Adverse pregnancy and perinatal outcomes associated with Mycoplasma genitalium: systematic review and meta-analysis.

OBJECTIVE To examine associations between Mycoplasma genitalium infection during pregnancy and adverse outcomes. METHODS We did a systematic review of observational studies. We searched Medline, EMBASE, the Cochrane Library and CINAHL up to 11 August 2021. Studies were included if they compared preterm birth, spontaneous abortion, premature rupture of membranes, low birth weight or perinatal death between women with and without M. genitalium. Two reviewers independently assessed articles for inclusion and extracted data. We used random-effects meta-analysis to estimate summary ORs and adjusted ORs, with 95% CIs, where appropriate. Risk of bias was assessed using established checklists. RESULTS We identified 116 records and included 10 studies. Women with M. genitalium were more likely to experience preterm birth in univariable analyses (summary unadjusted OR 1.91, 95% CI 1.29 to 2.81, I2=0%, 7 studies). The combined adjusted OR was 2.34 (95% CI 1.17 to 4.71, I2=0%, 2 studies). For spontaneous abortion, the summary unadjusted OR was 1.00 (95% CI 0.53 to 1.89, I2=0%, 6 studies). The adjusted OR in one case-control study was 0.9 (95% CI 0.2 to 3.8). Unadjusted ORs for premature rupture of membranes were 7.62 (95% CI 0.40 to 145.86, 1 study) and for low birth weight 1.07 (95% CI 0.02 to 10.39, 1 study). For perinatal death, the unadjusted OR was 1.07 (95% CI 0.49 to 2.36) in one case-control and 38.42 (95% CI 1.45 to 1021.43) in one cohort study. These two ORs were not combined, owing to heterogeneity. The greatest risk of bias was the failure in most studies to control for confounding. CONCLUSION M. genitalium might be associated with an increased risk of preterm birth. Further prospective studies, with adequate control for confounding, are needed to understand the role of M. genitalium in adverse pregnancy outcomes. There is insufficient evidence to indicate routine testing and treatment of asymptomatic M. genitalium in pregnancy. PROSPERO REGISTRATION NUMBER CRD42016050962

Adverse pregnancy and birth outcomes associated with Mycoplasma hominis, Ureaplasma urealyticum and Ureaplasma parvum: a systematic review and meta-analysis.

OBJECTIVES Mycoplasma hominis, Ureaplasma urealyticum and Ureaplasma parvum (genital mycoplasmas) commonly colonise the urogenital tract in pregnant women. This systematic review aims to investigate their role in adverse pregnancy and birth outcomes, alone or in combination with bacterial vaginosis (BV). METHODS We searched Embase, Medline and CINAHL databases from January 1971 to February 2021. Eligible studies tested for any of the three genital mycoplasmas during pregnancy and reported on the primary outcome, preterm birth (PTB) and/or secondary outcomes low birth weight (LBW), premature rupture of membranes (PROM), spontaneous abortion (SA) and/or perinatal or neonatal death (PND).Two reviewers independently screened titles and abstracts, read potentially eligible full texts and extracted data. Two reviewers independently assessed risks of bias using published checklists. Random effects meta-analysis was used to estimate summary ORs (with 95% CIs and prediction intervals). Multivariable and stratified analyses were synthesised descriptively. RESULTS Of 57/1194 included studies, 39 were from high-income countries. In meta-analysis of unadjusted ORs, M. hominis was associated with PTB (OR 1.87, 95% CI 1.49 to 2.34), PROM, LBW and PND but not SA. U. urealyticum was associated with PTB (OR 1.84, 95% CI 1.34 to 2.55), PROM, LBW, SA and PND. U. parvum was associated with PTB (1.60, 95% CI 1.12 to 2.30), PROM and SA. Nine of 57 studies reported any multivariable analysis. In two studies, analyses stratified by BV status showed that M. hominis and U. parvum were more strongly associated with PTB in the presence than in the absence of BV. The most frequent source of bias was a failure to control for confounding. CONCLUSIONS The currently available literature does not allow conclusions about the role of mycoplasmas in adverse pregnancy and birth outcomes, alone or with coexisting BV. Future studies that consider genital mycoplasmas in the context of the vaginal microbiome are needed. PROSPERO REGISTRATION NUMBER CRD42016050962

Adverse pregnancy and neonatal outcomes associated with Neisseria gonorrhoeae, Mycoplasma genitalium, M. hominis, Ureaplasma urealyticum and U. parvum: a systematic review and meta-analysis protocol.

