Invasive meningococcal disease is an important public health problem since, while its incidence is fortunately low, it is associated with a high fatality rate (10%) and a high probability of severe long-term sequelae.1–3

The causative agent is Neisseria meningitidis, commonly known as meningococcus, a gram-negative diplococcus whose polysaccharide capsule allows differentiation of up to 13 serogroups, of which 6 cause nearly 100% of cases of invasive meningococcal disease: serogroups A, B, C, W, X and Y.1–3 Among them, serogroup B (MenB) is the one that has caused the most cases in Spain overall and in the Community of Madrid in particular in the past two decades.4,5

Vaccination is the main preventive strategy against this disease available to us.1–3 The lifetime vaccination schedule proposed by the Interterritorial Council of the National Health System (ICNHS) calls for administration of the meningococcal C vaccine, first introduced in 2000, at 4 and 12 months post birth, and administration of the quadrivalent vaccine against serogroups A, C, W and Y, introduced in 2019, at age 12 years, in addition to catch-up vaccination through age 18 years.6 Since 2015,7,8 the Advisory Committee on Vaccines of the Asociación Española de Pediatría (Spanish Association of Pediatrics) recommends vaccination of infants against meningococcal group B disease, and routine vaccination of all infants with meningococcal B vaccine has been included in the publicly funded lifetime vaccination schedule of the national health system.6

The vaccine recently introduced in the vaccination schedule is 4CMenB, a protein-based vaccine that includes 4 subcapsular components.9 It was approved by the European Medicines Agency in 2013 for use from age 2 months.10 In recent years, several studies have been published estimating a high vaccine efficacy and effectiveness in different care settings in the United Kingdom,11 Portugal12 or Canada.13 In 2021, a nationwide case-control study conducted in Spain was published that reported an effectiveness of 73% in individuals who had completed the vaccination series in the past year and 97% in fully vaccinated infants aged less than 1 year.14 The vaccine has proven safe.9 The economic evaluation conducted in relation to its inclusion in the routine childhood vaccination schedule of Spain has been unfavourable to date.15,16 Although previous evaluations carried out by the Working Group of the Advisory Body on Vaccines of the National Health System resulted in the decision not to include this vaccine in the immunization schedule based on the current epidemiological trends,17 the regional governments of some of the autonomous communities, including Canary Islands,18 Castilla y León,19 Andalusia20 and Catalonia,21 decided to include it between years 2019 and 2022. In the last trimester of 2022, in light of the recent scientific evidence on its effectiveness in Spain, the Working Group on MenB of the Advisory Body on Vaccination Programmes and Records carried out a new evaluation regarding the inclusion of this vaccine in the lifetime vaccination schedule of the National Health System, resulting in the approval by the ICNHS of its introduction in the 2023 schedule as a series of 3 doses given at ages 2, 4 and 12 months.16

The availability of the vaccine and the recommendation of its administration by paediatricians (to be paid by the user) in the years prior to its introduction in the routine vaccination schedule of the ICNHS allowed us to assess, on one hand, the acceptability of this vaccine in the population and, on the other, the potential association between vaccination and socioeconomic status in the Community of Madrid during this period. These two factors are important ethical aspects to take into account in the evaluation of potential changes to the immunization schedule22 and, in fact, the findings of the study presented in this article supported the decision to include this vaccine in the schedule. The effectiveness criterion, in addition to other aspects that were discussed in light of the findings of our study, took precedence over economic considerations in this decision.

Thus, the aim of our study was, on one hand, to determine the meningococcal B vaccine coverage in children born between 2016 and 2019 in the Community of Madrid and to assess the association between vaccination coverage and the and the deprivation index (DI) in each basic health zone (BHZ, the smallest administrative division in the public health system) in the period preceding the inclusion of the vaccine in the routine vaccination schedule.

Given the characteristics of the study, it was not possible to obtain informed consent from the included subjects. All the data were retrieved from population databases and had been anonymised, and it was handled confidentially and in adherence with current personal data protection regulations and the working protocol of the Directorate General of Public Health; therefore, since the study was conducted within the framework of the use of population data for public health purposes, it did not require evaluation by an ethics committee.

