ABSTRACT
When the meningococcus B vaccine was introduced into Italy in 2017, it was recommended for newborns based on national epidemiological data indicating that they were at greater risk. However, the vaccination service of the local health authority of L'Aquila had already been receiving spontaneous parental requests to provide vaccination for children in lower-risk age groups from the beginning of 2016. We therefore decided to use a self-administered questionnaire in order to investigate the parents’ socio-demographic data; their children's history of other recommended vaccinations (against measles, mumps and rubella, varicella, meningococcus C and, for females, human papilloma virus); the information sources concerning meningococcal vaccination; and the timing of its administration.
The questionnaire was completed by 565 parents, and the results showed that the requests mainly came from the parents of children aged 5–11 years. The children whose mothers had received a high school education and were >35 years old were more likely to have received the first dose after the age of one year and to have perceived pain at the inoculation site, and less likely to have experienced mild general reactions. The requests were mainly trigged by the recommendations of healthcare professionals, and the overloading of the vaccination service led to delays in the administration of the doses after the first. The delays (reported by 74.07% of the parents) were mainly due to organisational problems in the service itself, which led 61.52% of the doses being more appropriately administered by staff working as private physicians inside public health facilities, albeit at extra cost.
These findings indicate that organisational factors and excessive demand had a considerable impact on both the efficacy of the immunisation and its appropriateness.
Introduction
Bacterial meningitis caused by Neisseria meningitidis is an important cause of morbidity and mortality. The main serogroups circulating in Europe are B (which accounts for 60–72% of cases and mainly affects children aged 0–5) and C (which is responsible for 16% of cases and mainly affects 25-44-year olds),Citation1-4 serogroup Y, which affects older subjects is less frequent.Citation3
In Italy, meningitis is reported by hospital discharge records (HDRs) and by Invasive Bacterial Disease (IBD) surveillance system. Between 2007 and 2012 a study carried out in two Italian regions found that 341 cases of IBDs of which 202 were of serogroup B.Citation5 In the same period in Italy the Istituto Superiore di Sanità (ISS, Italian National Health Institute) reported 991 cases IBDs, of which 455 were caused by serogroup B.Citation6 Overall, 81% of all cases of meningitis occurring during the first year of life are caused by serotype B,Citation6 and more than half occur in 4–8 months old infants.Citation7 Stefanelli reported that in children younger than 1 year an incidence of IMD (invasive meningococcal disease) was 10 times higher (3.6/100,000) than the population rate (0.28/100,000),Citation8 and serogroup B accounted for 65% of the cases. Recent data published by ISS show that 67 cases of serotype B were reported 2016,Citation9 with an incidence of 0.78/100,000 in children 0–4 years, and 0.11/100,000 in all age groups. However, underreporting can be as high as 23% as found by Neri,Citation10 and failure to identify the serogroup can reach 19% of cases (unkown serogroup).Citation9 As in 2016 when three cases of IMD due to N. meningitidis with an unspecified serogroup were reported in Abruzzo (0.23/100,000).Citation9
The Italian National Health Service (NHS) provides free of charge the vaccinations included in the vaccination schedule including Men B vaccine which was included in May 2017.
At the time of this survey, the meningococcus B (MenB) vaccination was not yet included in the schedule, thus 50% of the vaccine cost would be charged to anyone requesting vaccination according Abruzzo regional law.Citation11 Alternatively, they could choose to pay the total cost in order to access what is called the intramoenia regimen, which allows physicians to carry out their own freelance activities in public hospitals outside institutional hours, to avoid long waits due to high demand in the public services.
The Italian National Vaccination Prevention Plan (NVPP) 2017–2019.Citation12 approved by the Ministry of Health in February 2017, introduced free of charge MenB vaccinations with the following schedules: newborns should receive three initial doses at the ages of three, four and six months, with a fourth dose at the age of 13 months; infants aged >6 months should receive three doses, with the first two given at seven and nine months of age.
Although the low incidence of IMD, and the fact that the cost of vaccination would be substantial for parents as still not provided free of charge, the vaccination service of the local health authority of L'Aquila (ASL 01, Abruzzo, Italy) experienced an unexpected increase of the demand for MenB vaccination between the end of 2015 and the beginning of 2016.
We performed the present study to characterise the profile of the parents wishing to have their children vaccinated against meningococcus B, (4CMenB; Bexsero), their sources of information, and their compliance to other recommended vaccinations as measles, rubella and mumps, Varicella MenC, HPV for adolescents girls.
