Measles susceptibility of selected cohorts in EU countries

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1 Journal of Medical Sciences Volume 1 Issue 3 Research Article Open Access Measles susceptibility of selected cohorts in EU countries 1 Lucia Blazinska, Msc. 2 Martin Rusnak, prof., Dr., PhD. 3 Mark Steven Taylor, MSc., PhD. 4 Margareta Kacmarikova, PhD. Trnava University in Trnava, Faculty of Health Care and Social Work, Department of Public Health, Slovak Republic * Corresponding author: Lucia Blazinska, Msc., Faculty of Health Care and Social Work, Department of Public Health, Slovak Republic; blazinska.lucia@gmail.com Citation: Lucia Blazinska, Msc., (2018) Measles susceptibility of selected cohorts in EU countries: Nessa Journal Medical Sciences Received: 20 th March 2018 Accepted: 17 th April 2018 Published: 26 th April 2018 Copyright: 2018 Lucia Blazinska, Msc., This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Background: Susceptibility is one of the indicators affected potential measles outbreaks in countries. The aim of the study was to estimate the percentage of measles-susceptible individuals from birth cohorts controlled in in selected countries of the EU. The study assesses differences in measles incidence, and associations with the percentage of susceptible persons and selected factors like geographical differences or mandatory vaccination. Methods: Estimation of susceptibility focused on vaccination by the first dose of vaccine -MCV1. Data were obtained for 28 member countries of the EU, from Eurostat, WHO and UNICEF database and Health for All Database. Statistical environment R- project was used for processing data -Wilcoxon test, Kruskal-Wallis test and logistic regression with p<0.05. Results: The highest estimated percentage of susceptible individuals from verified birth cohorts was recorded in Malta (23.7 %), Austria (19.5 %), Ireland (15.4 %) and Italy (13.7 %). Median of arcsine transformed percentage was the highest in western countries of the EU (median: 17.5, p<0.05) and also the highest incidence in 2015 was recorded in western countries (3.05/ ). The countries with mandatory vaccination have lower percentage of people susceptible to measles (median: 10.9) in comparison with countries, where vaccination is recommended but not mandatory (median: 16.5, p<0.05). The countries with non-mandatory vaccination showed significantly higher incidence of measles (OR: 9.4, CI ( )), p<0.05. Conclusion: Susceptibility and measles incidence in countries is significantly influenced by mandatory vaccination. Keywords: susceptibility, measles, incidence, mandatory, vaccination Nessa Publishers Page 1

2 Introduction Measles can be best prevented by vaccination. More than % of a population must be vaccinated to establish stable herd immunity for the population preventing measles virus transmission and mediating protection for individuals who are not immune [1]. In several European nations less than 90 % of children have received at least 1 dose of a measles-containing vaccine [2]. There are also significant differences in vaccination coverage within countries, such as member of ethnic minority populations being less vaccinated than their neighbours [2]. Most high income countries aim to achieve coverage of at least 95 %, to minimize local transmission when cases are imported, and some mathematical models suggest that an even higher vaccination coverage rate of approximately 97 % required in some populations to achieve herd immunity against measles and protect small group of people, who are medically unable to be vaccinated [2]. Between 1 January and 31 December 2016, cases of measles were reported by 30 EU/EEA countries. Romania accounted for 42 % of all cases reported during this period. Twelve reporting countries had a notification rate above the elimination target (one case per million of population). The highest age- specific notification rate was observed in infants under one year of age (76.1 cases per million population), followed by children aged 1 4 years (55.3 cases per million population). Twenty eight percent of the cases were 20 years old [3]. It means that the last birth cohorts in countries are still in the highest risk of susceptibility and measles virus transmission. High rates of vaccination coverage in childhood are important indicators for public health. However, reaching and maintaining such a target is not always an easy task for public health institutions, and the spread of vaccine refusal and hesitancy is making this even harder [4]. Enforcing mandatory vaccinations is one of the strategies that some countries adopted and others are considering in order facing this issue. Depending on local legislations, legal consequences for those who do not accept the uptake can be very different, ranging from pecuniary penalties, to barriers to attending state schools [4]. Target groups for vaccination include children below one year, but also years adolescents and years adults. Measles is characterized by its high infectivity and it may represent a risk for transmission during mass gathering events. Younger populations meeting at events such as festivals can be a high risk setting [5]. Knowledge of how many people of these age groups are susceptible to measles may inform public health efforts in many countries. Nessa Publishers Page 2

