2.1 Characteristics of norovirus

2.1.1 History

Gastroenteritis, that was probably due to norovirus, was first described by Zahorsky in 1929 as ‘winter vomiting disease’. However the agent was not identified until 1972, when virus particles were first visualised by electron microscopy (EM) in faeces obtained from an outbreak. The outbreak had occurred in 1968 at a school in Norwalk, Ohio, US, with a high attack rate of illness among students and teachers. The illness was characterised by nausea, vomiting and diarrhoea with duration of illness of 12–24 hours [12].

In Australia, the first confirmed norovirus outbreak occurred in 1978 and was associated with oyster consumption [13]. The outbreak affected people across Australia, and norovirus was confirmed as the cause by visualisation of virus particles in patients’ faeces by EM and immuno-EM [13, 14]. This outbreak was one of the first recorded foodborne outbreaks of norovirus [13].

The discovery of the virus through EM was important because this was the first virus detected that was specifically associated with cases of acute gastroenteritis. For decades the role of the virus as a causative agent has been hampered by the insensitivity of microbiological diagnostics. It cannot be grown in cell culture and there is no small animal model. The only alternative is to test on human volunteers [12]. Since the 1970s, the viruses were known as ‘Norwalk-Like Viruses’ (NLV) and ‘Small Round Structured Viruses’ (SRSV). The early names of these viruses were determined by the location where each strain was detected (e.g. Hawaii, Norwalk) or by their physical appearance as visualised with EM [15, 16].

In 2002, norovirus became the official genus name, following further investigation of the viral taxonomy by sensitive molecular techniques. Improvement in diagnostic techniques has allowed for rapid recognition of the causative agent in outbreaks and has changed the understanding of the clinical significance and epidemiology of this virus [17].

2.1.2 Virology

Noroviruses (family Caliciviridae, genus Norovirus) are a genetically diverse group of single stranded ribonucleic acid (RNA), non-enveloped viruses. The RNA genome of the virus consists of approximately 7700 nucleotides (excluding the polyadenylated tail) and includes three open reading frames. The virus when visualised by EM is 26 to 34nm in diameter; small, round, with an amorphous surface and ragged outer edge (Figure 1). The open reading frame (ORF) 1 encodes for non-structural polyproteins including a helicase, protease and RNA-dependent RNA polymerase. ORF 2 encodes a viral capsid protein and ORF 3 a small structural protein [18].

Top of Page

Figure 1: Electron microscope picture of norovirus particles
 Electron microscope picture of norovirus particles
Image courtesy of John Marshall

2.1.3 Taxonomy

Norovirus is one of four genera within the Caliciviridae. The other three genera are Lagovirus, Vesivirus and Sapovirus. Sapovirus and Norovirus are the only two genera that cause gastroenteritis in humans. Noroviruses are currently classified into five genogroups designated GI to GV. GI, GII and GIV strains infect humans while the GIII and GV are detected in pigs, cattle and mice. Genogroups I and II are more commonly known to infect humans and cause outbreaks of acute gastroenteritis [19]. Genogroups comprise a range of genetically and antigenically diverse strains which can be further divided into genotypes or genetic clusters on the basis of sequence analysis. There are currently:
  • eight genogroup I (GI) genotypes: GI includes Norwalk virus, Desert Shield virus and Southampton virus.
  • 19 genogroup II (GII) genotypes: GII includes Bristol virus, Lordsdale virus, Toronto virus, Mexico virus, Hawaii virus and Snow Mountain virus.
  • two genogroup III (GIII) genotypes.
An example of GIV is Ft. Lauderdale virus [17].

Top of Page

2.1.4 Molecular epidemiology

Although a large number of norovirus strains co-circulate in the community at the same time, individual strains have dominated worldwide in recent years [20]. The genogroup II strain more commonly causes outbreaks of gastroenteritis, with genogroup II, genotype 4 (GII.4) the predominant strain that has circulated globally in recent years. Outbreaks in 2006–07 due to new variants of the GII.4 have been reported by health agencies globally [7]. Recent increased activity has been reported in Hungary, Germany, Japan and the US [21]. New variants within GII.4 coincided with high levels of outbreak reporting worldwide in 1996, 2002 and 2004 [11, 22, 23].

