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Biomedical subjects

S A Halperin

Publications and source records attributed to S A Halperin.

At least 37 records · Page 2Linked to original sources
PubMed1999

Comparison of a fifth dose of a five-component acellular or a whole cell pertussis vaccine in children four to six years of age.

BACKGROUND AND OBJECTIVES: Acellular pertussis vaccines are now preferred for all five childhood immunization doses; however, there are few data on the safety and immunogenicity of five consecutive doses. This study compared a fifth dose of an acellular and a whole cell pertussis vaccine in 4- to 6-year-old children previously immunized with four doses of acellular or whole cell pertussis vaccine. STUDY DESIGN: In a double blind, multicenter study, 366 healthy children were randomly allocated to receive a single injection of a 5-component acellular or a whole cell pertussis vaccine, each combined with diphtheria and tetanus toxoids and inactivated poliovirus vaccine. RESULTS: Although injection site redness > or =50 mm and swelling > or =50 mm were common in children who had received five doses of acellular (50% and 48.1%, respectively) or whole cell (66.2% and 59.7%) pertussis vaccine, limb soreness and limitation of motion were less frequently reported after acellular (1.9% and 0%) than after whole cell (49.2% and 36.3%; P < 0.0001) pertussis vaccine. Pre-fifth dose antipertussis antibody titers were higher in children who previously had received four doses of acellular pertussis vaccine. Postimmunization antibody titers against pertussis toxin, filamentous hemagglutinin, pertactin and tetanus toxin were higher in recipients of five doses of acellular pertussis vaccine, whereas antibody titers to diphtheria toxin, pertussis fimbriae and poliovirus serotypes were higher in recipients of five doses of the whole cell pertussis vaccine (P < 0.05 for all comparisons). CONCLUSIONS: A regimen consisting of five doses of a five-component acellular pertussis combination vaccine is safe and immunogenic in pre-school children. Local adverse reactions are common but are less painful and activity-limiting than a regimen of five doses of a whole cell pertussis vaccine.

Antibodies, Bacterial↗
PubMed1999

Surface expression of a protective recombinant pertussis toxin S1 subunit fragment in Streptococcus gordonii.

In this study, the expression of the Bordetella pertussis S1 subunit was tested in Streptococcus gordonii, a commensal oral bacterium which has the potential to be a live oral vaccine vehicle. The DNA fragment encoding the N-terminal 179 amino acids of the S1 subunit was ligated into the middle part of spaP, the surface protein antigen P1 gene originating from Streptococcus mutans. The resulting construct, carried on the Escherichia coli-Streptococcus shuttle vector pDL276, was introduced into S. gordonii DL-1 by natural transformation. One of the transformants (RJMIII) produced a 187-kDa protein (the predicted size of the SpaP-S1 fusion protein) which was recognized by both the anti-pertussis toxin (anti-PT) and anti-SpaP antibodies, suggesting that an in-frame fusion had been made. Results from immunogold-electron microscopic studies and cellular fractionation studies showed that the fusion protein was surface localized and was mainly associated with the cell wall of RJMIII, indicating that SpaP was able to direct the fusion protein to the cell surface. A rabbit antiserum raised against heat-killed S. gordonii RJMIII recognized the native S1 subunit of PT in Western blotting and showed a weak neutralization titer to PT by the Chinese hamster ovary cell-clustering assay. BALB/c mice immunized with the heat-killed S. gordonii RJMIII were protected from the toxic effect of PT in the leukocytosis-promoting and histamine sensitization assays. In conclusion, a fragment of the S1 subunit of PT was successfully surface expressed in S. gordonii; the recombinant S1 fragment was found to be immunogenic and could induce protection against the toxic effect of PT in mice.

Animals↗
PubMed1999

A randomized, placebo-controlled trial of erythromycin estolate chemoprophylaxis for household contacts of children with culture-positive bordetella pertussis infection.

