Editorial
Microcephaly and Zika virus
Microcefalia e vírus Zika
a Section of Arbovirology and Hemorrhagic Fevers, Instituto Evandro Chagas (IEC), Secretaria de Vigilância em Saúde (SVS), Ministério da Saúde (MS), Ananindeua, PA, Brazil
b Universidade do Estado do Pará, Belém, PA, Brazil
c Research and Reference in Arbovirus, World Health Organization (WHO) Collaborating Center, Organização Pan-Americana da Saúde (OPAS), Brasília, DF, Brazil
Read
3438
Timeswas read the article
1355
Total PDF
2083
Total HTML
Share statistics
array:24 [ "pii" => "S0021755716000395" "issn" => "00217557" "doi" => "10.1016/j.jped.2016.02.003" "estado" => "S300" "fechaPublicacion" => "2016-03-01" "aid" => "357" "copyright" => "Sociedade Brasileira de Pediatria" "copyrightAnyo" => "2016" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "sco" "cita" => "J Pediatr (Rio J). 2016;92:103-5" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1751 "formatos" => array:3 [ "EPUB" => 73 "HTML" => 1277 "PDF" => 401 ] ] "Traduccion" => array:1 [ "pt" => array:20 [ "pii" => "S2255553616000318" "issn" => "22555536" "doi" => "10.1016/j.jpedp.2016.02.013" "estado" => "S300" "fechaPublicacion" => "2016-03-01" "aid" => "357" "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). 2016;92:103-5" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2584 "formatos" => array:3 [ "EPUB" => 90 "HTML" => 1942 "PDF" => 552 ] ] "pt" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "Microcephaly and Zika virus" "tienePdf" => "pt" "tieneTextoCompleto" => "pt" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "103" "paginaFinal" => "105" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Microcefalia e vírus zika" ] ] "contieneTextoCompleto" => array:1 [ "pt" => true ] "contienePdf" => array:1 [ "pt" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Consuelo Silva de Oliveira, Pedro Fernando da Costa Vasconcelos" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Consuelo Silva" "apellidos" => "de Oliveira" ] 1 => array:2 [ "nombre" => "Pedro Fernando da Costa" "apellidos" => "Vasconcelos" ] ] ] ] ] "idiomaDefecto" => "pt" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S0021755716000395" "doi" => "10.1016/j.jped.2016.02.003" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0021755716000395?idApp=UINPBA000049" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2255553616000318?idApp=UINPBA000049" "url" => "/22555536/0000009200000002/v2_201604160036/S2255553616000318/v2_201604160036/pt/main.assets" ] ] "itemSiguiente" => array:20 [ "pii" => "S0021755716000085" "issn" => "00217557" "doi" => "10.1016/j.jped.2016.01.003" "estado" => "S300" "fechaPublicacion" => "2016-03-01" "aid" => "338" "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). 2016;92:106-8" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1312 "formatos" => array:3 [ "EPUB" => 152 "HTML" => 817 "PDF" => 343 ] ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "Daytime urinary incontinence: a chronic and comorbid condition of childhood" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "106" "paginaFinal" => "108" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Incontinência urinária diurnal: uma doença crônica e comorbidade infantil" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Anne J. Wright" "autores" => array:1 [ 0 => array:2 [ "nombre" => "Anne J." "apellidos" => "Wright" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "pt" => array:9 [ "pii" => "S2255553616000069" "doi" => "10.1016/j.jpedp.2016.01.002" "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/S2255553616000069?idApp=UINPBA000049" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0021755716000085?idApp=UINPBA000049" "url" => "/00217557/0000009200000002/v1_201603250033/S0021755716000085/v1_201603250033/en/main.assets" ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "Microcephaly and Zika virus" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "103" "paginaFinal" => "105" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Consuelo Silva de Oliveira, Pedro Fernando da Costa Vasconcelos" "autores" => array:2 [ 0 => array:4 [ "nombre" => "Consuelo Silva" "apellidos" => "de Oliveira" "email" => array:1 [ 0 => "consuelooliveira@iec.pa.gov.br" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Pedro Fernando" "apellidos" => "da Costa Vasconcelos" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Section