Viral Gastroenteritis



Viral Gastroenteritis


Angela J. Peck

Joseph S. Bresee



Viral gastroenteritis is a major cause of pediatric morbidity worldwide, and in developing countries, it is a leading cause of mortality. The medically important human gastroenteritis viruses include rotaviruses, caliciviruses, adenoviruses, and Astroviruses (Table 207.1). A variety of other viruses, such as coronaviruses, toroviruses, and picobirnaviruses, have been associated with gastroenteritis, but their clinical and public health importance remain unclear.


ROTAVIRUS

Rotaviruses are the most common cause of severe, dehydrating diarrhea among infants and young children worldwide. Rotaviruses cause an estimated 440,000 deaths each year among children younger than 5 years of age, and they cause 25% to 50% of all hospitalizations for gastroenteritis. Because of the high prevalence of rotavirus disease, several rotavirus vaccine candidates have been developed as a key strategy to prevent childhood mortality in developing countries and hospitalizations in developed countries.


Virology and Pathogenesis

Rotaviruses were discovered in 1973 by Bishop and colleagues in Australia, who found the viruses by using electron microscopy on duodenal biopsies from children with acute diarrhea. Soon after the initial discovery, virus also was detected in stool specimens of patients with gastroenteritis. By electron microscopy, rotaviruses are approximately 70 nm in diameter and have a wheel-shaped morphology (Latin, rota = “wheel”). Rotaviruses are nonenveloped viruses that belong to the family Reoviridae. They have three layers, including an inner and outer capsid surrounding an inner core, which contains a genome of 11 segments of double-stranded RNA. Rotaviruses are classified primarily by group (A to G) and serotype. Group designation is determined by antigenic type of the major capsid protein, VP6, which forms the inner capsid of rotavirus. Although seven distinct antigenic groups have been described, group A viruses are the major cause of most human rotavirus infections. Group B rotaviruses have been reported in large diarrheal outbreaks in China and sporadic cases in India and Bangladesh, and group C has been associated with occasional outbreaks of gastroenteritis and possibly with biliary atresia, but neither appears to be a common cause of illness. None of the other groups has been found to cause human disease.








TABLE 207.1. THE RELATIVE CONTRIBUTIONS OF VIRAL PATHOGENS AS CAUSES OF CHILDHOOD GASTROENTERITIS AMONG CHILDREN IN COMMUNITIES AND THOSE REQUIRING HOSPITALIZATION




































  Percent of Cases
Community-Based Hospital-Based
Rotaviruses 5–20 25–50
Caliciviruses 10–25 20–30
Astroviruses 10–25 5–10
Adenoviruses 40/41 10–15 5–12
Coronaviruses 1–3 1–2
Toroviruses Unknown 0–3.5
Picobirnaviruses Unknown <1

Group A rotaviruses are classified further on the basis of a dual classification scheme, based on two outer capsid proteins, that combines serotypic designation of VP7 (G serotype) and the genotypic designation of VP4 (P genotype). VP7 and VP4 are viral proteins that make up the outer capsid of the virus and are responsible primarily for eliciting an immune response to the virus in humans. Five (G1 to G4 and G9) of the 14 identified G types currently account for 80% to 90% of human infections. Of the 20 known P types, three (P[4], P[6], and P[8]) account for more than 90% of strains detected.

Although the genes that code for the VP7 and VP4 of rotaviruses segregate independently, only a few combinations of G and P types are responsible for the majority of infections. P[8],G1 strains are the predominant viruses worldwide, particularly in North America, with four other strains (P[4],G2; P[8],G3; P[8],G4; and P[6],G9) accounting for the majority of the other infections. Even so, rotavirus strains can be quite diverse, with a variety of strains prevalent in a community at any time, and serotype prevalence may change from season to season. Strain diversity is an especially common presence in developing countries. Thus, one challenge of developing vaccines has been to ensure that a vaccine can protect against a variety of naturally occurring strains.

Rotaviruses infect the mature upper villous enterocytes of the small intestine, which have both digestive and absorptive functions. The infectious dose is low (102 to 103 virus particles), but large amounts of rotavirus (1012 virus particles per gram) are shed in stool during acute infection, rendering transmission quite easy to occur. Diarrhea that occurs as a result of rotavirus infection is likely caused by a combination of osmotic diarrhea, resulting from loss of absorptive function due to loss of mature enterocytes, and secretory diarrhea, due to the opening of calcium channels, which results in an influx of calcium and efflux of sodium and water (associated with a nonstructural viral protein, NSP4). The intraenterocyte calcium concentration also leads to cell death. In a normal host, infection resolves as the number of susceptible mature enterocytes decreases due to cell death and as the host generates an immune response. Rotavirus is present in stool 1 to 2 days before onset of symptoms and generally is excreted for 2 to 3 weeks after cessation of diarrhea; however, by using sensitive molecular detection methods, researchers have detected virus in stool for up to 2 months after severe disease in young children. Recent studies have detected rotavirus antigen and nucleic acid in the blood of ill children and animals, indicating that rotavirus infection
may be associated with viremia in some cases. The implications for diagnostics from these findings and the rate of this manifestation are unclear.








