Willingness to participate in HIV vaccine trials among men who have sex with men in Chennai and Mumbai,India

Introduction

Men who have sex with men (MSM) are at disproportionately high risk for HIV in India and would benefit greatly from a safe and effective HIV vaccine. We assessed willingness to participate (WTP) in HIV vaccine trials and the impact of various trial characteristics on WTP among MSM in Mumbai and Chennai.

Methods

We used venue-based time-space sampling to recruit MSM at cruising sites and drop-in centers at community-based organizations. Structured survey interviews assessed sociodemographics, WTP and the impact of 10 trial characteristics on WTP. We tested for differences in WTP by sociodemographics and trial characteristics, and sociodemographic differences in the impact of trial characteristics on WTP.

Results

Among 400 participants (median age = 25 years), 46.9% identified as kothi, 40.0% panthi/double-decker, 13.0% gay/bisexual; 29.0% had primary school education or less; and 40.0% had monthly income < = 5000 INR (∼3USD/day). Overall, 48.1% reported being definitely willing to participate. Posttrial availability of an efficacious vaccine was the highest rated (90.98 on 100–point scale) trial characteristic, followed by availability of free medical treatment (90.79), life insurance (89.84) and side effects (79.81). Distance to the trial site, side effects, financial incentive, life insurance and free medical care had significant impacts on WTP, with differential importance of trial characteristics by sexual identity, education, income and living arrangement.

Conclusion

The prioritization of trial-related financial and healthcare provisions, including access to an efficacious vaccine posttrial, among MSM in India indicates the importance of trials providing such services, as well as the value of formative research in identifying key concerns among participating communities in resource-limited settings. The significant impact of trial characteristics on WTP suggests that providing trial benefits deemed fair and important, addressing logistical concerns, and supporting educational interventions to mitigate vaccine fears may support recruitment of MSM in India in fairly and ethically conducted HIV vaccine trials.     

Development of an HIV vaccine attitudes scale to predict HIV vaccine acceptability among vulnerable populations: L.A. VOICES

Background

Decade-long delays in successful implementation of Hepatitis B vaccines and ongoing obstacles in HPV vaccine roll-out suggest the importance of an implementation science approach to prepare for the effective translation of future HIV vaccines from clinical trials into routine practice. The objective of this study was to test HIV vaccine attitude items to develop reliable scales and to examine their association with HIV vaccine acceptability.

Methods

HIV vaccine attitude items were assessed as part of the L.A. VOICES survey, a large-scale study conducted among underserved residents of Los Angeles, to identify factors that may influence HIV vaccine acceptability. Participants (n = 1225) were randomly selected from public STD clinics, needle exchange sites and Latino community clinics using three-stage, venue-based time space sampling.

Results

Exploratory factor analysis across 20 items revealed four distinct factors – mistrust, HIV vaccine social concerns, risk compensation, and altruistic vaccination – with acceptable reliability coefficients for each subscale (Cronbach's α range 0.61–0.84). We found no significant differences in reliability by gender or by vaccine acceptability. Risk compensation (odds ratio (OR) = 1.49; 95% CI = [1.18, 1.89]; p = 0.001) and altruistic vaccination (OR = 1.40; 95% CI = [1.14, 1.71]; p = 0.001) were significantly and positively associated with HIV vaccine acceptability.

Conclusions

We identified four HIV vaccine attitude scales with sound internal reliability parameters. In the aftermath of the first candidate vaccine to demonstrate efficacy against HIV infection, these scales may be helpful in bridging expectable research-to-practice gaps in future HIV vaccine dissemination among populations at risk. As HIV vaccine trials progress in the United States and globally, these measures also may be useful as a tool to assess and facilitate effective responses to community concerns about HIV vaccine trials and to target interventions to support recruitment and mitigate risk compensation.     

Influenza vaccination and risk of hospitalization among adults with laboratory confirmed influenza illness

Background

Influenza vaccine is moderately effective for preventing influenza illness. It is not known if vaccination reduces the risk of subsequent hospital admission among patients with vaccine failure and laboratory confirmed influenza illness.