of Arbovirology and Hemorrhagic Fevers, Instituto Evandro Chagas (IEC), Secretaria de Vigilância em Saúde (SVS), Ministério da Saúde (MS), Ananindeua, PA, Brazil" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Universidade do Estado do Pará, Belém, PA, Brazil" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Research and Reference in Arbovirus, World Health Organization (WHO) Collaborating Center, Organização Pan-Americana da Saúde (OPAS), Brasília, DF, Brazil" "etiqueta" => "c" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Microcefalia e vírus Zika" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The original isolation of the Zika virus (ZIKV), a <span class="elsevierStyleItalic">Flavivirus</span> member of the Flaviviridae family, was obtained in 1947 from the blood of a febrile rhesus monkey exposed at the Zika forest near Lake Victoria, in the outskirts of Entebbe, the capital of Uganda.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> ZIKV was also isolated from wild mosquitoes in the same area and later periodic human febrile cases were attributed to ZIKV in Uganda and other countries in West and East Africa. Later, in the 1960s, ZIKV was detected in Asia and the virus was isolated from <span class="elsevierStyleItalic">Aedes aegypti</span> mosquitoes, initially in Malaysia and, subsequently, in several countries in Asia, showing that this arbovirus also occurred outside the African continent.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> This new facet of ZIKV, <span class="elsevierStyleItalic">i.e.</span>, ability to cause epidemic disease transmitted by <span class="elsevierStyleItalic">Aedes aegypti</span>, disclosed a new milestone in the epidemiology of this arbovirus infection. It was clear that ZIKV had managed to adapt to an old acquaintance of humans, <span class="elsevierStyleItalic">Aedes aegypti</span> mosquitoes, transmitters of urban yellow fever, four serotypes of dengue fever, chikungunya virus, and other arboviruses in Asia and Africa.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Since the 1960s, sporadic cases of ZIKV infection have been reported in humans<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>; due to its sporadic occurrence and low severity pattern, little importance was given to this arbovirus until a Zika fever epidemic occurred on Yap Island in the Republic of Micronesia in 2007, with the description of a rash febrile syndrome of mild intensity and a high percentage of asymptomatic cases.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> This episode on Yap Island was followed by others, in the Pacific Ocean region of Polynesia and in some Southeast Asian countries, with outbreaks confirmed by serology or polymerase chain reaction (PCR) for the ZIKV on Easter Island, and in the Solomon Islands, the Cook Islands, Indonesia, Malaysia, Thailand, and French Polynesia.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5–7</span></a> In the latter, retrospective epidemiological studies suggested the occurrence of approximately 30,000 infections and, for the first time, cases of Guillain-Barre syndrome (GBS) were observed associated with ZIKV infection, as well as the notification of the first cases of perinatal transmission,<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> warning of the potential complications of congenital arbovirus infections, based on previous reports of encephalopathy, hemorrhagic fever, and fetal death, among others, associated with chikungunya and dengue viruses. In a retrospective analysis of live births during this outbreak in Polynesia, 17 cases of central nervous system malformations, including microcephaly in fetuses and newborns, were identified from March 2014 to May 2015. None of the pregnant women reported signs of ZIKV infection, but antibodies (IgG) to <span class="elsevierStyleItalic">Flavivirus</span> were found in four women tested by serology, suggesting asymptomatic infection.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">9</span></a> Similarly as in Brazil, French Polynesia health authorities also believe that ZIKV may be associated with birth defects if pregnant women are infected during the first or second trimester of pregnancy.