TABLE 207.2. CHARACTERISTICS OF VIRAL AGENTS OF GASTROENTERITIS


































































Characteristic Rotavirus Calicivirus Astrovirus Adenovirus
Predominant age of illness <5 years All ages <2 years <2 years
Incubation period 1–3 days 12–48 hours 1–4 days 3–10 days
Symptoms
   Diarrhea Explosive, watery (5–10 episodes/day) Watery with acute onset Watery; milder than rotavirus Watery; milder than rotavirus; can be prolonged
   Vomiting 80%–90% >50% Less common than rotavirus Less common than rotavirus
   Fever Frequent Less common, usually mild Less common, usually mild Less common, usually mild
Illness duration 2–8 days Norovirus: 1–5 days
Sapovirus: 1–4 days
1–5 days 3–10 days
Mode of transmission Person to person via fecal–oral route, fomites Person to person via fecal–oral route, fomites, food/water Person to person via fecal–oral route Person to person via fecal–oral route
Principal methods of clinical diagnosis Stool EIA or LPA None available Stool EIA (not available in the United States) Stool EIA
Other diagnostic assays RT-PCR, EM, IEM, PAGE, serum EIA, virus isolation RT-PCR, EM, IEM, stool or serum EIA RT-PCR, EM, IEM, serum EIA, virus isolation RT-PCR, EM, IEM, virus isolation
EIA, enzyme immunoassay; EM, electron microscopy; IEM, immune electron microscopy; LPA, latex particle agglutination; PAGE, polyacrylamide gel electrophoresis; RT-PCR, reverse transcriptase-polymerase chain reaction.


Epidemiology

Rotavirus gastroenteritis may occur in any age group but is most common in the first 5 years of life (Table 207.2). Most cases of severe, dehydrating gastroenteritis occur among children between 4 and 24 months of age, corresponding to the period in which the first infection with rotavirus occurs after immunity wanes from maternally acquired antibodies. Rotavirus illness generally occurs less frequently and less severely with age as a child develops immunity after having recurrent infections. Infections generally are sporadic, but outbreaks also are common occurrences among children in child-care settings. Adults, particularly those caring for rotavirus-infected children, can be infected, and outbreaks can occur when new antigenic strains of rotavirus emerge. By the time they reach age 5, more than 80% of children have serologic evidence of infection.

Worldwide, rotavirus causes approximately 2 million hospitalizations and a median of 440,000 deaths per year in children younger than 5 years of age, with deaths among children in the poorest countries accounting for more than 90% of the total. In hospital-based studies, rotavirus has been found to be responsible for 25% to 50% of the cases of acute gastroenteritis, and rotavirus has been found to cause 5% to 40% of cases in community-based studies. A higher prevalence in hospital-based studies reflects the more severe disease caused by rotavirus compared with other agents causing gastroenteritis. Children living in developing countries are more likely to have rotavirus gastroenteritis at a younger age and to be infected with uncommon serotypes. Estimates of disease burden indicate that in developed countries, hospitalization rates for rotavirus are between 2.5 and 5 per 1,000 in children aged younger than 5 years, whereas in developing countries it may be as high as 30 per 1,000. In an assessment of the annual impact of rotavirus on the 1997 U.S. birth cohort, the Centers for Disease Control and Prevention (CDC) estimated that 70% (2,730,000) of the cohort was infected and 1 in 80 U.S. children were hospitalized for rotavirus infection. Deaths from rotavirus among children in the United States and other developed countries are rare occurrences (approximately 20 to 40 deaths occur annually in the United States) due to the availability of rehydration therapy and early access to health care. The total annual economic burden in the United States of rotavirus disease was $1 billion in 1997.

Rotavirus is transmitted person-to-person most likely by the fecal-oral routes, but researchers have hypothesized that respiratory transmission through large-droplet spread may play a role. Occasional outbreaks have occurred with evidence of foodborne and waterborne transmission, but these appear to occur rarely in developed countries. Rotavirus can be found on toys and hard surfaces in child-care centers, indicating that fomites also may play a role in transmission. Although rotavirus can infect many animal species and molecular analysis of some rotavirus strains has suggested the presence of animal and human genes, transmission from animals to humans is likely to be quite rare.

