Current Diagnosis & Treatment in Infectious Diseases

Section IV - Viral Infections

38. Other Gastrointestinal Viruses

Lawrence W. Drew MD, PhD

HUMAN ENTERIC CALICIVIRUSES: NORWALK & RELATED VIRUSES

Essentials of Diagnosis

  • Diarrhea, occurring in an outbreak especially in a closed environment.
  • Tends to infect older children and adults rather than infants.
  • Nausea and vomiting are common; bloody stools are rare.
  • Incubation period 1–2 days; illness 1–4 days.
  • Laboratory diagnosis by seroconversion; only performed in epidemiologic studies.

General Considerations

  1. Epidemiology.Even in developed countries, antibodies to caliciviruses are nearly universal by age 5. Infections tend to occur in family or community outbreaks. In underdeveloped countries, infection by these viruses occurs presumably as a result of poor sanitation. In developed countries, outbreaks that occur year-round have been described in schools, resorts, hospitals, nursing homes, restaurants, and cruise ships. The primary method of spread is fecal-oral, but contaminated water or shellfish has accounted for common-source outbreaks. A measure of the importance of these agents is that ~ 10% of all gastroenteritis outbreaks and up to 90–95% of those that are nonbacterial are attributed to them. In contrast to infants, who are more often infected by rotaviruses, calicilike viruses cause disease primarily in older children and adults (Box 38-1). Immunity is probably short-lived at best, suggesting that humoral antibody is not adequately protective. The incubation period is 1–2 days, and shedding can persist for 1–2 weeks. The virus is not inactivated by chlorine, freezing, or heating to 60(C.
  2. Microbiology.The Norwalk agent and related viruses are classified as caliciviruses, although they are also similar in appearance to parvoviruses and hepatitis A virus. Among the other human enteric caliciviruses are the Hawaii, Snow Mountain, and Sapporo viruses, which are named for where these strains were first detected. The human enteric caliciviruses are now divided into two genera, provisionally named “Norwalk-like viruses” and “Sapporo-like viruses.” None of these viruses can be isolated in tissue culture, but their viral nature was established by electron microscopic (EM) examination of feces, using antibodies to enhance detection (immune electron microscopy [IEM]).

Norwalk and human enteric caliciviruses are among the smallest of all viruses, only 27–38 nm in diameter. They are spherical, with 32 cup-shaped surface depressions. No envelope exists, and they exhibit icosahedral symmetry. The nucleoprotein of calicivirus is single-stranded RNA with a molecular weight of approximately 2.6 × 106 daltons. The details of attachment and penetration are uncertain. Replication occurs in the cytoplasm, with release of viral particles accomplished by cell destruction.

  1. Pathogenesis.Jejunal biopsy in human volunteers infected with Norwalk viruses reveals blunting of villi, cytoplasmic vacuolation, and infiltration with mononuclear cells, but virus particles are not detected by EM of epithelial cells. The virus appears to cause a decrease in brush border enzymes and in turn malabsorption. Infection is not associated with a leukocyte response in stool samples.

Clinical Findings

  1. Signs and Symptoms.Although calicilike viruses are typically associated with diarrheal illness, nausea and vomiting may occur frequently, especially in children. Bloody stools do not occur. Fever may be present in up to one-third of patients. The incubation period is 24–48 h, and the illness lasts 1–4 days.
  2. Laboratory Findings.There are no characteristic blood or stool abnormalities; fecal leukocytes are absent.
  3. Differential Diagnosis.The differential diagnosis includes gastroenteritis of any etiology, especially other viruses. Winter diarrhea in infants and children is more likely caused by rotavirus.

BOX 38-1 Other Gastrointestinal Infections

 

Children

Adults

More Common

· Norwalk virus and other enteric calciviruses

 

Less Common

· Astrovirus

· Adenovirus

· Norwalk virus

BOX 38-2 Treatment of Other Gastrointestinal Infections

 

Children

Adults

First Choice

· Symptomatic

· Symptomatic

Diagnosis

  1. Culture.None of the Norwalk or human enteric caliciviruses can be grown in tissue culture, although the development of a sensitive culture assay is a high priority.
  2. Direct Detection.Standard EM of feces is usually negative for the Norwalk agent because they are present in low titer. Other caliciviruses may be present in sufficient concentration to permit detection. IEM is the main method of detection of Norwalk-type viruses but is rarely used except in research settings. IEM consists of examining the sample by EM after the addition of an antibody directed against the suspected agent. The antibody causes the virus to aggregate, facilitating recognition. Reverse transcription-polymerase chain reaction, enzyme immunoassay, and radioimmunoassay (RIA) detection of Norwalk antigen are alternative methods that are more sensitive than IEM, but are generally available only in research settings.
  3. Serology.Seroconversion is the method used to identify most infections. Antibody to the Norwalk agent may be detected by RIA or immune adherence hemagglutination assay (IAHA). Antibodies to the other calicilike agents are more difficult to detect.

Treatment (Box 38-2)

No specific treatment is available. Bismuth subsalicylate may reduce gastrointestinal symptoms.

BOX 38-3 Control of Other Gastrointestinal Infections

Prophylactic Measures

Good personal hygiene

Isolation Precautions

 

Prognosis

The prognosis is excellent for full recovery.

Prevention & Control (Box 38-3)

Outbreaks may be minimized by handling food carefully and maintaining the purity of the water supply.

ASTROVIRUSES

General Considerations

Astroviruses are small (28- to 38-nm) RNA viruses that exhibit five or six points on their surface. They have been seen in fecal specimens by EM, especially in infants and children with mild gastroenteritis. There are at least seven human serotypes. The route of spread is probably fecal-oral; > 70% of children acquire antibody by age 5 years. Infections occur sporadically rather than in outbreaks. Although detection by culture procedures or techniques is only partly successful, astroviruses have been isolated from humans, cows, cats, dogs, pigs, and sheep.

ADENOVIRUS

Adenoviruses, particularly the high numbered serotypes (38 and, especially, 40 and 41) are associated with gastroenteritis. (See Chapter 32 for an extensive consideration of adenoviruses.) The enteric adenoviruses are very difficult to grow in tissue culture but are detected by EM or EIA. They cause 5–15% of viral gastroenteritis in young children. The average incubation period is 10 days, much longer than the average of 1–2 days for the other viral causes of gastroenteritis. Most disease is in infants and young children and occurs sporadically rather than in outbreaks. The method of spread is fecal-oral.

REFERENCES

Blacklow NR, Greenberg HB: Viral gastroenteritis. N Engl J Med 1992;325:252. (A review of the biology and epidemiology of enteric viruses.)

Hedberg CW, Osterholm MT: Outbreaks of food-borne and water-borne viral gastroenteritis. Clin Microbiol Rev 1993;6:199. (A review including the Norwalk agent.)

Kapikian AZ: Viral gastroenteritis. J Am Med Assoc 1993;269:627. (Concise, well-referenced overview of the relative importance of these various agents.)