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Non-typhoidal Salmonella enterica is a common cause of diarrhoeal disease; in humans, consumption of contaminated poultry meat is believed to be a major source. Brazil is the world's largest exporter of chicken meat globally, and previous studies have indicated the introduction of Salmonella serovars through imported food products from Brazil. Here we provide an in-depth genomic characterisation and evolutionary analysis to investigate the most prevalent serovars and antimicrobial resistance (AMR) in Brazilian chickens and assess the impact to public health of products contaminated with S. enterica imported into the United Kingdom from Brazil. To do so, we examine 183 Salmonella genomes from chickens in Brazil and 357 genomes from humans, domestic poultry and imported Brazilian poultry products isolated in the United Kingdom. S. enterica serovars Heidelberg and Minnesota were the most prevalent serovars in Brazil and in meat products imported from Brazil into the UK. We extended our analysis to include 1,259 publicly available Salmonella Heidelberg and Salmonella Minnesota genomes for context. The Brazil genomes form clades distinct from global isolates, with temporal analysis suggesting emergence of these Salmonella Heidelberg and Salmonella Minnesota clades in the early 2000s, around the time of the 2003 introduction of the Enteritidis vaccine in Brazilian poultry. Analysis showed genomes within the Salmonella Heidelberg and Salmonella Minnesota clades shared resistance to sulphonamides, tetracyclines and beta-lactams conferred by sul2, tetA and blaCMY-2 genes, not widely observed in other co-circulating serovars despite similar selection pressures. The sul2 and tetA genes were concomitantly carried on IncC plasmids, whereas blaCMY-2 was either co-located with the sul2 and tetA genes on IncC plasmids or independently on IncI1 plasmids. Long-term surveillance data collected in the UK showed no increase in the incidence of Salmonella Heidelberg or Salmonella Minnesota in human cases of clinical disease in the UK following the increase of these two serovars in Brazilian poultry. In addition, almost all of the small number of UK-derived genomes which cluster with the Brazilian poultry-derived sequences could either be attributed to human cases with a recent history of foreign travel or were from imported Brazilian food products. These findings indicate that even should Salmonella from imported Brazilian poultry products reach UK consumers, they are very unlikely to be causing disease. No evidence of the Brazilian strains of Salmonella Heidelberg or Salmonella Minnesota were observed in UK domestic chickens. These findings suggest that introduction of the Salmonella Enteritidis vaccine, in addition to increasing antimicrobial use, could have resulted in replacement of salmonellae in Brazilian poultry flocks with serovars that are more drug resistant, but less associated with disease in humans in the UK. The plasmids conferring resistance to beta-lactams, sulphonamides and tetracyclines likely conferred a competitive advantage to the Salmonella Minnesota and Salmonella Heidelberg serovars in this setting of high antimicrobial use, but the apparent lack of transfer to other serovars present in the same setting suggests barriers to horizontal gene transfer that could be exploited in intervention strategies to reduce AMR. The insights obtained reinforce the importance of One Health genomic surveillance.
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Salmonella enterica , Animais , Antibacterianos/farmacologia , Brasil/epidemiologia , Galinhas , Farmacorresistência Bacteriana/genética , Aves Domésticas , Saúde Pública , Salmonella , Salmonella enterica/genética , Sulfonamidas , Tetraciclinas , beta-LactamasRESUMO
Salmonella enterica serovar Infantis presents an ever-increasing threat to public health because of its spread throughout many countries and association with high levels of antimicrobial resistance (AMR). We analyzed whole-genome sequences of 5,284 Salmonella Infantis strains from 74 countries, isolated during 1989-2020 from a wide variety of human, animal, and food sources, to compare genetic phylogeny, AMR determinants, and plasmid presence. The global Salmonella Infantis population structure diverged into 3 clusters: a North American cluster, a European cluster, and a global cluster. The levels of AMR varied by Salmonella Infantis cluster and by isolation source; 73% of poultry isolates were multidrug resistant, compared with 35% of human isolates. This finding correlated with the presence of the pESI megaplasmid; 71% of poultry isolates contained pESI, compared with 32% of human isolates. This study provides key information for public health teams engaged in reducing the spread of this pathogen.
