Showing papers by "Michelle J Cole published in 2020"

Substantial underdiagnosis of lymphogranuloma venereum in men who have sex with men in Europe: preliminary findings from a multicentre surveillance pilot

Abstract: Objectives Understanding the public health impact of lymphogranuloma venereum (LGV) in Europe is hampered by inadequate diagnostics and surveillance systems in many European countries. We developed and piloted LGV surveillance in three European countries without existing systems and performed a preliminary investigation of LGV epidemiology, where little evidence currently exists. Methods We recruited STI or dermatovenereology clinics and associated laboratories serving men who have sex with men (MSM) in Austria, Croatia and Slovenia, using the UK for comparison. We undertook centralised LGV testing of Chlamydia trachomatis (CT)-positive rectal swabs collected between October 2016 and May 2017 from MSM attending these clinics. Stored specimens from Austria (2015–2016) and Croatia (2014) were also tested. Clinical and sociodemographic data were collected using a standardised proforma. The ompA gene of LGV-positive specimens was sequenced. Results In total, 500 specimens from CT-positive MSM were tested, and LGV positivity was 25.6% (128/500; 95% CI 22.0% to 29.6%) overall, and 47.6% (79/166; 40.1% to 55.2%) in Austria, 20.0% (3/15; 7.1% to 45.2%) in Croatia, 16.7% (1/6; 3.0% to 56.4%) in Slovenia and 14.4% (45/313; 10.9% to 18.7 %) in the UK. Proformas were completed for cases in Croatia, Slovenia and in the UK; proformas could not be completed for Austrian cases, but limited data were available from line listings. Where recorded, 83.9% (78/93) of LGV-CT cases were HIV-positive compared with 65.4% (149/228) of non-LGV-CT cases; MSM with LGV-CT were more likely to have proctitis (Austria, 91.8% vs 40.5%, p Conclusions LGV is substantially underdiagnosed in MSM across Europe. Unified efforts are needed to overcome barriers to testing, establish effective surveillance, and optimise diagnosis, treatment and prevention.

A community-driven resource for genomic epidemiology and antimicrobial resistance prediction of Neisseria gonorrhoeae at Pathogenwatch

Abstract: Background: Antimicrobial resistant (AMR) Neisseria gonorrhoeae is an urgent threat to public health, as strains resistant to at least one of the two last line antibiotics used in empiric therapy of gonorrhoea, ceftriaxone and azithromycin, have spread internationally. Whole genome sequencing (WGS) data can be used to identify new AMR clones, transmission networks and inform the development of point-of-care tests for antimicrobial susceptibility, novel antimicrobials and vaccines. Community driven tools that provide an easy access to and analysis of genomic and epidemiological data is the way forward for public health surveillance. Methods: Here we present a public health focussed scheme for genomic epidemiology of N. gonorrhoeae at Pathogenwatch (https://pathogen.watch/ngonorrhoeae). An international advisory group of experts in epidemiology, public health, genetics and genomics of N. gonorrhoeae was convened to inform on the utility of current and future analytics in the platform. We implement backwards compatibility with MLST, NG-MAST and NG-STAR typing schemes as well as an exhaustive library of genetic AMR determinants linked to a genotypic prediction of resistance to eight antibiotics. A collection of over 12,000 N. gonorrhoeae genome sequences from public archives has been quality-checked, assembled and made public together with available metadata for contextualization. Results: AMR prediction from genome data revealed specificity values over 99% for azithromycin, ciprofloxacin and ceftriaxone and sensitivity values around 99% for benzylpenicillin and tetracycline. A case study using the Pathogenwatch collection of N. gonorrhoeae public genomes showed the global expansion of an azithromycin resistant lineage carrying a mosaic mtr over at least the last 10 years, emphasizing the power of Pathogenwatch to explore and evaluate genomic epidemiology questions of public health concern. Conclusions: The N. gonorrhoeae scheme in Pathogenwatch provides customized bioinformatic pipelines guided by expert opinion that can be adapted to public health agencies and departments with little expertise in bioinformatics and lower resourced settings with internet connection but limited computational infrastructure. The advisory group will assess and identify ongoing public health needs in the field of gonorrhoea, particularly regarding gonococcal AMR, in order to further enhance utility with modified or new analytic methods.

Genomic and Phenotypic Variability in Neisseria gonorrhoeae Antimicrobial Susceptibility, England.

