Low 2012–13 Influenza Vaccine Effectiveness Associated with Mutation in the Egg-Adapted H3N2 Vaccine Strain Not Antigenic Drift in Circulating Viruses
Publication Date
March 25, 2014
Journal
PLOS ONE
Authors
Danuta M. Skowronski, Naveed Z. Janjua, Gaston De Serres, Suzana Sabaiduc, et al
Volume
9
Issue
3
Pages
e92153
DOI
http://doi.org/10.1371/journal.pone.0092153
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0092153
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/24667168
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3965421
Europe PMC
http://europepmc.org/abstract/MED/24667168
Web of Science
000333675600021
Scopus
84899838197
Mendeley
http://www.mendeley.com/research/low-201213-influenza-vaccine-effectiveness-associated-mutation-eggadapted-h3n2-vaccine-strain-not-an
Events
Loading … Spinner
Mendeley 9926 Mar 08:08 UTC

Mendeley | Further Information

{"title"=>"Low 2012-13 influenza vaccine effectiveness associated with mutation in the egg-adapted H3N2 vaccine strain not antigenic drift in circulating viruses", "type"=>"journal", "authors"=>[{"first_name"=>"Danuta M.", "last_name"=>"Skowronski", "scopus_author_id"=>"7004017482"}, {"first_name"=>"Naveed Z.", "last_name"=>"Janjua", "scopus_author_id"=>"7003951222"}, {"first_name"=>"Gaston", "last_name"=>"De Serres", "scopus_author_id"=>"7006630854"}, {"first_name"=>"Suzana", "last_name"=>"Sabaiduc", "scopus_author_id"=>"36601351900"}, {"first_name"=>"Alireza", "last_name"=>"Eshaghi", "scopus_author_id"=>"24832830500"}, {"first_name"=>"James A.", "last_name"=>"Dickinson", "scopus_author_id"=>"7202899853"}, {"first_name"=>"Kevin", "last_name"=>"Fonseca", "scopus_author_id"=>"6701367954"}, {"first_name"=>"Anne Luise", "last_name"=>"Winter", "scopus_author_id"=>"7202642920"}, {"first_name"=>"Jonathan B.", "last_name"=>"Gubbay", "scopus_author_id"=>"6603333644"}, {"first_name"=>"Mel", "last_name"=>"Krajden", "scopus_author_id"=>"7004178160"}, {"first_name"=>"Martin", "last_name"=>"Petric", "scopus_author_id"=>"16216941800"}, {"first_name"=>"Hugues", "last_name"=>"Charest", "scopus_author_id"=>"6602733802"}, {"first_name"=>"Nathalie", "last_name"=>"Bastien", "scopus_author_id"=>"6602480468"}, {"first_name"=>"Trijntje L.", "last_name"=>"Kwindt", "scopus_author_id"=>"16039811300"}, {"first_name"=>"Salaheddin M.", "last_name"=>"Mahmud", "scopus_author_id"=>"7005052871"}, {"first_name"=>"Paul", "last_name"=>"Van Caeseele", "scopus_author_id"=>"6602254381"}, {"first_name"=>"Yan", "last_name"=>"Li", "scopus_author_id"=>"55949861900"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pui"=>"373020704", "doi"=>"10.1371/journal.pone.0092153", "sgr"=>"84899838197", "scopus"=>"2-s2.0-84899838197", "isbn"=>"1932-6203", "pmid"=>"24667168"}, "id"=>"3392a9ec-d43a-3165-964e-7271f2033728", "abstract"=>"BACKGROUND: Influenza vaccine effectiveness (VE) is generally interpreted in the context of vaccine match/mismatch to circulating strains with evolutionary drift in the latter invoked to explain reduced protection. During the 2012-13 season, however, detailed genotypic and phenotypic characterization shows that low VE was instead related to mutations in the egg-adapted H3N2 vaccine strain rather than antigenic drift in circulating viruses.\\n\\nMETHODS/FINDINGS: Component-specific VE against medically-attended, PCR-confirmed influenza was estimated in Canada by test-negative case-control design. Influenza A viruses were characterized genotypically by amino acid (AA) sequencing of established haemagglutinin (HA) antigenic sites and phenotypically through haemagglutination inhibition (HI) assay. H3N2 viruses were characterized in relation to the WHO-recommended, cell-passaged vaccine prototype (A/Victoria/361/2011) as well as the egg-adapted strain as per actually used in vaccine production. Among the total of 1501 participants, influenza virus was detected in 652 (43%). Nearly two-thirds of viruses typed/subtyped were A(H3N2) (394/626; 63%); the remainder were A(H1N1)pdm09 (79/626; 13%), B/Yamagata (98/626; 16%) or B/Victoria (54/626; 9%). Suboptimal VE of 50% (95%CI: 33-63%) overall was driven by predominant H3N2 activity for which VE was 41% (95%CI: 17-59%). All H3N2 field isolates were HI-characterized as well-matched to the WHO-recommended A/Victoria/361/2011 prototype whereas all but one were antigenically distinct from the egg-adapted strain as per actually used in vaccine production. The egg-adapted strain was itself antigenically distinct from the WHO-recommended prototype, and bore three AA mutations at antigenic sites B [H156Q, G186V] and D [S219Y]. Conversely, circulating viruses were identical to the WHO-recommended prototype at these positions with other genetic variation that did not affect antigenicity. VE was 59% (95%CI:16-80%) against A(H1N1)pdm09, 67% (95%CI: 30-85%) against B/Yamagata (vaccine-lineage) and 75% (95%CI: 29-91%) against B/Victoria (non-vaccine-lineage) viruses.\\n\\nCONCLUSIONS: These findings underscore the need to monitor vaccine viruses as well as circulating strains to explain vaccine performance. Evolutionary drift in circulating viruses cannot be regulated, but influential mutations introduced as part of egg-based vaccine production may be amenable to improvements.", "link"=>"http://www.mendeley.com/research/low-201213-influenza-vaccine-effectiveness-associated-mutation-eggadapted-h3n2-vaccine-strain-not-an", "reader_count"=>94, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>9, "Researcher"=>28, "Student > Doctoral Student"=>6, "Student > Ph. D. Student"=>19, "Student > Master"=>11, "Other"=>7, "Student > Bachelor"=>8, "Lecturer"=>2, "Lecturer > Senior Lecturer"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>9, "Researcher"=>28, "Student > Doctoral Student"=>6, "Student > Ph. D. Student"=>19, "Student > Master"=>11, "Other"=>7, "Student > Bachelor"=>8, "Lecturer"=>2, "Lecturer > Senior Lecturer"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>10, "Engineering"=>2, "Biochemistry, Genetics and Molecular Biology"=>11, "Mathematics"=>2, "Medicine and Dentistry"=>25, "Agricultural and Biological Sciences"=>28, "Veterinary Science and Veterinary Medicine"=>1, "Psychology"=>1, "Social Sciences"=>2, "Computer Science"=>1, "Immunology and Microbiology"=>10, "Economics, Econometrics and Finance"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>25}, "Social Sciences"=>{"Social Sciences"=>2}, "Psychology"=>{"Psychology"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>10}, "Economics, Econometrics and Finance"=>{"Economics, Econometrics and Finance"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>28}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>11}, "Mathematics"=>{"Mathematics"=>2}, "Unspecified"=>{"Unspecified"=>10}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"Canada"=>2, "United States"=>1, "Japan"=>1, "Sudan"=>1}, "group_count"=>5}
CrossRef13 Dec 10:07 UTC

