Evaluation Of Serogroup C And Acwy Meningococcal Vaccine Programs: Projected Impact On Disease Burden According To A Stochastic Two-Strain Dynamic Model

Objective: Advisory committees in Canada and the United States have updated recommendations for quadrivalent meningococcal conjugate vaccines against serogroups A, C, W135, and Y. Our objective was to evaluate optimally effective meningococcal vaccination policies using a stochastic dynamic model. Canada was used as an example. Methods: Our stochastic dynamic model of Neisseria meningitidis (Nm) transmission in an age-structured population assumed partial cross-immunity among two aggregated serogroup categories: 'AWY' containing A, W135, and Y; and 'Other' containing B, C, and ungroupable types. We compared the impact of monovalent C versus quadrivalent ACWY vaccination on Nm carriage and invasive meningococcal disease (IMD). Our model was parameterized with Canadian epidemiological and demographic data and employed probabilistic sensitivity analysis. Results: Routine infant immunization at 12 months and boosting at 15 years with a quadrivalent vaccine is projected to have the largest impact on total IMD incidence: a 74% reduction over 40 years. Routine infant immunization with a monovalent vaccine at 12 months only has much less impact and also generates strain replacement appearing after approximately ten years of continuous use. Conclusions: Immunizing infants at 12 months and boosting adolescents at 15 years with an ACWY vaccine is predicted to be most effective at reducing IMD incidence.GlaxoSmithKline Biologicals S

A cost-utility analysis of cervical cancer vaccination in preadolescent Canadian females

<p>Abstract</p> <p>Background</p> <p>Despite the fact that approximately 70% of Canadian women undergo cervical cancer screening at least once every 3 years, approximately 1,300 women were diagnosed with cervical cancer and approximately 380 died from it in 2008. This study estimates the effectiveness and cost-effectiveness of vaccinating 12-year old Canadian females with an AS04-adjuvanted cervical cancer vaccine. The indirect effect of vaccination, via herd immunity, is also estimated.</p> <p>Methods</p> <p>A 12-health-state 1-year-cycle Markov model was developed to estimate lifetime HPV related events for a cohort of 12-year old females. Annual transition probabilities between health-states were derived from published literature and Canadian population statistics. The model was calibrated using Canadian cancer statistics. From a healthcare perspective, the cost-effectiveness of introducing a vaccine with efficacy against HPV-16/18 and evidence of cross-protection against other oncogenic HPV types was evaluated in a population undergoing current screening practices. The base-case analysis included 70% screening coverage, 75% vaccination coverage, $135/dose for vaccine, and 3$18,672-$31,687 per QALY-gained, the lower range representing inclusion of cross-protective efficacy and herd immunity. The cost per QALY-gained was most sensitive to duration of vaccine protection, discount rate, and the correlation between probability of screening and probability of vaccination.</p> <p>Conclusion</p> <p>In the context of current screening patterns, vaccination of 12-year old Canadian females with an ASO4-ajuvanted cervical cancer vaccine is estimated to significantly reduce cervical cancer and mortality, and is a cost-effective option. However, the economic attractiveness of vaccination is impacted by the vaccine's duration of protection and the discount rate used in the analysis.</p

Canadian oncogenic human papillomavirus cervical infection prevalence: Systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Oncogenic human papillomavirus (HPV) infection prevalence is required to determine optimal vaccination strategies. We systematically reviewed the prevalence of oncogenic cervical HPV infection among Canadian females prior to immunization.</p> <p>Methods</p> <p>We included studies reporting DNA-confirmed oncogenic HPV prevalence estimates among Canadian females identified through searching electronic databases (e.g., MEDLINE) and public health websites. Two independent reviewers screened literature results, abstracted data and appraised study quality. Prevalence estimates were meta-analyzed among routine screening populations, HPV-positive, and by cytology/histology results.</p> <p>Results</p> <p>Thirty studies plus 21 companion reports were included after screening 837 citations and 120 full-text articles. Many of the studies did not address non-response bias (74%) or use a representative sampling strategy (53%).</p> <p>Age-specific prevalence was highest among females aged < 20 years and slowly declined with increasing age. Across all populations, the highest prevalence estimates from the meta-analyses were observed for HPV types 16 (routine screening populations, 8 studies: 8.6% [95% confidence interval 6.5-10.7%]; HPV-infected, 9 studies: 43.5% [28.7-58.2%]; confirmed cervical cancer, 3 studies: 48.8% [34.0-63.6%]) and 18 (routine screening populations, 8 studies: 3.3% [1.5-5.1%]; HPV-infected, 9 studies: 13.6% [6.1-21.1%], confirmed cervical cancer, 4 studies: 17.1% [6.4-27.9%].</p> <p>Conclusion</p> <p>Our results support vaccinating females < 20 years of age, along with targeted vaccination of some groups (e.g., under-screened populations). The highest prevalence occurred among HPV types 16 and 18, contributing a combined cervical cancer prevalence of 65.9%. Further cancer protection is expected from cross-protection of non-vaccine HPV types. Poor study quality and heterogeneity suggests that high-quality studies are needed.</p

