Imported and autochthonous dengue in Spain | Revista Clínica Española

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Número de casos de dengue por comunidad autónoma en España. Periodos 2016-2021. Tomado del Centro Nacional de Epidemiología<a class="elsevierStyleCrossRef" href="#bib0305">9</a>. B Vigilancia entomológica de Aedes albopictus en España, municipios, 2021. Tomado del Centro Coordinador de Alertas y Emergencias Sanitarias<a class="elsevierStyleCrossRef" href="#bib0335">15</a>. Ausente: se vigila, pero no se detecta; establecido: se detecta de forma repetida durante más de un año; introducido: se ha detectado por primera vez." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J.M. Herrero-Martínez, M. Sánchez-Ledesma, J.M. Ramos-Rincón" "autores" => array:3 [ 0 => array:2 [ "nombre" => "J.M." "apellidos" => "Herrero-Martínez" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Sánchez-Ledesma" ] 2 => array:2 [ "nombre" => "J.M." 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Herrero-Martínez, M. Sánchez-Ledesma, J.-M. Ramos-Rincón" "autores" => array:3 [ 0 => array:3 [ "nombre" => "J.-M." "apellidos" => "Herrero-Martínez" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "1" "identificador" => "PC_fnXOFo5N652O" ] ] ] 1 => array:3 [ "nombre" => "M." "apellidos" => "Sánchez-Ledesma" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "1" "identificador" => "PC_fnXOFo5N652O" ] ] ] 2 => array:4 [ "nombre" => "J.-M." "apellidos" => "Ramos-Rincón" "email" => array:1 [ 0 => "jose.ramosr@umh.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Medicina Interna, Hospital Universitario 12 de Octubre-Imas12, Madrid, Dpto. de Medicina, Universidad Complutense de Madrid, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidad Enfermedades Infecciosas, Servicio de Medicina Interna, Hospital Universitario de Salamanca- IBSAL, Salamanca, Dpto. de Medicina, Universidad de Salamanca, IBSAL, Salamanca, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Medicina Interna, Hospital General Universitario Dr. Balmis; Dpto de Medicina Clínica Universidad Miguel Hernández; Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, España" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Dengue importado y autóctono en España" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2731 "Ancho" => 2925 "Tamanyo" => 600175 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "(a) Number of cases of dengue per Autonomous Community in Spain. Periods from 2016-2021. Available from Centro Nacional de Epidemiología.<a class="elsevierStyleCrossRef" href="#bib0045">9</a> (b) Epidemiological surveillance of Aedes albopictus in Spain, towns, 2021. Available from Centro Coordinador de Alertas y Emergencias.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> Note. Introduced: it has been detected for the first time; established: it is repeatedly detected for more than one year; absent: it is monitored, but not detected." ] ] ] "textoCompleto" => "IntroductionDengue is a disease caused by the dengue virus. It is generally transmitted through Aedes (Stegomyia) aegypti or Aedes (Stegomyia) albopictus mosquito bites. Most cases reported in Spain are imported by travelers from countries with dengue transmission,<a class="elsevierStyleCrossRef" href="#bib0005">1</a> although cases of autochthonous dengue have been described in recent years. This article aims to review the epidemiology of dengue with a particular emphasis on cases diagnosed in Spain, its symptoms, diagnostic methods, and treatment of the disease.Dengue virus. Replication cycle. PathogenesisThe causative agent of dengue is an RNA virus of the Flaviviridae family and Flavivirus genus. It is a small, enveloped virus with four closely related serotypes: DENV-1, DENV-2, DENV-3, and DENV-4. There is transient cross-protection among the four types, though there will only be lasting immunity against the specific serotype that caused the infection, not against the rest. In fact, sequential infections by other serotypes increase the risk of contracting the severe form of dengue. Individuals who live in a hyperendemic area and where there are various serotypes are at risk of infection by various types.Viral replication occurs according to the following process: (a) initially, the virus binds to the cell surface, fusing their membranes and (b) allowing its entry into the cell. (c) Once in the cytoplasm, RNA transcription occurs in a polyprotein which can be processed and gives rise to three structural (C, M, and E) and seven nonstructural (NS) proteins. (d) The formation of the replication complex allows for replication of the viral genome, the subsequent (e) encapsidation and formation of virions, and (f) their later release from the cell.<a class="elsevierStyleCrossRefs" href="#bib0005">1,2</a>In regard to its pathophysiology, the increase in capillary permeability is notable. It is responsible for intravascular volume depletion and ultimately shock, a cardinal symptoms of dengue hemorrhagic fever. This increase in capillary permeability is related to endothelial dysfunction, not direct damage to the endothelial cells.<a class="elsevierStyleCrossRefs" href="#bib0005">1,2</a> In addition, this endothelial dysfunction is probably indirect. Histological studies have demonstrated minimal damage at the capillary level and anatomic pathology studies do not show direct infection of endothelial cells. The increase in permeability is transitory and the phase of greatest permeability occurs days after peak viral RNA levels. Therefore, it is speculated that the reason for this dysfunction is circulating factors such as nitric oxide, TNF alpha, interferon gamma, interleukin-2, interleukin-8, vascular endothelial growth factor, and the reduction in complement C3a and C5a levels <a class="elsevierStyleCrossRef" href="#bib0010">2</a>. The source of these cytokines would be the infected monocytes, dendritic and mastoid cells, and specific CD4 and CD8 lymphocytes.TransmissionThe dengue virus is mainly transmitted through Aedes (Ae. aegypti or Ae. albopictus) genus mosquito bites. Humans serve as a virus reservoir (except in the sylvatic cycle in Southeast Asia). The incubation period in the mosquito is from eight to 12 days. They can transmit the virus throughout their life and can transmit it to their offspring (transovarial transmission).Dengue transmission is the result of a complex interaction between the population, vectors, the virus, and environmental factors. It occurs below 2000 m and is more frequent during rainy periods. On the other hand, the disease incidence varies from year to year, with greater transmission in intervals of three to four years.Transmission patternThere are two transmission patterns<a class="elsevierStyleCrossRef" href="#bib0015">3</a>: (A) Epidemic dengue due to a single virus strain when it is introduced into a region and affects susceptible people. The incidence can be high, up to 25% to 50%. The outbreak ends thanks to the development of herd immunity, climate changes, and vector control. (B) Hyperendemic dengue, in which various serotypes of the virus circulate in the same area with presence of mosquitos year-round. This form of transmission causes most cases and especially affects urban areas.Factors that influence transmissionThe worldwide incidence has increased in recent decades as a consequence of an increase in population; overcrowding of urban areas; inadequate sanitation (with stagnant water); greater movement of individuals; and the expansion and lack of control of vectors, in part due to the effects of climate change.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> Its control depends in large part on an adequate approach from a public health perspective.<a class="elsevierStyleCrossRef" href="#bib0010">2</a>Mechanism of transmissionAs stated above, vector transmission is the main route of transmission. Mosquitos of the Aedes genus tend to bite during the day, preferably at dawn and at dusk. Other much less common routes of transmission are through blood derivatives, transplantation, or from mother to child (perinatal).<a class="elsevierStyleCrossRef" href="#bib0025">5</a> Breastfeeding could be another mechanism of transmission. The possibility of transmission through sexual activity has also been described, but is uncommon.EpidemiologyDengue is distributed in all regions where there is a transmission vector (from latitudes 30° north to 20° south). The disease is endemic in more than 100 countries in tropical and subtropical regions and causes between 100 and 400 million infections worldwide each year. At present, around half of the world’s population is at risk of contracting this disease.Dengue is endemic in five of the six WHO regions (except for the European region): Africa, the Eastern Mediterranean, South-East Asia, the Americas, and the Western Pacific regions.<a class="elsevierStyleCrossRefs" href="#bib0030">6,7</a> The regions that are most affected by the disease are the Americas, South-East Asia, and the Western Pacific (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The information available on dengue in Africa is limited.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>In Europe, it was eradicated in the 20th century, along with the Ae. aegypti vector. Most cases reported in Europe are imported by travelers from countries with dengue transmission. Since 2010, there have been sporadic autochthonous cases and small autochthonous outbreaks in Croatia, France, Italy, and Madeira related to Ae. Albopictus.<a class="elsevierStyleCrossRef" href="#bib0040">8</a>Imported dengue in SpainSince 2015, it has been mandatory to report dengue cases in Spain to the National Epidemiological Surveillance Network (RENAVE, for its initials in Spanish). Most cases reported in Spain are imported by travelers from countries with dengue transmission. On average, approximately 200 cases are diagnosed annually, with a greater number of cases between June and September, though there are significant variations depending on the year.<a class="elsevierStyleCrossRef" href="#bib0045">9</a>After an increase in the number of cases reported in 2019, and as a result of the decrease in international travel after the SARS-CoV-2 pandemic in 2020, this incidence declined notably in 2020 and 2021 and the seasonal pattern also changed.<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>a shows the number of dengue cases per Autonomous Community in Spain in the periods from 2016 and 2021, according to the latest report on dengue in Spain from RENAVE.<a class="elsevierStyleCrossRef" href="#bib0045">9</a> Catalonia and Madrid reported the highest number of cases.<elsevierMultimedia ident="fig0010"></elsevierMultimedia>The most common place of contagion in recent years has been Latin America, in contrast to 2016–2018, in which more than half of the imported cases with information available came from Asia/Oceania, with the most frequent country being Thailand. The profile of a patient diagnosed with dengue is a traveler with a median age of 35 years whose reason for traveling is usually tourism or to visit family members. Nearly one in three patients are admitted to the hospital for a median of four days; this percentage is higher among those older than 55 years.<a class="elsevierStyleCrossRef" href="#bib0045">9</a>It is notable that a very significant percentage of cases are diagnosed in the viremic period and more than half are in Autonomous Communities where Ae. albopictus is established and during the vector’s period of peak activity.