3 Susceptibility to, and incidence of measles differs across EU member countries [6]. Some countries were deemed to be at risk of epidemics as a result of high susceptibility in children and also, in some cases, adults [7]. To measure progress towards elimination and to identify populations for vaccination campaigns, agegroup specific susceptibility targets were established that corresponded to an effective reproduction number less than one, and hence elimination [8,9]. These age-specific susceptibility levels could be estimated from high-quality historical vaccine coverage data (but only in populations with no measles transmission) or from population serological surveillance data [10]. Population susceptibility to measles is dependent on the uptake of MMR1 and MMR2, vaccine effectiveness, immunity as a result of prior infection and protection by maternal antibodies in infants. Therefore, using these factors, it is possible to estimate population susceptibility to measles using a well-defined formula [11]. The study focuses on estimating percentage of measles-susceptible individuals, based on historical vaccine coverage data from 20 years (in birth cohorts controlled in years of vaccine administration controls) from entire populations in EU member countries. The study also assesses differences in measles incidence associated with susceptibility, and factor of mandatory vaccination by country. Materials and Methods This cross-sectional study estimates susceptibility to measles in birth cohorts controlled between (in birth cohorts controlled in years of vaccine administration controls) across the countries of the EU according national vaccination coverage data. Susceptibility was estimated not from serologic surveys of countries, but only as a crude percentage of non-vaccinated population from the whole born cohort, based on records of vaccination coverage. This percentage was derived from publicly available vaccination rate data. Data were obtained for all 28 EU member countries. For calculation of the percentage of individuals susceptible to measles, it was necessary to gain data about population sizes for the years and vaccination coverage for these population age groups. Data concerning populations up to the age of 2 years was extracted from the Eurostat population database [12].The age of 2 years is usual used for vaccination administration control in countries after the first dose of MCV1. The percentage of measles-susceptible population was calculated based on information regarding the first dose of vaccine against measles (MCV1), for each country. Population covered by the first dose of MMR vaccine was considered as not susceptible. The susceptible population was considered as the percentages of birth cohorts without immunization. Data related to number of immune compromised persons form cohorts or seronegative population, were not taken into account. Nessa Publishers Page 3

4 Countries report their MMR vaccine coverage to the WHO and UNICEF according to a Joint Reporting Form and these data are publicly available through a centralized database [13]. Data were observed for the period for each country, except Croatia, where data was available only for Incidence of measles per during for each country was used from WHO, Health for All Database [14]. We obtained other geographical-related variables, i.e. the classification of the countries according to UN division [15]. The list classifies geographic regions as northern (Denmark, Estonia, Finland, Ireland, Latvia, Lithuania, Sweden, United Kingdom of Great Britain), southern (Croatia, Cyprus, Greece, Italy, Malta, Portugal, Slovenia, Spain), western (Austria, Belgium, France, Germany, Luxembourg, Netherlands), and eastern countries (Bulgaria, the Czech Republic, Hungary, Poland, Romania, Slovakia). According to this division we sought to identify any higher-risk area of the EU for spreading measles due to high susceptibility. The next variables were compulsory immunization if MMR/MCV1 vaccination is mandatory or merely recommended according to VENICE survey [16, 17]. Statistical environment R- project [18] was used for processing data. Wilcoxon test and Kruskal-Wallis test with p<0.05 were selected to analyze statistical differences between variables. Differences concerning the percentage of susceptible individuals in countries we used arcsine transformation according Zar's methodology [19], where each proportion from binomial distribution was in square root transformed to its arcsine. These values were closely aligned to normal distribution and comparison of medians was measured in degrees. Assessment of significant dependency of variables has been done by linear regression. Odds Ratio (OR) with confidence intervals was computed by logistic regression. Results In terms of estimation susceptible population in birth cohort controlled in were used population in two years and. Estimated susceptibility (in birth cohort from ), based on the vaccination rate for the first dose of MMR/MCV1 is compared to average incidence from for each country (Figure 1). Nessa Publishers Page 4

