DODGE: Automated point source bacterial outbreak detection using cumulative long term genomic surveillance.

SUMMARY: The reliable and timely recognition of outbreaks is a key component of public health surveillance for foodborne diseases. Whole genome sequencing (WGS) offers high resolution typing of foodborne bacterial pathogens and facilitates the accurate detection of outbreaks. This detection relies on grouping WGS data into clusters at an appropriate genetic threshold, however, methods and tools for selecting and adjusting such thresholds according to the required resolution of surveillance and epidemiological context are lacking. Here we present DODGE (Dynamic Outbreak Detection for Genomic Epidemiology), an algorithm to dynamically select and compare these genetic thresholds. DODGE can analyse expanding datasets over time and clusters that are predicted to correspond to outbreaks (or 'investigation clusters') can be named with the established genomic nomenclature systems to facilitate integrated analysis across jurisdictions. DODGE was tested in two real-world genomic surveillance datasets of different duration, two months from Australia and nine years from the UK. In both cases only a minority of isolates were identified as investigation clusters. Two known outbreaks in the UK dataset were detected by DODGE and were recognised at an earlier timepoint than the outbreaks were reported. These findings demonstrated the potential of the DODGE approach to improve the effectiveness and timeliness of genomic surveillance for foodborne diseases and the effectiveness of the algorithm developed. AVAILABILITY: DODGE is freely available at https://github.com/LanLab/dodge and can easily be installed using Conda. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Emergence of Poultry-Associated Human Salmonella enterica Serovar Abortusovis Infections, New South Wales, Australia.

Salmonella enterica serovar Abortusovis is a ovine-adapted pathogen that causes spontaneous abortion. Salmonella Abortusovis was reported in poultry in 2009 and has since been reported in human infections in New South Wales, Australia. Phylogenomic analysis revealed a clade of 51 closely related isolates from Australia originating in 2004. That clade was genetically distinct from ovine-associated isolates. The clade was widespread in New South Wales poultry production facilities but was only responsible for sporadic human infections. Some known virulence factors associated with human infections were only found in the poultry-associated clade, some of which were acquired through prophages and plasmids. Furthermore, the ovine-associated clade showed signs of genome decay, but the poultry-associated clade did not. Those genomic changes most likely led to differences in host range and disease type. Surveillance using the newly identified genetic markers will be vital for tracking Salmonella Abortusovis transmission in animals and to humans and preventing future outbreaks.

Community Outbreak of Pseudomonas aeruginosa Infections Associated with Contaminated Piercing Aftercare Solution, Australia, 2021.

In April 2021, the South Eastern Sydney Local Health District Public Health Unit (Sydney, New South Wales, Australia) was notified of 3 patients with Pseudomonas aeruginosa infections secondary to skin piercings performed at the same salon. Active case finding through laboratories, clinician alerts, and monitoring hospital visits for piercing-related infections identified additional cases across New South Wales, and consumers were alerted. We identified 13 confirmed and 40 probable case-patients and linked clinical isolates by genomic sequencing. Ten confirmed case-patients had used the same brand and batch of aftercare solution. We isolated P. aeruginosa from opened and unopened bottles of this solution batch that matched the outbreak strain identified by genomic sequencing. Piercing-related infections returned to baseline levels after this solution batch was recalled. Early outbreak detection and source attribution via genomic sequencing are crucial for controlling outbreaks linked to contaminated products. Manufacturing standards for nonsterile cosmetic products and guidance for piercing aftercare warrant review.

Genomic markers of drug resistance in Mycobacterium tuberculosis populations with minority variants.