CrossRef

Scopus 13417 Apr 10:14 UTC

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84899838197"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84899838197?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84899838197&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84899838197&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/84899838197", "dc:identifier"=>"SCOPUS_ID:84899838197", "eid"=>"2-s2.0-84899838197", "dc:title"=>"Low 2012-13 influenza vaccine effectiveness associated with mutation in the egg-adapted H3N2 vaccine strain not antigenic drift in circulating viruses", "dc:creator"=>"Skowronski D.", "prism:publicationName"=>"PLoS ONE", "prism:eIssn"=>"19326203", "prism:volume"=>"9", "prism:issueIdentifier"=>"3", "prism:pageRange"=>nil, "prism:coverDate"=>"2014-03-25", "prism:coverDisplayDate"=>"25 March 2014", "prism:doi"=>"10.1371/journal.pone.0092153", "citedby-count"=>"134", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"BC Centre for Disease Control", "affiliation-city"=>"Vancouver", "affiliation-country"=>"Canada"}, {"@_fa"=>"true", "affilname"=>"The University of British Columbia", "affiliation-city"=>"Vancouver", "affiliation-country"=>"Canada"}], "pubmed-id"=>"24667168", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "article-number"=>"e92153", "source-id"=>"10600153309", "openaccess"=>"1", "openaccessFlag"=>true}
Article Coverage 918 May 18:31 UTC

Article Coverage

Facebook 122 Jul 10:01 UTC

Facebook

  • {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fplosone%2Farticle%3Fid%3D10.1371%252Fjournal.pone.0092153", "share_count"=>1, "like_count"=>0, "comment_count"=>0, "click_count"=>0, "total_count"=>1}
Twitter 4821 Apr 16:12 UTC

