PurposeThis study investigates the role of bacterial vaginosis (BV) on pregnancy rates during various fertility treatments. BV is known to influence several obstetric outcomes, such as preterm... Show morePurposeThis study investigates the role of bacterial vaginosis (BV) on pregnancy rates during various fertility treatments. BV is known to influence several obstetric outcomes, such as preterm delivery and endometritis. Only few studies investigated the effect of BV in subfertile women, and studies found a negative effect on fecundity especially in the in vitro fertilisation population.MethodsObservational prospective study, 76 couples attending a fertility clinic in the Netherlands between July 2019 and June 2022, undergoing a total of 133 attempts of intra uterine insemination, in vitro fertilization or intra cytoplasmatic sperm injection. Vaginal samples taken at oocyte retrieval or insemination were analysed on qPCR BV and 16S rRNA gene microbiota analysis of V1-V2 region. Logistic regression with a Generalized Estimated Equations analysis was used to account for multiple observations per couples.ResultsA total of 26% of the 133 samples tested positive for BV. No significant differences were observed in ongoing pregnancy or live birth rates based on BV status (OR 0.50 (0.16-1.59), aOR 0.32 (0.09-1.23)) or microbiome community state type. There was a tendency of more miscarriages based on positive BV status (OR 4.22 (1.10-16.21), aOR 4.28 (0.65-28.11)) or community state type group III and IV. On baseline qPCR positive participants had significantly higher body mass index and smoked more often. Odds ratios were adjusted for smoking status, body mass index, and socioeconomic status.ConclusionBacterial vaginosis does not significantly impact ongoing pregnancy rates but could affect miscarriage rates. Show less
Tweel, M.M. van den; Struijs, S. van der; Munckhof, E.H.A. van den; Boers, K.E. 2022
Purpose Bacterial vaginosis (BV) is a dysbiosis of the vaginal microbiome and a condition found in 20-30% of all women. Literature describing the possible link between BV and subfertility is... Show morePurpose Bacterial vaginosis (BV) is a dysbiosis of the vaginal microbiome and a condition found in 20-30% of all women. Literature describing the possible link between BV and subfertility is increasing. Newer techniques such as quantitative polymerase chain reactions (qPCR) detect BV more accurately than traditional methods but come with high costs. The association between pH and BV as diagnosed using traditional methods is well-established in a symptomatic population. This study is the first to investigate the association between pH and BV diagnosed by qPCR in an asymptomatic subfertile population and to examine the usefulness of pH as a means of cost reduction.Methods Data of 170 pH-qPCR combinations were used from a prospective cohort study examining bacterial vaginosis in a subfertile population. 102 women received a vaginal swab and pH measurement at baseline and subsequent advanced reproductive technology (ART) treatments. The swabs are analysed using the -AmpliSens (R) Florocenosis/Bacterial vaginosisFRT qPCR kit.Results pH is strongly associated with BV as diagnosed by qPCR (OR 3.06, p = 0.000, CI 1.65-5.68). The cut-off point for pH >= 4.7 maximised diagnostic performance [AUC 0.74 (CI 0.66-0.83), sensitivity 76%] and reduced costs by 60%.Conclusion This study shows that the vaginal pH for a multi-ethnic, asymptomatic population of women attending fertility clinics is strongly associated with BV qPCR outcome. Using the cut-off of pH of 4.7 has a high sensitivity for diagnosis of BV by qPCR and can be achieved at a cost reduction of 60%. Show less
Munckhof, E.H.A. van den; Sitter, R.L. van; Lamont, R.F.; Cessie, S. le; Kuijper, E.J.; Knetsch, C.W.; ... ; Leverstein-van Hall, M.A. 2021
Abnormal vaginal discharge may be caused by bacterial vaginosis, vulvovaginal candidiasis, trichomoniasis and/or aerobic vaginitis. For the development of a diagnostic algorithm, tree-based... Show moreAbnormal vaginal discharge may be caused by bacterial vaginosis, vulvovaginal candidiasis, trichomoniasis and/or aerobic vaginitis. For the development of a diagnostic algorithm, tree-based classification analysis was performed on symptoms, signs and bedside test results of 56 patients, and laboratory tests (culture, Nugent score, qPCRs) were compared. Amplicon sequencing of the 16S rRNA gene was used as reference test for bacterial vaginosis and aerobic vaginitis, culture for vulvovaginal candidiasis and qPCR for trichomoniasis. For bacterial vaginosis, the best diagnostic algorithm was to screen at the bedside with a pH and odour test and if positive, to confirm by qPCR (sensitivity 94%; specificity 97%) rather than Nugent score (sensitivity of 59%; specificity 97%; P = 0.031). The analysis for the other infections was less conclusive due to the low num -ber of patients with these infections. For bacterial vaginosis, the developed algorithm is sensitive, specific, and reduces the need for laboratory tests in 50% of the patients. (c) 2021 Elsevier Inc. All rights reserved. Show less
