‘Are you sure Hank done it this way’ Whole genome sequencing and better global foodborne disease surveillance

In 1993, I thought the consummation of Hollywood and Nashville was complete when starlet Julia Roberts wed country music’s ugly duckling, Lyle Lovett.

They divorced less than two years later.

As the NHL Stanley Cup playoffs progressed, the last-seeded Nashville Predators demolished foe-after-foe, with star couple captain Mike Fischer and partner Carrie Underwood paving the way for another coupling of the weirdness and greatness that is America: Nashville and Smashville.

But I don’t think that Hank do it like that.

It didn’t happen, as Nashville finally lost to Pittsburgh in 6-games to close out a grueling National Hockey League season.

I write this while watching Sorenne and Amy on the ice, taking extra skating lessons, in the sub-tropics of Brisbane, as likely a hockey hotspot as Nashville.

Amy is happy Pittsburgh won because, she hates country music.

But baby … Lyle isn’t country, he’s something different.

I’ve been to Nashville several times, hung out on Music Row, hung out a Titans tailgate, and saw Lyle Lovett one night and John Prine the next at the Ryman Auditorium, The Mother Church of Country Music.

Now that my Nashville Predators have lost the Stanley Cup in a valiant, country-heartbreak ballad to Pittsburgh, I return to the more mundane mattes of foodborne illness.

PulseNet International advocates for public health institutes and laboratories around the world to move together towards the use of whole genome sequencing (WGS) to improve detection of and response to foodborne illnesses and outbreaks in the latest edition of Eurosurveillance.

This will save lives and money due to the superior ability of WGS to link human cases with contaminated food sources.

PulseNet International is a global network of public health laboratory networks, dedicated to bacterial foodborne disease surveillance. The network is comprised of the national and regional laboratory networks of USA, Canada, Latin America and the Caribbean, Europe, Africa, the Middle-East and Asia Pacific.

The European Centre for Disease Prevention and Control (ECDC) manages the EU/EEA food- and waterborne diseases and zoonoses network of public health institutes and laboratories, which work to ensure comparability of data and further ties to the global health community.

Mike Catchpole, Chief Scientist at ECDC says, “it is important for all partners worldwide to continue to work together towards the implementation and standardised analysis of whole genome sequencing.”

The article also states that a global standard method for primary sequence data analysis based on whole genome Multiple Locus Sequence Typing (wgMLST) and derived public nomenclature will be adopted.

This will facilitate the sharing of information within regional and global public health laboratory networks, increasing efficiency and enabling data to be compared across countries in real-time which is currently not the case. This is especially important due to international travel and trade.

Common steps for validation studies, development of standardised protocols, quality assurance programmes and nomenclature have been agreed.

Pulsenet international: Vision for the implementation of whole genome sequencing (WGS) for global food-borne disease surveillance

Eurosurveillance, vol. 22, issue, 23, 08 June 2017, C Nadon , I Van Walle, P Gerner-Smidt, J Campos, Chinen, J Concepcion-Acevedo, B Gilpin, AM Smith, KM Kam, E Perez, E Trees, K Kubota, J Takkinen, EM Nielsen, H Carleton, FWD-NEXT Expert Panel, DOI: http://dx.doi.org/10.2807/1560-7917.ES.2017.22.23.30544

http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=22807

PulseNet International is a global network dedicated to laboratory-based surveillance for food-borne diseases. The network comprises the national and regional laboratory networks of Africa, Asia Pacific, Canada, Europe, Latin America and the Caribbean, the Middle East, and the United States. The PulseNet International vision is the standardised use of whole genome sequencing (WGS) to identify and subtype food-borne bacterial pathogens worldwide, replacing traditional methods to strengthen preparedness and response, reduce global social and economic disease burden, and save lives. To meet the needs of real-time surveillance, the PulseNet International network will standardise subtyping via WGS using whole genome multilocus sequence typing (wgMLST), which delivers sufficiently high resolution and epidemiological concordance, plus unambiguous nomenclature for the purposes of surveillance. Standardised protocols, validation studies, quality control programmes, database and nomenclature development, and training should support the implementation and decentralisation of WGS. Ideally, WGS data collected for surveillance purposes should be publicly available, in real time where possible, respecting data protection policies. WGS data are suitable for surveillance and outbreak purposes and for answering scientific questions pertaining to source attribution, antimicrobial resistance, transmission patterns, and virulence, which will further enable the protection and improvement of public health with respect to food-borne disease.