Twitter

Counter 1520024 Apr 03:07 UTC

Counter

  • {"month"=>"3", "year"=>"2014", "pdf_views"=>"205", "xml_views"=>"14", "html_views"=>"856"}
  • {"month"=>"4", "year"=>"2014", "pdf_views"=>"294", "xml_views"=>"3", "html_views"=>"1075"}
  • {"month"=>"5", "year"=>"2014", "pdf_views"=>"71", "xml_views"=>"1", "html_views"=>"329"}
  • {"month"=>"6", "year"=>"2014", "pdf_views"=>"67", "xml_views"=>"1", "html_views"=>"279"}
  • {"month"=>"7", "year"=>"2014", "pdf_views"=>"38", "xml_views"=>"0", "html_views"=>"314"}
  • {"month"=>"8", "year"=>"2014", "pdf_views"=>"21", "xml_views"=>"3", "html_views"=>"243"}
  • {"month"=>"9", "year"=>"2014", "pdf_views"=>"28", "xml_views"=>"3", "html_views"=>"218"}
  • {"month"=>"10", "year"=>"2014", "pdf_views"=>"42", "xml_views"=>"3", "html_views"=>"267"}
  • {"month"=>"11", "year"=>"2014", "pdf_views"=>"29", "xml_views"=>"1", "html_views"=>"249"}
  • {"month"=>"12", "year"=>"2014", "pdf_views"=>"39", "xml_views"=>"2", "html_views"=>"415"}
  • {"month"=>"1", "year"=>"2015", "pdf_views"=>"36", "xml_views"=>"0", "html_views"=>"343"}
  • {"month"=>"2", "year"=>"2015", "pdf_views"=>"29", "xml_views"=>"0", "html_views"=>"340"}
  • {"month"=>"3", "year"=>"2015", "pdf_views"=>"31", "xml_views"=>"0", "html_views"=>"250"}
  • {"month"=>"4", "year"=>"2015", "pdf_views"=>"35", "xml_views"=>"1", "html_views"=>"172"}
  • {"month"=>"5", "year"=>"2015", "pdf_views"=>"26", "xml_views"=>"0", "html_views"=>"254"}
  • {"month"=>"6", "year"=>"2015", "pdf_views"=>"32", "xml_views"=>"0", "html_views"=>"236"}
  • {"month"=>"7", "year"=>"2015", "pdf_views"=>"28", "xml_views"=>"0", "html_views"=>"189"}
  • {"month"=>"8", "year"=>"2015", "pdf_views"=>"29", "xml_views"=>"0", "html_views"=>"152"}
  • {"month"=>"9", "year"=>"2015", "pdf_views"=>"35", "xml_views"=>"1", "html_views"=>"257"}
  • {"month"=>"10", "year"=>"2015", "pdf_views"=>"39", "xml_views"=>"0", "html_views"=>"436"}
  • {"month"=>"11", "year"=>"2015", "pdf_views"=>"42", "xml_views"=>"0", "html_views"=>"287"}
  • {"month"=>"12", "year"=>"2015", "pdf_views"=>"24", "xml_views"=>"0", "html_views"=>"159"}
  • {"month"=>"1", "year"=>"2016", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"134"}
  • {"month"=>"2", "year"=>"2016", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"143"}
  • {"month"=>"3", "year"=>"2016", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"150"}
  • {"month"=>"4", "year"=>"2016", "pdf_views"=>"22", "xml_views"=>"0", "html_views"=>"185"}
  • {"month"=>"5", "year"=>"2016", "pdf_views"=>"30", "xml_views"=>"0", "html_views"=>"143"}
  • {"month"=>"6", "year"=>"2016", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"192"}
  • {"month"=>"7", "year"=>"2016", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"161"}
  • {"month"=>"8", "year"=>"2016", "pdf_views"=>"22", "xml_views"=>"0", "html_views"=>"124"}
  • {"month"=>"9", "year"=>"2016", "pdf_views"=>"22", "xml_views"=>"0", "html_views"=>"213"}
  • {"month"=>"10", "year"=>"2016", "pdf_views"=>"19", "xml_views"=>"0", "html_views"=>"225"}
  • {"month"=>"11", "year"=>"2016", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"207"}
  • {"month"=>"12", "year"=>"2016", "pdf_views"=>"37", "xml_views"=>"2", "html_views"=>"127"}
  • {"month"=>"1", "year"=>"2017", "pdf_views"=>"27", "xml_views"=>"0", "html_views"=>"171"}
  • {"month"=>"2", "year"=>"2017", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"208"}
  • {"month"=>"3", "year"=>"2017", "pdf_views"=>"28", "xml_views"=>"0", "html_views"=>"247"}
  • {"month"=>"4", "year"=>"2017", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"216"}
  • {"month"=>"5", "year"=>"2017", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"126"}
  • {"month"=>"6", "year"=>"2017", "pdf_views"=>"27", "xml_views"=>"0", "html_views"=>"267"}
  • {"month"=>"7", "year"=>"2017", "pdf_views"=>"32", "xml_views"=>"4", "html_views"=>"264"}
  • {"month"=>"8", "year"=>"2017", "pdf_views"=>"17", "xml_views"=>"1", "html_views"=>"144"}
  • {"month"=>"9", "year"=>"2017", "pdf_views"=>"31", "xml_views"=>"2", "html_views"=>"220"}
  • {"month"=>"10", "year"=>"2017", "pdf_views"=>"31", "xml_views"=>"3", "html_views"=>"248"}
  • {"month"=>"11", "year"=>"2017", "pdf_views"=>"62", "xml_views"=>"3", "html_views"=>"449"}
  • {"month"=>"12", "year"=>"2017", "pdf_views"=>"33", "xml_views"=>"2", "html_views"=>"223"}
  • {"month"=>"1", "year"=>"2018", "pdf_views"=>"56", "xml_views"=>"1", "html_views"=>"220"}
  • {"month"=>"2", "year"=>"2018", "pdf_views"=>"74", "xml_views"=>"2", "html_views"=>"507"}
  • {"month"=>"3", "year"=>"2018", "pdf_views"=>"83", "xml_views"=>"3", "html_views"=>"211"}
  • {"month"=>"4", "year"=>"2018", "pdf_views"=>"26", "xml_views"=>"0", "html_views"=>"77"}
Figshare 17702 Apr 19:05 UTC

