Emerging viral respiratory tract infections—environmental risk factors and transmission
Identifieur interne : 001381 ( Pmc/Corpus ); précédent : 001380; suivant : 001382Emerging viral respiratory tract infections—environmental risk factors and transmission
Auteurs : Philippe Gautret ; Gregory C. Gray ; Remi N. Charrel ; Nnanyelugo G. Odezulu ; Jaffar A. Al-Tawfiq ; Alimuddin Zumla ; Ziad A. MemishSource :
- The Lancet. Infectious Diseases [ 1473-3099 ] ; 2014.
Abstract
The past decade has seen the emergence of several novel viruses that cause respiratory tract infections in human beings, including Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia, an H7N9 influenza A virus in eastern China, a swine-like influenza H3N2 variant virus in the USA, and a human adenovirus 14p1 also in the USA. MERS-CoV and H7N9 viruses are still a major worldwide public health concern. The pathogenesis and mode of transmission of MERS-CoV and H7N9 influenza A virus are poorly understood, making it more difficult to implement intervention and preventive measures. A united and coordinated global response is needed to tackle emerging viruses that can cause fatal respiratory tract infections and to fill major gaps in the understanding of the epidemiology and transmission dynamics of these viruses.
Url:
DOI: 10.1016/S1473-3099(14)70831-X
PubMed: 25189350
PubMed Central: 7106556
Links to Exploration step
PMC:7106556Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Emerging viral respiratory tract infections—environmental risk factors and transmission</title><author><name sortKey="Gautret, Philippe" sort="Gautret, Philippe" uniqKey="Gautret P" first="Philippe" last="Gautret">Philippe Gautret</name><affiliation><nlm:aff id="aff1">Assistance Publique Hôpitaux de Marseille, CHU Nord, Pôle Infectieux, Institut Hospitalo-Universitaire Méditerranée Infection, Marseille, France</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Aix Marseille Université, Unité de Recherche en Maladies Infectieuses et Tropicales Emergentes (URMITE), Faculté de Médecine, Marseille, France</nlm:aff></affiliation></author><author><name sortKey="Gray, Gregory C" sort="Gray, Gregory C" uniqKey="Gray G" first="Gregory C" last="Gray">Gregory C. Gray</name><affiliation><nlm:aff id="aff3">College of Public Health and Health Professions and Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA</nlm:aff></affiliation></author><author><name sortKey="Charrel, Remi N" sort="Charrel, Remi N" uniqKey="Charrel R" first="Remi N" last="Charrel">Remi N. Charrel</name><affiliation><nlm:aff id="aff4">Aix Marseille Université, IRD French Institute of Research for Development, EHESP French School of Public Health, EPV UMR-D 190 “Emergence des Pathologies Virales” and IHU Méditerranée Infection, APHM Public Hospitals of Marseille, Marseille, France</nlm:aff></affiliation></author><author><name sortKey="Odezulu, Nnanyelugo G" sort="Odezulu, Nnanyelugo G" uniqKey="Odezulu N" first="Nnanyelugo G" last="Odezulu">Nnanyelugo G. Odezulu</name><affiliation><nlm:aff id="aff3">College of Public Health and Health Professions and Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA</nlm:aff></affiliation></author><author><name sortKey="Al Tawfiq, Jaffar A" sort="Al Tawfiq, Jaffar A" uniqKey="Al Tawfiq J" first="Jaffar A" last="Al-Tawfiq">Jaffar A. Al-Tawfiq</name><affiliation><nlm:aff id="aff5">Johns Hopkins Aramco Healthcare, and Indiana University School of Medicine, Indiana, USA</nlm:aff></affiliation></author><author><name sortKey="Zumla, Alimuddin" sort="Zumla, Alimuddin" uniqKey="Zumla A" first="Alimuddin" last="Zumla">Alimuddin Zumla</name><affiliation><nlm:aff id="aff6">Center for Clinical Microbiology, Division of Infection and Immunity, University College London, and NIHR Biomedical Research Center, University College London Hospitals, London, UK</nlm:aff></affiliation></author><author><name sortKey="Memish, Ziad A" sort="Memish, Ziad A" uniqKey="Memish Z" first="Ziad A" last="Memish">Ziad A. Memish</name><affiliation><nlm:aff id="aff7">WHO Collaborating Center for Mass Gathering Medicine Ministry of Health and Al-Faisal University, Riyadh, Saudi Arabia</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25189350</idno><idno type="pmc">7106556</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106556</idno><idno type="RBID">PMC:7106556</idno><idno type="doi">10.1016/S1473-3099(14)70831-X</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">001381</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001381</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Emerging viral respiratory tract infections—environmental risk factors and transmission</title><author><name sortKey="Gautret, Philippe" sort="Gautret, Philippe" uniqKey="Gautret P" first="Philippe" last="Gautret">Philippe Gautret</name><affiliation><nlm:aff id="aff1">Assistance Publique Hôpitaux de Marseille, CHU Nord, Pôle Infectieux, Institut Hospitalo-Universitaire Méditerranée Infection, Marseille, France</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Aix Marseille Université, Unité de Recherche en Maladies Infectieuses et Tropicales Emergentes (URMITE), Faculté de Médecine, Marseille, France</nlm:aff></affiliation></author><author><name sortKey="Gray, Gregory C" sort="Gray, Gregory C" uniqKey="Gray G" first="Gregory C" last="Gray">Gregory C. Gray</name><affiliation><nlm:aff id="aff3">College of Public Health and Health Professions and Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA</nlm:aff></affiliation></author><author><name sortKey="Charrel, Remi N" sort="Charrel, Remi N" uniqKey="Charrel R" first="Remi N" last="Charrel">Remi N. Charrel</name><affiliation><nlm:aff id="aff4">Aix Marseille Université, IRD French Institute of Research for Development, EHESP French School of Public Health, EPV UMR-D 190 “Emergence des Pathologies Virales” and IHU Méditerranée Infection, APHM Public Hospitals of Marseille, Marseille, France</nlm:aff></affiliation></author><author><name sortKey="Odezulu, Nnanyelugo G" sort="Odezulu, Nnanyelugo G" uniqKey="Odezulu N" first="Nnanyelugo G" last="Odezulu">Nnanyelugo G. Odezulu</name><affiliation><nlm:aff id="aff3">College of Public Health and Health Professions and Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA</nlm:aff></affiliation></author><author><name sortKey="Al Tawfiq, Jaffar A" sort="Al Tawfiq, Jaffar A" uniqKey="Al Tawfiq J" first="Jaffar A" last="Al-Tawfiq">Jaffar A. Al-Tawfiq</name><affiliation><nlm:aff id="aff5">Johns Hopkins Aramco Healthcare, and Indiana University School of Medicine, Indiana, USA</nlm:aff></affiliation></author><author><name sortKey="Zumla, Alimuddin" sort="Zumla, Alimuddin" uniqKey="Zumla A" first="Alimuddin" last="Zumla">Alimuddin Zumla</name><affiliation><nlm:aff id="aff6">Center for Clinical Microbiology, Division of Infection and Immunity, University College London, and NIHR Biomedical Research Center, University College London Hospitals, London, UK</nlm:aff></affiliation></author><author><name sortKey="Memish, Ziad A" sort="Memish, Ziad A" uniqKey="Memish Z" first="Ziad A" last="Memish">Ziad A. Memish</name><affiliation><nlm:aff id="aff7">WHO Collaborating Center for Mass Gathering Medicine Ministry of Health and Al-Faisal University, Riyadh, Saudi Arabia</nlm:aff></affiliation></author></analytic><series><title level="j">The Lancet. Infectious Diseases</title><idno type="ISSN">1473-3099</idno><idno type="eISSN">1474-4457</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Summary</title><p>The past decade has seen the emergence of several novel viruses that cause respiratory tract infections in human beings, including Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia, an H7N9 influenza A virus in eastern China, a swine-like influenza H3N2 variant virus in the USA, and a human adenovirus 14p1 also in the USA. MERS-CoV and H7N9 viruses are still a major worldwide public health concern. The pathogenesis and mode of transmission of MERS-CoV and H7N9 influenza A virus are poorly understood, making it more difficult to implement intervention and preventive measures. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Lancet Infect Dis</journal-id><journal-id journal-id-type="iso-abbrev">Lancet Infect Dis</journal-id><journal-title-group><journal-title>The Lancet. Infectious Diseases</journal-title></journal-title-group><issn pub-type="ppub">1473-3099</issn><issn pub-type="epub">1474-4457</issn><publisher><publisher-name>Elsevier Ltd.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25189350</article-id><article-id pub-id-type="pmc">7106556</article-id><article-id pub-id-type="publisher-id">S1473-3099(14)70831-X</article-id><article-id pub-id-type="doi">10.1016/S1473-3099(14)70831-X</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Emerging viral respiratory tract infections—environmental risk factors and transmission</article-title></title-group><contrib-group><contrib contrib-type="author" id="au10"><name><surname>Gautret</surname><given-names>Philippe</given-names></name><degrees>Dr</degrees><degrees>MD</degrees><email>Philippe.gautret@club-internet.fr</email><xref rid="aff1" ref-type="aff">a</xref><xref rid="aff2" ref-type="aff">b</xref><xref rid="cor1" ref-type="corresp">*</xref></contrib><contrib contrib-type="author" id="au20"><name><surname>Gray</surname><given-names>Gregory C</given-names></name><degrees>Prof</degrees><degrees>MD</degrees><xref rid="aff3" ref-type="aff">c</xref></contrib><contrib contrib-type="author" id="au30"><name><surname>Charrel</surname><given-names>Remi N</given-names></name><degrees>Prof</degrees><degrees>MD</degrees><xref rid="aff4" ref-type="aff">d</xref></contrib><contrib contrib-type="author" id="au40"><name><surname>Odezulu</surname><given-names>Nnanyelugo G</given-names></name><degrees>MSi</degrees><xref rid="aff3" ref-type="aff">c</xref></contrib><contrib contrib-type="author" id="au50"><name><surname>Al-Tawfiq</surname><given-names>Jaffar A</given-names></name><degrees>MD</degrees><xref rid="aff5" ref-type="aff">e</xref></contrib><contrib contrib-type="author" id="au60"><name><surname>Zumla</surname><given-names>Alimuddin</given-names></name><degrees>Prof</degrees><degrees>FRCP</degrees><xref rid="aff6" ref-type="aff">f</xref></contrib><contrib contrib-type="author" id="au70"><name><surname>Memish</surname><given-names>Ziad A</given-names></name><degrees>Prof</degrees><degrees>MD</degrees><xref rid="aff7" ref-type="aff">g</xref></contrib></contrib-group><aff id="aff1"><label>a</label>Assistance Publique Hôpitaux de Marseille, CHU Nord, Pôle Infectieux, Institut Hospitalo-Universitaire Méditerranée Infection, Marseille, France</aff><aff id="aff2"><label>b</label>Aix Marseille Université, Unité de Recherche en Maladies Infectieuses et Tropicales Emergentes (URMITE), Faculté de Médecine, Marseille, France</aff><aff id="aff3"><label>c</label>College of Public Health and Health Professions and Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA</aff><aff id="aff4"><label>d</label>Aix Marseille Université, IRD French Institute of Research for Development, EHESP French School of Public Health, EPV UMR-D 190 “Emergence des Pathologies Virales” and IHU Méditerranée Infection, APHM Public Hospitals of Marseille, Marseille, France</aff><aff id="aff5"><label>e</label>Johns Hopkins Aramco Healthcare, and Indiana University School of Medicine, Indiana, USA</aff><aff id="aff6"><label>f</label>Center for Clinical Microbiology, Division of Infection and Immunity, University College London, and NIHR Biomedical Research Center, University College London Hospitals, London, UK</aff><aff id="aff7"><label>g</label>WHO Collaborating Center for Mass Gathering Medicine Ministry of Health and Al-Faisal University, Riyadh, Saudi Arabia</aff><author-notes><corresp id="cor1"><label>*</label>Correspondence to: Dr Philippe Gautret, Service des Maladies Infectieuses et Tropicales, Hôpital Nord, Chemin des Bourrelys, 13915, Marseille, Cedex 20, France <email>Philippe.gautret@club-internet.fr</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>1</day><month>9</month><year>2014</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub"><month>11</month><year>2014</year></pub-date><pub-date pub-type="epub"><day>1</day><month>9</month><year>2014</year></pub-date><volume>14</volume><issue>11</issue><fpage>1113</fpage><lpage>1122</lpage><permissions><copyright-statement>Copyright © 2014 Elsevier Ltd. All rights reserved.</copyright-statement><copyright-year>2014</copyright-year><copyright-holder>Elsevier Ltd</copyright-holder><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions><related-article related-article-type="article-reference" id="d32e1009" ext-link-type="doi" xlink:href="10.1016/S1473-3099(14)70899-0"></related-article><abstract id="ceab10"><title>Summary</title><p>The past decade has seen the emergence of several novel viruses that cause respiratory tract infections in human beings, including Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia, an H7N9 influenza A virus in eastern China, a swine-like influenza H3N2 variant virus in the USA, and a human adenovirus 14p1 also in the USA. MERS-CoV and H7N9 viruses are still a major worldwide public health concern. The pathogenesis and mode of transmission of MERS-CoV and H7N9 influenza A virus are poorly understood, making it more difficult to implement intervention and preventive measures. A united and coordinated global response is needed to tackle emerging viruses that can cause fatal respiratory tract infections and to fill major gaps in the understanding of the epidemiology and transmission dynamics of these viruses.</p></abstract></article-meta></front><body><p id="para10">This is the third in a <bold>Series</bold> of five papers on emerging respiratory tract infections</p><sec id="cesec10"><title>Introduction</title><p id="para20">Since the recognition of severe acute respiratory syndrome (SARS) in 2003, several new viruses have emerged in different parts of the world. Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia and Jordan in 2012, with several cases documented in European travellers who had visited the Middle East. More than 840 human cases of MERS-CoV infection have been confirmed as of July, 2014. Most patients had respiratory disease with a range of clinical manifestations from mild, asymptomatic cases to severe multisystem illness; mortality was about 38%. Human adenovirus 14 (HAdV14) was first recognised in 1955 and it re-emerged in 2006 in the USA in a slightly different form (HAdV-14p1). Outbreaks have been restricted to the USA and China, with cases totalling in the hundreds, and mortality has been low. Influenza A H7N9 virus emerged in eastern China in early 2013 with very few cases occurring outside of China. As of June, 2014, more than 448 confirmed human cases have been documented with an estimated 39% mortality rate. Avian influenza A H10N8, the first strain of which was isolated from birds several decades ago, emerged in 2013 to infect at least three people in China, leading to one death. Similarly, in 2011 a novel swine-like influenza H3N2 variant virus emerged in two states in the USA, causing disease in 12 people. By the end of 2013, the virus had spread to ten states and caused at least 340 people to be ill (with one death). In this paper, we review the epidemiology of these emerging viruses, including their geographical distribution, modes of transmission, and where appropriate their zoonotic characteristics.</p></sec><sec id="cesec20"><title>MERS</title><sec id="cesec30"><title>Geographical distribution</title><p id="para30">MERS-CoV infection is a new human disease that was first reported in Saudi Arabia in June, 2012 (<xref rid="fig1" ref-type="fig">figure</xref>).<xref rid="bib1" ref-type="bibr"><sup>1</sup></xref> Retrospective investigation of a hospital outbreak of 13 cases of respiratory infections in Zarqa, Jordan in April, 2012, identified two confirmed and 11 probable cases of which ten were among health-care workers.<xref rid="bib2" ref-type="bibr"><sup>2</sup></xref> As of the end of July, 2014, 841 confirmed cases, including 327 deaths (38·4%), have been reported by local authorities worldwide.