Editorial
Measles eradication: Still a long and winding road
Erradicación del sarampión: todavía un largo y difícil camino
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road" "tieneTextoCompleto" => true "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Fernando Moraga-Llop, Magda Campins-Martí" "autores" => array:2 [ 0 => array:4 [ "nombre" => "Fernando" "apellidos" => "Moraga-Llop" "email" => array:1 [ 0 => "fernandomoragallop@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "af0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cr0005" ] ] ] 1 => array:3 [ "nombre" => "Magda" "apellidos" => "Campins-Martí" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "af0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Societat Catalana de Pediatria, Asociación Española de Vacunología, Barcelona, Spain" "etiqueta" => "a" "identificador" => "af0005" ] 1 => array:3 [ "entidad" => "Medicina Preventiva y Salud Pública, Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain" "etiqueta" => "b" "identificador" => "af0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cr0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Erradicación del sarampión: todavía un largo y difícil camino" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="p0005" class="elsevierStylePara elsevierViewall">Measles is an extremely contagious viral disease, with a secondary attack rate of approximately 90 %. In a susceptible population without immunity, 1 case causes between 12 and 18 secondary cases, a figure known as the Ro or basic reproduction number, which is one of the highest in infectious diseases. The high transmissibility of the measles virus requires immunity levels of 95 % or more in the population to interrupt its transmission and eliminate it in the community.<a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0010"><span class="elsevierStyleSup">2</span></a> To achieve this, a highly effective vaccine is available, although it is necessary to achieve and maintain vaccination coverage of at least 95 % with the 2 recommended doses of the vaccine. Also, since there is no animal host or environmental reservoir and diagnostic means are adequate, measles is an eradicable disease.<a class="elsevierStyleCrossRef" href="#bb0015"><span class="elsevierStyleSup">3</span></a> In poor countries, measles has a high mortality rate among children, especially when it affects population groups that are malnourished and deficient in vitamin A. Complications such as pneumonia, diarrhoea with dehydration and encephalitis; sequelae with permanent disabilities such as blindness, hearing loss and brain damage; and thirdly, the so-called “immune amnesia”, an alteration of the immune system after infection that leaves children vulnerable to other infections, constitute the triad of the important and serious morbidity of measles.<a class="elsevierStyleCrossRef" href="#bb0020"><span class="elsevierStyleSup">4</span></a></p><span id="s0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0005">Measles prevention achievements</span><p id="p0010" class="elsevierStylePara elsevierViewall">In the 21st century so far, a number of actions have been taken to prevent measles. In 2001, the Measles and Rubella Initiative was launched which aimed at reducing deaths from measles worldwide by 90 % over the next 10 years. In 2010, the Strategic Advisory Group of Experts on Immunisation of the World Health Organisation (WHO) declared that measles can and should be eradicated, but did not propose a date for achieving this goal.<a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a> In 2012, the World Health Assembly approved the Global Action Plan on Vaccines, with the aim of having eliminated measles by 2020 in 5 of the 6 WHO regions.<a class="elsevierStyleCrossRef" href="#bb0030"><span class="elsevierStyleSup">6</span></a> In 2020, the Measles and Rubella Alliance, part of the 2021–2030 Immunisation Agenda (IA2030), committed to ensuring that no child dies from measles or is born with congenital rubella syndrome. The Alliance helps countries plan, finance, and measure efforts to totally eradicate end measles and rubella.<a class="elsevierStyleCrossRef" href="#bb0035"><span class="elsevierStyleSup">7</span></a> All 6 WHO regions have committed to eliminating measles. However, only the Americas region achieved this goal in 2017.<a class="elsevierStyleCrossRef" href="#bb0040"><span class="elsevierStyleSup">8</span></a></p><p id="p0015" class="elsevierStylePara elsevierViewall">It has been estimated that measles vaccination prevented 57 million deaths between 2000 and 2022. In 2022, there were 136 000 deaths worldwide from measles, the majority in unvaccinated or insufficiently immunised children under 5 years of age.