Significant increase in azithromycin “resistance” and susceptibility to ceftriaxone and cefixime in Neisseria gonorrhoeae isolates in 26 European countries, 2019

Euro-GASP network: Claudia Eder, Sonja Pleininger, Steliana Huhlescu, Irith de Baetselier, Blaženka Hunjak, Tatjana Nemeth Blažić, Panagiota Maikanti-Charalampous, Despo Pieridou, Hana Zákoucká, Helena Žemličková, Steen Hoffmann, Susan Cowan, Rita Peetso, Jelena Viktorova, Ndeindo Ndeikoundam, Beatrice Bercot, Anu Patari Sampo, Vesa Kirjavainen, Susanne Buder, Klaus Jansen, Vivi Miriagou, Eszter Balla, Mária Dudás, Guðrún Sigmundsdóttir, Lena Ros Asmundsdottir, Sinead Saab, Brendan Crowley, Anna Carannante, Paola Stefanelli, Gatis Pakarna, Violeta Mavcutko, Robert Cassar, Christopher Barbara, Francesca Vella, Alje Van Dam, Ineke Linde, Dominique Caugant, Hilde Kløvstad, Beata Mlynarczyk-Bonikowska, Maria-José Borrego, Peter Pavlik, Irena Klavs, Tanja Kustec, Julio Vazquez, Asuncion Diaz, Raquel Abad Torreblanca, Inga Velicko, Magnus Unemo, Helen Fifer, Kate TempletonBackground: The European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) performs annual sentinel surveillance of Neisseria gonorrhoeae susceptibility to therapeutically relevant antimicrobials across the European Union/European Economic Area (EU/EEA). We present the Euro-GASP results from 2019 (26 countries), linked to patient epidemiological data, and compared with data from previous years. Methods: Agar dilution and minimum inhibitory concentration (MIC) gradient strip methodologies were used to determine the antimicrobial susceptibility (using EUCAST clinical breakpoints, where available) of 3239 N. gonorrhoeae isolates from 26 countries across the EU/EEA. Significance of differences compared with Euro-GASP results in previous years was analysed using Z-test and the Pearson's χ2 test was used to assess significance of odds ratios for associations between patient epidemiological data and antimicrobial resistance. Results: European N. gonorrhoeae isolates collected between 2016 and 2019 displayed shifting MIC distributions for; ceftriaxone, with highly susceptible isolates increasing over time and occasional resistant isolates each year; cefixime, with highly-susceptible isolates becoming increasingly common; azithromycin, with a shift away from lower MICs towards higher MICs above the EUCAST epidemiological cut-off (ECOFF); and ciprofloxacin which is displaying a similar shift in MICs as observed for azithromycin. In 2019, two isolates displayed ceftriaxone resistance, but both isolates had MICs below the azithromycin ECOFF. Cefixime resistance (0.8%) was associated with patient sex, with resistance higher in females compared with male heterosexuals and men-who-have-sex-with-men (MSM). The number of countries reporting isolates with azithromycin MICs above the ECOFF increased from 76.9% (20/26) in 2016 to 92.3% (24/26) in 2019. Isolates with azithromycin MICs above the ECOFF (9.0%) were associated with pharyngeal infection sites. Following multivariable analysis, ciprofloxacin resistance remained associated with isolates from MSM and heterosexual males compared with females, the absence of a concurrent chlamydial infection, pharyngeal infection sites and patients ≥ 25 years of age. Conclusions: Resistance to ceftriaxone and cefixime remained uncommon in EU/EEA countries in 2019 with a significant decrease in cefixime resistance observed between 2016 and 2019. The significant increase in azithromycin "resistance" (azithromycin MICs above the ECOFF) threatens the effectiveness of the dual therapy (ceftriaxone + azithromycin), i.e., for ceftriaxone-resistant cases, currently recommended in many countries internationally and requires close monitoring.The study was funded by the European Centre for Disease Prevention and Control (Framework Contract No. ECDC/2017/004).info:eu-repo/semantics/publishedVersio

Europe-wide expansion and eradication of multidrug-resistant Neisseria gonorrhoeae lineages: a genomic surveillance study