Methods

Patients in a community cohort presenting with acute respiratory illness were prospectively enrolled and tested for influenza during 8 seasons to estimate seasonal vaccine effectiveness. Hospital admissions within 14 days after illness onset were identified for all participants aged ≥20 years with laboratory confirmed influenza. The association between vaccination and hospital admission was examined in a propensity score adjusted logistic regression model. The model was validated by examining the association between vaccination and hospital admission in participants without influenza.

Results

Influenza was identified in 1393 (28%) of 4996 participants. Sixty-two (6%) of 1020 with influenza A and 17 (5%) of 369 with influenza B were hospitalized. Vaccination was not associated with a reduced risk of hospital admission among all participants with influenza [adjusted odds ratio (aOR) = 1.08; 95% CI: 0.62, 1.88]; or among those with influenza A (aOR = 1.35; 95% CI: 0.71, 2.57) or influenza B (aOR = 0.67; 95% CI: 0.21, 2.15). Influenza vaccination was not associated with hospitalization after non-influenza respiratory illness (aOR = 1.14; 95% CI: 0.84, 1.54).

Conclusions

Influenza vaccination did not reduce the risk of subsequent hospital admission among patients with vaccine failure. These findings do not support the hypothesis that vaccination mitigates influenza illness severity.     

Risk factors associated with parents claiming personal-belief exemptions to school immunization requirements: community and other influences on more skeptical parents in Oregon, 2006

Background and objectives

With vaccine-preventable diseases at record lows, few studies investigate rising parent-claimed exemptions to school immunization requirements. After finding exemption clusters in Oregon, we hypothesized that exemption risk factors may vary among communities. We surveyed parents to identify risk factors for exemptions and evaluated risk factor differences among communities with differing exemption rates.

Design

Retrospective cohort study, multi-staged, population-proportionate sampling.

Setting and participants

Parents of 2004-05 Oregon elementary school children (N = 2900).

Main outcome measure

Parent-reported exemption status.

Results

The response rate was 55%. Compared to vaccinators, exemptors were significantly more likely to have: strong vaccine concerns (weighted adjusted odds ratio (aOR) = 15.3, 95% CI 6.4-36.7); “vaccine-hesitant” concerns (aOR = 2.3; 95% CI 1.0-5.0); >1 childbirth(s) at a non-hospital, alternative setting (aOR = 3.6; 95% CI 1.6-8.0); distrust of local doctors (aOR = 2.7; 95% CI 1.0-7.5); reported chiropractic healthcare for their youngest school-age child (aOR = 3.9; 95% CI 1.8-8.5); and reported knowledge of someone with a vaccine-hurt child (aOR = 1.8; 95% CI 0.9-3.4). Exemptors were less likely to have “pro-vaccine” beliefs (aOR = 0.2; 95% CI 0.0-0.6) and less likely to report relying on print materials (aOR = 0.4; 95% CI 0.2-0.8).The strengths of association differed significantly for those with strong vaccine concerns and those reporting knowledge of someone with a vaccine-hurt child, depending on residence in exemption-rate areas, e.g., exemptors in medium-rate areas were more likely to have strong vaccine concerns (aOR = 13.5; 95% CI 5.4-34.0) than those in high-rate areas (aOR = 9.7; 95% CI 3.7-25.4).

Conclusions

Vaccine beliefs were important risk factors. That differing community-level exemption use modified the effects of several individual-level factors suggests that communities also influence parent decisions. Therefore, understanding community contexts and norms may be important when designing interventions.     

Immune response after one or two doses of pandemic influenza A (H1N1) monovalent,AS03-adjuvanted vaccine in HIV infected adults

Introduction

Continued research is needed to evaluate and improve the immunogenicity of influenza vaccines in HIV infected patients. We aimed to determine the antibody responses after one or two doses of the AS03-adjuvanted pandemic influenza A (H1N1) vaccine in HIV infected patients.

Method

Following the influenza season 2009/2010, 219 HIV infected patients were included and divided into three groups depending on whether they received none (n = 60), one (n = 31) or two (n = 128) doses of pandemic influenza A (H1N1) vaccine. At inclusion, antibody titers for all patients were analyzed and compared to pre-pandemic antibody titers analyzed from serum samples in a local storage facility.

