Efficacy and safety of the RTS,S/AS01 malaria vaccine during 18 months after vaccination: a phase 3 randomized, controlled trial in children and young infants at 11 African sites
A malaria vaccine could be an important addition to current control strategies. We report the safety and vaccine efficacy (VE) of the RTS,S/AS01 vaccine during 18 mo following vaccination at 11 African sites with varying malaria transmission. 6,537 infants aged 6-12 wk and 8,923 children aged 5-17 m...
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| description | A malaria vaccine could be an important addition to current control strategies. We report the safety and vaccine efficacy (VE) of the RTS,S/AS01 vaccine during 18 mo following vaccination at 11 African sites with varying malaria transmission.
6,537 infants aged 6-12 wk and 8,923 children aged 5-17 mo were randomized to receive three doses of RTS,S/AS01 or comparator vaccine. VE against clinical malaria in children during the 18 mo after vaccine dose 3 (per protocol) was 46% (95% CI 42% to 50%) (range 40% to 77%; VE, p |
| doi_str_mv | 10.1371/journal.pmed.1001685 |
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6,537 infants aged 6-12 wk and 8,923 children aged 5-17 mo were randomized to receive three doses of RTS,S/AS01 or comparator vaccine. VE against clinical malaria in children during the 18 mo after vaccine dose 3 (per protocol) was 46% (95% CI 42% to 50%) (range 40% to 77%; VE, p<0.01 across all sites). VE during the 20 mo after vaccine dose 1 (intention to treat [ITT]) was 45% (95% CI 41% to 49%). VE against severe malaria, malaria hospitalization, and all-cause hospitalization was 34% (95% CI 15% to 48%), 41% (95% CI 30% to 50%), and 19% (95% CI 11% to 27%), respectively (ITT). VE against clinical malaria in infants was 27% (95% CI 20% to 32%, per protocol; 27% [95% CI 21% to 33%], ITT), with no significant protection against severe malaria, malaria hospitalization, or all-cause hospitalization. Post-vaccination anti-circumsporozoite antibody geometric mean titer varied from 348 to 787 EU/ml across sites in children and from 117 to 335 EU/ml in infants (per protocol). VE waned over time in both age categories (Schoenfeld residuals p<0.001). The number of clinical and severe malaria cases averted per 1,000 children vaccinated ranged across sites from 37 to 2,365 and from -1 to 49, respectively; corresponding ranges among infants were -10 to 1,402 and -13 to 37, respectively (ITT). Meningitis was reported as a serious adverse event in 16/5,949 and 1/2,974 children and in 9/4,358 and 3/2,179 infants in the RTS,S/AS01 and control groups, respectively.
RTS,S/AS01 prevented many cases of clinical and severe malaria over the 18 mo after vaccine dose 3, with the highest impact in areas with the greatest malaria incidence. VE was higher in children than in infants, but even at modest levels of VE, the number of malaria cases averted was substantial. RTS,S/AS01 could be an important addition to current malaria control in Africa.