A review of norovirus outbreaks in the US between 2000 and 2004 found GII.4 strains occurred more frequently in semi-closed environments (such as buses or aeroplanes) than other strains [22]. Settings where these strains were more commonly detected included health care facilities, schools, childcare centres and cruise ships. Person-to-person transmission occurred more frequently than did outbreaks involving food [22].

2.1.5 Symptoms

Noroviruses cause an infection of the digestive tract which presents with acute onset of diarrhoea, abdominal cramps, nausea and vomiting. Vomiting is more common among children while a greater proportion of adults experience diarrhoea. Systemic symptoms such as fever, headache, myalgia, malaise and abdominal pain can also occur [24].

The median incubation period is classically 32 hours, with a range of 24–48 hours, but can extend outside this range (12–50 hours). Symptoms usually resolve within 24–48 hours but may range from 12–72 hours [25]. However, in some people symptoms can last longer than previously thought, particularly among the elderly and in young children, as well as among transplant recipients and the immunosuppressed, such as people on immunosuppressive therapy, or ill with immune-modulating diseases (e.g. HIV) [17, 26].

The illness is usually self-limiting (resolves without treatment) and recovery is complete without any serious long-term sequelae. However, more severe clinical disease can be seen in the elderly and those with other underlying disease, such as cardiovascular disease, renal transplant recipients and those on immunosuppressive therapy [17]. Severe complications can be seen in these settings, with decreased potassium levels, increased C-reactive protein and creatine phosphokinase [26]. Deaths may occur among ACF residents due to aspiration or exacerbation of other chronic diseases [4, 27].

2.2 Epidemiology

Each year in Australia, there are an estimated 1.8 million (95% Credible Interval 1.4–2.3 million) cases of norovirus infection, making it the most common cause of gastroenteritis [28]. Norovirus occurs throughout the year, but is more common from late winter to early summer [29, 30]. A study in Melbourne found a seasonal trend observed for norovirus cases. Prevalence was highest during spring (September–November) and summer (December–February) [31]. However, epidemic strains of norovirus may result in outbreaks that do not follow usual seasonal patterns [32].

Norovirus is endemic in Australia and affects all age groups. An analysis of sera collected from a sample of patients admitted to Alice Springs Hospital in 1977, 1984 and 1986 found that 96% of sera from patients over two years of age and 70% of sera from patients up to two years showed the presence of norovirus antibodies suggesting exposure occurs at a young age [33].

Although norovirus infections occur in all age groups, they can be more severe in the very young and elderly, resulting in hospitalisation. A study in the Netherlands identified several risk factors associated with norovirus infection [34]. McIver describes similar risk factors for norovirus infection [18]. These included:
  • contact with persons or household members with gastroenteritis
  • being in semi-closed environments, such as buses or airplanes, with people ill with gastroenteritis
  • visiting or working in a health care facility during an outbreak
  • contact with areas contaminated by vomiting and/or faeces
  • consumption of contaminated food, by poor food-handling hygiene or cultivation of filter-feeding shellfish in contaminated environments.
Top of Page

2.2.1 Transmission

Norovirus transmission occurs through a variety of routes but is primarily person-to-person spread by the faecal-oral route, contact with contaminated surfaces and transmission via aerosolised vomit.Aerosolisation of vomit can result in contamination of surfaces such as furniture and carpets so that outbreaks spread via environmental contamination. Aerosolised vomit containing norovirus may also be inhaled and swallowed. It is unlikely that infection occurs via the respiratory tract as there is no evidence that the virus replicates in respiratory mucosal cells [35, 36]. Transmission may also occur through consumption of contaminated food, particularly oysters and shellfish, or water [24, 37].

