Socioeconomic disadvantage and human papillomavirus (HPV) vaccination uptake

ImportanceDespite availability of safe and effective human papillomavirus (HPV) vaccines, vaccination uptake remains low in the U.S. Research examining the impact of neighborhood socioeconomic status on HPV vaccination may help target interventions.ObjectiveTo examine the association between area deprivation and HPV vaccine initiation and completion.Design, setting, participantsRetrospective cohort study of individuals aged 11–18 years residing in the upper Midwest region. Receipt of HPV vaccination was examined over a three-year follow-up period (01/01/2016–12/31/2018).Main outcomes and measuresOutcomes of interest were initiation and completion of HPV vaccination. Demographic data were collected from the Rochester Epidemiology Project (REP). Area-level socioeconomic disadvantage was measured by calculating an Area Deprivation Index (ADI) score for each person, a measure of socioeconomic disadvantage derived from American Community Survey data. Multivariable mixed effect Cox proportional hazards models were used to examine the association of ADI quartiles (Q1-Q4) with HPV vaccine series initiation and completion, given initiation.ResultsIndividuals residing in census block groups with higher deprivation had significantly lower likelihood of HPV vaccine initiation (Q2: HR = 0.91, 0.84–0.99 Q3: HR = 0.83, 0.76–0.90; Q4: HR = 0.84, 0.74–0.96) relative to those in the least-deprived block groups (Q1). Similarly, those living in block groups with higher deprivation had significantly lower likelihood of completion (Q2: HR = 0.91, 0.86–0.97; Q3: HR = 0.87, 0.81–0.94; Q4: HR = 0.82, 0.74–0.92) compared to individuals in the least-deprived block groups (Q1).Conclusions and relevanceLower probability of both HPV vaccine-series initiation and completion were observed in areas with greater deprivation. Our results can inform allocation of resources to increase HPV vaccination rates in our primary care practice and provide an example of leveraging public data to inform similar efforts across diverse health systems.     

Patient and clinician factors associated with uptake of the human papillomavirus (HPV) vaccine among adolescent patients of a primary care network

BackgroundHuman papillomavirus (HPV) vaccination rates for adolescents remain relatively low. The purpose of this study is to examine patient and clinician factors associated with HPV vaccination among patients, ages 11–17, of a large community-based primary care network.MethodsElectronic health records and administrative data from a large primary care network from January 2017 – June 2018 for patients ages 11–17 (n = 10,682) and the 198 primary care clinicians that saw them were analyzed. Mixed effects logistic regression models examined the association of patient and clinician factors with HPV vaccine uptake.ResultsMost patients (63.0%) had at least one dose of the HPV vaccine, and 37.7% were up to date. In adjusted analyses, patients who received the tetanus, diphtheria, and pertussis (Tdap) vaccine (OR = 2.8, 95% CI: 2.1–3.9) compared to those who did not receive the vaccine and patients with five or more medical visits (OR = 1.9, 95% CI: 1.6–2.2) had the greatest odds of being up to date with the HPV vaccine series. Compared to White patients, African American/Black (OR = 0.8, 95% CI: 0.6 – 1.0) and Alaskan Native/American Indian (OR = 0.5, 95% CI: 0.3–0.9) patients were less likely to be up to date. Boys were also less likely to be up to date with the HPV vaccine series compared to girls (OR = 0.7, 95% CI: 0.7–0.8). Additionally, patients with family/general practice primary care clinicians were less likely to have their patients up to date than those with pediatricians (OR = 0.8, 95% CI: 0.6 – 1.0).ConclusionHPV vaccine uptake varied by patient characteristics, heath care utilization and primary care clinician specialty. These findings may inform future evidence-based interventions aimed at increasing HPV vaccine uptake among adolescents by targeting patient sub-groups and reducing missed opportunities for vaccination.     

Safety and immunogenicity of a pichia pastoris-expressed bivalent human papillomavirus (types 16 and 18) L1 virus-like particle vaccine in healthy Chinese women aged 9–45 years: A randomized,double-blind,placebo-controlled phase 1 clinical trial