www.ClinicalTrials.gov NCT00866619 Please see later in the article for the Editors' Summary.</description><identifier>ISSN: 1549-1676</identifier><identifier>ISSN: 1549-1277</identifier><identifier>EISSN: 1549-1676</identifier><identifier>DOI: 10.1371/journal.pmed.1001685</identifier><identifier>PMID: 25072396</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Africa South of the Sahara - epidemiology ; Analysis ; Biology and Life Sciences ; Clinical trials ; Complications and side effects ; Health aspects ; Humans ; Immunization ; Incidence ; Infant ; Infants ; Infants (Newborn) ; Malaria ; Malaria vaccine ; Malaria Vaccines - administration & dosage ; Malaria Vaccines - adverse effects ; Malaria Vaccines - immunology ; Malaria, Falciparum - epidemiology ; Malaria, Falciparum - prevention & control ; Medicine and Health Sciences ; Parasites ; Plasmodium falciparum - immunology ; Prevalence ; Prevention ; Risk factors ; Vaccination - standards ; Vaccines</subject><ispartof>PLoS medicine, 2014-07, Vol.11 (7), p.e1001685</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014</rights><rights>2014 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: The RTS,S Clinical Trials Partnership (2014) (2014) Efficacy and Safety of the RTS,S/AS01 Malaria Vaccine during 18 Months after Vaccination: A Phase 3 Randomized, Controlled Trial in Children and Young Infants at 11 African Sites. PLoS Med 11(7): e1001685. doi:10.1371/journal.pmed.1001685</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c839t-c066b89066212c2aba65b77da432773b788f7693630d76ca91996b2141dab36f3</citedby><cites>FETCH-LOGICAL-c839t-c066b89066212c2aba65b77da432773b788f7693630d76ca91996b2141dab36f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4114488/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4114488/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25072396$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Krishna, Sanjeev</contributor><creatorcontrib>Anon</creatorcontrib><creatorcontrib>RTS,S Clinical Trials Partnership</creatorcontrib><creatorcontrib>The RTS,S Clinical Trials Partnership</creatorcontrib><title>Efficacy and safety of the RTS,S/AS01 malaria vaccine during 18 months after vaccination: a phase 3 randomized, controlled trial in children and young infants at 11 African sites</title><title>PLoS medicine</title><addtitle>PLoS Med</addtitle><description>A malaria vaccine could be an important addition to current control strategies. We report the safety and vaccine efficacy (VE) of the RTS,S/AS01 vaccine during 18 mo following vaccination at 11 African sites with varying malaria transmission.
6,537 infants aged 6-12 wk and 8,923 children aged 5-17 mo were randomized to receive three doses of RTS,S/AS01 or comparator vaccine. VE against clinical malaria in children during the 18 mo after vaccine dose 3 (per protocol) was 46% (95% CI 42% to 50%) (range 40% to 77%; VE, p<0.01 across all sites). VE during the 20 mo after vaccine dose 1 (intention to treat [ITT]) was 45% (95% CI 41% to 49%). VE against severe malaria, malaria hospitalization, and all-cause hospitalization was 34% (95% CI 15% to 48%), 41% (95% CI 30% to 50%), and 19% (95% CI 11% to 27%), respectively (ITT). VE against clinical malaria in infants was 27% (95% CI 20% to 32%, per protocol; 27% [95% CI 21% to 33%], ITT), with no significant protection against severe malaria, malaria hospitalization, or all-cause hospitalization. Post-vaccination anti-circumsporozoite antibody geometric mean titer varied from 348 to 787 EU/ml across sites in children and from 117 to 335 EU/ml in infants (per protocol). VE waned over time in both age categories (Schoenfeld residuals p<0.001). The number of clinical and severe malaria cases averted per 1,000 children vaccinated ranged across sites from 37 to 2,365 and from -1 to 49, respectively; corresponding ranges among infants were -10 to 1,402 and -13 to 37, respectively (ITT). Meningitis was reported as a serious adverse event in 16/5,949 and 1/2,974 children and in 9/4,358 and 3/2,179 infants in the RTS,S/AS01 and control groups, respectively.
RTS,S/AS01 prevented many cases of clinical and severe malaria over the 18 mo after vaccine dose 3, with the highest impact in areas with the greatest malaria incidence. VE was higher in children than in infants, but even at modest levels of VE, the number of malaria cases averted was substantial. RTS,S/AS01 could be an important addition to current malaria control in Africa.