<xref rid="bib3" ref-type="bibr"><sup>3</sup></xref> Almost all confirmed cases were reported from the Middle East, notably Saudi Arabia, but also neighboring countries including Egypt, Iran, Jordan, Kuwait, Lebanon, Oman, Qatar, United Arab Emirates (UAE), and Yemen. According to the European Centre for Disease Prevention and Control (ECDC), cases have been reported in Algeria, France, Germany, Greece, Italy, Malaysia, the Netherlands, Philippines, Tunisia, the UK, and the USA. Overall, all cases originated from or had a history of travel to the Middle East, with few secondary cases.<xref rid="bib3" ref-type="bibr"><sup>3</sup></xref><fig id="fig1"><label>Figure</label><caption><p>Geographical distribution of human cases of emerging respiratory viruses</p></caption><graphic xlink:href="gr1_lrg"></graphic></fig></p><p id="para40"><boxed-text id="cetextbox10"><caption><title>Key messages</title></caption><p id="para50"><list list-type="simple" id="celist10"><list-item id="celistitem10"><label>•</label><p id="para60">Over the past decade, several new viruses causing respiratory tract disease in human beings have emerged in different parts of the world.</p></list-item><list-item id="celistitem20"><label>•</label><p id="para70">Human adenovirus (HAdV) 14p1 has been identified in people only, but Middle East respiratory syndrome coronavirus (MERS-CoV), influenza A H7N9, influenza A H10N8, and influenza A H3N2 variant are zoonotic diseases.</p></list-item><list-item id="celistitem30"><label>•</label><p id="para80">HAdV14 first recognised in 1955 re-emerged in 2006 in the USA and China.</p></list-item><list-item id="celistitem40"><label>•</label><p id="para90">As of June, 2014, more than 448 confirmed human cases of avian Influenza A H7N9 virus infection have been documented since its first discovery in early 2013.</p></list-item><list-item id="celistitem50"><label>•</label><p id="para100">Influenza A H7N9 virus can survive for months in the environment, and the absence of clinical signs in poultry, ducks, and wild birds makes it particularly difficult to control.</p></list-item><list-item id="celistitem60"><label>•</label><p id="para110">An avian influenza H10N8 virus has recently emerged in 2013 to infect at least three people in China.</p></list-item><list-item id="celistitem70"><label>•</label><p id="para120">In 2011 a novel swine-like influenza A H3N2 variant virus emerged in two states in the USA, and by the end of 2013 it had spread to ten states and caused illness in at least 340 people. The absence of clinical signs among influenza A H3N2 variant infected pigs is a major concern in that people are essentially serving as sentinels of infection.</p></list-item><list-item id="celistitem80"><label>•</label><p id="para130">First identified in Saudi Arabia in 2012, the number of human cases of MERS-CoV infection have steadily increased to more than 840. Nosocomial transmission to patients and health-care workers has been documented.</p></list-item><list-item id="celistitem90"><label>•</label><p id="para140">While geographically restricted to the Middle East, MERS-CoV is of major public health concern since millions of pilgrims from 184 countries visit Saudi Arabia for pilgrimage throughout the year.</p></list-item><list-item id="celistitem100"><label>•</label><p id="para150">There is a mounting evidence suggesting that camels are the likely reservoir of MERS-CoV human infections although the precise mode of transmission to humans remains unknown.</p></list-item><list-item id="celistitem110"><label>•</label><p id="para160">A united and coordinated global response is needed to tackle new infectious diseases threats posed by novel viruses that can cause fatal respiratory tract infections over the past decade and to fill major gaps that remain in the understanding of their epidemiology and transmission dynamics.</p></list-item></list></p></boxed-text></p><p id="para170">Most cases of MERS-CoV infection have been in Saudi Arabia where the Hajj, a large religious mass gathering, takes place each year. The Hajj draws 2–3 million pilgrims from within Saudi Arabia and around the world. Worldwide attention has focused on the potential spread of MERS-CoV after the Hajj pilgrimage because pilgrims have a high risk of respiratory tract infections because of crowded conditions.<xref rid="bib4" ref-type="bibr"><sup>4</sup></xref> In 2013, the Saudi Ministry of Health recommended that elderly people (older than 65 years), people with chronic diseases (eg, heart disease, kidney disease, respiratory disease, and diabetes), the immunocompromised (congenital and acquired), people with malignant disease or terminal illnesses, pregnant women, and children (age less than 12 years) postpone their participation in the Hajj and Umrah for their own safety.<xref rid="bib5" ref-type="bibr"><sup>5</sup></xref> Investigations done among French pilgrims participating in the 2013 Hajj showed that 48% had at least one disorder for which the Saudi Ministry of Health recommends participation in the Hajj be postponed.<xref rid="bib6" ref-type="bibr">6</xref>, <xref rid="bib7" ref-type="bibr">7</xref> None of 179 individuals at risk decided to cancel participation, even after receiving this advice during consultation.<xref rid="bib6" ref-type="bibr">6</xref>, <xref rid="bib7" ref-type="bibr">7</xref> All countries (particularly those with returning pilgrims) were advised by the International Health Regulations Emergency Committee to strengthen their surveillance capacities and ensure robust reporting of any identified cases.<xref rid="bib8" ref-type="bibr"><sup>8</sup></xref> Cohort surveys of returning French pilgrims with systematic screening of MERS-CoV nasal carriage by PCR were done in 2012 and 2013, and the results were negative despite high rates of respiratory symptoms.<xref rid="bib9" ref-type="bibr">9</xref>, <xref rid="bib10" ref-type="bibr">10</xref> However, pilgrims rapidly acquired other respiratory viruses during their stay in Saudi Arabia (especially rhinovirus and influenza viruses, which emphasises the potential of these infections to spread in the pilgrims' home countries on their return.<xref rid="bib10" ref-type="bibr">10</xref>, <xref rid="bib11" ref-type="bibr">11</xref> Screening of pilgrims from 22 countries before (3210 pilgrims) and after (2025) Hajj in 2013 did not reveal any positive cases by RT-PCR.<xref rid="bib12" ref-type="bibr"><sup>12</sup></xref></p></sec><sec id="cesec40"><title>Between human transmission of MERS-CoV</title><p id="para180">Most MERS-CoV cases reported have probably acquired infection through human-to-human transmission. Among 144 confirmed and 17 probable cases analysed by the MERS-CoV Research Group in November, 2013, 95 (59%) were classified as secondary cases with epidemiological links to other confirmed cases. Among these, most acquired the infection in health-care settings (63·2%), followed by those infected in household settings (13·7%).<xref rid="bib13" ref-type="bibr"><sup>13</sup></xref> In the same report, clusters of cases secondary to human-to-human transmission occurred with a cluster size ranging from two to 25 patients. The largest cluster was in Al-Hasa (Saudi Arabia) with 25 cases among patients undergoing hemodialysis, visiting family members, and health-care workers.<xref rid="bib14" ref-type="bibr"><sup>14</sup></xref> However, a description of the geographical distribution and phylogenetic relation of MERS-CoV infections across time suggests that the Al-Hasa hospital outbreak might have been caused by more than one virus introduction.<xref rid="bib15" ref-type="bibr"><sup>15</sup></xref> Other clusters in the health-care setting have been described in France, Jordan, Qatar, Saudi Arabia, and UAE.<xref rid="bib13" ref-type="bibr"><sup>13</sup></xref> Several clusters have been described in the context of the household setting in Saudi Arabia and Tunisia, or in both the contexts of health-care and household settings in the UK.<xref rid="bib13" ref-type="bibr">13</xref>, <xref rid="bib16" ref-type="bibr">16</xref>, <xref rid="bib17" ref-type="bibr">17</xref> Transmission in all reported clusters is restricted, and evidence from contact-tracing suggests that transmission did not extend beyond close contacts into the community. Assessment of the between-human transmissibility of MERS-CoV by two teams with available non-hospital epidemiological data confirmed the restricted pattern of transmission. The estimated R<sub>0</sub> was 0·60–0·69 in one study and 0·8–1·3 in another (<xref rid="tbl1" ref-type="table">table 1</xref>).