Serveur d'exploration MERS

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Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection

Identifieur interne : 002194 ( Main/Exploration ); précédent : 002193; suivant : 002195

Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection

Auteurs : Christian Drosten [Allemagne] ; Michael Seilmaier [Allemagne] ; Victor M. Corman [Allemagne] ; Wulf Hartmann [Allemagne] ; Gregor Scheible [Allemagne] ; Stefan Sack [Allemagne] ; Wolfgang Guggemos [Allemagne] ; Rene Kallies [Allemagne] ; Doreen Muth [Allemagne] ; Sandra Junglen [Allemagne] ; Marcel A. Müller [Allemagne] ; Walter Haas [Allemagne] ; Hana Guberina [Allemagne] ; Tim Röhnisch [Allemagne] ; Monika Schmid-Wendtner [Allemagne] ; Souhaib Aldabbagh [Allemagne] ; Ulf Dittmer [Allemagne] ; Hermann Gold [Allemagne] ; Petra Graf [Allemagne] ; Frank Bonin [Allemagne] ; Andrew Rambaut [Royaume-Uni, États-Unis] ; Clemens-Martin Wendtner [Allemagne]

Source :

RBID : Pascal:13-0311867

Descripteurs français

English descriptors

Abstract

Background The Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging virus involved in cases and case clusters of severe acute respiratory infection in the Arabian Peninsula, Tunisia, Morocco, France, Italy, Germany, and the UK. We provide a full description of a fatal case of MERS-CoV infection and associated phylogenetic analyses. Methods We report data for a patient who was admitted to the Klinikum Schwabing (Munich, Germany) for severe acute respiratory infection. We did diagnostic RT-PCR and indirect immunofluorescence. From time of diagnosis, respiratory, faecal, and urine samples were obtained for virus quantification. We constructed a maximum likelihood tree of the five available complete MERS-CoV genomes. Findings A 73-year-old man from Abu Dhabi, United Arab Emirates, was transferred to Klinikum Schwabing on March 19, 2013, on day 11 of illness. He had been diagnosed with multiple myeloma in 2008, and had received several lines of treatment. The patient died on day 18, due to septic shock. MERS-CoV was detected in two samples of bronchoalveolar fluid. Viral loads were highest in samples from the lower respiratory tract (up to 1.2×106 copies per mL). Maximum virus concentration in urine samples was 2691 RNA copies per mL on day 13; the virus was not present in the urine after renal failure on day 14. Stool samples obtained on days 12 and 16 contained the virus, with up to 1031 RNA copies per g (close to the lowest detection limit of the assay). One of two oronasal swabs obtained on day 16 were positive, but yielded little viral RNA (5370 copies per mL). No virus was detected in blood. The full virus genome was combined with four other available full genome sequences in a maximum likelihood phylogeny, correlating branch lengths with dates of isolation. The time of the common ancestor was halfway through 2011. Addition of novel genome data from an unlinked case treated 6 months previously in Essen, Germany, showed a clustering of viruses derived from Qatar and the United Arab Emirates. Interpretation We have provided the first complete viral load profile in a case of MERS-CoV infection. MERS-CoV might have shedding patterns that are different from those of severe acute respiratory syndrome and so might need alternative diagnostic approaches. Funding European Union; German Centre for Infection Research; German Research Council; and German Ministry for Education and Research.


