Scott Halperin

Safety and Immunogenicity of 26-Valent Group A Streptococcus Vaccine in Healthy Adult Volunteers

BACKGROUND Group A streptococcus (GAS) causes illness ranging from uncomplicated pharyngitis to life-threatening necrotizing fasciitis, toxic shock, and rheumatic fever. Attempts to develop an M protein-based vaccine have been hindered by the fact that some M proteins elicit both protective antibodies and antibodies that cross-react with human tissues. New molecular techniques have allowed the previous obstacles to be largely overcome. METHODS The vaccine is comprised of 4 recombinant proteins adsorbed to aluminum hydroxide that contain N-terminal peptides from streptococcal protective antigen and M proteins of 26 common pharyngitis, invasive, and/or rheumatogenic serotypes. Thirty healthy adult subjects received intramuscular 26-valent GAS vaccine (400 microg) at 0, 1, and 4 months, with clinical and laboratory follow-up for safety and immunogenicity using assays for tissue cross-reactive antibodies, type-specific M antibodies to 27 vaccine antigens, and functional (opsonization) activity of M protein antibodies. RESULTS The incidence of local reactogenicity was similar to that for other aluminum hydroxide-adsorbed vaccines in adults. No subject developed evidence of rheumatogenicity or nephritogenicity, and no induction of human tissue-reactive antibodies was detected. Overall, 26 of 27 antigenic peptides evoked a >4-fold increase in the geometric mean antibody titer over baseline. The mean log2 fold-increase in serum antibody titer (+/- standard error of the mean) for all 27 antigens was 3.67 +/- 0.21. A significant mean log2 reduction in streptococcal bacterial counts in serum samples obtained after immunization was seen in opsonization assays for all M serotypes. CONCLUSIONS On the basis of epidemiological data demonstrating that the majority of cases of pharyngitis, necrotizing fasciitis, and other invasive streptococcal infections are caused by a limited number of serotypes, this 26-valent vaccine could have significant impact on the overall burden of streptococcal disease.

Cost of Chickenpox in Canada: Part I. Cost of Uncomplicated Cases

Objective. The purpose of this study was to assess the direct medical costs and productivity losses associated with uncomplicated chickenpox (no hospitalization) in Canada. Methods. A total of 179 otherwise healthy 1- to 9-year-old children with active chickenpox were recruited from schools, day care centers, and physician offices in 5 provinces. Direct medical (physician contacts, medication, and diagnostic tests) and nonmedical (personal expenses including child care) resources expended during the illness were determined by caregiver interview. Productivity losses attributable to the disease were determined by assessing caregiver time lost from work and daily activities. Unit costs for all resources were obtained from sources in 2 provinces, and per-patient treatment costs were determined from the patient, Ministry of Health, and societal perspectives. Results. From a societal perspective, the per-case cost for children from 1 to 4 years of age and from 5 to 9 years of age was

Randomized Controlled Trial of the Safety and Immunogenicity of Revaccination With Tetanus-Diphtheria-Acellular Pertussis Vaccine (Tdap) in Adults 10 Years After a Previous Dose

370.2 and

Immunisation pendant la grossesse

236.5, respectively. Direct medical costs accounted for 10% of the total costs in both groups. The largest cost driver in patient care was caregiver productivity losses, which amounted to

Immunization in Pregnancy

316.5 in the younger age group and to

Safety and Immunogenicity of Two Acellular Pertussis Vaccines with Different Pertussis Toxoid and Filamentous Hemagglutinin Content in Infants 2-6 Months Old

182.7 in the older age group. Based on an estimated yearly incidence of 344 656 cases of uncomplicated chickenpox in Canada, the total annual societal burden of the disease can be estimated at

ImmunogenicityofaTetravalentMeningococcal Glycoconjugate Vaccine in Infants

109.2 million, with a cost to the Ministry of Health of

A double-blind, randomized phase II trial of the safety and immunogenicity of 26-valent group A streptococcus vaccine in healthy adults

11.2 million. Conclusion. Chickenpox is one of the last common childhood diseases prevalent in Canada, and the uncomplicated disease, despite its rather benign course, imparts a large annual economic burden.

Immunization in pregnancy: No. 220, December 2008.