 

Whole genome sequencing (WGS) for food-borne pathogen surveillance and control- Taking the pulse

Eurosurveillance, vol 22, issue 23, 08 June 2017, J Moran-Gilad, DOI: http://dx.doi.org/10.2807/1560-7917.ES.2017.22.23.30547

http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=22811

Next-generation sequencing (NGS) is transforming microbiology [1]. With the increased accessibility and decrease in the costs of sequencing and the optimisation of the ‘wet laboratory’ components of NGS i.e. the quality and throughput of DNA extraction, library preparation and sequencing reactions, whole genome sequencing (WGS) of bacterial isolates is rapidly revolutionising clinical and public health microbiology. WGS is a ‘disruptive technology’ that has the potential to become a one-stop-shop for routine bacterial analysis. By replacing multiple parallel steps in the microbiology diagnostic cycle, which currently involves traditional and molecular methods, it achieves accurate and speedy species identification, inference of antimicrobial susceptibility and virulence and high-resolution subtyping [2].

Typing of food-borne pathogens was one of the earliest applications of WGS [3] and proof-of-concept has been demonstrated for the superiority of WGS over traditional typing methods such as pulsed-field gel electrophoresis (PFGE), multilocus variable-number tandem repeat analysis (MLVA) and multilocus sequence typing (MLST), for a range of high priority food-borne pathogens, including Salmonella enterica, Listeria monocytogenes, Campylobacter species and Shiga-toxin producing Escherichia coli [4]. Applications of WGS include the investigation of food-related outbreaks and surveillance to delineate the local, regional and global genomic epidemiology of pathogens and to attribute the infection source. WGS thus supports risk assessment and guides interventions for prevention and control of infections.

A growing number of (public health microbiology) laboratories and governmental agencies employ WGS in their routine practice and food-borne pathogen surveillance and even more are expected to enter this field in the near future. Thus the maturation of food-borne pathogen surveillance into the WGS era is very timely.

In order for WGS to be adopted as the new gold standard for tracking of food-borne pathogens, a key element of food-borne disease control, there is a need for robust, standardised, portable and scalable methods for analysing WGS data. However, the notable diversity of bioinformatics tools and approaches used for bacterial WGS to date, as evident from a recent survey by the Global Microbial Identifier project [5], creates a tremendous challenge for harmonising surveillance and investigation of food-borne illness, especially across geographical borders and different sectors. Calling variants based on analysis of single nt polymorphisms (SNPs) as it is being done in many food-borne outbreak investigations, offers maximal resolution and discriminatory power but is very difficult to standardise. Therefore, approaches based on gene-by-gene analyses, collectively referred to as ‘extended MLST’, such as core genome (cg) or whole genome (wg)MLST may be advantageous [6], and have been advocated in other public health settings, such as Legionnaires’ disease control [7].

PulseNet was established in the United States (US) more than 20 years ago as a laboratory network for molecular epidemiology based on standardised PFGE analysis and later expanded globally. PulseNet has been successful in engaging many players in the field of food safety on a global scale and in creating a platform for data sharing and comparison of clinical, veterinary and food isolates in over 80 countries and it has a proven track-record in supporting molecular surveillance [8]. Nevertheless, some issues remained unresolved such as creation and implementation of a global nomenclature, which is important for communicating molecular epidemiology results, both scientifically as well as operationally.

