179 results found
Didelot X, Parkhill J, 2022, A scalable analytical approach from bacterial genomes to epidemiology, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 377, ISSN: 0962-8436
Carson J, Ledda A, Ferretti L, et al., 2022, The bounded coalescent model: Conditioning a genealogy on a minimum root date, JOURNAL OF THEORETICAL BIOLOGY, Vol: 548, ISSN: 0022-5193
Didelot X, Ribeca P, 2022, KPop: An assembly-free and scalable method for the comparative analysis of microbial genomes
<jats:title>Abstract</jats:title><jats:p>It has become increasingly difficult for traditional analysis techniques based on assembly and variant calling to cope with the recent explosion in the amount of available sequencing data, especially in the field of microbial genomics. Here we introduce KPop, a novel versatile method based on full <jats:italic>k</jats:italic>-mer spectra and dataset-specific transformations, that allows for the accurate comparison of hundreds of thousands of assembled or unassembled microbial genomes in a matter of hours. We validate the method on simulated datasets and show that it can correctly classify sequences into lineages and rapidly identify related sequences. We also demonstrate its usefulness on several real-life datasets, in the case of both viral and bacterial pathogens. The KPop open-source code is available on GitHub at <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://github.com/PaoloRibeca/KPop">https://github.com/PaoloRibeca/KPop</jats:ext-link>.</jats:p>
Ortiz AT, Kendall M, Storey N, et al., 2022, Within-host diversity improves phylogenetic and transmission reconstruction of SARS-CoV-2 outbreaks., bioRxiv
Accurate inference of who infected whom in an infectious disease outbreak is critical for the delivery of effective infection prevention and control. The increased resolution of pathogen whole-genome sequencing has significantly improved our ability to infer transmission events. Despite this, transmission inference often remains limited by the lack of genomic variation between the source case and infected contacts. Although within-host genetic diversity is common among a wide variety of pathogens, conventional whole-genome sequencing phylogenetic approaches to reconstruct outbreaks exclusively use consensus sequences, which consider only the most prevalent nucleotide at each position and therefore fail to capture low frequency variation within samples. We hypothesized that including within-sample variation in a phylogenetic model would help to identify who infected whom in instances in which this was previously impossible. Using whole-genome sequences from SARS-CoV-2 multi-institutional outbreaks as an example, we show how within-sample diversity is stable among repeated serial samples from the same host, is transmitted between those cases with known epidemiological links, and how this improves phylogenetic inference and our understanding of who infected whom. Our technique is applicable to other infectious diseases and has immediate clinical utility in infection prevention and control.
Volk D, Yang-Turner F, Didelot X, et al., 2022, Catwalk: identifying closely related sequences in large microbial sequence databases, MICROBIAL GENOMICS, Vol: 8, ISSN: 2057-5858
Dingle KE, Freeman J, Didelot X, et al., 2022, Penicillin Binding Protein Substitutions Co-occur with Fluoroquinolone Resistance in ‘Epidemic’ Lineages of Multi Drug-Resistant <i>Clostridioides difficile</i>
<jats:title>ABSTRACT</jats:title><jats:p><jats:italic>Clostridioides difficile</jats:italic> remains a key cause of healthcare-associated infection, with multi-drug-resistant (MDR) lineages causing high mortality (≥20%) outbreaks. Cephalosporin treatment is a long-established risk factor, and antimicrobial stewardship a key control. A mechanism underlying raised cephalosporin MICs has not been identified in <jats:italic>C. difficile</jats:italic>, but among other species resistance is often acquired <jats:italic>via</jats:italic> amino acid substitutions in cell wall transpeptidases (penicillin binding proteins, PBPs). Here, we investigated five <jats:italic>C. difficile</jats:italic> transpeptidases (PBP1-5) for recent substitutions. Previously published genome assemblies (n=7096) were obtained, representing sixteen geographically widespread lineages, including healthcare-associated MDR ST1(027), ST3(001) and ST17(018). Recent amino acid substitutions were found within PBP1 (n=50) and PBP3 (n=48), ranging from 1-10 substitutions per genome. β-lactam MICs were measured for closely related pairs of wild-type and PBP substituted isolates separated by 20-273 SNPs. Recombination-corrected, dated phylogenies were constructed to date substitution acquisition. Key substitutions such as PBP3 V497L and PBP1 T674I/N/V emerged independently across multiple lineages. They were associated with extremely high cephalosporin MICs; 1-4 doubling dilutions >wild-type up to ≤1506μg/ml. Substitution patterns varied by lineage and clade, showed geographic structure, and notably occurred post-1990, coincident with the acquisition of <jats:italic>gyrA</jats:italic>/<jats:italic>B</jats:italic> substitutions conferring fluoroquinolone resistance. In conclusion, recent PBP1 and PBP3 substitutions are associated with raised cephalosporin MICs in <jats:italic>C. difficile</ja
