Recurrent Vaginal Candidiasis Research Articles

Integrating Clinical and Microbiological Expertise to Improve Vaginal Candidiasis Management.

Vaginal candidiasis (VC) is a prevalent condition among women of reproductive age and poses a significant global public health challenge. However, the disease is often diagnosed and treated without mycological information. We investigated the epidemiology, laboratory diagnostics, and antifungal susceptibility of VC. We included 300 women from Çukurova University Obstetrics and Gynecology outpatient clinic in Adana, Türkiye. Participants underwent a health survey and provided vaginal swab samples for microscopic examination and fungal culture. The microscopic analysis involved wet-mount and gram-stained slides, whereas fungal identification involved CHROMAgar Candida, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and real-time polymerase chain reaction high-resolution melting analysis (RT-PCR HRMA). Antifungal susceptibility tests were conducted at pH 7 and 4 using the CLSI document M44-A2. Of the 106 women with positive fungal cultures, 86.8% were diagnosed with VC, whereas 13.2% showed Candida colonization. Among those with VC, 55.4% had acute and 44.6% had recurrent VC; a family history of allergies increased the risk for both types. We recovered 115 yeast isolates, predominantly C. albicans, C. glabrata, and C. krusei. Diagnostic accuracy of CHROMAgar Candida was 91.3% for the most common isolates, and HRMA was consistent in differential diagnosis. Antifungal resistance varied with pH; susceptibility to fluconazole, itraconazole, and ketoconazole decreased at pH 4, whereas susceptibility to miconazole increased. Our findings underscore the need for a diagnostic algorithm and enhanced collaboration between clinicians and microbiologists to improve VC management. Recommendations include using Gram staining, CHROMAgar Candida, MALDI-TOF MS, and antifungal susceptibility tests at both pH levels.

Vaginal candidiasis, predisposing factors, symptoms and treatment

Introduction: Vulvovaginal candidiasis is a disease caused by Candida species, mainly Candida albicans species, which can be colonizing the vaginal microbiota of healthy women, without causing disease. Due to its high prevalence, it is one of the most frequent causes of gynecological consultation. It occurs mainly in women after puberty, worldwide it is estimated that at least 75% of women have had candidiasis at least once in their lives. Its clinical signs are itching, vaginal inflammation and white discharge. It is diagnosed by laboratory tests or culture. A higher frequency of candidiasis occurs in women with high estrogen load or some degree of immunodeficiency. Treatment consists of azole antifungals, particularly fluconazole. The present study consists of a systematic review of the existing literature related to vulvovaginal candidiasis, focusing on epidemiology, clinical signs, diagnosis and treatment. Material and methods: The study design is a literature review for which a search and evaluation of the existing literature and previous research on vaginal candidiasis will be carried out through the databases PubMed, Google Academic, Scielo, Sciendirect, among others. For this purpose, inclusion criteria will be used through searches related to "Candida", "vaginal candidiasis", "recurrent vaginal candidiasis", "vaginal candidiasis predisposing factors" and "candidiasis literature review". Results: Vaginal candidiasis is an infection caused by the overgrowth of Candida albicans, a type of yeast-like fungus that normally lives in the vagina. Predisposing factors include antibiotic use, increased estrogen levels, uncontrolled diabetes, overweight, pregnancy, premenstrual period, taking corticosteroids, and high doses of estrogen. Treatment of vaginal candidiasis includes antifungal medications, such as single-dose oral fluconazole, and avoidance of excess moisture. In uncomplicated vulvovaginal candidiasis, all available forms of antifungals are highly effective, both oral and topical, whereas in complicated vulvovaginal candidiasis, a longer course of 5-7 to 10-14 days of conventional therapy should be performed. Patients who have frequent recurrences require their long-term pressure with oral medications. Conclusion: It is important for health care professionals and patients to be aware of the risks of recurrence so that timely treatment can be provided to patients

