Multihospital Outbreak of a Middle East Respiratory Syndrome Coronavirus Deletion Variant, Jordan: A Molecular, Serologic, and Epidemiologic Investigation
Identifieur interne : 000517 ( Pmc/Checkpoint ); précédent : 000516; suivant : 000518Multihospital Outbreak of a Middle East Respiratory Syndrome Coronavirus Deletion Variant, Jordan: A Molecular, Serologic, and Epidemiologic Investigation
Auteurs : Daniel C. Payne [Géorgie (pays)] ; Holly M. Biggs [Géorgie (pays)] ; Mohammad Mousa Al-Abdallat [Jordanie] ; Sultan Alqasrawi [Jordanie] ; Xiaoyan Lu [Géorgie (pays)] ; Glen R. Abedi [Géorgie (pays)] ; Aktham Haddadin [Jordanie] ; Ibrahim Iblan [Jordanie] ; Tarek Alsanouri [Jordanie] ; Mohannad Al Nsour [Jordanie] ; Sami Sheikh Ali [Jordanie] ; Brian Rha [Géorgie (pays)] ; Suvang U. Trivedi [Géorgie (pays)] ; Mohammed Ata Ur Rasheed [Géorgie (pays)] ; Azaibi Tamin [Géorgie (pays)] ; Mart M. Lamers [Pays-Bas] ; Bart L. Haagmans [Pays-Bas] ; Dean D. Erdman [Géorgie (pays)] ; Natalie J. Thornburg [Géorgie (pays)] ; Susan I. Gerber [Géorgie (pays)]Source :
- Open Forum Infectious Diseases [ 2328-8957 ] ; 2018.
Abstract
An outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in Jordan in 2015 involved a variant virus that acquired distinctive deletions in the accessory open reading frames. We conducted a molecular and seroepidemiologic investigation to describe the deletion variant’s transmission patterns and epidemiology.
We reviewed epidemiologic and medical chart data and analyzed viral genome sequences from respiratory specimens of MERS-CoV cases. In early 2016, sera and standardized interviews were obtained from MERS-CoV cases and their contacts. Sera were evaluated by nucleocapsid and spike protein enzyme immunoassays and microneutralization.
Among 16 cases, 11 (69%) had health care exposure and 5 (31%) were relatives of a known case; 13 (81%) were symptomatic, and 7 (44%) died. Genome sequencing of MERS-CoV from 13 cases revealed 3 transmissible deletions associated with clinical illness during the outbreak. Deletion variant sequences were epidemiologically clustered and linked to a common transmission chain. Interviews and sera were collected from 2 surviving cases, 23 household contacts, and 278 health care contacts; 1 (50%) case, 2 (9%) household contacts, and 3 (1%) health care contacts tested seropositive.
The MERS-CoV deletion variants retained human-to-human transmissibility and caused clinical illness in infected persons despite accumulated mutations. Serology suggested limited transmission beyond that detected during the initial outbreak investigation.
