Community-wide measles outbreak in the Region of Madrid, Spain, 10 years after the implementation of the Elimination Plan, 2011–2012

ABSTRACT

We describe a community-wide outbreak of measles due to a D4 genotype virus that took place in the Region of Madrid, Spain, between February 2011 and August 2012, along with the control measures adopted. The following variables were collected: date of birth, sex, symptoms, complications, hospital admission, laboratory test results, link with another cases, home address, places of work or study, travel during the incubation period, ethnic group, and Mumps-Measles-Rubella (MMR) vaccination status. Incidences were calculated by 100,000 inhabitants. A total of 789 cases were identified. Of all cases, 36.0% belonged to Roma community, among which 68.7% were 16 months to 19 y old. Non-Roma cases were predominantly patients from 6 to 15 months (28.1%) and 20 to 39 y (52.3%). Most cases were unvaccinated. We found out that 3.0% of cases were healthcare workers. The first vaccination dose was brought forward to 12 months, active recruitment of unvaccinated children from 12 months to 4 y of age was performed and the vaccination of healthcare workers and of members of the Roma community was reinforced. High vaccination coverage must be reached with 2 doses of MMR vaccine, aimed at specific groups, such as young adults, Roma population and healthcare workers.

KEYWORDS:

• control measures
• epidemiology
• measles
• outbreak
• vaccine

Introduction

Measles is one of the most contagious vaccine-preventable infectious disease. Before the widespread use of measles vaccination, almost everybody was infected in early childhood and acquired life-long immunity. The widespread adoption of the measles vaccine in National Immunisation Programmes since the establishment of the Expanded Program on Immunization in 1974 has marked a decrease in the number of reported cases.¹

Due to this important decrease in the global incidence of measles its elimination has been addressed in the WHO European Region through successive strategic plans.^2-4 The elimination goal was expected to be reached in 2015. Although many of the Member States have provided evidence for absence of endemic measles transmission within their borders,⁵ the Region has not met the 2015 measles elimination goal. Measles transmission continues, with large- scale outbreaks reported in Bosnia and Herzegovina, Germany, Kyrgyzstan and Serbia in 2015.^5,6 Sub-optimal coverage rates in some areas and immunity gaps in the population remain the primary cause of continued measles transmission in the European Region.⁶ High vaccination coverage (≥ 95%) with 2 doses of measles-containing vaccines is crucial to achieve elimination.

Following the WHO recommendations, the National Measles Elimination Plan ⁷ was established in Spain in 2001 and the Region of Madrid (RM) Measles Elimination Plan was started up in the same year.^8,9 Since then, measles must be notified to the RM Surveillance Network within 24 hours after the case identification.

Measles-Mumps-Rubella (MMR) vaccine was included in the Spanish Immunization Schedule calendar in 1981 for children aged 15 month. Vaccination coverage above 95% was reached in 1985. In November 1996 a second dose was introduced for children aged 11 y and in November 1999, the age of administration of this second dose was brought forward to 4 y. Additionally, the adult immunization schedule includes one dose of MMR for adults born after 1965. All doses are funded by the government. From 2004 on the RM Vaccination Information System collects nominally the vaccination status of the population. Although MMR coverage for the first dose is higher than 95%, the coverage for the second dose is lower (roughly 82–83%). Furthermore, population immunity in the RM is highly favorable for measles elimination. Serosurveillance Surveys have shown low population susceptibility level to measles in children (9.5%, 3.0% and 1.8% in children aged 2 to 5, 6 to 10 and 11 to 15 y respectively in 1999).^10,11 According to WHO, susceptibility level should not be higher than 15% in children aged 1 to 4 years, 10% in children aged 5 to 9, 5% in children aged 10 to 14 and 5% in people older than 14 y.²

The RM covers a population of almost 6,500,000 inhabitants. Measles incidence has been lower than 1 case per 100,000 inhabitants since 2001, except in 2006, with a peak of incidence of 3,0 due to a community-wide outbreak involving 174 cases. ¹² This study is aimed at describing a second community-wide outbreak of measles in the RM occurred between February 2011 and August 2012, as well as the control measures adopted.

