RESUMO
BACKGROUND: Recurrent vulvovaginal candidiasis (RVVC) is an important and underestimated fungal infection. OBJECTIVE: We aimed to determine the fungicidal and proliferative capacities of neutrophils and peripheral blood mononuclear cells (PBMCs), respectively and the clinical and microbiological characteristics of a cohort of Colombian patients diagnosed with RVVC. METHODS: A cross-sectional study was conducted. A total of 66 women were included (40 diagnosed with RVVC and 26 healthy women [HW]). Demographic and clinical data were recorded. Vaginal fluid samples were obtained for isolation, identification and antifungal susceptibility testing of Candida species using selective culture media and the Vitek 2.0® system. Blood samples were also obtained to evaluate cell subpopulations; furthermore, neutrophils and PBMCs were isolated to determine their fungicidal and proliferative capacities, respectively. RESULTS: The median age was 29 (IQR: 34-23) for RVVC and 24 (IQR: 30-23) for HW. Only two species of the genus Candida were identified: Candida albicans (92.5%) and Candida lusitaniae (7.5%). Resistance to fluconazole, voriconazole, flucytosine and amphotericin B was observed on six C. albicans isolates and one C. lusitaniae isolate. Only the family history of vulvovaginal candidiasis was associated with RVVC occurrence. The RVVC group exhibited a significantly higher number of neutrophils but with lower fungicidal activity in comparison to HW; likewise, PBMCs from RVVC patients presented a lower proliferation index when stimulated with C. albicans. CONCLUSION: Contrary to what has been reported worldwide, in Colombian patients with RVVC, C. albicans was the main isolated species without increased antifungal resistance. The diminished fungicidal and proliferative capacities of neutrophils and PBMCs, respectively, could suggest a possible alteration in the innate and adaptive immune responses.
Assuntos
Candidíase Mucocutânea Crônica , Candidíase Vulvovaginal , Humanos , Feminino , Adulto , Candidíase Vulvovaginal/microbiologia , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Neutrófilos , Estudos Transversais , Leucócitos Mononucleares , Fluconazol , Candida albicans , Candida , Proliferação de CélulasRESUMO
Miconazole-loaded nanoparticles coated with hyaluronic acid (miconazole-loaded nanoparticles/HA) were developed to overcome the limitations of the conventional therapy of the vulvovaginal candidiasis (VVC). They were synthesized by emulsification and solvent evaporation techniques, characterized by diameter, polydispersity index, zeta potential, encapsulation efficiency, atomic force microscopy (AFM), evaluated in terms of efficacy against C. albicans in vitro, and tested in a murine VVC model. Nanoparticles showed 211nm of diameter with a 0.32 polydispersity index, -53mV of zeta potential, and 90% miconazole encapsulation efficiency. AFM evidenced nanoparticles with a spherical shape. They inhibited the proliferation of C. albicans in vitro and in vivo after a single administration. Nanoparticles released the miconazole directly in the site of action at low therapeutic doses, which was enough to eliminate the fungal burden in the murine VVC model. These systems were rationally designed since the existence of the HA induces their adhesion on the vaginal mucus and their internalization via CD44 receptors, inhibiting the C. albicans. Therefore, miconazole-loaded nanoparticles/HA represent an innovative non-conventional pharmaceutical dosage form to treat the VVC and recurrent VVC.