BackgroundWe evaluated the safety and immunogenicity of high and low doses of a novel pichia pastoris-expressed bivalent (types 16 and 18) human papillomavirus (HPV) virus-like particle vaccine.MethodsIn this randomized, double-blind, placebo-controlled phase 1 trial, we enrolled 160 healthy females aged 9–45 years in Guangxi, China who were randomized (1:1:2) to receive either low (0.5 mL) or high (1.0 mL) dosages of bivalent HPV vaccine, or placebo (aluminum adjuvant) in a 0, 2, 6 months schedule. Adverse events and other significant conditions that occurred within 30 days after each vaccination were recorded throughout the trial. Sera were collected at days 0, 60, 180 and 210 to measure anti-HPV 16/18 neutralizing antibodies.ResultsA total of 160 participants received at least one dose of the HPV vaccine and 152 completed the three dose vaccination series. Reporting rates of adverse events in placebo, low dose (0.5 mL) and high dose (1.0 mL) groups were 47.5 %, 55.0 % and 55.0 %, respectively. No serious adverse events occurred during this trial. 100 % of the participants who received three doses of the HPV vaccine produced neutralizing antibodies against HPV 16/18 vaccine. For HPV 16 and HPV 18, the geometric mean titers (GMTs) were similar between the low dose group (GMT_{HPV 16} = 10816 [95 % CI: 7824–14953]), GMT_{HPV 18} = 3966 [95 % CI: 2693–5841]) and high dose group (GMT _{HPV 16} = 14482 [95 % CI: 10848–19333], GMT _{HPV 18} = 3428 [95 % CI: 2533–4639]).ConclusionThe pichia pastoris-expressed bivalent HPV vaccine was safe and immunogenic in Chinese females aged 9–45 years. The low dosage (0.5 mL) was selected for further immunogenicity and efficacy study.     

Serologic response to sequential vaccination with enhanced influenza vaccines: Open label randomized trial among adults aged 65–74 years

BackgroundThe effects of sequential vaccination with enhanced influenza vaccines are poorly understood. We conducted an exploratory open-label study to assess serologic response to sequential vaccination in older adults.Methods160 adults aged 65 through 74 years were randomized (1:1:1) to receive trivalent inactivated standard dose (SD), high-dose (HD), or MF59-adjuvanted (AD) vaccine in 2016/17. In 2017/18, HD and AD recipients received the same vaccine; SD recipients were re-randomized to HD or AD. Hemagglutination inhibition assays were performed using turkey erythrocytes against A/California/7/2009(H1N1)-like and B/Brisbane/60/2008(B/Victoria)-like in both seasons, and A/Michigan/45/2015(H1N1)-like in season 2. Microneutralization assays were performed against cell-propagated A/Hong Kong/4801/2014(H3N2)-like using MDCK-SIAT1 cells. Postvaccination geometric mean titer (GMT), percent with titer ≥ 40, and mean fold rise (MFR, ratio of postvaccination versus prevaccination titer) in season 2 were compared across groups, and ratio of MFR in season 2 versus season 1 was assessed for each strain.ResultsAnalysis included 152 participants (55 HD → HD, 58 AD → AD, 19 SD → HD, and 20 SD → AD). Season 2 postvaccination GMTs and percent with titer ≥ 40 did not differ between HD → HD and AD → AD recipients for vaccine strains examined. However, a higher percent of HD → HD and AD → AD recipients had postvaccination titer ≥ 40 than SD → AD recipients for A/H1N1 (86%-89% versus 60%) and SD → AD and SD → HD recipients for A/H3N2 (83%-87% versus 40%-53%). GMTs were higher in AD → AD versus SD → AD recipients for A/H1N1 (p = .01) and A/H3N2 (p = .002). MFRs in season 2 were low in all groups for A/H3N2 (1.5–2.2) and B/Victoria (1.7–2.3). MFR was lower in season 2 versus 1 for HD → HD and AD → AD recipients for all vaccine strains (1.6–3.7 versus 2.6–6.2).ConclusionsSequential vaccination with enhanced vaccines did not reduce immunogenicity in adults aged 65 through 74 years. Serologic response to cell-propagated A/H3N2 was suboptimal for all vaccines.ClinicalTrials.gov identifier. NCT02872311     

Cost-effectiveness analysis of quadrivalent and nonavalent human papillomavirus vaccines in Ethiopia

BackgroundIn Ethiopia, cervical cancer is the second most common cancer among women of the reproductive age group. Since 2018, the quadrivalent human papillomavirus (4vHPV) vaccine targeting four HPV types (6/11/16/18) has been introduced in the national immunization program in Ethiopia. Currently, however, a nonavalent HPV (9vHPV) vaccine which provides broader protection against nine HPV types (?6/11/16/18/31/33/45/52/58) is available for global use. Our study, therefore, aims to estimate the cost-effectiveness of 9vHPV vaccine compared to the current HPV vaccination program in Ethiopia.MethodA static Markov cohort model was used to simulate the progression of HPV infection to cervical cancer for a cohort of 12-years-old girls (N = 100,000) in Ethiopia. The model ran up to the age of 100 years, with a cycle length of 1 year. One-way and probabilistic sensitivity analyses were used to explore the robustness of the model and uncertainties around the parameters included in the model. Cost-effectiveness thresholds of one and three times gross domestic product (GDP) per quality-adjusted life-year (QALY) gained were considered.ResultsAt a price of US$ 6.9, the incremental cost-effectiveness ratio (ICER) per QALY gained for the 9vHPV vaccine was US$ 454 compared to the 4vHPV vaccine, which is less than one times GDP per capita of Ethiopia. The ICER was most sensitive to the change in the discount rate of QALYs. Compared to 4vHPV vaccine, for 9vHPV vaccine to remain very cost-effective and cost-effective, its price per dose should not exceed US$ 8.4 and US$ 15, respectively, at a threshold of one and three times GDP per capita.ConclusionCompared to the 4vHPV vaccine, the 9vHPV vaccine is a cost-effective option in Ethiopia, given that its price per dose does not exceed US$15.     