</p><p id="par0015" class="elsevierStylePara elsevierViewall">After the confirmation of the first cases of Zika fever in Brazil in May 2015, initially in the Northeast,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> there was a rapid spread of the virus to other parts of the country, followed by the significant increase in notifications of newborns with microcephaly in the Brazilian Live Birth Information System (Sistema de Informação de Nascidos Vivos [SINASC]), with the recording of 141 suspected cases of microcephaly in November 2015 in the state of Pernambuco, after which an excessive number of cases in other northeastern states (Paraíba and Rio Grande do Norte) were detected, in addition to the records of miscarriages and stillbirths. Faced with this new scenario, the Ministry of Health of Brazil declared the event as a public health emergency of national concern.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> It was also verified that the first months of pregnancy of children born with microcephaly matched the largest period of circulation of the ZIKV in the Northeast, and there was no correlation with family history of genetic disease, or tests demonstrating a pattern of other known infectious processes.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The causal association was carried out by Instituto Evandro Chagas (IEC) of the Ministry of Health through the isolation the ZIKV from brain tissue and detection of the virus in cerebral spinal fluid (CSF), brain tissue, and fragments of several viscera (heart, lungs, liver, spleen and kidney) of a newborn that died shortly after birth.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Subsequently, these results were reinforced with the detection of IgM antibodies to ZIKV in the CSF of 12 children born with microcephaly. All tests for other infectious agents associated with what is medically known as TORCH syndrome (toxoplasma gondii, other agents, rubella virus, cytomegalovirus, and herpes simplex virus, types 1 and 2), as well as dengue and chikungunya, were negative (Azevedo et al.; personal communication).</p><p id="par0025" class="elsevierStylePara elsevierViewall">Another important contribution to elucidate the causal association was the identification of ZIKV the amniotic fluid of two pregnant women from the state of Paraiba with a history of rash illness and fetuses with microcephaly detected at the fetal ultrasonography.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> After this finding, further studies were conducted, which allowed the complete sequencing of the virus isolated from the amniotic fluid, with the phylogenetic analysis disclosing that the virus shares 97-100% of its genomic identity with the Asian strain isolated during the outbreak in French Polynesia and that the presence of the viral genome in the patients for a few weeks after the acute phase suggests that the intrauterine viral load results from persistent replication.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> As additional evidence, the identification of the ZIKV genome in placental cells in an 8-week miscarriage using RT-PCR techniques reinforced the potential of placental transmission.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Recently, the Centers for Disease Control and Prevention (CDC) confirmed the presence of the virus, using RT-PCR and immunohistochemistry, in the brain tissue of four newborns with microcephaly and/or severe brain malformations that died after birth, and in the placentas of miscarried fetuses at 12 weeks of gestation.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Similar findings were identified by Mlakar et al.,<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> who identified the viral genome in the brain and placenta of a fetus miscarried in the 32nd week of gestation that had multiple brain lesions and intrauterine growth retardation detected after the 29th week of gestation, which confirms the virus neurotropism, with a possible viral persistence in brain tissue and severe placental impairment.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Furthermore, there has been increasing evidence that in addition to the brain, the eyes would be the next target organ of ZIKV, as the presence of ocular disorders (macular atrophy) has been observed in children with microcephaly<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> and, more recently, macular and perimacular lesions with optic nerve atrophy,<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> as described in ten children with microcephaly during the Zika outbreak in the capital city of Salvador, state of Bahia.