<a class="elsevierStyleCrossRef" href="#bib0045">9</a>However, according to data from the World Tourism Organization’s (WTO) barometer, international tourism has seen a big interannual increase again in 2022 and destinations worldwide received about 900 million international arrivals. Although tourism has not yet returned to 2019 levels, Europe and the Middle East as well as the Caribbean subregion have grown the most compared to prepandemic figures. Increases have also been recorded in Africa and other parts of the Americas and, to a lesser extent, Asia and the Pacific.<a class="elsevierStyleCrossRef" href="#bib0050">10</a>Therefore, as foreseen, there was an increase in cases in 2022,<a class="elsevierStyleCrossRef" href="#bib0055">11</a> a trend expected to continue in 2023. The most common country of contagion was Cuba in nearly all Autonomous Communities. July and August were the most common months for the onset of symptoms.Autochthonous dengueSuspected autochthonous cases of dengue must be urgently reported to public health services. Confirmation must be made in the National Microbiology Center.Until 2018, no cases of autochthonous transmission had been detected in Spain since the beginning of the 20th century. Then, that year, six autochthonous cases were reported. An outbreak of five cases in the Region of Murcia and a sixth isolated, unrelated case in Catalonia were documented.<a class="elsevierStyleCrossRef" href="#bib0060">12</a>In 2019, two more cases were reported: one in Catalonia through vector transmission and another in Madrid through sexual transmission of an imported case. In the latter, the virus was detected in semen by means of a PCR test and the presence of Aedes spp. was not detected in entomological investigations in either the place of residence or any of the places visited by the cases.<a class="elsevierStyleCrossRefs" href="#bib0065">13,14</a>More recently, in February 2023, another two cases of autochthonous dengue were reported in Ibiza (one confirmed and one probable) together with four more cases with compatible symptoms and epidemiological links. The cases were residents of Germany with a history of travel to Ibiza during the incubation period in August and October 2022. After the epidemiological investigations, it was concluded that the cases probably occurred through an index case of dengue imported after a trip to Mexico and that transmission occurred through an Aedes albopictus mosquito bite in the town where all the identified cases coincided.<a class="elsevierStyleCrossRef" href="#bib0075">15</a>Aedes albopictus was detected for the first time in Catalonia in 2004. At present, it has been expanding all along the Mediterranean coast and in the Balearic Islands, and more recently even in other regions in Spain’s interior, such as the communities of Basque Country, Navarre, La Rioja, Aragon, Castile-La Mancha, Madrid, Ceuta, and Extremadura (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>b).<a class="elsevierStyleCrossRefs" href="#bib0080">16,17</a>Spain is not exempt from new cases of autochthonous dengue in the near future. It is feasible that a percentage of cases imported during their viremic phase may not ever lead to a consultation, given that they can progress asymptomatically or with mild symptoms. Thus, they would avoid all possibility of an early diagnosis and public health control measures both in terms of vector control and individual protection.According to the latest rapid risk evaluation from the Coordination Center for Health Alerts and Emergencies of the Ministry of Health, Consumption, and Social Well-being, the risk that new autochthonous cases of dengue would continue to occur in Spain is moderate for areas where Aedes albopictus is established and during the period of greatest vector activity, namely the months from May to November. On the contrary, in the colder months from December to April, the risk is low and indeed non-existent in regions where Aedes albopictus is not currently present. However, this risk evaluation will depend on a possible future expansion of the vector, the vector’s density, the ambient humidity and temperature conditions, and the number of imported and autochthonous cases.<a class="elsevierStyleCrossRefs" href="#bib0075">15,18</a>Clinical manifestations of dengueThe infection can be asymptomatic or present a wide variety of clinical manifestations. Factors related to the host, the virus, and the vector facilitate risk of infection, the disease itself, and disease severity.<a class="elsevierStyleCrossRefs" href="#bib0095">19–21</a>Classification flowcharts<a class="elsevierStyleCrossRef" href="#bib0105">21</a> have been published that have classically described three categories of symptomatic dengue infection: dengue fever, hemorrhagic dengue fever, and dengue shock syndrome. Hemorrhagic fever is a cardinal manifestation of severe dengue. Shock and intravascular volume depletion are the most critical symptoms and the basis of therapeutic management.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> In 2011, the concept of expanded dengue syndrome was introduced, which includes multiple organ involvement (liver, kidney, heart, brain) but with no evidence of plasma loss.<a class="elsevierStyleCrossRef" href="#bib0115">23</a> In addition, clinical findings and findings from basic additional tests have been shown to identify patients at risk of progression to severe disease (alarm signs), as shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.<a class="elsevierStyleCrossRef" href="#bib0120">24</a><elsevierMultimedia ident="tbl0005"></elsevierMultimedia>The incubation period is from seven to 14 days and symptoms develop four to seven days after a bite by an infected mosquito. Symptomatic infection is more common in adults (40%–60% asymptomatic) than in children. Three phases of infection are recognized<a class="elsevierStyleCrossRef" href="#bib0105">21</a>:Febrile phaseHigh fever, with or without chills, associated with two or more of the following symptoms: headache, vomiting, arthralgia, and frequent macular rash (face, abdomen, limbs) that is sometimes itchy and more common in primary infection than in secondary infection.<a class="elsevierStyleCrossRef" href="#bib0125">25</a> Occasionally, there are respiratory symptoms (cough, nasal congestion)<a class="elsevierStyleCrossRef" href="#bib0130">26</a> and less frequently there are gastrointestinal symptoms (abdominal pain, diarrhea).Hemorrhagic manifestations can appear in the febrile phase or in the critical phase.<a class="elsevierStyleCrossRefs" href="#bib0105">21–23</a> The range and severity of hemorrhagic manifestations vary (skin and mucosa, gastrointestinal, metrorrhagia, hematemesis, melena, epistaxis, hematuria) and can sometimes be made more intense by previous diseases or associated thrombocytopenia.Conjunctival injection, skin or palatal petechiae, hematomas of varying sizes, maculopapular rash, pharyngeal erythema, small adenopathies, and hepatomegaly can be observed on physical examination. It is advised to perform the tourniquet test (blood pressure cuff inflated midway between systolic and diastolic for five minutes). The appearance of ten or more new petechiae in 2–3 cm2 is considered a positive test.<a class="elsevierStyleCrossRef" href="#bib0135">27</a>Leukopenia and thrombocytopenia and a modest increase in transaminases are commonly detected. Between seven and ten days of disease, it is possible to observe signs of loss of vascularity that reduces intravascular volume and decreases organ perfusion.<a class="elsevierStyleCrossRefs" href="#bib0130">26,28</a> When this process starts, persistent vomiting, intense abdominal pain, an increase in hepatomegaly, ascites, or pleural effusion can occur. On a blood test, a progressive increase in hematocrit together with a marked decline in platelets is observed.Critical phaseIn the fever effervescence period (at approximately four to seven days of infection), some patients may develop systemic syndrome of vascular permeability that leads to hypovolemic shock, with all of its clinical manifestations and pathological repercussions.<a class="elsevierStyleCrossRefs" href="#bib0105">21,28</a> Thrombocytopenia tends to become more marked and fibrinogen declines. The great majority of infections that progress to the critical phase are secondary dengue infections.Recovery phaseIn this phase, the loss of blood and plasma ceases, with stabilization of vital signs and progressive recovery. It lasts two to four days and tends to be accompanied by intense asthenia.On occasion, dengue can be accompanied by other complications, which tend to appear in the critical phase or later. They include liver involvement secondary to prolonged hypoperfusion<a class="elsevierStyleCrossRef" href="#bib0145">29</a>; neurological involvement such as encephalopathy and seizures; exceptionally, peripheral nervous involvement or Guillain-Barré syndrome<a class="elsevierStyleCrossRef" href="#bib0150">30</a>; cardiovascular involvement such as cardiomyopathy, arrhythmias, etc.<a class="elsevierStyleCrossRef" href="#bib0155">31</a>; or renal involvement due to shock, tubular necrosis,<a class="elsevierStyleCrossRef" href="#bib0160">32</a> or hemophagocytic syndrome.<a class="elsevierStyleCrossRef" href="#bib0165">33</a>Infection by one of the four serotypes (primary infection) provides long-term immunity against infection by the same serotype. However, immunity is transitory for other serotypes that can reinfect the patient again (secondary infection). The probability of developing severe disease is higher in individuals infected for a second time with a different virus than the first, that is, in secondary infection.<a class="elsevierStyleCrossRefs" href="#bib0095">19–21</a>Laboratory diagnosisIt can be done directly or indirectly:Direct diagnosisDetection of viral nucleic acid (PCR) typically positive during the first five days or positive antigen detection (NS1 protein) via ELISA (more sensitive) or immunochromatography during the first seven days (viremic phase).<a class="elsevierStyleCrossRef" href="#bib0170">34</a>Indirect diagnosis (serology)The sensitivity of each method depends on the particular moment of disease progression and duration of the disease.<a class="elsevierStyleCrossRef" href="#bib0175">35</a> IgM (ELISA) can be detected from four days to six months after disease onset. Its detection in a single sample in patients with compatible symptoms is a presumed diagnosis. A progressive increase indicates acute infection. The probability of IgG detection depends on whether the infection is primary or secondary. In the first case, the IgG antibody titer increases slowly and is low up to seven days after onset. With secondary infection, there is a rapid increase in the antibody titer four days after disease onset. Serological tests lack diagnostic value in acute infection for patients vaccinated several months beforehand.Virus culturing in cell cultures can also be performed, though they are not used in clinical practice. In some cases, tissue immunohistochemistry techniques can be used in the event of post-mortem diagnosis.Differential diagnosisThe initial clinical presentations of dengue, chikungunya, and Zika viruses can be indistinguishable and they all have the same mosquito vector.