One or two doses of live varicella virus-containing vaccines: Efficacy,persistence of immune responses,and safety six years after administration in healthy children during their second year of life

BackgroundThis phase III B follow-up of an initial multicenter study (NCT00226499) will evaluate the ten-year efficacy of two doses of the combined measles-mumps-rubella-varicella vaccine (MMRV) and one dose of the live attenuated varicella vaccine (V) versus a measles-mumps-rubella control group (MMR) for the prevention of clinical varicella disease. Here we present efficacy results for six years post-vaccination.MethodsIn phase A of the study, healthy children aged 12–22 months from ten European countries were randomized (3:3:1) and received either two doses of MMRV, or one dose of combined MMR and one dose of monovalent varicella vaccine (MMR+V), or two doses of the MMR vaccine (control), 42 days apart. Vaccine efficacy against all and against moderate or severe varicella (confirmed by detection of viral DNA or epidemiological link) was assessed from six weeks up to six years post-dose 2 for the MMRV and MMR+V groups, and was calculated with 95% confidence intervals (CI). The severity of varicella was calculated using the modified Vázquez scale (mild ≤ 7; moderately severe = 8–15; severe ≥ 16). Herpes zoster cases were also recorded.Results5289 children (MMRV = 2279, mean age = 14.2, standard deviation [SD] = 2.5; MMR+V = 2266, mean age = 14.2, SD = 2.4; MMR = 744, mean age = 14.2, SD = 2.5 months) were included in the efficacy cohort. 815 varicella cases were confirmed. Efficacy of two doses of MMRV against all and against moderate or severe varicella was 95.0% (95% CI: 93.6–96.2) and 99.0% (95% CI: 97.7–99.6), respectively. Efficacy of one dose of varicella vaccine against all and against moderate or severe varicella was 67.0% (95% CI: 61.8–71.4) and 90.3% (95% CI: 86.9–92.8), respectively. There were four confirmed herpes zoster cases (MMR+V = 2, MMR = 2), all were mild and three tested positive for the wild-type virus.ConclusionsTwo doses of the MMRV vaccine and one dose of the varicella vaccine remain efficacious through six years post-vaccination.     

Second dose of measles-mumps-rubella-varicella vaccine (MMRV) and the risk of febrile convulsions

IntroductionStudies have shown an increased risk of febrile convulsions (FC) after first immunization with the quadrivalent measles-mumps-rubella-varicella vaccine (MMRV) compared to a first dose of measles-mumps-rubella vaccine (MMR) only or in combination with separately administered varicella vaccine (MMR + V). Therefore, it is recommended to give MMR + V at first dose and MMRV or MMR + V at second dose. Little is known on the risk of FC after MMRV at second dose, especially whether the risk depends on age, sex, history of FC or type of first dose vaccine.MethodsA retrospective cohort study using claims data from the German Pharmacoepidemiological Research database (GePaRD) was performed in children born between January 1st, 2004 and October 31st, 2015 who received two doses of MMRV, MMR + V or MMR. Cases were defined as hospitalization with a diagnosis of FC without neurological conditions coded as main discharge diagnosis. Unadjusted and adjusted odds ratios (OR) with 95% confidence intevals (CIs) were calculated to compare the risk of FC. Stratified analyses were performed to examine potential effect modification by age, sex, history of FC or type of first dose vaccine.ResultsIn the first 30 days after second dose vaccination, 464 FCs were observed in a cohort of 528,639 children with a median age of 17 months. After adjustment for potential confounders, the adjusted OR for FC in the 30 days after vaccination was 1.25 (95% CI 0.67–2.30) for MMRV compared to MMR + V and 1.04 (0.82–1.32) for MMRV compared to MMR. History of FC was the most important risk factor with an OR of 36.26 (29.30–44.89). We found no effect modification by age, sex, history of FC, or type of first dose vaccine.ConclusionUse of MMRV at second dose is not associated with an increased risk of FC compared to MMR + V or MMR, irrespective of age, sex, history of FC, or type of first dose vaccine.     

