Whole-genome Sequencing for Tracing the Transmission Link between Two ARD Outbreaks Caused by a Novel HAdV Serotype 7 Variant, China

From December 2012 to February 2013, two outbreaks of acute respiratory disease caused by HAdV-7 were reported in China. We investigated possible transmission links between these two seemingly unrelated outbreaks by integration of epidemiological and whole-genome sequencing (WGS) data. WGS analyses showed that the HAdV-7 isolates from the two outbreaks were genetically indistinguishable; however, a 12 bp deletion in the virus-associated RNA gene distinguished the outbreak isolates from other HAdV-7 isolates. Outbreak HAdV-7 isolates demonstrated increased viral replication compared to non-outbreak associated HAdV-7 isolate. Epidemiological data supported that the first outbreak was caused by introduction of the novel HAdV-7 virus by an infected recruit upon arrival at the training base. Nosocomial transmission by close contacts was the most likely source leading to onset of the second HAdV-7 outbreak, establishing the apparent transmission link between the outbreaks. Our findings imply that in-hospital contact investigations should be encouraged to reduce or interrupt further spread of infectious agents when treating outbreak cases, and WGS can provide useful information guiding infection-control interventions.

[1]  M. Nawaz,et al.  Outbreak of acute respiratory disease caused by human adenovirus type 7 in a military training camp in Shaanxi, China , 2013, Microbiology and immunology.

[2]  Daniel J. Wilson,et al.  Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks: a retrospective observational study , 2013, The Lancet. Infectious diseases.

[3]  Xiaoyan Lu,et al.  A naturally occurring human adenovirus type 7 variant with a 1743 bp deletion in the E3 cassette. , 2011, The Journal of general virology.

[4]  S. Mendoza,et al.  Cross-Species Transmission of a Novel Adenovirus Associated with a Fulminant Pneumonia Outbreak in a New World Monkey Colony , 2011, PLoS pathogens.

[5]  Steven J. M. Jones,et al.  Whole-genome sequencing and social-network analysis of a tuberculosis outbreak. , 2011, The New England journal of medicine.

[6]  P. Shao,et al.  Community Outbreak of Adenovirus, Taiwan, 2011 , 2012, Emerging infectious diseases.

[7]  L. Anderson,et al.  Molecular Epidemiology of Adenovirus Type 7 in the United States, 1966–2000 , 2002, Emerging infectious diseases.

[8]  Jian He,et al.  Clinical findings in 111 cases of influenza A (H7N9) virus infection. , 2013, The New England journal of medicine.

[9]  Bin Cao,et al.  Clinical features of the initial cases of 2009 pandemic influenza A (H1N1) virus infection in China. , 2009, The New England journal of medicine.

[10]  Wenbo Xu,et al.  Outbreak of febrile respiratory illness associated with human adenovirus type 14p1 in Gansu Province, China , 2013, Influenza and other respiratory viruses.

[11]  A. Mellmann,et al.  Characterisation of the Escherichia coli strain associated with an outbreak of haemolytic uraemic syndrome in Germany, 2011: a microbiological study. , 2011, The Lancet. Infectious diseases.

[12]  Wenbo Xu,et al.  Adenovirus serotype 7 associated with a severe lower respiratory tract disease outbreak in infants in Shaanxi Province, China , 2011, Virology Journal.

[13]  L. Finelli,et al.  Emergence of a novel swine-origin influenza A (H1N1) virus in humans. , 2009, The New England journal of medicine.

[14]  Weizhong Yang,et al.  Fever with thrombocytopenia associated with a novel bunyavirus in China. , 2011, The New England journal of medicine.

[15]  G. Gray,et al.  A comparison of viral fitness and virulence between emergent adenovirus 14p1 and prototype adenovirus 14p strains. , 2012, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[16]  Ding-Ping Liu,et al.  A two decade survey of respiratory adenovirus in Taiwan: The reemergence of adenovirus types 7 and 4 , 2004, Journal of medical virology.

[17]  P. Marik,et al.  A Descriptive Study , 2015 .

[18]  R. Thayan,et al.  Human Adenovirus Type 7 Outbreak in Police Training Center, Malaysia, 2011 , 2012, Emerging infectious diseases.

[19]  Roderick C. Jones,et al.  Outbreak of human adenovirus type 3 infection in a pediatric long-term care facility--Illinois, 2005. , 2007, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[20]  Daniel J. Wilson,et al.  Transforming clinical microbiology with bacterial genome sequencing , 2012, Nature Reviews Genetics.

