Sapporo virus: history and recent findings

Morphologically distinct caliciviruses of human origin were first found in stools of children with gastroenteritis in 1976. Sapporo virus, or human calicivirus Sapporo, with typical surface morphology was first detected during a gastroenteritis outbreak in a home for infants in Sapporo, Japan, in 1977. Since then, morphologically and antigenically identical virus has been detected frequently in the same institution in association with outbreaks of gastroenteritis. Sapporo virus is widely distributed worldwide, as evidenced by the appearance of antigenically or genetically similar viruses and seroepidemiologic findings. Sapporo virus plays an important role in outbreaks of infantile gastroenteritis and is less important in foodborne outbreaks. Sapporo virus has been approved as the type species of the genus "Sapporo-like viruses in the family Caliciviridae. The history of and recent findings, as obtained by newly developed techniques, about Sapporo viruses are presented.     

The epidemiology of enteric caliciviruses from humans: a reassessment using new diagnostics

In the United States, acute gastroenteritis is one of the most commonly noted illnesses on hospital discharge records and death certificates, yet few of these cases have an etiologic diagnosis. The application of new molecular diagnostic methods has shown caliciviruses (previously referred to as the Norwalk family of viruses or small round structured viruses) to be the most common cause of acute gastroenteritis (AGE) outbreaks in the United States, and they may emerge as a common cause of sporadic cases of AGE among both children and adults. Novel molecular methods have permitted outbreak strains to be traced back to their common source and have led to the first identification of virus in implicated vehicles of infection-water, shellfish, and foods contaminated both at their source and by food handlers. The broad application of these methods to routine diagnosis in hospitals and public health laboratories is advancing our appreciation of the full burden of calicivirus-associated diarrhea, and it is opening new avenues for its prevention and control.     

Epidemiology of calicivirus infections in Sweden, 1994-1998

Outbreaks of acute gastroenteritis are frequently caused by caliciviruses. Electron microscopy was used to search for these viruses in fecal samples from patients with acute gastroenteritis. Of 5800 samples collected and analyzed from November 1994 to June 1998, 3700 were associated with outbreaks. A total of 676 outbreaks were analyzed, and viruses were found in 67%. Caliciviruses, usually Norwalk-like viruses (NLVs), were found in 407 (89%) of 455 outbreaks, while Sapporo-like viruses were identified in nine outbreaks, including six that were suspected to include foodborne transmission. Sixty percent of the 1041 patients with calicivirus infections were between 70 and 90 years of age. Food- and waterborne infections were associated with 66 calicivirus outbreaks. Virus-positive outbreaks were documented mainly during winter and spring. The longitudinal survey showed that caliciviruses, and especially the NLVs, cause most nosocomial and community-associated outbreaks in Sweden.     

A large nontypical outbreak of Norwalk virus. Gastroenteritis associated with exposing celery to nonpotable water and with Citrobacter freundii.

The US Air Force Academy experienced a point-source outbreak of gastroenteritis originally believed to be caused by Salmonella. The overall attack rate was 48% among approximately 3000 cadets and staff. Food-specific attack rates implicated chicken salad. The odds ratio for chicken salad consumption in ill cadets was 10.7 (95% confidence interval: 8.2; 13.8). The celery component had been exposed to nonpotable water. Citrobacter freundii were statistically associated with consumption of the suspected vehicle and subsequent illness. Most aspects were consistent with the epidemiology of Norwalk gastroenteritis. However, the clinical presentation was not typical of reported outbreaks. One hundred five cadets required intravenous rehydration. Serum samples implicated Norwalk virus as the most probable cause of this outbreak. The Centers for Disease Control (Atlanta, Ga) recently began national surveillance for viral gastroenteritis. All outbreaks of gastroenteritis associated with nonpotable water should be investigated for evidence of viral cause.     

Role of Norwalk virus in outbreaks of nonbacterial gastroenteritis.

Twenty-five separate outbreaks of nonbacterial gastrointestinal illnesses were studied serologically for evidence of infection with the Norwalk virus and the rotaviruses that affect humans. Eight of 25 outbreaks appeared to be related to the Norwalk virus. In one of the 25 outbreaks, there was evidence of rotavirus infection. These observations suggest that the Norwalk virus or serologically related agents play an important role in epidemic nonbacterial gastroenteritis in adults and older children.     

