{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T05:18:52Z","timestamp":1773465532653,"version":"3.50.1"},"reference-count":39,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T00:00:00Z","timestamp":1652918400000},"content-version":"unspecified","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000030","name":"Centers for Disease Control and Prevention","doi-asserted-by":"publisher","award":["00HCBBDB-2020-45767."],"award-info":[{"award-number":["00HCBBDB-2020-45767."]}],"id":[{"id":"10.13039\/100000030","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2022,4,22]]},"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>The oral polio vaccine (OPV) has substantial results in eliminating wild poliovirus and the vaccine of choice in polio eradication. However, the mucosal immunity induced by the OPV is still uncertain. Literature has shown that bovine lactoferrin (BLF) is a safe and useful protein found in cow\u2019s milk with extraordinary antimicrobial, antiviral, antiinflammatory and immune-modulatory functions that help children\u2019s gut to fight against micro-organisms like poliovirus. However, limited data exist regarding the effect of BLF on polio vaccine immune response. The primary objective is to evaluate the effect of BLF in enhancing mucosal and humoral immunity in children following the administration of oral and inactivated polio vaccines.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and analysis<\/jats:title>\n                  <jats:p>This is a two-arm double-blinded randomised controlled trial comparing 462 neonates (231 in both groups) receiving either BLF or placebo with breast milk. The intervention is administered from day 1 till 6 weeks of age to a full-term healthy singleton newborn born at the Aga Khan University Hospitals, Karachi, Pakistan. The primary outcome is the seroconversion, 1 month after the receipt of two doses of OPV (at 10 weeks). For descriptive statistical analysis, Stata will be used, the frequency with percentages will be reported to describe baseline characteristics of the participants. A \u03c7<jats:sup>2<\/jats:sup> test will be used to compare categorical variables and a simple t test to compare continuous variables. The proportion of seroconversion and shedding will be compared using \u03c7<jats:sup>2<\/jats:sup> test or Fisher\u2019s exact test.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Ethics and dissemination<\/jats:title>\n                  <jats:p>The Ethics approval has been granted by the Ethics Review Committee (ERC) of Aga Khan University for the proposed trial (ID: 2019-1955-5013). Furthermore, the National Bioethics Committee (NBC) of Pakistan has also approved the study for human subject research (ID: 4\u201387\/NBC-443\/19\/669). Study findings will be disseminated through presentations at scientific conferences and educational practice workshops and will be published in an international peer-reviewed scientific journal.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>\n                     <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04432935\">NCT04432935<\/jats:ext-link>; ClinicalTrials.gov.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjopen-2021-050849","type":"journal-article","created":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T04:00:48Z","timestamp":1653451248000},"page":"e050849","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Effect of bovine lactoferrin on seroconversion following polio vaccine administration in children: protocol for a double-blinded randomised controlled trial"],"prefix":"10.1136","volume":"12","clinical-trial-number":[{"clinical-trial-number":"nct04432935","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Atif","family":"Habib","sequence":"first","affiliation":[{"name":"Center of Excellence in Women & Child Health, The Aga Khan University, Karachi, Sindh, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sidrah","family":"Nausheen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, Aga Khan University, Karachi, Sindh, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanila","family":"Nooruddin","sequence":"additional","affiliation":[{"name":"Center of Excellence in Women & Child Health, The Aga Khan University, Karachi, Sindh, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tooba","family":"Javed","sequence":"additional","affiliation":[{"name":"Center of Excellence in Women & Child Health, The Aga Khan University, Karachi, Sindh, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tariq","family":"Samejo","sequence":"additional","affiliation":[{"name":"Center of Excellence in Women & Child Health, The Aga Khan University, Karachi, Sindh, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amjad","family":"Hussain","sequence":"additional","affiliation":[{"name":"Center of Excellence in Women & Child Health, The Aga Khan University, Karachi, Sindh, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suneeta","family":"Namdev","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Child Health, The Aga Khan University, Karachi, Sindh, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sehrish","family":"Amirali","sequence":"additional","affiliation":[{"name":"Center