Fungal infections in Algeria

Invasive and superficial fungal infections are increasingly reported in Algeria, testifying to the increase in their frequency in parallel with the increase in risk factors and the availability of diagnostic means, at least in university hospitals (CHU). The latter, located in the major northern cities, are equipped with high-performance diagnostic tools compared to hospitals in the interior of the country. A comprehensive search of published and grey literature was undertaken. Prevalence and incidence of discrete fungal diseases were estimated using a deterministic modelling approach based on populations at risk. Population (2021) and major underlying disease risk groups were obtained from UNAIDS, WHO Tuberculosis and the international transplant registries as well as published data for asthma and COPD. The health service profile was summarised from national documentation. Among the 43.6 million, including 12.9 million children, living in Algeria, the most prevalent fungal diseases are tinea capitis (>1.5 million), recurrent vaginal candidiasis (>500,000) and allergic fungal lung and sinus disorders (>110,000) and chronic pulmonary aspergillosis (>10,000). Life-threatening invasive fungal infection incidence includes 774 Pneumocystis pneumonia in AIDS, 361 cryptococcal meningitis, 2272 candidaemia and 2639 invasive aspergillosis cases. Fungal keratitis probably affects >6000 eyes each year. Fungal infections are underestimated in Algeria because they are sought in patients with risk factors only after bacterial infections when they should be sought in parallel. The diagnosis is only accessible in hospitals in large cities and the work carried out in mycology is rarely published, making the estimation of the burden of these conditions difficult.

Updated estimation of the burden of fungal disease in Vietnam.

Anecdotally, the burden of fungal diseases in Vietnam is rapidly rising, but there has been no updated estimate on this issue since a previous report in 2015. In this study, we aimed at estimating the incidence and prevalence of serious fungal infections for the year 2020. We made estimates with a previously described methodology, using reports on the incidence and prevalence of various established risk factors for fungal infections from local, regional or global sources. We estimated 2,389,661 cases of serious fungal infection occurred in Vietnam in 2020. The most common condition was recurrent vaginal candidiasis (4047/100,000 women annually). Among people living with HIV, we estimated 451 cases of cryptococcal meningitis, 1030 of pneumocystis pneumonia, 166 of histoplasmosis and 1612 of talaromycosis annually. Candidaemia incidence was estimated at 12/100,000 population each year. Owing to its high burden of tuberculosis and respiratory diseases, Vietnam had high rates of severe infections caused by Aspergillus species. Incidence of invasive aspergillosis is 24/100,000 population, allergic bronchopulmonary aspergillosis 78/100,000 and severe asthma with fungal sensitisation 102/100,000. Five-year period prevalence of chronic pulmonary aspergillosis is 120/100,000 population /5-year period. Mucormycosis, fungal keratitis and tinea capitis were estimated at 192, 14,431 and 201 episodes each year, respectively. The number of patients with mycoses in Vietnam is likely underestimated due to a lack of local data and limited diagnostic capacity, but at least 2.5% of the population might have some form of serious fungal disease.

Ezrin Peptide Therapy from HIV to COVID: Inhibition of Inflammation and Amplification of Adaptive Anti-Viral Immunity.

Human Ezrin Peptides (HEPs) are inhibitors of expression of IL-6 and other inflammatory cytokines, amplifiers of adaptive B cell and T cell immunity and enhancers of tissue repair. The mutation stable C-terminus of HIV gp120, mimics 69% of the “Hep-receptor”, a zipped α-helical structure in the middle of the α domain of human ezrin protein. Synthetic peptides homologous to the Hep-receptor of ezrin of five to fourteen amino acids, activate anti-viral immunity against a wide range of viruses (HIV, HCV, herpes, HPV, influenza and other human respiratory viruses). Human Ezrin Peptide One (HEP1) TEKKRRETVEREKE (brand name Gepon, registered for human use in Russia from 2001) is a successful treatment for opportunistic infections in HIV-infected patients. That treats HEP1and prevents mucosal candidiasis, herpes zoster outbreaks and infection-induced chronic diarrhea. There are clinical publications in Russian on the successful treatments of chronic recurrent vaginal candidiasis, acute and chronic enterocolitis and dysbacteriosis, which are accompanied by normalization of the mucosal microbiome, and the decline or disappearance of inflammation. HEP1 is also an effective treatment and prevention for recurrent inflammation and ulceration in the stomach, duodenum and colon. HEP1 and RepG3 GEKKRRETVEREGG (a derivative of HEP1) have been used successfully as an inhaled spray peptide solution to treat a small number of human volunteers with mild-to-moderate COVID, resulting from SARS-CoV-2 infection, based on earlier successes in treating acute viral respiratory disease with inflammatory complications. Ezrin peptides seem to correct a dysregulation of innate immune responses to SARS-CoV-2. They are also adjuvants of B cell adaptive immunity and increase antibody titres, resulting in protection from lethal virus infection of mice. In a clinical study in Moscow, orally administered HEP1 was shown to enhance antibody-titres produced in response to hepatitis-B vaccination. These very preliminary but promising results with ezrin peptide treatment of COVID must be replicated in large-scale randomised placebo controlled clinical studies, to be verified.

