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Biomedical subjects

Scott A Halperin

Publications and source records attributed to Scott A Halperin.

14 recordsLinked to original sources
PubMed2003

Safety and immunoenhancing effect of a Chlorella-derived dietary supplement in healthy adults undergoing influenza vaccination: randomized, double-blind, placebo-controlled trial.

BACKGROUND: Enhancement of immune function has been claimed as a benefit of some natural health products, although few have been subjected to randomized clinical trials. We evaluated the effect of an oral dietary supplement derived from the edible microalga Chlorella pyrenoidosa on immune response after influenza vaccination. METHODS: We conducted a randomized, double-blind, placebo-controlled community-based clinical trial in a convenience sample of 124 healthy adults at least 50 years of age randomly assigned to receive the study product (200 or 400 mg of a Chlorella-derived dietary supplement) or placebo. Participants took the study product or placebo once daily for 28 days. On day 21, we administered a single dose of a licensed trivalent, inactivated influenza vaccine. We obtained serum specimens to measure hemagglutination inhibition titres before and 7 and 21 days after vaccination. The primary immunological outcomes were the proportion of participants with a 4-fold or greater increase in antibodies and geometric mean antibody titres after vaccination; the proportion of participants reporting adverse events during therapy was the safety outcome. RESULTS: A total of 117 (94%) participants completed all aspects of the study. There were no differences in the proportions of recipients of 200 or 400 mg of the Chlorella-derived dietary supplement or placebo who achieved at least a 4-fold increase in antibodies (proportions for the 3 virus strains ranged from 17.9% to 28.2% for the 200-mg group, from 11.1% to 22.2% for the 400-mg group and from 19.0% to 21.4% for the placebo group; p > 0.05 for all comparisons). Reports of adverse events were similar for recipients of the supplement and placebo, except with regard to fatigue, which was reported more frequently by recipients of 200 mg of the supplement (18/41 or 44%) than by those who received 400 mg of the supplement (8/40 or 20%; p = 0.032) or placebo (8/42 or 19%; p = 0.019). Recipients of 400 mg of the supplement who were 55 years of age or younger had significantly higher geometric mean antibody titres against influenza A/New Caledonia 21 days after vaccination (p = 0.047) and against B/Yamanashi 7 days after vaccination (p = 0.034); the trends were nonsignificant for titres against A/Panama. We also observed similar increases for the proportions of subjects with a 2-fold or greater or a 4-fold or greater increase in antibodies. INTERPRETATION: The Chlorella-derived dietary supplement did not have any effect in increasing the antibody response to influenza vaccine in the overall study population, although there was an increase in antibody response among participants aged 50-55 years. Adverse events were similar among those receiving the supplement and the placebo. Further studies are warranted to explore the range of clinical effects resulting from ingestion of this dietary supplement.

Adjuvants, Immunologic↗
PubMed2003

A phase I study of the safety and immunogenicity of recombinant hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligonucleotide adjuvant.

Certain oligodeoxynuclotides with CpG motifs provide enhanced immune response to co-delivered antigens. We performed a phase I, observer-blinded, randomized study in healthy anti-hepatitis B surface antigen (anti-HBsAg) antibody negative adults to explore safety and immunogenicity of co-injection of recombinant HBsAg combined with an immunostimulatory DNA sequence (ISS) 1018 ISS. Four ISS dosage groups (N=12 per group) were used: 300, 650, 1000 or 3000 microg. For each group, two controls received 20 microg HBsAg alone, two controls received ISS alone, and eight subjects received ISS+20 microg HBsAg. Subjects received two doses 8 weeks apart. Injection site reactions (tenderness and pain on limb movement) were more frequent at higher ISS+HBsAg doses but were mainly mild and of short duration. Higher anti-HBsAg antibody levels were associated with higher ISS doses. Four weeks after the first dose, a seroprotective titer (>or=10 mIU/ml) was noted for 0, 25, 75, and 87.5% of subjects by increasing ISS dose group (P<0.05) for those who received ISS+HBsAg; 1 month after the second dose this increased to 62.5, 100, 100, and 100%, respectively. Geometric mean anti-HBsAg antibody levels by increasing ISS+HBsAg dose were 1.22, 5.78, 24.75, and 206.5 mIU/ml after the first dose and 65.37, 877.6, 1545, and 3045 mIU/ml after the second dose. We conclude that 1018 ISS+HBsAg was well tolerated and immunogenic in this phase I study in healthy adults and may offer the potential for enhancement of hepatitis B virus (HBV) immunization and protection after one or two doses or in individuals who fail to respond to the standard vaccine regimen.