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Saúde Única , Salmonella enterica , Animais , Humanos , Sorogrupo , Antibacterianos/farmacologia , Salmonella/genética , Aves Domésticas , Farmacorresistência Bacteriana Múltipla/genéticaRESUMO
Salmonella Typhi infection in a patient in Pakistan initially responded to standard treatment but failed to respond to subsequent treatment. The first strain was susceptible to carbapenems and azithromycin; subsequent strains harbored the NDM-5 gene. Treatment with a combination of intravenous meropenem and colistin was successful. Carbapenem-resistant Salmonella Typhi emergence will hinder treatment.
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Febre Tifoide , Humanos , Febre Tifoide/diagnóstico , Febre Tifoide/tratamento farmacológico , Febre Tifoide/epidemiologia , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Paquistão/epidemiologia , Salmonella typhi/genética , Testes de Sensibilidade MicrobianaRESUMO
AIMS: To compare the antimicrobial resistance (AMR) genes in a genetically diverse group of Salmonella enterica recovered from foods imported into England between 2014 and 2018. METHODS AND RESULTS: Whole genome sequence was used to detect AMR genes or chromosomal mutations associated with AMR in Salmonella recovered from edible leaves imported from Asia (n = 115) as compared to Salmonella (n = 231) isolated from raw chicken, 74% originated from South America. Among isolates from edible leaves, three (3%) showed resistance to at least one antimicrobial agent, two (2%) of which were multidrug resistant (MDR, resistance to three or more antimicrobial classes). Resistance to at least one antimicrobial agent was detected in 214 (93%) in the chicken isolates, with 164 (71%) showing MDR. Genetic diversity and AMR profiles were highly heterogeneous across the different serovars. CONCLUSIONS: Resistance was rare among the Salmonella isolates from edible leaves but common (including MDR) among those from raw chicken. SIGNIFICANCE AND IMPACT OF THE STUDY: Surveillance of AMR in imported foods is essential for monitoring the risk of transmission of resistance from the food chain to humans and provides added public health value to pre-existing controls of the food chain.
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Salmonella enterica , Animais , Antibacterianos/farmacologia , Galinhas , Farmacorresistência Bacteriana/genética , Farmacorresistência Bacteriana Múltipla/genética , Humanos , Testes de Sensibilidade Microbiana , Folhas de Planta , Salmonella/genética , Sequenciamento Completo do Genoma/métodosRESUMO
Rapid and accurate differentiation of Salmonella spp. causing enteric fever from nontyphoidal Salmonella is essential for clinical management of cases, laboratory risk management, and implementation of public health measures. Current methods used for confirmation of identification, including biochemistry and serotyping as well as whole-genome sequencing analyses, take several days. Here we report the development and evaluation of a real-time PCR assay that can be performed directly on crude DNA extracts from bacterial colonies for the rapid identification of typhoidal and nontyphoidal Salmonella.
