Middle East respiratory syndrome coronavirus: Implications for health care facilities
Identifieur interne : 001266 ( Pmc/Corpus ); précédent : 001265; suivant : 001267Middle East respiratory syndrome coronavirus: Implications for health care facilities
Auteurs : Helena C. Maltezou ; Sotirios TsiodrasSource :
- American Journal of Infection Control [ 0196-6553 ] ; 2014.
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel coronavirus that causes a severe respiratory disease with high case fatality rate. Starting in March 2014, a dramatic increase of cases has occurred in the Arabian Peninsula, many of which were acquired in health care settings. As of May 9, 2014, 536 laboratory-confirmed cases and 145 deaths have been reported globally.
Review of publicly available data about MERS-CoV health care–associated transmission.
We identified 11 events of possible or confirmed health care–associated transmission with high morbidity and mortality, mainly among patients with comorbidities. Health care workers are also frequently affected; however, they tend to have milder symptoms and better prognosis. Gaps in infection control were noted in all events. Currently, health care–associated outbreaks are playing a pivotal role in the evolution of the MERS-CoV epidemic in countries in the Arabian Peninsula.
There is a need to increase infection control capacity in affected areas and areas at increased risk of being affected to prevent transmission in health care settings. Vaccines and antiviral agents are urgently needed. Overall, our knowledge about the epidemiologic characteristics of MERS-CoV that impact health care transmission is very limited. As the MERS-CoV epidemic continues to evolve, issues concerning best infection control measures will arise, and studies to better define their effectiveness in real life are needed.
Url:
DOI: 10.1016/j.ajic.2014.06.019
PubMed: 25465253
PubMed Central: 7132773
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Middle East respiratory syndrome coronavirus: Implications for health care facilities</title><author><name sortKey="Maltezou, Helena C" sort="Maltezou, Helena C" uniqKey="Maltezou H" first="Helena C." last="Maltezou">Helena C. Maltezou</name><affiliation><nlm:aff id="aff1">Department for Interventions in Health-Care Facilities, Hellenic Center for Disease Control and Prevention, Athens, Greece</nlm:aff></affiliation></author><author><name sortKey="Tsiodras, Sotirios" sort="Tsiodras, Sotirios" uniqKey="Tsiodras S" first="Sotirios" last="Tsiodras">Sotirios Tsiodras</name><affiliation><nlm:aff id="aff2">Fourth Department of Internal Medicine, University of Athens Medical School, Attikon University Hospital, Athens, Greece</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25465253</idno><idno type="pmc">7132773</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132773</idno><idno type="RBID">PMC:7132773</idno><idno type="doi">10.1016/j.ajic.2014.06.019</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">001266</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001266</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Middle East respiratory syndrome coronavirus: Implications for health care facilities</title><author><name sortKey="Maltezou, Helena C" sort="Maltezou, Helena C" uniqKey="Maltezou H" first="Helena C." last="Maltezou">Helena C. Maltezou</name><affiliation><nlm:aff id="aff1">Department for Interventions in Health-Care Facilities, Hellenic Center for Disease Control and Prevention, Athens, Greece</nlm:aff></affiliation></author><author><name sortKey="Tsiodras, Sotirios" sort="Tsiodras, Sotirios" uniqKey="Tsiodras S" first="Sotirios" last="Tsiodras">Sotirios Tsiodras</name><affiliation><nlm:aff id="aff2">Fourth Department of Internal Medicine, University of Athens Medical School, Attikon University Hospital, Athens, Greece</nlm:aff></affiliation></author></analytic><series><title level="j">American Journal of Infection Control</title><idno type="ISSN">0196-6553</idno><idno type="eISSN">1527-3296</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel coronavirus that causes a severe respiratory disease with high case fatality rate. Starting in March 2014, a dramatic increase of cases has occurred in the Arabian Peninsula, many of which were acquired in health care settings. As of May 9, 2014, 536 laboratory-confirmed cases and 145 deaths have been reported globally.</p></sec><sec><title>Methods</title><p>Review of publicly available data about MERS-CoV health care–associated transmission.</p></sec><sec><title>Results</title><p>We identified 11 events of possible or confirmed health care–associated transmission with high morbidity and mortality, mainly among patients with comorbidities. Health care workers are also frequently affected; however, they tend to have milder symptoms and better prognosis. Gaps in infection control were noted in all events. Currently, health care–associated outbreaks are playing a pivotal role in the evolution of the MERS-CoV epidemic in countries in the Arabian Peninsula.