Noroviruses

Noroviruses are a group of related, single-stranded RNA (ribonucleic acid) viruses that cause infection resulting in acute gastroenteritis in humans. Gastroenteritis, also commonly called stomach flu, involves an inflammation of the gastrointestinal tract, which results in diarrhea, abdominal pain, and vomiting. The infection caused by noroviruses is very highly contagious, being commonly spread through water or food that has been contaminated with fecal matter; or through contact with an infected person. Norovirus infections occur frequently in closed, and often-times crowded, environments where the viruses can quickly spread. Such places include hospitals and medical facilities, schools, nursing/retirement homes and day-care facilities, and cruise ships.

Anyone can become infected with a 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 noroviruses. 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.

Norovirus infection is caused by a variety of viruses. All such viruses cause acute gastroenteritis, an inflammation of the stomach and intestines. The illness is highly contagious, and usually requires professional medical care to treat the most serious of the symptoms, which often times include dehydration, bloody stool, abdominal pain, and vomiting. Noroviruses are difficult to eliminate in the environment because they can withstand very high and low temperatures, along with being able to resist most disinfectants.

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 to 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.

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 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:

The U.S. Centers for Disease Control and Prevention (CDC) estimate, in 2012, that noroviruses are responsible for some 20 million cases of acute gastroenteritis in the United States every year. Epidemiologists estimate that about 50,000 Americans are hospitalized annually and about 400 people die each year because of norovirus infection. However, the CDC points out that many cases of acute gastroenteritis go unreported. Consequently, the U.S. health organization suggests that up to 300,000 hospitalizations occur annually and about 5,000 deaths occur each year, all due to noroviruses. In developing countries, noroviruses are a major cause of human illness. The CDC estimate that about 900,000 visits to clinics and other medical facilities by children in developed countries of the world result in about 64,000 hospitalizations. Even worse, about 200,000 children under the age of five years die from noroviruses each year in developing countries of the world.

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 to 60 hours.

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:

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:

Environmental contamination or contact with infected clothing or linen also may be a source of transmission. Although evidence is not available 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, published in 2010, showed that 21% of all norovirus outbreaks are caused by foodborne transmission. In addition, 25% of the outbreaks were initially reported to be “food handler-associated.” This was later found to be caused from contamination of the food source. In addition, 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:

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:

Norovirus infection can spread rapidly through daycare centers, schools, prisons, hospitals, nursing homes, camps, and other confined spaces. Norovirus is responsible for about 40% of group- or institution related-outbreaks of diarrhea. Outbreaks usually peak during the winter months.

In 2008, it was reported that outbreaks of the norovirus occurred on several university campuses in California, Michigan, and Wisconsin. The CDC, along with state and local health departments, found that approximately 1,000 cases of illness resulted from these outbreaks, including 10 hospitalizations. In addition, one college campus was closed temporarily due to an outbreak. In February 2012, an outbreak of norovirus at a basketball tournament in Kentucky was responsible for 242 cases of acute gastroenteritis, although no source for the disease was ever identified.

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. Close living quarters and the arrival of new, susceptible passengers every one to two weeks exacerbate outbreaks on cruise ships. Norovirus outbreaks have been reported to continue through more than 12 successive cruises on a single ship.

Noroviruses are relatively rare on cruise ships but they do happen. In 2006, the CDC reported that 34 cases of norovirus were reported, while 27 were reported in 2007, 15 in 2008, and 13 in 2009—all from cruises originating from U.S. ports. In 2010, for instance, the Celebrity Cruises company had about 15% of its passengers come down with norovirus-like symptoms on its cruise ship that departed from Charleston, South Carolina, on February 15, 2010. A year before the incident, a paper published in the medical journal Clinical Infectious Diseases found that a large number of norovirus outbreaks on cruise ships were the result of dirty public restroom facilities. However, in 2010, the CDC reported that the trend was down for contracting a norovirus on a cruise ship sailing from a U.S. port. In fact, the incidence of noroviruses on a cruise ship was at a decade-long low as of January 2010. The International Council of Cruise Lines reported that less than 1% of passengers become infected with norovirus each year. As reported by the CDC the outbreaks on cruise ships during the 2000s were on the decline. However, it is too early in the 2010s to tell if the trend will continue.

