Middle East respiratory syndrome coronavirus: quantification of the extent of the epidemic, surveillance biases, and transmissibility
Summary Background The novel Middle East respiratory syndrome coronavirus (MERS-CoV) had, as of Aug 8, 2013, caused 111 virologically confirmed or probable human cases of infection worldwide. We analysed epidemiological and genetic data to assess the extent of human infection, the performance of cas...
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creator | Cauchemez, Simon, PhD Fraser, Christophe, Prof Van Kerkhove, Maria D, PhD Donnelly, Christl A, Prof Riley, Steven, PhD Rambaut, Andrew, Prof Enouf, Vincent, PhD van der Werf, Sylvie, Prof Ferguson, Neil M, Prof |
description | Summary Background The novel Middle East respiratory syndrome coronavirus (MERS-CoV) had, as of Aug 8, 2013, caused 111 virologically confirmed or probable human cases of infection worldwide. We analysed epidemiological and genetic data to assess the extent of human infection, the performance of case detection, and the transmission potential of MERS-CoV with and without control measures. Methods We assembled a comprehensive database of all confirmed and probable cases from public sources and estimated the incubation period and generation time from case cluster data. Using data of numbers of visitors to the Middle East and their duration of stay, we estimated the number of symptomatic cases in the Middle East. We did independent analyses, looking at the growth in incident clusters, the growth in viral population, the reproduction number of cluster index cases, and cluster sizes to characterise the dynamical properties of the epidemic and the transmission scenario. Findings The estimated number of symptomatic cases up to Aug 8, 2013, is 940 (95% CI 290–2200), indicating that at least 62% of human symptomatic cases have not been detected. We find that the case-fatality ratio of primary cases detected via routine surveillance (74%; 95% CI 49–91) is biased upwards because of detection bias; the case-fatality ratio of secondary cases was 20% (7–42). Detection of milder cases (or clinical management) seemed to have improved in recent months. Analysis of human clusters indicated that chains of transmission were not self-sustaining when infection control was implemented, but that R in the absence of controls was in the range 0·8–1·3. Three independent data sources provide evidence that R cannot be much above 1, with an upper bound of 1·2–1·5. Interpretation By showing that a slowly growing epidemic is underway either in human beings or in an animal reservoir, quantification of uncertainty in transmissibility estimates, and provision of the first estimates of the scale of the epidemic and extent of case detection biases, we provide valuable information for more informed risk assessment. Funding Medical Research Council, Bill & Melinda Gates Foundation, EU FP7, and National Institute of General Medical Sciences. |
doi_str_mv | 10.1016/S1473-3099(13)70304-9 |
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We analysed epidemiological and genetic data to assess the extent of human infection, the performance of case detection, and the transmission potential of MERS-CoV with and without control measures. Methods We assembled a comprehensive database of all confirmed and probable cases from public sources and estimated the incubation period and generation time from case cluster data. Using data of numbers of visitors to the Middle East and their duration of stay, we estimated the number of symptomatic cases in the Middle East. We did independent analyses, looking at the growth in incident clusters, the growth in viral population, the reproduction number of cluster index cases, and cluster sizes to characterise the dynamical properties of the epidemic and the transmission scenario. Findings The estimated number of symptomatic cases up to Aug 8, 2013, is 940 (95% CI 290–2200), indicating that at least 62% of human symptomatic cases have not been detected. We find that the case-fatality ratio of primary cases detected via routine surveillance (74%; 95% CI 49–91) is biased upwards because of detection bias; the case-fatality ratio of secondary cases was 20% (7–42). Detection of milder cases (or clinical management) seemed to have improved in recent months. Analysis of human clusters indicated that chains of transmission were not self-sustaining when infection control was implemented, but that R in the absence of controls was in the range 0·8–1·3. Three independent data sources provide evidence that R cannot be much above 1, with an upper bound of 1·2–1·5. Interpretation By showing that a slowly growing epidemic is underway either in human beings or in an animal reservoir, quantification of uncertainty in transmissibility estimates, and provision of the first estimates of the scale of the epidemic and extent of case detection biases, we provide valuable information for more informed risk assessment. Funding Medical Research Council, Bill & Melinda Gates Foundation, EU FP7, and National Institute of General Medical Sciences.