Url:
DOI: 10.1093/ofid/ofy095
PubMed: 30294616
PubMed Central: 5965092
Affiliations:
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<author><name sortKey="Iblan, Ibrahim" sort="Iblan, Ibrahim" uniqKey="Iblan I" first="Ibrahim" last="Iblan">Ibrahim Iblan</name>
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<author><name sortKey="Alsanouri, Tarek" sort="Alsanouri, Tarek" uniqKey="Alsanouri T" first="Tarek" last="Alsanouri">Tarek Alsanouri</name>
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<author><name sortKey="Al Nsour, Mohannad" sort="Al Nsour, Mohannad" uniqKey="Al Nsour M" first="Mohannad" last="Al Nsour">Mohannad Al Nsour</name>
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<author><name sortKey="Sheikh Ali, Sami" sort="Sheikh Ali, Sami" uniqKey="Sheikh Ali S" first="Sami" last="Sheikh Ali">Sami Sheikh Ali</name>
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<author><name sortKey="Rha, Brian" sort="Rha, Brian" uniqKey="Rha B" first="Brian" last="Rha">Brian Rha</name>
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<author><name sortKey="Trivedi, Suvang U" sort="Trivedi, Suvang U" uniqKey="Trivedi S" first="Suvang U" last="Trivedi">Suvang U. Trivedi</name>
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<author><name sortKey="Erdman, Dean D" sort="Erdman, Dean D" uniqKey="Erdman D" first="Dean D" last="Erdman">Dean D. Erdman</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Multihospital Outbreak of a Middle East Respiratory Syndrome Coronavirus Deletion Variant, Jordan: A Molecular, Serologic, and Epidemiologic Investigation</title>
<author><name sortKey="Payne, Daniel C" sort="Payne, Daniel C" uniqKey="Payne D" first="Daniel C" last="Payne">Daniel C. Payne</name>
<affiliation wicri:level="1"><nlm:aff id="AF0001">Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia</nlm:aff>
<country xml:lang="fr">Géorgie (pays)</country>
<wicri:regionArea>Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta</wicri:regionArea>
<wicri:noRegion>Atlanta</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Biggs, Holly M" sort="Biggs, Holly M" uniqKey="Biggs H" first="Holly M" last="Biggs">Holly M. Biggs</name>
<affiliation wicri:level="1"><nlm:aff id="AF0001">Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia</nlm:aff>
<country xml:lang="fr">Géorgie (pays)</country>
<wicri:regionArea>Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta</wicri:regionArea>
<wicri:noRegion>Atlanta</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Al Abdallat, Mohammad Mousa" sort="Al Abdallat, Mohammad Mousa" uniqKey="Al Abdallat M" first="Mohammad Mousa" last="Al-Abdallat">Mohammad Mousa Al-Abdallat</name>
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<country xml:lang="fr">Jordanie</country>
<wicri:regionArea>Communicable Diseases Directorate, Amman</wicri:regionArea>
<wicri:noRegion>Amman</wicri:noRegion>
</affiliation>
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<author><name sortKey="Alqasrawi, Sultan" sort="Alqasrawi, Sultan" uniqKey="Alqasrawi S" first="Sultan" last="Alqasrawi">Sultan Alqasrawi</name>
<affiliation wicri:level="1"><nlm:aff id="AF0002">Communicable Diseases Directorate, Amman, Jordan</nlm:aff>
<country xml:lang="fr">Jordanie</country>
<wicri:regionArea>Communicable Diseases Directorate, Amman</wicri:regionArea>
<wicri:noRegion>Amman</wicri:noRegion>
</affiliation>
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<author><name sortKey="Lu, Xiaoyan" sort="Lu, Xiaoyan" uniqKey="Lu X" first="Xiaoyan" last="Lu">Xiaoyan Lu</name>
<affiliation wicri:level="1"><nlm:aff id="AF0001">Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia</nlm:aff>
<country xml:lang="fr">Géorgie (pays)</country>
<wicri:regionArea>Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta</wicri:regionArea>
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<author><name sortKey="Abedi, Glen R" sort="Abedi, Glen R" uniqKey="Abedi G" first="Glen R" last="Abedi">Glen R. Abedi</name>
