Bacterial vaginosis: a critical analysis of current knowledge.

Bacterial vaginosis (BV), the change from a Lactobacillus-dominant vaginal microbiota to an anaerobic and facultative bacterial dominance, is associated with pathological sequelae. In many BV-positive women their microbiota is in fact normal and unrelated to pathology. Whether or not the dominance of BV-associated bacteria persists depends upon interactions between host and bacterial factors. Inconsistencies in diagnosis and erroneous associations with pathology may be due to a failure to differentiate between sub-populations of women. It is only in those women with a BV diagnosis in which the identified bacteria are atypical and persist that BV may be a clinical problem requiring intervention. TWEETABLE ABSTRACT: Improved diagnosis of bacterial vaginosis is needed to accurately determine its role in pathology.

Differential expression of lactic acid isomers, extracellular matrix metalloproteinase inducer, and matrix metalloproteinase-8 in vaginal fluid from women with vaginal disorders.

OBJECTIVE: Do metabolites in vaginal samples vary between women with different vaginal disorders. DESIGN: Cross-sectional study. SETTING: Campinas, Brazil. SAMPLE: Seventy-seven women (39.9%) with no vaginal disorder, 52 women (26.9%) with vulvovaginal candidiasis (VVC), 43 women (22.3%) with bacterial vaginosis (BV), and 21 women (10.9%) with cytolytic vaginosis (CTV). METHOD: Concentrations of D- and L-lactic acid, extracellular matrix metalloproteinase inducer (EMMPRIN), and matrix metalloproteinase-8 (MMP-8), and the influence of Candida albicans on EMMPRIN production by cultured vaginal epithelial cells, were determined by enzyme-linked immunosorbent assay (ELISA). Associations were determined by the Mann-Whitney U-test and by Spearman's rank correlation test. MAIN OUTCOME MEASURES: Metabolite levels and their correlation with diagnoses. RESULTS: Vaginal concentrations of D- and L-lactic acid were reduced from control levels in BV (P < 0.0001); L-lactic acid levels were elevated in CTV (P = 0.0116). EMMPRIN and MMP-8 concentrations were elevated in VVC (P < 0.0001). EMMPRIN and L-lactic acid concentrations (P ≤ 0.008), but not EMMPRIN and D-lactic acid, were correlated in all groups. EMMPRIN also increased in proportion with the ratio of L- to D-lactic acid in controls and in women with BV (P ≤ 0.009). Concentrations of EMMPRIN and MMP-8 were correlated in controls and women with VVC (P ≤ 0.0002). Candida albicans induced EMMPRIN release from vaginal epithelial cells. CONCLUSIONS: Vaginal secretions from women with BV are deficient in D- and L-lactic acid, women with VVC have elevated EMMPRIN and MMP-8 levels, and women with CTV have elevated L-lactic acid levels. These deviations may contribute to the clinical signs, symptoms, and sequelae that are characteristic of these disorders.

Autophagy and female genital tract infections: new insights and research directions.

Autophagy is a highly conserved process by which defective organelles, non-functional proteins, and intracellular microorganisms become sequestered within structures called autophagosomes, which fuse with lysosomes and the engulfed components are degraded by lysosomal enzymes. In microbial autophagy degraded peptides are used to induce antigen-specific acquired immunity. Viruses, bacteria, fungi, and protozoa have developed strategies to subvert autophagy and/or to use this process to promote their replication and persistence. This review details the mechanisms by which microorganisms that infect the female genital tract and/or are detrimental to pregnancy interact with this host defence mechanism. Based on an understanding of autophagy-related pathological mechanisms, we propose new avenues for research to more effectively prevent and/or treat these infectious diseases.

Relationship between clinical diagnosis of recurrent vulvovaginal candidiasis and detection of Candida species by culture and polymerase chain reaction.

BACKGROUND: Recurring vulvovaginal candidiasis (RVVC) is a common vaginal discharge affecting 75% of all women at least once in their life. In 5% of these women, infection is recurring. Aim of the study was to determine the sensitivity of detecting Candida species by culture and polymerase chain reaction (PCR) in women with a clinical diagnosis of RVVC. METHODS: A total number of 104 patients referred with a clinical diagnosis of RVVC and therefore at least four episodes in the previous year were evaluated. In order to detect Candida, vaginal swabs were cultured on Sabouraud and chromagar. Furthermore, the supernatant from the vaginal lavage was examined for the presence of Candida by PCR. RESULTS: When the culture was analyzed, only 31 (29.8%) of the 104 patients diagnosed with RVVC were positive for Candida species in their vagina. Candida albicans was identified in 25 women and six were positive for Candida glabrata. When analyzed by PCR, 44 (42.3%) patients were positive for Candida species. In 13 women (12.5%) only the PCR was positive, while in 31 patients both culture and PCR were positive. CONCLUSION: The diagnostic method of PCR is more sensitive than culture in detecting Candida species in the vagina. The results also suggest further investigation to verify the complaints of the negative tested patients.