<a class="elsevierStyleCrossRef" href="#bb0045"><span class="elsevierStyleSup">9</span></a> This year, 2024, marks the 50th anniversary of the Expanded Programme on Immunisation, and we are reminded that in 1974, systematic vaccination against measles began around the world (one of the 7 vaccines included in this first schedule). During these 50 years, of the more than 154 million deaths prevented by immunisations, measles is the disease with the most deaths prevented (93 million).<a class="elsevierStyleCrossRef" href="#bb0050"><span class="elsevierStyleSup">10</span></a></p></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0010">Re-emergence of measles in 2017. The first two years of the COVID-19 pandemic</span><p id="p0020" class="elsevierStylePara elsevierViewall">In March 2020, we published an article in the journal <span class="elsevierStyleItalic">Vacunas</span> (<span class="elsevierStyleItalic">Sarampión. Reemergencia en el camino de la erradicación</span> - Measles. Re-emergence on the road to eradication) on the re-emergence of measles, which had been observed worldwide since 2017.<a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a> Between 2000 and 2016, the global incidence of measles decreased, but between 2017 and 2019, the impossibility of achieving eradication in 2020 was already evident, due to its re-emergence. In 2018, cases increased to 10 million worldwide, with 140 000 deaths, an increase of 58 % since 2016.<a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a></p><p id="p0025" class="elsevierStylePara elsevierViewall">During the first 2 years (2020–2021) of the COVID-19 pandemic, epidemiology and surveillance were compromised, and the protective measures adopted also contributed to a decrease in the number of respiratory infections. The incidence of measles, like that of influenza, respiratory syncytial virus, pneumococcus, whooping cough, and other infections, decreased very noticeably. However, especially from the end of 2022, alarm bells went off due to the notable re-emergence of measles in the world, and in 2023 in Europe. In Spain, in the first half of 2024, there was a large increase in the number of cases, which began at the end of 2023, but within discrete figures.<a class="elsevierStyleCrossRef" href="#bb0055"><span class="elsevierStyleSup">11</span></a></p><p id="p0030" class="elsevierStylePara elsevierViewall">The COVID-19 pandemic, which caused a serious health, social, and economic crisis throughout the world, has had a very disquieting impact on vaccination coverage which is alarming in low-income countries.<a class="elsevierStyleCrossRef" href="#bb0060"><span class="elsevierStyleSup">12</span></a> Decreased surveillance activities, discontinuation of routine immunisations, and suspension of vaccination campaigns in many countries (of the 93 discontinued campaigns, 27 were for measles)<a class="elsevierStyleCrossRef" href="#bb0060"><span class="elsevierStyleSup">12</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0065"><span class="elsevierStyleSup">13</span></a> have been responsible for this decline in immunisations, as the health system struggled to control the pandemic virus with a significant diversion of resources.</p><p id="p0035" class="elsevierStylePara elsevierViewall">During the period 2000–2019, estimated global coverage with the first dose of measles vaccine increased from 72 % to 86 %, and in 2021, it decreased to 81 % during the COVID-19 pandemic, representing the lowest coverage since 2008. In 2022, coverage increased to 83 %, but only 74 % of children received both doses of the vaccine. Approximately, 22 million infants did not receive at least one dose and 11 million were missing the second dose.<a class="elsevierStyleCrossRef" href="#bb0045"><span class="elsevierStyleSup">9</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0070"><span class="elsevierStyleSup">14</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a></p></span><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0015">Re-emergence of measles in the world, Europe and Spain after the COVID-19 pandemic</span><p id="p0040" class="elsevierStylePara elsevierViewall">Globally, after the decline of measles vaccination coverage in 2020 and 2021 due to the pandemic, cases increased by 18 % (from 7 802 000 to 9 232 300) and deaths by 43 % (from 95 000 to 136 200) in 2022 compared to 2021.