Centre for Genomic Pathogen Surveillance and the Euro-GASP study group: Sonja Pleininger, Alexander Indra, Irith De Baetselier, Wim Vanden Berghe, Blaženka Hunjak, Tatjana Nemeth Blažić, Panayiota Maikanti-Charalambous, Despo Pieridou, Hana Zákoucká, Helena Žemličková, Steen Hoffmann, Susan Cowan, Lasse Jessen Schwartz, Rita Peetso, Jevgenia Epstein, Jelena Viktorova, Ndeindo Ndeikoundam, Beatrice Bercot, Cécile Bébéar, Florence Lot, Susanne Buder, Klaus Jansen, Vivi Miriagou, Georgios Rigakos, Vasilios Raftopoulos, Eszter Balla, Mária Dudás, Lena Rós Ásmundsdóttir, Guðrún Sigmundsdóttir, Guðrún Svanborg Hauksdóttir, Thorolfur Gudnason, Aoife Colgan, Brendan Crowley, Sinéad Saab, Paola Stefanelli, Anna Carannante, Patrizia Parodi, Gatis Pakarna, Raina Nikiforova, Antra Bormane, Elina Dimina, Monique Perrin, Tamir Abdelrahman, Joël Mossong, Jean-Claude Schmit, Friedrich Mühlschlegel, Christopher Barbara, Francesca Mifsud, Alje Van Dam, Birgit Van Benthem, Maartje Visser, Ineke Linde, Hilde Kløvstad, Dominique Caugant, Beata Młynarczyk-Bonikowska, Jacinta Azevedo, Maria-José Borrego, Marina Lurdes Ramos Nascimento, Peter Pavlik, Irena Klavs, Andreja Murnik, Samo Jeverica, Tanja Kustec, Julio Vázquez Moreno, Asuncion Diaz, Raquel Abad, Inga Velicko, Magnus Unemo, Helen Fifer, Jill Shepherd, Lynsey PattersonBackground: Genomic surveillance using quality-assured whole-genome sequencing (WGS) together with epidemiological and antimicrobial resistance (AMR) data is essential to characterise the circulating Neisseria gonorrhoeae lineages and their association to patient groups (defined by demographic and epidemiological factors). In 2013, the European gonococcal population was characterised genomically for the first time. We describe the European gonococcal population in 2018 and identify emerging or vanishing lineages associated with AMR and epidemiological characteristics of patients, to elucidate recent changes in AMR and gonorrhoea epidemiology in Europe. Methods: We did WGS on 2375 gonococcal isolates from 2018 (mainly Sept 1-Nov 30) in 26 EU and EEA countries. Molecular typing and AMR determinants were extracted from quality-checked genomic data. Association analyses identified links between genomic lineages, AMR, and epidemiological data. Findings: Azithromycin-resistant N gonorrhoeae (8·0% [191/2375] in 2018) is rising in Europe due to the introduction or emergence and subsequent expansion of a novel N gonorrhoeae multi-antigen sequence typing (NG-MAST) genogroup, G12302 (132 [5·6%] of 2375; N gonorrhoeae sequence typing for antimicrobial resistance [NG-STAR] clonal complex [CC]168/63), carrying a mosaic mtrR promoter and mtrD sequence and found in 24 countries in 2018. CC63 was associated with pharyngeal infections in men who have sex with men. Susceptibility to ceftriaxone and cefixime is increasing, as the resistance-associated lineage, NG-MAST G1407 (51 [2·1%] of 2375), is progressively vanishing since 2009-10. Interpretation: Enhanced gonococcal AMR surveillance is imperative worldwide. WGS, linked to epidemiological and AMR data, is essential to elucidate the dynamics in gonorrhoea epidemiology and gonococcal populations as well as to predict AMR. When feasible, WGS should supplement the national and international AMR surveillance programmes to elucidate AMR changes over time. In the EU and EEA, increasing low-level azithromycin resistance could threaten the recommended ceftriaxone-azithromycin dual therapy, and an evidence-based clinical azithromycin resistance breakpoint is needed. Nevertheless, increasing ceftriaxone susceptibility, declining cefixime resistance, and absence of known resistance mutations for new treatments (zoliflodacin, gepotidacin) are promising.This study was supported by the European Centre for Disease Prevention and Control, the Centre for Genomic Pathogen Surveillance, the Li Ka Shing Foundation (Big Data Institute, University of Oxford), the Wellcome Genome Campus, the Foundation for Medical Research at Örebro University Hospital, and grants from Wellcome (098051 and 099202). LSB was funded by Conselleria de Sanitat Universal i Salut Pública, Generalitat Valenciana (Plan GenT CDEI-06/20-B), Valencia, Spain, and Ministry of Science, Innovation and Universities (PID2020–120113RA-I00), Spain, at the time of analysing and writing this manuscript.info:eu-repo/semantics/publishedVersio

