Emergence of a Neisseria gonorrhoeae clone with reduced cephalosporin susceptibility between 2014 and 2019 in Amsterdam, The Netherlands, revealed by genomic population analysis

Abstract Background Emerging resistance to cephalosporins in Neisseria gonorrhoeae (Ng) is a major public health threat, since these are considered antibiotics of last resort. Continuous surveillance is needed to monitor the circulation of resistant strains and those with reduced susceptibility. Objectives For the purpose of epidemiological surveillance, genomic population analysis was performed on Ng isolates from Amsterdam with a focus on isolates with reduced susceptibility to ceftriaxone. Methods WGS data were obtained from 318 isolates from Amsterdam, the Netherlands between 2014 and 2019. Isolates were typed according to MLST, Ng Multi-Antigen Sequence Typing (NG-MAST) and Ng Sequence Typing for Antimicrobial Resistance (NG-STAR) schemes and additional resistance markers were identified. Phylogenetic trees were created to identify genetic clusters and to compare Dutch and non-Dutch MLST7827 isolates. Results MLST7363 and MLST1901 were the predominant strains having reduced susceptibility to ceftriaxone during 2014–16; MLST7827 emerged and dominated during 2017–19. NG-STAR38 and NG-MAST2318/10386 were predominant among MLST7827 isolates. MLST7827 reduced susceptibility isolates carried a non-mosaic 13.001 penA allele with an A501V mutation and porB1b G120K/A121D mutations, which were lacking in susceptible MLST7827 isolates. Phylogenetic analysis of all publicly available MLST7827 isolates showed strong genetic clustering of Dutch and other European MLST7827 isolates. Conclusions MLST7827 isolates with reduced ceftriaxone susceptibility have emerged during recent years in Amsterdam. Co-occurrence of penA A501V and porB1b G120K/A121D mutations was strongly associated with reduced susceptibility to ceftriaxone. Genetic clustering of Dutch and other European MLST7827 isolates indicates extensive circulation of this strain in Europe. Close monitoring of the spread of this strain having an alarming susceptibility profile is needed.

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Emergence of a cephalosporin reduced susceptible Neisseria gonorrhoeae clone between 2014-2019 in Amsterdam, the Netherlands, revealed by a genomic population analysis

10.1101/2020.11.02.364463 ◽

2020 ◽

Author(s):

Jolinda de Korne-Elenbaas ◽

Sylvia M. Bruisten ◽

Henry J.C. de Vries ◽

Alje P. van Dam

Keyword(s):

The Netherlands ◽

Neisseria Gonorrhoeae ◽

Phylogenetic Trees ◽

Population Analysis ◽

Epidemiological Surveillance ◽

Close Monitoring ◽

Genetic Clusters ◽

Resistance Markers ◽

Resistant Strains ◽

Genetic Clustering

AbstractBackgroundEmerging resistance to cephalosporins in Neisseria gonorrhoeae (Ng) is a major public health threat, since these are considered antibiotics of last resort. Continuous surveillance is needed to monitor the circulation of reduced susceptible and resistant strains.AimFor the purpose of epidemiological surveillance, a genomic population analysis was performed on Ng isolates from Amsterdam with a focus on ceftriaxone reduced susceptible isolates.MethodsWhole genome sequences were obtained from 318 isolates from 2014-2019 from Amsterdam, the Netherlands. Isolates were typed according to the Multi-Locus Sequence Typing (MLST) scheme and resistance markers were identified. Phylogenetic trees were created to identify genetic clusters and to compare Dutch- and global MLST7827 isolates.ResultsThe majority of ceftriaxone reduced susceptible isolates belonged to MLST7363, MLST1901 and MLST7827. MLST7363 and MLST1901 were dominant reduced susceptible strains from 2014-2016 although MLST7827 emerged and became dominant during 2017-2019. MLST7827 reduced susceptible isolates carried a non-mosaic penA gene with A501V mutation and porB G121K/A121D mutations, which were lacking in susceptible MLST7827 isolates. Phylogenetic analysis of all publicly available MLST7827 isolates showed strong genetic clustering of Dutch- and other European MLST7827 isolates.ConclusionCeftriaxone reduced susceptible MLST7827 isolates emerged during recent years in Amsterdam. Co-occurrence of penA A501V and porB G121K/A121D mutations was strongly associated with ceftriaxone reduced susceptibility. Genetic clustering of Dutch- and other European MLST7827 isolates indicates extensive circulation of this strain in Europe. Therefore, close monitoring of the spread of this strain with an alarming susceptibility profile is needed.