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Infecções por Salmonella/microbiologia , Salmonella typhi/classificação , Salmonella/classificação , DNA Bacteriano/genética , Genoma Bacteriano , Humanos , Reação em Cadeia da Polimerase em Tempo Real , Infecções por Salmonella/diagnóstico , Salmonella enterica/classificação , Sensibilidade e Especificidade , Sorogrupo , Febre Tifoide/microbiologia , Sequenciamento Completo do GenomaRESUMO
Enteroinvasive Escherichia coli (EIEC) outbreaks are uncommon in Europe. In June 2014, two EIEC outbreaks occurred in Nottingham, UK, within 2 days; outbreak A was linked to a takeaway restaurant and outbreak B to a wedding party. We conducted 2 analytical studies: a case-control study for outbreak A and a cohort study for outbreak B. We tested microbiological and environmental samples, including by using whole-genome sequencing. For both outbreaks combined, we identified 157 probable case-patients; 27 were laboratory-confirmed as EIEC O96:H19-positive. Combined epidemiologic, microbiological, and environmental findings implicated lettuce as the vehicle of infection in outbreak A, but the source of the organism remained unknown. Whole-genome sequencing identified the same organism in cases from both outbreaks, but no epidemiologic link was confirmed. These outbreaks highlight that EIEC has the capacity to cause large and severe gastrointestinal disease outbreaks and should be considered as a potential pathogen in foodborne outbreaks in Europe.
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Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Escherichia coli/isolamento & purificação , Gastroenterite/epidemiologia , Gastroenterite/microbiologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Surtos de Doenças , Fezes/microbiologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Reino Unido/epidemiologia , Adulto JovemRESUMO
Genomic sequencing has revolutionized microbial typing methods and transformed high-throughput methods in reference, clinical, and research laboratories. The detection of antimicrobial-resistant (AMR) determinants using genomic methods can provide valuable information on the emergence of resistance. Here we describe an approach to detecting AMR determinants using an open access and freely available platform which does not require bioinformatic expertise.
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Biologia Computacional , Farmacorresistência Bacteriana , Genoma Bacteriano , Sequenciamento Completo do Genoma , Sequenciamento Completo do Genoma/métodos , Farmacorresistência Bacteriana/genética , Biologia Computacional/métodos , Humanos , Antibacterianos/farmacologia , Genômica/métodos , Software , Bactérias/genética , Bactérias/efeitos dos fármacos , Sequenciamento de Nucleotídeos em Larga Escala/métodosRESUMO
Introduction: The emergence and resurgence of pathogens have led to significant global health challenges. Wastewater surveillance has historically been used to track water-borne or fecal-orally transmitted pathogens, providing a sensitive means of monitoring pathogens within a community. This technique offers a comprehensive, real-time, and cost-effective approach to disease surveillance, especially for diseases that are difficult to monitor through individual clinical screenings. Methods: This narrative review examines the current state of knowledge on wastewater surveillance, emphasizing important findings and techniques used to detect potential pathogens from wastewater. It includes a review of literature on the detection methods, the pathogens of concern, and the challenges faced in the surveillance process. Results: Wastewater surveillance has proven to be a powerful tool for early warning and timely intervention of infectious diseases. It can detect pathogens shed by asymptomatic and pre-symptomatic individuals, providing an accurate population-level view of disease transmission. The review highlights the applications of wastewater surveillance in tracking key pathogens of concern, such as gastrointestinal pathogens, respiratory pathogens, and viruses like SARS-CoV-2. Discussion: The review discusses the benefits of wastewater surveillance in public health, particularly its role in enhancing existing systems for infectious disease surveillance. It also addresses the challenges faced, such as the need for improved detection methods and the management of antimicrobial resistance. The potential for wastewater surveillance to inform public health mitigation strategies and outbreak response protocols is emphasized. Conclusion: Wastewater surveillance is a valuable tool in the fight against infectious diseases. It offers a unique perspective on the spread and evolution of pathogens, aiding in the prevention and control of disease epidemics. This review underscores the importance of continued research and development in this field to overcome current challenges and maximize the potential of wastewater surveillance in public health.