Results

Magnitude of the outbreak and classification of cases

A total of 789 cases were found to meet the outbreak case definition, which represented 96.8% of all the indigenous cases notified in the years 2011 and 2012 (815 cases). Most cases (83.1%) were laboratory confirmed, 5.7% confirmed by epidemiological link and the remaining 11.2% were classified as compatible. The duration of the outbreak was 77 weeks. Most cases (69.1%) appeared between weeks 20 and 52 of 2011. Due to the outbreak, the global incidence in the RM reached the value of 9.6 cases per 100,000 inhabitants in 2011 and 3,0 in 2012. The D4 genotype was identified in 20.9% of all indigenous cases notified in both years (170 out of 815). Other genotypes identified in that period were B13 (14 cases), D8 (2 cases) and G3 (1 case). Genotype was not identified in 77,1% of cases (628 out of 815) (Fig. 1).

Figure 1. Community-wide outbreak of measles. Number of cases of measles per onset week of symptoms and genotype (n = 789). Region of Madrid, 2011–2012 (from week 6 of 2011 to week 30 of 2012).

Age and sex distribution

The proportion of men and women was similar (52.2% and 47.8% respectively). The age range was from under 1 month to 54 y. The greatest incidence was seen in children under 1 y of age (198.1 cases per 100,000), followed by the 1–3 y age group (54.6 cases per 100,000). The incidence in the age groups between 4 and 34 y reached a value of 18 to 19 cases per 100,000. Incidence by sex was similar in all age groups (Fig. 2). Regarding age distribution, 24.7% of cases were aged between 0 and 15 months old and 26.8% between 25 and 34 y old.

Figure 2. Community-wide outbreak of measles. Incidence by gender and age group. Region of Madrid, 2011–2012 (from week 6 of 2011 to week 30 of 2012).

Cases by age and ethnicity

Thirty 5 percent of cases were Roma people (284 cases). Roma cases were predominantly aged from 16 months to 19 y (68.7%), while non-Roma cases were mainly aged from 6 to 15 months old (28.1%) and from 20 to 39 y old (52.3%) (Fig. 3).

Figure 3. Community-wide outbreak of measles. Number of cases by age group and ethnicity. Region of Madrid, 2011–2012 (from week 6 of 2011 to week 30 of 2012).

Transmission chains and transmission places

A total of 86 transmission chains were identified, including 459 (58.1%) of all cases (Table 1). D4 genotype was identified in 46.5% of these cases. The size was 2–3 cases in 69.8% of chains. Six places of transmission were identified: community (including worship places), family, infant school, work center, healthcare center and social-healthcare center. The most important place of transmission was the community for the Roma cases (63.7% of all cases) and the family for the non-Roma cases (17.0% of all cases). The most important chain occurred within one urban district in the city of Madrid, with 134 cases, in which 97.8% were Roma cases. It lasted 35 weeks.

Table 1. Transmission chains according to transmission place. Community-wide outbreak of measles. Region of Madrid, 2011–2012.

	No. of chains		No. of cases^*
Transmission place	n	%	n	%
Community^**	4	4.7	195	42.5
Family	61	70.9	167	36.4
Infant School	13	15.1	75	16.3
Work Center	3	3.5	11	2.4
Health Center	4	4.7	7	1.5
Social-Health Center	1	1.2	4	0.9
Total	86	100.0	459	100.0

* The table include 58.1% of cases, those linked to any transmission chain

** It includes worship places.

The size of family chains ranged from 2 to 9 cases, and most of them were 2–3 cases in size (81.9%). Regarding the chains linked to infant schools, 30.7% were 2–3 cases in size; 61.5% 4–9 cases and one 16 cases. In the healthcare centers 7 cases were detected in 4 transmission chains.

Of the total of cases, 3.0% were healthcare center workers (24 cases), of which 5 were infected by contact with a case in the center itself.

Vaccination status of cases

Vaccination status was known in 74.8% of cases (590 out of 789). Most cases were not vaccinated (Table 2). A total of 36 cases were vaccinated: 29 had been vaccinated with 1 dose; 6 with 2 and 1 with 3. The proportion of cases belonging to cohorts of children targeted by the childhood immunization program (born from 1984 onwards) was 50.6%, and therefore, they were avoidable cases. The vaccination status was known in 76.4% of these cases. Among Roma cases, 97.9% were not vaccinated and among non-Roma cases this percentage was 75.2%. Regarding avoidable cases among adults, 29.5% of cases were adults born between 1966 and 1984, and therefore, they were targeted by the adult immunization program. The vaccination status was known in 55.3% of these cases, of which 96.8% were not vaccinated.