INTRODUCTION Several bacterial sexually transmitted and genital mycoplasma infections during pregnancy have been associated with poor pregnancy and perinatal outcomes. Comprehensive and systematic information about associations between sexually transmitted infections (STI) and genital infections in pregnancy and adverse perinatal outcomes is needed to improve understanding about the evidence for causal associations between these infections and adverse pregnancy and neonatal outcomes. Our primary objective is to systematically review the literature about associations between: (1) in pregnancy and preterm birth; (2) in pregnancy and preterm birth; (3) and/or in pregnancy and preterm birth. METHODS AND ANALYSIS We will undertake a systematic search of Medline, Excerpta Medica database and the Cochrane Library and Cumulative Index to Nursing and Allied Health Literature. Following an initial screening of titles by one reviewer, abstracts will be independently assessed by two reviewers before screening of full-text articles. To exclude a manuscript, both reviewers need to agree on the decision. Any discrepancies will be resolved by discussion, or the adjudication of a third reviewer. Studies will be included if they report testing for one or more of during pregnancy and report pregnancy and/or birth outcomes. In this review, the primary outcome is preterm birth. Secondary outcomes are premature rupture of membranes, low birth weight, spontaneous abortion, stillbirth, neonatal mortality and ophthalmia neonatorum. We will use standard definitions, or definitions reported by study authors. We will examine associations between exposure and outcome in forest plots, using the I statistic to examine between study heterogeneity. Where appropriate, we will use meta-analysis to combine results of individual studies. ETHICS AND DISSEMINATION This systematic review of published literature does not require ethical committee approval. Results of this review will be published in a peer reviewed, open access journal. PROSPERO REGISTRATION NUMBER CRD42016050962

Human papillomavirus genotype distribution and socio-behavioural characteristics in women with cervical pre-cancer and cancer at the start of a human papillomavirus vaccination programme: the CIN3+ plus study.

The Swiss Federal Office of Public Health has recommended vaccination against human papillomavirus (HPV) to prevent cervical cancer since 2008. To establish monitoring of the future public health impact of vaccination, baseline population-based data are required. The objectives of this study were to examine the distribution of oncogenic HPV genotypes in biopsies with cervical intraepithelial neoplasia stage 3 or more severe lesions (CIN3+) at the beginning of HPV vaccination programmes and to compare sociodemographic and behavioural factors of women with CIN3+ with women in the Swiss general population. We conducted a retrospective and prospective cross-sectional study with women diagnosed with CIN3+ in Switzerland. Ten pathology institutes from six cantons and three language regions participated. We conducted HPV typing on formaldehyde fixed-paraffin embedded specimens from 2014 and 2015. Women enrolled in 2015 were asked to complete a questionnaire. We described frequencies of HPV types. We also compared demographic characteristics and socioeconomic status in the CIN3 + plus group with the Swiss National Cohort in 2014 and compared risk factors for HPV infection with the Swiss Health Survey in 2012. We included 768 biopsies from 767 women. Four hundred and seventy-five (61.8%) biopsies were positive for HPV 16 and/or 18, 687 (89.5%) were positive for oncogenic HPV genotypes 16, 18, 31, 33, 45, 52, and/or 58 and five (0.7%) were HPV negative. Twenty-eight (10.3%) of the 273 women who completed the patient questionnaire reported having received at least one dose of an HPV vaccine. When compared with Swiss women in the six study cantons, fewer women in the CIN3+ plus study group were of Swiss nationality, more were born abroad and more were single. The study group also had a higher proportion of women with ≥2 partners in the last year, current smokers and was younger at age of first sexual intercourse. Introduction of the nonavalent vaccine could cover approximately 90% of CIN3+ lesions in Swiss women compared with around 60% with the quadrivalent vaccine. Surveillance of HPV genotype distribution in CIN3+, together with information about vaccination and CIN3+ incidence will allow monitoring of the public health impact of vaccination programmes. ClinicalTrials.gov, NCT02323997 . Registered 24 December 2014

Epidemiological, behavioural, and clinical factors associated with antimicrobial-resistant gonorrhoea: a review.

