title: Study of the BCG Vaccine-Induced Cellular Immune Response in Schoolchildren in Antananarivo, Madagascar.
abstract: OBJECTIVE
  Although the Bacillus Calmette-Guérin vaccine (BCG) protects young children against serious forms of TB, protection against pulmonary TB is variable. We assessed BCG vaccine-induced cellular immune responses and determined for how long they could be detected during childhood in Antananarivo, Madagascar.
  
  
  METHODS
  We assessed BCG vaccine-induced cellular immune responses by TST and IGRA (in-house ELISPOT assay) using BCG and PPD as stimulation antigen, and compared results between vaccinated and non-vaccinated schoolchildren of two age groups, 6-7 and 13-14 years old.
  
  
  RESULTS
  Three hundred and sixty-three healthy schoolchildren were enrolled. TST was performed on 351 children and IGRA on 142. A high proportion (66%; 229/343) of the children had no TST reactivity (induration size 0 mm). TST-positive responses (≥15 mm) were more prevalent among 13-14 year-old (31.7%) than 6-7 year old (16.5%) children, both in the non-vaccinated (43% vs. 9%, p<0.001) and vaccinated (29% vs. 13%, p=0.002) subgroups. There were no significant differences in TST responses between vaccinated and non-vaccinated children in either of the age groups. The IGRA response to BCG and to PPD stimulation was not significantly different according to BCG vaccination record or to age group. A high rate (15.5%; 22/142) of indeterminate IGRA responses was observed. There was very poor agreement between TST and IGRA-PPD findings (k= 0.08) and between TST and IGRA-BCG findings (k= 0.02).
  
  
  CONCLUSIONS
  Analysis of TST and IGRA response to stimulation with BCG and PPD revealed no difference in immune response between BCG-vaccinated and non-vaccinated children; also no decrease of the BCG vaccine-induced cellular immune response over time was observed. We conclude that TST and IGRA have limitations in assessing a role of BCG or tuberculosis-related immunity.
authors.affiliation: Mycobacteria Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar.
authors.forename: Paulo
authors.initials: P
authors.lastname: Ranaivomanana
authors.affiliation: Epidemiology Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar.
authors.forename: Vaomalala
authors.initials: V
authors.lastname: Raharimanga
authors.affiliation: Immunovacc Consulting, Hévillers, Belgium.
authors.forename: Patrice M
authors.initials: PM
authors.lastname: Dubois
authors.affiliation: Epidemiology Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar; Epidemiology Unit, Institut Pasteur de Dakar, Dakar, Sénégal.
authors.forename: Vincent
authors.initials: V
authors.lastname: Richard
authors.affiliation: Mycobacteria Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar.
authors.forename: Voahangy
authors.initials: V
authors.lastname: Rasolofo Razanamparany
mesh_terms: D000293:Adolescent; D001500:BCG Vaccine / Q000276:immunology*; D002648:Child; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D008270:Madagascar; D008297:Male; D015203:Reproducibility of Results; D013334:Students; D014374:Tuberculin Test; D014376:Tuberculosis / Q000276:immunology* / Q000517:prevention & control*
chemical_list: D001500:BCG Vaccine