Intravaginal cooling provides symptom relief in women with vulvovaginal candidiasis and reduces immunopathology in an accompanying mouse model

Junko Yano, Kimberly Langdon, Michael Swor, Mairi C Noverr, Paul L Fidel
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Abstract

Background Vulvovaginal candidiasis (VVC), caused primarily by Candida albicans, is currently treated with either prescription or over-the-counter antifungal drugs, often with variable efficacy and relapses. New and improved therapeutic strategies, including drug-free treatment alternatives, are needed. Upon overgrowth or environmental triggers, C. albicans yeast transitions into hyphae that results in an aberrant immunopathologic response by neutrophils, contributing to the characteristic vulvovaginal symptoms. The purpose of this study was to evaluate the efficacy of a patented intravaginal cooling device (Vlisse®) to provide symptom relief in women with VVC via putative reversal of C. albicans hyphae to the commensal yeast form, with additional proof of principle in an animal model. Methods This pilot clinical trial involved five women with VVC who used the device twice daily for three days. Vulvovaginal symptoms were monitored and scored for each use, followed by pelvic examination 30 days post-treatment. An established mouse model of VVC, using cooled magnetic micro stir rods for vaginal cooling, was employed to evaluate the effect on fungal morphology and vaginal immunopathology. Results Clinical cure, defined as complete reduction in symptoms without recurrence over a 30-day follow-up period, was achieved in all women. In the mouse model, the insertion of pre-cooled magnetic rods intravaginally for short periods, twice daily for 3 days, reduced the immunopathogenic neutrophil infiltration and hyphal presence. Conclusions Intravaginal cooling treatment provides clinical cure for VVC with strong proof of concept in an accompanying animal model. The therapeutic efficacy of Vlisse® warrants further testing in large-scale long-term clinical trials.
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阴道内降温可缓解患有外阴阴道念珠菌病的妇女的症状,并在伴随的小鼠模型中减少免疫病理反应
背景外阴阴道念珠菌病(VVC)主要由白色念珠菌引起,目前主要采用处方药或非处方药抗真菌治疗,但疗效往往不一,且易复发。我们需要新的、更好的治疗策略,包括无药治疗方案。在过度生长或环境诱因的作用下,白念珠菌酵母菌转变为菌丝,导致中性粒细胞产生异常免疫病理反应,从而引发特征性外阴阴道症状。本研究的目的是评估一种获得专利的阴道内冷却装置(Vlisse®)的疗效,该装置可通过将白带酵母菌菌丝逆转为共生酵母菌形态来缓解外阴阴道炎妇女的症状,并在动物模型中进行了进一步的原理验证。方法 这项试验性临床试验涉及五名患有外阴阴道炎的妇女,她们每天使用该装置两次,为期三天。每次使用都对外阴症状进行监测和评分,治疗后 30 天进行盆腔检查。使用冷却磁性微搅拌棒进行阴道冷却,建立了 VVC 小鼠模型,以评估对真菌形态学和阴道免疫病理学的影响。结果 所有妇女都达到了临床治愈,即在 30 天的随访期内症状完全减轻且未复发。在小鼠模型中,阴道内短时间插入预冷磁棒(每天两次,持续 3 天)可减少免疫致病性中性粒细胞浸润和真菌的存在。结论 阴道内冷却治疗可临床治愈 VVC,并在动物模型中有力地证明了这一概念。Vlisse® 的疗效值得在大规模长期临床试验中进一步检验。
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