Nursing and vaccination: evolution of the compliance with the combined measles-mumps-rubella (MMR) vaccine

Background: Immunization is an important activity performed by primary health care nurses in Portugal. Objectives: This study aims to assess the evolution of the compliance with the immunization strategy for the combined measles-mumps-rubella (MMR) vaccine. Methodology: A study was conducted with 411 individuals, born after 1970 in Portugal, by consulting immunization records (IRs) and health booklets (HBs). Results: The vaccination coverage rate was 38.88% in cohorts born before 1977 and higher than 95% in cohorts born after 1990. The administration according to the age criteria recommended by the Directorate-General for Health (DGS) was associated with the participants’ birth generation and improved over time (r = 0.239, p = 0.001). Conclusion: In this sample, the MMR vaccine strategy complied with the objectives of the World Health Organization and DGS concerning the vaccination coverage rate and the adequacy of the immunization schedules according to the recommended age criteria.


Introduction
In Portugal, the five decades of implementation of the National Vaccination Program (Programa Nacional de Vacinação, PNV) have been a success, also due to the major contribution of nurses who manage the PNV and put their efforts and commitment into its systematic and consistent implementation over time. This study will assess the evolution of the compliance with the measles-mumps-rubella (MMR) vaccine strategy among users of the Local Health Unit (Unidade Local de Saúde, ULS) of Guarda and the Cluster of Healthcare Centers (Agrupamento de Centros de Saúde, ACES) of Pinhal Litoral, with a view to showing nurses' importance in achieving the PNV objectives regarding disease control and elimination. It aims to assess the evolution of the compliance with the MMR vaccine strategy, since its introduction until today, concerning the fulfilment of the following objectives of the Directorate-General for Health (DGS) and the World Health Organization (WHO): adherence to vaccination, immunization according to the recommended age criteria, and immunization schedules used. The study also aims to check in what year did the vaccination coverage rate exceeded 95% in the study sample, and how the immunization schedules evolved from then on.

Background
In Portugal, nurses play a key role in achieving the PNV objectives, and vaccination is an important activity of primary health care nurses (Subtil, 2011). In the field of vaccination, nurses have shown to possess the necessary technical, scientific, ethical, and deontological skills to effectively and efficiently implement the PNV in Portugal, managing and administering it in an exemplary way and achieving a higher vaccination coverage rate than in most countries (Loureiro, 2004;Subtil, 2011). In practice, these skills translate into the administration of vaccines according to the DGS plan and guidelines, the maintenance of adherence to vaccination behaviors, the implementation of reliable vaccination records, the epidemiological surveillance of PNV implementation, and the management of stocks (Loureiro, 2004;Subtil, 2011). It is scientifically proven that vaccination coverage rates above 95% are a guarantee of control and possible elimination of some vaccine-preventable diseases, including measles, mumps, and rubella (DGS, 2016;Plans, 2010;Tharmaphornpilas, Yoocharean, Rasdjarmrearnsook, Theamboonlers, & Poovarawan, 2009;WHO, 2011). Vaccination coverage rate represents the number of vaccine doses administered to the target population. As it was previously mentioned, in the case of measles, mumps, and rubella, vaccination coverage rates above 95% produce the so-called herd immunity effect that ensures protection for the entire population without 100% immunization coverage due to the difficulty of virus circulation among immunized individuals. In addition to vaccination coverage rates above 95%, it is equally important that vaccines are administered at the recommended ages in order to ensure the efficacy and effectiveness of the immune response to vaccination (Cutts, Lessler, & Metcalf, 2013;DGS, 2016;WHO, 2011). In Portugal, the MMR vaccine was introduced to the PNV in 1987, replacing the monovalent measles vaccine that had been introduced in 1973. Initially, this vaccine (MMR I) was administered at the age of 15 months (DGS, 1990) and was later brought forward to the age of 12 months in 2012 (DGS, 2013a). A second MMR dose (MMR II) between the age of 10 and 13 years was introduced in 1990 and brought forward to the age of 5-6 years in 1999 (DGS, 1990). The cohorts of children born in 1992-1993 were the last ones to follow the MMR-II recommendation at the age of 10-13 years and the cohorts of children born in 1994-1995 were the first to follow the recommendation currently in force. The history of the introduction of the measles vaccine in Portugal allows identifying five different, but complementary, vaccination generations. The first generation of immunized individuals was born before 1977 and did not have the opportunity to be vaccinated with two MMR doses at the ages recommended by the DGS (1990). The second generation was born between 1977 and 1984 and had the opportunity to be vaccinated with two measles vaccine doses at the ages recommended by the DGS (DGS, 1987(DGS, , 1990. This generation first received the monovalent measles vaccine and then the combined MMR vaccine, if the individuals were initially vaccinated at the age recommended by the DGS (DGS, 1987(DGS, , 1990. The third generation was born between 1985 and 1990 and met the criteria to be vaccinated with two doses of the trivalent MMR vaccine, both at the recommended age for both doses. However, since these schemes were not always complied with, this generation has very heterogeneous vaccination statuses (DGS, 1987). The fourth generation was vaccinated with two measles vaccine doses, followed by the administration of the second MMR dose at the age of 10-13 years. However, this generation has more homogeneous vaccination statuses. Finally, the fifth generation is similar to the previous one, except that the second MMR dose was brought forward to the age of 5-6 years (DGS, 2011a, b, c).