</description><identifier>ISSN: 1473-3099</identifier><identifier>EISSN: 1474-4457</identifier><identifier>DOI: 10.1016/S1473-3099(13)70304-9</identifier><identifier>PMID: 24239323</identifier><identifier>CODEN: LANCAO</identifier><language>eng</language><publisher>London: Elsevier Ltd</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Basic Reproduction Number ; Biological and medical sciences ; Child ; Child, Preschool ; Cluster Analysis ; Coronavirus ; Coronavirus - classification ; Coronavirus - genetics ; Coronavirus - isolation & purification ; Coronavirus Infections - epidemiology ; Coronavirus Infections - transmission ; Coronavirus Infections - virology ; Epidemics ; Epidemiological Monitoring ; Female ; Human viral diseases ; Humans ; Infectious Disease ; Infectious diseases ; Male ; Medical research ; Medical sciences ; Middle Aged ; Middle East - epidemiology ; Respiratory Tract Infections - epidemiology ; Respiratory Tract Infections - transmission ; Respiratory Tract Infections - virology ; Risk Assessment ; Survival Analysis ; Viral diseases ; Viral diseases of the respiratory system and ent viral diseases ; Young Adult</subject><ispartof>The Lancet infectious diseases, 2014-01, Vol.14 (1), p.50-56</ispartof><rights>Cauchemez et al. Open Access article distributed under the terms of CC BY</rights><rights>2014 Cauchemez et al. Open Access article distributed under the terms of CC BY</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2014 Cauchemez et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Limited Jan 2014</rights><rights>2014 Cauchemez et al. Open Access article distributed under the terms of CC BY 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c764t-c79f08b337b353a18b0d7e4be65cab49a9912a9c68889e3bc4874f41c35662803</citedby><cites>FETCH-LOGICAL-c764t-c79f08b337b353a18b0d7e4be65cab49a9912a9c68889e3bc4874f41c35662803</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1473309913703049$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28091108$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24239323$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cauchemez, Simon, PhD</creatorcontrib><creatorcontrib>Fraser, Christophe, Prof</creatorcontrib><creatorcontrib>Van Kerkhove, Maria D, PhD</creatorcontrib><creatorcontrib>Donnelly, Christl A, Prof</creatorcontrib><creatorcontrib>Riley, Steven, PhD</creatorcontrib><creatorcontrib>Rambaut, Andrew, Prof</creatorcontrib><creatorcontrib>Enouf, Vincent, PhD</creatorcontrib><creatorcontrib>van der Werf, Sylvie, Prof</creatorcontrib><creatorcontrib>Ferguson, Neil M, Prof</creatorcontrib><title>Middle East respiratory syndrome coronavirus: quantification of the extent of the epidemic, surveillance biases, and transmissibility</title><title>The Lancet infectious diseases</title><addtitle>Lancet Infect Dis</addtitle><description>Summary Background The novel Middle East respiratory syndrome coronavirus (MERS-CoV) had, as of Aug 8, 2013, caused 111 virologically confirmed or probable human cases of infection worldwide. We analysed epidemiological and genetic data to assess the extent of human infection, the performance of case detection, and the transmission potential of MERS-CoV with and without control measures. Methods We assembled a comprehensive database of all confirmed and probable cases from public sources and estimated the incubation period and generation time from case cluster data. Using data of numbers of visitors to the Middle East and their duration of stay, we estimated the number of symptomatic cases in the Middle East. We did independent analyses, looking at the growth in incident clusters, the growth in viral population, the reproduction number of cluster index cases, and cluster sizes to characterise the dynamical properties of the epidemic and the transmission scenario. Findings The estimated number of symptomatic cases up to Aug 8, 2013, is 940 (95% CI 290–2200), indicating that at least 62% of human symptomatic cases have not been detected. We find that the case-fatality ratio of primary cases detected via routine surveillance (74%; 95% CI 49–91) is biased upwards because of detection bias; the case-fatality ratio of secondary cases was 20% (7–42). Detection of milder cases (or clinical management) seemed to have improved in recent months. Analysis of human clusters indicated that chains of transmission were not self-sustaining when infection control was implemented, but that R in the absence of controls was in the range 0·8–1·3. Three independent data sources provide evidence that R cannot be much above 1, with an upper bound of 1·2–1·5. Interpretation By showing that a slowly growing epidemic is underway either in human beings or in an animal reservoir, quantification of uncertainty in transmissibility estimates, and provision of the first estimates of the scale of the epidemic and extent of case detection biases, we provide valuable information for more informed risk assessment. Funding Medical Research Council, Bill & Melinda Gates Foundation, EU FP7, and National Institute of General Medical Sciences.