Abstract Background Reduced-antigen-content tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is recommended in many countries for boosting immunity in adolescents and adults. Although immunity to these antigens wanes with time, currently available Tdap products are not labeled for repeat administration in the United States. Methods We performed an observer-blinded, randomized controlled trial in 1330 adults aged 18 to <65 years who received either the Tdap (n = 1002) or tetanus-diphtheria (Td) (n = 328) vaccine 8 to 12 years after a dose of Tdap vaccine administered previously. Solicited adverse events following immunization were documented for 7 days after vaccination, and serious adverse events and adverse events of medical significance were documented for 6 months after vaccination. Levels of antibodies against component vaccine antigens were measured before and 1 month after vaccination. Results A solicited adverse event was reported by 87.7% of Tdap and 88.0% of Td vaccine recipients. We found no significant differences in the rates of injection-site reactions, systemic reactions, or serious adverse events between the vaccine groups. A robust antibody response to each pertussis antigen in the Tdap-vaccinated group was found; postvaccination-to-prevaccination geometric mean antibody concentration ratios were 8:1 (pertussis toxoid), 5.9 (filamentous hemagglutinin), 6.4 (pertactin), and 5.2 (fimbriae 2 and 3). Postvaccination geometric mean concentrations of tetanus antibody (4.20 and 4.74 IU/mL, respectively) and diphtheria antibody (10.1 and 12.6 IU/mL, respectively) were similar in the Tdap and Td groups, and the rates of seroprotection against tetanus and diphtheria were >99% in both groups. Conclusions A second dose of Tdap vaccine in adults approximately 10 years after a previous dose was well tolerated and immunogenic. These data might facilitate consideration of providing Tdap booster doses to adults.

VARICELLA-RELATED HOSPITALIZATIONS IN IMPACT CENTERS AFTER INTRODUCTION OF 1- AND 2-DOSE VARICELLA VACCINATION PROGRAMS BETWEEN 2000 AND 2015

Resume Objectif Analyser les resultats et offrir des recommandations quant a l’immunisation pendant la grossesse. Issues Parmi les issues evaluees, on trouve l’efficacite de l’immunisation, les risques et les avantages pour la mere et le fœtus. Resultats Des recherches ont ete menees dans les bases de donnees Medline et Cochrane en vue d’en tirer les articles, publies avant juillet 2007, portant sur l’immunisation pendant la grossesse. Valeurs Les donnees obtenues ont ete analysees et evaluees par le comite sur les maladies infectieuses de la Societe des obstetriciens et gynecologues du Canada (SOGC), sous la supervision des auteurs principaux, et des recommandations ont ete formulees conformement aux lignes directrices etablies par le Groupe d’etude canadien sur les soins de sante preventifs. Avantages, desavantages et couts La mise en œuvre des recommandations de la presente directive clinique devrait mener a une meilleure immunisation des femmes enceintes et des femmes qui allaitent, a une attenuation du risque d’immunisation contre-indiquee et a une meilleure prevention de la maladie. Recommandations 1. Avant de proceder a l’immunisation de toute femme en âge de procreer, le fournisseur de soins devrait chercher a ecarter la presence possible d’une grossesse chez celle-ci. (III-A) 2. Les fournisseurs de soins devraient obtenir les antecedents quant a l’immunisation de toutes les femmes qui les consultent afin d’obtenir des soins prenatals. (III-A) 3. En general, les vaccins a virus vivant et/ou a virus vivant-attenue sont contre-indiques pendant la grossesse, et ce, en raison de la presence d’un risque (essentiellement theorique) pour le fœtus. (II-3B) 4. Les femmes qui ont recu, par inadvertance, une immunisation au moyen de vaccins vivants ou vivants-attenues pendant la grossesse ne devraient pas etre avisees de proceder a une interruption de grossesse motivee par la presence d’un risque de teratogenicite. (II-2A) 5. Les femmes n’etant pas enceintes qui ont ete immunisees au moyen d’un vaccin vivant ou vivant-attenue devraient etre avisees de reporter la grossesse pendant au moins quatre semaines. (III-B) 6. L’administration de vaccins viraux inactives, de vaccins bacteriens et de toxoides pendant la grossesse est consideree comme etant sure. (II-1A) 7. Les femmes qui allaitent peuvent tout de meme etre immunisees (immunisation passive-active, vaccins vivants ou morts). (II-1A) 8. Les femmes enceintes devraient se voir offrir le vaccin antigrippal lorsque leur grossesse coincide avec la saison de la grippe. (II-1A)