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Genetic Relatedness within Serotypes of Penicillin-Susceptible Streptococcus pneumoniaeIsolates

Journal of Clinical Microbiology ◽

10.1128/jcm.38.12.4548-4553.2000 ◽

2000 ◽

Vol 38 (12) ◽

pp. 4548-4553 ◽

Cited By ~ 14

Author(s):

Karin Overweg ◽

Debby Bogaert ◽

Marcel Sluijter ◽

Janet Yother ◽

Jacob Dankert ◽

...

Keyword(s):

United States ◽

The Netherlands ◽

Horizontal Transfer ◽

Genetic Relatedness ◽

The United States ◽

Invasive Disease ◽

Genetic Clusters ◽

Genetic Clustering ◽

Type 3 ◽

Epidemiological Characteristics

The molecular epidemiological characteristics of allStreptococcus pneumoniae strains isolated in a nationwide manner from patients with meningitis in The Netherlands in 1994 were investigated. Restriction fragment end labeling analysis demonstrated 52% genetic clustering among these penicillin-susceptible strains, a value substantially lower than the percentage of clustering among Dutch penicillin-nonsusceptible strains. Different serotypes were found within 8 of the 28 genetic clusters, suggesting that horizontal transfer of capsular genes is common among penicillin-susceptible strains. The degree of genetic clustering was much higher among serotype 3, 7F, 9V, and 14 isolates than among isolates of other serotypes, i.e., 6A, 6B, 18C, 19F, and 23F. We further studied the molecular epidemiological characteristics of pneumococci of serotype 3, which is considered the most virulent serotype and which is commonly associated with invasive disease in adults. Fifty epidemiologically unrelated penicillin-susceptible serotype 3 invasive isolates originating from the United States (n = 27), Thailand (n = 9), The Netherlands (n = 8), and Denmark (n = 6) were analyzed. The vast majority of the serotype 3 isolates (74%) belonged to two genetically distinct clades that were observed in the United States, Denmark, and The Netherlands. These data indicate that two serotype 3 clones have been independently disseminated in an international manner. Seven serotype 3 isolates were less than 85% genetically related to the other serotype 3 isolates. Our observations suggest that the latter isolates originated from horizontal transfer of the capsular type 3 gene locus to other pneumococcal genotypes. In conclusion, epidemiologically unrelated serotype 3 isolates were genetically more related than those of other serotypes. This observation suggests that serotype 3 has evolved only recently or has remained unchanged over long periods.

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Global emergence and dissemination of Neisseria gonorrhoeae ST-9363 isolates with reduced susceptibility to azithromycin

10.1101/2021.08.05.455198 ◽

2021 ◽

Author(s):

Sandeep J Joseph ◽

Jesse C Thomas ◽

Matthew Schmerer ◽

John Cartee ◽

Sancta St, Cyr ◽

...

Keyword(s):

Neisseria Gonorrhoeae ◽

Clonal Expansion ◽

Population Based ◽

Multiple Introductions ◽

Fitness Advantage ◽

Show Evidence ◽

Evolutionary Trajectories ◽

Additional Resistance ◽

Resistance Markers ◽

The U.S

Neisseria gonorrhoeae multi-locus sequence type (ST) 9363 genogroup isolates have been associated with reduced azithromycin susceptibility (AZMrs) and show evidence of clonal expansion in the U.S. Here we analyze a global collection of ST-9363 genogroup genomes to shed light on the emergence and dissemination of this strain. The global population structure of ST-9363 genogroup falls into three lineages: Basal, European, and North American; with 32 clades within all lineages. Although, ST-9363 genogroup is inferred to have originated from Asia in the mid-19th century; we estimate the three modern lineages emerged from Europe in the late 1970s to early 1980s. The European lineage appears to have emerged and expanded from around 1986 to 1998, spreading into North America and Oceania in the mid-2000s with multiple introductions, along with multiple secondary reintroductions into Europe. Our results suggest two separate acquisition events of mosaic mtrR and mtrR promoter alleles: first during 2009-2011 and again during the 2012-2013 time, facilitating the clonal expansion of this genogroup with AZMrs in the U.S. By tracking phylodynamic evolutionary trajectories of clades that share distinct demography as well as population-based genomic statistics, we demonstrate how recombination and selective pressures in the mtrCDE efflux operon granted a fitness advantage to establish ST-9363 as a successful gonococcal lineage in the U.S. and elsewhere. Although it is difficult to pinpoint the exact timing and emergence of this young genogroup, it remains critically important to continue monitoring it, as it could acquire additional resistance markers.

