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Biomedical subjects

Danuta M Skowronski

Publications and source records attributed to Danuta M Skowronski.

At least 19 recordsLinked to original sources
PubMed2007

Protective measures and human antibody response during an avian influenza H7N3 outbreak in poultry in British Columbia, Canada.

BACKGROUND: In 2004 an outbreak of avian influenza of the H7N3 subtype occurred among poultry in British Columbia, Canada. We report compliance with recommended protective measures and associated human infections during this outbreak. METHODS: We sought voluntary participation by anyone (cullers, farmers and their families) involved in efforts to control the poultry outbreak. Recruitment was by advertisements at the worker deployment site, in local media and through newsletters sent directly to farmers. Sera were tested for antibody to H7N3 by microneutralization assay. A subset of 16 sera (including convalescent sera from 2 unprotected workers with conjunctivitis from whom virus had been isolated) was further tested by Western blot and routine and modified hemagglutination inhibition assays. RESULTS: A total of 167 people (20% to 25% of all workers) participated between May 7 and July 26, 2004. Of these, 19 had experienced influenza-like illness and 21 had experienced red or watery eyes. There was no significant association between illness reports and exposure to infected birds. Among 65 people who entered barns with infected birds, 55 (85%) had received influenza vaccine, 48 (74%) had received oseltamivir, and 55 (85%), 54 (83%) and 36 (55%) reported always wearing gloves, mask or goggles, respectively. Antibody to the H7 subtype was not detected in any sera. INTERPRETATION: During the BC outbreak, compliance with recommended protective measures, especially goggles, was incomplete. Multiple back-up precautions, including oseltamivir prophylaxis, may prevent human infections and should be readily accessible and consistently used by those involved in the control of future outbreaks of avian influenza in poultry. Localized human avian influenza infections may not result in serologic response despite confirmed viral detection and culture.

Adolescent↗
PubMed2006

Potential cost-effectiveness of annual influenza immunization for infants and toddlers: experience from Canada.

BACKGROUND: In 2004, expert groups in North America recommended annual influenza immunization for healthy infants and toddlers aged 6-23 months with a goal of reducing high hospitalization rates (HR). We assess cost-effectiveness of this program in Canada. METHODS: Analysis was from third-party payer and societal perspectives in preventing hospitalization and other outcomes among 500,000 vaccinated or non-vaccinated infants/toddlers. Base-case assumptions include: 25% attack rate (AR), 1% case hospitalization rate (HR), 0.002% case fatality, vaccine effectiveness (VE) of 66%, CDN dollar 15 per dose for vaccine and administration, half of mothers requiring 2h from work per dose to immunize and two doses required by 100% (first year) or 33% (subsequent years) of infants/toddlers immunized. RESULTS: After the first year, infant/toddler influenza immunization costs the third-party approximately CDN dollar 9 per day of illness averted, CDN dollar 120 per physician visit averted, CDN dollar 7000 per hospitalization averted, CDN dollar 3 million per death averted and CDN dollar 450,000 per life year gained. Corresponding costs from societal perspective are approximately CDN dollar 3, CDN dollar 45, CDN dollar 2500, CDN dollar 1 million and CDN dollar 170,000. The program becomes cost-saving from the third-party perspective at AR>55%, HR>4%, or cost per dose (for vaccine and its administration) 74%. CONCLUSIONS: In the base case, infant/toddler influenza immunization is not cost-saving but could become more cost-effective in settings of higher attack rate and lower immunization cost. In this context, immunization of children in daycare or other group settings should be preferentially considered. Economic analyses should routinely inform expansions to influenza immunization programs.

Canada↗
PubMed2006

Comparative evaluation of two severe acute respiratory syndrome (SARS) vaccine candidates in mice challenged with SARS coronavirus.

