title: The tuberculin skin test (TST) is affected by recent BCG vaccination but not by exposure to non-tuberculosis mycobacteria (NTM) during early life.
abstract: The tuberculin skin test (TST) is widely used in TB clinics to aid Mycobacterium tuberculosis (M.tb) diagnosis, but the definition and the significance of a positive test in very young children is still unclear. This study compared the TST in Gambian children at 4(1/2) months of age who either received BCG vaccination at birth (Group 1) or were BCG naïve (Group 2) in order to examine the role of BCG vaccination and/or exposure to environmental mycobacteria in TST reactivity at this age. Nearly half of the BCG vaccinated children had a positive TST (>or=5 mm) whereas all the BCG naïve children were non-reactive, confirming that recent BCG vaccination affects TST reactivity. The BCG naïve children demonstrated in vitro PPD responses in peripheral blood in the absence of TST reactivity, supporting exposure to and priming by environmental mycobacterial antigens. Group 2 were then vaccinated at 4(1/2) months of age and a repeat TST was performed at 20-28 months of age. Positive reactivity (>or=5 mm) was evident in 11.1% and 12.5% infants from Group 1 and Group 2 respectively suggesting that the timing of BCG vaccination had little effect by this age. We further assessed for immune correlates in peripheral blood at 4(1/2) months of age. Mycobacterial specific IFNgamma responses were greater in TST responders than in non-responders, although the size of induration did not correlate with IFNgamma. However the IFNgamma: IL-10 ratio positively correlated with TST induration suggesting that the relationship between PPD induced IFNgamma and IL-10 in the peripheral blood may be important in controlling TST reactivity. Collectively these data provide further insights into how the TST is regulated in early life, and how a positive response might be interpreted.
authors.affiliation: Infant Immunology, Medical Research Council UK The Gambia, Fajara, The Gambia. sburl0712@gmail.com
authors.forename: Sarah
authors.initials: S
authors.lastname: Burl
authors.forename: Uche J
authors.initials: UJ
authors.lastname: Adetifa
authors.forename: Momodou
authors.initials: M
authors.lastname: Cox
authors.forename: Ebrima
authors.initials: E
authors.lastname: Touray
authors.forename: Hilton
authors.initials: H
authors.lastname: Whittle
authors.forename: Helen
authors.initials: H
authors.lastname: McShane
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Rowland-Jones
authors.forename: Katie L
authors.initials: KL
authors.lastname: Flanagan
mesh_terms: D002675:Child, Preschool; D002921:Cicatrix / Q000276:immunology; D015331:Cohort Studies; D004781:Environmental Exposure; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D016753:Interleukin-10 / Q000096:biosynthesis / Q000097:blood; D008297:Male; D009163:Mycobacterium bovis / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013997:Time Factors; D014374:Tuberculin Test / Q000379:methods*; D014611:Vaccination
chemical_list: D016753:Interleukin-10; D007371:Interferon-gamma
references.citation: Pediatrics. 2003 Oct;112(4):e298
references.pmid: 14523215
references.citation: J Immunol. 2003 Dec 1;171(11):5760-8
references.pmid: 14634084
references.citation: Lancet Infect Dis. 2003 Oct;3(10):624-32
references.pmid: 14522261
references.citation: J Trop Pediatr. 2006 Apr;52(2):136-40
references.pmid: 16126802
references.citation: N Engl J Med. 1964 Feb 20;270:386-91
references.pmid: 14087040
references.citation: Genes Immun. 2004 Mar;5(2):122-9
references.pmid: 14737096
references.citation: Tuberculosis (Edinb). 2007 May;87(3):202-11
references.pmid: 17049309
references.citation: Am Rev Respir Dis. 1992 Mar;145(3):621-5
references.pmid: 1546843
references.citation: Am J Respir Crit Care Med. 1994 Jun;149(6):1699-709
references.pmid: 7710481
references.citation: J Am Geriatr Soc. 1989 May;37(5):435-43
references.pmid: 2703641
references.citation: PLoS One. 2008 Aug 06;3(8):e2905
references.pmid: 18682836
references.citation: Proc Natl Acad Sci U S A. 2002 May 28;99(11):7576-81
references.pmid: 12032325
references.citation: Tuber Lung Dis. 1996 Apr;77(2):117-23
references.pmid: 8762845
references.citation: Int J Tuberc Lung Dis. 2006 Nov;10(11):1192-204
references.pmid: 17131776
references.citation: Clin Immunol. 2004 Apr;111(1):119-25
references.pmid: 15093560
references.citation: Tuber Lung Dis. 1996 Feb;77(1):52-8
references.pmid: 8733415
references.citation: J Immunol Methods. 1994 Nov 10;176(1):93-101
references.pmid: 7963598
references.citation: Lancet Infect Dis. 2010 May;10(5):338-49
references.pmid: 20417416
references.citation: Thorax. 2002 Sep;57(9):804-9
references.pmid: 12200526
references.citation: Pediatrics. 1964 May;33:769-72
references.pmid: 14143277
references.citation: Pediatr Infect Dis J. 1995 Dec;14(12):1060-3
references.pmid: 8745018
references.citation: Clin Infect Dis. 2000 Sep;31 Suppl 3:S71-4
references.pmid: 11010826
references.citation: J Infect Dis. 2006 Feb 15;193(4):531-6
references.pmid: 16425132
references.citation: N Engl J Med. 1964 Dec 17;271:1294-6
references.pmid: 14214636
references.citation: Int J Tuberc Lung Dis. 2006 Dec;10(12):1337-41
references.pmid: 17167949
references.citation: Int J Tuberc Lung Dis. 2000 Dec;4(12):1133-42
references.pmid: 11144455
references.citation: Int J Tuberc Lung Dis. 2008 Dec;12(12):1401-6
references.pmid: 19017449
references.citation: Clin Exp Immunol. 2003 Feb;131(2):206-16
references.pmid: 12562379
references.citation: J Immunol. 2010 Aug 15;185(4):2620-8
references.pmid: 20644160
references.citation: Tuber Lung Dis. 1994 Apr;75(2):138-43
references.pmid: 8032047