Gilbert Donders

Definition of a type of abnormal vaginal flora that is distinct from bacterial vaginosis: aerobic vaginitis

Objective To define an entity of abnormal vaginal flora: aerobic vaginitis

Predictive value for preterm birth of abnormal vaginal flora, bacterial vaginosis and aerobic vaginitis during the first trimester of pregnancy.

Introduction  Abnormal vaginal flora (AVF) before 14 gestational weeks is a risk factor for preterm birth (PTB). The presence of aerobic microorganisms and an inflammatory response in the vagina may also be important risk factors.

Pathogenesis of abnormal vaginal bacterial flora

OBJECTIVE This study was undertaken to determine the relationships between microscopy findings on wet mounts, such as lactobacillary grade or vaginal leukocytosis, and results of vaginal culture, lactate and succinate content of the vagina, and levels of selected cytokines. STUDY DESIGN In a population of 631 unselected women seeking treatment at an obstetrics and gynecology outpatient clinic, vaginal fluid was obtained by wooden Ayre spatula for wet mounting and pH measurement, by high vaginal swab for culture, and by standardized vaginal rinsing with 2 mL 0.9% sodium chloride solution for measurements of lactate, succinate, interleukin 1beta, interleukin 8, leukemia inhibitory factor, and interleukin 1 receptor antagonist concentrations. Lactate and succinate levels were measured by gas-liquid chromatography and the cytokine concentrations were measured by specific immunoassays. Both univariate analysis (Student t test, Welch test, chi(2) test, and Fisher exact test) and multivariate regression analysis (Cox analysis) were used. RESULTS Increasing disturbance of the lactobacillary flora (lactobacillary grades I, IIa, IIb, and III) was highly correlated with the presence of Gardnerella vaginalis, Trichomonas vaginalis, enterococci, group B streptococci, and Escherichia coli. Vaginal pH and interleukin 8 and interleukin 1beta concentrations increased linearly with increasing lactobacillary grade, whereas lactate concentrations and the presence of epithelial cell lysis decreased. A similar pattern of associations with increasing leukocyte count was clear, but in addition there was an increase in leukemia inhibitory factor concentration. Multivariate analysis of vaginal leukocytosis, lactobacillary grades, and the presence of positive vaginal culture results showed that interleukin 1beta concentration was most closely related to the lactobacillary grade, leukemia inhibitory factor concentration was most closely related to the lactobacillary grade and positive culture results, interleukin 8 concentration was most closely related to positive culture results, and interleukin 1 receptor antagonist concentration was most closely related to vaginal leukocytosis and positive culture results. The concentration ratio of interleukin 1beta to interleukin 1 receptor antagonist remained stable, except when vaginal leukocytosis increased. In its most severe form, with >10 leukocytes per epithelial cell present, a decompensation of the vaginal flora with a collapse in interleukin 1beta and interleukin 1 receptor antagonist concentrations was seen, but there was a concurrent sharp increase in leukemia inhibitory factor concentration. This pattern was completely different from the course of the cytokine concentrations associated with a lactobacillary grade increase. CONCLUSION Both disturbed lactobacillary grade and the presence of increasing vaginal leukocytosis were correlated with lactobacillary substrate (lactate) concentration, pH, and the concentrations of a variety of cytokines. There was a remarkably linear increase in these cytokines as either leukocytosis or lactobacillary grade became more severe. In circumstances in which leukocytosis was extreme, however, interleukin 1beta was no longer produced but leukemia inhibitory factor concentrations increased. We speculate that in extreme inflammation the body tries to limit the damage that can be done by exaggerated cytokine production.

Prediction of recurrence after treatment for high-grade cervical intraepithelial neoplasia: the role of human papillomavirus testing and age at conisation

Objectives  The aim of this study was to examine the accuracy of the presence of high‐risk human papillomavirus (HR‐HPV) DNA (HR‐HPV DNA test) postconisation as prediction of recurrent or residual cervical intraepithelial neoplasia (CIN) after treatment of high‐grade cervical intraepithelial lesions (CIN2+) in a prospective study and to compare this with follow‐up cytology and the marginal status of the excised tissue.

Dynamics of Vaginal Bacterial Communities in Women Developing Bacterial Vaginosis, Candidiasis, or No Infection, Analyzed by PCR-Denaturing Gradient Gel Electrophoresis and Real-Time PCR

ABSTRACT The microbial flora of the vagina plays a major role in preventing genital infections, including bacterial vaginosis (BV) and candidiasis (CA). An integrated approach based on PCR-denaturing gradient gel electrophoresis (PCR-DGGE) and real-time PCR was used to study the structure and dynamics of bacterial communities in vaginal fluids of healthy women and patients developing BV and CA. Universal eubacterial primers and Lactobacillus genus-specific primers, both targeted at 16S rRNA genes, were used in DGGE and real-time PCR analysis, respectively. The DGGE profiles revealed that the vaginal flora was dominated by Lactobacillus species under healthy conditions, whereas several potentially pathogenic bacteria were present in the flora of women with BV. Lactobacilli were the predominant bacterial population in the vagina for patients affected by CA, but changes in the composition of Lactobacillus species were observed. Real-time PCR analysis allowed the quantitative estimation of variations in lactobacilli associated with BV and CA diseases. A statistically significant decrease in the relative abundance of lactobacilli was found in vaginal fluids of patients with BV compared to the relative abundance of lactobacilli in the vaginal fluids of healthy women and patients with CA.

