Outbreaks of Middle East Respiratory Syndrome in Two Hospitals Initiated by a Single Patient in Daejeon, South Korea
Identifieur interne : 000A48 ( Pmc/Checkpoint ); précédent : 000A47; suivant : 000A49Outbreaks of Middle East Respiratory Syndrome in Two Hospitals Initiated by a Single Patient in Daejeon, South Korea
Auteurs : Sun Hee Park [Corée du Sud] ; Yeon-Sook Kim [Corée du Sud] ; Younghee Jung [Corée du Sud] ; Soo Young Choi [Corée du Sud] ; Nam-Hyuk Cho [Corée du Sud] ; Hye Won Jeong [Corée du Sud] ; Jung Yeon Heo [Corée du Sud] ; Ji Hyun Yoon [Corée du Sud] ; Jacob Lee [Corée du Sud] ; Shinhye Cheon [Corée du Sud] ; Kyung Mok Sohn [Corée du Sud]Source :
- Infection & Chemotherapy [ 2093-2340 ] ; 2016.
Abstract
A Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreak in South Korea in 2015 started by a single imported case and was amplified by intra- and inter-hospital transmission. We describe two hospital outbreaks of MERS-CoV infection in Daejeon caused by a single patient who was infected by the first Korean case of MERS.
Demographic and clinical information involving MERS cases in the Daejeon cluster were retrospectively collected and potential contacts and exposures were assessed. The incubation periods and serial intervals were estimated. Viral RNAs were extracted from respiratory tract samples obtained from the index case, four secondary cases and one tertiary case from each hospital. The partial S2 domain of the MERS-CoV spike was sequenced.
In Daejeon, a MERS patient (the index case) was hospitalized at Hospital A in the first week of illness and was transferred to Hospital B because of pneumonia progression in the second week of illness, where he received a bronchoscopic examination and nebulizer therapy. A total of 23 secondary cases (10 in Hospital A and 13 in Hospital B) were detected among patients and caregivers who stayed on the same ward with the index case. There were no secondary cases among healthcare workers. Among close hospital contacts, the secondary attack rate was 15.8% (12/76) in Hospital A and 14.3% (10/70) in Hospital B. However, considering the exposure duration, the incidence rate was higher in Hospital B (7.7/100 exposure-days) than Hospital A (3.4/100 exposure-days). In Hospital B, the median incubation period was shorter (4.6 days vs. 10.8 days), the median time to pneumonia development was faster (3 days vs. 6 days) and mortality was higher (70% vs. 30.8%) than in Hospital A. MERS-CoV isolates from 11 cases formed a single monophyletic clade, with the closest similarity to strains from Riyadh.
Exposure to the MERS case in the late stage (2nd week) of diseases appeared to increase the risk of transmission and was associated with shorter incubation periods and rapid disease progression among those infected. Early detection and isolation of cases is critical in preventing the spread of MERS in the hospital and decreasing the disease severity among those infected.
