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      Unexplained diarrhoea in HIV-1 infected individuals

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          Abstract

          Background

          Gastrointestinal symptoms, in particular diarrhoea, are common in non-treated HIV-1 infected individuals. Although various enteric pathogens have been implicated, the aetiology of diarrhoea remains unexplained in a large proportion of HIV-1 infected patients. Our aim is to identify the cause of diarrhoea for patients that remain negative in routine diagnostics.

          Methods

          In this study stool samples of 196 HIV-1 infected persons, including 29 persons with diarrhoea, were examined for enteropathogens and HIV-1. A search for unknown and unexpected viruses was performed using virus discovery cDNA-AFLP combined with Roche-454 sequencing (VIDISCA-454).

          Results

          HIV-1 RNA was detected in stool of 19 patients with diarrhoea (66%) compared to 75 patients (45%) without diarrhoea. In 19 of the 29 diarrhoea cases a known enteropathogen could be identified (66%). Next to these known causative agents, a range of recently identified viruses was identified via VIDISCA-454: cosavirus, Aichi virus, human gyrovirus, and non-A non-B hepatitis virus. Moreover, a novel virus was detected which was named immunodeficiency-associated stool virus (IASvirus). However, PCR based screening for these viruses showed that none of these novel viruses was associated with diarrhoea. Notably, among the 34% enteropathogen-negative cases, HIV-1 RNA shedding in stool was more frequently observed (80%) compared to enteropathogen-positive cases (47%), indicating that HIV-1 itself is the most likely candidate to be involved in diarrhoea.

          Conclusion

          Unexplained diarrhoea in HIV-1 infected patients is probably not caused by recently described or previously unknown pathogens, but it is more likely that HIV-1 itself plays a role in intestinal mucosal abnormalities which leads to diarrhoea.

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          Most cited references39

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          1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults.

          (1992)
          CDC has revised the classification system for HIV infection to emphasize the clinical importance of the CD4+ T-lymphocyte count in the categorization of HIV-related clinical conditions. This classification system replaces the system published by CDC in 1986 (1) and is primarily intended for use in public health practice. Consistent with the 1993 revised classification system, CDC has also expanded the AIDS surveillance case definition to include all HIV-infected persons who have < 200 CD4+ T-lymphocytes/microL, or a CD4+ T-lymphocyte percentage of total lymphocytes of < 14. This expansion includes the addition of three clinical conditions--pulmonary tuberculosis, recurrent pneumonia, and invasive cervical cancer--and retains the 23 clinical conditions in the AIDS surveillance case definition published in 1987 (2); it is to be used by all states for AIDS case reporting effective January 1, 1993.
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            OpenEpi: a web-based epidemiologic and statistical calculator for public health.

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              Isolation of cytopathic small round viruses with BS-C-1 cells from patients with gastroenteritis.

              Fecal extracts from 12 subjects in outbreaks of oyster-associated nonbacterial gastroenteritis were inoculated with BS-C-1 cells for isolation of the causative viruses. Cytopathic agents were isolated from 3 patients. No cross-neutralizing reactions were observed between the isolates and prototypes of human enteroviruses. The isolates were approximately 30 nm in diameter and had a distinct ultrastructure resembling that of astroviruses. Four polypeptide bands with molecular sizes of 42, 28, 27, and 22 kDa were seen on SDS-PAGE analyses. Seroconversion against the isolate was observed in 18 (31.6%) of 57 patients involved in five of seven outbreaks examined by neutralization test. A protein band characteristically reactive with the paired serum samples was detectable at 42 kDa by immunoblot assay. These results suggested that some small round viruses resembling astroviruses might show cytopathic effect in BS-C-1 cells and may be associated with an oyster-related gastroenteritis.
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                Author and article information

                Journal
                BMC Infect Dis
                BMC Infect. Dis
                BMC Infectious Diseases
                BioMed Central
                1471-2334
                2014
                13 January 2014
                : 14
                : 22
                Affiliations
                [1 ]Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands
                [2 ]CBS-KNAW Fungal Biodiversity Center, Utrecht, The Netherlands
                [3 ]Laboratory of Clinical Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands
                [4 ]Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK
                [5 ]Beatrix Hospital, Gorinchem, The Netherlands
                Article
                1471-2334-14-22
                10.1186/1471-2334-14-22
                3925291
                24410947
                a95c51fe-555b-4088-9fb5-dbb03a997651
                Copyright © 2014 Oude Munnink et al.; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 May 2013
                : 8 January 2014
                Categories
                Research Article

                Infectious disease & Microbiology
                vidisca-454,human gyrovirus,hiv-1,norovirus,diarrhoea,immunodeficiency-associated stool virus,nona-nonb hepatitis virus,aichi virus,cosavirus,sapovirus

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