Research questions
Does the sample meet the DGS guidelines for the administration of the MMR vaccine concerning adherence to vaccination, recommended ages, and immunization schedules used? Was the MMR vaccination coverage rate in the generation born after 1990 higher than 95% and did it remain above this percentage from then on?

Methodology
This study was developed based on the consultation of the immunization records (IRs) and health booklets (HBs) of patients born after 1970 that were part of the ACS and the ULS of Guarda. Data were collected between 2012 and 2013. Through the convenience sampling method, users were selected among the individuals who attended these health units in 2012-2013. However, only users who agreed to participate by signing the informed consent form were included in the study and only these patients' IRs and health booklets (HBs) were consulted. Individuals without their HB at the time of signing the informed consent form were asked to photocopy it and send it later by mail in pre-paid envelopes. Only individuals who were registered as users of the respective health units and whose vaccine information was recorded in at least one of the two documents (HB or IR) were included in the study. All individuals without updated vaccine information in their vaccination records were encouraged to update their immunization status.

Data processing
Data on the vaccination history were inserted into a database to be treated using the Statistical Package for the Social Sciences, version 23.0. First, the most important variables in the study -Birth generation as independent variable and Vaccination status as dependent variable -were descriptively analyzed. Confidence intervals were set at 95%. Spearman's correlation coefficient was used to measure the degree of association between variables. Odds ratio was used in the variables where an association was found with the purpose of assessing its strength and direction, followed by the estimation of the 95% confidence intervals.

Ethical-Legal considerations
All ethical considerations inherent to a research study were followed. The Coordination of the Public Health Unit of the ACES Pinhal Litoral and the Ethics Committee of the ULS of Guarda gave their ethical approval for the development of study. All subjects gave their informed consent for participation in this study. Data were collected and analyzed by maintaining the study participants' anonymity.

Results
Due to the great heterogeneity of the vaccination statuses of the different vaccination generations identified in this study, and in Nursing and vaccination: evolution of the compliance with the combined measles-mumps-rubella (MMR) vaccine order to facilitate data analysis and interpretation, results are shown in two major groups: individuals born before 1990 and those born after this year.

Vaccination information and its source
The vaccination records of 423 male and female individuals born in mainland Portugal after 1970 were consulted. In a first analysis, 12 subjects were excluded from the analysis because there was no vaccination information in their IRs or HBs. Thus, the final sample was composed of 411 individuals. The vaccination coverage rate was very similar to that recorded in the region and in mainland Portugal, where the rate only became exceeded 95% in at least one vaccine dose after the generation of individuals born after 1990 (DGS, 2012b,c; DGS, 2013b,c; Table 1).

