Comparing the cost-effectiveness of two- and three-dose schedules of human papillomavirus vaccination: a transmission-dynamic modelling study.

BACKGROUND: Recent evidence suggests that two doses of HPV vaccines may be as protective as three doses in the short-term. We estimated the incremental cost-effectiveness of two- and three-dose schedules of girls-only and girls & boys HPV vaccination programmes in Canada. METHODS: We used HPV-ADVISE, an individual-based transmission-dynamic model of multi-type HPV infection and diseases (anogenital warts, and cancers of the cervix, vulva, vagina, anus, penis and oropharynx). We conducted the analysis from the health payer perspective, with a 70-year time horizon and 3% discount rate, and performed extensive sensitivity analyses, including duration of vaccine protection and vaccine cost. FINDINGS: Assuming 80% coverage and a vaccine cost per dose of $85, two-dose girls-only vaccination (vs. no vaccination) produced cost/quality-adjusted life-year (QALY)-gained varying between$7900-24,300. The incremental cost-effectiveness ratio of giving the third dose to girls (vs. two doses) was below $40,000/QALY-gained when: (i) three doses provide longer protection than two doses and (ii) two-dose protection was shorter than 30 years. Vaccinating boys (with two or three doses) was not cost-effective (vs. girls-only vaccination) under most scenarios investigated. INTERPRETATION: Two-dose HPV vaccination is likely to be cost-effective if its duration of protection is at least 10 years. A third dose of HPV vaccine is unlikely to be cost-effective if two-dose duration of protection is longer than 30 years. Finally, two-dose girls & boys HPV vaccination is unlikely to be cost-effective unless the cost per dose for boys is substantially lower than the cost for girls

Human Papilloma Virus vaccine and cervical cancer screening acceptability among adults in Quebec, Canada

<p>Abstract</p> <p>Background</p> <p>The Pap test has been used for cervical cancer screening for more than four decades. A human papillomavirus (HPV) vaccine has been approved for use in Canada and is commercially available now. These two preventive interventions should be considered simultaneously. General population support is an important factor for the successful combination of these interventions. The study had two objectives: 1) To assess practices, beliefs, and attitudes regarding Pap test screening and HPV immunization; 2) To identify socio-demographic factors for Pap screening and vaccine acceptability.</p> <p>Methods</p> <p>In 2006, 500 adults were invited to participate in a telephone survey in the region of Quebec City (urban and rural population, 600 000), Canada. Some neutral and standardized information on Pap test and HPV was provided before soliciting opinions.</p> <p>Results</p> <p>471 adults (18–69 year-olds) answered the questionnaire, the mean age was 45 years, 67% were female, and 65% had college or university degree. Eighty-six percent of women had undergone at least one Pap-test in their life, 55% in the last year, and 15% from 1 to 3 years ago. Among screened women, the test had been performed in the last three years in 100% of 18–30 year-olds, but only in 67% of 60–69 year-olds (P < 0.0001). Only 15% of respondents had heard of HPV. Eighty-seven percent agreed that HPV vaccines could prevent cervical cancer, 73% that the vaccine has to be administered before the onset of sexual activity, 89% would recommend vaccination to their daughters and nieces. Among respondents < 25 years, 91% would agree to receive the vaccine if it is publicly funded, but only 72% would agree to pay $100/dose.</p> <p>Conclusion</p> <p>There is an important heterogeneity in cervical cancer screening frequency and coverage. Despite low awareness of HPV infection, the majority of respondents would recommend or are ready to receive the HPV vaccine, but the cost could prevent its acceptability.</p

Feasibility and impact of providing feedback to vaccinating medical clinics: evaluating a public health intervention