</p></sec><sec><title>Conclusion</title><p>There is a need to increase infection control capacity in affected areas and areas at increased risk of being affected to prevent transmission in health care settings. Vaccines and antiviral agents are urgently needed. Overall, our knowledge about the epidemiologic characteristics of MERS-CoV that impact health care transmission is very limited. As the MERS-CoV epidemic continues to evolve, issues concerning best infection control measures will arise, and studies to better define their effectiveness in real life are needed.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Assiri, A" uniqKey="Assiri A">A. Assiri</name></author><author><name sortKey="Al Tawfiq, J A" uniqKey="Al Tawfiq J">J.A. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Am J Infect Control</journal-id><journal-id journal-id-type="iso-abbrev">Am J Infect Control</journal-id><journal-title-group><journal-title>American Journal of Infection Control</journal-title></journal-title-group><issn pub-type="ppub">0196-6553</issn><issn pub-type="epub">1527-3296</issn><publisher><publisher-name>Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25465253</article-id><article-id pub-id-type="pmc">7132773</article-id><article-id pub-id-type="publisher-id">S0196-6553(14)00931-6</article-id><article-id pub-id-type="doi">10.1016/j.ajic.2014.06.019</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Middle East respiratory syndrome coronavirus: Implications for health care facilities</article-title></title-group><contrib-group><contrib contrib-type="author" id="au1"><name><surname>Maltezou</surname><given-names>Helena C.</given-names></name><degrees>MD, PhD</degrees><email>helen-maltezou@ath.forthnet.gr</email><xref rid="aff1" ref-type="aff">a</xref><xref rid="cor1" ref-type="corresp">∗</xref></contrib><contrib contrib-type="author" id="au2"><name><surname>Tsiodras</surname><given-names>Sotirios</given-names></name><degrees>MD, PhD</degrees><xref rid="aff2" ref-type="aff">b</xref></contrib></contrib-group><aff id="aff1"><label>a</label>Department for Interventions in Health-Care Facilities, Hellenic Center for Disease Control and Prevention, Athens, Greece</aff><aff id="aff2"><label>b</label>Fourth Department of Internal Medicine, University of Athens Medical School, Attikon University Hospital, Athens, Greece</aff><author-notes><corresp id="cor1"><label>∗</label>Address correspondence to Helena C. Maltezou, MD, PhD, Department for Interventions in Health-Care Facilities, Hellenic Center for Disease Control and Prevention, 3-5 Agrafon St, Athens, 15123 Greece. <email>helen-maltezou@ath.forthnet.gr</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>25</day><month>11</month><year>2014</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub"><month>12</month><year>2014</year></pub-date><pub-date pub-type="epub"><day>25</day><month>11</month><year>2014</year></pub-date><volume>42</volume><issue>12</issue><fpage>1261</fpage><lpage>1265</lpage><permissions><copyright-statement>Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.</copyright-statement><copyright-year>2014</copyright-year><copyright-holder>Association for Professionals in Infection Control and Epidemiology, Inc.</copyright-holder><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions><abstract id="abs0010"><sec><title>Background</title><p>Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel coronavirus that causes a severe respiratory disease with high case fatality rate. Starting in March 2014, a dramatic increase of cases has occurred in the Arabian Peninsula, many of which were acquired in health care settings. As of May 9, 2014, 536 laboratory-confirmed cases and 145 deaths have been reported globally.</p></sec><sec><title>Methods</title><p>Review of publicly available data about MERS-CoV health care–associated transmission.</p></sec><sec><title>Results</title><p>We identified 11 events of possible or confirmed health care–associated transmission with high morbidity and mortality, mainly among patients with comorbidities. Health care workers are also frequently affected; however, they tend to have milder symptoms and better prognosis. Gaps in infection control were noted in all events. Currently, health care–associated outbreaks are playing a pivotal role in the evolution of the MERS-CoV epidemic in countries in the Arabian Peninsula.</p></sec><sec><title>Conclusion</title><p>There is a need to increase infection control capacity in affected areas and areas at increased risk of being affected to prevent transmission in health care settings. Vaccines and antiviral agents are urgently needed. Overall, our knowledge about the epidemiologic characteristics of MERS-CoV that impact health care transmission is very limited. As the MERS-CoV epidemic continues to evolve, issues concerning best infection control measures will arise, and studies to better define their effectiveness in real life are needed.</p></sec></abstract><abstract abstract-type="author-highlights" id="abs0015"><title>Highlights</title><p><list list-type="simple" id="ulist0010"><list-item id="u0010"><label>•</label><p id="p0010">Health care–associated transmission plays a pivotal role in the Middle East respiratory syndrome coronavirus epidemic.</p></list-item><list-item id="u0015"><label>•</label><p id="p0015">Gaps in infection control were noted in all health care–associated events.</p></list-item><list-item id="u0020"><label>•</label><p id="p0020">There is a need to increase infection control capacity.