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. 2020 Feb 3;221(4):566-577.
doi: 10.1093/infdis/jiz489.

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

Kristen K Coleman  1 , Chui Ching Wong  2 , Jayanthi Jayakumar  1 , Tham T Nguyen  1 , Abigail W L Wong  3 , Su Yadana  1 , Koh C Thoon  4 , Kwai Peng Chan  2   5 , Jenny G Low  1   3 , Shirin Kalimuddin  3 , Shoaleh Dehghan  6   7 , June Kang  6 , Amirhossein Shamsaddini  6 , Donald Seto  6 , Yvonne C F Su  1 , Gregory C Gray  1   8   9
Affiliations

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

Kristen K Coleman et al. J Infect Dis. .

Abstract

Background: A 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).

Methods: To 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.

Results: The 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.

Conclusions: Singapore 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.

Keywords: adenovirus; genotyping; molecular epidemiology; pediatric disease; respiratory disease.

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Figures

Figure 1.
Figure 1.
Human adenovirus (HAdV) genotype frequencies among HAdV-positive patients hospitalized in Singapore, by year. Years 2012–2013 represent an adult cohort among which 35 cases have been previously described [13]. Year 2014 represents pediatric cases only. Patient recruitment ceased in March of year 2018. “Unknown” represents samples of which genotyping failed. “Other” represents HAdV-C5, -C6, -B11p, -B21, -B35, -D8, or -D53.
Figure 2.
Figure 2.
Evolutionary relationships of full genomes of human adenovirus (HAdV)-C, inferred by the maximum-likelihood method with the GTR+GAMMA model in RAxML. Colored branches represent viruses isolated from different genotypes. Red isolates denote new isolates collected from patients in Singapore. Bootstrap support values greater than 50% are displayed at major nodes. The scale bar indicates the number of nucleotide substitutions per site.
Figure 3.
Figure 3.
Evolutionary relationships of full genomes of human adenovirus (HAdV)-E, inferred by the maximum-likelihood method with the GTR+GAMMA model in RAxML. Red isolates denote new isolates collected from patients in Singapore. Bootstrap support values greater than 50% are displayed at major nodes. The scale bar indicates the number of nucleotide substitutions per site.
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