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Considering the severity of the situation, the rapid spread of ZIKV in the American continent, and the difficulties of diagnosis for an emerging arbovirus infection in the Americas, as well as the high risk of the virus spreading to other continents, the WHO declared the ZIKV epidemic an important international public health event, according to the International Health Regulations, and convened an emergency committee. The disclosure of the WHO note was followed by a description of the event.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">One of the major limitations to be overcome is the lack of commercial serological and molecular tests for the diagnosis of ZIKV, as the existing in-house tests are currently limited to reference laboratories, which are unable to meet the demands of public health laboratories. In fact, there is an urgent necessity to develop rapid tests (immunochromatographic), serological (IgM- and IgG-ELISA) and molecular tests for the early diagnosis of ZIKV infection, especially for the most vulnerable groups, <span class="elsevierStyleItalic">i.e.</span>, pregnant women and individuals with autoimmune conditions and chronic diseases.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> There have been recent records of deaths in patients with chronic diseases, lupus, hemolytic anemia, sickle-cell anemia, and others, which means these groups should have prioritized access to the diagnosis of ZIKV infection.</p><p id="par0050" class="elsevierStylePara elsevierViewall">There is a clear need to reinforce antivectorial measures, which is the only currently available concrete measure to reduce cases of ZIKV infections. It is urgent that concrete actions be taken at all public levels together with the participation of society to reduce vector infestation indices; by reducing the number of vectors, we will reduce incidence rates and, obviously, the number of cases of microcephaly and other congenital malformations.</p><p id="par0055" class="elsevierStylePara elsevierViewall">The Brazilian Ministry of Health made the political decision to develop a vaccine against ZIKV. Regarding this subject, there are several possible approaches to the development of a vaccine to prevent ZIKV infection, which include: inactivated virus vaccine, attenuated live virus vaccine, chimeric live virus vaccine, DNA vaccine, and subunit vaccine. Undoubtedly, the subunit and DNA vaccines are those that do not pose risks to pregnant women and special groups, and can be obtained quickly, the same occurring with the inactivated virus vaccine. It is important to note, however, that whatever the adopted formulation is, pre-clinical and clinical trials phases I, II, and III will take some years until a licensed product for use in humans is obtained.</p><p id="par0060" class="elsevierStylePara elsevierViewall">In conclusion, the emergence of an “almost unknown” arbovirus and its causal association with different clinical manifestations and a degree of severity, especially observed in fetuses and adults with immune suppression and autoimmune disorders, opens up a range of opportunities for many studies, but the perspective of dissemination of this arbovirus to other continents in a globalized world will require a prompt response coordinated by the WHO, together with the assistance and financial support of all member states and civil society worldwide.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors declare 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:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: de Oliveira CS, da Costa Vasconcelos PF. Microcephaly and Zika virus. J Pediatr (Rio J). 2016;92:103–5.