Two different severe acute respiratory syndrome (SARS) vaccine strategies were evaluated for their ability to protect against live SARS coronavirus (CoV) challenge in a murine model of infection. A whole killed (inactivated by beta-propiolactone) SARS-CoV vaccine and a combination of two adenovirus-based vectors, one expressing the nucleocapsid (N) and the other expressing the spike (S) protein (collectively designated Ad S/N), were evaluated for the induction of serum neutralizing antibodies and cellular immune responses and their ability to protect against pulmonary SARS-CoV replication. The whole killed virus (WKV) vaccine given subcutaneously to 129S6/SvEv mice was more effective than the Ad S/N vaccine administered either intranasally or intramuscularly in inhibiting SARS-CoV replication in the murine respiratory tract. This protective ability of the WKV vaccine correlated with the induction of high serum neutralizing-antibody titres, but not with cellular immune responses as measured by gamma interferon secretion by mouse splenocytes. Titres of serum neutralizing antibodies induced by the Ad S/N vaccine administered intranasally or intramuscularly were significantly lower than those induced by the WKV vaccine. However, Ad S/N administered intranasally, but not intramuscularly, significantly limited SARS-CoV replication in the lungs. Among the vaccine groups, SARS-CoV-specific IgA was found only in the sera of mice immunized intranasally with Ad S/N, suggesting that mucosal immunity may play a role in protection for the intranasal Ad S/N delivery system. Finally, the sera of vaccinated mice contained antibodies to S, further suggesting a role for this protein in conferring protective immunity against SARS-CoV infection.

Administration, Intranasal↗
PubMed2006

Solicited adverse events after influenza immunization among infants, toddlers, and their household contacts.

OBJECTIVES: We assessed adverse events, including oculorespiratory syndrome, following influenza immunization during the first year of a publicly-funded program for infants, toddlers and their household members in Canada. METHODS: Parents bringing infants and toddlers for influenza immunization to clinics in Quebec or British Columbia consented to structured telephone interview 5 to 10 days later. One adult provided information for all household members. Symptom experience commencing before and after immunization was assessed. Non-immunized persons also served as a comparison group for immunized household members. RESULTS: Sample included 690 immunized infants and toddlers and 1801 household members, 1374 immunized. Only fussiness, fever, decreased appetite, drowsiness, and nasal congestion/coryza were reported for >5% of infants/ toddlers within 72 hours of immunization, but only arm discomfort was reported among >5% of immunized household contacts. In multivariate analysis, muscle ache was the only systemic symptom reported more often by immunized household members compared to non-immunized persons. Oculorespiratory symptoms were infrequent and there was no difference between immunized and non-immunized household members in their report. Less than 1% of adults required time off work because of adverse events following influenza immunization in the household. Less than 2% of subjects experiencing an adverse event following influenza immunization were considered unlikely to be vaccinated again. CONCLUSION: Influenza vaccine is well-tolerated by infants, toddlers and their household members. Post-marketing observational designs are an expedient way to assess adverse events following influenza immunization. These methods should be established and rehearsed annually in preparation for a pandemic.

Child, Preschool↗
PubMed2006

Coordinated response to SARS, Vancouver, Canada.

Two Canadian urban areas received travelers with severe acute respiratory syndrome (SARS) before the World Health Organization issued its alert. By July 2003, Vancouver had identified 5 cases (4 imported); Toronto reported 247 cases (3 imported) and 43 deaths. Baseline preparedness for pandemic threats may account for the absence of sustained transmission and fewer cases of SARS in Vancouver.

Adult↗
PubMed2005

Oculo-respiratory syndrome after influenza vaccination: trends over four influenza seasons.

BACKGROUND: Oculo-respiratory syndrome (ORS) following influenza vaccination was identified in Canada in 2000. This report describes trends of ORS reported during four consecutive seasons 2000, 2001, 2002 and 2003 in the province of Quebec, Canada. METHODS: Data come from the vaccine-associated adverse event (VAAE) passive reporting system of the Province of Quebec. RESULTS: The rate of ORS reported per 100000 doses distributed declined from 46.6 in 2000 to 34.2, 20.6 and 9 in 2001, 2002 and 2003, respectively. There was no significant difference in rates for ORS between the two vaccines in use in Canada (Fluviral and Vaxigrip) both in 2001 and 2002. During the 4 years, incidence was highest in people aged 40-59 years and declined in older age groups. The clinical profile of ORS has remained remarkably stable over years. Overall, ocular, respiratory symptoms or facial edema were reported by 58%, 84% and 31% of patients, respectively, and 15% had symptoms including all three symptom categories. ORS lasted more than a week in 8-13% of the cases. CONCLUSION: ORS is an adverse event that occurred with both influenza vaccines used in Canada. Its frequency has declined substantially but is still present after 4 years. It constitutes a clinical entity distinct from anaphylactic allergy. Unlike anaphylaxis, ORS does not constitute an absolute contraindication to further doses.