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<author><name sortKey="Haddadin, Aktham" sort="Haddadin, Aktham" uniqKey="Haddadin A" first="Aktham" last="Haddadin">Aktham Haddadin</name>
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<wicri:regionArea>Laboratory Directorate, Amman</wicri:regionArea>
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<author><name sortKey="Iblan, Ibrahim" sort="Iblan, Ibrahim" uniqKey="Iblan I" first="Ibrahim" last="Iblan">Ibrahim Iblan</name>
<affiliation wicri:level="1"><nlm:aff id="AF0004">Field Epidemiology Training Program, Jordan Ministry of Health, Amman, Jordan</nlm:aff>
<country xml:lang="fr">Jordanie</country>
<wicri:regionArea>Field Epidemiology Training Program, Jordan Ministry of Health, Amman</wicri:regionArea>
<wicri:noRegion>Amman</wicri:noRegion>
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<author><name sortKey="Alsanouri, Tarek" sort="Alsanouri, Tarek" uniqKey="Alsanouri T" first="Tarek" last="Alsanouri">Tarek Alsanouri</name>
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<country xml:lang="fr">Jordanie</country>
<wicri:regionArea>Eastern Mediterranean Public Health Network, Amman</wicri:regionArea>
<wicri:noRegion>Amman</wicri:noRegion>
</affiliation>
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<author><name sortKey="Al Nsour, Mohannad" sort="Al Nsour, Mohannad" uniqKey="Al Nsour M" first="Mohannad" last="Al Nsour">Mohannad Al Nsour</name>
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<author><name sortKey="Sheikh Ali, Sami" sort="Sheikh Ali, Sami" uniqKey="Sheikh Ali S" first="Sami" last="Sheikh Ali">Sami Sheikh Ali</name>
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<country xml:lang="fr">Jordanie</country>
<wicri:regionArea>Communicable Diseases Directorate, Amman</wicri:regionArea>
<wicri:noRegion>Amman</wicri:noRegion>
</affiliation>
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<author><name sortKey="Rha, Brian" sort="Rha, Brian" uniqKey="Rha B" first="Brian" last="Rha">Brian Rha</name>
<affiliation wicri:level="1"><nlm:aff id="AF0001">Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia</nlm:aff>
<country xml:lang="fr">Géorgie (pays)</country>
<wicri:regionArea>Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta</wicri:regionArea>
<wicri:noRegion>Atlanta</wicri:noRegion>
</affiliation>
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<author><name sortKey="Trivedi, Suvang U" sort="Trivedi, Suvang U" uniqKey="Trivedi S" first="Suvang U" last="Trivedi">Suvang U. Trivedi</name>
<affiliation wicri:level="1"><nlm:aff id="AF0007">IHRC, Inc, contracting agency for the Centers for Disease Control and Prevention, Atlanta, Georgia</nlm:aff>
<country xml:lang="fr">Géorgie (pays)</country>
<wicri:regionArea>IHRC, Inc, contracting agency for the Centers for Disease Control and Prevention, Atlanta</wicri:regionArea>
<wicri:noRegion>Atlanta</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Rasheed, Mohammed Ata Ur" sort="Rasheed, Mohammed Ata Ur" uniqKey="Rasheed M" first="Mohammed Ata Ur" last="Rasheed">Mohammed Ata Ur Rasheed</name>
<affiliation wicri:level="1"><nlm:aff id="AF0007">IHRC, Inc, contracting agency for the Centers for Disease Control and Prevention, Atlanta, Georgia</nlm:aff>
<country xml:lang="fr">Géorgie (pays)</country>
<wicri:regionArea>IHRC, Inc, contracting agency for the Centers for Disease Control and Prevention, Atlanta</wicri:regionArea>
<wicri:noRegion>Atlanta</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Tamin, Azaibi" sort="Tamin, Azaibi" uniqKey="Tamin A" first="Azaibi" last="Tamin">Azaibi Tamin</name>
<affiliation wicri:level="1"><nlm:aff id="AF0001">Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia</nlm:aff>
<country xml:lang="fr">Géorgie (pays)</country>
