Immunogenicity and safety of 3-dose primary vaccination with combined DTPa-HBV-IPV/Hib vaccine in Canadian Aboriginal and non-Aboriginal infants.

This study compared immune responses of healthy Aboriginal and non-Aboriginal infants to Haemophilus influenzae type b (Hib) and hepatitis B virus (HBV) components of a DTaP-HBV-IPV/Hib combination vaccine, 1 month after completing dosing at 2, 4 and 6 months of age. Of 112 infants enrolled in each group, 94 Aboriginal and 107 non-Aboriginal infants qualified for the immunogenicity analysis. Anti-PRP concentrations exceeded the protective minimum (≥0.15 µg/ml) in ≥97% of infants in both groups but geometric mean concentrations (GMCs) were higher in Aboriginal infants (6.12 µg/ml versus 3.51 µg/ml). All subjects were seroprotected (anti-HBs ≥10 mIU/mL) against HBV, with groups having similar GMCs (1797.9 versus 1544.4 mIU/mL, Aboriginal versus non-Aboriginal, respectively). No safety concerns were identified. We conclude that 3-dose primary vaccination with DTaP-HBV-IPV/Hib combination vaccine elicited immune responses to Hib and HBV components that were at least as high in Aboriginal as in non-Aboriginal Canadian infants. Clinical Trial Registration NCT00753649.

Comparison of safety and immunogenicity of two doses of investigational hepatitis B virus surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide and three doses of a licensed hepatitis B vaccine in healthy adults 18-55 years of age.

BACKGROUND: The currently licensed aluminum-hydroxide-adjuvanted hepatitis B vaccines require three doses over a 6-month period to achieve high rates of protection in adults. We compared tolerability and immunogenicity of two doses of an investigational hepatitis B vaccine using hepatitis B surface antigen adjuvanted with an immunostimulatory phosphorothioate oligodeoxyribonucleotide (HBV-ISS) to three doses of a licensed alum-adjuvanted vaccine (HBV-Eng). METHODS: In this randomized, observer-blind study, healthy adults received two doses of HBV-ISS at 0 and 4 weeks or three doses of HBV-Eng at 0, 4, and 24 weeks. The primary immunogenicity endpoint was the seroprotection rate (antibody ≥ 10 mIU/mL) 8 weeks after the second dose of HBV-ISS compared to 4 weeks after the third dose of HBV-Eng. RESULTS: A total of 2415 participants were randomized in a ratio of 3:1 to HBV-ISS (n=1809) and HBV-Eng (n=606). The percentage of subjects exhibiting a seroprotective immune response at the primary time point was significantly higher (95.1%) for HBV-ISS than for HBV-Eng (81.1%). Superiority of the seroprotective rates for HBV-ISS was demonstrated at all time points measured. Geometric mean concentrations were also significantly higher in the HBV-ISS group at all time points measured except at week 28 (24 weeks post-second dose of HBV-ISS and 4 weeks post-third dose HBV-ISS) at which time the antibody concentrations were similar. Both vaccines were welltolerated although injection-site reactions were reported at a higher rate in HBV-ISS recipients. CONCLUSIONS: A short, two-dose regimen of HBV-ISS induced a superior antibody response than a three-dose regimen of a licensed hepatitis B vaccine and was well tolerated.

The responses of Aboriginal Canadians to adjuvanted pandemic (H1N1) 2009 influenza vaccine.

