Review
Measles. Re-emergence on its path to eradication
Sarampión. Reemergencia en el camino de la erradicación
F.A. Moraga-Llop
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Societat Catalana de Pediatria, Asociación Española de Vacunología, Barcelona, Spain
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Re-emergence on its path to eradication" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "41" "paginaFinal" => "49" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "F.A. Moraga-Llop" "autores" => array:1 [ 0 => array:4 [ "nombre" => "F.A." "apellidos" => "Moraga-Llop" "email" => array:1 [ 0 => "fmoraga@acmcb.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Societat Catalana de Pediatria, Asociación Española de Vacunología, Barcelona, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Sarampión. Reemergencia en el camino de la erradicación" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 851 "Ancho" => 1501 "Tamanyo" => 129734 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Measles. A. Measles facies (conjunctivitis, rhinitis and stomatitis). B. Characteristic maculopapular exanthema.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0010" class="elsevierStylePara elsevierViewall">It was 40 years ago now, in 1980, when the World Health Organisation (WHO) certified the eradication of smallpox. After having overcome many obstacles, for some time we have been progressing towards doing the same with poliomyelitis. Two of its causal agents (poliovirus 2 and 3) have now been eradicated, and only type 1, which is endemic in Pakistan and Afghanistan, is still circulating. The WHO had set the objective of eradicating a third disease, measles, by 2020.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Nevertheless, in 2017 this goal was seen to be impossible to achieve because the disease had re-emerged, and in 2019 morbidity worldwide due to this disease tripled, with high rates of mortality.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Measles was the first infectious exanthematous disease to be, classified, in as 1627, Sydenham differentiated it from scarlet fever, they became known as, the first, second disease, respectively. In it was recognised as 1881, different from the third disease, which was designated rubella or German Measles (in honour of the German authors who were interested in studying it). In and 1885| 1894, Filatow(in honour of the German authors who were interested in studying it), Dukes described a fourth disease, which was denominated scarlet fever-like rubella, which eventually “disappeared” as, such, it consisted of clinically mild forms of scarlet fever. In as 1905, a fifth disease or infectious erythema was defined, in 1910, roseola infantum was mentioned for the first time, as, exanthema subitum or a sixth disease.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> From then on exanthematic diseases ceased to be, given ordinal numbers.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Before the introduction of widespread vaccination campaigns measles infected from 95%-98% of children under the age of 18 years old, causing approximately 135 million cases and more than 6 million deaths per year worldwide, with mortality rates of approximately 3%-34% in developing countries, from 10 to 20 times higher than the rates in industrialised countries.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The worldwide incidence of measles has now increased, making it necessary to know or recall its clinical signs. This is so above all in the case of doctors who did not become familiar with this disease during their training, as diagnosis must be a suspicion during anamnesis and patient examination. This review analyses the most relevant epidemiological, clinical and diagnostic aspects of measles, together with preventive measures.</p></span><span id="sec1005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect1025">Epidemiology</span><p id="par0030" class="elsevierStylePara elsevierViewall">Measles is a highly contagious disease, with a secondary attack rate close to or above 90%. It is seasonal, and is most common at the end of winter and the beginning of spring. In a susceptible population one case will originate from 12 to 18 secondary cases. This figure is denominated R° or the basic reproduction number, and it is one of the highest in infectiology. As measles is one of the most contagious diseases, immunity levels of 95% or higher are needed in the population to interrupt its transmission and eliminate it from the community.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6–9</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The disease has an exclusively human reservoir, and its mechanism of transmission is direct by person to person contact through Flügge droplets (> 5 µ) of respiratory secretions that are swiftly deposited when coughing, sneezing or talking. This means that transmission is only possible at a distance of somewhat less than 1 m. It may also be transmitted through the air by aerosols of small droplets (< 5 µ), and by direct contact with nasal and pharyngeal secretions. Another less common mechanism is by indirect contact through fomites recently contaminated by nasopharyngeal secretions.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6–8</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The duration of transmittability or contagiousness lasts from one to two days prior to the start of symptoms (4 days prior to the start of the exanthema) until 4 days after the appearance of the eruption. Children may not return to their kindergarten or school until at least 5 days have passed after the start of the exanthema, always on condition that their general state makes this possible. Immunodepressed patients have a longer period of viral secretion, and they may still be contagious for several weeks after the appearance of the exanthema.