The study universe amounted to 232 901 children.

Over the study period, the MenB1d vaccination coverage was 58.65%, increasing over time from 47% of children born in 2016 to 71% of children born in 2019. The overall MenB2d vaccination coverage was 55.83% for the study period, increasing from 44% in the 2016 birth cohort to 68% in the 2019 cohort. The overall MenB3d vaccination coverage was 41.64% overall, increasing from 25% in the 2016 cohort to 56% in the 2019 cohort (Fig. 1).

Figure 1.

Vaccination coverage in the total study period and temporal trends (by birth cohort): MenB1d (a), MenB2d (b) and MenB3d (c).

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In the analysis of the factors associated with vaccination status, we found a statistically significant association between vaccination status and DI. The probability of being vaccinated in children who lived in BHZs above the last quintile (DI5) was 62% smaller for the primary series (MenB2d adjusted OR, 0.38; 95% CI, 0.37−0.39; P<.001) and 51% smaller for full vaccination (MenB3d adjusted OR, 0.49; 95% CI, 0.47−0.50; P<.001) compared to children living in BHZs below the first DI quintile (DI1), independently of sex and country of origin. We also found significant differences in the probability of being vaccinated based on the country of origin, with a substantially lower coverage in children of immigrant origin compared to children of Spanish descent. We did not find statistically significant differences in the probability of being vaccinated based on sex (Table 1).

Figs. 2 and 3 present the spatial distribution of DI and the MenB2d and MenB3d coverage by BHZ. They show significant heterogeneity between BHZs, especially within the city of Madrid, although there is a predominance of a high DI and low vaccination coverage in the southern area of the city in addition to the south and southwest areas of the Community of Madrid.

Figure 2.

Spatial distribution of the deprivation index by basic health zone in the Community of Madrid.

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Figure 3.

Spatial distribution of vaccination coverage by basic health zone in the Community of Madrid: MenB2d (a) and MenB3d (b).

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After spatial smoothing (Figs. 4 and 5), the distribution patterns emerge more clearly: low DIs and high vaccination coverage rates can be seen in the northern area of the city of Madrid and the municipalities north of the city, and high DIs and low vaccination coverage rates in the southern area of the city and the periphery of the Community of Madrid, chiefly in the south and south-west.

Figure 4.

Smoothed spatial distribution of the deprivation index by basic health zone in the Community of Madrid.

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Figure 5.

Smoothed spatial distribution of vaccination coverage by basic health zone in the Community of Madrid: MenB2d (a) and MenB3d (b).

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The exploratory spatial analysis showed a moderate spatial autocorrelation in vaccination coverage, both for the MenB2d (Moran I, 0.297) and the MenB3d (Moran I, 0.225). In the LISA cluster analysis, we found 39 BHZs with a high MenB2d vaccination coverage and 24 with a high MenB3d coverage surrounded by other BHZs with high vaccination coverages, chiefly in the northern part of the city of Madrid and municipalities north of the city. There were also 31 BHZs with a low MenB2d coverage and 24 BHZs with a low MenB3d coverage surrounded by other BHZs with low vaccination coverage in the southern part of the city of Madrid in addition to the southern and southwestern areas of the Community of Madrid (Fig. 6).

Figure 6.

Cluster analysis of vaccination coverage with local indicators of spatial association (LISA): MenB2d (a) and MenB3d (b).

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We found a moderate inverse correlation between DI and vaccination coverage within BHZs both for the MenB2d (R2=0.464) as well as the MenB3d (R2=0.33) (Fig. 7).

Figure 7.

Scatterplots of the association between the deprivation index and vaccination coverage in the basic health zones of the Community of Madrid: MenB2d (a) and MenB3d (b).

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The spatial regression analysis showed that for each point the DI of a BHZ increased, the MenB2d vaccination coverage decreased by 7.31% (P<.001) and the MenB3d coverage by 5.44% (P<.001), accounting for spatial effects.