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:20 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Zika virus I. Isolations and serological specificity" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "G.W. Dick" 1 => "S.F. Kitchen" 2 => "A.J. Haddow" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Trans R Soc Trop Med Hyg" "fecha" => "1952" "volumen" => "46" "paginaInicial" => "509" "paginaFinal" => "520" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12995440" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Isolation of Zika virus from <span class="elsevierStyleItalic">Aedes aegypti</span> mosquitoes in Malaysia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "N.J. Marchette" 1 => "R. Garcia" 2 => "A. Rudnik" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Trop Med Hyg" "fecha" => "1969" "volumen" => "18" "paginaInicial" => "411" "paginaFinal" => "415" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/4976739" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Zika virus: a report on three cases of human infection during an epidemic of jaundice in Nigeria" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "F.N. Macnamara" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Trans R Soc Trop Med Hyg" "fecha" => "1954" "volumen" => "48" "paginaInicial" => "139" "paginaFinal" => "145" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/13157159" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Zika virus outside Africa" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "E.B. Hayes" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3201/eid1509.090442" "Revista" => array:6 [ "tituloSerie" => "Emerg Infect Dis" "fecha" => "2009" "volumen" => "15" "paginaInicial" => "1347" "paginaFinal" => "1350" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19788800" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.S. Lanciotti" 1 => "O.L. Kosoy" 2 => "J.J. Laven" 3 => "J.O. Velez" 4 => "A.J. Lambert" 5 => "A.J. Johnson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3201/eid1408.080287" "Revista" => array:6 [ "tituloSerie" => "Emerg Infect Dis" "fecha" => "2008" "volumen" => "14" "paginaInicial" => "1232" "paginaFinal" => "1239" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18680646" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Zika virus, French Polynesia, South Pacific, 2013" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "V.M. Cao-Lormeau" 1 => "C. Roche" 2 => "A. Teissier" 3 => "E. Robin" 4 => "A.L. Berry" 5 => "H.P. Mallet" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3201/eid2006.140138" "Revista" => array:6 [ "tituloSerie" => "Emerg Infect Dis" "fecha" => "2014" "volumen" => "20" "paginaInicial" => "1085" "paginaFinal" => "1086" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24856001" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rapid spread of emerging Zika virus in the Pacific area" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "D. Musso" 1 => "E.J. Nilles" 2 => "V.M. Cao-Lormeau" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/1469-0691.12707" "Revista" => array:6 [ "tituloSerie" => "Clin Microbiol Infect" "fecha" => "2014" "volumen" => "20" "paginaInicial" => "O595" "paginaFinal" => "O596" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24909208" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evidence of perinatal transmission of Zika virus, French Polynesia, December 2013 and February 2014" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. Besnard" 1 => "S. Lastere" 2 => "A. Teissier" 3 => "V. Cao-Lormeau" 4 => "D. Musso" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Euro Surveill" "fecha" => "2014" "paginaInicial" => "19" ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0105" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rapid risk assessment. Zika virus epidemic in the Americas: potential association with microcephaly and Guillain-Barré syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "European Centre for Disease Prevention and Control" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ "fecha" => "2015" "editorial" => "European Centre for Disease Prevention and Control" "editorialLocalizacion" => "Stockholm, Sweden" ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "First report of autochthonous transmission of Zika virus in Brazil" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "C. Zanluca" 1 => "V.C. de Melo" 2 => "A.L. Mosimann" 3 => "G.I. dos Santos" 4 => "C.N. dos Santos" 5 => "K. Luz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1590/0074-02760150192" "Revista" => array:6 [ "tituloSerie" => "Mem Inst Oswaldo Cruz" "fecha" => "2015" "volumen" => "110" "paginaInicial" => "569" "paginaFinal" => "572" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26061233" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Zika: the origin and spread of a mosquito-borne virus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M.K. Kindhauser" 1 => "T. Allen" 2 => "V. Frank" 3 => "R.S. Santhana" 4 => "C. Dye" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2471/BLT.16" "Revista" => array:3 [ "tituloSerie" => "Bull World Health Organ" "fecha" => "2016" "paginaInicial" => "171082" ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Zika virus intrauterine infection causes fetal brain abnormality and microcephaly: tip of the iceberg?