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1433829"], "description"=>"<p>TIV = trivalent influenza vaccine; VE = vaccine effectiveness.</p>a<p>. Including any one or more of heart, pulmonary, renal, metabolic, blood, cancer, or conditions that compromise immunity or the management of respiratory secretions, or morbid obesity <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0092153#pone.0092153-National3\" target=\"_blank\">[20]</a>.</p>b<p>. For the 2012–13 season, of 319 participants reporting vaccine receipt ≥2 weeks before symptom onset, 298 reported this was given through injection, 5 through nasal spray (all children except one) with route of administration unspecified for 16.</p>c<p>. Children <2 years of age in 2012–13 were excluded from 2011–12 vaccine uptake analysis as they may not have been vaccine-eligible during the fall 2011–12 immunization campaign on the basis of age <6 months.</p>d<p>. Children <3 years of age in 2012–13 were excluded from 2010–11 vaccine uptake analyses.</p>e<p>. In Canada, AS03-adjuvanted monovalent A(H1N1)pdm09 vaccine comprised >95% of doses distributed <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0092153#pone.0092153-Skowronski6\" target=\"_blank\">[17]</a>.</p>f<p>. Children <4 years of age in 2012–13 were excluded from monovalent A(H1N1)pdm09 vaccine uptake analyses.</p>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "epidemiology", "Infectious disease epidemiology", "Infectious diseases", "Viral diseases", "influenza", "Public and occupational health", "included", "ve"], "article_id"=>973216, "categories"=>["Biological Sciences"], "users"=>["Danuta M. Skowronski", "Naveed Z. Janjua", "Gaston De Serres", "Suzana Sabaiduc", "AliReza Eshaghi", "James A. Dickinson", "Kevin Fonseca", "Anne-Luise Winter", "Jonathan B. Gubbay", "Mel Krajden", "Martin Petric", "Hugues Charest", "Nathalie Bastien", "Trijntje L. Kwindt", "Salaheddin M. Mahmud", "Paul Van Caeseele", "Yan Li"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0092153.t001", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Profile_of_participants_included_in_primary_influenza_VE_analysis_2012_8211_13_Canada_/973216", "title"=>"Profile of participants included in primary influenza VE analysis, 2012–13, Canada.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-03-25 02:54:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1433827"], "description"=>"<p>TIV: trivalent influenza vaccine; HI: haemagglutination inhibition assay.</p>a<p>. H3N2 prototype reference strain recommended as 2012–13 TIV component by the World Health Organization (WHO), as passaged in Madin Darby canine kidney cells; assessed using turkey erythrocytes, validated with guinea pig erythrocytes.</p>b<p>. 2012–13 H3N2 vaccine strain as passaged in eggs and with HA1 sequence identical to the A/Victoria/361/2011 IVR-165 egg-adapted high growth reassortant vaccine strain; assessed based on guinea pig erythrocytes.</p>c<p>. Nineteen of the 129 viruses (19%) manifesting ≥8-fold reduction had been collected from vaccinated participants, comparable to the proportion immunized among H3 detections overall (17%) and among whom 12/19 (63%) showed 16-fold and 4/19 (21%) showed 32-fold reduction.</p>d<p>. 2012–13 TIV component.</p>e<p>. 2011–12 TIV component.</p>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "epidemiology", "Infectious disease epidemiology", "Infectious diseases", "Viral diseases", "influenza", "Public and occupational health", "sentinel"], "article_id"=>973214, "categories"=>["Biological Sciences"], "users"=>["Danuta M. Skowronski", "Naveed Z. Janjua", "Gaston De Serres", "Suzana Sabaiduc", "AliReza Eshaghi", "James A. Dickinson", "Kevin Fonseca", "Anne-Luise Winter", "Jonathan B. Gubbay", "Mel Krajden", "Martin Petric", "Hugues Charest", "Nathalie Bastien", "Trijntje L. Kwindt", "Salaheddin M. Mahmud", "Paul Van Caeseele", "Yan Li"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0092153.t002", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Laboratory_profile_2012_8211_13_sentinel_season_/973214", "title"=>"Laboratory profile, 2012–13 sentinel season.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-03-25 02:54:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1433824"], "description"=>"<p>NOTE: exclusions shown here in stepwise fashion to arrive at total case and control tally (i.e. those meeting multiple exclusion criteria are counted on the basis of the first exclusion criterion met in the list shown). Missing collection dates were imputed as the laboratory accession date minus two days, the average time period between collection date and laboratory accession date for records with valid data for both fields.</p>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "epidemiology", "Infectious disease epidemiology", "Infectious diseases", "Viral diseases", "influenza", "Public and occupational health", "exclusion", "sentinel"], "article_id"=>973211, "categories"=>["Biological Sciences"], "users"=>["Danuta M. Skowronski", "Naveed Z. Janjua", "Gaston De Serres", "Suzana Sabaiduc", "AliReza Eshaghi", "James A. Dickinson", "Kevin Fonseca", "Anne-Luise Winter", "Jonathan B. Gubbay", "Mel Krajden", "Martin Petric", "Hugues Charest", "Nathalie Bastien", "Trijntje L. Kwindt", "Salaheddin M. Mahmud", "Paul Van Caeseele", "Yan Li"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0092153.g001", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Specimen_exclusion_for_influenza_vaccine_effectiveness_analysis_Canada_2012_8211_13_sentinel_surveillance_system_/973211", "title"=>"Specimen exclusion for influenza vaccine effectiveness analysis, Canada, 2012–13 sentinel surveillance system.