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Genetic detective helps investigate food poisoning

ATLANTA – In the investigation of the ongoing food poisoning outbreak in conjunction with romaine lettuce which is revolutionizing the detection of food-borne germs, disease-hunters are using genetic sequencing.

Genetic analysis is used to support investigations and, in some cases, to link the dots between seemingly unrelated diseases. It also uncovers previously unfathomable sources of food poisoning, including a outbreak of caramel-dipped apples .

So far, most of the work has focused mainly on one germ, Listeria. But it is expanding. By the end of this year, laboratories in all 50 states are expected to use gene sequencing for much more common causes of food poisoning outbreaks, including Salmonella and EE coli bacteria associated with recent lettuce outbreaks .

This means that the number of identifiable outbreaks will likely explode, even if the number of diseases does not.

"There are many outbreaks where they do not occur. Now they are connected," said Michael Doyle, a retired professor at the University of Georgia who is a food poisoning expert.

Not only that, the new DNA tests allow detectives to find food contamination before anyone perceives a resulting human disease – the equivalent of starting a murder investigation by first finding a weapon and then someone with one Gunshot seeks.

"It's about how outbreaks are found out," said Bill Marler, a prominent lawyer from Seattle, who has set herself the task of knocking out companies whose products make people sick.

Marler added that the program is at an early stage and it is too early to call it a success. But he said the new approach has the potential to transform how and when outbursts come to light.

Centers for Disease Control and Prevention drive the program forward. It estimates that 48 million Americans suffer from food poisoning every year – and 3,000 die.

The new technique relies on sequencing the entire genome, which has been used in biology for more than two decades. The laboratory process determines almost the entire DNA of an organism, the genetic material needed to build and maintain an organism. And scientists use software to compare the DNA of samples to see if they are the same strains and how resistant they are to topical drugs.

The technology makes analysis faster, cheaper, and more automated, Dr. Robert Tauxe, one of the leading experts of the CDC for food poisoning.

It is planned to use the technology against several germs that cause food poisoning, but so far all the work has been focused on Listeria. The bacteria cause about 1,600 diseases a year, a tiny fraction of the diagnosis of foodborne diseases in the US. But it is a particularly deadly infection that kills almost every fifth person who gets it.

Historically, Listeria-induced outbreaks were known as "the cemetery of epidemiology". It could take weeks for people to develop symptoms, meaning that food evidence was discarded – and some of the patients were dead – when officials began to clarify things.

From 1983 to 1997, only five Listeria in the region were identified United States. They were obvious and large – with a median of 54 cases per outbreak.

It was the same with other food poisoning outbreaks.

"Most food-borne outbreaks were discovered because it happened in one place," as in a city where the customers of a popular restaurant got sick, Tauxe said.

Outbreaks were investigated by asking people what they ate before they got sick, and then comparing comments to see what patients had in common.

The field took a big step in the 1990s, after a frightening eruption erupted in the Seattle area. Four deaths and more than 700 diseases in four states were eventually attributed to insufficiently E. coli-contaminated hamburgers in the restaurant "Jack in the Box".

The outbreak prompted the CDC to develop a program based on pulsed gel electrophoresis in which researchers could view the DNA of a seed in lumps. It helped health officials to link diseases more easily, but it was imperfect: it could not make exact matches and was sometimes overlooked when cases were related.

Then came the full genome sequencing.

The CDC began using the technique in food poisoning investigations in 2013. Initially, test labs sent samples to a CDC lab in Atlanta for testing. Now, the CDC is working to get labs running in all 50 states.

Last year, the federal agency awarded approximately $ 32 million to state and city health departments working on food, water and fungal diseases. This included $ 12 million to help them build genome sequencing technology.

Since the entire genome sequencing began, the CDC says it detects more Listeria outbreaks with an identified food source. By this measure, the number increased from about two per year to an average of more than six per year from 2014 to 2016.

One of the first success stories came a few weeks after Halloween in 2014, when Listeria cases began to pop in Arizona, New Mexico and the Midwest. Through full genome sequencing, the researchers found that about three dozen people were ill.

In interviews, patients and their families did not mention foods commonly associated with Listeria. But most said they had eaten packaged caramel apples.

Scientists did not consider them a threat, as apples and caramel are not individually suitable for Listeria. But it turns out that plugging a stick into a caramel-covered apple germ opens the door into tiny spaces between caramel and apple skin.

In addition to staining food that was previously considered non-threatening, genome sequencing has the potential to redirect research: in recent outbreaks of recent lately, germs found in food inspections have led to product recalls before any of them knew an outbreak. Then genome sequencing helped to find and confirm diseases.

In 2015, state officials in South Carolina and Texas found listeria in tests of Blue Bell ice cream products . The researchers used pulsed-field gel electrophoresis to find 11 diseases with a similar genetic pattern, but complete genome sequencing was definitely linked to 10, which made them look unrelated. Some of the diseases had already occurred in 2010.

"They take up cases that are five years old, that's revolutionary," Doyle said.

Sequencing the entire genome is becoming increasingly important, but it is not the basis for the solution to the outbreak. It was used in the recent study of E. coli bacteria found in romaine lettuce grown in Arizona, which has sickened at least 84 people in 19 states, according to a CDC update will be released on Wednesday. But "that's not how we discovered the outbreak for the first time," says Matthew Wise, a CDC food poisoning investigator.

It was more important last year to investigate a 21st-stage salmonella outbreak that was ultimately associated with ground beef. Sequencing the entire genome allowed health authorities to go through a wave of cases to analyze the most closely related diseases and then search for a common origin, Wise said.

"With our previous technology," said Wise, "we would have been really difficult to solve this."

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