Generally, outbreaks of norovirus appear on the increase. Near the end of the 2000s, the CDC reported that norovirus outbreaks were increasing in many closed, crowded facilities across the country.

Humans are at increased risk from contracting noroviruses if they:

Noroviruses lack outer envelopes and their genetic material is carried as single-stranded RNA rather than DNA (deoxyribonucleic acid). 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:

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 10 distinct genogroups of norovirus have been found in various parts of the world. There are five common genogroups and, of those, three (GI, GII, and GIV) affect humans. 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. As of 2012, GII strains, especially GII4, are the most prevalent, and have caused the most norovirus outbreaks since 2002. However the most common method of identifying noroviruses—the reverse transcriptionpolymerase chain reaction (RT-PCR)—may not always identify GII genetic clusters correctly.

The increased number of norovirus outbreaks in European countries in the early 2000s—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' outer protective layer—were used to determine the predominant routes of norovirus transmission.

Then, in the first quarter of 2010, 334 cases of norovirus were reported at 65 different locations within the United Kingdom, Norway, France, Sweden, and Denmark. All of the cases were associated with the eating of raw oysters. The International Society of Infectious Diseases reports that the Rapid Alert System for Food and Feed (RASFF) database contained 19 reports of norovirus in oysters between March 2006 and March 2010—all within the European Union.

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:

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:

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:

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.

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' 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 norovirusspecific 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.

Research continues on commercial devices for detecting norovirsuses. For example, scientists at the Department of Infectious Diseases, Osaka Prefectural Institute of Public Health (Osaka, Japan) are developing modified reagent kits for norovirus genogroups I and II. They reported their advancement in the Journal of Medical Virology (December 2009).

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:

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—1–25 gallons (5–100 liters)—of water are processed through specially designed filters, the norovirus can be concentrated and assayed by RT-PCR.

Gastroenteritis caused by noroviruses usually resolves itself without treatment within a very few days. As of 2012, medications or vaccines are not available 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:

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. In fact, drinks containing sugar may make diarrhea worse. 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:

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 liveculture yogurt or as powder or capsules, may be useful for restoring the native flora of the digestive tract. Scientific evidence for the safety and efficacy of most herbal, Chinese, alternative and other complementary medicines is often lacking, so they should be used only with caution.

Public health responses to norovirus outbreaks pose distinctly difficult problems for public health agencies. Since the virus can not be cultured in the laboratory, a great deal of basic information is not readily available about the virus or the diseases it causes. Thus far, most guidelines for public health responses to outbreaks of gastroenteritis caused by noroviruses have been developed based on experiences in hospitals, cruise ships, and adult care facilities. The first step in the public health response to a suspected norovirus outbreak consists of data collection on reported cases that includes information such as the number of individuals affected, the time at which the outbreak occurred, the environmental conditions involved, especially the type of food that may have been involved, and the results of any laboratory tests that may have been conducted.

These items of information allow a public health agency to develop a plan of action that focuses on identifying and eliminating the suspected cause of the epidemic (such as the type of food involved) and initiate clean-up programs to eliminate that causative agent. Efforts to provide palliative care for those affected by the epidemic are also initiated. On a long term basis, information obtained about any specific outbreak of norovirus infection can be used to bolster and improve existing programs of education for the general public as well as for professionals in the field or, if such programs do not exist, to plan, develop, and implement such programs.

Norovirus infection is usually followed by complete recovery. Any long-term health effects are not known. Infected persons do not become long-term carriers of the virus. However, in some cases dehydration can become a very serious possible consequence of noroviral infection and can be fatal, particularly among young children, older people, and anyone with debilitating medical conditions or impaired immune systems.

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:

To prevent further transmission of norovirus:

Scientific studies have found that detergent-based cleaning with a cloth consistently fails to eliminate norovirus contamination. With fecal contamination, detergent-based cleaning, followed by cleaning with a combination hypochlorite/detergent formula containing 5,000 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 gastroenteritis not return to work until two to three 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 minutes. 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 (St. Louis, Missouri) became the first to grow a norovirus in a laboratory setting. They grew a mouse norovirus, with the goal of studying the virus and developing a vaccine against it. Research is ongoing. New surveillance systems also are being developed to detect norovirus outbreaks at an early stage.

See also Centers for Disease Control and Prevention ; Parasites ; Sanitation ; Viruses .