BACKGROUND: Because many Aboriginal Canadians had severe cases of pandemic (H1N1) 2009 influenza, they were given priority access to vaccine. However, it was not known if the single recommended dose would adequately protect people at high risk, prompting our study to assess responses to the vaccine among Aboriginal Canadians. METHODS: We enrolled First Nations and Métis adults aged 20-59 years in our prospective cohort study. Participants were given one 0.5-mL dose of ASO3-adjuvanted pandemic (H1N1) 2009 vaccine (Arepanrix, GlaxoSmithKline Canada). Blood samples were taken at baseline and 21-28 days after vaccination. Paired sera were tested for hemagglutination-inhibiting antibodies at a reference laboratory. To assess vaccine safety, we monitored the injection site symptoms of each participant for seven days. We also monitored patients for general symptoms within 7 days of vaccination and any use of the health care system for 21-28 days after vaccination. RESULTS: We enrolled 138 participants in the study (95 First Nations, 43 Métis), 137 of whom provided all safety data and 136 of whom provided both blood samples. First Nations and Métis participants had similar characteristics, including high rates of chronic health conditions (74.4%-76.8%). Pre-existing antibody to the virus was detected in 34.3% of the participants, all of whom boosted strongly with vaccination (seroprotection rate [titre ≥ 40] 100%, geometric mean titre 531-667). Participants with no pre-existing antibody also responded well. Fifty-eight of 59 (98.3%) First Nations participants showed seroprotection and a geometric mean titre of 353.6; all 30 Métis participants with no pre-existing antibody showed seroprotection and a geometric mean titre of 376.2. Pain at the injection site and general symptoms frequently occurred but were short-lived and generally not severe, although three participants (2.2%) sought medical attention for general symptoms. INTERPRETATION: First Nations and Métis adults responded robustly to ASO3-adjuvanted pandemic (H1N1) 2009 vaccine. Virtually all participants showed protective titres, including those with chronic health conditions.

Efficacy and Safety of CVT-E002, a Proprietary Extract of Panax quinquefolius in the Prevention of Respiratory Infections in Influenza-Vaccinated Community-Dwelling Adults: A Multicenter, Randomized, Double-Blind, and Placebo-Controlled Trial.

CVT-E002 (a proprietary extract) was found to be effective in the prevention of upper respiratory infections (URIs) in healthy adults, and institutionalized and community-dwelling seniors. A multicenter, randomized, double-blind, placebo-controlled trial was carried out to determine effects of CVT-E002 in the prevention of URIs in influenza-vaccinated community-dwelling adults. 783 community-dwelling adults were randomized to receive placebo, 400 mg or 800 mg treatment/d (1 : 1 : 1) for 6 months. Primary analysis on the incidence of laboratory-confirmed-clinical URIs (LCCUs), including influenza A and B, was performed on those receiving at least one dose. Secondary analysis was performed on study completers and included incidence, severity, and duration of URIs meeting a Jackson-based criteria and safety of CVT-E002. The incidence of LCCUs in the ITT group was 5.5%, 5.2%, and 4.6% in the placebo, 400 mg and 800 mg groups, respectively (P = 0.89). Jackson-confirmed URIs were significantly lower in the treated groups (P < 0.04). CVT-E002 supplementation reduced the severity and duration of Jackson-confirmed URIs. The results indicate that CVT-E002 can be safely used by similar groups and may prevent symptoms of URIs; larger sample size is warranted.

Identification and epidemiology of severe respiratory disease due to novel swine-origin influenza A (H1N1) virus infection in Alberta.

BACKGROUND: In March 2009, global surveillance started detecting cases of influenza-like illness in Mexico. By mid-April 2009, two pediatric patients were identified in the United States who were confirmed to be infected by a novel influenza A (H1N1) strain. The present article describes the first identified severe respiratory infection and the first death associated with pandemic H1N1 (pH1N1) in Canada. METHODS: Enhanced public health and laboratory surveillance for pH1N1 was implemented throughout Alberta on April 24, 2009. Respiratory specimens from all patients with a respiratory illness and travel history or those presenting with a severe respiratory infection requiring hospitalization underwent screening for respiratory viruses using molecular methods. For the first severe case identified and the first death due to pH1N1, histocompatibility leukocyte antigens were compared by molecular methods. RESULTS: The first death (a 39-year-old woman) occurred on April 28, 2009, and on May 1, 2009, a 10-year-old child presented with severe respiratory distress due to pH1N1. Both patients had no travel or contact with anyone who had travelled to Mexico; the cases were not linked. Histocompatibility antigen comparison of both patients did not identify any notable similarity. pH1N1 strains identified in Alberta did not differ from the Mexican strain. CONCLUSION: Rapid transmission of pH1N1 continued to occur in Alberta following the first death and the first severe respiratory infection in Canada, which were identified without any apparent connection to Mexico or the United States. Contact tracing follow-up suggested that oseltamivir may have prevented ongoing transmission of pH1N1.