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-25 02:54:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1433832", "https://ndownloader.figshare.com/files/1433833", "https://ndownloader.figshare.com/files/1433834", "https://ndownloader.figshare.com/files/1433835", "https://ndownloader.figshare.com/files/1433836", "https://ndownloader.figshare.com/files/1433837", "https://ndownloader.figshare.com/files/1433838", "https://ndownloader.figshare.com/files/1433839", "https://ndownloader.figshare.com/files/1433840"], "description"=>"<div><p>Background</p><p>Influenza vaccine effectiveness (VE) is generally interpreted in the context of vaccine match/mismatch to circulating strains with evolutionary drift in the latter invoked to explain reduced protection. During the 2012–13 season, however, detailed genotypic and phenotypic characterization shows that low VE was instead related to mutations in the egg-adapted H3N2 vaccine strain rather than antigenic drift in circulating viruses.</p><p>Methods/Findings</p><p>Component-specific VE against medically-attended, PCR-confirmed influenza was estimated in Canada by test-negative case-control design. Influenza A viruses were characterized genotypically by amino acid (AA) sequencing of established haemagglutinin (HA) antigenic sites and phenotypically through haemagglutination inhibition (HI) assay. H3N2 viruses were characterized in relation to the WHO-recommended, cell-passaged vaccine prototype (A/Victoria/361/2011) as well as the egg-adapted strain as per actually used in vaccine production. Among the total of 1501 participants, influenza virus was detected in 652 (43%). Nearly two-thirds of viruses typed/subtyped were A(H3N2) (394/626; 63%); the remainder were A(H1N1)pdm09 (79/626; 13%), B/Yamagata (98/626; 16%) or B/Victoria (54/626; 9%). Suboptimal VE of 50% (95%CI: 33–63%) overall was driven by predominant H3N2 activity for which VE was 41% (95%CI: 17–59%). All H3N2 field isolates were HI-characterized as well-matched to the WHO-recommended A/Victoria/361/2011 prototype whereas all but one were antigenically distinct from the egg-adapted strain as per actually used in vaccine production. The egg-adapted strain was itself antigenically distinct from the WHO-recommended prototype, and bore three AA mutations at antigenic sites B [H156Q, G186V] and D [S219Y]. Conversely, circulating viruses were identical to the WHO-recommended prototype at these positions with other genetic variation that did not affect antigenicity. VE was 59% (95%CI:16–80%) against A(H1N1)pdm09, 67% (95%CI: 30–85%) against B/Yamagata (vaccine-lineage) and 75% (95%CI: 29–91%) against B/Victoria (non-vaccine-lineage) viruses.</p><p>Conclusions</p><p>These findings underscore the need to monitor vaccine viruses as well as circulating strains to explain vaccine performance. Evolutionary drift in circulating viruses cannot be regulated, but influential mutations introduced as part of egg-based vaccine production may be amenable to improvements.</p></div>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "epidemiology", "Infectious disease epidemiology", "Infectious diseases", "Viral diseases", "influenza", "Public and occupational health", "mutation", "egg-adapted", "h3n2", "antigenic", "circulating"], "article_id"=>973219, "categories"=>["Biological Sciences"], "users"=>["Danuta M. Skowronski", "Naveed Z. Janjua", "Gaston De Serres", "Suzana Sabaiduc", "AliReza Eshaghi", "James A. Dickinson", "Kevin Fonseca", "Anne-Luise Winter", "Jonathan B. Gubbay", "Mel Krajden", "Martin Petric", "Hugues Charest", "Nathalie Bastien", "Trijntje L. Kwindt", "Salaheddin M. Mahmud", "Paul Van Caeseele", "Yan Li"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0092153.s001", "https://dx.doi.org/10.1371/journal.pone.0092153.s002", "https://dx.doi.org/10.1371/journal.pone.0092153.s003", "https://dx.doi.org/10.1371/journal.pone.0092153.s004", "https://dx.doi.org/10.1371/journal.pone.0092153.s005", "https://dx.doi.org/10.1371/journal.pone.0092153.s006", "https://dx.doi.org/10.1371/journal.pone.0092153.s007", "https://dx.doi.org/10.1371/journal.pone.0092153.s008", "https://dx.doi.org/10.1371/journal.pone.0092153.s009"], "stats"=>{"downloads"=>30, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Low_2012_8211_13_Influenza_Vaccine_Effectiveness_Associated_with_Mutation_in_the_Egg_Adapted_H3N2_Vaccine_Strain_Not_Antigenic_Drift_in_Circulating_Viruses_/973219", "title"=>"Low 2012–13 Influenza Vaccine Effectiveness Associated with Mutation in the Egg-Adapted H3N2 Vaccine Strain Not Antigenic Drift in Circulating Viruses", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-03-25 02:54:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1433831"], "description"=>"<p>HA1 = haemagglutinin 1 protein.</p><p>Mutations are highlighted in bold in the first row that they are represented in the table.</p><p>HA1 antigenic site positions [A–E] affected are annotated in bold the first time they appear.</p><p>“(x n)” following a specified amino acid residue indicates the number of viruses with that specific mutation.