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6–8</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Systematic vaccination has changed the epidemiological pattern: cases are observed in children not vaccinated with 2 doses after one year of age, or when they had not received their first vaccination (failure to receive their second vaccination is very rare). The global number of cases has now undergone a major increase, and this seriously threatens the possibility of eradication in the next few years.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Although there are several reasons why measles has resurged, they always coincide in the reduction of vaccination coverage. Reluctance to vaccinate predominates in developed countries. This is a broad concept that runs from people who deeply reject all vaccines, to those that accept them with doubts and concerns. It also includes people who belong to certain political, religious, cultural and lifestyle groups. Isolation from the healthcare system may in some cases be decisive in not vaccinating. A range of causes and situations exist in countries that lack economic resources: political, social conflict or war, a shortage of supplies or fear about the safety of vaccination. Other factors that should be considered and studied are the early loss of transplacental immunity in the children of vaccinated mothers,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> the age when the first dose is administered<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11,12</span></a> and concordance between the circulating virus genotype and those of the vaccines.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">This situation must not continue, as measles fulfils all of the criteria for eradication: it is an infection which is limited to humans and is transmitted from person to person, there are no chronic carriers, there is a single causal agent, the transmissibility period is short, a safe and effective vaccine is available and natural or vaccinated immunity lasts for a long time.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">If the global situation of measles continues as it is, the WHO should consider declaring this resurgence to be an international public health emergency, so that firstly the disease can be controlled, followed by its eradication.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Measles in the world</span><p id="par0065" class="elsevierStylePara elsevierViewall">According to WHO data corresponding to December 2019, before the vaccine came into general use in 1963, every 2-3 years there were major epidemics that caused up to 2 million deaths per year. From 2000 to 2016 vaccination against measles reduced the number of deaths by 84%, down from 550,000 to 90,000 individuals, most of them under the age of 5 years old. Nevertheless, this figure rose to 110,000 in 2017 (total incidence: 6.7 million cases) and to 140,000 in 2018.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> It is estimated that during the period from 2000-2018 vaccination against measles prevented 23.2 million deaths worldwide.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> In 2018, 86% of newborn babies received their first vaccine dose before their first birthday, vs. 72% in the year 2000, although only 69% received the second dose.</p><p id="par0070" class="elsevierStylePara elsevierViewall">The number of cases of measles tripled from 2017 to 2019, although the WHO, taking into account the fragility of monitoring systems in many countries, estimates that this increase is probably up to 10 times greater. Current worldwide mortality is higher than 300 deaths per day, the majority of them younger than 5 years old. This increase in the incidence of measles has varied from one WHO region to another, and Africa stands out with an increase of 900% in 2019 over the previous year.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Although North and South America were free of measles from 2016, more than 15,000 cases were reported in 2019 in 14 countries, with 18 deaths. Brazil stands out with more than 13,000 cases and 15 deaths, together with the United States with 1,282 cases and Venezuela with more than 500 cases and 2 deaths.</p><p id="par0080" class="elsevierStylePara elsevierViewall">The largest outbreak in the United States since 1992 occurred from 30 September 2018 to 3 September 2019. There were 654 cases in New York, the majority in Brooklyn and Rockland County, caused by a fall in vaccination rates, most especially in the community of Orthodox Jews. Although measles had been declared to have been eliminated from the United States in the year 2000, there were a total of 1,282 cases in 2019.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Outbreaks of measles have been reported in many South East Asian and Pacific countries since 2017. An outbreak has been running in the Philippines since the end of 2017, with more than 20,000 cases and 199 deaths in 2018. This outbreak increased notably in 2019, as the population ceased vaccinating due to a loss of trust after the failure and controversies arising from the introduction of a Dengue fever vaccine. An outbreak was declared in the islands of Samoa in October 2019. This affected 5,697 people and caused 83 deaths, and it occurred due to a fall in vaccination coverage because of an error in administering a vaccine that led to the deaths of 2 children.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Another major outbreak occurred in the Democratic Republic of the Congo in June 2019, simultaneously with an outbreak of Ebola, with more than 250,000 cases and 6,000 deaths.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Measles in Europe</span><p id="par0090" class="elsevierStylePara elsevierViewall">A highly important fact that must be pointed out is that, according to data from the first half of 2019, the WHO withdrew measles elimination certification from 4 countries: the United Kingdom, Greece, Albania and the Czech Republic, because their vaccination programs did not maintain coverage of 95% or more.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> The current situation regarding the elimination of measles in the world is that it has been achieved in 83 (42%) of the 194 WHO member states, and in 70% of the countries in the WHO European region.