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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">MERS: Progress on the global response, remaining challenges and the way forward</title></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">30236531</idno><idno type="pmc">7113883</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113883</idno><idno type="RBID">PMC:7113883</idno><idno type="doi">10.1016/j.antiviral.2018.09.002</idno><date when="2018">2018</date><idno type="wicri:Area/Pmc/Corpus">001289</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001289</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">MERS: Progress on the global response, remaining challenges and the way forward</title></analytic><series><title level="j">Antiviral Research</title><idno type="ISSN">0166-3542</idno><idno type="eISSN">1872-9096</idno><imprint><date when="2018">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>This article summarizes progress in research on Middle East Respiratory Syndrome (MERS) since a FAO-OIE-WHO Global Technical Meeting held at WHO Headquarters in Geneva on 25–27 September 2017. The meeting reviewed the latest scientific findings and identified and prioritized the global activities necessary to prevent, manage and control the disease. Critical needs for research and technical guidance identified during the meeting have been used to update the WHO R&D MERS-CoV Roadmap for diagnostics, therapeutics and vaccines and a broader public health research agenda. Since the 2017 meeting, progress has been made on several key actions in animal populations, at the animal/human interface and in human populations. This report also summarizes the latest scientific studies on MERS since 2017, including data from more than 50 research studies examining the presence of MERS-CoV infection in dromedary camels.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Abdulaziz, A B S" uniqKey="Abdulaziz A">A.B.S. Abdulaziz</name></author><author><name sortKey="Glen, R A" uniqKey="Glen R">R.A. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Antiviral Res</journal-id><journal-id journal-id-type="iso-abbrev">Antiviral Res</journal-id><journal-title-group><journal-title>Antiviral Research</journal-title></journal-title-group><issn pub-type="ppub">0166-3542</issn><issn pub-type="epub">1872-9096</issn><publisher><publisher-name>The Author. Published by Elsevier B.V.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">30236531</article-id><article-id pub-id-type="pmc">7113883</article-id><article-id pub-id-type="publisher-id">S0166-3542(18)30530-8</article-id><article-id pub-id-type="doi">10.1016/j.antiviral.2018.09.002</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>MERS: Progress on the global response, remaining challenges and the way forward</article-title></title-group><contrib-group><contrib contrib-type="author"><collab>FAO-OIE-WHO MERS Technical Working Group<contrib-group><contrib contrib-type="author" id="au1"><name><surname>Aguanno</surname><given-names>Ryan</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au2"><name><surname>ElIdrissi</surname><given-names>Ahmed</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au3"><name><surname>Elkholy</surname><given-names>Amgad A.</given-names></name><xref rid="aff2" ref-type="aff">b</xref></contrib><contrib contrib-type="author" id="au4"><name><surname>Ben Embarek</surname><given-names>Peter</given-names></name><xref rid="aff2" ref-type="aff">b</xref></contrib><contrib contrib-type="author" id="au5"><name><surname>Gardner</surname><given-names>Emma</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au6"><name><surname>Grant</surname><given-names>Rebecca</given-names></name><xref rid="aff3" ref-type="aff">c</xref></contrib><contrib contrib-type="author" id="au7"><name><surname>Mahrous</surname><given-names>Heba</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au8"><name><surname>Malik</surname><given-names>Mamunur Rahman</given-names></name><xref rid="aff2" ref-type="aff">b</xref></contrib><contrib contrib-type="author" id="au9"><name><surname>Pavade</surname><given-names>Gounalan</given-names></name><xref rid="aff4" ref-type="aff">d</xref></contrib><contrib contrib-type="author" id="au10"><name><surname>VonDobschuetz</surname><given-names>Sophie</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au11"><name><surname>Wiersma</surname><given-names>Lidewij</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au12"><name><surname>Van Kerkhove</surname><given-names>Maria D.</given-names></name><email>vankerkhovem@who.int</email><xref rid="aff2" ref-type="aff">b</xref></contrib></contrib-group><aff id="aff1"><label>a</label>Food and Agriculture Organization of the United Nations, Italy</aff><aff id="aff2"><label>b</label>Health Emergencies Programme, World Health Organization, Switzerland</aff><aff id="aff3"><label>c</label>Center for Global Health, Institut Pasteur, France</aff><aff id="aff4"><label>d</label>World Organization for Animal Health, France</aff></collab><xref rid="cor1" ref-type="corresp">∗</xref></contrib></contrib-group><author-notes><corresp id="cor1"><label>∗</label>Corresponding author. MERS-CoV Technical Lead, High Threat Pathogens, Global Infectious Hazards Management, Health Emergencies Program, World Health Organization, Geneva Switzerland.</corresp></author-notes><pub-date pub-type="pmc-release"><day>17</day><month>9</month><year>2018</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub"><month>11</month><year>2018</year></pub-date><pub-date pub-type="epub"><day>17</day><month>9</month><year>2018</year></pub-date><volume>159</volume><fpage>35</fpage><lpage>44</lpage><history><date date-type="received"><day>30</day><month>8</month><year>2018</year></date><date date-type="accepted"><day>4</day><month>9</month><year>2018</year></date></history><permissions><copyright-statement>© 2018 The Author. Published by Elsevier B.V.</copyright-statement><copyright-year>2018</copyright-year><copyright-holder></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"><p>This article summarizes progress in research on Middle East Respiratory Syndrome (MERS) since a FAO-OIE-WHO Global Technical Meeting held at WHO Headquarters in Geneva on 25–27 September 2017. The meeting reviewed the latest scientific findings and identified and prioritized the global activities necessary to prevent, manage and control the disease. Critical needs for research and technical guidance identified during the meeting have been used to update the WHO R&D MERS-CoV Roadmap for diagnostics, therapeutics and vaccines and a broader public health research agenda. Since the 2017 meeting, progress has been made on several key actions in animal populations, at the animal/human interface and in human populations. This report also summarizes the latest scientific studies on MERS since 2017, including data from more than 50 research studies examining the presence of MERS-CoV infection in dromedary camels.</p></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">A global technical meeting on MERS was held in Geneva in September, 2017, organized by WHO, FAO and OIE.</p></list-item><list-item id="u0015"><label>•</label><p id="p0015">This report summarizes the latest scientific literature and progress in research on MERS since that meeting.</p></list-item><list-item id="u0020"><label>•</label><p id="p0020">It includes a summary of more than 50 field studies examining the presence of MERS-CoV infection in dromedary camels.