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UK's HPA and University of Oxford Adopt MiSeq for Public Health Protocol During Olympics

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Next-generation sequencing for public health surveillance could be put to the test these Olympic games. The UK's Health Protection Agency has implemented the technology as part of its public health protocol for monitoring outbreaks during the London Olympics.

In collaboration with the University of Oxford, the HPA will use the university's Illumina MiSeq to sequence pathogens responsible for any disease outbreaks that may arise during the Olympics. The agency is also looking into acquiring its own NGS system for use in public health surveillance but has not yet decided on a specific technology.

The decision to use the MiSeq for monitoring potential outbreaks follows on a proof-of-principle study by researchers at the University of Oxford who used the instrument to monitor outbreaks in a hospital setting, published in June in BMJ Open (CSN 6/20/2012).

While the likelihood of an outbreak occurring during the Olympics is not high, because there are so many people coming to London for the games, there is a "heightened state of awareness," explained Derrick Crook, professor of microbiology in the Nuffield Department of Clinical Medicine at the University of Oxford.

In the case of an outbreak, the Oxford and HPA team will use the MiSeq to sequence potential culprits such as Staphylococcus aureus, Clostridium difficile, or Escherichia coli, Crook said.

The technology was included in the protocol because, as described in the BMJ Open study, it demonstrated a much higher resolution than current methods for typing microorganisms, such as pulsed-field gel electrophoresis or multilocus sequence typing. Additionally, it has a much quicker turnaround time than those methods — days compared to weeks or months, said Crook, who was also a senior author of that study.

In a hypothetical example, such as if a number of people all staying in the same hotel developed pneumonia, "One of the things you'd like to be able to do is very rapidly type those microorganisms," said Crook. That would give information about whether the infections all came from the same source and did in fact represent an outbreak, or if they came from separate sources.

In another example, if athletes in the Olympic village came down with food poisoning, it would be important to quickly identify whether the pathogen was coming from the same source, such as a specific kitchen or food vendor, or whether it was just random chance.

Sequencing the pathogens can identify how closely related the strains are and determine whether it is a single-source outbreak, Crook said.

The MiSeq instrument being used in the project is an upgraded version, which has the ability to sequence 2x250 base reads and generate 7 gigabases of data per sequence run, said Geoff Smith, senior director of research at Illumina.

Illumina provided Oxford with the MiSeq and is also providing technical support for the instrument as well as training around its new Nextera sample-prep methods, Smith said.

The type of sequencing the HPA would use in the case of an outbreak will likely depend on the situation, said Smith. While the machine can do 2x250 reads, shorter read lengths will enable faster turnaround times. For instance, a 75-base run would essentially allow the team to obtain a result overnight, he said.

Crook said the HPA is now going through the process of obtaining its own NGS system for public health purposes, which involves a bidding process to "give all competitors a fair chance." He said that would likely be completed by the end of the year.

"I can foresee by this time next year, sequencing will be in use in many centers around the world for typing microorganisms for public health," he said.

Crook is also a member of the Modernizing Medical Microbiology Consortium, a research project funded by the UK Department of Health that includes the University of Oxford, the HPA, and the Wellcome Trust Sanger Institute.

The consortium recently received a four-year grant to conduct research toward implementing sequencing in the public health setting, Crook said. As part of this effort, the researchers plan to develop "the sample pathways, methodologies, and software" necessary for routine use of sequencing in this setting, as well as protocols for "managing large-scale typing projects for implementation in the HPA and National Health Service hospitals," he said.

All the consortium's work is currently being done on the Illumina platform but Crook said that the protocols it is developing will be platform independent — a necessary feature given that the technology is advancing so rapidly.

"Illumina themselves may develop other technologies that will overtake the current technologies," Crook said. Additionally, "we know that there are startups such as Oxford Nanopore that have a completely different approach."

"There is no way it makes sense for researchers like ourselves trying to develop approaches that will be effective in the long term to be tied to a single technology, a single chemistry," he added. "We have to be as platform agnostic as we can."

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