Chickenpox: sufficient reasons for the introduction of vaccination

The incidence of chickenpox and its complications is high enough to favour introducing varicella vaccination into the Dutch immunisation programme for children, although current Dutch figures may even underestimate the incidence. Safe and effective MMRV vaccines, in which varicella (V) vaccine is combined with measles, mumps and rubella (MMR), could well replace the MMR vaccine used at present. MMRV vaccines should be administered subcutaneously in two doses. Ten years after the introduction of varicella vaccination in the United States of America, the incidence of complications has decreased impressively. An effect on the incidence of herpes zoster has not (yet) been seen.     

Incidence of herpes zoster among varicella-vaccinated children,by number of vaccine doses and simultaneous administration of measles,mumps, and rubella vaccine

IntroductionChildren may receive measles-mumps-rubella (MMR) and varicella (VAR) vaccines separately or as measles-mumps-rubella-varicella (MMRV). We examined whether pediatric herpes zoster (HZ) incidence varied by pattern of varicella vaccine administration.MethodsIn six integrated health systems, we examined HZ incidence among children turning 12 months old during 2003–2008. All received varicella and MMR vaccines on recommended schedules. Cases were identified through 2014 using ICD-9 codes. Incidence was examined by number of varicella vaccine doses and same-day MMR.ResultsAmong 199,797 children, overall HZ incidence was 18.6/100,000 person-years in the first-dose MMR + VAR group, 17.9/100,000 person-years in the MMRV group, and 7.5/100,000 person-years in the VAR-alone group. HZ incidence was lower following the second dose than before the second dose in all first-dose groups.ConclusionsHZ incidence was not meaningfully different between the MMRV and MMR + VAR first-dose groups. Overall and within first-dose groups, HZ incidence was lower among children receiving two varicella vaccine doses.     

Ten-year follow-up on efficacy,immunogenicity and safety of two doses of a combined measles-mumps-rubella-varicella vaccine or one dose of monovalent varicella vaccine: Results from five East European countries

BackgroundWe assessed the 10-year efficacy, immunogenicity and safety of two doses of a combined measles-mumps-rubella-varicella vaccine (MMRV) or one dose of a monovalent varicella vaccine (V) in children from Czech Republic, Lithuania, Poland, Romania and Slovakia.MethodsThis was a phase IIIB follow-up of an observer-blind, randomized, controlled trial (NCT00226499). In phase A, healthy children aged 12–22 months from 10 European countries were randomized in a 3:3:1 ratio to receive two doses of MMRV (MMRV group), one dose of MMR followed by one dose of V (MMR + V group), or two doses of MMR (MMR; control group), 42 days apart. Vaccine efficacy (VE) against varicella (confirmed by viral DNA detection or epidemiological link and clinical assessment) was calculated with 95% confidence intervals using Cox proportional hazards regression model. Immunogenicity was assessed as seropositivity rates and geometric mean concentrations (GMCs). Solicited and unsolicited adverse events (AEs) and serious AEs (SAEs) were recorded.ResultsA total of 3705 children were vaccinated (1590, MMRV group; 1586, MMR + V group; 529, MMR group). There were 663 confirmed varicella cases (47, MMRV group; 349, MMR + V group; 267, MMR group). VE ranged between 95.4% (Lithuania) and 97.4% (Slovakia) in the MMRV group and between 59.3% (Lithuania) and 74% (Slovakia) in the MMR + V group. At year 10, seropositivity rates were 99.5%–100% in the MMRV group, 98%–100% in the MMR + V group and 50%–100% in the MMR control group, and the anti-VZV antibody GMCs were comparable between MMRV and MMR + V groups. The occurrence of solicited and unsolicited AEs was similar across groups and no SAE was considered as vaccination-related. No new safety concerns were identified.ConclusionsOur results indicated that two doses of varicella zoster virus-containing vaccine provided better protection than one dose against varicella and induced antibody responses that persisted 10 years post-vaccination.     