<p>Abstract</p> <p>Background</p> <p>Vaccine coverage (VC) at a given age is a widely-used indicator for measuring the performance of vaccination programs. However, there is increasing data suggesting that measuring delays in administering vaccines complements the measure of VC. Providing feedback to vaccinators is recognized as an effective strategy for improving vaccine coverage, but its implementation has not been widely documented in Canada. The objective of this study was to evaluate the feasibility of providing personalized feedback to vaccinators and its impact on vaccination delays (VD).</p> <p>Methods</p> <p>In April and May 2008, a one-hour personalized feedback session was provided to health professionals in vaccinating medical clinics in the Quebec City region. VD for vaccines administered at two and twelve months of age were presented. Data from the regional vaccination registry were analysed for participating clinics. Two 12-month periods before and after the intervention were compared, namely from April 1^st, 2007 to March 31^st, 2008 and from June 1^st, 2008 to May 31^st, 2009.</p> <p>Results</p> <p>Ten medical clinics out of the twelve approached (83%), representing more than 2500 vaccinated children, participated in the project. Preparing and conducting the feedback involved 20 hours of work and expenses of $1000 per clinic. Based on a delay of one month, 94% of first doses of DTaP-Polio-Hib and 77% of meningococcal vaccine doses respected the vaccination schedule both before and after the intervention. Following the feedback, respect of the vaccination schedule increased for vaccines planned at 12 months for the four clinics that had modified their vaccination practices related to multiple injections (depending on the clinic, VD decreased by 24.4%, 32.0%, 40.2% and 44.6% respectively, p < 0.001 for all comparisons).</p> <p>Conclusions</p> <p>The present study shows that it is feasible to provide personalized feedback to vaccinating clinics. While it may have encouraged positive changes in practice concerning multiple injections, this intervention on its own did not impact vaccination delays of the clinics visited. It is possible that feedback integrated into other types of effective interventions and sustained over time may have more impact on VD.</p

Absence of association between Guillain-Barré syndrome hospitalizations and HPV-vaccine

Background: In 2008, a school-based human papilloma virus (HPV) vaccination program was implemented in the province of Québec. Grade 4 girls (9–10 years old) are routinely vaccinated and grade 9 to 12 girls (14–17 years old) were eligible for the catch-up vaccination. Vaccine coverage of the targeted cohorts was estimated at 76–81%. To assess if HPV vaccination is associated with an increase in GBS hospitalisation, we compared the hospitalization rates of GBS in HPV vaccination targeted and non-targeted groups. Methods: Hospital discharge records with a GBS code as the main diagnosis during the 1999–2014 period were retrieved. Incidence rates according to program eligibility were computed and adjusted relative risk in the targeted groups was estimated by Poisson regression. Results: The overall incidence rate in the 7 to 17 year-olds was 0.73/100,000 p-y. There was no increase in GBS incidence in HPV vaccination targeted groups (adjusted IRR = 0.81, 95%CI: 0.29–2.26). Conclusion: No signal of increase GBS hospitalisation incidence in the HPV-vaccine targeted group was detected in the hospitalisation database

Herpes Zoster Burden in Canadian Provinces: A Narrative Review and Comparison with Quebec Provincial Data