Minority variants of Mycobacterium tuberculosis harboring mutations conferring resistance can become dominant populations during tuberculosis (TB) treatment, leading to treatment failure. Our understanding of drug-resistant within-host subpopulations and the frequency of resistance-conferring mutations in minority variants remains limited. M. tuberculosis sequences recovered from liquid cultures of culture-confirmed TB cases notified between January 2017 and December 2021 in New South Wales, Australia were examined. Potential drug resistance-conferring minority variants were identified using LoFreq, and mixed populations of different M. tuberculosis strains (≥100 SNPs apart) were examined using QuantTB. A total of 1831 routinely sequenced M. tuberculosis strains were included in the analysis. Drug resistance-conferring minority variants were detected in 3.5% (65/1831) of sequenced cultures; 84.6% (55/65) had majority strains that were drug susceptible and 15.4% (10/65) had majority strains that were drug resistant. Minority variants with high-confidence drug resistance-conferring mutations were 1.5 times more common when the majority strains were drug resistant. Mixed M. tuberculosis strain populations were documented in 10.0% (183/1831) of specimens. Minority variants with high-confidence drug resistance-conferring mutations were more frequently detected in mixed M. tuberculosis strain populations (2.7%, 5/183) than in single strain populations (0.6%, 10/1648; P = 0.01). Drug-resistant minority variants require monitoring in settings that implement routine M. tuberculosis sequencing. The frequency with which drug-resistant minority variants are detected is likely influenced by pre-culture requirement. Culture-independent sequencing methods should provide a more accurate reflection of drug-resistant subpopulations.

Genome entropy and network centrality contrast exploration and exploitation in evolution of foodborne pathogens.

Modelling evolution of foodborne pathogens is crucial for mitigation and prevention of outbreaks. We apply network-theoretic and information-theoretic methods to trace evolutionary pathways ofSalmonellaTyphimurium in New South Wales, Australia, by studying whole genome sequencing surveillance data over a five-year period which included several outbreaks. The study derives both undirected and directed genotype networks based on genetic proximity, and relates the network's structural property (centrality) to its functional property (prevalence). The centrality-prevalence space derived for the undirected network reveals a salient exploration-exploitation distinction across the pathogens, further quantified by the normalised Shannon entropy and the Fisher information of the corresponding shell genome. This distinction is also analysed by tracing the probability density along evolutionary paths in the centrality-prevalence space. We quantify the evolutionary pathways, and show that pathogens exploring the evolutionary search-space during the considered period begin to exploit their environment (their prevalence increases resulting in outbreaks), but eventually encounter a bottleneck formed by epidemic containment measures.

SABRes: in silico detection of drug resistance conferring mutations in subpopulations of SARS-CoV-2 genomes.

The emergence of resistance to antiviral drugs increasingly used to treat SARS-CoV-2 infections has been recognised as a significant threat to COVID-19 control. In addition, some SARS-CoV-2 variants of concern appear to be intrinsically resistant to several classes of these antiviral agents. Therefore, there is a critical need for rapid recognition of clinically relevant polymorphisms in SARS-CoV-2 genomes associated with significant reduction of drug activity in virus neutralisation experiments. Here we present SABRes, a bioinformatic tool, which leverages on expanding public datasets of SARS-CoV-2 genomes and allows detection of drug resistance mutations in consensus genomes as well as in viral subpopulations. We have applied SABRes to detect resistance-conferring mutations in 25,197 genomes generated over the course of the SARS-CoV-2 pandemic in Australia and identified 299 genomes containing resistance conferring mutations to the five antiviral therapeutics that retain effectiveness against currently circulating strains of SARS-CoV-2 - Sotrovimab, Bebtelovimab, Remdesivir, Nirmatrelvir and Molnupiravir. These genomes accounted for a 1.18% prevalence of resistant isolates discovered by SABRes, including 80 genomes with resistance conferring mutations found in viral subpopulations. Timely recognition of these mutations within subpopulations is critical as these mutations can provide an advantage under selective pressure and presents an important step forward in our ability to monitor SARS-CoV-2 drug resistance.

Pneumococcal bacteraemia in adults over a 10-year period (2011-2020): a clinical and serotype analysis.

