Editorial
The burden of Epstein-Barr virus infections in children⁎
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"apellidos" => "Imoto" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S002175572100098X?idApp=UINPBA000049" "url" => "/00217557/0000009800000002/v1_202203240553/S002175572100098X/v1_202203240553/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S0021755721001716" "issn" => "00217557" "doi" => "10.1016/j.jped.2021.12.003" "estado" => "S300" "fechaPublicacion" => "2022-03-01" "aid" => "1054" "copyright" => "Sociedade Brasileira de Pediatria" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "sco" "cita" => "J Pediatr (Rio J). 2022;98:113-4" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:9 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "Behind the curtain of a weak diagnosis of acute SARS-CoV-2 infection in children<a class="elsevierStyleCrossRef" href="#fn1"><span class="elsevierStyleSup">⁎</span></a>" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "113" "paginaFinal" => "114" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Mauricio T. 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"apellidos" => "Caballero" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0021755721001716?idApp=UINPBA000049" "url" => "/00217557/0000009800000002/v1_202203240553/S0021755721001716/v1_202203240553/en/main.assets" ] "asociados" => array:1 [ 0 => array:19 [ "pii" => "S0021755721000863" "issn" => "00217557" "doi" => "10.1016/j.jped.2021.05.006" "estado" => "S300" "fechaPublicacion" => "2022-03-01" "aid" => "1001" "copyright" => "Sociedade Brasileira de Pediatria" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "J Pediatr (Rio J). 2022;98:142-6" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Prevalence of Epstein-Barr Viral DNA among children at a single hospital in Suzhou, China" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "142" "paginaFinal" => "146" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0001" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1541 "Ancho" => 2500 "Tamanyo" => 229016 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0001" "detalle" => "Fig " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spara001" class="elsevierStyleSimplePara elsevierViewall">Positive rate of plasma EBV-DNA in different age and sex groups.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ting Shi, Linlin Huang, Jianmei Tian" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Ting" "apellidos" => "Shi" ] 1 => array:2 [ "nombre" => "Linlin" "apellidos" => "Huang" ] 2 => array:2 [ "nombre" => "Jianmei" "apellidos" => "Tian" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0021755721000863?idApp=UINPBA000049" "url" => "/00217557/0000009800000002/v1_202203240553/S0021755721000863/v1_202203240553/en/main.assets" ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "The burden of Epstein-Barr virus infections in children<a class="elsevierStyleCrossRef" href="#fn1"><span class="elsevierStyleSup">⁎</span></a>" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "115" "paginaFinal" => "116" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Henry H. BalfourJr." "autores" => array:1 [ 0 => array:4 [ "nombre" => "Henry H." "apellidos" => "BalfourJr." "email" => array:1 [ 0 => "balfo001@umn.edu" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0001" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0002" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "University of Minnesota Medical School, Department of Laboratory Medicine and Pathology, Minneapolis, United States" "etiqueta" => "a" "identificador" => "aff0001" ] 1 => array:3 [ "entidad" => "University of Minnesota Medical School, Department of Pediatrics, Minneapolis, United States" "etiqueta" => "b" "identificador" => "aff0002" ] ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="para0001" class="elsevierStylePara elsevierViewall">Epstein-Barr virus (EBV) arguably is the cause of the most common infection on the planet. By the time we reach adulthood, nearly 90% of us have been infected.<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a> Some of us will get infectious mononucleosis and some of us will develop chronic EBV-driven diseases such as lymphoma or multiple sclerosis. While we know something about EBV infections in adolescents and young adults, and something about EBV infections in immunocompromised hosts, there is surprisingly little known about EBV infections in preadolescent children.</p><p id="para0002" class="elsevierStylePara elsevierViewall">The article by Shi et al. in this issue provides some information to fill that gap.