Noroviruses

Definition

Noroviruses are a group of related, single-stranded RNA (ribonucleic acid) viruses that cause acute gastroenteritis in humans.

Description

Noroviral infection

Noroviruses are a major cause of viral gastroenteritis—an inflammation of the linings of the stomach and small and large intestines that causes vomiting and diarrhea. Viruses are responsible for 30-40% of all cases of infectious diarrhea and viral gastroenteritis is the second most common illness in the United States, exceeded only by the common cold.

Anyone can become infected with norovirus. During norovirus outbreaks there are high rates of infection among people of all ages. There are a large number of genetically-distinct strains of norovirus. Immunity appears to be specific for the norovirus strain and lasts for only a few months. Therefore norovirus infection can recur throughout a person s lifetime. Because of genetic (inherited) differences among humans, some people appear to be more susceptible to norovirus infection and may suffer more severe illness. People with type O blood are at the highest risk for severe infection.

Infected individuals are contagious from the first onset of symptoms until at least three days after full recovery. Some people may remain contagious for as long as two weeks after recovery.

Gastroenteritis

Gastroenteritis often is referred to as the stomach flu even though the flu is a respiratory illness caused by an influenza virus. Other common names for viral gastroenteritis include:

• food poisoning
• winter-vomiting disease
• non-bacterial gastroenteritis
• calicivirus infection.

The U.S. Centers for Disease Control and Prevention (CDC) estimate that noroviruses are responsible for some 23 million cases of acute gastroenteritis in the United States every year. Epidemiologists estimate that about 50,000 Americans are hospitalized annually and about 400 die as a result of norovirus infection. In developing countries noroviruses are a major cause of human illness.

Gastroenteritis caused by infection with a norovirus is rarely a serious illness. Typically an infected person suddenly feels very ill and may vomit many times in a single day. The symptoms, although quite unpleasant, usually last only 24-60 hours.

Transmission

Noroviruses are ubiquitous in the environment. They are highly contagious and are considered to be among the most infectious of viruses. The reasons for this include:

• Only a small number of viral particles—fewer than 100—are required for infection.
• Although noroviruses cannot reproduce outside of their human hosts, they can remain viable for weeks or even months on objects and surfaces.
• Human immunity to norovirus is short-lived and strain-specific.

Noroviruses are transmitted among people by a fecal-oral route, either by ingestion of food or water contaminated with feces or by contact with the vomit or feces of an infected person. Norovirus infection can occur by:

• consuming contaminated food or liquids
• hand contact with contaminated objects or surfaces, followed by hand contact with the mouth
• contact with an infected person, including caring for the sick person or sharing food or utensils
• aerosolized vomit that is swallowed or contaminates surfaces.

Environmental contamination or contact with infected clothing or linen also may be a source of transmission. Although there is no evidence that norovirus infection can occur via the respiratory system, the sudden and violent vomiting of noroviral gastroenteritis can lead to contamination of the surroundings and of public areas. Particles laden with virus can be suspended in the air and swallowed.

FOODBORNE TRANSMISSION. Noroviruses account for at least 50% of food-related outbreaks of gastroenteritis. A European study found that between 1995 and 2000 noroviruses were responsible for more than 85% of all foodborne non-bacterial gastroenteritis outbreaks. Restaurant or catered foods are common sources of norovirus transmission, with subsequent infection of household members. The majority of norovirus outbreaks occur via contamination by a food handler immediately before the food is consumed.

Foods that frequently are associated with norovirus outbreaks include:

• foods that are eaten without further cooking, including sandwiches, salads, and bakery products
• liquids such as salad dressing or cake icing in which the virus becomes evenly distributed
• food that is contaminated at its source, including oysters and clams from contaminated waters and raspberries irrigated with sewage-contaminated water
• food that becomes contaminated before distribution, including salads and frozen fruit.
• Shellfish, including oysters and clams, concentrate norovirus from contaminated water in their tissues. Steaming shellfish may not completely inactivate the virus.

WATERBORNE TRANSMISSION. There is widespread norovirus contamination of rivers and seas, often with more than one strain of the virus. Waterborne outbreaks of norovirus have been associated with:

• sewage-contaminated wells
• contaminated municipal water systems
• stream and lake water
• swimming pools and spas
• commercial ice.

