Page 5: Guidelines for Canadian Drinking Water Quality: Guideline Technical Document – Enteric Viruses
Part II. Science and Technical Considerations
4.0 Description and health effects
Viruses range in size from 20 to 350 nm. They consist of a nucleic acid genome core (either ribonucleic acid [RNA] or deoxyribonucleic acid [DNA]) surrounded by a protective protein shell, called the capsid. Some viruses have a lipoprotein envelope surrounding the capsid; these are referred to as enveloped viruses. Non-enveloped viruses lack this lipoprotein envelope. Viruses can replicate only within a living host cell. Although the viral genome does encode for viral structural proteins and other molecules necessary for replication, viruses must rely on the host's cell metabolism to synthesize these molecules.
Viral replication in the host cells results in the production of infective virions and numerous incomplete particles that are non-infectious (Payment and Morin, 1990). The ratio between physical virus particles and the actual number of infective virions ranges from 10:1 to over 1000:1. In the context of waterborne diseases, a "virus" is thus defined as an infectious "complete virus particle," or "virion," with its DNA or RNA core and protein coat as it exists outside the cell. This would be the simplest form in which a virus can infect a host. Infective virions released in the environment will degrade and lose their infectivity. They can still be seen by electron microscopy or detected by molecular methods, but will have lost their potential for infection.
In general, viruses are host specific. Therefore, viruses that infect humans do not usually infect non-human hosts, such as animals or plants. The reverse is also true: viruses that infect animals and viruses that infect plants do not usually infect humans, although a small number of enteric viruses have been detected in both humans and animals. Most viruses also infect only specific types of cells within a host. The types of susceptible cells are dependent on the virus, and consequently the health effects associated with a viral infection vary widely, depending on where susceptible cells are located in the body. In addition, viral infection can trigger immune responses that result in non-specific symptoms. Viruses that can multiply in the gastrointestinal tract of humans or animals are known as "enteric viruses." Enteric viruses are excreted in the faeces of infected individuals, and some enteric viruses can also be excreted in urine. These excreta can contaminate water sources. Non-enteric viruses, such as respiratory viruses, are not considered waterborne pathogens, as non-enteric viruses are not readily transmitted to water sources from infected individuals.
More than 140 different serological types of enteric viruses known to infect humans have been described (AWWA, 1999a; Taylor et al., 2001). The illnesses associated with enteric viruses are diverse. In addition to gastroenteritis, enteric viruses can cause serious acute illnesses, such as meningitis, poliomyelitis and non-specific febrile illnesses. They have also been implicated in the aetiology of some chronic diseases, such as diabetes mellitus and chronic fatigue syndrome. Further information on the enteric viruses commonly associated with human waterborne illnesses, including noroviruses, hepatitis A virus (HAV), hepatitis E virus (HEV), rotaviruses and enteroviruses, and on other viruses of potential concern is included below.
4.1 Noroviruses
Noroviruses are non-enveloped, single-stranded RNA viruses, 27-32 nm in diameter, belonging to the family Caliciviridae. Noroviruses are currently subdivided into five genogroups (GI, GII, GIII, GIV, GV), which are composed of 22 distinct genotypes. However, new norovirus variants continue to be identified (Jiang et al., 1999). Genogroups GI and GII contain the norovirus genotypes that are usually associated with human illnesses. For example, Norwalk virus is included in the GI genogroup. Genogroup GIV has also been associated with human illness, but much less frequently than the GI and GII genogroups (Bon et al., 2005). Although most noroviruses appear to be host specific, there is some recent research showing human norovirus GII variants isolated from farm animals (Mattison et al., 2007). Other genogroups, such as GIII and GV, have been detected only in non-human hosts (Vinje et al., 2004).
Norovirus infections occur in infants, children and adults. The incubation period is 24-48 h (Kapikian et al., 1996; Chin, 2000). Health effects associated with norovirus infections are self-limiting, typically lasting 24-48 h. Symptoms include nausea, vomiting, diarrhoea, abdominal pain and fever. In healthy individuals, the symptoms are generally highly unpleasant but are not considered life threatening. In vulnerable groups, such as the elderly, illness is considered more serious. Theoretically, a single infectious virus particle is sufficient to cause infection, with or without disease symptoms. However, the median dose required to initiate infection is usually more than a single infectious particle. For noroviruses, this dose is unknown, but presumed to be low. Immunity to norovirus infection seems to be short-lived, on the order of several months. After this period, individuals appear to become susceptible to the same strain of virus again (Parrino et al., 1977). There is some research showing an inherent resistance in some individuals to infection with noroviruses. It is thought that these individuals may lack a cell surface receptor necessary for virus binding or may have a memory immune response that prevents infection (Hutson et al., 2003; Lindesmith et al., 2003; Cheetham et al., 2007).