Assuntos
Candidíase Vulvovaginal , Nanopartículas , Humanos , Feminino , Camundongos , Animais , Miconazol/uso terapêutico , Candidíase Vulvovaginal/tratamento farmacológico , Ácido Hialurônico , Antifúngicos , Candida albicansRESUMO
BACKGROUND: Recurrent vulvovaginal candidiasis affects nearly 138 million women globally each year. In the United States, fluconazole is considered the standard of care for acute vulvovaginal candidiasis, but until recently there was no US Food and Drug Administration-approved drug for the treatment of recurrent vulvovaginal candidiasis. Oteseconazole is a novel oral selective inhibitor of fungal lanosterol demethylase (sterol 14α-demethylase cytochrome P450, an enzyme required for fungal growth) approved for the treatment of recurrent vulvovaginal candidiasis. OBJECTIVE: This study was conducted to evaluate the efficacy and safety of oral oteseconazole (VT-1161) in the prevention of recurrent culture-verified acute vulvovaginal candidiasis episodes through 50 weeks in participants with recurrent vulvovaginal candidiasis and to compare the efficacy of oteseconazole and fluconazole in the treatment of the presenting acute vulvovaginal candidiasis episode. STUDY DESIGN: Women and postmenarcheal girls aged ≥12 years with a history of recurrent vulvovaginal candidiasis (N=219) were enrolled at 38 US sites. Eligible participants presenting with an active vulvovaginal candidiasis infection entered an induction phase in which they were randomly assigned 2:1 to receive 600 mg oral oteseconazole on day 1 and 450 mg on day 2, with matching placebo capsules, or to 3 sequential 150-mg oral doses (once every 72 hours) of fluconazole, with matching placebo capsules. Following the 2-week induction phase, the 185 participants with resolved acute vulvovaginal candidiasis infection (a clinical signs and symptoms score of <3) entered the maintenance phase and received 150 mg of oteseconazole or placebo weekly for 11 weeks. Participants were observed for an additional 37 weeks. RESULTS: In the induction phase, oteseconazole was noninferior to fluconazole in the proportion of participants in the intent-to-treat population with resolved acute vulvovaginal candidiasis infection at the week 2 (day 14) test-of-cure visit, with 93.2% of participants on oteseconazole vs 95.8% on fluconazole achieving resolution. In the maintenance phase, oteseconazole was superior to placebo in the proportion of participants in the intent-to-treat population with ≥1 culture-verified acute vulvovaginal candidiasis episode through 50 weeks, 5.1% compared with 42.2%, respectively (P<.001). Overall, treatment-emergent adverse event rates were similar in both groups: 54% for participants who received oteseconazole in the induction and maintenance phases vs 64% for participants who received fluconazole in the induction phase and placebo in the maintenance phase. Most treatment-emergent adverse events in each group were mild or moderate, with 3.4% of treatment-emergent adverse events graded as severe or higher in the OTESECONAZOLE/oteseconazole group vs 4.2% in FLUCONAZOLE/placebo group. CONCLUSION: In participants with recurrent vulvovaginal candidiasis, oteseconazole was safe and efficacious in the treatment and prevention of recurrent acute vulvovaginal candidiasis episodes and was noninferior to vulvovaginal candidiasis standard-of-care fluconazole in the treatment of the presenting acute vulvovaginal candidiasis infection.
Assuntos
Candidíase Vulvovaginal , Infecções , Feminino , Humanos , Candidíase Vulvovaginal/tratamento farmacológico , Candidíase Vulvovaginal/induzido quimicamente , Fluconazol/uso terapêutico , Fluconazol/efeitos adversos , Administração Oral , Antifúngicos/efeitos adversosRESUMO
PURPOSE: More than 370 million women will experience recurrent vulvovaginal candidiasis (RVVC) during their lifetime. However, RVVC is often trivialized as clinically insignificant and not worthy of research funding. We evaluated the influence of RVVC on the quality of life in affected women. METHODS: The validated World Health Organization Quality of Life Abbreviated Assessment (WHOQOL-Bref) questionnaire was administered to 100 women with RVVC and to 101 epidemiologically matched women with no history of vulvovaginal candidiasis. RVVC was defined as at least four episodes of clinical and culture-positive vaginal candidiasis within a 1 year period. Data were analyzed by Chi square, Student t test and analysis of variance. Internal consistency of responses to questions was evaluated by Cronbach alpha. RESULTS: The Cronbach alpha coefficient was > 0.80 for responses to generalized questions and > 0.65 for answers to more specific questions, indicating substantial internal consistency. Perception of quality of life and satisfaction with their health was greatly reduced in the RVVC group (p < 0.001). Diminished responses to physical and psychological well-being were also reported by women with RVVC (p < 0.001). Various aspects of social relations including sexual activity were similarly reduced (p < 0.001) as were satisfaction with issues such as home environment, financial resources and employment (p < 0.001). CONCLUSION: RVVC affects multiple aspects of a woman's well-being. Women with this condition deserve serious attention from clinicians and research into susceptibility, prevention and treatment of this infection deserves much greater emphasis.
