosis HIV+, with oral candidosis HIV-, and a control group. All patients filled out a clinical data questionnaire and signed an informed consent document. A 2 ml sample of non-stimulated saliva was obtained from each patient. The pH was measured and the sample was cultured on dextrose Sabouraud agar. The Candida species determinations were performed by the API 20 C AUX system and statistically analyzed. In the HIV+ group, the pH mean was 6.17, with most prevalence of Candida albicans type I and pseudomembranous candidosis. In the HIV- group prosthesis users, the pH mean was 6.29, with most prevalence of C. albicans type I, but with erythematous candidosis. The control group showed a mean pH of 6.78. A statistically significant difference among pH values was found (F= 15.45 p<0.01). The present study revealed that in HIV+ patients, the most significant predisposing factors are: immunosuppression, antibiotic therapy, bad hygiene, anemia, leucoplakia, and diabetes. The salivary pH with acidic values (more in HIV+ patients) significantly favors candidosis development, specially for C. albicans and C. glabrata species and primarily the pseudomembranous and erythematous clinic types. The pH is not a determinant for Candida growth, but could affect the adherence and invasiveness of the yeast.     

Pathogenic Dermatophytes Survive in Nail Lesions During Oral Terbinafine Treatment for Tinea Unguium

Tinea unguium caused by dermatophyte species are usually treated with oral antimycotic, terbinafine (TBF). To understand the mechanisms of improvement and recalcitrance of tinea unguium by oral TBF treatment, a method of quantifying dermatophyte viability in the nail was developed, and the viability of dermatophytes was analyzed in toenail lesions of 14 patients with KOH-positive tinea unguium treated with oral TBF 125 mg/day for up to 16 weeks. Mycological tests, including KOH examination and fungal culture, and targeted quantitative real-time PCR for internal transcribed spacer (ITS) region, including rRNA, were demonstrated at the initial visit and after 8 and 16 weeks of treatment. Assays in eight patients showed that average ITS DNA amount significantly decreased, to 44% at 8 weeks and 36% at 16 weeks compared with 100% at initial visit. No significant difference was observed between at 8 and 16 weeks, despite the TBF concentration in the nail supposedly more than 10-fold higher than the minimum fungicidal concentration for dermatophytes. This finding suggests the pathogenic dermatophytes in nail lesions could survive in a dormant form, such as arthroconidia, during oral TBF treatment. Both antimycotic activity and nail growth are important factors in treatment of tinea unguium.     

Clotrimazole as a pharmaceutical: past,present and future.

Clotrimazole is a broad‐spectrum antimycotic drug mainly used for the treatment of Candida albicans and other fungal infections. A synthetic, azole antimycotic, clotrimazole is widely used as a topical treatment for tinea pedis (athlete's foot), as well as vulvovaginal and oropharyngeal candidiasis. It displays fungistatic antimycotic activity by targeting the biosynthesis of ergosterol, thereby inhibiting fungal growth. As well as its antimycotic activity, clotrimazole has become a drug of interest against several other diseases such as sickle cell disease, malaria and some cancers. It has also been combined with other molecules, such as the metals, to produce clotrimazole complexes that show improved pharmacological efficacy. Moreover, several new, modified‐release pharmaceutical formulations are also undergoing development. Clotrimazole is a very well‐tolerated product with few side effects, although there is some drug resistance appearing among immunocompromised patients. Here, we review the pharmaceutical chemistry, application and pharmacology of clotrimazole and discuss future prospects for its further development as a chemotherapeutic agent.     

Cell surface hydrophobicity of Candida albicans isolated from elder patients undergoing denture‐related candidosis

Background: The virulence potential of Candida albicans strains enrolled in denture‐related candidosis still remains uncertain. Candida albicans cells with higher cell surface hydrophobicity (CSH) rates, so‐called hydrophobic, present higher adhesion success in different host tissues than cells with lower rates, or even hydrophilic. Objective: The proposition of this study was to evaluate the differences in the CSH of strains isolated from denture users with and without denture‐related candidosis. Material and methods: The strains were obtained from two paired groups of patients living a same retirement house. Fungal cells were submitted to CSH evaluation by the hydrocarbon partition test using xylene. Results: The measures revealed that the yeasts from patients with candidosis had CSH values ranging from 4.52% to 12.24%, with an average of 8.22 ± 2.92%. In the countergroup, the CSH ranged from 3.86% to 14.36%, with an average of 8.38 ± 3.76%. The difference between the groups were considered not relevant (p = 0.997). Conclusion: The results let to the inference that natural populations of C. albicans from patients with and without clinical manifestation denture‐related candidosis do not differ one from the other regarding to CSH.     