</p></list-item><list-item id="u0025"><label>•</label><p id="p0025">Zoonotic transmission of MERS requires a One Health approach is necessary to prevent, detect, and respond to the disease.</p></list-item><list-item id="u0030"><label>•</label><p id="p0030">The critical needs identified in this report inform the WHO R&D MERS Roadmap and a broader public health research agenda.</p></list-item></list></p></abstract><kwd-group id="kwrds0010"><title>Keywords</title><kwd>MERS-CoV</kwd><kwd>Research</kwd><kwd>Animal-human interface</kwd><kwd>Dromedary camels</kwd><kwd>Zoonosis</kwd><kwd>Vaccine</kwd></kwd-group></article-meta></front><body><sec id="sec1"><label>1</label><title>Background: Middle East Respiratory Syndrome</title><p id="p0035">Since its identification in the Kingdom of Saudi Arabia (KSA) (<xref rid="bib135" ref-type="bibr">Zaki et al., 2012</xref>) and Jordan (<xref rid="bib57" ref-type="bibr">Hijawi et al., 2013</xref>) in 2012, Middle East Respiratory Syndrome (MERS) has become a global public health threat. Typical of an emerging zoonosis, Middle East respiratory syndrome coronavirus (MERS-CoV) has an animal reservoir, i.e. dromedary camels in which the virus causes little to no disease (<xref rid="bib81" ref-type="bibr">Mohd et al., 2016</xref>). Many details about the extent of circulation and the mechanisms of transmission within dromedary camel herds, or factors related to zoonotic transmission and differences in circulating MERS-CoV strains, remain unknown. The virus has repeatedly spilled over from dromedary camels to humans, principally in countries on the Arabian Peninsula, causing significant morbidity and mortality (<xref rid="bib129" ref-type="bibr">World Health Organization, 2017a</xref>; <xref rid="bib27" ref-type="bibr">Azhar et al., 2014</xref>). Clusters of cases in the community and among family members are rare (<xref rid="bib129" ref-type="bibr">World Health Organization, 2017a</xref>; <xref rid="bib43" ref-type="bibr">Drosten et al., 2014</xref>). However, delays in diagnosis in hospitals has sometimes led to secondary cases among health care workers, patients sharing rooms or family members as a result of unprotected direct contact with a patient before isolation. This human-to-human transmission in health care facilities can sometimes be amplified, causing very large outbreaks, as has been seen in the Middle East and in the Republic of Korea, with significant public health and economic impacts (<xref rid="bib57" ref-type="bibr">Hijawi et al., 2013</xref>; <xref rid="bib25" ref-type="bibr">Assiri et al., 2013</xref>; <xref rid="bib5" ref-type="bibr">Al-Abdallat et al., 2014</xref>; <xref rid="bib44" ref-type="bibr">Drosten et al., 2015</xref>; <xref rid="bib4" ref-type="bibr">Al Hosani et al., 2016</xref>; <xref rid="bib62" ref-type="bibr">Ki, 2015</xref>; <xref rid="bib97" ref-type="bibr">Park et al., 2015</xref>). As of August 2018, more than 2249 human cases from 27 countries have been reported to the <xref rid="bib126" ref-type="bibr">World Health Organization</xref> (WHO) (<xref rid="bib129" ref-type="bibr">World Health Organization, 2017a</xref>).</p><p id="p0040">The FAO, OIE and WHO Tripartite have regularly brought together affected member states, public health and animal officials, and academics to discuss what is known and unknown about the zoonotic origin of MERS-CoV (<xref rid="bib128" ref-type="bibr">World Health Organization, 2016</xref>; <xref rid="bib48" ref-type="bibr">FAO, 2016</xref>, <xref rid="bib89" ref-type="bibr">2014</xref>; <xref rid="bib120" ref-type="bibr">WHO Regional office for the Eastern Mediterranean, 2013a</xref>). The purposes of these meetings and workshops have been to advocate for more surveillance and research on MERS-CoV in animals and humans, to share information about how MERS-CoV is transmitted between animals, from animals to humans and between humans, to describe the diseases it causes, and to develop policies and guidelines for detection, reporting of animal and human infections, and prevention of human cases and clusters.</p><p id="p0045">In the two years since the last international technical consultation on MERS-CoV in 2016 <sup>13</sup>, there have been notable improvements in surveillance and reporting of human cases, multidisciplinary research, cross-sectoral collaboration at country level, public awareness about the disease, and laboratory and surveillance capacity in affected countries. In addition, a number of countries in the Arabian Peninsula and in Africa have engaged in research activities and surveillance of camel populations to shed light on the wider distribution of this virus or investigate transmission patterns and routes for viral shedding. As a follow-up to previous meetings (<xref rid="bib128" ref-type="bibr">World Health Organization, 2016</xref>; <xref rid="bib48" ref-type="bibr">FAO, 2016</xref>, <xref rid="bib89" ref-type="bibr">2014</xref>; <xref rid="bib123" ref-type="bibr">WHO Regional office for the Eastern Mediterranean, 2014</xref>; <xref rid="bib121" ref-type="bibr">WHO Regional office for the Eastern Mediterranean, 2013b</xref>, <xref rid="bib122" ref-type="bibr">2013c</xref>), FAO, OIE and WHO Tripartite held a Global Technical Meeting on MERS-CoV with representatives from Ministries of Health and Ministries of Agriculture, subject matter experts, researchers, funders and industrial partners from 25 to 27 September 2017 in Geneva, Switzerland (see <xref rid="appsec1" ref-type="sec">Supplementary Information</xref>) (<xref rid="bib132" ref-type="bibr">World Health Organization et al., 2017</xref>). The objectives were to review the latest scientific evidence on MERS-CoV, further enhance cross-sectoral collaboration and communication during preparedness and response activities, and identify research priorities given the advancements in our knowledge.</p><p id="p0050">With 130 participants, this was the largest MERS-CoV Technical Meeting to date and the first meeting attended by representatives from both affected and at risk countries. That is, countries which have reported human infection, countries with evidence of MERS-CoV in dromedary camels but no reported human cases, and countries at risk for importation (countries without infected camels that have close ties to affected countries through expatriate workers, travel to affected countries for medical procedures and/or frequent international travel).</p></sec><sec id="sec2"><label>2</label><title>Findings from the global technical meeting</title><p id="p0055">There is strong consensus among all stakeholders that dromedary camels are the main source of transmission to humans. In 2014, OIE identified MERS-CoV as an emerging disease with zoonotic potential in camels and thereby creating expectations of reporting positive camels by countries (<xref rid="bib91" ref-type="bibr">OIE, 2014a</xref>) and recently published a MERS-CoV case definition (<xref rid="bib93" ref-type="bibr">OIE, 2017</xref>) for the reporting of confirmed and suspected infection in camels.</p><p id="p0060">Not all countries face the same risks. For example, countries that have the infected reservoir (dromedary camels) differ from those countries in which dromedary camels show no evidence of current or past infection (<xref rid="fig1" ref-type="fig">Fig. 1</xref>). There may also be differences in spillover potential in countries with documented zoonotic transmission, compared to those without, due to several factors including potential differences in husbandry practices, cultural, social, medicinal, occupational exposures, prevalence of underlying chronic medical conditions, or genetic factors in human populations, and MERS-CoV viral differences (<xref rid="bib125" ref-type="bibr">Wong et al., 2015</xref>). As such, technical and risk mitigation guidance to protect human health and research priorities differ by region.