137 research outputs found
Barking up the Wrong Evidence Tree. Comment on Lurie & Rosenthal, “Concurrent Partnerships as a Driver of the HIV Epidemic in Sub-Saharan Africa? The Evidence is Limited”
Comparison of oral and vaginal metronidazole for treatment of bacterial vaginosis in pregnancy: impact on fastidious bacteria
<p>Abstract</p> <p>Background</p> <p>Bacterial vaginosis (BV) is a common condition that is associated with preterm birth and acquisition of complex communities of vaginal bacteria that include several fastidious species. Treatment of BV in pregnancy has mixed effects on the risk of preterm delivery, which some hypothesize is due to variable antibiotic efficacy for the fastidious bacteria. Both oral and intravaginal metronidazole can be used to treat bacterial vaginosis in pregnancy, but little is known about the impact of different routes of antibiotic administration on concentrations of fastidious vaginal bacteria.</p> <p>Methods</p> <p>This was a sub-study of a larger randomized trial of oral versus vaginal metronidazole for treatment of BV in pregnancy. Fifty-three women were evaluated, including 30 women who received oral metronidazole and 23 who received intravaginal metronidazole. Bacterial taxon-specific quantitative PCR assays were used to measure concentrations of bacterial vaginosis associated bacterium (BVAB) 1, 2, and 3, <it>Gardnerella vaginalis, Atopobium </it>species, <it>Leptotrichia/Sneathia </it>species, <it>Megasphaera </it>species, and <it>Lactobacillus crispatus </it>before and after antibiotic treatment.</p> <p>Results</p> <p>Concentrations of <it>Leptotrichia </it>and <it>Sneathia </it>spp. and the fastidious Clostridia-like bacterium designated BVAB1 decreased significantly with oral (p = .002, p = .02) but not vaginal therapy (p = .141, p = .126). The fastidious bacterium BVAB3 did not significantly decrease with either treatment. Concentrations of <it>Atopobium </it>spp., reportedly resistant to metronidazole <it>in vitro</it>, dropped significantly with oral (p = .002) and vaginal (p = .001) treatment. There was no significant difference in the magnitude of change in bacterial concentrations between oral and vaginal treatment arms for any of the bacterial species. <it>Lactobacillus crispatus </it>concentrations did not change.</p> <p>Conclusion</p> <p>Both oral and vaginal metronidazole therapy in pregnant women result in a significant decrease in concentrations of most BV-associated anaerobic bacteria, with the exception that <it>Leptotrichia, Sneathia </it>and BVAB1 do not significantly decrease with vaginal metronidazole therapy. These data suggest that the route of antibiotic administration has a minor impact on bacterial eradication in pregnant women with BV.</p> <p>Trail Registration</p> <p>This trial is registered with ClinicalTrials.gov, number NCT00153517</p
Bacterial vaginosis
Bacterial vaginosis is the most prevalent cause of abnormal vaginal discharge in women of childbearing age. It can have a major impact on quality of life and psychological wellbeing if frequently recurrent and strongly symptomatic. The use of molecular techniques to study the vaginal microbiome is increasing our understanding of the dynamic changes in flora that occur in health and disease. It might soon be possible to separate Gardnerella into different pathogenic and non-pathogenic species. Many groups are studying compounds that can disrupt the biofilm which is dominated by Gardnerella and Atopobium vaginae. Several studies in the last decade support the concept of bacterial vaginosis as a sexually transmitted infection
Antibody-Based Detection and Inhibition of Vaginolysin, the Gardnerella vaginalis Cytolysin
Bacterial vaginosis (BV) is the most common vaginal infection worldwide and is associated with significant adverse sequelae. We have recently characterized vaginolysin (VLY), the human-specific cytotoxin produced by Gardnerella vaginalis and believed to play a critical role in the pathogenesis of BV and its associated morbidities. We hypothesize that novel antibody-based strategies may be useful for detection of VLY and for inhibition of its toxic effects on human cells. Using purified toxin as an immunogen, we generated polyclonal rabbit immune serum (IS) against VLY. A western blot of G. vaginalis lysate was probed with IS and a single band (57 kD) identified. Immunofluorescence techniques using IS detected VLY production by G. vaginalis. In addition, we have developed a sandwich ELISA assay capable of VLY quantification at ng/ml concentrations in the supernatant of growing G. vaginalis. To investigate the potential inhibitory role of IS on VLY-mediated cell lysis, we exposed human erythrocytes to VLY or VLY pretreated with IS and determined the percent hemolysis. Pretreatment with IS resulted in a significant reduction in VLY-mediated lysis. Similarly, both human cervical carcinoma cells and vaginal epithelial cells exhibited reduced cytolysis following exposure to VLY with IS compared to VLY alone. These results confirm that antibody-based techniques are an effective means of VLY detection. Furthermore, VLY antiserum functions as an inhibitor of VLY–CD59 interaction, mitigating cell lysis. These strategies may have a potential role in the diagnosis and treatment of BV
Partner notification for sexually transmitted infections in developing countries: a systematic review
