Bacterial vaginosis : current diagnostic avenues and future opportunities

A healthy female genital tract harbors a microbiome dominated by lactic acid and hydrogen peroxide producing bacteria, which provide protection against infections by maintaining a low pH. Changes in the bacterial compositions of the vaginal microbiome can lead to bacterial vaginosis (BV), which is often associated with vaginal inflammation. Bacterial vaginosis increases the risk of acquiring sexually transmitted infections (STIs) like human immunodeficiency virus (HIV) and affects women’s reproductive health negatively. In pregnant women, BV can lead to chorioamnionitis and adverse pregnancy outcomes, including preterm premature rupture of the membranes and preterm birth. In order to manage BV effectively, good diagnostic procedures are required. Traditionally clinical and microscopic methods have been used to diagnose BV; however, these methods require skilled staff and time and suffer from reduced sensitivity and specificity. New diagnostics, including highly sensitive and specific point-of-care (POC) tests, treatment modalities and vaccines can be developed based on the identification of biomarkers from the growing pool of vaginal microbiome and vaginal metabolome data. In this review the current and future diagnostic avenues will be discussed.http://www.frontiersin.org/Cellular_and_Infection_Microbiologyam2020BiochemistryGeneticsMedical MicrobiologyMicrobiology and Plant Patholog

Assessment of Atopobium vaginae and Gardnerella vaginalis concentrations in a cohort of pregnant South African women

OBJECTIVES : The purpose of this cross-sectional study was to assess Atopobium vaginae and Gardnerella vaginalis concentrations in pregnant women of different age groups, gestational age groups, vaginal flora categories and HIV status, and also to determine which DNA concentrations best discriminated between bacterial vaginosis (BV)-positive and non-BV categories. METHODS : Self-collected vaginal swabs were obtained from 220 pregnant women attending an antenatal clinic in Pretoria, Gauteng, South Africa, from July 2012 to December 2012. BV was detected with the Nugent scoring system, and A. vaginae and G. vaginalis DNA was quantified with a multiplex quantitative real-time PCR assay. RESULTS : Median concentrations of A. vaginae and G. vaginalis were not significantly different among various age groups (A. vaginae p=0.98 and G. vaginalis p=0.18) or different trimesters (A. vaginae p=0.31 and G. vaginalis p=0.19), but differed significantly among the vaginal flora categories (A. vaginae p<0.001 and G. vaginalis p<0.001) and HIV status (A. vaginae p<0.001 and G. vaginalis p=0.004). The presence of A. vaginae (OR=5.8; 95% CI 1.34 to 25.21 and p value=0.02) but not that of G. vaginalis (OR=1.90; 95% CI 0.81 to 4.43 and p value=0.14) was associated with HIV infection. An A. vaginae DNA concentration of ≥107 copies/mL together with a positive G. vaginalis result (≥100 copies/mL) best discriminated between BV-positive (39/220) and non-BV categories (181/220) with a sensitivity of 85% (95% CI 0.70 to 0.94) and a specificity of 82% (95% CI 0.76 to 0.88). CONCLUSION : A. vaginae and G. vaginalis were present in high numbers and concentrations in this pregnant cohort. Threshold concentrations should be established for specific populations to ensure sensitive molecular assays for BV detection.The University of Pretoria and the Medical Research Council (South Africa).http://sti.bmj.com2018-09-30hj2017Medical Microbiolog

Antimicrobial susceptibility patterns of Ureaplasma species and Mycoplasma hominis in pregnant women