In general, the first episode of rotavirus diarrhea is the most likely to be severe and confers protection against subsequent symptomatic infection. Each subsequent infection generally leads to milder illness. Asymptomatic rotavirus infection does occur and may account for most of infections in older children, but stools from asymptomatic controls rarely are rotavirus-positive. Hence, detection of rotavirus in stool samples of children with gastroenteritis should be considered as confirmation of the cause of the illness and not as an incidental finding.

Rotavirus gastroenteritis occurs predominantly during winter months in countries with temperate climates. In North America, the annual season starts in autumn in Mexico and the southwestern United States and moves sequentially from the Southwest to the Northeast, ending in spring in maritime
Canada. In the United States, summertime rotavirus infections are rare occurrences and often are associated with immunocompromised children or with errors in laboratory tests. Seasonality is less evident within tropical climates, where year-round disease commonly occurs, although disease often peaks in cool, dry months even in tropical areas.


Clinical Characteristics

Rotavirus has a mean incubation period of 1 to 3 days. Neonates are more likely to have asymptomatic infection because they have protection by transplacentally acquired maternal antibody and by antibodies and other factors in breast milk. Infants and young children typically have fever and abrupt onset of vomiting, followed by frequent, foul-smelling, watery stools. Vomiting and fever often precede diarrhea and resolve by the second or third day of illness, whereas diarrhea persists for several more days. In hospitalized patients, diarrhea lasts a median of 6 days (range 2 to 23 days). Stools generally do not contain blood or fecal leukocytes. Symptoms and asymptomatic viral shedding can be prolonged substantially in immunocompromised patients.

Other common clinical features include isotonic dehydration, compensated metabolic acidosis, and malabsorption. Simultaneous respiratory symptoms may occur but likely are due to concurrent wintertime respiratory viral infections. Recent case reports have indicated that rotavirus may be an uncommon cause of encephalitis. In addition, other extraintestinal rotavirus manifestations, including acute myositis, hemophagocytic lymphohistiocytosis, and polio-like paralysis, have been described, but their relationship to rotavirus infection remains unclear.


Diagnosis

Sensitive and specific assays to detect rotavirus antigen in stools are available and offer an easy and inexpensive method to diagnose the disease in children. Both enzyme immunoassays (EIAs) and latex particle agglutination tests for group A rotavirus detection are available commercially. These tests generally have a high (90% to 95%) sensitivity and specificity. Stool samples collected during the acute phase of illness are likely to contain sufficient virus for detection, and these assays sometimes can detect virus in stool samples obtained the week after symptoms have resolved.

Other methods for rotavirus detection include electron microscopy, viral isolation, polyacrylamide gel electrophoresis (PAGE) of RNA extracted directly from stool, and reverse transcriptage-polymerase chain reaction (RT-PCR), but these methods are used primarily in research or public health settings rather than for clinical diagnosis. PAGE has an advantage of being relatively simple and having good specificity (100%) and sensitivity (80% to 90%), and it can be performed relatively inexpensively in tropical countries without specific rotavirus reagents. PAGE also can be used for typing strains because the electrophoretic pattern of the 11 double-stranded RNA segments varies among human rotavirus strains. RT-PCR is more sensitive than are other methods and allows for detection of rotavirus in settings in which the virus titer might be quite low, such as late in the course of illness or in extraintestinal sites. However, the expense and expertise required to perform RT-PCR render its use impractical in most clinical settings. Serologic testing for rotavirus infection is possible but impractical, so it is not widely available in clinical care settings. Immune histochemical stains have been developed that allow for the identification of rotavirus antigen in pathologic tissues, and they are available in some research and public health settings. In some cases, rotavirus can be detected using simple EIA for antigen detection on serum from ill children.


CALICIVIRUSES

Human caliciviruses were the first viral agents to be associated with gastroenteritis, when in 1972, Norwalk virus was identified by Kapikian and colleagues from the U.S. National Institutes of Health. The virus was detected using immune electron microscopy on stool specimens from human volunteers infected with stool filtrates collected during an outbreak of gastroenteritis in Norwalk, Ohio. Caliciviruses may be the most common causes of gastroenteritis outbreaks and are appreciated increasingly as common causes of sporadic childhood vomiting and diarrhea.

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Jul 24, 2016 | Posted by in ORTHOPEDIC | Comments Off on Viral Gastroenteritis
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