TY - JOUR
T1 - Next generation sequencing of human enterovirus strains from an outbreak of enterovirus A71 shows applicability to outbreak investigations
AU - Stelzer-Braid, Sacha
AU - Wynn, Matthew
AU - Chatoor, Richard
AU - Scotch, Matthew
AU - Ramachandran, Vidiya
AU - Teoh, Hooi Ling
AU - Farrar, Michelle A.
AU - Sampaio, Hugo
AU - Andrews, Peter Ian
AU - Craig, Maria E.
AU - MacIntyre, C. Raina
AU - Varadhan, Hemalatha
AU - Kesson, Alison
AU - Britton, Philip N.
AU - Newcombe, James
AU - Rawlinson, William D.
N1 - Funding Information:
The authors acknowledge funding received from the following sources: NSW Ministry of Health Public Health Pathogen Genomics Partnership (to WR and SSB); SPHERE Triple I Clinical Academic Group Seed Funding (to WR and SSB); National Health and Medical Research Council (Fellowships to MC and PB); Motor Neurone Diseases Research Institute of Australia (to MF); Sydney Children's Hospital Foundation (to MF); Brain Foundation (to MF); Thyne Reid Foundation (to MF); Biogen (to MF) and the National Library of Medicine of the National Institutes of Health under Award Number R01LM012080 (to MS). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Funding Information:
The authors acknowledge funding received from the following sources: NSW Ministry of Health Public Health Pathogen Genomics Partnership (to WR and SSB); SPHERE Triple I Clinical Academic Group Seed Funding (to WR and SSB); National Health and Medical Research Council (Fellowships to MC and PB); Motor Neurone Diseases Research Institute of Australia (to MF); Sydney Children’s Hospital Foundation (to MF); Brain Foundation (to MF); Thyne Reid Foundation (to MF); Biogen (to MF) and the National Library of Medicine of the National Institutes of Health under Award Number R01LM012080 (to MS). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2020/1
Y1 - 2020/1
N2 - Background: The most recent documented Australian outbreak of enterovirus A71 (EV-A71) occurred in Sydney from 2012 to 2013. Over a four-month period more than 100 children presented to four paediatric hospitals with encephalitic presentations including fever and myoclonic jerks. The heterogeneous presentations included typical encephalomyelitis, and cardiopulmonary complications. Objectives: To characterise the genomes of enterovirus strains circulating during the 2013 Sydney EV-A71 outbreak and determine their phylogeny, phylogeography and association between genome and clinical phenotype. Study design: We performed an analysis of enterovirus (EV) positive specimens from children presenting to hospitals in the greater Sydney region of Australia during the 2013 outbreak. We amplified near full-length genomes of EV, and used next generation sequencing technology to sequence the virus. We used phylogenetic/phylogeographic analysis to characterize the outbreak viruses. Results: We amplified and sequenced 23/63 (37 %) genomes, and identified the majority (61 %) as EV-A71. The EV-A71 sequences showed high level sequence homology to C4a genogroups of EV-A71 circulating in China and Vietnam during 2012-13. Phylogenetic analysis showed EV-A71 strains associated with more severe symptoms, including encephalitis or cardiopulmonary failure, grouped together more closely than those from patients with hand, foot and mouth disease. Amongst the non-EV-A71 sequences were five other EV subtypes (representing enterovirus subtypes A and B), reflecting the diversity of EV co-circulation within the community. Conclusions: This is the first Australian study investigating the near full-length genome of EV strains identified during a known outbreak of EV-A71. EV-A71 sequences were very similar to strains circulating in Asia during the same time period. Whole genome sequencing offers additional information over routine diagnostic testing such as characterisation of emerging recombinant strains and inform vaccine design.
AB - Background: The most recent documented Australian outbreak of enterovirus A71 (EV-A71) occurred in Sydney from 2012 to 2013. Over a four-month period more than 100 children presented to four paediatric hospitals with encephalitic presentations including fever and myoclonic jerks. The heterogeneous presentations included typical encephalomyelitis, and cardiopulmonary complications. Objectives: To characterise the genomes of enterovirus strains circulating during the 2013 Sydney EV-A71 outbreak and determine their phylogeny, phylogeography and association between genome and clinical phenotype. Study design: We performed an analysis of enterovirus (EV) positive specimens from children presenting to hospitals in the greater Sydney region of Australia during the 2013 outbreak. We amplified near full-length genomes of EV, and used next generation sequencing technology to sequence the virus. We used phylogenetic/phylogeographic analysis to characterize the outbreak viruses. Results: We amplified and sequenced 23/63 (37 %) genomes, and identified the majority (61 %) as EV-A71. The EV-A71 sequences showed high level sequence homology to C4a genogroups of EV-A71 circulating in China and Vietnam during 2012-13. Phylogenetic analysis showed EV-A71 strains associated with more severe symptoms, including encephalitis or cardiopulmonary failure, grouped together more closely than those from patients with hand, foot and mouth disease. Amongst the non-EV-A71 sequences were five other EV subtypes (representing enterovirus subtypes A and B), reflecting the diversity of EV co-circulation within the community. Conclusions: This is the first Australian study investigating the near full-length genome of EV strains identified during a known outbreak of EV-A71. EV-A71 sequences were very similar to strains circulating in Asia during the same time period. Whole genome sequencing offers additional information over routine diagnostic testing such as characterisation of emerging recombinant strains and inform vaccine design.
KW - Australia
KW - EV-A71
KW - Enterovirus
KW - Hand, foot and mouth disease
KW - Phylogeny
KW - Whole genome sequencing
UR - http://www.scopus.com/inward/record.url?scp=85075727959&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85075727959&partnerID=8YFLogxK
U2 - 10.1016/j.jcv.2019.104216
DO - 10.1016/j.jcv.2019.104216
M3 - Article
C2 - 31790967
AN - SCOPUS:85075727959
SN - 1386-6532
VL - 122
JO - Journal of Clinical Virology
JF - Journal of Clinical Virology
M1 - 104216
ER -