Vaccination status of individuals born before 1990 (n = 206)
The analysis of the vaccination status of individuals born before 1990 (Table 2) showed that, out of the 206 individuals with vaccination information, 54 (26.2% of the total sample) had no information on the measles vaccine in their vaccination records. Out of these 54 individuals, 51 (94.4%) were born between 1970 and 1984 but were not vaccinated, although the Portuguese vaccination schedule already included a dose of measles vaccine by that time (Table 2). In this sample, 62 individuals (30.09%) had records of having taken only a single dose of the vaccine. Most of them (47; 75.8%) were born between 1977 and 1984, when the Portuguese PNV only included a single dose of measles vaccine (Table 2). Ninety individuals (41.3% of the total sample) had records of two doses of the measles vaccine. All of them were born after 1977, which means that they could have taken two vaccine doses by that time ( Table 2). The analysis of the evolution of the vaccination history showed that the vaccination coverage rate was 38.88% in the generation born before 1977, 76.03% in the generation born between 1977 and 1984, and 93.88% in the generation born between 1985 and 1990 (Table 2). With regard to the age at the first dose of measles vaccine, only 3/152 (1.97%) took it before the age of 12 months, and most of them (98/152; 64.47%) took it at the age recommended by the DGS, that is, at the age of 12 to 24 months. However, 51/152 (33.55%)

Analysis of the evolution of the compliance with the vaccination schedule in the sample of the generation born between 1970 and 1990
Over time (cohorts born more recently), the age at first dose drew closer to the time interval between 12 and 24 months (r = -0.239; p =0.001; see Table 3). However, it seems that there were no changes over time in terms of the compliance with the age at the second dose of measles vaccine in this sample, since the recommended age at second dose was always complied with throughout this period (r = 0.162; p = 0.122; Table 3).
On the other hand, the vaccination schedule was strongly associated with the birth cohort (r = 0.684; p = 0.038

Vaccination status of individuals born after 1990 (n = 205)
In this group, all subjects were vaccinated with the MMR vaccine. Table 4 describes in detail the distribution of the groups of individuals according to the vaccination schedule (age at first and second doses) and the vaccination coverage rate.

Age at first dose
In the group of individuals born after 1990, both in the generations born before and after 1993, most individuals 196/205 (95.61%) took the MMR I at the age recommended by the DGS (12 to 24 months of age; Figure  1). The vaccination coverage rate for the first dose was 95.51% in the cohort born before 1993, and 100% in the cohort born after 1993 (Table 4).  1977 1977-1984 1984-1990 Age of 1 st dose

Age at second dose
Most individuals born before 1993 took the MMR II at 10-13 years of age 67/89 (75.28%) and those born after 1993 took the MMR II at 5-6 years of age 106/116 (91.38%). However, 12 individuals born before 1993 and one born after 1993 took the vaccine between 7 and 9 years of age, which does not correspond to any vaccination strategy. The vaccination coverage rate for the second dose of the measles vaccine was 91.01% in the generations born between 1990 and 1993, and 95.68% in the generation born after 1993 (Table 4).  In the group of individuals born between 1977 and 1984, 92/121 (76.03%) took at least one vaccine dose. The four possible vaccination schedules were complied with, beginning with the measles vaccine or the MMR. The ages at first and second doses depend on this schedule. Although the vaccines were administered at the recommended ages in most cases, this generation has the highest proportion of late first doses (after 24 months of age). The late doses may correspond to additional vaccination campaigns and efforts carried out by health professionals with the purpose of increasing adherence to vaccination (Subtil, 2011

