ABSTRACT
Rabies neutralizing antibody concentrations in serum (SRNA) elicited by experimental post-exposure prophylaxis (PEP) regimens are used to assess their potential clinical efficacy. Although PEP with human rabies immunoglobulin (HRIG) plus human diploid-cell culture vaccine (HDCV) is almost completely protective, the limited availability of these components has stimulated the search for alternative regimens. Since 33% to over 60% of PEP is administered to children, a need exists for data on the SRNA response to HRIG plus HDCV in children, to be used to assess the potential value of alternative PEP treatments. We measured SRNA by the rapid fluorescent focus inhibition test on days 0, 1, 3, 7, 14, 28, 56 and 90 after initiation of PEP with HRIG (20 IU/kg) and HDCV (1.0 ml on day 0, 3, 7, 14, 28) in 10 children [8 +/- 4 (mean +/- SD) years of age] and 32 adult control patients (38 +/- 16 years of age). Early, uniform appearance of SRNA was observed with no differences between groups. These data are consistent with the demonstrated efficacy of PEP with HRIG plus HDCV in children as in adults and provide results that can be used for initial evaluation of experimental pediatric PEP regimens in the future.
Subject(s)
Antibodies, Viral/blood , Rabies Vaccines/administration & dosage , Rabies virus/immunology , Rabies/prevention & control , Adult , Age Factors , Child , Child, Preschool , Female , Humans , Immunoglobulins/administration & dosage , Infant , Male , Neutralization Tests , Rabies Vaccines/isolation & purificationABSTRACT
The beneficial effect of passive immunization for post-exposure rabies prophylaxis is associated with the appearance of serum neutralizing antibody (SNA) earlier than occurs with vaccine alone. We compared the SNA response and the side-effects in 30 previously unimmunized healthy volunteers given a commercially available human rabies immunoglobulin (HRIG) intramuscularly (i.m.) or an experimental HRIG prepared by DEAE Sephadex column chromatography, intravenously (i.v.) with or without human diploid-cell culture rabies vaccine (HDCS). The subjects were divided into five equal groups: HDCS alone, HDCS + i.m. HRIG 20 IU/kg (currently recommended), i.v. HRIG alone 15 IU/kg, HDCS + i.v. HRIG 15 IU/kg or HDCS + HRIG 5 IU/kg i.v. plus 10 IU/kg i.m. to simulate local bite wound infiltration. HDCS, 1.0 ml, was injected subcutaneously (s.c.) on days 0, 3, 7, 14 and 28. Only local discomfort at injection sites was observed without differences between groups. SNA was demonstrated in all HRIG recipients at day 1, but the concentrations were higher in those receiving it intravenously. No difference in the SNA response to vaccine was observed between the i.v. and i.m. HRIG groups given the same vaccine lot. It would appear that i.v. HRIG 15 IU/kg can be substituted for i.m. HRIG 20 IU/kg for post-exposure prophylaxis. Since the current regimen is almost 100% protective, there is no way of proving that i.v. HRIG 15 IU/kg is more efficacious. The immediate SNA level and economy are the chief advantages of i.v. HRIG 15 IU/kg.
Subject(s)
Antibodies, Viral/administration & dosage , Rabies virus/immunology , Rabies/prevention & control , Antibodies, Viral/biosynthesis , Clinical Trials as Topic , Humans , Immunization, Passive/adverse effects , Immunoglobulins/administration & dosage , Injections, Intramuscular , Injections, Intravenous , Neutralization Tests , Rabies/immunology , Rabies Vaccines/administration & dosage , Rabies Vaccines/adverse effects , Random AllocationABSTRACT
A method is described using double diffusion with a perspex template for determining tetanus antitoxin levels in the plasma of volunteers who have been hyperimmunized with tetanus toxoid for the purpose of producing human tetanus immune globulin. This test is simple to perform, economical, sentitive, reproducible and is in excellent agreement with the standard toxin neutralization test in mice. Comparisons with the in vivo toxin neutralization test are presented for this test, the passive hemagglutination, radial immunodiffusion and counter electrophoresis methods.
Subject(s)
Tetanus Antitoxin/analysis , Counterimmunoelectrophoresis/methods , Hemagglutination Tests/methods , Humans , Immunization , Immunodiffusion/methods , Neutralization Tests/methodsABSTRACT
Five tetanus toxoids of different manufacture and of different concentrations were used to determine the most effective formulation and strength of toxoid for the production in human volunteers of sustained high levels of tetanus antitoxin suitable for the production of human tetanus immune globulin. The most satisfactory results were obtained with a fluid, low-protein, column-purified tetanus toxoid. 79% of volunteers injected with a 36 Lf dose of this material achieved antitoxin levels of greater than or equal to 10 antitoxin units/ml. The mean duration of these levels was 125 days.