Adjuvants, Immunologic↗
PubMed2003

Nature, evolution, and appraisal of adverse events and antibody response associated with the fifth consecutive dose of a five-component acellular pertussis-based combination vaccine.

We performed a randomized, controlled clinical trial to characterize the evolution of the adverse events associated with the fifth consecutive dose of an acellular pertussis vaccine, and to assess the level of discomfort associated with the injection and the attitude of parents concerning these events. A total of 505 children who had received either four doses of acellular pertussis vaccine or whole-cell pertussis vaccine were given a fifth dose of one of the two vaccines. Adverse events were monitored by parents and collected by telephone or home visit at 4, 8, 12, 24, 48 and 72 h, and 7 and 28 days after immunization. Rates of injection site redness >or=50mm were similar in recipients of five doses of acellular pertussis vaccine (32.8%) or five doses of whole-cell pertussis vaccine (43.3%). Injection site swelling, tenderness, and decreased arm movement were all more frequent in children who received five doses of whole-cell pertussis vaccine. Antibody levels before or after immunization did not predict those children who had increased injection site reactions. The children rated the injection site reactions as significantly more severe after five consecutive doses of whole-cell vaccine. Parent satisfaction was higher after the acellular vaccine. We conclude that a fifth consecutive dose of a whole-cell pertussis vaccine is associated with high rates of tender redness and swelling at the injection site, in contrast to a fifth consecutive dose of an acellular pertussis vaccine which is associated with high rates of non-painful redness. However, parents will still need to be aware of the high rates of injection site reactions expected after a fifth dose of acellular pertussis vaccine.

Child↗
PubMed2003

Mucosal immunization with a genetically engineered pertussis toxin S1 fragment-cholera toxin subunit B chimeric protein.

A chimeric protein consisting of a divalent pertussis toxin (PT) S1 fragment linked to the cholera toxin (Ctx) A(2)B fragment was constructed. The chimera induced a mucosal immunoglobulin A (IgA) and a serum IgG immune response to PT and CtxB in BALB/c mice following intranasal immunization. The immune sera neutralized PT in vitro. In the mouse model of Bordetella pertussis respiratory infection, the chimera-immunized animals showed a significant reduction in bacterial lung counts (P = 0.01) from that of the sham control group. Thus, a divalent S1 fragment CtxA2B chimera is an immunogenic antigen and can elicit a protective immunity.

Administration, Intranasal↗
PubMed2002

Carotid artery dissection as a possible severe complication of pertussis in an adult: clinical case report and review.

Adults can experience typical symptoms of pertussis. Complications due to severe paroxysmal coughing have been reported in this age group. We report carotid artery dissection as a possible severe complication of pertussis in a previously healthy adult. Adult booster immunization against pertussis should be considered to protect adults themselves from this illness and its potential complications.

Adult↗
PubMed2002

The changing age and seasonal profile of pertussis in Canada.

During the postvaccine era in Canada, most cases of pertussis have been reported in children <5 years of age, with the highest incidence, morbidity, and mortality in infants <1 year old. Population-based data, with very high laboratory confirmation rates and hospital separation and mortality statistics, chronicle the changing age and seasonal profile associated with pertussis over recent successive outbreaks in British Columbia, Canada. A large outbreak during 2000 highlights 2 important changes to the postvaccine profile. For the first time in Canada, the incidence of pertussis among preteens and teens surpassed that of all other age groups. At the same time, a decreasing incidence of pertussis among infants and preschool children highlights reduced susceptibility in the very young. Recent changes in the childhood immunization program (including introduction of an acellular pertussis vaccine), waning immunity, and changes in laboratory methods are considered in explaining these 2 simultaneous but divergent trends in the pertussis profile.

Adolescent↗
PubMed2002

Safety and immunogenicity of a trivalent, inactivated, mammalian cell culture-derived influenza vaccine in healthy adults, seniors, and children.

