Etiology

Rotavirus, astrovirus, caliciviruses such as the Norwalk agent, and enteric adenovirus are the medically important pathogens of human viral gastroenteritis (Chapter 332).

Rotaviruses are in the Reoviridae family and cause disease in virtually all mammals and birds. These viruses are a wheel-like, triple-shelled icosahedron containing 11 segments of double-stranded RNA. The diameter of the particles on electron microscopy is approximately 80 nm. Rotaviruses are classified by serogroup (A, B, C, D, E, F, and G) and subgroup (I or II). Rotavirus strains are species specific and do not cause disease in heterologous hosts. Group A includes the common human pathogens as well as a variety of animal viruses. Group B rotavirus is reported as a cause of severe disease in infants and adults in China only. Occasional human outbreaks of group C rotavirus are reported. The other serogroups infect only nonhumans.

Subgrouping of rotaviruses is determined by the antigenic structure of the inner capsid protein, VP6. Serotyping of rotaviruses, described for group A only, is determined by classic cross-neutralization testing and depends on the outer capsid glycoproteins, VP7 and VP4. The VP7 serotype is referred to as the G type (for glycoprotein). There are 10 G serotypes, of which 4 cause most illness and vary in occurrence from year to year and region to region. The VP4 serotype is referred to as the P type. There are 11 P serotypes. Although both VP4 and VP7 elicit neutralizing immunoglobulin (Ig) G antibodies, the relative role of these systemic antibodies compared with that of mucosal IgA antibodies and cellular responses in protective immunity remains unclear.

Caliciviruses, which constitute the Caliciviridae family, are small 27- to 35-nm viruses that are the most common cause of gastroenteritis outbreaks in older children and adults. Caliciviruses also cause a rotavirus-like illness in young infants. They are positive-sense, single-stranded RNA viruses with a single structural protein. Human caliciviruses are divided into 2 genera, the noroviruses and sapoviruses. Caliciviruses have been named for locations of initial outbreaks: Norwalk, Snow Mountain, Montgomery County, Sapporo, and others. Caliciviruses and astroviruses are sometimes referred to as small, round viruses on the basis of appearance on electron microscopy.

Astroviruses, which constitute the Astroviridae family, are important agents of viral gastroenteritis in young children, with a high incidence in both the developing and developed worlds. Astroviruses are positive-sense, single-stranded RNA viruses. They are small particles, approximately 30 nm in diameter, with a characteristic central 5- or 6-pointed star when viewed on electron microscopy. The capsid consists of 3 structural proteins. There are 8 known human serotypes.

Enteric adenoviruses are a common cause of viral gastroenteritis in infants and children. Although many adenovirus serotypes exist and are found in human stool, especially during and after typical upper respiratory tract infections (Chapter 254), only serotypes 40 and 41 cause gastroenteritis. These strains are very difficult to grow in tissue culture. The virus consists of an 80-nm-diameter icosahedral particle with a relatively complex double-stranded DNA genome.

Aichi virus is a picornavirus that has been associated with gastroenteritis and was initially described in Asia. Several other viruses that may cause diarrheal disease in animals have been postulated but not well established as human gastroenteritis viruses. These include coronaviruses, toroviruses, and pestiviruses. The picobirnaviruses are an unclassified group of small (30 nm), single-stranded RNA viruses that have been found in 10% of patients with HIV-associated diarrhea.

Epidemiology

Worldwide, rotavirus is estimated to cause >111 million cases of diarrhea annually in children younger than 5 yr. Of these, 18 million cases are considered at least moderately severe, with approximately 500,000 deaths per year. Rotavirus causes 3 million cases of diarrhea, 80,000 hospitalizations, and 20-40 deaths annually in the USA.

Rotavirus infection is most common in winter months in temperate climates. In the USA, the annual winter peak spreads from west to east (Fig. 257-1). Unlike the spread of other winter viruses, such as influenza, this wave of increased incidence is not due to a single prevalent strain or serotype. Typically, several serotypes predominate in a given community for 1 or 2 seasons, while nearby locations may harbor unrelated strains. Disease tends to be most severe in patients 3-24 mo of age, although 25% of the cases of severe disease occur in children >2 yr of age, with serologic evidence of infection developing in virtually all children by 4-5 yr of age. Infants younger than 3 mo are relatively protected by transplacental antibody and possibly breast-feeding. Infections in neonates and in adults in close contact with infected children are generally asymptomatic. Some rotavirus strains have stably colonized newborn nurseries for years, infecting virtually all newborns without causing any overt illness.

Figure 257-1 Peak rotavirus activity by month in the USA for July 1996–June 1997. This pattern is typical of the annual rotavirus activity each year.

(From the Centers for Disease Control and Prevention: Laboratory-based surveillance for rotavirus—United States, July 1996-June 1997, MMWR Morb Mortal Wkly Rep 46:1092–1094, 1997.)

Rotavirus and the other gastrointestinal viruses spread efficiently via a fecal-oral route, and outbreaks are common in children’s hospitals and child-care centers. The virus is shed in stool at very high concentration before and for days after the clinical illness. Very few infectious virions are needed to cause disease in a susceptible host.

The epidemiology of astroviruses is not as thoroughly studied as that of rotavirus, but they are a common cause of mild to moderate watery winter diarrhea in children and infants and an uncommon pathogen in adults. Hospital outbreaks are common. Enteric adenovirus gastroenteritis occurs year-round, mostly in children younger than 2 yr. Nosocomial outbreaks occur but are less common than with rotavirus and astrovirus. Calicivirus is best known for causing large, explosive outbreaks among older children and adults, particularly in settings such as schools, cruise ships, and hospitals. Often a single food, such as shellfish or water used in food preparation, is identified as a source. Like astrovirus and rotavirus, caliciviruses are also commonly found in winter infantile gastroenteritis.

Pathogenesis

Viruses that cause human diarrhea selectively infect and destroy villus tip cells in the small intestine. Biopsies of the small intestines show variable degrees of villus blunting and round cell infiltrate in the lamina propria. Pathologic changes may not correlate with the severity of clinical symptoms and usually resolve before the clinical resolution of diarrhea. The gastric mucosa is not affected despite the commonly used term gastroenteritis, although delayed gastric emptying has been documented during Norwalk virus infection.