Noroviruses are shed in both faecal matter and vomitus from infected individuals and can be transmitted through contaminated water. They are also easily spread by person-to-person contact. Many of the cases of norovirus gastroenteritis have been associated with groups of people living in a close environment, such as schools, recreational camps, institutions and cruise ships. Infections with noroviruses show seasonality, with a peak in norovirus infections most common during winter months (Mounts et al., 2000; Haramoto et al., 2005; Maunula et al., 2005; Westrell et al., 2006b).
4.2 Hepatitis viruses
To date, six types of hepatitis viruses have been identified (A, B, C, D, E and G), but only two types, hepatitis A (HAV) and hepatitis E (HEV), appear to be transmitted via the faecal-oral route and therefore associated with waterborne transmission. Although HAV and HEV can both result in the development of hepatitis, they are two distinct viruses.
4.2.1 HAV
HAV is a 27- to 32-nm non-enveloped, small, single-stranded RNA virus with an icosahedral symmetry. HAV belongs to the Picornaviridae family and was originally placed within the Enterovirus genus; however, because HAV has some unique genetic structural and replication properties, this virus has been placed into a new genus, Hepatovirus, of which it is the only member (Carter, 2005).
HAV infections, commonly known as infectious hepatitis, result in numerous symptoms, including fever, malaise (fatigue), anorexia, nausea and abdominal discomfort, followed within a few days by jaundice. HAV infection can also cause liver damage, resulting from the host's immune response to the infection of the hepatocytes by HAV. In some cases, the liver damage can result in death. The incubation period of HAV infection is between 10 and 50 days, with an average of approximately 28-30 days. The incubation period is inversely related to dose: the greater the dose, the shorter the incubation period (Hollinger and Emerson, 2007). Theoretically, a single infectious virus particle is sufficient to cause infection, with or without disease symptoms. However, the median dose required to initiate infection is generally more than a single infectious particle. The median dose for HAV is unknown, but is presumed to be low.
Infection with HAV occurs in both children and adults. Illness resulting from HAV infection is usually self-limiting; however, the severity of the illness increases with age. For example, minimal or no symptoms are seen in younger children (Yayli et al., 2002); however, in a study looking at HAV cases in persons over 50 years of age, a case fatality rate 6-fold higher than the average rate (average rate 0.3%) was observed (Fiore, 2004). The virus is excreted in the faeces of infected persons for 3-10 days before the development of hepatitis symptoms, leading to transmission via the faecal-oral route (Chin, 2000; Hollinger and Emerson, 2007). HAV is also excreted in the urine of infected individuals (Giles et al., 1964; Hollinger and Emerson, 2007). Convalescence may be prolonged (8-10 weeks), and in some HAV cases, individuals may experience relapses for 12 months or more (Carter, 2005).
4.2.2 HEV
HEV is a non-enveloped virus with a diameter of 30-34 nm and a single-stranded polyadenylated RNA genome. HEV was initially placed in the family Caliciviridae; however, based on its genomic organization and enzymatic capabilities, it has since been moved out of this family and currently is not assigned to a family. However, it does belong to the genus Hepevirus (Fauquet et al., 2005).
HEV infection, previously referred to as enterically transmitted non-A non-B hepatitis, is clinically indistinguishable from HAV infection. Symptoms include malaise, anorexia, abdominal pain, arthralgia, fever and jaundice. Theoretically, a single virus infectious particle is sufficient to cause infection, with or without disease symptoms. However, the median dose required to initiate infection is usually more than a single infectious particle. The median dose for HEV is unknown. The incubation period for HEV varies from 14 to 63 days. HEV infection usually resolves in 1-6 weeks after onset. Virions are shed in the faeces for a week or more after the onset of symptoms (Percival et al., 2004). The illness is most often reported in young to middle-aged adults (15-40 years old). The fatality rate is 0.5-3%, except in pregnant women, for whom the fatality rate can approach 20-25% (Matson, 2004). Illnesses associated with HEV are rare in developed countries, with most infections being linked to international travel. Although most human enteric viruses do not have non-human reservoirs, HEV has been reported to be zoonotic (transmitted from animals to humans, with non-human natural reservoirs) (AWWA, 1999a; Meng et al., 1999; Wu et al., 2000; Halbur et al., 2001; Smith et al., 2002).
4.3 Rotaviruses
Rotaviruses are non-enveloped, double-stranded RNA viruses approximately 70 nm in diameter, belonging to the family Reoviridae. These viruses have been divided into six serological groups, three of which (groups A, B and C) infect humans. Group A rotaviruses are further divided into serotypes using characteristics of their outer surface proteins, VP7 and VP4. There are 14 types of VP7 (termed G types) and approximately 20 types of VP4 (P types), generating great antigenic diversity (Carter, 2005). Although most rotaviruses appear to be host specific, there is some research indicating the potential for zoonotic transmission of rotaviruses (Cook et al., 2004; Kang et al., 2005; Gabbay et al., 2008; Steyer et al., 2008); however, it occurs infrequently.