BACKGROUND: Streptococcus pneumoniae (pneumococcus) is a human nasopharyngeal tract coloniser responsible for invasive pneumococcal disease, which is largely vaccine preventable. Vaccination is recommended from birth for all, and through adulthood for those with risk conditions. AIMS: To describe the clinical and serotype analysis of pneumococcus bacteraemia over a 10-year period. METHODS: A 10-year (February 2011-December 2020) retrospective review was performed on all adult (age ≥18 years) pneumococcus bacteraemia presenting to the four public hospitals in Western Sydney, Australia. Comorbidities and risk factors were recorded. RESULTS: Three hundred unique episodes of S. pneumoniae bloodstream infection (SPBI) were identified during the study period. The median age for SPBI was 63 years with 31.7% aged 70 years or older. A 94.7% had one or more risks factors for SPBI. Pneumonia was reported in 80% of all SPBI, whereas meningitis was reported in 6% and infective endocarditis in <1%. Asplenia was noted in 2.4%. Seven- and 30-day mortality was 6.6% and 11.9%, with a higher 30-day mortality in those aged ≥70 years (24.4%). The serotype distribution showed 7-valent conjugate vaccine covered 11.0% of all isolates, whereas 13-valent conjugate vaccine (13vPCV) and a 23-valent polysaccharide vaccine (23vPPV) covered 41.7% and 69.0% respectively. Immunisation details were available for 110 individuals, of whom, only 7.3% had received pneumococcal vaccination. CONCLUSIONS: Most patients with pneumococcal bacteraemia had age- or comorbidity-related risk factors but were not vaccinated. Two-thirds of cases occurred in people aged <70 years. 13vPCV and 23vPPV covered 41.7% and 69.0% of bacteraemic isolates.

Multistate Outbreak of Salmonella enterica Serovar Heidelberg with Unidentified Source, Australia, 2018-2019.

We report a multistate Salmonella enterica serovar Heidelberg outbreak in Australia during 2018-2019. Laboratory investigation of cases reported across 5 jurisdictions over a 7-month period could not identify a source of infection but detected indicators of severity and invasiveness. The hospitalization rate of 36% suggested a moderately severe clinical picture.

Community-wide Screening for Tuberculosis in a High-Prevalence Setting.

BACKGROUND: The World Health Organization has set ambitious targets for the global elimination of tuberculosis. However, these targets will not be achieved at the current rate of progress. METHODS: We performed a cluster-randomized, controlled trial in Ca Mau Province, Vietnam, to evaluate the effectiveness of active community-wide screening, as compared with standard passive case detection alone, for reducing the prevalence of tuberculosis. Persons 15 years of age or older who resided in 60 intervention clusters (subcommunes) were screened for pulmonary tuberculosis, regardless of symptoms, annually for 3 years, beginning in 2014, by means of rapid nucleic acid amplification testing of spontaneously expectorated sputum samples. Active screening was not performed in the 60 control clusters in the first 3 years. The primary outcome, measured in the fourth year, was the prevalence of microbiologically confirmed pulmonary tuberculosis among persons 15 years of age or older. The secondary outcome was the prevalence of tuberculosis infection, as assessed by an interferon gamma release assay in the fourth year, among children born in 2012. RESULTS: In the fourth-year prevalence survey, we tested 42,150 participants in the intervention group and 41,680 participants in the control group. A total of 53 participants in the intervention group (126 per 100,000 population) and 94 participants in the control group (226 per 100,000) had pulmonary tuberculosis, as confirmed by a positive nucleic acid amplification test for Mycobacterium tuberculosis (prevalence ratio, 0.56; 95% confidence interval [CI], 0.40 to 0.78; P<0.001). The prevalence of tuberculosis infection in children born in 2012 was 3.3% in the intervention group and 2.6% in the control group (prevalence ratio, 1.29; 95% CI, 0.70 to 2.36; P = 0.42). CONCLUSIONS: Three years of community-wide screening in persons 15 years of age or older who resided in Ca Mau Province, Vietnam, resulted in a lower prevalence of pulmonary tuberculosis in the fourth year than standard passive case detection alone. (Funded by the Australian National Health and Medical Research Council; ACT3 Australian New Zealand Clinical Trials Registry number, ACTRN12614000372684.).