Table 2. Vaccination status of cases according to age group and ethnicity. Community-wide outbreak of measles. Region of Madrid, 2011–2012.

Age group	Vaccinated^*		Unvaccinated		Total
Roma cases	n	%	n	%	n	%
0–5m	0	0.0	13	100.0	13	100
6–11m	0	0.0	19	100.0	19	100
12–15m	0	0.0	8	100.0	8	100
16m-3y	1	2.3	42	97.7	43	100
4–9y	2	3.9	49	96.1	51	100
10–14y	0	0.0	43	100.0	43	100
15–19y	0	0.0	31	100.0	31	100
20–24y	0	0.0	13	100.0	13	100
25–29y	1	12.5	7	87.5	8	100
30–34y	0	0.0	6	100.0	6	100
Total	4	1.7	231	98.3	235	100
Non-Roma cases	n	%	n	%	n	%
0–5m	0	0.0	12	100.0	12	100
6–11m	0	0.0	97	100.0	97	100
12–15m	2	4.4	43	95.6	45	100
16m-3y	14	60.9	9	39.1	23	100
4–9y	3	30.0	7	70.0	10	100
10–14y	1	12.5	7	87.5	8	100
15–19y	4	36.4	7	63.6	11	100
20–24y	2	10.5	17	89.5	19	100
25–29y	3	9.4	29	90.6	32	100
30–34y	1	1.9	53	98.1	54	100
35–39y	2	7.4	25	92.6	27	100
40–44y	0	0.0	13	100.0	13	100
45–49y	0	0.0	1	100.0	1	100
>49y	0	0.0	2	100.0	2	100
Unknown	0	0.0	1	100.0	1	100
Total	32	9.0	323	91.0	355	100

* Vaccinated with at least one dose of MMR vaccine

Hospital admissions and complications

Hospital admission was required by 20.3% of cases. The largest number of admissions was seen in the 30–34 y age group (31 admissions; 29.6%), followed by the 6–11 month age group (20 admissions; 17.2%). Complications occurred in 10.9% of cases (86 cases). Among complicated cases, 73.2% were admitted to a hospital. The most common complication was pneumonia (24 cases), followed by hepatitis (23 cases). Three miscarriages and one premature stillborn baby were attributable to the measles infection. The largest number of complications was observed in the 30–34 y age group (19 complications; 17.7%), followed by the 35–39 y age group (11 complications; 25.0%) and the 6 to 11 month age group (11 complications; 9.4%).

Public health measures adopted

Several public health measures were adopted to stop transmission. Isolation of every suspected case and vaccination of the susceptible contacts in the first 72 hours after exposure were implemented. Regarding the population-wide interventions, the first dose of the MMR vaccination was brought to 12 months from the 1st of June 2011 on. Children aged between 12 months and 4 y old with no record of vaccination in the RM Vaccination Information System were identified and listed. The lists were sent to the appropriate healthcare centers for an active catch-up of these children to complete their vaccination series. In addition, an informative note was distributed to all public and private schools of the RM, reminding the parents of children in the first cycle of pre-school education (children aged from 0 to 2 y old) of the need to vaccinate their children if they had not already received the doses corresponding to their age. The vaccine was recommended to children aged 6 months or older in transmission places with children under 12 months of age. Regarding the measures adopted to prevent measles transmission in healthcare centers, meetings were organized and a document was distributed to all healthcare centers, recalling the main measures to minimise the propagation of the disease inside the centers. Health professionals vaccination was reinforced through the Occupational Risk Prevention Services.

Due to the identification of spaces devoted to Evangelical worship as transmission, meetings with the leaders of Roma communities were held and Roma health mediators were involved to facilitate the transmission of the recommendation for vaccination and the access to the healthcare services. Likewise, to facilitate the fulfilment of this recommendation, the vaccination appointment times in healthcare centers were lengthened and mobile vaccination teams were made available in areas with high concentration of Roma population.