3D printed clotrimazole intravaginal ring for the treatment of recurrent vaginal candidiasis

Vulvovaginal candidiasis is a vaginal infection caused by the fungal pathogen Candida albicans that, most commonly, affects women of reproductive age. Its first-line treatment consists in topical applications of conventional drug formulations (e.g., creams, gels, tablets) containing imidazole drugs. The treatment involves single or multiple daily applications and, in the case of recurrences, daily administration of oral antifungal drugs for up to one month.Intravaginal rings are flexible, biocompatible medical devices that, compared to conventional drug formulations, offer the possibility of a controlled vaginal drug delivery over a determined period with a single application, thus increasing patient compliance. Among innovative manufacturing techniques, in recent years, fused deposition modeling 3D printing has emerged in the pharmaceutical field to produce different therapeutics combining drugs and polymers. This technique allows to print objects layer by layer with many different thermoplastic materials after a computer-assisted design.Thermoplastic polyurethanes are flexible and biocompatible materials that can be efficiently employed for the manufacturing of drug release systems, already utilized to prepare vaginal devices.In this work, we produced a clotrimazole-loaded intravaginal ring by fused deposition modeling 3D printing combining the drug with thermoplastic polyurethane using hot melt extrusion. The rings were computer-designed and then printed with two different drug concentrations (i.e., 2% and 10% w/w).The intravaginal rings were first tested in an agar-diffusion test to evaluate their effectiveness against C. albicans; and the 10% loaded ring was selected for further studies. Drug release was evaluated in two different media (i.e., 50% ethanol and vaginal fluid simulant) showing a sustained release over a period of seven days. Next, in vitro time-kill analysis against C. albicans in simulated vaginal fluid was performed and displayed a complete growth inhibition after 5 days, compared to the control.These results suggest a potential application of these 3D printed intravaginal rings for the treatment of vulvovaginal candidiasis and for the long-time treatment of recurrences.

In-situ Gelling System for Mucoadhesive Site- Specific Drug Delivery for Treatment of Recurrent Vaginal Candidiasis

In-situ Gelling System for Mucoadhesive Site- Specific Drug Delivery for Treatment of Recurrent Vaginal Candidiasis

Oral versus topical antifungal treatment for recurrent vulvovaginal candidiasis

Objective To evaluate the effect of using oral versus topical antimycotic preparations in treatment of recurrent vulvovaginal candidiasis. Background Vaginal candidiasis is a common disease in women during their lifetime. Although several antifungal drugs are routinely used for treatment, recurrent vaginal candidiasis is a challenge for patients and gynecologists. Patients and methods This was a randomized control trial that included 88 cases complaining of recurrent vaginal candidiasis, with occurrence ranging from 4 to 8 episodes/year, with confirmed clinical and mycological diagnosis of vaginal candidiasis. Patients were divided into two groups by randomized number sequence: group A received oral fluconazole and group B received local clotrimazole vaginal tablets. This trial was conducted at the Department of Obstetrics and Gynecology, Zawyet Aal-Naoora Hospital, in Menoufia from March 2017 to June 2018. Results This study revealed a total clinical cure rate of 81% for fluconazole group and 76.1% for clotrimazole group. Total mycological cure rate was 80.5% for group A and 77.3% for group B. There was no statistically significant difference regarding clinical or mycological cure rates in all visits between the two groups. The most frequent adverse effect in group A was nausea and for group B was vaginal burning sensation. Conclusion Response to treatment of recurrent vulvovaginal candidiasis was similar among fluconazole and long-term use of clotrimazole vaginal tablets.

Vaginal tablets of dequalinium chloride 10 mg versus clotrimazole 100 mg for vaginal candidiasis: a double-blind, randomized study

To compare the clinical response, microscopic examination and fungal culture between dequalinium chloride (DQC) and clotrimazole (CT) for treating vaginal candidiasis (VC). The double-blind, randomized study was conducted from September 2014 to September 2016 at Siriraj Hospital, Thailand. Eligible participants were Thai women diagnosed with VC by microscopic examination. The exclusion criteria included immunocompromised conditions, consumption of antifungal drugs, and having recurrent VC. Each participant was randomized with a 1:1 allocation to receive six vaginal tablets of 100mg CT or 10mg DQC. Two visits included 10 ± 2days (C1) and 38 ± 4days (C2). Outcome measures were improvement of VC symptoms, microscopic examination, culture, satisfaction and tolerability. Of 155 eligible participants, 150 were randomized and allocated into CT (N = 76) and DQC (N = 74). The average age was 31.1 ± 7.2years. Comparable improvement of clinical response was demonstrated (OR at C1 0.79, 95% CI 0.56-1.10, p = 0.197; and OR at C2 0.99, 95% CI 0.69-1.43, p = 0.985). Of CT and DQC groups, the microscopic examination was positive at 11/75 (14.9%) vs 18/72 (25.3%) at C1 and 18/74 (24.3%) vs 28/66 (42.4%) at C2. And the culture was positive at 25/75 (33.8%) vs 46/72 (65.7%) at C1 and at 26/74 (36.6%) vs 46/66 (69.7%) at C2. Most participants had high satisfaction and tolerability and none reported any side effects. DQC and CT show comparable clinical response but CT results in greater improvement of microscopic examination and fungal culture. The Clinical Trial Registry number was NCT02242695. (September 17, 2014).

618. Fluconazole-Resistant Candida albicans Vaginitis with Cross-Resistance to Azoles: A Case Report

BackgroundLocal and systemic use of azole derivatives are common in the treatment of vulvovaginal candidiasis. However, there are cases unresponsive to these agents. Herein, we present treatment and follow-up of a patient with fluconazole–itraconazole and voriconazole-resistant recurrent vaginal candidiasis.MethodsA 37-year-old woman with no comorbidity used topical and oral antifungal/antibacterial medications (including fluconazole and itraconazole) in the treatment of recurrent vulvovaginitis, was hospitalized due to continuous complaints. Intense, white-colored, odorless vaginal discharge was observed on physical examination. Urine and vaginal swab samples were taken for mycological and bacteriological culture. Metronidazole (500 mg 3x1 i.v.) and high dose fluconazole (600 mg/day i.v.) were initiated empirically for the possibility of dose-dependent resistant Candida infection, but there was no clinical response.ResultsCandida albicans was isolated in vaginal swab culture, but response to systemic fluconazole treatment for one week was inadequate. Antifungal susceptibility test was performed by microdilution method according to CLSI M27A3 guidelines and MIC values were reported respectively; fluconazole 4 µg/mL (SDD), itraconazole 1 µg/mL (R), posaconazole 0.06 µg/mL (WT), voriconazole 0.25 µg/mL (SDD), anidulafungin ≤ 0.015 µg/mL (S), amphotericin B 0.06 µg/mL (WT). For the resistance mechanism, point mutation in the ERG11 gene and MDR1 and MDR2 from efflux pumps were investigated and only the G464S mutation was detected in the ERG11 gene. Treatment was switched to IV anidulafungin (200 mg on day 1 followed by 100 mg/day). Clinical response was achieved in the patient whose complaints were reduced, and there was no Candida in the repeated vaginal swab culture taken on day 3 of treatment. The patient was discharged after 2 weeks of treatment. She had no recurrence after 2 years follow-up.ConclusionIt should be kept in mind that resistant strains may be responsible for recurrent and unresponsive vulvovaginal candidiasis cases. Although there is no case report in which anidulafungin is used for treatment and it should be kept in mind that the anidulafungin is also in the treatment as it is summarized.Disclosures All authors: No reported disclosures.