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DOI: 10.3947/ic.2016.48.2.99
PubMed: 27433380
PubMed Central: 4945733
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and Immunology, Department of Biomedical Science, Seoul National University College of Medicine and Bundang Hospital, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Jeong, Hye Won" sort="Jeong, Hye Won" uniqKey="Jeong H" first="Hye Won" last="Jeong">Hye Won Jeong</name><affiliation wicri:level="1"><nlm:aff id="A6">Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, Chungbuk National University, Cheongju, Korea.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Corée du Sud</country><wicri:regionArea>Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, Chungbuk National University, Cheongju</wicri:regionArea><wicri:noRegion>Cheongju</wicri:noRegion></affiliation></author><author><name sortKey="Heo, Jung Yeon" sort="Heo, Jung Yeon" uniqKey="Heo J" first="Jung Yeon" last="Heo">Jung Yeon Heo</name><affiliation wicri:level="1"><nlm:aff id="A6">Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, Chungbuk National University, Cheongju, Korea.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Corée du Sud</country><wicri:regionArea>Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, Chungbuk National University, Cheongju</wicri:regionArea><wicri:noRegion>Cheongju</wicri:noRegion></affiliation></author><author><name sortKey="Yoon, Ji Hyun" sort="Yoon, Ji Hyun" uniqKey="Yoon J" first="Ji Hyun" last="Yoon">Ji Hyun Yoon</name><affiliation wicri:level="1"><nlm:aff id="A7">Division of Infectious diseases, Department of Internal Medicine, Eulji University hospital, Daejeon, Korea.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Corée du Sud</country><wicri:regionArea>Division of Infectious diseases, Department of Internal Medicine, Eulji University hospital, Daejeon</wicri:regionArea><wicri:noRegion>Daejeon</wicri:noRegion></affiliation></author><author><name sortKey="Lee, Jacob" sort="Lee, Jacob" uniqKey="Lee J" first="Jacob" last="Lee">Jacob Lee</name><affiliation wicri:level="3"><nlm:aff id="A8">Division of Infectious diseases, Department of Internal Medicine, College of Medicine, Hallym University, Seoul, Korea.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Corée du Sud</country><wicri:regionArea>Division of Infectious diseases, Department of Internal Medicine, College of Medicine, Hallym University, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Cheon, Shinhye" sort="Cheon, Shinhye" uniqKey="Cheon S" first="Shinhye" last="Cheon">Shinhye Cheon</name><affiliation wicri:level="1"><nlm:aff id="A2">Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Corée du Sud</country><wicri:regionArea>Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon</wicri:regionArea><wicri:noRegion>Daejeon</wicri:noRegion></affiliation></author><author><name sortKey="Sohn, Kyung Mok" sort="Sohn, Kyung Mok" uniqKey="Sohn K" first="Kyung Mok" last="Sohn">Kyung Mok Sohn</name><affiliation wicri:level="1"><nlm:aff id="A2">Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Corée du Sud</country><wicri:regionArea>Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon</wicri:regionArea><wicri:noRegion>Daejeon</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27433380</idno><idno type="pmc">4945733</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4945733</idno><idno type="RBID">PMC:4945733</idno><idno type="doi">10.3947/ic.2016.48.2.99</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">000093</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000093</idno><idno type="wicri:Area/Pmc/Curation">000093</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000093</idno><idno type="wicri:Area/Pmc/Checkpoint">000A48</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000A48</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Outbreaks of Middle East Respiratory Syndrome in Two Hospitals Initiated by a Single Patient in Daejeon, South Korea</title><author><name sortKey="Park, Sun Hee" sort="Park, Sun Hee" uniqKey="Park S" first="Sun Hee" last="Park">Sun Hee Park</name><affiliation wicri:level="3"><nlm:aff id="A1">Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Corée du Sud</country><wicri:regionArea>Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Kim, Yeon Sook" sort="Kim, Yeon Sook" uniqKey="Kim Y" first="Yeon-Sook" last="Kim">Yeon-Sook Kim</name><affiliation wicri:level="1"><nlm:aff id="A2">Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Corée du Sud</country><wicri:regionArea>Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon</wicri:regionArea><wicri:noRegion>Daejeon</wicri:noRegion></affiliation></author><author><name sortKey="Jung, Younghee" sort="Jung, Younghee" uniqKey="Jung Y" first="Younghee" last="Jung">Younghee Jung</name><affiliation wicri:level="1"><nlm:aff id="A3">Division of infectious disease, Department of internal medicine, Hallym Sacred Heart Hospital, Anayang, Korea.