<xref rid="bib18" ref-type="bibr">18</xref>, <xref rid="bib19" ref-type="bibr">19</xref> In the absence of appropriate hospital infection control, R<sub>0</sub> might be greater than 1 in hospitals admitting patients with MERS-CoV.<table-wrap position="float" id="tbl1"><label>Table 1</label><caption><p>Emerging respiratory viruses as of June, 2014</p></caption><table frame="hsides" rules="groups"><thead><tr><th></th><th align="left"><bold>Total human cases</bold></th><th align="left"><bold>Total human deaths</bold></th><th align="left"><bold>Clusters</bold></th><th align="left"><bold>Environmental properties</bold></th><th align="left"><bold>R<sub>0</sub></bold></th></tr></thead><tbody><tr><td align="left">MERS-CoV<xref rid="tbl1fn1" ref-type="table-fn">*</xref></td><td align="left">841</td><td align="left">327</td><td align="left">Family and health-care settings</td><td align="left">Stable at low temperature and low humidity</td><td align="left">0·60–0·69 <italic>vs</italic> 0·8–1·3</td></tr><tr><td align="left">Human adenovirus 14p1</td><td align="left">Many</td><td align="left">13</td><td align="left">Military and school settings</td><td align="left">Unknown</td><td align="left">Unknown</td></tr><tr><td align="left">H7N9 avian influenza virus</td><td align="left">448</td><td align="left">157</td><td align="left">Family settings</td><td align="left">Survives for months in the environment</td><td align="left">0·11–0·45</td></tr><tr><td align="left">H10N8 avian influenza virus</td><td align="left">3</td><td align="left">1</td><td align="left">None</td><td align="left">Water persistence</td><td align="left">Unknown</td></tr><tr><td align="left">H3N2 variant influenza virus</td><td align="left">340</td><td align="left">1</td><td align="left">Geriatric ward settings</td><td align="left">··</td><td align="left">Unknown</td></tr></tbody></table><table-wrap-foot><fn><p>MERS-CoV=Middle East respiratory syndrome coronavirus.</p></fn></table-wrap-foot><table-wrap-foot><fn id="tbl1fn1"><label>*</label><p id="cenpara10">Data to end of July, 2014.</p></fn></table-wrap-foot></table-wrap></p></sec><sec id="cesec50"><title>Evidence for a zoonotic source for MERS-CoV</title><p id="para190">MERS-CoV belongs to the lineage C βcoronaviruses, which are associated with bats.<xref rid="bib20" ref-type="bibr"><sup>20</sup></xref> Close relatives of MERS-CoV have been identified in European, Asian, Central American, and South African bats.<xref rid="bib21" ref-type="bibr">21</xref>, <xref rid="bib22" ref-type="bibr">22</xref>, <xref rid="bib23" ref-type="bibr">23</xref>, <xref rid="bib24" ref-type="bibr">24</xref>, <xref rid="bib25" ref-type="bibr">25</xref>, <xref rid="bib26" ref-type="bibr">26</xref>, <xref rid="bib27" ref-type="bibr">27</xref> A new β-coronavirus related to MERS-CoV has also been characterised in European hedgehogs.<xref rid="bib28" ref-type="bibr"><sup>28</sup></xref> The genome diversity of human MERS-CoV isolates suggests that human infections result from several independent zoonotic events from an unknown reservoir in the Middle East.<xref rid="bib15" ref-type="bibr">15</xref>, <xref rid="bib29" ref-type="bibr">29</xref> Among 161 patients with MERS-CoV analysed by the MERS-CoV Research Group in November, 2013, 51 (32%) were classified as probably sporadic (<xref rid="tbl2" ref-type="table">table 2</xref>) or index cases (no exposure to other known cases). Contact of patients with camels was documented in only five of 51 cases; however, reliable information was available from only 28 cases.<xref rid="bib13" ref-type="bibr"><sup>13</sup></xref> MERS-CoV spike-protein-binding antibodies and virus neutralising antibodies are reported in high proportions of camels from the Canary Islands, Egypt, Jordan, Oman, Qatar, Saudi Arabia, UAE, but not from other livestock including sheep, goats, cattle, and chickens.<xref rid="bib30" ref-type="bibr">30</xref>, <xref rid="bib31" ref-type="bibr">31</xref>, <xref rid="bib32" ref-type="bibr">32</xref>, <xref rid="bib33" ref-type="bibr">33</xref>, <xref rid="bib34" ref-type="bibr">34</xref>, <xref rid="bib35" ref-type="bibr">35</xref>, <xref rid="bib36" ref-type="bibr">36</xref>, <xref rid="bib37" ref-type="bibr">37</xref> A higher seroprevalence was reported in adults than in juvenile camels.<xref rid="bib33" ref-type="bibr">33</xref>, <xref rid="bib36" ref-type="bibr">36</xref> Furthermore, MERS-CoV was detected by quantitative (q) RT-PCR from nasal samples in 11 of 14 camels from a farm in Qatar linked to two confirmed human cases, five of 76 camels from Oman, 36 of 104 juvenile camels from Saudi Arabia, 15 of 98 adult camels from Saudi Arabia, and four of 110 camels from Egypt, two of which were imported from Sudan and Ethiopia.<xref rid="bib31" ref-type="bibr">31</xref>, <xref rid="bib33" ref-type="bibr">33</xref>, <xref rid="bib38" ref-type="bibr">38</xref>, <xref rid="bib39" ref-type="bibr">39</xref> Genomic sequences of MERS-CoV isolates from two patients and from their infected camels were almost identical, suggesting camel-to-human transmission.<xref rid="bib40" ref-type="bibr">40</xref>, <xref rid="bib41" ref-type="bibr">41</xref><table-wrap position="float" id="tbl2"><label>Table 2</label><caption><p>Potential sources and transmission patterns of emerging respiratory viruses</p></caption><table frame="hsides" rules="groups"><thead><tr><th></th><th align="left"><bold>Potential sources</bold></th><th align="left"><bold>Transmission patterns</bold></th></tr></thead><tbody><tr><td align="left">Middle East respiratory syndrome coronavirus</td><td align="left">Human patients, camels, bats, and environment (camel farms)</td><td align="left">Human-to-human (59%), sporadic</td></tr><tr><td align="left">Human adenovirus 14p1</td><td align="left">Human patients and asymptomatic shedders</td><td align="left">Sporadic, human-to-human (close and frequent contact)</td></tr><tr><td align="left">H7N9 avian influenza virus</td><td align="left">Live birds, poultry, environment (bird markets, poultry farms, wet markets — soil and surface waters), and human patients</td><td align="left">Direct contact with live poultry, human-to-human (possible but restricted and non-sustainable)</td></tr><tr><td align="left">H10N8 avian influenza virus</td><td align="left">Live birds and poultry, environment (soil and surface water)</td><td align="left">Exposure to poultry</td></tr><tr><td align="left">H3N2 variant influenza virus</td><td align="left">Pigs, pig environments (agriculture fairs), and human patients</td><td align="left">Direct or indirect contact with pigs, human-to-human (possible but restricted and non-sustainable)</td></tr></tbody></table></table-wrap></p><p id="para200">A novel coronavirus (DcCoV UAE-HKU23) was detected by qRT-PCR in 21% of faecal samples from dromedary calves in UAE. 97–100% of camels were positive for MERS-CoV antibody testing by various methods, whereas 52% only had antibodies against DcCoV UAE-HKU23, which shows that little correlation exists between seropositivity to the two viruses.<xref rid="bib35" ref-type="bibr"><sup>35</sup></xref> Additionally, a gene fragment was recovered from a faecal sample from a bat in Saudi Arabia, near the home of a confirmed human case; bat and human isolates were 100% homologous.<xref rid="bib42" ref-type="bibr"><sup>42</sup></xref> Studies addressing the seroprevalence of MERS-CoV among human beings are highly demanding from a technical perspective, because titres are generally low, and there is crossreactivity between coronaviruses.<xref rid="bib43" ref-type="bibr"><sup>43</sup></xref></p><p id="para210">Studies done on 624 serum specimens from people in Saudi Arabia, including slaughterhouse workers, by discriminative methods failed to show evidence for the presence of antibodies.