Monika Naus

Immunogenicity of 2 Doses of HPV Vaccine in Younger Adolescents vs 3 Doses in Young Women: A Randomized Clinical Trial

IMPORTANCE Global use of human papillomavirus (HPV) vaccines to prevent cervical cancer is impeded by cost. A 2-dose schedule for girls may be possible. OBJECTIVE To determine whether mean antibody levels to HPV-16 and HPV-18 among girls receiving 2 doses was noninferior to women receiving 3 doses. DESIGN, SETTING, AND PATIENTS Randomized, phase 3, postlicensure, multicenter, age-stratified, noninferiority immunogenicity study of 830 Canadian females from August 2007 through February 2011. Follow-up blood samples were provided by 675 participants (81%). INTERVENTION Girls (9-13 years) were randomized 1:1 to receive 3 doses of quadrivalent HPV vaccine at 0, 2, and 6 months (n = 261) or 2 doses at 0 and 6 months (n = 259). Young women (16-26 years) received 3 doses at 0, 2, and 6 months (n = 310). Antibody levels were measured at 0, 7, 18, 24, and 36 months. MAIN OUTCOMES AND MEASURES Primary outcome was noninferiority (95% CI, lower bound >0.5) of geometric mean titer (GMT) ratios for HPV-16 and HPV-18 for girls (2 doses) compared with young women (3 doses) 1 month after last dose. Secondary outcomes were noninferiority of GMT ratios of girls receiving 2 vs 3 doses of vaccine; and durability of noninferiority to 36 months. RESULTS The GMT ratios were noninferior for girls (2 doses) to women (3 doses): 2.07 (95% CI, 1.62-2.65) for HPV-16 and 1.76 (95% CI, 1.41-2.19) for HPV-18. Girls (3 doses) had GMT responses 1 month after last vaccination for HPV-16 of 7736 milli-Merck units per mL (mMU/mL) (95% CI, 6651-8999) and HPV-18 of 1730 mMU/mL (95% CI, 1512-1980). The GMT ratios were noninferior for girls (2 doses) to girls (3 doses): 0.95 (95% CI, 0.73-1.23) for HPV-16 and 0.68 (95% CI, 0.54-0.85) for HPV-18. The GMT ratios for girls (2 doses) to women (3 doses) remained noninferior for all genotypes to 36 months. Antibody responses in girls were noninferior after 2 doses vs 3 doses for all 4 vaccine genotypes at month 7, but not for HPV-18 by month 24 or HPV-6 by month 36. CONCLUSIONS AND RELEVANCE Among girls who received 2 doses of HPV vaccine 6 months apart, responses to HPV-16 and HPV-18 one month after the last dose were noninferior to those among young women who received 3 doses of the vaccine within 6 months. Because of the loss of noninferiority to some genotypes at 24 to 36 months in girls given 2 doses vs 3 doses, more data on the duration of protection are needed before reduced-dose schedules can be recommended. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00501137.

A Population-Based Evaluation of a Publicly Funded, School-Based HPV Vaccine Program in British Columbia, Canada: Parental Factors Associated with HPV Vaccine Receipt

Analysis of a telephone survey by Gina Ogilvie and colleagues identifies the parental factors associated with HPV vaccine uptake in a school-based program in Canada.

Intention of parents to have male children vaccinated with the human papillomavirus vaccine