<wicri:regionArea>Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta</wicri:regionArea>
<wicri:noRegion>Atlanta</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Lamers, Mart M" sort="Lamers, Mart M" uniqKey="Lamers M" first="Mart M" last="Lamers">Mart M. Lamers</name>
<affiliation wicri:level="3"><nlm:aff id="AF0006">Viroscience Department, Erasmus University Medical Center, Rotterdam, the Netherlands</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Viroscience Department, Erasmus University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Haagmans, Bart L" sort="Haagmans, Bart L" uniqKey="Haagmans B" first="Bart L" last="Haagmans">Bart L. Haagmans</name>
<affiliation wicri:level="3"><nlm:aff id="AF0006">Viroscience Department, Erasmus University Medical Center, Rotterdam, the Netherlands</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Viroscience Department, Erasmus University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Erdman, Dean D" sort="Erdman, Dean D" uniqKey="Erdman D" first="Dean D" last="Erdman">Dean D. Erdman</name>
<affiliation wicri:level="1"><nlm:aff id="AF0001">Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia</nlm:aff>
<country xml:lang="fr">Géorgie (pays)</country>
<wicri:regionArea>Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta</wicri:regionArea>
<wicri:noRegion>Atlanta</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Thornburg, Natalie J" sort="Thornburg, Natalie J" uniqKey="Thornburg N" first="Natalie J" last="Thornburg">Natalie J. Thornburg</name>
<affiliation wicri:level="1"><nlm:aff id="AF0001">Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia</nlm:aff>
<country xml:lang="fr">Géorgie (pays)</country>
<wicri:regionArea>Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta</wicri:regionArea>
<wicri:noRegion>Atlanta</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Gerber, Susan I" sort="Gerber, Susan I" uniqKey="Gerber S" first="Susan I" last="Gerber">Susan I. Gerber</name>
<affiliation wicri:level="1"><nlm:aff id="AF0001">Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia</nlm:aff>
<country xml:lang="fr">Géorgie (pays)</country>
<wicri:regionArea>Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta</wicri:regionArea>
<wicri:noRegion>Atlanta</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Open Forum Infectious Diseases</title>
<idno type="eISSN">2328-8957</idno>
<imprint><date when="2018">2018</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><title>Abstract</title>
<sec id="s1"><title>Background</title>
<p>An outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in Jordan in 2015 involved a variant virus that acquired distinctive deletions in the accessory open reading frames. We conducted a molecular and seroepidemiologic investigation to describe the deletion variant’s transmission patterns and epidemiology.</p>
</sec>
<sec id="s2"><title>Methods</title>
<p>We reviewed epidemiologic and medical chart data and analyzed viral genome sequences from respiratory specimens of MERS-CoV cases. In early 2016, sera and standardized interviews were obtained from MERS-CoV cases and their contacts. Sera were evaluated by nucleocapsid and spike protein enzyme immunoassays and microneutralization.</p>
</sec>
<sec id="s3"><title>Results</title>
<p>Among 16 cases, 11 (69%) had health care exposure and 5 (31%) were relatives of a known case; 13 (81%) were symptomatic, and 7 (44%) died. Genome sequencing of MERS-CoV from 13 cases revealed 3 transmissible deletions associated with clinical illness during the outbreak. Deletion variant sequences were epidemiologically clustered and linked to a common transmission chain. Interviews and sera were collected from 2 surviving cases, 23 household contacts, and 278 health care contacts; 1 (50%) case, 2 (9%) household contacts, and 3 (1%) health care contacts tested seropositive.</p>
</sec>
<sec id="s4"><title>Conclusions</title>
