Adenoviral Infections in Singapore: Should New Antiviral Therapies and Vaccines Be Adopted?

Author:

Coleman Kristen K1ORCID,Wong Chui Ching2,Jayakumar Jayanthi1,Nguyen Tham T1,Wong Abigail W L3,Yadana Su1,Thoon Koh C4,Chan Kwai Peng25,Low Jenny G13,Kalimuddin Shirin3,Dehghan Shoaleh67,Kang June6,Shamsaddini Amirhossein6,Seto Donald6,Su Yvonne C F1,Gray Gregory C189ORCID

Affiliation:

1. Emerging Infectious Diseases Programme, Duke-NUS Medical School, Singapore

2. Department of Microbiology, Singapore General Hospital, Singapore

3. Department of Infectious Diseases, Singapore General Hospital, Singapore

4. Department of Paediatrics, Infectious Disease Service, KK Women’s and Children’s Hospital, Singapore

5. Academic Clinical Programme for Pathology, Duke-NUS Medical School, Singapore

6. Bioinformatics and Computational Biology Program, School of Systems Biology, George Mason University, Manassas, Virginia, USA

7. Chemistry Department, American University, Washington, District of Columbia, USA

8. Division of Infectious Diseases, Global Health Institute, and Nicholas School of the Environment, Duke University, Durham, North Carolina, USA

9. Global Health Center, Duke Kunshan University, Kunshan, China

Abstract

AbstractBackgroundA number of serious human adenovirus (HAdV) outbreaks have been recently reported: HAdV-B7 (Israel, Singapore, and USA), HAdV-B7d (USA and China), HAdV-D8, -D54, and -C2 (Japan), HAdV-B14p1 (USA, Europe, and China), and HAdV-B55 (China, Singapore, and France).MethodsTo understand the epidemiology of HAdV infections in Singapore, we studied 533 HAdV-positive clinical samples collected from 396 pediatric and 137 adult patients in Singapore from 2012 to 2018. Genome sequencing and phylogenetic analyses were performed to identify HAdV genotypes, clonal clusters, and recombinant or novel HAdVs.ResultsThe most prevalent genotypes identified were HAdV-B3 (35.6%), HAdV-B7 (15.4%), and HAdV-E4 (15.2%). We detected 4 new HAdV-C strains and detected incursions with HAdV-B7 (odds ratio [OR], 14.6; 95% confidence interval [CI], 4.1–52.0) and HAdV-E4 (OR, 13.6; 95% CI, 3.9–46.7) among pediatric patients over time. In addition, immunocompromised patients (adjusted OR [aOR], 11.4; 95% CI, 3.8–34.8) and patients infected with HAdV-C2 (aOR, 8.5; 95% CI, 1.5–48.0), HAdV-B7 (aOR, 3.7; 95% CI, 1.2–10.9), or HAdV-E4 (aOR, 3.2; 95% CI, 1.1–8.9) were at increased risk for severe disease.ConclusionsSingapore would benefit from more frequent studies of clinical HAdV genotypes to identify patients at risk for severe disease and help guide the use of new antiviral therapies, such as brincidofovir, and potential administration of HAdV 4 and 7 vaccine.

Funder

SingHealth and Duke-NUS Medical School

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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