Background. The main aim of this review was to assess incidence rates and trends of medically attended and death cases of herpes zoster in Canada. Methods. The search was conducted in five databases (PubMed, Cochrane, Embase, PsycNET, and Web of Science). Data on herpes zoster-related consultations and hospitalisations and deaths were also extracted from three Quebec provincial administrative databases (RAMQ, MED-ECHO, and ISQ). Results. The electronic search yielded 587 publications. Seventeen publications satisfied inclusion criteria. These publications reported data from eleven studies. Ten studies used provincial databases, and one study used the Canadian Primary Care Sentinel Surveillance Network electronic database. Seven studies evaluated overall rates of medically attended cases (consultations and hospitalisations). Four of these studies reported an increase in rates of medically attended cases during the study period; one study reported stable rates, and two studies reported only an average rate. The rates varied from 316 to 450/100,000 p.y. The Quebec analysis shows similar rates with a slight decreasing trend (from 369 to 350/100,000 p.y.). Incidence rates of consultations were reported separately in three studies. Two studies reported an increase in rates (from 258 to 348/100,000 p.y. and from 324 to 366/100,000 p.y.), and the third study reported a decrease (from 525 to 479/100,000 p.y.). Hospitalization rates were reported separately in two studies, both reporting a decrease (from 12 to 8 cases/100,000 p.y. and from 9 to 4 cases/100,000 p.y.). Quebec data also showed a decrease, from 9 to 6 cases/100,000 p.y. One study reported herpes zoster-related deaths. In this study, the reported death rate was 0.7/1,000,000 p.y. in the overall population and 5.5/1,000,000 p.y. in those aged ≥65 years. Quebec analysis showed a death rate of 1.2/1,000,000 p.y. in the overall population and 8.6/1,000,000 p.y. in those aged ≥65 years. Conclusions. The results of the reviewed studies and our analysis of Quebec provincial data indicate important variations in the reported overall incidence rates of medically attended herpes zoster cases in Canada. The trends in time are heterogeneous in studies in which hospitalisations and medical consultations were pooled together. We observed a decrease in hospitalization rates and a slight increase in consultation rates in studies reporting hospitalisations and consultations separately. These results consolidate the understanding of the herpes zoster burden in Canada and might be used as a tool in decision-making regarding future preventive interventions

How do Midwives and Physicians Discuss Childhood Vaccination with Parents?

Even if vaccination is often described as one of the great achievements of public health, results of recent studies have shown that parental acceptance of vaccination is eroding. Health providers’ knowledge and attitudes about vaccines are important determinants of their own vaccine uptake, their intention to recommend vaccines to patients and the vaccine uptake of their patients. The purpose of this article is to compare how midwives and physicians address vaccination with parents during pregnancy and in postpartum visits. Thirty semi-structured interviews were conducted with midwives and physicians practicing in the province of Quebec, Canada. Results of our analysis have shown that physicians adopt an “education-information” stance when discussing vaccination with parents in the attempt to “convince” parents to vaccinate. In contrast, midwives adopted a neutral stance and gave information on the pros and cons of vaccination to parents while leaving the final decision up to them. Findings of this study highlight the fact that physicians and midwives have different views regarding their role and responsibilities concerning vaccination. It may be that neither of these approaches is optimal in promoting vaccination uptake

Antibody persistence after a single dose of quadrivalent HPV vaccine and the effect of a dose of nonavalent vaccine given 3-8 years later – an exploratory study

The objective of this study was to assess the persistence of antibodies after a single dose of quadrivalent HPV vaccine (4vHPV) and the effect of a dose of nonavalent HPV vaccine (9vHPV) given 3–8 years later. Such data might be of interest in the decision-making process regarding the 2-dose course completion in non-compliant vaccinees in jurisdictions which switched from 4vHPV to 9vHPV. Girls who previously received a single dose of 4vHPV were eligible to participate. Blood specimens were collected just before and one month post-9vHPV administration. The specimens were tested by ELISA for the presence of antibodies to 9 HPV types included in the 9vHPV. Thirty-one girls aged 13–18 years (mean 15.5 years) participated in the study. Pre-9vHPV administration, all participants were seropositive to 4 HPV types included in 4vHPV and 58%-87% were seropositive to the five other HPV types included in the 9vHPV. GMTs were 6.1 AU/ml, 7.7 AU/ml, 20.1 IU/ml and 6.3 IU/ml to HPV6, HPV11, HPV16 and HPV18, respectively. The GMTs for the other five HPV types varied from 1.0 to 2.9 AU/ml. One month post-9vHPV administration all 31 participants were seropositive to all 9 HPV types with a 36.1 to 89.1-fold increase of GMTs. High seropositivity rates observed several years after a single dose of 4vHPV and 100% seropositivity after a dose of 9vHPV suggest that this schedule might be used in non-compliant vaccinees or when switching immunization programs from 4vHPV to 9vHPV

Participation in an action research project on vaccine services for children: relationship with vaccine delays