Chlamydia trachomatis infection, Fallopian tube damage and a mannose-binding lectin codon 54 gene polymorphism.

BACKGROUND: Mannose-binding lectin (MBL), a component of the innate immune system, provides a first-line defense against invading microorganisms. Polymorphisms in the MBL gene have been associated with increased risk of infection. Chlamydia trachomatis genital tract infections are a major cause of Fallopian tube occlusion. Our objective was to test whether an MBL codon 54 polymorphism might contribute to development of C. trachomatis-associated tubal damage. METHODS: In a case-control study, 97 women with occluded and 104 women with patent Fallopian tubes were tested for a history of chlamydial infection by serology and for their MBL codon 54 genotype by PCR and restriction fragment length polymorphism analysis. Clinical data were blinded to those performing all laboratory analyses. RESULTS: Women with tubal occlusion who also had a positive chlamydial serology had the highest rate of variant MBL B allele carriage (P<0.001). Among women who were chlamydial antibody negative, allele B carriage was also more frequent in those with blocked, as opposed to patent, Fallopian tubes (P<0.01). CONCLUSIONS: Wild-type allele A homozygosity is protective against, while carriage of the variant allele B is a risk factor for, Fallopian tube occlusion in women who are seropositive or seronegative for C. trachomatis.

Efficacy of nonhormonal vaginal contraceptives from a hydrogel delivery system.

This investigation describes the synthesis of a biodegradable hydrogel composed of a core surrounded by four concentric sheaths containing dextran, copolymers of polylactide and epsilon-caprolactone. The hydrogel was impregnated with iron (II) d-gluconate dihydrate, which causes complete spermiostasis due to lipid peroxidation, ascorbic acid to increase the viscosity of the cervical mucus and mixtures of polyamino and polycarboxylic acids to sustain vaginal pH close to 4.5. The combined effects of the agents in the daily eluates of the hydrogel were efficacious up to 16 days, within 30 s, as shown by sperm penetration tests. For in vivo studies, rabbits were chosen as the experimental model because they are easy to handle and the female is always in estrus. The anterior vagina of estrous female rabbits was instilled with the hydrogel, and then inseminated with the semen from a fertile male. Postinsemination flush from the female rabbits showed that all of the sperm were dead. These observations demonstrate the potential for the development of a biocompatible, nonhormonal, intravaginal contraceptive device.

Hepatitis B immunization in postpartum women.

OBJECTIVE: To investigate the acceptance and efficacy of hepatitis B immunization in women during the postpartum period. STUDY DESIGN: A group of 157 consecutive women who were delivered of neonates between 1994 and 1999 under the care of a private, full-time faculty-based practice of obstetrics and gynecology participated in the study. All patients were screened for hepatitis B surface antigen and antibody during their pregnancy. Susceptible patients eligible for hepatitis B immunization were offered the vaccine in the immediate postpartum period. The planned vaccine administration was a series of 3 intramuscular injections, with the second injection given 4 weeks later and the third given 6 months after the initial injection. Rescreening for hepatitis B surface antibody titers was performed at a visit after the last injection. Response to the immunization series was evaluated according to rate of acceptance, compliance, and achievement of seroprotection. RESULTS: Thirteen (8%) patients had been immunized previously and had antibodies, whereas 8 (5%) patients had serologic evidence of a previous infection. Of the 136 patients eligible for the study, 113 (83%) agreed to participate, 16 (12%) declined, and 7 (5%) moved away from New York right after delivery. Of the 113 participants, 104 (92%) patients received at least 2 vaccine injections, with 80 (71%) completing 3 injections. Among patients who had postvaccinal antibody titers, 66 of 69 (96%) of the group that received 3 injections and 9 (75%) of 12 of the group that received 2 injections were found to have antibodies. CONCLUSION: Hepatitis B immunization in the postpartum period is feasible and effective.

Concerns regarding the Centers for Disease Control's published guidelines for pelvic inflammatory disease.