A dose-ranging study of a subunit Respiratory Syncytial Virus subtype A vaccine with and without aluminum phosphate adjuvantation in adults > or =65 years of age.

We studied the safety and immunogenicity of a Respiratory Syncytial Virus (RSV)-A vaccine containing subunit antigens F, G and M in older persons, and its effect on influenza vaccine immunogenicity. In a dose-ranging, placebo-controlled, blinded trial 561 adults > or =65 years of age at five Canadian sites were randomized to one intramuscular injection of either 100, 50 or 25 microg RSV-A-alum vaccine or 100 microg non-adjuvanted RSV-A vaccine, or alum-placebo. All participants were offered inactivated influenza vaccine on day 32. Immunization was well tolerated and reactogenicity was similar between the RSV and influenza vaccines and the alum-placebo. Only the 100 microg non-adjuvanted RSV vaccine achieved the primary immunogenicity outcome of eliciting a > or =4-fold rise in neutralizing antibody (NA) titres against RSV-A in > or =50% of participants at day 32. Geometric mean titres against RSV-A and -B at all points were comparable in 100 microg adjuvanted and non-adjuvanted groups. At day 32, a > or =4-fold haemagluttinin inhibition (HI) antibody response or HI > or =40 to Influenza (A-H3N2) was seen in >74% of participants; no difference was seen between groups. A subunit non-alum-containing RSV-A vaccine was well tolerated in a large population > or =65 years and did not interfere with influenza vaccine immunogenicity. This RSV-A-based vaccine demonstrated NA rise which could provide seasonal protection against severe RSV illnesses from RSV-A or -B and warrants further testing to determine its efficacy in the prevention of clinical illness in elderly persons.

Safety and immunogenicity of a measles-mumps-rubella-varicella vaccine given as a second dose in children up to six years of age.

Two doses of measles-mumps-rubella vaccine (MMR) are widely recommended and consideration is being given to a similar schedule for varicella vaccine. A combined measles-mumps-rubella-varicella vaccine (MMRV) could be considered for this second dose in children previously vaccinated separately with MMR and varicella vaccines. Healthy children (N=390) aged 15-75 months (median 54 months) previously immunized with MMR and varicella vaccines were randomly allocated to receive MMRV or separate injections of MMR and varicella vaccines. Before administration of study vaccines, seropositivity rates were 96.4% for measles, 94.3% for mumps, 99.5% for rubella, and 97.9% for varicella. Post-immunization, seropositivity rates were 99.5% for measles and mumps and 100% for rubella and varicella in the MMR+varicella group and 100% for all four antigens in the MMRV group; a 26.2- and 27.2-fold increase in varicella titer was observed in the MMR+varicella vaccine and MMRV groups, respectively. Except for more frequent pain in the MMRV group (33.3% vs. 23.7%, p=0.043), there were no differences in the incidence of local and solicited symptoms between groups. In children primed with MMR and varicella vaccine, MMRV had non-inferior immunogenicity and similar safety profiles as a second dose of licensed MMR and varicella vaccine administered concomitantly.

Comparison of the safety and immunogenicity of concomitant and sequential administration of an adult formulation tetanus and diphtheria toxoids adsorbed combined with acellular pertussis (Tdap) vaccine and trivalent inactivated influenza vaccine in adults.