</p></list-item><list-item id="u0025"><label>•</label><p id="p0025">Studies about the effectiveness of infection control measures are needed.</p></list-item><list-item id="u0030"><label>•</label><p id="p0030">Vaccines and antiviral agents against Middle East respiratory syndrome coronavirus are urgently needed.</p></list-item></list></p></abstract><kwd-group id="kwrds0010"><title>Key Words</title><kwd>Middle East respiratory syndrome coronavirus</kwd><kwd>Middle East respiratory syndrome</kwd><kwd>Hospital</kwd><kwd>Health care associated</kwd><kwd>Outbreak</kwd><kwd>Health care workers</kwd></kwd-group></article-meta></front><body><p id="p0035">Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel betacoronavirus of the <italic>Coronaviridae</italic> family that causes a severe respiratory disease with a high case fatality rate.<xref rid="bib1" ref-type="bibr">1</xref>, <xref rid="bib2" ref-type="bibr">2</xref>, <xref rid="bib3" ref-type="bibr">3</xref>, <xref rid="bib4" ref-type="bibr">4</xref> The virus was isolated for the first time in September 2012 from a 60-year-old patient with fatal pneumonia in Saudi Arabia.<xref rid="bib5" ref-type="bibr"><sup>5</sup></xref> However, the earliest identified human cases were traced back to March 2012, to a cluster of severe respiratory infections in a hospital in Jordan.<xref rid="bib6" ref-type="bibr"><sup>6</sup></xref> Up until now, all MERS-CoV infected cases are directly or indirectly linked to the Middle East; therefore, the name MERS-CoV was established.<xref rid="bib4" ref-type="bibr"><sup>4</sup></xref> Over the first 2 years after the emergence of MERS-CoV, the World Health Organization (WHO) has been notified of 191 laboratory-confirmed cases, of which 82 were fatal.<xref rid="bib7" ref-type="bibr"><sup>7</sup></xref> However, starting in mid- to late March 2014, a dramatic increase of cases has been recorded, many which were acquired in health care settings and concerned health care workers (HCWs).<xref rid="bib8" ref-type="bibr"><sup>8</sup></xref> As of May 9, 2014, 536 laboratory-confirmed cases and 145 deaths have been reported to the WHO globally.<xref rid="bib8" ref-type="bibr"><sup>8</sup></xref> As a result, concerns have been expressed about the possibility of a virus genetic change conferring increased transmissibility, and the novel virus received media attention globally. In the context of uncertainties about its epidemiology, the high case fatality rate, the urgent need for a specific antiviral treatment, and the unavailability of a vaccine, MERS-CoV has been a major public health concern of global dimensions. Given the current local epidemiologic trends of MERS-CoV<xref rid="bib8" ref-type="bibr"><sup>8</sup></xref> and the large numbers of travelers that fly out of the Arabian Peninsula,<xref rid="bib9" ref-type="bibr"><sup>9</sup></xref> it is almost certain that an increasing number of cases will be exported to other countries; these cases, especially when that patient is seriously ill, will require medical attention and hospitalization. Herein, we review publicly available data about MERS-CoV focusing on health care–associated transmission. Aspects relevant to infection control are also discussed.</p><sec id="sec1"><title>Search strategy</title><p id="p0040">We searched PubMed from September 2012 through June 19, 2014, using the terms <italic>Middle East respiratory syndrome</italic>, <italic>MERS</italic>, and <italic>novel coronavirus</italic>. The abstracts of articles identified through the first PubMed search were screened, and articles presenting original data on health care–associated infections and outbreaks were included. The reference lists of these articles were also reviewed as were any relevant review articles. In addition, we searched the Web sites of the WHO, United States Centers for Disease Control and Prevention (CDC), and European Centre for Disease Prevention and Control (ECDC). In total, we reviewed 252 articles on MERS-CoV and identified 10 articles presenting original data about 11 possible or confirmed health care–associated transmission events. Details about the health care–associated transmission ranged widely among these articles. To the best of our efforts, we avoided presenting duplicated data. In addition, we selected 30 original and review articles. All articles were studied by both authors independently.</p><sec id="sec1.1"><title>Epidemiology and clinical aspects</title><p id="p0045">MERS-CoV infection so far has been described in 10 countries in the Middle East (Saudi Arabia, United Arab Emirates, Qatar, Jordan, Oman, Kuwait, Egypt, Yemen, Lebanon, Iran), 6 countries in Europe (United Kingdom, Germany, France, Italy, Greece, the Netherlands), 2 country in Africa (Tunisia, Algeria), 2 countries in Asia (Malaysia, the Philippines), and 1 county in the Americas (United States).<xref rid="bib10" ref-type="bibr"><sup>10</sup></xref></p><p id="p0050">Molecular analyses of MERS-CoV or similar viruses from bats and camels suggest that these 2 species are the natural reservoirs of the virus.<xref rid="bib11" ref-type="bibr">11</xref>, <xref rid="bib12" ref-type="bibr">12</xref> Whole genome sequencing showed that human and camel viruses from Saudi Arabia are indistinguishable.