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Corée du Sud</country><wicri:regionArea>Division of infectious disease, Department of internal medicine, Hallym Sacred Heart Hospital, Anayang</wicri:regionArea><wicri:noRegion>Anayang</wicri:noRegion></affiliation></author><author><name sortKey="Choi, Soo Young" sort="Choi, Soo Young" uniqKey="Choi S" first="Soo Young" last="Choi">Soo Young Choi</name><affiliation wicri:level="1"><nlm:aff id="A4">Department of Neurology, Dae-Chung Hospital, Daejeon, Korea.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Corée du Sud</country><wicri:regionArea>Department of Neurology, Dae-Chung Hospital, Daejeon</wicri:regionArea><wicri:noRegion>Daejeon</wicri:noRegion></affiliation></author><author><name sortKey="Cho, Nam Hyuk" sort="Cho, Nam Hyuk" uniqKey="Cho N" first="Nam-Hyuk" last="Cho">Nam-Hyuk Cho</name><affiliation wicri:level="3"><nlm:aff id="A5">Department of Microbiology and Immunology, Department of Biomedical Science, Seoul National University College of Medicine and Bundang Hospital, Seoul, Korea.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Corée du Sud</country><wicri:regionArea>Department of Microbiology and Immunology, Department of Biomedical Science, Seoul National University College of Medicine and Bundang Hospital, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Jeong, Hye Won" sort="Jeong, Hye Won" uniqKey="Jeong H" first="Hye Won" last="Jeong">Hye Won Jeong</name><affiliation wicri:level="1"><nlm:aff id="A6">Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, Chungbuk National University, Cheongju, Korea.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Corée du Sud</country><wicri:regionArea>Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, Chungbuk National University, Cheongju</wicri:regionArea><wicri:noRegion>Cheongju</wicri:noRegion></affiliation></author><author><name sortKey="Heo, Jung Yeon" sort="Heo, Jung Yeon" uniqKey="Heo J" first="Jung Yeon" last="Heo">Jung Yeon Heo</name><affiliation wicri:level="1"><nlm:aff id="A6">Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, Chungbuk National University, Cheongju, Korea.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Corée du Sud</country><wicri:regionArea>Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, Chungbuk National University, Cheongju</wicri:regionArea><wicri:noRegion>Cheongju</wicri:noRegion></affiliation></author><author><name sortKey="Yoon, Ji Hyun" sort="Yoon, Ji Hyun" uniqKey="Yoon J" first="Ji Hyun" last="Yoon">Ji Hyun Yoon</name><affiliation wicri:level="1"><nlm:aff id="A7">Division of Infectious diseases, Department of Internal Medicine, Eulji University hospital, Daejeon, Korea.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Corée du Sud</country><wicri:regionArea>Division of Infectious diseases, Department of Internal Medicine, Eulji University hospital, Daejeon</wicri:regionArea><wicri:noRegion>Daejeon</wicri:noRegion></affiliation></author><author><name sortKey="Lee, Jacob" sort="Lee, Jacob" uniqKey="Lee J" first="Jacob" last="Lee">Jacob Lee</name><affiliation wicri:level="3"><nlm:aff id="A8">Division of Infectious diseases, Department of Internal Medicine, College of Medicine, Hallym University, Seoul, Korea.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Corée du Sud</country><wicri:regionArea>Division of Infectious diseases, Department of Internal Medicine, College of Medicine, Hallym University, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Cheon, Shinhye" sort="Cheon, Shinhye" uniqKey="Cheon S" first="Shinhye" last="Cheon">Shinhye Cheon</name><affiliation wicri:level="1"><nlm:aff id="A2">Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Corée du Sud</country><wicri:regionArea>Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon</wicri:regionArea><wicri:noRegion>Daejeon</wicri:noRegion></affiliation></author><author><name sortKey="Sohn, Kyung Mok" sort="Sohn, Kyung Mok" uniqKey="Sohn K" first="Kyung Mok" last="Sohn">Kyung Mok Sohn</name><affiliation wicri:level="1"><nlm:aff id="A2">Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Corée du Sud</country><wicri:regionArea>Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon</wicri:regionArea><wicri:noRegion>Daejeon</wicri:noRegion></affiliation></author></analytic><series><title level="j">Infection & Chemotherapy</title><idno type="ISSN">2093-2340</idno><idno type="eISSN">2092-6448</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>A Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreak in South Korea in 2015 started by a single imported case and was amplified by intra- and inter-hospital transmission. We describe two hospital outbreaks of MERS-CoV infection in Daejeon caused by a single patient who was infected by the first Korean case of MERS.