Outbreaks

Norovirus infection can spread rapidly through daycare centers, schools, prisons, hospitals, nursing homes, camps, and other confined spaces. About 40% of group- or institutionally-related outbreaks of diarrhea are caused by norovirus. Outbreaks usually peak during the winter months.

Between July of 1997 and June of 2000, 232 norovirus outbreaks were reported to the CDC. It was determined that 57% of these outbreaks were due to foodborne transmission, 16% were spread by human contact, and 3% were due to waterborne transmission. The mode of transmission could not be determined in 23% of the outbreaks. Restaurants or catered food accounted for 36% of the outbreaks, 23% occurred in nursing homes, 13% in schools, and 10% at resorts or on cruise ships. Outbreaks also have occurred at large family gatherings.

Cruise ships have become notorious for norovirus outbreaks among passengers and staff. Cruise ships and naval vessels are at increased risk for contamination when docking in regions that lack adequate sanitation and where contaminated food or water may be brought onboard. Outbreaks on cruise ships are exacerbated by close living quarters and the arrival of new, susceptible passengers every one to two weeks. Norovirus outbreaks have been reported to continue through more than 12 successive cruises on a single ship.

A study of 12 calicivirus outbreaks on cruise ships in 2002 found that 11 of the outbreaks were caused by noroviruses and seven of these were due to a previously unreported strain. In the same year, 10 out of 22 land-based outbreaks were attributed to this new strain.

Outbreaks of norovirus appear on the increase. In 2005 the CDC reported that norovirus outbreaks were increasing in hospitals, daycare centers, nursing homes, and schools across the country. The International Council of Cruise Lines reported that, although less than 1% of passengers become infected with norovirus each year, outbreaks on cruise ships also were on the increase. In the summer of 2004 an outbreak at Yellowstone National Park sickened 134 people. More than 1,100 people became ill in early 2004 after a norovirus outbreak at Las Vegas hotels. The following autumn more than 1,200 people became sick from a norovirus outbreak at a single Las Vegas hotel-casino.

Causes & symptoms

Norovirus strains

Noroviruses lack outer envelopes and their genetic material is carried as single-stranded RNA rather than DNA. Although noroviruses are not new, the extent of norovirus infection was not recognized until the 1990s. This has led to increased research on noroviruses and more monitoring of outbreaks.

Until 2004 noroviruses were commonly referred to as:

• Norwalk virus
• Norwalk-like viruses (NLVs)
• caliciviruses
• small, round-structured viruses (SRSVs).

Noroviruses are named after the original strain—the Norwalk virus—that caused an outbreak of gastroenteritis in a Norwalk, Ohio, school in 1968. The virus was identified in 1972. Since then many related viruses have been identified. In 2004 these viruses were grouped together in the genus Norovirus within the Caliciviridae family of viruses. Eight to ten distinct genogroups of norovirus have been found in various parts of the world. The most common genogroups are GI, GII, GIII, and GIV. Each of these groups can be further differentiated into at least 20 genetic clusters. Evidence suggests that noroviruses in different genetic clusters can recombine to form new, genetically-distinct noroviruses. GII strains, especially GII4, are the most prevalent. However the most common method of identifying noroviruses—the reverse transcription-polymerase chain reaction (RT-PCR)—may not always identify GII genetic clusters correctly.

The increased number of norovirus outbreaks in European countries in 2002—occurring in the spring and summer rather than in winter—were found to be associated with the emergence of a new variant of the GII4 strain. Increased international outbreaks in 2003 and 2004 also were caused by a GII4-related norovirus that was found to mutate rapidly. Mutations in the viral capsid—the virus s outer protective layer—were used to determine the predominant routes of norovirus transmission.

Symptoms

Symptoms of norovirus infection usually appear within 24-48 hours after exposure, with a median incubation period during outbreaks of 33-36 hours. However symptoms can occur as early as 12 hours or less after exposure.

Typical symptoms of norovirus infection are:

• nausea
• vomiting
• watery diarrhea without blood
• abdominal cramping.