<a class="elsevierStyleCrossRef" href="#bb0070"><span class="elsevierStyleSup">14</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a> Provisional surveillance data indicate a 64 % increase in confirmed measles cases in 2023 (280 933) compared to 2022 (171 156 cases), and in the first 4 months of 2024, the number of cases for the entire year of 2022<a class="elsevierStyleCrossRef" href="#bb0080"><span class="elsevierStyleSup">16</span></a> were almost reached.</p><p id="p0045" class="elsevierStylePara elsevierViewall">In the WHO European Region, the re-emergence of measles is very striking. In December 2023, a widely reported WHO press release warned of an alarming 30-fold increase in cases of measles between January and October 2023 compared to those reported in 2022.<a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a> However, once the data for the entire year were available, the increase was more than 65-fold (936 cases in 2022 and 61 077 in 2023). In 2024, as of 6 June, 70 879 cases have been officially reported, which is already higher than last year.<a class="elsevierStyleCrossRef" href="#bb0095"><span class="elsevierStyleSup">19</span></a> In the WHO European Region, coverage with the first dose of measles vaccine decreased from 96 % in 2019 to 93 % in 2022, while with the second dose, it was 92 % and 91 %, respectively.<a class="elsevierStyleCrossRef" href="#bb0095"><span class="elsevierStyleSup">19</span></a></p><p id="p0050" class="elsevierStylePara elsevierViewall">In the countries of the European Union/European Economic Area (EU/EEA), the epidemiological pattern is similar. A February 2024 statement from the European Centre for Disease Prevention and Control (ECDC)<a class="elsevierStyleCrossRef" href="#bb0100"><span class="elsevierStyleSup">20</span></a> warned of an increase in 2023, with 2361 cases of measles in 23 countries. Most cases occurred in Romania (1755), with lower numbers in Austria (186), France (118), Germany (82), Belgium (69), Italy (44), Poland (37), Spain (13), and Sweden (11). The outbreak in Romania was significant, as it has continued into 2024 and has already caused 16 deaths.</p><p id="p0055" class="elsevierStylePara elsevierViewall">On 14 June, the ECDC<a class="elsevierStyleCrossRef" href="#bb0090"><span class="elsevierStyleSup">18</span></a> published the cases reported so far in 2024 (up to the beginning of June in most countries): 15 341 in Romania, 446 in Austria, 348 in Italy, 333 in Germany, 191 in Poland, 165 in France, 88 in Belgium, and 14 in Sweden. Compared to the whole of 2023, in less than half a year, the previous number of cases has already been exceeded, with significant increases in some countries, such as Romania, and to a lesser extent Germany and Italy.</p><p id="p0060" class="elsevierStylePara elsevierViewall">The average vaccination coverage in EU/EEA countries in 2022 was 92 % for the first dose and 89 % for the second. Half of the countries achieved coverage equal to or greater than 95 % for the first dose, but only 17 % for the second.<a class="elsevierStyleCrossRef" href="#bb0100"><span class="elsevierStyleSup">20</span></a> It should be noted that in Romania, 90.5 % of the more than 16 000 cases in the last 2 years were not vaccinated.<a class="elsevierStyleCrossRef" href="#bb0090"><span class="elsevierStyleSup">18</span></a></p><p id="p0065" class="elsevierStylePara elsevierViewall">Also, of note is the increase in the number of cases in the United Kingdom in the first few months of the year, which amounts to more than 1570 (compared to 332 cases in 2023).<a class="elsevierStyleCrossRef" href="#bb0090"><span class="elsevierStyleSup">18</span></a> Since last year, the UK Health Security Agency has been making urgent calls to parents and guardians to update their children's vaccination cards in view of this increase, due to the low immunisation coverage against measles.</p><p id="p0070" class="elsevierStylePara elsevierViewall">In Spain, in 2024, until June 23, 131 cases of measles had been confirmed in 12 autonomous communities, which represents more than 9 times the number of cases (13) for the entire year of 2023.<a class="elsevierStyleCrossRef" href="#bb0055"><span class="elsevierStyleSup">11</span></a> This figure is the highest since 2014, taking into account the still partial data for this year.<a class="elsevierStyleCrossRef" href="#bb0105"><span class="elsevierStyleSup">21</span></a></p><p id="p0075" class="elsevierStylePara elsevierViewall">The following information is available on the first 106 confirmed cases: 22 are imported, 44 are related to importation, and another 40 are provisionally classified as of unknown origin, while epidemiological and genomic vaccinated, 9.7 % had one dose, and 18.1 % had both doses (all adults). 40.4 % of cases required hospitalisation.