Characterization of the Vaginal Micro- and Mycobiome in Asymptomatic Reproductive-Age Estonian Women

The application of high-throughput sequencing methods has raised doubt in the concept of the uniform healthy vaginal microbiota consisting predominantly of lactobacilli by revealing the existence of more variable bacterial community composition. As this needs to be analyzed more extensively and there is little straightforward data regarding the vaginal mycobiome of asymptomatic women we aimed to define bacterial and fungal communities in vaginal samples from 494 asymptomatic, reproductive-age Estonian women. The composition of the vaginal microbiota was determined by amplifying bacterial 16S rRNA and fungal internal transcribed spacer-1 (ITS-1) regions and subsequently sequencing them using 454 Life Sciences pyrosequencing. We delineated five major bacterial community groups with distinctive diversity and species composition. Lactobacilli were among the most abundant bacteria in all groups, but also members of genus Gardnerella had high relative abundance in some of the groups. Microbial diversity increased with higher vaginal pH values, and was also higher when a malodorous discharge was present, indicating that some of the women who consider themselves healthy may potentially have asymptomatic bacterial vaginosis (BV). Our study is the first of its kind to analyze the mycobiome that colonizes the healthy vaginal environment using barcoded pyrosequencing technology. We observed 196 fungal operational taxonomic units (OTUs), including 16 OTUs of Candida spp., which is more diverse than previously recognized. However, assessing true fungal diversity was complicated because of the problems regarding the possible air-borne contamination and bioinformatics used for identification of fungal taxons as significant proportion of fungal sequences were assigned to unspecified OTUs.

The association of gonorrhoea and syphilis with premature birth and low birthweight

OBJECTIVE--Provide evidence from prospective data that Neisseria gonorrhoeae may be an important cause of premature delivery and low birth weight in areas with high prevalence of genital infections. SETTING--Department of Obstetrics and Gynaecology, Kalafong University Hospital, Pretoria, South Africa in collaboration with the Departments of Microbiology and of Gynaecology and Obstetrics, Katholieke Universiteit, Leuven, Belgium. SUBJECTS--Two hundred and fifty six consecutive black pregnant women were examined during the first antenatal visit, and one to four weeks later a second culture for N gonorrhoeae was taken at random in 67 of them. Hundred and sixty seven were analysable, 75 were lost to follow up. METHODS--After obtaining detailed clinical history, an endocervical specimen for N gonorrhoeae culture (Thayer-Martin) and C trachomatis antigen detection (Chlamydiazyme (R)) was taken. Syphilis was diagnosed when both reactive plasma protein (RPR) and T pallidum haemagglutination inhibition assay (TPHA) were positive. Prematurity was defined as delivery at less than 37 gestational weeks. RESULTS--Infection with N gonorrhoeae (n = 9) and untreated syphilis (n = 7) were both associated with prematurity and low birth weight. After multi-variate regression analysis, age-adjusted parity, late sexual debut, number of recent sexual partners, infection with N gonorrhoeae and infection with syphilis revealed significant associations with low birth weight. However, infection with C trachomatis, presence of abundant vaginal discharge, social class, Trichomonas vaginalis infection, gestational weeks at first antenatal visit and number of previous miscarriages did not reveal such an association. Attributable risk of untreated gonorrhoea for premature birth was 72% and routine cultures were cost-benefit efficient. CONCLUSIONS--At least in countries where the prevalence is high, genital infections as well as the risk factors for acquiring them (young age, late sexual debut, number of recent partners) play a major role in the aetiogenesis of prematurity and low birth weight. N. gonorrhoeae is a main contributor, and in high prevalence areas it should be routinely looked for and treated for during pregnancy.

Aerobic vaginitis in pregnancy.

Please cite this paper as: Donders G, Bellen G, Rezeberga D. Aerobic vaginitis in pregnancy. BJOG 2011; DOI: 10.1111/j.1471‐0528.2011.03020.x.

Amniotic Fluid Interleukin-1 Beta and Interleukin-6, but not Interleukin-8 Correlate with Microbial Invasion of the Amniotic Cavity in Preterm Labor

Citation 
Marconi C, Ramos BRA,
Peraçoli JC, Donders GGG, Silva MG. Amniotic fluid interleukin‐1 betaand interleukin‐6, but not interleukin‐8 correlate with microbial invasion of the amniotic cavity in preterm labor. Am J Reprod Immunol 2011; 65: 549–556

Diagnosis and Management of Bacterial Vaginosis and Other Types of Abnormal Vaginal Bacterial Flora: A Review

Bacterial vaginosis (BV) is a common cause of abnormal vaginal discharge. It is characterised by an overgrowth of predominantly anaerobic organisms (Gardnerella vaginalis, Prevotella spp., Peptostreptocci, Mobiluncus spp.) in the vagina leading to a replacement of lactobacilli and an increase in vaginal pH. BV can arise and remit spontaneously, but often presents as a chronic or recurrent disease. BV is found most often in women of childbearing age, but may also be encountered in menopausal women, and is rather rare in children. The clinical and microscopic features and diagnosis of BV are herein reviewed, and antibiotic and non-antibiotic treatment approaches discussed. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this educational activity, the participant should be better able to analyze bacterial vaginosis clinically, formulate an oral antibiotic treatment regimen for bacterial vaginosis and use vaginal treatments for bacterial vaginosis.