Role of Molecular Biology in Diagnosis and Characterization of Vulvo-Vaginitis in Clinical Practice.

The diagnosis of vulvo-vaginal complaints has always been enigmatic in obstetrics and gynecology. Patients with clear, pathognomonic symptoms end up with a proper diagnosis and treatment most of the time, but unfortunately we are now living in a world where women reach out to the Internet and readily get all information as to which disease their symptoms correspond to and also find the appropriate treatment "over-the-counter." Because of this trend, we as specialists are increasingly confronted with patients with complex and combined conditions. At the same time, extremely sensitive and accurate diagnostic tools are now being developed at a rapid pace, allowing the physicians to diagnose vulvo-vaginal disease with a substantially increased precision. Moreover, many of these molecular biology (MB)-based tests have become so common and affordable that self-sampling and self-testing are no longer utopia. On the other hand, too much information that is too readily available and that is too affordable also encompasses pitfalls, leading to gross overtreatment and psychological burden. As experienced caregivers, we should supervise these evolutions, define their place and proper use as diagnostic tools, utilize their potential as ad hoc tools to follow-up treatment efficacy and guide how such tools can be used for responsible self-testing. In the present paper, responding to the need for appropriate, quality assured and accessible tests for vulvo-vaginitis and the huge potential delivered by the rapidly developing MB methods, we recommend the need for a broad and regular discussion forum, composed of both clinical and technical experts and opinion makers, in order to match the needs with the huge opportunities and ideally combine the initiatives and forces into the same direction. This forum should then translate conceived strategies into regularly updated, evidence-based national and international guidelines.

In vitro/in vivo performance of different complexes of itraconazole used in the treatment of vaginal candidiasis

A large majority of new chemical entities and many existing drug molecules exhibit poor aqueous solubility, which may limit their potential use in developing drug formulations, with optimum bioavailability. One of the approaches to improve the solubility of a poorly water soluble drug and eventually its bioavailability is complexation with agents like humic acid (HA), fulvic acid (FA), β-cyclodextrin (β-CD), 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and caffeine (Caff). The current work emphasized at employing these agents to prepare different complexes and their in vitro/in vivo assessment. All the complexes evaluated for their complexation efficiency and authenticated by molecular modeling; conformational analysis, differential scanning calorimetry (DSC), X-ray diffraction (XRD), nuclear magnetic resonance (NMR) and mass spectroscopy. Furthermore, the complexes were assessed in an in vivo, rat vaginal model for their efficacy in treatment of vaginal candidiasis. Amongst the five tested complexes, fulvic acid-itraconazole complex yielded better solubility as well as in vivo efficacy and therefore may further be explored for developing a commercial formulation for treating vaginal candidiasis.

A maioria das novas entidades químicas e muitas moléculas de fármacos existentes apresenta fraca solubilidade em água, o que pode limitar seu uso potencial no desenvolvimento de formulações com biodisponibilidade ideal. Uma das abordagens para melhorar a solubilidade de um fármaco pouco solúvel em água e, eventualmente, a sua biodisponibilidade é a complexação com agentes como o ácido húmico (HA), ácido fúlvico (FA), β-ciclodextrina (β-CD), 2-hidroxipropil-β-ciclodextrina (HP-β-CD) e cafeína (Caff). O presente trabalho baseia-se no uso desses agentes para preparar diferentes complexos e suas avaliações in vitro/in vivo. Todos os complexos foram avaliados quanto à eficiência de complexação por modelação molecular, análise conformacional, calorimetria de varredura diferencial (DSC), difração de raios-X (XRD), ressonância magnética nuclear (RMN) e espectroscopia de massas. Além disso, os complexos foram avaliados in vivo, em ratas, no tocante à sua eficácia no tratamento de candidíase vaginal. Entre os cinco complexos testados, o complexo de ácido fúlvico-itraconazol foi o que apresentou melhor solubilidade, bem como melhor eficácia in vivo e, portanto, pode ser explorado para o desenvolvimento de uma formulação comercial para o tratamento de candidíase vaginal.