</p>a<p>. The 2012–13 egg-passaged H3N2 strain used in haemagglutination inhibition (HI) assay was identical in its HA1 to the egg-adapted A/Victoria/361/2011-IVR-165 high growth reassortant vaccine strain.</p>b<p>. In addition to the 3 AA differences (at positions 156, 186, and 219) present in the egg-passaged H3N2 strain used in the HI assay and the egg-adapted A/Victoria/361/2011 IVR-165 high growth reassortant vaccine strain.</p>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "epidemiology", "Infectious disease epidemiology", "Infectious diseases", "Viral diseases", "influenza", "Public and occupational health", "fold-reduction", "haemagglutination", "inhibition", "titres", "egg-passaged", "h3n2", "amino", "mutations", "ha1", "antigenic", "sites", "circulating"], "article_id"=>973218, "categories"=>["Biological Sciences"], "users"=>["Danuta M. Skowronski", "Naveed Z. Janjua", "Gaston De Serres", "Suzana Sabaiduc", "AliReza Eshaghi", "James A. Dickinson", "Kevin Fonseca", "Anne-Luise Winter", "Jonathan B. Gubbay", "Mel Krajden", "Martin Petric", "Hugues Charest", "Nathalie Bastien", "Trijntje L. Kwindt", "Salaheddin M. Mahmud", "Paul Van Caeseele", "Yan Li"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0092153.t005", "stats"=>{"downloads"=>2, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Distribution_of_fold_reduction_in_haemagglutination_inhibition_HI_titres_relative_to_the_2012_8211_13_egg_passaged_H3N2_strain_by_nature_and_location_of_additional_amino_acid_AA_mutations_present_in_HA1_antigenic_sites_of_circulating_viruses_/973218", "title"=>"Distribution of fold-reduction in haemagglutination inhibition (HI) titres relative to the 2012–13 egg-passaged H3N2 strain by nature and location of additional amino acid (AA) mutations present in HA1 antigenic sites of circulating viruses.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-03-25 02:54:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1433826"], "description"=>"<p>One HA1 monomer is shown with five previously defined antigenic site residues of A–E colored in light green, dark green, light blue, dark blue and purple, respectively, mapped onto a related crystal structure (A/X-31(H3N2), PDB, 1HGG) <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0092153#pone.0092153-Sauter1\" target=\"_blank\">[27]</a> using PyMOL <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0092153#pone.0092153-The1\" target=\"_blank\">[28]</a>. The most prevalent antigenic site amino acid differences between circulating clade 3C viruses in Canada relative to the egg-adapted A/Victoria/361/2011 IVR-165 vaccine reassortant strain are shown in red and labelled with coloured font representing their antigenic sites, viewed from the front (A) or side (B). Three amino acid differences (Q156H, V186G and Y219S) are owing to mutation in the egg-adapted IVR-165 vaccine strain rather than circulating viruses which instead share identity with the MDCK-passaged WHO reference prototype at these positions. RBS indicates approximate location of the receptor-binding site.</p>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "epidemiology", "Infectious disease epidemiology", "Infectious diseases", "Viral diseases", "influenza", "Public and occupational health", "antigenic-site", "differences", "circulating", "h3n2", "viruses", "egg-adapted", "ivr-165", "reassortant"], "article_id"=>973213, "categories"=>["Biological Sciences"], "users"=>["Danuta M. Skowronski", "Naveed Z. Janjua", "Gaston De Serres", "Suzana Sabaiduc", "AliReza Eshaghi", "James A. Dickinson", "Kevin Fonseca", "Anne-Luise Winter", "Jonathan B. Gubbay", "Mel Krajden", "Martin Petric", "Hugues Charest", "Nathalie Bastien", "Trijntje L. Kwindt", "Salaheddin M. Mahmud", "Paul Van Caeseele", "Yan Li"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0092153.g003", "stats"=>{"downloads"=>3, "page_views"=>32, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Three_dimensional_model_of_antigenic_site_differences_between_circulating_H3N2_viruses_and_the_2012_8211_13_egg_adapted_A_Victoria_361_2011_IVR_165_high_growth_reassortant_vaccine_strain_/973213", "title"=>"Three-dimensional model of antigenic-site differences between circulating H3N2 viruses and the 2012–13 egg-adapted A/Victoria/361/2011 IVR-165 high growth reassortant vaccine strain.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-25 02:54:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1433825"], "description"=>"<p>NOTE: excludes specimens from patients failing to meet the influenza-like illness case definition or unknown; specimens collected >7 days after influenza-like illness onset or interval unknown; comorbidity unknown; age unknown or <1 year and influenza test results unavailable or inconclusive on typing. Missing collection dates were imputed as the laboratory accession date minus two days, the average time period between collection date and laboratory accession date for records with valid data for both fields. One specimen diagnosed with both A/H3N2 and A(H1N1)pdm09 in week 2 is not presented in the graph. Vaccine effectiveness analysis spans week 44 to week 18.