Results

4–9 months after a single immunization, we found a seroprotection rate of 77.4% and seroconversion rate of 67.7%. After two immunizations the rates increased significantly to seroprotection rate of 97.7% and seroconversion rate of 86.7%.

Conclusion

A single dose of AS03-adjuvanted pandemic influenza A (H1N1) vaccine created an adequate immune response in HIV infected patients lasting as long as 4–9 months. Two doses improved the immunogenicity further.     

Prevalencia de consumo de tabaco en vehículos privados

Objective

To determine the prevalence of smoking among drivers of private vehicles in the city of Lleida (Spain).

Methods

A random sample of 1600 cars passing through six intersections regulated by traffic lights were selected. The variables were age, sex, smoking driver, adult passengers, intersection (urban/interurban), day (working day/weekend), hour (morning/evening) and simultaneous smokers. We calculated the prevalence of smoking drivers and the corresponding odds ratios (ORs), adjusted for the potential confounding variables, as well as their 95% confidence intervals (95% CI).

Results

The prevalence was 6.0% (95% CI: 4.9-7.3) and was higher in men (6.4%), in the group aged 41 to 60 years (6.9%), and in unaccompanied drivers (6.5%). The probability of the driver smoking increased if there was a smoking passenger (aOR = 10.8; 95% CI: 3.6-32.5). The frequency of smoking drivers was higher on working days (aOR = 1.7; 95% CI: 1.0-2.8) and in the morning (aOR = 1.6; 95% CI: 1.0-2.4).

Conclusions

The prevalence of smoking drivers can be considered dangerously high. We recommend avoiding smoking while driving.     

Cognitive factors and willingness to participate in an HIV vaccine trial among HIV-negative injection drug users

This cross-sectional study involving a cohort of injection drug users (IDU) examined the relationship between cognitive factors (HIV treatment optimism, self-efficacy and knowledge of vaccine trial concepts) as well as risk factors for seroconversion, and willingness to participate (WTP) in a preventive phase 3 HIV vaccine trial. Willingness to participate overall was 56%. In a multivariate analysis, for a 20-unit increase in a 100-point composite scale, self-efficacy was positively related to WTP (adjusted odds ratio [AOR] = 1.95, 95% CI = 1.40–2.70). HIV treatment optimism and knowledge of vaccine trial concepts were unrelated to WTP. Aboriginal ethnicity (AOR = 3.47, 95% CI = 1.68–7.18) and a higher educational level (≥high school) (AOR = 1.96, 95% CI = 1.07–3.59) were positively related to WTP. This study provides information on WTP for an HIV vaccine trial. Limitations and future directions are also discussed.     

Counseling and provision of long-acting reversible contraception in the US: National survey of nurse practitioners

Objective

Nurse practitioners (NPs) provide frontline care in women's health, including contraception, an essential preventive service. Their importance for contraceptive care will grow, with healthcare reforms focused on affordable primary care. This study assessed practice and training needs to prepare NPs to offer high-efficacy contraceptives — intrauterine devices (IUDs) and implants.

Method

A US nationally representative sample of nurse practitioners in primary care and women's health was surveyed in 2009 (response rate 69%, n = 586) to assess clinician knowledge and practices, guided by the CDC US Medical Eligibility Criteria for Contraceptive Use.

Results

Two-thirds of women's health NPs (66%) were trained in IUD insertions, compared to 12% of primary care NPs. Contraceptive counseling that routinely included IUDs was low overall (43%). Nurse practitioners used overly restrictive patient eligibility criteria, inconsistent with CDC guidelines. Insertion training (aOR = 2.4, 95%CI: 1.10 5.33) and knowledge of patient eligibility (aOR = 2.9, 95%CI: 1.91 4.32) were associated with IUD provision. Contraceptive implant provision was low: 42% of NPs in women's health and 10% in primary care. Half of NPs desired training in these methods.

Conclusion

Nurse practitioners have an increasingly important position in addressing high unintended pregnancy in the US, but require specific training in long-acting reversible contraceptives.     