BACKGROUND : Genital mycoplasmas colonise up to 80% of sexually mature women and may invade the amniotic cavity during pregnancy and cause complications. Tetracyclines and fluoroquinolones are contraindicated in pregnancy and erythromycin is often used to treat patients. However, increasing resistance to common antimicrobial agents is widely reported. The purpose of this study was to investigate antimicrobial susceptibility patterns of genital mycoplasmas in pregnant women. METHODS : Self-collected vaginal swabs were obtained from 96 pregnant women attending an antenatal clinic in Gauteng, South Africa. Specimens were screened with the Mycofast Revolution assay for the presence of Ureaplasma species and Mycoplasma hominis. The antimicrobial susceptibility to levofloxacin, moxifloxacin, erythromycin, clindamycin and tetracycline were determined at various breakpoints. A multiplex polymerase chain reaction assay was used to speciate Ureaplasma positive specimens as either U. parvum or U. urealyticum. RESULTS : Seventy-six percent (73/96) of specimens contained Ureaplasma spp., while 39.7% (29/73) of Ureaplasma positive specimens were also positive for M. hominis. Susceptibilities of Ureaplasma spp. to levofloxacin and moxifloxacin were 59% (26/44) and 98% (43/44) respectively. Mixed isolates (Ureaplasma species and M. hominis) were highly resistant to erythromycin and tetracycline (both 97% resistance). Resistance of Ureaplasma spp. to erythromycin was 80% (35/44) and tetracycline resistance was detected in 73% (32/44) of Ureaplasma spp. Speciation indicated that U. parvum was the predominant Ureaplasma spp. conferring antimicrobial resistance. CONCLUSIONS : Treatment options for genital mycoplasma infections are becoming limited. More elaborative studies are needed to elucidate the diverse antimicrobial susceptibility patterns found in this study when compared to similar studies. To prevent complications in pregnant women, the foetus and the neonate, routine screening for the presence of genital mycoplasmas is recommended. In addition, it is recommended that antimicrobial susceptibility patterns are determined.University of Pretoria, the Medical Research Council (South Africa) and the National Health Laboratory Service (NHLS)http://www.biomedcentral.com/bmcinfectdis/hb201

Diversity of the gut, vaginal and oral microbiome among pregnant women in South Africa with and without pre-eclampsia

The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: NCBI SRA database, accession number PRJNA798597 (BioProjectID).BACKGROUND : Changes in microbial communities are a known characteristic of various inflammatory diseases and have been linked to adverse pregnancy outcomes, such as preterm birth. However, there is a paucity of information regarding the taxonomic composition and/or diversity of microbial communities in pre-eclampsia. The aim of this study was to determine the diversity of the gut, vaginal and oral microbiome in a cohort of South African pregnant women with and without pre-eclampsia. The diversity of the gut, vaginal and oral microbiome was determined by targeted next generation sequencing (NGS) of the V3 and V4 region of the 16S rRNA gene on the Illumina MiSeq platform. RESULTS : In this study population, pre-eclampsia was associated with a significantly higher alpha diversity (P = 0.0472; indicated by the Shannon index) in the vaginal microbiome accompanied with a significant reduction in Lactobacillus spp. (P = 0.0275), compared to normotensive pregnant women. Lactobacillus iners was identified as the predominant species of the vaginal microbiome in both cohorts. High inter-individual variation in alpha diversity was observed in the gut and oral microbiome in both cohorts. Although differences in the relative abundance of bacteria at all phylogenetic levels were observed, overall microbial composition of the gut, oral and vaginalmicrobiome was not significantly different in the pre-eclampsia cohort compared to the normotensive cohort. CONCLUSION : Collectively, a reduction of Lactobacillus spp., and predominance of L. iners in pregnant women with pre-eclampsia could suggest an unstable vaginal microbiome that might predispose pregnant women to develop pre- eclampsia. The lack of significant structural changes in the gut, oral and vaginal microbiome does not suggest that the characterized communities play a role in pre-eclampsia, but could indicate a characteristic unique to the study population. The current study provided novel information on the diversity of the gut, oral and vaginal microbiome among pregnant women in South Africa with and without pre-eclampsia. The current study provides a baseline for further investigations on the potential role of microbial communities in pre-eclampsia.The University of Pretoria and the National Health Laboratory Service (NHLS).https://www.frontiersin.org/journals/global-womens-healtham2023BiochemistryGeneticsMedical MicrobiologyMicrobiology and Plant Patholog