<xref rid="bib12" ref-type="bibr"><sup>12</sup></xref> Multiple transmission routes are suspected; however, their exact contribution has not been elucidated so far. A phylogenetic study of 21 MERS-CoV genomes from Saudi Arabia suggested that both human-to-human transmission and sporadic zoonotic events occur.<xref rid="bib13" ref-type="bibr"><sup>13</sup></xref> The stability of the virus for prolonged periods in camel milk suggests the potential of excretion of the virus into camel milk and spread through consuming raw milk.<xref rid="bib14" ref-type="bibr"><sup>14</sup></xref></p><p id="p0055">The upsurge of cases since mid-March in the Arabian Peninsula (mainly in Saudi Arabia) is possibly attributed to an increase in the number of primary cases and hospital-acquired cases, some as a part of mainly small (1-2 cases), but in a few instances large, outbreaks.<xref rid="bib8" ref-type="bibr"><sup>8</sup></xref> A change in the transmissibility pattern of the virus and increased efficacy for sustained transmission could facilitate in-hospital transmission; however, epidemiologic and molecular data to this effect do not exist. Family clusters of MERS-CoV have been recorded.<xref rid="bib15" ref-type="bibr"><sup>15</sup></xref> The secondary attack rate in families was 1.35% in Saudi Arabia in 2014.<xref rid="bib8" ref-type="bibr"><sup>8</sup></xref> Among imported travel-associated cases, very few instances of person-to-person transmission have been verified.<xref rid="bib16" ref-type="bibr">16</xref>, <xref rid="bib17" ref-type="bibr">17</xref>, <xref rid="bib18" ref-type="bibr">18</xref> Recent phylogenetic analysis using human sequences from Jeddah suggests that the virus has not changed from previous strains.<xref rid="bib8" ref-type="bibr"><sup>8</sup></xref> Overall, it seems unlikely that the virus has increased its transmissibility or patterns of transmission. The basic reproductive number has been estimated to be <1 using real-time data until June and August 2013, respectively,<xref rid="bib19" ref-type="bibr">19</xref>, <xref rid="bib20" ref-type="bibr">20</xref> even though the upper range of estimates exceeded 1 in a scenario where infection control was not implemented.<xref rid="bib20" ref-type="bibr"><sup>20</sup></xref> These findings indicate no pandemic potential for MERS-CoV so far. Recently, a committee appointed by the WHO concluded that the conditions for a public health emergency of international concern have not yet been met. Moreover, increased testing rates of less ill or asymptomatic cases may have contributed to the upsurge of detected cases.</p><p id="p0060">Regarding characteristics of affected patients, most are men (male-to-female ratio: 2:1), with a median age of 49 years (range, 9 months-94 years).<xref rid="bib8" ref-type="bibr"><sup>8</sup></xref> The spectrum of MERS-CoV infections ranges from asymptomatic infection to very severe pneumonia with acute respiratory distress syndrome, septic shock, and multiorgan failure resulting in death. In an analysis of 144 confirmed and 17 possible cases, symptomatic patients typically had fever and cough, chills, sore throat, myalgia, and arthralgia, whereas vomiting and diarrhea were present in at least one third of patients.<xref rid="bib21" ref-type="bibr"><sup>21</sup></xref> In the same study, 63.4% of patients developed severe respiratory disease. It appears that severe disease predominantly occurs in patients with comorbidities; 76% of the patients in this report had at least 1.<xref rid="bib21" ref-type="bibr"><sup>21</sup></xref> The overall case fatality with the latest WHO figures is 27%.<xref rid="bib8" ref-type="bibr"><sup>8</sup></xref></p></sec><sec id="sec1.2"><title>MERS-CoV in health care facilities</title><p id="p0065">From the very first events of the MERS-CoV epidemic, the virus showed its health care–associated dynamic.<xref rid="bib6" ref-type="bibr"><sup>6</sup></xref> Apart of sporadic community cases and family clusters, health care–associated transmission has been reported on several occasions during the last 2 years, indicating human-to-human, although inconsistent, transmission (<xref rid="tbl1" ref-type="table">Table 1</xref>).<xref rid="bib2" ref-type="bibr">2</xref>, <xref rid="bib3" ref-type="bibr">3</xref>, <xref rid="bib6" ref-type="bibr">6</xref>, <xref rid="bib8" ref-type="bibr">8</xref>, <xref rid="bib22" ref-type="bibr">22</xref>, <xref rid="bib23" ref-type="bibr">23</xref>, <xref rid="bib24" ref-type="bibr">24</xref>, <xref rid="bib25" ref-type="bibr">25</xref>, <xref rid="bib26" ref-type="bibr">26</xref>, <xref rid="bib27" ref-type="bibr">27</xref> Gaps in infection control were the common denominator in the events of health care associated–transmission.<xref rid="bib2" ref-type="bibr">2</xref>, <xref rid="bib3" ref-type="bibr">3</xref>, <xref rid="bib6" ref-type="bibr">6</xref>, <xref rid="bib8" ref-type="bibr">8</xref>, <xref rid="bib22" ref-type="bibr">22</xref>, <xref rid="bib24" ref-type="bibr">24</xref> During the largest so far–published outbreak of MERS-CoV that occurred in Al-Hasa, Saudi Arabia, in 2013, 4 health care facilities were affected through transfer of patients but also possibly because of repeated introductions of cases from the community.