Prevalence and associated factors of intention to participate in HIV voluntary counseling and testing for the first time among men who have sex with men in Hong Kong,China

Objective

We investigated the prevalence and associated factors of men who have sex with men (MSM) and had never participated in Human Immunodeficiency Virus (HIV) voluntary counseling and testing (VCT) but intended to do so in the next six months.

Method

An anonymous cross-sectional survey interviewed 577 MSM in Hong Kong, China, face-to-face or through an electronic questionnaire.

Results

We identified 245 MSM who had never participated in VCT (never-testers), among whom 12.7% intended to do so in the next six months. Factors associated positively with high behavioral intention were: 1) perceived necessity to participate in HIV test regularly (multivariate odds ratios (ORm) = 4.54, 95% confidence interval (CI): 1.30–15.83), 2) perception that > 20% of the local MSM had participated in VCT (ORm = 17.86, 95% CI: 1.89–169.08) and 3) perceived higher chance to have sex with people living with HIV (PLWH) in the next six months (ORm = 2.92, 95% CI: 1.08–7.93). Negatively associated factors were: local residency (ORm = 0.06, 95% CI: 0.01–0.34) and perceived higher chance of having unprotected anal intercourse (UAI) in the next six months (ORm = 0.27, 95% CI: 0.09–0.84). In addition, no interaction term between the independent variable and UAI status was found to be statistically significant.

Conclusion

Many sampled never-testers had low intention to take up VCT and were in the pre-contemplation stage of the Transtheoretical Model. Stage-matched promotions are warranted.     

Parental and community acceptance of the benefits and risks associated with meningococcal B vaccines

Objective

A new meningococcal serogroup B (Men B) vaccine has been licensed in the European Union (EU) and Australia. This study aimed to assess community and parental attitudes to introduction of new Men B vaccines and identify facilitators and barriers to vaccine implementation.

Methods

Cross-sectional survey including face-to-face interviews with adolescents, parents and adults from randomly selected households in South Australia in 2012. Survey data were weighted to the age, gender and geographical area profile of the population.

Results

3055 interviews were conducted with individuals aged 15–97 years, including 966 parents. Participation rate was 66.4%. 82.5% (95% CI 79.7–85.4) of parents (797/966) wanted their child to receive the Men B vaccine, with 12.2% (9.7–14.7) (118/966) unsure. Main parental concerns included potential side effects (41.3% (26.7–46.0)) and adequate vaccine testing (11.7% (9.4–14.1)). Potential for an extra injection at an immunisation visit resulted in 15.7% (12.8–18.5) of parents (n = 152/966) less likely to have their child immunised. Potential redness/swelling at the injection site or mild/moderate fever resulted in only 8.5% (6.3–10.7) and 10.8% (8.5–13.2) of parents, respectively, less likely to have their child immunised. Children being up to date with vaccinations and recommendation from family physician were the strongest independent predictors of parents agreeing their children should be immunised with Men B vaccine (OR = 6.58; p = 0.006 and OR = 4.15; p < 0.001, respectively). Only 16.4% (14.9–17.9) of adults (501/3055) stated that they would not want to receive a Men B vaccine, with family physician recommendation the strongest independent predictor of acceptance (OR = 3.81; p < 0.001).

Conclusions

There is strong community support for introduction of Men B vaccines, with parental willingness to have children immunised, impacted more by number of injections than potential for adverse events such as local reactions or fever.     

Interaction between neonatal vitamin A supplementation and timing of measles vaccination: A retrospective analysis of three randomized trials from Guinea-Bissau

Background

In Guinea-Bissau we conducted three trials of neonatal vitamin A supplementation (NVAS) from 2002 to 2008. None of the trials found a beneficial effect on mortality. From 2003 to 2007, an early measles vaccine (MV) trial was ongoing, randomizing children 1:2 to early MV at 4.5 months or no early MV, in addition to the usual MV at 9 months. We have previously found interactions between vitamin A and vaccines.

Objective

We investigated whether there were interactions between NVAS and early MV.

Design

We compared the mortality of NVAS and placebo recipients: first, from 4.5 to 8 months for children randomized to early MV or no early MV; and second, from 9 to 17 months in children who had received two MV or one MV. Mortality rates (MR) were compared in Cox models producing mortality rate ratios (MRR).