We performed randomized, double-blind, controlled trials to assess the safety and immunogenicity of an inactivated, Madin Darby Canine Kidney (MDCK)-derived cell line produced influenza vaccine in healthy adults (19-50 years), children (3-12 years) and the elderly (> or =65 years). We studied three lots of cell culture-derived vaccine and one lot of licensed egg-derived vaccine in healthy adults (n=462), two lots of cell culture-derived vaccine and one lot of egg-derived vaccine in seniors (n=269), and one lot of each vaccine in children (n=209). Adverse events were collected during the first 3 days post-immunization; serum was collected before and 1 month after immunization. Rates of local and systemic adverse reactions were similar with both vaccines. An injection site adverse event rated at least moderate severity was reported by 21.9% of children who received the egg-derived vaccine and 25.0% of those who received the cell culture-derived vaccine. In healthy adults the proportions were 12.1 and 15.3%, respectively and 6.7 and 6.3%, respectively in seniors. Systemic events of at least moderate severity were 12.4 and 12.5% in children, 19.8 and 13.6% in healthy adults, and 14.1 and 9.7% in seniors; none of these differences were statistically significant. The antibody response against all three viruses was similar between the two vaccines. From 83 to 100% of children, healthy adults and seniors achieved hemagglutination inhibition titers in excess of 40 post-immunization. We conclude that the cell culture-derived vaccine was safe and immunogenic in children, healthy adults and seniors.

Adolescent↗
PubMed2002

Use of lidocaine-prilocaine patch to decrease intramuscular injection pain does not adversely affect the antibody response to diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b conjugate and hepatitis B vaccines in infants from birth to six months of age.

BACKGROUND: Topical lidocaine-prilocaine (EMLA) effectively decreases the pain associated with minor procedures including immunization, although the effect on the antibody response to diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b conjugate (DTaP-IPV-Hib) and hepatitis B vaccines has not been assessed. OBJECTIVE: To measure the antibody response to DTaP-IPV-Hib and hepatitis B vaccines; to measure pain reduction associated with the use of the lidocaine-prilocaine (EMLA) patch; and to assess safety by comparing adverse reactions. PARTICIPANTS AND SETTING: One hundred nine healthy 6-month-old infants (Part A of study) and 56 healthy infants birth to 2 months of age (Part B of study) undergoing primary immunization with DTaP-IPV-Hib and hepatitis B vaccines in an ambulatory setting. DESIGN AND INTERVENTIONS: Two center, randomized, double blind, controlled trial of EMLA patch or placebo before DTaP-IPV-Hib and hepatitis B immunization. Antibody titers measured at 0 to 2, 6 and 7 months. OUTCOME MEASURES: The primary outcome measure was the antibody response to diphtheria, tetanus, pertussis antigens, Haemophilus influenzae type b and hepatitis B by enzyme immunoassay; and poliovirus 1, 2 and 3 by neutralization. The secondary outcomes were pain scores by the Modified Behavioral Pain Scale and drug- and vaccine-associated adverse events collected with a parent diary and structured questionnaire. RESULTS: There was no difference in the antibody response between the EMLA- and placebo-treated groups as assessed by geometric mean antibody titers, rates of seroconversion or the proportion of participants achieving protective or positive antibody titers postimmunization. At the 6-month visit, EMLA recipients had less pain after immunization (total pain score, 6.75 vs. 7.35; P = 0.005; pain score increase, 3.99 vs. 4.74; P = 0.004) than did placebo recipients. Skin pallor and erythema at the patch application site were more frequently reported after EMLA use. Rates of vaccine-associated adverse events were similar in the two groups. CONCLUSIONS: The EMLA patch has no adverse effect on the antibody response to the vaccine antigens, is effective in reducing pain associated with DTaP-IPV-Hib and hepatitis B immunizations and does not result in any significant or unexpected adverse reactions.

Administration, Topical↗
PubMed2002

Outcome of penicillin-nonsusceptible Streptococcus pneumoniae meningitis: a nested case-control study.