<xref rid="bib43" ref-type="bibr">43</xref>, <xref rid="bib44" ref-type="bibr">44</xref> Dromedary camels harbour the virus and shed MERS-CoV in respiratory secretions. The frequency of positive serology in camels versus human beings strongly suggests that camels are the reservoir for human exposure. Unpasteurised camel milk is a possible route of transmission, but so far few studies have assessed the prevalence of MERS-CoV in camel milk. A study in April, 2014 showed that camel milk was positive for MERS-CoV by qRT-PCR.<xref rid="bib45" ref-type="bibr"><sup>45</sup></xref> Finally, the reservoirs might have complex ecology, and bats might play a part.</p></sec><sec id="cesec60"><title>Evidence for environmental source for MERS-CoV</title><p id="para220">Only one study has investigated the stability of MERS-CoV under different environmental conditions.<xref rid="bib46" ref-type="bibr"><sup>46</sup></xref> MERS-CoV was stable at low temperatures and low humidity and could be recovered after 48 h at 20°C and 40% relative humidity. Aerosolisation of MERS-CoV did not affect its stability. These data show the potential for MERS-CoV to be transmitted via contact or fomite transmission as a result of prolonged environmental presence.</p></sec><sec id="cesec70"><title>Putative mode of transmission of MERS-CoV</title><p id="para230">The exact mode of transmission of MERS-CoV is unknown. However, several MERS-CoV clusters have implicated human-to-human transmission among health-care worker, hospital inpatient, and family cluster case series.<xref rid="bib47" ref-type="bibr"><sup>47</sup></xref> Such transmission could be through respiratory droplets or direct or indirect contact.<xref rid="bib48" ref-type="bibr"><sup>48</sup></xref> With a model developed by measurement of the hardness of coronavirus inner and outer protein shells, MERS-CoV was predicted to be readily transmitted through an oral–faecal route and also possibly via respiratory secretions.<xref rid="bib49" ref-type="bibr"><sup>49</sup></xref></p></sec></sec><sec id="cesec80"><title>Human adenovirus 14</title><sec id="cesec90"><title>Geographical distribution</title><p id="para240">HAdDV-14 was first discovered in 1955 during an outbreak of acute respiratory infections among military trainees in the Netherlands.<xref rid="bib50" ref-type="bibr"><sup>50</sup></xref> Soon after, other outbreaks were reported in Czechoslovakia, England, and Uzbekistan (<xref rid="fig1" ref-type="fig">figure</xref>).<xref rid="bib51" ref-type="bibr">51</xref>, <xref rid="bib52" ref-type="bibr">52</xref>, <xref rid="bib53" ref-type="bibr">53</xref>, <xref rid="bib54" ref-type="bibr">54</xref> The circulation and case reports of HAdV-14 infections ceased during the early 1960s until the beginning of the 1970s when the virus was again detected in the Netherlands.<xref rid="bib53" ref-type="bibr"><sup>53</sup></xref> In the early part of this century, suspected cases of HAdV-14 were identified in Taiwan.<xref rid="bib55" ref-type="bibr"><sup>55</sup></xref> During 2006, a variant of HAdV-14 (later dubbed HAdV-14p1) caused epidemics among US military trainees in five states: California, Georgia, Illinois, Montana, and Texas.<xref rid="bib53" ref-type="bibr">53</xref>, <xref rid="bib56" ref-type="bibr">56</xref>, <xref rid="bib57" ref-type="bibr">57</xref> From 2003 until now, sporadic HAdV-14p1 cases and clusters of cases were also described among civilians throughout the USA (Alaska, California, Kansas, New York, Oklahoma, Oregon, Pennsylvania, South Carolina, Texas, Washington, and Wisconsin)<xref rid="bib53" ref-type="bibr">53</xref>, <xref rid="bib58" ref-type="bibr">58</xref>, <xref rid="bib59" ref-type="bibr">59</xref>, <xref rid="bib60" ref-type="bibr">60</xref>, <xref rid="bib61" ref-type="bibr">61</xref> In 2009–10, nine sporadic cases were reported in Ireland.<xref rid="bib61" ref-type="bibr"><sup>61</sup></xref> In October 2010, HAdV-14p1 was detected by culture in a 17-month-old child with tonsillitis living in Guangzhou, southern China.<xref rid="bib62" ref-type="bibr"><sup>62</sup></xref> In December 2010, HAdV-14p1 was isolated from a 6-month-old child presenting with pneumonia in Beijing, China.<xref rid="bib63" ref-type="bibr"><sup>63</sup></xref> In April 2011, an outbreak occurred affecting 43 children (8–15 years old) attending school in the Tongwei County of the Gansu province (northwestern China), of whom 11 were identified with infection of HAdV-14p1.<xref rid="bib64" ref-type="bibr"><sup>64</sup></xref> During summer 2011, three sporadic epidemiologically unrelated HAdV-14p1 cases were identified in the Canadian province of New Brunswick.<xref rid="bib65" ref-type="bibr"><sup>65</sup></xref></p></sec><sec id="cesec100"><title>Between-human transmission of HAdV-14p1</title><p id="para250">HAdVs are chiefly transmitted via direct contact, aerosol, or contact with fomites. HAdV-14 strains are predominantly associated with upper and lower respiratory infections, and hence respiratory secretions are infectious. Adenoviruses are ubiquitous in military training facilities.<xref rid="bib66" ref-type="bibr"><sup>66</sup></xref> People at risk of HAdV-14p1 infection include military trainees, young children, and the immunocompromised (<xref rid="tbl1" ref-type="table">table 1</xref>). During HAdV outbreaks, the high prevalence of asymptomatic infected individuals renders the surveillance and targeted countermeasures very difficult to enforce (<xref rid="tbl2" ref-type="table">table 2</xref>). So far, the basic reproductive rate (R<sub>0</sub>) has not been estimated for HAdV-14p1.</p></sec><sec id="cesec110"><title>Evidence for a zoonotic source for HAdV-14p1</title><p id="para260">Cross-species transmission of a simian adenovirus from monkeys to man has been documented with scarce human-to-human infection.<xref rid="bib67" ref-type="bibr">67</xref>, <xref rid="bib68" ref-type="bibr">68</xref> HAdV-14 strains are human adenovirus B (mastadenoviruses of the family Adenoviridae); all other adenovirus B are human viruses (HAdV-3, 7, 11, 16, 21, 34, 35, 50) except for the simian adenovirus 21.<xref rid="bib69" ref-type="bibr"><sup>69</sup></xref> Most of the simian adenoviruses isolated from non-human primates are phylogenetically related to human adenoviruses and belong to the species B, C, and E.<xref rid="bib70" ref-type="bibr"><sup>70</sup></xref> However, there are no observational data to suggest that human HAdV-14p1 infections might be epidemiologically linked to contact with non-human primates. There is no evidence that HAdV-14p1 is zoonotic.</p></sec><sec id="cesec120"><title>Evidence for environmental sources of HAdV-14p1</title><p id="para270">No specific data for HAdV-14p1 suggest either an environmental reservoir or an environmental source of infection. However, other human adenoviruses are stable in the environment, and HAdV-B14p1 probably has similar characteristics. The infectivity of mastadenoviruses is suppressed after 10 min at 56°C or above; they are infectious when frozen, stable when exposed to mild acids, and insensitive to lipid solvents.<xref rid="bib69" ref-type="bibr"><sup>69</sup></xref></p></sec><sec id="cesec130"><title>Putative mode of transmission of HAdV-14</title><p id="para280">No study is specifically dedicated to the transmissions of HAdV-14p1; however, this virus is probably transmitted through mechanisms similar to those recorded for other human adenoviruses that cause respiratory tract infections. Adenoviruses frequently cause epidemics among military trainees, children (especially newborns), institutionalised people in hospitals and nursing homes, and immunocompromised people.<xref rid="bib71" ref-type="bibr">71</xref>, <xref rid="bib72" ref-type="bibr">72</xref>, <xref rid="bib73" ref-type="bibr">73</xref>, <xref rid="bib74" ref-type="bibr">74</xref> Because of their innate nature, adenoviruses are hardy and resistant to environmental changes; they can be transmitted directly from person to person, and indirectly from environment to person.<xref rid="bib69" ref-type="bibr"><sup>69</sup></xref> For HAdV-14p1, the substantial proportion of epidemic episodes that occurred in a community (eg, schools and military camps) suggests that close proximity is a key factor for outbreaks.