<p>The MERS-CoV deletion variants retained human-to-human transmissibility and caused clinical illness in infected persons despite accumulated mutations. Serology suggested limited transmission beyond that detected during the initial outbreak investigation.</p>
</sec>
</div>
</front>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Open Forum Infect Dis</journal-id>
<journal-id journal-id-type="iso-abbrev">Open Forum Infect Dis</journal-id>
<journal-id journal-id-type="publisher-id">ofid</journal-id>
<journal-title-group><journal-title>Open Forum Infectious Diseases</journal-title>
</journal-title-group>
<issn pub-type="epub">2328-8957</issn>
<publisher><publisher-name>Oxford University Press</publisher-name>
<publisher-loc>US</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">30294616</article-id>
<article-id pub-id-type="pmc">5965092</article-id>
<article-id pub-id-type="doi">10.1093/ofid/ofy095</article-id>
<article-id pub-id-type="publisher-id">ofy095</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Major Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Multihospital Outbreak of a Middle East Respiratory Syndrome Coronavirus Deletion Variant, Jordan: A Molecular, Serologic, and Epidemiologic Investigation</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Payne</surname>
<given-names>Daniel C</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
<xref ref-type="author-notes" rid="fn-0001"></xref>
<xref ref-type="corresp" rid="c1"></xref>
<pmc-comment>dvp6@cdc.gov </pmc-comment>
</contrib>
<contrib contrib-type="author"><name><surname>Biggs</surname>
<given-names>Holly M</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
<xref ref-type="author-notes" rid="fn-0001"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Al-Abdallat</surname>
<given-names>Mohammad Mousa</given-names>
</name>
<xref ref-type="aff" rid="AF0002">2</xref>
<xref ref-type="author-notes" rid="fn-0001"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Alqasrawi</surname>
<given-names>Sultan</given-names>
</name>
<xref ref-type="aff" rid="AF0002">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lu</surname>
<given-names>Xiaoyan</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Abedi</surname>
<given-names>Glen R</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Haddadin</surname>
<given-names>Aktham</given-names>
</name>
<xref ref-type="aff" rid="AF0003">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Iblan</surname>
<given-names>Ibrahim</given-names>
</name>
<xref ref-type="aff" rid="AF0004">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Alsanouri</surname>
<given-names>Tarek</given-names>
</name>
<xref ref-type="aff" rid="AF0005">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Al Nsour</surname>
<given-names>Mohannad</given-names>
</name>
<xref ref-type="aff" rid="AF0005">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sheikh Ali</surname>
<given-names>Sami</given-names>
</name>
<xref ref-type="aff" rid="AF0002">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rha</surname>
<given-names>Brian</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Trivedi</surname>
<given-names>Suvang U</given-names>
</name>
<xref ref-type="aff" rid="AF0007">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rasheed</surname>
<given-names>Mohammed Ata Ur</given-names>
</name>
<xref ref-type="aff" rid="AF0007">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Tamin</surname>
<given-names>Azaibi</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lamers</surname>
<given-names>Mart M</given-names>
</name>
<xref ref-type="aff" rid="AF0006">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Haagmans</surname>
<given-names>Bart L</given-names>
</name>
<xref ref-type="aff" rid="AF0006">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Erdman</surname>
<given-names>Dean D</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Thornburg</surname>