</p><p id="par0095" class="elsevierStylePara elsevierViewall">In 2017, several countries in the WHO European Region recorded outbreaks in children and adults, including France, Georgia, Greece, Italy, Rumania, the Russian Federation, Serbia and Ukraine. Since then (as the lowest figure was achieved in 2016, with 5,273 cases) the number of cases has quadrupled (25,863, 88,693 and 101,280 cases in 2017, 2018 and January - October 2019, respectively). It should be underlined that there were 74 deaths in 2018, vs. 42 in 2017.</p><p id="par0100" class="elsevierStylePara elsevierViewall">The largest outbreak with a death in a decade occurred in Israel in 2018. This affected the Orthodox population of Jerusalem above all due to their refusal to vaccinate, with vaccination rates of 85% that in the schools with the highest rates of morbidity did not attain 50%.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Measles in Spain</span><p id="par0105" class="elsevierStylePara elsevierViewall">On 26 September 2017 the WHO declared Spain free of endemic measles transmission, recognising that the few cases and outbreaks reported in the previous 3 years had been the result of importations (while in Catalonia the disease had been declared to have been eliminated in the year 2000<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>); in 2019 the WHO ratified the elimination of measles in our country.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">The number of confirmed cases of measles has risen from a rate of 0.8 cases per million inhabitants in 2015 up to 4.8 in 2018 and approximately 6 (provisional data) in 2019. Of the 287 cases in the past year (vs. 222 in 2018), 36 were imported, 237 were connected and 14 were of unknown origin; there were no autochthonous cases.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Of the 157 cases of measles recorded in 2017, 66.9% were in individuals over the age of 19 years old, and all of them were imported or connected with imported cases, of which 86% corresponded to European countries (Rumania, Italy, the United Kingdom and France) while 14% correspond to Asia (China, Indonesia and Japan).<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Clinical manifestations</span><p id="par0115" class="elsevierStylePara elsevierViewall">Measles is an infectious disease caused by a virus of the <span class="elsevierStyleItalic">Morbillivirus</span> genus of the <span class="elsevierStyleItalic">Paramyxoviridae</span> family. Only one serotype of the measles virus exists, and there are a great many circulating genotypes due to its high genetic variability. It is a very labile virus, and it is vulnerable to external agents such as light and heat, which render it inactive. This disease is the first of the long list of maculopapular exanthemas, and it gave the name of “morbiliform” exanthemas to cutaneous eruptions with different aetiologies with morphological characteristics similar to those of measles.</p><p id="par0120" class="elsevierStylePara elsevierViewall">Measles has highly uniform clinical manifestations (<a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>), and 4 periods after contagion are distinguished in its evolution:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1</span><p id="par0125" class="elsevierStylePara elsevierViewall">The incubation period: this runs from the moment of exposure to the virus and its penetration in the organism until the start of prodromic or catarrhal symptoms. This coincides with the secondary viremia and involvement of the respiratory mucosa, and it lasts for 8-12 days. The time lapse until the moment exanthema commences may be up to 21 days, with an average of 14 days. The duration is longer after the administration of general purpose immunoglobulin, which forms part of the post-exposure prophylaxis or in patients undergoing replacement therapy, in breast-feeding babies due to the persistence of maternal antibodies, and in immunodeficient individuals. This period may be shortened in exceptional cases, such as direct infection of a cutaneous wound with infected secretions, or parenteral infection. This is an asymptomatic period, except for fleeting temperature variations, slight discomfort or mild respiratory symptoms that are almost always hard to notice and detect.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2</span><p id="par0130" class="elsevierStylePara elsevierViewall">The prodromic, catarrhal or pre-exanthematic period: this lasts for an average of 4 days, although not uncommonly it may last longer, up to 10 days. As is the case during the exanthematic period, the symptoms may vary or attenuate due to the previous administration of immunoglobulin or vaccine. Prodromes are manifested by constant high fever which may sometimes give rise to feverish convulsions, cephalea, somnolence, general discomfort and catarrhal symptoms due to involvement of the conjunctival, nasal and oropharyngeal mucosa and that in the upper airways (the larynx and trachea). Ocular, nasal and oral alterations, with a certain degree of facial swelling, configure the characteristic measles facies. The oral exanthema (Koplik spots) was described by Flindt in 1860; Koplik described their pathognomic nature in 1896, and Rembold and Flindt published this observation in 1905. They consist of small pointed raised spots, white in colour (“like salt spots”), surrounded by a reddish halo or an erythematous base. They occur in the jugular mucosa and on the internal face of the cheeks opposite to the molars in 70%-90% of cases. They appear at the end of the prodromic period immediately before the exanthema (1-2 days), and they disappear within 24-48 hours of the start of the latter. The exanthema makes it possible to diagnose measles prior to the appearance of the characteristic exanthema. Similar spots to Koplik spots may appear on the mucosa of the lips, eyelid, conjunctiva, nose and vagina, as well as on the outer wall of the pharynx, although these locations are rarely involved.