www.ClinicalTrials.gov NCT00866619 Please see later in the article for the Editors' Summary.</description><subject>Africa South of the Sahara - epidemiology</subject><subject>Analysis</subject><subject>Biology and Life Sciences</subject><subject>Clinical trials</subject><subject>Complications and side effects</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Immunization</subject><subject>Incidence</subject><subject>Infant</subject><subject>Infants</subject><subject>Infants (Newborn)</subject><subject>Malaria</subject><subject>Malaria vaccine</subject><subject>Malaria Vaccines - administration & dosage</subject><subject>Malaria Vaccines - adverse effects</subject><subject>Malaria Vaccines - immunology</subject><subject>Malaria, Falciparum - epidemiology</subject><subject>Malaria, Falciparum - prevention & control</subject><subject>Medicine and Health Sciences</subject><subject>Parasites</subject><subject>Plasmodium falciparum - immunology</subject><subject>Prevalence</subject><subject>Prevention</subject><subject>Risk factors</subject><subject>Vaccination - standards</subject><subject>Vaccines</subject><issn>1549-1676</issn><issn>1549-1277</issn><issn>1549-1676</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNqVk91qFDEUxwdRbK2-gWhAEIXuNpnMJhMvhKVULRQL3eptOJNJdlOyyTaZKa6P5ROa6W5LF3qhDGRC8jv_c3I-iuI1wWNCOTm6Cn304MarpW7HBGPC6smTYp9MKjEijLOnD_Z7xYuUrjAuBRb4ebFXTjAvqWD7xZ8TY6wCtUbgW5TA6G6NgkHdQqOLy9nh7Gg6wwQtwUG0gG5AKes1avto_RyRGi2D7xYJgel03F5DZ4P_hACtFpA0oihm7bC0v3V7iFTmY3BOt6jLig5Zj9TCujZqfxvDOvRZ2XoDvsu6HSIETU3MQXqUbKfTy-KZAZf0q-3_oPjx5eTy-Nvo7Pzr6fH0bKRqKrqRwow1tchrSUpVQgNs0nDeQkVLzmnD69pwJiijuOVMgSBCsKYkFWmhoczQg-LtRnflQpLbdCc55JlyTjjJxOmGaANcyVW0S4hrGcDK24MQ5xJiZ5XTEovshAuFG1NXDakFBaaqyjBalroqB2-ft976JldU6ZwmcDuiuzfeLuQ83MiKkKqq6yzwYSsQw3WvUyeXNintHHgd-hz3hGFCa8xwRt9t0Dnk0HKqQ1ZUAy6ntC7FhOD8xoNi9Ag1115n98FrY_PxDj9-hM9fq5dWPWrwccdgaA39q5tDn5I8nV38B_v939nzn7vs-wfsQoPL3RxcP7Rw2gWrDahiSClqc18aguUwkHcdIoeBlNuBzGZvHpb13uhuAulfW9YuiA</recordid><startdate>20140701</startdate><enddate>20140701</enddate><creator>Anon</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISN</scope><scope>ISR</scope><scope>C1K</scope><scope>F1W</scope><scope>H95</scope><scope>H97</scope><scope>L.G</scope><scope>M7N</scope><scope>5PM</scope><scope>DOA</scope><scope>CZK</scope></search><sort><creationdate>20140701</creationdate><title>Efficacy and safety of the RTS,S/AS01 malaria vaccine during 18 months after vaccination: a phase 3 randomized, controlled trial in children and young infants at 11 African sites</title><author>Anon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c839t-c066b89066212c2aba65b77da432773b788f7693630d76ca91996b2141dab36f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Africa South of the Sahara - epidemiology</topic><topic>Analysis</topic><topic>Biology and Life Sciences</topic><topic>Clinical trials</topic><topic>Complications and side effects</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Immunization</topic><topic>Incidence</topic><topic>Infant</topic><topic>Infants</topic><topic>Infants (Newborn)</topic><topic>Malaria</topic><topic>Malaria vaccine</topic><topic>Malaria Vaccines - administration & dosage</topic><topic>Malaria Vaccines - adverse effects</topic><topic>Malaria Vaccines - immunology</topic><topic>Malaria, Falciparum - epidemiology</topic><topic>Malaria, Falciparum - prevention & control</topic><topic>Medicine and Health Sciences</topic><topic>Parasites</topic><topic>Plasmodium falciparum - immunology</topic><topic>Prevalence</topic><topic>Prevention</topic><topic>Risk factors</topic><topic>Vaccination - standards</topic><topic>Vaccines</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Anon</creatorcontrib><creatorcontrib>RTS,S Clinical Trials Partnership</creatorcontrib><creatorcontrib>The RTS,S Clinical Trials Partnership</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 3: Aquatic Pollution & Environmental