Among children, vomiting is the predominant symptom, whereas diarrhea is more common in adults. Vomiting can be frequent and violent and may occur without warning.

Additional symptoms of norovirus infection may include:

• low-grade fever
• chills
• headache
• muscle aches
• fatigue.

Dehydration is the major risk from gastroenteritis caused by norovirus, particularly among infants, young children, the elderly, and those with underlying health conditions.Symptoms of dehydration include:

• dry mouth
• increased or excessive thirst
• low urine output
• nausea
• dizziness or faintness
• sunken eyes
• sunken fontanelle—the soft spot on an infant s head
• confusion.

As many as 30-50% of norovirus infections do not produce symptoms. It is not known whether individuals with asymptomatic infections can transmit the virus.

Diagnosis

Identifying noroviruses

Viral gastroenteritis usually is diagnosed on the basis of the symptoms. Many types of viruses cause gastroenteritis. Rotoviruses are a leading cause of gastroenteritis in children who then transmit the virus to adults. In addition to noroviruses, viral gastroenteritis in humans can be caused by another genus of viruses within the Caliciviridae family. Formerly known as the Sapporo-like virus, or classic or typical calicivirus, these now are grouped in the genus Sapovirus. Other genera in the Caliciviridae family are not pathogenic in humans. Some bacteria and parasites also cause illnesses that are similar to norovirus infection.

The cloning and sequencing of noroviruses in the early 1990s made it easier to identify norovirus outbreaks. RT-PCR is the most commonly used method for identifying norovirus. With this technique the virus s RNA is used as the template for transcribing the corresponding DNA using the enzyme reverse transcriptase. The DNA is amplified into many copies using the polymerase chain reaction. Many state public health laboratories use this method to detect norovirus in vomit and stools. The best identification usually comes from stool samples taken within 48-72 hours after the onset of symptoms; however norovirus can be detected in stool samples taken five days after the onset of symptoms and sometimes even in samples taken up to two weeks after recovery.

Norovirus from fecal samples can be visualized using electron microscopy. With immune electron microscopy (IEM), antibodies against norovirus are collected from blood serum and used to trap and visualize the virus from fecal samples. However these methods require high concentrations of norovirus in the stool, as well as a fourfold increase in norovirus-specific antibodies in blood samples taken during the acute or recovery phases of gastroenteritis.

Enzyme-linked immunosorbent assays may be used to detect noroviruses in fecal samples. In these assays noroviral-specific antibodies bound to the virus are detected by the reaction of an enzyme that is attached to the antibody. Nucleic acid probes that hybridize with noroviral RNA also can be used for virus detection in feces.

As of 2005 a Japanese chemical company was producing a reagent kit that can be used to detect norovirus in two hours rather than the 12-24 hours needed for conventional detection. Other simpler methods for rapidly identifying norovirus are under development.

Investigating outbreaks

Epidemiological studies often involve sequencing the norovirus RNA. This can help to determine whether outbreaks in different geographical locations are connected to each other and can help trace the source of the norovirus to contaminated food or water. CaliciNet is a database that stores the RNA sequences of all norovirus strains that cause gastroenteritis in the United States.

Criteria that are sometimes used to determine whether an outbreak of gastroenteritis is caused by a norovirus include:

• a mean incubation period of 24-48 hours
• a mean duration time for illness of 12-60 hours
• vomiting in more than 50% of patients
• failure to find a bacterial cause for the illness.

During investigations of norovirus outbreaks, food handlers may be asked to provide a stool sample and possibly a blood sample. Food rarely is tested for norovirus since each type of food requires a specific assay. However tests are used to detect the virus in shellfish. When large amounts—1-26 gal. (5-100 L)—of water are processed through specially designed filters, the norovirus can be concentrated and assayed by RT-PCR.

Treatment

Gastroenteritis caused by noroviruses usually resolves itself without treatment within a very few days. As of 2005 there are no medications or vaccines that are effective against the norovirus. Viruses are not affected by antibiotics and antidiarrheal medications may prolong the infection.