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Basic Reproduction Number</subject><subject>Biological and medical sciences</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Cluster Analysis</subject><subject>Coronavirus</subject><subject>Coronavirus - classification</subject><subject>Coronavirus - genetics</subject><subject>Coronavirus - isolation & purification</subject><subject>Coronavirus Infections - epidemiology</subject><subject>Coronavirus Infections - transmission</subject><subject>Coronavirus Infections - virology</subject><subject>Epidemics</subject><subject>Epidemiological Monitoring</subject><subject>Female</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Infectious Disease</subject><subject>Infectious diseases</subject><subject>Male</subject><subject>Medical research</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Middle East - epidemiology</subject><subject>Respiratory Tract Infections - epidemiology</subject><subject>Respiratory Tract Infections - transmission</subject><subject>Respiratory Tract Infections - virology</subject><subject>Risk Assessment</subject><subject>Survival Analysis</subject><subject>Viral diseases</subject><subject>Viral diseases of the respiratory system and ent viral diseases</subject><subject>Young Adult</subject><issn>1473-3099</issn><issn>1474-4457</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNkstu1DAUhiMEoqXwCCBLCKlIHbBjx7G7KKqqcpGKWABry3FO6CmZeGo7I-YB-t44M8MUuikbX7_z61z-onjO6BtGmXz7lYmazzjV-pDx1zXlVMz0g2I_P4uZEFX9cH3eIHvFkxivKGU1o-JxsVeKkmte8v3i5jO2bQ_k3MZEAsQFBpt8WJG4Gtrg50CcD36wSwxjPCbXox0SduhsQj8Q35F0CQR-JRjS7rbAFubojkgcwxKw7-3ggDRoI8QjYoeWpGCHOMcYscEe0-pp8aizfYRn2_2g-P7-_NvZx9nFlw-fzk4vZq6WIuVVd1Q1nNcNr7hlqqFtDaIBWTnbCG21ZqXVTiqlNPDGCVWLTjDHKylLRflBcbLRXYzNHFqXsw62N4uAcxtWxls0__4MeGl--KXhSle8LLPA4VYg-OsRYjK5CgdTieDHaFglBKUTfD8q9JSnrNj_oLQWUokJfXkHvfJjGHLTMiWVlHVZy0xVG8oFH2OAblcio2ayj1nbx0zeMIybtX2MznEv_u7PLuqPXzLwagvY6Gzf5Tk6jLecopoxqjL3bsNBnuYSIZjoELINWgzgkmk93pvKyR0F1-OQjdf_hBXE26pNLA3diEwajK8VNP8Njn74QQ</recordid><startdate>20140101</startdate><enddate>20140101</enddate><creator>Cauchemez, Simon, PhD</creator><creator>Fraser, Christophe, Prof</creator><creator>Van Kerkhove, Maria D, PhD</creator><creator>Donnelly, Christl A, Prof</creator><creator>Riley, Steven, PhD</creator><creator>Rambaut, Andrew, Prof</creator><creator>Enouf, Vincent, PhD</creator><creator>van der Werf, Sylvie, Prof</creator><creator>Ferguson, Neil M, Prof</creator><general>Elsevier Ltd</general><general>Lancet Publishing Group</general><general>Elsevier Limited</general><general>Cauchemez et al. 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Published by Elsevier Ltd</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>0TZ</scope><scope>3V.</scope><scope>7QL</scope><scope>7RV</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8C2</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>7T2</scope><scope>7U1</scope><scope>7U2</scope><scope>5PM</scope></search><sort><creationdate>20140101</creationdate><title>Middle East respiratory syndrome coronavirus: quantification of the extent of the epidemic, surveillance biases, and transmissibility</title><author>Cauchemez, Simon, PhD ; Fraser, Christophe, Prof ; Van Kerkhove, Maria D, PhD ; Donnelly, Christl A, Prof ; Riley, Steven, PhD ; Rambaut, Andrew, Prof ; Enouf, Vincent, PhD ; van der Werf, Sylvie, Prof ; Ferguson, Neil M, Prof</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c764t-c79f08b337b353a18b0d7e4be65cab49a9912a9c68889e3bc4874f41c35662803</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Basic Reproduction Number</topic><topic>Biological and medical sciences</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Cluster Analysis</topic><topic>Coronavirus</topic><topic>Coronavirus - classification</topic><topic>Coronavirus - genetics</topic><topic>Coronavirus - isolation & purification</topic><topic>Coronavirus Infections - epidemiology</topic><topic>Coronavirus Infections - transmission</topic><topic>Coronavirus Infections - virology</topic><topic>Epidemics</topic><topic>Epidemiological Monitoring</topic><topic>Female</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Infectious Disease</topic><topic>Infectious diseases</topic><topic>Male</topic><topic>Medical research</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Middle East - epidemiology</topic><topic>Respiratory Tract Infections - epidemiology</topic><topic>Respiratory Tract Infections - transmission</topic><topic>Respiratory Tract Infections - virology</topic><topic>Risk Assessment</topic><topic>Survival Analysis</topic><topic>Viral diseases</topic><topic>Viral diseases of the respiratory system and ent viral diseases</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cauchemez, Simon, PhD</creatorcontrib><creatorcontrib>Fraser, Christophe, Prof</creatorcontrib><creatorcontrib>Van