Clinical characteristics of children with congenital Zika syndrome: a case series / Características clínicas de crianças com síndrome do zika congênita: uma série de casos

ABSTRACT Background: The congenital Zika syndrome involves structural brain changes, including ventriculomegaly, thin cerebral cortices, abnormal gyral pattern, cortical malformations, hypoplasia of the corpus callosum, myelination delay, subcortical diffuse calcifications, brainstem hypoplasia, and microcephaly in newborns. Objective: This study aimed to describe the clinical characteristics of children with congenital Zika syndrome; to compare the outcomes of infants infected in the first (1T, n=20) and second trimesters of pregnancy (2T, n=11); to investigate correlations between birth weight, birth and follow-up head circumference, birth gestational age, and gross motor scores. Methods: Participants were evaluated with Alberta Infant Motor Scale (AIMS) and part A of the Gross Motor Function Measure (GMFM-A). ANOVA compared head circumference, birth gestational age, birth weight, and gross motor performance of 1T and 2T. Results: The correlations were investigated by Pearson correlation coefficients. ANOVA showed differences in birth and follow-up head circumferences. Head circumference was smaller in 1T, compared to 2T. Motor performance was classified as below the fifth percentile in AIMS in all children and 1T showed lower scores in prone, sitting, and total AIMS score, compared to 2T. Children ranged from 8 to 78% on GMFM-A and there was a poorer motor performance of 1T. Nineteen children showed hypertonia, six showed normal tone and six showed hypotonia. Birth head circumference was correlated with AIMS prone postural control. Follow-up head circumference was correlated to prone, supine and total AIMS scores. Smaller head circumference at birth and follow-up denoted poorer postural control. Discussion: Children with congenital Zika syndrome showed microcephaly at birth and follow-up. Smaller head circumferences and poorer motor outcomes were observed in 1T. Infants showed poor visual and motor outcomes. Moderate positive correlations between birth and follow-up head circumference and gross motor function were found.

RESUMO Introdução: A síndrome congênita do zika envolve alterações estruturais do cérebro, incluindo ventriculomegalia, córtices finos do cérebro, padrão giral anormal, malformações corticais, hipoplasia do corpo caloso, atraso de mielinização, calcificações difusas subcorticais, hipoplasia do tronco cerebral e microcefalia em recém-nascidos. Objetivo: Este estudo teve como objetivo descrever as características clínicas de crianças com síndrome congênita do zika; comparar os resultados de bebês infectados no primeiro (1T, n=20) e no segundo trimestres da gravidez (2T, n=11); investigar correlações entre peso ao nascer, perímetro cefálico ao nascer e acompanhamento, idade gestacional ao nascer e escores motores brutos. Método: Os participantes foram avaliados com a Escala Motora Infantil de Alberta (Alberta Infant Motor Scale - AIMS) e a parte A da Medida da Função Motora Grossa (Gross Motor Function Measure - GMFM-A). A ANOVA comparou a circunferência da cabeça, a idade gestacional ao nascer, o peso ao nascer e o desempenho motor bruto de 1T e 2T. As correlações foram investigadas pelos coeficientes de correlação de Pearson. A ANOVA mostrou diferenças no perímetro cefálico ao nascimento e acompanhamento. A circunferência da cabeça foi menor no 1T, em comparação ao 2T. Resultados: O desempenho motor foi classificado como abaixo do quinto percentil na AIMS para todas as crianças e o 1T apresentou escores mais baixos na posição de bruços, sentado e no escore total da AIMS, em comparação ao 2T. As crianças variaram de 8 a 78% no GMFM-A e houve um desempenho motor pior de 1T. Dezenove crianças apresentaram hipertonia, seis apresentaram tônus normal e seis apresentaram hipotonia. A circunferência da cabeça no nascimento foi correlacionada com o controle postural em posição de bruços à AIMS. Discussão: O perímetro cefálico de acompanhamento foi correlacionado aos escores AIMS em posição de bruços, em supino e no escore total. Menor perímetro cefálico ao nascimento e acompanhamento indicaram pior controle postural. Crianças com síndrome congênita do zika apresentaram microcefalia ao nascimento e acompanhamento. Circunferências da cabeça menores e piores resultados motores foram observados no 1T. Os bebês apresentaram maus resultados visuais e motores. Foram encontradas correlações moderadas positivas entre o nascimento e a circunferência da cabeça de acompanhamento, e a função motora grossa.