Assuntos
Candidíase Vulvovaginal/psicologia , Nível de Saúde , Qualidade de Vida , Adulto , Candida/isolamento & purificação , Candidíase Vulvovaginal/diagnóstico , Estudos de Casos e Controles , Feminino , Humanos , Recidiva , Comportamento Sexual , Inquéritos e QuestionáriosRESUMO
Resumen OBJETIVO: determinar, mediante reacción en cadena de la polimerasa (PCR), si C. albicans y C. glabrata son causantes de las recurrencias de candidiasis vulvovaginal y si suelen colonizar la vagina de mujeres mexicanas asintomáticas en edad reproductiva. MATERIALES Y MÉTODOS: estudio analítico, transversal, prospectivo, experimental, de casos y controles, efectuado en mujeres de 18 a 45 años de edad, atendidas en el servicio de Ginecología del Centro Médico ABC de la Ciudad de México y el Cinvestav del Instituto Politécnico Nacional. Identificar C. albicans y C. glabrata en muestras vaginales por medio de reacción en cadena de la polimerasa con iniciadores específicos para cada especie. RESULTADOS: se estudiaron 93 pacientes: 46 casos y 47 controles. En los casos se encontraron: 2.17% con C. albicans, 80.4% con C. glabrata y 17.3% con coinfección por ambas especies. En los controles se encontraron: 61.7% con C. albicans, 4.2% con C. glabrata, 19.1% con coinfección por ambas especies y 14.8% con ausencia de Candida spp. CONCLUSIONES: el agente causal de la mayor parte de las candidiasis vulvovaginales recurrentes es C. glabrata. La colonización por esta especie y por C. albicans es común y no provoca síntoma alguno, por lo que para su identificación es importante utilizar métodos de diagnóstico como la reacción en cadena de la polimerasa.
Abstract BACKGROUND: 75% of women are affected with vulvovaginal candidiasis and 10% of them will have at least 4 episodes during one year. The most common etiological agents are C. albicans and C. glabrata, which is usually the responsible of the recurrent cases when the patients have received inadequate treatment. Up to 55% of asymptomatic women can have different species of Candida spp. as vaginal commensals, but there are no recent studies that identify this yeast through molecular techniques in healthy women and with history of vulvovaginal candidiasis. OBJECTIVE: Determine using polymerase chain reaction if C. albicans and C. glabrata are responsible of recurrent vulvovaginal candidiasis and if they usually colonize Mexican asymptomatic women in reproductive age. MATERIAL AND METHODS: An analytical, transversal, prospective, experimental, case control study was carried out in women age 18 to 45 in the Gynecology Service of ABC Medical Centre of México City and IPN Cinvestav. C. albicans and C. glabrata were identified in vaginal samples using polymerase chain reaction with specific primers for each specie. RESULTS: A total of 93 patients were studied, 46 cases and 47 controls. 2.17% of the case patients were positive C. albicans, 80.43% for C. glabrata, and 17.39% for both species. 61.70% of the control patients were positive for C. albicans, 4.20% for C. glabrata, 19.14% for both species, and 14.89% were negative for Candida. CONCLUSIONS: The main etiological agent of recurrent vulvovaginal candidiasis is C. glabrata. The vaginal colonization of this specie and C. albicans is common and causes no symptoms, thus, it is important to use diagnostic tools such as polymerase chain reaction to identify them. It is relevant to investigate the factors that help this yeast to cause a symptomatic infection and stop being just a vaginal commensal.