Les déterminants du recours aux soins des patients tuberculeux en milieu urbain au Tchad

Introduction : TB is a leading cause of morbidity and mortality in the world. Delayed and and incomplete treatments sustain the epidemic. This study aimed to assess the delay of diagnosis of TB; to describe patient health care seeking; and to analyze treatment adherence, in a context of high endemicity. Method : A questionnaire survey was conducted in N'Djamena and Moundou hospitals. 286 newly diagnosed pulmonary TB patients were interviewed. Medical records completed the data. Logistic regression models were used to identify factors associated with the outcomes. Statistical analyzes were performed using SAS 9.2 software. Results : Informal care were used by 41% of patients. Median patient delay, median health system delay and median total delay were respectively 15 days, 36 days and 57.5 days. A third of patients discontinued the treatment. Low income, low educational level, the site of treatment and poor knowledge of TB were associated with longer delays, use of informal care and treatment interruption. Conclusion : The delay of TB diagnosis is too long and a poor treatment adherence was observed. Reducing the financial impact of TB care and health education may improve use of TB careIntroduction : La tuberculose est l'une des premières causes de morbidité et de mortalité au monde. Les traitements tardifs et incomplets entretiennent l'épidémie. L'objectif de cette étude était de mesurer les délais du diagnostic de la tuberculose; de décrire les parcours de soins des malades ; d'analyser les abandons du traitement ; et d'identifier les facteurs les expliquant dans un contexte de forte endémicité. Méthode : Une enquête par passation d'un questionnaire a été conduite au près de 286 patients adultes, présentant une tuberculose pulmonaire nouvellement diagnostiquée dans les hôpitaux de Ndjaména et de Moundou. Une revue des dossiers médicaux a permis de compléter ce recueil des données. Les trajectoires des patients ont été analysées de la survenue de la tuberculose à l'issue du traitement étiologique. Des modèles de régression logistique ont été utilisés pour identifier les déterminants associés aux variables d'intérêt. Les analyses statistiques ont été réalisées à l'aide du logiciel SAS 9.2. Résultats : Les soins informels ont été utilisés par 41% des patients. Le délai médian dû au patient, le délai médian dû au système de soins et le délai total médian étaient respectivement de 15 jours, de 36 jours et de 57,5 jours. Un tiers des patients ont abandonné leur traitement. Les bas revenus, un faible niveau d'instruction, le site de traitement et une méconnaissance de la tuberculose ont été associés à . Conclusion : Les délais de diagnostic sont trop longs et les abandons thérapeutiques trop fréquents. La réduction de l'impact financier de la tuberculose pour les malades et leur information sur la maladie peuvent améliorer leur recours aux soin

Les déterminants du recours aux soins des patients tuberculeux en milieu urbain au Tchad

Introduction : La tuberculose est l une des premières causes de morbidité et de mortalité au monde. Les traitements tardifs et incomplets entretiennent l épidémie. L objectif de cette étude était de mesurer les délais du diagnostic de la tuberculose; de décrire les parcours de soins des malades ; d analyser les abandons du traitement ; et d identifier les facteurs les expliquant dans un contexte de forte endémicité. Méthode : Une enquête par passation d un questionnaire a été conduite au près de 286 patients adultes, présentant une tuberculose pulmonaire nouvellement diagnostiquée dans les hôpitaux de Ndjaména et de Moundou. Une revue des dossiers médicaux a permis de compléter ce recueil des données. Les trajectoires des patients ont été analysées de la survenue de la tuberculose à l issue du traitement étiologique. Des modèles de régression logistique ont été utilisés pour identifier les déterminants associés aux variables d intérêt. Les analyses statistiques ont été réalisées à l aide du logiciel SAS 9.2. Résultats : Les soins informels ont été utilisés par 41% des patients. Le délai médian dû au patient, le délai médian dû au système de soins et le délai total médian étaient respectivement de 15 jours, de 36 jours et de 57,5 jours. Un tiers des patients ont abandonné leur traitement. Les bas revenus, un faible niveau d instruction, le site de traitement et une méconnaissance de la tuberculose ont été associés à . Conclusion : Les délais de diagnostic sont trop longs et les abandons thérapeutiques trop fréquents. La réduction de l impact financier de la tuberculose pour les malades et leur information sur la maladie peuvent améliorer leur recours aux soinsIntroduction : TB is a leading cause of morbidity and mortality in the world. Delayed and and incomplete treatments sustain the epidemic. This study aimed to assess the delay of diagnosis of TB; to describe patient health care seeking; and to analyze treatment adherence, in a context of high endemicity. Method : A questionnaire survey was conducted in N'Djamena and Moundou hospitals. 286 newly diagnosed pulmonary TB patients were interviewed. Medical records completed the data. Logistic regression models were used to identify factors associated with the outcomes. Statistical analyzes were performed using SAS 9.2 software. Results : Informal care were used by 41% of patients. Median patient delay, median health system delay and median total delay were respectively 15 days, 36 days and 57.5 days. A third of patients discontinued the treatment. Low income, low educational level, the site of treatment and poor knowledge of TB were associated with longer delays, use of informal care and treatment interruption. Conclusion : The delay of TB diagnosis is too long and a poor treatment adherence was observed. Reducing the financial impact of TB care and health education may improve use of TB carePARIS-BIUSJ-Biologie recherche (751052107) / SudocSudocFranceF