<xref rid="bib3" ref-type="bibr"><sup>3</sup></xref> The outbreak extended for almost 2 months and involved 34 cases, including 2 HCWs. Most cases were confined in the hemodialysis unit with rapid transmission and high attack rates.<xref rid="bib3" ref-type="bibr"><sup>3</sup></xref> This outbreak gave the opportunity to elucidate several epidemiologic parameters of secondary MERS-CoV infection, such as the incubation period (5.2 days; 95% confidence interval, 1.92-14.7 days), serial interval (7.6 days; 95% confidence interval, 2.5-23.1 days), and heterogeneity in transmission, with many infected patients not transmitting the infection at all and 1 infected patient transmitting the infection to 7 others.<xref rid="bib3" ref-type="bibr"><sup>3</sup></xref> Moreover, this outbreak raised the possibility of transmission through direct or indirect contact and between rooms in the same ward.<xref rid="bib3" ref-type="bibr"><sup>3</sup></xref> A recent study showed that MERS-CoV remained viable for up to 48 hours under specific environmental conditions, which mimic the hospital environment (20°C with 40% relative humidity), whereas its stability was not reduced during aerosolization.<xref rid="bib28" ref-type="bibr"><sup>28</sup></xref> These data show that MERS-CoV has the potential to spread through contact or fomites caused by prolonged survival. A model-based study found that the virus structural characteristics render it very likely to remain viable in the environment for a long period and support fecal-oral transmission.<xref rid="bib29" ref-type="bibr"><sup>29</sup></xref><table-wrap position="float" id="tbl1"><label>Table 1</label><caption><p>Published events of possible or confirmed health care–associated transmission of MERS-CoV globally</p></caption><table frame="hsides" rules="groups"><thead><tr><th>Author/country/year</th><th>Setting</th><th>Number of cases (laboratory confirmed/probable)</th><th>Number of HCWs (% of total cases)</th><th>Nurses (% of HCWs)</th><th>Median age of cases, years (range)</th><th>Median age of HCWs, years (range)</th><th>Fatal cases (% of total)</th><th>Fatalities in HCWs (% of HCWs)</th><th>Comments</th></tr></thead><tbody><tr><td>Hijawi et al<xref rid="bib6" ref-type="bibr"><sup>6</sup></xref> and Al-Abdallat et al<xref rid="bib26" ref-type="bibr"><sup>26</sup></xref>/Jordan/2012</td><td>ICU, CCU, medical and emergency wards</td><td align="char">13 (8/5)<xref rid="tbl1fnlowast" ref-type="table-fn">∗</xref></td><td align="char">10 (76.9)</td><td align="char">8 (80)</td><td align="char">33 (25-65)</td><td align="char">31.5 (25-47.5)</td><td align="char">2 (15.4)</td><td align="char">1 (10)</td><td>Biphasic outbreak; no use of PPE apart from gloves; HCW at work while symptomatic; retrospective investigation and testing</td></tr><tr><td>Arabi et al<xref rid="bib2" ref-type="bibr"><sup>2</sup></xref>/Saudi Arabia/2012-2013</td><td>2 medical-surgical ICUs, 1 cardiac ICU</td><td align="char">15 (14/1)</td><td align="char">4 (26.7)</td><td align="char">4 (100)</td><td align="char">59 (36-83)<xref rid="tbl1fndagger" ref-type="table-fn">†</xref></td><td>36 (1 HCW with data)</td><td align="char">7 (46.6)</td><td>3 HCWs survived; no data about the critically ill HCW</td><td>2 hospitals; 11 critically ill patients and 4 HCWs (1 severe course, 1 mild symptoms, 2 asymptomatic); 3 cases in patients and 3 in HCWs were health care associated; the 3 HCWs did not use PPE</td></tr><tr><td>Assiri et al<xref rid="bib3" ref-type="bibr"><sup>3</sup></xref>/Saudi Arabia/2013</td><td>Hemodialysis unit, ICUs, medical wards</td><td align="char">34 (23/11)</td><td align="char">2 (5.9)</td><td align="char">1 (50)</td><td align="char">56 (24-94)</td><td align="char">43.5 (42-45)</td><td align="char">15 (65)</td><td align="char">0 (0)</td><td>2-month outbreak in 4 health care facilities; high attack rate in hemodialysis unit; transfer of patients important for spread; gaps in infection control</td></tr><tr><td>Memish et al<xref rid="bib24" ref-type="bibr"><sup>24</sup></xref>/Saudi Arabia/2012-2013</td><td>NR</td><td align="char">7 (7/0)</td><td align="char">7 (100)</td><td align="char">6 (86)</td><td>n/a</td><td align="char">42 (28-59)</td><td>n/a</td><td align="char">0 (0)</td><td>7 HCWs from 6 hospitals, 2 asymptomatic, 5 with mild symptoms; 4 of 7 with <1 hour exposure; gaps in infection control; 1 PCR positive for 8 days</td></tr><tr><td>Guery et al<xref rid="bib22" ref-type="bibr"><sup>22</sup></xref>/France/2013</td><td>Medical ward</td><td align="char">2 (2/0)</td><td align="char">0 (0)</td><td>n/a</td><td align="char">57.5 (51-64)</td><td>n/a</td><td align="char">1 (50)</td><td>n/a</td><td>Second patient was identified through contact tracing; patients had common room and bathroom; gaps in infection control</td></tr><tr><td>Omrani et al<xref rid="bib23" ref-type="bibr"><sup>23</sup></xref>/Saudi Arabia/2013</td><td>Emergency department/rooms</td><td align="char">3 (2/1)</td><td align="char">0 (0)</td><td>n/a</td><td align="char">40 (39-51)</td><td>n/a</td><td align="char">2 (66.7)</td><td>n/a</td><td>Family cluster most likely health care acquired</td></tr><tr><td>Tsiodras et al<xref rid="bib27" ref-type="bibr"><sup>27</sup></xref>/Greece/2014</td><td>Extensive contact with the health care environment in Jeddah</td><td align="char">1 (1/0)</td><td