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</placeName>
</affiliation>
</author>
<author>
<name sortKey="Corman, Victor M" sort="Corman, Victor M" uniqKey="Corman V" first="Victor M." last="Corman">Victor M. Corman</name>
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<region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
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<settlement type="city">Bonn</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Hartmann, Wulf" sort="Hartmann, Wulf" uniqKey="Hartmann W" first="Wulf" last="Hartmann">Wulf Hartmann</name>
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</author>
<author>
<name sortKey="Scheible, Gregor" sort="Scheible, Gregor" uniqKey="Scheible G" first="Gregor" last="Scheible">Gregor Scheible</name>
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</author>
<author>
<name sortKey="Sack, Stefan" sort="Sack, Stefan" uniqKey="Sack S" first="Stefan" last="Sack">Stefan Sack</name>
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<country>Allemagne</country>
<placeName>
<region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Haute-Bavière</region>
<settlement type="city">Munich</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Guggemos, Wolfgang" sort="Guggemos, Wolfgang" uniqKey="Guggemos W" first="Wolfgang" last="Guggemos">Wolfgang Guggemos</name>
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<s1>Klinikum Schwabing</s1>
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</inist:fA14>
<country>Allemagne</country>
<placeName>
<region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Haute-Bavière</region>
<settlement type="city">Munich</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Kallies, Rene" sort="Kallies, Rene" uniqKey="Kallies R" first="Rene" last="Kallies">Rene Kallies</name>
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<s1>Institute of Virology, University of Bonn Medical Centre</s1>
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</inist:fA14>
<country>Allemagne</country>
<placeName>
<region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Bonn</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Muth, Doreen" sort="Muth, Doreen" uniqKey="Muth D" first="Doreen" last="Muth">Doreen Muth</name>
<affiliation wicri:level="3">
<inist:fA14 i1="01">
<s1>Institute of Virology, University of Bonn Medical Centre</s1>
<s2>Bonn</s2>
<s3>DEU</s3>
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<country>Allemagne</country>
<placeName>
<region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Bonn</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Junglen, Sandra" sort="Junglen, Sandra" uniqKey="Junglen S" first="Sandra" last="Junglen">Sandra Junglen</name>
<affiliation wicri:level="3">
<inist:fA14 i1="01">
<s1>Institute of Virology, University of Bonn Medical Centre</s1>
<s2>Bonn</s2>
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</inist:fA14>
<country>Allemagne</country>
<placeName>
<region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Bonn</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Muller, Marcel A" sort="Muller, Marcel A" uniqKey="Muller M" first="Marcel A." last="Müller">Marcel A. Müller</name>
<affiliation wicri:level="3">
<inist:fA14 i1="01">
<s1>Institute of Virology, University of Bonn Medical Centre</s1>
<s2>Bonn</s2>
<s3>DEU</s3>
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<country>Allemagne</country>
<placeName>
<region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Bonn</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Haas, Walter" sort="Haas, Walter" uniqKey="Haas W" first="Walter" last="Haas">Walter Haas</name>
<affiliation wicri:level="3">
<inist:fA14 i1="03">
<s1>Department of Infection Epidemiology, Robert Koch Institute</s1>
<s2>Berlin</s2>
<s3>DEU</s3>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>Allemagne</country>
<placeName>
<region type="land" nuts="3">Berlin</region>
<settlement type="city">Berlin</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Guberina, Hana" sort="Guberina, Hana" uniqKey="Guberina H" first="Hana" last="Guberina">Hana Guberina</name>