Kerkhove, Maria D, PhD</creatorcontrib><creatorcontrib>Donnelly, Christl A, Prof</creatorcontrib><creatorcontrib>Riley, Steven, PhD</creatorcontrib><creatorcontrib>Rambaut, Andrew, Prof</creatorcontrib><creatorcontrib>Enouf, Vincent, PhD</creatorcontrib><creatorcontrib>van der Werf, Sylvie, Prof</creatorcontrib><creatorcontrib>Ferguson, Neil M, Prof</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Pharma and Biotech Premium PRO</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Nursing & Allied Health Database</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Lancet Titles</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Risk Abstracts</collection><collection>Safety Science and Risk</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Lancet infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cauchemez, Simon, PhD</au><au>Fraser, Christophe, Prof</au><au>Van Kerkhove, Maria D, PhD</au><au>Donnelly, Christl A, Prof</au><au>Riley, Steven, PhD</au><au>Rambaut, Andrew, Prof</au><au>Enouf, Vincent, PhD</au><au>van der Werf, Sylvie, Prof</au><au>Ferguson, Neil M, Prof</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Middle East respiratory syndrome coronavirus: quantification of the extent of the epidemic, surveillance biases, and transmissibility</atitle><jtitle>The Lancet infectious diseases</jtitle><addtitle>Lancet Infect Dis</addtitle><date>2014-01-01</date><risdate>2014</risdate><volume>14</volume><issue>1</issue><spage>50</spage><epage>56</epage><pages>50-56</pages><issn>1473-3099</issn><eissn>1474-4457</eissn><coden>LANCAO</coden><abstract>Summary Background The novel Middle East respiratory syndrome coronavirus (MERS-CoV) had, as of Aug 8, 2013, caused 111 virologically confirmed or probable human cases of infection worldwide. We analysed epidemiological and genetic data to assess the extent of human infection, the performance of case detection, and the transmission potential of MERS-CoV with and without control measures. Methods We assembled a comprehensive database of all confirmed and probable cases from public sources and estimated the incubation period and generation time from case cluster data. Using data of numbers of visitors to the Middle East and their duration of stay, we estimated the number of symptomatic cases in the Middle East. We did independent analyses, looking at the growth in incident clusters, the growth in viral population, the reproduction number of cluster index cases, and cluster sizes to characterise the dynamical properties of the epidemic and the transmission scenario. Findings The estimated number of symptomatic cases up to Aug 8, 2013, is 940 (95% CI 290–2200), indicating that at least 62% of human symptomatic cases have not been detected. We find that the case-fatality ratio of primary cases detected via routine surveillance (74%; 95% CI 49–91) is biased upwards because of detection bias; the case-fatality ratio of secondary cases was 20% (7–42). Detection of milder cases (or clinical management) seemed to have improved in recent months. Analysis of human clusters indicated that chains of transmission were not self-sustaining when infection control was implemented, but that R in the absence of controls was in the range 0·8–1·3. Three independent data sources provide evidence that R cannot be much above 1, with an upper bound of 1·2–1·5. Interpretation By showing that a slowly growing epidemic is underway either in human beings or in an animal reservoir, quantification of uncertainty in transmissibility estimates, and provision of the first estimates of the scale of the epidemic and extent of case detection biases, we provide valuable information for more informed risk assessment. Funding Medical Research Council, Bill & Melinda Gates Foundation, EU FP7, and National Institute of General Medical Sciences.</abstract><cop>London</cop><pub>Elsevier Ltd</pub><pmid>24239323</pmid><doi>10.1016/S1473-3099(13)70304-9</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adolescent Adult Aged Aged, 80 and over Basic Reproduction Number Biological and medical sciences Child Child, Preschool Cluster Analysis Coronavirus Coronavirus - classification Coronavirus - genetics Coronavirus - isolation & purification Coronavirus Infections - epidemiology Coronavirus Infections - transmission Coronavirus Infections - virology Epidemics Epidemiological Monitoring Female Human viral diseases Humans Infectious Disease Infectious diseases Male Medical research Medical sciences Middle Aged Middle East - epidemiology Respiratory Tract Infections - epidemiology Respiratory Tract Infections - transmission Respiratory Tract Infections - virology Risk Assessment Survival Analysis Viral diseases Viral diseases of the respiratory system and ent viral diseases Young Adult |
title | Middle East respiratory syndrome coronavirus: quantification of the extent of the epidemic, surveillance biases, and transmissibility |
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