Jan. 15, 2003

Comments, Suggestions?

Norwalk Virus: At sea and at home

By Ruth SoRelle, MPH

Calicivirus (NV) 7.6 kb ss (+) RNA 1 major structural protein

Outbreaks of gastroenteritis; foodborne and waterborne disease. 23 million cases/US annually (Image courtesy of Estes lab)

In 1968, more than half the students and teachers at an elementary school in Norwalk, Ohio, developed a stomach illness that involved nausea and vomiting. When they went home, 32 percent of the people who lived with them also became ill. This disease called “winter vomiting” occurred frequently across the United States.

The cause of their distress was not identified until 1972, when Albert Z. Kapikian, MD, now with the National Institute of Allergy and Infectious Diseases, discovered a 27-nanometer virus-like particle in an infectious stool filtrate from that Norwalk, Ohio, outbreak. The virus was named Norwalk, making the Ohio town of 16,000 famous worldwide. The federal Centers for Disease Control and Prevention estimate that as many as 23 million people in the United States become ill from the virus or its cousins each year. Most recently, the virus has hit the cruise ship industry hard, with large numbers of people reported as ill on more than four ships sailing out of Florida ports within a month.

Little information was available about Norwalk virus and less could be done until 1990 when its genome was cloned in the laboratory of Mary Estes, PhD, a professor in the department of molecular virology and microbiology at Baylor College of Medicine.

Mary Estes, PhD

“That opened up a molecular era,” said Estes. “It made a big difference.”

In addition to new ways to diagnose the disease, this information also gave researchers information they needed to understand the natural history of the disease. Estes and members of her laboratory have even developed a vaccine that is beginning human testing.

Norwalk virus is a member of the calicivirus group, so named because of the cup-like structures found on its surface. It is a small virus consisting of a coat made of a single protein that surrounds a single strand of RNA – the virus’s genetic material.

The virus itself is difficult to study. It does not cause illness in animals and it cannot be grown in cell culture. It is very stable and fairly resistant to chlorine, the sterilizing ingredient in bleach, which is used to clean areas affected by a Norwalk outbreak.

“Knowing the virus structure is important,” said Estes. “It can help you make a better vaccine. From a basic science point of view, the more we understand what keeps a particle together, the closer we are to fighting it effectively.” She and B. V. Venkataram Prasad, PhD, an associate professor of biochemistry and molecular biology as well as molecular virology and microbiology, have worked together to elucidate the structure of Norwalk virus.

For example, she said, “We attempt to detect its genome or protein coat. We are making better tests. People using these are finding out how important these viruses are,” said Estes.

It takes only a few viruses per spoonful to confer infection and illness. Often it is passed by people involved in food preparation who have been sick and do not wear gloves or do a good job of hand washing. Other people who have recovered from the disease or who are infected but not sick can also transmit the virus.

New information about the virus and its spread could shed new light on the cruise ship phenomenon as well as on other outbreaks of gastroenteritis in hospitals and nursing homes in the United Kingdom and Britain. For example, said Estes, there is now evidence that people may be short-term carriers of the virus after they recover from the illness and that there are people infected with the virus who have no symptoms at all.

“If they get sick, we have found that the virus can be excreted for two weeks after they have recovered,” said Estes. “Think of a food handler who is sick for two days and then comes back to work. He or she doesn’t think about shedding virus or being infectious.” Because the virus is spread by the fecal-oral route, any breakdown in hand-washing practice can pass the virus on to other people.

“Individuals who may be shedding the virus but unaware that they have the infection are an important component of how the virus gets spread around,” she said.

“It has changed our thinking about how this is transmitted,” she said.

Norwalk virus can cause fatal infections in the elderly, said Estes, and it affects children as well as adults. While rotavirus is still the most common cause of life-threatening viral diarrheal disease worldwide, Norwalk virus has been identified in investigation of disease among children as well.

“We now appreciate how big the problem is,” she said. “Many people are frail and this infection can push them over the edge.”

“It’s the number one cause of food-borne disease that is not caused by bacteria,” said Estes.

When an outbreak of stomach ailments hit students at Sam Houston State University in Huntsville, Tex., a few years ago, Estes and Robert Atmar, MD, an associate professor of medicine who specializes in infectious disease, helped in the investigation. Again, it was Norwalk virus.

“It was the first time we had developed methods that allowed us to detect the virus in lunch meats. The state health people sent us the lunch meats that were associated with the outbreak,” she said.

Recently, Estes and members of her laboratory published research in the Journal of Infectious Diseases that showed that blood type affects an individual’s susceptibility to infection by Norwalk. “Type O is more likely to get very ill,” she said. “People with type B blood are resistant.”

She does not know why. “People with O blood type also become more ill with cholera,” she said. “This, however, was a totally unexpected finding.”

She credits the determination of graduate student Anne M. Hutson in her laboratory with finding a way to study the virus and its interaction with blood cells.

With the genetic blueprint of the virus available, researchers and public health officials now find the virus in places they had not expected.

One place no one wants to find it is at a vacation spot, and she understands the frustrations of people seeking a relaxing vacation onboard a cruise ship only to become sick for two days of a five-day vacation.

“Think about when you go to a developing country,” she said. “There are lots of things to see and do. You still go, even though there is a risk that you could get sick for a couple of days.”

Recently, British troops in Afghanistan became severely ill and some had to be medically evacuated by helicopter. Two members of the flight crew became ill, as did some of the health care personnel in London. Using a three-hour test on which Estes and her laboratory collaborated, the health personnel in London confirmed that the cause was Norwalk virus.

The troops were stressed and living at 6,000 to 8,000 feet above sea level, she said. They were also dehydrated. She thinks that may explain the severity of the disease.

However, the virus causes only short-term illness for most people, she said. Some of what has been called Norwalk onboard cruise ships may even be seasickness.

“Rehydrate yourself and you will get over it in a day or two,” she said.

Diseases associated with Norwalk are not limited to cruise ships. There have been outbreaks in schools, nursing homes, hospitals, hotels, at contact sporting events, summer camps, water sports, families, the military and almost anywhere people congregate.

Estes hopes to find a silver lining associated with this virulent bug. The structure of its capsid, the protein covering that surrounds the virus’ core, is a single protein. If she can produce virus-like particles that are non-infectious and non-replicating, they can be candidate vaccines against Norwalk virus and, possibly, used to introduce antigens of other viruses into the gastrointestinal tract to induce the immune system to protect against them as well.

© Copyright 2003 Baylor College of Medicine. All Rights Reserved. MLE.