Vaccination status of individuals born after 1990
Almost all individuals born after 1990 are vaccinated with two doses of MMR (vaccination coverage rate is very close to 100% for the first and second MMR doses), which indicates a compliance with DGS (2011a,b,c) and WHO (2011) guidelines with the purpose of eliminating measles by maintaining vaccination coverage rates above 95% in the entire population.
In comparison to those born before 1990, the individuals in this group are more and better vaccinated. In other words, the vaccination coverage rates are higher and complied better with the ages of vaccination recommended by the DGS. DGS data (DGS, 2012b) confirm that the measles vaccination coverage in Portugal is above 95% for the first dose since at least 1990 and 95% for the second dose since at least 2006. With regard to the compliance with the recommended ages for the administration of the first and second vaccine doses, a large percentage of individuals born after 1990 complied with the ages recommended by the DGS (DGS, 2012a,b,c), with an age average of 15 months for the first dose, and 5-6 years and 10-13 years for the second dose in groups born after 1993 and before 1993, respectively.
In 1990, when the DGS recommended the administration of a second vaccine dose (MMR II) at the age of 10 to 13 years, individuals born between 1990 and 1993 should have followed this strategy. Indeed, most of them followed 66/81 (81.5%); however, two individuals born in this cohort antici- pated this dose and took it at 5-6 years of age, and 13 individuals took it at the ages of 7 to 9 years, which does not correspond to any of the DGS guidelines. In the first case, this anticipation can be explained by the fact that both individuals were vaccinated outside of Portugal, namely in Brazil and Canada, where the second vaccine dose was probably taken at 5-6 years of age in those birth cohorts. In the second case, it may be related with vaccination opportunities, since the vaccine was administered very close to 10 years of age -of the 13 subjects, 11 took the vaccine at the age of 9 and two took it at 8.42 and 8.46 years of age, which is very close to the age of 10. These children probably attended healthcare center for another reason and took the opportunity to take the vaccine. Individuals born after 1993 should have been the first ones to take the second vaccine dose at 5-6 years of age. In fact, in this sample, the majority of individuals born between 1990 and 1993 took the second vaccine dose at the age of 10 to 13 years, and individuals born after 1993 took the second vaccine dose when they were 5-6 years old, which is in line with the DGS guidelines in its various notices (DGS, 1987(DGS, , 1990(DGS, , 1999(DGS, , 2001. However, three individuals born after 1993 still took the vaccine according to the old strategy (at the age of 10 to 13 years) and one individual took it at 9 years of age, probably because they lost the first opportunity to be vaccinated when they were 5-6 years old and were then vaccinated in their second vaccination opportunity at the age of 9 to 13 years. The data in this study are in line with data from the region where the sample was selected (DGS, 2013b,c) and from mainland Portugal (DGS, 2012a). The main limitations of this study relate to the fact that the convenience sample is not representative of the entire population. For this reason, these results should be generalized to the Portuguese population with caution. However, it should be noted that the results obtained in this sample were similar to the national statistics, namely regarding the vaccination coverage rates and the general characteristics of the sample. In addition, the vaccination information resulted from the consultation of reliable and detailed vaccination records (IRs and HBs).

Conclusion
In this sample, which covers 20 years of vaccination history, the measles vaccination coverage rate increased from just above 30% for the first dose in the generations born in the 1970s to above 95% for the first and second doses in the generations born after 1993. Individuals' age and the corresponding years of birth influenced their vaccination status. Younger generations are more and better vaccinated. As the MMR strategy was applied in Portugal, the vaccination coverage rate increased for both vaccine doses, as well as the compliance with the ages for the first and second vaccine doses in accordance with the several DGS guidelines in its various notices. The immunization of older generations (born before 1984) started with the monovalent measles vaccine, whereas the newer generations (born after 1984) started to be vaccinated with the trivalent MMR vaccine. However, some individuals born before 1984 were vaccinated with MMR, which represents an additional effort to raise the vaccination coverage rate to the extent that most of these individuals were vaccinated at the age of 15 months or older. This was a result of the complementary strategies to fight measles which were developed in Portugal over time. The vaccination coverage rate above 95% for both vaccine doses found in the younger groups (born after 1990) indicates the country's compliance with the goals of eliminating measles, mumps and rubella by maintaining the vaccination coverage rate above 95%. The levels of health promotion and disease prevention achieved in Portugal through the high adherence to vaccination have turned the country into a worldwide example of implementation of vaccination programs, with results that are only comparable to the distribution of drinking water to the populations. This objective was only achieved thanks to the contribution of the nurses working in the immunization area in Primary Health Nursing and vaccination: evolution of the compliance with the combined measles-mumps-rubella (MMR) vaccine Care in Portugal. Besides vaccinating people, nurses have also encouraged high levels of adherence to vaccination by administering vaccines at the ages recommended by the DGS and performing epidemiological surveillance in the application of the PNV. The importance of this study is evidenced in the retrospective analysis of the compliance with the objectives of the DGS and WHO for the implementation of the vaccine to protect against measles, mumps, and rubella in Portugal, and also in the study of nurses' contributions towards the achievement of those goals. At a time when anti-vaccination movements begin to emerge all over the world, the development of interventions, activities, and strategies to promote the adequate maintenance of high vaccine coverage rates is essential, because vaccination coverage rates above 95%, along with the administration at the recommended ages, seem to be the best method to control and eliminate the diseases targeted in the PNV. Within this scope, nurses have been and will certainly continue to be essential in maintaining this goal.