The annual contact for influenza vaccination provides an opportunity to ensure that adults have received other recommended vaccines such as Tdap. Healthy 19-64 year-olds were randomized to receive concomitant administration of Tdap and influenza vaccines or influenza vaccine followed (in 4-6 weeks by) Tdap. 720 participants were enrolled. No clinically relevant between-group differences were observed in the rates or severities of erythema, swelling, or pain at the Tdap injection site. Injection-site pain was the most commonly reported adverse event (66.6% concomitant administration group versus 60.8% sequential administration group); most pain was graded as mild and resolved by day 3. Seroprotection and seroresponse rates for all influenza strains were comparable between the two groups. For diphtheria and tetanus, seroprotection rates and post-vaccination GMTs were non-inferior in the concomitant administration group compared to the sequential administration group. A trend for lower antibody responses to pertussis antigens PT, FHA, and FIM was observed after concomitant administration and, for PRN, this difference failed the non-inferiority criteria. While there is a small diminution in antibody response to tetanus and pertussis antigens, concomitant administration of Tdap and influenza vaccine was well tolerated and immunogenic and may offer practical advantages including convenience, compliance, and cost-savings.

An adolescent-adult formulation tetanus and diptheria toxoids adsorbed combined with acellular pertussis vaccine has comparable immunogenicity but less reactogenicity in children 4-6 years of age than a pediatric formulation acellular pertussis vaccine and diphtheria and tetanus toxoids adsorbed combined with inactivated poliomyelitis vaccine.

In Canada, the fifth dose of the routine childhood immunization schedule against diphtheria, tetanus, pertussis and polio is given at 4-6 years of age. Up to 30% of children may have significant local reactions (redness, swelling) and this may be related to pertussis and diphtheria antigen content. We sought to determine if a combination product with lower content of pertussis and diphtheria toxoids (dTap) would result in fewer local reactions and not have inferior immunogenicity to a combination vaccine with higher pertussis and diphtheria content (diphtheria-tetanus-acellular pertussis-inactivated polio virus, DTaP-IPV). Healthy children aged 4-6 years with complete primary immunization series and a fourth dose of diphtheria and tetanus toxoids component pertussis inactivated polio and Haemophilus influenzae type B conjugate vaccine were randomized to one dose of dTap, followed in 4-6 weeks by one dose of IPV or control DTaP-IPV. Immediate reactions within 30 min, solicited injection site and systemic reactions within 14 days, and unsolicited adverse events (AE) within 6 weeks post-vaccination were monitored. Serum was collected prior to immunization, and 4-6 weeks after vaccine for diphtheria, tetanus and pertussis antibodies (Ab). Sample size was designed to detect > or =10% difference in injection site erythema, pain or swelling between groups 593 children at eight Canadian sites completed the study; no participant withdrew because of an AE. All safety endpoints on days 0-14 were less frequent in children randomized to the dTap than DTaP-IPV group: erythema (34.6% versus 51.7%), swelling (24.2% versus 33.8%) and pain (39.6% versus 67.2%). Fever was also less common (8.72% versus 16.9%). All children in both study groups had seroprotective Ab levels to diphtheria and tetanus at 4-6 weeks (> or =0.10 IU/mL). The majority of children in each vaccine arm had a four-fold increase in pertussis antibodies. Fever and injection site reactions are less common in 4-6 year-old-children who receive a dTap vaccine compared to DTaP-IPV, without inferior immunogenicity.

Health promotion and disease prevention in the emergency department: a feasibility study.

BACKGROUND: Health promotion and disease prevention have been increasingly recognized as activities that may be within the scope of emergency medicine. The purpose of this feasibility study was to identify health risks and offer immediate interventions to adult patients who have drug and/or alcohol problems, incomplete immunization, are overdue for a Pap (Papanicolaou) smear, and/or are smokers. METHODS: The study took place in a busy tertiary Emergency Department (ED) serving an inner-city population with a significant proportion of patients who are homeless, substance abusers, working poor, and/or recent immigrants. A convenience sample of patients completed a computer-based health-risk survey. Trained health promotion nurses offered appropriate interventions to patients following review and discussion of their self-reported data. Interventions included counseling for problem drinking, substance abuse, and smoking cessation, screening for cervical cancer, and immunization. RESULTS: From October 20, 2000 to June 30, 2003, we enrolled 2366 patients. One thousand and eleven subjects (43%) reported substance abuse and 1095 (46%) were smokers. Of the 158 smokers contacted in follow-up, 19 (12%) had quit, 63 (40%) had reduced the number of cigarettes/day and 76 (48%) reported no change. Of 1248 women surveyed, 307 (25%) were overdue for a Pap smear and 54 (18%) received this intervention. Forty-four percent of subjects were overdue for at least one immunization and of those, 414 (40%) were immunized in the ED. CONCLUSION: At-risk patients can be identified using a computer-based screening tool, and appropriate interventions can be given to a proportion of these patients in a busy inner city ED without increasing wait time.

Public health preparedness in Alberta: a systems-level study.

BACKGROUND: Recent international and national events have brought critical attention to the Canadian public health system and how prepared the system is to respond to various types of contemporary public health threats. This article describes the study design and methods being used to conduct a systems-level analysis of public health preparedness in the province of Alberta, Canada. The project is being funded under the Health Research Fund, Alberta Heritage Foundation for Medical Research. METHODS/DESIGN: We use an embedded, multiple-case study design, integrating qualitative and quantitative methods to measure empirically the degree of inter-organizational coordination existing among public health agencies in Alberta, Canada. We situate our measures of inter-organizational network ties within a systems-level framework to assess the relative influence of inter-organizational ties, individual organizational attributes, and institutional environmental features on public health preparedness. The relative contribution of each component is examined for two potential public health threats: pandemic influenza and West Nile virus. DISCUSSION: The organizational dimensions of public health preparedness depend on a complex mix of individual organizational characteristics, inter-agency relationships, and institutional environmental factors. Our study is designed to discriminate among these different system components and assess the independent influence of each on the other, as well as the overall level of public health preparedness in Alberta. While all agree that competent organizations and functioning networks are important components of public health preparedness, this study is one of the first to use formal network analysis to study the role of inter-agency networks in the development of prepared public health systems.

Efficacy of an extract of North American ginseng containing poly-furanosyl-pyranosyl-saccharides for preventing upper respiratory tract infections: a randomized controlled trial.

BACKGROUND: Upper respiratory tract infections are a major source of morbidity throughout the world. Extracts of the root of North American ginseng (Panax quinquefolium) have been found to have the potential to modulate both natural and acquired immune responses. We sought to examine the efficacy of an extract of North American ginseng root in preventing colds. METHODS: We conducted a randomized, double-blind, placebo-controlled study at the onset of the influenza season. A total of 323 subjects 18-65 years of age with a history of at least 2 colds in the previous year were recruited from the general population in Edmonton, Alberta. The participants were instructed to take 2 capsules per day of either the North American ginseng extract or a placebo for a period of 4 months. The primary outcome measure was the number of Jackson-verified colds. Secondary variables measured included symptom severity, total number of days of symptoms and duration of all colds. Cold symptoms were scored by subjects using a 4-point scale. RESULTS: Subjects who did not start treatment were excluded from the analysis (23 in the ginseng group and 21 in the placebo group), leaving 130 in the ginseng group and 149 in the placebo group. The mean number of colds per person was lower in the ginseng group than in the placebo group (0.68 [standard deviation (SD) 0.82] v. 0.93 [SD 0.91], difference 0.25%, 95% confidence interval [CI] 0.04-0.45). The proportion of subjects with 2 or more Jackson-verified colds during the 4-month period (10.0% v. 22.8%, 12.8% difference, 95% CI 4.3-21.3) was significantly lower in the ginseng group than in the placebo group, as were the total symptom score (77.5 [SD 84.6] v. 112.3 [SD 102.5], difference 1.5%, 95% CI 1.2-2.0) and the total number of days cold symptoms were reported (10.8 [SD 9.7] v. 16.5 [SD 13.8] days, difference 1.6%, 95% CI 1.3-2.0) for all colds. INTERPRETATION: Ingestion of a poly-furanosyl-pyranosyl-saccharide-rich extract of the roots of North American ginseng in a moderate dose over 4 months reduced the mean number of colds per person, the proportion of subjects who experienced 2 or more colds, the severity of symptoms and the number of days cold symptoms were reported.