Physician clinical decision support system prompts and administration of subsequent doses of HPV vaccine: A randomized clinical trial

BackgroundHPV vaccine is effective in preventing several cancers and anogenital warts, yet rates of HPV vaccination series completion in the United States are low. A primary reason identified by parents for vaccinating children against HPV is a health care provider’s recommendation. Although most clinicians embrace vaccine recommendations, they are not always carried out evenly and subsequent HPV vaccines are missed.MethodsUsing an electronic health records-based decision support system (CHICA) clinicians were randomized to either usual practice or to receive an automated reminder to recommend the 2nd or 3rd dose of HPV vaccine. The reminder was delivered to clinicians of all intervention group eligible adolescents who had already initiated the vaccine series. Logistic regression models with generalized estimating equations were used for data analysis.ResultsA total of 1285 clinical encounters were observed across 29 randomized pediatric providers over a 13-month time frame (50.7% control group, 49.3% intervention group). Overall, patients were 44.9% female, 59.4% Black, 22.1% Hispanic, and 48.8% were ages 11–12 yrs. Within the control group, 421 (64.7%) received a subsequent HPV vaccine, compared to 481 (75.9%) (OR: 1.72, (95% CI 1.35–2.19)). Adjusted analysis showed no difference between the groups (aOR 1.52 (95% CI 0.88–2.62)) or when examined by age (11-12yrs aOR 1.66, (95% CI 0.79–3.48)) and 13-17yrs (aOR 1.19, (95% CI 0.76–1.85)) or gender female (aOR 1.39 (95% CI 0.71–2.72)) and males (aOR 1.67 (95% CI 0.95–2.92)). When results were stratified by both age and gender, there was similarly no statistically significant effect between the two groups.ConclusionsAutomated physician reminders for subsequent 2nd and 3rd doses of HPV vaccination were used. Despite increased rates of vaccination in the intervention group, the differences did not reach the level of statistical significance. Future studies with multifaceted approaches may be needed to examine the efficacy of computer-based reminders.Clinical Trial Registration: NCT02558803, “HPV Vaccination: Evaluation of Reminder Prompts for Doses 2 & 3”.     

Effectiveness of a multimodal intervention to increase vaccination in obstetrics/gynecology settings

ObjectiveTo test the effectiveness of a multimodal intervention in obstetrics/gynecology (ob-gyn) clinics to increase uptake of influenza and tetanus-diphtheria-acellular pertussis (Tdap) vaccines in pregnant women and these vaccines plus human papillomavirus (HPV) vaccine in non-pregnant women.MethodsA cluster randomized controlled trial among 9 private ob-gyn practices in Colorado from 9/2011 to 5/2014. The intervention consisted of: designation of immunization champions, staff/provider trainings, assistance with vaccine purchasing/management, identification of eligible patients, standing order implementation, chart review/feedback, and patient education materials. Control practices continued usual care. Primary outcomes were receipt of influenza and Tdap vaccines among pregnant women and these vaccines plus HPV vaccine among non-pregnant women, comparing a Baseline period (Year 0/Year 1) to Year 2, intervention versus control. With an estimated sample size of 32,590 per arm, there would be >80% power to detect a 10% difference between groups.ResultsIn the Baseline period, 27% of pregnant women in both intervention and control practices received influenza vaccine. In Year 2, 29% of pregnant women in intervention practices received influenza vaccine versus 41% in control practices. In the Baseline period, 18% of pregnant women in intervention practices received Tdap vaccine versus 22% in control practices. Both intervention and control practices increased to 51% in Year 2, representing an increase of 33% for intervention practices and 29% for control practices, consistent with a change in Tdap recommendations. Relatively few HPV, influenza or Tdap vaccines (≤6% of eligible patients) were given to non-pregnant patients in either intervention or control practices at any time during the study.ConclusionIn this cluster randomized trial designed to increase vaccination uptake, both intervention and control practices showed improved vaccination of pregnant but not non-pregnant patients. Future work should focus on tailoring evidence-based immunization practices or developing new approaches to specifically fit busy ob-gyn offices.     