Abstract: Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a global concern. Phylogenetic analyses resolve uncertainties regarding genetic relatedness of isolates with identical phenotypes and inform whether AMR is due to new mutations and clonal expansion or separate introductions by importation. We sequenced 1,277 isolates with associated epidemiologic and antimicrobial susceptibility data collected during 2013-2016 to investigate N. gonorrhoeae genomic variability in England. Comparing genetic markers and phenotypes for AMR, we identified 2 N. gonorrhoeae lineages with different antimicrobial susceptibility profiles and 3 clusters with elevated MICs for ceftriaxone, varying mutations in the penA allele, and different epidemiologic characteristics. Our results indicate N. gonorrhoeae with reduced antimicrobial susceptibility emerged independently and multiple times in different sexual networks in England, through new mutation or recombination events and by importation. Monitoring and control for AMR in N. gonorrhoeae should cover the entire population affected, rather than focusing on specific risk groups or locations.

Phylogenomic analysis of Neisseria gonorrhoeae transmission to assess sexual mixing and HIV transmission risk in England: a cross-sectional, observational, whole-genome sequencing study.

Abstract: Summary Background Characterising sexual networks with transmission of sexually transmitted infections might allow identification of individuals at increased risk of infection. We aimed to investigate sexual mixing in Neisseria gonorrhoeae transmission networks between women, heterosexual men, and men who report sex with men (MSM), and between people with and without HIV. Methods In this cross-sectional observational study, we whole-genome sequenced N gonorrhoeae isolates from the archive of the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP).w Isolates that varied by five single nucleotide polymorphisms or fewer were grouped into clusters that represented sexual networks with N gonorrhoeae transmission. Clusters were described by gender, sexual risk group, and HIV status. Findings We sequenced 1277 N gonorrhoeae isolates with linked clinical and sociodemographic data that were collected in five clinics in England during 2013–16 (July 1 to Sept 30 in 2013–15; July 1 to Sept 9 in 2016). The isolates grouped into 213 clusters. 30 (14%) clusters contained isolates from heterosexual men and MSM but no women and three (1%) clusters contained isolates from only women and MSM. 146 (69%) clusters comprised solely people with negative or unknown HIV status and seven (3%) comprised only HIV-positive people. 60 (28%) clusters comprised MSM with positive and negative or unknown HIV status. Interpretation N gonorrhoeae molecular data can provide information indicating risk of HIV or other sexually transmitted infections for some individuals for whom such risk might not be known from clinical history. These findings have implications for sexual health care, including offering testing, prevention advice, and preventive treatment, such as HIV pre-exposure prophylaxis. Funding National Institute for Health Research Health Protection Research Unit; Wellcome; Public Health England.

Antimicrobial resistance in Mycoplasma genitalium sampled from the British general population.

Abstract: Background Mycoplasma genitalium is a common sexually transmitted infection. Treatment guidelines focus on those with symptoms and sexual contacts, generally with regimens including doxycycline and/or azithromycin as first-line and moxifloxacin as second-line treatment. We investigated the prevalence of antimicrobial resistance (AMR)-conferring mutations in M. genitalium among the sexually-active British general population. Methods The third national survey of sexual attitudes and lifestyles (Natsal-3) is a probability sample survey of 15 162 men and women aged 16–74 years in Britain conducted during 2010–12. Urine test results for M. genitalium were available for 4507 participants aged 16–44 years reporting >1 lifetime sexual partner. In this study, we sequenced regions of the 23S rRNA and parC genes to detect known genotypic determinants for resistance to macrolides and fluoroquinolones respectively. Results 94% (66/70) of specimens were re-confirmed as M. genitalium positive, with successful sequencing in 85% (56/66) for 23S rRNA and 92% (61/66) for parC genes. Mutations in 23S rRNA gene (position A2058/A2059) were detected in 16.1% (95%CI: 8.6% to 27.8%) and in parC (encoding ParC D87N/D87Y) in 3.3% (0.9%–11.2%). Macrolide resistance was more likely in participants reporting STI diagnoses (past 5 years) (44.4% (18.9%–73.3%) vs 10.6% (4.6%–22.6%); p=0.029) or sexual health clinic attendance (past year) (43.8% (23.1%–66.8%) vs 5.0% (1.4%–16.5%); p=0.001). All 11 participants with AMR-conferring mutations had attended sexual health clinics (past 5 years), but none reported recent symptoms. Conclusions This study highlights challenges in M. genitalium management and control. Macrolide resistance was present in one in six specimens from the general population in 2010–2012, but no participants with AMR M. genitalium reported symptoms. Given anticipated increases in diagnostic testing, new strategies including novel antimicrobials, AMR-guided therapy, and surveillance of AMR and treatment failure are recommended.