Vaccination against meningococcal disease is an important public health strategy whose implementation must be guaranteed. Our study shows that in the years preceding the introduction of the MenB vaccine in the vaccination schedule of the ICNHS, the vaccination coverage in the paediatric population of the Community of Madrid exceeded the coverage predicted on account of it not being included in the official vaccination schedule, in addition to exhibiting an increasing trend. This reflects not only that the vaccine was acceptable to the population, but that there was an increasing demand for it.

Based on the current evidence, one of the main factors contributing to the acceptability of the vaccine would be the recommendation by paediatricians,27 in addition to parental perceptions regarding the vulnerability of the infant to meningococcal disease.28 Many other aspects may be involved in the acceptability of the vaccine, including demographic, social, cultural and, needless to say, socioeconomic factors.27,28 It is reasonable to expect that the meningococcal B vaccination coverage, which, based on the findings of our study already neared 70% for primary vaccination in the 2019 cohort, will increase considerably after the introduction of the vaccine in the nationwide routine vaccination schedule. In fact, given that some autonomous communities in Spain included this vaccine in their vaccination schedules earlier on, regional data are already available: in Andalusia, where the vaccine was introduced in the 2021 schedule for infants born between October 2021 and March 2022, the primary vaccination coverage for this cohort reached 98%.29 We can also consider the data available for other vaccines. For example, the pneumococcal conjugate vaccine, recommended by paediatricians since it was authorised for distribution in Spain in 2001,30 but not introduced in the routine vaccination schedule of ICNHS until 2015.31 In the years before it was included in the official schedule, the vaccination coverage was low (around 46%),30 but once it was publicly funded, the coverage for primary vaccination reached 95% in the 2016 cohort and 97.7% in the 2017 cohort.32

Our study also contributes evidence of the association between socioeconomic status and vaccination against meningococcal B disease, revealing health inequality in the period preceding the inclusion of the vaccine in the routine schedule. Our findings showed that the probability of having completed the primary vaccination series against MenB was 62% lower in children residing in areas of lower socioeconomic status compared to children in areas of higher socioeconomic status. Studies in the international literature have reported similar findings. A study conducted in Japan in 2018 showed that the probability of vaccination against rotavirus (not publicly funded in the country) was 51% lower in children of low-income families.33 In 2013, Ganczak et al. reported that in Poland, children from families of high socioeconomic status were 3.46 times more likely to receive self-paid vaccines compared to children from families of low socioeconomic status.34

The conditions required to introduce changes to the vaccination schedule were established by the Advisory Body on Vaccination Programmes and Records in 2011. There are 5 criteria that, together, set a framework for the systematic analysis of the arguments in favour and against the implementation and prioritising of changes to the vaccination schedule: burden of disease, vaccine effectiveness and safety, repercussions of introducing the change to the vaccination schedule, ethical considerations and economic evaluation.22

The results of our study support the decision to include the meningococcal B vaccine in the routine lifetime vaccination schedule recommended for 2023 for ethical reasons in light of the potential repercussions of the decision,21 about which there used to be no evidence for the Madrid area.

Among the main limitations of the study, we ought to highlight both the exclusion of children vaccinated through health care systems other than the public health system of Madrid—amounting to 3% of the population, based on data from 202135,36―and the likely under-recording of vaccines not included in the routine schedule at the time of vaccination, due to which we may have underestimated vaccination coverages. On the other hand, since DI values were generated based on indicators from the 2011 census, it is possible that the DI data were outdated. Furthermore, since this was an ecological study, it is important to consider the bias that may result from it. The spatial analysis yielded findings for BHZs as a whole, and it is important not to make inferences regarding individual BHZs based on the resulting data to avoid ecological fallacy. Our study did not analyse how other sociocultural factors (religious, ideological…) may mediate the association between socioeconomic status and vaccination.

Reproducing this study would be useful to monitor inequality and to verify whether public funding of the vaccine increases access to it in the segments of the population with the lowest socioeconomic status, as expected. This would make it possible to assess the impact of the inclusion of this vaccine in the routine schedule in terms of health inequality.

This research did not receive any external funding.

The authors have no conflicts of interest to declare.