Is the current prevention strategy based on vaccination coverage and epidemiological surveillance sufficient to achieve measles and rubella elimination in Europe?

Abstract

Elimination of measles and rubella in Europe is a feasible objective, but it requires achieving a maintaining a high prevalence of protected individuals in order to prevent cases and outbreaks from imported cases. The epidemiology of measles and rubella in Europe in the period 2003–2013 suggests that we are far away from the elimination target for measles, while the situation is better for rubella. In this situation, a new preventive strategy based on serological surveillance systems should be developed in Europe in order to identify and immunise individuals in population groups without sufficient herd immunity against measles and rubella.

Keywords::

• Europe
• measles and rubella elimination
• preventive strategies
• epidemiology
• herd immunity

In 2010, the European region of the WHO renewed their commitment to the elimination of measles and rubella and the prevention of congenital rubella by the year 2015 [1,2]. Since 1985, great efforts have been made in Europe to eliminate measles and rubella, but cases and outbreaks of measles and rubella are still occurring [3]. The annual number of measles cases reported in Europe during the 2003–2013 period was >25,000 almost all years; and the number of confirmed cases of measles was >7000 since 2006 [4]. In 2013, 18,043 confirmed cases of measles were reported in Europe through the WHO Centralized Information System for Infectious Diseases (CISID) [4]. The annual number of rubella cases reported during the 2003–2013 period was <100 until 2007, but 22,391 cases were reported in 2012 and 778 cases in 2013 [4]. Is the current prevention strategy based on vaccination coverage and epidemiological surveillance sufficient to achieve measles and rubella elimination in Europe?

The elimination of measles and rubella in Europe is feasible for the following reasons: humans are the only reservoir for measles and rubella viruses; effective vaccines are available; highly sensitive and specific diagnostic tests are available; and efforts can be combined in order to eliminate measles and rubella. Nevertheless, several factors make measles and rubella elimination a difficult task. First, the measles-mumps-rubella (MMR) vaccination coverage during childhood (2 months–6 years) and/or the MMR vaccine effectiveness can be low in some population groups. Second, people carrying measles and rubella infections can propagate measles and rubella viruses within their countries and across Europe. Third, the lack of sufficient herd immunity in some population groups can generate new measles and rubella epidemics from imported cases [5,6].

The elimination target is defined as ‘the absence of endemic measles or rubella cases in a defined geographical area (European country or region within a country) for a period of at least 12 months, in the presence of a well-performing surveillance system’ [2,7]. Regional elimination can be declared after 36 or more months of the absence of endemic measles or rubella in all Member States (all European countries) [2,7]. Endemic transmission is defined as the continuous transmission of indigenous or imported measles and rubella viruses that persist for a period of 1 year or more in a defined geographical area [2]. Therefore, it implies the absence of endemic measles and rubella transmission, but it does not imply a zero incidence since indigenous cases can be generated by imported cases. The interruption of endemic measles and rubella transmission is a feasible objective, but it requires achieving and maintaining a high prevalence of protected individuals in order to prevent cases and outbreaks from imported cases [5].

In 1996, the European Commission funded the European Sero-Epidemiology Network (ESEN) with the aim to standardize the serological surveillance for vaccine-preventable diseases [8]. The ESEN2 project was established in 2001 to standardize the serological surveillance for MMR and other five vaccine-preventable diseases (pertussis, diphtheria, varicella, hepatitis A and hepatitis B) [8]. This involved the achieving comparability both in laboratory methods and results and sampling methodology in different countries. Standardization of enzyme-linked immunoassay results was achieved through the development of common panels of sera, and regression equations were used to standardize serological results [9]. The standard sampling method, however, was not the optimal one since serum samples were obtained by utilizing serum left over from specimens submitted to laboratories for diagnostic purposes [8,9]. The main reason for selecting this sampling method in the ESEN project was that population-based sampling is difficult and expensive, and informed consent must be obtained from participants. The ESEN project [10] evaluated progression toward measles elimination by comparing the proportion of seronegative in each country in 2001–2003 with the WHO elimination target of <15% in those aged 2–4 years, <10% in those aged 5–9 years and <5% in those aged 10–19, 20–29 and <39 years, showing that seven countries had a higher risk for measles outbreaks due to a >15% prevalence of seronegatives in children aged 2–4 years or >10% in those aged 5–9 years, three countries had an intermediate risk of outbreaks due to a >5% prevalence of seronegatives in adults and seven countries had a low risk due to a <15% prevalence of seronegatives in children aged 2–4 years and <10% in those aged 5–9 years [10]. Spain had a low risk for measles outbreaks in the ESEN study [10], but multiple outbreaks have occurred since 2003 [3,4]. The ESEN project [11] evaluated the risk of rubella outbreaks in Europe in 2001–2003, classifying European countries based on the prevalence of seronegative children aged 2–14 years in three groups: group I for <5% seronegative, group II for 5–10% seronegative and group III for >10% seronegative. The study found that four countries in group I, seven countries in group II and four countries in group III [11]. The ESEN project standardized serological results from different ELISA tests, but a consistent analysis of the risk of measles and rubella outbreaks requires to assess herd immunity levels in representative samples of the population.