<given-names>Natalie J</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gerber</surname>
<given-names>Susan I</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
</contrib>
</contrib-group>
<aff id="AF0001"><label>1</label>
Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia</aff>
<aff id="AF0002"><label>2</label>
Communicable Diseases Directorate, Amman, Jordan</aff>
<aff id="AF0003"><label>3</label>
Laboratory Directorate, Amman, Jordan</aff>
<aff id="AF0004"><label>4</label>
Field Epidemiology Training Program, Jordan Ministry of Health, Amman, Jordan</aff>
<aff id="AF0005"><label>5</label>
Eastern Mediterranean Public Health Network, Amman, Jordan</aff>
<aff id="AF0006"><label>6</label>
Viroscience Department, Erasmus University Medical Center, Rotterdam, the Netherlands</aff>
<aff id="AF0007"><label>7</label>
IHRC, Inc, contracting agency for the Centers for Disease Control and Prevention, Atlanta, Georgia</aff>
<author-notes><fn id="fn-0001"><p>Equal contribution, co-first authors</p>
</fn>
<corresp id="c1">Correspondence: D. C. Payne, PhD, MSPH, Centers for Disease Control and Prevention, 1600 Clifton Road, NE, Mailstop A34, Atlanta, GA 30329 (<email>dvp6@cdc.gov</email>
).</corresp>
</author-notes>
<pub-date pub-type="collection"><month>5</month>
<year>2018</year>
</pub-date>
<pub-date pub-type="epub" iso-8601-date="2018-04-28"><day>28</day>
<month>4</month>
<year>2018</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>28</day>
<month>4</month>
<year>2018</year>
</pub-date>
<pmc-comment> PMC Release delay is 0 months and 0 days and was based on the . </pmc-comment>
<volume>5</volume>
<issue>5</issue>
<elocation-id>ofy095</elocation-id>
<history><date date-type="received"><day>30</day>
<month>3</month>
<year>2018</year>
</date>
<date date-type="accepted"><day>25</day>
<month>4</month>
<year>2018</year>
</date>
</history>
<permissions><copyright-statement>Published by Oxford University Press on behalf of Infectious Diseases Society of America 2018.</copyright-statement>
<copyright-year>2018</copyright-year>
<license license-type="us-gov"><license-p>This work is written by (a) US Government employee(s) and is in the public domain in the US.</license-p>
</license>
<license><license-p>This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.</license-p>
</license>
</permissions>
<self-uri xlink:href="ofy095.pdf"></self-uri>
<abstract><title>Abstract</title>
<sec id="s1"><title>Background</title>
<p>An outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in Jordan in 2015 involved a variant virus that acquired distinctive deletions in the accessory open reading frames. We conducted a molecular and seroepidemiologic investigation to describe the deletion variant’s transmission patterns and epidemiology.</p>
</sec>
<sec id="s2"><title>Methods</title>
<p>We reviewed epidemiologic and medical chart data and analyzed viral genome sequences from respiratory specimens of MERS-CoV cases. In early 2016, sera and standardized interviews were obtained from MERS-CoV cases and their contacts. Sera were evaluated by nucleocapsid and spike protein enzyme immunoassays and microneutralization.</p>
</sec>
<sec id="s3"><title>Results</title>
<p>Among 16 cases, 11 (69%) had health care exposure and 5 (31%) were relatives of a known case; 13 (81%) were symptomatic, and 7 (44%) died. Genome sequencing of MERS-CoV from 13 cases revealed 3 transmissible deletions associated with clinical illness during the outbreak. Deletion variant sequences were epidemiologically clustered and linked to a common transmission chain. Interviews and sera were collected from 2 surviving cases, 23 household contacts, and 278 health care contacts; 1 (50%) case, 2 (9%) household contacts, and 3 (1%) health care contacts tested seropositive.</p>
</sec>
<sec id="s4"><title>Conclusions</title>