Avaliação da armadilha ovitrampa iscada com atraente natural para o monitoramento de Aedes spp. em Dili, capital do Timor-Leste / Evaluation of the baited ovitrap with natural attractant for monitoring Aedes spp. in Dili, capital of East Timor

Resumo A dengue ocorre no Timor-Leste desde 2005, porém não existe um programa de monitoramento e controle do "Aedes aegypti". O objetivo deste estudo foi de avaliar a armadilha ovitrampa iscada com atraente natural como uma possível ferramenta para monitorar o vetor das arboviroses: Dengue (DENV), Chikungunya (CHIKV) e Zika (ZIKV). O estudo foi realizado na cidade de Dili, capital do Timor-Leste, entre as semanas epidemiológicas 32 (02/08) a 48 (02/12) de 2016. Foram instaladas 70 armadilhas Ovitrampa, em residências de 15 sucos (ruas), de quatro Postos Administrativos (bairros) da cidade. Para as analises dos dados utilizou-se os indicadores entomológicos: Índice de Positividade de Ovitrampa (IPO), Índice de Densidade Vetorial (IDV) e Índice de Densidade de Ovos (IDO). Durante o experimento foram coletados 158.904 ovos de Aedes spp.. O IPO demonstrou que todas as áreas tiveram 98% a 100% de armadilhas contendo ovos de Aedes spp.. Os indicadores IDO e IPO apresentaram correlações positivas e significativa com a temperatura. A defasagem de duas e três semanas para precipitação indicou correlação positiva significativa para IDV e IDO. Portanto, a armadilha ovitrampa é uma ferramenta que pode integrar as ações de um programa de monitoramento e controle de Aedes spp. no Timor-Leste.

Zika virus RNA excretion in sweat with concomitant detection in other body fluid specimens

We evaluated sweat, blood and urine specimens obtained from an ongoing cohort study in Brazil. Samples were collected at pre-established intervals after the initial rash presentation and tested for Zika virus (ZIKV) RNA presence by real-time reverse transcriptase polymerase chain reaction (rRT-PCR). From 254 participants with confirmed infection, ZIKV RNA was detected in the sweat of 46 individuals (18.1%). Sweat presented a median cycle threshold (Ct) of 34.74 [interquartile range (IQR) 33.44-36.04], comparable to plasma (Ct 35.96 - IQR 33.29-36.69) and higher than urine (Ct 30.78 - IQR 28.72-33.22). Concomitant detection with other specimens was observed in 33 (72%) of 46 participants who had a positive result in sweat. These findings represent an unusual and not yet investigated virus shedding through eccrine glands.

Auditory findings associated with Zika virus infection: an integrative review / Achados auditivos associados à infecção pelo Zika vírus: uma revisão integrativa

Abstract Introduction: Possible associations between Zika virus infection and hearing loss were observed during the epidemic in the Americas. Objective: To describe the auditory alterations, pathogenesis and recommendations for follow-up in individuals with prenatal or acquired Zika virus infection. Methods: Bibliographic research conducted in March/2018-April/2019 at the main available databases. Article selection, data extraction and quality evaluation were carried out by two independent reviewers. Studies containing auditory evaluation of patients with congenital or acquired Zika virus infection; and/or hypotheses or evidences on the pathophysiology of auditory impairment associated with Zika virus; and/or recommendations on screening and follow-up of patients with auditory impairment by Zika virus were included. Results: A total of 27 articles were selected. Sensorineural and transient hearing loss were reported in six adults with acquired Zika virus infection. Of the 962 studied children, 482 had microcephaly and 145 had diagnostic confirmation of Zika virus; 515 of the 624 children with auditory evaluation performed only screening tests with otoacoustic emissions testing and/or automated click-stimuli auditory brainstem response testing. Studies in prenatally exposed children were very heterogeneous and great variations in the frequency of altered otoacoustic emissions and automated click-stimuli auditory brainstem response occurred across the studies. Altered otoacoustic emissions varied from 0% to 75%, while altered automated click-stimuli auditory brainstem response varied from 0% to 29.2%. Sensorineural, retrocochlear or central origin impairment could not be ruled out. One study with infected mice found no microscopic damage to cochlear hair cells. Studies on the pathogenesis of auditory changes in humans are limited to hypotheses and recommendations still include points of controversy. Conclusion: The available data are still insufficient to understand the full spectrum of the involvement of the auditory organs by Zika virus, the pathogenesis of this involvement or even to confirm the causal association between auditory involvement and virus infection. The screening and follow-up recommendations still present points of controversy.