</p>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "epidemiology", "Infectious disease epidemiology", "Infectious diseases", "Viral diseases", "influenza", "Public and occupational health", "specimens", "sentinel"], "article_id"=>973212, "categories"=>["Biological Sciences"], "users"=>["Danuta M. Skowronski", "Naveed Z. Janjua", "Gaston De Serres", "Suzana Sabaiduc", "AliReza Eshaghi", "James A. Dickinson", "Kevin Fonseca", "Anne-Luise Winter", "Jonathan B. Gubbay", "Mel Krajden", "Martin Petric", "Hugues Charest", "Nathalie Bastien", "Trijntje L. Kwindt", "Salaheddin M. Mahmud", "Paul Van Caeseele", "Yan Li"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0092153.g002", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Influenza_specimens_by_week_and_subtype_2012_8211_13_sentinel_surveillance_period_N_8202_8202_1682_/973212", "title"=>"Influenza specimens by week and subtype, 2012–13 sentinel surveillance period (N = 1682).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-25 02:54:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1433830"], "description"=>"<p>N = number of sentinel viruses with that sequence. Bold font signifies amino acid (AA) substitutions compared with IVR-165. Clade designation, number of antigenic site differences and percent antigenic site pairwise identity are also displayed. Only the 31/131 antigenic site positions showing differences between circulating H3N2 viruses and IVR-165 are displayed. AA sequences at those positions for other recent vaccine viruses are also displayed.</p>a<p>. IVR-165 is the egg-adapted high growth reassortant strain substituted by manufacturers for the MDCK-passaged A/Victoria/361/2011 (H3N2) prototype virus recommended as 2012–13 vaccine component by the World Health Organization (WHO) designated here as A/Victoria/361/2011 (MDCK).</p>b<p>. Number of antigenic site AA differences and percent antigenic site identity relative to IVR-165. Percent identity derived as per <b><a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0092153#pone.0092153.s009\" target=\"_blank\">Text S1</a></b>.</p>c<p>. A/Victoria/210/2009 (X-187) is the egg-adapted high growth reassortant strain used by manufacturers for the 2011–12 influenza vaccine for the northern hemisphere., shown for historic comparison.</p>d<p>. A/Texas/50/2012 (MDCK) and (X-223) are the WHO-recommended prototype and egg-adapted high growth reassortant strains, respectively, for the 2013–14 influenza vaccine for the northern hemisphere, shown for added comparison.</p>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "epidemiology", "Infectious disease epidemiology", "Infectious diseases", "Viral diseases", "influenza", "Public and occupational health", "antigenic", "differences", "circulating", "h3n2", "viruses", "egg-adapted", "reassortant"], "article_id"=>973217, "categories"=>["Biological Sciences"], "users"=>["Danuta M. Skowronski", "Naveed Z. Janjua", "Gaston De Serres", "Suzana Sabaiduc", "AliReza Eshaghi", "James A. Dickinson", "Kevin Fonseca", "Anne-Luise Winter", "Jonathan B. Gubbay", "Mel Krajden", "Martin Petric", "Hugues Charest", "Nathalie Bastien", "Trijntje L. Kwindt", "Salaheddin M. Mahmud", "Paul Van Caeseele", "Yan Li"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0092153.t004", "stats"=>{"downloads"=>2, "page_views"=>30, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Haemagglutinin_antigenic_site_differences_in_circulating_H3N2_viruses_relative_to_the_2012_13_egg_adapted_A_Victoria_361_2011_IVR_165_a_high_growth_reassortant_vaccine_strain_/973217", "title"=>"Haemagglutinin antigenic site differences in circulating H3N2 viruses relative to the 2012–13 egg-adapted A/Victoria/361/2011 IVR-165<sup>a</sup> high growth reassortant vaccine strain.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-03-25 02:54:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1433828"], "description"=>"<p>BC = British Columbia, AB = Alberta, MB = Manitoba, ON = Ontario, QC = Québec; d = days; NE = not estimable owing to sparse data.</p>a<p>. Adjusted for age (1–8, 9–19, 20–49, ≥50 years), province, interval, week.</p>b<p>. Adjusted for age (1–8, 9–19 years), comorbidity, province, interval, week; except B/Yamagata not adjusted for province.</p>c<p>. Adjusted for comorbidity, province, interval, week; except B/Victoria not adjusted for province.</p>d<p>. Adjusted for age (50–64, ≥65 years), province, interval, week; except A(H1N1)pdm09, influenza B, B/Victoria, B/Yamagata not adjusted for province.</p>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "epidemiology", "Infectious disease epidemiology", "Infectious diseases", "Viral diseases", "influenza", "Public and occupational health", "restricted", "sentinel", "canada"], "article_id"=>973215, "categories"=>["Biological Sciences"], "users"=>["Danuta M. Skowronski", "Naveed Z. Janjua", "Gaston De Serres", "Suzana Sabaiduc", "AliReza Eshaghi", "James A. Dickinson", "Kevin Fonseca", "Anne-Luise Winter", "Jonathan B. Gubbay", "Mel Krajden", "Martin Petric", "Hugues Charest", "Nathalie Bastien", "Trijntje L. Kwindt", "Salaheddin M. Mahmud", "Paul Van Caeseele", "Yan Li"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0092153.t003", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Primary_and_restricted_analysis_influenza_vaccine_effectiveness_based_on_sentinel_system_in_Canada_2012_8211_13_season_/973215", "title"=>"Primary and restricted analysis - influenza vaccine effectiveness based on sentinel system in Canada 2012–13 season.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-03-25 02:54:03"}
PMC Usage Stats 189317 Apr 18:06 UTC