Novel agents of viral enteritis in humans

Considerable information has recently emerged regarding certain "groups" of novel viruses associated with gastroenteritis in humans. The viruses reviewed here are 20-35 nm in diameter and can be detected in the stools of acutely ill individuals with gastroenteritis. These viruses can be conveniently divided into four "groups": Norwalk-like agents, caliciviruses, astroviruses, and other small round viruses. The evidence for the etiologic association of these agents with gastroenteritis varies from agent to agent but is most extensive for the Norwalk-like agents, of which the Norwalk serotype is a major cause of epidemic gastroenteritis. Human caliciviruses appear to be relatively common causes of gastroenteritis in children, particularly in Japan and the United Kingdom. Astroviruses have been reported as occasional causes of gastroenteritis in children and adults in various parts of the world. The epidemiological significance of the other small round viruses is unknown. Because of the difficulty of cultivating these agents in vitro, biochemical and antigenic characterization of these agents is incomplete. An understanding of the pathogenesis of disease and of the roles of immune responses to infection is similarly at a primitive stage. The recent development of sensitive and efficient assays for detection of several of these agents and the reports that certain strains of human caliciviruses and astroviruses can be cultivated in vitro should facilitate characterization and epidemiological studies of these agents. Systematic, prospective epidemiological studies of these agents in well-defined populations of various age groups are sorely needed for definition of the relative importance of each agent in human disease. Such information is essential for the consideration of appropriate control measures.     

A predominant role for Norwalk-like viruses as agents of epidemic gastroenteritis in Maryland nursing homes for the elderly.

Stool specimens from 156 Maryland nursing home residents, who became ill during 20 outbreaks of gastroenteritis from November 1987 through February 1988, were analyzed. All tested negative for astroviruses, enteroviruses, Group A rotaviruses, Sapporo-like caliciviruses, and enteric bacteria (i.e., Salmonella, Clostridium, and Shigella species). Eighty-two (52%) were positive for Norwalk-like viruses (NLVs), members of the family Caliciviridae. Six distinct genetic clusters within genogroups I and II of the NLVs were detected; a genogroup II (GII) virus closely related to the Camberwell virus in the NLV GII/4 genetic cluster was the predominant strain. Serologic evidence of infection with > or = 1 NLV was detected in 61 (56%) of 109 patients tested against 3 NLV antigens (i.e., Norwalk, Hawaii, and Toronto viruses). Sixteen (80%) outbreaks met the definition for an NLV outbreak. Taken together with a retrospective analysis of bacterial gastroenteritis in this same setting, these data support a major role for NLVs as etiologic agents of gastroenteritis in elderly persons.     

Norwalk virus vaccines: challenges and progress

Human caliciviruses (HuCVs) are the major cause of outbreaks of acute nonbacterial gastroenteritis throughout the world. An increasing recognition of the clinical significance of these viruses as human pathogens causing foodborne and waterborne disease indicates that an effective vaccine would be useful. This article reviews the current challenges that exist for the development of a vaccine for the HuCVs as well as the status of development of a candidate vaccine. HuCVs are viruses that exhibit a restricted tropism for infection of the gastrointestinal tract of humans, and a volunteer model of infection and disease is available. As pathogens with a restricted host range, the HuCVs are excellent models for understanding the mechanisms that mediate and regulate viral infection of the gastrointestinal tract and mucosal immunity in humans.     

Viral infections of the gastrointestinal tract

Acute gastroenteritis is common in adults. It can occur in institutional epidemics or epidemics of food-borne illness; in these cases, caliciviruses are the major cause of the condition. When acute gastroenteritis occurs in nonepidemic form, its causes are less clear. It may be due to caliciviruses or to the less common serotypes of childhood gastroenteritis viruses, such as rotavirus, astrovirus, and adenovirus. The pathogenesis of acute viral gastroenteritis is not completely understood. Old evidence suggests that mild villus damage is responsible, but new evidence indicates that active secretion and motility disturbance may be involved in the production of symptoms. Five common viruses can remain latent in gastrointestinal tissues and produce disease many years after initial infection. Two major herpesviruses, cytomegalovirus and herpes simplex virus, cause ulcerative disease of the gastrointestinal tract. This disease occurs in healthy persons but is more common and more severe in immunocompromised patients. Three other viruses — Epstein-Barr virus, human papilloma virus, and human herpesvirus-8 — are implicated in benign and malignant proliferative diseases of the gastrointestinal tract. Epstein-Barr virus has been associated with immunoproliferative disease after transplantation and may also cause small-bowel and colonic lymphoma in healthy adults. It causes most AIDS-related lymphomas. Human papillomaviruses cause anorectal condyloma and anal cancer. Human herpesvirus-8 causes gastrointestinal Kaposi sarcoma.     

Viral hepatitis and gastroenteritis transmitted by shellfish and water

The epidemiology and clinical presentation of water-borne viral diseases, including shellfish-associated viral illnesses, are discussed in this article. Hepatitis A virus, Non A-Non B hepatitis and the agents of viral gastroenteritis, Norwalk agent, Snow Mountain agent, rotavirus, the small round viruses, caliciviruses, and astroviruses are included. The technical problems associated with evaluating the viral contamination of water or shellfish are noted.     