Quality</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><collection>PLoS Medicine</collection><jtitle>PLoS medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Anon</au><au>Krishna, Sanjeev</au><aucorp>RTS,S Clinical Trials Partnership</aucorp><aucorp>The RTS,S Clinical Trials Partnership</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy and safety of the RTS,S/AS01 malaria vaccine during 18 months after vaccination: a phase 3 randomized, controlled trial in children and young infants at 11 African sites</atitle><jtitle>PLoS medicine</jtitle><addtitle>PLoS Med</addtitle><date>2014-07-01</date><risdate>2014</risdate><volume>11</volume><issue>7</issue><spage>e1001685</spage><pages>e1001685-</pages><issn>1549-1676</issn><issn>1549-1277</issn><eissn>1549-1676</eissn><abstract>A malaria vaccine could be an important addition to current control strategies. We report the safety and vaccine efficacy (VE) of the RTS,S/AS01 vaccine during 18 mo following vaccination at 11 African sites with varying malaria transmission.
6,537 infants aged 6-12 wk and 8,923 children aged 5-17 mo were randomized to receive three doses of RTS,S/AS01 or comparator vaccine. VE against clinical malaria in children during the 18 mo after vaccine dose 3 (per protocol) was 46% (95% CI 42% to 50%) (range 40% to 77%; VE, p<0.01 across all sites). VE during the 20 mo after vaccine dose 1 (intention to treat [ITT]) was 45% (95% CI 41% to 49%). VE against severe malaria, malaria hospitalization, and all-cause hospitalization was 34% (95% CI 15% to 48%), 41% (95% CI 30% to 50%), and 19% (95% CI 11% to 27%), respectively (ITT). VE against clinical malaria in infants was 27% (95% CI 20% to 32%, per protocol; 27% [95% CI 21% to 33%], ITT), with no significant protection against severe malaria, malaria hospitalization, or all-cause hospitalization. Post-vaccination anti-circumsporozoite antibody geometric mean titer varied from 348 to 787 EU/ml across sites in children and from 117 to 335 EU/ml in infants (per protocol). VE waned over time in both age categories (Schoenfeld residuals p<0.001). The number of clinical and severe malaria cases averted per 1,000 children vaccinated ranged across sites from 37 to 2,365 and from -1 to 49, respectively; corresponding ranges among infants were -10 to 1,402 and -13 to 37, respectively (ITT). Meningitis was reported as a serious adverse event in 16/5,949 and 1/2,974 children and in 9/4,358 and 3/2,179 infants in the RTS,S/AS01 and control groups, respectively.
RTS,S/AS01 prevented many cases of clinical and severe malaria over the 18 mo after vaccine dose 3, with the highest impact in areas with the greatest malaria incidence. VE was higher in children than in infants, but even at modest levels of VE, the number of malaria cases averted was substantial. RTS,S/AS01 could be an important addition to current malaria control in Africa.
www.ClinicalTrials.gov NCT00866619 Please see later in the article for the Editors' Summary.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25072396</pmid><doi>10.1371/journal.pmed.1001685</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Africa South of the Sahara - epidemiology Analysis Biology and Life Sciences Clinical trials Complications and side effects Health aspects Humans Immunization Incidence Infant Infants Infants (Newborn) Malaria Malaria vaccine Malaria Vaccines - administration & dosage Malaria Vaccines - adverse effects Malaria Vaccines - immunology Malaria, Falciparum - epidemiology Malaria, Falciparum - prevention & control Medicine and Health Sciences Parasites Plasmodium falciparum - immunology Prevalence Prevention Risk factors Vaccination - standards Vaccines |
| title | Efficacy and safety of the RTS,S/AS01 malaria vaccine during 18 months after vaccination: a phase 3 randomized, controlled trial in children and young infants at 11 African sites |
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