Results
The investigation lasted seven months, during which we interviewed the children's parents after having administered 4CMen B vaccinations. Out of 600 questionnaires administered, 565 were considered valid for the analysis. As showed in the valid questionnaires were compiled mainly by the mothers (78.33%) than the fathers (21.67%) in great majority of Italian nationality (94.34% of mothers and 98.05% of fathers); the majority was older than 35 years, and mothers had higher education than fathers (55.22% and 33.27% had a university degree, respectively). More men than women were employed (94.66% vs 78.47%), and 1.78% and 5.34% of these worked in the healthcare sector, respectively. The gender distribution of their children was 52.39% of males and 47.61% of females. Their age group was distributed as follows: 42.30% were 5–11 years, 33.27% aged 1–4 years, 15.22% aged ≥12 years, and 9.20% aged <1 year.
Table 1. Characteristics of the parents and children.
shows the ages of the children receiving the first dose MenB vaccine, the timing of the administrations, and the reasons for not respecting the recommended timing. Of the 565 children receiving the vaccination, 40.18% were aged 5–11 years, 25.84% were aged 1–4 years, 19.82% were aged <1 year, and 14.16% were aged ≥12 years. The results VAS showed that the mother's opinion weighed “a great deal” more frequently than that of the father (83.96% vs 69.98%) (data not shown).
Table 2. Age ranges of the children receiving MenB vaccination, the timing of its administration, and reasons for any delays
The time between the first and second dose was 3–6 months in 55.15% of cases, two months in 38.18%, and more than seven months in 6.67%, and the time between the second and third dose (among those who needed it) was 2–6 months in 42.59% of cases, 7–12 months in 33.33%, and >12 months in 24.07%. The main reason for the delays in administering the doses after the first (74.07% of cases) was the timing imposed by the vaccination service, followed by delays due to illness of the child (19.87%), and other reasons (6.06%).
shows the organisational regimen under which the vaccination was administered (ordinary or intramoenia). It can be seen that the parents of newborns aged <1 year more frequently used the ordinary regimen (30.72%), whereas those of the children aged >5 years more often had recourse to the intramoenia regimen (73.73%). The time between the first and second dose was respected more frequently by the parents who paid for the administration (60.19% vs 27.48%), whereas intervals of >3 months were more frequent under the ordinary regimen (72.52% vs 39.82%). There were therefore significant differences between the two regimens in terms of the children's age (p<0.001) and the time interval between the two vaccine doses (p<0.001).
Table 3. Percentage distribution of MenB vaccine by children's age, and the timing and organisational type of administration
compares the parents’ socio-demographic characteristics and their information sources, and the side effects of Men B vaccination in the children who received their first vaccine dose in the first year of life (group A) and those who received it later (group B). There was a statistically significant between-group difference in the percentage of mothers and fathers aged >35 years (50.00% vs 82.56%; p<0.001), and (66.96% vs 88.52%; p<0.001). The percentage of mothers with a university degree was higher in group A (68.75% vs 51.88) and, although the percentage of fathers with a degree was similar in the two groups, the frequency of fathers with a medium-low level of education was lower in group A. The percentage of mothers who were healthcare workers was significantly higher in group A (21.62% vs 14.86%; p = 0.002). There were also significant between-group differences in the side effects reported after the vaccination: pain at the inoculation site (p<0.001) and functional impotence (p = 0.002) were most frequently reported in group B, whereas mild general reactions were more frequent in group A (p<0.001). Finally, the sources of information regarding MenB vaccinations were more frequently institutional in group A (p = 0.018).
Table 4. Comparison of the parents’ socio-demographic characteristics, their sources of information, and the reactions to MenB vaccination in the group of children who received the first vaccine dose in their first year of life (group A) and those who received it later (group B)
Multiple logistic regression analysis () showed that the children with mothers aged 31–35 years (OR 7.38, 95% CI 1.83-29.87; p = 0.005) and >35 years (OR 32.80, 95% CI 7.17-50.05; p<0.001), and those whose mothers had had a high school education (OR 3.72, 95% CI 1.73-8.03; p = 0.001) were at higher risk of receiving their first MenB dose after the age of one year, whereas children with fathers aged >35 years were at lower risk of receiving their first MenB dose after the age of one year (OR 0.17, 95% CI 0.03-0.92; p = 0.040).
Table 5. Multivariate logistic regression analysis of the factors associated with receiving the first dose of Men B vaccination after the age of one year
The children who received their first vaccine dose after the age of one year were more likely to have perceived pain at the inoculation site (OR 4.82, 95% CI 1.99-11.70; p = 0.001), and less likely to have experienced mild general reactions (OR 0.32, 95% CI 0.14-0.72; p = 0.006).