<affiliation wicri:level="1">
<inist:fA14 i1="04">
<s1>Department of Internal Medicine, University of Duisburg-Essen</s1>
<s2>Essen</s2>
<s3>DEU</s3>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>Allemagne</country>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>University of Duisburg-Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Rohnisch, Tim" sort="Rohnisch, Tim" uniqKey="Rohnisch T" first="Tim" last="Röhnisch">Tim Röhnisch</name>
<affiliation wicri:level="3">
<inist:fA14 i1="06">
<s1>Interdisziplinäres Onkologisches Zentrum</s1>
<s2>Munich</s2>
<s3>DEU</s3>
<sZ>14 aut.</sZ>
<sZ>15 aut.</sZ>
</inist:fA14>
<country>Allemagne</country>
<placeName>
<region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Haute-Bavière</region>
<settlement type="city">Munich</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Schmid Wendtner, Monika" sort="Schmid Wendtner, Monika" uniqKey="Schmid Wendtner M" first="Monika" last="Schmid-Wendtner">Monika Schmid-Wendtner</name>
<affiliation wicri:level="3">
<inist:fA14 i1="06">
<s1>Interdisziplinäres Onkologisches Zentrum</s1>
<s2>Munich</s2>
<s3>DEU</s3>
<sZ>14 aut.</sZ>
<sZ>15 aut.</sZ>
</inist:fA14>
<country>Allemagne</country>
<placeName>
<region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Haute-Bavière</region>
<settlement type="city">Munich</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Aldabbagh, Souhaib" sort="Aldabbagh, Souhaib" uniqKey="Aldabbagh S" first="Souhaib" last="Aldabbagh">Souhaib Aldabbagh</name>
<affiliation wicri:level="3">
<inist:fA14 i1="01">
<s1>Institute of Virology, University of Bonn Medical Centre</s1>
<s2>Bonn</s2>
<s3>DEU</s3>
<sZ>1 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>Allemagne</country>
<placeName>
<region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Bonn</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Dittmer, Ulf" sort="Dittmer, Ulf" uniqKey="Dittmer U" first="Ulf" last="Dittmer">Ulf Dittmer</name>
<affiliation wicri:level="1">
<inist:fA14 i1="05">
<s1>Institute of Virology, University of Duisburg-Essen</s1>
<s2>Essen</s2>
<s3>DEU</s3>
<sZ>17 aut.</sZ>
</inist:fA14>
<country>Allemagne</country>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>University of Duisburg-Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Gold, Hermann" sort="Gold, Hermann" uniqKey="Gold H" first="Hermann" last="Gold">Hermann Gold</name>
<affiliation wicri:level="3">
<inist:fA14 i1="07">
<s1>Department of Health and the Environment</s1>
<s2>Munich</s2>
<s3>DEU</s3>
<sZ>18 aut.</sZ>
<sZ>19 aut.</sZ>
</inist:fA14>
<country>Allemagne</country>
<placeName>
<region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Haute-Bavière</region>
<settlement type="city">Munich</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Graf, Petra" sort="Graf, Petra" uniqKey="Graf P" first="Petra" last="Graf">Petra Graf</name>
<affiliation wicri:level="3">
<inist:fA14 i1="07">
<s1>Department of Health and the Environment</s1>
<s2>Munich</s2>
<s3>DEU</s3>
<sZ>18 aut.</sZ>
<sZ>19 aut.</sZ>
</inist:fA14>
<country>Allemagne</country>
<placeName>
<region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Haute-Bavière</region>
<settlement type="city">Munich</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Bonin, Frank" sort="Bonin, Frank" uniqKey="Bonin F" first="Frank" last="Bonin">Frank Bonin</name>
<affiliation wicri:level="1">
<inist:fA14 i1="08">
<s1>Department of Intensive Care, Ruhrlandklinik</s1>
<s2>Essen</s2>
<s3>DEU</s3>
<sZ>20 aut.</sZ>
</inist:fA14>
<country>Allemagne</country>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Ruhrlandklinik</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Rambaut, Andrew" sort="Rambaut, Andrew" uniqKey="Rambaut A" first="Andrew" last="Rambaut">Andrew Rambaut</name>
<affiliation wicri:level="4">
<inist:fA14 i1="09">
<s1>Institute of Evolutionary Biology, University of Edinburgh</s1>
<s2>Edinburgh</s2>
<s3>GBR</s3>
<sZ>21 aut.</sZ>
</inist:fA14>
<country>Royaume-Uni</country>
<placeName>
<settlement type="city">Édimbourg</settlement>