Ledda A, Cummins M, Shaw LP, et al., 2022, Hospital outbreak of carbapenem-resistant Enterobacterales associated with a bla OXA-48 plasmid carried mostly by Escherichia coli ST399, Microbial Genomics, Vol: 8, ISSN: 2057-5858
A hospital outbreak of carbapenem-resistant Enterobacterales was detected by routine surveillance. Whole genome sequencing and subsequent analysis revealed a conserved promiscuous blaOXA-48 carrying plasmid as the defining factor within this outbreak. Four different species of Enterobacterales were involved in the outbreak. Escherichia coli ST399 accounted for 35 of all the 55 isolates. Comparative genomics analysis using publicly available E. coli ST399 genomes showed that the outbreak E. coli ST399 isolates formed a unique clade. We developed a mathematical model of pOXA-48-like plasmid transmission between host lineages and used it to estimate its conjugation rate, giving a lower bound of 0.23 conjugation events per lineage per year. Our analysis suggests that co-evolution between the pOXA-48-like plasmid and E. coli ST399 could have played a role in the outbreak. This is the first study to report carbapenem-resistant E. coli ST399 carrying blaOXA-48 as the main cause of a plasmid-borne outbreak within a hospital setting. Our findings suggest complementary roles for both plasmid conjugation and clonal expansion in the emergence of this outbreak.
Larsen J, Raisen CL, Ba X, et al., 2022, Emergence of methicillin resistance predates the clinical use of antibiotics, NATURE, Vol: 602, Pages: 135-+, ISSN: 0028-0836
Fountain-Jones NM, Kraberger S, Gagne RB, et al., 2022, Hunting alters viral transmission and evolution in a large carnivore, NATURE ECOLOGY & EVOLUTION, Vol: 6, Pages: 174-+, ISSN: 2397-334X
Carson J, Ledda A, Ferretti L, et al., 2022, The bounded coalescent model: conditioning a genealogy on a minimum root date
<jats:title>Abstract</jats:title><jats:p>The coalescent model represents how individuals sampled from a population may have originated from a last common ancestor. The bounded coalescent model is obtained by conditioning the coalescent model such that the last common ancestor must have existed after a certain date. This conditioned model arises in a variety of applications, such as speciation, horizontal gene transfer or transmission analysis, and yet the bounded coalescent model has not been previously analysed in detail. Here we describe a new algorithm to simulate from this model directly, without resorting to rejection sampling. We show that this direct simulation algorithm is more computationally efficient than the rejection sampling approach. We also show how to calculate the probability of the last common ancestor occurring after a given date, which is required to compute the probability of realisations under the bounded coalescent model. Our results are applicable in both the isochronous (when all samples have the same date) and heterochronous (where samples can have different dates) settings. We explore the effect of setting a bound on the date of the last common ancestor, and show that it affects a number of properties of the resulting phylogenies. All our methods are implemented in a new R package called BoundedCoalescent which is freely available online.</jats:p>
Didelot X, Evans CM, 2022, London parochial burial records from 1563 to 1665 indicate higher plague death rates for males than females: Some possible demographic and social explanations., PLoS One, Vol: 17
The burial rates of males and females in early modern central London were compared to investigate a possible bias towards male mortality in the plague years of 1563, 1593, 1603, 1625 and 1665. The burial records of sixteen parishes were examined and compared with the five-year periods immediately preceding each plague year when recorded burials were substantially less. A markedly higher burial rate for males was detected in each plague year but this can be partly attributed to a general preponderance of males in the central London population since there was a similar but lesser bias in non-plague years. In the plague years the difference between the frequency of male and female adult burials appears to have been enhanced by the preferential migration of women of childbearing age out of the city since fewer births were recorded in months when plague was rife. Furthermore, when a sample of households was investigated, husbands were significantly more likely to have been buried than their wives. These findings were largely applicable to the plague years of 1603, 1625 and 1665 but were far less apparent in 1563 and 1593. In general, there were more burials of boys than girls in non-plague years which is the expected consequence of their greater vulnerability to childhood diseases. This difference diminished in plague years so that the burials of girls and boys approached parity at a time when burials of children of both sexes were significantly increased. Possibly, plague did not discriminate between the sexes and this characteristic tended to mask the usual vulnerability of boys.