SAT-242 Pigmented Paravenous Retinochorodial Atrophy: A Novel Manifestation of Autoimmune Polyglandular Syndrome Type 1

Autoimmune polyglandular Syndrome Type 1 (APS-1) is an autoimmune disease due to defects in the AIRE gene. It is characterized by a triad of hypoparathyroidism, mucocutaneous candidiasis, and Addison’s disease. We present a case of pigmented paravenous retinochoroidal atrophy associated with APS-1. Case description: A 14 year old female who was admitted for cramps in her hands secondary to hypocalcemia. Past medical history is significant for recurrent vaginal candidiasis and panic attacks. Laboratory assessment revealed low parathyroid hormone and hypocalcemia confirming the diagnosis of hypoparathyroidism. After 4 months she presented with vomiting, and dizziness. Serum cortisol levels were low consistent with the diagnosis of adrenal insufficiency. Further evaluation revealed a mutation in the APS-1 gene. At 28 years she presented with complaints of blurred vision and blind spots for a year. Initial ophthalmologic evaluation revealed a visual acuity of 20/60 in the right eye and 20/50 in the left eye. Anterior segment assessment was normal. Fundoscopy revealed presence of speculated pigment and atrophy of the macula long with attenuated retinal vessels. Optical coherence tomography did not show any macular edema. Visual field assessment was normal. She was diagnosed with pigmented paravenous chorioretinal atrophy. Anti-retinal antibodies were positive for 30-kDa, 36-kDa, 40-kDa, and 46-kDa confirming the autoimmune etiology of the disorder. Over the next 2 years, her visual acuity decreased to 20/400 in the right eye and 20/80 in the left eye. Conclusion: APS-1 is a rare disease associated with numerous autoimmune disorders, beyond the classic clinical triad. Pigmented paravenous chorioretinal atrophy is a previously unreported manifestation of APS-1. Unfortunately no definitive treatment exists for retinal degeneration.

FIXED DRUG ERUPTION TO FLUCONAZOLE IN A 28 YEAR OLD WOMAN WITH RECURRENT VAGINAL CANDIDIASIS

Introduction Fixed Drug eruption (FDE) is a delayed type hypersensitivity reaction to certain drugs, characterized by single or multiple round patches, which may or may not have vesicles, often healing with hyper pigmentation (1) (2). FDE to Fluconazole is not common and few cases have been reported (2) (3). Case Description 28-year old woman with past medical history of chronic urticaria, eczema and hypothyroidism presenting with recurrent rash in the same exact locations after every Fluconazole use for recurrent vaginal candidiasis. Her first episode of rash was 12 months ago. Within minutes of taking Fluconazole for a vaginal yeast infection (previously used) she developed an erythematous flat, 2×2 cm rash on her nose, upper lip, right ankle and upper leg. Within 24 hours rash developed small vesicles followed by crusting. Since then she has taken Fluconazole three separate times and every time she developed the same rash on the same exact locations. The rash is pruritic in the first few days and heals with post inflammatory hyper pigmentation. She denies lesions in the genital area or on palms or soles. At the time of examination, the rash had healed with post inflammatory hyper pigmentation. Discussion Fluconazole is often used in the treatment of vaginal or esophageal candidiasis (1). FDE with Fluconazole may be more common than previously thought and should be kept in mind when patients have recurrent, classic rashes after Fluconazole use. Fluconazole should be re-prescribed with caution, since recurrent FDE lesions can be greater in size and number on repeat exposure (3). Fixed Drug eruption (FDE) is a delayed type hypersensitivity reaction to certain drugs, characterized by single or multiple round patches, which may or may not have vesicles, often healing with hyper pigmentation (1) (2). FDE to Fluconazole is not common and few cases have been reported (2) (3). 28-year old woman with past medical history of chronic urticaria, eczema and hypothyroidism presenting with recurrent rash in the same exact locations after every Fluconazole use for recurrent vaginal candidiasis. Her first episode of rash was 12 months ago. Within minutes of taking Fluconazole for a vaginal yeast infection (previously used) she developed an erythematous flat, 2×2 cm rash on her nose, upper lip, right ankle and upper leg. Within 24 hours rash developed small vesicles followed by crusting. Since then she has taken Fluconazole three separate times and every time she developed the same rash on the same exact locations. The rash is pruritic in the first few days and heals with post inflammatory hyper pigmentation. She denies lesions in the genital area or on palms or soles. At the time of examination, the rash had healed with post inflammatory hyper pigmentation. Fluconazole is often used in the treatment of vaginal or esophageal candidiasis (1). FDE with Fluconazole may be more common than previously thought and should be kept in mind when patients have recurrent, classic rashes after Fluconazole use. Fluconazole should be re-prescribed with caution, since recurrent FDE lesions can be greater in size and number on repeat exposure (3).