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A.S. Oliveira Melo" 1 => "G. Malinger" 2 => "R. Ximenes" 3 => "P.O. Szejnfeld" 4 => "S. Alves Sampaio" 5 => "M. Bispo de Filippis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/uog.15831" "Revista" => array:6 [ "tituloSerie" => "Ultrasound Obstet Gynecol" "fecha" => "2016" "volumen" => "47" "paginaInicial" => "6" "paginaFinal" => "7" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26731034" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Detection and sequencing of Zika virus from amniotic fluid of fetuses with microcephaly in Brazil: a case study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. Calvet" 1 => "R.S. Aguiar" 2 => "A.S. Melo" 3 => "A.S. Sampaio" 4 => "I. de Filippis" 5 => "A. Fabri" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S1473-3099(16)00095-5" "Revista" => array:2 [ "tituloSerie" => "Lancet Infect Dis" "fecha" => "2016" ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Provisional remarks on Zika virus infection in pregnant women: Document for health care professionals." "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "Pan American Health Organization (PAHO), World Health Organization (WHO)" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ "fecha" => "Jan 25, 2016" "editorial" => "PAHO" "editorialLocalizacion" => "Montevideo, Uruguay" ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Notes from the field: evidence of Zika virus infection in brain and placental tissues from two congenitally infected newborns and two fetal losses — Brazil, 2015" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.B. Martines" 1 => "J. Bhatnagar" 2 => "M.K. Keating" 3 => "L. Silva-Flannery" 4 => "A. Muehlenbachs" 5 => "J. Gary" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.15585/mmwr.mm6506e1" "Revista" => array:6 [ "tituloSerie" => "MMWR Morb Mortal Wkly Rep" "fecha" => "2016" "volumen" => "65" "paginaInicial" => "159" "paginaFinal" => "160" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26890059" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Zika virus associated with microcephaly" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Mlakar" 1 => "M. Korva" 2 => "N. Tul" 3 => "M. Popović" 4 => "M. Poljšak-Prijatelj" 5 => "J. Mraz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1600651" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2016" "volumen" => "374" "paginaInicial" => "951" "paginaFinal" => "958" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26862926" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Zika virus in Brazil and macular atrophy in a child with microcephaly" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "C.V. Ventura" 1 => "M. Maia" 2 => "V. Bravo-Filho" 3 => "A.L. Góis" 4 => "R. Belfort Jr." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(16)00054-4" "Revista" => array:5 [ "tituloSerie" => "Lancet" "fecha" => "2016" "volumen" => "387" "paginaInicial" => "228" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26842298" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ocular findings in infants with microcephaly associated with presumed Zika virus congenital infection in Salvador, Brazil" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B. de Paula Freitas" 1 => "J.R. de Oliveira Dias" 2 => "J. Prazeres" 3 => "G.A. Sacramento" 4 => "A.I. Ko" 5 => "M. Maia" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/jamaophthalmol.2016.0267" "Revista" => array:2 [ "tituloSerie" => "JAMA Ophthalmol" "fecha" => "2016" ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Zika virus and microcephaly: why is this situation a PHEIC?" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.L. Heymann" 1 => "A. Hodgson" 2 => "A.A. Sall" 3 => "D.O. Freedman" 4 => "J.E. Staples" 5 => "F. Althabe" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(16)00320-2" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2016" "volumen" => "387" "paginaInicial" => "719" "paginaFinal" => "721" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26876373" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "State of knowledge on Zika virus for an adequate laboratory response" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "R.N. Charrel" 1 => "I. Leparc-Goffart" 2 => "S. Pas" 3 => "X. de Lamballerie" 4 => "M. Koopmans" 5 => "C. Reusken" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2471/BLT.16.171207" "Revista" => array:2 [ "tituloSerie" => "Bull World Health Organ" "fecha" => "2016" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/00217557/0000009200000002/v1_201603250033/S0021755716000395/v1_201603250033/en/main.assets" "Apartado" => array:4 [ "identificador" => "10177" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Editorials" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/00217557/0000009200000002/v1_201603250033/S0021755716000395/v1_201603250033/en/main.pdf?idApp=UINPBA000049&text.app=https://jped.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0021755716000395?idApp=UINPBA000049" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 5 | 4 | 9 |
| 2024 October | 23 | 25 | 48 |
| 2024 September | 25 | 26 | 51 |
| 2024 August | 36 | 30 | 66 |
| 2024 July | 31 | 34 | 65 |
| 2024 June | 24 | 19 | 43 |
| 2024 May | 14 | 9 | 23 |
| 2024 April | 16 | 20 | 36 |
| 2024 March | 17 | 16 | 33 |
| 2024 February | 20 | 29 | 49 |
| 2024 January | 49 | 26 | 75 |
| 2023 December | 12 | 28 | 40 |
| 2023 November | 14 | 24 | 38 |
| 2023 October | 25 | 28 | 53 |
| 2023 September | 21 | 33 | 54 |
| 2023 August | 13 | 19 | 32 |
| 2023 July | 19 | 20 | 39 |
| 2023 June | 9 | 6 | 15 |
| 2023 May | 20 | 13 | 33 |
| 2023 April | 11 | 10 | 21 |
| 2023 March | 11 | 21 | 32 |
| 2023 February | 10 | 11 | 21 |
| 2023 January | 14 | 20 | 34 |
| 2022 December | 16 | 19 | 35 |
| 2022 November | 18 | 26 | 44 |
| 2022 October | 27 | 23 | 50 |
| 2022 September | 9 | 31 | 40 |
| 2022 August | 19 | 25 | 44 |
| 2022 July | 14 | 18 | 32 |
| 2022 June | 19 | 30 | 49 |
| 2022 May | 23 | 35 | 58 |
| 2022 April | 38 | 26 | 64 |
| 2022 March | 20 | 19 | 39 |
| 2022 February | 15 | 20 | 35 |
| 2022 January | 6 | 18 | 24 |
| 2021 December | 14 | 21 | 35 |
| 2021 November | 5 | 11 | 16 |
| 2021 October | 11 | 17 | 28 |
| 2021 September | 3 | 4 | 7 |
| 2021 August | 5 | 11 | 16 |
| 2021 July | 3 | 6 | 9 |
| 2021 June | 3 | 6 | 9 |
| 2021 May | 7 | 11 | 18 |
| 2021 April | 7 | 16 | 23 |
| 2021 March | 16 | 13 | 29 |
| 2021 February | 5 | 7 | 12 |
| 2021 January | 4 | 8 | 12 |
| 2020 December | 7 | 7 | 14 |
| 2020 November | 6 | 9 | 15 |
| 2020 October | 5 | 6 | 11 |
| 2020 September | 13 | 14 | 27 |
| 2020 August | 1 | 3 | 4 |
| 2020 July | 5 | 3 | 8 |
| 2020 June | 5 | 6 | 11 |
| 2020 May | 5 | 2 | 7 |
| 2020 April | 3 | 7 | 10 |
| 2020 March | 8 | 3 | 11 |
| 2020 February | 10 | 8 | 18 |
| 2020 January | 11 | 13 | 24 |
| 2019 December | 7 | 8 | 15 |
| 2019 November | 4 | 3 | 7 |
| 2019 October | 9 | 10 | 19 |
| 2019 September | 8 | 7 | 15 |
| 2019 August | 13 | 6 | 19 |
| 2019 July | 17 | 10 | 27 |
| 2019 June | 13 | 11 | 24 |
| 2019 May | 10 | 9 | 19 |
| 2019 April | 16 | 8 | 24 |
| 2019 March | 11 | 5 | 16 |
| 2019 February | 5 | 5 | 10 |
| 2019 January | 9 | 7 | 16 |
| 2018 December | 11 | 8 | 19 |
| 2018 November | 33 | 4 | 37 |
| 2018 October | 172 | 21 | 193 |
| 2018 September | 57 | 5 | 62 |
| 2018 August | 21 | 15 | 36 |
| 2018 July | 7 | 8 | 15 |
| 2018 June | 24 | 5 | 29 |
| 2018 May | 49 | 8 | 57 |
| 2018 April | 23 | 1 | 24 |
| 2018 March | 64 | 4 | 68 |
| 2018 February | 68 | 3 | 71 |
| 2018 January | 46 | 3 | 49 |
| 2017 December | 53 | 4 | 57 |
| 2017 November | 21 | 2 | 23 |
| 2017 October | 10 | 3 | 13 |
| 2017 September | 4 | 9 | 13 |
| 2017 August | 3 | 1 | 4 |
| 2017 July | 1 | 4 | 5 |
| 2017 June | 10 | 2 | 12 |
| 2017 May | 5 | 7 | 12 |
| 2017 April | 7 | 3 | 10 |
| 2017 March | 6 | 6 | 12 |
| 2017 February | 12 | 1 | 13 |
| 2017 January | 11 | 5 | 16 |
| 2016 December | 16 | 4 | 20 |
| 2016 November | 17 | 9 | 26 |
| 2016 October | 26 | 9 | 35 |
| 2016 September | 36 | 7 | 43 |
| 2016 August | 37 | 8 | 45 |
| 2016 July | 40 | 13 | 53 |
| 2016 June | 42 | 20 | 62 |
| 2016 May | 83 | 40 | 123 |
| 2016 April | 94 | 43 | 137 |
| 2016 March | 27 | 8 | 35 |
Show all