The International-Infectious Disease Society for Obstetrics and Gynecology-USA (I-IDSOG-USA) has concerns about the most recently published Centers for Disease Control and Prevention (CDC) guidelines for pelvic inflammatory disease (PID). I-IDSOG-USA advocates the following changes when the guidelines are revised. We recommend the use of the term "upper genital tract infection" (UGTI), followed by the designation of the etiologic agent, instead of the currently employed term, "pelvic inflammatory disease," or PID. In diagnoses, there should be greater emphasis on signs and symptoms related to subclinical or occult UGTI. Therapeutic recommendation for the treatment of UGTI should be documented for various stages of this diverse disease entity. There should be greater emphasis on hospitalization for infected nulligravida teenagers. This permits monitoring of antibiotic treatment and provides a site for medical educational efforts to teach this medically underserved segment of our society how to protect their future fertility, their health, and their lives.

Differentiation between women with vulvovaginal symptoms who are positive or negative for Candida species by culture.

OBJECTIVE: To investigate whether clinical criteria could differentiate between women with vulvovaginitis who were culture positive or negative for vaginal Candida species. METHODS: Vulvovaginal specimens were obtained from 501 women with a vaginal discharge and/or pruritus. Clinical information and wet mount microscopy findings were obtained. All specimens were sent to a central laboratory for species identification. RESULTS: A positive culture for Candida species was obtained from 364 (72.7%) of the specimens. C. albicans was identified in 86.4% of the positive cultures, followed by C. glabrata in 4.5%, C parapsilosis in 3.9%, C. tropicalis in 2.7% and other Candida species in 1.4%. Women with a positive Candida culture had an increased utilization of oral contraceptives (26.1% vs. 16.8%, p = 0.02) and antibiotics (8.2% vs. 0.7%, p = 0.001), and were more likely to be pregnant (9.1% vs. 3.6%, p = 0.04) than the culture-negative women. Dyspareunia was more frequent in women without Candida (38.0% vs. 28.3%, p = 0.03) while vaginal erythema (p = 0.01) was more common in women with a positive Candida culture. CONCLUSIONS: Although quantitative differences were observed, the presence of vaginal Candida vulvovaginitis cannot be definitively identified by clinical criteria.

Individual immunity and susceptibility to female genital tract infection.

The responses to genital tract infection vary among different women to a far greater extent than has previously been appreciated. All women are not genetically identical and have not been exposed to identical environments; therefore it is naive to expect that a particular microorganism will elicit the identical response and have the identical sequelae for each infected individual. The genes inherited from one's parents, which contain specific polymorphisms in immune response genes, greatly influence the direction and magnitude of the immune response to microorganisms. Similarly, extrinsic variables, such as the type or quantity of a specific infection, whether there is a coinfection with another microorganism, such as an intracellular parasite, and whether an immediate hypersensitivity response is concurrently induced also determine the nature of the host response and thus the consequences of microbial exposure. Finally, factors such as the frequency of sexual intercourse and previous immune sensitization to spermatozoa or other components of a particular ejaculate also influence the outcome. An increased awareness of the uniqueness of each host will lead to the development of more precise individualized treatments and improvements in combating infectious diseases of the female genital tract.

Syphilis in pregnancy.

Syphilis can seriously complicate pregnancy and result in spontaneous abortion, stillbirth, non-immune hydrops, intrauterine growth restriction, and perinatal death, as well as serious sequelae in liveborn infected children. While appropriate treatment of pregnant women often prevents such complications, the major deterrent has been inability to identify the infected women and get them to undergo treatment. Screening in the first trimester with non-treponemal tests such as rapid plasma reagin (RPR) or venereal disease research laboratory (VDRL) test combined with confirmation of reactive individuals with treponemal tests such as the fluorescent treponemal antibody absorption (FTA-ABS) assay is a cost effective strategy. Those at risk should be retested in the third trimester. Treatment during pregnancy should be with penicillin. In determining a penicillin regimen, the clinician must consider the stage of the maternal infection and the HIV status of the mother. Patients who are allergic to penicillin should be desensitized before treatment. Despite appropriate treatment, as many as 14% will have a fetal death or deliver infected infants. Treatment may further be complicated by the Jarich-Herxheimer reaction, a complex allergic response to antigens released from dead micro-organisms, which can cause fetal distress and uterine contractions. Thanks to effective intervention strategies and inexpensive penicillin, syphilis rarely complicates pregnancy in the Western world today. In parts of the world where the traditional sexually transmitted diseases have not been controlled, the magnitude of problems associated with syphilis during pregnancy is reminiscent of that faced by the West during the early 1900's.