<a class="elsevierStyleCrossRef" href="#bib0180">36</a> Abdominal and hemorrhagic manifestations, leukopenia, and thrombocytopenia are more common in dengue. Joint inflammation is more characteristic in chikungunya virus infection and conjunctivitis is very common in Zika virus infection. The three infections can coexist in a single patient (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Hemorrhagic manifestations can be caused by other hemorrhagic viruses such as Ebola, Crimean-Congo hemorrhagic fever, and yellow fever virus, with multi-organ manifestations. Other disease such as leptospirosis, malaria, parvovirus B19 infection, rickettsia, and even COVID-19 can be considered in the differential diagnosis.<a class="elsevierStyleCrossRef" href="#bib0180">36</a>Treatment of dengueThe treatment is symptomatic, with special attention to intravascular volume loss.<a class="elsevierStyleCrossRef" href="#bib0185">37</a> The classification of dengue with and without alarm signs, as shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>, can be useful for previous screening and treatment decisions.<a class="elsevierStyleCrossRef" href="#bib0105">21</a>Patients with suspected or confirmed dengue must be carefully evaluated and have a defined pattern of care.<a class="elsevierStyleCrossRefs" href="#bib0120">24,38</a> In regard to the scope of care, the following is recommended:<ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0175">-Outpatient follow-up: patients with a presumed diagnosis without alarm signs or associated comorbidity (pregnant people, children, older adults, diabetes, kidney failure, underlying hemolytic disease, obesity, social situation) who tolerate fluids normally and with normal follow-up blood tests.</li><li class="elsevierStyleListItem" id="lsti0180">-Inpatient follow-up: patients with alarm signs of severe infection or with associated comorbidity. The period of maximum risk of shock is between the third and seventh day of disease, typically coinciding with fever remission. The admission criteria can be seen in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.</li></ul>Paracetamol should be used to control fever. Neither non-steroidal anti-inflammatory drugs nor acetylsalicylic acid should be used due to their effect on platelet function, risk of Reye's syndrome in children, and potential increase in bleeding.Plasma loss must be carefully managed through the careful restoration of intravascular volume (fluids, blood) to prevent or revert hypovolemic shock.The treatment of shock must be approached using various algorithms.<a class="elsevierStyleCrossRef" href="#bib0190">38</a> Attention must be paid to the various complications that can arise (acidosis, hypo- and hyperglycemia, hypocalcemia, and other fluid and electrolyte imbalances, etc.). Volume monitoring must be done with suitable follow-up tests. If a sudden decline in hematocrit not accompanied by clinical improvement is observed in the patient, or if there are signs of hypovolemia with a decline in hematocrit, a hemorrhagic complication should be suspected and the need for a blood transfusion should be considered.The most common severe hemorrhagic complications are in the form of epistaxis, gastrointestinal or gynecologic hemorrhage, and less commonly pulmonary or intracranial hemorrhage. There is no indication for the prophylactic use of platelet transfusion, even with marked thrombocytopenia without bleeding.<a class="elsevierStyleCrossRefs" href="#bib0120">24,39,40</a> However, it may be necessary in the case of emergency surgery or active bleeding with severe thrombocytopenia. In this last scenario, coagulation, including fibrinogen, must also be evaluated in case a transfusion of cryoprecipitate or fresh frozen plasma and vitamin K is necessary.After admission, patients may be discharged from the hospital provided that they meet all the following criteria: clinical improvement (good overall condition, good appetite, normal hemodynamic status, normal or increased diuresis, no respiratory distress, and no evidence of bleeding), absence of fever for 48 h without the use of antipyretics, an increasing platelet count, and stable hematocrit without intravenous fluids (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<a class="elsevierStyleCrossRef" href="#bib0190">38</a>The efficacy of using corticosteroids, intravenous immunoglobulins, pentoxifylline, activated factor VII, chloroquine, lovastatin, balapiravir, or celgosivir has not been demonstrated.<a class="elsevierStyleCrossRefs" href="#bib0205">41,42</a> Some specific factors for dengue are being investigated: direct inhibitors and virus-host interaction modifiers, inhibiting molecules of essential viral enzymes (3NSB, etc.), and virus entry and fusion inhibitor antibodies.Dengue preventionDengue infection prevention in endemic areas includes:<ul class="elsevierStyleList" id="lis0040"><li class="elsevierStyleListItem" id="lsti0185">a)Vector control. This consists of reducing the place of reproduction, larval control, and possible endosymbiotic control as well as the use of mosquito repellents and insecticides.</li><li class="elsevierStyleListItem" id="lsti0190">b)Indications for travelers. All travelers who are going to travel to endemic areas should avoid mosquito bites. The general recommendations are to use clothes that cover the largest area of the body possible, use insect repellents, wear clothing coated in permethrin, avoid exposure to mosquitos as much as possible, and stay in places that have air conditioning or which have screens on doors and windows to prevent insects from entering. It should be remembered that this disease is mainly in urban areas and one should protect oneself from it when in the city.</li><li class="elsevierStyleListItem" id="lsti0195">c)Vaccine development. Ideally, any candidate vaccine should produce long-lasting tetravalent immunity (against the four virus types described). <a class="elsevierStyleCrossRefs" href="#bib0215">43,44</a></li></ul>Regarding vaccine types,<a class="elsevierStyleCrossRefs" href="#bib0225">45–47</a> there are two vaccines available at present: <ul class="elsevierStyleList" id="lis0045"><li class="elsevierStyleListItem" id="lsti0200">-CYD-TDV (Dengvaxia®). This vaccine is a chimeric yellow fever-dengue virus formulation. It is recommended for individuals between nine and 45 years of age with confirmation (serological) of prior dengue infection who live in endemic areas. It is not indicated for individuals who have not had dengue infection. It is administered in three doses in months zero, six, and 12 with an efficacy of 57%–61% for the four virus types (more effective for serotypes 3 and 4 than for 1 and 2). It has a low efficacy (34%–36%) in children two to five years of age and in children in whom antibodies have not been detected prior to vaccination.</li></ul>In 2021, the United States Centers for Disease Control and Prevention (CDC) officially recommended it for children from nine to 16 years of age and in older adults with serological evidence of previous dengue infection who live in endemic areas. It has a good safety profile. It is not available for travelers who visit endemic areas.<ul class="elsevierStyleList" id="lis0050"><li class="elsevierStyleListItem" id="lsti0205">-TAK-003 (QDENGA®). It is a tetravalent vaccine made from attenuated dengue virus with DENV-2 providing the genetic key for all four viruses. Its efficacy varies according to virus type: it is not efficacious against DENV-3 and is insufficient against DENV-4. The available data suggest that the TAK-003 vaccine can be administered to seropositive and seronegative individuals and it is highly efficacious against hospitalization, reducing the burden of severe disease.</li></ul>This vaccine has recently been authorized by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA)<a class="elsevierStyleCrossRef" href="#bib0240">48</a> and also by the Brazilian National Health Surveillance Agency (ANVISA).<a class="elsevierStyleCrossRef" href="#bib0245">49</a> This approval was based on the results of 19 phase 1, 2, and 3 studies with more than 28,000 adults and children. Follow-up was as long as four and a half years in the TIDES (Tetravalent Immunization against Dengue Efficacy Study) study.<a class="elsevierStyleCrossRefs" href="#bib0250">50–52</a> This study met the primary outcome measure, preventing 80.2% of symptomatic dengue in 12 months after vaccination. The secondary outcome measure was also reached: it prevented 90.4% of hospitalizations in the 18 months after vaccination.ConclusionsThe number of dengue cases reported in Spain is increasing. The majority are imported cases. The Ae. albopictus mosquito is present in the Mediterranean basin and can transmit dengue virus. Therefore, it is not surprising that cases of autochthonous dengue have been described since 2016. It is expected that cases will continue to increase due to an increase in travel, an increase in cases of dengue worldwide, and the geographical expansion of Ae. albopictus in Spain.FundingThis research received no specific grants from agencies in the public, commercial, or non-profit sectors.Conflicts of interestThe authors declare that they do not have any conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:19 [ 0 => array:3 [ "identificador" => "xres2120204" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1806206" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres2120203" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1806205" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Dengue virus. Replication cycle. Pathogenesis" ] 6 => array:3 [ "identificador" => "sec0015" "titulo" => "Transmission" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Transmission pattern" ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Factors that influence transmission" ] 2 => array:2 [ "identificador" => "sec0030" "titulo" => "Mechanism of transmission" ] ] ] 7 => array:2 [ "identificador" => "sec0035" "titulo" => "Epidemiology" ] 8 => array:2 [ "identificador" => "sec0040" "titulo" => "Imported dengue in Spain" ] 9 => array:2 [ "identificador" => "sec0045" "titulo" => "Autochthonous dengue" ] 10 => array:3 [ "identificador" => "sec0050" "titulo" => "Clinical manifestations of dengue" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0055" "titulo" => "Febrile phase" ] 1 => array:2 [ "identificador" => "sec0060" "titulo" => "Critical phase" ] 2 => array:2 [ "identificador" => "sec0065" "titulo" => "Recovery phase" ] ] ] 11 => array:3 [ "identificador" => "sec0070" "titulo" => "Laboratory diagnosis" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0075" "titulo" => "Direct diagnosis" ] 1 => array:2 [ "identificador" => "sec0080" "titulo" => "Indirect diagnosis (serology)" ] ] ] 12 => array:2 [ "identificador" => "sec0085" "titulo" => "Differential diagnosis" ] 13 => array:2 [ "identificador" => "sec0090" "titulo" => "Treatment of dengue" ] 14 => array:2 [ "identificador" => "sec0095" "titulo" => "Dengue prevention" ] 15 => array:2 [ "identificador" => "sec0100" "titulo" => "Conclusions" ] 16 => array:2 [ "identificador" => "sec0105" "titulo" => "Funding" ] 17 => array:2 [ "identificador" => "sec0110" "titulo" => "Conflicts of interest" ] 18 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2023-05-05" "fechaAceptado" => "2023-06-28" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1806206" "palabras" => array:6 [ 0 => "Dengue" 1 => "Epidemiology" 2 => "Clinical manifestations" 3 => "Diagnosis" 4 => "Imported dengue" 5 => "Autochthonous dengue" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1806205" "palabras" => array:6 [ 0 => "Dengue" 1 => "Epidemiología" 2 => "Manifestaciones clínicas" 3 => "Diagnóstico" 4 => "Dengue importado" 5 => "Dengue autóctono" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Dengue is globally the most important arboviral infection. It is caused by the dengue virus and it is generally transmitted by Aedes mosquitoes’ bites (Ae aegypti or Ae albopictus). In Spain it was initially eradicated in the 20th century, together with the Ae aegypti vector, and currently most of the cases reported in Spain are imported by travelers from countries with dengue transmission (imported dengue). However, in recent years, cases of dengue have been described in people residing in Spain who had not traveled to areas with known transmission (autochthonous dengue), transmitted by Aedes albopictus (the so-called tiger mosquito), present especially in the Mediterranean basin. Therefore, a good knowledge of this potentially severe disease is required, so that it can be diagnosed early, and managed correctly, thus reducing its mortality, as well as its eventual autochthonous transmission." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "El dengue es, globalmente, la arbovirosis más importante. Está causado por el virus del dengue y transmitido generalmente por la picadura de mosquitos del género Aedes (Ae aegypti o Ae albopictus). En España fue inicialmente erradicado en el siglo XX, junto con el vector Ae aegypti, y en la actualidad la mayoría de los casos notificados en España son importados por viajeros procedentes de países con transmisión de dengue (dengue importado). Sin embargo, en los últimos años se han descrito casos de dengue de personas residentes en España que no habían viajado a zonas con transmisión conocida del virus (dengue autóctono), transmitidos por Aedes albopictus (el denominado mosquito tigre), presente especialmente en la cuenca mediterránea. Se requiere por lo tanto un buen conocimiento de esta enfermedad, ya que puede dar lugar a cuadros clínicos graves, de modo que pueda ser diagnosticada precozmente, y manejada correctamente, disminuyendo con ello su mortalidad, así como su eventual transmisión autóctona." ] ] "NotaPie" => array:1 [ 0 => array:3 [ "etiqueta" => "1" "nota" => "Equal contributions." "identificador" => "PC_fnXOFo5N652O" ] ] "multimedia" => array:4 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2155 "Ancho" => 2508 "Tamanyo" => 255346 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Dengue in the World. Fundación iO Available at: https://fundacionio.com/salud-io/enfermedades/virus/dengue/" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2731 "Ancho" => 2925 "Tamanyo" => 600175 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "(a) Number of cases of dengue per Autonomous Community in Spain. Periods from 2016-2021. Available from Centro Nacional de Epidemiología.<a class="elsevierStyleCrossRef" href="#bib0045">9</a> (b) Epidemiological surveillance of Aedes albopictus in Spain, towns, 2021. Available from Centro Coordinador de Alertas y Emergencias.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> Note. Introduced: it has been detected for the first time; established: it is repeatedly detected for more than one year; absent: it is monitored, but not detected." ] ] 2 => array:9 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Modified from Organización Panamericana de la Salud.<a class="elsevierStyleCrossRef" href="#bib0190">38</a>" "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "tablatextoimagen" => array:3 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Criteria for dengue with and without alarm signs</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Criteria of severe dengue<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Probable dengue: \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Alarm signs<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Severe plasma extravasation that leadsto: \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- Living in endemic dengue areas/travel to these areas in the last 14 days, and- Fever and two or more of the followingcriteria: \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">•Intense abdominal pain or painful abdomen upon palpation</li><li class="elsevierStyleListItem" id="lsti0010">•Persistent vomiting</li><li class="elsevierStyleListItem" id="lsti0015">•Clinical accumulation of liquids<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a></li><li class="elsevierStyleListItem" id="lsti0020">•Mucosal bleeding<a class="elsevierStyleCrossRef" href="#tblfn0015">b</a></li><li class="elsevierStyleListItem" id="lsti0025">•Lethargy, agitation</li><li class="elsevierStyleListItem" id="lsti0030">•Orthostatic hypotension</li><li class="elsevierStyleListItem" id="lsti0035">•Hepatomegaly >2 cm</li><li class="elsevierStyleListItem" id="lsti0040">•Laboratory: progressive increase in hematocrit together with rapid decline in platelet numbers</li></ul></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0045">•Shock (evidenced through a weak pulse, tachycardia, cold limbs, and capillary refill >2 s, pulse pressure ≤20 mmHg)</li><li class="elsevierStyleListItem" id="lsti0050">•Fluid accumulation with respiratory failure</li></ul> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0055">•Nausea, vomiting</li><li class="elsevierStyleListItem" id="lsti0060">•Exanthem</li><li class="elsevierStyleListItem" id="lsti0065">•Myalgia/arthralgia</li><li class="elsevierStyleListItem" id="lsti0070">•Positive tourniquet test or petechiae</li><li class="elsevierStyleListItem" id="lsti0075">•Leukopenia</li><li class="elsevierStyleListItem" id="lsti0080">•Any alarm sign</li></ul></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Severe bleeding \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Severe organ compromise \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Confirmed dengue: laboratory(important when there are no signs of plasma extravasation) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0085">•Liver: AST or ALT ≥ 1000 IU/L</li><li class="elsevierStyleListItem" id="lsti0090">•Central nervous system: alteration of</li><li class="elsevierStyleListItem" id="lsti0095">•consciousness</li><li class="elsevierStyleListItem" id="lsti0100">•Heart (myocarditis) or other organs</li></ul> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3505660.png" ] ] 1 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Clinical or analytical parameters which identify patients who require hospital management \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0105">•Dengue with alarm signs (previously defined)</li><li class="elsevierStyleListItem" id="lsti0110">•Dengue with criteria of severe disease, according the 2009 WHO criteria</li><li class="elsevierStyleListItem" id="lsti0115">•Intolerance of oral intake</li><li class="elsevierStyleListItem" id="lsti0120">•Respiratory distress</li><li class="elsevierStyleListItem" id="lsti0125">•Narrowing of pulse pressure</li><li class="elsevierStyleListItem" id="lsti0130">•Hypotension</li><li class="elsevierStyleListItem" id="lsti0135">•Acute kidney failure</li><li class="elsevierStyleListItem" id="lsti0140">•Increase in capillary refill time</li><li class="elsevierStyleListItem" id="lsti0145">•Pregnancy</li><li class="elsevierStyleListItem" id="lsti0150">•Coagulation disorders</li></ul> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3505658.png" ] ] 2 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Criteria for hospital discharge (all must be met) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0155">•Afebrile for 48 h without the use of antipyretics</li><li class="elsevierStyleListItem" id="lsti0160">•Good appetite and good overall condition</li><li class="elsevierStyleListItem" id="lsti0165">•Hemodynamic stability with diuresis conserved, without respiratory distress</li><li class="elsevierStyleListItem" id="lsti0170">•No evidence of bleeding. Rising platelet count with stable hematocrit without the administration of intravenous fluids</li></ul> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3505659.png" ] ] ] "notaPie" => array:3 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "*" "nota" => "Requires strict observation and medical intervention." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "a" "nota" => "Due to symptoms or imaging tests, at the end of the febrile stage." ] 2 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "b" "nota" => "Gingivorrhagia, epistaxis, vaginal bleeding not associated with menstruation or greater menstrual bleeding than usual, and hematuria." ] ] ] "descripcion" => array:1 [ "en" => "Classification of dengue cases, degrees of severity, and clinical and analytical parameters upon admission." ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Symptoms/Laboratory test \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dengue \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Zika \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Chikungunya \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fever \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+++ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Exanthem \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">++ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Arthralgia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+++ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Myalgia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Arthritis (morning stiffness) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+++ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Conjunctivitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Headache \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">++ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bleeding \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Shock \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anemia/Increased hematocrit \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">++/+++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Leukopenia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">++ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Thrombocytopenia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">++/+++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cytolytic hepatitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">++/+++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">++ \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3505657.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Clinical differential diagnosis of the virus (dengue, Zika, and chikungunya)." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:52 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dengue outbreak among travellers returning from Cuba-GeoSentinel surveillance network, January-September 2022" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. 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Special article

Imported and autochthonous dengue in Spain

Dengue importado y autóctono en España

J.-M. Herrero-Martíneza,1, M. Sánchez-Ledesmab,1, J.-M. Ramos-Rincónc,

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jose.ramosr@umh.es

Corresponding author.