5 Malta Austria Ireland Italy Cyprus Belgium United Kingdom (the) Denmark Germany France Estonia Greece Slovenia Bulgaria Latvia Portugal Luxembourg Romania Croatia Spain Netherlands (the) Sweden Lithuania Finland Poland Czech Republic (the) Slovakia Hungary ,06- value exceeds axis % of susceptible, Average incidence per , *Croatia - data available only for Figure 1: Estimated percentage of susceptible to measles from birth cohorts uptake in , and the average measles incidence during The highest estimated percentage of susceptible individuals was recorded in Malta (23.7 %), Austria (19.5 %), Ireland (15.4 %) and Italy (13.7 %). Seventeen countries from 28 show population susceptibility for measles of 5 % and over. The lowest percentage was found in Hungary (1 %) and Slovakia (1.5 %). Average incidence of measles for the last six years was highest in Bulgaria (49.06/ ), Romania (9.54/ ) and France (8.17/ ), and lowest in Slovakia, Hungary and Portugal. Countries with percentage of susceptible individuals over 5 % recorded a trend towards a higher value of average measles incidence (0.76/ ) in comparison with countries with percentage of susceptible 5 % and under (0.29/ ), but the difference was not significant (p>0.05). Nessa Publishers Page 5

6 The estimated percentage of the population susceptible to measles differs between countries from different regions of Europe (Figure 2). The highest median of arcsine transformed percentage to degrees was found in western countries of the EU (median: 17.5). For southern and northern countries the value is similar, at 4.3 % and in eastern countries the susceptible population was 9.2 %. There is a significant difference in medians between eastern and western regions, p<0.05. The incidence of measles in 2015 was also analysed by region. Regions ranked as they did for the susceptibility percentage, with the highest median of incidence was recorded in western countries (3.05/ ), then in southern (0.28/ ), northern (0.16/ ) and eastern (0) countries, but the results of a regression between susceptibility percentage and measles incidence were not significant (reg. coef. = 0.04; p>0.05). Figure 2: Estimated percentage of susceptible to measles from and measles incidence per in 2015 according regions Countries of the EU were divided into two groups in terms of compulsory immunization against measles. In those countries where vaccination is mandatory have a lower percentage of their population susceptible to measles in observed birth cohorts (median of transformed percentage: 10.9) when compared with countries where vaccination is only recommended (median of transformed percentage: 16.5) (Figure3). This difference is statistically significant, p<0.05. Significant differences were also found in measles incidence according compulsory immunization. Countries with mandatory vaccination recorded a median incidence of zero in 2015 and those with recommended vaccination showed an incidence of 0.22/ Nessa Publishers Page 6

7 Figure 3: Estimated percentage of susceptible to measles from and measles incidence per in 2015 according compulsory immunization Countries with non-mandatory vaccination MCV1 have a significantly higher incidence of measles in 2015 (OR: 9.4, CI ( )), p<0.05. Discussion The WHO European Region agreed to target the elimination of measles in Europe from The member states try to focus on ensuring the routine programme (high coverage > 95 %), undertaking catch-up campaigns to address older susceptible cohorts, strengthening surveillance through case-based reporting and laboratory confirmation of suspect cases, and improving communication about the benefits and risks of vaccination [20]. Measles infections in Europe are still causing illness and vaccine preventable deaths, and have implications regarding the global elimination goal. The increase in susceptible persons among older children and young adults, because of low coverage in the past and administration of only one measles vaccination in the past, and the decline in natural exposure to measles virus have resulted in an increase in the median age of measles patients in Europe [21]. Susceptible individuals and population groups need to be identified and catch-up vaccination programs are needed to close immunity gaps [22]. On the base of vaccination coverage it is possible to estimate susceptibility of a population to measles, and how this varies between countries. This paper provides an overview of measles susceptibility in EU member countries, using selected birth cohorts, and factors likely to affect susceptibility to and incidence of measles. Nessa Publishers Page 7