A combined measles,mumps, rubella and varicella vaccine (Priorix-Tetra™): Immunogenicity and safety profile

Priorix-Tetra™ (GlaxoSmithKline Biologicals) is a combined measles, mumps, rubella and varicella (MMRV) vaccine. Eight studies involving more than 3000 children were reviewed. Compared with co-administration of MMR (Priorix™) and varicella (Varilrix™) vaccines, the MMRV vaccine showed: similar immunogenicity, with immunity shown up to 3 years post-vaccination; a higher rate of fever after the first dose; a slight increase in mild local reactions after the second dose. This MMRV vaccine can be used either as a two-dose vaccine or as a second dose in children primed with separate MMR and/or varicella vaccines, offering a convenient way to introduce varicella vaccination into routine vaccination programmes.     

Attitudes towards varicella vaccination in parents and paediatric healthcare providers in Hungary

BackgroundVaricella vaccination is important in prevention of childhood infection. Aim of this cross-sectional study was to survey attitudes and determinants of support or refusal of varicella vaccination in parents and in paediatric healthcare professionals, mainly health visitors in Hungary prior to the introduction of this vaccine in National Immunization Program in 2019.MethodsBetween October 2018 and February 2019, 1042 parents and 198 healthcare professionals completed a self-administered anonymous questionnaire regarding sociodemographic background, knowledge and attitudes towards varicella vaccination, and reasons for non-vaccination.ResultsFrom the participating parents 53.3% have vaccinated at least one of their children. Vaccination rate was significantly higher in families with <3 children, living in the capital, among those who have seen complications of varicella and among parents with university degree. Most important positive determinant was recommendation of the vaccine by healthcare professionals: 77.8% of parents accepted vaccination when recommended by the paediatrician, despite the cost of the vaccine, whereas only 17.3% of parents vaccinated their children when the vaccine was not recommended by paediatrician. Most important reasons for non-vaccination was finding the vaccine unnecessary, concerns regarding side effects, and not believing in the vaccine’s effectiveness. Among paediatric healthcare professionals, support rate of universal varicella vaccination was 76.3%. Support rate was higher among those who have seen complications of varicella more often and those who consider varicella a severe infection. Reasons of professionals who do not support universal varicella vaccination were similar to those of vaccine hesitant parents. Practice of intentional exposure of non-immune child to infected ones still exist.ConclusionsEducational programs are needed for parents and health visitors to address concerns regarding vaccination. Paediatricians are the most trusted source of information for parents hence they have a significant responsibility and parents likely follow their recommendations.     

Reactogenicity and immunogenicity of a live attenuated tetravalent measles-mumps-rubella-varicella (MMRV) vaccine

In countries where routine varicella vaccination is implemented, it is usually given at the same age as that recommended for measles-mumps-rubella (MMR) vaccination. A combined multivalent measles-mumps-rubella-varicella (MMRV) vaccine would offer the convenience of a single injection and facilitate implementation of varicella vaccination into routine childhood immunisation schedules. We evaluated the immunogenicity and reactogenicity of a tetravalent MMRV candidate vaccine compared to an extemporaneous mix of a measles-mumps-rubella vaccine and varicella vaccine (MMR/V), and to a measles-mumps-rubella (MMR) vaccine alone. A multicentre study was conducted in which a total of 240 healthy children aged 12 months (80 per group) were randomised to receive MMRV, MMR/V, or MMR alone. Active surveillance for adverse events was undertaken for 43 days post-vaccination. Blood samples were taken prior to vaccination and at 60 days post-vaccination. There were no significant differences between groups in rates of pain, redness, or swelling at the site of vaccination. There was no significant difference in the rate of any fever (axillary temperature >or=37.5 degrees C) and grade 3 fever (axillary temperature >39.0 degrees C) between the groups receiving MMRV and MMR during the 43-day follow-up period. Although, a significant increase was found for fever of any cause with onset between days 0 and 14 for MMRV compared to the MMR group, there was no significant difference in grade 3 fever rates during the same period. With respect to immunogenicity, MMRV and MMR/V demonstrated similar seroconversion rates to each component compared to MMR alone, with at least 91.9% of subjects in all groups seroconverting to each vaccine component 60 days after vaccination. Decreased GMTs for varicella antibody at day 60 indicated that there may have been inhibition of this response compared to MMR/V. This tetravalent MMRV candidate vaccine showed promising results, although further examination of the possible increase in minor fever and decreased varicella immunogenicity should be assessed in future studies.     