Reduction of HPV16/18 prevalence in young women after eight years of three- and two-dose vaccination schemes

BackgroundRecommendations for human papillomavirus vaccination have relied on immunogenicity studies and efficacy results derived from adult women. Insufficient information exists regarding HPV effectiveness in vaccinated girls as they become sexually active, regardless of dose scheme. We aimed to compare the prevalence of high-risk HPV between unvaccinated and vaccinated young women eight years after immunization.MethodsAfter eight years, we recontacted women who received two-dose of bivalent or three-dose—either bivalent or quadrivalent—, HPV vaccine when aged 9–10 years-old as part of a clinical trial. Additionally, we recruited a contemporaneous unvaccinated woman group for comparison. Only those sexually active were included. High-risk HPV DNA was determined in urine samples and compared across groups.ResultsThe prevalence of HPV16/18 types was 6.8% (95 %CI 3.2–14.1%) in the unvaccinated (n = 6/88), 1.1% (95 %CI 0.2–5.8%) in the three-dose (n = 1/93), and 0.0% (95 %CI 0.0–7.0%) in the two-dose group (n = 0/51).ConclusionHPV vaccination, with two-dose of bivalent or three-dose schemes—either with the bivalent or quadrivalent vaccine—, was associated with a lower prevalence of HPV16/18 types eight years after primary immunization.     

An innovative housing-related measure for individual socioeconomic status and human papillomavirus vaccination coverage: A population-based cross-sectional study

BackgroundHuman papillomavirus (HPV) is a known cause of anogenital (eg, cervical) and oropharyngeal cancers. Despite availability of effective HPV vaccines, US vaccination-completion rates remain low. Evidence is conflicting regarding the association of socioeconomic status (SES) and HPV vaccination rates. We assessed the association between SES, defined by an individual validated Housing-based Index of Socioeconomic Status (HOUSES), and HPV vaccination status.MethodsWe conducted a cross-sectional study of children/adolescents 9–17 years as of December 31, 2016, living in southeastern Minnesota by using a health-record linkage system to identify study-eligible children/adolescents, vaccination dates, and home addresses matched to HOUSES data. We analyzed the relationship between HPV vaccination status and HOUSES using multivariable Poisson regression models stratifying by age, sex, race, ethnicity, and county.ResultsOf 20,087 study-eligible children/adolescents, 19,363 (96.4%) were geocoded and HOUSES measures determined. In this cohort, 57.9% did not receive HPV vaccination, 15.8% initiated (only), and 26.3% completed the series. HPV vaccination-initiation and completion rates increased over higher SES HOUSES quartiles (P < .001). Rates of HPV vaccination initiation versus unvaccinated increased across HOUSES quartiles in multivariable analysis adjusted for age, sex, race, ethnicity, and county (1st quartile, referent; 2nd quartile, 0.97 [0.87–1.09]; 3rd quartile, 1.05 [0.94–1.17]; 4th quartile, 1.15 [1.03–1.28]; test for trend, P = .002). HOUSES was a stronger predictor of HPV vaccination completion versus unvaccinated (1st quartile referent; 2nd quartile, 1.06 [0.96–1.16]; 3rd quartile, 1.12 [1.03–1.23]; 4th quartile, 1.32 [1.21–1.44]; test for trend, P < .001). Significant interactions were shown for HPV vaccination initiation by HOUSES for sex (P = .009) and age (P = .006).ConclusionThe study showed disparities in HPV vaccination by SES, with the highest HOUSES quartiles associated with increased rates of initiating and even greater likelihood of completing the series. HOUSES data may be used to target and tailor HPV vaccination interventions to undervaccinated populations.     