In general, rotaviruses cause gastroenteritis, including vomiting and diarrhoea. Vomiting can occur for up to 48 h prior to the onset of diarrhoea. The severity of the gastroenteritis can range from mild, lasting for less than 24 h, to, in some instances, severe, which can be fatal. In young children, extra-intestinal manifestations, such as respiratory symptoms and seizures can occur and are due to the infection being systemic rather than localized to the jejunal mucosa (Candy, 2007). The incubation period is about 4-7 days (Carter, 2005). The illness generally lasts between 5 and 8 days. Theoretically, a single infectious virus particle is capable of causing infection, although more than one infectious virus particle is generally required. The median infectious dose for rotavirus is 5.597 (Haas et al., 1999). The virus is shed in extremely high numbers from infected individuals, possibly as high as 109/g of stool. Some rotaviruses may also produce a toxin protein that can induce diarrhoea during virus cell contact (Ball et al., 1996; Zhang et al., 2000). This is unusual, as most viruses do not have toxin-like effects.
Group A rotavirus is endemic worldwide and is the most common and widespread rotavirus group. Infections are referred to as infantile diarrhoea, winter diarrhoea, acute non-bacterial infectious gastroenteritis and acute viral gastroenteritis. Children 6 months to 2 years of age, premature infants, the elderly and the immunocompromised are particularly prone to more severe symptoms caused by infection with group A rotavirus. Group A rotavirus is the leading cause of severe diarrhoea among infants and children and accounts for about half of the cases requiring hospitalization, usually from dehydration. In the United States, approximately 3.5 million cases occur each year (Glass et al., 1996). Asymptomatic infections can occur in adults, providing another means for the virus to be spread in the community. In temperate areas, illness associated with rotavirus occurs primarily in the cooler months, whereas in the tropics, it occurs throughout the year (Moe and Shirley, 1982; Nakajima et al., 2001; Estes and Kapikian, 2007). Illness associated with group B rotavirus, also called adult diarrhoea rotavirus, has been limited mainly to China, where outbreaks of severe diarrhoea affecting thousands of persons have been reported (Ramachandran et al., 1998). Group C rotavirus has been associated with rare and sporadic cases of diarrhoea in children in many countries and regions, including North America (Jiang et al., 1995). The first reported outbreaks occurred in Japan and England (Caul et al., 1990; Hamano et al., 1999).
4.4 Enteroviruses
The enteroviruses are a large group of viruses belonging to the genus Enterovirus and the Picornaviridae family. They are 20- to 30-nm non-enveloped, single-stranded RNA viruses with an icosahedral symmetry. The members of this group that are associated with illness in humans include the polioviruses (3 serotypes), coxsackieviruses A (23 serotypes) and B (6 serotypes), echoviruses (31 serotypes) and numerous ungrouped enteroviruses (types 68-91) (Nwachuku and Gerba, 2006). Further enterovirus serotypes continue to be identified.
The incubation period and the health effects associated with enterovirus infections are varied. The incubation period for enteroviruses ranges from 2 to 35 days, with a median of 7-14 days. Many enterovirus infections are asymptomatic. However, when symptoms are present, they can range in severity from mild to life threatening. Viraemia (i.e., passage in the bloodstream) often occurs, providing transport for enteroviruses to various target organs and resulting in a range of symptoms. Mild symptoms include fever, malaise, sore throat, vomiting, rash and upper respiratory tract illnesses. Acute gastroenteritis is less common. The most serious complications include meningitis, encephalitis, poliomyelitis, myocarditis and non-specific febrile illnesses of newborns and young infants (Rotbart, 1995; Roivainen et al., 1998). Other complications include myalgia, Guillain-Barré syndrome, hepatitis and conjunctivitis. Enteroviruses have also been implicated in the aetiology of chronic diseases, such as inflammatory myositis, dilated cardiomyopathy, amyotrophic lateral sclerosis, chronic fatigue syndrome and post-poliomyelitis muscular atrophy (Pallansch and Roos, 2007; Chia and Chia, 2008). There is also some work that supports a link between enterovirus infection and the development of insulin-dependent diabetes mellitus (Nairn et al., 1999; Lönnrot et al., 2000). Although many enterovirus infections are asymptomatic, it is estimated that approximately 50% of coxsackievirus A infections and 80% of coxsackievirus B infections result in illness (Cherry, 1992). Coxsackievirus B has also been reported to be the non-polio enterovirus that has most often been associated with serious illness (Mena et al., 2003). Enterovirus infections are reported to peak in summer and early fall (Nwachuku and Gerba, 2006; Pallansch and Roos, 2007).