<fig id="fig1"><label>Fig. 1</label><caption><p>MERS-CoV transmission and geographic range. Countries highlighted in red and orange indicate the geographic range of MERS-CoV in dromedary camels. Those in red have had documented spillover (camel-to-human) transmission with subsequent human-to-human transmission. Countries in blue are those with reported human-to-human transmission. (Source: WHO). (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)</p></caption><alt-text id="alttext0015">Fig. 1</alt-text><graphic xlink:href="gr1_lrg"></graphic></fig></p><p id="p0065">The findings from the Global Technical Meeting are summarized below:<list list-type="simple" id="olist0010"><list-item id="o0010"><label>i.</label><p id="p0070">Surveillance needs: Surveillance in animals and humans to limit zoonotic transmission</p></list-item></list></p><p id="p0075">Routine human surveillance for MERS-CoV in KSA (<xref rid="bib1" ref-type="bibr">Abdulaziz et al., 2017</xref>) and throughout the Middle East has improved since the identification of the virus in humans in 2012, but there is significant variation in the quality and extent of surveillance between countries. In other parts of the world, surveillance is limited. Since it is known that MERS-CoV is enzootic in areas of Africa and Asia where dromedary camels are found, heighted awareness and surveillance for zoonotic MERS is required. This is currently lacking and remains a knowledge gap.</p><p id="p0080">One exception is the notable effort to identify potential MERS-CoV infection among pilgrims travelling back from the Middle East. Since 2012, event-based surveillance among pilgrims returning from Hajj, Umrah and other religious events in KSA has been conducted by KSA and countries sending pilgrims. While many return reporting respiratory symptoms, no MERS-CoV infections have been identified among returning pilgrims (<xref rid="bib86" ref-type="bibr">Muraduzzaman et al., 2018</xref>; <xref rid="bib29" ref-type="bibr">Barasheed et al., 2014</xref>; <xref rid="bib26" ref-type="bibr">Atabani et al., 2016</xref>; <xref rid="bib66" ref-type="bibr">Koul et al., 2017</xref>; <xref rid="bib19" ref-type="bibr">Annan et al., 2015</xref>; <xref rid="bib69" ref-type="bibr">Ma et al., 2017</xref>; <xref rid="bib73" ref-type="bibr">Memish et al., 2014a</xref>, <xref rid="bib74" ref-type="bibr">2014b</xref>; <xref rid="bib101" ref-type="bibr">Refaey et al., 2017</xref>; <xref rid="bib6" ref-type="bibr">Al-Abdallat et al., 2017</xref>; <xref rid="bib72" ref-type="bibr">Matthew et al., 2015</xref>; <xref rid="bib17" ref-type="bibr">Alqahtani et al., 2016</xref>; <xref rid="bib124" ref-type="bibr">Win et al., 2016</xref>; <xref rid="bib133" ref-type="bibr">Yavarian et al., 2018</xref>; <xref rid="bib60" ref-type="bibr">Kapoor et al., 2014</xref>).</p><p id="p0085">Among animals, field surveys conducted to date have included several domestic and wildlife species including dromedary camels (<italic>Camelus dromedarius</italic>) and Bactrian camels (<italic>Camelus bactrianus</italic>), goats, bats, cattle, sheep, chickens, swine, ducks, buffalo and equids. Field studies in dromedary camels have been conducted in a number of countries (<xref rid="tbl1" ref-type="table">Table 1</xref>). To date, MERS-CoV RNA or MERS-CoV-specific antibodies have been identified in dromedary camels a number of countries (<xref rid="tbl1" ref-type="table">Table 1</xref>) except Australia (<xref rid="bib55" ref-type="bibr">Hemida et al., 2014</xref>), Kazakhstan (<xref rid="bib77" ref-type="bibr">Miguel et al., 2016</xref>), and the Netherlands (<xref rid="bib102" ref-type="bibr">Reusken et al., 2013a</xref>). Other livestock such as alpacas (<italic>Vicugna pacos</italic>), llamas (<italic>Llama pacos</italic>), young goats, rabbits and pigs have been shown to be susceptible to experimental infection (<xref rid="bib40" ref-type="bibr">Crameri et al., 2016</xref>; <xref rid="bib2" ref-type="bibr">Adney et al., 2016</xref>; <xref rid="bib118" ref-type="bibr">Vergara-Alert et al., 2017</xref>).<table-wrap position="float" id="tbl1"><label>Table 1</label><caption><p>Field studies of evidence of MERS-CoV infection in dromedary camels. ppNT: pseudoparticle neutralization; MN: microneutralization; CI: confidence interval; VNT: virus neutralizing antibodies test.</p></caption><alt-text id="alttext0020">Table 1</alt-text><table frame="hsides" rules="groups"><thead><tr><th>Country</th><th>Number of camels</th><th>Evidence of MERS-CoV infection</th></tr></thead><tbody><tr><td align="left">Australia</td><td align="left">25</td><td align="left">No evidence for MERS-CoV infection in dromedary camels (<xref rid="bib55" ref-type="bibr">Hemida et al., 2014</xref>)</td></tr><tr><td align="left">Bangladesh</td><td align="left">55</td><td align="left">17 (31%) samples were seropositive (<xref rid="bib24" ref-type="bibr">Ariful et al., 2018</xref>)</td></tr><tr><td align="left">Burkina Faso</td><td align="left">525</td><td align="left">Seropositivity rates ranged from 73.2% (95% CI): 48.6–88.8) to 84.6% (95% CI: 77.2–89.9) and virus detection from 0% (95% CI: 0–0) to 12.2% (95%CI: 7–20.4) (<xref rid="bib78" ref-type="bibr">Miguel et al., 2017</xref>)</td></tr><tr><td rowspan="5" align="left">Egypt</td><td align="left">2825</td><td align="left">Of 2825 nasal swabs, RNA detection rate was 15% by RT-PCR. Of 2541 sera samples, the overall seroprevalence was 71%. (<xref rid="bib16" ref-type="bibr">Ali et al., 2017</xref>)</td></tr><tr><td align="left">1078</td><td align="left">Of 1031 serological tests, 871 (84.5%) had MERS-CoV neutralizing antibodies. Of 1078 nasal samples, 41 (3.8%) were positive for MERS-CoV using MERS-CoV PCR (<xref rid="bib15" ref-type="bibr">Ali et al., 2015</xref>)</td></tr><tr><td align="left">110</td><td align="left">4 (3.6%) nasal swab specimens tested positive for presence of MERS-CoV RNA. Antibodies against MERS-CoV were detected in 48 (92.3%) of 52 serum samples (ref 48) (<xref rid="bib34" ref-type="bibr">Chu et al., 2014</xref>)</td></tr><tr><td align="left">110</td><td align="left">103 (93.6%) sera collected neutralized MERS-CoV using ppNT (<xref rid="bib99" ref-type="bibr">Perera et al., 2013b</xref>)</td></tr><tr><td align="left">43</td><td align="left">34 (79.1%) dromedary camels were positive for MERS-CoV antibodies using MN (<xref rid="bib85" ref-type="bibr">Muller MA et al., 2014</xref>)</td></tr><tr><td align="left">Ethiopia</td><td align="left">632</td><td align="left">Seropositivity rates ranged from 85.1% (95% CI: 71.8–92.7) to 99.4% (95% CI: 95.4–99.9) and the viral RNA detection rates from 0% (95% CI: 0–0) to 15.7% (95% CI: 8.2–28.0)<sup>95</sup></td></tr><tr><td></td><td align="left">188</td><td align="left">Seropositivity was 93% in adult dromedary camels and 97% for juvenile dromedary camels (<xref rid="bib32" ref-type="bibr">Chantal et al., 2014</xref>)</td></tr><tr><td align="left">Iran</td><td align="left">186</td><td align="left">8 (4.3%) samples positive using RT-PCR (<xref rid="bib92" ref-type="bibr">OIE, 2014b</xref>)</td></tr><tr><td rowspan="2" align="left">Israel</td><td align="left">411</td><td align="left">254 (61.8%) were positive for MERS-CoV antibodies using VNT; All nasal samples were negative for the presence of MERS-CoV RNA (<xref rid="bib41" ref-type="bibr">David