Multiple Sources of Genetic Diversity of Influenza A Viruses during the Hajj.
Outbreaks of respiratory virus infection at mass gatherings pose significant health risks to attendees, host communities, and ultimately the global population if they help facilitate viral emergence. However, little is known about the genetic diversity, evolution, and patterns of viral transmission during mass gatherings, particularly how much diversity is generated byin situtransmission compared to that imported from other locations. Here, we describe the genome-scale evolution of influenza A viruses sampled from the Hajj pilgrimages at Makkah during 2013 to 2015. Phylogenetic analysis revealed that the diversity of influenza viruses at the Hajj pilgrimages was shaped by multiple introduction events, comprising multiple cocirculating lineages in each year, including those that have circulated in the Middle East and those whose origins likely lie on different continents. At the scale of individual hosts, the majority of minor variants resulted fromde novomutation, with only limited evidence of minor variant transmission or minor variants circulating at subconsensus level despite the likely identification of multiple transmission clusters. Together, these data highlight the complexity of influenza virus infection at the Hajj pilgrimages, reflecting a mix of global genetic diversity drawn from multiple sources combined with local transmission, and reemphasize the need for vigilant surveillance at mass gatherings.IMPORTANCELarge population sizes and densities at mass gatherings such as the Hajj (Makkah, Saudi Arabia) can contribute to outbreaks of respiratory virus infection by providing local hot spots for transmission followed by spread to other localities. Using a genome-scale analysis, we show that the genetic diversity of influenza A viruses at the Hajj gatherings during 2013 to 2015 was largely shaped by the introduction of multiple viruses from diverse geographic regions, including the Middle East, with only little evidence of interhost virus transmission at the Hajj and seemingly limited spread of subconsensus mutational variants. The diversity of viruses at the Hajj pilgrimages highlights the potential for lineage cocirculation during mass gatherings, in turn fuelling segment reassortment and the emergence of novel variants, such that the continued surveillance of respiratory pathogens at mass gatherings should be a public health priority.
Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Life and Environmental Sciences and Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
Joanna C A
JCA
Cobbin
National Centre for Immunisation Research and Surveillance, The Children's Hospital at Westmead, and the Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.|Department of Family and Community Medicine, Faculty of Medicine in Rabigh, King Abdulaziz University, Jeddah, Saudi Arabia.
Mohammad
M
Alfelali
National Centre for Immunisation Research and Surveillance, The Children's Hospital at Westmead, and the Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.|Research Center, King Abdullah Medical City, Makkah, Saudi Arabia.
Osamah
O
Barasheed
Institute for Clinical Pathology and Medical Research, NSW Health Pathology, Westmead Hospital and University of Sydney, Sydney, New South Wales, Australia.
Janette
J
Taylor
Institute for Clinical Pathology and Medical Research, NSW Health Pathology, Westmead Hospital and University of Sydney, Sydney, New South Wales, Australia.
Dominic E
DE
Dwyer
Institute for Clinical Pathology and Medical Research, NSW Health Pathology, Westmead Hospital and University of Sydney, Sydney, New South Wales, Australia.
Jen
J
Kok
Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Life and Environmental Sciences and Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.|National Centre for Immunisation Research and Surveillance, The Children's Hospital at Westmead, and the Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
Robert
R
Booy
Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Life and Environmental Sciences and Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia edward.holmes@sydney.edu.au harunor.rashid@health.nsw.gov.au.
Edward C
http://orcid.org/0000-0001-9596-3552
EC
Holmes
Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Life and Environmental Sciences and Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia edward.holmes@sydney.edu.au harunor.rashid@health.nsw.gov.au.|National Centre for Immunisation Research and Surveillance, The Children's Hospital at Westmead, and the Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
Harunor
H
Rashid
D004196:Disease Outbreaks; D019143:Evolution, Molecular; D014644:Genetic Variation; D006801:Humans; D009980:Influenza A virus / Q000235:genetics*; D007251:Influenza, Human / Q000453:epidemiology* / Q000635:transmission / Q000821:virology*; D007514:Islam; D008399:Mass Behavior; D008877:Middle East / Q000453:epidemiology; D009154:Mutation; D010802:Phylogeny; D011634:Public Health; D012141:Respiratory Tract Infections / Q000453:epidemiology / Q000821:virology*; D012529:Saudi Arabia / Q000453:epidemiology; D014195:Travel
Hajj; epidemiology; evolution; influenza; phylogeny; transmission