Candida glabrata, Candida parapsilosis and Candida tropicalis: biology, epidemiology, pathogenicity and antifungal resistance

The incidence of infections caused by Candida species (candidosis) has increased considerably over the past three decades, mainly due to the rise of the AIDS epidemic, an increasingly aged population, higher numbers of immunocompromised patients and the more widespread use of indwelling medical devices. Candida albicans is the main cause of candidosis; however, non-C. albicans Candida (NCAC) species such as Candida glabrata, Candida tropicalis and Candida parapsilosis are now frequently identified as human pathogens. The apparent increased emergence of these species as human pathogens can be attributed to improved identification methods and also associated with the degree of diseases of the patients, the interventions that they were subjected and the drugs used. Candida pathogenicity is facilitated by a number of virulence factors, most importantly adherence to host surfaces including medical devices, biofilm formation and secretion of hydrolytic enzymes (e.g. proteases, phospholipases and haemolysins). Furthermore, despite extensive research to identify pathogenic factors in fungi, particularly in C. albicans, relatively little is known about NCAC species. This review provides information on the current state of knowledge on the biology, identification, epidemiology, pathogenicity and antifungal resistance of C. glabrata, C. parapsilosis and C. tropicalis.     

Persistent colonization and transient suppression of DTH responses in an estrogen-dependent vaginal candidosis murine model

Recurrence of vaginal candidosis in women of childbearing age has been attributed to several predisposing factors including the presence of significant amounts of estrogen in the reproductive tract. In this study, the effect of estrogen on the level of C. albicans colonization, persistence of infection and suppression of DTH responses was investigated in an estrogen-dependent vaginal candidosis murine model. Mice were first injected subcutaneously with 0.5 mg of estradiol valerate 72 hours prior to C. albicans intravaginal inoculation and at weekly intervals thereafter for a period of up to 4 weeks; the inoculum consisted of 2 x 10(7) stationary-phase C. albicans blastoconidia in a volume of 20 microl. C. albicans colonization was evaluated in the spleen, liver, kidney, small intestine and reproductive tract of estrogen-treated and control mice 72 hours following inoculation, DTH responses were evaluated 2 and 5 weeks following primary inoculation and persistence of infection was evaluated at days 2, 3, 4, 8, 12, 19 and 26 post inoculation. Estrogen-treated mice exhibited higher levels of C. albicans colonization compared with control mice; this was most evident in the small intestine and reproductive tract. Estrogen treatment resulted in pronounced suppression of C. albicans-specific DTH responses; in that average footpad swelling was 4.7 mm in untreated mice compared with 2.3 mm in estrogen-treated mice. Long-term estrogen treatment resulted in the persistence of infection; in contrast, C. albicans infection resolved by day 8 post inoculation in untreated mice. DTH responses assayed 5 weeks post primary inoculation in treated mice were on average 4.1 mm, this was similar to that observed in untreated mice tested for DTH response 2 and 5 weeks post primary inoculation. These results suggest that, on the one hand, estrogen has an enhancing effect on C. albicans colonization and persistence of infection. On the other, estrogen seems to suppress DTH responses within the first 2 weeks post infection; persistence of infection under the influence of estrogen, however, seems to coexist with detectable systemic cell-mediated immunity.     

Detection of Candida albicans in disseminated candidosis by immunofluorescence staining

An indirect immunofluorescence (IF) method using rabbit anti-Candida albicans was used to detect C. albicans in blood samples of 12 patients with systemic candidosis defined clinically, histologically and by blood cultures. Positive staining of C. albicans could be detected in all of the patients. The findings suggest that IF-method offers a more rapid method in the diagnosis of disseminated candidosis.     

