Silvia Driussi

Prevalence of Bacterial Vaginosis and Vaginal Flora Changes in Peri- and Postmenopausal Women

ABSTRACT Our aim was to evaluate the prevalence of bacterial vaginosis and decrease in lactobacillus colonization in women 40 years old or older in relation to menopausal status by evaluation of Gram-stained smears. A total of 1,486 smears from Italian Caucasian women aged 40 to 79 years were examined. Women were classified as follows: fertile (regular cycles) (n = 328), perimenopausal (irregular cycles) (n = 237), and postmenopausal (n = 921), including 331 women on estroprogestinic hormone replacement therapy (HRT). The prevalences of bacterial vaginosis (assessed as a Nugent score of ≥7) in fertile (9.8%) and perimenopausal (11.0%) women were not statistically different, whereas the prevalence was significantly lower overall in postmenopausal women (6.0%) (P = 0.02). Specifically, 6.3% of postmenopausal women without HRT and 5.4% of postmenopausal women with HRT were positive for bacterial vaginosis. The Nugent score system was not adequate for evaluating the normal and intermediate vaginal flora in women over the age of 40 years. High numbers of peri- and postmenopausal women had no lactobacilli and no bacterial-vaginosis-associated microorganisms. This nonpathological absence of lactobacilli in women with a Nugent score of 4 was scored as 4∗, and this group was considered separately from the intermediate flora group. A score of 4∗ was obtained for 2.1% of fertile women, 11.4% of perimenopausal women, 44.1% of postmenopausal women without HRT, and 6.9% of postmenopausal women with HRT. The physiological reduction in lactobacillus colonization of the vagina in postmenopausal women does not cause an increase in bacterial-vaginosis prevalence. Reversion of lactobacillus flora to premenopausal levels due to HRT does not increase the prevalence of bacterial vaginosis in postmenopausal women.

Immunoglobulin A response against Gardnerella vaginalis hemolysin and sialidase activity in bacterial vaginosis

OBJECTIVE The aim of this study was to investigate the correlation between the immunoglobulin A immune response to Gardnerella vaginalis hemolysin and sialidase activity in vaginal fluids from patients with bacterial vaginosis. STUDY DESIGN Nonpregnant women who were examined at a gynecologic clinic, in an age range of 18 to 62 years, were enrolled. The study population comprised 131 healthy volunteers, 32 women with bacterial vaginosis that was positive for immunoglobulin A to Gardnerella vaginalis hemolysin, 40 women with bacterial vaginosis that was negative for immunoglobulin A to Gardnerella vaginalis hemolysin, and 19 women with Candida vaginitis. Bacterial vaginosis was diagnosed by clinical criteria and Gram stain. RESULTS Sialidase activity was present in 75% (54/72) of patients with bacterial vaginosis. Women having bacterial vaginosis and lacking a specific immunoglobulin A response had a significantly higher level of sialidase activity than patients who had an immune response against Gardnerella vaginalis hemolysin. Sialidase activity was detected in 87% (35/40) of the former subgroup of patients with bacterial vaginosis and in 59% (19/32) of women of the latter subgroup. No sialidase activity was measured in patients with candidiasis. Specificity of the assay for healthy controls was 95% (124/131 women without sialidase activity). CONCLUSIONS Sialidases produced by Prevotella bivia and other microorganisms present in the microflora of patients with bacterial vaginosis are very likely a virulence factor not only by destroying the mucins and enhancing adherence of bacteria but also by impairing a specific immunoglobulin A immune response against other virulence factors such as cytotoxin from Gardnerella vaginalis.

Correlation of Local Interleukin-8 with Immunoglobulin A against Gardnerella vaginalis Hemolysin and with Prolidase and Sialidase Levels in Women with Bacterial Vaginosis

Mucosal immune system activation may represent a critical determinant of adverse consequences associated with bacterial vaginosis (BV), such as sexual human immunodeficiency virus transmission, upper genital tract infections, postsurgical infections, and adverse pregnancy outcomes. Concentrations of sialidase, prolidase, and anti-Gardnerella vaginalis hemolysin (Gvh) immunoglobulin A (IgA) were higher in vaginal fluids of 75 fertile women with BV, compared with concentrations in vaginal fluids of 85 healthy control subjects. Interleukin (IL)-8 levels were positively associated with anti-Gvh IgA response and inversely correlated with high levels of prolidase and sialidase in women with BV. IL-8 concentration was strongly associated with leukocyte count in both healthy and BV-positive women. The absence of leukocytes in most women with BV likely is due to lack of IL-8 induction. Parallel impairment of innate and adaptive mucosal immune factors, likely through microbial hydrolytic effects, may allow for the ascent of microorganisms to the upper genital tract and may facilitate viral infections.

Impairment of the Mucosal Immune System: IgA and IgM Cleavage Detected in Vaginal Washings of a Subgroup of Patients with Bacterial Vaginosis

The integrity of the immunoglobulins in vaginal washings of patients with bacterial vaginosis was examined to answer the question of the lack of immune response against Gardnerella vaginalis cytolysin. Clinically diagnosed patients (n=100) were recruited and their vaginal washings examined by Western blotting. Many showed IgA and IgM partially or extensively degraded. According to the degradation pattern, the patients were subdivided into 4 subsets, from intact (score 0) to completely degraded IgA (score +3). Statistical analysis of the data showed a correlation between IgA degradation and absence of immune response to G. vaginalis cytolysin. The extent of IgA degradation correlated also with the sialidase (but not with the prolidase) activity level. All women showed intact IgG and human serum albumin and no trypsin-like activity. Patients with bacterial vaginosis having high sialidase activity and extensive IgA degradation in their secretions could incur more dangerous infections and adverse pregnancy outcomes.