a Servicio de Medicina Interna, Hospital Universitario 12 de Octubre-Imas12, Madrid, Dpto. de Medicina, Universidad Complutense de Madrid, Madrid, Spain

b Unidad Enfermedades Infecciosas, Servicio de Medicina Interna, Hospital Universitario de Salamanca- IBSAL, Salamanca, Dpto. de Medicina, Universidad de Salamanca, IBSAL, Salamanca, Spain

c Servicio de Medicina Interna, Hospital General Universitario Dr. Balmis; Dpto de Medicina Clínica Universidad Miguel Hernández; Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, España

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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">&#40;a&#41; Number of cases of dengue per Autonomous Community in Spain&#46; Periods from 2016-2021&#46; Available from Centro Nacional de Epidemiolog&#237;a&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p> <p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">&#40;b&#41; Epidemiological surveillance of <span class="elsevierStyleItalic">Aedes albopictus</span> in Spain&#44; towns&#44; 2021&#46; Available from Centro Coordinador de Alertas y Emergencias&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Note&#46; Introduced&#58; it has been detected for the first time&#59; established&#58; it is repeatedly detected for more than one year&#59; absent&#58; it is monitored&#44; but not detected&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0175" class="elsevierStylePara elsevierViewall">Dengue is a disease caused by the dengue virus&#46; It is generally transmitted through <span class="elsevierStyleItalic">Aedes &#40;Stegomyia&#41; aegypti</span> or <span class="elsevierStyleItalic">Aedes &#40;Stegomyia&#41; albopictus</span> mosquito bites&#46; Most cases reported in Spain are imported by travelers from countries with dengue transmission&#44;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> although cases of autochthonous dengue have been described in recent years&#46; This article aims to review the epidemiology of dengue with a particular emphasis on cases diagnosed in Spain&#44; its symptoms&#44; diagnostic methods&#44; and treatment of the disease&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Dengue virus&#46; Replication cycle&#46; Pathogenesis</span><p id="par0180" class="elsevierStylePara elsevierViewall">The causative agent of dengue is an RNA virus of the <span class="elsevierStyleItalic">Flaviviridae</span> family and <span class="elsevierStyleItalic">Flavivirus</span> genus&#46; It is a small&#44; enveloped virus with four closely related serotypes&#58; DENV-1&#44; DENV-2&#44; DENV-3&#44; and DENV-4&#46; There is transient cross-protection among the four types&#44; though there will only be lasting immunity against the specific serotype that caused the infection&#44; not against the rest&#46; In fact&#44; sequential infections by other serotypes increase the risk of contracting the severe form of dengue&#46; Individuals who live in a hyperendemic area and where there are various serotypes are at risk of infection by various types&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Viral replication occurs according to the following process&#58; &#40;a&#41; initially&#44; the virus binds to the cell surface&#44; fusing their membranes and &#40;b&#41; allowing its entry into the cell&#46; &#40;c&#41; Once in the cytoplasm&#44; RNA transcription occurs in a polyprotein which can be processed and gives rise to three structural &#40;C&#44; M&#44; and E&#41; and seven nonstructural &#40;NS&#41; proteins&#46; &#40;d&#41; The formation of the replication complex allows for replication of the viral genome&#44; the subsequent &#40;e&#41; encapsidation and formation of virions&#44; and &#40;f&#41; their later release from the cell&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">In regard to its pathophysiology&#44; the increase in capillary permeability is notable&#46; It is responsible for intravascular volume depletion and ultimately shock&#44; a cardinal symptoms of dengue hemorrhagic fever&#46; This increase in capillary permeability is related to endothelial dysfunction&#44; not direct damage to the endothelial cells&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> In addition&#44; this endothelial dysfunction is probably indirect&#46; Histological studies have demonstrated minimal damage at the capillary level and anatomic pathology studies do not show direct infection of endothelial cells&#46; The increase in permeability is transitory and the phase of greatest permeability occurs days after peak viral RNA levels&#46; Therefore&#44; it is speculated that the reason for this dysfunction is circulating factors such as nitric oxide&#44; TNF alpha&#44; interferon gamma&#44; interleukin-2&#44; interleukin-8&#44; vascular endothelial growth factor&#44; and the reduction in complement C3a and C5a levels <a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#46; The source of these cytokines would be the infected monocytes&#44; dendritic and mastoid cells&#44; and specific CD4 and CD8 lymphocytes&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Transmission</span><p id="par0195" class="elsevierStylePara elsevierViewall">The dengue virus is mainly transmitted through <span class="elsevierStyleItalic">Aedes</span> &#40;<span class="elsevierStyleItalic">Ae&#46; aegypti</span> or <span class="elsevierStyleItalic">Ae&#46; albopictus</span>&#41; genus mosquito bites&#46; Humans serve as a virus reservoir &#40;except in the sylvatic cycle in Southeast Asia&#41;&#46; The incubation period in the mosquito is from eight to 12 days&#46; They can transmit the virus throughout their life and can transmit it to their offspring &#40;transovarial transmission&#41;&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Dengue transmission is the result of a complex interaction between the population&#44; vectors&#44; the virus&#44; and environmental factors&#46; It occurs below 2000&#160;m and is more frequent during rainy periods&#46; On the other hand&#44; the disease incidence varies from year to year&#44; with greater transmission in intervals of three to four years&#46;</p><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Transmission pattern</span><p id="par0205" class="elsevierStylePara elsevierViewall">There are two transmission patterns<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>&#58; &#40;A&#41; Epidemic dengue due to a single virus strain when it is introduced into a region and affects susceptible people&#46; The incidence can be high&#44; up to 25&#37; to 50&#37;&#46; The outbreak ends thanks to the development of herd immunity&#44; climate changes&#44; and vector control&#46; &#40;B&#41; Hyperendemic dengue&#44; in which various serotypes of the virus circulate in the same area with presence of mosquitos year-round&#46; This form of transmission causes most cases and especially affects urban areas&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Factors that influence transmission</span><p id="par0210" class="elsevierStylePara elsevierViewall">The worldwide incidence has increased in recent decades as a consequence of an increase in population&#59; overcrowding of urban areas&#59; inadequate sanitation &#40;with stagnant water&#41;&#59; greater movement of individuals&#59; and the expansion and lack of control of vectors&#44; in part due to the effects of climate change&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Its control depends in large part on an adequate approach from a public health perspective&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Mechanism of transmission</span><p id="par0215" class="elsevierStylePara elsevierViewall">As stated above&#44; vector transmission is the main route of transmission&#46; Mosquitos of the <span class="elsevierStyleItalic">Aedes</span> genus tend to bite during the day&#44; preferably at dawn and at dusk&#46; Other much less common routes of transmission are through blood derivatives&#44; transplantation&#44; or from mother to child &#40;perinatal&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Breastfeeding could be another mechanism of transmission&#46; The possibility of transmission through sexual activity has also been described&#44; but is uncommon&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Epidemiology</span><p id="par0220" class="elsevierStylePara elsevierViewall">Dengue is distributed in all regions where there is a transmission vector &#40;from latitudes 30&#176; north to 20&#176; south&#41;&#46; The disease is endemic in more than 100 countries in tropical and subtropical regions and causes between 100 and 400 million infections worldwide each year&#46; At present&#44; around half of the world&#8217;s population is at risk of contracting this disease&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">Dengue is endemic in five of the six WHO regions &#40;except for the European region&#41;&#58; Africa&#44; the Eastern Mediterranean&#44; South-East Asia&#44; the Americas&#44; and the Western Pacific regions&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a> The regions that are most affected by the disease are the Americas&#44; South-East Asia&#44; and the Western Pacific &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The information available on dengue in Africa is limited&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0230" class="elsevierStylePara elsevierViewall">In Europe&#44; it was eradicated in the 20th century&#44; along with the <span class="elsevierStyleItalic">Ae&#46; aegypti</span> vector&#46; Most cases reported in Europe are imported by travelers from countries with dengue transmission&#46; Since 2010&#44; there have been sporadic autochthonous cases and small autochthonous outbreaks in Croatia&#44; France&#44; Italy&#44; and Madeira related to <span class="elsevierStyleItalic">Ae&#46; Albopictus</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Imported dengue in Spain</span><p id="par0235" class="elsevierStylePara elsevierViewall">Since 2015&#44; it has been mandatory to report dengue cases in Spain to the National Epidemiological Surveillance Network &#40;RENAVE&#44; for its initials in Spanish&#41;&#46; Most cases reported in Spain are imported by travelers from countries with dengue transmission&#46; On average&#44; approximately 200 cases are diagnosed annually&#44; with a greater number of cases between June and September&#44; though there are significant variations depending on the year&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0240" class="elsevierStylePara elsevierViewall">After an increase in the number of cases reported in 2019&#44; and as a result of the decrease in international travel after the SARS-CoV-2 pandemic in 2020&#44; this incidence declined notably in 2020 and 2021 and the seasonal pattern also changed&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>a shows the number of dengue cases per Autonomous Community in Spain in the periods from 2016 and 2021&#44; according to the latest report on dengue in Spain from RENAVE&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Catalonia and Madrid reported the highest number of cases&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0250" class="elsevierStylePara elsevierViewall">The most common place of contagion in recent years has been Latin America&#44; in contrast to 2016&#8211;2018&#44; in which more than half of the imported cases with information available came from Asia&#47;Oceania&#44; with the most frequent country being Thailand&#46; The profile of a patient diagnosed with dengue is a traveler with a median age of 35 years whose reason for traveling is usually tourism or to visit family members&#46; Nearly one in three patients are admitted to the hospital for a median of four days&#59; this percentage is higher among those older than 55 years&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0255" class="elsevierStylePara elsevierViewall">It is notable that a very significant percentage of cases are diagnosed in the viremic period and more than half are in Autonomous Communities where <span class="elsevierStyleItalic">Ae&#46; albopictus</span> is established and during the vector&#8217;s period of peak activity&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0260" class="elsevierStylePara elsevierViewall">However&#44; according to data from the World Tourism Organization&#8217;s &#40;WTO&#41; barometer&#44; international tourism has seen a big interannual increase again in 2022 and destinations worldwide received about 900 million international arrivals&#46; Although tourism has not yet returned to 2019 levels&#44; Europe and the Middle East as well as the Caribbean subregion have grown the most compared to prepandemic figures&#46; Increases have also been recorded in Africa and other parts of the Americas and&#44; to a lesser extent&#44; Asia and the Pacific&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0265" class="elsevierStylePara elsevierViewall">Therefore&#44; as foreseen&#44; there was an increase in cases in 2022&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> a trend expected to continue in 2023&#46; The most common country of contagion was Cuba in nearly all Autonomous Communities&#46; July and August were the most common months for the onset of symptoms&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Autochthonous dengue</span><p id="par0270" class="elsevierStylePara elsevierViewall">Suspected autochthonous cases of dengue must be urgently reported to public health services&#46; Confirmation must be made in the National Microbiology Center&#46;</p><p id="par0275" class="elsevierStylePara elsevierViewall">Until 2018&#44; no cases of autochthonous transmission had been detected in Spain