</p></sec><sec><title>Materials and Methods</title><p>Demographic and clinical information involving MERS cases in the Daejeon cluster were retrospectively collected and potential contacts and exposures were assessed. The incubation periods and serial intervals were estimated. Viral RNAs were extracted from respiratory tract samples obtained from the index case, four secondary cases and one tertiary case from each hospital. The partial S2 domain of the MERS-CoV spike was sequenced.</p></sec><sec><title>Results</title><p>In Daejeon, a MERS patient (the index case) was hospitalized at Hospital A in the first week of illness and was transferred to Hospital B because of pneumonia progression in the second week of illness, where he received a bronchoscopic examination and nebulizer therapy. A total of 23 secondary cases (10 in Hospital A and 13 in Hospital B) were detected among patients and caregivers who stayed on the same ward with the index case. There were no secondary cases among healthcare workers. Among close hospital contacts, the secondary attack rate was 15.8% (12/76) in Hospital A and 14.3% (10/70) in Hospital B. However, considering the exposure duration, the incidence rate was higher in Hospital B (7.7/100 exposure-days) than Hospital A (3.4/100 exposure-days). In Hospital B, the median incubation period was shorter (4.6 days vs. 10.8 days), the median time to pneumonia development was faster (3 days vs. 6 days) and mortality was higher (70% vs. 30.8%) than in Hospital A. MERS-CoV isolates from 11 cases formed a single monophyletic clade, with the closest similarity to strains from Riyadh.</p></sec><sec><title>Conclusion</title><p>Exposure to the MERS case in the late stage (2nd week) of diseases appeared to increase the risk of transmission and was associated with shorter incubation periods and rapid disease progression among those infected. Early detection and isolation of cases is critical in preventing the spread of MERS in the hospital and decreasing the disease severity among those infected.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Oboho, Ik" uniqKey="Oboho I">IK Oboho</name></author><author><name sortKey="Tomczyk, Sm" uniqKey="Tomczyk S">SM Tomczyk</name></author><author><name sortKey="Al Asmari, Am" uniqKey="Al Asmari A">AM Al-Asmari</name></author><author><name sortKey="Banjar, Aa" uniqKey="Banjar A">AA Banjar</name></author><author><name sortKey="Al Mugti, H" uniqKey="Al Mugti H">H Al-Mugti</name></author><author><name sortKey="Aloraini, Ms" uniqKey="Aloraini M">MS Aloraini</name></author><author><name sortKey="Alkhaldi, Kz" uniqKey="Alkhaldi K">KZ Alkhaldi</name></author><author><name sortKey="Almohammadi, El" uniqKey="Almohammadi E">EL Almohammadi</name></author><author><name sortKey="Alraddadi, Bm" uniqKey="Alraddadi B">BM 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Infect Chemother</journal-id><journal-id journal-id-type="iso-abbrev">Infect Chemother</journal-id><journal-id journal-id-type="publisher-id">IC</journal-id><journal-title-group><journal-title>Infection & Chemotherapy</journal-title></journal-title-group><issn pub-type="ppub">2093-2340</issn><issn pub-type="epub">2092-6448</issn><publisher><publisher-name>The Korean Society of Infectious Diseases and Korean Society for Chemotherapy</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">27433380</article-id><article-id pub-id-type="pmc">4945733</article-id><article-id pub-id-type="doi">10.3947/ic.2016.48.2.99</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Article</subject></subj-group></article-categories><title-group><article-title>Outbreaks of Middle East Respiratory Syndrome in Two Hospitals Initiated by a Single Patient in Daejeon, South Korea</article-title></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">http://orcid.org/0000-0001-5648-9237</contrib-id><name><surname>Park</surname><given-names>Sun Hee</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid" authenticated="true">http://orcid.org/0000-0003-1142-5488</contrib-id><name><surname>Kim</surname><given-names>Yeon-Sook</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">http://orcid.org/0000-0002-9034-7635</contrib-id><name><surname>Jung</surname><given-names>Younghee</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">http://orcid.org/0000-0001-5541-4479</contrib-id><name><surname>Choi</surname><given-names>Soo young</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">http://orcid.org/0000-0003-3673-6397</contrib-id><name><surname>Cho</surname><given-names>Nam-Hyuk</given-names></name><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">http://orcid.org/0000-0002-1063-8476</contrib-id><name><surname>Jeong</surname><given-names>Hye