The spread of infection during outbreaks is facilitated by the specific characteristics of the virus. A low infectious dose, coupled with the ability of the virus to be transmitted from contaminated environments or infected persons, allows for many people to be affected, as shown by spread among contacts and household members [2]. Similarly, the virus is stable in the environment and survives high levels of chlorine, freezing and heating to 600C, making it difficult to eliminate from contaminated water, food and surfaces [38]. Prolonged viral shedding in asymptomatic people increases the risk for secondary transmission and is of concern among healthcare workers and food handlers, even when symptoms have resolved [24]. Strain diversity and lack of long-term immunity contribute to the facilitation of transmission and potential for outbreaks [17, 39].

Outbreaks occur in a variety of settings but are more common in environments where people are in close quarters, such as in ACFs, hospitals, schools, ships and restaurants. In these settings, people may be at greater risk of person-to-person transmission. Infected food handlers are often suspected as the source of foodborne outbreaks and can contaminate food prior to consumption [40]. Food items that are ready-to-eat and require handling but no cooking such as salads, sandwiches and bakery products are at greatest risk of being contaminated [24, 41-43]. Foods can also be infected with norovirus prior to preparation via faecal contamination. Shellfish, in particular oysters, are filter feeders that concentrate microorganisms from contaminated water. Outbreaks of oyster-associated norovirus infection have occurred even where oysters have been grilled [44] or steamed, probably due to inadequate cooking [45, 46]. Contaminated raspberries have also been implicated in outbreaks, as have other fruits, pastry glazes and icing [47, 48]

Waterborne outbreaks of norovirus have also been reported and include contaminated well water, ice, lake water, drinking water and swimming pool water [49-54]. Waterborne norovirus outbreaks occur when sewage contaminates the water that is either used as a drinking water supply or unintentionally consumed during recreational activities. Norovirus is resistant to chlorine in the presence of organic matter [55] and higher levels of chlorine may be required for contaminated water supplies [56].

2.2.2 Immunity

Exposure to norovirus usually occurs in childhood, with antibody prevalence rising to greater than 50% by the fifth decade of an individual’s life. It appears that individuals develop short-term immunity following infection and immunity is strain specific. The genetic variability in circulating norovirus indicates that individuals are likely to be repeatedly infected during their lifetime [57]. Short-lived immunity may explain in part the high attack rates in all age groups in an outbreak. There is evidence suggesting susceptibility to norovirus infection to be based on histo-blood group antigens [58].

2.2.3 Period of shedding and infectivity

Previous human volunteer studies have found that viral shedding in stools coincided with onset of illness and did not extend more than 72 hours after the onset of the first symptom. However, viral RNA has been detected using molecular techniques for up to three weeks after onset of illness [59, 60]. Studies have shown prolonged viral shedding and duration of illness due to norovirus infection, and demonstrated that excretion of virus occurred after cessation of symptoms and in infected individuals with no clinical symptoms [24, 61, 62]. A study in Victoria examined clinical symptoms and norovirus excretion among elderly residents during an outbreak of gastroenteritis at an ACF. The study found that acute symptoms lasted 3–4 days and the median excretion time for norovirus was 8.6 days [60]. Viral excretion was not related to clinical symptoms or the appearance of stools [60]. Similarly, a study of the natural history of calicivirus in the Netherlands found that norovirus occurred in all age groups, clinical symptoms lasted a median of 5 days and stool samples were positive by PCR for norovirus up to three weeks after the of onset of illness [25].

Prolonged viral shedding, either symptomatic or asymptomatic, has implications for transmission. While asymptomatic food handlers may be important in spreading disease, the significance of viral excretion in the absence of symptoms is unclear [24]. Marshall et al. suggest that excretion of norovirus by people who are asymptomatic may act as a significant potential infectious reservoir in the community [61].

Viral shedding is greatest during the acute illness and the amount of virus excreted decreases rapidly with recovery. Viral shedding in stools is greatest over the first 24–48 hours. There is no evidence that infected food handlers and health care workers should be excluded from the workplace for longer than 48 hours after cessation of symptoms (see Chapter 8).