of Excellence in Women & Child Health, The Aga Khan University, Karachi, Sindh, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Umer","sequence":"additional","affiliation":[{"name":"Center of Excellence in Women & Child Health, The Aga Khan University, Karachi, Sindh, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lumaan","family":"Sheikh","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, Aga Khan University, Karachi, Sindh, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Imtiaz","family":"Hussain","sequence":"additional","affiliation":[{"name":"Center of Excellence in Women & Child Health, The Aga Khan University, Karachi, Sindh, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9627-2662","authenticated-orcid":false,"given":"Shabina","family":"Ariff","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Child Health, The Aga Khan University, Karachi, Sindh, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4192-8406","authenticated-orcid":false,"given":"Sajid","family":"Soofi","sequence":"additional","affiliation":[{"name":"Center of Excellence in Women & Child Health, The Aga Khan University, Karachi, Sindh, Pakistan"},{"name":"Paediatric & Child Health, The Aga Khan University, Karachi, Sindh, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2022,5,24]]},"reference":[{"key":"2025101810362073000_12.5.e050849.1","unstructured":"Cases of wild poliovirus by country and year. Available: http:\/\/polioeradication.org\/wp-content\/uploads\/2020\/01\/Weekly-GPEI-Polio-Analyses-wpv-20191231.pdf"},{"key":"2025101810362073000_12.5.e050849.2","unstructured":"Global polio eradication initiative, endemic countries. Available: http:\/\/polioeradication.org\/where-we-work\/polio-endemic-countries\/"},{"key":"2025101810362073000_12.5.e050849.3","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6718a4"},{"key":"2025101810362073000_12.5.e050849.4","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.15.19"},{"key":"2025101810362073000_12.5.e050849.5","unstructured":"World Health Organization, . Available: https:\/\/www.who.int\/biologicals\/areas\/vaccines\/polio\/opv\/en\/"},{"key":"2025101810362073000_12.5.e050849.6","first-page":"1141","article-title":"Antibody response to three doses of standard and double dose of trivalent oral polio vaccine","volume":"28","author":"Agarwal","year":"1991","journal-title":"Indian Pediatr"},{"key":"2025101810362073000_12.5.e050849.7","first-page":"141","article-title":"Vaccination against poliomyelitis in economically underdeveloped countries","volume":"58","author":"Sabin","year":"1980","journal-title":"Bull World Health Organ"},{"key":"2025101810362073000_12.5.e050849.8","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1093\/oxfordjournals.aje.a121457","article-title":"Oral polio vaccination of children in the tropics. I. The poor seroconversion rates and the absence of viral interference","volume":"96","author":"John","year":"1972","journal-title":"Am J Epidemiol"},{"key":"2025101810362073000_12.5.e050849.9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200009143431103"},{"key":"2025101810362073000_12.5.e050849.10","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(97)00001-7"},{"key":"2025101810362073000_12.5.e050849.11","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.vaccine.2018.05.080","article-title":"Oral polio vaccine response in the MAL-ED birth cohort study: considerations for polio eradication strategies","volume":"37","author":"Pan","year":"2019","journal-title":"Vaccine"},{"key":"2025101810362073000_12.5.e050849.12","doi-asserted-by":"crossref","first-page":"97","DOI":"10.2217\/fmb-2017-0128","article-title":"Causes of impaired oral vaccine efficacy in developing countries","volume":"13","author":"Parker","year":"2018","journal-title":"Future Microbiol"},{"key":"2025101810362073000_12.5.e050849.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2013.11.056"},{"key":"2025101810362073000_12.5.e050849.14","doi-asserted-by":"crossref","first-page":"2757","DOI":"10.1016\/j.vaccine.2015.04.055","article-title":"Immunogenicity of poliovirus vaccines in chronically malnourished infants: a randomized controlled trial in Pakistan","volume":"33","author":"Saleem","year":"2015","journal-title":"Vaccine"},{"key":"2025101810362073000_12.5.e050849.15","doi-asserted-by":"crossref","unstructured":"Newell E , Sigal N , Haque R , et al . Oral polio vaccination failure in urban slum children is associated with malnutrition and evidence of chronic inflammation (166.2).","DOI":"10.4049\/jimmunol.188.Supp.166.2"},{"key":"2025101810362073000_12.5.e050849.16","unstructured":"Government of Pakistan and UNICEF . National Nutrition Survey 2018 - Key Findings Report. Available: https:\/\/www.unicef.org\/pakistan\/reports\/national-nutrition-survey-2018-key-findings-report"},{"key":"2025101810362073000_12.5.e050849.17","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph8041174"},{"key":"2025101810362073000_12.5.e050849.18","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2014.0141"},{"key":"2025101810362073000_12.5.e050849.19","doi-asserted-by":"crossref","first-page":"474","DOI":"10.26719\/2004.10.4-5.474","article-title":"[Evaluation of the response