Effect of 2-Phenylethanol as Antifungal Agent and Common Antifungals (Amphotericin B, Fluconazole, and Itraconazole) on Candida Species Isolated from Chronic and Recurrent Cases of Candidal Vulvovaginitis.

The antifungal effects of 2-phenylethanol are clearly visible through its intervention in Candida morphogenesis. Chronic and recurrent vulvovaginitis, however, does not respond to this standard experimental therapy; therefore, the study presented in this article investigated the effect of common antifungal drugs (amphotericin B [AMB], fluconazole [FLU], and itraconazole [ITC]), in combination with 2-phenylethanol, on the Candida species isolated from cases of chronic and recurrent vulvovaginitis, thereby allowing the recommendation of a more appropriate treatment option. Forty isolates from patients with chronic and recurrent vaginal candidiasis were investigated in this experimental study. The specimens were examined by direct microscopy, culturing, and PCR to identify the species. The antifungal effects of 2-phenylethanol and conventional drugs, both alone and in combination, were determined in duplicate. Finally, the findings were analyzed. In this study, 40 strains of Candida species were identified, whose agents were Candida albicans (95%) and Candida africana (5%). After 48 h, the minimum inhibitory concentration (MIC) range of the 2-phenylethanol was 800-3,200 μg/mL. Also, in the final study on the MIC levels of common antifungal drugs, AMB (0.42 μg/mL) had the lowest MIC, FLU (40.51 μg/mL) had the highest MIC, and the combination of ITC and 2-phenylethanol had the lowest fractional inhibitory concentration index (FICI) of any of the combinations (FICI range, 0.26-1.03). Combining FLU and ITC with 2-phenylethanol can effectively increase their antifungal effect.

Estimation of the Burden of Serious Human Fungal Infections in Malaysia.

Fungal infections (mycoses) are likely to occur more frequently as ever-increasingly sophisticated healthcare systems create greater risk factors. There is a paucity of systematic data on the incidence and prevalence of human fungal infections in Malaysia. We conducted a comprehensive study to estimate the burden of serious fungal infections in Malaysia. Our study showed that recurrent vaginal candidiasis (>4 episodes/year) was the most common of all cases with a diagnosis of candidiasis (n = 501,138). Oesophageal candidiasis (n = 5850) was most predominant among individuals with HIV infection. Candidemia incidence (n = 1533) was estimated in hospitalized individuals, some receiving treatment for cancer (n = 1073), and was detected also in individuals admitted to intensive care units (ICU) (n = 460). In adults with asthma, allergic bronchopulmonary aspergillosis (ABPA) was the second most common respiratory mycoses noticed (n = 30,062) along with severe asthma with fungal sensitization (n = 39,628). Invasive aspergillosis was estimated in 184 cases undergoing anti-cancer treatment and 834 ICU cases. Cryptococcal meningitis was diagnosed in 700 subjects with HIV/AIDS and Pneumocystis jirovecii pneumonitis (PCP) in 1286 subjects with underlying HIV disease. The present study indicates that at least 590,214 of the Malaysian population (1.93%) is affected by a serious fungal infection annually. This problem is serious enough to warrant the further epidemiological studies to estimate the burden of human fungal infections in Malaysia.

Generalized Fixed Drug Eruption Induced by Fluconazole Without Cross-Reactivity to Itraconazole: Lymphocyte Transformation Test Confirms the Diagnosis.