Norovirus infections should be treated by:

• drinking plenty of fluids, such as water and juice, to prevent dehydration caused by vomiting and diarrhea
• intravenous fluids if severe nausea prevents drinking, particularly in small children
• drinking oral rehydration fluids (ORFs) to prevent dehydration and to replace electrolytes (salt and minerals ) and glucose
• avoiding alcohol and caffeine which can increase urination.

Commercially available ORFs include Naturalyte, Pedialyte, Infalyte, and Rehydralyte.

Juice, soda, and water do not replace lost electrolytes; nor do sports drinks replace nutrients and minerals lost through vomiting and diarrhea. Those taking diuretics should ask their healthcare provider whether to stop taking the medication during acute diarrhea.

Since the risk of dehydration is higher for infants and young children, the number of wet diapers per day should be closely monitored. Severely dehydrated children may receive rapid intravenous rehydration in a hospital or emergency-room setting.

A health care provider should be consulted if:

• symptoms of dehydration appear
• diarrhea persists for longer than a few days
• there is blood in the stool.

Alternative treatment

An infusion of meadowsweet (Filipendula ulmaria ) may reduce nausea. Once the symptoms are reduced, slippery elm (Ulmus fulva may calm the digestive system. Castor oil packs placed on the abdomen can reduce inflammation and discomfort.

Homeopathic remedies for gastroenteritis include Arsenicum album, ipecac, and Nux vomica. Chinese patent herbal remedies include Po Chai and Pill Curing.

During recovery from viral gastroenteritis, live cultures of Lactobacillus acidophilus, found in live-culture yogurt or as powder or capsules, may be useful for restoring the native flora of the digestive tract.

Prognosis

Norovirus infection is followed by complete recovery and there are no known long-term health effects. Infected persons do not become long-term carriers of the virus. Dehydration is the most serious possible consequence of noroviral infection and can be fatal, particularly among older people with debilitating medical conditions or impaired immune systems.

Prevention

Noroviruses are difficult to destroy. They can survive freezing as well as temperatures as high as 140°F (60°C). Noroviruses can survive chlorine levels as high as 10 parts per million (ppm), far higher than the levels present in most public water systems. A 2004 study from the Netherlands found that inactivation of norovirus with 70% ethanol was inefficient and that sodium hypochlorite solutions were effective only at concentrations above 300 ppm.

The best prevention against noroviral infection is frequent, thorough hand washing with soap and water. All soaped hand surfaces should be rubbed vigorously for at least 10 seconds. The hands should be thoroughly rinsed under a stream of water. In particular hands always should be washed before handling food and after using the toilet or changing diapers.

Other important measures for preventing norovirus infection include:

• proper handling of cold foods
• careful washing of fruits and vegetables
• steaming oysters before eating, although even this may be insufficient for destroying norovirus
• taking particular care when handing the diapers of children with diarrhea
• properly disposing of sewage and diapers
• excluding sick infants and children from food preparation areas.

To prevent further transmission of norovirus:

• All surfaces exposed to vomit or otherwise contaminated should be immediately cleaned and disinfected with a solution of 10% bleach, followed by rinsing.
• Contaminated clothing and linens should be removed immediately and washed with hot water and detergent on the maximum machine cycle and with a minimum of handling, followed by machine drying.
• Vomit and feces should be discarded or flushed immediately and the toilet area should be kept clean.
• Exposed or contaminated food should be discarded.
• Masks may be worn while cleaning areas that have been badly contaminated with vomit or feces, such as in hospitals or nursing homes.

A 2004 study found that detergent-based cleaning with a cloth consistently failed to eliminate norovirus contamination. With fecal contamination, detergent-based cleaning, followed by cleaning with a combination hypochlorite/detergent formula containing 5000 ppm of available chlorine significantly reduced contamination. However norovirus still could be detected on as much as 28% of the surfaces. When this procedure failed to eliminate contamination, the virus was transmitted to the cleaner's hands. Contaminated fingers consistently transferred norovirus to up to seven different surfaces including doorknobs and telephones. However the contamination was diluted during secondary transmission and treatment with the combined bleach/detergent eliminated the virus without prior cleaning.

In situations where there is a periodic renewal of susceptible people, such as on cruise ships and at camps, the facility may have to be closed until cleaning is complete. Although many state and local health departments require that food handlers with gastro-enteritis not return to work until 2-3 days following recovery, this may not be an adequate length of time to prevent noroviral transmission.

