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Clinical and In Vitro Evidence Favoring Immunoglobulin Treatment of a Chronic Norovirus Infection in a Patient With Common Variable Immunodeficiency
BACKGROUND: Immunocompromised individuals can become chronically infected with norovirus, but effective antiviral therapies are not yet available. METHODS: Treatments with nitazoxanide, ribavirin, interferon alpha-2a, and nasoduodenally administered immunoglobulins were evaluated sequentially in an...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9650502/ https://www.ncbi.nlm.nih.gov/pubmed/35255136 http://dx.doi.org/10.1093/infdis/jiac085 |
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author | van Kampen, Jeroen J A Dalm, Virgil A S H Fraaij, Pieter L A Oude Munnink, Bas B Schapendonk, Claudia M E Izquierdo-Lara, Ray W Villabruna, Nele Ettayebi, Khalil Estes, Mary K Koopmans, Marion P G de Graaf, Miranda |
author_facet | van Kampen, Jeroen J A Dalm, Virgil A S H Fraaij, Pieter L A Oude Munnink, Bas B Schapendonk, Claudia M E Izquierdo-Lara, Ray W Villabruna, Nele Ettayebi, Khalil Estes, Mary K Koopmans, Marion P G de Graaf, Miranda |
author_sort | van Kampen, Jeroen J A |
collection | PubMed |
description | BACKGROUND: Immunocompromised individuals can become chronically infected with norovirus, but effective antiviral therapies are not yet available. METHODS: Treatments with nitazoxanide, ribavirin, interferon alpha-2a, and nasoduodenally administered immunoglobulins were evaluated sequentially in an immunocompromised patient chronically infected with norovirus. In support, these components were also applied to measure norovirus inhibition in intestinal enteroid cultures in vitro. Viral RNA levels were determined in fecal and plasma samples during each treatment and viral genomes were sequenced. RESULTS: None of the antivirals resulted in a reduction of viral RNA levels in feces or plasma. However, during ribavirin treatment, there was an increased accumulation of virus genome mutations. In vitro, an effect of interferon alpha-2a on virus replication was observed and a genetically related strain was neutralized effectively in vitro using immunoglobulins and post-norovirus–infection antiserum. In agreement, after administration of immunoglobulins, the patient cleared the infection. CONCLUSIONS: Intestinal enteroid cultures provide a relevant system to evaluate antivirals and the neutralizing potential of immunoglobulins. We successfully treated a chronically infected patient with immunoglobulins, despite varying results reported by others. This case study provides in-depth, multifaceted exploration of norovirus treatment that can be used as a guidance for further research towards norovirus treatments. |
format | Online Article Text |
id | pubmed-9650502 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-96505022022-11-14 Clinical and In Vitro Evidence Favoring Immunoglobulin Treatment of a Chronic Norovirus Infection in a Patient With Common Variable Immunodeficiency van Kampen, Jeroen J A Dalm, Virgil A S H Fraaij, Pieter L A Oude Munnink, Bas B Schapendonk, Claudia M E Izquierdo-Lara, Ray W Villabruna, Nele Ettayebi, Khalil Estes, Mary K Koopmans, Marion P G de Graaf, Miranda J Infect Dis Major Article BACKGROUND: Immunocompromised individuals can become chronically infected with norovirus, but effective antiviral therapies are not yet available. METHODS: Treatments with nitazoxanide, ribavirin, interferon alpha-2a, and nasoduodenally administered immunoglobulins were evaluated sequentially in an immunocompromised patient chronically infected with norovirus. In support, these components were also applied to measure norovirus inhibition in intestinal enteroid cultures in vitro. Viral RNA levels were determined in fecal and plasma samples during each treatment and viral genomes were sequenced. RESULTS: None of the antivirals resulted in a reduction of viral RNA levels in feces or plasma. However, during ribavirin treatment, there was an increased accumulation of virus genome mutations. In vitro, an effect of interferon alpha-2a on virus replication was observed and a genetically related strain was neutralized effectively in vitro using immunoglobulins and post-norovirus–infection antiserum. In agreement, after administration of immunoglobulins, the patient cleared the infection. CONCLUSIONS: Intestinal enteroid cultures provide a relevant system to evaluate antivirals and the neutralizing potential of immunoglobulins. We successfully treated a chronically infected patient with immunoglobulins, despite varying results reported by others. This case study provides in-depth, multifaceted exploration of norovirus treatment that can be used as a guidance for further research towards norovirus treatments. Oxford University Press 2022-03-07 /pmc/articles/PMC9650502/ /pubmed/35255136 http://dx.doi.org/10.1093/infdis/jiac085 Text en © The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Major Article van Kampen, Jeroen J A Dalm, Virgil A S H Fraaij, Pieter L A Oude Munnink, Bas B Schapendonk, Claudia M E Izquierdo-Lara, Ray W Villabruna, Nele Ettayebi, Khalil Estes, Mary K Koopmans, Marion P G de Graaf, Miranda Clinical and In Vitro Evidence Favoring Immunoglobulin Treatment of a Chronic Norovirus Infection in a Patient With Common Variable Immunodeficiency |
title | Clinical and In Vitro Evidence Favoring Immunoglobulin Treatment of a Chronic Norovirus Infection in a Patient With Common Variable Immunodeficiency |
title_full | Clinical and In Vitro Evidence Favoring Immunoglobulin Treatment of a Chronic Norovirus Infection in a Patient With Common Variable Immunodeficiency |
title_fullStr | Clinical and In Vitro Evidence Favoring Immunoglobulin Treatment of a Chronic Norovirus Infection in a Patient With Common Variable Immunodeficiency |
title_full_unstemmed | Clinical and In Vitro Evidence Favoring Immunoglobulin Treatment of a Chronic Norovirus Infection in a Patient With Common Variable Immunodeficiency |
title_short | Clinical and In Vitro Evidence Favoring Immunoglobulin Treatment of a Chronic Norovirus Infection in a Patient With Common Variable Immunodeficiency |
title_sort | clinical and in vitro evidence favoring immunoglobulin treatment of a chronic norovirus infection in a patient with common variable immunodeficiency |
topic | Major Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9650502/ https://www.ncbi.nlm.nih.gov/pubmed/35255136 http://dx.doi.org/10.1093/infdis/jiac085 |
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