Risk of febrile seizure after measles–mumps–rubella–varicella vaccine: A systematic review and meta-analysis

BackgroundConsidering the febrile seizure rate, there is no longer a clear preference for use of measles–mumps–rubella–varicella (MMRV) vaccine over separate measles–mumps–rubella (MMR) and varicella (V) vaccine. This work was undertaken to assess the risk of febrile seizure after MMRV vaccine in children.MethodsWe searched PubMed, Embase, BIOSIS Previews, Scopus, Web of Science, Cochrane Library and other databases through 12 December 2014. Meta-analysis was conducted using R version 3.1.2 and Stata version 12.0.ResultsA total of thirty-nine studies were included. Thirty-one published or unpublished clinical trials involving about 40,000 subjects did not show significant differences in incidence of febrile seizure or vaccine related febrile seizure between MMRV and MMR with or without varicella vaccine after any doses, in the risk windows of 0–28, 0–42 or 0–56 days and 7–10 days. In addition, these studies showed that the receipt of concomitant use of MMRV and other pediatric vaccines was not a significant predictor of febrile seizure. Eight post-marketing observations involving more than 3,200,000 subjects were included. No evidence suggested elevated risk of febrile seizure associated with MMRV vaccine among children aged 4–6 years old during 7–10 days or 0–42 days after vaccination. However, an approximately 2-fold increase in risk of seizure or febrile seizure during 7–10 days or 5–12 days after MMRV vaccination was found among children aged 10–24 months, although the highest incidence of seizure was still lower than 2.95‰.ConclusionsFirst MMRV vaccine dose in children aged 10–24 months was associated with an elevated risk of seizure or febrile seizure. Further post-marketing restudies based on more rigorous study design are needed to confirm the findings.     

Social inequalities in COVID-19 vaccine acceptance and uptake for children and adolescents in Montreal,Canada

BackgroundThe success of current and prospective COVID-19 vaccine campaigns for children and adolescents will in part depend on the willingness of parents to accept vaccination. This study examined social determinants of parental COVID-19 vaccine acceptance and uptake for children and adolescents.MethodsWe used cross-sectional data from an ongoing COVID-19 cohort study in Montreal, Canada and included all parents of 2 to 18-year-olds who completed an online questionnaire between May 18 and June 26, 2021 (n = 809). We calculated child age-adjusted prevalence estimates of vaccine acceptance by parental education, race/ethnicity, birthplace, household income, and neighbourhood, and used multinomial logistic regression to estimate adjusted prevalence differences (aPD) and ratios (aPR). Social determinants of vaccine uptake were examined for the vaccine-eligible sample of 12 to 18 year-olds (n = 306).ResultsIntention to vaccinate children against COVID-19 was high, with only 12.4% of parents unlikely to have their child vaccinated. Parents with younger children were less likely to accept vaccination, as were those from lower-income households, racialized groups, and those born outside Canada. Children from households with annual incomes <$100,000 had 18.4 percent lower prevalence of being vaccinated/very likely vaccinated compared to household incomes ≥$150,000 (95% CI: 10.1 to 26.7). Racialized parents reported greater unwillingness to vaccinate vs. White parents (aPD = 10.3; 95% CI: 1.5, 19.1). Vaccine-eligible adolescents from the most deprived neighbourhood were half as likely to be vaccinated compared to those from the least deprived neighbourhood (aPR = 0.48; 95% CI: 0.18 to 0.77).Interpretation.This study identified marked social inequalities in COVID-19 vaccine acceptance and uptake for children and adolescents. Efforts are needed to reach disadvantaged and marginalized populations with tailored strategies that promote informed decision making and facilitate access to vaccination.     