With the aim of assessing compliance to the use of vaccinations in general, we investigated the self-reported adherence to the other recommended vaccinations. The results indicated 99.80% adherence for MMR, 65.74% for varicella, 92.83% for Men C, and 72.60% for HPV (girls only) Two of the main reasons for non-adherence to varicella vaccinations were its high cost (20.81%) and the fact that it was not considered necessary (16.77%).
Discussion
This study was carried out in response to an unusually high parental demand for MenB vaccination in 2016. Although only three cases of IMD had occurred in our region,Citation9 none of which involved our local health authority, the unexpected demand for vaccination prompted us to investigate the profile of the parents who spontaneously requested the vaccination, their sources of information, and whether they had adhered to the other recommended childhood vaccinations. The results of our study showed that the demand for vaccination with MenB vaccine mainly concerned children aged 5–11 years (42% of the sample), whereas those aged <1 year, considered to be at highest risk, accounted for only 9% of the total.
The choice of vaccination was most likely motivated by the parents’ perception of the severity of meningitis as almost all of them answered the specific question affirmatively, with the mothers’ opinions more prevalent in the determining the request than those of the fathers (83.96% vs 69.98%). It is also possible that the many cases of meningitis caused by meningococcus C reported in Italy in 2016 prompted the parents to immunise their children also against meningococcus B.Citation9
The parents participating in this study showed a positive attitude towards vaccination in general, as demonstrated by the high rate of immunisation against MMR, meningococcus C, varicella and HPV that were higher than the national and regional averages.Citation13,Citation14,Citation15,Citation16,Citation17 HPV coverage was higher than that. The most frequent time interval between the first and second dose of MenB vaccine was 3–6 months (up to seven months in some cases), and about 47% of the newborns were not immunised within the recommended.Citation12 A number of studies have found that there is a more or less marked, dose-related decrease in the persistence of antibody titles in adolescents after six months,Citation18,Citation19 in adults after 12 monthsCitation20 and in newborns and infants up to the age of two years.Citation21-24 A large proportion of parents (74.07%) reported that the delays were mainly due to the organisational needs of the vaccination service, in fact more than half of the vaccinations (61.52%) were given under the intramoenia regimen in an attempt to overcome the long waiting times in ordinary regimen.
We therefore considered the type of administration regimen (ordinary or intramoenia) in relation to the children's age and the time interval between the first and second dose, and found some significant differences. The time between the first two doses was longer under the ordinary regimen than with the intramoenia regimen (72.52% vs 39.82%). It can therefore be said that the vaccination health service satisfied the requests of parents whose children were aged <1 year by postponing the vaccination of older children, whose parents resorted to the intramoenia regimen even though their children were not at risk.
MenB vaccinations were first authorised in Italy in 2015 but, before they were included in the free-of-charge NVPP in 2017, it was necessary to pay in order ensure regular scheduled immunisation. As the age of the children at the time of the first dose varied, we investigated the difference between those who received it during the first year of life (group A) and those who received it later (group B) in terms of their parents’ socio-demographic characteristics and sources of information, and the side effects of the vaccinations on the children. Both parents of the children in group A were younger and had a higher educational level than those of the children in group B, and a higher proportion of the mothers worked in the healthcare sector. Mothers with a university education were well represented in both groups, which contrasts with the finding of MameliCitation26 and AnelloCitation27 that a willingness to have children vaccinated inversely correlates with their parents’ educational level but is in line with those of Morrone.Citation15 Comparison of the adverse effects reported by the parents showed that the children in group B significantly more frequently experienced pain with functional impotence and pain at the inoculation site, whereas those in group A more frequently experienced mild general reactions such as restlessness, fever, headache and diarrhea. These findings are in line with those of many studies of MenBCitation21,Citation28,Citation29 and other vaccinationsCitation30-32 and indicate that the onset of adverse events is age related. No serious side effects were reported.
There was also a statistically significant between-group difference in the parents’ sources of information. As found in other studies,Citation26,Citation33-36 the main source was healthcare professionals. The willingness to bear 50% of the cost of the vaccine (€ 82.00 a dose) is in line with data showing that parents are prepared to pay in order to ensure the immunisation of their children.Citation37
It can therefore be seen that these parents were well disposed to vaccination protection, sensitive to indications of healthcare professionals, and free of economic and organisational problems. Under such favourable conditions, the appropriateness and efficacy of vaccinations for the people involved and society as a whole is in the responsibility of public healthcare services and healthcare professionals.