et al., 2018</xref>)</td></tr><tr><td align="left">71</td><td align="left">51 (71.8%) sera samples had MERS-CoV neutralizing antibodies (<xref rid="bib52" ref-type="bibr">Harcourt et al., 2018</xref>)</td></tr><tr><td rowspan="2" align="left">Jordan</td><td align="left">11</td><td align="left">Neutralizing antibodies to MERS-CoV were found in all sera from dromedary camels (<xref rid="bib104" ref-type="bibr">Reusken et al., 2013c</xref>)</td></tr><tr><td align="left">45</td><td align="left">42 nasal swabs tested positive for the presence of MERS-CoV nucleic acid (<xref rid="bib117" ref-type="bibr">van Doremalen et al., 2017</xref>)</td></tr><tr><td align="left">Kazakhstan</td><td align="left">455</td><td align="left">No evidence for MERS-CoV infection in dromedary camels (<xref rid="bib77" ref-type="bibr">Miguel et al., 2016</xref>)</td></tr><tr><td rowspan="2" align="left">Kenya</td><td align="left">774</td><td align="left">228 (29.5%) were positive using rELISA test (<xref rid="bib39" ref-type="bibr">Corman et al., 2014</xref>)</td></tr><tr><td align="left">335</td><td align="left">Seroprevalence of MERS-CoV antibodies in the sampled population was 46.9% (95% CI 41.4–52.5) (<xref rid="bib42" ref-type="bibr">Deem et al., 2015</xref>)</td></tr><tr><td rowspan="9" align="left">Kingdom of Saudi Arabia (<xref rid="bib27" ref-type="bibr">Azhar et al., 2014</xref>; <xref rid="bib54" ref-type="bibr">Hemida et al., 2013</xref>, <xref rid="bib55" ref-type="bibr">2014</xref>, <xref rid="bib56" ref-type="bibr">2017</xref>; <xref rid="bib12" ref-type="bibr">Alagaili et al., 2014</xref>; <xref rid="bib31" ref-type="bibr">Briese et al., 2014</xref>; <xref rid="bib70" ref-type="bibr">Maged et al., 2014</xref>, <xref rid="bib71" ref-type="bibr">2015</xref>; <xref rid="bib61" ref-type="bibr">Kasem et al., 2017</xref>; <xref rid="bib136" ref-type="bibr">Ziad et al., 2014</xref>)</td><td align="left">203</td><td align="left">150 (74%) sampled were found to have antibodies to MERS-CoV by ELISA (<xref rid="bib12" ref-type="bibr">Alagaili et al., 2014</xref>)</td></tr><tr><td align="left">1309</td><td align="left">158 (12.1%) nasal swabs were positive for MERS-CoV (<xref rid="bib107" ref-type="bibr">Sabir et al., 2016</xref>)</td></tr><tr><td align="left">698</td><td align="left">The overall prevalence of MERS infection in camels in animal markets and slaughterhouses by rtRT-PCR was 56.4%</td></tr><tr><td align="left">99</td><td align="left">High levels of seropositivity in two herds demonstrated – in on herd, all samples had MERS-CoV antibodies (<xref rid="bib56" ref-type="bibr">Hemida et al., 2017</xref>)</td></tr><tr><td align="left">310</td><td align="left">280 (90.3%) samples were positive using ppNT (<xref rid="bib54" ref-type="bibr">Hemida et al., 2013</xref>)</td></tr><tr><td align="left">171</td><td align="left">144 (84.2%) sera samples had specific antibodies against MERS-CoV (<xref rid="bib53" ref-type="bibr">Harrath and Abu Duhier, 2018</xref>)</td></tr><tr><td align="left">9</td><td align="left">2 (22.2%) nasal samples were positive using RT-PCR (<xref rid="bib136" ref-type="bibr">Ziad et al., 2014</xref>)</td></tr><tr><td align="left">9</td><td align="left">1 (11.1%) nasal samples were negative for MERS-CoV RNA. All serum samples had high titers of MER-CoV antibodies (<xref rid="bib27" ref-type="bibr">Azhar et al., 2014</xref>)</td></tr><tr><td align="left">131 archived sera</td><td align="left">118 (90.1%) had detectable ppNT antibody titres to MERS-CoV (<xref rid="bib55" ref-type="bibr">Hemida et al., 2014</xref>)</td></tr><tr><td align="left">Kuwait</td><td align="left">63</td><td align="left">5 (7.9%) nasal samples were positive using RT-PCR (<xref rid="bib119" ref-type="bibr">WAHIS Interface, 2014</xref>)</td></tr><tr><td align="left">Mali</td><td align="left">570</td><td align="left">502 (88.1%) were positive for antibodies against MERS-CoV (<xref rid="bib46" ref-type="bibr">Falzarano et al., 2017</xref>)</td></tr><tr><td align="left">Morocco</td><td align="left">343</td><td align="left">Seropositivity rates ranged from 48.3% (95% CI: 18.3–79.5) to 100% (95% CI:100-100) and viral RNA detection rates from 0% (95% CI: 0–0) to 7.6% (95% CI: 1.9–26.1)<sup>95</sup></td></tr><tr><td rowspan="2" align="left">Nigeria</td><td align="left">358</td><td align="left">Seropositivity was 94% in adult dromedary camels and 93% for juvenile dromedary camels (<xref rid="bib32" ref-type="bibr">Chantal et al., 2014</xref>; <xref rid="bib35" ref-type="bibr">Chu et al., 2015</xref>)</td></tr><tr><td align="left">132</td><td align="left">14 (11%) nasal swabs were positive using RT-qPCR (<xref rid="bib32" ref-type="bibr">Chantal et al., 2014</xref>; <xref rid="bib35" ref-type="bibr">Chu et al., 2015</xref>)</td></tr><tr><td></td><td align="left">2529</td><td align="left">MERS-CoV RNA was detected in 4/38 (10.5%) of camels aged < 2 years, in 31/1400 (2.2%) aged 2–4 years and in 20/1091 (1.8%) aged > 4 years (<xref rid="bib110" ref-type="bibr">So et al., 2018</xref>)</td></tr><tr><td rowspan="2" align="left">Oman</td><td align="left">76</td><td align="left">5 (6.6%) proved positive in all applied RT-qPCR and RT-PCR assays. (<xref rid="bib88" ref-type="bibr">Nowotny and Kolodziejek, 2014</xref>)</td></tr><tr><td align="left">50</td><td align="left">50 (100%) had protein-specific antibodies against MERS-CoV (<xref rid="bib105" ref-type="bibr">Reusken et al., 2013d</xref>)</td></tr><tr><td align="left">Pakistan</td><td align="left">565</td><td align="left">315 (55.8%) samples exceeded the ELISA signal cutoff. Of these, 223 (39.5%) were confirmed using MN (<xref rid="bib108" ref-type="bibr">Saqib et al., 2017</xref>)</td></tr><tr><td rowspan="5" align="left">Qatar</td><td align="left">14</td><td align="left">3 (21.4%) nasal samples were positive using RT-PCR (<xref rid="bib50" ref-type="bibr">Haagmans et al., 2014</xref>)</td></tr><tr><td align="left">105</td><td align="left">62 (59.0%) camels showed evidence for virus shedding in at least one type of swab at the time of slaughter (<xref rid="bib49" ref-type="bibr">Farag et al., 2015</xref>)<break></break>Antibodies to MERS-CoV S1 were found in 100 of 103 (97.1%) dromedary camels tested by micro-array technology (<xref rid="bib49" ref-type="bibr">Farag et al., 2015</xref>)</td></tr><tr><td align="left">53</td><td align="left">1 (1.9%) nasal swab had full viral genome isolated (<xref rid="bib100" ref-type="bibr">Raj et al., 2014</xref>)</td></tr><tr><td align="left">33</td><td align="left">7 (21.1%) showed evidence for active virus shedding and 5 (15.2%) had viral RNA in camel milk (<xref rid="bib106" ref-type="bibr">Reusken et al., 2014</xref>)</td></tr><tr><td align="left">10</td><td align="left">9 (90%) sera samples had MERS-CoV–specific antibodies. All nasal swab specimens were negative by PCR (<xref rid="bib33" ref-type="bibr">Chantal et al., 2016</xref>)</td></tr><tr><td align="left">Spain (Canary Islands)</td><td align="left">105</td><td align="left">15 (14%) had protein-specific antibodies against MERS-CoV (<xref rid="bib105" ref-type="bibr">Reusken et al., 2013d</xref>)</td></tr><tr><td align="left">Somalia</td><td align="left">86</td><td align="left">25 (87.5%) dromedary camels were positive for MERS-CoV antibodies using MN (<xref rid="bib85" ref-type="bibr">Muller MA et al., 2014</xref>)</td></tr><tr><td align="left">Sudan</td><td align="left">60</td><td align="left">49 (81.7%) dromedary camels were positive for MERS-CoV antibodies using MN (<xref rid="bib85" ref-type="bibr">Muller MA et al., 2014</xref>)</td></tr><tr><td