<xref rid="bib53" ref-type="bibr"><sup>53</sup></xref></p></sec></sec><sec id="cesec140"><title>Avian influenza H7N9 virus</title><sec id="cesec150"><title>Geographical distribution</title><p id="para290">The outbreak of a human novel influenza A H7N9 virus infection that occurred in early 2013 in eastern China (<xref rid="fig1" ref-type="fig">figure</xref>) raised serious concerns among public health professionals about the possibility of an imminent influenza pandemic.<xref rid="bib75" ref-type="bibr">75</xref>, <xref rid="bib76" ref-type="bibr">76</xref> As of June, 2014, more than 440 laboratory-confirmed cases and more than 150 deaths from influenza A H7N9 have occurred.<xref rid="bib77" ref-type="bibr"><sup>77</sup></xref> Novel influenza A H7N9 spread rapidly, involving numerous provinces in China, Hong Kong, Malaysia, and Taiwan.<xref rid="bib76" ref-type="bibr">76</xref>, <xref rid="bib78" ref-type="bibr">78</xref> Influenza A H7N9 virus infections are associated with fever, chills, shivering, cough, chest pain, dyspnoea, nausea and vomiting,<xref rid="bib79" ref-type="bibr"><sup>79</sup></xref> lymphocytopenia, leucopenia,<xref rid="bib80" ref-type="bibr"><sup>80</sup></xref> hyperpyrexia, respiratory failure, acute respiratory distress syndrome, multiorgan failure,<xref rid="bib81" ref-type="bibr"><sup>81</sup></xref> fulminant pneumonia, septic shock, rhabdomyolysis, and encephalopathy.<xref rid="bib82" ref-type="bibr"><sup>82</sup></xref></p></sec><sec id="cesec160"><title>Between-human transmission</title><p id="para300">The poorly understood pathogenesis and unknown mode of transmission of H7N9,<xref rid="bib83" ref-type="bibr"><sup>83</sup></xref> coupled with the absence of mass deaths in poultry and wild birds before disease outbreaks makes public health intervention measures difficult to implement.<xref rid="bib84" ref-type="bibr"><sup>84</sup></xref> The risk of human-to-human transmission of influenza A H7N9 is controversial since cases of family clustering could be a result of between-human transmission or a result of common exposure to infected poultry or other environmental risk factors.<xref rid="bib85" ref-type="bibr"><sup>85</sup></xref> Some researchers argue that routes of human infections are only through exposure to poultry, wild birds, or via avian environmental exposures.<xref rid="bib75" ref-type="bibr"><sup>75</sup></xref> They claim that between-human transmission is unlikely since many close contacts of confirmed H7N9 cases did not have evidence for influenza A H7N9 infection.<xref rid="bib80" ref-type="bibr"><sup>80</sup></xref> Supporters of the bird-exposure hypothesis also argue that the reduction in human H7N9 cases after the April 2013 closure of live poultry and bird markets supports their view.<xref rid="bib86" ref-type="bibr"><sup>86</sup></xref> Furthermore, they argue that recorded family clustering can be explained as a result of common exposure to birds or their environments and not as a result of human-to-human transmission.<xref rid="bib79" ref-type="bibr"><sup>79</sup></xref> Some researchers also used mathematical models to suggest that the reproduction number for human-to-human transmission of the novel influenza A H7N9 is well below unity<xref rid="bib87" ref-type="bibr"><sup>87</sup></xref> Other researchers argue that there is a strong possibility of restricted and non-sustainable H7N9 human-to-human transmission.<xref rid="bib81" ref-type="bibr"><sup>81</sup></xref> They argue that a confirmed case, without exposure to live birds or live poultry markets, developed the disease and died of multiorgan failure after taking care of a confirmed sick close relative who also died of the disease, with the genome sequencing of the viruses isolated from the two patients being almost identical.<xref rid="bib81" ref-type="bibr"><sup>81</sup></xref> A case-control study also excluded a participant from the study on the grounds of being infected with a possible human-to-human transmission.<xref rid="bib88" ref-type="bibr"><sup>88</sup></xref> Another study showed that some close relatives of confirmed cases developed respiratory symptoms but did not give positive results for influenza A H7N9 virus, thereby stating that, although low, the risk of human-to-human transmission is still a possibility.<xref rid="bib89" ref-type="bibr"><sup>89</sup></xref></p></sec><sec id="cesec170"><title>Evidence for a zoonotic source</title><p id="para310">Exposure to infected poultry seems to be the major cause of human infection with influenza A H7N9 (<xref rid="tbl2" ref-type="table">table 2</xref>)<xref rid="bib75" ref-type="bibr">75</xref>, <xref rid="bib76" ref-type="bibr">76</xref>, <xref rid="bib87" ref-type="bibr">87</xref> because of the strong similarity between influenza A H7N9 isolates detected among human beings and poultry.<xref rid="bib80" ref-type="bibr"><sup>80</sup></xref> Almost all cases had either a direct contact with live poultry<xref rid="bib89" ref-type="bibr"><sup>89</sup></xref> or were exposed to environmental sources such as live bird markets, poultry farms, and wet markets where live birds are slaughtered and processed.<xref rid="bib75" ref-type="bibr">75</xref>, <xref rid="bib76" ref-type="bibr">76</xref>, <xref rid="bib79" ref-type="bibr">79</xref> Most outbreaks occurred in provinces along the eastern Asian–Australian flyway, along which migratory birds travel, flying over areas with densely populated poultry farms, live bird markets, rice farms, and free grazing ducks.<xref rid="bib84" ref-type="bibr">84</xref>, <xref rid="bib90" ref-type="bibr">90</xref>, <xref rid="bib91" ref-type="bibr">91</xref> Influenza A H7N9 viruses have been isolated from chickens and pigeons in markets in some of the affected provinces,<xref rid="bib79" ref-type="bibr">79</xref>, <xref rid="bib80" ref-type="bibr">80</xref> and from poultry cages and faeces in some live poultry and bird markets in the provinces.<xref rid="bib88" ref-type="bibr"><sup>88</sup></xref></p></sec><sec id="cesec180"><title>Evidence for an environmental source</title><p id="para320">Environmental factors have important roles in the onset and maintenance of H7N9 outbreaks.<xref rid="bib90" ref-type="bibr"><sup>90</sup></xref> Many of the confirmed cases had occupational exposures such as being a poultry worker, slaughtering birds in wet poultry markets, or visiting or purchasing live birds or poultry from live bird markets.<xref rid="bib76" ref-type="bibr">76</xref>, <xref rid="bib85" ref-type="bibr">85</xref>, <xref rid="bib89" ref-type="bibr">89</xref> Environmental samples in live poultry markets yielded positive results for the novel influenza H7N9 virus,<xref rid="bib76" ref-type="bibr"><sup>76</sup></xref> which was also isolated from contaminated soils and surface water<xref rid="bib90" ref-type="bibr"><sup>90</sup></xref> and from the immediate environment of a confirmed case.<xref rid="bib76" ref-type="bibr"><sup>76</sup></xref> H7N9 can survive for months in the environment thereby leading to risk of infections to poultry or human beings long after initial detection (<xref rid="tbl1" ref-type="table">table 1</xref>).<xref rid="bib76" ref-type="bibr">76</xref>, <xref rid="bib90" ref-type="bibr">90</xref> Since the closure of live bird markets, which create environments allowing prolonged and repeated exposure of live birds and people (thereby increasing the risk of disease outbreaks), there has been a substantial decrease in the number of human cases of H7N9 in the affected regions.<xref rid="bib92" ref-type="bibr"><sup>92</sup></xref></p></sec><sec id="cesec190"><title>Putative modes of transmission</title><p id="para330">The transmissibility and pathogenesis of the novel influenza A H7N9 are still poorly understood,<xref rid="bib76" ref-type="bibr"><sup>76</sup></xref> but direct contact to host agents and exposure to environmental risk factors seem to be the generally approved means of transmission to human beings.<xref rid="bib90" ref-type="bibr"><sup>90</sup></xref> Bird-to-human route, poultry-to-human route, and exposure to environmental risk factors are probably the major causes of human infection with the novel influenza A H7N9,<xref rid="bib75" ref-type="bibr">75</xref>, <xref rid="bib76" ref-type="bibr">76</xref>, <xref rid="bib79" ref-type="bibr">79</xref> though some researchers believe that human-to-human transmission is thus far non-sustainable.