Ortiz AT, Coronel J, Vidal JR, et al., 2021, Genomic signatures of pre-resistance in Mycobacterium tuberculosis, NATURE COMMUNICATIONS, Vol: 12
Helekal D, Ledda A, Volz E, et al., 2021, Bayesian Inference of Clonal Expansions in a Dated Phylogeny, SYSTEMATIC BIOLOGY, ISSN: 1063-5157
Didelot X, Parkhill J, 2021, A scalable analytical approach from bacterial genomes to epidemiology
<jats:title>Summary</jats:title><jats:p>Recent years have seen a remarkable increase in the practicality of sequencing whole genomes from large numbers of bacterial isolates. The availability of this data has huge potential to deliver new insights into the evolution and epidemiology of bacterial pathogens, but the scalability of the analytical methodology has been lagging behind that of the sequencing technology. Here we present a step-by-step approach for such large-scale genomic epidemiology analyses, from bacterial genomes to epidemiological interpretations. A central component of this approach is the dated phylogeny, which is a phylogenetic tree with branch lengths measured in units of time. The construction of dated phylogenies from bacterial genomic data needs to account for the disruptive effect of recombination on phylogenetic relationships, and we describe how this can be achieved. Dated phylogenies can then be used to perform fine-scale or large-scale epidemiological analyses, depending on the proportion of cases for which genomes are available. A key feature of this approach is computational scalability, and in particular the ability to process hundreds or thousands of genomes within a matter of hours. This is a clear advantage of the step-by-step approach described here. We discuss other advantages and disadvantages of the approach, as well as potential improvements and avenues for future research.</jats:p>
Boonyasiri A, Myall AC, Wan Y, et al., 2021, Integrated patient network and genomic plasmid analysis reveal a regional, multi-species outbreak of carbapenemase-producing Enterobacterales carrying both <i>bla</i><sub>IMP</sub> and <i>mcr-9</i> genes
<jats:title>Abstract</jats:title><jats:p>The incidence of carbapenemase-producing Enterobacterales (CPE) is rising globally, yet Imipenemase (IMP) carbapenemases remain relatively rare. This study describes an investigation of the emergence of IMP-encoding CPE amongst diverse Enterobacterales species between 2016 and 2019 in patients across a London regional hospital network.</jats:p><jats:p>A network analysis approach to patient pathways, using routinely collected electronic health records, identified previously unrecognised contacts between patients who were IMP CPE positive on screening, implying potential bacterial transmission events. Whole genome sequencing of 85 Enterobacterales isolates from these patients revealed that 86% (73/85) were diverse species (predominantly <jats:italic>Klebsiella</jats:italic> spp, <jats:italic>Enterobacter</jats:italic> spp, <jats:italic>E. coli</jats:italic>) and harboured an IncHI2 plasmid, which carried both <jats:italic>bla</jats:italic><jats:sub>IMP</jats:sub> and the putative mobile colistin resistance gene <jats:italic>mcr-9</jats:italic>. Detailed phylogenetic analysis identified two distinct IncHI2 plasmid lineages, A and B, both of which showed significant association with patient movements between four hospital sites and across medical specialities.</jats:p><jats:p>Combined, our patient network and plasmid analyses demonstrate an interspecies, plasmid-mediated outbreak of <jats:italic>bla</jats:italic><jats:sub>IMP</jats:sub>CPE, which remained unidentified during standard microbiology and infection control investigations. With whole genome sequencing (WGS) technologies and large-data incorporation, the outbreak investigation approach proposed here provides a framework for real-time identification of key factors causing pathogen spread. Analysing outbreaks at the plasmid level reveal
Didelot X, Geidelberg L, COVID-19 Genomics UK COG-UK consortium, et al., 2021, Model design for non-parametric phylodynamic inference and applications to pathogen surveillance., bioRxiv
Inference of effective population size from genomic data can provide unique information about demographic history, and when applied to pathogen genetic data can also provide insights into epidemiological dynamics. The combination of non-parametric models for population dynamics with molecular clock models which relate genetic data to time has enabled phylodynamic inference based on large sets of time-stamped genetic sequence data. The methodology for non-parametric inference of effective population size is well-developed in the Bayesian setting, but here we develop a frequentist approach based on non-parametric latent process models of population size dynamics. We appeal to statistical principles based on out-of-sample prediction accuracy in order to optimize parameters that control shape and smoothness of the population size over time. We demonstrate the flexibility and speed of this approach in a series of simulation experiments, and apply the methodology to reconstruct the previously described waves in the seventh pandemic of cholera. We also estimate the impact of non-pharmaceutical interventions for COVID-19 in England using thousands of SARS-CoV-2 sequences. By incorporating a measure of the strength of these interventions over time within the phylodynamic model, we estimate the impact of the first national lockdown in the UK on the epidemic reproduction number.