Adolescent↗
PubMed2005

Disparities in varicella vaccine coverage in the absence of public funding.

Varicella vaccine has been licensed in Canada since December 1998 but not provided free in all provinces. Through a cross-sectional telephone survey to a random sample of parents, we assessed factors associated with varicella vaccine uptake in the absence of public funding. Parents of children aged 2-3 years (Group I) and 6-7 years (Group II) were contacted between March and May 2003 in British Columbia, Canada. Response rate was 82% (Group I=571; Group II=704). Among susceptible children, varicella vaccine coverage was 21% (95% CI 18-25%) and 28% (95% CI 22-33%), respectively. There were significant disparities in vaccine coverage based on income and residence. Physician or nurse recommendation was a strong determinant of vaccine uptake as were belief in the safety and efficacy of vaccine. Among parents of susceptible children, 59% (343/582) would vaccinate their child if it were provided free; 25% (148/582) were undecided.

British Columbia↗
PubMed2005

Prevalence of hearing loss in primary school children in Zimbabwe.

OBJECTIVE: The objective of the study was to determine the prevalence of significant hearing impairment in children attending primary school in the country of Zimbabwe. METHODS: A cross-sectional study of the prevalence of hearing impairment in primary school children was undertaken as part of The Rotary Hearing Health Care Program in Zimbabwe. The sampling unit was primary schools in Manicaland, a province of Zimbabwe. All students in selected schools were screened. In total, 5528 students were screened for significant hearing impairment defined as greater than 30 dB HL at 1, 2 and 4 kHz in a quiet classroom. RESULTS: Overall, 135 students (2.4%, 95% CI 2.0-2.8) were identified as having a hearing threshold of greater than 30 dB in at least one ear and for at least one of the test frequencies. A conductive hearing loss was found in 79 students, or 1.4% of the total, and a sensorineural hearing loss was found in 56 students or 1.0% of the total. Disabling hearing impairment was found in 0.9% of children. CONCLUSIONS: The prevalence of hearing impairment in children in Zimbabwe is significant, even as a conservative measure amongst children attending school. Hearing impairment challenges the academic, career and social potential of young children. Regular screening, such as this could help target preventative measures that may improve the hearing impaired child's potential in terms of social interaction, academic achievement, and work opportunities.

Adolescent↗
PubMed2005

Network theory and SARS: predicting outbreak diversity.

Many infectious diseases spread through populations via the networks formed by physical contacts among individuals. The patterns of these contacts tend to be highly heterogeneous. Traditional "compartmental" modeling in epidemiology, however, assumes that population groups are fully mixed, that is, every individual has an equal chance of spreading the disease to every other. Applications of compartmental models to Severe Acute Respiratory Syndrome (SARS) resulted in estimates of the fundamental quantity called the basic reproductive number R0--the number of new cases of SARS resulting from a single initial case--above one, implying that, without public health intervention, most outbreaks should spark large-scale epidemics. Here we compare these predictions to the early epidemiology of SARS. We apply the methods of contact network epidemiology to illustrate that for a single value of R0, any two outbreaks, even in the same setting, may have very different epidemiological outcomes. We offer quantitative insight into the heterogeneity of SARS outbreaks worldwide, and illustrate the utility of this approach for assessing public health strategies.

Adult↗
PubMed2005

Oculorespiratory syndrome after influenza immunization in children.

BACKGROUND: During the 2000-2001 season, an oculorespiratory syndrome (ORS) was identified in association with 1 manufacturer's influenza vaccine in Canada. ORS included bilateral red eyes, facial edema or respiratory symptoms beginning within 24 hours of influenza immunization. Few reports involved children. We assessed the rate of ORS in a pediatric cohort. METHODS: In February 2001, invitation to participate in an influenza vaccine safety survey was sent to the parents of children who attend a diabetes clinic. A questionnaire elicited influenza immunization history and adverse event experience beginning within 1 day of vaccination for the child with diabetes and up to 3 siblings. Follow-up telephone interviews collected information from those who failed to return a questionnaire by mail. RESULTS: Of the 959 households sent a questionnaire, 780 participated (81%). Among 780 children with diabetes, 418 (54%) received influenza vaccine in 2000. Adverse event experience was collected from an additional 242 immunized siblings. Among immunized children, 13% (95% confidence interval, 10-16%) experienced ORS, consisting primarily of respiratory symptoms. The majority (72%) resolved within 2 days. There was association between ORS and first time receipt of influenza vaccine (OR 2.7; 95% confidence interval, 1.6-4.4). Fewer parents of ORS-affected compared with unaffected children indicated that they were likely or very likely to have their child revaccinated (87 versus 97%; P < 0.001). CONCLUSIONS: In 2000-2001, children experienced ORS in Canada at a rate comparable with that of adults. ORS should be incorporated into influenza vaccine safety monitoring and discussed with parents, especially those contemplating influenza vaccine for their child for the first time.

