<h2>Summary</h2> Historically, epidemiological investigation and surveillance for bacterial antimicrobial resistance (AMR) has relied on low-resolution isolate-based phenotypic analyses undertaken at local and national reference laboratories. Genomic sequencing has the potential to provide a far more high-resolution picture of AMR evolution and transmission, and is already beginning to revolutionise how public health surveillance networks monitor and tackle bacterial AMR. However, the routine integration of genomics in surveillance pipelines still has considerable barriers to overcome. In 2022, a workshop series and online consultation brought together international experts in AMR and pathogen genomics to assess the status of genomic applications for AMR surveillance in a range of settings. Here we focus on discussions around the use of genomics for public health and international AMR surveillance, noting the potential advantages of, and barriers to, implementation, and proposing recommendations from the working group to help to drive the adoption of genomics in public health AMR surveillance. These recommendations include the need to build capacity for genome sequencing and analysis, harmonising and standardising surveillance systems, developing equitable data sharing and governance frameworks, and strengthening interactions and relationships among stakeholders at multiple levels. 

Genomics for public health and international surveillance of antimicrobial resistance.

Abstract The genus Bordetella includes bacteria that are found in the environment and/or associated with humans and other animals. A few closely related species, including Bordetella pertussis , are human pathogens that cause diseases such as whooping cough. Here, we present a large database of Bordetella isolates and genomes and develop genotyping systems for the genus and for the B. pertussis clade. To generate the database, we merge previously existing databases from Oxford University and Institut Pasteur, import genomes from public repositories, and add 83 newly sequenced B. bronchiseptica genomes. The public database currently includes 2582 Bordetella isolates and their provenance data, and 2085 genomes ( https://bigsdb.pasteur.fr/bordetella/ ). We use core-genome multilocus sequence typing (cgMLST) to develop genotyping systems for the whole genus and for B. pertussis , as well as specific schemes to define antigenic, virulence and macrolide resistance profiles. Phylogenetic analyses allow us to redefine evolutionary relationships among known Bordetella species, and to propose potential new species. Our database provides an expandable resource for genotyping of environmental and clinical Bordetella isolates, thus facilitating evolutionary and epidemiological research on whooping cough and other Bordetella infections. 

/pdf/a-comprehensive-resource-for-bordetella-genomic-epidemiology-3vorc9f3.pdf

A comprehensive resource for Bordetella genomic epidemiology and biodiversity studies

Next-generation whole-genome sequencing is essential for high-resolution surveillance of bacterial pathogens, for example, during outbreak investigations or for source tracking and escape variant analysis. However, current global sequencing and bioinformatic bottlenecks and a long time to result with standard technologies demand new approaches. ABSTRACT Next-generation whole-genome sequencing is essential for high-resolution surveillance of bacterial pathogens, for example, during outbreak investigations or for source tracking and escape variant analysis. However, current global sequencing and bioinformatic bottlenecks and a long time to result with standard technologies demand new approaches. In this study, we investigated whether novel nanopore Q20+ long-read chemistry enables standardized and easily accessible high-resolution typing combined with core genome multilocus sequence typing (cgMLST). We set high requirements for discriminatory power by using the slowly evolving bacterium Bordetella pertussis as a model pathogen. Our results show that the increased raw read accuracy enables the description of epidemiological scenarios and phylogenetic linkages at the level of gold-standard short reads. The same was true for our variant analysis of vaccine antigens, resistance genes, and virulence factors, demonstrating that nanopore sequencing is a legitimate competitor in the area of next-generation sequencing (NGS)-based high-resolution bacterial typing. Furthermore, we evaluated the parameters for the fastest possible analysis of the data. By combining the optimized processing pipeline with real-time basecalling, we established a workflow that allows for highly accurate and extremely fast high-resolution typing of bacterial pathogens while sequencing is still in progress. Along with advantages such as low costs and portability, the approach suggested here might democratize modern bacterial typing, enabling more efficient infection control globally.

