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      Norwalk Virus Shedding after Experimental Human Infection

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          Abstract

          Noroviruses are shed in feces up to 8 weeks after infection.

          Abstract

          Noroviruses are the most common cause of viral gastroenteritis in the United States. To determine the magnitude and duration of virus shedding in feces, we evaluated persons who had been experimentally infected with Norwalk virus. Of 16 persons, clinical gastroenteritis (watery diarrhea and/or vomiting) developed in 11; symptomatic illness lasted 1–2 days. Virus shedding was first detected by reverse transcription–PCR (RT-PCR) 18 hours after participant inoculation and lasted a median of 28 days after inoculation (range 13–56 days). The median peak amount of virus shedding was 95 × 10 9 (range 0.5–1,640 ×10 9) genomic copies/g feces as measured by quantitative RT-PCR. Virus shedding was first detected by antigen ELISA ≈33 hours (median 42 hours) after inoculation and lasted 10 days (median 7 days) after inoculation. Understanding of the relevance of prolonged fecal norovirus excretion must await the development of sensitive methods to measure virus infectivity.

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          Most cited references23

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          Natural history of human calicivirus infection: a prospective cohort study.

          We investigated the natural history of human Calicivirus infection in the community. Clinical information was obtained from 99 subjects infected with Norwalk-like viruses (NLV) and 40 subjects infected with Sapporo-like viruses (SLV) in a prospective, community-based cohort study. NLV infection was common in all age groups, whereas SLV infection was mainly restricted to children aged /=1 year (>75% for NLV and >67% for SLV). Overall, NLV was detected in 26% of patients up to 3 weeks after the onset of illness. This proportion was highest (38%) for children aged <1 year. SLV shedding subsided after 14 days. These data show that the durations of disease and viral shedding of caliciviruses are longer than has been described elsewhere. Therefore, the impact of these infections may have been underestimated.
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            Clinical immunity in acute gastroenteritis caused by Norwalk agent.

            To examine immunity in viral gastroenteritis, we challenged and then rechallenged 12 volunteers with Norwalk agent and evaluated symptoms, jejunal biopsies and serum antibody. With the first challenge, gastroenteritis developed in six volunteers but not in the others. When rechallenged 27 to 42 months later, the six who became ill initially again had gastroenteritis with jejunal lesions; in the six previously immune volunteers illness or jejunal lesions did not develop. Four of five ill volunteers had increases in serum antibody to Norwalk agent after both challenges. Serum antibody did not increase in three immune volunteers after either challenge. Four volunteers who had twice become ill underwent a third challenge four to eight weeks after their second illness. In one gastroenteritis developed; in three, it did not. These findings indicate two forms of immunity for viral gastroenteritis, one of short and the other of long duration. Factors other than serum antibody appear important in immunity to Norwalk gastroenteritis.
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              Detection by PCR of eight groups of enteric pathogens in 4,627 faecal samples: re-examination of the English case-control Infectious Intestinal Disease Study (1993-1996).

              The English case-control Infectious Intestinal Disease Study (1993-1996) failed to detect an enteric pathogen or toxin in 49% of cases of gastroenteritis. In the present study, polymerase chain reaction (PCR) assays were applied to DNA and cDNA generated from 4,627 faecal samples from cases and controls archived during the original study for the detection of norovirus, rotavirus, sapovirus, Campylobacter spp., Salmonella spp., enteroaggregative Escherichia coli, Cryptosporidium spp., and Giardia spp. The percentage of archived samples from cases and from controls in which at least one agent (or toxin) was detected increased from 53% in the original study to 75% and from 19 to 42%, respectively, after the application of PCR assays. Among cases, the following percentages of enteric pathogens were detected: norovirus 36%, rotavirus A 31%, sapovirus 4%, Salmonella spp. 6%, Campylobacter jejuni 13%, Campylobacter coli 2%, other Campylobacter spp. 8%, enteroaggregative E. coli 6%, Giardia spp. 2%, and Cryptosporidium spp. 2%. The present study provides additional insight into the aetiology of infectious intestinal disease in England and highlights the occurrence of viral infections in cases as well as in asymptomatic individuals. Other notable findings include the frequent presence of Campylobacter spp. other than C. jejuni or C. coli, the high frequency of multiple agents in 41% of cases and in 13% of controls, and the variation in the aetiology and rate of infection found for different age groups. The results demonstrate the greater sensitivity of PCR-based methods compared to current conventional methods.
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                Author and article information

                Journal
                Emerg Infect Dis
                EID
                Emerging Infectious Diseases
                Centers for Disease Control and Prevention
                1080-6040
                1080-6059
                October 2008
                : 14
                : 10
                : 1553-1557
                Affiliations
                [1]Baylor College of Medicine, Houston, Texas, USA
                Author notes
                Address for correspondence: Robert L. Atmar, Baylor College of Medicine, Molecular Virology and Microbiology, 1 Baylor Plaza, MS BCM280, Houston, TX 77030, USA; email: ratmar@ 123456bcm.tmc.edu
                Article
                08-0117
                10.3201/eid1410.080117
                2609865
                18826818
                293e3334-9b53-4d80-a2f5-a79913f0e3af
                History
                Categories
                Research

                Infectious disease & Microbiology
                human,gastroenteritis,rt-pcr,norovirus,adult,norwalk virus,research
                Infectious disease & Microbiology
                human, gastroenteritis, rt-pcr, norovirus, adult, norwalk virus, research

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