Sensitivity, specificity, inclusivity and exclusivity of the updated Aptima Combo 2 assay, which provides detection coverage of the new diagnostic-escape Chlamydia trachomatis variants

Abstract: Four new variants of Chlamydia trachomatis (nvCTs), detected in several countries, cause false-negative or equivocal results using the Aptima Combo 2 assay (AC2; Hologic). We evaluated the clinical sensitivity and specificity, as well as the analytical inclusivity and exclusivity of the updated AC2 for the detection of CT and Neisseria gonorrhoeae (NG) on the automated Panther system (Hologic). We examined 1004 clinical AC2 samples and 225 analytical samples spiked with phenotypically and/or genetically diverse NG and CT strains, and other potentially cross-reacting microbial species. The clinical AC2 samples included CT wild type (WT)-positive (n = 488), all four described AC2 diagnostic-escape nvCTs (n = 170), NG-positive (n = 214), and CT/NG-negative (n = 202) specimens. All nvCT-positive samples (100%) and 486 (99.6%) of the CT WT-positive samples were positive in the updated AC2. All NG-positive, CT/NG-negative, Trichomonas vaginalis (TV)-positive, bacterial vaginosis-positive, and Candida-positive AC2 specimens gave correct results. The clinical sensitivity and specificity of the updated AC2 for CT detection was 99.7 and 100%, respectively, and for NG detection was 100% for both. Examining spiked samples, the analytical inclusivity and exclusivity were 100%, i.e., in clinically relevant concentrations of spiked microbe. The updated AC2, including two CT targets and one NG target, showed a high sensitivity, specificity, inclusivity and exclusivity for the detection of CT WT, nvCTs, and NG. The updated AC2 on the fully automated Panther system offers a simple, rapid, high-throughput, sensitive, and specific diagnosis of CT and NG, which can easily be combined with detection of Mycoplasma genitalium and TV.

SIREN protocol: Impact of detectable anti-SARS-CoV-2 on the subsequent incidence of COVID-19 in 100,000 healthcare workers: do antibody positive healthcare workers have less reinfection than antibody negative healthcare workers?

Abstract: Background The overall risk of reinfection in individuals who have previously had COVID-19 is unknown. To determine if prior SARS-CoV-2 infection (as determined by at least one positive commercial antibody test performed in a laboratory) in healthcare workers confers future immunity to reinfection, we are undertaking a large-scale prospective longitudinal cohort study of healthcare staff across the United Kingdom. Methods Population and Setting: staff members of healthcare organisations working in hospitals in the UK At recruitment, participants will have their serum tested for anti-SARS-CoV-2 at baseline and using these results will be initially allocated to either antibody positive or antibody negative cohorts. Participants will undergo antibody and viral RNA testing at 1-4 weekly intervals throughout the study period, and based on these results may move between cohorts. Any results from testing undertaken for other reasons (e.g. symptoms, contact tracing etc.) or prior to study entry will also be included. Individuals will complete enrolment and fortnightly questionnaires on exposures and symptoms. Follow-up will be for at least 12 months from study entry. Outcome The primary outcome of interest is a reinfection with SARS -CoV-2 during the study period. Secondary outcomes will include incidence and prevalence (both RNA and antibody) of SARS-CoV-2, viral genomics, viral culture, symptom history and antibody/neutralising antibody titres. Conclusion This large study will help us to understand the impact of the presence of antibodies on the risk of reinfection with SARS-CoV-2; the results will have substantial implications in terms of national and international policy, as well as for risk management of contacts of COVID-19 cases. Trial Registration IRAS ID 284460, HRA and Health and Care Research Wales approval granted 22 May 2020.

Antimicrobial resistance in Neisseria gonorrhoeae isolates from foreign-born population in the European Gonococcal Antimicrobial Surveillance Programme

Abstract: Objectives International spread has contributed substantially to the high prevalence of antimicrobial resistant (AMR) Neisseria gonorrhoeae infections worldwide. We compared the prevalence of AMR gonococcal isolates among native persons to foreign-born (reporting country different from country of birth) persons, and describe the epidemiological and clinical characteristics of foreign-born patients and their associations to AMR. Methods We analysed isolates and patient data reported to the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) 2010–2014 (n=9529). Results Forty-three per cent of isolates had known country of birth and 17.2% of these were from persons born abroad. Almost 50% of foreign-born were from the WHO European Region (13.1% from non-European Union [EU] and the European Economic Area [EEA] countries). Compared with isolates from natives, isolates from foreign-born had a similar level (p>0.05) of azithromycin resistance (7.5% vs 7.2%), ciprofloxacin resistance (50.0% vs 46.3%) and of decreased susceptibility to ceftriaxone (1.9% vs 2.8%); a lower rate of cefixime resistance (5.7% vs 3.6%, p=0.02), and a higher proportion of isolates producing penicillinase (8.4% vs 11.7%, p=0.02). Among isolates from persons born outside EU/EEA, the level of decreased susceptibility to ceftriaxone was higher (1.8% vs 3.5%, p=0.02), particularly in those from the WHO Eastern Mediterranean Region and non-EU/EEA WHO European countries (1.9% vs 9.6% and 8.7%, respectively, p Conclusions Importation of AMR strains remains an important threat in the EU/EEA. Research to improve understanding of sexual networks within foreign born and sexual tourism populations could help to inform effective tailor-made interventions. The Euro-GASP demonstrates the public health value of quality-assured surveillance of gonococcal AMR and the need for strengthened AMR surveillance, particularly in the non-EU/EEA WHO European Region.