</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3</span><p id="par0135" class="elsevierStylePara elsevierViewall">The period corresponding to the condition or exanthematic period: fever rises when the cutaneous eruption starts, when catarrhal eye-nose-pharynx-larynx-trachea-bronchial symptoms and general involvement are at their most intense, while the Koplik spots disappear. This period lasts from 3 to 5 days (up to 7 days), during which the symptoms evolve. The exanthema is maculopapular, violet red in colour and very numerous, not confluent at first and generally not pruriginous; it commences in the area behind the ears and spreads over 3 days, descending over the rest of the face and neck, the trunk and limbs, without involving the palms of the hands or the soles of the feet and converging. If the fever increases or reappears then a complication of the measles must be suspected.</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4</span><p id="par0140" class="elsevierStylePara elsevierViewall">The convalescence, decline or desquamation period: this starts on the third or fourth day of the exanthematic period, with reduction and disappearance of the fever and catarrhal symptoms except for the cough, which may last for a few days or weeks, and the skin eruption, in the same order in which they arose, together with an important improvement in general condition. The presence of a bran-like small scale desquamation is characteristic of this phase, leaving the skin violet or brown in colour and enabling retrospective diagnosis. The cough and bronchial symptoms are the last to disappear.<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24–28</span></a></p></li></ul></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">Other infections are often present while convalescing from measles (influenza, whooping cough, diphtheria, tuberculosis, parotitis, scarlet fever, varicella and aphthous stomatitis). This had been observed in the time before vaccination, when measles was described as an anergising disease because the measles virus eliminates antibodies that protect against infections which the body had been immune to, and specific immunity memory cells that had been generated against other diseases. This phenomenon of amnesia or immunity dysfunction against other infectious diseases may still be observed five years after suffering measles, so that anti-measles vaccine may be said to protect against more than measles itself, as it also protects against other infectious diseases.<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29,30</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Clinical forms</span><p id="par0150" class="elsevierStylePara elsevierViewall">The clinical manifestations of measles may change and have characteristics other than those described. It takes the following clinical forms:<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24,26,31</span></a><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0155" class="elsevierStylePara elsevierViewall">Abortive or modified measles: the exanthema has fewer elements and colouration is paler, while the symptoms are mild; sometimes this is experienced in a subclinical form. The incubation period is longer. This clinical form occurs after the administration of general purpose immunoglobulin during the incubation period or in the first half of the prodromic period, or after the previous administration of anti-measles vaccine. This form may also be seen in breastfeeding babies due to the persistence of maternal antibodies. These patients may suffer a second clinical infection if conferred immunity is incomplete.</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0160" class="elsevierStylePara elsevierViewall">Attenuated measles: this is an adverse reaction which occurs 5 to 12 days after vaccination. It develops with little fever and mild catarrhal symptoms, with a pale maculopapular exanthema with few elements.</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0165" class="elsevierStylePara elsevierViewall">Measles without exanthema or without fever: both of these forms are very rare and may occur in one family member during an outbreak. Retrospective diagnosis is by means of specific IgM determination, as the disease does not appear in anamnesis.</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">-</span><p id="par0170" class="elsevierStylePara elsevierViewall">Black and haemorrhagic measles: the exanthema elements undergo a haemorrhagic transformation due to the rupture of the papular capillaries (black form). This clinical form does not indicate greater severity if there is no haemorrhagic diathesis with cutaneous and mucosal manifestations in other locations, due to thrombocytopenia or more severe disseminated intravascular coagulation (haemorrhagic form).</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">-</span><p id="par0175" class="elsevierStylePara elsevierViewall">Vesiculosus or blistering measles: this may appear in children with intense hyperhydrosis in hot humid environments.</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">-</span><p id="par0180" class="elsevierStylePara elsevierViewall">Converging scarlatiniform measles: catarrhal symptoms help to differentiate this from scarlet fever.</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">-</span><p id="par0185" class="elsevierStylePara elsevierViewall">Pseudoappendicular measles: abdominal pains frequently occur in the prodromic and condition periods. They are sometimes intense and located in the right iliac fossa, and this may lead to an appendectomy, in which the existence of mesenteric adenitis is observed, and more rarely true appendicitis.