CONTEXT: Household contacts of patients with pertussis are at increased risk of acquiring infection. Chemoprophylaxis has been recommended to decrease transmission, particularly to young infants who are at increased risk of severe disease. Although epidemiologic investigations of outbreaks have suggested a benefit, there have been no prospective studies evaluating the efficacy of chemoprophylaxis in preventing secondary cases of pertussis. OBJECTIVE: To determine whether erythromycin estolate chemoprophylaxis is effective in household contacts of children with culture-positive pertussis. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Community based. SUBJECTS: All household contacts of 152 children with culture-positive pertussis who provided consent (n = 362). After withdrawals, there were 135 households with 310 contacts. Exclusions included pregnancy, age <6 months, already receiving an erythromycin-containing antibiotic, and erythromycin allergy. INTERVENTUINS: Erythromycin estolate (40 mg/kg/day in 3 divided doses; maximum dose 1 g) or placebo for 10 days. Nasopharyngeal cultures, pertussis antibodies, and clinical symptoms were assessed before and after treatment. PRIMARY OUTCOME: Measure efficacy of erythromycin estolate chemoprophylaxis calculated by the proportion of households in each group with a member who developed a nasopharyngeal culture positive for Bordetella pertussis. RESULTS: There was no difference in the development of respiratory tract symptoms compatible with a case definition of pertussis in the erythromycin- and placebo-treated groups. There were 20 households with secondary culture-positive cases of pertussis; 4 households in the erythromycin-treated group and 15 in the placebo-treated group (efficacy of erythromycin chemoprophylaxis for bacterial eradication 67.5% [95% confidence interval: 7.6-88.7]). However, medication-associated adverse reactions were reported by 34.0% of erythromycin and 15.7% of placebo recipients. CONCLUSIONS: Under the conditions of this study, erythromycin estolate prevented culture-positive pertussis in household contacts of patients with pertussis but did not prevent clinical pertussis.

Adolescent↗
PubMed1998

Induction of immunologic memory by conjugated vs plain meningococcal C polysaccharide vaccine in toddlers: a randomized controlled trial.

CONTEXT: Meningococcal polysaccharide vaccines are not used routinely in infants and toddlers, the groups at highest risk of invasive disease, because of poor immunologic responses to the Neisseria meningitidis serogroup C polysaccharide in these age groups. Meningococcal C conjugate vaccines offer the prospect of circumventing this problem. OBJECTIVE: To assess the immunogenicity and the induction of immunologic memory in toddlers by meningococcal C conjugate vaccine. DESIGN: A multicenter, randomized, observer-blinded controlled trial. SETTING: Urban and suburban family medicine or pediatric practices. PARTICIPANTS: Two hundred eleven healthy toddlers aged 15 to 23 months. INTERVENTION: Two injections at 2 months apart of meningococcal C conjugate (group 1, n = 69), plain meningococcal polysaccharide (group 2, n = 72), or hepatitis B virus vaccine (group 3, n = 70). All toddlers received a follow-up dose of plain meningococcal polysaccharide vaccine 12 months later. MAIN OUTCOME MEASURES: IgG meningococcal C anticapsular antibody concentrations determined by enzyme-linked immunosorbent assay and complement-mediated bactericidal antibody. RESULTS: In group 1, the magnitude of the IgG response to meningococcal C conjugate vaccine was more than 4-fold higher after dose 1 and more than 10-fold higher after dose 2 compared with meningococcal polysaccharide vaccine (group 2) (P<.001). Higher titers persisted in the meningococcal C conjugate group for at least 12 months (P<.001). Group 1, primed with meningococcal C conjugate, had 25-fold higher IgG responses to the meningococcal polysaccharide 1-year booster dose than the controls who had received hepatitis B virus vaccine initially and were given meningococcal polysaccharide vaccine 1 year later for the first time (P<.001). In contrast, group 2, primed with meningococcal polysaccharide, had a 2-fold lower response to the 1-year booster meningococcal polysaccharide dose than the hepatitis B virus control group (P = .006). Serum bactericidal responses paralleled the enzyme-linked immunosorbent assay responses. CONCLUSIONS: Immunization of toddlers with meningococcal C conjugate vaccine induces high titers of anticapsular and bactericidal antibody. Furthermore, this vaccine induces immunologic memory to meningococcal C polysaccharide. In contrast, meningococcal polysaccharide vaccine is less immunogenic than the conjugate vaccine and also induces a hyporesponsive state that persists for at least 12 months.

Antibodies, Bacterial↗
PubMed1998

Safety and immunogenicity of a new influenza vaccine grown in mammalian cell culture.