Background: Although already approved for use in males in some jurisdictions, there is little information about parental attitudes toward having their sons receive the human papillomavirus (HPV) vaccine. The goal of this study was to ascertain parental intentions to vaccinate their sons with an HPV vaccine and to determine factors that predict this intention. Methods: Parents of children aged 8–18 years were recruited from across Canada through random digit dialling. Participants were asked to respond to a series of questions in the context of a Grade 6 (age 11/12 years old), publicly funded school-based HPV vaccine programme, including their intention to vaccinate their sons with the HPV vaccine. Parents were also asked about a series of characteristics thought to predict intention to vaccinate as well as demographic characteristics. Backwards logistic regression was conducted to calculate adjusted odds ratios (AOR) to identify the factors that are predictive of parents’ intention to vaccinate their son(s) against HPV. Results: Of the 1381 respondents with male children, 67.8% (95% CI 65.3 to 70.3) intend to vaccinate their son(s) against HPV. Parents who had positive attitudes toward vaccines and the HPV vaccine in particular (AOR 41.5, 95% CI 9.5 to 181.7), parents who were influenced by subjective norms (AOR 7.8, 95% CI 5.8 to 10.5), parents who felt that the vaccine had limited influence on sexual behaviour (AOR 2.3, 95% CI 1.6 to 3.3) and parents who were aware of HPV (AOR 1.4, 95% CI 1.1 to 2.0) were significantly more likely to report an intention to vaccinate boys against HPV. In contrast, residence in British Columbia compared to Atlantic Canada (AOR 0.4, 95% CI 0.2 to 0.8) and higher education (AOR 0.7, 95% CI 0.5 to 0.9) were negatively associated with intention to vaccinate. Parents who reported an intention to vaccinate their daughters were also highly likely to report an intention to vaccinate their sons (κ = 0.9, p<0.001). Discussion: The majority of Canadian parents would intend to have their male children receive the HPV vaccine in the context of a publicly funded school-based immunisation programme. Overall attitudes toward vaccine, recommendations from health professionals and impact of the vaccine on sexual practices are important predictors of intention to have a male child receive the HPV vaccine.

A Population‐based Comparison between Travelers Who Consulted Travel Clinics and Those Who Did Not

BACKGROUND Travel to hepatitis A-endemic countries is frequent among North Americans. Such travel carries significant risks for the individuals themselves and for the general population. We documented the patterns of use of travel clinics in a large Canadian adult population. METHODS Travelers who had visited a hepatitis A-endemic country between 1990 and the time of the survey in 1999 were eligible. Subjects were identified from a representative sample of 4,002 adults from the two largest Canadian provinces. They were contacted by random digit dialing and interviewed by telephone. RESULTS Only 15% of trips had been preceded by a visit to a travel clinic. The probability of visiting a travel clinic was approximately 10 times greater for travelers considered to be in the high-risk category than for those in the low-risk category, but the former represented only 2% of the total. The probability of visiting a travel clinic was approximately 23 times greater for travelers who were aware of the health risks in their country of destination. Income level was not associated with attendance at a travel clinic, and cost was rarely mentioned as a reason for not attending such a travel clinic before departure. CONCLUSIONS Each year, millions of Canadian travelers go to hepatitis A-endemic countries without consulting a travel clinic. Active steps must be taken by public health authorities to improve their utilization of health services and prevent the accrued health risk for these travelers.

Oculo-respiratory Syndrome: A New Influenza Vaccine-Associated Adverse Event?

During the 2000-2001 influenza immunization campaign in Canada, a new adverse event, oculo-respiratory syndrome (ORS), was noted in association with administration of vaccine supplied by one manufacturer. The original case definition for ORS specified bilateral conjunctivitis, facial edema, or respiratory symptoms beginning 2-24 h after influenza vaccination and resolving within 48 h after onset. To characterize the spectrum, severity, and impact of ORS, we contacted persons who had reported any influenza vaccine-associated adverse event in British Columbia, Canada, during the 2000-2001 vaccination campaign. With use of a standardized telephone interview, we collected information from 609 (79%) of 769 eligible persons. Thirteen percent of ORS-affected persons reported onset <or=2 h after vaccination, 27% experienced symptoms for >48 h, and 42% considered the symptoms to be severe. The surveillance case definition for ORS for 2001-2002 was revised to include onset <or=24 h after vaccination, with no restriction on duration. ORS should be incorporated into annual influenza vaccine safety monitoring.

Protecting the Next Generation: What Is the Role of the Duration of Human Papillomavirus Vaccine-Related Immunity?