<region type="country">Écosse</region>
</placeName>
<orgName type="university">Université d'Édimbourg</orgName>
</affiliation>
<affiliation wicri:level="2">
<inist:fA14 i1="10">
<s1>Forgarty International Center, National Institutes of Health</s1>
<s2>Bethesda, MD</s2>
<s3>USA</s3>
<sZ>21 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName>
<region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Wendtner, Clemens Martin" sort="Wendtner, Clemens Martin" uniqKey="Wendtner C" first="Clemens-Martin" last="Wendtner">Clemens-Martin Wendtner</name>
<affiliation wicri:level="3">
<inist:fA14 i1="02">
<s1>Klinikum Schwabing</s1>
<s2>Munich</s2>
<s3>DEU</s3>
<sZ>2 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>22 aut.</sZ>
</inist:fA14>
<country>Allemagne</country>
<placeName>
<region type="land" nuts="1">Bavière</region>
<region type="district" nuts="2">District de Haute-Bavière</region>
<settlement type="city">Munich</settlement>
</placeName>
</affiliation>
</author>
</analytic>
<series>
<title level="j" type="main">Lancet. Infectious diseases : (print)</title>
<title level="j" type="abbreviated">Lancet. Infect. dis. : (print)</title>
<idno type="ISSN">1473-3099</idno>
<imprint>
<date when="2013">2013</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt>
<title level="j" type="main">Lancet. Infectious diseases : (print)</title>
<title level="j" type="abbreviated">Lancet. Infect. dis. : (print)</title>
<idno type="ISSN">1473-3099</idno>
</seriesStmt>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Case study</term>
<term>Coronavirus</term>
<term>Diagnosis</term>
<term>Human</term>
<term>Middle East respiratory syndrome</term>
<term>Respiratory tract</term>
<term>Symptomatology</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr">
<term>Symptomatologie</term>
<term>Homme</term>
<term>Voie respiratoire</term>
<term>Coronavirus</term>
<term>Diagnostic</term>
<term>Etude cas</term>
<term>Syndrome respiratoire du Moyen-Orient</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr">
<term>Homme</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">Background The Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging virus involved in cases and case clusters of severe acute respiratory infection in the Arabian Peninsula, Tunisia, Morocco, France, Italy, Germany, and the UK. We provide a full description of a fatal case of MERS-CoV infection and associated phylogenetic analyses. Methods We report data for a patient who was admitted to the Klinikum Schwabing (Munich, Germany) for severe acute respiratory infection. We did diagnostic RT-PCR and indirect immunofluorescence. From time of diagnosis, respiratory, faecal, and urine samples were obtained for virus quantification. We constructed a maximum likelihood tree of the five available complete MERS-CoV genomes. Findings A 73-year-old man from Abu Dhabi, United Arab Emirates, was transferred to Klinikum Schwabing on March 19, 2013, on day 11 of illness. He had been diagnosed with multiple myeloma in 2008, and had received several lines of treatment. The patient died on day 18, due to septic shock. MERS-CoV was detected in two samples of bronchoalveolar fluid. Viral loads were highest in samples from the lower respiratory tract (up to 1.2×10
<sup>6</sup>
copies per mL). Maximum virus concentration in urine samples was 2691 RNA copies per mL on day 13; the virus was not present in the urine after renal failure on day 14. Stool samples obtained on days 12 and 16 contained the virus, with up to 1031 RNA copies per g (close to the lowest detection limit of the assay). One of two oronasal swabs obtained on day 16 were positive, but yielded little viral RNA (5370 copies per mL). No virus was detected in blood. The full virus genome was combined with four other available full genome sequences in a maximum likelihood phylogeny, correlating branch lengths with dates of isolation. The time of the common ancestor was halfway through 2011. Addition of novel genome data from an unlinked case treated 6 months previously in Essen, Germany, showed a clustering of viruses derived from Qatar and the United Arab Emirates. Interpretation We have provided the first complete viral load profile in a case of MERS-CoV infection. MERS-CoV might have shedding patterns that are different from those of severe acute respiratory syndrome and so might need alternative diagnostic approaches. Funding European Union; German Centre for Infection Research; German Research Council; and German Ministry for Education and Research.</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>Allemagne</li>