Genomic and transcriptomic variation in Bordetella spp. following induction of erythromycin resistance.

BACKGROUND: The emergence of macrolide resistance in Bordetella pertussis, the causative agent of pertussis, due to mutations in the 23S rRNA gene has been recently recognized. However, resistance mechanisms to macrolides in Bordetella parapertussis and Bordetella holmesii remain unknown. OBJECTIVES: This study investigated genomic changes induced by in vitro exposure to erythromycin in these three main pathogens responsible for pertussis-like disease. METHODS: A set of 10 clinical and reference strains of B. pertussis, B. parapertussis and B. holmesii was exposed to erythromycin for 15 weeks or 30 subculture passages. Antibiotic pressure was achieved by growth on the selective media with erythromycin Etest strips or impregnated discs. Genome polymorphisms and transcriptomic profiles were examined by short- and long-read sequencing of passaged isolates. RESULTS: B. parapertussis and B. holmesii isolates developed significant in vitro resistance to erythromycin (MIC >256 mg/L) within 2 to 7 weeks and at 5 to 12 weeks, respectively. B. pertussis remained phenotypically susceptible to the antibiotic following 15 weeks of exposure, with the MIC between 0.032 to 0.38 mg/L. Genomic analysis revealed that B. holmesii developed resistance due to mutations in the 23S rRNA gene. The resistance mechanism in B. parapertussis was hypothesized as being due to upregulation of an efflux pump mechanism. CONCLUSIONS: These findings indicate that both B. holmesii and B. parapertussis can be more prone to induced resistance following exposure to treatment with erythromycin than B. pertussis. The surveillance of macrolide resistance in Bordetella isolates recovered from patients with pertussis, especially persistent disease, is warranted.

Cell-based Culture Informs Infectivity and Safe De-Isolation Assessments in Patients with Coronavirus Disease 2019.

BACKGROUND: The detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA by reverse-transcription polymerase chain reaction (PCR) does not necessarily indicate shedding of infective virions. There are limited data on the correlation between the isolation of SARS-CoV-2, which likely indicates infectivity, and PCR. METHODS: A total of 195 patients with Coronavirus disease 2019 were tested (outpatients, n = 178; inpatients, n = 12; and critically unwell patients admitted to the intensive care unit [ICU] patients, n = 5). SARS-CoV-2 PCR-positive samples were cultured in Vero C1008 cells and inspected daily for cytopathic effect (CPE). SARS-CoV-2-induced CPE was confirmed by PCR of culture supernatant. Where no CPE was observed, PCR was performed on day 4 to confirm absence of virus replication. The cycle thresholds (Cts) of the day 4 PCR (Ctculture) and the PCR of the original clinical sample (Ctsample) were compared, and positive cultures were defined where Ctsample - Ctculture was ≥3. RESULTS: Of 234 samples collected, 228 (97%) were from the upper respiratory tract. SARS-CoV-2 was isolated from 56 (24%), including in 28 of 181 (15%), 19 of 42 (45%), and 9 of 11 samples (82%) collected from outpatients, inpatients, and ICU patients, respectively. All 56 samples had Ctsample ≤32; CPE was observed in 46 (20%). The mean duration from symptom onset to culture positivity was 4.5 days (range, 0-18). SARS-CoV-2 was significantly more likely to be isolated from samples collected from inpatients (P < .001) and ICU patients (P < .0001) compared with outpatients, and in samples with lower Ctsample. CONCLUSIONS: SARS-CoV-2 culture may be used as a surrogate marker for infectivity and inform de-isolation protocols.

Epidemiologic Evidence for Airborne Transmission of SARS-CoV-2 during Church Singing, Australia, 2020.