Treatment of vaginal Candida infections.

Candida vaginitis is most commonly caused by Candida albicans (> 85%) with little evidence of an increase in vaginitis due to non-C. albicans species. Epidemiological studies are no longer possible in the US in the era of self-diagnosis and -treatment by women empowered by the availability of over-the-counter antimycotics. A new classification of vulvovaginal candidiasis into uncomplicated and complicated vaginitis has simplified choice and duration of antifungal therapy. Vaginitis due to C. albicans responds well to available therapy. In contrast, vaginitis due to Candida glabrata is associated with a high treatment failure rate. Candida vaginitis infection rates in HIV-positive women remain undetermined and reports of refractory fungal vaginitis have not been substantiated. In spite of the wide array of antifungal agents currently available, considerable limitations in available therapy exist in the effective management of complicated vaginitis.

[Susceptibility to itraconazole and miconazole of fungi strains isolated from the vaginal ontocenosis]. / Wrazliwosc na itrakonazol i mikonazol szczepów grzybów wyizolowanych z ontocenozy pochwy.

The activity of itraconazole (RO 51211, molecular weight 705,64) and miconazole (RO 14889, molecular weight 479,15) obtained from Janssen Pharmaceutica NV, against 100 fungi strains, was studied. These strains were isolated from vaginal materials of patients with recognized candidosis. The axenic fungal strains were assessed by own methods and unified tests (bioMérieux: API 20 C, API 20 C AUX). The minimal inhibitory concentration (MIC) values calculated from dose-response curves on agar diffusion-test (Kadlubowski's method), were also examined by analysing the variation (mean x +/- standard error, median Me, mode Mo, Min-Max). The drug MIC values for all strains were characterized by a wide range of variation itraconazole 0.0001 - 5.30 mg/L, miconazole 0.0045 - 4.70 mg/L; the shape of MIC values variation polygons was similar to normal distribution.

A comparative clinical evaluation of econazole nitrate, miconazole, and nystatin in the treatment of vaginal candidiasis.

A controlled triple open clinical study on three vaginal tablets--Econazole nitrate, Miconazole and Nystatin, was carried out. Seventy-five patients, aged between 18 and 45 years, presenting with mycologically proven cases of vaginal candidiasis, met certain set criteria and were admitted into the study. Twenty-five patients were randomly assigned to each of the three treatment groups. Results of the study showed that at the 4th week after treatment, Econazole was comparable in antifungal action to Miconazole (x2 = 0.2128; p > 0.05) but significantly more antifungal than Nystatin (x2 = 8.8540; P < 0.05), although the overall clinicomycological assessment of the drugs showed no significant difference in their ratings (F = 21.34; P > 0.05).

Genetic similarity of Candida albicans strains from vaginitis patients and their partners.

The moderately repetitive sequence Ca3 was used to fingerprint strains of Candida albicans isolated from vulvovaginal infections of 10 women and strains isolated from their male partners. The Dendron software package was then used to compare the DNA fingerprints of these strains with those of vaginal commensals from women from the same geographical locale, vaginal commensals from women from a different geographical locale, and commensals from male partners of asymptomatic women from the same geographical locale. The results demonstrate that, in the majority of cases (8 of 10), strains from symptomatic patients and their partners are either identical or more similar to each other than to other strains, infecting strains do not represent a group genetically distinguishable from vaginal commensal isolates from women from the same geographical locale, and both infecting strains and commensals from individuals in the test locale can be distinguished from commensals obtained in another geographical locale. The results also suggest that women with vaginal infections are responsible for strain replacement in their male partners.

Classification and pathogenesis of vulvovaginal candidiasis.

Although candidiasis of the female genital tract is one of the most common of the vaginitides, it is a poorly understood disease entity. Vulvovaginal candidiasis is a monoetiologic disease, but the pathways by which pathogenic expression is attained are sufficiently divergent to constitute a classification schema that influences therapy. For selection of appropriate therapy, the following three broad categories are proposed: (1) primary candidiasis, (2) antibiotic-induced candidiasis, and (3) systemically induced candidiasis.