</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">-</span><p id="par0190" class="elsevierStylePara elsevierViewall">Atypical measles: this occurs in individuals immunised with inactivated virus vaccine that was used from 1963 to 1967 in the United States and Canada, and atypical measles occurs when they are subsequently exposed to the wild virus. The disease usually runs in two phases, at first as immunisation-modified measles, followed after 2 weeks by high fever and atypical exanthema. The latter spreads centripetally and involves the hands and feet, and it is occasionally vesiculosus and purpuric. Pulmonary complications are common, with hilar adenopathies, pleural bleeding and diffuse nodular infiltrates. This is considered to be an immunocomplex-delayed hypersensitivity phenomenon.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a></p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">-</span><p id="par0195" class="elsevierStylePara elsevierViewall">Adult measles: this clinical form is more severe than measles in childhood and it has more complications, chiefly pneumonia, bacterial respiratory infections, bronchospasm and hepatitis.</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">-</span><p id="par0200" class="elsevierStylePara elsevierViewall">Severe measles in patients with cellular immunity disorders: this may develop without exanthema and it frequently leads to complications, among which progressive acute encephalitis with measles inclusion bodies stands out, together with giant cell pneumonia.</p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">-</span><p id="par0205" class="elsevierStylePara elsevierViewall">Measles during pregnancy: the most important effect of the virus on the mother is that it increases her risk of suffering complications, most especially respiratory ones (pneumonitis), and for the foetus, as it may cause an abortion or premature birth. The measles virus has not been proven to have teratogenic effects.</p></li></ul></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Complications</span><p id="par0210" class="elsevierStylePara elsevierViewall">The most important and frequent complications of measles are respiratory and neurological, and they almost always occur during or after the exanthematic period. In general, complications with measles should always be suspected when the fever persists or reappears. The most common complications are acute otitis media, diarrhoea, mastoiditis, sinusitis, cervical lymphadenitis, stenosing laryngitis, laryngotracheobronchitis, pneumothorax, pneumomediastinum and subcutaneous emphysema, pneumonia or bronchopneumonia (viral, bacterial or mixed), enteritis, thrombocytopenic purpura, pyodermitis, feverish convulsions, hepatitis, appendicitis, myocarditis and acute post-infectious encephalitis with permanent brain damage (one in every 1,000-2,000 cases of measles). The most frequent microorganisms in bacterial infections are <span class="elsevierStyleItalic">Streptococcus pneumoniae</span>, <span class="elsevierStyleItalic">Streptococcus pyogenes</span> and <span class="elsevierStyleItalic">Staphylococcus</span> aureus.<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24,26,28</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">Subacute sclerosing panencephalitis is a chronic degenerative disease of the central nervous system which develops with behavioural disorders, intellectual deterioration and myoclonic epilepsy, and it is caused by the chronic activation of the measles virus. More than half of patients had been diagnosed with measles in the first 2 years of life. Clinical manifestations commence after an average 7-11 year period of latency after having had the disease. The risk of subacute sclerosing panencephalitis amounts to 4-11 cases per 100,000 cases of measles.</p><p id="par0220" class="elsevierStylePara elsevierViewall">Death caused by measles is due to respiratory and neurological complications, and the mortality rate is higher in children younger than 5 years old, adults and immunodepressed individuals, including children with leukaemia, individuals with human immunodeficiency virus infection and those with severe malnutrition. Lethality varies from 1% to 15% in developing countries.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">31,33</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Diagnosis</span><p id="par0225" class="elsevierStylePara elsevierViewall">Although diagnosis is based on symptoms and epidemiology, it must always be confirmed in the current stage of resurgence to ensure proper epidemiological vigilance. This has to include the determination of the specific IgM after the fourth day of the appearance of the exanthema (preferentially from day 4 to 8 and before day 28), or the specific IgG in 2 samples separated by an interval of 2-4 weeks; diagnosis is late in the latter case. Early confirmation of IgM positivity is very important to enable the urgent adoption of preventive measures in contacts and in the social circle of the patient (their home, kindergarten, school, waiting rooms, primary care emergency services and in hospitals). Another method is the detection of the virus in urine or pharyngeal swab by polymerase chain reaction in the 8 days following the appearance of the exanthema. Genotyping the virus is important for epidemiological vigilance, the study of outbreaks and evaluation of the efficacy of vaccines.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,8,34</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Actions, preventive measures and treatment</span><p id="par0230" class="elsevierStylePara elsevierViewall">If there is the suspicion of measles in a patient the epidemiological vigilance service must be notified urgently, the specific IgM must be determined and the patient is to be isolated or wear a surgical mask. If the case if confirmed the epidemiological questionnaire will be applied, together with post-exposure prophylaxis for susceptible contacts.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a></p><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Post-exposure prophylaxis</span><p id="par0235" class="elsevierStylePara elsevierViewall">After exposure to the measles virus a susceptible individual will act according to the time that has transpired from the moment of contact:<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a><ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">-</span><p id="par0240" class="elsevierStylePara elsevierViewall">In the first 72 hours after contact: vaccination if this is not contraindicated. In babies younger than 6 months old, pregnant women and immunodepressed patients, general purpose immunoglobulin will be administered even if they have been vaccinated.