align="left">Tunisia</td><td align="left">204</td><td align="left">Seropositivity was 30% for animals ≤2 years of age and 54% for adult dromedary camels (<xref rid="bib32" ref-type="bibr">Chantal et al., 2014</xref>)</td></tr><tr><td rowspan="7" align="left">UAE</td><td align="left">1113</td><td align="left">42 (3.7%) nasal swabs yielded positive results (<xref rid="bib83" ref-type="bibr">Muhairi et al., 2016</xref>)</td></tr><tr><td align="left">843</td><td align="left">786 (93.2%) sera samples were positive for antibodies against MERS-CoV (<xref rid="bib112" ref-type="bibr">Sung Sup et al., 2015</xref>)</td></tr><tr><td align="left">11</td><td align="left">9 (81.8%) sera samples were positive for antibodies supported by similar results in a MERS-CoV recombinant partial spike protein antibody ELISA (<xref rid="bib13" ref-type="bibr">Alexandersen et al., 2014</xref>)</td></tr><tr><td align="left">651</td><td align="left">632 (97.1%) had antibodies against MERS-CoV (<xref rid="bib76" ref-type="bibr">Meyer et al., 2014</xref>)</td></tr><tr><td align="left">376</td><td align="left">108 (28.7%) nasopharyngeal samples positive for MERS-CoV (<xref rid="bib67" ref-type="bibr">Li et al., 2017</xref>)</td></tr><tr><td align="left">254</td><td align="left">234 (92.1%) sera samples were positive for MERS-CoV IgG (<xref rid="bib112" ref-type="bibr">Sung Sup et al., 2015</xref>)</td></tr><tr><td align="left">6</td><td align="left">6 (100%) nasopharyngeal swabs tested positive for MERS-CoV (<xref rid="bib96" ref-type="bibr">Paden et al., 2018</xref>)</td></tr></tbody></table></table-wrap></p><p id="p0090">Despite improvements, routine surveillance in dromedary populations is limited. The lack of surveillance information about MERS-CoV circulation in dromedary camels restricts our understanding of the transmission dynamics and epidemiology in dromedary camel populations. Meeting participants agreed that surveillance should be integrated into existing surveillance systems, particularly in at-risk countries, similar to One Health approaches developed for avian influenza, and existing human respiratory disease surveillance systems set up for influenza-like illness (ILI) or severe acute respiratory infections (SARI).</p><p id="p0095">Currently, a limitation in our ability to mitigate spillover from dromedary camels to humans is a lack of clarity on the mode(s) of transmission between dromedary camels and humans, the extent and epidemiology of MERS-CoV circulation in dromedary camels in large parts of Africa and South Asia, and on why zoonotic transmission is limited across Africa, large parts of the Middle East, and some parts of South Asia despite high seroprevalence in dromedary camels (<xref rid="bib36" ref-type="bibr">Chu et al., 2018</xref>) (<xref rid="tbl1" ref-type="table">Table 1</xref>).</p><p id="p0100">FAO has outlined the meeting participants conclusions on priorities for MERS-CoV surveillance and management of PCR positive dromedary camels, coordinated outbreak investigation of community acquired cases with dromedary exposure, testing of animals at quarantine and entry points, food safety and environmental contamination, risk communication and awareness raising for MERS-CoV among animal owners and intersectoral collaboration and coordination in an updated Doha Declaration first published in 2015 (<xref rid="bib47" ref-type="bibr">FAO, 2015</xref>) (REF/hyperlink). In dromedary camels, longitudinal studies to evaluate the natural history, shedding profile and immunity were highlighted as key research priorities. Meeting participants agreed that further understanding of differences in viral strains and transmission dynamics, including the role of immunity in acquiring infection and shedding virus, the geographic range of spillover events, and environmental, behavioral or host-related risk factors for zoonotic transmission should be prioritized.<list list-type="simple" id="olist0015"><list-item id="o0015"><label>ii.</label><p id="p0105">Research needs: Hospital transmission and infection prevention and control</p></list-item></list></p><p id="p0110">Countries face significant challenges in the early identification and diagnosis of MERS in humans due to the non-specificity of clinical symptoms (<xref rid="bib20" ref-type="bibr">Arabi et al., 2017a</xref>; <xref rid="bib113" ref-type="bibr">TheS-Coesearch, 2013</xref>; <xref rid="bib21" ref-type="bibr">Arabi et al., 2017b</xref>; <xref rid="bib11" ref-type="bibr">Al-Tawfiq et al., 2017</xref>; <xref rid="bib10" ref-type="bibr">Al-Tawfiq and Hinedi, 2018</xref>; <xref rid="bib58" ref-type="bibr">Hui et al.,</xref> ). The spectrum of illness ranges from no symptoms (or asymptomatic infection) to severe disease including pneumonia, acute respiratory disease syndrome, organ failure and death, with a case fatality ratio 35.5% among reported cases (<xref rid="bib127" ref-type="bibr">World Health Organization, 2012</xref>). The delay in identification and recognition of signs and symptoms compatible with MERS and delay in early isolation of patients has reduced the ability to prevent transmission between people in health care settings, notably in emergency departments, cardiac care centers and renal dialysis units (<xref rid="bib57" ref-type="bibr">Hijawi et al., 2013</xref>; <xref rid="bib25" ref-type="bibr">Assiri et al., 2013</xref>; <xref rid="bib5" ref-type="bibr">Al-Abdallat et al., 2014</xref>; <xref rid="bib44" ref-type="bibr">Drosten et al., 2015</xref>; <xref rid="bib4" ref-type="bibr">Al Hosani et al., 2016</xref>; <xref rid="bib62" ref-type="bibr">Ki, 2015</xref>; <xref rid="bib97" ref-type="bibr">Park et al., 2015</xref>; <xref rid="bib3" ref-type="bibr">Ahmed et al., 2018</xref>; <xref rid="bib18" ref-type="bibr">Amer et al., 2018</xref>).</p><p id="p0115">Our understanding of human-to-human transmission in health care settings has improved through experimental and observational studies conducted in countries during such outbreaks. For example, studies of respiratory pathogens (<xref rid="bib134" ref-type="bibr">Yu et al., 2007</xref>; <xref rid="bib115" ref-type="bibr">Tran et al., 2012</xref>; <xref rid="bib114" ref-type="bibr">Thompson et al., 2013</xref>) and MERS-CoV conducted in the Middle East (<xref rid="bib25" ref-type="bibr">Assiri et al., 2013</xref>; <xref rid="bib90" ref-type="bibr">Oboho et al., 2015</xref>; <xref rid="bib59" ref-type="bibr">Hunter et al., 2016</xref>; <xref rid="bib28" ref-type="bibr">Balkhy et al., 2016</xref>) and the Republic of Korea (<xref rid="bib30" ref-type="bibr">Bin et al., 2016</xref>; <xref rid="bib63" ref-type="bibr">Kim et al., 2016a</xref>, <xref rid="bib64" ref-type="bibr">2016b</xref>; <xref rid="bib87" ref-type="bibr">Nam et al., 2017</xref>) illustrate that aerosol-generating procedures and non-invasive ventilation, combined with inappropriate infection prevention and control practices and lack of adherence to standard practices had an important role in facilitating human-to-human transmission in health care settings. The role of environmental contamination has been evaluated in a number of hospitals following the 2015 outbreak in the Republic of Korea and collaborative, experimental studies are being conducted to evaluate the viability and persistence of MERS-CoV on surfaces and in the air (<xref rid="bib30" ref-type="bibr">Bin et al., 2016</xref>; <xref rid="bib63" ref-type="bibr">Kim et al., 2016a</xref>; <xref rid="bib116" ref-type="bibr">van Doremalen et al., 2013</xref>). The role of mild or asymptomatic cases in transmission chains, however, remains unclear (<xref rid="bib95" ref-type="bibr">Omrani et al., 2013</xref>; <xref rid="bib75" ref-type="bibr">Memish et al., 2014c</xref>; <xref rid="bib9" ref-type="bibr">Al-Gethamy et al., 2015</xref>; <xref rid="bib82" ref-type="bibr">Moon and Son, 2017</xref>; <xref rid="bib7" ref-type="bibr">Al-Abdely et al., 2018</xref>), warranting targeted epidemiological and clinical studies to be conducted among contacts during outbreaks, especially in health care facilities.