Herd immunity can be defined as the indirect protection of susceptible individuals brought about by the presence of immune individuals in the population. The herd immunity theory proposes that in diseases passed from person to person, the chain of infection extinguishes quickly when the prevalence of protected individuals in the population is higher than a critical proportion or prevalence of protected individuals (I_c), known as the herd immunity threshold [12]. The generation of epidemics depends on the average number of individuals directly infected by one infectious case (secondary cases) during the entire infectious period when the infectious agent has entered a totally susceptible population. This number is called the basic reproductive number R_o. R_o is specific to a microorganism and a population ranging between extreme values depending on the agent and population characteristics. The R_o values obtained in the prevaccination era ranged from 11 to 18 for measles and from 6 to 16 for rubella [13]. Since R_o is the number of secondary cases in a totally susceptible population, vaccination programs and natural infection can reduce the average number of secondary cases from R_o to the effective basic reproductive number R = R_o – R_o I = R_o (1 – I). The effective R must be <1 to interrupt indigenous measles and rubella transmission in a population, and herd immunity can be considered established when the prevalence of protected individuals is higher than I_c = 1 – (1/R_o) [5,12]. Values obtained for the herd immunity threshold in terms of prevalence of protected individuals (I_c) ranged from 91 to 94% for measles and from 83 to 94% for rubella, while in terms of prevalence of positive serological results (p_c) observed in serological surveys, it ranged from 96 to 99% for measles and from 87 to 99% for rubella [5,12]. When the prevalence of protected individuals or positive serological results is higher than the threshold, the number of secondary cases per infected case is lower than one, and transmission is blocked in the community. Consequently, to achieve the elimination target, it is necessary to achieve and maintain a prevalence of positive serological results >96–99% for measles and >87–99% for rubella [5,12].

To ensure that the necessary herd immunity has been established, the WHO’s Regional Office for Europe has set the elimination target for measles and rubella at less than one case per one million population [2]. Other indicators proposed to assess the absence of indigenous measles and rubella transmission are the following: short duration of outbreaks, low number of cases in outbreaks, high percentage of imported cases and overall effective R < 1 [14]. Nevertheless, a more precise and useful indicator to assess the establishment of herd immunity and the absence of endemic transmission in the population is to find prevalences of positive serological results higher than the herd immunity threshold for measles (p > 96–99%) and rubella (p > 88–99%) in all population groups in representative samples of the population, since herd immunity can be considered established when the prevalence of positive serological results is higher than the critical prevalence associated with herd immunity (p_c) in all population groups [5,6].

The incidence, transmission and seroprevalence of measles in Europe during the period 2003–2013 suggests that Europe is far away from the elimination target and that the current prevention strategy to achieve measles elimination is possibly not correct. In 2012, the overall measles incidence rate in Europe was 20.9 per million inhabitants, and 19 countries had incidence rates >1 per million inhabitants [3]. The ESEN project found low immunity levels to measles in many European countries in 2001–2003 [10], and a seroepidemiological study carried out in Spain in 2003 in a representative sample of the population aged >5 years showed that herd immunity against measles was established only in individuals aged >35 years [5,6]. By contrast, the incidence and seroprevalence of rubella during the period 2003–2013 are better than that for measles, suggesting that Europe is closer to the elimination objective for rubella than for measles. During the 2003–2013 period, the number of rubella cases was >6000 only in 2012 due to a large outbreak of 20,772 cases in Poland, but rubella cases were reduced to 778 in 2013 [3]. Results obtained in the serological survey carried out in Spain in 2003 showed that herd immunity against rubella was established in all age groups [5], and the ESEN project found a prevalence of susceptible children >10% only in four countries [11].

In this situation, a new preventive strategy based on serological surveillance should be developed in Europe in order to achieve and maintain measles and rubella elimination. Serological surveillance is an important tool for the evaluation of vaccination programs as it monitors immunity in the population and provides information to identify control measures [5,8]. Serological surveillance data, on the other hand, avoid the limitations of passive disease reporting systems. In this new preventive strategy, serological surveillance should be used to identify population groups without sufficient herd immunity against measles and rubella, recommending complementary vaccinations in individuals from these population groups [5]. Three different complementary vaccination strategies could be developed to immunize individuals from population groups without sufficient herd immunity against measles and rubella [5]: vaccination of all individuals from these groups, regardless of their vaccination and disease status (catch-up strategy); vaccination of susceptible individuals from these groups identified by means of a prevaccination screening (catch-up of susceptibles strategy); and vaccination of individuals who have no documentation of completed vaccination, unless they have laboratory evidence of immunity or medical documentation of measles. The ‘catch-up strategy’ could be recommended in countries with low percentages of MMR vaccination coverage during childhood or low vaccination effectiveness, and the ‘catch-up of susceptibles strategy’ in countries with high percentages of vaccination coverage.

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.