We present a rare case of generalized fixed drug eruption caused by fluconazole. A 45-year-old female patient was referred to our outpatient clinic because of suspicious drug eruptions that occurred 5 months earlier and resolved within a month. The patient had sequela of hyperpigmentation on her arms, legs, back, and abdomen after oral administration of the fourth dose of 150 mg of fluconazole once daily because of vaginal candidiasis. Patch tests with the culprit drug applied both on unaffected skin areas and over one of the lesions were negative. A lymphocyte transformation test was performed and in response to fluconazole, CD4+ T cells significantly proliferated. Because the patient needed a safe antifungal drug for her recurrent vaginal candidiasis symptoms, a single-blind placebo-controlled drug provocation test was performed with itraconazole and was negative. Accordingly, 200 mg of itraconazole once daily was given for 10 days safely.

Quantitation of ergosterol content and gene expression profile of ERG11 gene in fluconazole-resistant Candida albicans.

Background and Purpose:The frequency of opportunistic fungal infections in immunocompromised patients, especially by Candida species, has sharply increased in the last few decades. The objective of this study was to analyse the ergosterol content and gene expression profiling of clinical isolates of fluconazole-resistant Candida albicans. Materials and Methods:Sixty clinical samples were identified and collected from immunocompromised patients, namely recurrent oral, vaginal, and cutaneous candidiasis, during 2015-16. Antifungal susceptibility testing of fluconazole against clinical Candida species was performed according to Clinical and Laboratory Standards Institute guidelines. Ergosterol content and gene expression profiling of sterol 14α-demethylase (ERG11) gene in fluconazole-susceptible and –resistant C. albicans were investigated. Results: The specimens consisted of C. albicans (46.67%), Candida krusei (41.67%), and Candida tropicalis (11.67%). All the isolates were resistant to fluconazole. No significant reduction was noted in total cellular ergosterol content in comparison with untreated controls in terms of fluconazole-resistant C. albicans. The expressionlevel of ERG11 gene was down-regulated in fluconazole-susceptible C. albicans. Eventually, the expression pattern of ERG11 gene revealed no significant changes in fluconazole-resistant isolates compared to untreated controls. The results revealed no significant differences between fluconazole-susceptible and –resistant C. albicans sequences by comparison with ERG11 reference sequence. Conclusion:Our findings provide an insight into the mechanism of fluconazole resistance in C. albicans. The mechanisms proposed for clinical isolates of fluconazole-resistant C. albicans are alteration in sterol biosynthesis, analysis of expression level of ERG11 gene, and analysis of gene sequences. Nonetheless, further studies are imperative to find molecular mechanisms that could be targeted to control fluconazole resistance.

Testing Antifungal Vaccines in an Animal Model of Invasive Candidiasis and in Human Mucosal Candidiasis.

The following article will concentrate on the NDV-3 anti-Candida and Staphylococcus vaccine. The vaccine is composed of the N-terminal portion of the Candida albicans agglutinin-like sequence 3 protein (Als3p) and aluminum hydroxide as adjuvant. The vaccine conferred protection to mice against experimental vaginal, oral, and intravenous challenge with C. albicans. Due to the sequence and structural homology of the Als3p with Staphylococcus aureus surface proteins, the vaccine also protected against experimental skin and IV infection with S. aureus. The vaccine has reached the stage of human trials: phase 1 clinical studies have shown that the vaccine is safe and immunogenic. The latest brief conference abstract reports of vaccination in women suffering from recurrent vaginal candidiasis, indicating that the recurrence rates were lower in the women receiving the vaccine.

An estimation of burden of serious fungal infections in France

An estimation of burden of serious fungal diseases in France is essential data to inform public health priorities on the importance of resources and research needed on these infections. In France, precise data are available for invasive fungal diseases but estimates for several other diseases such as chronic and immunoallergic diseases are by contrast less known. A systematic literature search was conducted using the Web of Science Platform. Published epidemiology papers reporting fungal infection rates from France were identified. Where no data existed, we used specific populations at risk and fungal infection frequencies in those populations to estimate national incidence or prevalence, depending on the condition. The model predicts high prevalences of severe asthma with fungal sensitization episodes (189 cases/100,000 adults per year), of allergic bronchopulmonary aspergillosis (145/100,000) and of chronic pulmonary aspergillosis (5.24/100,000). Besides, estimated incidence for invasive aspergillosis is 1.8/100,000 annually based on classical high risk factors. Estimates for invasive mucormycosis, pneumocystosis and cryptococcosis are 0.12/100,000, 1/100,000 and 0.2/100,000, respectively. Regarding invasive candidiasis, more than 10,000 cases per year are estimated, and a much higher number of recurrent vaginal candidiasis is probable but must be confirmed. Finally, this survey was an opportunity to report a first picture of the frequency of tinea capitis in France. Using local and literature data of the incidence or prevalence of fungal infections, approximately 1,000,000 (1.47%) people in France are estimated to suffer from serious fungal infections each year.

