Cargando…
2492. Clinical, Virologic, and Immunologic Characteristics of Zika Virus Infection in a Cohort of US Patients
BACKGROUND: The clinical, virologic and immunologic characteristics of Zika virus (ZIKV) infections in US patients are poorly defined. METHODS: US patients with suspected Zika virus (ZIKV) infection were enrolled and clinical data and specimens were prospectively collected. Body fluids were tested f...
Autores principales: | , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6255666/ http://dx.doi.org/10.1093/ofid/ofy210.2144 |
_version_ | 1783373995198906368 |
---|---|
author | Sahly, Hana M El Gorchakov, Rodion Murray, Kristy Patel, Shital Atmar, Robert L Keitel, Wendy Hoft, Daniel Barrett, Jill Bailey, Jason Rouphael, Nadine Edupuganti, Srilatha Raabe, Vanessa Wu, Henry Fairley, Jessica Natrajan, Muktha Lai, Lilin Mulligan, Mark J |
author_facet | Sahly, Hana M El Gorchakov, Rodion Murray, Kristy Patel, Shital Atmar, Robert L Keitel, Wendy Hoft, Daniel Barrett, Jill Bailey, Jason Rouphael, Nadine Edupuganti, Srilatha Raabe, Vanessa Wu, Henry Fairley, Jessica Natrajan, Muktha Lai, Lilin Mulligan, Mark J |
author_sort | Sahly, Hana M El |
collection | PubMed |
description | BACKGROUND: The clinical, virologic and immunologic characteristics of Zika virus (ZIKV) infections in US patients are poorly defined. METHODS: US patients with suspected Zika virus (ZIKV) infection were enrolled and clinical data and specimens were prospectively collected. Body fluids were tested for ZIKV RNA by PCR and blood was tested using serologic and cellular immune assays. Findings from those with confirmed ZIKV infections (cases) and ZIKV-negative controls were compared. RESULTS: We enrolled 45 cases and 14 controls. The most commonly reported symptoms among cases and controls were maculopapular rash (97.8% and 81.8%), fatigue (86.7% and 81.8%) and arthralgia (82.2% and 54.5%), respectively. The sensitivity and duration of detection by PCR were highest in whole blood samples (94% of 35 cases who had samples collected up to day 79 post illness onset were positive); strikingly, 84% of those were still positive at 65–79 days post illness onset (Figure 1). ZIKV neutralizing antibodies were detected in all cases and none of the controls, and titers were significantly higher in dengue virus (DENV)-experienced subjects than in DENV-naïve ones (Figure 2). Among cases, anti-ZIKV IgG antibodies were also significantly higher in DENV-experienced patients, while anti-ZIKV IgM antibodies were no higher in DENV-experienced compared with naïve ones. Using intracellular cytokine staining, the highest frequencies of T cells producing IFN-γ, IL-2 and/or TNF-α were against the NS1, NS3, and NS5 proteins for CD4+ T cells, and against the E, NS3, and NS5 proteins for CD8+ T cells (Figure 3). CONCLUSION: Detection of ZIKV RNA was more frequent and much more prolonged in whole blood samples compared with other body fluids. Diagnostic molecular assays on this easily obtained fluid should be prioritized for point-of-care development. Robust cellular responses to E, NS3 and NS5 proteins could have implications for vaccine development. [Image: see text] [Image: see text] [Image: see text] DISCLOSURES: R. L. Atmar, Takeda Vaccines, Inc.: Investigator, Research grant. |
format | Online Article Text |
id | pubmed-6255666 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-62556662018-11-28 2492. Clinical, Virologic, and Immunologic Characteristics of Zika Virus Infection in a Cohort of US Patients Sahly, Hana M El Gorchakov, Rodion Murray, Kristy Patel, Shital Atmar, Robert L Keitel, Wendy Hoft, Daniel Barrett, Jill Bailey, Jason Rouphael, Nadine Edupuganti, Srilatha Raabe, Vanessa Wu, Henry Fairley, Jessica Natrajan, Muktha Lai, Lilin Mulligan, Mark J Open Forum Infect Dis Abstracts BACKGROUND: The clinical, virologic and immunologic characteristics of Zika virus (ZIKV) infections in US patients are poorly defined. METHODS: US patients with suspected Zika virus (ZIKV) infection were enrolled and clinical data and specimens were prospectively collected. Body fluids were tested for ZIKV RNA by PCR and blood was tested using serologic and cellular immune assays. Findings from those with confirmed ZIKV infections (cases) and ZIKV-negative controls were compared. RESULTS: We enrolled 45 cases and 14 controls. The most commonly reported symptoms among cases and controls were maculopapular rash (97.8% and 81.8%), fatigue (86.7% and 81.8%) and arthralgia (82.2% and 54.5%), respectively. The sensitivity and duration of detection by PCR were highest in whole blood samples (94% of 35 cases who had samples