Serogroup B meningococcal vaccination practice patterns on college campuses

BackgroundMost Neisseria meningitidis involved in invasive disease among American college students express serogroup B antigen. The Advisory Committee on Immunization Practices (ACIP) recommends healthcare providers (HCPs) share clinical decision making with patients to determine individual value of meningococcal serogroup B vaccination (MenB) rather than routinely recommend vaccination as with the meningococcal A,C,W,Y vaccine (MenACWY). This study examines the attitudes and practices of HCPs working in college student health centers (SHCs) regarding the recommendation and administration of MenB to students.MethodsThe study was conducted as an online and phone survey of SHC HCPs from a sample of colleges across the United States between May 2017 and July 2018. Items compared college SHC policies and practices for MenB to those for MenACWY. It also assessed perceived barriers to and facilitators of MenB delivery to students.ResultsAmong the 147 respondents, almost 50% more reported their SHC stocked and administered MenACWY (54.1%) than MenB (37%) (p = .004). Almost five times as many colleges required their students receive MenACWY as MenB (53.5% vs. 10.5%, p < .001). A greater percentage requested students to submit records for MenACWY than MenB (77.3% vs. 46.9%, p < .001), and over three times as many tracked student-body coverage rates for MenACWY than MenB (55.6% vs. 15.8%, p < .001). Nearly three quarters of respondents estimated their college’s student body MenB coverage rate to be ≤ 10% or were unable to provide any estimate. Factors perceived by over half of the participants as moderate to extreme barriers to administering MenB included high upfront costs for SHCs to purchase and stock MenB (68.7%), and high out-of-pocket costs for students to receive it (82.8%).ConclusionsA minority of college SHCs require, offer or track Men B vaccination on their campuses. Financial concerns are common barriers to SHCs’ stocking and administering MenB to students.     

Immunogenicity and safety of the 9-valent human papillomavirus vaccine in Chinese females 9–45 years of age: A phase 3 open-label study

BackgroundThe 9-valent human papillomavirus (9vHPV; HPV6/11/16/18/31/33/45/52/58) vaccine was approved for use in Chinese women aged 16–26 years in 2018. This phase 3, open-label study (NCT03903562) compared 9vHPV vaccine immunogenicity and safety in Chinese females aged 9–19 years and 27–45 years with Chinese females aged 20–26 years; we report results from day 1 through 1 month post-Dose 3. The study will continue through 54 months post-Dose 3 to assess antibody persistence in Chinese girls aged 9–19 years.MethodsParticipants aged 9–45 years received three doses of the 9vHPV vaccine. Geometric mean titers (GMTs) and seroconversion percentages for anti-HPV6/11/16/18/31/33/45/52/58 antibodies were determined by competitive Luminex immunoassay in serum samples obtained at day 1 and 1 month post-Dose 3. Adverse events (AEs) within 30 days post-vaccination and serious AEs (SAEs) occurring at any time were recorded.ResultsIn total, 1990 participants (690 aged 9–19 years; 650 aged 20–26 years; 650 aged 27–45 years) were enrolled. At 1 month post-Dose 3, >99% of participants in the per-protocol immunogenicity population seroconverted to each vaccine HPV type. Anti-HPV6/11/16/18/31/33/45/52/58 antibody GMTs in the 9–19-year age group were non-inferior to those in participants aged 20–26 years. Anti-HPV6/11/16/18/31/33/45/52/58 seroconversion percentages in the 27–45-year age group were non-inferior to those in participants aged 20–26 years. Injection-site and systemic AEs were reported by 43.3% and 50.9%, 50.5% and 57.1%, and 43.8% and 43.4% of participants aged 9–19, 20–26, and 27–45 years, respectively. There were no vaccine-related SAEs, discontinuations due to AEs, and deaths.ConclusionAntibody responses induced by 9vHPV vaccination in Chinese females aged 9–19 years and 27–45 years were non-inferior to those in Chinese females aged 20–26 years. The vaccine was generally well tolerated.ClinicalTrials.gov Identifier: NCT03903562.     

Association between vaccination status,symptom identification and healthcare use: Implications for test negative design observational studies

AimTo test the internal validity of the test-negative design (TND) by investigating associations between maternal influenza vaccination, and new virus detection episodes (VDEs), acute respiratory illness, and healthcare visits in their children.MethodsEighty-five children from a birth cohort provided daily symptoms, weekly nasal swabs, and healthcare use data until age 2-years. Effect estimates are summarised as incidence rate ratios (IRR).ResultsThere was no association between maternal vaccination and VDEs in children (IRR = 1.1; 95 %CI = 0.9–1.2). Influenza-vaccinated mothers were more likely than unvaccinated mothers to both report, and seek healthcare for, acute lower respiratory illness in their children, IRR = 2.4; 95 %CI = 1.2–4.8 and IRR = 2.2; 95 %CI = 1.1–4.3, respectively.ConclusionA key assumption of the TND, that healthcare seeking behaviour for conditions of the same severity is not associated with vaccine receipt, did not hold. Further studies of the performance of the TND in different populations are required to confirm its validity.     