<a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a></p><p id="para0003" class="elsevierStylePara elsevierViewall">Their article is almost as important for what it does not say than for what it says. What the article says is that 7.3% of 38,175 children from eastern China tested as inpatients or outpatients had EBV DNA in their plasma. The sample size is large and the relatively high prevalence of plasma EBV DNA is noteworthy, especially considering that EBV DNA is found more often in whole blood rather than plasma during primary EBV infection,<a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a> and plasma EBV DNA correlates with the clinical outcome of Hodgkin lymphoma whereas whole blood EBV DNA does not.<a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a></p><p id="para0004" class="elsevierStylePara elsevierViewall">What this article does not say, or more correctly cannot say, is that EBV caused the illnesses that brought the children to medical attention. Because of its notorious proclivity to reactivate after primary infection, finding EBV DNA in plasma may simply reflect a prior EBV infection unrelated to the cause of the present illness.</p><p id="para0005" class="elsevierStylePara elsevierViewall">Had the authors tested the children's plasma for EBV-specific antibodies, the stage of EBV infection could have been characterized as primary (acute), convalescent, or past.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a> The point is that primary (acute) EBV infection is much more likely to be responsible for the present illness than reactivation or reinfection.</p><p id="para0006" class="elsevierStylePara elsevierViewall">The diagnosis of infectious mononucleosis, which is the most common clinical expression of primary EBV infection, can be confirmed in children with EBV-specific antibody tests. At the University of Minnesota, we use enzyme immunoassays to measure IgG and IgM antibodies against EBV viral capsid antigen (VCA) and IgG antibodies against EBV nuclear antigen-1 (EBNA-1).<a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a> The patterns of VCA IgM positive only, or VCA IgM and IgG positive but EBNA-1 IgG negative, signify acute primary EBV infection. In contrast, the non-specific heterophile antibody tests may be falsely negative in children, especially those 4 years of age and younger.<a class="elsevierStyleCrossRef" href="#bib0007"><span class="elsevierStyleSup">7</span></a></p><p id="para0007" class="elsevierStylePara elsevierViewall">At the University of Minnesota, we do not test body fluids by polymerase chain reaction (PCR) to diagnose EBV diseases because such tests do not distinguish primary infection from reactivation or reinfection. The major value of quantitative PCR testing is to monitor the clinical course of chronic EBV infections in the immunocompromised host.<a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a></p><p id="para0008" class="elsevierStylePara elsevierViewall">The prevalence of plasma EBV DNA differed by age in this study. The highest prevalence occurred in Chinese children between 2 and 6 years old, which is consistent with their age at acquisition of EBV antibodies,<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0009"><span class="elsevierStyleSup">9</span></a> and recently acquired EBV infections are more often accompanied by viremia.</p><p id="para0009" class="elsevierStylePara elsevierViewall">Plasma EBV DNA was statistically significantly more prevalent in outpatients than in inpatients. The reason for this is not immediately evident. Because the study was retrospective, the indications for obtaining a plasma PCR test were not uniform. An explanation could be that outpatient clinicians were more selective in ordering the assay, reserving it for infectious mononucleosis-like illnesses that have a higher probability of being EBV-positive. In that regard, when the authors looked at the association of plasma viral load with the clinical syndromes, they reported higher quantities of plasma EBV DNA in children with the diagnoses of infectious mononucleosis, "atypical EBV infection," or hemophagocytic lymphohistiocytosis—the three diseases studied that were probably caused by EBV.</p><p id="para0010" class="elsevierStylePara elsevierViewall">This paper encourages us as pediatricians to consider EBV in the\differential diagnosis of acute infections Recognition that an illness is due to EBV helps us avoid unnecessary prescription of antibacterial drugs and to give some consideration to the use of valacyclovir.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">10</span></a> A caveat is that causality for any of the six reported clinical entities could not be established by this study. Also, genetics and the environment play a major role in disease expression and its severity. Therefore, the data by Shi et al.<a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a> are not necessarily applicable to patients of different races/ethnicities or who live in geographical locations other than eastern China.</p><p id="para0011" class="elsevierStylePara elsevierViewall">EBV has two "EBNA types," which differ from each other in their EBNA-3A, EBNA-3B, and EBNa-3C genes.