Text message reminders for timely routine MMR vaccination: A randomized controlled trial

ObjectiveMeasles–mumps–rubella (MMR) vaccination is important for preventing disease outbreaks, yet pockets of under-vaccination persist. Text message reminders have been employed successfully for other pediatric vaccines, but studies examining their use for MMR vaccination are limited. This study assessed the impact of text message reminders on timely MMR vaccination.Study designParents (n = 2054) of 9.5–10.5-month-old children from four urban academically-affiliated pediatric clinics were randomized to scheduling plus appointment text message reminders, appointment text message reminder-only, or usual care. The former included up to three text reminders to schedule the one-year preventive care visit. Both text messaging arms included a text reminder sent 2 days before that visit. Outcomes included appointment scheduling, appointment attendance, and MMR vaccination by age 13 months, the standard of care at study sites.ResultsChildren of parents in the scheduling plus appointment text message reminders arm were more likely to have a scheduled one-year visit than those in the other arms (71.9% vs. 67.4%, relative risk ratio (RRR) 1.07 [95% CI 1.005–1.13]), particularly if no appointment was scheduled before randomization (i.e., no baseline appointment) (62.1% vs. 54.7%, RRR 1.14 [95% CI 1.04–1.24]). One-year visit attendance and timely MMR vaccination were similar between arms. However, among children without a baseline appointment, those with parents in the scheduling plus appointment text message reminders arm were more likely to undergo timely MMR vaccination (61.1% vs. 55.1%, RRR 1.11 [95% CI 1.01–1.21]).ConclusionText message reminders improved timely MMR vaccination of high-risk children without a baseline one-year visit.     

Safety and immunogenicity of a measles–mumps–rubella–varicella vaccine given as a second dose in children up to six years of age

Two doses of measles–mumps–rubella vaccine (MMR) are widely recommended and consideration is being given to a similar schedule for varicella vaccine. A combined measles–mumps–rubella–varicella vaccine (MMRV) could be considered for this second dose in children previously vaccinated separately with MMR and varicella vaccines. Healthy children (N = 390) aged 15–75 months (median 54 months) previously immunized with MMR and varicella vaccines were randomly allocated to receive MMRV or separate injections of MMR and varicella vaccines. Before administration of study vaccines, seropositivity rates were 96.4% for measles, 94.3% for mumps, 99.5% for rubella, and 97.9% for varicella. Post-immunization, seropositivity rates were 99.5% for measles and mumps and 100% for rubella and varicella in the MMR + varicella group and 100% for all four antigens in the MMRV group; a 26.2- and 27.2-fold increase in varicella titer was observed in the MMR + varicella vaccine and MMRV groups, respectively. Except for more frequent pain in the MMRV group (33.3% vs. 23.7%, p = 0.043), there were no differences in the incidence of local and solicited symptoms between groups. In children primed with MMR and varicella vaccine, MMRV had non-inferior immunogenicity and similar safety profiles as a second dose of licensed MMR and varicella vaccine administered concomitantly.     

Influences on immunization rates: Vaccination coverage of mumps,measles, rubella and varicella before and after the STIKO intervention 2011 – A retrospective study

BackgroundIn September 2011, the German Standing Committee on Vaccinations (STIKO) changed their recommendation regarding the mumps–measles–rubella–varicella vaccination (MMRV). We compared the immunization rates against MMRV in Germany before and after the STIKO intervention.MethodsWe recorded the immunization status of children born between 09/2008 and 08/2012 in 35 selected doctor’s surgeries in Germany.ResultsAfter the STIKO intervention, the ratio of the combined MMRV vaccine as the first dose immunization was reduced to approximately 25% of the initial value. A slight increase in the number of children not sufficiently vaccinated against varicella (1.2%) was observed, but the immunization rates against measles, mumps, rubella and varicella did not significantly decrease.ConclusionsThe STIKO intervention led to a significant change in physicians’ vaccination procedures. The separate administration MMR + V vaccination may be a helpful option to improve the immunization rates in general.     