</p><p id="p0120">Countries which have reported health care-associated outbreaks have implemented a variety of strategies to improve infection prevention and control and reduce human-to-human transmission in hospitals, including the introduction of a visual triage system prior to entrance to the emergency departments, the restructure of emergency department layouts for better triage of patients with respiratory symptoms, the standardization and training and re-training of infection prevention and control practices at facilities with high hospital staff turnover, and the auditing of health care facilities for adherence to infection prevention and control measures.<list list-type="simple" id="olist0020"><list-item id="o0020"><label>iii.</label><p id="p0125">Product research and development needs: Clinical management, diagnostics and medical interventions</p></list-item></list></p><p id="p0130">The WHO R&D Blueprint, a global strategy and preparedness plan that allows the rapid activation of R&D of epidemic pathogens, aims to fast-track the development and use of effective point-of-care diagnostic tests, vaccines and medicines that can be used to save lives and avert large scale crises. Since 2015, MERS-CoV has been included in the annual WHO R&D Blueprint list of prioritized pathogens for accelerated research and development on diagnostics, vaccines and therapeutics (<xref rid="bib126" ref-type="bibr">World Health Organization</xref>). In addition, MERS-CoV has a specific roadmap for product research and development, outlined by WHO in 2015 (<xref rid="bib80" ref-type="bibr">Modjarrad et al., 2016</xref>). Recent updates on product research and development, presented at the Global Technical Meeting, are below.</p><sec id="sec2.1"><label>2.1</label><title>Diagnostics</title><p id="p0135">The nonspecific, and sometimes unusual, clinical presentation of MERS in humans, makes early diagnosis difficult in health care facilities. While several highly specific and sensitive molecular and serologic assays exist for diagnosis in animals and humans (<xref rid="bib43" ref-type="bibr">Drosten et al., 2014</xref>; <xref rid="bib37" ref-type="bibr">Corman et al., 2012a</xref>, <xref rid="bib38" ref-type="bibr">2012b</xref>; <xref rid="bib68" ref-type="bibr">Lu et al., 2014</xref>; <xref rid="bib98" ref-type="bibr">Perera et al., 2013a</xref>; <xref rid="bib103" ref-type="bibr">Reusken et al., 2013b</xref>; <xref rid="bib84" ref-type="bibr">Müller et al., 2015</xref>; <xref rid="bib111" ref-type="bibr">Song et al., 2015</xref>), there was a clear call from representatives from affected countries for the development of a rapid diagnostic test to improve identification and isolation of primary human cases in health care facilities. A full landscape analysis of MERS-CoV diagnostics will be published separately (Van Kerkhove, personal communication).</p><sec id="sec2.1.1"><label>2.1.1</label><title>Therapeutics</title><p id="p0140">At the Global Technical Meeting, several therapeutics (including convalescent plasma, lopinavir/ritonavir, ribavirin, interferon and novel therapies including polyclonal antibodies and broad-spectrum antivirals) in development were presented. However, small case numbers make the evaluation of their impact on morbidity and mortality from MERS-CoV infection difficult (<xref rid="bib20" ref-type="bibr">Arabi et al., 2017a</xref>; <xref rid="bib21" ref-type="bibr">Arabi et al., 2017b</xref>; <xref rid="bib23" ref-type="bibr">Arabi et al.</xref>; <xref rid="bib8" ref-type="bibr">Al-Dorzi et al., 2016</xref>; <xref rid="bib109" ref-type="bibr">Sheahan et al., 2017</xref>; <xref rid="bib65" ref-type="bibr">Ko et al., 2018</xref>; <xref rid="bib22" ref-type="bibr">Arabi et al., 2017c</xref>). Several pre-clinical and phase I-III studies are under way or in the design phase (outlined by the WHO R&D Blueprint: <ext-link ext-link-type="uri" xlink:href="http://who-blueprint-mapping-tool.surge.sh/" id="intref0010">http://who-blueprint-mapping-tool.surge.sh/</ext-link>). WHO is currently evaluating all available evidence on therapeutics to update guidance on clinical management of patients and in the process to develop standardized clinical trial protocols that could be used in affected countries to evaluate promising therapeutic candidates.</p></sec></sec><sec id="sec2.2"><label>2.2</label><title>Vaccines for humans</title><p id="p0145">WHO has identified target product profiles for MERS-CoV vaccines which include a dromedary camel vaccine for the reduction of zoonotic transmission, a human vaccine for long term protection of high risk individuals, such as those working with infected dromedary camels or health care workers, and a human vaccine for reactive use in outbreak settings (<xref rid="bib130" ref-type="bibr">World Health Organization, 2017b</xref>).</p><p id="p0150">Currently, no MERS-CoV-specific or licensed human vaccines are available (<xref rid="bib80" ref-type="bibr">Modjarrad et al., 2016</xref>; <xref rid="bib131" ref-type="bibr">World Health Organization, 2017c</xref>). Several human vaccine candidates for coronaviruses, including MERS-CoV, are at various stages of development and five general vaccine technology platforms have been developed and target the MERS-CoV spike protein (<xref rid="bib80" ref-type="bibr">Modjarrad et al., 2016</xref>; <xref rid="bib94" ref-type="bibr">Okba et al., 2017</xref>). WHO, the Ministry of Health in KSA and the International Vaccine Institute (IVI) have continued to further align efforts to develop coronavirus vaccines (<xref rid="bib45" ref-type="bibr">Excler et al., 2016</xref>) and the Coalition for Epidemic Preparedness and Innovation (CEPI) has included MERS-CoV as one of three priority pathogens for financing of a human vaccine. Understanding correlates for protection and having a reliable animal model remain essential for evaluating coronavirus vaccine candidates, including MERS-CoV.</p></sec><sec id="sec2.3"><label>2.3</label><title>Vaccines for camels</title><p id="p0155">There was a clear call from Global Technical Meeting participants to accelerate the development of a dromedary camel vaccine in order to evaluate the potential to reduce spillover transmission to humans. The acceptability, cost-effectiveness and feasibility of a dromedary camel vaccine will also need to be evaluated and compared to other intervention strategies, such as human vaccination of high risk groups (e.g., those with occupational exposure). Because MERS-CoV is endemic in dromedary camel populations in the Middle East and elsewhere, multiple intervention strategies, including personal protective measures and the strategic implementation of a camel vaccine, are likely needed to reduce transmission from dromedary camels to humans.