</p></li><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">-</span><p id="par0245" class="elsevierStylePara elsevierViewall">From 4 to 6 days after contact: general purpose immunoglobulin will be administered to all susceptible and immunodepressed individuals, even if they have been vaccinated.</p></li></ul></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Treatment</span><p id="par0250" class="elsevierStylePara elsevierViewall">The patient will continue in isolation, preferentially in their own home, although if their clinical situation makes it necessary they will be admitted to hospital in a negative pressure room. If a vulnerable person has to enter the room, as well as the standard safety measures they will have to take precautions to prevent airborne transmission while the disease is transmissible.</p><p id="par0255" class="elsevierStylePara elsevierViewall">Treatment will be symptomatic and supportive, as well as preventing possible bacterial complications. Additionally, vitamin A will be administered once a day during 2 days, at the following doses: 200,000 UI for children over 12 months old, 100,000 UI in babies aged from 6 to 11 months old, and 50,000 UI for those under the age of 6 months old. A third dose will be given from 2 to 4 weeks afterwards to children with clinical signs of vitamin A deficiency.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Vaccination</span><p id="par0260" class="elsevierStylePara elsevierViewall">The first vaccines were developed by Enders, who together with Peebles isolated and cultivated the measles virus in 1954. It originated in a student named Edmonston, who gave its name to one of the most widely used vaccine strains of live attenuated virus. The first vaccine was approved in the United States in 1963.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0265" class="elsevierStylePara elsevierViewall">Research was conducted into inactivated vaccines in the United States in the 1960s, and in 1963 the first one derived from the Edmonston strain was authorised. Al though this vaccine had fewer side effects, it was also less effective, and when a vaccinated individual subsequently came into contact with the wild virus they developed atypical measles. This disease is caused by antigen-antibody immune complexes (delayed reaction hypersensitivity) (see the <span class="elsevierStyleItalic">Clinical Forms</span> section), so that it ceased to be used 4 years later.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,32</span></a></p><p id="par0270" class="elsevierStylePara elsevierViewall">Two attenuated Edmonston B strain vaccines were used in Barcelona in 2 pioneering clinical trials in Europe in 1961 and 1962.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> Given the high reactogenicity (high fever and exanthema) observed in the first clinical trial, in the second one immunoglobulin was administered after vaccination in 3 groups, on the same day and on the third and sixth days, to reduce the side effects.</p><p id="par0275" class="elsevierStylePara elsevierViewall">The first measles vaccination campaign in Spain commenced in 1968 in 11 provinces, vaccinating children aged from 9 to 24 months old; the vaccine used contained the Beckenham 31 strain, which was found to be highly reactogenic.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> With this strain a severe reaction (encephalitis) was observed in England, and it was withdrawn. This contributed to the suspension of vaccination in Spain in 1970.</p><p id="par0280" class="elsevierStylePara elsevierViewall">Parallel research took place into obtaining hyperattenuated strains, one of which, the Schwarz strain (1964), originated in the Edmonston A strain but was far less reactogenic. This was used in the first monovalent anti-measles vaccine (Rouvax®), which was utilised in the first systematic vaccination calendar in Spain by Barcelona Town Hall in 1973, at 12 months of age.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> This vaccine was included in Spain in the calendar drawn up by the Dirección General de Sanidad in 1977, for use at 9 months old.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> In comparison with the previous attenuated vaccine, this hyperattenuated strain caused side effects less often and they were less severe, making it possible to eliminate the use of immunoglobulin.</p><p id="par0285" class="elsevierStylePara elsevierViewall">Two live hyperattenuated vaccines were authorised in 1965 and 1968. These too were derived from the Edmonston strain, and they contained the Schwarz and Moraten strains <span class="elsevierStyleItalic">(MORe ATtenuated ENders)</span>, respectively.</p><p id="par0290" class="elsevierStylePara elsevierViewall">The current attenuated live virus vaccine which is administered in the form of the triple viral vaccine is available in Spain in two forms, one with the Schwarz strain and the other with the Enders’ Edmonston strain. This vaccine was included in the calendar of all of the autonomous communities in 1981, and in the second dose in 1996,<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> although Catalonia had already done so in 1988.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> The vaccine must not be administered prior to the age of 12 months old, except in situations of pre-exposure and post-exposure prophylaxis, in which case it can be given after the age of 6 months (although the technical data sheet states that it is for after the age of 9 months, the medical authorities have authorised this). When the vaccine is administered at 6-11 months it is indispensible to prescribe 2 further doses after the age of 12 months.