Helekal D, Ledda A, Volz E, et al., 2021, Bayesian inference of clonal expansions in a dated phylogeny
<jats:title>ABSTRACT</jats:title><jats:p>Microbial population genetics models often assume that all lineages are constrained by the same population size dynamics over time. However, many neutral and selective events can invalidate this assumption, and can contribute to the clonal expansion of a specific lineage relative to the rest of the population. Such differential phylodynamic properties between lineages result in asymmetries and imbalances in phylogenetic trees that are sometimes described informally but which are difficult to analyse formally. To this end, we developed a model of how clonal expansions occur and affect the branching patterns of a phylogeny. We show how the parameters of this model can be inferred from a given dated phylogeny using Bayesian statistics, which allows us to assess the probability that one or more clonal expansion events occurred. For each putative clonal expansion event we estimate their date of emergence and subsequent phylodynamic trajectories, including their long-term evolutionary potential which is important to determine how much effort should be placed on specific control measures. We demonstrate the applicability of our methodology on simulated and real datasets.</jats:p>
Wang L, Didelot X, Bi Y, et al., 2021, Assessing the extent of community spread caused by mink-derived SARS-CoV-2 variants, INNOVATION, Vol: 2, ISSN: 2666-6758
Knight DR, Imwattana K, Kullin B, et al., 2021, Major genetic discontinuity and novel toxigenic species in Clostridioides difficile taxonomy, ELIFE, Vol: 10, ISSN: 2050-084X
Nimmo C, van Dorp L, Ortiz AT, et al., 2021, BEDAQUILINE RESISTANCE IN MYCOBACTERIUM TUBERCULOSIS PREDATES ITS CLINICAL USE, Publisher: BMJ PUBLISHING GROUP, Pages: A51-A52, ISSN: 0040-6376
Didelot X, Kendall M, Xu Y, et al., 2021, Genomic epidemiology analysis of infectious disease outbreaks using TransPhylo., Current Protocols, Vol: 1, Pages: 1-23, ISSN: 2691-1299
Comparing the pathogen genomes from several cases of an infectious disease has the potential to help us understand and control outbreaks. Many methods exist to reconstruct a phylogeny from such genomes, which represents how the genomes are related to one another. However, such a phylogeny is not directly informative about transmission events between individuals. TransPhylo is a software tool implemented as an R package designed to bridge the gap between pathogen phylogenies and transmission trees. TransPhylo is based on a combined model of transmission between hosts and pathogen evolution within each host. It can simulate both phylogenies and transmission trees jointly under this combined model. TransPhylo can also reconstruct a transmission tree based on a dated phylogeny, by exploring the space of transmission trees compatible with the phylogeny. A transmission tree can be represented as a coloring of a phylogeny where each color represents a different host of the pathogen, and TransPhylo provides convenient ways to plot these colorings and explore the results. This article presents the basic protocols that can be used to make the most of TransPhylo. © 2021 The Authors. Basic Protocol 1: First steps with TransPhylo Basic Protocol 2: Simulation of outbreak data Basic Protocol 3: Inference of transmission Basic Protocol 4: Exploring the results of inference.