The immunogenicity and safety of a tetravalent measles-mumps-rubella-varicella vaccine when co-administered with conjugated meningococcal C vaccine to healthy children: A phase IIIb,randomized, multi-center study in Italy

IntroductionMultiple vaccination visits and administrations can be stressful for infants, parents and healthcare providers. Multivalent combination vaccines can deliver the required number of antigens in fewer injections and clinic visits, while vaccine co-administration can also reduce the number of visits. This non-inferiority study was undertaken to evaluate the feasibility of co-administering a combined measles-mumps-rubella-varicella (MMRV) vaccine with conjugated meningococcal C (MenC) vaccine in a large cohort of healthy Italian toddlers.MethodsHealthy subjects aged 13–15 months were randomized (2:1:1) to receive single doses of either: co-administered MMRV + MenC at the same visit (MMRV + MenC group); or MMRV followed 42 days later by MenC (MMRV group); or MenC followed 42 days later by MMRV (MenC group). Blood samples were collected before and 43 days after vaccination. Antibody titers against MMRV were measured using ELISA. Functional-anti-meningococcal-serogroup activity (rSBAMenC) was assessed using a serum bactericidal test. Solicited local and general reactions were recorded for up to 4 and 42 days post-vaccination, respectively. Non-inferiority of MMRV + MenC to MMRV (post-dose-1 seroconversion rates) and MMRV + MenC to MenC (post-dose-1 seroprotection rates) was achieved if the lower limit (LL) of the 95% confidence interval (CI) for the group difference was ⩾−10% for each antigen.Results716 subjects were enrolled in the study. At 42 days post-vaccination, the MMRV seroconversion rates were 99.3% (measles), 94.5% (mumps), 100% (rubella) and 99.7% (varicella) in the MMRV + MenC group, and 99.4%, 93.2%, 100% and 100%, respectively, in the MMRV group. The seroprotection rates against rSBA-MenC were 98.3% in the MMRV + MenC group and 99.3% in the MenC group. Non-inferiority was reached for all the vaccine antigens. The safety profiles were as expected for these vaccines.ConclusionThe immune responses elicited by co-administered MMRV + MenC were non-inferior to those elicited by MMRV or MenC alone and support vaccination of children with both vaccines at a single visit.Clinical Trials registration: NCT01506193.     

Decline of varicella vaccination in German surveillance regions after recommendation of separate first-dose vaccination for varicella and measles–mumps–rubella

Background

Germany introduced routine varicella (V) vaccination in 2004. Due to a slightly increased risk of febrile convulsions after first-dose application of combined measles–mumps–rubella–varicella (MMRV) vaccine separate first-dose vaccinations with MMR and monovalent V vaccine were recommended in September 2011.

Methods

We compared V and MMR vaccinations in paediatric practices from two surveillance regions (Munich and Würzburg) one year before and after the change in the recommendation.

Results

A total of 1405/326 monthly reports were provided by a monthly average of 79/14 practices participating in Munich/Würzburg. V first-dose vaccinations (monovalent V or MMRV vaccine) declined by 12% in Munich (from 10.1 to 8.9 vaccinations per month and practice; p < 0.005) and by 4% in Würzburg (from 9.9 to 9.5; p = 0.620), respectively. First-dose vaccinations for MMR (MMR or MMRV vaccine) did not change significantly in both regions.

Conclusion

Acceptance of V vaccination depends in part on the use of combination vaccine.     