Modeling the impact of the difference in cross-protection data between a human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and a human papillomavirus (HPV)-6/11/16/18 vaccine in Canada

<p>Background</p> <p>In Canada, two vaccines that have demonstrated high efficacy against infection with human papillomavirus (HPV) types −16 and −18 are available. The HPV-6/11/16/18 vaccine provides protection against genital warts (GW) while the HPV-16/18 vaccine may provide better protection against other oncogenic HPV types. In this analysis, the estimated clinical and economic benefit of each of these vaccines was compared in the Canadian setting.</p> <p>Methods</p> <p>A Markov model of the natural history of HPV infection among women, cervical cancer (CC) and GW was used to estimate the impact of vaccinating a cohort of 100,000 12-year-old females on lifetime outcomes and healthcare system costs (no indirect benefit in males included). A budget impact model was used to estimate the impact of each vaccine by province.</p> <p>Results</p> <p>In the base case, vaccination with the HPV-16/18 vaccine was predicted to prevent 48 additional CC cases, and 16 additional CC deaths, while vaccination with the HPV-6/11/16/18 vaccine was predicted to prevent 6,933 additional GW cases. Vaccination with the HPV-16/18 vaccine was estimated to save 1 additional discounted quality adjusted life year (QALY) at an overall lower lifetime cost to the healthcare system compared to the HPV-6/11/16/18 vaccine (assuming vaccine price parity). In sensitivity analyses, the HPV-6/11/16/18 vaccine was associated with greater QALYs saved when the cross-protection efficacy of the HPV-16/18 vaccine was reduced, or the burden of GW due to HPV-6/11 was increased. In most scenarios with price parity, the lifetime healthcare cost of the strategy with the HPV-16/18 vaccine was predicted to be lower than the HPV-6/11/16/18 vaccine. In the probabilistic sensitivity analyses, the HPV-16/18 vaccine provided more QALY benefit than the HPV-6/11/16/18 vaccine in 49.2% of scenarios, with lower relative lifetime costs in 83.5% of scenarios.</p> <p>Conclusions</p> <p>Overall, the predicted lifetime healthcare costs and QALYs saved by implementing each of the vaccines are similar. Vaccination with the HPV-16/18 vaccine is expected to be associated with reduced CC disease morbidity and mortality compared to vaccination with the HPV-6/11/16/18 vaccine. Differences in these outcomes depend on the extent of cervical disease prevented by cross-protection and the burden of GW caused by HPV-6/11.</p

Canadian oncogenic human papillomavirus cervical infection prevalence: Systematic review and meta-analysis

Abstract Background Oncogenic human papillomavirus (HPV) infection prevalence is required to determine optimal vaccination strategies. We systematically reviewed the prevalence of oncogenic cervical HPV infection among Canadian females prior to immunization. Methods We included studies reporting DNA-confirmed oncogenic HPV prevalence estimates among Canadian females identified through searching electronic databases (e.g., MEDLINE) and public health websites. Two independent reviewers screened literature results, abstracted data and appraised study quality. Prevalence estimates were meta-analyzed among routine screening populations, HPV-positive, and by cytology/histology results. Results Thirty studies plus 21 companion reports were included after screening 837 citations and 120 full-text articles. Many of the studies did not address non-response bias (74%) or use a representative sampling strategy (53%). Age-specific prevalence was highest among females aged < 20 years and slowly declined with increasing age. Across all populations, the highest prevalence estimates from the meta-analyses were observed for HPV types 16 (routine screening populations, 8 studies: 8.6% [95% confidence interval 6.5-10.7%]; HPV-infected, 9 studies: 43.5% [28.7-58.2%]; confirmed cervical cancer, 3 studies: 48.8% [34.0-63.6%]) and 18 (routine screening populations, 8 studies: 3.3% [1.5-5.1%]; HPV-infected, 9 studies: 13.6% [6.1-21.1%], confirmed cervical cancer, 4 studies: 17.1% [6.4-27.9%]. Conclusion Our results support vaccinating females < 20 years of age, along with targeted vaccination of some groups (e.g., under-screened populations). The highest prevalence occurred among HPV types 16 and 18, contributing a combined cervical cancer prevalence of 65.9%. Further cancer protection is expected from cross-protection of non-vaccine HPV types. Poor study quality and heterogeneity suggests that high-quality studies are needed

A review of interventions triggered by hepatitis A infected food-handlers in Canada