Won</given-names></name><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">http://orcid.org/0000-0002-6548-1939</contrib-id><name><surname>Heo</surname><given-names>Jung Yeon</given-names></name><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">http://orcid.org/0000-0001-7523-2699</contrib-id><name><surname>Yoon</surname><given-names>Ji Hyun</given-names></name><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">http://orcid.org/0000-0002-7041-065X</contrib-id><name><surname>Lee</surname><given-names>Jacob</given-names></name><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">http://orcid.org/0000-0002-1783-121X</contrib-id><name><surname>Cheon</surname><given-names>Shinhye</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">http://orcid.org/0000-0002-3237-044X</contrib-id><name><surname>Sohn</surname><given-names>Kyung Mok</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib></contrib-group><aff id="A1"><label>1</label>Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.</aff><aff id="A2"><label>2</label>Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea.</aff><aff id="A3"><label>3</label>Division of infectious disease, Department of internal medicine, Hallym Sacred Heart Hospital, Anayang, Korea.</aff><aff id="A4"><label>4</label>Department of Neurology, Dae-Chung Hospital, Daejeon, Korea.</aff><aff id="A5"><label>5</label>Department of Microbiology and Immunology, Department of Biomedical Science, Seoul National University College of Medicine and Bundang Hospital, Seoul, Korea.</aff><aff id="A6"><label>6</label>Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, Chungbuk National University, Cheongju, Korea.</aff><aff id="A7"><label>7</label>Division of Infectious diseases, Department of Internal Medicine, Eulji University hospital, Daejeon, Korea.</aff><aff id="A8"><label>8</label>Division of Infectious diseases, Department of Internal Medicine, College of Medicine, Hallym University, Seoul, Korea.</aff><author-notes><corresp>Corresponding Author: Yeon-Sook Kim, MD, PhD. Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Munhwa-ro 282, Jung-gu, Daejeon 35015, Korea. Tel: +82-42-280-8109, Fax: +82-42-257-5753, <email>alice@cnuh.co.kr</email></corresp></author-notes><pub-date pub-type="ppub"><month>6</month><year>2016</year></pub-date><pub-date pub-type="epub"><day>30</day><month>6</month><year>2016</year></pub-date><volume>48</volume><issue>2</issue><fpage>99</fpage><lpage>107</lpage><history><date date-type="received"><day>12</day><month>3</month><year>2016</year></date><date date-type="rev-recd"><day>20</day><month>4</month><year>2016</year></date><date date-type="accepted"><day>27</day><month>4</month><year>2016</year></date></history><permissions><copyright-statement>Copyright © 2016 by The Korean Society of Infectious Diseases and Korean Society for Chemotherapy</copyright-statement><copyright-year>2016</copyright-year><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/"><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/">http://creativecommons.org/licenses/by-nc/3.0/</ext-link>) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><abstract><sec><title>Background</title><p>A Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreak in South Korea in 2015 started by a single imported case and was amplified by intra- and inter-hospital transmission. We describe two hospital outbreaks of MERS-CoV infection in Daejeon caused by a single patient who was infected by the first Korean case of MERS.</p></sec><sec><title>Materials and Methods</title><p>Demographic and clinical information involving MERS cases in the Daejeon cluster were retrospectively collected and potential contacts and exposures were assessed. The incubation periods and serial intervals were estimated. Viral RNAs were extracted from respiratory tract samples obtained from the index case, four secondary cases and one tertiary case from each hospital. The partial S2 domain of the MERS-CoV spike was sequenced.</p></sec><sec><title>Results</title><p>In Daejeon, a MERS patient (the index case) was hospitalized at Hospital A in the first week of illness and was transferred to Hospital B because of pneumonia progression in the second week of illness, where he received a bronchoscopic examination and nebulizer therapy. A total of 23 secondary cases (10 in Hospital A and 13 in Hospital B) were detected among patients and caregivers who stayed on the same ward with the index case. There were no secondary cases among healthcare workers. Among close hospital contacts, the secondary attack rate was 15.8% (12/76) in Hospital A and 14.3% (10/70) in Hospital B. However, considering the exposure duration, the incidence rate was higher in Hospital B (7.7/100 exposure-days) than Hospital A (3.4/100 exposure-days). In Hospital B, the median incubation period was shorter (4.6 days vs. 10.8 days), the median time to pneumonia development was faster (3 days vs. 6 days) and mortality was higher (70% vs. 30.8%) than in Hospital A. MERS-CoV isolates from 11 cases formed a single monophyletic clade, with the closest similarity to strains from Riyadh.