title: Safety and reactogenicity of BCG revaccination with isoniazid pretreatment in TST positive adults.
abstract: BACKGROUND
  Global tuberculosis (TB) control may require mass vaccination with a new TB vaccine, such as a recombinant bacille Calmette Guerin (BCG) or attenuated Mycobacterium tuberculosis (MTB). The safety profile of live mycobacterial vaccines in latently infected adults with prior infant BCG vaccination is unknown.
  
  
  OBJECTIVE
  Evaluate safety and reactogenicity of BCG revaccination, with or without isoniazid (INH) pretreatment, in adults with latent MTB infection (LTBI).
  
  
  METHODS
  Eighty-two healthy, HIV uninfected, South African adults, with a BCG scar and tuberculin skin test (TST) diameter ≥ 15 mm, were randomized to receive 6 months of INH, starting either before, or 6 months after, intradermal revaccination with BCG Vaccine SSI (Statens Serum Institut, Copenhagen). Safety and reactogenicity data are reported through 3 months post BCG revaccination.
  
  
  RESULTS
  Baseline characteristics were similar between treatment arms. Mean baseline TST diameter was 20 ± 4 mm. Seventy-two subjects received BCG revaccination. Injection site erythema (68%) and induration (86%) peaked 1 week after revaccination. Ulceration (76%) peaked at 2 weeks, and resolved by 3 months in all but 3 subjects. Diameter of ulceration was >10mm in only 8%, but a residual scar was common (85%). No regional lymphadenitis or serious morbidity related to BCG was seen. Reactogenicity was not affected by INH pretreatment.
  
  
  CONCLUSIONS
  BCG revaccination of MTB infected adults is safe, well tolerated, and reactogenicity is similar to that of primary BCG vaccination. Clinical trials of live recombinant BCG or attenuated MTB vaccines may be considered in latently infected adults, with or without INH pretreatment (ClinicalTrials.gov identifier: NCT01119521).
authors.affiliation: South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease & Molecular Medicine, School of Child & Adolescent Health, University of Cape Town, Cape Town, South Africa. Electronic address: Mark.Hatherill@uct.ac.za.
authors.forename: Mark
authors.initials: M
authors.lastname: Hatherill
authors.affiliation: South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease & Molecular Medicine, School of Child & Adolescent Health, University of Cape Town, Cape Town, South Africa.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Geldenhuys
authors.affiliation: South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease & Molecular Medicine, School of Child & Adolescent Health, University of Cape Town, Cape Town, South Africa.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Pienaar
authors.affiliation: South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease & Molecular Medicine, School of Child & Adolescent Health, University of Cape Town, Cape Town, South Africa.
authors.forename: Sara
authors.initials: S
authors.lastname: Suliman
authors.affiliation: Tuberculosis Research Unit, Department of Medicine, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, OH, USA.
authors.forename: Phalkun
authors.initials: P
authors.lastname: Chheng
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Debanne
authors.affiliation: Division of Immunobiology, Departments of Internal Medicine and Molecular Biology, Saint Louis University Medical Center, and Center for Vaccine Development, Saint Louis, MO, USA.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hoft
authors.affiliation: Tuberculosis Research Unit, Department of Medicine, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, OH, USA.
authors.forename: W Henry
authors.initials: WH
authors.lastname: Boom
authors.affiliation: South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease & Molecular Medicine, School of Child & Adolescent Health, University of Cape Town, Cape Town, South Africa.
authors.forename: Willem A
authors.initials: WA
authors.lastname: Hanekom
authors.affiliation: Tuberculosis Research Unit, Department of Medicine, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, OH, USA.
authors.forename: John L
authors.initials: JL
authors.lastname: Johnson
mesh_terms: D000328:Adult; D001500:BCG Vaccine / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007117:Immunization, Secondary / Q000009:adverse effects; D007538:Isoniazid / Q000008:administration & dosage*; D055985:Latent Tuberculosis / Q000175:diagnosis / Q000517:prevention & control*; D008297:Male; D013019:South Africa; D014374:Tuberculin Test; D055815:Young Adult
chemical_list: D001500:BCG Vaccine; D007538:Isoniazid
keywords: BCG; Isoniazid; LTBI; Revaccination; Safety