General Obstetrics and Gynecology Gynecology
Pathogenesis of abnormal vaginal bacterial flora

https://doi.org/10.1016/S0002-9378(00)70338-3Get rights and content

Abstract

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 1β, 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, χ2 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 1β 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 1β 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 1β 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 1β 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 1β 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. (Am J Obstet Gynecol 2000;182:872-8.)

Section snippets

Patient population

After oral consent was given, vaginal samples were obtained from 631 unselected women who sought treatment at the obstetrics and gynecology clinic at Gasthuisberg University Hospital, Leuven, Belgium. Among these women, 263 were undergoing examination for a pregnancy follow-up visit and 368 were examined for a contraceptive checkup or because of genital infection.

Menopausal women who were not receiving hormonal replacement therapy, women with genital prolapse, and women with overt genital

Results

Lactobacillary grades were normal (lactobacillary grade I) in 256 of 631 cases (40%), slightly disturbed (lactobacillary grade IIa) in 201 (32%), moderately disturbed (lactobacillary grade IIb) in 58 (9%), and severely disturbed (lactobacillary grade III) in 116 (18%). Vaginal leukocytosis was <5 leukocytes per high-power field in 21 of 593 (3.5%), >10 leukocytes per high-power field but <5 leukocytes per epithelial cell in 381 (64%), 5 to 10 leukocytes per epithelial cell in 141 (25%), and

Comment

This study demonstrated a good correlation between lactobacillary grades and pH, lactate content, and increased cytokine production in the vagina. Lactobacillary grade III corresponds to a complete disruption of the normal lactobacillary resistance of the vagina, with no lactobacillary morphotyes present on microscopic examination of the vaginal fluid. Although it is tempting to equate lactobacillary grade III with bacterial vaginosis, the two conditions should be seen as overlapping but

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Reprint requests: Gilbert G.G. Donders, MD, PhD, University Hospital Gasthuisberg, Herestraat 49, Leuven 3000, Belgium.

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