<p>The MERS-CoV deletion variants retained human-to-human transmissibility and caused clinical illness in infected persons despite accumulated mutations. Serology suggested limited transmission beyond that detected during the initial outbreak investigation.</p>
</sec>
</abstract>
<kwd-group><kwd>coronavirus</kwd>
<kwd>emerging infectious disease</kwd>
<kwd>genome deletion</kwd>
<kwd>Jordan</kwd>
<kwd>MERS-CoV</kwd>
<kwd>Middle East respiratory syndrome</kwd>
<kwd>outbreak investigation</kwd>
<kwd>sero-epidemiology</kwd>
</kwd-group>
<funding-group><award-group award-type="grant"><funding-source><named-content content-type="funder-name">Erasmus Graduate Program Infection & Immunity</named-content>
</funding-source>
<award-id>022.005.032</award-id>
</award-group>
</funding-group>
<counts><page-count count="9"></page-count>
</counts>
</article-meta>
</front>
</pmc>
<affiliations><list><country><li>Géorgie (pays)</li>
<li>Jordanie</li>
<li>Pays-Bas</li>
</country>
<region><li>Hollande-Méridionale</li>
</region>
<settlement><li>Rotterdam</li>
</settlement>
</list>
<tree><country name="Géorgie (pays)"><noRegion><name sortKey="Payne, Daniel C" sort="Payne, Daniel C" uniqKey="Payne D" first="Daniel C" last="Payne">Daniel C. Payne</name>
</noRegion>
<name sortKey="Abedi, Glen R" sort="Abedi, Glen R" uniqKey="Abedi G" first="Glen R" last="Abedi">Glen R. Abedi</name>
<name sortKey="Biggs, Holly M" sort="Biggs, Holly M" uniqKey="Biggs H" first="Holly M" last="Biggs">Holly M. Biggs</name>
<name sortKey="Erdman, Dean D" sort="Erdman, Dean D" uniqKey="Erdman D" first="Dean D" last="Erdman">Dean D. Erdman</name>
<name sortKey="Gerber, Susan I" sort="Gerber, Susan I" uniqKey="Gerber S" first="Susan I" last="Gerber">Susan I. Gerber</name>
<name sortKey="Lu, Xiaoyan" sort="Lu, Xiaoyan" uniqKey="Lu X" first="Xiaoyan" last="Lu">Xiaoyan Lu</name>
<name sortKey="Rasheed, Mohammed Ata Ur" sort="Rasheed, Mohammed Ata Ur" uniqKey="Rasheed M" first="Mohammed Ata Ur" last="Rasheed">Mohammed Ata Ur Rasheed</name>
<name sortKey="Rha, Brian" sort="Rha, Brian" uniqKey="Rha B" first="Brian" last="Rha">Brian Rha</name>
<name sortKey="Tamin, Azaibi" sort="Tamin, Azaibi" uniqKey="Tamin A" first="Azaibi" last="Tamin">Azaibi Tamin</name>
<name sortKey="Thornburg, Natalie J" sort="Thornburg, Natalie J" uniqKey="Thornburg N" first="Natalie J" last="Thornburg">Natalie J. Thornburg</name>
<name sortKey="Trivedi, Suvang U" sort="Trivedi, Suvang U" uniqKey="Trivedi S" first="Suvang U" last="Trivedi">Suvang U. Trivedi</name>
</country>
<country name="Jordanie"><noRegion><name sortKey="Al Abdallat, Mohammad Mousa" sort="Al Abdallat, Mohammad Mousa" uniqKey="Al Abdallat M" first="Mohammad Mousa" last="Al-Abdallat">Mohammad Mousa Al-Abdallat</name>
</noRegion>
<name sortKey="Al Nsour, Mohannad" sort="Al Nsour, Mohannad" uniqKey="Al Nsour M" first="Mohannad" last="Al Nsour">Mohannad Al Nsour</name>
<name sortKey="Alqasrawi, Sultan" sort="Alqasrawi, Sultan" uniqKey="Alqasrawi S" first="Sultan" last="Alqasrawi">Sultan Alqasrawi</name>
<name sortKey="Alsanouri, Tarek" sort="Alsanouri, Tarek" uniqKey="Alsanouri T" first="Tarek" last="Alsanouri">Tarek Alsanouri</name>
<name sortKey="Haddadin, Aktham" sort="Haddadin, Aktham" uniqKey="Haddadin A" first="Aktham" last="Haddadin">Aktham Haddadin</name>
<name sortKey="Iblan, Ibrahim" sort="Iblan, Ibrahim" uniqKey="Iblan I" first="Ibrahim" last="Iblan">Ibrahim Iblan</name>
<name sortKey="Sheikh Ali, Sami" sort="Sheikh Ali, Sami" uniqKey="Sheikh Ali S" first="Sami" last="Sheikh Ali">Sami Sheikh Ali</name>
</country>
<country name="Pays-Bas"><region name="Hollande-Méridionale"><name sortKey="Lamers, Mart M" sort="Lamers, Mart M" uniqKey="Lamers M" first="Mart M" last="Lamers">Mart M. Lamers</name>
</region>
<name sortKey="Haagmans, Bart L" sort="Haagmans, Bart L" uniqKey="Haagmans B" first="Bart L" last="Haagmans">Bart L. Haagmans</name>
</country>
</tree>
</affiliations>
</record>
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