Associations between physical activity and mental health and behaviour in early adolescence

BackgroundWe examined associations between objectively-measured physical activity, depressive-symptoms, and emotional and behavioural difficulties in adolescents from a UK cohort.MethodData from 4755 participants (45% male) from the Avon Longitudinal Study of Parents and Children (ALSPAC) with physical activity assessed by accelerometry at age 11 was analysed. Indication of depressive symptoms (Short Moods and Feelings questionnaire) were obtained from parental reports at age 11 and self-reports at age 13. Behavioural and emotional problems were assessed by parents and teachers at age 11 and 13 using the Strengths and Difficulties Questionnaire (SDQ).ResultsAt age 11, males averaged 29 minutes (SD = 17) of daily moderate-to-vigorous physical activity (MVPA) compared with 18 minutes (SD = 12) among females. Higher MVPA at age 11 was associated with decreased depressive-symptoms in females at age 11 after adjusting for confounders. Among males, a positive change in MVPA between the ages of 11 and 13 was associated with a reduction in depressive symptoms. Negative associations were also found between MVPA at age 11 and the emotional symptoms scale of the SDQ at age 11 and age 13 in females. Higher MVPA predicted a decreased score on the hyperactivity subscale of the SDQ at 11 and 13 for both sexes. All effect sizes were small.ConclusionsHigher MVPA was associated with reduced depressive symptoms, behavioural and emotional-difficulties in early adolescence, however the magnitude of effects was small. Efforts to support MVPA in this age group are therefore warranted.     

Immunogenicity and safety of the quadrivalent human papillomavirus vaccine in Chinese females aged 9 to 26 years: A phase 3, open-label,immunobridging study

BackgroundThe quadrivalent human papillomavirus (qHPV; HPV6/11/16/18) vaccine was approved for use in Chinese women aged 20–45 years in 2017. This Phase 3, open-label study (NCT03493542) aimed to assess immunogenicity and safety of the qHPV vaccine in Chinese girls aged 9–19 years versus Chinese young women aged 20–26 years; we report results from Day 1 through Month 7. The study will continue through Month 60 to assess antibody persistence in Chinese girls aged 9–19 years.MethodsParticipants aged 9–26 years received three doses of the qHPV vaccine (Day 1, Month 2, Month 6). Geometric mean titers (GMTs) and seroconversion percentages for anti-HPV6/11/16/18 antibodies were determined by competitive Luminex immunoassay (cLIA) in serum samples obtained on Day 1 and at Month 7. Injection-site adverse events (AEs) and systemic AEs within 30 days post-vaccination, and serious AEs (SAEs) occurring at any time during the study, were recorded.ResultsIn total, 766 participants (383 aged 9–19 years; 383 aged 20–26 years) were enrolled and received ≥1 vaccine dose. All participants in the per-protocol immunogenicity population of both age groups seroconverted to each of the vaccine HPV types at Month 7. Anti-HPV6/11/16/18 antibody GMTs at Month 7 in participants aged 9–19 years were non-inferior to those in participants aged 20–26 years. Injection-site AEs and systemic AEs were reported by 36.6% and 49.3% of 9–19-year-olds, and 40.7% and 54.8% of 20–26-year-olds, respectively. There were no vaccine-related SAEs. No participants discontinued the vaccine due to an AE and no deaths were reported.ConclusionAntibody responses induced by the 3-dose qHPV vaccination regimen in Chinese girls aged 9–19 years were non-inferior to those in Chinese young women aged 20–26 years. The vaccine was generally well tolerated in the study population.ClinicalTrials.gov Identifier: NCT03493542.     

Human papillomavirus vaccine coverage in Rwanda: A population-level analysis by birth cohort

BackgroundIn 2011, Rwanda became the first African nation to implement a national human papillomavirus (HPV) vaccination program, conceived to protect girls aged <15 years (i.e. born ≥1997). After an initial school-grade-targeted catch-up campaign, there was a transition to routine vaccination of 12 year-olds only. We aimed to produce population-level vaccine coverage estimates.MethodsThe Rwandan Expanded Program on Immunization (EPI) collected data on number of eligible girls and HPV vaccines delivered, stratified by calendar year (2011–2018), girl’s age, district and vaccination round. HPV vaccine coverage was estimated by birth cohort (reconstituted using calendar year and age), as a proportion of (1) eligible target, and (2) the 2012 Rwandan census population.Results1,156,863 girls received first dose of HPV vaccine between 2011 and 2018, corresponding to 98% of the eligible target. Median vaccination age was 15 years (interquartile range [IQR] 13–16) in 2011–2013 (school grade-targeted catch-up), 13 years (IQR 12–14) in 2014 (transition) and 12 years in 2015–2018 (routine). Population-level coverage versus the census increased from 10 to 40% for girls born in 1993–1995 (median vaccination age = 17 years) to 50–65% for 1996–2000 birth cohorts (14 years), and 80–90% for 2001–2006 birth cohorts (12 years). Coverage trends were similar across provinces and in the capital, Kigali. Second and third round coverage suggested most vaccinated girls completed their recommended dosing regimen (which reduced from 3 to 2 doses in 2015).ConclusionsBirth cohorts provide a clear picture of population-level HPV vaccine coverage after a pragmatic catch-up campaign, particularly in Rwanda where eligible school grades included wide age ranges. Whilst the catch-up campaign resulted in some coverage gaps in out-of-school teenagers, coverage remains high in cohorts routinely targeted as 12 year-olds.     