Growth forms of Gardnerella spp. and Lactobacillus spp. on vaginal cells

Bacterial vaginosis (BV) is a common vaginal condition in women of reproductive age. During BV development, BV-associated bacteria may form a polymicrobial biofilm, which predispose women to recurrent BV. The aim of the study was to investigate the growth forms of Gardnerella spp. and Lactobacillus spp. and to determine the association between the bacterial growth forms and clinical characteristics [urinary tract infection (UTI) symptoms, human immunodeficiency virus (HIV) infection and abnormal vaginal discharge] in women attending a tertiary hospital in Pretoria, South Africa. A first-void urine specimen was collected from 196 women and BV was diagnosed using the Nugent scoring and the Ison-Hay criteria (vaginal smear microscopy). Fluorescence in situ hybridisation (FISH) was performed to classify the growth forms [“dispersed” or “biofilm”]. Bacterial cells were categorized as “dispersed” if cells were scattered separately and as “biofilm” if bacterial aggregates on the vaginal epithelial cells were observed. BV was detected in 52 women (52/196; 27%) and in these women, Gardnerella spp. were predominantly present in biofilms (46/52; 88% for Nugent scoring; and 45/50; 90% for Ison-Hay criteria), whereas Lactobacillus spp. were predominantly present in a dispersed form (38/52; 73% for Nugent scoring; and 37/50; 74% for Ison-Hay criteria). The odds of having BV increased when Gardnerella biofilms were present (p < 0.001), whereas the opposite was observed for Lactobacillus biofilms (p = 0.001). Neither Gardnerella spp. or Lactobacillus spp. (both dispersed or biofilms) had an association with the presence of UTI symptoms, HIV coinfection or abnormal vaginal discharge. In conclusion, this study demonstrated and confirmed that Gardnerella biofilms are associated with BV and that Lactobacillus spp. may form biofilms to protect against BV.The Medical Research Council (MRC) of South Africa and National Health Laboratory Service (NHLS) of South Africa.http://frontiersin.org/Cellular_and_Infection_Microbiologypm2021Medical MicrobiologySchool of Health Systems and Public Health (SHSPH

Microbial ligand costimulation drives neutrophilic steroid-refractory asthma

Funding: The authors thank the Wellcome Trust (102705) and the Universities of Aberdeen and Cape Town for funding. This research was also supported, in part, by National Institutes of Health GM53522 and GM083016 to DLW. KF and BNL are funded by the Fonds Wetenschappelijk Onderzoek, BNL is the recipient of an European Research Commission consolidator grant and participates in the European Union FP7 programs EUBIOPRED and MedALL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Chlamydia trachomatis biovar L2 infection in women in South Africa

We detected Chlamydia trachomatis biovar L2 in vaginal swab specimens of 7 women with vaginal discharge in South Africa. Whole-genome sequencing directly from clinical specimens identified a closely related cluster of strains. The clinical role of this infection in the context of syndromic management should be clarified

MICL controls inflammation in rheumatoid arthritis

Acknowledgments We thank G Milne, D MacCallum, S Hardison, G Wilson, C Wallace, S Hadebe and A Richmond for assistance; H. El-Gabalawy for tissues and the animal facility staff for the care of our animals. Flow cytometry was undertaken in the Iain Fraser Cytometry Centre, University of Aberdeen. Funding: GDB was funded by the Wellcome Trust and MRC (UK). AA and CDB are supported by the Arthritis Research UK Tissue Engineering Centre (grant 19429). This study makes use of data generated by the Wellcome Trust Case Control Consortium. A full list of the investigators who contributed to the generation of the data is available from http://www.wtccc.org.uk, and was funded by the Wellcome Trust (076113). MJGF was funded by The Arthritis Society and the Canadian Arthritis Network and J-ML by a scholarship from the Canadian Arthritis Network.Peer reviewedPublisher PD

Recognition and control of neutrophil extracellular trap formation by MICL

Acknowledgements We thank the staff of the animal facilities at the University of Aberdeen and the University of Exeter for support and care for animals; C. Paterson from the University of Glasgow for assistance in establishing a Material Transfer Agreement; C. Parkin and D. Thompson for support with microscopy; and M. Stacey for valuable input. We acknowledge funding from the Wellcome Trust (102705 and 097377), Versus Arthritis (21164, 20775 and 21156), the US National Institutes of Health (R01DK121977 and R01AI163007), Versus Arthritis Centre of Excellence, Medical Research Council (MR/L020211/1) and the MRC Centre for Medical Mycology (MR/N006364/1). SLE tissue samples were provided by the Imperial College Healthcare Tissue Bank funded by the National Institute for Health Research (NIHR), Biomedical Research Centre based at the Imperial College Healthcare NHS Trust and Imperial College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.Peer reviewe