<a class="elsevierStyleCrossRef" href="#bib0011"><span class="elsevierStyleSup">11</span></a> A recent study from northern Brazil reported that of 76 patients with infectious mononucleosis, 54 (71%) had type 1, 13 (17%) had type 2, and 9 (12%) had mixtures of the two EBNA serotypes.<a class="elsevierStyleCrossRef" href="#bib0012"><span class="elsevierStyleSup">12</span></a> The authors suggested that patients were sicker if they harbored EBNA type 2. Of 79 Minneapolis-St. Paul students with infectious mononucleosis, 69 (87%) had type 1, 8 (10%) had type 2, and 2 (2.5%) had mixtures.<a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a> The distribution pattern in Minneapolis-St. Paul was somewhat similar to that found in Belém, but the proportion of patients with EBNA type 1 genotypes was higher in Minnesota. Also, in Minnesota, there was no difference in the severity of illness according to the EBNA genotype.</p><p id="para0012" class="elsevierStylePara elsevierViewall">A prophylactic EBV vaccine could prevent EBV diseases from ever happening in the first place.<a class="elsevierStyleCrossRef" href="#bib0013"><span class="elsevierStyleSup">13</span></a> A rationale to give it early in life would be that early acquisition of EBV is a risk factor for developing chronic EBV-driven malignancy or autoimmune diseases. There is some evidence to support this. A multinational study reported that children with multiple sclerosis were statistically significantly more likely to be EBV-infected than EBV-naïve.<a class="elsevierStyleCrossRef" href="#bib0014"><span class="elsevierStyleSup">14</span></a> Younger age at the time of primary EBV infection among Kenyan infants was accompanied by a higher level of EBV viremia, suggesting that those children were at a higher risk for Burkitt lymphoma.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">15</span></a></p><p id="para0013" class="elsevierStylePara elsevierViewall">The other and perhaps more compelling reason to give EBV vaccine as early in life as possible would be to demonstrate that EBV can permanently scar the immune system even if it causes few if any symptoms. Thus, the burning question yet to be answered: what is the burden of EBV disease in young children? Will the risk-benefit equation be favorable? Shi et al. have told us that finding a part of the virus in children's plasma is relatively common. It doesn't belong there but is it causing harm and if so how much? We need to find out.</p><span id="sec0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0002">Funding</span><p id="para0014" class="elsevierStylePara elsevierViewall">Supported by grants from the <span class="elsevierStyleGrantSponsor" id="gs0001">University of Minnesota International Center</span> for Antiviral Research and Epidemiology, the Richard M. Schulze Family Foundation, the Randy Shaver Cancer Research and Community Fund, the Matt Cwiertny Memorial Foundation, and the University of Minnesota Foundation.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0001" "titulo" => "Funding" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:3 [ "etiqueta" => "⁎" "nota" => "<p class="elsevierStyleNotepara" id="notep0001a">See paper by Shi et al. in pages 142–6.</p>" "identificador" => "fn1" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "cebibsec1" "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib0001" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sero-epidemiology of the Epstein-Barr virus: preliminary analysis of an international study—a review" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. de-Thė" 1 => "NE Day" 2 => "A. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 3 | 1 | 4 |
| 2024 October | 49 | 23 | 72 |
| 2024 September | 59 | 40 | 99 |
| 2024 August | 72 | 48 | 120 |
| 2024 July | 69 | 94 | 163 |
| 2024 June | 56 | 40 | 96 |
| 2024 May | 49 | 24 | 73 |
| 2024 April | 48 | 29 | 77 |
| 2024 March | 48 | 25 | 73 |
| 2024 February | 69 | 27 | 96 |
| 2024 January | 81 | 42 | 123 |
| 2023 December | 45 | 38 | 83 |
| 2023 November | 109 | 43 | 152 |
| 2023 October | 56 | 36 | 92 |
| 2023 September | 89 | 37 | 126 |
| 2023 August | 54 | 25 | 79 |
| 2023 July | 59 | 91 | 150 |
| 2023 June | 43 | 15 | 58 |
| 2023 May | 49 | 27 | 76 |
| 2023 April | 46 | 24 | 70 |
| 2023 March | 96 | 33 | 129 |
| 2023 February | 85 | 28 | 113 |
| 2023 January | 77 | 50 | 127 |
| 2022 December | 86 | 75 | 161 |
| 2022 November | 63 | 35 | 98 |
| 2022 October | 142 | 41 | 183 |
| 2022 September | 142 | 56 | 198 |
| 2022 August | 98 | 47 | 145 |
| 2022 July | 200 | 63 | 263 |
| 2022 June | 195 | 52 | 247 |
| 2022 May | 132 | 59 | 191 |
| 2022 April | 222 | 108 | 330 |
| 2022 March | 212 | 93 | 305 |
| 2022 February | 19 | 17 | 36 |
| 2022 January | 20 | 22 | 42 |
| 2021 December | 15 | 23 | 38 |
| 2021 November | 16 | 28 | 44 |
| 2021 October | 9 | 16 | 25 |
| 2021 September | 8 | 10 | 18 |
| 2021 August | 5 | 3 | 8 |
| 2021 July | 11 | 13 | 24 |
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