Antimicrobial-resistant is a global public health problem in the 21st century. has developed resistance to all classes of antibiotics used for empirical treatment, and clinical treatment failure caused by extensively resistant strains has been reported. Identifying specific factors associated with an increased risk of antimicrobial-resistant might help to develop strategies to improve antimicrobial stewardship. In this review, we describe the findings of 24 studies, published between 1989 and 2017, that examined epidemiological, behavioural, and clinical factors and their associations with a range of antimicrobial agents used to treat gonorrhoea. Antimicrobial-resistant is more common in older than younger adults and in men who have sex with men compared with heterosexual men and women. Antimicrobial-resistant is less common in some black minority and Aboriginal ethnic groups than in the majority white population in high-income countries. The factors associated with antimicrobial-resistant gonorrhoea are not necessarily those associated with a higher risk of gonorrhoea

P643 Adverse pregnancy and neonatal outcomes associated with neisseria gonorrhoeae: a systematic review and meta-analysis [abstract].

Background Neisseria gonorrhoeae (NG) infections during pregnancy have been reported to be associated with a range of adverse pregnancy outcomes, but systematic information is lacking. The objective of this study was to systematically review data about associations between NG and: preterm birth (PTB); low birth weight (LBW); premature rupture of membranes; spontaneous abortion; perinatal mortality; and ophthalmia neonatorum. Methods We searched Medline, Excerpta Medica, Cochrane Library and the Cumulative Index to Nursing and Allied Health Literature databases up to October 2017. Two researchers selected studies, extracted data and assessed risk of bias independently. We used meta-analysis to calculate summary odds ratios (OR with 95% confidence intervals, CI) separately for unadjusted and adjusted results, stratified by study design. We assessed heterogeneity using the I2 statistic. Results We screened 2,290 articles and included 15 studies, published from 1976–2017, of which seven were from low or lower-middle income countries. For PTB, the summary unadjusted OR was 1.47 (95% CI 1.17–1.78, I2=0%) in four case-control studies, 1.93 (1.24–2.63, I2=86%) in two cross-sectional studies and 0.78 (0.49–1.06, I2=0%) in three cohort studies. Adjusted ORs were only available in three case-control studies, summary OR 1.14 (0.85–1.44, I2=16%). For LBW, the summary unadjusted OR was 1.57 (1.15–1.99, I2=53%) in three case-control studies, 1.20 (0.30–4.30) in one cross-sectional study and 0.99 (0.73–1.25, I2=47%) in two cohort studies. The adjusted summary OR was 1.33 (0.96–1.71, I2=0%) in the case-control studies. For other outcomes, unadjusted summary ORs varied, generally being lower for cohort than cross-sectional or case-control studies. Conclusion In this systematic review of observational studies, the strength of associations between NG and adverse pregnancy outcomes were weaker than expected and, where data were available, attenuated after adjusting for confounding. Ongoing randomised controlled trials will now determine whether screening and treatment of NG in pregnancy reduces adverse outcomes

Mycoplasma genitalium incidence, persistence, concordance between partners and progression: systematic review and meta-analysis.

BACKGROUND Mycoplasma genitalium is increasingly seen as an emerging sexually transmitted pathogen, and has been likened to Chlamydia trachomatis, but its natural history is poorly understood. The objectives of this systematic review were to determine M. genitalium incidence, persistence, concordance between sexual partners and the risk of pelvic inflammatory disease (PID). METHODS We searched Medline, EMBASE, LILACS, IndMed and African Index Medicus from 1 January 1981 until 17 March 2018. Two independent researchers screened studies for inclusion and extracted data. We examined results in forest plots, assessed heterogeneity and conducted meta-analysis where appropriate. Risk of bias was assessed for all studies. RESULTS We screened 4634 records and included 18 studies; six (4201 women) reported on incidence, five (636 women) on persistence, 10 (1346 women and men) on concordance and three (5139 women) on PID. Incidence in women in two very highly developed countries was 1.07 per 100 person-years (95% CI 0.61 to 1.53, I2 0%). Median persistence of M. genitalium was estimated from one to three months in four studies but 15 months in one study. In 10 studies measuring M. genitalium infection status in couples, 39%-50% of male or female sexual partners of infected participants also had M. genitalium detected. In prospective studies, PID incidence was higher in women with M. genitalium than those without (risk ratio 1.73, 95% CI 0.92 to 3.28, I2 0%, two studies). DISCUSSION Incidence of M. genitalium in very highly developed countries is similar to that for C. trachomatis, but concordance might be lower. Taken together with other evidence about age distribution and antimicrobial resistance in the two infections, M. genitalium is not the new chlamydia. Synthesised data about prevalence, incidence and persistence of M. genitalium infection are inconsistent. These findings can be used for mathematical modelling to investigate the dynamics of M. genitalium. REGISTRATION NUMBERS CRD42015020420, CRD42015020405

