title: Effectiveness of a bivalent Haemophilus influenzae type B-hepatitis B vaccine in preventing hepatitis B virus infection among children born to hepatitis B e antigen-positive carrier mothers.
abstract: BACKGROUND
  This observational study evaluated a modified immunoprophylactic regimen (hepatitis B immune globulin [HBIG]) and a dose of thimerosal-free monovalent hepatitis B (HB) vaccine shortly after birth followed by doses of thimerosal-free bivalent Haemophilus influenzae type b (Hib)-HB vaccine at 2 and 4 months of age, and a booster at 12 months of age) in infants at high risk of hepatitis B virus (HBV) infection (mothers HBeAg+).
  
  
  METHODS
  Children >or=6 months of age vaccinated in routine clinical practice were tested twice (>or=6 months apart) for HBV antigens surface antigen (HBsAg) and "e" antigen, and for antibody to HBsAg. Partial nucleotide sequence analysis was performed on HBV DNA isolated from infants identified with a breakthrough chronic HBV infection. A fully sequential statistical design was used to maximize patient safety and study efficiency.
  
  
  RESULTS
  Four of 60 children developed chronic HBV infection despite vaccination, but at no point did the cumulative number of cases reach the boundary of statistical significance. Overall, the analysis adjusted for sequential testing yielded an estimated breakthrough rate of 6.7% (90% CI: 2.3%-14.6%). In a subset of uninfected children tested for antibody to HBsAg 1 to 4 months after the second dose of Hib-HB vaccine, 90% (9/10) had >or=10 milli-International Units per milliliter (mIU/mL). The third dose of Hib-HB vaccine induced a secondary increase in the level of antibody; 94.7% (18/19) of a second group developed >or=100 mIU/mL, with a geometric mean concentration of 771 mIU/mL (95% CI: 351.4-1692.1 mIU/mL).
  
  
  CONCLUSIONS
  The tested regimen is comparably effective to historical experience with a standard one employing HBIG plus monovalent thimerosal-containing HB vaccine given at 0, 1, and 6 months of age.
authors.affiliation: Monash Medical Centre, Monash University/Clayton, VIC, Australia.
authors.forename: Richard
authors.initials: R
authors.lastname: Doherty
authors.forename: Suzanne
authors.initials: S
authors.lastname: Garland
authors.forename: Martin
authors.initials: M
authors.lastname: Wright
authors.forename: Monique
authors.initials: M
authors.lastname: Bulotsky
authors.forename: Charles
authors.initials: C
authors.lastname: Liss
authors.forename: Hassan
authors.initials: H
authors.lastname: Lakkis
authors.forename: Alexander
authors.initials: A
authors.lastname: Nikas
authors.forename: Walter
authors.initials: W
authors.lastname: Straus
mesh_terms: D002675:Child, Preschool; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D018073:Haemophilus Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D006509:Hepatitis B / Q000175:diagnosis / Q000453:epidemiology* / Q000517:prevention & control*; D006514:Hepatitis B Surface Antigens / Q000097:blood; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D008297:Male; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000175:diagnosis*; D017422:Sequence Analysis, DNA; D014611:Vaccination / Q000379:methods*
chemical_list: C104289:COMVAX; D004279:DNA, Viral; D018073:Haemophilus Vaccines; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D006513:Hepatitis B e Antigens