Western blot analysis of cerebrospinal fluid for detection ofAspergillus antigens

Western-blot immunoassay of cerebrospinal fluid (CSF) specimens of patients with central nervous system (CNS) aspergillosis (3), CNS candidosis (1) and bacterial meningitis (2) was carried out using pooled serum from histopathologically proven deep-seated aspergillosis cases to detect unique antigenic fractions for aspergillosis in CSF. No reactivity was observed in patients with non-fungal meningitis. Four cross-reactive bands (40, 90, 200 and >200 KD) were detectable in CSF from patients with both aspergillosis and candidosis of the CNS. Four additional bands (90–200 KD) were consistently present only in patients with aspergillosis. One prominent band (110 KD) was found only in the patient with aspergillosis who had a fatal outcome and raised the possibility of being a poor prognostic marker.     

Oral candidosis: characterization of a sample of recurrent infections and study of resistance determinants

Recurrent oral candidosis is a common problem in immunocompromised patients, and it is frequently triggered by resistance induced by antifungal treatment. Knowledge of the mechanisms by which the yeast persists in the host could allow the management of this type of infection. This study used electrophoretic karyotyping and restriction fragment length polymorphism based on the use of 27A probe to study 12 pairs of Candida albicans isolates from patients with recurrent candidosis to distinguish new infections from relapses caused by the same strain responsible for the first episode. Subsequently, RT-PCR was used to evaluate expression of CDR1, CDR2 and MDR1 genes, which are involved in C. albicans azole resistance, in the three pairs that consisted of variants of the same strain. Restriction polymorphism resulted in better discrimination than with karyotyping in defining differences between strains. In one case, RT-PCR allowed us to identify deregulation of efflux pump genes as the possible underlying mechanism in recurrent candidosis. The techniques employed resulted effective for the characterization of recurrent oral candidosis. Broader analysis could help to control better these infections and choose adequate therapy.     

Structure-Biological Activity Relationships in Alfalfa Antimycotic Saponins: The Relative Activity of Medicagenic Acid and Synthetic Derivatives Thereof Against Plant Pathogenic Fungi1

The antimycotic activity of medicagenic acid and of some synthetic derivatives thereof was tested against plant pathogenic fungi. In general they all possess antimycotic activity. Furthermore, in the case of Sclerotium rolfsii, compounds where the hydroxyl functions of the aglycon remained unchanged (medicagenic acid and its dimethyl ester) or could be enzymically released (3-0-β-D-glucoside of medicagenic acid dimethyl ester) were significantly more active than compounds where these functions were modified by acetylation or methylation. Selective 2-0-methylation of medicagenic acid and comparison of the antimycotic activity of the resulting derivative against S. rolfsii to that of other derivatives suggests that a potential free hydroxyl at position 3 is essential to antimycotic activity.     

Outbreak of systemic Candida albicans in intensive care unit caused by cross infection.

The first documented outbreak of systemic candidosis shown to be due to cross infection with a particular strain of Candida albicans is reported. Over nine months in an intensive care unit 13 patients developed definite and one probable systemic candidosis. Twenty five further patients had superficial candidal infections. The strain that caused the outbreak (serotype A, morphotype A1, biotype 0/(1)5 5/7) was responsible for all the cases of systemic candidosis acquired in the intensive care unit, 11 (44%) of the superficial candidal infections in the unit, and 17% of candidal infections outside the unit but in the same hospital. The strain was also isolated from oral swabs taken from four nurses working in the unit and the hands of one of these nurses. Two out of 17 nurses were shown to have acquired the strain on their hands when examined immediately after nursing systemically infected patients. No environmental source could be identified. The strain also showed enhanced survival in handwashing experiments and was relatively resistant to Hibiscrub. Management of patients with systemic candidosis might include measures to prevent cross infection and handwashing with disinfectants that are active against candida.     

Contribution to the study of dermatomycosis in Catalonia

We report the results of a study which aim was the mycological identification of specimens coming from patients included in a clinical trial. A total of 445 specimens from patients with clinical diagnosis of dermatomicosis were processed during 8 months (138 pityriasis versicolor, 28 cutaneous candidosis and 279 dermatophytosis). A 48% of pityriasis versicolor cultures were positive for Malassezia furfur, 50% of candidosis cultures were positive for yeasts and 67% of dermatophytosis cultures were positive for dermatophytes. According to our results Candida albicans was the principal causative agent for cutaneous candidosis and Trichophyton mentagrophytes and Trichophyton rubrum were the most frequent isolated species causing dermatophytosis.     