Enteroviruses are endemic worldwide, but few water-related outbreaks have been reported. The large number of serotypes, the usually benign nature of the infections and the fact that they are highly transmissible in a community by personal contact probably explain why so little is known of their transmission by the water route (Field et al., 1968; Lenaway et al., 1989; Ikeda et al., 1993; Kee et al., 1994; Melnick, 1996; Jaykus, 2000; Lees, 2000; Amvrosieva et al., 2001; Mena et al., 2003).
4.5 Adenoviruses
Adenoviruses are members of the Adenoviridae family. Members of this family include 70- to 100-nm non-enveloped icosahedral viruses containing double-stranded DNA. At present, there are 51 serotypes of adenoviruses; about 30% of these are pathogenic in humans, most causing upper respiratory tract infections (Carter, 2005; Wold and Horwitz, 2007). Serotypes 40 and 41 are the cause of the majority of adenovirus-related gastroenteritis. The majority of waterborne isolates are types 40 and 41; however, other serotypes have also been isolated (Van Heerden et al., 2005). Symptoms of adenovirus gastroenteritis include diarrhoea and vomiting. The incubation period lasts 3-10 days, and illness may last a week (Carter, 2005).
Adenoviruses are a common cause of acute viral gastroenteritis in children (Nwachuku and Gerba, 2006). Infections are generally confined to children under 5 years of age (FSA, 2000; Lennon et al., 2007) and are rare in adults. The viral load in faeces of infected individuals is high (~106 particles/g of faecal matter) (Jiang, 2006). This aids in transmission via the faecal-oral route, either through direct contact with contaminated objects or through recreational water and, potentially, drinking water. In the past, adenoviruses have been implicated in drinking water outbreaks, although they were not the main cause of the outbreaks (Kukkula et al., 1997; Divizia et al., 2004). The main route of exposure to adenoviruses is not through drinking water.
4.6 Astroviruses
Astroviruses are members of the Astroviridae family. Astroviruses are divided into eight serotypes (HAst1-8) that comprise two genogroups (A and B) capable of infecting humans (Carter, 2005). Members of this family include 28- to 30-nm non-enveloped viruses containing a single-stranded RNA. Astrovirus infection typically results in diarrhoea lasting 2-3 days, with an initial incubation period of anywhere from 1 to 4 days. Infection generally results in milder diarrhoea than that caused by rotavirus and does not lead to significant dehydration. Other symptoms that have been recorded as a result of astrovirus infection include headache, malaise, nausea, vomiting and mild fever (Percival et al., 2004; Méndez and Arias, 2007). Serotypes 1 and 2 are commonly acquired during childhood (Palombo and Bishop, 1996). The other serotypes (4 and above) may not occur until adulthood (Carter, 2005). Outbreaks of astrovirus in adults are infrequent, but do occur (Gray et al., 1987; Oishi et al., 1994; Caul, 1996). Healthy individuals generally acquire good immunity to the disease, so reinfection is rare. Astrovirus infections generally peak during winter and spring (Gofti-Laroche et al., 2003).
4.7 Potential emerging viruses in drinking water
Coronaviruses are members of the Coronaviridae family. Coronaviruses are enveloped, single-strand RNA viruses. Coronaviruses are primarily respiratory pathogens; they are a frequent cause of the common cold in both children and adults (McIntosh, 1970; Mäkelã, 1998). In the past, coronaviruses have not been a concern for waterborne transmission. However, a new coronavirus, the causative agent of severe acute respiratory syndrome (SARS), has been detected in faeces of infected patients. In one location during the SARS epidemic, sewage was suspected as the vehicle of transmission (WHO, 2003). Although the SARS coronavirus is potentially spread through the faecal-oral route, its major mode of transmission is person-to-person contact through respiratory secretions. However, further research is still needed to understand the persistence of this virus in the environment and, consequently, its potential transmission through a waterborne route.
Other viruses that have the potential to be transmitted by the faecal-oral route include parvoviruses, TT virus and JC virus. These viruses have all been detected in sewage (Vaidya et al., 2002; Bofill-Mass and Girones, 2003; AWWA, 2006). JC virus is also excreted in urine. It is important to note that new enteric viruses continue to be detected and recognized. These viruses have been associated with illnesses in immunocompromised individuals, such as gastroenteritis, respiratory illnesses and other more serious diseases, including progressive multifocal leukoencephalopathy and colon cancer (AWWA, 2006). Although these viruses have been detected in sewage, their transmission through water has not been documented.