[Determinants of tuberculosis diagnosis delay in limited resources countries].

International audienceBACKGROUND: Delayed diagnoses of pulmonary tuberculosis contribute to the spread of the epidemic. METHODS: This study aims to identify risk factors associated with patient delay (from symptoms onset to the first visit), health system delay (from the first visit to the tuberculosis treatment initiation) and total delay (sum of the patient and the health system delay) in low income and high tuberculosis burden countries. A systematic literature review has been performed using the keywords: "tuberculosis"; "delay", care seeking"; "health care seeking behavior"; "diagnosis" and "treatment". Only quantitative studies showing delays for pulmonary tuberculosis adult cases were included in this review. RESULTS: Low income, gender, rural life, unemployment, ageing and misunderstanding the microbial cause of tuberculosis are associated with delayed diagnoses. Systemic factors including low health care coverage, patient expenditures and entry into the health system by consulting a traditional healer or a non-skilled professional delay the beginning of tuberculosis treatment. CONCLUSION: Delays can be used as indicators to evaluate tuberculosis control programs. Active case finding in the households of contagious patients can help to diminish diagnostic delays in low-income countries with high endemicity

An Automated Surveillance System (SurCeGGID) for the French Sexually Transmitted Infection Clinics: Epidemiological Monitoring Study

BackgroundViral and bacterial sexually transmitted infections (STIs) are public health concerns worldwide, but surveillance systems are not comprehensive enough to design and monitor accurately STI control strategies in most countries. In 2016, 320 STI clinics (CeGIDDs in French) were implemented in France, primarily targeting most exposed populations, although access is free of charge for anybody. ObjectiveThis article describes the mandatory surveillance system (SurCeGIDD) based on CeGIDD’s individual data aiming to better guide STI prevention. MethodsA decree ensured the use of software to manage consultations in CeGIDDs and to transfer surveillance data. A web service was implemented to secure data transfer from CeGIDDs’ software to a centralized database. CeGIDDs can also transfer data in CSV format via a secured data-sharing platform. Then, data are automatically checked before integration. Data on sociodemographic variables, sexual exposure, blood exposure, symptoms, STI tests, STI diagnoses, and sexual health services delivery were collected for the previous year (n–1). Preliminary and descriptive analyses of 2017-2018 data transmitted in 2018 and 2019, respectively, were performed using numbers and proportions for qualitative variables. ResultsIn 2017, 54/320 (16.9%) CeGIDDs transmitted their data. In 2018, this number of participants increased to 143/320 (44.7%) CeGIDDs. The corresponding volume of records increased from 2414 in 2017 to 382,890 in 2018. In 2018, most attendances were hospital based (263,480/382,890, 68.81%). In 2018, attendees were mostly men 227,326/379,921 (59.84%), while 151,963/379,921 (40%) were women 632/379,921 (0.17%) transgenders. The median age was 27 years for men, 23 years for women, and 30 years for transgender. Half of the attendees (81,964/174,932, 46.85%) were heterosexual men, 69,016/174,932 (39.45%) heterosexual women, 20,764/174,932 (11.87%) men who have sex with men, and 3188/174,932 (1.82%) women who have sex with women. A majority of them were born in France (227,698/286,289, 79.53%) and unemployed 115,913/211,707 (54.75%). The positivity rates were 0.37% for 205,348 HIV serologies, 1.31% for 131,551 hepatitis B virus serologies, 7.16% for 161,241 Chlamydia trachomatis PCR, 2.83% for 146,649 gonorrhea PCR, 1.04% for the syphilis combination of treponema and nontreponema serologies, and 5.96% for 13,313 Mycoplasma genitalium PCR. ConclusionsDespite challenges, the effectiveness of the SurCeGIDD surveillance based on routine patients’ records was demonstrated. The wide range of information, including socioeconomic determinants, might help to better guide and evaluate the prevention policies and services delivery. However, the growing volumes of information will require adapted tools and algorithms for the data management and analyses