Testing for high-risk human papillomavirus types will become a standard of clinical care.

Testing for high-risk human papillomavirus types should become a standard of care for women in the United States because cervical cancer is an infectious disease. Current care is based on cytologic screening and a pathologic staging of cellular tissue changes. Before these cellular modifications, there is a demonstrable pattern of human papillomavirus infection. Human papillomavirus is the most frequently acquired sexually transmitted disease in women and is usually eliminated without treatment. Persistence of high-risk human papillomavirus types can lead to abnormal cervical cellular changes. When these cervical cellular changes occur, physician interventions hasten human papillomavirus elimination. Currently, adding human papillomavirus screening to the Papanicolaou smear identifies a population for closer follow-up studies. In the future a vaccine should be introduced to prevent infections, and medical treatments to hasten the elimination of high-risk human papillomavirus types should become part of standard medical practice.

Interleukin 1 receptor antagonist gene polymorphism in women with vulvar vestibulitis.

OBJECTIVE: Vulvar vestibulitis is a chronic inflammatory syndrome of unknown cause and pathogenesis. We examined the relation between vulvar vestibulitis and polymorphisms in the gene coding for the interleukin 1 receptor antagonist, a naturally occurring down-regulator of proinflammatory immune responses. STUDY DESIGN: Cells from the lower genital tract of 68 women with vulvar vestibulitis, 343 women with no history of vulvodynia, and 40 women with human papillomavirus cervical infection were tested by polymerase chain reaction for the different alleles of the gene encoding for interleukin 1 receptor antagonist. The presence of human papillomavirus in the specimens was determined by polymerase chain reaction with the use of degenerate consensus primers to the conserved L1 gene. RESULTS: Allele 2 of the gene encoding the interleukin 1 receptor antagonist was present in homozygous form in 52.9% of women with vulvar vestibulitis. In marked contrast only 8. 5% of the control women and 2.5% of women with human papillomavirus were homozygous for this allele (P

Value of Candida polymerase chain reaction and vaginal cytokine analysis for the differential diagnosis of women with recurrent vulvovaginitis.

OBJECTIVES: Recurrent vulvovaginitis remains difficult to diagnose accurately and to treat. The present investigation evaluated the utility of testing vaginal specimens from women with symptomatic recurrent vulvovaginitis for Candida species by polymerase chain reaction (PCR) and for cytokine responses. METHODS: Sixty-one consecutive symptomatic women with pruritus, erythema, and/or a thick white discharge and a history of recurrent vulvovaginitis and 31 asymptomatic women with no such history were studied. Vaginal swabs were tested for Candida species by PCR, for the antiinflammatory cytokine interleukin (IL)-10, and for the proinflammatory cytokine IL-12. RESULTS: C. albicans was detected in 19 (31.1%) of the patients as well as in three (9.7%) controls (P = 0.03). Both IL-10 (31.1% vs. 0%) and IL-12 (42.6% vs. 6.5%) were also more prevalent in the recurrent vulvovaginitis patients (P < 0.001). However, there was no relation between the presence or absence of Candida and either cytokine. Detection of IL-12 in 14 women indicated the stimulation of a vaginal cell-mediated immune response possibly from an infectious agent. The presence of only IL-10 in six patients indicated a suppression of vaginal cell-mediated immunity and was consistent with a possible allergic etiology. The absence of both IL-10 and IL-12 in other patients, similar to that found in healthy controls, suggested a noninfectious, nonallergic etiology of their symptoms. CONCLUSION: Many women with recurrent vulvovaginitis are not infected with Candida. Testing for Candida should be required in this population. Treatment with only anti-Candida medication will clearly be inadequate for the majority of women with this condition.

Vulvovaginal candidiasis: epidemiologic, diagnostic, and therapeutic considerations.

Although it is the second most common vaginal infection in North America, vulvovaginal candidiasis is a non-notifiable disease and has been excluded from the ranks of sexually transmitted diseases. Not surprisingly, vulvovaginal candidiasis has received scant attention by public health authorities, funding agencies, and researchers. Epidemiologic data on risk factors and pathogenic mechanisms remain inadequately studied. Most important, standards of care, including diagnosis and therapy, remain undefined. A conference was held in April 1996 to define and summarize what is known and supported by scientific data in the areas of epidemiology, diagnosis, and treatment of vulvovaginal candidiasis; but, more important, the conference aimed at defining what is not known, poorly studied, and controversial. Guidelines for the treatment and diagnosis of the different forms of vulvovaginal candidiasis are suggested.