Febrile seizures following measles and varicella vaccines in young children in Australia

BackgroundFebrile seizures (FS) are common in childhood with incidence peaking in the second year of life when measles and varicella-containing vaccines are administered. This study aimed to examine the vaccine-attributable risk of FS following separate administration of MMR and monovalent varicella vaccines (VV) prior to a planned change to MMRV as the second dose of measles-containing vaccine at 18 months of age.MethodsAll FS cases in children aged <5 years from 1st January 2012 to 30th April 2013 were identified from emergency department (ED) and inpatient databases at five Australian tertiary paediatric hospitals participating in PAEDS (Paediatric Active Enhanced Disease Surveillance). Immunization records were obtained from the Australian Childhood Immunization Register (ACIR). The relative incidence (RI) of FS following MMR dose 1 (MMR1) and VV in children aged 11–23 months was determined using the self-controlled case series (SCCS) method and used to calculate attributable risk.ResultsThere were 2013 FS episodes in 1761 children. The peak age at FS was 18 months. The risk of FS was significantly increased 5–12 days post receipt of MMR1 at 12 months (RI = 1.9 [95% CI: 1.3–2.9]), but not after VV at 18 months (RI = 0.6 [95% CI: 0.3–1.2]. The estimated excess annual number of FS post MMR1 was 24 per 100,000 vaccinated children aged 11–23 months (95% CI = 7–49 cases per 100,000) or 1 per 4167 doses.ConclusionsOur study detected the expected increased FS risk post MMR1 vaccine at 12 months, but monovalent varicella vaccine at age 18 months was not associated with increased risk of FS. This provides baseline data to assess the risk of FS post MMRV, introduced in Australia as the second dose of measles-containing vaccine at 18 months of age in July 2013.     

Simultaneous vaccination with MMR and DTaP-IPV-Hib and rate of hospital admissions with any infections: A nationwide register based cohort study

BackgroundIn Denmark, live measles, mumps, and rubella vaccine (MMR) is associated with a reduced risk of infectious disease admissions, particularly for lower respiratory tract infections. In low-income countries, simultaneous vaccination (i.e. vaccination at the same visit) with live and inactivated vaccines may increase child mortality compared with the live vaccine alone. We examined the hypothesis that simultaneous administration of MMR and the inactivated DTaP-IPV-Hib vaccine compared with MMR alone is associated with higher incidence of infectious disease admissions.MethodsNationwide, retrospective, register based cohort study of 520,859 children born in Denmark 1997–2006, who were followed from 15 months to 4 years of age. Incidence rate ratios (IRRs) of hospital admissions were estimated by Cox regression and adjusted for background factors including exact age.ResultsBy 2 years of age, 4965 children had simultaneous MMR and DTaP-IPV-Hib as their most recent vaccination. Compared with MMR alone, simultaneous administration was associated with a higher rate of lower respiratory tract infections (adjusted incidence rate ratio (IRR), 1.27; 95% confidence interval (CI), 1.13–1.42). There was no effect on other infections. Overall, simultaneous administration was associated with a 7% (95% CI, 0–15%) increase in infectious disease admissions.ConclusionsSimultaneous administration of MMR and DTaP-IPV-Hib compared with MMR alone may increase the rate of hospital admissions related to lower respiratory tract infections. These findings require replication in other high-income settings.     

Provider response and follow-up to parental declination of HPV vaccination

ObjectiveParents often decline HPV vaccination, but little is known about how healthcare providers should promote vaccination at a later visit for secondary acceptance. We examined the associations of two factors, providers’ response to declination during the visit and follow-up after the visit, with secondary acceptance.MethodsWe conducted a cross-sectional survey of US parents whose 9- to 17-year-old child had not yet completed the HPV vaccination series. Parents who declined HPV vaccination during an initial discussion with a provider (n = 447) reported whether their provider engaged in any active response during the visit (e.g., giving information, trying to change their mind) or any follow-up after the visit (e.g., scheduling another visit). We conducted multivariable logistic regression to determine whether an active response or follow-up was associated with secondary acceptance of HPV vaccination.ResultsOnly about one-third of parents reported an active response during the visit (35%) or follow-up after the visit (39%) following HPV vaccination declination. Parents had higher odds of secondary acceptance of HPV vaccine if they received any provider follow-up after the visit (43% vs. 20%, aOR:3.19; 95% CI:2.00:5.07). Receipt of an active provider response was not associated with secondary acceptance. More parents thought a provider should actively respond and follow-up (61% and 68% respectively), compared with those who received such a response (both p < .01).ConclusionsProviders’ follow-up after the visit may be important for promoting secondary acceptance of HPV vaccination. Parents who decline HPV vaccination often prefer to receive an active response or follow-up from a provider.     