align="char">0 (0)</td><td>n/a</td><td>69</td><td>n/a</td><td align="char">0 (0)</td><td>n/a</td><td>Imported case; most likely health care associated transmission</td></tr><tr><td>WHO<xref rid="bib8" ref-type="bibr"><sup>8</sup></xref>/Saudi Arabia/2014</td><td>NR</td><td align="char">128 (128/0)</td><td align="char">39 (30.4)</td><td>NR</td><td align="char">48.5 (NR)</td><td>Younger than non-HCW cases</td><td>NR</td><td>NR</td><td>14 hospitals in Jeddah; >60% of cases were hospital acquired; HCWs more likely to be younger, women, and exhibit mild or no symptoms; 15% of HCWs had severe disease or died; gaps in infection control</td></tr><tr><td>WHO<xref rid="bib8" ref-type="bibr"><sup>8</sup></xref>/Saudi Arabia/2014</td><td>NR</td><td align="char">127 (127/0)</td><td align="char">26 (20.4)</td><td>NR</td><td>NR</td><td>NR</td><td>NR</td><td>NR</td><td>From Tabuk, Riyadh, and Medina</td></tr><tr><td>WHO<xref rid="bib8" ref-type="bibr"><sup>8</sup></xref>/United Arab Emirates/2014</td><td>NR</td><td align="char">37 (37/0)</td><td align="char">(67)</td><td>NR</td><td align="char">41 (4-73)</td><td>NR</td><td>NR</td><td>NR</td><td>28 of 37 cases were identified in a hospital cluster; 1 HCW with severe disease; the remaining HCWs mild or no symptoms</td></tr><tr><td>Bialek et al<xref rid="bib25" ref-type="bibr"><sup>25</sup></xref>/United States/2014</td><td>NR</td><td align="char">2 (3/0)</td><td align="char">2 (100)</td><td>NR</td><td>NR</td><td>NR</td><td align="char">0 (0)</td><td align="char">0 (0)</td><td>2 imported MERS-CoV cases in HCWs in Saudi Arabia</td></tr></tbody></table><table-wrap-foot><fn><p><italic>CCU</italic>, coronary care unit; <italic>HCW</italic>, health care worker; <italic>ICU</italic>, intensive care unit; <italic>MERS-CoV</italic>, Middle East respiratory syndrome coronavirus; <italic>n/a</italic>, nonapplicable; <italic>NR</italic>, not reported; <italic>PCR</italic>, polymerase chain reaction; <italic>PPE</italic>, personal protective equipment; <italic>WHO</italic>, World Health Organization.</p></fn></table-wrap-foot><table-wrap-foot><fn id="tbl1fnlowast"><label>∗</label><p id="ntpara0025">Data about laboratory confirmation were obtained from Al-Abdallat et al<xref rid="bib26" ref-type="bibr"><sup>26</sup></xref>; the remaining data were obtained from Hijawi et al.<xref rid="bib6" ref-type="bibr"><sup>6</sup></xref></p></fn></table-wrap-foot><table-wrap-foot><fn id="tbl1fndagger"><label>†</label><p id="ntpara0030">Median age and range concerns the 12 critically ill patients out of the 15 MERS-CoV infected cases.</p></fn></table-wrap-foot></table-wrap></p><p id="p0070">Vomiting and diarrhea are common in patients with MERS-CoV<xref rid="bib1" ref-type="bibr">1</xref>, <xref rid="bib22" ref-type="bibr">22</xref>, <xref rid="bib27" ref-type="bibr">27</xref> and may contribute to transmission. The MERS-CoV case imported in France shared his bathroom with the secondary hospital-acquired case, which raises the possibility of spread through stools.<xref rid="bib22" ref-type="bibr"><sup>22</sup></xref> MERS-CoV is predominantly shed through respiratory secretions during cough. MERS-CoV has been detected through polymerase chain reaction for up to 16 days in respiratory specimens and stools and up to 13 days in urine.<xref rid="bib22" ref-type="bibr">22</xref>, <xref rid="bib30" ref-type="bibr">30</xref>, <xref rid="bib31" ref-type="bibr">31</xref> Our knowledge about virus shedding and viral load kinetics throughout the clinical course of ill patients is scarce and therefore can provide limited guidance about the duration of implementation of infection control measures.<xref rid="bib31" ref-type="bibr"><sup>31</sup></xref> The possibility of prolonged shedding under an immunocompromised status should also be investigated and considered for infection control purposes.</p><p id="p0075">Health care–associated MERS-CoV infections and outbreaks have been associated with high morbidity, high rates and prolonged use of mechanical ventilation, and fatality rates up to 65%.<xref rid="bib2" ref-type="bibr">2</xref>, <xref rid="bib3" ref-type="bibr">3</xref>, <xref rid="bib23" ref-type="bibr">23</xref> Given the fact that health care services are often used by older people with comorbidities and in association with the severe course of MERS-CoV among these groups,<xref rid="bib2" ref-type="bibr"><sup>2</sup></xref> it is not surprising that patients with comorbidities are overrepresented in such outbreaks.<xref rid="bib3" ref-type="bibr"><sup>3</sup></xref> Beyond the considerable morbidity and mortality, such outbreaks are costly because of the high-level health care required, need for strict infection control measures, and extensive contact tracing among hundreds of patients, family members, and HCWs.<xref rid="bib3" ref-type="bibr">3</xref>, <xref rid="bib16" ref-type="bibr">16</xref>, <xref rid="bib17" ref-type="bibr">17</xref>, <xref rid="bib22" ref-type="bibr">22</xref>, <xref rid="bib27" ref-type="bibr">27</xref>, <xref rid="bib32" ref-type="bibr">32</xref>, <xref rid="bib33" ref-type="bibr">33</xref>, <xref rid="bib34" ref-type="bibr">34</xref> Regarding frequency of secondary transmission to HCWs in health care settings, Memish et al<xref rid="bib32" ref-type="bibr"><sup>32</sup></xref> presented data from 5,065 contacts in Saudi Arabia during a 12-month period (October 1, 2012-September 30, 2013). Of 1,695 HCW contacts of laboratory-confirmed MERS-CoV cases, 19 (1.12%) tested positive, less than the 3.4% (17 of 462) rate of infection among family contacts. These findings indicate a rather small risk of transmission to HCWs and that the recommended infection control measures are adequate thus far.