</p></sec></sec><sec id="cesec200"><title>Avian influenza H10N8</title><sec id="cesec210"><title>Geographical distribution</title><p id="para340">In December, 2013, WHO reported the first human case of avian influenza A H10N8 virus in China (<xref rid="fig1" ref-type="fig">figure</xref>),<xref rid="bib93" ref-type="bibr">93</xref>, <xref rid="bib94" ref-type="bibr">94</xref> but the virus was first isolated from birds in Italy in 1965.<xref rid="bib95" ref-type="bibr"><sup>95</sup></xref> Though usually without clinical signs in birds,<xref rid="bib96" ref-type="bibr"><sup>96</sup></xref> H10N8 has been isolated in both North America and Asia.<xref rid="bib95" ref-type="bibr"><sup>95</sup></xref> All three human cases (including one death) were detected in Nanchang City, Jiangxi Province, China.<xref rid="bib93" ref-type="bibr">93</xref>, <xref rid="bib94" ref-type="bibr">94</xref> Signs and symptoms are consistent with other influenza-like illnesses and include chills,<xref rid="bib93" ref-type="bibr">93</xref>, <xref rid="bib94" ref-type="bibr">94</xref> cough, chest pain, shivering, pneumonia, respiratory failure, acute respiratory distress syndrome, and multiorgan failure.<xref rid="bib79" ref-type="bibr">79</xref>, <xref rid="bib82" ref-type="bibr">82</xref>, <xref rid="bib94" ref-type="bibr">94</xref> Despite the few human cases,<xref rid="bib92" ref-type="bibr"><sup>92</sup></xref> these H10N8 infections are a cause for concern because this is the first H10N8 influenza virus to affect human beings. <xref rid="bib95" ref-type="bibr"><sup>95</sup></xref></p></sec><sec id="cesec220"><title>Between-human transmission</title><p id="para350">The small number of human cases of illness caused by influenza A H10N8 infection<xref rid="bib94" ref-type="bibr"><sup>94</sup></xref> and absence of adequate information with respect to the reported human cases<xref rid="bib95" ref-type="bibr"><sup>95</sup></xref> have made it difficult to fully understand the transmission potential of influenza A H10N8 virus. So far, there is no evidence of between-human transmission of influenza A H10N8 virus because close contacts of the cases have not yet developed influenza A H10N8 infection.<xref rid="bib93" ref-type="bibr"><sup>93</sup></xref></p></sec><sec id="cesec230"><title>Evidence for a zoonotic source</title><p id="para360">Evidence points to zoonotic sources as the major cause of infection with influenza A H10N8 virus. All three human cases had live bird market exposures (<xref rid="tbl2" ref-type="table">table 2</xref>).<xref rid="bib94" ref-type="bibr">94</xref>, <xref rid="bib96" ref-type="bibr">96</xref> Avian sources seem to be the major reservoir for H10N8 since the viruses are believed to be circulating without clinical signs among poultry and have been isolated from migratory species.<xref rid="bib95" ref-type="bibr"><sup>95</sup></xref></p></sec><sec id="cesec240"><title>Evidence for environmental source</title><p id="para370">Environmental factors seem to have key roles in maintaining the transmission of influenza A H10N8 virus with persistence in water being particularly important to transmission both among birds and to human beings.<xref rid="bib96" ref-type="bibr"><sup>96</sup></xref> Influenza A H10N8 has been isolated from water samples from Dongting Lake in Hunan province China in 2007,<xref rid="bib96" ref-type="bibr"><sup>96</sup></xref> and a live poultry market in southern China in 2012, thereby showing the importance of environmental factors in its transmission (<xref rid="tbl1" ref-type="table">table 1</xref>).</p></sec><sec id="cesec250"><title>Putative modes of transmission</title><p id="para380">Since human-to-human transmission of influenza A H10N8 has not been documented,<xref rid="bib94" ref-type="bibr"><sup>94</sup></xref> the avian-to-human route of transmission seems to be the main route of human infection.<xref rid="bib93" ref-type="bibr"><sup>93</sup></xref> Despite being considered as having low or non-pathogenicity in avian species,<xref rid="bib96" ref-type="bibr"><sup>96</sup></xref> the small number of patients might make it difficult to know the actual virulence of influenza A H10N8 virus in people.<xref rid="bib93" ref-type="bibr"><sup>93</sup></xref> Studies suggest that nucleotide changes or substitution can increase the transmissibility of the virus in human beings,<xref rid="bib95" ref-type="bibr"><sup>95</sup></xref> since wild strains that were non-pathogenic in mice later caused weight loss and death in mice after two lung passages;<xref rid="bib96" ref-type="bibr"><sup>96</sup></xref> and genetic analysis of all influenza A H10N8 isolates obtained from the NCBI Influenza Virus Resource Database showed the presence of genetic markers that favour mammalian adaptation or increased virulence in mammals.<xref rid="bib95" ref-type="bibr"><sup>95</sup></xref></p></sec></sec><sec id="cesec260"><title>Influenza A H3N2 virus</title><sec id="cesec270"><title>Geographical distribution</title><p id="para390">Pig H3N2 virus is believed to have circulated among human beings since 1968,<xref rid="bib97" ref-type="bibr"><sup>97</sup></xref> with more than 30 human cases reported from 2005 to June 2011 in the USA and Canada (<xref rid="fig1" ref-type="fig">figure</xref>).<xref rid="bib98" ref-type="bibr">98</xref>, <xref rid="bib99" ref-type="bibr">99</xref>, <xref rid="bib100" ref-type="bibr">100</xref> The emergence of a variant swine-like influenza A H3N2 virus in July, 2011,<xref rid="bib101" ref-type="bibr"><sup>101</sup></xref> however, alarmed public health officials. The variant virus likely evolved from the 2009 pandemic influenza A H1N1,<xref rid="bib102" ref-type="bibr"><sup>102</sup></xref> many cases had direct or indirect exposure to pigs in agricultural fairs,<xref rid="bib98" ref-type="bibr">98</xref>, <xref rid="bib99" ref-type="bibr">99</xref>, <xref rid="bib103" ref-type="bibr">103</xref>, <xref rid="bib104" ref-type="bibr">104</xref> and this virus seemingly has more pandemic potential than other swine-like viruses.<xref rid="bib105" ref-type="bibr"><sup>105</sup></xref> As of June 5, 2014, 340 laboratory-confirmed cases of human influenza A H3N2 and one death have been documented in 13 US states.<xref rid="bib101" ref-type="bibr">101</xref>, <xref rid="bib103" ref-type="bibr">103</xref>, <xref rid="bib105" ref-type="bibr">105</xref>, <xref rid="bib106" ref-type="bibr">106</xref>, <xref rid="bib107" ref-type="bibr">107</xref>, <xref rid="bib108" ref-type="bibr">108</xref> Additional cases of human influenza A H3N2 have been reported in various countries including Denmark,<xref rid="bib109" ref-type="bibr"><sup>109</sup></xref> the UK,<xref rid="bib110" ref-type="bibr"><sup>110</sup></xref> Italy,<xref rid="bib111" ref-type="bibr"><sup>111</sup></xref> Hong Kong,<xref rid="bib112" ref-type="bibr"><sup>112</sup></xref> France,<xref rid="bib100" ref-type="bibr"><sup>100</sup></xref> Japan,<xref rid="bib113" ref-type="bibr"><sup>113</sup></xref> Taiwan, and Singapore.<xref rid="bib114" ref-type="bibr"><sup>114</sup></xref> Disease symptoms are consistent with other influenza-like symptoms, which include fever (temperature >38°C), sore throat, cough, rhinorrhoea, vomiting or diarrhoea, fatigue, myalgia or joint pain,<xref rid="bib103" ref-type="bibr">103</xref>, <xref rid="bib115" ref-type="bibr">115</xref> headache, lethargy, rhinorrhoea, emesis, dyspnoea, and eye irritation.<xref rid="bib99" ref-type="bibr">99</xref>, <xref rid="bib100" ref-type="bibr">100</xref></p></sec><sec id="cesec280"><title>Between human transmission</title><p id="para400">Seroepidemiological studies suggest that roughly 90% of US children less than 10 years of age were susceptible to influenza A H3N2 infection.<xref rid="bib115" ref-type="bibr">115</xref>, <xref rid="bib116" ref-type="bibr">116</xref>, <xref rid="bib117" ref-type="bibr">117</xref> Although many studies suggest the occurrence of no or restricted and unsustainable human-to-human transmission of influenza A H3N2,<xref rid="bib98" ref-type="bibr">98</xref>, <xref rid="bib113" ref-type="bibr">113</xref>, <xref rid="bib118" ref-type="bibr">118</xref> some researchers believe there is every possibility of human-to-human transmission.