Editorial
Predictors of dengue severity
Preditores de gravidade da dengue
Scott B. Halstead
Uniformed University of the Health Sciences, Department of Preventive Medicine and Biometrics, Bethesda, United States
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"apellidos" => "Michelow" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "pt" => array:9 [ "pii" => "S2255553616300659" "doi" => "10.1016/j.jpedp.2016.06.004" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "pt" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2255553616300659?idApp=UINPBA000049" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0021755716300651?idApp=UINPBA000049" "url" => "/00217557/0000009200000005/v1_201609220038/S0021755716300651/v1_201609220038/en/main.assets" ] "en" => array:15 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "Predictors of dengue severity" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "429" "paginaFinal" => "431" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Scott B. Halstead" "autores" => array:1 [ 0 => array:3 [ "nombre" => "Scott B." "apellidos" => "Halstead" "email" => array:1 [ 0 => "halsteads@erols.com" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Uniformed University of the Health Sciences, Department of Preventive Medicine and Biometrics, Bethesda, United States" "identificador" => "aff0005" ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Preditores de gravidade da dengue" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 824 "Ancho" => 1662 "Tamanyo" => 168617 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Dengue vascular permeability syndrome (DVPS).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Pone et al., in a study published in this Journal, have attempted to identify historical or observable signs or symptoms that reliably predict worsening of dengue disease in children.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">1</span></a> In so doing, they have coined a new term “serious dengue disease” and adopted a new clinical outcome metric, “treatment modality.” The “treatment modalities” chosen include administration of “amines, inotropes, colloids, mechanical ventilation, non-invasive ventilation, peritoneal dialysis or hemodialysis.” Lethargy, abdominal distension, pleural effusion, and hypoalbuminemia were the most reliable markers of serious dengue disease identified in 145 children hospitalized in Rio de Janeiro in 2007–2008, who had direct or indirect evidence of recent dengue infection. The authors are among those who would agree that a more accurate identification of dengue predictors would best be derived from large protocol-based prospective studies of physiologically characterized laboratory confirmed dengue illnesses.</p><p id="par0010" class="elsevierStylePara elsevierViewall">There is considerable historical precedent for this effort. Ever since the 1950s, when it was recognized that dengue viruses caused a severe and often fatal acute febrile disease of children, it has been the goal of researchers to describe the pathophysiology of dengue disease aiming to provide better treatment and to identify predictive early warning markers to improve triage.<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">2,3</span></a> This was the motivation behind the creation of the case definitions, dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), in wide use since their adoption by WHO in 1975, and the new case definitions introduced in 2009.<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">4,5</span></a> In the 1960s, dengue research programs in Southeast Asia found that children were dying of a new clinical entity, the dengue vascular permeability syndrome (DVPS; <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), characterized by a complex of physiologic abnormalities affecting multiple organ systems including the liver, blood coagulation, complement, hematopoiesis, serum proteins, and the vascular system that reach a maximal expression at defervescence.<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">3,6–10</span></a> It soon was well understood that children with DVPS benefitted from early, physiologically relevant fluid resuscitation.