to vaccination against poliomyelitis and measles in malnourished children in Morocco]","volume":"10","author":"Caidi","year":"2004","journal-title":"East Mediterr Health J"},{"key":"2025101810362073000_12.5.e050849.20","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1016\/j.vaccine.2013.02.003","article-title":"A study evaluating poliovirus antibodies and risk factors associated with polio seropositivity in low socioeconomic areas of Pakistan","volume":"31","author":"Habib","year":"2013","journal-title":"Vaccine"},{"key":"2025101810362073000_12.5.e050849.21","doi-asserted-by":"crossref","first-page":"e230","DOI":"10.1097\/INF.0000000000001622","article-title":"Seroprevalence of Anti-polio antibodies in children from polio high-risk areas of Pakistan: a cross-sectional survey 2015-2016","volume":"36","author":"Hussain","year":"2017","journal-title":"Pediatr Infect Dis J"},{"key":"2025101810362073000_12.5.e050849.22","first-page":"203","article-title":"Breastfeeding, the immune response, and long-term health","volume":"106","author":"Jackson","year":"2006","journal-title":"J Am Osteopath Assoc"},{"key":"2025101810362073000_12.5.e050849.23","first-page":"5","article-title":"The impact of breastmilk on infant and child health","volume":"10","author":"Oddy","year":"2002","journal-title":"Breastfeed Rev"},{"key":"2025101810362073000_12.5.e050849.24","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00584"},{"key":"2025101810362073000_12.5.e050849.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.clp.2014.02.011"},{"key":"2025101810362073000_12.5.e050849.26","unstructured":"World Health Organization . Breastfeeding gives babies the best possible start in life and breastmilk works like a baby\u2019s first vaccine, 2020. Available: http:\/\/www.emro.who.int\/pak\/pakistan-news\/breastfeeding-gives-babies-the-best-possible-start-in-life-and-breastmilk-works-like-a-babys-first-vaccine.html"},{"key":"2025101810362073000_12.5.e050849.27","unstructured":"National Institute of Population Studies (NIPS) [Pakistan] and ICF . Pakistan demographic and health survey 2017-18. Islamabad, Pakistan, and Rockville, Maryland, USA: NIPS and ICF, 2018."},{"key":"2025101810362073000_12.5.e050849.28","doi-asserted-by":"publisher","DOI":"10.1097\/MCO.0b013e328328d13e"},{"key":"2025101810362073000_12.5.e050849.29","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1111\/j.1651-2227.1987.tb10526.x","article-title":"The nutritional role of breast-milk IgA and lactoferrin","volume":"76","author":"Prentice","year":"1987","journal-title":"Acta Paediatr Scand"},{"key":"2025101810362073000_12.5.e050849.30","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1080\/15216540600577897","article-title":"What are the structure and the biological function of lactoferrin in human breast milk?","volume":"58","author":"Roseanu","year":"2006","journal-title":"IUBMB Life"},{"key":"2025101810362073000_12.5.e050849.31","doi-asserted-by":"publisher","DOI":"10.1023\/B:BIOM.0000027708.27142.bc"},{"key":"2025101810362073000_12.5.e050849.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2008.04.006"},{"key":"2025101810362073000_12.5.e050849.33","doi-asserted-by":"crossref","first-page":"457","DOI":"10.17221\/1978-VETMED","article-title":"Lactoferrin: a review","volume":"53","author":"Adlerova","year":"2008","journal-title":"Veterinarni Medicina"},{"key":"2025101810362073000_12.5.e050849.34","doi-asserted-by":"publisher","DOI":"10.1007\/s10534-010-9297-1"},{"key":"2025101810362073000_12.5.e050849.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2007.07.005"},{"key":"2025101810362073000_12.5.e050849.36","doi-asserted-by":"crossref","first-page":"S49","DOI":"10.1016\/S1472-9792(09)70012-5","article-title":"Lactoferrin enhances efficacy of the BCG vaccine: comparison between two inbred mice strains (C57BL\/6 and BALB\/c)","volume":"89 Suppl 1","author":"Hwang","year":"2009","journal-title":"Tuberculosis"},{"key":"2025101810362073000_12.5.e050849.37","unstructured":"World Health Organization . WHO guidelines on drawing blood: best practices in phlebotomy. Available: http:\/\/www.euro.who.int\/__data\/assets\/pdf_file\/0005\/268790\/WHO-guidelines-on-drawing-blood-best-practices-in-phlebotomy-Eng.pdf?ua-1"},{"key":"2025101810362073000_12.5.e050849.38","unstructured":"WHO Department of Immunization, Vaccines and Biologicals . Polio laboratory manual. Geneva: World Health Organization, 2004."},{"key":"2025101810362073000_12.5.e050849.39","unstructured":"Centers of Disease Control (CDC) . Diagnostic methods for polio. Available: https:\/\/www.cdc.gov\/polio\/what-is-polio\/lab-testing\/diagnostic.html"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2021-050849","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T17:36:31Z","timestamp":1760808991000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2021-050849"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5]]},"references-count":39,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5,24]]},"published-print":{"date-parts":[[2022,5]]}},"alternative-id":["10.1136\/bmjopen-2021-050849"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2021-050849","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5]]}}}