A community-driven resource for genomic surveillance of Neisseria gonorrhoeae at Pathogenwatch

Abstract: Background: Antimicrobial resistant (AMR) Neisseria gonorrhoeae is an urgent threat to public health, as strains resistant to at least one of the two last line antibiotics used in empiric therapy of gonorrhoea, ceftriaxone and azithromycin, have spread internationally. With new treatment options not yet available, this has prompted a call for collaborative action on global surveillance for this sexually transmitted pathogen. Whole genome sequencing (WGS) data can be used to identify new AMR clones, outbreaks, transmission networks and inform the development of point-of-care tests for antimicrobial susceptibility, novel antimicrobials and vaccines. Community driven tools that provide an easy access to and analysis of genomic and epidemiological data is the way forward for public health surveillance. Methods: Here we present a public health focussed scheme for genomic epidemiology of N. gonorrhoeae using Pathogenwatch (https://pathogen.watch/ngonorrhoeae), which enables the processing of raw or assembled genomic data. We implement backwards compatibility with MLST, NG-MAST and NG-STAR typing schemes as well as an exhaustive library of genetic AMR determinants associated with resistance to eight antibiotics. A collection of over 12,000 N. gonorrhoeae genome sequences from public archives has been quality-checked, assembled and made public together with available metadata for contextualization. Results: An international advisory group of experts in epidemiology, public health, genetics and genomics of N. gonorrhoeae was convened to identify public health needs in the field and inform on the utility of current and future analytics in the platform, including a customised library of genetic AMR determinants. After uploading genome data, this platform automatically provides typing information, detects genetic determinants of AMR for eight antibiotics including azithromycin and the extended-spectrum cephalosporins ceftriaxone and cefixime, and infers resistance based on the specific combination of mechanisms. Furthermore, genomes are contextualised with globally available genomic data to aid epidemiological investigation. Conclusions: The N. gonorrhoeae scheme in Pathogenwatch provides customized bioinformatic pipelines guided by expert opinion that can be adapted to public health agencies and departments with little expertise in bioinformatics and lower resourced settings with internet connection but limited computational infrastructure. This advisory group will assess and identify ongoing public health needs in the field of gonococcal AMR in order to further enhance utility with modified or new analytic methods.

Investigating the decline in Lymphogranuloma venereum diagnoses in men who have sex with men in the United Kingdom since 2016: an analysis of surveillance data

Abstract: Background Following an upward trajectory in Lymphogranuloma venereum (LGV) diagnoses in the UK from 2004 to 2016, with annual diagnoses increasing from 28 to 904, diagnoses fell to 641 in 2017; this was inconsistent with the upward trend in other bacterial sexually transmissible infections (STIs) between 2016 and 2017. An analysis of surveillance data from multiple sources to investigate the possible factors contributing to this decline in LGV was performed. Methods: LGV tests and diagnoses in the UK from 2004 to 2018 were captured through laboratory data from the LGV Reference Laboratories and laboratories conducting in-house LGV testing. These data and clinical diagnoses data from England were analysed alongside the national management guidelines issued over the course of the epidemic. Results: LGV diagnoses increased between 2004 and 2015 and then decreased between 2016 and 2018. LGV testing increased from 2010 to 2018 (2690–10 850). Test positivity halved between 2015 (14.8%, 929–6272) and 2018 (7.3%, 791–10 850). Peaks in LGV testing and diagnoses appeared to coincide with the publication of national LGV management guidelines and changes to clinical practice. The proportion of LGV diagnoses among HIV-positive men who have sex with men (MSM) fell between 2013 and 2018 (74–48%). Conclusions: The fall in diagnoses and positivity were likely due to increasing earlier clinical diagnosis and treatment. Changes to the national management guidelines, the clinical policy and practice of some larger clinics and potentially changes to the guidelines for the treatment of chlamydia broadened the scope of testing and increased testing in asymptomatic patients which, in combination, likely had a positive effect on the control of LGV infection.