BACKGROUND: There are few data comparing the clinical features, management and outcome of penicillin-nonsusceptible (PNSP) meningitis patients with penicillin-susceptible (PSSP) meningitis patients. METHODS: We performed a retrospective, nested case-control study comparing cases with PNSP meningitis with controls with PSSP meningitis obtained from the Immunization Monitoring Program, Active (IMPACT) cross-Canada surveillance study of invasive infections. RESULTS: There were 30 PNSP meningitis cases (10.1% of total) and 45 PSSP meningitis controls from 6 centers obtained from 297 meningitis cases in the IMPACT database from 1991 through 1999. Vancomycin was used for empiric therapy in no cases and controls in 1991 to 1993 and in all cases in 1999. A third generation cephalosporin was used in 93.3% of confirmed PNSP cases, and 70.0% also received vancomycin and/or rifampin. Penicillin was used in 66.7% of confirmed PSSP cases. PNSP cases were more likely than PSSP controls to have a second lumbar puncture (odds ratio, 4.1; P= 0.01). PNSP cases were treated with intravenous antibiotics for an average of 15.6 days compared with 12.3 days for controls ( P= 0.04). Among PNSP cases, those patients who did not receive empiric vancomycin were treated with intravenous antibiotics for an average of 18.5 days compared with 12.0 days for those who did receive empiric vancomycin ( P= 0.04). The overall mortality was 5.3%, and 36.6% of survivors had >or=1 neurologic sequelae, including 19.7% with hearing loss. In multivariate statistical models, PNSP was not a risk factor for intensive care unit admission or neurologic sequelae. CONCLUSIONS: Management of suspected bacterial meningitis and confirmed meningitis in Canadian children changed in the past decade. Treatment of PNSP meningitis is significantly different from that for PSSP meningitis. These changes have occurred in response to the emergence of PNSP in Canada. Neurologic sequelae remain common after meningitis, but there are no differences between PNSP cases and PSSP cases.

Adolescent↗
PubMed2002

Population-based epidemiology of invasive pneumococcal infection in children in nine urban centers in Canada, 1994 through 1998.

PURPOSE: To describe the epidemiology of invasive pneumococcal infections in Canadian children 0 to 12 years old. METHODS: At each of nine urban centers, active surveillance was conducted to identify all cases of invasive pneumococcal infection in children during 1994 to 1998. Postal codes were used to distinguish cases resident in defined urban areas from referral cases. Census data were obtained for each defined area to calculate age-specific incidence rates. Features of population-based cases were described. RESULTS: From an average defined population of approximately 1 million children, 937 eligible cases arose. Those 6 to 17 months old had the highest average incidence rate of 98.6/100 000/year. The average cumulative risk of infection was 1 in 460 between birth and 59 months, by which age 92% of cases had occurred. Among cases younger than 2 years of age, simple bacteremia accounted for 66%, pneumonia with bacteremia accounted for 14.7% and meningitis accounted for 11% (average incidence rate, 9.0/100 000/year). An underlying illness was present in 16% of all cases. The mortality rate was 1.8%. CONCLUSIONS: Invasive pneumococcal infections are relatively common in early childhood, based on 5 years of data from nearly 20% of the Canadian population ages 0 to 12 years. These data will be valuable for calculating the economic case for universal infant vaccination with newly available vaccines.

Age Distribution↗
PubMed2002

Purification and immunogenicity of a recombinant Bordetella pertussis S1S3FHA fusion protein expressed by Streptococcus gordonii.

Acellular pertussis vaccines typically consist of antigens isolated from Bordetella pertussis, and pertussis toxin (PT) and filamentous hemagglutinin (FHA) are two prominent components. One of the disadvantages of a multiple-component vaccine is the cost associated with the production of the individual components. In this study, we constructed an in-frame fusion protein consisting of PT fragments (179 amino acids of PT subunit S1 and 180 amino acids of PT subunit S3) and a 456-amino-acid type I domain of FHA. The fusion protein was expressed by the commensal oral bacterium Streptococcus gordonii. The fusion protein was secreted into the culture medium as an expected 155-kDa protein, which was recognized by a polyclonal anti-PT antibody, a monoclonal anti-S1 antibody, and a monoclonal anti-FHA antibody. The fusion protein was purified from the culture supernatant by affinity and gel permeation chromatography. The immunogenicity of the purified fusion protein was assessed in BALB/c mice by performing parenteral and mucosal immunization experiments. When given parenterally, the fusion protein elicited a very strong antibody titer against the FHA type I domain, a moderate titer against native FHA, and a weak titer against PT. When given mucosally, it elicited a systemic response and a mucosal response to FHA and PT. In Western blots, the immune sera recognized the S1, S3, and S2 subunits of PT. These data collectively indicate that fragments of the pertussis vaccine components can be expressed in a single fusion protein by S. gordonii and that the fusion protein is immunogenic. This multivalent fusion protein approach may be used in designing a new generation of acellular pertussis vaccines.