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Águas Residuárias , Águas Residuárias/microbiologia , Águas Residuárias/virologia , Humanos , COVID-19/epidemiologia , COVID-19/diagnóstico , SARS-CoV-2 , Microbiologia da ÁguaRESUMO
Salmonella osteomyelitis is rare in patients without sickling hemoglobinopathies. Invasive disease caused by Salmonella Paratyphi C is rarer still with only one case reported in the United Kingdom in the last 15 years. We report a case of relapsing S. Paratyphi C osteomyelitis in a newly diagnosed diabetic patient from Ghana. Our patient was initially treated successfully with surgical debridement followed by 6 weeks of IV ceftriaxone before recrudescence 9 months later. Due to the rarity of S. Paratyphi C and the lack of recent travel, genomic analysis was undertaken to assess possible sources with the closest related strain being from Cote d'Ivoire. The patient had likley picked up the strain several years before presentation. We review current Salmonella osteomyelitis literature and audit all cases referred to the England and Wales Salmonella national reference laboratory over the last 15 years.
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Osteomielite , Infecções por Salmonella , Humanos , Salmonella paratyphi C , Infecções por Salmonella/diagnóstico , Infecções por Salmonella/tratamento farmacológico , Salmonella , Osteomielite/diagnóstico , Osteomielite/tratamento farmacológico , CeftriaxonaRESUMO
We aim to provide an evidence-based evaluation of whole genome sequence (WGS) methods, employed at the Salmonella reference laboratory in England, in terms of its impact on public health and whether these methods remain a fit for purpose test under UKAS ISO 15189. The evaluation of the genomic methods were mapped against the value of detecting microbiological clusters to support the investigation of food-borne outbreaks of Salmonella in England between 2012-2020. The analysis of WGS with both SNP- and allelic-based methods provided an unprecedented level of strain discrimination and detection of additional clusters when comparing to all of the previous typing methods. The robustness of the routine genomic sequencing at the reference laboratory ensured confidence in the microbiological identifications, even in large outbreaks with complex international food distribution networks. There was evidence that the phylogeny derived from the WGS data can be used to inform the provenance of strains and support discrimination between domestic and non-domestic transmission events. Further insight on the evolutionary context of the emerging pathogenic strains was enabled with a deep dive of the phylogenetic data, including the detection of nested clusters. The public availability of the WGS data linked to the clinical, epidemiological and environmental context of the sequenced strains has improved the trace-back investigations during outbreaks. The global expansion in the use of WGS-based typing in reference laboratories has shown that the WGS methods are a fit for purpose test in public health as it has ensured the rapid implementation of interventions to protect public health, informed risk assessment and has facilitated the management of national and international food-borne outbreaks of Salmonella.
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Introduction: Outbreak investigation of foodborne salmonellosis is hindered when the food source is contaminated by multiple strains of Salmonella, creating difficulties matching an incriminated organism recovered from patients with the specific strain in the suspect food. An outbreak of the rare Salmonella Adjame was caused by multiple strains of the organism as revealed by single-nucleotide polymorphism (SNP) variation. The use of highly discriminatory prophage analysis to characterize strains of Salmonella should enable a more precise strain characterization and aid the investigation of foodborne salmonellosis. Methods: We have carried out genomic analysis of S. Adjame strains recovered during the course of a recent outbreak and compared them with other strains of the organism (n = 38 strains), using SNPs to evaluate strain differences present in the core genome, and prophage sequence typing (PST) to evaluate the accessory genome. Phylogenetic analyses were performed using both total prophage content and conserved prophages. Results: The PST analysis of the S. Adjame isolates showed a high degree of strain heterogeneity. We observed small clusters made up of 2-6 isolates (n = 27) and singletons (n = 11) in stark contrast with the three clusters observed by SNP analysis. In total, we detected 24 prophages of which only four were highly prevalent, namely: Entero_p88 (36/38 strains), Salmon_SEN34 (35/38 strains), Burkho_phiE255 (33/38 strains) and Edward_GF (28/38 strains). Despite the marked strain diversity seen with prophage analysis, the distribution of the four most common prophages matched the clustering observed using core genome. Discussion: Mutations in the core and accessory genomes of S. Adjame have shed light on the evolutionary relationships among the Adjame strains and demonstrated a convergence of the variations observed in both fractions of the genome. We conclude that core and accessory genomes analyses should be adopted in foodborne bacteria outbreak investigations to provide a more accurate strain description and facilitate reliable matching of isolates from patients and incriminated food sources. The outcomes should translate to a better understanding of the microbial population structure and an 46 improved source attribution in foodborne illnesses.
