{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:07:01Z","timestamp":1772168821767,"version":"3.50.1"},"reference-count":46,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2018,2,23]],"date-time":"2018-02-23T00:00:00Z","timestamp":1519344000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"VALIDATE Network"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>A high burden of TB mortality persists despite the long-term availability of the bacillus Calmette-Gu\u00e9rin (BCG) vaccine, whose efficacy has been highly variable across populations. Innovative and alternative approaches to TB prevention are urgently needed while optimal biomedical tools continue to be developed. We call for new interdisciplinary collaborations to expand and integrate our understanding of how social determinants influence the biological processes that lead to TB disease, how this translates into differential BCG efficacy and, ultimately, how social protection interventions can play a role in reducing the global burden of TB. After providing an overview of the immune pathways important for the establishment of a response to the BCG vaccine, we outline how social determinants and psychosocial stressors can contribute to the observed variation in BCG efficacy above and beyond these biological factors. We conclude by proposing a new interdisciplinary research model based on the integration of social epidemiology theories with biomedical knowledge.<\/ns4:p>","DOI":"10.12688\/f1000research.14085.1","type":"journal-article","created":{"date-parts":[[2018,2,23]],"date-time":"2018-02-23T09:15:11Z","timestamp":1519377311000},"page":"224","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Social determinants and BCG efficacy: a call for a socio-biological approach to TB prevention"],"prefix":"10.12688","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2006-5656","authenticated-orcid":false,"given":"Jennifer B.","family":"Dowd","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0435-1006","authenticated-orcid":false,"given":"Helen 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A quasi-experimental investigation of Mexico\u2019s Oportunidades programme.","volume":"40","author":"E Ozer","year":"2011","journal-title":"Int J Epidemiol."},{"key":"ref-43","doi-asserted-by":"publisher","first-page":"210-218","DOI":"10.1016\/j.socscimed.2016.06.034","article-title":"Cash transfers, maternal depression and emotional well-being: Quasi-experimental evidence from India\u2019s Janani Suraksha Yojana programme.","volume":"162","author":"T Powell-Jackson","year":"2016","journal-title":"Soc Sci Med."},{"key":"ref-44","doi-asserted-by":"publisher","DOI":"10.1002\/pam.22044","article-title":"Paying for Happiness: Experimental Results from a Large Cash Transfer Program in Malawi.","author":"K Kilburn","year":"2018","journal-title":"J Policy Anal Manage."},{"key":"ref-45","doi-asserted-by":"publisher","DOI":"10.1016\/j.ssmph.2018.02.002","article-title":"Does money buy happiness? Evidence from an unconditional cash transfer in Zambia.","author":"L Natali","year":"2018","journal-title":"SSM-Population Health."},{"key":"ref-46","article-title":"WHA approves Post-2015 Global TB Strategy and Targets","year":"2014"}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/7-224\/v1\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/7-224\/v1\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/7-224\/v1\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,12,6]],"date-time":"2018-12-06T06:31:35Z","timestamp":1544077895000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/7-224\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,23]]},"references-count":46,"URL":"https:\/\/doi.org\/10.12688\/f1000research.14085.1","relation":{"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.15321.r33031","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.15321.r31152","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.15321.r31152","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.15321.r33031","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,23]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/7-224\/v1#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.15321.r31152, Aric A. Prather, Department of Psychiatry, University of California,\u00a0San Francisco\u00a0(UCSF), San Francisco, CA, USA, 21 Mar 2018, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/7-224\/v1#referee-response-31152","order":0,"name":"referee-response-31152","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.15321.r33031, Marie-Claude Rousseau, Epidemiology and Biostatistics Unit, INRS-Institut Armand-Frappier, Universit\u00e9 du Qu\u00e9bec, Laval, QC, Canada, 29 May 2018, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/7-224\/v1#referee-response-33031","order":1,"name":"referee-response-33031","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This paper is supported by pump-priming funding from the VALIDATE network. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}