Lassalle F, Dastgheib SMM, Zhao F-J, et al., 2021, Phylogenomics reveals the basis of adaptation of Pseudorhizobium species to extreme environments and supports a taxonomic revision of the genus, Systematic and Applied Microbiology, Vol: 44, Pages: 1-14, ISSN: 0172-5564
The family Rhizobiaceae includes many genera of soil bacteria, often isolated for their association with plants. Herein, we investigate the genomic diversity of a group of Rhizobium species and unclassified strains isolated from atypical environments, including seawater, rock matrix or polluted soil. Based on whole-genome similarity and core genome phylogeny, we show that this group corresponds to the genus Pseudorhizobium. We thus reclassify Rhizobium halotolerans, R. marinum, R. flavum and R. endolithicum as P. halotolerans sp. nov., P. marinum comb. nov. , P. flavum comb. nov. and P. endolithicum comb. nov. , respectively, and show that P. pelagicum is a synonym of P. marinum . We also delineate a new chemolithoautotroph species, P. banfieldiae sp. nov. , whose type strain is NT-26 T (= DSM 106348 T = CFBP 8663 T ) . This genome-based classification was supported by a chemotaxonomic comparison, with increasing taxonomic resolution provided by fatty acid, protein and metabolic profiles. In addition, we used a phylogenetic approach to infer scenarios of duplication, horizontal transfer and loss for all genes in the Pseudorhizobium pangenome. We thus identify the key functions associated with the diversification of each species and higher clades, shedding light on the mechanisms of adaptation to their respective ecological niches. Respiratory proteins acquired at the origin of Pseudorhizobium were combined with clade-specific genes to enable different strategies for detoxification and nutrition in harsh, nutrient- poor environments.
Didelot X, Siveroni I, Volz EM, 2021, Additive uncorrelated relaxed clock models for the dating of genomic epidemiology phylogenies, Molecular Biology and Evolution, Vol: 38, Pages: 307-317, ISSN: 0737-4038
Phylogenetic dating is one of the most powerful and commonly used methods of drawing epidemiological interpretations from pathogen genomic data. Building such trees requires considering a molecular clock model which represents the rate at which substitutions accumulate on genomes. When the molecular clock rate is constant throughout the tree then the clock is said to be strict, but this is often not an acceptable assumption. Alternatively, relaxed clock models consider variations in the clock rate, often based on a distribution of rates for each branch. However, we show here that the distributions of rates across branches in commonly used relaxed clock models are incompatible with the biological expectation that the sum of the numbers of substitutions on two neighbouring branches should be distributed as the substitution number on a single branch of equivalent length. We call this expectation the additivity property. We further show how assumptions of commonly used relaxed clock models can lead to estimates of evolutionary rates and dates with low precision and biased confidence intervals. We therefore propose a new additive relaxed clock model where the additivity property is satisfied. We illustrate the use of our new additive relaxed clock model on a range of simulated and real datasets, and we show that using this new model leads to more accurate estimates of mean evolutionary rates and ancestral dates.
Didelot X, 2021, Phylogenetic Methods for Genome-Wide Association Studies in Bacteria., Methods Mol Biol, Vol: 2242, Pages: 205-220
Genome-wide association studies in bacteria have great potential to deliver a better understanding of the genetic basis of many biologically important phenotypes, including antibiotic resistance, pathogenicity, and host adaptation. Such studies need however to account for the specificities of bacterial genomics, especially in terms of population structure, homologous recombination, and genomic plasticity. A powerful way to tackle this challenge is to use a phylogenetic approach, which is based on long-standing methodology for the evolutionary analysis of bacterial genomic data. Here we present both the theoretical and practical aspects involved in the use of phylogenetic methods for bacterial genome-wide association studies.
Hennart M, Panunzi LG, Rodrigues C, et al., 2020, Population genomics and antimicrobial resistance in Corynebacterium diphtheriae, GENOME MEDICINE, Vol: 12, ISSN: 1756-994X
Fountain-Jones NM, Appaw RC, Carver S, et al., 2020, Emerging phylogenetic structure of the SARS-CoV-2 pandemic., Virus Evol, Vol: 6, ISSN: 2057-1577
Since spilling over into humans, SARS-CoV-2 has rapidly spread across the globe, accumulating significant genetic diversity. The structure of this genetic diversity and whether it reveals epidemiological insights are fundamental questions for understanding the evolutionary trajectory of this virus. Here, we use a recently developed phylodynamic approach to uncover phylogenetic structures underlying the SARS-CoV-2 pandemic. We find support for three SARS-CoV-2 lineages co-circulating, each with significantly different demographic dynamics concordant with known epidemiological factors. For example, Lineage C emerged in Europe with a high growth rate in late February, just prior to the exponential increase in cases in several European countries. Non-synonymous mutations that characterize Lineage C occur in functionally important gene regions responsible for viral replication and cell entry. Even though Lineages A and B had distinct demographic patterns, they were much more difficult to distinguish. Continuous application of phylogenetic approaches to track the evolutionary epidemiology of SARS-CoV-2 lineages will be increasingly important to validate the efficacy of control efforts and monitor significant evolutionary events in the future.