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Source attribution has traditionally involved combining epidemiological data with different pathogen characterisation methods, including 7-gene multi locus sequence typing (MLST) or serotyping, however, these approaches have limited resolution. In contrast, whole genome sequencing data provide an overview of the whole genome that can be used by attribution algorithms. Here, we applied a random forest (RF) algorithm to predict the primary sources of human clinical Salmonella Typhimurium (S. Typhimurium) and monophasic variants (monophasic S. Typhimurium) isolates. To this end, we utilised single nucleotide polymorphism diversity in the core genome MLST alleles obtained from 1,061 laboratory-confirmed human and animal S. Typhimurium and monophasic S. Typhimurium isolates as inputs into a RF model. The algorithm was used for supervised learning to classify 399 animal S. Typhimurium and monophasic S. Typhimurium isolates into one of eight distinct primary source classes comprising common livestock and pet animal species: cattle, pigs, sheep, other mammals (pets: mostly dogs and horses), broilers, layers, turkeys, and game birds (pheasants, quail, and pigeons). When applied to the training set animal isolates, model accuracy was 0.929 and kappa 0.905, whereas for the test set animal isolates, for which the primary source class information was withheld from the model, the accuracy was 0.779 and kappa 0.700. Subsequently, the model was applied to assign 662 human clinical cases to the eight primary source classes. In the dataset, 60/399 (15.0%) of the animal and 141/662 (21.3%) of the human isolates were associated with a known outbreak of S. Typhimurium definitive type (DT) 104. All but two of the 141 DT104 outbreak linked human isolates were correctly attributed by the model to the primary source classes identified as the origin of the DT104 outbreak. A model that was run without the clonal DT104 animal isolates produced largely congruent outputs (training set accuracy 0.989 and kappa 0.985; test set accuracy 0.781 and kappa 0.663). Overall, our results show that RF offers considerable promise as a suitable methodology for epidemiological tracking and source attribution for foodborne pathogens.
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BACKGROUND: Dried non-heat-treated meat treats, such as ears, skin and tails, are popular supplementary dog foods. Previous studies have demonstrated Salmonella spp. contamination on treats, particularly in pig ears and chicken products. This small, exploratory, cross-sectional study investigated Salmonella spp. presence in dried treats available in the UK. METHODS: A selection of dried treats from local pet shops and online retailers underwent bacterial culture for Salmonella spp. and subsequent antimicrobial susceptibility testing, with Salmonella serotype determined by whole genome sequencing. RESULTS: Eighty-four samples were tested, with 16% being Salmonella spp. positive. Five Salmonella serotypes were identified, each associated with specific treat types. An antimicrobial-resistant phenotype was identified in 39% of isolates. All serotypes identified are known to cause human infection. LIMITATIONS: This study was limited by a small sample size and limited number of retail sources. CONCLUSION: Salmonella spp. of public health concern were present in some dried dog treats in this study. Dog owners, pet food retailers and veterinary professionals should be aware of the potential zoonotic disease risk associated with these treats, and appropriate hygiene measures, including thorough hand washing, should be utilised if they are fed.
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Anti-Infecciosos , Saúde Pública , Cães , Humanos , Animais , Suínos , Estudos Transversais , Salmonella , Carne/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Testes de Sensibilidade Microbiana/veterinária , Microbiologia de AlimentosRESUMO
Salmonella Paratyphi B infections in England are the least common imported typhoidal infection but can still cause invasive disease. Sentinel surveillance at the reference laboratory detected an outbreak from Iraq due to reported travel history, enabling enhanced PCR testing for a quick diagnosis.