Results

A total of 5141 children were randomized to NVAS (N = 3015) or placebo (N = 2126) and were later randomized to early MV (N = 1700) or no early MV (N = 3441). Between 4.5 and 8 months, NVAS compared with placebo was associated with higher mortality in early MV recipients (MR = 30 versus MR = 0, p = 0.01), but not in children who did not receive early MV (p for interaction between NVAS and early MV = 0.03). From 9 to 17 months NVAS was not associated with mortality. Overall, from 4.5 to 17 months NVAS was associated with increased mortality in early MV recipients (Mortality rate ratio = 5.39 (95% confidence interval: 1.62, 17.99)).

Conclusions

These observations indicate that NVAS may interact with vaccines given several months later. This may have implications for the planning of future child intervention programs.     

Parent perceptions important for HPV vaccine initiation among low income adolescent girls

Objective

The study aims were to assess the influence of provider recommendations on parental vaccine perceptions and identify the most potent parent vaccine perceptions for HPV vaccine series initiation considering provider recommendation strength.

Methods

We administered a questionnaire and assessed HPV vaccine claims among a stratified-random sample of parents of 9–17 year old girls enrolled in Florida's Medicaid and the Children's Health Insurance Program. Using multivariate analyses, we evaluated the associations between: (1) parent vaccine perceptions and provider recommendation strength, and (2) parent vaccine perceptions and HPV vaccine series initiation (≥1 vaccine claim or positive parental report) controlling for provider recommendation strength.

Results

The majority of the 2422 participating parents agreed that the HPV vaccine was safe (61%), would not make girls more likely to have sex (69%), and prevented cervical cancer (71%). About half (44%) reported receiving a strong provider recommendation. Compared to parents without recommendations, parents with strong recommendations had 2 to 7 times higher odds of agreeing that: vaccines are safe, the HPV vaccine is safe, not concerned about side effects, and the vaccine prevents cervical cancer. Even when considering provider recommendation strength, HPV vaccine series initiation was more likely among girls of parents who agreed rather than disagreed that the HPV vaccine was safe [odds ratio (OR) = 5.8, 95% confidence interval (CI) = 3.1, 11.1], does not cause sex (OR = 2.0, 95% CI = 1.2, 3.4), prevents cervical cancer (OR = 2.0, 95% CI = 1.0, 3.4), and prevents HPV infections (OR = 1.8, 95% CI = 1.0, 3.0).

Conclusions

Parent concerns about HPV vaccine are similar to their concerns about other vaccines. Providers should focus HPV vaccine discussions with parents on vaccine safety and illness prevention.     

Vaccine-related standard of care and willingness to respond to public health emergencies: A cross-sectional survey of California vaccine providers

Introduction

Responding to a vaccine-related public health emergency involves a broad spectrum of provider types, some of whom may not routinely administer vaccines including obstetricians, pharmacists and other specialists. These providers may have less experience administering vaccines and thus less confidence or self-efficacy in doing so. Self-efficacy is known to have a significant impact on provider willingness to respond in emergency situations.

Methods

We conducted a survey of 800 California vaccine providers to investigate standard of care, willingness to respond, and how vaccine-related standard of care impacts willingness to respond among these providers. We used linear regression to examine how willingness to respond was impacted by vaccine-related standard of care.

Results

Forty percent of respondents indicated that they had participated in emergency preparedness training, actual disaster response, or surge capacity initiatives with significant differences among provider types for all measures (p = 0.007). When asked to identify barriers to responding to a public health emergency, respondents indicated that staff size or capacity, training and resources were the top concerns. Respondents in practices with a higher vaccine-related standard of care had a higher willing to respond index (β = 0.190, p = 0.001). Respondents who had participated in emergency training or actual emergency response had a higher willing to respond index (β = 1.323, p < 0.0001).

Conclusion

Our study suggests that concerns about staff size and surge capacity need to be more explicitly addressed in current emergency preparedness training efforts. In the context of boosting response willingness, larger practice environments stand to benefit from self-efficacy focused training and exercise efforts that also incorporate standard of care.     