since the beginning of the 20th century&#46; Then&#44; that year&#44; six autochthonous cases were reported&#46; An outbreak of five cases in the Region of Murcia and a sixth isolated&#44; unrelated case in Catalonia were documented&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0280" class="elsevierStylePara elsevierViewall">In 2019&#44; two more cases were reported&#58; one in Catalonia through vector transmission and another in Madrid through sexual transmission of an imported case&#46; In the latter&#44; the virus was detected in semen by means of a PCR test and the presence of <span class="elsevierStyleItalic">Aedes</span> spp&#46; was not detected in entomological investigations in either the place of residence or any of the places visited by the cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14</span></a></p><p id="par0285" class="elsevierStylePara elsevierViewall">More recently&#44; in February 2023&#44; another two cases of autochthonous dengue were reported in Ibiza &#40;one confirmed and one probable&#41; together with four more cases with compatible symptoms and epidemiological links&#46; The cases were residents of Germany with a history of travel to Ibiza during the incubation period in August and October 2022&#46; After the epidemiological investigations&#44; it was concluded that the cases probably occurred through an index case of dengue imported after a trip to Mexico and that transmission occurred through an <span class="elsevierStyleItalic">Aedes albopictus</span> mosquito bite in the town where all the identified cases coincided&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="par0290" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Aedes albopictus</span> was detected for the first time in Catalonia in 2004&#46; At present&#44; it has been expanding all along the Mediterranean coast and in the Balearic Islands&#44; and more recently even in other regions in Spain&#8217;s interior&#44; such as the communities of Basque Country&#44; Navarre&#44; La Rioja&#44; Aragon&#44; Castile-La Mancha&#44; Madrid&#44; Ceuta&#44; and Extremadura &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>b&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;17</span></a></p><p id="par0295" class="elsevierStylePara elsevierViewall">Spain is not exempt from new cases of autochthonous dengue in the near future&#46; It is feasible that a percentage of cases imported during their viremic phase may not ever lead to a consultation&#44; given that they can progress asymptomatically or with mild symptoms&#46; Thus&#44; they would avoid all possibility of an early diagnosis and public health control measures both in terms of vector control and individual protection&#46;</p><p id="par0300" class="elsevierStylePara elsevierViewall">According to the latest rapid risk evaluation from the Coordination Center for Health Alerts and Emergencies of the Ministry of Health&#44; Consumption&#44; and Social Well-being&#44; the risk that new autochthonous cases of dengue would continue to occur in Spain is moderate for areas where <span class="elsevierStyleItalic">Aedes albopictus</span> is established and during the period of greatest vector activity&#44; namely the months from May to November&#46; On the contrary&#44; in the colder months from December to April&#44; the risk is low and indeed non-existent in regions where <span class="elsevierStyleItalic">Aedes albopictus</span> is not currently present&#46; However&#44; this risk evaluation will depend on a possible future expansion of the vector&#44; the vector&#8217;s density&#44; the ambient humidity and temperature conditions&#44; and the number of imported and autochthonous cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;18</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Clinical manifestations of dengue</span><p id="par0305" class="elsevierStylePara elsevierViewall">The infection can be asymptomatic or present a wide variety of clinical manifestations&#46; Factors related to the host&#44; the virus&#44; and the vector facilitate risk of infection&#44; the disease itself&#44; and disease severity&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#8211;21</span></a></p><p id="par0310" class="elsevierStylePara elsevierViewall">Classification flowcharts<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> have been published that have classically described three categories of symptomatic dengue infection&#58; dengue fever&#44; hemorrhagic dengue fever&#44; and dengue shock syndrome&#46; Hemorrhagic fever is a cardinal manifestation of severe dengue&#46; Shock and intravascular volume depletion are the most critical symptoms and the basis of therapeutic management&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> In 2011&#44; the concept of expanded dengue syndrome was introduced&#44; which includes multiple organ involvement &#40;liver&#44; kidney&#44; heart&#44; brain&#41; but with no evidence of plasma loss&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> In addition&#44; clinical findings and findings from basic additional tests have been shown to identify patients at risk of progression to severe disease &#40;alarm signs&#41;&#44; as shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0315" class="elsevierStylePara elsevierViewall">The incubation period is from seven to 14 days and symptoms develop four to seven days after a bite by an infected mosquito&#46; Symptomatic infection is more common in adults &#40;40&#37;&#8211;60&#37; asymptomatic&#41; than in children&#46; Three phases of infection are recognized<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&#58;</p><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Febrile phase</span><p id="par0320" class="elsevierStylePara elsevierViewall">High fever&#44; with or without chills&#44; associated with two or more of the following symptoms&#58; headache&#44; vomiting&#44; arthralgia&#44; and frequent macular rash &#40;face&#44; abdomen&#44; limbs&#41; that is sometimes itchy and more common in primary infection than in secondary infection&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> Occasionally&#44; there are respiratory symptoms &#40;cough&#44; nasal congestion&#41;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> and less frequently there are gastrointestinal symptoms &#40;abdominal pain&#44; diarrhea&#41;&#46;</p><p id="par0325" class="elsevierStylePara elsevierViewall">Hemorrhagic manifestations can appear in the febrile phase or in the critical phase&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21&#8211;23</span></a> The range and severity of hemorrhagic manifestations vary &#40;skin and mucosa&#44; gastrointestinal&#44; metrorrhagia&#44; hematemesis&#44; melena&#44; epistaxis&#44; hematuria&#41; and can sometimes be made more intense by previous diseases or associated thrombocytopenia&#46;</p><p id="par0330" class="elsevierStylePara elsevierViewall">Conjunctival injection&#44; skin or palatal petechiae&#44; hematomas of varying sizes&#44; maculopapular rash&#44; pharyngeal erythema&#44; small adenopathies&#44; and hepatomegaly can be observed on physical examination&#46; It is advised to perform the tourniquet test &#40;blood pressure cuff inflated midway between systolic and diastolic for five minutes&#41;&#46; The appearance of ten or more new petechiae in 2&#8211;3&#160;cm<span class="elsevierStyleSup">2</span> is considered a positive test&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a></p><p id="par0335" class="elsevierStylePara elsevierViewall">Leukopenia and thrombocytopenia and a modest increase in transaminases are commonly detected&#46; Between seven and ten days of disease&#44; it is possible to observe signs of loss of vascularity that reduces intravascular volume and decreases organ perfusion&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;28</span></a> When this process starts&#44; persistent vomiting&#44; intense abdominal pain&#44; an increase in hepatomegaly&#44; ascites&#44; or pleural effusion can occur&#46; On a blood test&#44; a progressive increase in hematocrit together with a marked decline in platelets is observed&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Critical phase</span><p id="par0340" class="elsevierStylePara elsevierViewall">In the fever effervescence period &#40;at approximately four to seven days of infection&#41;&#44; some patients may develop systemic syndrome of vascular permeability that leads to hypovolemic shock&#44; with all of its clinical manifestations and pathological repercussions&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21&#44;28</span></a> Thrombocytopenia tends to become more marked and fibrinogen declines&#46; The great majority of infections that progress to the critical phase are secondary dengue infections&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Recovery phase</span><p id="par0345" class="elsevierStylePara elsevierViewall">In this phase&#44; the loss of blood and plasma ceases&#44; with stabilization of vital signs and progressive recovery&#46; It lasts two to four days and tends to be accompanied by intense asthenia&#46;</p><p id="par0350" class="elsevierStylePara elsevierViewall">On occasion&#44; dengue can be accompanied by other complications&#44; which tend to appear in the critical phase or later&#46; They include liver involvement secondary to prolonged hypoperfusion<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a>&#59; neurological involvement such as encephalopathy and seizures&#59; exceptionally&#44; peripheral nervous involvement or Guillain-Barr&#233; syndrome<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a>&#59; cardiovascular involvement such as cardiomyopathy&#44; arrhythmias&#44; etc&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a>&#59; or renal involvement due to shock&#44; tubular necrosis&#44;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> or hemophagocytic syndrome&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a></p><p id="par0355" class="elsevierStylePara elsevierViewall">Infection by one of the four serotypes &#40;primary infection&#41; provides long-term immunity against infection by the same serotype&#46; However&#44; immunity is transitory for other serotypes that can reinfect the patient again &#40;secondary infection&#41;&#46; The probability of developing severe disease is higher in individuals infected for a second time with a different virus than the first&#44; that is&#44; in secondary infection&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#8211;21</span></a></p></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Laboratory diagnosis</span><p id="par0360" class="elsevierStylePara elsevierViewall">It can be done directly or indirectly&#58;</p><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Direct diagnosis</span><p id="par0365" class="elsevierStylePara elsevierViewall">Detection of viral nucleic acid &#40;PCR&#41; typically positive during the first five days or positive antigen detection &#40;NS1 protein&#41; via ELISA &#40;more sensitive&#41; or immunochromatography during the first seven days &#40;viremic phase&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Indirect diagnosis &#40;serology&#41;</span><p id="par0370" class="elsevierStylePara elsevierViewall">The sensitivity of each method depends on the particular moment of disease progression and duration of the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> IgM &#40;ELISA&#41; can be detected from four days to six months after disease onset&#46; Its detection in a single sample in patients with compatible symptoms is a presumed diagnosis&#46; A progressive increase indicates acute infection&#46; The probability of IgG detection depends on whether the infection is primary or secondary&#46; In the first case&#44; the IgG antibody titer increases slowly and is low up to seven days after onset&#46; With secondary infection&#44; there is a rapid increase in the antibody titer four days after disease onset&#46; Serological tests lack diagnostic value in acute infection for patients vaccinated several months beforehand&#46;</p><p id="par0375" class="elsevierStylePara elsevierViewall">Virus culturing in cell cultures can also be performed&#44; though they are not used in clinical practice&#46; In some cases&#44; tissue immunohistochemistry techniques can be used in the event of post-mortem diagnosis&#46;</p></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Differential diagnosis</span><p id="par0380" class="elsevierStylePara elsevierViewall">The initial clinical presentations of dengue&#44; chikungunya&#44; and Zika viruses can be indistinguishable and they all have the same mosquito vector&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> Abdominal and hemorrhagic manifestations&#44; leukopenia&#44; and thrombocytopenia are more common in dengue&#46; Joint inflammation is more characteristic in chikungunya virus infection and conjunctivitis is very common in Zika virus infection&#46; The three infections can coexist in a single patient &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0385" class="elsevierStylePara elsevierViewall">Hemorrhagic manifestations can be caused by other hemorrhagic viruses such as Ebola&#44; Crimean-Congo hemorrhagic fever&#44; and yellow fever virus&#44; with multi-organ manifestations&#46; Other disease such as leptospirosis&#44; malaria&#44; parvovirus B19 infection&#44; rickettsia&#44; and even COVID-19 can be considered in the differential diagnosis&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a></p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Treatment of dengue</span><p id="par0390" class="elsevierStylePara elsevierViewall">The treatment is symptomatic&#44; with