</p><p id="p0160">At least two promising camel vaccine candidates are currently in development and being evaluated in field trials (<xref rid="bib51" ref-type="bibr">Haagmans et al., 2016</xref>; <xref rid="bib14" ref-type="bibr">Alharbi et al., 2017</xref>). Stakeholders agreed that the current funding mechanisms need to include risk-mitigating options that target the animal-human interface to prevent zoonotic transmission. These funding pathways would enable the development of camel vaccine candidates. Stakeholders also agreed that prior to camel vaccine implementation, consultation with camel owners and government agencies, feasibility studies including exploring opportunities for commercial manufacturing and incentives for camel vaccination and an assessment of potential trade implications, would all be critical.</p><p id="p0165">In June 2018, WHO and the International Vaccine Institut (IVI) held a joint workshop update the status of human and animal MERS-CoV vaccine development, and identify and prioritize activities to accelerate vaccine research and development. The meeting was held in Seoul, Korea on 26–27 June and included 120 experts and professionals from industry, academia, international organizations and government agencies around the world, including the Coalition for Epidemic Preparedness Innovations (CEPI), the Korean Ministry of Food and Drug Safety (KMFDS) and the Korea Centers for Disease Control and Prevention (KCDC).</p></sec></sec><sec id="sec3"><label>3</label><title>The way forward</title><p id="p0170">The Global Technical Meeting served as an opportunity to review the available evidence and best practices for control of this epidemic threat six years after the virus was first detected in humans. This covered our understanding of the virus, our ability to detect and respond to cases in animal and human populations, how we communicate our findings and how our work impacts policy decisions to protect animals and prevent human infections.</p><p id="p0175">During the Global Technical Meeting, the latest findings from scientific studies and knowledge gained from collaborative research and surveillance were shared across animal, environmental and human sectors. FAO, OIE and WHO strongly believe that to effectively address zoonoses, including MERS-CoV, a One Health approach to prevent, detect, contain, eliminate and respond to animal and public health risks from zoonotic high threat respiratory pathogens such as MERS-CoV and should involve all relevant sectors, the public and animal health and academic research community, industry and affected communities. We acknowledged the progress that has been made, and importantly, discussed the challenges that need to be addressed so that we can minimize the future public health and economic impacts of this epidemic prone virus. Our aim was to articulate a clear action plan to address these remaining unknowns and to foster better collaboration between sectors and with subject matter experts willing to support member states.</p><p id="p0180">Given the marked expansion in research related to MERS-CoV conducted in the past two years, FAO, OIE and WHO agree that global surveillance and research activities must now be focused on achieving the following major public health goals: reducing zoonotic transmission, detecting and identifying suspected cases early, providing safe and effective treatment to reduce human morbidity and mortality, and significantly reducing human-to-human transmission in health care settings.</p><p id="p0185">The critical needs for research and technical guidance identified during the Global Technical Meeting have been used to inform the WHO R&D MERS-CoV Roadmap (<xref rid="bib80" ref-type="bibr">Modjarrad et al., 2016</xref>) and a broader Research Agenda for MERS-CoV and other high threat coronaviruses. This research agenda serves as a catalyst to focus, align and mobilize partners to address outstanding knowledge gaps in relation to MERS-CoV across five technical areas:<list list-type="simple" id="olist0025"><list-item id="o0025"><label>i)</label><p id="p0190">virus origin and characteristics,</p></list-item><list-item id="o0030"><label>ii)</label><p id="p0195">epidemiology and transmission,</p></list-item><list-item id="o0035"><label>iii)</label><p id="p0200">clinical management and infection prevention and control,</p></list-item><list-item id="o0040"><label>iv)</label><p id="p0205">product development and implementation (<xref rid="bib80" ref-type="bibr">Modjarrad et al., 2016</xref>) and</p></list-item><list-item id="o0045"><label>v)</label><p id="p0210">impact of interventions and operational research. The meeting identified a large number of remaining priorities and the organizing committee has summarized the main research needs in <xref rid="tbl2" ref-type="table">Table 2</xref>.<table-wrap position="float" id="tbl2"><label>Table 2</label><caption><p>List of prioritized research and progress on MERS-CoV research, as discussed at the September 2017 meeting. *Based on an enhanced understanding of the virus, the Doha Declaration (<xref rid="bib47" ref-type="bibr">FAO, 2015</xref>) is undergoing revision with a focus on guiding surveillance techniques, management of dromedary camels shedding the virus, research, regional and inter-sectoral coordination, risk communication, food and environmental safety practices, and biosecurity measures. The update includes explicit guidance on import testing, quarantine procedures, and management of shedding animals. These recommendations and priority actions in the Doha Declaration will be delivered as a separate document after validation by stakeholders in affected and at risk countries.</p></caption><alt-text id="alttext0025">Table 2</alt-text><table frame="hsides" rules="groups"><thead><tr><th>Population focus</th><th>Prioritized research*</th><th>Progress since the September, 2017 Meeting</th></tr></thead><tbody><tr><td align="left">In dromedary camel populations*</td><td align="left"><list list-type="simple" id="ulist0015"><list-item id="u0035"><label>•</label><p id="p0245">Conduct natural history studies and evaluate evidence of re-infection</p></list-item><list-item id="u0040"><label>•</label><p id="p0250">Conduct value chain and production system analyses</p></list-item><list-item id="u0045"><label>•</label><p id="p0255">Improve surveillance to evaluate seasonal/temporal variation, if any, in camel viral shedding</p></list-item><list-item id="u0050"><label>•</label><p id="p0260">Identify critical points for interventions and interruption of within species and zoonotic transmission</p></list-item><list-item id="u0055"><label>•</label><p id="p0265">Accelerate the development of vaccine candidates</p></list-item></list></td><td align="left"><list list-type="simple" id="ulist0020"><list-item id="u0060"><label>•</label><p id="p0270">The report “MERS-CoV at the Animal-Human Interface – An Update of the 2015 Doha Declaration” published outlining priority actions in surveillance, testing of animals at quarantine and entry points, management of PCR positive dromedary camels, coordinated outbreak investigation of community acquired cases with dromedary exposure, food safety and environmental contamination, risk communication and awareness raising for MERS-CoV among animal owners and intersectoral collaboration and coordination</p></list-item><list-item id="u0065"><label>•</label><p id="p0275">Repeat cross-sectional and cohort surveillance studies ongoing in dromedary camels in Jordan, Egypt, Ethiopia, Kenya.</p></list-item><list-item id="u0070"><label>•</label><p id="p0280">FAO protocol on repeat cross-sectional and cohort surveillance studies dromedary camels <italic>available upon request.</italic></p></list-item><list-item id="u0075"><label>•</label><p id="p0285">Camel value chain analysis ongoing in Jordan, Egypt, Ethiopia, Kenya.