<xref rid="bib99" ref-type="bibr">99</xref>, <xref rid="bib100" ref-type="bibr">100</xref>, <xref rid="bib101" ref-type="bibr">101</xref>, <xref rid="bib102" ref-type="bibr">102</xref>, <xref rid="bib103" ref-type="bibr">103</xref>, <xref rid="bib104" ref-type="bibr">104</xref>, <xref rid="bib119" ref-type="bibr">119</xref> Evidence includes an outbreak of influenza A H3N2 in three geriatric wards in France (<xref rid="tbl1" ref-type="table">table 1</xref>),<xref rid="bib100" ref-type="bibr"><sup>100</sup></xref> a US daycare centre,<xref rid="bib99" ref-type="bibr"><sup>99</sup></xref> and other US case series involving infected people without exposure to pigs.<xref rid="bib101" ref-type="bibr">101</xref>, <xref rid="bib103" ref-type="bibr">103</xref></p></sec><sec id="cesec290"><title>Evidence for a zoonotic source</title><p id="para410">Pig species are mixing bowls through which avian influenza viruses might mix with other influenza viruses and cross over to human beings (<xref rid="tbl2" ref-type="table">table 2</xref>).<xref rid="bib120" ref-type="bibr"><sup>120</sup></xref> Many studies suggest that zoonotic sources had important roles in the outbreak of influenza A H3N2 since most confirmed human cases had direct or indirect exposure to pigs during agricultural fairs.<xref rid="bib99" ref-type="bibr">99</xref>, <xref rid="bib100" ref-type="bibr">100</xref>, <xref rid="bib104" ref-type="bibr">104</xref>, <xref rid="bib105" ref-type="bibr">105</xref> Pig samples taken from agricultural fairs have tested positive for H3N2,<xref rid="bib97" ref-type="bibr">97</xref>, <xref rid="bib121" ref-type="bibr">121</xref>, <xref rid="bib122" ref-type="bibr">122</xref> and one study documented antigenic similarity between H3N2 taken from pigs in agricultural fairs and those associated with commercial pig farms,<xref rid="bib107" ref-type="bibr"><sup>107</sup></xref> thereby showing the importance of pigs in the transmission and maintenance of H3N2 among human beings.</p></sec><sec id="cesec300"><title>Evidence for an environmental source</title><p id="para420">The high rate of outbreaks of human influenza A H3N2 among people that attended or exhibited at the agricultural fairs,<xref rid="bib98" ref-type="bibr">98</xref>, <xref rid="bib99" ref-type="bibr">99</xref>, <xref rid="bib103" ref-type="bibr">103</xref>, <xref rid="bib104" ref-type="bibr">104</xref> suggests that there is a substantial association between disease outbreaks and physical location of individuals. Agricultural fairs are recognised as a potential place for pigs and human beings to share pathogens,<xref rid="bib98" ref-type="bibr"><sup>98</sup></xref> thereby creating enabling environments for the re-assortment of pig and human viruses with the potential of generating novel viruses.<xref rid="bib118" ref-type="bibr"><sup>118</sup></xref></p></sec><sec id="cesec310"><title>Putative modes of transmission</title><p id="para430">The pig-to-human route is probably the main transmission route for influenza A H3N2, whereas human-to-human transmission is likely a secondary mechanism.<xref rid="bib98" ref-type="bibr">98</xref>, <xref rid="bib99" ref-type="bibr">99</xref>, <xref rid="bib103" ref-type="bibr">103</xref>, <xref rid="bib104" ref-type="bibr">104</xref> As a respiratory virus, common means of H3N2 transmission include direct contact, respiratory droplets, and aerosol particles from infected pigs or people. The acquisition of the matrix gene from the 2009 pandemic virus is believed to have caused influenza A H3N2 to be more virulent than the seasonal H3N2 strains.<xref rid="bib101" ref-type="bibr"><sup>101</sup></xref></p></sec></sec><sec id="cesec320"><title>Conclusion</title><p id="para440">While HAdV-14p1 has been identified in humans only, MERS-CoV, influenza A H7N9, influenza A H10N8, and influenza A H3N2 are zoonotic diseases. There is a mounting evidence suggesting that camels are the likely reservoir of human exposure to MERS-CoV. Influenza A H7N9 and influenza A H10N8 reservoirs consist of poultry, ducks, and wild birds. The influenza A H3N2 reservoir consists of pigs. One possible way to prevent these zoonotic infections is avoiding direct contact with these animals or their dairy products in the respective areas of endemicity. It is advisable avoiding staying in environments where such animals are concentrated, including farms and markets. The absence of massive deaths and even of clinical signs among the reservoir animals leaves little or no time for public health preparations and intervention measures to curtail the impacts by culling. Given the possible interhuman transmission of these viruses (notably MERS-Cov and HAdV-14p1), the individual preventive measures aiming at reducing the risk of respiratory infections (use of face-mask, hand hygiene, cough etiquette, social distancing) should be reinforced.</p><p id="para450">Because of the poor current knowledge of the specific pathogenesis and mode of transmission of HAdV-14p1, recommendations for control and preventive measures have to be extrapolated by reference to other human adenoviruses causing respiratory infections.<xref rid="bib123" ref-type="bibr"><sup>123</sup></xref> Fortunately, most HAdV-14p1 infections do not cause severe illness.<xref rid="bib124" ref-type="bibr"><sup>124</sup></xref> Thus, direct methods to detect and identify HAdV-14p1, which have been recently described, will help to improve rapidly surveillance and diagnosis.<xref rid="bib125" ref-type="bibr"><sup>125</sup></xref> The high mutation or reassortment rate of influenza viruses could lead to the emergence of more virulent and transmissible strains.<xref rid="bib76" ref-type="bibr">76</xref>, <xref rid="bib126" ref-type="bibr">126</xref> The identification of several novel viruses that can cause fatal respiratory tract infections over the past decade, and major gaps that remain in the understanding of their epidemiology and transmission dynamics, calls for a more united and coordinated global response for tackling new infectious diseases threats.</p></sec><sec id="cesec330"><title>Search strategy and selection criteria</title><p id="para460"><boxed-text id="cetextbox20"><p id="para470">References for this Series paper were identified through searches of PubMed for articles published in the English and French languages from January, 1994, to June, 2014, through use of the terms “respiratory tract infections”, “Middle East Respiratory Syndrome”, “MERS-CoV”, “influenza”, “human adenovirus 14”, “H7N9”, “H10N8”, “H3N2 variant”, “Environmental”, and “Risk factor”. 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person-group-type="author"><name><surname>Lam</surname><given-names>TT</given-names></name><name><surname>Wang</surname><given-names>J</given-names></name><name><surname>Shen</surname><given-names>Y</given-names></name></person-group><article-title>The genesis and source of the H7N9 influenza viruses causing human infections in China</article-title><source>Nature</source><volume>502</volume><year>2013</year><fpage>241</fpage><lpage>244</lpage><pub-id pub-id-type="pmid">23965623</pub-id></element-citation></ref></ref-list><ack id="ceack10"><sec><title>Acknowledgments</title><p>AZ receives support from the European Developing Countries Clinical trials Partnership (EDCTP), UBS Optimus Foundation, Switzerland, and the NIHR Biomedical Research Centre, University College London Hospital, London, UK.</p></sec></ack><ack><title>Contributors</title><p>ZAM, AIZ, and JAA-T developed the outlines and assigned lead authors. PG coordinated this Series paper, further developed the manuscript outline, contributed specific text, and oversaw the manuscript development. The other authors all contributed relevant text and tables according to their expertise, and helped in drafting the final manuscript.</p></ack><ack><title>Declaration of interests</title><p>AZ is the principal investigator of the European Union FP7 grant, RiD-RTI. All other authors declare no competing interests.</p></ack></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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