In a phase I safety and immunogenicity study, 112 healthy adult volunteers were randomly allocated to receive a new bivalent (A/Texas/36/91[H1N1-like], B/Harbin/7/94) split virion influenza vaccine propagated in Madin-Darby Canine Kidney cell culture or an identical vaccine manufactured using currently licensed egg propagated virus technology. Soreness at the injection site was common but generally mild (75% of the cell culture-derived vaccine group and 62.5% of the egg-derived vaccine group; p = not significant). General reactions were less common; headache was the most frequently reported adverse effect (26.8 and 30.4%, respectively; p = not significant). Geometric mean haemagglutination inhibition titres post-immunization against the A/Texas strain were 1012 reciprocal dilution in the cell culture-derived vaccine group and 790 in the egg-derived vaccine group; against the B/Harbin strain titres were 420 and 447, respectively (all comparisons, p = not significant). It is concluded that the cell culture-derived split virion influenza vaccine is safe and immunogenic in healthy adult volunteers.

Adolescent↗
PubMed1998

Comparison of parental and health care professional preferences for the acellular or whole cell pertussis vaccine.

OBJECTIVE: To compare the preferences of mothers, physicians and nurses for use of a new generic acellular pertussis vaccine which is less reactogenic than and as effective as a conventional whole cell vaccine, but which would require multiple injections rather than a single injection to deliver all other recommended vaccines. METHODS: A convenience sample of 400 mothers of 1-month-old infants, 100 immunizing physicians and 100 immunizing nurses were surveyed over a 2 1/2-month period. Information about pertussis and both whole cell and acellular pertussis vaccines was provided, and a questionnaire was used to assess knowledge and attitudes about pertussis vaccine, vaccine preference and reasons for selection. In addition to their own preferences health care professionals were asked to predict which vaccine mothers would prefer and to predict why mothers would choose a particular vaccine. RESULTS: Mothers preferred the acellular vaccine over the whole cell vaccine by a nearly 2:1 margin (57.3% vs. 29.5%). Health care professionals preferred the whole cell vaccine by the same 2:1 margin (61.1% vs. 29.3%). Only 19.1% of health care professionals predicted that mothers would accept the acellular vaccine if it meant multiple injections. More mothers were concerned by the common reactions caused by the whole cell vaccine (75.8% vs. 52%; P = 0.001); more health care professionals felt that multiple injections were stressful (89% vs. 70%; P = 0.001) and that they could be associated with long term effects (17% vs. 8.8%; P = 0.003). More health care professionals than mothers said that the need for multiple injections would influence their decision to accept the acellular vaccine (76.5% vs. 38.3%; P = 0.001). CONCLUSIONS: Mothers prefer a less reactogenic vaccine product even if it requires multiple injections. Health care professionals are more concerned about multiple injections and are poor predictors of mothers' vaccine preference. Multiple injections may be more a barrier to immunization for health care professionals than for mothers.

Choice Behavior↗
PubMed1998

Parental willingness to enter a child in a controlled vaccine trial.

OBJECTIVE: To determine the reasons that motivate parents to enrol or not enrol their child in a randomized, controlled vaccine trial. DESIGN: Cross-sectional survey. SETTING: Offices of primary care physicians in Dartmouth, Nova Scotia, and Montreal, Quebec. PARTICIPANTS: At the 2 sites, parents of 2-month-old infants at their first immunization visit who had decided to enrol (221) or not enrol (208) their child in 2 randomized pertussis vaccine trials. OUTCOME MEASURES: Rates of enrolment in vaccine trials; attitudes about medical research; sources of information about pertussis. RESULTS: Enrolment rates were 68% and 43% at the 2 sites. All parents agreed to answer questions about their decision to enrol or not enrol their child. The most common concerns resulting in nonenrolment were extra immunization 54% (26/48) and blood procurement 42% (20/48). Parents who did enrol their children were motivated to participate by the desire to contribute to medical knowledge (77% [170/221]), the desire to help others (48% [106/221]) and by the participation of their family physician (54% [120/221]). The enrollees' major sources of information about pertussis was health professionals or study personnel rather than the media. CONCLUSIONS: Altruistic reasons motivate parents' decision to enrol a child in a randomized, controlled vaccine trial. Nonparticipating parents seem most concerned about painful procedures in the study. Parents' decisions regarding participation do not appear to be affected by adverse media attention regarding the purported adverse sequelae of pertussis vaccines.