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Febre Paratifoide , Salmonella paratyphi B , Humanos , Salmonella paratyphi B/genética , Febre Paratifoide/epidemiologia , Vigilância de Evento Sentinela , Iraque , Eventos de Massa , Genômica , Surtos de DoençasRESUMO
The Anderson phage typing scheme has been successfully used worldwide for epidemiological surveillance of Salmonella enterica serovar Typhimurium. Although the scheme is being replaced by whole genome sequence subtyping methods, it can provide a valuable model system for study of phage-host interaction. The phage typing scheme distinguishes more than 300 definitive types of Salmonella Typhimurium based on their patterns of lysis to a unique collection of 30 specific Salmonella phages. In this study, we sequenced the genomes of 28 Anderson typing phages of Salmonella Typhimurium to begin to characterize the genetic determinants that are responsible for the differences in these phage type profiles. Genomic analysis of typing phages reveals that Anderson phages can be classified into three different groups, the P22-like, ES18-like and SETP3-like clusters. Most Anderson phages are short tailed P22-like viruses (genus Lederbergvirus); but phages STMP8 and STMP18 are very closely related to the lambdoid long tailed phage ES18, and phages STMP12 and STMP13 are related to the long noncontractile tailed, virulent phage SETP3. Most of these typing phages have complex genome relationships, but interestingly, two phage pairs STMP5 and STMP16 as well as STMP12 and STMP13 differ by a single nucleotide. The former affects a P22-like protein involved in DNA passage through the periplasm during its injection, and the latter affects a gene whose function is unknown. Using the Anderson phage typing scheme would provide insights into phage biology and the development of phage therapy for the treatment of antibiotic resistant bacterial infections.
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Bacteriófagos , Bacteriófagos/genética , Genômica , Bactérias , Salmonella typhimurium/genética , Tipagem de BacteriófagosRESUMO
Raw meat diets (RMD) for dogs are an increasingly popular alternative pet food choice, however studies worldwide have demonstrated them to be contaminated with zoonotic and antimicrobial resistant (AMR) bacteria, including bacteria resistant to critically important antibiotics. Despite this, few data exist surrounding the presence of these bacteria in RMD in the United Kingdom. The present study aimed to identify the most commonly selected RMD and non-raw diets (NRMD) by United Kingdom dog owners. Additionally, it investigated the presence of AMR-Enterobacteriaceae in samples of pre-prepared RMD and cooked commercial kibble dog foods. An online survey investigating diet preferences of United Kingdom dog owners was open for 6 weeks between February-March 2020. From this, the top 10 brands of pre-prepared raw and cooked kibble diets were ascertained and 134 samples purchased (110 RMD, 24 kibble) and subjected to microbiological testing. Bacterial enumeration of E. coli and other Enterobacteriaceae was undertaken, and the presence of Salmonella spp. and AMR-E. coli within samples determined. Whole genome sequencing was undertaken on Salmonella spp. and third-generation cephalosporin-resistant 3GCR-E. coli isolates. Pre-prepared RMD was most commonly selected by dog owners who fed RMD, and cooked commercial complete dry food was most frequently fed by owners who fed NRMD. Damaged and leaking packaging was observed in samples of RMD, alongside variability in information provided surrounding product traceability. Counts of E. coli and other Enterobacteriaceae exceeding >5,000 CFU/g were identified in samples of RMD. AMR-, extended-spectrum beta-lactamase (ESBL)-producing and 3GCR-E. coli was isolated from 39, 14 and 16% of RMD samples, respectively. Multiple antimicrobial resistance genes were identified in 3GCR-E. coli isolates. Of the ESBL encoding genes, blaCTX-M-15 was most commonly identified. S. enterica was isolated from 5% of RMD samples. No Enterobacteriaceae were isolated from any of the cooked kibble samples. The present study suggests that pre-prepared RMD available for dogs in the United Kingdom can be contaminated with zoonotic and AMR-Enterobacteriaceae. RMDs, therefore, are potentially an important One Health concern. Veterinary and medical professionals, pet food retailers and pet owners should be aware of these risks; and stringent hygiene measures should be practiced if owners choose to feed RMD.