Surveillance of viral gastroenteritis in Japan: pediatric cases and outbreak incidents

Surveillance results from pediatric cases and outbreaks of viral gastroenteritis in Japan are presented. In winter, both small round structured virus (SRSV, or Norwalk-like viruses) and rotavirus were detected from infants with gastroenteritis; however, in recent years, the prevailing time of SRSV infection has preceded that of rotavirus infection. Most nonbacterial gastroenteritis outbreaks were related to SRSV infection, and >60% of the outbreaks were caused by contaminated food. In small-sized outbreaks, raw oysters were the primary source of transmission. In large-sized outbreaks, school lunches and catered meals that were served at schools, banquet halls, and hospitals were most often implicated in the transmission of foodborne gastroenteritis.     

Molecular epidemiology of human enteric caliciviruses in The Netherlands

In The Netherlands, illness due to Norwalk-like viruses (NLVs) of the family Caliciviridae is quite common. NLVs cause >80% of the outbreaks of gastroenteritis reported to municipal public health centers and at least 5% of the cases of gastroenteritis for which a general practitioner is consulted. In addition, up to 18% of community cases of gastroenteritis in the 1998/1999 winter season have been attributed to NLVs. Patterns of disease activity differ remarkably, with "normal years, when outbreaks occur that are caused by different types of NLV, and "epidemic years, when outbreaks appear to be caused by a single strain. This observation suggests selection of antigenic variants with increased virulence or altered modes of transmission. In addition, since caliciviruses related to the NLVs from humans have been detected in stool specimens from calves at 45% of the dairy farms in The Netherlands, the possibility of spillover of epidemic strains from an animal reservoir to humans should be considered.     

Diagnosis of astrovirus gastroenteritis by antigen detection with monoclonal antibodies

An enzyme-linked immunosorbent assay (ELISA), based on monoclonal antibodies to the astrovirus group antigen, was designed for the detection of astroviruses in stools of patients with gastroenteritis. Compared to immune electron microscopy used as the standard test, the sensitivity of the astrovirus ELISA was 91% (31/34) and the specificity was 96% (54/56). All five of the known astrovirus serotypes could be detected in 16 samples on which serotyping was done. In tests on 155 stools containing other enteric viruses, including adenoviruses, rotaviruses, caliciviruses, Hawaii virus, Snow Mountain virus, and Norwalk virus (30, 20, 70, 24, 4, and 7 samples, respectively), only 3 were positive in the astrovirus ELISA. The combined specificity for all astrovirus immune electron microscopy-negative samples was 98% (206/211). The results demonstrate that the new ELISA provides a sensitive and specific means for the diagnosis of astrovirus gastroenteritis.     

A review of viral gastroenteritis

PURPOSE OF REVIEW: Since Kapakian first identified a virus in the stool of a patient with diarrhoea in 1972, many viruses have been described that cause diarrhoea directly or indirectly. It is now appreciated that viruses are the most common cause of diarrhoeal illness worldwide. Although bacteria and other pathogens cause significant numbers of gastroenteritis, it is the viruses that are dealt with in this review. The viruses responsible will be discussed individually. RECENT FINDINGS: Rotavirus remains the leading cause of diarrhoeal disease overall, with the newly designated calicivirus family causing the most outbreaks in the industrialized nations. As diagnostic techniques improve, however, the importance of astrovirus and other previously under-reported pathogens is becoming more apparent and the number of viruses associated with gastroenteritis continues to increase. The emergence of severe acute respiratory syndrome coronavirus, arguably the most important emerging infection of recent years and a cause of significant gastrointestinal disease, is also discussed. SUMMARY: No effective treatments have been developed for viral gastroenteritis. Current efforts are targeted at the development of suitable vaccines and the implementation of infection control measures.     

Immunity to calicivirus infection

The evolution of our understanding of immunity to calicivirus infection, using Norwalk virus as the prototype, is discussed in three stages: (1) "ancient times (1972-1978), when human volunteer studies prevailed, (2) the "middle ages (1978-1990), which were characterized by the development and implementation of solid-phase immunoassays based on native viral antigens, and (3) "modern times (1990 to present), which began with the cloning of the genome of the noncultivatable 8FIIa strain of Norwalk virus and resulted in a readily available source of recombinant virus-like particles that have revolutionized the study of caliciviruses. Throughout these stages, it has been shown repeatedly that short-term immunity develops to homologous virus. However, the search for determinants of long-term immunity continues. These studies will likely be facilitated by the newest reagents-the noninfectious recombinant virus-like particles-used in the setting of human volunteer studies and large epidemiologic studies.