special attention to intravascular volume loss&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> The classification of dengue with and without alarm signs&#44; as shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#44; can be useful for previous screening and treatment decisions&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="par0395" class="elsevierStylePara elsevierViewall">Patients with suspected or confirmed dengue must be carefully evaluated and have a defined pattern of care&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24&#44;38</span></a> In regard to the scope of care&#44; the following is recommended&#58;<ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0175"><span class="elsevierStyleLabel">-</span><p id="par0400" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleUnderline">Outpatient follow-up&#58;</span> patients with a presumed diagnosis without alarm signs or associated comorbidity &#40;pregnant people&#44; children&#44; older adults&#44; diabetes&#44; kidney failure&#44; underlying hemolytic disease&#44; obesity&#44; social situation&#41; who tolerate fluids normally and with normal follow-up blood tests&#46;</p></li><li class="elsevierStyleListItem" id="lsti0180"><span class="elsevierStyleLabel">-</span><p id="par0405" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleUnderline">Inpatient follow-up&#58;</span> patients with alarm signs of severe infection or with associated comorbidity&#46; The period of maximum risk of shock is between the third and seventh day of disease&#44; typically coinciding with fever remission&#46; The admission criteria can be seen in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p></li></ul></p><p id="par0410" class="elsevierStylePara elsevierViewall">Paracetamol should be used to control fever&#46; Neither non-steroidal anti-inflammatory drugs nor acetylsalicylic acid should be used due to their effect on platelet function&#44; risk of Reye&#39;s syndrome in children&#44; and potential increase in bleeding&#46;</p><p id="par0415" class="elsevierStylePara elsevierViewall">Plasma loss must be carefully managed through the careful restoration of intravascular volume &#40;fluids&#44; blood&#41; to prevent or revert hypovolemic shock&#46;</p><p id="par0420" class="elsevierStylePara elsevierViewall">The treatment of shock must be approached using various algorithms&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> Attention must be paid to the various complications that can arise &#40;acidosis&#44; hypo- and hyperglycemia&#44; hypocalcemia&#44; and other fluid and electrolyte imbalances&#44; etc&#46;&#41;&#46; Volume monitoring must be done with suitable follow-up tests&#46; If a sudden decline in hematocrit not accompanied by clinical improvement is observed in the patient&#44; or if there are signs of hypovolemia with a decline in hematocrit&#44; a hemorrhagic complication should be suspected and the need for a blood transfusion should be considered&#46;</p><p id="par0425" class="elsevierStylePara elsevierViewall">The most common severe hemorrhagic complications are in the form of epistaxis&#44; gastrointestinal or gynecologic hemorrhage&#44; and less commonly pulmonary or intracranial hemorrhage&#46; There is no indication for the prophylactic use of platelet transfusion&#44; even with marked thrombocytopenia without bleeding&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24&#44;39&#44;40</span></a> However&#44; it may be necessary in the case of emergency surgery or active bleeding with severe thrombocytopenia&#46; In this last scenario&#44; coagulation&#44; including fibrinogen&#44; must also be evaluated in case a transfusion of cryoprecipitate or fresh frozen plasma and vitamin K is necessary&#46;</p><p id="par0430" class="elsevierStylePara elsevierViewall">After admission&#44; patients may be discharged from the hospital provided that they meet all the following criteria&#58; clinical improvement &#40;good overall condition&#44; good appetite&#44; normal hemodynamic status&#44; normal or increased diuresis&#44; no respiratory distress&#44; and no evidence of bleeding&#41;&#44; absence of fever for 48&#160;h without the use of antipyretics&#44; an increasing platelet count&#44; and stable hematocrit without intravenous fluids &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a></p><p id="par0435" class="elsevierStylePara elsevierViewall">The efficacy of using corticosteroids&#44; intravenous immunoglobulins&#44; pentoxifylline&#44; activated factor VII&#44; chloroquine&#44; lovastatin&#44; balapiravir&#44; or celgosivir has not been demonstrated&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">41&#44;42</span></a> Some specific factors for dengue are being investigated&#58; direct inhibitors and virus-host interaction modifiers&#44; inhibiting molecules of essential viral enzymes &#40;3NSB&#44; etc&#46;&#41;&#44; and virus entry and fusion inhibitor antibodies&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Dengue prevention</span><p id="par0440" class="elsevierStylePara elsevierViewall">Dengue infection prevention in endemic areas includes&#58;<ul class="elsevierStyleList" id="lis0040"><li class="elsevierStyleListItem" id="lsti0185"><span class="elsevierStyleLabel">a&#41;</span><p id="par0445" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleUnderline">Vector control&#46;</span> This consists of reducing the place of reproduction&#44; larval control&#44; and possible endosymbiotic control as well as the use of mosquito repellents and insecticides&#46;</p></li><li class="elsevierStyleListItem" id="lsti0190"><span class="elsevierStyleLabel">b&#41;</span><p id="par0450" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleUnderline">Indications for travelers&#46;</span> All travelers who are going to travel to endemic areas should avoid mosquito bites&#46; The general recommendations are to use clothes that cover the largest area of the body possible&#44; use insect repellents&#44; wear clothing coated in permethrin&#44; avoid exposure to mosquitos as much as possible&#44; and stay in places that have air conditioning or which have screens on doors and windows to prevent insects from entering&#46; It should be remembered that this disease is mainly in urban areas and one should protect oneself from it when in the city&#46;</p></li><li class="elsevierStyleListItem" id="lsti0195"><span class="elsevierStyleLabel">c&#41;</span><p id="par0455" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleUnderline">Vaccine development&#46;</span> Ideally&#44; any candidate vaccine should produce long-lasting tetravalent immunity &#40;against the four virus types described&#41;&#46; <a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">43&#44;44</span></a></p></li></ul></p><p id="par0460" class="elsevierStylePara elsevierViewall">Regarding vaccine types&#44;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">45&#8211;47</span></a> there are two vaccines available at present&#58; <ul class="elsevierStyleList" id="lis0045"><li class="elsevierStyleListItem" id="lsti0200"><span class="elsevierStyleLabel">-</span><p id="par0465" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic"><span class="elsevierStyleUnderline">CYD-TDV &#40;Dengvaxia&#174;&#41;</span></span>&#46; This vaccine is a chimeric yellow fever-dengue virus formulation&#46; It is recommended for individuals between nine and 45 years of age with confirmation &#40;serological&#41; of prior dengue infection who live in endemic areas&#46; It is not indicated for individuals who have not had dengue infection&#46; It is administered in three doses in months zero&#44; six&#44; and 12 with an efficacy of 57&#37;&#8211;61&#37; for the four virus types &#40;more effective for serotypes 3 and 4 than for 1 and 2&#41;&#46; It has a low efficacy &#40;34&#37;&#8211;36&#37;&#41; in children two to five years of age and in children in whom antibodies have not been detected prior to vaccination&#46;</p></li></ul></p><p id="par0470" class="elsevierStylePara elsevierViewall">In 2021&#44; the United States Centers for Disease Control and Prevention &#40;CDC&#41; officially recommended it for children from nine to 16 years of age and in older adults with serological evidence of previous dengue infection who live in endemic areas&#46; It has a good safety profile&#46; It is not available for travelers who visit endemic areas&#46;<ul class="elsevierStyleList" id="lis0050"><li class="elsevierStyleListItem" id="lsti0205"><span class="elsevierStyleLabel">-</span><p id="par0475" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic"><span class="elsevierStyleUnderline">TAK-003 &#40;QDENGA</span></span>&#174;<span class="elsevierStyleItalic"><span class="elsevierStyleUnderline">&#41;</span></span>&#46; It is a tetravalent vaccine made from attenuated dengue virus with DENV-2 providing the genetic key for all four viruses&#46; Its efficacy varies according to virus type&#58; it is not efficacious against DENV-3 and is insufficient against DENV-4&#46; The available data suggest that the TAK-003 vaccine can be administered to seropositive and seronegative individuals and it is highly efficacious against hospitalization&#44; reducing the burden of severe disease&#46;</p></li></ul></p><p id="par0480" class="elsevierStylePara elsevierViewall">This vaccine has recently been authorized by the Committee for Medicinal Products for Human Use &#40;CHMP&#41; of the European Medicines Agency &#40;EMA&#41;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">48</span></a> and also by the Brazilian National Health Surveillance Agency &#40;ANVISA&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a> This approval was based on the results of 19 phase 1&#44; 2&#44; and 3 studies with more than 28&#44;000 adults and children&#46; Follow-up was as long as four and a half years in the TIDES &#40;Tetravalent Immunization against Dengue Efficacy Study&#41; study&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">50&#8211;52</span></a> This study met the primary outcome measure&#44; preventing 80&#46;2&#37; of symptomatic dengue in 12 months after vaccination&#46; The secondary outcome measure was also reached&#58; it prevented 90&#46;4&#37; of hospitalizations in the 18 months after vaccination&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conclusions</span><p id="par0485" class="elsevierStylePara elsevierViewall">The number of dengue cases reported in Spain is increasing&#46; The majority are imported cases&#46; The <span class="elsevierStyleItalic">Ae&#46; albopictus</span> mosquito is present in the Mediterranean basin and can transmit dengue virus&#46; Therefore&#44; it is not surprising that cases of autochthonous dengue have been described since 2016&#46; It is expected that cases will continue to increase due to an increase in travel&#44; an increase in cases of dengue worldwide&#44; and the geographical expansion of <span class="elsevierStyleItalic">Ae&#46; albopictus</span> in Spain&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Funding</span><p id="par0490" class="elsevierStylePara elsevierViewall">This research received no specific grants from agencies in the public&#44; commercial&#44; or non-profit sectors&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conflicts of interest</span><p id="par0495" class="elsevierStylePara elsevierViewall">The authors declare that they do not have any conflicts of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Dengue is globally the most important arboviral infection&#46; It is caused by the dengue virus and it is generally transmitted by <span class="elsevierStyleItalic">Aedes</span> mosquitoes&#8217; bites &#40;<span class="elsevierStyleItalic">Ae aegypti</span> or <span class="elsevierStyleItalic">Ae albopictus</span>&#41;&#46; In Spain it was initially eradicated in the 20th century&#44; together with the <span class="elsevierStyleItalic">Ae aegypti</span> vector&#44; and currently most of the cases reported in Spain are imported by travelers from countries with dengue transmission &#40;imported dengue&#41;&#46; However&#44; in recent years&#44; cases of dengue have been described in people residing in Spain who had not traveled to areas with known transmission &#40;autochthonous dengue&#41;&#44; transmitted by <span class="elsevierStyleItalic">Aedes albopictus</span> &#40;the so-called tiger mosquito&#41;&#44; present especially in the Mediterranean basin&#46; Therefore&#44; a good knowledge of this potentially severe disease is required&#44; so that it can be diagnosed early&#44; and managed correctly&#44; thus reducing its mortality&#44; as well as its eventual autochthonous transmission&#46;</p></span>"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">&#40;a&#41; Number of cases of dengue per Autonomous Community in Spain&#46; Periods from 2016-2021&#46; Available from Centro Nacional de Epidemiolog&#237;a&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p> <p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">&#40;b&#41; Epidemiological surveillance of <span class="elsevierStyleItalic">Aedes albopictus</span> in Spain&#44; towns&#44; 2021&#46; Available from Centro Coordinador de Alertas y Emergencias&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Note&#46; Introduced&#58; it has been detected for the first time&#59; established&#58; it is repeatedly detected for more than one year&#59; absent&#58; it is monitored&#44; but not detected&#46;</p>"
        ]
      ]
      2 => array:9 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "fuente" => "Modified from Organizaci&#243;n Panamericana de la Salud&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a>"
        "detalles" => array:1 [