collected up to day 79 post illness onset were positive); strikingly, 84% of those were still positive at 65–79 days post illness onset (Figure 1). ZIKV neutralizing antibodies were detected in all cases and none of the controls, and titers were significantly higher in dengue virus (DENV)-experienced subjects than in DENV-naïve ones (Figure 2). Among cases, anti-ZIKV IgG antibodies were also significantly higher in DENV-experienced patients, while anti-ZIKV IgM antibodies were no higher in DENV-experienced compared with naïve ones. Using intracellular cytokine staining, the highest frequencies of T cells producing IFN-γ, IL-2 and/or TNF-α were against the NS1, NS3, and NS5 proteins for CD4+ T cells, and against the E, NS3, and NS5 proteins for CD8+ T cells (Figure 3). CONCLUSION: Detection of ZIKV RNA was more frequent and much more prolonged in whole blood samples compared with other body fluids. Diagnostic molecular assays on this easily obtained fluid should be prioritized for point-of-care development. Robust cellular responses to E, NS3 and NS5 proteins could have implications for vaccine development. [Image: see text] [Image: see text] [Image: see text] DISCLOSURES: R. L. Atmar, Takeda Vaccines, Inc.: Investigator, Research grant. Oxford University Press 2018-11-26 /pmc/articles/PMC6255666/ http://dx.doi.org/10.1093/ofid/ofy210.2144 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://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 (http://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 | Abstracts Sahly, Hana M El Gorchakov, Rodion Murray, Kristy Patel, Shital Atmar, Robert L Keitel, Wendy Hoft, Daniel Barrett, Jill Bailey, Jason Rouphael, Nadine Edupuganti, Srilatha Raabe, Vanessa Wu, Henry Fairley, Jessica Natrajan, Muktha Lai, Lilin Mulligan, Mark J 2492. Clinical, Virologic, and Immunologic Characteristics of Zika Virus Infection in a Cohort of US Patients |
title | 2492. Clinical, Virologic, and Immunologic Characteristics of Zika Virus Infection in a Cohort of US Patients |
title_full | 2492. Clinical, Virologic, and Immunologic Characteristics of Zika Virus Infection in a Cohort of US Patients |
title_fullStr | 2492. Clinical, Virologic, and Immunologic Characteristics of Zika Virus Infection in a Cohort of US Patients |
title_full_unstemmed | 2492. Clinical, Virologic, and Immunologic Characteristics of Zika Virus Infection in a Cohort of US Patients |
title_short | 2492. Clinical, Virologic, and Immunologic Characteristics of Zika Virus Infection in a Cohort of US Patients |
title_sort | 2492. clinical, virologic, and immunologic characteristics of zika virus infection in a cohort of us patients |
topic | Abstracts |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6255666/ http://dx.doi.org/10.1093/ofid/ofy210.2144 |
work_keys_str_mv | AT sahlyhanamel 2492clinicalvirologicandimmunologiccharacteristicsofzikavirusinfectioninacohortofuspatients AT gorchakovrodion 2492clinicalvirologicandimmunologiccharacteristicsofzikavirusinfectioninacohortofuspatients AT murraykristy 2492clinicalvirologicandimmunologiccharacteristicsofzikavirusinfectioninacohortofuspatients AT patelshital 2492clinicalvirologicandimmunologiccharacteristicsofzikavirusinfectioninacohortofuspatients AT atmarrobertl 2492clinicalvirologicandimmunologiccharacteristicsofzikavirusinfectioninacohortofuspatients AT keitelwendy 2492clinicalvirologicandimmunologiccharacteristicsofzikavirusinfectioninacohortofuspatients AT hoftdaniel 2492clinicalvirologicandimmunologiccharacteristicsofzikavirusinfectioninacohortofuspatients AT barrettjill 2492clinicalvirologicandimmunologiccharacteristicsofzikavirusinfectioninacohortofuspatients AT baileyjason 2492clinicalvirologicandimmunologiccharacteristicsofzikavirusinfectioninacohortofuspatients AT rouphaelnadine 2492clinicalvirologicandimmunologiccharacteristicsofzikavirusinfectioninacohortofuspatients AT edupugantisrilatha 2492clinicalvirologicandimmunologiccharacteristicsofzikavirusinfectioninacohortofuspatients AT raabevanessa 2492clinicalvirologicandimmunologiccharacteristicsofzikavirusinfectioninacohortofuspatients AT wuhenry 2492clinicalvirologicandimmunologiccharacteristicsofzikavirusinfectioninacohortofuspatients AT fairleyjessica 2492clinicalvirologicandimmunologiccharacteristicsofzikavirusinfectioninacohortofuspatients AT natrajanmuktha 2492clinicalvirologicandimmunologiccharacteristicsofzikavirusinfectioninacohortofuspatients AT laililin 2492clinicalvirologicandimmunologiccharacteristicsofzikavirusinfectioninacohortofuspatients AT mulliganmarkj 2492clinicalvirologicandimmunologiccharacteristicsofzikavirusinfectioninacohortofuspatients |