Zhao L, Chen H, Didelot X, et al., 2020, Co-existence of multiple distinct lineages in Vibrio parahaemolyticus serotype O4:K12, MICROBIAL GENOMICS, Vol: 6, ISSN: 2057-5858
Osnes MN, Didelot X, de Korne-Elenbaas J, et al., 2020, Sudden emergence of a Neisseria gonorrhoeae Glade with reduced susceptibility to extended-spectrum cephalosporins, Norway, MICROBIAL GENOMICS, Vol: 6, ISSN: 2057-5858
Celma CC, Beard S, Douglas A, et al., 2020, Retrospective analysis on confirmation rates for referred positive rotavirus samples in England, 2016 to 2017: implications for diagnosis and surveillance, Eurosurveillance, Vol: 25, Pages: 1-8, ISSN: 1025-496X
BackgroundRapid diagnostic tests are commonly used by hospital laboratories in England to detect rotavirus (RV), and results are used to inform clinical management and support national surveillance of the infant rotavirus immunisation programme since 2013. In 2017, the Public Health England (PHE) national reference laboratory for enteric viruses observed that the presence of RV could not be confirmed by PCR in a proportion of RV-positive samples referred for confirmatory detection.AimWe aimed to compare the positivity rate of detection methods used by hospital laboratories with the PHE confirmatory test rate.MethodsRotavirus specimens testing positive at local hospital laboratories were re-tested at the PHE national reference laboratory using a PCR test. Confirmatory results were compared to original results from the PHE laboratory information management system.ResultsHospital laboratories screened 70.1% (2,608/3,721) of RV samples using immunochromatographic assay (IC) or rapid tests, 15.5% (578/3,721) using enzyme immunoassays (EIA) and 14.4% (535/3,721) using PCR. Overall, 1,011/3,721 (27.2%) locally RV-positive samples referred to PHE in 2016 and 2017 failed RV detection using the PHE reference laboratory PCR test. Confirmation rates were 66.9% (1,746/2,608) for the IC tests, 87.4% (505/578) for the EIA and 86.4% (465/535) for the PCR assays. Seasonal confirmation rate discrepancies were also evident for IC tests.ConclusionsThis report highlights high false positive rates with the most commonly used RV screening tests and emphasises the importance of implementing verified confirmatory tests for RV detections. This has implications for clinical diagnosis and national surveillance.
Whittles LK, White PJ, Didelot X, 2020, Assessment of the potential of vaccination to combat antibiotic resistance in gonorrhea: a modeling analysis to determine preferred product characteristics, Clinical Infectious Diseases, Vol: 71, Pages: 1912-1919, ISSN: 1058-4838
BACKGROUND: Gonorrhea incidence is increasing rapidly in many countries, whilst antibiotic resistance is making treatment more difficult. Combined with evidence that MeNZB and Bexsero meningococcal vaccines are likely partially-protective against gonorrhea, this has renewed interest in a gonococcal vaccine, and several candidates are in development. Key questions are how protective a vaccine needs to be, how long protection needs to last, and how should it be targeted. We assessed vaccination's potential impact, and the feasibility of achieving WHO's target 90% reduction in gonorrhea incidence 2016-2030, by comparing realistic vaccination strategies under a range of scenarios of vaccine efficacy and duration of protection, and emergence of extensively-resistant gonorrhea. METHODS: We developed a stochastic transmission-dynamic model, incorporating asymptomatic and symptomatic infection and heterogeneous sexual behavior in men-who-have-sex-with-men (MSM). We used data from England, which has a comprehensive, consistent nationwide surveillance system. Using particle Markov Chain Monte Carlo methods we fitted the model to gonorrhea incidence in 2008-17, and then used Bayesian forecasting to examine an extensive range of scenarios. RESULTS: Even in the worst-case scenario of untreatable infection emerging, the WHO target is achievable if all MSM attending sexual health clinics receive a vaccine offering ≥52% protection for ≥6 years. A vaccine conferring 31% protection (as estimated for MeNZB) for 2-4 years, could reduce incidence in 2030 by 45% in the worst-case scenario, and by 75% if >70% of resistant gonorrhea remains treatable. CONCLUSIONS: Even a partially-protective vaccine, delivered through a realistic targeting strategy, could substantially reduce gonorrhea incidence, despite antibiotic resistance.
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