Discussion

In the years 2011 and 2012, the incidence of measles in the RM greatly exceeded the threshold of 1 case per million inhabitants, the maximum value established by the WHO to monitor the progress toward elimination. This increase occurred due to a community-wide outbreak, responsible for 96.8% of the notified indigenous cases during this period. A high incidence has also been observed in Spain and in other countries in the Western World. The most important outbreak in Spain occurred in Seville (1760 cases). Most of the outbreaks were due to a D4 genotype virus as in other countries in Europe. Other genotypes detected were B3, G3 and D8.¹³ In the European Union, the incidence of measles was high in 2011 (60 cases per million) and it has dropped in later years, although the number of cases remains high (7.7 cases per million in 2015).¹⁴

The high spreading capacity of the measles virus makes it necessary to reach and maintain vaccination coverage over 95% with both doses. This implies the need to identify susceptible individuals and population groups. This outbreak has proved measles susceptibility among young adults, infants, Roma population and healthcare workers.

Most young adults (roughly 28–35 year-olds) were not vaccinated because they were not targeted when measles vaccination program was implemented and they were not exposed to measles due to the decline in the virus spread as a result of the increase in vaccination coverage. Every opportunity should be used to check the vaccination status of adults and offer the vaccine when it is indicated. It should be recalled that the RM adult immunization schedule recommends giving a dose of MMR to any adult born after 1965, provided that there are no medical objections, history of measles disease, history of documented vaccination or serologic evidence of immunity. Furthermore, vaccination is especially recommended for susceptible persons who work in healthcare institutions and schools or who intend to travel to countries where measles is endemic.¹⁵

On the other hand, the identification of outbreaks in nursery schools was the reason behind the recommendation to bring the first dose of MMR forward from 15 to 12 months of age.¹⁶ Therefore, the childhood immunization schedule starting 1 June 2012 recommends the administration of 2 doses of vaccine, the first at 12 months of age and the second at the age of 4 y. Besides, MMR childhood vaccination coverage in the RM is over 95% with one dose (98.9% in 2011 and 96.7% in 2012), but not with 2 doses (83.8% in 2011 and 82.7% in 2012).¹⁷ Efforts should be made to increase the vaccination coverage with 2 doses, such as an active catch-up of children to complete their vaccination status.

Regarding Roma cases, the virus has predominantly affected unvaccinated children and young people. It has been estimated that 0.7% of population in the RM belongs to the Roma community (roughly 43,000 persons).¹⁸ The MMR vaccination coverage in Roma population has been estimated in several European countries with figures of 76% (Bulgaria, 2006), 82% (Greece, 2006) and 56% (Poland, 2009) vaccinated with one dose and of 45% (Greece, 2006), 37% (Poland, 2009) and 33% (Slovenia, 2001) vaccinated with 2 doses. In France, only 55% of Roma population under the age of 30 y was vaccinated in 2011. This low vaccination coverage is related to the access to health services. In general, Roma population shows a worse state of health and less access to health services than the rest of the population, according to many European Agencies, non-governmental organisations, and scientific publications.¹⁹ To improve vaccine coverage it is necessary to identify the barriers to this access. These may be related to the lack of official documentation, geographical isolation and mobility, insufficient information, cultural and linguistic differences or discrimination. Thus, improvement in access to vaccinations requires the integration of Roma population through intersectorial strategies. In different Member States programmes involving qualified Roma agents as mediators have managed to decrease the inequalities in health and have improved access to health services, including an increase in vaccination coverage. Vaccination is accepted if it is made accessible, as suggested by the improvements in vaccination coverage observed when the healthcare authorities have supported vaccination campaigns aimed at the Roma population during outbreaks.²⁰ In this outbreak the leaders from the Roma community and Roma health mediators were key facilitators of the access to vaccination.

Measles transmission has occurred in social-healthcare and healthcare facilities, which proves the presence of susceptible healthcare workers and their role in sustaining transmission. To protect them and limit transmission of measles, they should be vaccinated. Additionally, it is important to maintain a high level of clinical suspicion of measles in cases with rash, particularly in young adults, and in travelers returning from endemic countries.²¹

Measles has re-emerged in community-wide outbreaks in Spain and other European countries despite reported high vaccination coverage.^22-24 Immunity gaps have been found across similar segments of the population (Roma communities, young adults and healthcare professionals) and control measures adopted are also similar, including the deployment of special outreach teams in collaboration with Roma health mediators to vaccinate Roma communities, immunisation of healthcare profesionals and activities to increase awareness of the outbreak among the public and healthcare professionals.