<a class="elsevierStyleCrossRef" href="#bb0105"><span class="elsevierStyleSup">21</span></a></p><p id="p0080" class="elsevierStylePara elsevierViewall">MMR vaccination coverage in Spain is high, but it urgently needs to be improved. In 2023, for the first dose, at 12 months of age, it was 96.1 % (slightly lower than in 2022, 97.2 %), but in 7 autonomous communities, it was below 95 %. The second dose, at 3–4 years, had a low coverage, of 91.8 % (2 points less than in 2022), and in 8 communities, it was below this figure.<a class="elsevierStyleCrossRef" href="#bb0110"><span class="elsevierStyleSup">22</span></a> In order to try to improve coverage, consideration should be given to advancing the second dose to the second year of life, which is when children frequent health centres more.</p><p id="p0085" class="elsevierStylePara elsevierViewall">The epidemiological situation in Spain should be one of alert, not alarm, due to the possibility of importing cases from countries where there is a high circulation of the virus, due to the increase in international travel, the holding of mass events (musical, sporting) and because there is no vaccination coverage with the 2 doses of 95 % or more. The Ministry of Health's risk assessment indicates that the risk is low in the general population, but in susceptible people exposed to the measles virus it is high and can cause serious illness.<a class="elsevierStyleCrossRef" href="#bb0105"><span class="elsevierStyleSup">21</span></a></p><p id="p0090" class="elsevierStylePara elsevierViewall">Vaccine hesitancy, one of the 10 major threats to public health identified by the WHO in 2019, has continued to be highly present in high- and middle-income countries that had achieved high vaccination coverage.<a class="elsevierStyleCrossRef" href="#bb0115"><span class="elsevierStyleSup">23</span></a> Doubts and concerns about the link between the MMR vaccine and autism, which has been shown to lack scientific evidence, still persist in some areas. In a survey conducted in the United States (April 2024), it was surprising to discover that 24 % of respondents do not accept the falsity of the claims that the MMR vaccine causes autism.<a class="elsevierStyleCrossRef" href="#bb0120"><span class="elsevierStyleSup">24</span></a> This happens 26 years after Wakefield's article published in <span class="elsevierStyleItalic">The Lancet</span>, which was withdrawn due to its falsity. A cause for concern.</p></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0020">Prevention of measles</span><p id="p0095" class="elsevierStylePara elsevierViewall">Vaccination is the most effective means of preventing measles. The vaccine is safe and effective and low cost. Children should receive 2 doses to guarantee their immunity. The first dose, which is administered at 12 months of age (at 9 months in measles-endemic countries), induces an immune response with seroconversion in more than 95 % of those vaccinated; the second dose enables the rescue of almost all the remaining (4.5 %) non-responders, i.e., primary vaccine failures. Susceptible adults should also receive 2 doses separated by a minimum interval of 1 month. Vaccine-conferred immunity has been shown to persist for at least 20 years, but is thought to last a lifetime in most people. According to various studies, the protective effectiveness of the measles vaccine ranges from 93 % for the first dose to 97 % for the second. It has been established that to achieve herd immunity, a vaccination coverage rate of 95 % or more is required with the second dose. The vaccine is also effective in post-exposure prophylaxis to prevent the spread of outbreaks, the risk of which is high in certain population groups, such as refugees, who should be vaccinated as soon as possible.<a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0015"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0125"><span class="elsevierStyleSup">25</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0130"><span class="elsevierStyleSup">26</span></a></p><p id="p0100" class="elsevierStylePara elsevierViewall">Could another type of vaccine exist that would be better accepted and achieve better coverage? A logistical drawback of the current live attenuated virus measles vaccine is its thermostability, and therefore, the possibility of a new technology under investigation, a novel vaccine administration system using skin patches composed of microneedles (microneedle array patch or microneedle patch) containing a small amount of lyophilised live virus, would be an excellent alternative for easier dissemination of the vaccine. This preparation is thermostable, takes up little space, does not have to be reconstituted or diluted and avoids parenteral administration. It does not require the participation of health personnel given the ease of application, which is not painful, and it is available in a single-dose presentation. These characteristics will favour the increase in vaccination coverage by not having to maintain the cold chain required by current preparations, which represents a logistical barrier for developing countries.