</p><p id="par0295" class="elsevierStylePara elsevierViewall">A dose administered at 12 months of age induces an immune response with seroconversion in more than 95% of vaccinated individuals; a second dose between 2 to 4 years old makes it possible to rescue nearly all of the others (4.5%), i.e., the initial failures. After modification of the first strategy a second recall dose is administered after at least 4 weeks, with the aim of rescuing those who have not responded. The maximum response occurs at from 6-8 weeks after vaccination. It has been found that vaccine-conferred immunity lasts for at least 20 years, and it is believed that it lasts for the whole life of the majority of individuals.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7–9</span></a> The most frequent adverse reactions after vaccination are local, although sometimes a case of attenuated measles may occur (as described under the heading <span class="elsevierStyleItalic">Clinical forms</span>).</p><p id="par0300" class="elsevierStylePara elsevierViewall">The protective efficacy of the measles vaccines in several studies was found to range from 93% to 97% after one and 2 doses, respectively.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7–9</span></a> To achieve herd immunity a second dose vaccination coverage rate higher than 95% is necessary. Excellent vaccination was achieved in Spain in 2017 and 2018, higher than 97% for the first dose but only 93.1% and 94.1% for the second dose, respectively; moreover, 9 autonomous communities were below 95%, and this aspect must be improved.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a></p><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Pre-exposure prophylaxis</span><p id="par0305" class="elsevierStylePara elsevierViewall">When a susceptible individual has to travel to a place where the measles virus is circulating, the following action will be taken:<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,8</span></a><ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">-</span><p id="par0310" class="elsevierStylePara elsevierViewall">Babies under 6 months old: if the mother is susceptible, intramuscular general purpose immunoglobulin will be administered.</p></li><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">-</span><p id="par0315" class="elsevierStylePara elsevierViewall">Babies aged from 6 to 11 months: a dose of triple viral vaccine will be administered and this will be considered to be dose 0. At 12 months a 2 dose pattern will commence, with an interval of at least 28 days.</p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">-</span><p id="par0320" class="elsevierStylePara elsevierViewall">Children over the age of 12 months and adults: it must be confirmed whether they have received the recommended 2 doses after the age of 12 months, or if they have had the disease. If the individual is susceptible they will be vaccinated with 2 triple viral vaccine doses separated by an interval of one month (and if they had been vaccinated with a single dose, they will be given a second dose).</p></li><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">-</span><p id="par0325" class="elsevierStylePara elsevierViewall">Susceptible children and adults for whom the vaccine is contraindicated (those under the age of 6 months, pregnant women and immunodepressed individuals, including those who have been vaccinated): general purpose intramuscular immunoglobulin at a dose of 0.5 ml/kg (maximum dose: 15 ml); in high risk immunodepressed individuals this dose will be administered intravenously.</p></li></ul></p></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conclusions</span><p id="par0330" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0110"><span class="elsevierStyleLabel">-</span><p id="par0335" class="elsevierStylePara elsevierViewall">After the continuous fall in the morbidity and mortality caused by measles during this century, from 2017 onwards a global resurgence of the disease has occurred due to a range of reasons. This situation has arisen when progress was being made towards the eradication of the disease, which had been foreseen to take place in this year, 2020. This resurgence has even occurred in Europe and in countries where measles had been eliminated, and the primary cause is very worrying: the fall in vaccination coverage due to reluctance to vaccinate.</p></li><li class="elsevierStyleListItem" id="lsti0115"><span class="elsevierStyleLabel">-</span><p id="par0340" class="elsevierStylePara elsevierViewall">Doctors (pedestrians and family doctors) must suspect measles in any individual, after anamnesis to evaluate their immunity status and possible contacts, who has fever and catarrhal symptoms that have evolved over several days, with the subsequent appearance of a generalised maculopapular exanthema.</p></li><li class="elsevierStyleListItem" id="lsti0120"><span class="elsevierStyleLabel">-</span><p id="par0345" class="elsevierStylePara elsevierViewall">The epidemiological vigilance department is to be urgently informed when there is the suspicion of a case of measles, determining its specific IgM and isolating the patient.</p></li><li class="elsevierStyleListItem" id="lsti0125"><span class="elsevierStyleLabel">-</span><p id="par0350" class="elsevierStylePara elsevierViewall">If the suspected case is confirmed then an epidemiological survey will be performed and post-exposure prophylaxis will be administered to susceptible contacts.</p></li><li class="elsevierStyleListItem" id="lsti0130"><span class="elsevierStyleLabel">-</span><p id="par0355" class="elsevierStylePara elsevierViewall">Systematic vaccination must take place infancy with the 2 dose triple viral vaccine after the age of 12 months, with a check that vaccination has taken place in all age groups for susceptible individuals, if vaccination is not contraindicated. Pre-exposure prophylaxis by vaccination must take place over the age of 6 months.</p></li><li class="elsevierStyleListItem" id="lsti0135"><span class="elsevierStyleLabel">-</span><p id="par0360" class="elsevierStylePara elsevierViewall">The great paradox is that vaccines save us from diseases and then lead us to forget the ones they saved us from.