Trends and disparity in zoster vaccine uptake in a managed care population

Objectives

Zoster vaccine is recommended for prevention of herpes zoster among adults aged 60 years and older. We examined the zoster vaccination rates during 2007–2011 and assessed association with age, sex, race/ethnicity, neighborhood income and education attainment in eligible adults at Kaiser Permanente Southern California, a managed care organization in the US.

Methods

We calculated annual zoster vaccination rate among members ≥60 years without documented contraindications. Multivariable logistic regression was performed to examine factors associated with zoster vaccine uptake in an open cohort of 819,466 adults.

Results

The zoster vaccination rates increased annually in all groups and the overall rate reached 21.7% in 2011 (P-trend < 0.001). Coverage was highest among individuals aged 65–74 years, who were female and non-Hispanic White. In the adjusted analysis, odds of vaccination decreased by age. Females (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.17–1.20) and those who lived in neighborhoods with higher education attainment were more likely to be vaccinated (>75% vs. <50% adults with some college education: OR = 1.76, 95% CI = 1.73–1.80). Compared to Whites, non-Hispanic Blacks and Hispanics were less likely to receive the vaccine (non-Hispanic Blacks: OR = 0.56, 95% CI = 0.55–0.58; Hispanics: OR = 0.59, 95% CI = 0.58–0.60).

Conclusion

The zoster vaccine coverage is higher in this insured population than previously reported in the US general population, but it remains low. Significant racial/ethnic disparity was observed and worsened even among individuals with relatively equal access to zoster vaccination.     

Immunogenicity of a 7-valent pneumococcal conjugate vaccine (PCV7) and impact on carriage in Venezuelan children at risk of invasive pneumococcal diseases

Background and aims

We evaluated the immunogenicity of the 7-valent pneumococcal conjugate vaccine (PCV7), and its impact on pneumococcal carriage in Venezuelan children at high risk for invasive pneumococcal disease (IPD).

Methods

82 children (age 2–59 months) with sickle cell anemia (n = 22), chronic heart disease (n = 19), HIV infection (n = 12), immune-suppressive therapy (n = 11) and other IPD-predisposing conditions (n = 18) were vaccinated with PCV7 according to CDC-recommended age-related immunization schedules. Blood samples were taken to determine the concentration of IgG antibody, and nasopharyngeal swabs were obtained to isolate Streptococcus pneumoniae, before the first vaccine dose and 1 month after completion of the vaccination schedule.

Results

Pneumococcal carriage prior to the first immunization was 27% (n = 22), with the most frequently carried serotypes being vaccine serotypes 6B (22%) and 14 (13%). One month after completion of the vaccination scheme pneumococcal carriage was 22% (n = 17), dominated by non-vaccine serotypes 19A (24%) and 7F (12%). Before immunization, 65% of the subjects had IgG antibody titers >0.35 μg/mL for five serotypes tested. Post-vaccination, 100% of the subjects showed titers >1.0 μg/mL for all PCV7 serotypes with geometric mean concentrations (GMC) ranging from 1.75 μg/mL (serotype 23F) to 17.16 μg/mL (serotype 14). Children previously colonized with serotype 6B had a significantly lower GMC to this serotype following immunization than children not carrying 6B prior to the first PCV dose (p < 0.05).

Conclusions

PCV7 is highly immunogenic in Venezuelan children at high-risk for IPD. Vaccination was associated with an immediate shift in nasopharyngeal carriage toward non-PCV7 serotypes. Finally, we observed serotype-specific hyporesponsiveness to immunization after natural carriage with the same serotype in high-risk children.     

Staying on track: A cluster randomized controlled trial of automated reminders aimed at increasing human papillomavirus vaccine completion

Objectives

To evaluate whether automated reminders increase on-time completion of the three-dose human papillomavirus (HPV) vaccine series.

Methods

Ten reproductive health centers enrolled 365 women aged 19–26 to receive dose one of the HPV vaccine. Health centers were matched and randomized so that participants received either routine follow-up (control) or automated reminder messages for vaccine doses two and three (intervention). Intervention participants selected their preferred method of reminders – text, e-mail, phone, private Facebook message, or standard mail. We compared vaccine completion rates between groups over a period of 32 weeks.