In this issue of Eurosurveillance, an article by Nadon et al. [9] describes the next generation of PulseNet International, which is evolving into harnessing WGS. This initiative represents a wide collaboration between many leading agencies and stakeholders in this area, including the US Centers for Disease Control and Prevention (CDC), the European Centre for Disease Prevention and Control (ECDC) and the Public Health Agency Canada (PHAC), just to name a few. The authors illustrate the technical and practical aspects of adapting the network. Notably, PulseNet International has chosen an extended MLST approach, specifically, wgMLST, as its default phylogenetic analysis tool, which should underpin a standardised and efficient nomenclature-based system. Different technical and practical aspects are reviewed and discussed, mainly focusing on information technology (IT) and bioinformatics aspects (data storage, computing power, nomenclature, data sharing), methods for validation and quality control/quality assurance. Nadon et al. highlight complexities surrounding the implementation of WGS for food-borne disease surveillance, with respect to readiness at individual country and regional levels and delineate how PulseNet plans to address these.

The evolution of PulseNet International is very encouraging and will reinforce the use of NGS in the area of food safety. That said, challenges remain that need to be addressed by the public health community. There is a need for user-friendly bioinformatics solutions that will enable automated analysis of bacterial genomes by non-experts in bioinformatics to extract valuable information in a time-efficient manner. Such solutions should offer as much backwards compatibility as possible with current typing methods since the global transition to WGS is expected to be gradual. It should also offer an efficient strain/allele nomenclature that facilitates inter-laboratory work. Moreover, bioinformatics solutions should also factor in the developments in the field of DNA sequencing, particularly long-read single molecule sequencing platforms and portable sequencing devices which are increasingly being used. While WGS of food-borne pathogens has now become the new gold standard for food-borne pathogen typing, other techniques such as strain typing and characterisation using proteomics (particularly matrix-assisted laser desorption/ionisation (MALDI) time-of-flight (TOF) mass spectroscopy) or DNA arrays are rapidly evolving and should be carefully evaluated [10]. The field of metagenomics is also rapidly advancing and culture-independent microbiology, enabling genomic analysis of pathogens directly from sequenced clinical or environmental samples (as opposed to cultured isolates), is just around the corner [11]. When laying the foundations for global food pathogen surveillance networks for the coming years, we need to be mindful of such future developments.

Different from current protocols in which only typing results are shared, the transition to genome-based surveillance inevitably involves the sharing of complete sequence data. This has many implications, not only with respect to data storage, analysis and sharing infrastructures, but also aspects such as data ownership, privacy and transparency, pertaining to both genomic sequences and the related metadata. These issues should be proactively addressed in order to provide reassurance concerning data protection and create flexible solutions that will facilitate the timely sharing of public health data by as many partners as possible.

Finally, the transition to WGS-based surveillance needs to ensure sufficient quality is maintained in order to meet national and international regulatory requirements. Nadon et al. rightfully emphasise in their paper, the importance of validation, quality control and standardisation. One major aspect in making this transition and that needs to be considered is the human factor. The successful implementation of WGS-based surveillance on a global scale requires careful planning, building of capacity and training of public health and microbiology personnel to develop local readiness, especially in limited resource settings. Care should be taken to address the ‘softer’ issues, including possible cultural, political and cross-sector barriers, which together with economical, management and operational aspects could greatly influence the successful implementation of WGS.

This is a fascinating time for public health microbiology, and initiatives such as the integration of WGS as proposed by PulseNet International, are central for leveraging recent technological advancements for the benefit of public health surveillance.

 

20 years of PulseNet: The national molecular subtyping network for foodborne disease surveillance

The U.S. Centers for Disease Control reports PulseNet is celebrating 20 years of public health achievements in transforming the way foodborne disease outbreaks are detected and investigated.

pulse-net-20-200PulseNet is a national surveillance network of federal, state, and local public health laboratories that work together to detect foodborne disease outbreaks by connecting DNA fingerprints of bacteria that cause illness. The network facilitates the early identification of common sources of foodborne outbreaks and helps regulatory agencies identify areas where implementation of new measures are likely to improve the safety of the food supply.

