Norovirus: The perfect pathogen

This year alone, norovirus has sickened burrito lovers at a Virginia Chipotle, cruisers traveling the South Pacific, and thousands of California schoolchildren, among others. And that’s fairly typical for this sturdy virus. Norovirus causes “stomach flu” in about 20 million Americans every year, and kills up to 800. Chances are you’ve had it, and you’ll probably get it again; it’s responsible for 58 percent of food-borne illness in the United States, according to the Centers for Disease Control. Globally, norovirus is among the leading causes of food-borne disease and deaths. The sheer number affected, and particular risk to the young and the old, make norovirus a big deal.

Yet scientists know comparatively little about what some call the “perfect pathogen.” An RNA virus, norovirus is highly infectious and easy to pass around, but much less likely to be lethal than viruses such as influenza, which kills thousands of Americans each year. It can lie in wait on tabletops or toilet seats for weeks or longer. Although soap and running water can wash the virus down the drain, it’s hard to destroy with disinfectants.

Vaccines are under development, but that’s tricky because noroviruses are a diverse, constantly changing group. That makes it hard for the human immune system to recognize and combat them.

Another major challenge has been that until recently, scientists were unable to grow it in the lab, limiting their efforts to study it.

Symptoms and treatment

Within a day or two of exposure to norovirus, people may experience inflammation in the lining of the gut, causing vomiting and diarrhea, nausea and abdominal pain, fever and flu-like discomfort or muscle aches.

It’s generally a mild illness, and people get better within a few days; some have no symptoms at all. But norovirus can be serious in babies, older people and those with other conditions.

There is no cure for norovirus, and infected people risk dehydration thanks to all that vomiting and diarrhea. So it’s important to drink liquids; in severe cases, physicians can provide intravenous fluids.

History

Norovirus has been known to medicine since at least 1929, when a pediatrician described “winter vomiting disease.” In 1968, an outbreak at an elementary school in Norwalk, Ohio, was tentatively linked to a virus, christened the “Norwalk virus.” Scientists began more detailed studies of the virus’s genes and proteins in the 1990s, and eventually determined Norwalk was one of a group of related human viruses — now known to be 150 or more in number and renamed “noroviruses” — that all cause similar symptoms.

As scientists came to understand norovirus better, it gained the “perfect pathogen” nickname. What makes it so spectacular? Infected people produce a lot of the virus, but it may take as few as 20 individual virus particles to make someone sick, a pretty low number compared with other viruses. And that handful of virus particles will wait happily in the environment, for weeks or longer, even resisting most active ingredients in cleaning products.

A person who feels better after a few days may still be shedding virus for many more, so they can spread it to others. Moreover, the various noroviruses are diverse, so even if your immune system learns to fight off one, it’ll be helpless against the others. And immunity doesn’t seem to last long. Norovirus’s only fault as a virus: It can’t replicate unless it’s inside a person, so it can’t make more virus when on your doorknobs or in your entrée.

Norovirus’s toll

The CDC estimates that in the United States, those who live to be 79 years old have probably had norovirus about five times. One in 5,000 to 7,000 people will die of the virus before reaching that age. And every year, the virus costs the U.S. economy about $2 billion in healthcare costs and lost worker productivity. Globally, the figure is estimated to add up to nearly $65 billion.

Transmission

Norovirus usually moves from person to person. Virus from vomitus or feces can get on someone’s hands and be transmitted to another who touches them. If it gets in the air, the virus can land in another person’s mouth and infect them that way.

Contaminated food is a common transmission route, usually if food workers don’t wash their hands well. An infected person might touch a surface or object, like a doorknob, and leave behind virus that can be picked up by the next person to touch it.

Water can also be contaminated with norovirus; this happens more often in the developing world than in developed nations, according to norovirus researcher Lee-Ann Jaykus of North Carolina State University in Raleigh. Though there are scores of strains of norovirus, the most outbreaks are caused by the GII.4 strain. (Data on transmission of GII genotype norovirus shown below).

Vomiting Larry

Catherine Makison Booth, at the Health and Safety Laboratory in Harpur Hill, UK, wanted to know how far norovirus particles could travel on the force of projectile vomiting – the kind that comes on suddenly. She built a machine, dubbed “Vomiting Larry.” It hurled fluorescent water so Makison Booth could measure how far the splatter went.

She found that vomit can fly more than 3 meters or up to 10 feet. Such data are important for understanding how much cleanup is required after a virus-spiked projectile vomiting incident. Makison Booth recommended disinfecting an area of at least 84 square feet.

NoroCORE

Norovirus is the leading cause of food-borne illness in the United States, where dozens to hundreds of outbreaks (both food-borne and non-food-borne) occur every month. It’s also the most common cause of gastroenteritis worldwide.

In an effort to combat this, the U.S. Department of Agriculture funded NoroCORE, a seven-year, $25-million effort, spread across more than a dozen institutions, to combat and study food-borne norovirus and hepatitis A.

Started in 2011, NoroCORE produced guidelines and resources for food producers, restaurants and senior-care facilities. Scientists banded together to share resources and made several new discoveries. For example, NoroCORE collaborators proved that enough of the virus to infect someone can be aerosolized during vomiting, reaffirming the importance of cleaning a wide area after a vomit incident.

They also tested various potential ways to kill the virus. Hand-washing is the gold standard for preventing the spread of norovirus, but it doesn’t kill the virus. Instead the friction of running water, helped by soap’s surfactant abilities, lifts viral particles up and away.

But what about cleaning surfaces? Alcohol can kill some strains, but not all, researchers found. Bleach is best — the CDC recommends 1,000 to 5,000 parts per million, which should kill the virus, but is well above the 200 ppm commonly used in food prep areas. That much bleach is unpleasant, and can damage fabrics and other materials. Unfortunately, no common household cleaner will fully eliminate norovirus from a surface, says Jaykus, who heads NoroCORE.

NoroCORE researchers also found that copper surfaces, which are antimicrobial, can destroy norovirus, suggesting that by incorporating copper in commonly touched surfaces such as doorknobs and bedrails, hospitals and other locations could reduce transmission.

An obstacle overcome

Scientists have been trying — and failing — to grow norovirus in the lab for more than 40 years. They had to make do studying similar viruses, or infecting nonhuman animals such as chimpanzees. Or they could recruit human volunteers to undergo norovirus infection for a study.

In August of 2016, researchers were thrilled to learn that a lab at Baylor College of Medicine in Houston, led by Mary Estes and part of the NoroCORE effort, managed to grow norovirus in human cells.

The keys to their success were using unmodified gut cells direct from human biopsies, and adding bile, a liver secretion that aids in digesting. Within three days of adding norovirus to the cultures, the scientists observed a 10,000-fold to 100,000-fold increase in the virus’s genetic material, indicating it was replicating itself. Now, Estes and her colleagues are studying how bile components make the cells vulnerable to infection.

Estes’s group is also training others to use their system, and scientists expect it will be useful both to study the basic biology of norovirus infection and to check how well medicines or disinfectants deactivate the virus’s ability to infect gut cells.