Rapid enzyme-linked immunosorbent assay (ELISA) for detection of IgG antibodies to Candida albicans

A rapid enzyme-linked immunosorbent assay (ELISA) where the performance time was shortened to 4h was compared with counter-immunoelectrophoresis (CIE) and a standard ELISA procedure for the detection of IgG antibodies to Candida albicans in 61 patients with suspected invasive candidosis. Using a C. albicans cytoplasmic antigen the rapid ELISA compared well with CIE and the standard ELISA. Seventeen sera that reacted with two concentrations of C. albicans antigen in CIE were also positive in both forms of ELISA. Four sera that were CIE-negative were positive in the standard ELISA and three were also positive in the rapid ELISA. The rapid ELISA provides a sensitive and reproducible test for routine serological investigation of different forms of candidosis.     

Miconazole Gel Increases the Cure Rate of Helicobacter pylori Infection When Added to Lansoprazole and Amoxicillin in a Randomized Trial

Background. Miconazole is an antimycotic agent with bacteriocidal activity against Helicobacter pylori in vitro. Its role in the clinical eradication of H. pylori has not been studied. The objective of this study was to investigate the efficacy and side effect profile of miconazole for the treatment of H. pylori.
Materials and Methods. We studied 65 patients with gastritis or peptic ulcer disease in whom H. pylori infection was confirmed by a rapid urease test and microbiologic assessment. In vitro miconazole sensitivity was assessed for the H. pylori strains isolated from the enrolled patients. All patients were randomized to receive either dual therapy consisting of lansoprazole 30 mg daily and amoxicillin 500 mg three times a day for 14 days (LA, n = 33) or triple therapy using the LA regimen plus miconazole gel 100 mg three times a day for 14 days (LAM, n = 32). At least 8 weeks after the treatment, successful therapy was validated by the histological and microbiologic assessment. Adverse effects and drug adherence were monitored by direct questioning.
Results. The minimum inhibitory concentrations of miconazole ranged from 3.13 to 6.25 mg/L. H. pylori was eradicated in 16 of 33 patients (48%, 95% CI = 31% to 67%) after LA therapy, and 24 of 32 patients (75%, 95% CI = 59% to 91%) after LAM therapy ( p < .03). There was no significant difference in the occurrence of adverse events between the two groups.
Conclusion. The addition of miconazole gel to the LA regimen significantly improved the cure rate of H. pylori without an increase in adverse effects.     

IgA and IgG antibodies to Candida albicans in the genital tract secretions of women with or without vaginal candidosis

Levels of anti-Candida albicans immunoglobulin A (IgA) and IgG were measured by enzyme-linked immunosorbent assay in serum and cervicovaginal secretions from 64 non-pregnant women with vaginal candidosis and 158 uninfected non-pregnant women. Specific IgA and IgG were detected in the serum and secretions of all 222 women. There was no significant difference between the mean levels of specific IgA or IgG in secretions from women with candidosis and those of uninfected women. Neither was there a significant difference between mean levels of specific IgA or IgG when women using oral contraception were compared with others who were not. There was a significant correlation between the levels of IgA and IgG in serum and secretions from women with candidosis and from uninfected women. Blastospore and hyphal forms of C. albicans were seen in vaginal smears from 29 of the 64 women with culture-proven candidosis: in nine, both IgA- and IgG-coated C. albicans cells were recovered from the genital tract; in a tenth, IgG-coated cells were found.     

The vaccine metaphor. From inoculation to vaccination]

The episodes of cowpox inoculation (1798) and rabies preventive treatment (1885) are celebrated as the landmark of modern medicine. Paradoxically, these two advances have been accomplished without any theoretical breakthrough in the understanding of immunity. Going further, they were made possible by a long past of empirical procedures among which smallpox inoculation played an outstanding role. The paper explores the paradox of 'Immunization without Immunology' and Pasteur's reconstruction of the past, through his successful use of a metaphor. 'Vaccine', originally linked to the jennerian method, was meant by Pasteur to designate a general program of virus attenuation. The paper investigates the scientific factors accounting for why viruses played such a leading role in immunization. The longlasting immunity, the easy transmission from man to man characteristic of smallpox allowing in vivo experimentation, may explain how crude procedures of early immunizers shaped scientific ideologies and strategies of public health and family initiated modern 'vaccinology'.