</p><p id="p0080">In the description of demographics of secondary MERS-CoV cases, a drop of the median age from 59 to 43 years old compared with primary cases has been reported.<xref rid="bib21" ref-type="bibr"><sup>21</sup></xref> This depends on the conditions of each outbreak and may be affected by the preponderance of affected HCWs in each instance. For example, in the most recent WHO report,<xref rid="bib8" ref-type="bibr"><sup>8</sup></xref> the HCWs who tested positive for MERS-CoV in the 2014 Jeddah outbreaks were more likely to be younger, women, and to exhibit mild or no symptoms compared with primary cases. However, 15% of HCWs developed a severe disease, which resulted in admission to an intensive care unit or death.<xref rid="bib8" ref-type="bibr"><sup>8</sup></xref></p><p id="p0085">Unsuspected cases are the main source for the introduction of MERS-CoV virus from the community or another health care facility.<xref rid="bib3" ref-type="bibr"><sup>3</sup></xref> Although such patients may present with compatible symptoms, the diagnosis may not be considered early or symptoms may be mild.<xref rid="bib2" ref-type="bibr">2</xref>, <xref rid="bib24" ref-type="bibr">24</xref>, <xref rid="bib33" ref-type="bibr">33</xref> In the hospital outbreak that occurred in Saudi Arabia in 2013, 3 patients exhibited no fever during initial presentation.<xref rid="bib3" ref-type="bibr"><sup>3</sup></xref> HCWs may acquire MERS-CoV infection either in the community or through occupational exposure.<xref rid="bib2" ref-type="bibr">2</xref>, <xref rid="bib3" ref-type="bibr">3</xref>, <xref rid="bib32" ref-type="bibr">32</xref> Nurses are mostly affected, which is attributed to their prolonged, repeated, and closer physical contact with patients. HCWs may continue working despite being symptomatic.<xref rid="bib6" ref-type="bibr"><sup>6</sup></xref> An asymptomatic or mildly symptomatic course has been described in HCWs,<xref rid="bib2" ref-type="bibr">2</xref>, <xref rid="bib8" ref-type="bibr">8</xref>, <xref rid="bib24" ref-type="bibr">24</xref> which raises the possibility of transmission of the infection to their vulnerable patients during an asymptomatic phase or early incubation. Patient-to-patient transmission has been noted as well.<xref rid="bib3" ref-type="bibr">3</xref>, <xref rid="bib22" ref-type="bibr">22</xref></p><p id="p0090">Currently, health care–associated outbreaks are playing a pivotal role in the evolution of the MERS-CoV epidemic.<xref rid="bib8" ref-type="bibr"><sup>8</sup></xref> In the recent mission report by the WHO authorities evaluating data on 128 laboratory-confirmed cases in 14 hospitals in Jeddah, Saudi Arabia, with onset of symptoms between February 17 and April 26, 2014, one-third of the cases were considered to be primary cases (some of the investigations are still ongoing), whereas >60% of the cases (including 39 HCWs) were classified as hospital acquired.<xref rid="bib8" ref-type="bibr"><sup>8</sup></xref> In the rest of Saudi Arabia, 26 out of 127 (20.5%) recent cases were identified in HCWs.<xref rid="bib8" ref-type="bibr"><sup>8</sup></xref> Overall, 65 of the 290 (22.4%) cases reported from Saudi Arabia from March 27 to May 9, 2014, were HCWs.<xref rid="bib23" ref-type="bibr"><sup>23</sup></xref> In Mecca, another large outbreak in a hospital was described with 28 laboratory-confirmed cases, including 27 HCWs.<xref rid="bib8" ref-type="bibr"><sup>8</sup></xref> Both outbreaks were larger than the originally described outbreak in Saudi Arabia.<xref rid="bib3" ref-type="bibr"><sup>3</sup></xref> In the United Arab Emirates, HCWs accounted for more than two-thirds of 37 cases reported during the same period.<xref rid="bib8" ref-type="bibr"><sup>8</sup></xref> Although the WHO points to infection control gaps for the recent propagation of MERS-CoV within health care facilities in Saudi Arabia and the United Arab Emirates, we do not know if this concerns the use of personal protective equipment, hand hygiene, procedures, environmental cleaning, or triage.</p></sec><sec id="sec1.3"><title>Infection control in health care facilities</title><p id="p0095">Given that no vaccines or specific antiviral prophylaxis against MERS-CoV are available,<xref rid="bib35" ref-type="bibr">35</xref>, <xref rid="bib36" ref-type="bibr">36</xref> the prevention and control of transmission of MERS-CoV within health care facilities relies solely on early detection, isolation, and strict implementation of infection control measures. Rapid and accurate diagnosis is crucial to trigger contact tracing in the hospital and the community and should be ordered as soon as possible in the context of a relevant epidemiologic profile but also in the event of a health care–associated cluster of severe respiratory illness cases.