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">6</span></a> It was also observed that the fluid leak varied in severity from child to child and that a physiologically irreversible penalty might occur in just a matter of hours due to failure to maintain adequate blood volume.<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">5,11–13</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The signs and symptoms of dengue and DVPS change from day to day. Those that precede shock have been identified as “warning signs.” Warning signs of dengue infections were described long ago. Siler and Simmons, who recorded daily clinical and laboratory features of several hundred experimental dengue illnesses mostly in seronegative young adult male US Army volunteers, observed a profound mid-illness dengue leukopenia.<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">14,15</span></a> More importantly, they found this leukopenia consisted of two components, a reduction in circulating lymphocytes and a destruction of mature polymorphonuclear leukocytes. The latter produced a diagnostic “cross,” where there were greater numbers of immature than mature polys in blood smears.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">15</span></a> It has been speculated that leukopenia and thrombocytopenia might be related to a remarkable phenomenon that regularly occurs in dengue infections before the onset of fever, a profound suppression of all cellular elements in the bone marrow.<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">16,17</span></a> In Thailand, three early warning signs were used in patient triage: thrombocytopenia and a positive tourniquet test were thought to herald dengue vascular permeability, while a fingertip microhematocrit was taken to establish a baseline value to monitor hemoconcentration.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">18</span></a> Because platelet numbers decline and hematocrits rise quickly, multiple measurements must be performed and disease severity eventually is most accurately scored using modal high or low values. Some workers found that high levels of aspartate aminotransferase identified those children who proceeded to DVPS.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">18</span></a> Careful physiological characterization of dengue illnesses in children has resulted in significant improvement in treatment and sharply reduced case fatality rates.<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">11,19</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">There has been considerable disagreement about the utility of most warning signs or laboratory tests in wide use for predicting the outcome of dengue infections.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">20</span></a> One approach to identify predictors has been to look for universal components in DSS. A meta-analysis identified the significant associations of shock as age, female sex, neurological signs, nausea/vomiting, abdominal pain, gastrointestinal bleeding, hemoconcentration, ascites, pleural effusion, hypoalbuminemia, hypoproteinemia, hepatomegaly, levels of alanine transaminase and aspartate transaminase, thrombocytopenia, prothrombin time, activated partial thromboplastin time, fibrinogen level, primary/secondary infection, and DENV-2.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">21</span></a> The vast expansion of dengue infection globally has placed great stress on clinical facilities, generating further efforts to improve patient triage by validating early warning signs.<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">22–25</span></a> One such study will enroll 7000–8000 children with a febrile disease who are admitted to outpatient departments in eight dengue-endemic countries.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">22</span></a> This large prospective study, now in progress, includes three sites in Brazil. As of December 2015, a total of 7096 participants had been enrolled, with dengue confirmed in 2510/5996 (42%). Enrolment will continue until June 2016. It is hoped that sufficient numbers of children with acute dengue infections will proceed on to severe dengue, providing unequivocal laboratory or clinical predictors, specifically for DSS.