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Faculty Opinions recommendation of Multidrug-resistant Neisseria gonorrhoeae with reduced cefotaxime susceptibility is increasingly common in men who have sex with men, Amsterdam, the Netherlands.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1247957.716056 ◽

2009 ◽

Author(s):

Philippe Lagacé-Wiens

Keyword(s):

The Netherlands ◽

Neisseria Gonorrhoeae ◽

Multidrug Resistant ◽

Sex With Men

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Estimating the asymptomatic proportion of SARS-CoV-2 infection in the general population: Analysis of nationwide serosurvey data in the Netherlands

European Journal of Epidemiology ◽

10.1007/s10654-021-00768-y ◽

2021 ◽

Author(s):

Scott A. McDonald ◽

Fuminari Miura ◽

Eric R. A. Vos ◽

Michiel van Boven ◽

Hester E. de Melker ◽

...

Keyword(s):

The Netherlands ◽

Population Analysis ◽

Large Population ◽

Population Based ◽

Attributable Risk ◽

Case Definition ◽

Aggregated Data ◽

Age Dependent ◽

Additive Regression ◽

June July

Abstract Background The proportion of SARS-CoV-2 positive persons who are asymptomatic—and whether this proportion is age-dependent—are still open research questions. Because an unknown proportion of reported symptoms among SARS-CoV-2 positives will be attributable to another infection or affliction, the observed, or 'crude' proportion without symptoms may underestimate the proportion of persons without symptoms that are caused by SARS-CoV-2 infection. Methods Based on two rounds of a large population-based serological study comprising test results on seropositivity and self-reported symptom history conducted in April/May and June/July 2020 in the Netherlands (n = 7517), we estimated the proportion of reported symptoms among those persons infected with SARS-CoV-2 that is attributable to this infection, where the set of relevant symptoms fulfills the ECDC case definition of COVID-19, using inferential methods for the attributable risk (AR). Generalised additive regression modelling was used to estimate the age-dependent relative risk (RR) of reported symptoms, and the AR and asymptomatic proportion (AP) were calculated from the fitted RR. Results Using age-aggregated data, the 'crude' AP was 37% but the model-estimated AP was 65% (95% CI 63–68%). The estimated AP varied with age, from 74% (95% CI 65–90%) for < 20 years, to 61% (95% CI 57–65%) for the 50–59 years age-group. Conclusion Whereas the 'crude' AP represents a lower bound for the proportion of persons infected with SARS-CoV-2 without COVID-19 symptoms, the AP as estimated via an attributable risk approach represents an upper bound. Age-specific AP estimates can inform the implementation of public health actions such as targetted virological testing and therefore enhance containment strategies.

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Ceftriaxone Reduced Susceptible Neisseria gonorrhoeae in the Netherlands, 2009 to 2017

Sexually Transmitted Diseases ◽

10.1097/olq.0000000000001031 ◽

2019 ◽

Vol 46 (9) ◽

pp. 594-601 ◽

Cited By ~ 4

Author(s):

Myrthe M. de Laat ◽

Carolien M. Wind ◽

Sylvia M. Bruisten ◽

Mirjam Dierdorp ◽

Henry J.C. de Vries ◽

...

Keyword(s):

The Netherlands ◽

Neisseria Gonorrhoeae

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The influence of a priori grouping on inference of genetic clusters: simulation study and literature review of the DAPC method

Heredity ◽

10.1038/s41437-020-0348-2 ◽

2020 ◽

Vol 125 (5) ◽

pp. 269-280 ◽

Cited By ~ 1

Author(s):

Joshua M. Miller ◽

Catherine I. Cullingham ◽

Rhiannon M. Peery

Keyword(s):

Discriminant Analysis ◽

Literature Review ◽

Simulation Study ◽

De Novo ◽

A Priori ◽

Principal Component ◽

Migration Rates ◽

Genetic Clusters ◽

Genetic Clustering ◽

Structure Versus

Abstract Inference of genetic clusters is a key aim of population genetics, sparking development of numerous analytical methods. Within these, there is a conceptual divide between finding de novo structure versus assessment of a priori groups. Recently developed, Discriminant Analysis of Principal Components (DAPC), combines discriminant analysis (DA) with principal component (PC) analysis. When applying DAPC, the groups used in the DA (specified a priori or described de novo) need to be carefully assessed. While DAPC has rapidly become a core technique, the sensitivity of the method to misspecification of groups and how it is being empirically applied, are unknown. To address this, we conducted a simulation study examining the influence of a priori versus de novo group designations, and a literature review of how DAPC is being applied. We found that with a priori groupings, distance between genetic clusters reflected underlying FST. However, when migration rates were high and groups were described de novo there was considerable inaccuracy, both in terms of the number of genetic clusters suggested and placement of individuals into those clusters. Nearly all (90.1%) of 224 studies surveyed used DAPC to find de novo clusters, and for the majority (62.5%) the stated goal matched the results. However, most studies (52.3%) omit key run parameters, preventing repeatability and transparency. Therefore, we present recommendations for standard reporting of parameters used in DAPC analyses. The influence of groupings in genetic clustering is not unique to DAPC, and researchers need to consider their goal and which methods will be most appropriate.

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