Zika virus infection as a cause of congenital brain abnormalities and Guillain-Barré syndrome: From systematic review to living systematic review [version 1]

The Zika virus (ZIKV) outbreak in the Americas has caused international concern due to neurological sequelae linked to the infection, such as microcephaly and Guillain-Barré syndrome (GBS). The World Health Organization stated that there is "sufficient evidence to conclude that Zika virus is a cause of congenital abnormalities and is a trigger of GBS". This conclusion was based on a systematic review of the evidence published until 30.05.2016. Since then, the body of evidence has grown substantially, leading to this update of that systematic review with new evidence published from 30.05.2016 - 18.01.2017, update 1. We review evidence on the causal link between ZIKV infection and adverse congenital outcomes and the causal link between ZIKV infection and GBS or immune-mediated thrombocytopaenia purpura. We also describe the transition of the review into a living systematic review, a review that is continually updated. Between 30.05.2016 and 18.01.2017, we identified 2413 publications, of which 101 publications were included. The evidence added in this update confirms the conclusion of a causal association between ZIKV and adverse congenital outcomes. New findings expand the evidence base in the dimensions of biological plausibility, strength of association, animal experiments and specificity. For GBS, the body of evidence has grown during the search period for update 1, but only for dimensions that were already populated in the previous version. There is still a limited understanding of the biological pathways that potentially cause the occurrence of autoimmune disease following ZIKV infection. This systematic review confirms previous conclusions that ZIKV is a cause of congenital abnormalities, including microcephaly, and is a trigger of GBS. The transition to living systematic review techniques and methodology provides a proof of concept for the use of these methods to synthesise evidence about an emerging pathogen such as ZIKV

P637 Neisseria gonorrhoeae genomic diversity in high risk groups in Switzerland [abstract].

Background Neisseria gonorrhoeae cases are increasing in Europe, with decreasing susceptibility to first line antibiotics. Whole genome sequencing (WGS) provides detailed information about gonococcal molecular epidemiology and prediction of antimicrobial resistance (AMR), especially if linked to epidemiological data. The aim of this study was to examine molecular, clinical and social epidemiological aspects of gonorrhoea infections in Switzerland. Methods In 2015–2016, we cultured urethral, cervical, vaginal, rectal, and pharyngeal specimens from patients in three clinics predominantly attended by men who have sex with men (MSM) and female sex workers (FSW). MSM also completed a sexual behaviour questionnaire. Minimal inhibitory concentrations (MIC) were assessed by Etest, interpreted using EUCAST breakpoints except azithromycin (≥2 mg/L); WGS used an Illumina Miseq. Results We sequenced 140 isolates from 116 participants, MSM (107, 92%, mean age 35.8 years) and FSW (6, 5%, mean age 25.3 years). Amongst MSM, 48/105 respondents (45.7%) reported recent sex abroad. Three patients (two MSM and one FSW) carried different strains at different body sites. The isolates show large genomic diversity, with 69 NG-MAST types and 37 MLST sequence types, largely embedded within characterised European Union clusters. NG-MAST 1407 was identified in n=4 isolates from two patients (FSW, not travel-associated and MSM, sex elsewhere in Europe). Mosaic penAXXXIV was seen in these isolates, and also in an NG-MAST 13488 from an MSM, which was also not travel associated. One isolate (heterosexual male, not travel-associated) with elevated cefixime MIC (0.19 μg/ml) carried a mosaic penAX in an NG-MAST 10557 background. Ciprofloxacin resistance was seen in these six isolates, and overall in 59/140 (42%), all containing GyrA mutations S91F and D95A/G/N. Conclusion Switzerland has a high diversity of circulating gonorrhoea, generally related to European clusters. Multidrug resistant isolates were not identified in this study, but NG-MAST 1407 and penA mosaics, associated with elevated cephalosporin MICs, are circulating