Addressing logistical barriers to childhood vaccination using an automated reminder system and online resource intervention: A randomized controlled trial

BackgroundAs the rates of vaccination decline in children with logistical barriers to vaccination, new strategies to increase vaccination are needed. The goal of this study was to develop and evaluate the effectiveness of the Vaccines For Babies (VFB) intervention, an automated reminder system with online resources to address logistical barriers to vaccination in caregivers of children enrolled in an integrated healthcare system. Effectiveness was evaluated in a randomized controlled trial.MethodsQualitative interviews were conducted with parents of children less than two years old to identify logistical barriers to vaccination that were used to develop the VFB intervention. VFB included automated reminders to schedule the 6- and 12-month vaccine visit linking caregivers to resources to address logistic barriers, sent to the preferred mode of outreach (text, email, and/or phone). Parents of children between 3 and 10 months of age with indicators of logistical barriers to vaccination were randomized to receive VFB or usual well child care (UC). The primary outcome was percentage of days undervaccinated at 2 years of life. A difference in differences analysis was conducted.ResultsQualitative interviews with 6 parents of children less than 2 years of age identified transportation, scheduling challenges, and knowledge of vaccine timing as logistical barriers to vaccination. We enrolled 250 participants in the trial, 45% were loss to follow-up. There were no significant differences in vaccination uptake between those enrolled in UC or the VFB intervention (0.51%, p = 0.86). In Medicaid enrolled participants, there was a modest decrease in percentage of days undervaccinated in the VFB intervention compared to UC (6.3%, p = 0.07).ConclusionAutomated Reminders and with links to heath system resources was not shown to increase infant vaccination uptake demonstrating additional resources are needed to address the needs of caregivers experiencing logistical barriers to vaccination.     

Motivational interviewing for maternal Immunizations: Intervention development

Background and ObjectiveVaccine uptake during pregnancy remains low. Our objectives were to describe 1) development and adaptation of a clinician communication training intervention for maternal immunizations and 2) obstetrics and gynecology (ob-gyn) clinician and staff perspectives on the intervention and fit for the prenatal care context.MethodsDesign of the Motivational Interviewing for Maternal Immunizations (MI4MI) intervention was based on similar communication training interventions for pediatric settings and included presumptive initiation of vaccine recommendations (“You’re due for two vaccines today”) combined with motivational interviewing (MI) for hesitant patients. Interviews and focus group discussions were conducted with ob-gyn clinicians and staff in five Colorado clinics including settings with obstetric physicians, certified nurse midwives (CNMs), and clinician-trainees. Participants were asked about adapting training to the ob-gyn setting and their implementation experiences. Feedback was incorporated through iterative changes to training components.ResultsInterview and focus group discussion results from participants before (n = 3), during (n = 11) and after (n = 25) implementation guided intervention development and adaptation. Three virtual, asynchronous training components were created: a video and two interactive modules. This virtual format was favored due to challenges attending group meetings; however, participants noted opportunities to practice skills through role-play were lacking. Training modules were adapted to include common challenging vaccine conversations and live-action videos. Participants liked interactive training components and use of adult learning strategies. Some participants initially resisted the presumptive approach but later found it useful after applying it in their practices. Overall, participants reported that MI4MI training fit well with the prenatal context and recommended more inclusion of non-clinician staff.ConclusionsMI4MI training was viewed as relevant and useful for ob-gyn clinicians and staff. Suggestions included making training more interactive, and including more complex scenarios and non-clinician staff.     

A detailed analysis of possible efficacy signals of NTHi-Mcat vaccine against severe COPD exacerbations in a previously reported randomised phase 2b trial