Real-Time Nanopore Q20+ Sequencing Enables Extremely Fast and Accurate Core Genome MLST Typing and Democratizes Access to High-Resolution Bacterial Pathogen Surveillance

Immunogenicity and safety of BPZE1, an intranasal live attenuated pertussis vaccine, versus tetanus–diphtheria–acellular pertussis vaccine: a randomised, double-blind, phase 2b trial

After the pertussis vaccine had been introduced in the 1940s and was shown to be very successful in reducing the morbidity and mortality associated with the disease, the possibility of improving both vaccine composition and vaccination schedules has become the subject of continuous interest. As a result, we are witnessing a considerable heterogeneity in pertussis vaccination policies, which remains beyond universal consensus. Many pertussis-related deaths still occur in low- and middle-income countries; however, these deaths are attributable to gaps in vaccination coverage and limited access to healthcare in these countries, rather than to the poor efficacy of the first generation of pertussis vaccine consisting in inactivated and detoxified whole cell pathogen (wP). In many, particularly high-income countries, a switch was made in the 1990s to the use of acellular pertussis (aP) vaccine, to reduce the rate of post-vaccination adverse events and thereby achieve a higher percentage of children vaccinated. However the epidemiological data collected over the past few decades, even in those high-income countries, show an increase in pertussis prevalence and morbidity rates, triggering a wide-ranging debate on the causes of pertussis resurgence and the effectiveness of current pertussis prevention strategies, as well as on the efficacy of available pertussis vaccines and immunization schedules. The current article presents a systematic review of scientific reports on the evaluation of the use of whole-cell and acellular pertussis vaccines, in the context of long-term immunity and vaccines efficacy.

/pdf/evaluation-of-whole-cell-and-acellular-pertussis-vaccines-in-fg25ci9h.pdf

Evaluation of Whole-Cell and Acellular Pertussis Vaccines in the Context of Long-Term Herd Immunity

As with other pathogens, competitive interactions between Bordetella pertussis strains drive infection risk. Vaccines are thought to perturb strain diversity through shifts in immune pressures; however, this has rarely been measured because of inadequate data and analytical tools. We used 3344 sequences from 23 countries to show that, on average, there are 28.1 transmission chains circulating within a subnational region, with the number of chains strongly associated with host population size. It took 5 to 10 years for B. pertussis to be homogeneously distributed throughout Europe, with the same time frame required for the United States. Increased fitness of pertactin-deficient strains after implementation of acellular vaccines, but reduced fitness otherwise, can explain long-term genotype dynamics. These findings highlight the role of vaccine policy in shifting local diversity of a pathogen that is responsible for 160,000 deaths annually. Description Genomic analyses of Bordetella pertussis reveal spatial structure, rate of geographic spread, and fitness shifts in response to vaccine changes. Immunity-induced pathogen evolution Population immunity is thought to drive pathogen evolutionary dynamics, but this can be hard to measure. Considering the switch from whole-cell vaccines to acellular vaccines (ACVs) as a natural experiment, Lefrancq et al. analyzed the diversity of B. pertussis genome isolates from five continents to infer local changes in strain fitness after ACV introduction. Their analysis provides evidence that ACVs have led to the increased fitness of strains lacking the virulence factor pertactin and may have implications for understanding asymptomatic B. pertussis infection.

Global spatial dynamics and vaccine-induced fitness changes of Bordetella pertussis

Clostridioides difficile infections (CDIs) in Sweden are mostly hospital‐associated (HA) with limited knowledge regarding community‐associated (CA) infections. Here, we investigated the molecular epidemiology of clinical isolates of CA‐CDI and HA‐CDI in a Swedish county. Data and isolates (n = 156) of CDI patients (n = 122) from Jönköping county, October 2017–March 2018, were collected and classified as CA (without previous hospital care or onset ≤2 days after admission or >12 weeks after discharge from hospital) or HA (onset >3 days after hospital admission or within 4 weeks after discharge). Molecular characterization of isolates included PCR ribotyping (n = 156 isolates) and whole genome sequencing with single nucleotide polymorphisms (SNP) analysis (n = 53 isolates). We classified 47 patients (39%) as CA‐CDI and 75 (61%) as HA‐CDI. Between CA‐CDI and HA‐CDI patients, we observed no statistically significant differences regarding gender, age, 30‐day mortality or recurrence. Ribotype 005 (RR 3.1; 95% CI: 1.79–5.24) and 020 (RR 2.5; 95% CI: 1.31–4.63) were significantly associated with CA‐CDI. SNP analysis identified seven clusters (0–2 SNP difference) involving 17/53 isolates of both CA‐CDI and HA‐CDI. Molecular epidemiology differed between CA‐CDI and HA‐CDI and WGS analysis suggests transmission of CDI within and between hospitals and communities.

Molecular epidemiology of community‐ and hospital‐associated Clostridioides difficile infections in Jönköping, Sweden, October 2017 – March 2018

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Global spatial dynamics and vaccine-induced fitness changes of Bordetella pertussis

Molecular epidemiology of community‐ and hospital‐associated Clostridioides difficile infections in Jönköping, Sweden, October 2017 – March 2018