The prevention of norovirus outbreaks include reducing contamination of water supplies with human waste and using high-level chlorination—at least 10 ppm for more than 30 min. Surveillance of shorelines for potential sources of fecal contamination and for boats that are dumping human waste may help prevent shellfish-associated norovirus outbreaks.

In 2004 researchers at Washington University announced that they had succeeded in growing a mouse norovirus in the laboratory for the first time, with the goal of studying the virus and developing a vaccine against it. New surveillance systems also are being developed to detect norovirus outbreaks at an early stage.

Resources

BOOKS

Richman, Douglas D., et al., editors. Clinical Virology. 2nd ed. Washington, D.C.: ASM Press, 2002.

PERIODICALS

Blevins, L. Zanardi, et al. "An Outbreak of Norovirus Gastroenteritis at a Swimming Club—Vermont, 2004." MMWR. Morbidity and Mortality Weekly Report 53, no. 34 (September 3, 2004): 793-5.

Centers for Disease Control and Prevention, National Center for Infectious Diseases. "Norwalk-Like Viruses: Public Health Consequences and Outbreak Management." MMWR. Morbidity and Mortality Weekly Report 50, no. RR-9 (June 1, 2001).

Kirkwood, Chris. "Viral Gastroenteritis in Europe: A New Norovirus Variant?" The Lancet 363, no. 9410 (February 28, 2004): 671-2.

Lopman, Ben, et al. "Increase in Viral Gastrocenteritis Outbreaks in Europe and Epidemic Spread of New Norovirus Variant." The Lancet 363, no. 9410 (February 28, 2004): 682-8.

"Norovirus; Cruise Ships Experience Increase in Norovirus Incidents." Science Letter February 22, 2005: 1140.

"Norovirus; Detergent Followed by Bleach/Detergent Reduces Norovirus Contamination." Science Letter December 14, 2004: 843.

"Norovirus Outbreak; Alterations to Norovirus Capsid Structure Explains 2002–2003 Outbreaks." Science Letter November 30, 2004: 1008.

ORGANIZATIONS

National Health Information Center. Office of Disease Prevention and Health Promotion. U.S. Department of Health & Human Services. P.O. Box 1133, Washington, DC 20013-1133. [email protected]. 〈http://www.healthfinder.gov/〉.

Office of Health Communication. National Center for Infectious Diseases. Centers for Disease Control and Prevention. Mailstop C-14, 1600 Clifton Road, Atlanta, GA 30333. 800-311-3435. 〈http://www.cdc.gov/ncidod/index.htm〉.

OTHER

PM Medical Health News. 21st Century Complete Medical Guide to Gastroenteritis, Norwalk Virus, Norovirus, Authoritative Government Documents, Clinical References, and Practical Information for Patients and Physicians. CD-ROM. Progressive Management, 2004.

Norovirus. Respiratory and Enteric Viruses Branch, National Center for Infectious Diseases. January 20, 2005 [cited February 21, 2005]. 〈http://www.cdc.gov/ncidod/dvrd/revb/gastro.norovirus.htm〉.

"Norovirus Cultured for the First Time." Public Library of Science Biology 2.12 (2004). November 30, 2004 [cited February 26, 2005]. 〈http://www.plosbiology.org/plosonline/?request=get-document&doi=10.1371%2Fjournal.pbio.0020445〉.

KEY TERMS

Antibody— A blood protein produced in response to foreign material such as a virus; the antibody attaches to the virus and destroys it.

Calicivirus— A member of the Caliciviridae family of viruses that includes noroviruses.

Capsid— The outer protein coat of a virus.

Gastroenteritis— An inflammation of the lining of the stomach and intestines, usually caused by a viral or bacterial infection.

Genetic cluster— A group of viral strains with very similar, yet distinct, nucleic acid sequences.

Genogroup— Related viruses within a genus; may be further subdivided into genetic clusters.

Reverse transcription-polymerase chain reaction; RT-PCR— A method of polymerase-chain-reaction amplification of nucleic acid sequences that uses RNA as the template for transcribing the corresponding DNA using reverse transcriptase.