PMC Usage Stats | Further Information

  • {"unique-ip"=>"8", "full-text"=>"6", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2014", "month"=>"3"}
  • {"unique-ip"=>"27", "full-text"=>"24", "pdf"=>"26", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2014", "month"=>"5"}
  • {"unique-ip"=>"21", "full-text"=>"22", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"6"}
  • {"unique-ip"=>"60", "full-text"=>"69", "pdf"=>"34", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"12", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2014", "month"=>"4"}
  • {"unique-ip"=>"30", "full-text"=>"33", "pdf"=>"20", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"9", "cited-by"=>"0", "year"=>"2015", "month"=>"4"}
  • {"unique-ip"=>"18", "full-text"=>"22", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2015", "month"=>"5"}
  • {"unique-ip"=>"17", "full-text"=>"20", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2015", "month"=>"6"}
  • {"unique-ip"=>"24", "full-text"=>"23", "pdf"=>"13", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"12", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"7"}
  • {"unique-ip"=>"32", "full-text"=>"36", "pdf"=>"27", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2015", "month"=>"3"}
  • {"unique-ip"=>"28", "full-text"=>"44", "pdf"=>"14", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"8", "cited-by"=>"0", "year"=>"2015", "month"=>"2"}
  • {"unique-ip"=>"29", "full-text"=>"36", "pdf"=>"14", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"8"}
  • {"unique-ip"=>"31", "full-text"=>"27", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"8", "cited-by"=>"0", "year"=>"2015", "month"=>"9"}
  • {"unique-ip"=>"38", "full-text"=>"48", "pdf"=>"14", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"6", "cited-by"=>"0", "year"=>"2015", "month"=>"10"}
  • {"unique-ip"=>"31", "full-text"=>"24", "pdf"=>"15", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2014", "month"=>"7"}
  • {"unique-ip"=>"23", "full-text"=>"18", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2014", "month"=>"8"}
  • {"unique-ip"=>"28", "full-text"=>"22", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2014", "month"=>"9"}
  • {"unique-ip"=>"29", "full-text"=>"33", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2014", "month"=>"10"}
  • {"unique-ip"=>"25", "full-text"=>"27", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"11", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"27", "full-text"=>"32", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2014", "month"=>"11"}
  • {"unique-ip"=>"26", "full-text"=>"22", "pdf"=>"16", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"8", "cited-by"=>"0", "year"=>"2014", "month"=>"12"}
  • {"unique-ip"=>"37", "full-text"=>"35", "pdf"=>"19", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"21", "cited-by"=>"0", "year"=>"2015", "month"=>"1"}
  • {"unique-ip"=>"42", "full-text"=>"34", "pdf"=>"17", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"11"}
  • {"unique-ip"=>"43", "full-text"=>"49", "pdf"=>"16", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
  • {"unique-ip"=>"32", "full-text"=>"35", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
  • {"unique-ip"=>"37", "full-text"=>"40", "pdf"=>"12", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
  • {"unique-ip"=>"22", "full-text"=>"33", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"11", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
  • {"unique-ip"=>"19", "full-text"=>"23", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
  • {"unique-ip"=>"25", "full-text"=>"23", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"27", "full-text"=>"31", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"20", "full-text"=>"18", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"23", "full-text"=>"21", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"19", "full-text"=>"18", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"20", "full-text"=>"19", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"18", "full-text"=>"15", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"25", "full-text"=>"20", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2017", "month"=>"1"}
  • {"unique-ip"=>"17", "full-text"=>"15", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
  • {"unique-ip"=>"13", "full-text"=>"17", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"12", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
  • {"unique-ip"=>"10", "full-text"=>"11", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
  • {"unique-ip"=>"16", "full-text"=>"16", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"20", "full-text"=>"20", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"10", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"17", "full-text"=>"19", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"22", "full-text"=>"24", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"15", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"25", "full-text"=>"23", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"25", "full-text"=>"26", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"7", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"64", "full-text"=>"99", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
  • {"unique-ip"=>"12", "full-text"=>"13", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"24", "full-text"=>"25", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"2"}
  • {"unique-ip"=>"60", "full-text"=>"74", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
Relative Metric 330606 Apr 06:40 UTC

Relative Metric

{"start_date"=>"2014-01-01T00:00:00Z", "end_date"=>"2014-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[291]}, {"subject_area"=>"/Biology and life sciences/Biochemistry", "average_usage"=>[282]}, {"subject_area"=>"/Biology and life sciences/Microbiology", "average_usage"=>[317]}, {"subject_area"=>"/Biology and life sciences/Organisms", "average_usage"=>[310]}, {"subject_area"=>"/Engineering and technology", "average_usage"=>[282]}, {"subject_area"=>"/Engineering and technology/Technology development", "average_usage"=>[394, 576]}, {"subject_area"=>"/Medicine and health sciences/Immunology", "average_usage"=>[289]}, {"subject_area"=>"/Medicine and health sciences/Pathology and laboratory medicine", "average_usage"=>[287]}, {"subject_area"=>"/Medicine and health sciences/Physiology", "average_usage"=>[278]}]}
Loading … Spinner
There are currently no alerts