Bordetella pertussis↗
PubMed2002

History of penicillin allergy and referral for skin testing: evaluation of a pediatric penicillin allergy testing program.

INTRODUCTION: Penicillin allergy, commonly reported in children, leads to use of more expensive, broad-spectrum drugs. The results and effectiveness of a skin testing program for immediate hypersensitivity to penicillin in children were studied. METHODS: Children seen at the IWK Health Centre in Halifax between 1986 and 2000 with a history of suspected penicillin allergy were referred by their family physician or pediatrician. Two-stage skin testing (scratch, intradermal) of benzylpenicilloyl-polylysin and penicillin G sodium, with histamine and saline as positive and negative controls, was carried out. If the test results were negative, an oral challenge was conducted and the child observed for 60 minutes. If no adverse reaction was noted, a letter was sent to the referring physician and to Health Records at the IWK Health Centre, indicating that warning labels should be removed from the chart. RESULTS: Of 72 children tested, 32% described their past cutaneous eruption as hives and 68% had other rashes; 96% of rashes were generalized. The mean age at the time of the suspected penicillin allergy was 4.4 years; it was 7.4 years at the time of testing. There was no positive response to the scratch testing, but 4% of children had a positive response to intradermal testing. No adverse responses to oral challenge were observed. Letters confirming negative status were not received in 4% (3 of 69) cases, resulting in ongoing avoidance of penicillins and falsely labelling of the child as penicillin allergic. CONCLUSIONS: In this referral setting, true penicillin allergy was uncommon, suggesting that many children are incorrectly labelled as penicillin-allergic. Communication of test results to family and care providers and health records administration must be effective if testing is to affect prescribing behaviour.

Canada↗
PubMed2002

Simultaneous administration of meningococcal C conjugate vaccine and diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine in children: a randomized double-blind study.

BACKGROUND: Meningococcal C disease can be life-threatening in infants, young children and adolescents. New conjugate vaccines are immunogenic in young infants and induce immunologic memory, so we should consider incorporating them into the routine childhood immunization program. The objective of this study was to measure the safety and immunogenicity of a meningococcal C conjugate vaccine when given with routine childhood vaccines. METHODS: We carried out a randomized, double-blind, controlled clinical trial at children's hospitals in 3 Canadian cities. A convenience sample of 351 healthy 2-month-old infants was enrolled from the community and randomly allocated to receive either meningococcal C conjugate vaccine or the control (hepatitis B) vaccine. All participants received a concurrent injection of the combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (DTaP-IPV-Hib) conjugate vaccine in the opposite limb. Participants were immunized at 2, 4, 6 and 15 months of age; adverse events were recorded after each dose. Serum bactericidal and ELISA meningococcal antibody levels in the participants were measured at 6, 7, 15 and 16 months of age; diphtheria, tetanus, H. influenzae type b, poliovirus and pertussis antibodies were measured at 7 months of age. A total of 323 (92%) participants completed all aspects of the study. The proportion of participants who suffered adverse events after each vaccine dose was the primary safety outcome. Geometric mean antibody titres and the proportion of participants with protective antibody levels after immunization were the primary immunologic outcomes. RESULTS: After 2 doses of the meningococcal C conjugate vaccine 99% of participants achieved a protective ( > or = 1:8) bactericidal meningococcal serogroup C antibody level, and after 3 doses this rate increased to 100%. Antibody levels to the concomitant vaccine antigens in the group receiving meningococcal C vaccine were similar to those in the control group except for higher antidiphtheria antibody titres (p < 0.001). Local injection site reactions (redness and induration) after the meningococcal conjugate vaccine were more frequent than after hepatitis B vaccine but less frequent than after the DTaP-IPV-Hib vaccine. CONCLUSIONS: The meningococcal C conjugate vaccine can be safely and effectively administered at the same visit as the other vaccine antigens routinely given to infants in Canada.

Antibody Formation↗