</p></list-item><list-item id="u0080"><label>•</label><p id="p0290">WHO-IVI Joint Workshop on MERS-CoV human and dromedary vaccines, 26–27 June 2018 Seoul, Korea</p></list-item></list></td></tr><tr><td align="left">At the animal-human interface</td><td align="left"><list list-type="simple" id="ulist0025"><list-item id="u0085"><label>•</label><p id="p0295">Map virus circulation and geographic range of MERS-CoV in humans and dromedary camels</p></list-item><list-item id="u0090"><label>•</label><p id="p0300">Evaluate geographic extent of spillover to humans in Africa, the Middle East and South Asia</p></list-item><list-item id="u0095"><label>•</label><p id="p0305">Conduct animal/human serological and virological studies in specific locations to evaluate risk factors for human infection and exact routes of zoonotic transmission, including food/oral routes, if any</p></list-item><list-item id="u0100"><label>•</label><p id="p0310">Conduct social science and anthropological studies to describe and quantify exposures to dromedary camels and identify opportunities for risk-mitigating interventions</p></list-item></list></td><td align="left"><list list-type="simple" id="ulist0030"><list-item id="u0105"><label>•</label><p id="p0315">Revision of camel/human field study methodology (WHO-Protocol and questionnaires available: Cross-sectional seroepidemiologic study of MERS-CoV infection in high-risk population sin contact with dromedary camels) published</p></list-item><list-item id="u0110"><label>•</label><p id="p0320">Camel/human field studies are ongoing/or planned in Algeria, Egypt, Ethiopia, Kenya, Mauritania, Niger, Pakistan and Sudan.</p></list-item><list-item id="u0115"><label>•</label><p id="p0325">Protocol developed: Anthropological study to describe and general population contact patterns with dromedary camels (WHO protocol available upon request: <italic>Multi-site study to describe frequency and patterns of contact with dromedary camels, and assess other potential and known risk factors for MERS-CoV infection</italic></p></list-item><list-item id="u0120"><label>•</label><p id="p0330">National and sub-national Rapid-response team training involving human and animal health sectors developed and implemented in several at risk countries in the Middle East and Africa</p></list-item><list-item id="u0125"><label>•</label><p id="p0335">MERS-CoV Situational Updates provided by FAO and WHO monthly</p></list-item></list></td></tr><tr><td align="left">In human populations</td><td align="left"><list list-type="simple" id="ulist0035"><list-item id="u0130"><label>•</label><p id="p0340">Accelerate the research, development, implementation and evaluation of medical countermeasures to reduce morbidity and mortality associated with MERS</p></list-item><list-item id="u0135"><label>•</label><p id="p0345">Identify the risk factors for healthcare workers in hospital settings and role of administrative and environmental control for transmission of infection</p></list-item><list-item id="u0140"><label>•</label><p id="p0350">Understand the role of silent/asymptomatic cases in transmission of infections in humans and whether any specific behaviors may result in human infection form non-human sources;</p></list-item><list-item id="u0145"><label>•</label><p id="p0355">Conduct targeted epidemiological studies in clinical settings to better understand immune response and duration of infectiousness</p></list-item><list-item id="u0150"><label>•</label><p id="p0360">Integrate testing for MERS-CoV into existing respiratory disease surveillance systems to identify extent and spectrum of mild infection in the community</p></list-item></list></td><td align="left"><list list-type="simple" id="ulist0040"><list-item id="u0155"><label>•</label><p id="p0365">WHO-IVI Joint Workshop on MERS-CoV human and dromedary vaccines, 26–27 June 2018 Seoul, Korea</p></list-item><list-item id="u0160"><label>•</label><p id="p0370">Funding for development of clinical trial protocols for MERS treatment and vaccines received and protocols in development in consultation with WHO R&D Blueprint and affected member states.</p></list-item><list-item id="u0165"><label>•</label><p id="p0375">Country workshops held to integrated MERS-CoV preparedness and response plans into larger national respiratory disease preparedness and response plans</p></list-item><list-item id="u0170"><label>•</label><p id="p0380">MERS-CoV virus persistence studies ongoing under experimental conditions</p></list-item><list-item id="u0175"><label>•</label><p id="p0385">Protocol developed (available upon request) to provide guidance on the collection of surface samples to evaluate MERS-CoV persistence in hospital settings where MERS patients are treated</p></list-item></list></td></tr></tbody></table></table-wrap></p></list-item></list></p><p id="p0215">Now is the time to devote more effort to long term planning for MERS-CoV. We believe more focused efforts in our activities and investments to address scientific and public health research questions, accelerate promising medical interventions and are more strategic on where activities are conducted globally will go further to address remaining public health unknowns. While there have been improvements in the ability to prevent human-to-human transmission once a MERS case is identified, these are not sufficient to prevent a large event with substantial public health and economic consequences.</p></sec><sec id="sec4"><title>Competing financial interests</title><p id="p0220">The authors have no competing financial interests.</p></sec></body><back><ref-list id="cebib0010"><title>References</title><ref id="bib1"><element-citation publication-type="journal" id="sref1"><person-group person-group-type="author"><name><surname>Abdulaziz</surname><given-names>A.B.S.</given-names></name><name><surname>Glen</surname><given-names>R.A.</given-names></name><name><surname>Abdullah</surname><given-names>G.A.</given-names></name></person-group><article-title>Surveillance and testing for Middle East respiratory syndrome coronavirus, Saudi Arabia, April 2015–February 2016</article-title><source>Emerg. Infect. Dis. 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J.</source><volume>20</volume><year>2014</year><fpage>1012</fpage></element-citation></ref></ref-list><sec id="appsec1" sec-type="supplementary-material"><label>Appendix A</label><title>Supplementary data</title><p id="p0230">The following is the supplementary data to this article:<supplementary-material content-type="local-data" id="mmc1"><caption><title>Multimedia component 1</title></caption><media xlink:href="mmc1.pdf"><alt-text>Multimedia component 1</alt-text></media></supplementary-material></p></sec><ack id="ack0010"><title>Acknowledgements</title><p>We gratefully acknowledge the input from all those who attended the FAO-OIE-WHO Global Technical Meeting on MERS-CoV in September 2017. The authors also thank Malik Peiris for his review of the final manuscript. The opinions expressed in this article are those of the authors and do not necessarily reflect those of the institutions or organizations with which they are affiliated.</p></ack><fn-group><fn id="appsec2" fn-type="supplementary-material"><label>Appendix A</label><p id="p0235">Supplementary data to this article can be found online at <ext-link ext-link-type="uri" xlink:href="https://doi.org/mmcdoin" id="intref0015">https://doi.org/mmcdoin</ext-link>o.</p></fn></fn-group></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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