</p><p id="p0100">Patients with confirmed or suspected MERS-CoV infection should be cared under contact and droplet precautions until testing results. In accordance with WHO guidelines, a high protection mask (eg, N95 respirator) along with eye goggles, gowns, and gloves should be used during aerosol-generating procedures; the latter should be performed in an adequately ventilated room (minimum of 6-12 air changes per hour) (airborne infection isolation room).<xref rid="bib37" ref-type="bibr"><sup>37</sup></xref> For consistency with the recommendations during the 2009 H1N1 pandemic, the United States CDC recommends the use of N95 respirators in all contacts with a laboratory-confirmed or suspected MERS-CoV infected case.<xref rid="bib38" ref-type="bibr"><sup>38</sup></xref> The rationale for this recommendation relies on the gaps of knowledge about the potential for airborne transmission of the novel coronavirus. However, N95 respirators are less tolerated by HCWs and are more expensive.<xref rid="bib39" ref-type="bibr"><sup>39</sup></xref> The United States CDC also recommends that patients with confirmed or suspected MERS-CoV infection are placed in an airborne infection isolation room.<xref rid="bib38" ref-type="bibr"><sup>38</sup></xref> HCWs with MERS-CoV infection should be strictly excluded from patient care, even with mild symptoms. The role of asymptomatic HCWs is under question. Overall, there is a need to increase infection control capacity in affected areas and areas at increased risk of being affected to prevent transmission in health care settings.</p></sec></sec><sec id="sec2"><title>Unanswered questions</title><p id="p0105">Our knowledge about the epidemiologic characteristics of MERS-CoV that impact health care transmission is very limited. To interrupt in-hospital transmission, routes of efficient exposure and virus shedding should be well studied. The contribution of primary cases to the so-called hospital-acquired cases in the recent upsurge of detected cases in the Arabian Peninsula is still unclear, and further epidemiologic data and analyses are necessary. In 1 analysis, 60 of 95 (63.2%) cases with evidence of secondary transmission acquired the infection in the hospital environment; nevertheless, 49 of them had additionally reported exposure to animals, therefore not eliminating an alternative source of infection.<xref rid="bib21" ref-type="bibr"><sup>21</sup></xref></p><p id="p0110">The stability of the proportion of asymptomatic versus symptomatic cases is an argument against increasing testing as a possible explanation for either primary or secondary cases.<xref rid="bib10" ref-type="bibr"><sup>10</sup></xref> On the other hand, a reverse scenario could be that additional cases are missed because cases at the early incubation period or with low viral loads may be missed with molecular testing. A transmission event under similar circumstances has been described in the community for the first imported MERS-CoV case in the United States that tested negative by molecular assays but subsequently tested positive by serology.<xref rid="bib25" ref-type="bibr">25</xref>, <xref rid="bib40" ref-type="bibr">40</xref></p><sec id="sec2.1"><title>Research for the future</title><p id="p0115">Active surveillance and testing are of outmost importance to provide answers about the epidemiology of MERS-CoV and evolution of the current epidemic. Case-control, serologic studies in exposed HCWs are needed to better define the effectiveness of infection control measures. Transmission of the virus via asymptomatic shedding in feces or other routes (eg, fomites, environment) is another topic for investigation. Studies of viral kinetics in affected patients with molecular analyses of samples from various body sites will provide answers for infection control as well. A vaccine against MERS-CoV should be developed along with specific antiviral agents.</p></sec></sec><sec id="sec3"><title>Conclusions</title><p id="p0120">There is no doubt that MERS-CoV remains a serious threat and has exhibited a significant public health impact in the affected countries. Currently, health care–associated transmission plays a pivotal role in the evolution of the MERS-CoV epidemic in countries in the Arabian Peninsula. A significant cost has been encountered in terms of personnel and time required for contact tracing and means of implementing infection control and prevention measures in health care settings. So far, there is no evidence of sustained human-to-human transmission. However, significant concerns exist in terms of the increased number of health care–associated cases, gaps in knowledge regarding transmission routes, and limited infection control capacity in affected countries. As the MERS-CoV epidemic continues to evolve, vaccine and specific antiviral agents against MERS-CoV are urgently needed. 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Accessed May 17, 2014.</mixed-citation></ref></ref-list><fn-group><fn id="d32e738"><p id="ntpara0010">The opinions presented in this article are those of the authors and do not necessarily represent those of their institutions.</p></fn><fn id="d32e741"><p id="ntpara0015">Conflicts of interest: None to report.</p></fn></fn-group></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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