</p></sec><sec><title>Conclusion</title><p>Exposure to the MERS case in the late stage (2nd week) of diseases appeared to increase the risk of transmission and was associated with shorter incubation periods and rapid disease progression among those infected. Early detection and isolation of cases is critical in preventing the spread of MERS in the hospital and decreasing the disease severity among those infected.</p></sec></abstract><kwd-group><kwd>Middle East Respiratory Syndrome coronavirus</kwd><kwd>Hospital</kwd><kwd>Outbreak</kwd><kwd>Superspreading</kwd><kwd>Daejeon</kwd><kwd>South Korea</kwd></kwd-group></article-meta></front><floats-group><fig id="F1" orientation="portrait" position="float"><label>Figure 1</label><caption><title>Epidemic curve of all cases with Middle East respiratory syndrome-coronavirus (MERS-CoV) infection linked to the index case in Daejeon, South Korea. All cases with MERS-CoV infection are plotted by the date of symptom onset, according to the hospital. The implementation of infection control measures is also shown in the graph.</title></caption><graphic xlink:href="ic-48-99-g001"></graphic></fig><fig id="F2" orientation="portrait" position="float"><label>Figure 2</label><caption><title>Transmission map of outbreak of Middle East respiratory syndrome-coronavirus infection in Daejeon and chest CT scans of the index case.</title></caption><graphic xlink:href="ic-48-99-g002"></graphic></fig><fig id="F3" orientation="portrait" position="float"><label>Figure 3</label><caption><title>Distributions of incubation periods of cases with Middle East respiratory syndrome-coronavirus infection in two hospitals in Daejeon. The fitted distributions of incubation periods of Hospital A (blue line) and B (red line) are plotted against the empirical cumulative density function of observed incubation periods (midpoint of exposure to symptom onset) (black line). The 95% confidence intervals for the medians of these fitted distributions are also plotted. Bootstrap estimates are shown in grey shading.</title></caption><graphic xlink:href="ic-48-99-g003"></graphic></fig><fig id="F4" orientation="portrait" position="float"><label>Figure 4</label><caption><title>Phylogenetic analysis of S2 fragment sequences of Middle East respiratory syndrome-coronavirus (MERS-CoV) from 11 cases from the Daejeon cluster. The partial S2 fragment sequences of MERS-CoV spike genes were obtained from the index case (Index), 4 secondary cases (A1, A2, A3, A8) from the Hospital A cluster and 4 secondary cases (B1, B2, B6, B7) from the Hospital B cluster. The S2 fragment sequences isolated from two tertiary cases (A14, B11) were also analyzed. The new 2 sequences of spike genes identified in this study are highlighted in blue, and compared with the previously published 20 MERS-CoV genomes (<xref ref-type="supplementary-material" rid="S2">Supplementary Table 2</xref>). Values on nodes correspond to posterior probability values obtained from the approximate likelihood ratio test based on a Shimodaira-Hasegawa-like procedure.</title></caption><graphic xlink:href="ic-48-99-g004"></graphic></fig><table-wrap id="T1" orientation="portrait" position="float"><label>Table 1</label><caption><title>Demographic and clinical characteristics of cases in the Daejeon cluster of Middle East respiratory syndrome-coronavirus infection, 2015</title></caption><alternatives><graphic xlink:href="ic-48-99-i001"></graphic><table frame="hsides" rules="rows"><col width="45.21%" span="1"></col><col width="19.18%" span="1"></col><col width="19.18%" span="1"></col><col width="16.44%" span="1"></col><thead><tr><th valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)"></th><th valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">Secondary cases in Hospital A (N = 13)</th><th valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">Secondary cases in Hospital B (N = 10)</th><th valign="middle" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)"><italic>P</italic>-value</th></tr></thead><tbody><tr><td valign="top" align="left" rowspan="1" colspan="1">Male-no. (%)</td><td valign="top" align="center" rowspan="1" colspan="1">6 (46.2)</td><td valign="top" align="center" rowspan="1" colspan="1">7 (70)</td><td valign="top" align="center" rowspan="1" colspan="1">0.40</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">Age-year, median (range)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">66 (31-87)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">74.5 (60-82)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">0.71</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Role</td><td