<li>Royaume-Uni</li>
<li>États-Unis</li>
</country>
<region>
<li>Bavière</li>
<li>Berlin</li>
<li>District de Cologne</li>
<li>District de Haute-Bavière</li>
<li>Maryland</li>
<li>Rhénanie-du-Nord-Westphalie</li>
<li>Écosse</li>
</region>
<settlement>
<li>Berlin</li>
<li>Bonn</li>
<li>Munich</li>
<li>Édimbourg</li>
</settlement>
<orgName>
<li>Université d'Édimbourg</li>
</orgName>
</list>
<tree>
<country name="Allemagne">
<region name="Rhénanie-du-Nord-Westphalie">
<name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name>
</region>
<name sortKey="Aldabbagh, Souhaib" sort="Aldabbagh, Souhaib" uniqKey="Aldabbagh S" first="Souhaib" last="Aldabbagh">Souhaib Aldabbagh</name>
<name sortKey="Bonin, Frank" sort="Bonin, Frank" uniqKey="Bonin F" first="Frank" last="Bonin">Frank Bonin</name>
<name sortKey="Corman, Victor M" sort="Corman, Victor M" uniqKey="Corman V" first="Victor M." last="Corman">Victor M. Corman</name>
<name sortKey="Dittmer, Ulf" sort="Dittmer, Ulf" uniqKey="Dittmer U" first="Ulf" last="Dittmer">Ulf Dittmer</name>
<name sortKey="Gold, Hermann" sort="Gold, Hermann" uniqKey="Gold H" first="Hermann" last="Gold">Hermann Gold</name>
<name sortKey="Graf, Petra" sort="Graf, Petra" uniqKey="Graf P" first="Petra" last="Graf">Petra Graf</name>
<name sortKey="Guberina, Hana" sort="Guberina, Hana" uniqKey="Guberina H" first="Hana" last="Guberina">Hana Guberina</name>
<name sortKey="Guggemos, Wolfgang" sort="Guggemos, Wolfgang" uniqKey="Guggemos W" first="Wolfgang" last="Guggemos">Wolfgang Guggemos</name>
<name sortKey="Haas, Walter" sort="Haas, Walter" uniqKey="Haas W" first="Walter" last="Haas">Walter Haas</name>
<name sortKey="Hartmann, Wulf" sort="Hartmann, Wulf" uniqKey="Hartmann W" first="Wulf" last="Hartmann">Wulf Hartmann</name>
<name sortKey="Junglen, Sandra" sort="Junglen, Sandra" uniqKey="Junglen S" first="Sandra" last="Junglen">Sandra Junglen</name>
<name sortKey="Kallies, Rene" sort="Kallies, Rene" uniqKey="Kallies R" first="Rene" last="Kallies">Rene Kallies</name>
<name sortKey="Muller, Marcel A" sort="Muller, Marcel A" uniqKey="Muller M" first="Marcel A." last="Müller">Marcel A. Müller</name>
<name sortKey="Muth, Doreen" sort="Muth, Doreen" uniqKey="Muth D" first="Doreen" last="Muth">Doreen Muth</name>
<name sortKey="Rohnisch, Tim" sort="Rohnisch, Tim" uniqKey="Rohnisch T" first="Tim" last="Röhnisch">Tim Röhnisch</name>
<name sortKey="Sack, Stefan" sort="Sack, Stefan" uniqKey="Sack S" first="Stefan" last="Sack">Stefan Sack</name>
<name sortKey="Scheible, Gregor" sort="Scheible, Gregor" uniqKey="Scheible G" first="Gregor" last="Scheible">Gregor Scheible</name>
<name sortKey="Schmid Wendtner, Monika" sort="Schmid Wendtner, Monika" uniqKey="Schmid Wendtner M" first="Monika" last="Schmid-Wendtner">Monika Schmid-Wendtner</name>
<name sortKey="Seilmaier, Michael" sort="Seilmaier, Michael" uniqKey="Seilmaier M" first="Michael" last="Seilmaier">Michael Seilmaier</name>
<name sortKey="Wendtner, Clemens Martin" sort="Wendtner, Clemens Martin" uniqKey="Wendtner C" first="Clemens-Martin" last="Wendtner">Clemens-Martin Wendtner</name>
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<name sortKey="Rambaut, Andrew" sort="Rambaut, Andrew" uniqKey="Rambaut A" first="Andrew" last="Rambaut">Andrew Rambaut</name>
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<country name="États-Unis">
<region name="Maryland">
<name sortKey="Rambaut, Andrew" sort="Rambaut, Andrew" uniqKey="Rambaut A" first="Andrew" last="Rambaut">Andrew Rambaut</name>
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