The human body is colonized by microorganisms, collectively referred to as the human microbiota. Microbiota disturbance has been associated with a wide range of diseases and is the focus of many... Show moreThe human body is colonized by microorganisms, collectively referred to as the human microbiota. Microbiota disturbance has been associated with a wide range of diseases and is the focus of many research initiatives. The most widely used approach is based on sequencing of the 16S rRNA gene. This method can also be very valuable for clinical microbiology as it enables identification of a theoretically unlimited number of bacteria present in a specimen and permits (semi)quantitative information about the composition of a microbial community. In this thesis we investigated whether 16S rRNA gene profiling would have added value for direct diagnostics and/or as an indirect tool for evaluating cheaper diagnostic tests or evaluating treatments. The studies in this thesis were focused on respiratory tract infections, bacterial vaginosis, atopic dermatitis or male genital lichen sclerosus. The main challenge of 16S rRNA gene profiling is the clinical interpretation of relative abundance of the identified bacteria in clinical specimens. More clinical studies with appropriate control groups are needed to define and validate clinically relevant cut-off values, to measure microbiota variability over time and to determine microbial phenotypes. The clinical value of 16S rRNA gene profiling will probably become clear in the forthcoming years. Show less
Niemeyer-van der Kolk, T.; Wall, H. van der; Hogendoorn, G.K.; Rijneveld, R.; Luijten, S.; Alewijk, D.C.J.G. van; ... ; Doorn, M.B.A. van 2020
Omiganan is an indolicidin analog with antimicrobial properties that could be beneficial for patients with atopic dermatitis. In this randomized, double-blind, placebo-controlled, phase II trial we... Show moreOmiganan is an indolicidin analog with antimicrobial properties that could be beneficial for patients with atopic dermatitis. In this randomized, double-blind, placebo-controlled, phase II trial we explored the efficacy, pharmacodynamics, and safety of topical omiganan once daily in 36 patients with mild to moderate atomic dermatitis. Patients were randomized to apply topical omiganan 1%, omiganan 2.5%, or vehicle gel to one target lesion once daily for 28 consecutive days. Small but significant improvements in local objective SCORing Atopic Dematitis index and morning itch were observed in the omiganan 2.5% group compared with the vehicle gel group (-18.5%; 95% confidence interval, -32.9 to -1.0; P = 0.04; and -8.2; 95% confidence interval, -16.3 to -0.2; P = 0.05, respectively). A shift from lesional to nonlesional skin microbiota was observed in both omiganan treatment groups, in contrast to the vehicle group. Thus, treatment with topical omiganan improved dysbiosis in patients with mild to moderate atopic dermatitis, and small but statistically significant improvements in clinical scores were detected. Our findings warrant further exploration in future clinical trials. Show less
Background Male genital lichen sclerosus (MGLSc) is a chronic inflammatory scarring dermatosis associated with penile carcinoma. The prepuce is pivotal in its etiology. Other proposed etiological... Show moreBackground Male genital lichen sclerosus (MGLSc) is a chronic inflammatory scarring dermatosis associated with penile carcinoma. The prepuce is pivotal in its etiology. Other proposed etiological factors are the subject of dispute and include occluded urinary exposure, autoimmunity, immunodysregulation, and infectious agents.Objective To determine whether the bacterial microbiota of the balanopreputial sac and urine are associated with MGLSc. Subjects and methods Twenty uncircumcised patients with MGLSc and 20 healthy uncircumcised males were enrolled in a prospective case-control study. Balanopreputial swabs and urine specimens were subjected to 16S rRNA gene amplicon sequencing.Results Microbiota analysis indicated differences between the groups. In the balanopreputial sac, the median relative abundance of Finegoldia spp. was lower (9% [range 0-60%]) in MGLSc patients than in controls (28% [range 0-62%]). Conversely, the median relative abundance of Fusobacterium spp. was higher in MGLSc patients (4% [range 0-41%]) than in controls (0% [range 0-28%]). In the urine, the median relative abundance of Finegoldia spp. was comparable between groups, whereas that of Fusobacterium spp. was higher in MGLSc patients (0% [range 0-18%] vs. 0% [range 05%]). There was a strong association between the microbiota composition of the balanopreputial sac and urine in MGLSc.Conclusion Dysbiosis could be involved in the etiopathogenesis of MGLSc. Further studies are required to confirm the association suggested herein and to determine its nature. Show less