<p>Abstract</p> <p>Background</p> <p>The feasibility and acceptability of partner notification (PN) for sexually transmitted infections (STIs) in developing countries was assessed through a comprehensive literature review, to help identify future intervention needs.</p> <p>Methods</p> <p>The Medline, Embase, and Google Scholar databases were searched to identify studies published between January 1995 and December 2007 on STI PN in developing countries. A systematic review of the research extracted information on: (1) willingness of index patients to notify partners; (2) the proportion of partners notified or referred; (3) client-reported barriers in notifying partners; (4) infrastructure barriers in notifying partners; and (5) PN approaches that were evaluated in developing countries.</p> <p>Results</p> <p>Out of 609 screened articles, 39 met our criteria. PN outcome varied widely and was implemented more often for spousal partners than for casual or commercial partners. Reported barriers included sociocultural factors such as stigma, fear of abuse for having an STI, and infrastructural factors related to the limited number of STD clinics, and trained providers and reliable diagnostic methods. Client-oriented counselling was found to be effective in improving partner referral outcomes.</p> <p>Conclusions</p> <p>STD clinics can improve PN with client-oriented counselling, which should help clients to overcome perceived barriers. The authors speculate that well-designed PN interventions to evaluate the impact on STI prevalence and incidence along with cost-effectiveness components will motivate policy makers in developing countries to allocate more resources towards STI management.</p
Multiplex Immunoassay of Lower Genital Tract Mucosal Fluid from Women Attending an Urban STD Clinic Shows Broadly Increased IL1ß and Lactoferrin
BACKGROUND: More than one million new cases of sexually transmitted diseases (STDs) occur each day. The immune responses and inflammation induced by STDs and other frequent non-STD microbial colonizations (i.e. Candida and bacterial vaginosis) can have serious pathologic consequences in women including adverse pregnancy outcomes, infertility and increased susceptibility to infection by other pathogens. Understanding the types of immune mediators that are elicited in the lower genital tract by these infections/colonizations can give important insights into the innate and adaptive immune pathways that are activated and lead to strategies for preventing pathologic effects. METHODOLOGY/PRINCIPAL FINDINGS: 32 immune mediators were measured by multiplexed immunoassays to assess the immune environment of the lower genital tract mucosa in 84 women attending an urban STD clinic. IL-3, IL-1ß, VEGF, angiogenin, IL-8, ß2Defensin and ß3Defensin were detected in all subjects, Interferon-α was detected in none, while the remaining mediators were detected in 40% to 93% of subjects. Angiogenin, VEGF, FGF, IL-9, IL-7, lymphotoxin-α and IL-3 had not been previously reported in genital mucosal fluid from women. Strong correlations were observed between levels of TNF-α, IL-1ß and IL-6, between chemokines IP-10 and MIG and between myeloperoxidase, IL-8 and G-CSF. Samples from women with any STD/colonization had significantly higher levels of IL-8, IL-3, IL-7, IL-1ß, lactoferrin and myeloperoxidase. IL-1ß and lactoferrin were significantly increased in gonorrhea, Chlamydia, cervicitis, bacterial vaginosis and trichomoniasis. CONCLUSIONS/SIGNIFICANCE: These studies show that mucosal fluid in general appears to be an environment that is rich in immune mediators. Importantly, IL-1ß and lactoferrin are biomarkers for STDs/colonizations providing insights into immune responses and pathogenesis at this mucosal site
Association of Atopobium vaginae, a recently described metronidazole resistant anaerobe, with bacterial vaginosis
BACKGROUND: Bacterial vaginosis (BV) is a polymicrobial syndrome characterized by a change in vaginal flora away from predominantly Lactobacillus species. The cause of BV is unknown, but the condition has been implicated in diverse medical outcomes. The bacterium Atopobium vaginae has been recognized only recently. It is not readily identified by commercial diagnostic kits. Its clinical significance is unknown but it has recently been isolated from a tuboovarian abcess. METHODS: Nucleotide sequencing of PCR amplified 16S rRNA gene segments, that were separated into bands within lanes on polyacrylamide gels by denaturing gradient gel electrophoresis (DGGE), was used to examine bacterial vaginal flora in 46 patients clinically described as having normal (Lactobacillus spp. predominant; Nugent score ≤ 3) and abnormal flora (Nugent score ≥ 4). These women ranged in age from 14 to 48 and 82% were African American. RESULTS: The DGGE banding patterns of normal and BV-positive patients were recognizably distinct. Those of normal patients contained 1 to 4 bands that were focused in the centre region of the gel lane, while those of BV positive patients contained bands that were not all focused in the center region of the gel lane. More detailed analysis of patterns revealed that bands identified as Atopobium vaginae were present in a majority (12/22) of BV positive patients, while corresponding bands were rare (2/24) in normal patients. (P < 0.001) Two A. vaginae isolates were cultivated from two patients whose DGGE analyses indicated the presence of this organism. Two A. vaginae 16S rRNA gene sequences were identified among the clinical isolates. The same two sequences were obtained from DGGE bands of the corresponding vaginal flora. The sequences differed by one nucleotide over the short (~300 bp) segment used for DGGE analysis and migrated to slightly different points in denaturing gradient gels. Both isolates were strict anaerobes and highly metronidazole resistant. CONCLUSION: The results suggest that A. vaginae may be an important component of the complex bacterial ecology that constitutes abnormal vaginal flora. This organism could play a role in treatment failure if further studies confirm it is consistently metronidozole resistant