An outbreak of severe acute respiratory syndrome coronavirus 2 infection occurred among church attendees after an infectious chorister sang at multiple services. We detected 12 secondary case-patients. Video recordings of the services showed that case-patients were seated in the same section, up to 15 m from the primary case-patient, without close physical contact, suggesting airborne transmission.

SARS-CoV-2 neutralizing antibodies: Longevity, breadth, and evasion by emerging viral variants.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antibody neutralization response and its evasion by emerging viral variants and variant of concern (VOC) are unknown, but critical to understand reinfection risk and breakthrough infection following vaccination. Antibody immunoreactivity against SARS-CoV-2 antigens and Spike variants, inhibition of Spike-driven virus-cell fusion, and infectious SARS-CoV-2 neutralization were characterized in 807 serial samples from 233 reverse transcription polymerase chain reaction (RT-PCR)-confirmed Coronavirus Disease 2019 (COVID-19) individuals with detailed demographics and followed up to 7 months. A broad and sustained polyantigenic immunoreactivity against SARS-CoV-2 Spike, Membrane, and Nucleocapsid proteins, along with high viral neutralization, was associated with COVID-19 severity. A subgroup of "high responders" maintained high neutralizing responses over time, representing ideal convalescent plasma donors. Antibodies generated against SARS-CoV-2 during the first COVID-19 wave had reduced immunoreactivity and neutralization potency to emerging Spike variants and VOC. Accurate monitoring of SARS-CoV-2 antibody responses would be essential for selection of optimal responders and vaccine monitoring and design.

Inferring evolutionary pathways and directed genotype networks of foodborne pathogens.

Modelling the emergence of foodborne pathogens is a crucial step in the prediction and prevention of disease outbreaks. Unfortunately, the mechanisms that drive the evolution of such continuously adapting pathogens remain poorly understood. Here, we combine molecular genotyping with network science and Bayesian inference to infer directed genotype networks-and trace the emergence and evolutionary paths-of Salmonella Typhimurium (STM) from nine years of Australian disease surveillance data. We construct networks where nodes represent STM strains and directed edges represent evolutionary steps, presenting evidence that the structural (i.e., network-based) features are relevant to understanding the functional (i.e., fitness-based) progression of co-evolving STM strains. This is argued by showing that outbreak severity, i.e., prevalence, correlates to: (i) the network path length to the most prevalent node (r = -0.613, N = 690); and (ii) the network connected-component size (r = 0.739). Moreover, we uncover distinct exploration-exploitation pathways in the genetic space of STM, including a strong evolutionary drive through a transition region. This is examined via the 6,897 distinct evolutionary paths in the directed network, where we observe a dominant 66% of these paths decrease in network centrality, whilst increasing in prevalence. Furthermore, 72.4% of all paths originate in the transition region, with 64% of those following the dominant direction. Further, we find that the length of an evolutionary path strongly correlates to its increase in prevalence (r = 0.497). Combined, these findings indicate that longer evolutionary paths result in genetically rare and virulent strains, which mostly evolve from a single transition point. Our results not only validate our widely-applicable approach for inferring directed genotype networks from data, but also provide a unique insight into the elusive functional and structural drivers of STM bacteria.

Long-term Impact of Pneumococcal Conjugate Vaccines on Invasive Disease and Pneumonia Hospitalizations in Indigenous and Non-Indigenous Australians.

