title: Safety and immunogenicity of subcutaneous hepatitis A vaccine in children with haemophilia.
abstract: Individuals with Haemophilia are at risk from hepatitis A virus (HAV) infection through exposure to blood products. Havrix(R), an intramuscular hepatitis A vaccine, is currently recommended for the prevention of disease caused by hepatitis A virus. Because bleeding may complicate intramuscular injections in those with bleeding disorders, we conducted a randomized, Phase IV clinical trial to compare the safety and immunogenicity of Havrix(R) given by the subcutaneous (s.c) vs. intramuscular (i.m.) route. A total of 45 children with Haemophilia were vaccinated subcutaneously, while their 41 nonhaemophlic siblings were vaccinated intramuscularly, at a dose of 720 Elisa units (EL.U.) at time 0 and 6 months. All children were anti-HAV and anti-HIV negative at baseline, and the haemophilic group did not differ from their siblings in alanine aminotransferase (ALT; 25 IU L-1 vs. 22 IU L-1), or in age; 8.5 years vs. 8.7 years. The vaccine was well tolerated, with minor adverse events being similar between groups; 21 (47%) vs. 24 (58%), P > 0.05. Local symptoms included soreness in 39 (45%), erythema in 25 (29%), swelling in 21 (24%), and bruising in six (7%), with no differences between groups. The proportion seroconverting to anti-HAV IgG positive did not differ between groups; 98% vs. 97% at month 1; 82% vs. 93% at month 6; and 100% vs. 100% at month 8, respectively. The HAV geometric mean titre was lower in those with Haemophilia, 185 vs. 233 mIU mL-1 at month 1; 68 vs. 94 mIU mL-1 at month 6; and 584 vs. 1082 mIU mL-1 at month 8, respectively. We conclude that Havrix(R) is safe and immunogenic when administered s. c. in children with Haemophilia.
authors.affiliation: Haemophilia Center of Western Pennsylvania, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: M V
authors.initials: MV
authors.lastname: Ragni
authors.forename: J M
authors.initials: JM
authors.lastname: Lusher
authors.forename: M A
authors.initials: MA
authors.lastname: Koerper
authors.forename: M
authors.initials: M
authors.lastname: Manco-Johnson
authors.forename: D S
authors.initials: DS
authors.lastname: Krause
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003257:Consumer Product Safety / Q000592:standards*; D003288:Contusions / Q000209:etiology; D004890:Erythema / Q000209:etiology; D005169:Factor VIII / Q000276:immunology / Q000627:therapeutic use; D005260:Female; D005334:Fever / Q000209:etiology; D006261:Headache / Q000209:etiology; D022362:Hepatitis A Vaccines; D006508:Hepatitis Antibodies / Q000097:blood; D006801:Humans; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000097:blood; D007249:Inflammation / Q000209:etiology; D007273:Injections, Intramuscular / Q000009:adverse effects; D007279:Injections, Subcutaneous / Q000009:adverse effects; D007518:Isoantibodies / Q000097:blood; D008297:Male; D010146:Pain / Q000209:etiology; D011446:Prospective Studies; D013810:Therapeutic Equivalency; D013997:Time Factors; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage* / Q000276:immunology* / Q000493:pharmacokinetics
chemical_list: D022362:Hepatitis A Vaccines; D006508:Hepatitis Antibodies; D007074:Immunoglobulin G; D007518:Isoantibodies; D014761:Viral Hepatitis Vaccines; D005169:Factor VIII