Attitude to Health↗
PubMed1997

Safety and immunogenicity of two inactivated poliovirus vaccines in combination with an acellular pertussis vaccine and diphtheria and tetanus toxoids in seventeen- to nineteen-month-old infants.

OBJECTIVES: To compare the safety and immunity of an acellular pertussis vaccine containing pertussis toxoid, filamentous hemagglutinin, 69 kd protein, fimbriae 2 and 3 combined with diphtheria and tetanus toxoids given as single or separate injection with inactivated poliovirus vaccine (MRC-5-or Vero cell-derived) or live attenuated polio vaccine. METHODS: A total of 425 healthy children between 17 and 19 months of age who were receiving the fourth dose of their routine immunization series were randomly allocated to receive either the acellular pertussis vaccine and oral poliovirus vaccine or one of two inactivated poliovirus vaccines as a combined injection or separate injections. RESULTS: Although minor adverse events were commonly reported, differences between the groups were few. Fever and decreased feeding were less common in recipients of live attenuated poliovirus vaccine than the combination vaccine containing MRC-5 cell-derived inactivated poliovirus vaccine. A significant antibody response was demonstrated in all groups against all the antigens contained in the vaccines. Antibodies against poliovirus were higher in the groups immunized with the inactivated poliovirus vaccine than the live attenuated vaccine. Anti-69 kd protein antibodies were higher in the group given the MRC-5 cell-derived inactivated poliovirus vaccine as a combined injection than in the group given the separate injection or the group immunized with the live attenuated poliovirus vaccine. CONCLUSION: The five-component acellular pertussis vaccine combined with diphtherid and tetanus toxoids is safe and immunogenic when combined with either MRC-5- or Vero cell-derived inactivated poliovirus vaccine. This will facilitate the implementation of acellular pertussis vaccine and the movement to inactivated poliovirus vaccine programs.

Antibody Formation↗
PubMed1997

Estimates of the effectiveness of a whole-cell pertussis vaccine from an outbreak in an immunized population.

Pertussis has re-emerged as a public health problem in Canada in recent years, emphasizing concerns about the effectiveness of the currently licensed whole-cell vaccine. Following a 1994 outbreak in Nova Scotia, we conducted a case-control study of 483 children aged < 10 years to assess vaccine effectiveness. Ninety-three percent of children aged 6 months and above had received three or more doses of vaccine, however, only 78% had received age-appropriate immunization. Among children aged 4 years and more, vaccine effectiveness against laboratory-confirmed pertussis was 57% (95% CI, 23-77%) for age-appropriate immunization (five doses) vs partial or no immunization. Vaccine effectiveness increased with increasing number of doses from 25% (95% CI, -58-65%) for three or more doses to 55% (95% CI, -15-83%) for five doses, compared with 0-2 doses.

Age Factors↗
PubMed1997

Safety and immunogenicity of an acellular pertussis diphtheria tetanus vaccine given as a single injection with Haemophilus influenzae b conjugate vaccine.

To determine if an acellular pertussis-diphtheria-tetanus vaccine could be combined with a Haemophilus influenzae b conjugate vaccine as a single injection, we randomized 468 children between 17 and 21 months of age previously immunized with three doses of each vaccine to receive a five-component acellular pertussis vaccine combined with diphtheria and tetanus toxoids, and Haemophilus influenzae b-tetanus toxoid conjugate vaccine either as separate injections on separate days, separate injections on the same day, or as a single combined injection. Rates of adverse reactions were similar amongst the groups except for increased injection site tenderness (29.2% vs 17%, RR 1.76, 95% CI 1.09-2.85) and fussiness (36.4% vs 23.3%, RR 1.59, 95% CI 1.05-2.41) in the group given the combined injection rather than separate injections on separate days. Antibody levels against the capsular polysaccharide of H. influenzae b after the single combined injection (47.1 micrograms ml-1) were lower than after separate injections on the same day (66.0 micrograms ml-1; P < 0.05) but higher than when the injections were administered on separate days (28.4 micrograms ml-1; P < 0.001). We conclude that the five-component acellular pertussis vaccine is safe and immunogenic when combined with diphtheria and tetanus toxoids and H. influenzae b-tetanus toxoid conjugate vaccine in children receiving the fourth dose of the immunization series.