Adolescent↗
PubMed2005

A modified vaccine reduces the rate of large injection site reactions to the preschool booster dose of diphtheria-tetanus-acellular pertussis vaccine: results of a randomized, controlled trial.

BACKGROUND: Large injection site reactions commonly follow booster doses of diphtheria-tetanus-acellular pertussis (DTaP) vaccines at 4-6 years of age. A vaccine with lower diphtheria and pertussis dosage (Tdap) might be better tolerated for this dose. METHODS: We conducted a randomized, controlled, evaluator-blinded comparison of local reactions to DTaP.inactivated poliomyelitis vaccine (IPV) or Tdap booster vaccinations, in 4- to 5.5-year-old children. Reactions were assessed daily by parents and after 48 hours by study nurses. Serologic responses were measured before and 4 weeks after vaccination and examined in relation to large local reactions (>or=50 mm redness and/or swelling). RESULTS: 288 children were vaccinated, 145 with DTaP.IPV and 143 with Tdap, and after 48 hours examiners noted local redness >or= 50mm in 17.2 and 6.3%, respectively (P = 0.004). DTaP.IPV vaccinees initially experienced local pain (in 54%) which limited arm motion (in 37%), but symptoms largely resolved by 48 hours. Tdap vaccinees had fewer symptoms (pain in 20%, limited arm motion in 14%). Children with large reactions to DTaP.IPV more often than nonreactors had elevated preimmunization antibody concentrations to 1 or more of diphtheria, pertussis toxin or pertactin and elevated postimmunization antibody concentrations to all antigens except fimbriae. Booster responses to Tdap were reduced with the smaller antigen doses but were generally satisfactory. CONCLUSIONS: This preschool DTaP.IPV booster vaccination caused large local reactions in 1 in 5 children, with transient discomfort. With Tdap vaccine, such reactions were significantly fewer but not eliminated. A Tdap.IPV vaccine warrants study for routine use at 4-6 years of age.

Antibody Formation↗
PubMed2005

Severe acute respiratory syndrome (SARS): a year in review.

Severe acute respiratory syndrome (SARS) emerged from China as an untreatable and rapidly spreading respiratory illness of unknown etiology. Following point source exposure in February 2003, more than a dozen guests infected at a Hong Kong hotel seeded multi-country outbreaks that persisted through the spring of 2003. The World Health Organization responded by invoking traditional public health measures and advanced technologies to control the illness and contain the cause. A novel coronavirus was implicated and its entire genome was sequenced by mid-April 2003. The urgency of responding to this threat focused scientific endeavor and stimulated global collaboration. Through real-time application of accumulating knowledge, the world proved capable of arresting the first pandemic threat of the twenty-first century, despite early respiratory-borne spread and global susceptibility. This review synthesizes lessons learned from this remarkable achievement. These lessons can be applied to re-emergence of SARS or to the next pandemic threat to arise.

Anti-Inflammatory Agents↗
PubMed2005

Modeling control strategies of respiratory pathogens.

Effectively controlling infectious diseases requires quantitative comparisons of quarantine, infection control precautions, case identification and isolation, and immunization interventions. We used contact network epidemiology to predict the effect of various control policies for a mildly contagious disease, such as severe acute respiratory syndrome, and a moderately contagious disease, such as smallpox. The success of an intervention depends on the transmissibility of the disease and the contact pattern between persons within a community. The model predicts that use of face masks and general vaccination will only moderately affect the spread of mildly contagious diseases. In contrast, quarantine and ring vaccination can prevent the spread of a wide spectrum of diseases. Contact network epidemiology can provide valuable quantitative input to public health decisionmaking, even before a pathogen is well characterized.

British Columbia↗
PubMed2004

Adult tetanus, diphtheria and pertussis immunization: knowledge, beliefs, behavior and anticipated uptake.