A recent economic evaluation of PulseNet activities suggests that the network prevents at least 270,000 illnesses from infection with Salmonella, E. coli, and Listeria and saves an estimated $500 million each year. In 2013, PulseNet began using whole genome sequencing (WGS) to detect outbreaks caused by Listeria, the most deadly foodborne pathogen. PulseNet is quickly expanding the use of WGS in state laboratories and has begun using WGS in investigations of other foodborne pathogens such as Campylobacter, E. coli, and Salmonella. With incorporation of WGS and other advanced molecular detection methods, PulseNet will continue to improve foodborne disease detection and identify outbreaks faster and with more accuracy.

Additional information regarding CDC’s Advanced Molecular Detection initiative is available at http://www.cdc.gov/amd/. Additional materials on the 20th anniversary of PulseNet, including success stories from state public health laboratories and fact sheets are available at the CDC PulseNet website.

Pulsenet prevents 276,000 foodborne illnesses a year

An elderly woman in Phoenix. A Toledo toddler. An accountant in Indianapolis. All poisoned by food. Quickly uncovering that their illnesses are connected can make all the difference in halting a deadly
outbreak.

pulsenet-lab-network-575pxAbout 276,000 cases of foodborne illness are avoided each year because of PulseNet, a 20-year-old network coordinated by the Centers for Disease Control and Prevention, new research has found. PulseNet links U.S. public health laboratories so that they can speedily share details about E. coli, Salmonella and other bacterial illnesses.

The averted illnesses translate to $507 million in annual savings on medical bills and lost productivity, according to a study led by Robert L. Scharff of The Ohio State University and Craig Hedberg of the University of Minnesota.

PulseNet has created a climate that encourages better business practices and swift response to trouble, Scharff said, and that likely explains most of the avoided illnesses in the study.

In the face of public scrutiny, lawsuits and lost revenue, businesses have responded with better self-policing, he said.

“Companies are saying, ‘We can’t have this risk. This risk is too big for us,'” said Scharff, an associate professor of consumer sciences.

“What’s exciting for me is this shows the power of information in the market to force change on industry. It’s not just a way of tracking illness, but of allowing markets to work better.”

Scharff worked with experts from the CDC and elsewhere to assign a value to PulseNet, both in terms of illnesses prevented and dollars saved. The team analyzed data from 1994 to 2009.

The results, published in conjunction with PulseNet’s 20th anniversary, appear in the American Journal of Preventive Medicine.

pulsenetPulseNet’s annual price tag is $7.3 million, according to the analysis. The network includes 83 state and federal laboratories where microbiologists uncover DNA fingerprints of illness-causing bacteria that tie cases together and confirm outbreaks.

“If more agencies used information as a tool instead of trying to fight the markets, I think we would all be better off,” said Scharff, also an economist who is part of Ohio State’s Food Innovation Center.

Tainted food is responsible for about 48 million illnesses, 128,000 hospitalizations and 3,000 deaths in the United States each year.

PulseNet’s purpose is to use DNA fingerprinting techniques to link illnesses that are likely to have a shared cause, even if the cases are widely dispersed. Food moves far and wide in the modern world and the first clues of an outbreak aren’t always clustered geographically.

Until now, health officials have not been able to assign a value to the service.

“PulseNet has been very impactful. We’ve known this for many years, but it’s been anecdotal. This gives us some hard figures,” said John Besser, deputy chief of the CDC’s enteric diseases laboratory branch.

PulseNet identifies about 1,750 clusters of disease a year, including nearly 250 that span multiple states.

