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No.69
Norovirus infections

By Shigeo Matsuno
National Institute of Infectious Diseases (NIID)

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Introduction
  Norovirus causes infectious gastroenteritis and often food-born disease during fall and winter every year (around October-March). They have been the focus of the attention following successive outbreaks during this season in special nursing homes and the death of seven residents in a home for the nursing of the elderly in Fukuyama City, Hiroshima Prefecture. According to a survey conducted by the Ministry of Health, Labour and Welfare on cases of widespread outbreaks of infectious gastroenteritis, there were 7,821 patients (of whom 5,371 were found to harbor the norovirus) in 236 facilities and 12 fatalities as of January 12, 2005, although the outbreak did not reach a larger scale this winter than that of normal years, and there is no evidence that the virus pathogenicity has increased.
Description of the virus
  Norovirus, the causative agent of infectious gastroenteritis and viral food poisoning, was discovered in 1972 by Kapikian and co-workers of US National Institutes of Health (NIH) with the aid of immune-electron microscopy. It was named "Norwalk virus", since it was detected in the feces of children afflicted with gastroenteritis in groups in elementary schools in Norwalk City, Ohio, USA, in 1968. Afterward similar viruses were detected successively all over the world. They were called small round-structured virus (SRSV) or Norwalk-like viruses (NLVs) until the International Committee on Taxonomy of Viruses (ICTV) named them "norovirus" in 2002. Norovirus is icosahedron having a diameter of about 30 nm. Norovirus has a single stranded RNA of a total length of 7.5~7.7 Kb with ORF1 encoding a nonstructural protein, ORF2 encoding structural protein VP1 and ORF3 encoding structural protein VP2. It is divided into two genogroups I and II, based upon the base sequence homology of the gene. Since isolation of norovirus by means of tissue culture cells has not been successful, the number of serotypes has not been determined. However, the presence of ten and more genotypes and serotypes in each genogroup has been confirmed by means of ELISA using virus-like particles manifested with the aid of genotyping and genetic recombinant technology.
Route of infection and clinical symptoms
  The route of infection of noroviruses is primarily fecal-oral transmission. Infection may occur through the hands containment with feces or vomit of norovirus patients, infection from the hands of food handlers harboring inapparent infection or from food materials contaminated with norovirus and infection caused by eating raw shellfish contaminated with norovirus. The incubation period of norovirus infection is 24~48 hours. The clinical symptoms are nausea, vomiting, abdominal pain, chills, fever, headache, diarrhea and associated dehydration. Normally the symptoms subside in approximately three days, and the prognosis is good. Nevertheless one should be careful since the virus is excreted for about a week in the stools of the patients.
Epidemiology
  The number of viral gastroenteritis patients increases each year from around October. The pattern followed is a peak reached in December to January, a gradual decrease in the number of patients and termination of the illness in April to May. The sporadic cases observed mainly in infants, young children and schoolchildren that occur in fall to winter are primarily due to fecal-oral transmission. Although the attention was focused on cases of food poisoning, patients with fecal-oral infection occurring sporadically are overwhelmingly numerous. It is estimated that, several millions of subjects develop the illness every year.
Food poisoning caused by bivalves such as oyster, etc.
Norovirus is the primary cause of food poisoning due to bivalves, notably oysters. Norovirus was detected directly in oysters when the RT-PCR technique was developed in 1990s. The ecology of bivalves is thought to be deeply involved in food poisoning by norovirus due to the consumption of raw oysters. Bivalves pass through a large amount of sea water in order to breathe and catch feed. If the feces and vomit containing norovirus excreted from patients flow into bivalve marine culture beds after passing through rivers without treatment in sewage disposal plants, they enter into the midgut glands of oysters together with feeds, such as plankton, etc., and they eventually cause food poisoning in consumers.
Epidemiological Characteristics of this season
  Such large scale outbreaks of norovirus infection in care facilities for the aged as observed during this season have never been experienced before. I tried to verify why this could happen. Norovirus outbreaks usually begin around October as mentioned in the above. However, during this season the start of the epidemic was slow and the number of patients was relatively small perhaps because the temperature was unusually high. According to the Meteorological Agency, the nationwide average temperature was 2~3C higher compared to normal years till around December 20. This was followed by an increase in the cases of infectious gastroenteritis caused by noroviruses. In normal years outbreaks of norovirus Infection occur in kindergartens, day nurseries, elementary schools, care facilities for the aged, hospitals, etc. However, since last winter the outbreak of gastroenteritis due to norovirus started after December 20, children of kindergartens and elementary schools were not involved in norovirus infection because they were on the winter holidays. This apparently made widespread norovirus outbreaks in nursing facilities for the elderly stand out. Another reason is that the epidemic of influenza virus started more slowly than normal years, probably because the average temperature was high during this season. Accordingly, the norovirus epidemic masked by the differential influenza virus outbreaks in normal years apparently drew the attention. In addition the diagnosis of the influenza virus with other infectious diseases has become easy with handy influenza virus detection kits available on the market.
Prevention and treatment of norovirus infection
  Prevention of secondary infection triggered by the vomit and the feces of patients infected with norovirus drew a greater attention this winter rather than prevention of food poisoning caused by contaminated foods (including oysters). The presence of a high level of norovirus in the stools (at least 106 copies/g) and the vomit (103~ 107 copies/g) of patients has been reported. These excretions containing the virus must be cautiously handled,since their infectivity is extremely high. Disposable gloves must be used during contacts with them and patients as well. The feces and vomit must be disposed of with disposable paper towels and put into sealed garbage bags for disposal. Then It is important to wash hands thoroughly under running water with a detergent. In addition in case of a norovirus outbreak, it is essential to rapidly isolate the patients, with the precautions mentioned above, in order to prevent the other residents and hospitalized patients from infection.
Numerous reports mention that once norovirus outbreak occurs inside facilities such as nursing homes for the aged, hospitals, etc., the outbreak eventually abates at the time when many susceptible individuals have contracted the illness.

 

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