<a class="elsevierStyleCrossRef" href="#bb0135"><span class="elsevierStyleSup">27</span></a></p><p id="p0105" class="elsevierStylePara elsevierViewall">The results of a phase 1/2 clinical trial carried out in Gambia show that the measles and rubella vaccine administered through microneedle patches is well tolerated, safe, and immunogenic in infants, children, and adults, which supports its accelerated development.<a class="elsevierStyleCrossRef" href="#bb0140"><span class="elsevierStyleSup">28</span></a></p><p id="p0110" class="elsevierStylePara elsevierViewall">The Vaccine Innovation Prioritisation Strategy is a collaboration between the Gavi Secretariat, WHO, the Bill and Melinda Gates Foundation, UNICEF, and PATH. Its purpose is to develop a unique integrated framework to evaluate, prioritise, and drive innovations in vaccines. Microneedle patches have been ranked as the highest global priority innovation to overcome barriers to immunisation in low- and middle-income countries and achieve greater equity in vaccination coverage.<a class="elsevierStyleCrossRef" href="#bb0145"><span class="elsevierStyleSup">29</span></a></p></span><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025">Final reflections</span><p id="p0115" class="elsevierStylePara elsevierViewall">Epidemiological surveillance; early diagnosis of cases; contact tracing; implementation of outbreak control measures, and systematic vaccination of the population are essential to achieve control and elimination of measles. Health professionals must be up to date in the knowledge and diagnosis of this re-emerging disease.</p><p id="p0120" class="elsevierStylePara elsevierViewall">The decrease in vaccination coverage is the cause of the re-emergence of measles, so it is of great importance to implement good communication strategies for the population and use new technologies to improve information for new generations.</p><p id="p0125" class="elsevierStylePara elsevierViewall">Vaccination coverage must be evaluated in each region in order to determine barriers and social inequalities between different groups, and also to implement specific strategies to increase coverage in them.<a class="elsevierStyleCrossRef" href="#bb0150"><span class="elsevierStyleSup">30</span></a></p><p id="p0130" class="elsevierStylePara elsevierViewall">Information on vaccines and accessibility to vaccination must be equal for all people: vaccine equity is a priority. Measles vaccination must reach and maintain coverage of 95 % or more of the population, which is essential to achieve its eradication, a process that can still be long and difficult.<a class="elsevierStyleCrossRef" href="#bb0155"><span class="elsevierStyleSup">31</span></a></p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:6 [ 0 => array:2 [ "identificador" => "s0005" "titulo" => "Measles prevention achievements" ] 1 => array:2 [ "identificador" => "s0010" "titulo" => "Re-emergence of measles in 2017. The first two years of the COVID-19 pandemic" ] 2 => array:2 [ "identificador" => "s0015" "titulo" => "Re-emergence of measles in the world, Europe and Spain after the COVID-19 pandemic" ] 3 => array:2 [ "identificador" => "s0020" "titulo" => "Prevention of measles" ] 4 => array:2 [ "identificador" => "s0025" "titulo" => "Final reflections" ] 5 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="np4005">Please cite this article as: Moraga-Llop F, Campins-Martí M. Erradicación del sarampión: todavía un largo y difícil camino. Vacunas. 2024. <span class="elsevierStyleInterRef" id="ir3005" href="https://doi.org/10.1016/j.vacune.2024.10.002">https://doi.org/10.1016/j.vacune.2024.10.002</span>.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0005" "bibliografiaReferencia" => array:31 [ 0 => array:3 [ "identificador" => "bb0005" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sarampión. Reemergencia en el camino de la erradicación" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "F.A. Moraga-Llop" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.vacun.2020.04.001" "Revista" => array:5 [ "tituloSerie" => "Vacunas" "fecha" => "2020" "volumen" => "21" "paginaInicial" => "41" "paginaFinal" => "49" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bb0010" "etiqueta" => "2." 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