In summary, it is essential to maintain a high quality surveillance system to monitor the vaccination coverage and the incidence of the disease, since this epidemiological situation could be repeated in the future if vaccination coverage is not enough to quickly interrupt measles transmission. Catch-up immunization or supplementary immunization activities should be considered to close immunity gaps in the population. Health authorities should provide health care workers and the general public with easy access to reliable information on measles vaccination. Suspected cases of measles should be notified promptly to the Surveillance Network so that timely epidemiological investigation can be performed, aimed at limiting the duration of transmission of measles [15]. Thus, healthcare professionals should also be well informed on the existence and content of the strategic plan for the elimination of measles.

Methods

In February 2011, a measles outbreak was identified in the RM, after detecting values of measles incidence higher than expected according to the incidence in the latest years. A suspected case was defined as a person with a maculopapular rash, body temperature ≥ 38°C and at least one of the following symptoms: cough, coryza or conjunctivitis, staying in the RM between 7 and 21 d before the onset of the rash. A case showing positive laboratory tests results for measles (measles virus specific antibody response characteristic for acute infection in serum, isolation of measles virus or detection of measles virus nucleid acid from a clinical specimen) was classified as laboratory confirmed. A case was considered as confirmed by epidemiological link when the clinical criteria were present but there were not any laboratory tests available, and a link with a laboratory confirmed case of measles between 7 and 21 d before the onset of symptoms could be proved. When only clinical criteria were met the case was considered as clinically suspicious or compatible.

The outbreak lasted from 7th of February 2011 to 31st of August 2012, during which there was not any period longer than 21 d without detecting cases. Genotype D4 was identified throughout the epidemic period. All cases identified in the epidemic period caused by a measles virus of genotype D4 or of unknown genotype were considered as outbreak cases, even if no epidemiological link to another case was detected. Cases caused by measles viruses other than D4 and those with a history of travel during the incubation period were excluded from the outbreak. The following variables were collected: date of birth, sex, symptoms, complications, hospital admission, laboratory test results, link with another cases, home address, places of work or study, travel during the incubation period, ethnic group, and MMR vaccination status. We considered the following age groups: 0–5 months, 6–11 months, 12–15 months, 16 months-3 years, 5-year groups from then on until 49 y of age and 50 y or older. We defined transmission chain as a group of cases epidemiologically linked and transmission place as the location where one case was exposed to an infective case. Community was the transmission place when only a specific geographical exposure area was identified (including areas where Roma people gather for worship). We performed a descriptive analysis of data with the software IBM SPSS Statistics version 21.0.

Members of the outbreak research work group

M.C. Álvarez Castillo, A. Aragón Peña, J.F. Barbas del Buey, S. Cañellas Llabrés, C. Cevallos García, J.C. Diezma Criado, F. Domínguez Berjón, M.J. Esteban Niveiro, C. Estrada Ballesteros, R. Fernández Muñoz, N. García Marín, M.J. Gascón Sancho, D. González Hernández, M.J. Iglesias Iglesias, S. Jiménez Bueno, M. Jiménez Maldonado, M.D. Lasheras Carbajo, M.A. Lópaz Pérez, D. López-Gay Lucio-Villegas, J. López Limaña, F. Martín Martín, F. Martín Martinez, N. Mata Pariente, I. Méndez Navas, A. Miguel Benito, L. Moratilla Monzó, R. Noguerales de la Obra, H. Ortiz Marrón, A. Pérez Meixeira, C. Sanz Ortiz, S. Sánchez Buenosdías, J.A. Taveira Jiménez, M.J. Velasco Rodríguez.

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Acknowledgments

We would like to thank all those who made it possible to identify the outbreak and to adopt the control measures. We would also like to thank E. Barceló González and L.M. Blanco Ancos for their contribution to the data recovering on the children with no record of vaccination from the RM's Vaccination Information System.