Antibodies, Bacterial↗
PubMed1997

Seven days of erythromycin estolate is as effective as fourteen days for the treatment of Bordetella pertussis infections.

OBJECTIVE AND METHODS: Although 14 days of erythromycin is recommended for the treatment of Bordetella pertussis infection, there have been no prospective controlled studies to support the contention that this long course of therapy is required to eradicate the microorganism from the nasopharynx or to prevent bacteriological relapse. We randomly allocated children and adults with culture-positive community-acquired pertussis to either 7 or 14 days of erythromycin estolate treatment (40 mg/kg/d; maximum dose 1 g/d). Nasopharyngeal aspirate cultures were obtained by study nurses during home visits before and at the end of treatment, and 1 week after the completion of treatment. B pertussis-specific antibodies were measured before treatment and 1 month later. Information about clinical symptoms, adverse reactions, and compliance were collected at each scheduled contact. RESULTS AND CONCLUSIONS: A total of 168 participants were eligible for analysis (74 treated for 7 days and 94 treated for 14 days). Bacteriological persistence (positive end of therapy culture) occurred once in each group, and bacteriological relapse (positive culture 1 week after completion of treatment) occurred in one participant treated for 7 days. The overall failure rate (persistence plus relapse) of 2.70% in the 7-day group was not different than the rate of 1.06% in the 14-day group. The study had a power of 99.99% at the 5% level to detect a difference in failure rates of 10% and a power of 80% to detect a difference of 5%. We conclude that 7 days of erythromycin estolate is as effective as 14 days for the eradication of B pertussis.

Adolescent↗
PubMed1996

Adverse reactions and antibody response to four doses of acellular or whole cell pertussis vaccine combined with diphtheria and tetanus toxoids in the first 19 months of life.

To assess the safety, immunogenicity, and lot consistency of a five-component acellular pertussis vaccine combined with diphtheria and tetanus toxoid (Connaught Laboratories Limited), we randomly allocated 432 infants to receive one of three lots of an acellular pertussis vaccine or a single lot of whole cell pertussis vaccine. Infants were immunized at 2, 4 and 6 months of age and between 17 and 19 months of age. Local and systemic adverse reactions were reported significantly more frequently by recipients of the whole cell than acellular vaccine after each dose. The antibody response against pertussis toxin, filamentous hemagglutinin, and 69 kDa protein was of greater magnitude in acellular pertussis vaccine recipients than whole cell pertussis vaccine recipients. Small differences were detected amongst the vaccine lots tested. We conclude that the acellular pertussis vaccine is safe and immunogenic for the first four doses in children under 2 years of age.

Antibodies, Bacterial↗
PubMed1996

Effect of inactivated poliovirus vaccine on the antibody response to Bordetella pertussis antigens when combined with diphtheria-pertussis-tetanus vaccine.

To determine if inactivated poliovirus vaccine combined with diphtheria and tetanus toxoids and whole-cell pertussis vaccine interferes with the immunogenicity of pertussis vaccine, we performed a randomized trial of diphtheria and tetanus toxoids and pertussis vaccine combined with inactivated poliovirus vaccine given as a single injection or as two separate injections at the same visit to infants immunized at 2, 4, and 6 months of age. A total of 84 infants were enrolled in the study; 44 received the single injection, and 40 received separate injections. Before immunization, there were no differences in antibody values between the two groups. After two vaccine doses, infants immunized with the single injection had significantly lower values of antibody to filamentous hemagglutinin (8.3 vs. 23.7 ELISA units; P < .001), fimbriae (266.5 vs. 771.8 ELISA units; P < 0.01), and the 69-kD membrane protein (442.2 vs. 1,352 ELISA units; P < .001). After the third dose, these differences persisted, and differences were also detected for antibody to pertussis toxin (10.0 vs. 35.5 ELISA units; P < .001) and a whole-bacteria antigen preparation (2,667 vs. 3,829 ELISA units; P < .05). We conclude that there is a diminished antibody response to the pertussis vaccine when inactivated poliovirus vaccine is combined with the diphtheria and tetanus toxoids and pertussis vaccine.

Antibodies, Bacterial↗