title: Multiple consecutive infections might explain the lack of protection by BCG.
abstract: Although contacts between tuberculosis patients may result in multiple consecutive infections (MCI), no experimental animal models consider this fact when used in basic studies. Moreover, the current TB vaccine (BCG) has demonstrated a limited protection in humans. In this study we evaluate the effect of tuberculosis MCI by way of a simple mathematical analysis using data from the low dose aerosol murine experimental model. The results show that a higher number of, or shorter intervals between, multiple consecutive infections reduce the protective effect of BCG. This is due to both the increase in bacillary load at the stationary level of the infection, and the protective immune response induced by the infection itself. This factor must therefore be taken into account when designing new prophylactic strategies as candidate vaccines for the replacement of BCG.
authors.affiliation: Unitat de Tuberculosi Experimental, Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Catalonia, Spain; Universitat Autònoma de Barcelona (UAB), Bellaterra, Catalonia, Spain; Centro de Investigaciones Biomédicas En Red Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Pere-Joan
authors.initials: PJ
authors.lastname: Cardona
authors.affiliation: Unitat de Tuberculosi Experimental, Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Catalonia, Spain; Universitat Autònoma de Barcelona (UAB), Bellaterra, Catalonia, Spain; Centro de Investigaciones Biomédicas En Red Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Vilaplana
mesh_terms: D000465:Algorithms; D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D051379:Mice; D018448:Models, Immunological; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D015203:Reproducibility of Results; D013997:Time Factors; D014374:Tuberculin Test; D014376:Tuberculosis / Q000175:diagnosis / Q000276:immunology* / Q000517:prevention & control; D014611:Vaccination / Q000592:standards
chemical_list: D001500:BCG Vaccine
references.citation: Lancet. 2013 Mar 23;381(9871):1021-8
references.pmid: 23391465
references.citation: PLoS One. 2010 Apr 06;5(4):e10030
references.pmid: 20386605
references.citation: J Infect Dis. 2004 Aug 1;190(3):588-97
references.pmid: 15243936
references.citation: Int J Tuberc Lung Dis. 2003 Dec;7(12 Suppl 3):S333-6
references.pmid: 14677818
references.citation: PLoS One. 2010 Sep 23;5(9):e12985
references.pmid: 20886087
references.citation: J Exp Med. 2005 Jun 20;201(12):1915-24
references.pmid: 15955839
references.citation: Tuberculosis (Edinb). 2007 Jan;87(1):71-6
references.pmid: 16723276
references.citation: J Exp Med. 2008 Jan 21;205(1):105-15
references.pmid: 18158321
references.citation: Am J Respir Crit Care Med. 2007 Mar 15;175(6):529-31
references.pmid: 17341646
references.citation: Eur Respir J. 2004 Dec;24(6):1044-51
references.pmid: 15572551
references.citation: Tuberculosis (Edinb). 2005 Jan-Mar;85(1-2):13-7
references.pmid: 15687022
references.citation: Lancet. 2006 Apr 8;367(9517):1173-80
references.pmid: 16616560
references.citation: Clin Microbiol Infect. 2014 May;20 Suppl 5:59-65
references.pmid: 24283256
references.citation: Tuberculosis (Edinb). 2012 Mar;92 Suppl 1:S6-13
references.pmid: 22441160
references.citation: Trends Microbiol. 1998 Mar;6(3):107-12
references.pmid: 9582936
references.citation: Immunol Rev. 2011 Mar;240(1):25-39
references.pmid: 21349084
references.citation: Infect Immun. 2002 Aug;70(8):4501-9
references.pmid: 12117962
references.citation: Infection. 2009 Apr;37(2):80-6
references.pmid: 19308318