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Salmonella enterica serovar Enteritidis is one of the most frequent causes of Salmonellosis globally and is commonly transmitted from animals to humans by the consumption of contaminated foodstuffs. In the UK and many other countries in the Global North, a significant proportion of cases are caused by the consumption of imported food products or contracted during foreign travel, therefore, making the rapid identification of the geographical source of new infections a requirement for robust public health outbreak investigations. Herein, we detail the development and application of a hierarchical machine learning model to rapidly identify and trace the geographical source of S. Enteritidis infections from whole genome sequencing data. 2313 S. Enteritidis genomes, collected by the UKHSA between 2014-2019, were used to train a 'local classifier per node' hierarchical classifier to attribute isolates to four continents, 11 sub-regions, and 38 countries (53 classes). The highest classification accuracy was achieved at the continental level followed by the sub-regional and country levels (macro F1: 0.954, 0.718, 0.661, respectively). A number of countries commonly visited by UK travelers were predicted with high accuracy (hF1: >0.9). Longitudinal analysis and validation with publicly accessible international samples indicated that predictions were robust to prospective external datasets. The hierarchical machine learning framework provided granular geographical source prediction directly from sequencing reads in <4 min per sample, facilitating rapid outbreak resolution and real-time genomic epidemiology. The results suggest additional application to a broader range of pathogens and other geographically structured problems, such as antimicrobial resistance prediction, is warranted.
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Infecções por Salmonella , Salmonella enterica , Animais , Humanos , Salmonella enteritidis/genética , Estudos Prospectivos , Infecções por Salmonella/epidemiologia , Surtos de Doenças , Aprendizado de MáquinaRESUMO
Background: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000). Methods: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch. Results: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal 'sentinel' surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. Conclusions: The consortium's aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies. Funding: No specific funding was awarded for this meta-analysis. Coordinators were supported by fellowships from the European Union (ZAD received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 845681), the Wellcome Trust (SB, Wellcome Trust Senior Fellowship), and the National Health and Medical Research Council (DJI is supported by an NHMRC Investigator Grant [GNT1195210]).
Salmonella Typhi (Typhi) is a type of bacteria that causes typhoid fever. More than 110,000 people die from this disease each year, predominantly in areas of sub-Saharan Africa and South Asia with limited access to safe water and sanitation. Clinicians use antibiotics to treat typhoid fever, but scientists worry that the spread of antimicrobial-resistant Typhi could render the drugs ineffective, leading to increased typhoid fever mortality. The World Health Organization has prequalified two vaccines that are highly effective in preventing typhoid fever and may also help limit the emergence and spread of resistant Typhi. In low resource settings, public health officials must make difficult trade-off decisions about which new vaccines to introduce into already crowded immunization schedules. Understanding the local burden of antimicrobial-resistant Typhi and how it is spreading could help inform their actions. The Global Typhoid Genomics Consortium analyzed 13,000 Typhi genomes from 110 countries to provide a global overview of genetic diversity and antimicrobial-resistant patterns. The analysis showed great genetic diversity of the different strains between countries and regions. For example, the H58 Typhi variant, which is often drug-resistant, has spread rapidly through Asia and Eastern and Southern Africa, but is less common in other regions. However, distinct strains of other drug-resistant Typhi have emerged in other parts of the world. Resistance to the antibiotic ciprofloxacin was widespread and accounted for over 85% of cases in South Africa. Around 70% of Typhi from Pakistan were extensively drug-resistant in 2020, but these hard-to-treat variants have not yet become established elsewhere. Variants that are resistant to both ciprofloxacin and ceftriaxone have been identified, and azithromycin resistance has also appeared in several different variants across South Asia. The Consortium's analyses provide valuable insights into the global distribution and transmission patterns of drug-resistant Typhi. Limited genetic data were available fromseveral regions, but data from travel-associated cases helped fill some regional gaps. These findings may help serve as a starting point for collective sharing and analyses of genetic data to inform local public health action. Funders need to provide ongoing supportto help fill global surveillance data gaps.
