{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T23:44:00Z","timestamp":1767829440331,"version":"3.49.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2019,11,3]],"date-time":"2019-11-03T00:00:00Z","timestamp":1572739200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001732","name":"Danish National Research Foundation","doi-asserted-by":"crossref","award":["DNRF108"],"award-info":[{"award-number":["DNRF108"]}],"id":[{"id":"10.13039\/501100001732","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100006356","name":"Syddansk Universitet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006356","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Bacille Calmette-Gu\u00e9rin (BCG) vaccination remains a cornerstone against tuberculosis. Randomized controlled trials (RCTs) have demonstrated that BCG-Denmark lowers all-cause mortality, but a recent RCT found no effect of BCG-Russia. Observational studies indicate that the genetically divergent BCG strains have different effects.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This was a parallel-group, open-label RCT conducted at the National Hospital in Guinea-Bissau. Healthy neonates were randomized 1:1 to BCG-Denmark (2851 randomized, 2840 analyzed) vs BCG-Russia (2845 randomized, 2837 analyzed). We hypothesized that BCG-Denmark would reduce morbidity (primary outcome) and mortality while inducing more BCG reactions and purified protein derivative (PPD) responses (secondary outcomes). Halfway through the trial, production of BCG-Denmark was halted, and the trial continued comparing BCG-Japan (3191 neonates randomized, 3184 analyzed) with BCG-Russia (3170 randomized, 3160 analyzed). Mortality and morbidity data were collected by telephone, at home visits, and at the National Hospital and assessed in Cox models providing 6-week mortality rate ratios (MRRs) and hospitalization incidence rate ratios (IRRs).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>By age 6 weeks, there were 140 and 130 admissions among neonates vaccinated with BCG-Denmark and BCG-Russia, respectively (IRR, 1.08 [95% confidence interval {CI}, .84\u20131.37]). For BCG-Japan, there were 185 admissions vs 161 admissions for BCG-Russia (IRR, 1.15 [95% CI, .93\u20131.43]). The 6-week mortality did not differ: BCG-Denmark\/BCG-Russia (MRR, 1.15 [95% CI, .74\u20131.80]); BCG-Japan\/BCG-Russia (MRR, 0.71 [95% CI, .43\u20131.19]). BCG-Denmark and BCG-Japan induced more BCG scars and PPD reactions than BCG-Russia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>BCG strains did not affect morbidity. BCG-Denmark and BCG-Japan were more immunogenic than BCG-Russia by the measures traditionally viewed as surrogates for successful immunization. The implications of strain differences for tuberculosis protection and overall health warrant further study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trials Registration<\/jats:title>\n                  <jats:p>NCT02447536.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciz1080","type":"journal-article","created":{"date-parts":[[2019,10,29]],"date-time":"2019-10-29T20:10:12Z","timestamp":1572379812000},"page":"1883-1893","source":"Crossref","is-referenced-by-count":33,"title":["Early Vaccination With Bacille Calmette-Gu\u00e9rin-Denmark or BCG-Japan Versus BCG-Russia to Healthy Newborns in Guinea-Bissau: A Randomized Controlled Trial"],"prefix":"10.1093","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7643-8322","authenticated-orcid":false,"given":"Frederik","family":"Schaltz-Buchholzer","sequence":"first","affiliation":[{"name":"Institute of Clinical Research, University of Southern Denmark and Odense University Hospital, Odense, Denmark"},{"name":"Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau"},{"name":"Research Center for Vitamins and Vaccines, Statens Serum Institut, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morten","family":"Bjerregaard-Andersen","sequence":"additional","affiliation":[{"name":"Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau"},{"name":"Research Center for Vitamins and Vaccines, Statens Serum Institut, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian Bjerreg\u00e5rd","family":"\u00d8land","sequence":"additional","affiliation":[{"name":"Research Center for Vitamins and Vaccines, Statens Serum Institut, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Golding","sequence":"additional","affiliation":[{"name":"Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau"},{"name":"Research Center for Vitamins and Vaccines, Statens Serum Institut, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elise Brenno","family":"Stjernholm","sequence":"additional","affiliation":[{"name":"Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau"},{"name":"Research Center for Vitamins and Vaccines, Statens Serum Institut, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Aaby","sequence":"additional","affiliation":[{"name":"Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine Stabell","family":"Benn","sequence":"additional","affiliation":[{"name":"Institute of Clinical Research, University of Southern Denmark and Odense University Hospital, Odense, Denmark"},{"name":"Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau"},{"name":"Research Center for Vitamins and Vaccines, Statens Serum Institut, Copenhagen, Denmark"},{"name":"Danish Institute of Advanced Science, University of Southern Denmark, Odense, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,11,3]]},"reference":[{"key":"2020110510413378400_CIT0001","first-page":"53","article-title":"History of BCG vaccine","volume":"8","author":"Luca","year":"2013","journal-title":"Maedica (Buchar)"},{"key":"2020110510413378400_CIT0002","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1093\/cid\/cit790","article-title":"Protection by BCG vaccine against tuberculosis: a systematic review of randomized controlled trials","volume":"58","author":"Mangtani","year":"2014","journal-title":"Clin Infect 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