8 The results show that the highest percentages of populations without vaccination coverage in birth cohorts from (years of administration controls) were estimated in Malta (23.7 %), Austria (19.5 %), Ireland (15.4 %) and Italy (13.7 %). The average measles incidence from was highest in Bulgaria (49.06/ ), Romania (9.54/ ) and France (8.17/ ). One factor contributing to these differences may be endemicity of measles infection. Endemic countries for measles are: Belgium, France, Germany, Italy, Poland, Romania, Belgium, Bulgaria, Denmark, France, Germany, Italy, Poland and Romania [23]. Since Malta and Ireland don't belong to this group, the probability of spreading measles is lower despite of high percentage of susceptibility. According to a survey from 2008, four countries of European Region WHO (Australia, Israel, Lithuania and Malta) had susceptibility levels above WHO targets in some older age groups indicating possible gaps in protection [24]. Our results support this finding for Malta. The seroprevalence survey has also shown high susceptibility in several age groups for other countries. Coverage in Ireland was low in the five years up to 2001, below 90 % for the first dose. This lower coverage has only been a recent phenomenon in England and Wales, and to some extent in Ireland (which also has high susceptibility in adults), this probably reflects the impact of parental concern regarding the safety of MMR vaccine on uptake [25]. The next important question is if home doctors administration and notification of vaccinated individuals was correctly recorded in these countries, in the past. The European Sero-Epidemiology Network 2 (ESEN2) survey shows the most successful countries in measles elimination: Seven countries (Czech Republic, Hungary, Luxembourg, Spain, Slovakia, Slovenia and Sweden) met or came very close to the elimination targets [24]. This corresponds to our findings where Hungary, Slovakia, Czech Republic and Poland were found to have a very low percentage of susceptibility and incidence. When pockets of measles susceptibility are concentrated in the same geographical area or belong to the same population group, outbreaks may occur. The reasons for this accumulation can vary. They may include limited or difficult access to services for vulnerable or high-risk populations, cultural or religious beliefs, vaccine hesitancy due to vaccine safety concerns, and complacency whereby immunisation is considered a low priority with no real perceived risk of vaccine preventable diseases [26]. The results of our study illustrate differences in susceptibility in terms of geographical parts of the Europe. Western countries recorded the highest percentage of susceptible population accumulated between and also the highest measles incidence in 2015 in compare to countries of other European parts. These countries have recommended, but not mandatory vaccination. Mandatory vaccination may be considered as a way of improving the compliance to vaccination programmes. However, many programmes in Europe are effective even though voluntary [17]. Only eight countries have an established mandatory vaccination. In Nessa Publishers Page 8

9 these countries was estimated lower percentage of susceptible to measles in compare to countries, where vaccination is only recommended. Differences in susceptibility and incidence were significant. One of the most important findings was evidence, that countries without obligation to vaccine proved higher chance to record incidence of measles (OR:9.4, CI( )), p<0.05. Opinions on recommended or mandatory vaccinations are divided, and ethical issues are involved [27]. The issue of mandatory versus recommended vaccinations has been widely discussed in Europe. The situation might change over the coming years following the example of countries where high coverage is achieved, taking advantage of communication strategies and the awareness of the citizen of public health problems and solutions [17]. While many public health campaigners welcome the latest move to make several vaccines mandatory, some have questioned whether the health system is ready to meet the surge in demand that this may generate. Others worry that the move will generate resistance [28]. Measles outbreaks are influenced by a lot of factors, such as susceptibility in population, geography, duty to immunize or socioeconomic conditions in countries. To exceed a vaccination rate of 90 %, without regulation by law, is a challenge for the public health system. Measles outbreaks are more likely when this target is not met. For these reasons, additional efforts are necessary to increase vaccine acceptance [1]. Research is essential to identify additional tools and strategies to ensure sufficient vaccination rates and to avoid gaps in herd immunity [29]. We realize limitations of our study results. Our figures should be considered as an estimate of the susceptible population, because countries use different methodologies and definitions for assessing vaccination uptake, and direct comparisons of coverage between countries should be made with caution. Analyzing only 28 nations, with relatively few measles cases in any single country, leads to wide confidence intervals around our statistical results. Our study estimated susceptibility to measles partly in terms of the administration of the first dose MCV1, however, younger individuals who have received only 1 dose could be still susceptible to measles [30]. It is likely that the probability that these individuals will receive the second dose is higher. Also mobility of vaccinated population (i.e. those who may have emigrated since recommended vaccination age) is not taken into consider in this investigation, but we do not believe this movement is likely to bias the results. Conclusion Susceptibility of a population, based on the proportion of individuals who have not received immunisation, is one of the most important factors in the spread of measles infection. However, health legislation regarding mandatory immunization might be considered by more EU countries based on its apparent relationship with measles incidence. Elimination can be achieved only by suitable measures which are specific for an individual country with its own heterogeneous risk factors. Nessa Publishers Page 9

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