</p></li></ul></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Informed consent</span><p id="par0365" class="elsevierStylePara elsevierViewall">The author declares that he has the informed consent of all of the tutors of the patient for the publication of the clinical images in this paper, and that their personal data have been protected, according to the protocols of the institution.</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflict of interests</span><p id="par0370" class="elsevierStylePara elsevierViewall">The author has no conflict of interests to declare. The author of this paper declares that he is a member of the Editorial Committee of the journal <span class="elsevierStyleItalic">Vacunas</span>.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:16 [ 0 => array:3 [ "identificador" => "xres1510434" "titulo" => "Summary" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1370088" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1510435" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1370089" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec1005" "titulo" => "Epidemiology" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Measles in the world" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Measles in Europe" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Measles in Spain" ] ] ] 6 => array:2 [ "identificador" => "sec0030" "titulo" => "Clinical manifestations" ] 7 => array:2 [ "identificador" => "sec0035" "titulo" => "Clinical forms" ] 8 => array:2 [ "identificador" => "sec0040" "titulo" => "Complications" ] 9 => array:2 [ "identificador" => "sec0045" "titulo" => "Diagnosis" ] 10 => array:3 [ "identificador" => "sec0050" "titulo" => "Actions, preventive measures and treatment" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0055" "titulo" => "Post-exposure prophylaxis" ] 1 => array:2 [ "identificador" => "sec0060" "titulo" => "Treatment" ] ] ] 11 => array:3 [ "identificador" => "sec0065" "titulo" => "Vaccination" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0070" "titulo" => "Pre-exposure prophylaxis" ] ] ] 12 => array:2 [ "identificador" => "sec0075" "titulo" => "Conclusions" ] 13 => array:2 [ "identificador" => "sec0080" "titulo" => "Informed consent" ] 14 => array:2 [ "identificador" => "sec0085" "titulo" => "Conflict of interests" ] 15 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-03-04" "fechaAceptado" => "2020-04-14" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1370088" "palabras" => array:4 [ 0 => "Measle" 1 => "Exantematic disease" 2 => "Epidemiology" 3 => "Measles vaccine" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1370089" "palabras" => array:4 [ 0 => "Sarampión" 1 => "Enfermedades exantemáticas" 2 => "Epidemiología" 3 => "Vacunas antisarampión" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Summary" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar9005" class="elsevierStyleSimplePara elsevierViewall">After the continued decline in measles morbidity and mortality during this century, since 2017 there has been, for various reasons (vaccination reticence is very important), a re-emergence of the disease around the world, when walking towards its eradication. Clinicians should suspect measles to anyone susceptible to fever and a clinical flulike presentation of several days of evolution, with the subsequent appearance of a generalized maculopapulous rash. When a measles case is suspected, epidemiological surveillance service shall be urgently declared, the specific IgM shall be determined and the patient isolated. If the case is confirmed, an epidemiological survey and post-exposure prophylaxis of the susceptible contacts will be carried out. Routine vaccination in childhood with a triple viral vaccine with two doses from 12 months and in all persons with any age is essential, and vaccine coverage of 95% or more in the population is essential.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar9010" class="elsevierStyleSimplePara elsevierViewall">Después de la disminución continuada de la morbilidad y la mortalidad del sarampión durante este siglo, desde 2017 se observa, por diversas razones (la reticencia vacunal es muy importante), una reemergencia de la enfermedad en todo el mundo, cuando se caminaba hacia su erradicación. Los clínicos deben sospechar el sarampión ante cualquier persona susceptible que presente fiebre y un cuadro catarral de varios días de evolución, con la aparición posterior de un exantema maculopapuloso generalizado. Cuando se sospeche un caso de sarampión se declarará de manera urgente al servicio de vigilancia epidemiológica, se determinará la IgM específica y se aislará al paciente. Si el caso se confirma, se realizarán una encuesta epidemiológica y la profilaxis post-exposición de los contactos susceptibles. Es fundamental la vacunación sistemática en la infancia con vacuna triple vírica con dos dosis a partir de los 12 meses y en todas las personas susceptibles de cualquier edad, y es imprescindible mantener coberturas vacunales del 95% o más en la población.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Moraga-Llop FA. Sarampión. Reemergencia en el camino de la erradicación. Vacunas. 2020. <span class="elsevierStyleInterRef" id="intr0005" href="https://doi.org/10.1016/j.vacun.2020.04.001">https://doi.org/10.1016/j.vacun.2020.04.001</span></p>" ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 870 "Ancho" => 1499 "Tamanyo" => 153680 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Measles. A. Koplik spots in the oral mucosa. B. Start of exanthema behind the ears.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 851 "Ancho" => 1501 "Tamanyo" => 129734 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Measles. A. Measles facies (conjunctivitis, rhinitis and stomatitis). B. Characteristic maculopapular exanthema.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:39 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Organización Mundial de la Salud. 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