BACKGROUND There is strong evidence that human papillomavirus (HPV) is necessary for the development of cervical cancer. A prophylactic HPV vaccine with high reported efficacy was approved in North America in 2006. METHODS A mathematical model of HPV transmission dynamics was used to simulate different scenarios of natural disease outcomes and intervention strategies. A sensitivity analysis was performed to compensate for uncertainties surrounding key epidemiological parameters. RESULTS The expected impact that HPV vaccines have on cervical cancer incidence and HPV prevalence in the province of British Columbia in Canada revealed that, for lifelong vaccine-related protection, an immunization routine targeting younger females (grade 6), combined with a 3-year program for adolescent females (grade 9), is the most effective strategy. If vaccine-related protection continues for <10 years, then the targeting of adolescent females would be more beneficial than the targeting of younger females. The incremental benefit if boys, as well as girls, are vaccinated is small. CONCLUSIONS Optimization of the design of immunization strategies for treatment of HPV depends substantially on the duration of vaccine-induced immunity. Given the uncertainty in estimating this duration, it may be prudent to assume a value close to the lower limit reported and adjust the program when more-accurate information for the length of vaccine-induced immunity becomes available.

Protection after Two Doses of Measles Vaccine Is Independent of Interval between Doses

The protection provided by one or two doses of measles vaccine was compared, as was the effect of the timing of delivery of the doses on the protection provided. A total of 5542 measles cases occurred in Ontario, Canada, between January 1990 and December 1996. Three controls per case were matched for age and residence. Children who received a single dose at age 15 months and older were 5 times more likely to contract measles than were children who received two doses of vaccine after their first birthday. Among children given two doses of vaccines, the risk of measles was 3 times greater in those who had their first vaccination at age 11 months compared with children who first received vaccine after age 1 year, but the protection was independent of the interval between doses. Delaying the second dose >6 months after the first does not increase protection.

Whole-Genome Sequencing of Measles Virus Genotypes H1 and D8 During Outbreaks of Infection Following the 2010 Olympic Winter Games Reveals Viral Transmission Routes

We used whole-genome sequencing to investigate a dual-genotype outbreak of measles occurring after the XXI Olympic Winter Games in Vancouver, Canada. By sequencing 27 complete genomes from H1 and D8 genotype measles viruses isolated from outbreak cases, we estimated the virus mutation rate, determined that person-to-person transmission is typically associated with 0 mutations between isolates, and established that a single introduction of H1 virus led to the expansion of the outbreak beyond Vancouver. This is the largest measles genomics project to date, revealing novel aspects of measles virus genetics and providing new insights into transmission of this reemerging viral pathogen.

Reduction in cervical intraepithelial neoplasia in young women in British Columbia after introduction of the HPV vaccine: An ecological analysis

We report on the rates of cervical intraepithelial neoplasia (CIN) in young women aged 15–22 years of age in British Columbia before and after the introduction of an HPV vaccine program. Rates of cervical intraepithelial neoplasia (CIN) 2+ for each age stratum (15–22) in the calendar years 2004–2012 for the province of British Columbia were obtained from the BC Cancer Agency‘s population‐based cervical cancer program. Incidence rate ratios (IRR) of CIN2+ were described and compared before and after HPV vaccine program introduction in cohorts born in vaccine eligible years, and in non‐vaccine eligible years using piece‐wise Poisson regression analysis, and adjusted for age. Between 2004 and 2012, rates of CIN2 and CIN2+ in young women aged 15–22 years in the province of British Columbia have decreased overall. After the introduction of the HPV vaccine program, the age adjusted IRR for CIN2+ for young women aged 15–17 years decreased significantly from 0.91 (95% CI: 0.86–0.98 p < 0.01) to 0.36 (95% CI: 0.18–0.73 p < 0.01). During the same time period, no similar reduction was found in young women 18–22 years. After introduction of HPV vaccine program, IRR for CIN2+ in young women 15–17 was significantly reduced for CIN2+ (0.14; 95% CI: 0.04– 0.47; p < 0.01) and CIN2 (0.1; 95% CI: 0.02–0.54; p < 0.01). This ecological analysis shows a significant reduction in CIN2+ lesions in young women aged 15–17 years in British Columbia after the introduction of the HPV vaccine in young women despite vaccine uptake levels below 70%.

Comparison of trip characteristics of children and adults with travel-acquired hepatitis A infection.

We compared the trip characteristics of 84 child and 99 adult cases with travel-acquired hepatitis A (HA). Most pediatric cases had traveled in Asia for more than 30 days and had stayed and eaten most of their meals in the homes of friends and relatives in a country where they had not been born. In contrast, the adults with travel-acquired HA had visited Latin America or the Caribbean for 14 days or less and had stayed primarily in hotels. Specific public health interventions should be undertaken to prevent HA in traveling children.