Epidemiology of Human Adenoviruses: A 20-Year Retrospective Observational Study in Hospitalized Patients in Bern, Switzerland

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Abstract

Background

Human adenovirus (HAdV) is an important pathogen seen in clinical practice. Long-term studies may help better understand epidemiological trends and changes in circulating genotypes over time.

Purpose

Using a large biobank of samples from hospitalized, adenovirus-positive patients over a 20-year period, we aimed to analyze long-term epidemiological trends and genotypic relatedness among circulating HAdV strains.

Methods

Based on samples from hospitalized patients confirmed to be HAdV positive in Bern, Switzerland, from 1998 to 2017, and on their associated demographic and clinical data, we identified epidemiological trends and risk factors associated with HAdV infection. HAdV genotyping was performed by PCR amplification and sequencing of the hypervariable hexon gene. The obtained sequences were phylogenetically compared with sequences from international HAdV strains.

Results

HAdV was identified in 1302 samples tested. Cases of HAdV infection were reported throughout the years with no clear seasonality. Upper respiratory tract samples, conjunctivitis swabs, and stool had the highest positivity rate (56.2%, 18.7%, and 14.2% of the cases, respectively). HAdV infection was highest among children ≤4 years old. Increased number of HAdV cases were observed in years 2009 (n = 110) and 2010 (n =112). HAdV8 was the predominant genotype among patients older than 20 years, and was mostly associated with ophthalmic infection. Predominant genotypes among children ≤4 years old were HAdV1, HAdV2, and HAdV3, which were mostly associated with respiratory tract infections. Recurring peaks of increased HAdV cases were evidenced every 4 years among children ≤4 years old.

Conclusion

Our study gives novel insights on long-term epidemiological trends and phylogenetic relatedness among circulating HAdV strains in Switzerland, country in which little data on HAdV prevalence and diversity was so far available.

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Most cited references 39

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Adenovirus infections in immunocompetent and immunocompromised patients.

Thomas Lion (2014)

Human adenoviruses (HAdVs) are an important cause of infections in both immunocompetent and immunocompromised individuals, and they continue to provide clinical challenges pertaining to diagnostics and treatment. The growing number of HAdV types identified by genomic analysis, as well as the improved understanding of the sites of viral persistence and reactivation, requires continuous adaptions of diagnostic approaches to facilitate timely detection and monitoring of HAdV infections. In view of the clinical relevance of life-threatening HAdV diseases in the immunocompromised setting, there is an urgent need for highly effective treatment modalities lacking major side effects. The present review summarizes the recent progress in the understanding and management of HAdV infections.

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A community-based outbreak of severe respiratory illness caused by human adenovirus serotype 14.

David Gilbert, La Grenz, Brian Kendall … (2009)

Human adenoviruses (Ads) typically cause mild illnesses in otherwise healthy hosts. We investigated a community-based outbreak that had substantial morbidity caused primarily by Ad14, an uncommon serotype. We retrospectively reviewed the medical records of all patients with confirmed cases of Ad infection from 1 November 2006 through 31 July 2007 in Oregon. Isolates were typed by sequencing. We analyzed clinical and laboratory variables to identify risk factors for severe Ad14 disease. Ad14 first emerged in Oregon in 2005. Of 67 cases of Ad infection detected during the study period, 40 (60%) involved Ad14. Most of the 38 Ad14-infected patients who had medical records available for review presented with fever and cough; 29 (76%) required hospitalization, 23 (61%) required supplemental oxygen, 18 (47%) required critical care, 9 (24%) required vasopressors, and 7 (18%) died. Lobar infiltrates on chest radiographs suggestive of bacterial pneumonia were common among those needing hospitalization. Older age, chronic underlying condition, low absolute lymphocyte counts, and elevated creatinine levels were associated with severe illness. Except for 1 case of possible hospital transmission, we identified no epidemiological links among patients. Ad14 emerged in Oregon in 2005 and became the predominant circulating type by 2007. Infection with this uncommon virus was primarily associated with a community-acquired pneumonia syndrome and caused substantial morbidity and mortality.

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Persistence and reactivation of human adenoviruses in the gastrointestinal tract.

K Kosulin, E. Geiger, A K Vécsei … (2016)

Reactivation of persistent human adenoviruses (HAdVs) is associated with high morbidity and mortality in paediatric haematopoietic stem cell transplant (HSCT) recipients. Although invasive HAdV infections mainly arise from the gastrointestinal (GI) tract, the specific sites of HAdV persistence are not well characterised. We prospectively screened biopsies from 143 non-HSCT paediatric patients undergoing GI endoscopy and monitored serial stool specimens from 148 paediatric HSCT recipients for the presence of HAdV by real-time PCR. Persistence of HAdV in the GI tract was identified in 31% of children, with the highest prevalence in the terminal ileum. In situ hybridisation and immunohistochemistry identified HAdV persistence in lymphoid cells of the lamina propria, whereas biopsies from five transplant recipients revealed high numbers of replicating HAdV in intestinal epithelial cells. The prevalence of HAdV species, the frequencies of persistence in the GI tract and reactivations post transplant indicated a correlation of intestinal HAdV shedding pre-transplant with high risk of invasive infection. HAdV persistence in the GI tract is a likely origin of infectious complications in immunocompromised children. Intestinal lymphocytes represent a reservoir for HAdV persistence and reactivation, whereas the intestinal epithelium is the main site of viral proliferation preceding dissemination. The findings have important implications for assessing the risk of life-threatening invasive HAdV infections.

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Author and article information

Journal

Journal ID (nlm-ta): Clin Epidemiol

Journal ID (iso-abbrev): Clin Epidemiol

Journal ID (publisher-id): CLEP

Journal ID (pmc): clinepid

Title: Clinical Epidemiology

Publisher: Dove

ISSN (Electronic): 1179-1349

Publication date (Electronic): 05 April 2020

Publication date Collection: 2020

Volume: 12

Pages: 353-366

Affiliations

[1 ]Institute for Infectious Diseases, University of Bern , Bern, Switzerland

[2 ]Biology Division, Spiez Laboratory, Swiss Federal Office for Civil Protection , Spiez, Switzerland

[3 ]Graduate School for Cellular and Biomedical Sciences, University of Bern , Bern, Switzerland

Author notes

Correspondence: Alban Ramette Institute for Infectious Diseases, University of Bern , Friedbühlstrasse 51, Bern3001, SwitzerlandTel +41 31 632 9540 Email alban.ramette@ifik.unibe.ch

Author information

Joyce Odeke Akello http://orcid.org/0000-0002-0483-426X

Stephen L Leib http://orcid.org/0000-0002-1106-6123

Alban Ramette http://orcid.org/0000-0002-3437-4639

Article

Publisher ID: 246352

DOI: 10.2147/CLEP.S246352

PMC ID: 7147615

PubMed ID: 32308491

SO-VID: d7ea3aa3-fa54-4f9f-ae0b-fb86277f5b30

License:

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

History

Date received : 17 January 2020

Date accepted : 20 March 2020

Page count

Figures: 6, Tables: 2, References: 46, Pages: 14

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Epidemiology of Human Adenoviruses: A 20-Year Retrospective Observational Study in Hospitalized Patients in Bern, Switzerland

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Most cited references 39

Adenovirus infections in immunocompetent and immunocompromised patients.

A community-based outbreak of severe respiratory illness caused by human adenovirus serotype 14.

Persistence and reactivation of human adenoviruses in the gastrointestinal tract.

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