valign="top" align="center" rowspan="1" colspan="1"></td><td valign="top" align="center" rowspan="1" colspan="1"></td><td valign="top" align="center" rowspan="4" colspan="1">0.63</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"> Patients</td><td valign="top" align="center" rowspan="1" colspan="1">8 (61.5)</td><td valign="top" align="center" rowspan="1" colspan="1">6 (60)</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"> Caregivers</td><td valign="top" align="center" rowspan="1" colspan="1">4 (30.8)</td><td valign="top" align="center" rowspan="1" colspan="1">4 (40)</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"> Healthcare workers</td><td valign="top" align="center" rowspan="1" colspan="1">1 (7.7)</td><td valign="top" align="center" rowspan="1" colspan="1">0 (0)</td></tr><tr><td valign="top" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">Underlying diseases<sup>a</sup>-no. (%)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">8 (61.5)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">8 (80)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)"></td></tr><tr><td valign="top" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)"> Pulmonary diseases</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">2 (15.4)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">6 (60)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">0.04</td></tr><tr><td valign="top" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)"> Diabetes</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">6 (46.2)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">1 (10)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">0.09</td></tr><tr><td valign="top" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)"> Cerebrovascular disease</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">5 (38.5)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">0 (0)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">0.05</td></tr><tr><td valign="top" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)"> Malignancy</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">1 (7.7)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">3 (30)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">0.28</td></tr><tr><td valign="top" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)"> Cardiovascular disease</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">2 (15.4)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">2 (20)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">1.00</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Symptoms at initial presentation<sup>b</sup>-no. (%)</td><td valign="top" align="center" rowspan="1" colspan="1"></td><td valign="top" align="center" rowspan="1" colspan="1"></td><td valign="top" align="center" rowspan="1" colspan="1"></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"> Fever</td><td valign="middle" align="center" rowspan="1" colspan="1">13 (100)</td><td valign="middle" align="center" rowspan="1" colspan="1">9 (90)</td><td valign="middle" align="center" rowspan="1" colspan="1">0.43</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"> Myalgia</td><td valign="top" align="center" rowspan="1" colspan="1">8 (61.5)</td><td valign="top" align="center" rowspan="1" colspan="1">3 (60)</td><td valign="top" align="center" rowspan="1" colspan="1">0.21</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"> Cough</td><td valign="top" align="center" rowspan="1" colspan="1">4 (30.8)</td><td valign="top" align="center" rowspan="1" colspan="1">6 (60)</td><td valign="top" align="center" rowspan="1" colspan="1">0.22</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"> Sputum</td><td valign="top" align="center" rowspan="1" colspan="1">7 (53.85)</td><td valign="top" align="center" rowspan="1" colspan="1">3 (30)</td><td valign="top" align="center" rowspan="1" colspan="1">0.40</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"> Shortness of breath</td><td valign="top" align="center" rowspan="1" colspan="1">3 (23.1)</td><td valign="top" align="center" rowspan="1" colspan="1">4 (40)</td><td valign="top" align="center" rowspan="1" colspan="1">0.65</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"> Headache</td><td valign="top" align="center" rowspan="1" colspan="1">2 (15.4)</td><td valign="top" align="center" rowspan="1" colspan="1">2 (20)</td><td valign="top" align="center" rowspan="1" colspan="1">1.00</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"> Gastrointestinal symptoms</td><td valign="top" align="center" rowspan="1" colspan="1">4 (30.8)</td><td valign="top" align="center" rowspan="1" colspan="1">4 (40)</td><td valign="top" align="center" rowspan="1" colspan="1">0.68</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">Pneumonia