BackgroundAn investigational vaccine containing non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) surface proteins did not show vaccine efficacy (VE) against combined moderate and severe (moderate/severe) exacerbations in a randomised, observer-blinded, placebo-controlled phase 2b trial of patients with chronic obstructive pulmonary disease (COPD). Nevertheless, observations on rates of severe exacerbations and hospitalisations encouraged further evaluation.MethodsPatients with stable COPD (moderate to very severe airflow limitation, Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 2–4), 40–80 years and at least one moderate/severe exacerbation in the last year received two doses of NTHi-Mcat vaccine or placebo plus standard care. Secondary analyses were conducted on VE against exacerbations according to severity. Potential predictive factors at baseline for VE against severe exacerbations were explored in post-hoc analyses.ResultsOf 606 patients enrolled, 571 were included in the efficacy analysis (279 in NTHi-Mcat vaccine group, 292 in placebo group). VE against severe acute exacerbations of COPD (AECOPD) in various subgroups was 52.11 % (p = 0.015; frequent exacerbators), 65.43 % (p = 0.015; baseline GOLD grade 4), 38.24 % (p = 0.034; previous pneumococcal and/or influenza vaccination). VE was 52.49 % (p = 0.044) for the 6–12 months period after 1 month post-dose 2. Multivariable analysis identified two factors (frequent exacerbator status plus inhaled corticosteroid use at baseline) associated with significant VE against severe AECOPD; in this subpopulation, VE was 74.99 % (p < 0.001).ConclusionResults suggest potential efficacy with the NTHi-Mcat vaccine against severe exacerbations in certain patients with COPD, in particular those who have frequent exacerbations and use inhaled corticosteroids. This potential signal requires confirmation in an appropriately designed prospective clinical trial.Trial registrationClinicalTrials.gov, NCT03281876.     

Effect of a vaccine information statement (VIS) on immunization status and parental knowledge,attitudes, and beliefs regarding infant immunization in Japan

BackgroundBecause of the overabundance of vaccination information on the internet, in the media, and on social media, providing clear and correct information on immunization is critical for parental decision-making. In 2018, the Japan Pediatric Society created and distributed a Vaccine Information Statement (VIS) to provide appropriate immunization information to caregivers. The objectives of the present study were to evaluate the effect of the VIS on immunization rates, adherence to schedule, and parental understanding of immunization in Japan.MethodsThis cross-sectional study was conducted at 18 centers in 2 prefectures in Japan. Caregivers were assigned to an intervention group, which received the VIS and a questionnaire when their child reached the age of 1 month, and a control group, which received only the questionnaire. Using the self-reported questionnaires, we evaluated vaccination rates and schedule adherence at age 2 months, and parental knowledge, attitudes, and beliefs regarding immunization. Three months later, the questionnaires were returned, and the findings were compared between the 2 groups.ResultsWe contacted 422 and 428 persons in the intervention and control groups, respectively, and 111/422 (26.3%) and 119/428 (27.8%) returned the surveys. Vaccination rates and adherence rates for the first dose of 4 recommended vaccines did not differ significantly (P > 0.25); however, there were some positive effects on items related to vaccine knowledge (P = 0.03), perceived benefits (P = 0.02), perceived barriers (P < 0.001), and perceived behavioral control (P = 0.01).ConclusionThe VIS improved parent comprehension of infant immunization. Future studies should examine if the effects of such an intervention persist and affect vaccine uptake throughout childhood.     

Motivational interviewing and vaccine acceptance in children: The MOTIVE study

Background and ObjectiveVaccine coverage have been less than desired in young children in part due to parental vaccine hesitancy. Addressing health beliefs through patient-centered communication approaches such as motivational interviewing (MI) may improve vaccine confidence. Thus, the objective of this study was to determine the difference in paediatric vaccination coverage rates based on the Advisory Committee on Immunization Practices (ACIP) and Centers for Disease Control and Prevention (CDC) recommended schedule in children 0–6 years of age after an educational intervention for providers and integration of an MI-based communication tool, MOTIVE (MOtivational Interviewing Tool to Improve Vaccine AcceptancE).MethodsPaediatric and family practice providers in a federally qualified health center in the United States completed an educational intervention regarding vaccine hesitancy and use of the MOTIVE tool. Providers then implemented the MOTIVE tool to address common health beliefs using strong, presumptive vaccine recommendations and an MI framework during encounters with patients 0–6 years of age. Data were collected from 1-year pre-educational intervention (July 2018-June 2019, N = 2504) and post-intervention (July 2019-March 2020, N = 1954) to examine differences in vaccination coverage rates and documented vaccine refusals.ResultsUse of the MOTIVE tool was associated with a statistically significant increase in IIV vaccination coverage rate in children 6 months to 6 years of age (32.4% versus 43.9%, p < 0.01). A significantly increased Hib vaccination coverage rate was observed in children 0–18 months of age. Patients with commercial insurance also had significantly higher vaccination coverage rates for the DTaP, IPV, and VAR vaccines during the intervention period. Use of the MOTIVE tool was associated with a decrease in documented vaccine refusals per 100 patients in children 0–6 years of age (31.5 versus 17.6, p < 0.01).ConclusionUse of an MI-based communication tool may decrease vaccine refusals and improve childhood vaccination coverage rates, particularly for IIV.Clinical Trial Registration: ClinicalTrials.gov, NCT03934008, https://clinicaltrials.gov/ct2/show/NCT03934008, deidentified individual participant data will not be made available.