The present study has some limitations. First of all, we could not evaluate the differences in opinions between the fathers who were alone and those who were with mothers at the moment of vaccination because the questionnaire was distributed at the time of vaccination when only one parent is present and was returned after the 20-minute period needed to observe possible acute adverse events. Secondly, given the recent introduction of MenB vaccination, it was difficult to compare our findings with those of others because of the lack of similar studies in Italy. The only data accessible to us came from the Ministry of Health and related to coverage in 2014 cohort,Citation13 which showed that coverage in Abruzzo was below the national average. Thirdly, our findings relate to a specific group of people who spontaneously requested the MenB vaccination before it was introduced into the childhood immunisation schedule, and so our data may not apply to the general population. Finally, as more than 60% of the parents opted for the intramoenia regimen, the economic factor might be a bias.
Conclusions
The introduction of a new vaccine is generally accompanied by an analysis of epidemiological data, the impact of the vaccination on health, and the cost/benefit ratio. The incidence of meningococcus B is low in Italy (and in Abruzzo), and the many studies of the vaccination's cost/benefit ratio (including direct and indirect costs, and the reduction in disease-related costs) agree in concluding that, when the incidence of the disease is low, the vaccination is good value for money only if it is cheapCitation38-40 and if the children are <1 year old.Citation41 All of this was confirmed by the recent Ministry of Health decree recommending MenB vaccinations only for children in their first year of life. It can therefore be said that the high level of parental compliance generated by the advice of pediatricians and GPs revealed in this study is not supported by epidemiological evidence or economic analyses. The willingness to bear half of the cost of the vaccine does not justify its inappropriate administration insofar as part of the cost is borne by the National Health Service. Furthermore, having recourse to the intramoenia regimen does not assure the equity underlying Italian healthcare. The failure to respect the administration schedule of a newly introduced vaccine whose medium- and long-term efficacy had not been defined may also have led to an inadequate level of protection. Our findings suggest that organisational factors had a determining impact on the efficacy of the immunisation: the vaccination service was overwhelmed by the excessive demand encouraged by the favourable attitude of pediatricians and responded in a manner that was inconsistent with the criteria of appropriateness. However, it is comforting that the opinions of pediatricians and GPs were considered important or very important in favouring compliance, and they should be involved in the implementation of any new vaccine in order to better adherence (see varicella coverage).
Methods
This was a study including 600 parents who spontaneously attended the Vaccination Service of the Department of Prevention of the local health authority (ASL 01) in L'Aquila, Abruzzo, Italy to have their children vaccinated against MenB and was conducted between April and November 2016. The study was approved by the Ethics Committee of ASL 01. A questionnaire was administered to each parent included into the study and asked to be compiled in anonymous way. The questionnaire was adapted from a template previously used in other studiesCitation42 and before study start was validated with a sample of 25 parents. The test-retest results indicated a Cohen kappa coefficient of 0.92.
The items were designed to investigate the parents’ socio-demographic characteristics (age, nationality, education level and employment status), the characteristics of the children receiving the vaccination (sex, age, and condition at birth), parental adhesion to other recommended vaccinations, and the reasons for any non-adhesion, the sources of information concerning MenB vaccination, the timing of its administration, and any adverse events related to its administration. The visual analogue scale (VAS) ranging from “not at all” to a “a great deal” used to answer the question “How much did the opinion of the mother and father weigh on the decision to have the MenB vaccination administered?” was used. Every questionnaire was accompanied by a description of the design and purpose of the study, and an informed consent form.
Statistical analysis
Descriptive statistics were used to describe the socio-demographic characteristics of the parents and children. Percentage adhesion to the main vaccinations recommended for childhood and reasons for any non-adherence were calculated, as was the age distribution of the children receiving the vaccine. A record was also made of the timing of its administration and the reasons for any delays.
The sample was divided into two groups: one consisting of the children who started receiving the vaccination at an age of <1 year, when the incidence of the disease is greatest (group A), and the other of the children who started receiving the vaccination after the age of one year (group B). The two groups were compared in terms of their socio-demographic characteristics, the sources of information concerning MenB vaccination, and the adverse reactions occurring after its administration. The statistical significance of the differences in frequency distributions between the two groups were analysed using the χ2 or Fisher's exact test, with a 5% level of significance. Backward stepwise selection using the Akaike information criterion (AIC) was used for the multiple logistic regression analysis of the factors associated with receiving the first dose of Men B vaccination after the recommended age of one year, which are reported as odds ratios (ORs) with their 95% confidence intervals (95% CIs). The analyses were made using the STATA/IC12.0 statistical package.
Disclosure of potential conflicts of interest
No potential conflicts of interest were disclosed.
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