Multicomponent interventions are effective in improving vaccine coverage. However, few studies have assessed their effect on timely vaccination. The aim of this study was to compare the proportion of children with vaccine delays at 2- and 12-month visits according to whether or not health centers have participated in an action research project on the organization of vaccination services for 0-5-year-olds. The action research project included a multicomponent intervention and was conducted between 2011 and 2015 in Quebec, Canada. An ecological before/after design was used for this analysis. A total of 264,579 DTaP-IPV-Hib (2-month visits) and 240,541 Men-C-C (12-month visits) vaccine doses were administered during 2011–2012 to 2014–2015 fiscal years, including 19% in 14 participating health centers and the remaining in 78 nonparticipating centers. Vaccine delays demonstrated a more pronounced decreasing trend in participating versus nonparticipating health centers (p < .0001 at 2 and 12 months). Between 2011–2012 and 2014–2015, participating centers managed to eliminate 35% of their vaccine delays at 2-month visits and 33% at 12-month visits, whereas nonparticipating centers eliminated 19% of delays at both visits. Our results are consistent with a positive impact of the multicomponent intervention, despite the fact that it had not specifically aimed at decreasing vaccine delays

Long intervals between two doses of HPV vaccines and magnitude of the immune response: a post hoc

The objective of this analysis was to compare the anti-HPV GMTs and their distribution after a 6-month or a 3–8 -y interval between two HPV vaccine doses. The results from two clinical trials, conducted by the same team in the same region, with serological assays performed at the same laboratory using the same ELISA methodology were compared. In the first study, 173 9–10-y-old girls and boys received two doses of 9vHPV vaccine at a 6-month interval; in the second study, 31 girls vaccinated with one dose of 4vHPV at the age of 9–14 y received a dose of 9vHPV 3–8 y later (mean 5.4 y). In both studies, blood samples were collected before and 1 month post second dose. Despite large differences in the time since the first dose, all subjects (100%) were seropositive to the common 4 HPV types (6, 11, 16 and 18) to both vaccines, with comparable GMTs and titer distributions before the second dose. One month post second dose, the GMTs increased 40–91-fold for those with a 6-month interval between doses and 60–82-fold for those with a 3–8-y interval. Titer distributions after the booster dose were comparable in the two studies. These results indicate that 2-dose HPV vaccination schedules with an interval of several years could be used for pre-adolescents. Intervals longer than 6 months may facilitate logistics for immunization programs and could be useful during periods of vaccine shortage or as a transition while the effectiveness of a one-dose schedule is being evaluated

Priming effect of bivalent and quadrivalent vaccine for HPV 31/33/45/52: an exploratory analysis from two clinical trials

The main objective of this post hoc analysis is to compare the magnitude of the immune response to HPV31/33/45/52 and 58 after a dose of 9vHPV vaccine given to naïve (previously unvaccinated) subjects and subjects previously vaccinated with a dose of 2vHPV or 4vHPV vaccine. Results from two clinical trials conducted in the same region, in comparable populations and by the same research team were included in this analysis. In study A, a dose of 9vHPV was administered 6 months after a single dose of 2vHPV as well as to naïve subjects. In study B, a dose of 9vHPV was administered 36–96 months (mean 65 months) after a single dose of 4vHPV. Blood samples were collected just before and one month post-9vHPV vaccine administration. For both studies, antibody responses were measured using the same 9-plex virus-like particle based IgG ELISA (M9ELISA). One month after 9vHPV dose administration, all subjects were seropositive to HPV 31/33/45/52 and 58. Subjects who had previously received 2vHPV or 4vHPV had significantly higher (1.8–8.0-fold) GMTs than naive subjects for HPV31/33/45/52 types but not for HPV58. GMTs to HPV31/33/45/52 and 58 were not significantly different between subjects who received a 2vHPV or 4vHPV dose prior to 9vHPV. The strong anamnestic response to one dose of 9vHPV given as late as 3–8 years after a single dose of 2vHPV or 4vHPV vaccine indicates these vaccines induced priming to types only included in the 9vHPV vaccine