BACKGROUND: Lifetime protection against pertussis has been adopted as a goal of immunization programs in Canada. To anticipate adult coverage with a combined product containing tetanus (T) and diphtheria (d) toxoids and acellular pertussis (aP) vaccine as a booster dose, we conducted a survey of households in British Columbia, Canada. METHODS: In a random telephone survey involving 800 adults, 25 years of age and older, we assessed current behaviors related to adult Td immunization and beliefs regarding pertussis vaccine under various scenarios relevant to adult decision-making. RESULTS: Forty-five percent of participants reported having received tetanus vaccine within the previous 10 years; this rate was lowest amongst elderly persons 65 years of age or more (28%). On multi-variate analysis, being up-to-date with tetanus immunization was independently associated with belief that an adult should be immunized against tetanus and perception that tetanus is life-threatening and inversely associated with being elderly. At baseline, 59% of respondents indicated willingness to receive pertussis immunization if provided free; this increased to 76% following sequential information about communicability and severity of pertussis illness and safety, efficacy and convenience of vaccine and up to 87% if accompanied by physician or nurse recommendation. Sixty-three percent of adults indicated they would receive the vaccine if required to pay $40.00 (Cdn) for it. CONCLUSIONS: Personal risk perception, public funding and physician recommendation are important to adults when considering tetanus and pertussis immunization. These factors may be relevant as immunization programs are expanded to include more adults generally.

Adult↗
PubMed2004

Recurrence risk of oculorespiratory syndrome after influenza vaccination: randomized controlled trial of previously affected persons.

BACKGROUND: Oculorespiratory syndrome (ORS) after influenza vaccination has many features of an allergic reaction. METHODS: The objective of the study was to estimate the recurrence rate of ORS after receipt of either of 2 influenza vaccines available in Canada for the 2002-2003 influenza season in individuals who experienced ORS in 2000 or 2001. We designed a randomized, crossover, double-blind, placebo-controlled trial in which patients received the vaccine and the placebo 7 days apart. Patients were contacted by telephone at 24 hours and seen at 7 days to collect information about the recurrence of ORS symptoms. The 146 patients belonged to 3 groups: group A (46 patients) had ORS in 2000 but were not revaccinated in 2001, group B (50 patients) had ORS in 2000 and were revaccinated in 2001, and group C (50 patients) had ORS in 2001 but not in 2000. Half of the participants received Fluviral S/F (Shire Biologics) and half received Vaxigrip (Aventis Pasteur). The main outcome measure was the risk difference in ORS symptoms in the 24 hours after receiving the vaccine and after receiving placebo. RESULTS: Recurrence attributable to the vaccine occurred in 34% (95% confidence interval, 21%-47%) of patients after receiving Fluviral S/F and in 15% (95% confidence interval, 2%-28%) after receiving Vaxigrip. The rate was twice as high in group A vs groups B and C. The risk of ORS was highest and most significant in group A patients vaccinated with Fluviral S/F. Most cases were mild, with 94% of patients with recurrence indicating that they would still be revaccinated the next year. CONCLUSIONS: Despite high recurrence rates, revaccination of persons previously affected by ORS seems to be safe. Oculorespiratory syndrome is not anaphylactic, and most recurrences are benign. Most patients remain willing to be revaccinated.

Adolescent↗
PubMed2004

Aggregate content influences the Th1/Th2 immune response to influenza vaccine: evidence from a mouse model.

During the 2000-2001 season, a newly identified oculo-respiratory syndrome (ORS) was detected across Canada as an adverse effect to one influenza vaccine. The implicated vaccine contained a higher than expected proportion of unsplit and aggregated influenza virions. Clinical and epidemiologic features of ORS were suggestive of type 2-like influences on the immune response. We hypothesized that the implicated vaccine from the 2000-2001 season would induce greater Th2-like polarization relative to the non-implicated vaccine from the same season. Three groups consisting of eight mice each were either immunized with implicated vaccine, immunized with non-implicated vaccine or not immunized. Antigen-specific cellular responses were characterized based on the balance of Th2 (IL-4, IL-5) and Th1 (IFN-gamma) cytokines in vitro. We confirm that vaccine aggregates deviate the immune response to a greater Th2 cytokine pattern with potential implications for vaccine screening, safety, and efficacy.

Animals↗