“PulseNet is an integral part of our food-safety system and it helps improve the quality and safety of all the food that we eat,” said Besser, who formerly worked with PulseNet in Minnesota, one of the first states to embrace the program.

“Part of that effect is containing outbreaks, but a really significant portion of the benefit is giving feedback to the food industry and the regulatory agencies so they can make food safer,” he said.

Besser said he’s hopeful the federal government will be able to sustain PulseNet as changes in laboratory testing methods evolve. Placing a value on the service should help, he said.

To participate in PulseNet, state, county and city labs evaluate samples from people sickened by food and look for the DNA fingerprint of the bacteria, molecular subtyping that goes deeper than simply naming the responsible pathogen.

genetic-pfge-329pxSalmonella cases, for example, arise all the time. And most are sporadic, meaning the strain of bacteria in one person’s stool sample isn’t likely to match the strain in the sample across town, or across the country. When they do match, there could be big trouble.

Scharff and his colleagues found that in states that put more DNA data into the system, the chance of future illnesses declined significantly.

Their work focused on E. coli, Listeria and Salmonella – the bacteria that have been analyzed by the network the longest. The team used two models. One was designed to capture indirect effects of PulseNet – the food contamination that never happened because the network exists.

This was possible because states have adopted PulseNet to differing degrees and at different times, opening the door for a calculation based on how rates of illness differ by PulseNet participation level.

“The more that a state uploads into the system, the lower reported illnesses will be,” Scharff said.

The second model estimated the direct effects of product recalls when outbreaks arise and are linked to a specific food. Faster identification of outbreaks, resulting in more timely recalls, led to 16,994 fewer Salmonella cases and 2,819 fewer E. coli cases a year at a savings of $37 million, the study found.

Though the study provides estimates of illness reduction, it’s unclear how many illnesses are being prevented because of improvements in fields, factories and slaughterhouses or how many are avoided due to better-informed government and consumer actions.

It is also impossible to know about spillover effects – reductions in foodborne illnesses from pathogens not included in this analysis.

“The calculations probably underestimate the impact of PulseNet,” Scharff said. “We did not examine whether illnesses from pathogens outside of the three in question were reduced as a result of industry efforts, though they likely were.”

The economic model also may not fully include all of the costs.

“We used a very conservative economic method of measuring health costs,” he said. The study did not assign a dollar value to losses from premature death and reduced quality of life, a number that could be quite large, the researchers wrote.

On the other side, “we aren’t able to estimate the cost to industry from remedial actions,” he said. “These could be significant for affected companies, but are lower than the costs of having foodborne illnesses associated with their products.”

Will next disease detection system be faster, cheaper?

Those who monitor disease detection policy note that it’s cheaper and faster to move away from a system that relies heavily on the time-consuming growth in the lab of cultures of disease-causing bugs.

But moving to “advanced molecular detection” technology to reap those advantages could bureaucratcreate new problems if the transition isn’t managed properly, experts say.

Roll Call reports that the PulseNet system of labs for tracking foodborne illness relies on cultures to make a diagnosis rather than the culture-free approach AMD allows. That may make it important to move to the new system now, while the nation still has that PulseNet capability as a backup.

That would also retain scientists’ ability to identify certain strains of diseases and the power to trace foodborne outbreaks back to their source. 

From 8 to 1: US shutdown hampers foodborne illness tracking

The U.S. government shutdown is, according to NPR, pushing the nation’s food safety system to its limits.

There is normally a team of eight people overseeing Pulsenet, the critical foodborne illness tracking database. Centers for Disease Control Director Tom Frieden said pulsenetpost-shutdown, there’s only one. Some research and reference labs have gone from a staff of 80 to 2, and staff at the 20 quarantine stations dotted along the country’s borders and ports has been reduced by 85 percent.

The CDC is currently monitoring about 30 clusters of foodborne illnesses around the country, which is typical at any given time. About half the CDC staffers involved in surveillance and outbreak response have also been furloughed.