Results

The reminder system did not increase completion rates, which overall were low at 17.2% in the intervention group and 18.9% in the control group (p = 0.881). Exploratory analyses revealed that participants who completed the series on-time were more likely to be older (OR = 1.15, 95% CI 1.01–1.31), report having completed a four-year college degree or more (age-adjusted OR = 2.51, 95% CI 1.29–4.90), and report three or more lifetime sexual partners (age-adjusted OR = 3.45, 95% CI 1.20–9.92).

Conclusions

The study intervention did not increase HPV vaccine series completion. Despite great public health interest in HPV vaccine completion and reminder technologies, completion rates remain low.     

Cluster randomized trial of a toolkit and early vaccine delivery to improve childhood influenza vaccination rates in primary care

Purpose

To increase childhood influenza vaccination rates using a toolkit and early vaccine delivery in a randomized cluster trial.

Methods

Twenty primary care practices treating children (range for n = 536–8183) were randomly assigned to Intervention and Control arms to test the effectiveness of an evidence-based practice improvement toolkit (4 Pillars Toolkit) and early vaccine supplies for use among disadvantaged children on influenza vaccination rates among children 6 months–18 years. Follow-up staff meetings and surveys were used to assess use and acceptability of the intervention strategies in the Intervention arm. Rates for the 2010–2011 and 2011–2012 influenza seasons were compared. Two-level generalized linear mixed modeling was used to evaluate outcomes.

Results

Overall increases in influenza vaccination rates were significantly greater in the Intervention arm (7.9 percentage points) compared with the Control arm (4.4 percentage points; P < 0.034). These rate changes represent 4522 additional doses in the Intervention arm vs. 1390 additional doses in the Control arm. This effect of the intervention was observed despite the fact that rates increased significantly in both arms – 8/10 Intervention (all P < 0.001) and 7/10 Control sites (P-values = 0.04 to <0.001). Rates in two Intervention sites with pre-intervention vaccination rates >58% did not significantly increase. In regression analyses, a child's likelihood of being vaccinated was significantly higher with: younger age, white race (Odds ratio [OR] = 1.29; 95% confidence interval [CI] = 1.23–1.34), having commercial insurance (OR = 1.30; 95%CI = 1.25–1.35), higher pre-intervention practice vaccination rate (OR = 1.25; 95%CI = 1.16–1.34), and being in the Intervention arm (OR = 1.23; 95%CI = 1.01–1.50). Early delivery of influenza vaccine was rated by Intervention practices as an effective strategy for raising rates.

Conclusions

Implementation of a multi-strategy toolkit and early vaccine supplies can significantly improve influenza vaccination rates among children in primary care practices but the effect may be less pronounced in practices with moderate to high existing vaccination rates.Clinical trial registry name/number: From Innovation to Solutions: Childhood Influenza/NCT01664793.     

DNA vaccination protects against an influenza challenge in a double-blind randomised placebo-controlled phase 1b clinical trial

Background

We have developed a Trivalent DNA vaccine for influenza consisting of three plasmids expressing haemagglutinin from different seasonal influenza virus strains delivered using PMED™ (particle mediated epidermal delivery). We set out to determine whether this vaccine (with and without a molecular adjuvant DNA Encoded Immunostimulator-Labile Toxin (DEI-LT)) could protect subjects from a controlled influenza virus challenge.

Methods

Healthy adult subjects were screened for susceptibility to infection with influenza A/H3 Panama/2007/99 then vaccinated with 4 μg Trivalent influenza DNA vaccine, 2 μg Trivalent influenza DNA vaccine plus DEI-LT or placebo. Safety and serological responses to vaccination were assessed and on Day 56 subjects were challenged with A/H3 Panama/2007/99 virus.

Results

Vaccination with 4 μg Trivalent or 2 μg Trivalent/DEI-LT was well tolerated and induced antibody responses to two of the three influenza virus vaccine strains. Post challenge, subjects in the 4 μg Trivalent group (N = 27) showed reductions in disease symptoms and viral shedding compared to placebo (N = 27), with an overall vaccine efficacy of 41% (95% confidence interval (CI) = −1.5, 67.7) for ‘Any illness with or without fever’ and 53% for ‘Upper respiratory tract infection’ (95% CI = 8.0, 77.7).