[21]  G. Smith,et al.  A pilot study of rapid whole-genome sequencing for the investigation of a Legionella outbreak , 2013, BMJ Open.

[22]  Junhua Li,et al.  Open-source genomic analysis of Shiga-toxin-producing E. coli O104:H4. , 2011, The New England journal of medicine.

[23]  D. Seto,et al.  Re-emergent Human Adenovirus Genome Type 7d Caused an Acute Respiratory Disease Outbreak in Southern China After a Twenty-one Year Absence , 2014, Scientific Reports.

[24]  P. Cieslak,et al.  A community-based outbreak of severe respiratory illness caused by human adenovirus serotype 14. , 2009, The Journal of infectious diseases.

[25]  Complete genome analysis of a novel E3-partial-deleted human adenovirus type 7 strain isolated in Southern China , 2011, Virology Journal.

[26]  N. Woodford,et al.  Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study , 2010, The Lancet. Infectious diseases.

[27]  W. Liu,et al.  Genomic analysis of HAdV-B14 isolate from the outbreak of febrile respiratory infection in China , 2013, Genomics.

[28]  Julian Parkhill,et al.  Rapid whole-genome sequencing for investigation of a neonatal MRSA outbreak. , 2012, The New England journal of medicine.

[29]  P. Shao,et al.  Adenovirus Serotype 3 and 7 Infection with Acute Respiratory Failure in Children in Taiwan, 2010–2011 , 2013, PloS one.

[30]  Jie Dong,et al.  Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus. , 2018 .

[31]  D. Seto,et al.  Genome Sequence of Human Adenovirus Type 55, a Re-Emergent Acute Respiratory Disease Pathogen in China , 2012, Journal of Virology.

[32]  Einar Everitt,et al.  TCID50 determination by an immuno dot blot assay as exemplified in a study of storage conditions of infectious pancreatic necrosis virus. , 1999, Journal of virological methods.

[33]  Julian Parkhill,et al.  Whole-genome sequencing for analysis of an outbreak of meticillin-resistant Staphylococcus aureus: a descriptive study , 2013, The Lancet. Infectious Diseases.

[34]  Donald Seto,et al.  Using the Whole-Genome Sequence To Characterize and Name Human Adenoviruses , 2011, Journal of Virology.

[35]  Pengbo Yu,et al.  Complete Genome Sequence of Human Adenovirus Type 7 Associated with Fatal Infant Pneumonia , 2013, Genome Announcements.

[36]  Stefan Niemann,et al.  Whole Genome Sequencing versus Traditional Genotyping for Investigation of a Mycobacterium tuberculosis Outbreak: A Longitudinal Molecular Epidemiological Study , 2013, PLoS medicine.

[37]  Guixia Yu,et al.  A Novel Adenovirus Species Associated with an Acute Respiratory Outbreak in a Baboon Colony and Evidence of Coincident Human Infection , 2013, mBio.

[38]  Jingcao Pan,et al.  Two Adenovirus Serotype 3 Outbreaks Associated with Febrile Respiratory Disease and Pharyngoconjunctival Fever in Children under 15 Years of Age in Hangzhou, China, during 2011 , 2012, Journal of Clinical Microbiology.

[39]  Wenbo Xu,et al.  Outbreak of Acute Respiratory Disease in China Caused by B2 Species of Adenovirus Type 11 , 2009, Journal of Clinical Microbiology.

[40]  D. Seto,et al.  Computational Analysis Identifies Human Adenovirus Type 55 as a Re-Emergent Acute Respiratory Disease Pathogen , 2009, Journal of Clinical Microbiology.

[41]  D. Wolf,et al.  An Outbreak of Adenovirus Type 7 in a Residential Facility for Severely Disabled Children , 2011, The Pediatric infectious disease journal.

[42]  J. Ackelsberg,et al.  Adenovirus Type 7 Genomic-Type Variant, New York City, 1999 , 2004, Emerging infectious diseases.

[43]  A. Heim,et al.  Phylogenetic Analysis of the Main Neutralization and Hemagglutination Determinants of All Human Adenovirus Prototypes as a Basis for Molecular Classification and Taxonomy , 2005, Journal of Virology.

[44]  Evan S Snitkin,et al.  Tracking a Hospital Outbreak of Carbapenem-Resistant Klebsiella pneumoniae with Whole-Genome Sequencing , 2012, Science Translational Medicine.

[45]  Julian Parkhill,et al.  Bacterial epidemiology and biology - lessons from genome sequencing , 2011, Genome Biology.