development</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">10 (76.9)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">10 (100)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)"></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)"> At presentation-no. (%)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">2 (15.4)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">3 (30)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">0.62</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)"> Within 7 days-no. (%)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">7 (53.8)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">10 (100)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">0.02</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)"> Median time to pneumonia, days (IQR)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">6 (3-7)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">3 (1-4)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">0.04</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1">Treatment-no. (%)</td><td valign="top" align="center" rowspan="1" colspan="1"></td><td valign="top" align="center" rowspan="1" colspan="1"></td><td valign="top" align="center" rowspan="1" colspan="1"></td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"> Ventilator care<sup>c</sup></td><td valign="top" align="center" rowspan="1" colspan="1">1 (7.7)</td><td valign="top" align="center" rowspan="1" colspan="1">4 (40)</td><td valign="top" align="center" rowspan="1" colspan="1">0.13</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1"> Antiviral therapy</td><td valign="top" align="center" rowspan="1" colspan="1">8 (61.5)</td><td valign="top" align="center" rowspan="1" colspan="1">7 (70)</td><td valign="top" align="center" rowspan="1" colspan="1">1.00</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">Case fatality ratio-no. (%)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">4 (30.8)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">7 (70)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">0.10</td></tr><tr><td valign="top" align="left" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)"> Median time to death, days (IQR)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">12.5 (5.5-19)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">11 (9-16)</td><td valign="top" align="center" rowspan="1" colspan="1" style="background-color:rgb(228,222,238)">0.92</td></tr></tbody></table></alternatives><table-wrap-foot><fn><p>IQR, interquartile range.</p><p><sup>a</sup>Two cases had chronic liver disease and one had chronic kidney disease. The index case had received total colectomy for familial adenomatous polyposis. Pulmonary diseases included chronic obstructive pulmonary disease in four cases, lung cancer in two, pulmonary tuberculosis in one, and chronic pneumonia in one.</p><p><sup>b</sup>Four cases (A8, A9, A13, and A15) had only mild symptoms and fever.</p><p><sup>c</sup>Six cases died of respiratory failure before receiving ventilator care. One tertiary case (A15) received a ventilator care with an extracorporeal membrane oxygenation therapy.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc><affiliations><list><country><li>Corée du Sud</li></country><region><li>Région capitale de Séoul</li></region><settlement><li>Séoul</li></settlement></list><tree><country name="Corée du Sud"><region name="Région capitale de Séoul"><name sortKey="Park, Sun Hee" sort="Park, Sun Hee" uniqKey="Park S" first="Sun Hee" last="Park">Sun Hee Park</name></region><name sortKey="Cheon, Shinhye" sort="Cheon, Shinhye" uniqKey="Cheon S" first="Shinhye" last="Cheon">Shinhye Cheon</name><name sortKey="Cho, Nam Hyuk" sort="Cho, Nam Hyuk" uniqKey="Cho N" first="Nam-Hyuk" last="Cho">Nam-Hyuk Cho</name><name sortKey="Choi, Soo Young" sort="Choi, Soo Young" uniqKey="Choi S" first="Soo Young" last="Choi">Soo Young Choi</name><name sortKey="Heo, Jung Yeon" sort="Heo, Jung Yeon" uniqKey="Heo J" first="Jung Yeon" last="Heo">Jung Yeon Heo</name><name sortKey="Jeong, Hye Won" sort="Jeong, Hye Won" uniqKey="Jeong H" first="Hye Won" last="Jeong">Hye Won Jeong</name><name sortKey="Jung, Younghee" sort="Jung, Younghee" uniqKey="Jung Y" first="Younghee" last="Jung">Younghee Jung</name><name sortKey="Kim, Yeon Sook" sort="Kim, Yeon Sook" uniqKey="Kim Y" first="Yeon-Sook" last="Kim">Yeon-Sook Kim</name><name sortKey="Lee, Jacob" sort="Lee, Jacob" uniqKey="Lee J" first="Jacob" last="Lee">Jacob Lee</name><name sortKey="Sohn, Kyung Mok" sort="Sohn, Kyung Mok" uniqKey="Sohn K" first="Kyung Mok" last="Sohn">Kyung Mok Sohn</name><name sortKey="Yoon, Ji Hyun" sort="Yoon, Ji Hyun" uniqKey="Yoon J" first="Ji Hyun" last="Yoon">Ji Hyun Yoon</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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