Conclusion

It was concluded that PMED vaccination with 4 μg Trivalent influenza DNA vaccine was safe and elicited immunological responses that protected human subjects from influenza; this is the first report of protection of human subjects from disease by DNA vaccination.     

Associations of the correlates of protection and implication on the statistical power for demonstrating non-inferiority: Application of a re-sampling method on a large phase III influenza vaccine clinical trial

Background

In the later stage of the clinical development of new vaccines it is required to demonstrate their efficacy with the immunogenicity measures established as correlates for disease protection.Evaluation of interpandemic trivalent influenza vaccines is commonly assessed by three immunogenicity measures for each strain in different age groups: Seroprotection, Seroconversion and Geometric Mean Titers. US and European guidelines with respect to this topic have been issued for the licensure of new influenza vaccines. The statistical power of comparative trials, which consider these endpoint variables, could be affected to the extent that these measures are correlated. Results from a large non-inferiority trial in the clinical development of a novel cell-derived influenza vaccine have been analyzed with the aim of evaluating how statistical dependency between the above-mentioned three immunogenicity measures might affect the power to demonstrate non-inferiority.

Methods

The statistical non-inferiority criteria, which were met in the trial, were applied to different subsets (n = 250, n = 370 and n = 500) using a re-sampling method from the original dataset (re-samples = 10,000).

Results

The measures of immunogenicity were highly correlated, and the fulfillment or failure of any of the non-inferiority criteria for a specific measure partially predicted the same outcome for the other measures. Due to this dependency within each strain, the levels of power obtained by re-sampling methods were always higher than those obtained by theoretical calculations, which were based on the assumptions of independency between the three measures of immunogenicity. Seroconversion and Geometric Mean Ratio (GMR) showed a higher correlation. A failure in the fulfillment of the non-inferiority criteria for GMR predicted the failure for Seroconversion in >76% of cases.

Conclusions

The correlation between different measures of immunogenicity should be taken into account when evaluating statistical power for non-inferiority in influenza vaccine trials and in establishing sample sizes. Statistical approaches that include either all three measures of immunogenicity or both Seroconversion and the ratio of GMTs as co-primary non-inferiority endpoints might create redundancy and could increase the probability of not meeting at least one non-inferiority criterion by chance, due to multiplicity.     

Observational safety study of febrile convulsion following first dose MMRV vaccination in a managed care setting

Background

A combined measles, mumps, rubella, varicella live vaccine (MMRV, Merck and Co., Inc., US) was recently licensed in the US. Pre-licensure clinical trial data showed a significant increase in fever in days 5–12 following MMRV vaccination as compared to the vaccines given separately (MMR + V). This post-licensure retrospective cohort study was undertaken to assess the incidence of febrile convulsion following MMRV.

Methods

Children ages 12–60 months who received a first dose of MMRV in February 2006–June 2007 in a managed care organization were included in the study. Subjects were optimally matched on age, sex, and calendar date of vaccination to children who received MMR + V concomitantly in November 2003–January 2006, before MMRV licensure. Potential cases of febrile convulsion were identified through administrative data and adjudicated by expert panel, according to pre-specified criteria.

Results

During the 30 days post-vaccination, there were 128 and 94 potential convulsion cases among the 31,298 children in the MMRV and MMR + V cohorts, respectively. After review of available medical charts and adjudication, there were 84 cases of confirmed febrile convulsion, 44 (1.41/1000) and 40 (1.28/1000) in the MMRV and MMR + V cohorts, respectively (RR = 1.10, 95% CI = 0.72, 1.69). In days 5–12 following vaccination, a pre-specified period of interest, the respective numbers were 22 (0.70/1000) and 10 (0.32/1000) (RR = 2.20, 95% CI = 1.04, 4.65).

Conclusion

These data suggest that the risk of febrile convulsion is increased in days 5–12 following vaccination with MMRV as compared to MMR + V given separately during the same visit, when post-vaccination fever and rash are also increased in clinical trials. While there was no evidence of an increase in the overall month following vaccination, the elevated risk during this time period should be communicated and needs to be balanced with the potential benefit of a combined vaccine.