BACKGROUND: Universal pneumococcal conjugate vaccine (PCV) programs began in Indigenous Australian children in 2001 and all children in 2005, changing to 13-valent PCV (PCV13) in 2011. We used laboratory data for invasive pneumococcal disease (IPD) and coded hospitalizations for noninvasive pneumococcal community-acquired pneumonia (PnCAP) to evaluate long-term impact. METHODS: Annual incidence (per 100 000 population) was calculated for age-specific total IPD, PCV13 non-7-valent PCV (PCV7) serotypes, and PnCAP by Indigenous status. Incidence in the pre-universal PCV7 (2002-2004), early PCV7 (2005-2007), pre-PCV13 (2008 to mid-2011), and post-PCV13 (mid-2011 to 2016) periods was used to calculate incidence rate ratios (IRRs). RESULTS: In the total population, all-age incidence of IPD declined from 11.8 pre-PCV7 to 7.1 post-PCV13 (IRR, 0.61 [95% confidence interval {CI}, .59-.63]) but for PnCAP declined among ages <1 year (IRR, 0.34 [95% CI, .25-.45]) and 1-4 years (IRR, 0.50 [95% CI, .43-.57]) but increased significantly among age ≥5 years (IRRs, 1.08-1.14). In Indigenous people, baseline PCV13 non-PCV7 IPD incidence was 3-fold higher, amplified by a serotype 1 epidemic in 2011. By 2015-2016, although incidence of IPD and PnCAP in children aged <5 years decreased by 38%, neither decreased in people aged ≥5 years. CONCLUSIONS: Fifteen years post-PCV and 5 years post-PCV13, direct and indirect impact on IPD and PnCAP differed by age and between Indigenous and non-Indigenous people, with potential implications for long-term PCV impact in comparable settings.Fifteen years after pneumococcal conjugate vaccine (PCV) introduction and 5 years post-PCV13, direct and indirect impact on invasive pneumococcal disease and pneumococcal community-acquired pneumonia differed by age and between Indigenous and non-Indigenous people, with potential implications for long-term PCV impact in comparable settings.

Genomic Surveillance Enables Suitability Assessment of Salmonella Gene Targets Used for Culture-Independent Diagnostic Testing.

Salmonella is a highly diverse genus consisting of over 2,600 serovars responsible for high-burden food- and waterborne gastroenteritis worldwide. Sensitivity and specificity of PCR-based culture-independent diagnostic testing (CIDT) systems for Salmonella, which depend on a highly conserved gene target, can be affected by single nucleotide polymorphisms (SNPs), indels, and genomic rearrangements within primer and probe sequences. This report demonstrates the value of prospectively collected genomic data for verifying CIDT targets. We utilized the genomes of 3,165 Salmonella isolates prospectively collected and sequenced in Australia. The sequences of Salmonella CIDT PCR gene targets (ttrA, spaO, and invA) were systematically interrogated to measure nucleotide dissimilarity. Analysis of 52 different serovars and 79 multilocus sequencing types (MLST) demonstrated dissimilarity within and between PCR gene targets ranging between 0 and 81.3 SNP/kbp (0 and 141 SNPs). The lowest average dissimilarity was observed in the ttrA target gene used by the Roche LightMix at 2.0 SNP/kbp (range, 0 to 46.7); however, entropy across the gene demonstrates that it may not be the most stable CIDT target. While debate continues over the benefits and pitfalls of replacing bacterial culture with molecular assays, the growing volumes of genomic surveillance data enable periodic regional reassessment and validation of CIDT targets against both prevalent and emerging serovars. If PCR systems are to become the primary screening and diagnostic tool for laboratory diagnosis of salmonellosis, ongoing monitoring of the genomic diversity in PCR target regions is warranted, as is the potential inclusion of two Salmonella PCR targets in frontline diagnostic systems.

An outbreak of multidrug-resistant Salmonella Kentucky infection in long-nosed fur seals.

An outbreak of salmonellosis occurred in a group of 7 long-nosed fur seals Arctocephalus forsteri undergoing rehabilitation after being found injured and malnourished on beaches along the northern New South Wales and southern Queensland coasts of Australia. Three of the 7 individuals developed clinical disease and died within 3 d. Clinical signs included profuse diarrhea, vomiting, depression, and lethargy. Salmonella enterica subsp. enterica serovar Kentucky (S. Kentucky) was cultured from 2 of the 3 deceased animals. The other 4 animals showed similar signs and recovered following treatment. S. Kentucky (antigenic formula 8,20:i:z6) was isolated from the survivors and tissues recovered from post-mortem samples of deceased animals. The bacterium was susceptible to cephalothin and sulfamethoxazole/trimethoprim and resistant to amoxicillin-clavulanate, ampicillin/amoxicillin, tetracycline, and enrofloxacin. This organism has the potential to cause disease in aquatic wildlife, as well as posing a zoonotic threat to people who utilise the aquatic environment.

