title: Treatment of severe pertussis: a study of the safety and pharmacology of intravenous pertussis immunoglobulin.
abstract: BACKGROUND
  Pertussis in infants is often severe, resulting in complications and prolonged hospitalization. Treatment is limited to supportive care. Antibiotics do not significantly alter the course of the disease. Therapies directed at pertussis toxin, a major virulence factor of Bordetella pertussis, might be beneficial. This study examines the safety and pharmacology of intravenous pertussis immunoglobulin (P-IGIV), which has high levels of pertussis toxin antibodies.
  
  
  METHODS
  P-IGIV was prepared as a 4% IgG solution from the pooled plasma from donors immunized with inactivated pertussis toxoid. The IgG pertussis toxin antibody concentration of 733 microg/ml is >7-fold higher than contained in conventional intravenous immunoglobulin products. Children with presumptive pertussis were allocated to one of three treatment doses of P-IGIV.
  
  
  RESULTS
  Twenty-six of 30 enrolled children had confirmed pertussis. There were no adverse events associated with P-IGIV except one patient who had transient hypotension that responded to an infusion rate decrease. P-IGIV doses of 1500, 750 and 250 mg/kg achieved > or =4-fold, 3-fold and >2-fold rises in peak geometric mean titers of pertussis toxin IgG antibodies, respectively. P-IGIV exhibited a half-life of 38.4 days and a volume of distribution of 87.8 ml/kg. All three treatment groups showed declines in lymphocytosis (P < 0.05) and paroxysmal coughing by the third day after P-IGIV infusion compared with preinfusion values.
  
  
  CONCLUSIONS
  P-IGIV is safe and achieves high pertussis toxin antibody titers in infants. This study provides data for a prospective, controlled trial of P-IGIV.
authors.affiliation: Children's Hospital, Harvard Medical School, Dana Farber Cancer Institute, Boston, MA, USA. JBBRUSS@am.pnu.com
authors.forename: J B
authors.initials: JB
authors.lastname: Bruss
authors.forename: R
authors.initials: R
authors.lastname: Malley
authors.forename: S
authors.initials: S
authors.lastname: Halperin
authors.forename: S
authors.initials: S
authors.lastname: Dobson
authors.forename: M
authors.initials: M
authors.lastname: Dhalla
authors.forename: J
authors.initials: J
authors.lastname: Mciver
authors.forename: G R
authors.initials: GR
authors.lastname: Siber
mesh_terms: D000907:Antibodies, Bacterial / Q000276:immunology*; D001886:Bordetella pertussis / Q000276:immunology*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007223:Infant; D037342:Pertussis Toxin; D010566:Virulence Factors, Bordetella / Q000276:immunology*; D014917:Whooping Cough / Q000188:drug therapy* / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D016756:Immunoglobulins, Intravenous; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin