Conforming to ICMJE principles.
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Biomedical Research↗
Biomedical subjects
David Scheifele
Publications and source records attributed to David Scheifele.
Progress in the prevention of pneumococcal infection.
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Adult↗
Canadian Association for Immunization Research and Evaluation (CAIRE) guidelines for industry-sponsored clinical trial and epidemiology contract research.
In response to concerns about interactions of academic and public health investigators with industry, the Canadian Association for Immunization Research and Evaluation (CAIRE), in collaboration with six major vaccine manufacturers, developed guidelines for participation in industry-sponsored clinical trial and epidemiology contract research within Canada. Topics addressed include definition of investigators, data ownership, protocol development, data management, data analysis, producing a study report and publication of the results of the study.
Canada↗
Invasive Haemophilus influenzae type b infections in vaccinated and unvaccinated children in Canada, 2001-2003.
BACKGROUND: Although vaccination of infants against Haemophilus influenzae type b (Hib) invasive infections is effective and has been routinely available in Canada since 1992, cases of the disease continue to occur. We were interested in determining whether recent cases of Hib infection reflected progressive loss of protection with time since vaccination, increasing nonacceptance of vaccination or a deleterious effect of coadministration of recently introduced vaccines such as those for pneumococcal and meningococcal conjugates and hepatitis B. We report on the causes of Hib infections among vaccinated and unvaccinated children between 2001 and 2003 in Canada. METHODS: Through our established network of 12 pediatric tertiary care hospitals we actively searched for cases in each centre by reviewing daily admissions and laboratory reports, visiting the wards and checking discharge diagnosis codes. Culture-confirmed cases were summarized by nurse monitors using a standardized reporting system. RESULTS: We identified 29 cases during the 3 years: 16 in 2001, 10 in 2002 and 3 in 2003. Half of the 29 patients had meningitis. Hib infection was more common among children less than 6 months of age (11 cases) and in boys (20 cases). Two deaths occurred (7% case-fatality ratio). A total of 20 children had received no or incomplete primary vaccination because of parental refusal (7 cases), because they were too young to have completed the primary series (11 cases, including 1 in which parental refusal was also a factor) or because of delays in completing the primary series (2 cases); the vaccination history was uncertain in the remaining case. Infection despite primary vaccination occurred in 9 children: 2 previously healthy children and 7 who were immunocompromised or who had a predisposing condition. None of the cases identified in 2003 involved children who had received any of the newly introduced vaccines. INTERPRETATION: Invasive Hib infections remain rare in Canada, with most cases occurring in children too young to have completed the primary series. Protection after vaccination appears to extend into later childhood and does not appear to be diminished by coadministration of newer infant vaccines.
Canada↗
Nationwide canadian study of hepatitis a antibody prevalence among children eight to thirteen years old.
BACKGROUND: Hepatitis A vaccines provide consistent, long-lasting protection and have been available for almost 10 years in Canada, but their use remains limited. It is difficult to assess their optimal utilization given that our knowledge of hepatitis A epidemiology in Canada is fragmentary. Unlike the United States, no nationwide study of hepatitis A prevalence has ever been done in Canada. Consequently we do not know the incidence of infection in children and what would be the most appropriate age for hepatitis A vaccination. OBJECTIVE: To estimate the proportion of 8- to 13-year-old children who have been infected with hepatitis A virus (HAV) and the risk factors for this infection on a nationwide scale. METHODS: Children were sampled in 10 Canadian provinces, comprising 5 regions, using random digit dialing methodology with regional stratification. Demographic data and information about risk factors for hepatitis A were collected by the telephone interviewers. Oral fluid samples were self-collected and mailed to the laboratory, where they were tested for anti-HAV IgG. RESULTS: Of 6740 contacted families with a child of required age, 1688 (25%) agreed to participate and answered the questionnaire. From these, 1074 oral fluid samples were received, and 1057 could be analyzed. Anti-HAV IgG was detected in 2.7% of subjects, with variation by region from 0.8 to 3.4%. The parents of 54 subjects (5.1%) reported that their child had previously been vaccinated against HAV. Anti-HAV IgG was present in 2.0% of unvaccinated subjects, among whom antibody prevalence was 19.4% in children born in HAV-endemic countries, 6.1% in Native children and 4.2% in travelers to endemic countries. In multivariate analysis of all subjects, the presence of anti-HAV IgG was significantly associated with birth in an endemic country, travel to an endemic country, Native status (American Indian and Inuit population), female gender and vaccination against HAV. In nonvaccinated, non-Native children born in Canada who did not travel to endemic countries, anti-HAV prevalence was 1.1%. CONCLUSIONS: The risk for hepatitis A during childhood is low in Canada. Almost all teenagers (>97%) would be at risk for infection in case of contact with HAV. Changes in immunization policy against hepatitis A should be considered.
Adolescent↗
Lack of evidence of encephalopathy related to pertussis vaccine: active surveillance by IMPACT, Canada, 1993-2002.
To assess whether pertussis-containing vaccines cause encephalitis or encephalopathy, the IMPACT network of Canadian pediatric centers screened more than 12,000 admissions for neurologic disorders between 1993 and 2002. Seven cases of encephalopathy began within 7 days after pertussis vaccination, but a more likely cause was found in each instance. No attributable case followed administration of >6.5 million doses of vaccine.
Age Distribution↗
Randomized, double-blind, placebo-controlled trial to assess the rate of recurrence of oculorespiratory syndrome following influenza vaccination among persons previously affected.
During the 2000-2001 influenza immunization campaign in Canada, an oculorespiratory syndrome (ORS) was recognized as adverse event associated with one of the vaccines administered. The initial surveillance case definition for ORS in 2000-2001 specified onset within 24 h after vaccination and resolution within 48 h after onset; the restriction on the duration of ORS was removed from the case definition for the vaccine distributed during the 2001-2002 influenza season. The implicated vaccine contained large aggregates of unsplit virions; alterations to the manufacturing process for the vaccine distributed during 2001-2002 addressed this. A randomized, double-blind, placebo-controlled trial assessed the safety of the reformulated version in previously affected adults. The trial was halted early, after 61 participants had received an injection (34 had received vaccine, and 27 had received placebo). The vaccine-attributable recurrence rate for onset of ORS within 24 h after injection was 33% (95% confidence interval [CI], 10%-53%); for cases that resolved within 48 h, this rate was 27% (95% CI, 5%-47%). Previously affected persons should be informed of the risk of ORS recurrence but also that episodes of such recurrence are mild and well tolerated.
Adult↗
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↗
Unique roles of a data and safety monitoring board in vaccine safety trials with compressed timelines and urgent implications.
Studies with urgent implications for public policy and programs represent a special case for monitoring boards, whose responsibilities must include ensuring applicability to policy making and timely communication of results as well as data and safety monitoring. We recently conducted two preseason evaluations of an influenza vaccine, results of which would influence the supply of vaccine for the Canadian annual program. Only 12 weeks were available for planning the studies and 6 weeks for fieldwork and data analysis. The enlisted board played key roles in determining appropriate study design, setting and enforcing rules for study initiation and early termination, monitoring safety, and encouraging timely dissemination of results. An extended role in data monitoring would have been desirable. Providing a safety valve for inevitable tensions between investigators and sponsor was an understated but significant role. Lessons from our experience will be particularly pertinent to future studies of pandemic influenza vaccines.
Canada↗
Predictors of death in infants hospitalized with pertussis: a case-control study of 16 pertussis deaths in Canada.
OBJECTIVES: To describe the clinical course of fatal cases of pertussis and identify predictors of death at the time of presentation for medical care. METHODS: Case-control study of 16 deaths from pertussis identified by the Immunization Monitoring Program, Active (IMPACT) surveillance network (January 1991-December 2001) matched with 32 nonfatal cases by age, date, and geography. Differences were compared by Fisher exact test and logistic regression. A multivariate model was developed using stepwise logistic regression. RESULTS: All 16 fatal cases were < or =6 months old; 13 were <2 months old. Fatal cases were less likely to have had cough complications during pregnancy (48% vs 14%; P=.046) and more likely to have pneumonia (63% vs 16%; P=.0024) before hospital admission and more likely to have seizures, pneumonia, leukocytosis, and hypoxemia after admission (P<.001 for all comparisons). White blood cell count and pneumonia were independent predictors of fatal outcome in the multivariate model. CONCLUSIONS: Infants too young to have begun their immunizations are at highest risk of fatal pertussis infection. Leukocytosis and pneumonia are predictors of a poor outcome; however, rapid progression of the disease may make interventions difficult.
Breast Feeding↗
Thrombocytopenia after immunization of Canadian children, 1992 to 2001.
BACKGROUND: Thrombocytopenia occasionally follows immunization of children, especially after administration of measles-containing vaccines. The purpose of this study was to describe the clinical features of postimmunization thrombocytopenia, with emphasis on the rate of complications and outcome. METHODS: A prospective survey was conducted by 12 pediatric centers in Canada during 1992 to 2001. At each center a nurse monitor searched for inpatient cases. Cases were defined as having onset of clinical signs or laboratory measures of thrombocytopenia (platelet count, <50 x 10(9)/l) within 30 days after immunization. Cases were described in a standardized manner, including follow-up data as available. RESULTS: Sixty-one cases were detected, an average of 6 per year or approximately 1 case per 15,000 general hospital admissions. Median age of cases was 13 months. The mean platelet count at diagnosis was 8.6 x 10(9)/l. Most cases (79%) followed measles-containing vaccines. Only 1 child had a serious (fatal) complication. Platelet counts returned to normal within 30 days of onset in 46 of 57 children (80.7%) with information available. Five children (8.2%) had persistent or intermittent thrombocytopenia for 3 months or more. CONCLUSION: Thrombocytopenia associated with routine immunization of children is rare and usually benign, resolving within 1 month in most children.
Age Distribution↗
Decrease in hospital admissions for febrile seizures and reports of hypotonic-hyporesponsive episodes presenting to hospital emergency departments since switching to acellular pertussis vaccine in Canada: a report from IMPACT.
OBJECTIVE: Acellular pertussis vaccines were introduced with the promise of an improved safety profile compared with whole-cell vaccines. In 1997-1998, Canada adopted 1 combination acellular pertussis vaccine, having previously used 1 particular combination whole-cell pertussis vaccine. We hypothesized that the change would result in a decrease in hospitalization rates for seizures and reports of hypotonic-hyporesponsive episodes (HHEs) temporally related to pertussis vaccination. METHODS: Active surveillance was performed between 1995 and 2001 by the Immunization Monitoring Program-Active monitors at 12 hospitals using standard case definitions. Seizures had to occur within 72 hours after immunization with a pertussis-containing vaccine or 5 to 30 days after immunization with measles-mumps-rubella vaccine. HHE episodes had to occur within 48 hours of receipt of a pertussis-containing vaccine. Poisson regression models were used to compare the average number of monthly admissions for seizures and HHEs before and after introduction of the acellular pertussis vaccine. RESULTS: We found a 79% decrease in febrile seizures associated with receipt of pertussis vaccine but no significant decrease in febrile seizures temporally related to measles-mumps-rubella between 1995-1996 and 1998-2001. There was a 60% to 67% reduction in HHEs associated with pertussis-containing vaccines between the same time periods, depending on case definition. CONCLUSIONS: The risks of febrile seizures and HHEs after pertussis-containing vaccine declined significantly with the introduction of acellular pertussis vaccine in Canada. Active surveillance systems are important for detecting trends in uncommon adverse events after routine immunizations.
Adverse Drug Reaction Reporting Systems↗
Injection-site reactions to booster doses of acellular pertussis vaccine: rate, severity, and anticipated impact.
BACKGROUND: Acellular pertussis (aP)-containing vaccines cause fewer adverse events than whole-cell versions for primary doses. Booster doses, however, may be followed by extensive injection-site reactions. This study compares the frequency, severity, and impact of local reactions among children receiving 5 consecutive doses of an aP combination vaccine (including inactivated polio virus, conjugated Haemophilus influenzae type b antigen, and diphtheria and tetanus toxoids) to children receiving a mixed series of whole-cell and aP combination vaccines. METHODS: Participants were parents or guardians of children 4 to 6 years old immunized at public health clinics across British Columbia, Canada. This included 398 children receiving the fifth consecutive dose of an aP combination vaccine and 402 receiving the fifth dose in a mixed series consisting of at least 1 prior dose of whole-cell pertussis combination vaccine with the remainder as aP combination vaccine. A cross-sectional telephone survey evaluated the extent of local reactions 48 to 96 hours after immunization by asking participants to compare the size of redness and swelling with familiar household items such as Oreo cookies or coins. Associated discomfort and impact on recreational activities, health care utilization, parental time off work, and attitudes toward immunization were also assessed. RESULTS: Children who received the fifth consecutive dose of an aP combination vaccine more often experienced redness (24%) or swelling (16%) the size of an Oreo cookie or larger (>or=46 mm) than children given a mixed series (10% and 9%, respectively) but less often experienced tenderness or limitation of movement at the injection site. Related health care utilization was low. There was no discernible effect on participation in recreational activities or parental attitudes toward vaccine; 90% would recommend the same vaccine to others with children of the same age. CONCLUSIONS: We conclude that injection-site reactions are more extensive after the fifth consecutive dose of an aP combination vaccine compared with the fifth dose in a mixed series of whole-cell and aP combination vaccines. These reactions are unlikely to affect parental acceptance of immunization recommendations or health care utilization.
Attitude↗