Community perspectives on the benefits and risks of technologically enhanced communicable disease surveillance systems: a report on four community juries.

BACKGROUND: Outbreaks of infectious disease cause serious and costly health and social problems. Two new technologies - pathogen whole genome sequencing (WGS) and Big Data analytics - promise to improve our capacity to detect and control outbreaks earlier, saving lives and resources. However, routinely using these technologies to capture more detailed and specific personal information could be perceived as intrusive and a threat to privacy. METHOD: Four community juries were convened in two demographically different Sydney municipalities and two regional cities in New South Wales, Australia (western Sydney, Wollongong, Tamworth, eastern Sydney) to elicit the views of well-informed community members on the acceptability and legitimacy of: making pathogen WGS and linked administrative data available for public health researchusing this information in concert with data linkage and machine learning to enhance communicable disease surveillance systems Fifty participants of diverse backgrounds, mixed genders and ages were recruited by random-digit-dialling and topic-blinded social-media advertising. Each jury was presented with balanced factual evidence supporting different expert perspectives on the potential benefits and costs of technologically enhanced public health research and communicable disease surveillance and given the opportunity to question experts. RESULTS: Almost all jurors supported data linkage and WGS on routinely collected patient isolates for the purposes of public health research, provided standard de-identification practices were applied. However, allowing this information to be operationalised as a syndromic surveillance system was highly contentious with three juries voting in favour, and one against by narrow margins. For those in favour, support depended on several conditions related to system oversight and security being met. Those against were concerned about loss of privacy and did not trust Australian governments to run secure and effective systems. CONCLUSIONS: Participants across all four events strongly supported the introduction of data linkage and pathogenomics to public health research under current research governance structures. Combining pathogen WGS with event-based data surveillance systems, however, is likely to be controversial because of a lack of public trust, even when the potential public health benefits are clear. Any suggestion of private sector involvement or commercialisation of WGS or surveillance data was unanimously rejected.

Multilevel genome typing: genomics-guided scalable resolution typing of microbial pathogens.

BackgroundBoth long- and short-term epidemiology are fundamental to disease control and require accurate bacterial typing. Genomic data resulting from implementation of whole genome sequencing in many public health laboratories can potentially provide highly sensitive and accurate descriptions of strain relatedness. Previous typing efforts using these data have mainly focussed on outbreak detection.AimWe aimed to develop multilevel genome typing (MGT), using consecutive multilocus sequence typing (MLST) schemes of increasing sizes, stepping up from seven-gene MLST to core genome MLST, to allow examination of genetic relatedness at multiple resolution levels.MethodsThe system was applied to Salmonellaenterica serovar Typhimurium. The MLST scheme used at each step (MGT level), defined a given MGT-level specific sequence type (ST). The list of STs generated from all of these increasing MGT levels, was named a genome type (GT). Using MGT, we typed 9,096 previously characterised isolates with publicly available data.ResultsOur approach could identify previously described S. Typhimurium populations, such as the DT104 multidrug resistance lineage (GT 19-2-11) and two invasive lineages of African isolates (GT 313-2-3 and 313-2-752). Further, we showed that MGT-derived clusters can accurately distinguish five outbreaks from each other and five background isolates.ConclusionMGT provides a universal and stable nomenclature at multiple resolutions for S. Typhimurium strains and could be implemented as an internationally standardised strain identification system. While established so far only for S. Typhimurium, the results here suggest that MGT could form the basis for typing systems in other similar microorganisms.