Estimate of male urethritis incidences in France between 2007 and 2017 with a specific focus on Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis infections

International audienceBACKGROUND:In a context of increasing use of Nucleic Acid Amplification Test, diagnoses of Neisseria gonorrhoeae and Chlamydia trachomatis infections among men increased in Europe and USA since 2007. We aimed to describe trends in the incidence of male urethritis in France between 2007 and 2017.METHODS:We analysed male urethritis clinical cases reported by the French GPs' Sentinelles network.RESULTS:GPs reported 1944 cases of male urethritis during the study period. The estimated annual incidence rates in men aged 15 years and older remained stable between 226 cases per 100,000 seen in 2007 and 196 in 2017 (P value = 0.9). A third-generation cephalosporin with macrolide or tetracycline was prescribed in 17.5% of cases in 2009 (27/154) and 32.4% in 2017 (47/145) (P value = 0.0327).CONCLUSIONS:The incidence rates for adult male urethritis diagnosed in primary care have remained stable since 2007 in France in contrast with the increasing trend of Neisseria gonorrhoeae and Chlamydia trachomatis infections based on microbiological surveillance. Using stable clinical definition for male urethritis seems essential to follow correctly epidemiological dynamic

Multidrug-resistant Neisseria gonorrhoeae failing treatment with ceftriaxone and doxycycline in France, November 2017

We report a multidrug-resistant Neisseria gonorrhoeae urogenital and pharyngeal infection with ceftriaxone resistance and intermediate resistance to azithromycin in a heterosexual woman in her 20s in France. Treatment with ceftriaxone plus doxycycline failed for the pharyngeal localisation. Whole-genome sequencing of isolate F90 identified MLST1903, NG-MAST ST3435, NG-STAR233, and relevant resistance determinants. F90 showed phenotypic and genotypic similarities to an internationally spreading multidrug-resistant and ceftriaxone-resistant clone detected in Japan and subsequently in Australia, Canada and Denmark

Pulmonary tuberculosis diagnostic delays in Chad: a multicenter, hospital-based survey in Ndjamena and Moundou

<p>Abstract</p> <p>Background</p> <p>Tuberculosis remains one of the leading causes of morbidity and mortality in low-resource countries. One contagious patient can infect 10 to 20 contacts in these settings. Delays in diagnosing TB therefore contribute to the spread of the disease and sustain the epidemic.</p> <p>Objectives</p> <p>The aim of this study was to assess delays in diagnosing tuberculosis and the factors associated with these delays in the public hospitals in Moundou and Ndjamena, Chad.</p> <p>Methods</p> <p>A structured questionnaire was administered to 286 new tuberculosis patients to evaluate patient delay (time from the onset of symptoms to the first formal or informal care), health-care system delay (time from the first health care to tuberculosis treatment) and total delay (sum of the patient and system delays). Logistic regression was used to identify risk factors associated with long diagnostic delays (defined as greater than the median).</p> <p>Results and discussion</p> <p>The median [interquartile range] patient delay, system delay and total delay were 15 [7–30], 36 [19–65] and 57.5 [33–95] days, respectively. Low economic status (aOR [adjusted odds ratio] =2.38 [1.08-5.25]), not being referred to a health service (aOR = 1.75 [1.02- 3.02]) and a secondary level education (aOR = 0.33 [0.12-0.92]) were associated with a long patient delay. Risk factors for a long system delay were a low level of education (aOR = 4.71 [1.34-16.51]) and the belief that traditional medicine and informal care can cure TB (aOR = 5.46 [2.37-12.60]).</p> <p>Conclusion</p> <p>Targeted strengthening of the health-care system, including improving patient access, addressing deficiencies in health-related human resources, and improving laboratory networks and linkages as well as community mobilization will make for better outcomes in tuberculosis diagnosis.</p