The epidemiology of bacterial vaginosis in relation to sexual behaviour
<p>Abstract</p> <p>Background</p> <p>Bacterial vaginosis (BV) has been most consistently linked to sexual behaviour, and the epidemiological profile of BV mirrors that of established sexually transmitted infections (STIs). It remains a matter of debate however whether BV pathogenesis does actually involve sexual transmission of pathogenic micro-organisms from men to women. We therefore made a critical appraisal of the literature on BV in relation to sexual behaviour.</p> <p>Discussion</p> <p><it>G. vaginalis </it>carriage and BV occurs rarely with children, but has been observed among adolescent, even sexually non-experienced girls, contradicting that sexual transmission is a necessary prerequisite to disease acquisition. <it>G. vaginalis </it>carriage is enhanced by penetrative sexual contact but also by non-penetrative digito-genital contact and oral sex, again indicating that sex <it>per se</it>, but not necessarily coital transmission is involved. Several observations also point at female-to-male rather than at male-to-female transmission of <it>G. vaginalis</it>, presumably explaining the high concordance rates of <it>G. vaginalis </it>carriage among couples. Male antibiotic treatment has not been found to protect against BV, condom use is slightly protective, whereas male circumcision might protect against BV. BV is also common among women-who-have-sex-with-women and this relates at least in part to non-coital sexual behaviours. Though male-to-female transmission cannot be ruled out, overall there is little evidence that BV acts as an STD. Rather, we suggest BV may be considered a sexually enhanced disease (SED), with frequency of intercourse being a critical factor. This may relate to two distinct pathogenetic mechanisms: (1) in case of unprotected intercourse alkalinisation of the vaginal niche enhances a shift from lactobacilli-dominated microflora to a BV-like type of microflora and (2) in case of unprotected and protected intercourse mechanical transfer of perineal enteric bacteria is enhanced by coitus. A similar mechanism of mechanical transfer may explain the consistent link between non-coital sexual acts and BV. Similar observations supporting the SED pathogenetic model have been made for vaginal candidiasis and for urinary tract infection.</p> <p>Summary</p> <p>Though male-to-female transmission cannot be ruled out, overall there is incomplete evidence that BV acts as an STI. We believe however that BV may be considered a <it>sexually enhanced disease</it>, with frequency of intercourse being a critical factor.</p
Bacterial Vaginosis (BV) Candidate Bacteria: Associations with BV and Behavioural Practices in Sexually-Experienced and Inexperienced Women
BACKGROUND: In recent years several new fastidious bacteria have been identified that display a high specificity for BV; however no previous studies have comprehensively assessed the behavioural risk associations of these bacterial vaginosis-candidate organisms (BV-COs). METHODS: We examined the associations between 8 key previously described BV-COs and BV status established by Nugent's score (NS). We also examined the sexual practices associated with each BV-CO. We incorporated 2 study populations: 193 from a sexually-inexperienced university population and 146 from a highly sexually-active clinic population. Detailed behavioural data was collected by questionnaire and vaginal smears were scored by the Nugent method. Stored samples were tested by quantitative PCR assays for the 8 BV-COs: Atopobium vaginae, Gardnerella vaginalis, Leptotrichia spp., Megasphaera type I, Sneathia spp., and the Clostridia-like bacteria BVAB1, BVAB2 and BVAB3. Associations between BV-COs and BV and behaviours were examined by univariate and multivariable analyses. RESULTS: On univariate analysis, all BV-COs were more common in BV compared to normal flora. However, only Megasphaera type I, BVAB2, A. vaginae and G. vaginalis were significantly independently associated with BV by multivariable analysis. Six of the eight BV-COs (Megasphaera type I, BVAB2, BVAB3, Sneathia, Leptotrichia and G. vaginalis) were rare or absent in sexually-unexposed women, and demonstrated increasing odds of detection with increasing levels of sexual activity and/or numbers of lifetime sexual partners. Only G. vaginalis and A. vaginae were commonly detected in sexually-unexposed women. Megasphaera type I was independently associated with women-who-have-sex-with women (WSW) and lifetime sexual partner numbers, while unprotected penile-vaginal-sex was associated with BVAB2 detection by multivariate analysis. CONCLUSIONS: Four of eight key BV-COs were significantly associated with BV after adjusting for the presence of other BV-COs. The majority of BV-COs were absent or rare in sexually-unexposed women, and associated with increasing sexual exposure, suggesting potential sexual transmission of BV-COs
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