Abstract Background In countries with low hepatitis A (HA) endemicity, infected food handlers are the source of most reported foodborne outbreaks. In Canada, accessible data repositories of infected food handler incidents are not available. We undertook a systematic review of such incidents to evaluate the extent of viral transmission through food contamination and the scope of post-exposure prophylaxis (PEP) interventions. Methods A systematic search of MEDLINE and EMBASE was conducted to identify published reports of incidents in Canada. An expanded search of a news repository (i.e., transcripts from newspapers and newscasts) was also conducted to identify the location and timing of an incident, which was used to retrieve the related report by contacting local public health departments. Data pertaining to case identification, public health risk, PEP interventions, and associated costs was independently abstracted by two reviewers and summarized according to incidents with and without large PEP interventions. Results A total of 16 incidents were identified from 1998–2004. There were approximately 3 incidents requiring public notification per year. Only 12.5% of incidents were described in published reports, indicating that published data significantly underestimated the number of incidents and PEP interventions. Data pertaining to the remaining incidents was unpublished, sparse and highly dispersed at the local public health level. Six of the 16 incidents required large PEP interventions to immunize on average 5000 potentially exposed individuals. Secondary transmission was low. Characteristics of incidents requiring large PEP interventions included potentially infectious food handlers working with uncooked food for a prolonged duration in high-volume grocery stores in high-density urban areas. Conclusion Infected food handlers with hepatitis A virus (HAV) requiring public notification are not infrequent in Canada. Published data severely underestimated the burden of PEP intervention. Better and consistent reporting at the local and national level as well as a national data repository should be considered for the management of future incidents.</p

A review of interventions triggered by hepatitis A infected food-handlers in Canada

Background: In countries with low hepatitis A (HA) endemicity, infected food handlers are the source of most reported foodborne outbreaks. In Canada, accessible data repositories of infected food handler incidents are not available. We undertook a systematic review of such incidents to evaluate the extent of viral transmission through food contamination and the scope of post-exposure prophylaxis (PEP) interventions. Methods: A systematic search of MEDLINE and EMBASE was conducted to identify published reports of incidents in Canada. An expanded search of a news repository (i.e., transcripts from newspapers and newscasts) was also conducted to identify the location and timing of an incident, which was used to retrieve the related report by contacting local public health departments. Data pertaining to case identification, public health risk, PEP interventions, and associated costs was independently abstracted by two reviewers and summarized according to incidents with and without large PEP interventions. Results: A total of 16 incidents were identified from 1998–2004. There were approximately 3 incidents requiring public notification per year. Only 12.5% of incidents were described in published reports, indicating that published data significantly underestimated the number of incidents and PEP interventions. Data pertaining to the remaining incidents was unpublished, sparse and highly dispersed at the local public health level. Six of the 16 incidents required large PEP interventions to immunize on average 5000 potentially exposed individuals. Secondary transmission was low. Characteristics of incidents requiring large PEP interventions included potentially infectious food handlers working with uncooked food for a prolonged duration in high-volume grocery stores in high-density urban areas. Conclusion: Infected food handlers with hepatitis A virus (HAV) requiring public notification are not infrequent in Canada. Published data severely underestimated the burden of PEP intervention. Better and consistent reporting at the local and national level as well as a national data repository should be considered for the management of future incidents.Health Care and Epidemiology, Department ofNon UBCMedicine, Faculty ofReviewedFacult

Cost-Effectiveness Analyses of Hepatitis A Vaccine: A Systematic Review to Explore the Effect of Methodological Quality on the Economic Attractiveness of Vaccination Strategies

Hepatitis A vaccines have been available for more than a decade. Because the burden of hepatitis A virus has fallen in developed countries, the appropriate role of vaccination programmes, especially universal vaccination strategies, remains unclear. Cost-effectiveness analysis is a useful method of relating the costs of vaccination to its benefits, and may inform policy. This article systematically reviews the evidence on the cost effectiveness of hepatitis A vaccination in varying populations, and explores the effects of methodological quality and key modelling issues on the cost-effectiveness ratios. Cost-effectiveness/cost-utility studies of hepatitis A vaccine were identified via a series of literature searches (MEDLINE, EMBASE, HSTAR and SSCI). Citations and full-text articles were reviewed independently by two reviewers. Reference searching, author searches and expert consultation ensured literature saturation. Incremental cost-effectiveness ratios (ICERs) were abstracted for base-case analyses, converted to $US, year 2005 values, and categorised to reflect various levels of cost effectiveness. Quality of reporting, methodological issues and key modelling issues were assessed using frameworks published in the literature. Thirty-one cost-effectiveness studies (including 12 cost-utility analyses) were included from full-text article review (n = 58) and citation screening (n = 570). These studies evaluated universal mass vaccination (n = 14), targeted vaccination (n = 17) and vaccination of susceptibles (i.e. individuals initially screened for antibody and, if susceptible, vaccinated) [n = 13]. For universal vaccination, 50% of the ICERs wereCost-effectiveness, Cost-utility, Hepatitis-A, Hepatitis-A-hepatitis-B-vaccine, Hepatitis-A-vaccine, Modelling