Treatment of genital warts: focus on vaginal dysbiosis

Бактериальный вагиноз является частым спутником папилломавирусной инфекции. Он также может сочетаться с вагинальным кандидозом и склонен рецидивировать, что связано с наличием комменсалов влагалища Atopobium vaginae. Бактериальный вагиноз патогенетически связан с блокадой воспалительной реакции на уровне слизистой влагалища. Поэтому для санации необходимо использовать лекарственные средства, действующее вещество которых эффективно влияет на анаэробы, Gardnerella vaginalis, Atopobium vaginae, дрожжевые грибы, обладает иммуномодулирующими свойствами, не угнетает рост лактобацилл и не образует перекрестной резистентности с другими антибактериальными средствами. Всем указанным требованиям удовлетворяет мирамистин. Проведено изучение эффективности влагалищного применения свечей с мирамистином (препарат тамистол) в комплексном лечении пациенток с остроконечными кондиломами. Всего было обследовано 142 женщины. В I группу вошли 30 практически здоровых женщин, во II группу – 55 пациенток с остроконечными кондиломами (28 участниц подгруппы IIA с бактериальным вагинозом и 27 пациенток подгруппы IIБ с бактериальным вагинозом и хроническим рецидивирующим вагинальным кандидозом). В III группу вошли 57 женщин с остроконечными кондиломами (29 пациенток с бактериальным вагинозом в подгруппе IIIА и 28 женщин с бактериальным вагинозом и хроническим рецидивирующим вагинальным кандидозом в подгруппе IIIБ). Пациенткам II группы проводили химическую деструкцию остроконечных кондилом после ректального использования свечей с рекомбинантным интерфероном в течение 10 дней. Пациенткам III группы дополнительно назначали курс санации влагалища с помощью вагинальных свечей тамистол в течение 10 дней. Результаты выполненного исследования свидетельствуют, что применение свечей тамистол в комплексном лечении пациенток с остроконечными кондиломами значительно повышает эффективность лечебных мероприятий. Восстановление микробного пейзажа влагалища с помощью тамистола снижало необходимость повторных сеансов химической деструкции кондилом и количество рецидивов. Полученные результаты позволяют считать использование иммуномодуляторов и санации влагалища в комплексе лечения папилломавирусной инфекции теоретически обоснованным.

Development and Characterization of Nisin Nanoparticles as Potential Alternative for the Recurrent Vaginal Candidiasis Treatment.

The aim of this work was the development and characterization of nisin-loaded nanoparticles and the evaluation of its potential antifungal activity. Candidiasis is a fungal infection caused by Candida sp. considered as one of the major public health problem currently. The discovery of antifungal agents that present a reduced or null resistance of Candida sp. and the development of more efficient drug release mechanisms are necessary for the improvement of candidiasis treatment. Nisin, a bacteriocin commercially available for more than 50years, exhibits antibacterial action in food products with potential antifungal activity. Among several alternatives used to modulate antifungal activity of bacteriocins, polymeric nanoparticles have received great attention due to an effective drug release control and reduction of therapeutic dose, besides the minimization of adverse effects by the preferential accumulation in specific tissues. The nisin nanoparticles were prepared by double emulsification and solvent evaporation methods. Nanoparticles were characterized by dynamic light scattering, zeta potential, Fourier transform infrared, X-ray diffraction, differential scanning calorimetry, and scanning electron microscopy. Antifungal activity was accessed by pour plate method and cell counting using Candida albicans strains. The in vitro release profile and in vitro permeation studies were performed using dialysis bag method and pig vaginal mucosa in Franz diffusion cell, respectively. The results revealed nisin nanoparticles (300nm) with spherical shape and high loading efficiency (93.88 ± 3.26%). In vitro test results suggest a promising application of these nanosystems as a prophylactic agent in recurrent vulvovaginal candidiasis and other gynecological diseases.