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0025" class="elsevierStylePara elsevierViewall">The author declares no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Halstead S. Predictors of dengue severity. J Pediatr (Rio J). 2016;92:429–31.</p>" ] 1 => array:2 [ "etiqueta" => "☆☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Ver artigo de Pone et al. in pages 464–71.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 824 "Ancho" => 1662 "Tamanyo" => 168617 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Dengue vascular permeability syndrome (DVPS).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:25 [ 0 => array:3 [ "identificador" => "bib0130" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical and laboratory signs associated to serious dengue disease in hospitalized children" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.M. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 2 | 4 | 6 |
| 2024 October | 30 | 18 | 48 |
| 2024 September | 27 | 29 | 56 |
| 2024 August | 49 | 45 | 94 |
| 2024 July | 39 | 38 | 77 |
| 2024 June | 22 | 14 | 36 |
| 2024 May | 17 | 11 | 28 |
| 2024 April | 22 | 23 | 45 |
| 2024 March | 19 | 19 | 38 |
| 2024 February | 21 | 20 | 41 |
| 2024 January | 20 | 24 | 44 |
| 2023 December | 16 | 22 | 38 |
| 2023 November | 30 | 30 | 60 |
| 2023 October | 33 | 31 | 64 |
| 2023 September | 31 | 32 | 63 |
| 2023 August | 17 | 19 | 36 |
| 2023 July | 16 | 18 | 34 |
| 2023 June | 19 | 14 | 33 |
| 2023 May | 23 | 13 | 36 |
| 2023 April | 14 | 6 | 20 |
| 2023 March | 39 | 14 | 53 |
| 2023 February | 25 | 24 | 49 |
| 2023 January | 22 | 29 | 51 |
| 2022 December | 42 | 37 | 79 |
| 2022 November | 32 | 26 | 58 |
| 2022 October | 38 | 25 | 63 |
| 2022 September | 32 | 31 | 63 |
| 2022 August | 38 | 35 | 73 |
| 2022 July | 32 | 33 | 65 |
| 2022 June | 35 | 28 | 63 |
| 2022 May | 28 | 19 | 47 |
| 2022 April | 49 | 34 | 83 |
| 2022 March | 29 | 32 | 61 |
| 2022 February | 20 | 21 | 41 |
| 2022 January | 31 | 29 | 60 |
| 2021 December | 11 | 19 | 30 |
| 2021 November | 12 | 23 | 35 |
| 2021 October | 25 | 50 | 75 |
| 2021 September | 10 | 24 | 34 |
| 2021 August | 15 | 12 | 27 |
| 2021 July | 9 | 10 | 19 |
| 2021 June | 12 | 10 | 22 |
| 2021 May | 9 | 12 | 21 |
| 2021 April | 9 | 32 | 41 |
| 2021 March | 6 | 16 | 22 |
| 2021 February | 8 | 6 | 14 |
| 2021 January | 10 | 10 | 20 |
| 2020 December | 11 | 10 | 21 |
| 2020 November | 28 | 24 | 52 |
| 2020 October | 12 | 12 | 24 |
| 2020 September | 12 | 12 | 24 |
| 2020 August | 15 | 6 | 21 |
| 2020 July | 7 | 9 | 16 |
| 2020 June | 16 | 14 | 30 |
| 2020 May | 14 | 12 | 26 |
| 2020 April | 13 | 7 | 20 |
| 2020 March | 14 | 12 | 26 |
| 2020 February | 17 | 9 | 26 |
| 2020 January | 20 | 23 | 43 |
| 2019 December | 14 | 11 | 25 |
| 2019 November | 10 | 6 | 16 |
| 2019 October | 15 | 14 | 29 |
| 2019 September | 18 | 10 | 28 |
| 2019 August | 22 | 14 | 36 |
| 2019 July | 28 | 14 | 42 |
| 2019 June | 24 | 18 | 42 |
| 2019 May | 13 | 12 | 25 |
| 2019 April | 14 | 8 | 22 |
| 2019 March | 9 | 7 | 16 |
| 2019 February | 7 | 7 | 14 |
| 2019 January | 7 | 8 | 15 |
| 2018 December | 6 | 6 | 12 |
| 2018 November | 28 | 4 | 32 |
| 2018 October | 119 | 23 | 142 |
| 2018 September | 35 | 8 | 43 |
| 2018 August | 25 | 10 | 35 |
| 2018 July | 8 | 4 | 12 |
| 2018 June | 20 | 4 | 24 |
| 2018 May | 14 | 11 | 25 |
| 2018 April | 40 | 3 | 43 |
| 2018 March | 6 | 2 | 8 |
| 2018 February | 3 | 3 | 6 |
| 2018 January | 8 | 6 | 14 |
| 2017 December | 6 | 2 | 8 |
| 2017 November | 8 | 5 | 13 |
| 2017 October | 9 | 4 | 13 |
| 2017 September | 5 | 7 | 12 |
| 2017 August | 2 | 4 | 6 |
| 2017 July | 2 | 2 | 4 |
| 2017 June | 5 | 9 | 14 |
| 2017 May | 2 | 1 | 3 |
| 2017 April | 4 | 9 | 13 |
| 2017 March | 4 | 5 | 9 |
| 2017 February | 6 | 3 | 9 |
| 2017 January | 10 | 6 | 16 |
| 2016 December | 9 | 12 | 21 |
| 2016 November | 18 | 28 | 46 |
| 2016 October | 27 | 27 | 54 |
| 2016 September | 21 | 15 | 36 |
| 2016 August | 13 | 4 | 17 |
| 2016 July | 13 | 10 | 23 |
Show all