Correlation of local interleukin-1beta levels with specific IgA response against Gardnerella vaginalis cytolysin in women with bacterial vaginosis.

PROBLEM: Mucosal immune system activation may represent a critical determinant of adverse sequelae correlated with bacterial vaginosis, as HIV sexual transmission, upper genital tract infections, cervicitis, endometritis, postsurgical infections, and adverse pregnancy outcomes as preterm delivery (PTD), low birth weight (LBW).

Specific immune response against Gardnerella vaginalis hemolysin in patients with bacterial vaginosis

OBJECTIVE Our goal was to study the mucosal host response in bacterial vaginosis by evaluating the presence of a specific immune response elicited against the Gardnerella vaginalis hemolysin in vaginal fluids of patients and by verifying its correlation with usual criteria adopted to diagnose bacterial vaginosis. STUDY DESIGN A total of 123 white women attending the gynecologic care unit for urogenital complaints or for screening of uterine malignancies (Papanicolaou test) aged from 20 to 60 years, nonmenstruating, were enrolled. Bacterial vaginosis was diagnosed by clinical criteria and a Gram stain score > 6. RESULTS We performed the determination of the antibody response in vaginal fluid against the hemolysin produced by G. vaginalis, a common agent present in bacterial vaginosis. The purified G. vaginalis toxin was a suitable antigen for detecting the presence of an immune response in the vaginal fluids of patients with bacterial vaginosis regardless of the strain of G. vaginalis present. A specific immunoglobulin A response was detected in 60% of women with overt bacterial vaginosis (Gram stain score > 6) and in 18.5% of women with intermediate vaginal flora (Gram stain score 4 to 6). The specificity of the test was 91%. CONCLUSIONS We found a correlation between the specific local immune response to G. vaginalis toxin and bacterial vaginosis. The highly purified form of the toxin is able to discriminate disorders from the opportunistic colonization by G. vaginalis.

Correlation of Innate Immune Response with IgA against Gardnerella vaginalis Cytolysin in Women with Bacterial Vaginosis

SABINA CAUCI,a SECONDO GUASCHINO,b DOMENICO DE ALOYSIO,c SILVIA DRIUSSI,a,d DAVIDE DE SANTO,b PAOLA PENACCHIONI,c ALINE BELLONI,a PAOLO LANZAFAME,e AND FRANCO QUADRIFOGLIOa aDepartment of Biomedical Sciences and Technologies, School of Medicine, University of Udine, Udine, Italy bObstetric and Gynecologic Unit, Department of Reproductive and Development Sciences, IRCCS Burlo Garofolo Hospital, School of Medicine, University of Trieste, Trieste, Italy cDepartment of Obstetrics and Gynecology, Sant’Orsola Hospital, School of Medicine, University of Bologna, Bologna, Italy dAzienda Servizi Sanitari N. 4 Medio Friuli, Udine, Italy eMicrobiology Unit, Santa Maria della Misericordia Hospital, Udine, Italy

Respuesta inmune específica contra hemolisina de Gardnerella vaginalis en pacientes con vaginosis bacteriana

Objetivo: Estudiar la respuesta mucosa del hospedero en vaginosis bacteriana evaluando la presencia de una respuesta inmune especifica contra la hemolisina de Gardnerella vaginalis en fluidos vaginales de pacientes y verificar su correlacion con los criterios adoptados para diagnosticar la vaginosis bacteriana. Diseno del estudio: Se incluyeron un total de 123 mujeres blancas que consultaron a una unidad de cuidado ginecologico por quejas urogenitales o para tamizaje de cancer uterino (prueba de Papanicolaou), con edades entre 20 y 60 anos y no menstruando. La vaginosis bacteriana se diagnostico por criterios clinicos y un puntaje de la tincion de Gram > 6. Resultados: Se determino la respuesta de anticuerpos en el fluido vaginal contra la hemolisisna producida por G. vaginalis, un agente comun presente en la vaginosis bacteriana. La toxina purificada de G. vaginalis fue un antigeno util para detectar la presencia de una respuesta inmune en los fluidos vaginales de las pacientes con vaginosis bacteriana independientemente de la cepa de G. Vaginalis presente. Se detecto una respuesta especifica de inmunoglobulina A en el 60% de las mujeres con vaginosis bacteriana evidente (puntaje de la tincion de Gram > 6) y en 18.5% de las mujeres con flora vaginal intermedia (puntaje de la tincion de Gram 4 a 6). La especificidad de la prueba fue de 91%. Conclusiones: Encontramos una correlacion entre la respuesta inmune local especifica contra la toxina de G. vagainalis y la vagnosis bacteriana. La forma altamente purificada de la toxina permite discriminar los desordenes de la colonizacion oportunista por G. vaginalis.