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Salmonella typhi , Febre Tifoide , Humanos , Salmonella typhi/genética , Febre Tifoide/epidemiologia , Antibacterianos/farmacologia , Viagem , Farmacorresistência Bacteriana/genética , CiprofloxacinaRESUMO
Salmonella is a leading cause of foodborne outbreaks and systemic infections worldwide. Emerging multi-drug resistant Salmonella lineages such as a ciprofloxacin-resistant subclade (CIPR) within Salmonella enterica serovar Kentucky ST198 threaten the effective prevention and treatment of infections. To understand the genomic diversity and antimicrobial resistance gene content associated with S. Kentucky in Switzerland, we whole-genome sequenced 70 human clinical isolates obtained between 2010 and 2020. Most isolates belonged to ST198-CIPR. High- and low-level ciprofloxacin resistance among CIPR isolates was associated with variable mutations in ramR and acrB in combination with stable mutations in quinolone-resistance determining regions (QRDRs). Analysis of isolates from patients with prolonged ST198 colonization indicated subclonal adaptions with the ramR locus as a mutational hotspot. SNP analyses identified multiple clusters of near-identical isolates, which were often associated with travel but included spatiotemporally linked isolates from Switzerland. The largest SNP cluster was associated with travellers returning from Indonesia, and investigation of global data linked >60 additional ST198 salmonellosis isolates to this cluster. Our results emphasize the urgent need for implementing whole-genome sequencing as a routine tool for Salmonella surveillance and outbreak detection.
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Anti-Infecciosos , Salmonella enterica , Humanos , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Testes de Sensibilidade Microbiana , Suíça/epidemiologia , Metagenômica , Farmacorresistência Bacteriana/genética , Ciprofloxacina/farmacologia , Genômica , Anti-Infecciosos/farmacologiaRESUMO
Antimicrobial-resistance (AMR) genes can be transferred between microbial cells via horizontal gene transfer (HGT), which involves mobile and integrative elements such as plasmids, bacteriophages, transposons, integrons and pathogenicity islands. Bacteriophages are found in abundance in the microbial world, but their role in virulence and AMR has not fully been elucidated in the Enterobacterales. With short-read sequencing paving the way to systematic high-throughput AMR gene detection, long-read sequencing technologies now enable us to establish how such genes are structurally connected into meaningful genomic units, raising questions about how they might cooperate to achieve their biological function. Here, we describe a novel ~98 kbp circular P1-bacteriophage-like plasmid termed ph681355 isolated from a clinical Salmonella enterica serovar Typhi isolate. It carries bla CTX-M-15, an IncY plasmid replicon (repY gene) and the ISEcP1 mobile element and is, to our knowledge, the first reported P1-bacteriophage-like plasmid (phage-plasmid) in S. enterica Typhi. We compared ph681355 to two previously described phage-plasmids, pSJ46 from S. enterica serovar Indiana and pMCR-1-P3 from Escherichia coli, and found high nucleotide similarity across the backbone. However, we saw low ph681355 backbone similarity to plasmid p60006 associated with the extensively drug-resistant S. enterica Typhi outbreak isolate in Pakistan, providing evidence of an alternative route for bla CTX-M-15 transmission. Our discovery highlights the importance of utilizing long-read sequencing in interrogating bacterial genomic architecture to fully understand AMR mechanisms and their clinical relevance. It also raises questions regarding how widespread bacteriophage-mediated HGT might be, suggesting that the resulting genomic plasticity might be higher than previously thought.