Parental preferences for HPV vaccination in junior middle school girls in China: A discrete choice experiment

BackgroundCervical cancer is the second most common cancer in Chinese women. Human papillomavirus (HPV) vaccines have not yet been introduced in the Chinese national immunization program, and people vaccinate voluntarily at their own expense. Therefore, it is important to study the factors that could impact parents' decisions for HPV vaccination.ObjectiveTo quantify parental preferences regarding HPV vaccination for junior middle school-aged girls.MethodA discrete choice experiment (DCE) survey was conducted to assess parents' preferences for HPV vaccines. Data were collected from parents of girls aged 12–16 years in 11 middle schools of Shandong Province. We evaluated preferences for five attributes of HPV vaccination (vaccine effectiveness, protection duration, risk of side effects, cost, and vaccination location). Conditional logit regressions were adopted for analyses.Results995 parents completed valid DCE questions. All attributes influenced parents’ willingness to vaccinate. Comparatively highly educated parents preferred more on higher vaccine effectiveness and lower side effects risks while more intended to accept higher prices. Parents were willing to trade 2326.32 CNY for an increase in HPV vaccine effectiveness from 50% to 90%. Nearly 70% percent of the respondents were predicted to prefer multiple improvements in HPV vaccination (protection increased from 70% to 95%, duration increased from 9 years to 15 years, and vaccination location changed from vaccination center to school) to the base case.ConclusionVarious vaccine characteristics and implementation strategies influence respondents’ preferences. Health education with evidence-based information about HPV vaccines would help parents make informed decisions. The findings can also assist agencies responsible for HPV vaccination implementation and cervical cancer prevention in China in decisions regarding vaccination financing and vaccine approval.     

Association of parent influenza vaccination and early childhood vaccinations using linked electronic health record data

IntroductionParent and child vaccination behavior is related for human papillomavirus (HPV) and flu vaccine. Thus, it is likely that parental vaccination status is also associated with their children’s adherence to guideline-concordant childhood vaccination schedules. We hypothesized that parent influenza (flu) vaccination would be associated with their child’s vaccination status at age two.MethodsWe used electronic health record data to identify children and linked parents seen in a community health center (CHC) within the OCHIN network (292 CHCs in 16 states). We randomly selected a child aged <2 years with ≥1 ambulatory visit between 2009-2018.Employing a retrospective, cohort study design, we used general estimating equations logistic regression to estimate the odds of a child being up-to-date on vaccinations based on their linked parents’ flu vaccination status. We adjusted for relevant parent and child covariates and stratified by mother only, father only, and two-parent samples.ResultsThe study included 40,007 family-units: mother only = 35,444, father only = 2,784, and two parents = 1,779. A higher percentage of children were fully vaccinated if their parent or parents received a flu vaccine. Children in the two-parent sample whose parents both received a flu vaccine had more than twice the odds of being fully vaccinated, and two and a half times the odds of being fully vaccinated except flu vaccine compared to children with two parents who did not receive a flu vaccine (covariate-adjusted odds ratio [aOR] = 2.39, 95% CI = 1.67, 3.43 and aOR = 2.54, 95% CI = 1.54, 4.19, respectively).ConclusionsParent flu vaccination is associated with routine child vaccination. Future research is needed to understand if this relationship persists over time and in different settings.