Bacterial vaginosis (BV) is perceived as a condition of disrupted vaginal microbiota, but remains of unknown aetiology. In this study, vaginal microbiota composition was determined in twenty-one... Show moreBacterial vaginosis (BV) is perceived as a condition of disrupted vaginal microbiota, but remains of unknown aetiology. In this study, vaginal microbiota composition was determined in twenty-one women with BV, before and after treatment with metronidazole or clindamycin. Microbiota composition varied greatly between women and defining a (un)healthy vaginal microbiota state remains elusive, challenging BV diagnosis and treatment. While relative abundance ofLactobacillusincreased after antibiotic treatment in two-third of women, its abundance was not associated with treatment outcome. Instead, remaining complaints of abnormal vaginal discharge were more common after metronidazole treatment and associated with increased relative abundance ofUreaplasma. Show less
Kolk, T.N. van der; Buters, T.P.; Krouwels, L.; Boltjes, J.; Kam, M.L. de; Wall, H. van der; ... ; Doorn, M.B.A. van 2020
BACKGROUND\nOBJECTIVE\nMETHODS\nRESULTS\nCONCLUSION\nDysbiosis and colonization with Staphylococcus aureus is considered to play an important role in the pathogenesis of atopic dermatitis (AD).... Show moreBACKGROUND\nOBJECTIVE\nMETHODS\nRESULTS\nCONCLUSION\nDysbiosis and colonization with Staphylococcus aureus is considered to play an important role in the pathogenesis of atopic dermatitis (AD). Recovering this dysbiosis may improve AD symptoms. Omiganan is a synthetic indolicidin analogue antimicrobial peptide with activity against S. aureus and could be a viable new treatment option for AD.\nTo explore the tolerability, clinical efficacy and pharmacodynamics of omiganan in mild-to-moderate AD.\nEighty patients were randomized to omiganan 1%, 1.75%, 2.5% or vehicle twice daily for 28 days on all lesions. Weekly visits included clinical scores, and microbiological and pharmacodynamic assessments of one 'target lesion'.\nIn all omiganan treatment groups dysbiosis was recovered by reducing Staphylococcus abundance and increasing diversity. A reduction of cultured S. aureus was observed in all omiganan treatment groups, with a significant reduction for omiganan 2.5% compared to vehicle (-93.5%, 95%CI=-99.2%/-28.5% p=0.02). No significant clinical improvement was observed.\nTopical administration of omiganan twice daily for up to 28 days in patients with mild-to-moderate AD led to a recovery of dysbiosis, but without clinical improvement. Therefore, a mono-treatment that selectively targets the microbiome does not appear to be a successful treatment strategy in mild-to-moderate AD. Show less
Munckhof, E.H.A. van den; Hafkamp, H.C.; Kluijver, J. de; Kuijper, E.J.; Koning, M.N.C. de; Quint, W.G.V.; Knetsch, C.W. 2020
BackgroundThe elderly (>= 65years) are one of the populations most at risk for respiratory tract infections (RTIs). The aim of this study was to determine whether nasal and/or oropharyngeal... Show moreBackgroundThe elderly (>= 65years) are one of the populations most at risk for respiratory tract infections (RTIs). The aim of this study was to determine whether nasal and/or oropharyngeal microbiota profiles are associated with age and RTIs.MethodsNasal and oropharyngeal swabs of 152 controls and 152 patients with an RTI were included. The latter group consisted of 72 patients with an upper respiratory tract infection (URTI) and 80 with a lower respiratory tract infection (LRTI). Both nasal and oropharyngeal swabs were subjected to microbiota profiling using amplicon sequencing of the 16S rRNA gene. Moraxella species were determined using quantitative real-time PCR and culture.ResultsBased on the microbiota profiles of the controls and the patients with an RTI, eight nasal and nine oropharyngeal microbiota clusters were defined. Nasal microbiota dominated by either Moraxella catarrhalis or Moraxella nonliquefaciens was significantly more prevalent in elderly compared to mid-aged adults in the control group (p=0.002). Dominance by M. catarrhalis/nonliquefaciens was significantly less prevalent in elderly with an LRTI (p=0.001) compared to controls with similar age.ConclusionsNasal microbiota dominated by M. catarrhalis/nonliquefaciens is associated with respiratory health in the elderly population. Show less
Munckhof, E.H.A. van den; Niemeyer-Van der Kolk, T.; Wall, H.E.C. van der; Alewijk, D.C.J.G. van; Doorn, M.B.A. van; Burggraaf, J.; ... ; Rissmann, R. 2020