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            "identificador" => "at0015"
            "detalle" => "Table "
            "rol" => "short"
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        "tabla" => array:2 [
          "tablatextoimagen" => array:3 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Criteria for dengue with and without alarm signs</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Criteria of severe dengue<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Probable dengue&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Alarm signs<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Severe plasma extravasation that leadsto&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Living in endemic dengue areas&#47;travel to these areas in the last 14 days&#44; and- Fever and two or more of the followingcriteria&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowgroup " rowspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0005" class="elsevierStylePara elsevierViewall">Intense abdominal pain or painful abdomen upon palpation</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0010" class="elsevierStylePara elsevierViewall">Persistent vomiting</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0015" class="elsevierStylePara elsevierViewall">Clinical accumulation of liquids<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a></p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0020" class="elsevierStylePara elsevierViewall">Mucosal bleeding<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">b</span></a></p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8226;</span><p id="par0025" class="elsevierStylePara elsevierViewall">Lethargy&#44; agitation</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#8226;</span><p id="par0030" class="elsevierStylePara elsevierViewall">Orthostatic hypotension</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">&#8226;</span><p id="par0035" class="elsevierStylePara elsevierViewall">Hepatomegaly &#62;2 cm</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">&#8226;</span><p id="par0040" class="elsevierStylePara elsevierViewall">Laboratory&#58; progressive increase in hematocrit together with rapid decline in platelet numbers</p></li></ul></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">&#8226;</span><p id="par0045" class="elsevierStylePara elsevierViewall">Shock &#40;evidenced through a weak pulse&#44; tachycardia&#44; cold limbs&#44; and capillary refill &#62;2&#160;s&#44; pulse pressure &#8804;20 mmHg&#41;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">&#8226;</span><p id="par0050" class="elsevierStylePara elsevierViewall">Fluid accumulation with respiratory failure</p></li></ul>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">&#8226;</span><p id="par0055" class="elsevierStylePara elsevierViewall">Nausea&#44; vomiting</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">&#8226;</span><p id="par0060" class="elsevierStylePara elsevierViewall">Exanthem</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">&#8226;</span><p id="par0065" class="elsevierStylePara elsevierViewall">Myalgia&#47;arthralgia</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">&#8226;</span><p id="par0070" class="elsevierStylePara elsevierViewall">Positive tourniquet test or petechiae</p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">&#8226;</span><p id="par0075" class="elsevierStylePara elsevierViewall">Leukopenia</p></li><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">&#8226;</span><p id="par0080" class="elsevierStylePara elsevierViewall">Any alarm sign</p></li></ul></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Severe bleeding&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Severe organ compromise&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Confirmed dengue&#58; laboratory&#40;important when there are no signs of plasma extravasation&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">&#8226;</span><p id="par0085" class="elsevierStylePara elsevierViewall">Liver&#58; AST or ALT&#160;&#8805;&#160;1000 IU&#47;L</p></li><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">&#8226;</span><p id="par0090" class="elsevierStylePara elsevierViewall">Central nervous system&#58; alteration of</p></li><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">&#8226;</span><p id="par0095" class="elsevierStylePara elsevierViewall">consciousness</p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">&#8226;</span><p id="par0100" class="elsevierStylePara elsevierViewall">Heart &#40;myocarditis&#41; or other organs</p></li></ul>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab3505660.png"
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            1 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Clinical or analytical parameters which identify patients who require hospital management&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">&#8226;</span><p id="par0105" class="elsevierStylePara elsevierViewall">Dengue with alarm signs &#40;previously defined&#41;</p></li><li class="elsevierStyleListItem" id="lsti0110"><span class="elsevierStyleLabel">&#8226;</span><p id="par0110" class="elsevierStylePara elsevierViewall">Dengue with criteria of severe disease&#44; according the 2009 WHO criteria</p></li><li class="elsevierStyleListItem" id="lsti0115"><span class="elsevierStyleLabel">&#8226;</span><p id="par0115" class="elsevierStylePara elsevierViewall">Intolerance of oral intake</p></li><li class="elsevierStyleListItem" id="lsti0120"><span class="elsevierStyleLabel">&#8226;</span><p id="par0120" class="elsevierStylePara elsevierViewall">Respiratory distress</p></li><li class="elsevierStyleListItem" id="lsti0125"><span class="elsevierStyleLabel">&#8226;</span><p id="par0125" class="elsevierStylePara elsevierViewall">Narrowing of pulse pressure</p></li><li class="elsevierStyleListItem" id="lsti0130"><span class="elsevierStyleLabel">&#8226;</span><p id="par0130" class="elsevierStylePara elsevierViewall">Hypotension</p></li><li class="elsevierStyleListItem" id="lsti0135"><span class="elsevierStyleLabel">&#8226;</span><p id="par0135" class="elsevierStylePara elsevierViewall">Acute kidney failure</p></li><li class="elsevierStyleListItem" id="lsti0140"><span class="elsevierStyleLabel">&#8226;</span><p id="par0140" class="elsevierStylePara elsevierViewall">Increase in capillary refill time</p></li><li class="elsevierStyleListItem" id="lsti0145"><span class="elsevierStyleLabel">&#8226;</span><p id="par0145" class="elsevierStylePara elsevierViewall">Pregnancy</p></li><li class="elsevierStyleListItem" id="lsti0150"><span class="elsevierStyleLabel">&#8226;</span><p id="par0150" class="elsevierStylePara elsevierViewall">Coagulation disorders</p></li></ul>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab3505658.png"
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            ]
            2 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Criteria for hospital discharge &#40;all must be met&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0155"><span class="elsevierStyleLabel">&#8226;</span><p id="par0155" class="elsevierStylePara elsevierViewall">Afebrile for 48&#160;h without the use of antipyretics</p></li><li class="elsevierStyleListItem" id="lsti0160"><span class="elsevierStyleLabel">&#8226;</span><p id="par0160" class="elsevierStylePara elsevierViewall">Good appetite and good overall condition</p></li><li class="elsevierStyleListItem" id="lsti0165"><span class="elsevierStyleLabel">&#8226;</span><p id="par0165" class="elsevierStylePara elsevierViewall">Hemodynamic stability with diuresis conserved&#44; without respiratory distress</p></li><li class="elsevierStyleListItem" id="lsti0170"><span class="elsevierStyleLabel">&#8226;</span><p id="par0170" class="elsevierStylePara elsevierViewall">No evidence of bleeding&#46; Rising platelet count with stable hematocrit without the administration of intravenous fluids</p></li></ul>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3505659.png"
              ]
            ]
          ]
          "notaPie" => array:3 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "&#42;"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Requires strict observation and medical intervention&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Due to symptoms or imaging tests&#44; at the end of the febrile stage&#46;</p>"
            ]
            2 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Gingivorrhagia&#44; epistaxis&#44; vaginal bleeding not associated with menstruation or greater menstrual bleeding than usual&#44; and hematuria&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Classification of dengue cases&#44; degrees of severity&#44; and clinical and analytical parameters upon admission&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0020"
            "detalle" => "Table "
            "rol" => "short"
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        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Symptoms&#47;Laboratory test&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dengue&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Zika&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Chikungunya&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fever&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&#43;&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&#43;&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Exanthem&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&#43;&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Arthralgia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&#43;&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Myalgia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Arthritis &#40;morning stiffness&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&#43;&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Conjunctivitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#43;&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Headache&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#43;&#43;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bleeding&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Shock&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anemia&#47;Increased hematocrit&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&#43;&#47;&#43;&#43;&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leukopenia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Thrombocytopenia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&#43;&#47;&#43;&#43;&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cytolytic hepatitis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#43;&#43;&#47;&#43;&#43;&#43;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#43;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#43;&#43;&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Clinical differential diagnosis of the virus &#40;dengue&#44; Zika&#44; and chikungunya&#41;&#46;</p>"
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                          "etal" => false
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                            1 => "J&#46;A&#46; Rodr&#237;guez"
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "L&#46;L&#46;M&#46; Santos"
                            1 => "E&#46;C&#46; de Aquino"
                            2 => "S&#46;M&#46; Fernandes"
                            3 => "Y&#46;M&#46;F&#46; Ternes"
                            4 => "V&#46;C&#46;R&#46; Feres"
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                      "doi" => "10.26633/RPSP.2023.34"
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
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                            1 => "N&#46; Fournet"
                            2 => "C&#46; Frank"
                            3 => "B&#46; Fern&#225;ndez-Mart&#237;nez"
                            4 => "M&#46; Del Manso"
                            5 => "J&#46; Gomes Dias"
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                        ]
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                    ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Euro Surveill"
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                  "referenciaCompleta" => "Informe epidemiol&#243;gico sobre la situaci&#243;n de dengue en Espa&#241;a&#46; A&#241;os 2019&#44; 2020 y 2021&#46; Centro Nacional de Epidemiolog&#237;a&#46; Instituto de Salud Carlos III&#46; Madrid&#44; 14 noviembre 2022&#46; Available from&#58; <a target="_blank" href="https://www.isciii.es/QueHacemos/Servicios/VigilanciaSaludPublicaRENAVE/EnfermedadesTransmisibles/Documents/archivos%20A-Z/Dengue/INFORME_RENAVE_DENGUE%202019-2021.pdf">https&#58;&#47;&#47;www&#46;isciii&#46;es&#47;QueHacemos&#47;Servicios&#47;VigilanciaSaludPublicaRENAVE&#47;EnfermedadesTransmisibles&#47;Documents&#47;archivos&#37;20A-Z&#47;Dengue&#47;INFORME&#95;RENAVE&#95;DENGUE&#37;202019-2021&#46;pdf</a>&#46;"
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              "identificador" => "bib0050"
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              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "UNWTO World Tourism Barometer&#46; Available from&#58; <a target="_blank" href="https://www.e-unwto.org/loi/wtobarometeresp">https&#58;&#47;&#47;www&#46;e-unwto&#46;org&#47;loi&#47;wtobarometeresp</a> &#91;Accessed 02 April 2023&#93;&#46;"
                ]
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Article information

ISSN: 22548874
Original language: English

DOI:10.1016/j.rceng.2023.07.007

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