Resumo Introdução: Possíveis associações entre a infecção pelo Zika vírus e perda auditiva foram observadas durante a epidemia nas Américas. Objetivo: Descrever as alterações auditivas, a patogênese e as recomendações de seguimento em indivíduos com infecção por Zika vírus pré-natal ou adquirida. Método: Uma pesquisa bibliográfica foi realizada em março/2018 a abril/2019 nas principais bases de dados disponíveis. A seleção dos artigos, extração de dados e avaliação de qualidade foram realizadas por dois revisores independentes. Estudos com avaliação auditiva de pacientes com infecção por Zika vírus congênita ou adquirida; e/ou hipóteses ou evidências sobre a fisiopatologia do comprometimento auditivo associado ao Zika vírus; e/ou recomendações sobre triagem e seguimento de pacientes com comprometimento auditivo pelo Zika vírus foram incluídos na pesquisa. Resultados: Um total de 27 artigos foram selecionados. Perdas auditivas neurossensorial e transitória foram relatadas em seis adultos com infecção pelo Zika vírus adquirida. Das 962 crianças estudadas, 482 apresentavam microcefalia e 145 tinham confirmação diagnóstica do Zika vírus; 515 das 624 crianças com avaliação auditiva haviam realizado apenas testes de triagem com teste de emissões otoacústicas e/ou teste de potencial evocado auditivo de tronco encefálico automático com estímulo clique. Estudos em crianças expostas no período pré-natal foram muito heterogêneos e grandes variações na frequência de emissões otoacústicas e potencial evocado auditivo de tronco encefálico automático alterados ocorreram ao longo dos estudos; alterações nas emissões otoacústicas variaram de 0% a 75%, enquanto as alterações no potencial evocado auditivo de tronco encefálico automático variaram de 0% a 29,2%. Não foi possível descartar comprometimento neurossensorial, retrococlear ou de origem central. Um estudo com camundongos infectados não encontrou dano microscópico nas células ciliadas da cóclea. Estudos sobre a patogênese das alterações auditivas em humanos estão limitados a hipóteses e recomendações ainda apresentam pontos de controvérsia. Conclusão: Os dados disponíveis ainda são insuficientes para compreender todo o espectro do envolvimento dos órgãos auditivos pelo Zika vírus, a patogênese desse envolvimento ou até mesmo para confirmar a associação causal entre o envolvimento auditivo e a infecção pelo vírus. As recomendações de triagem e seguimento ainda apresentam pontos de controvérsia.

Desarrollo y validación del método de amplificación isotérmica mediada en lazo para la detección del virus Zika / Development and validation of loop-mediated isothermal amplification for the detection of the Zika virus

RESUMEN Se desarrolló un método de amplificación isotérmica mediada en lazo de transcriptasa inversa (RT-LAMP) para detectar Zika. Los primers se diseñaron basándose en la región NS5 de 64 genomas completos. Se usó reactivo LAMP liofilizado. Inicialmente, se probaron siete arbovirus diferentes y solo las muestras de Zika resultaron positivas. Además, las diluciones seriadas de una de los ARN de Zika se compararon mediante RT-LAMP y qRT-PCR, demostrando que RTLAMP es 1000 veces más sensible. También se evaluó 300 muestras de suero usando RT-LAMP y los resultados se compararon con los métodos de qRT-PCR estándar y obtuvimos un 99,3% (IC95%: 97,7 - 100,0) de sensibilidad, 100% (IC95%: 99,7 - 100,0) de especificidad, 100% (IC95%: 99,7 -100,0) de valor predictivo positivo y 99,3% (IC95%: 97,7 - 100,0) de valor predictivo negativo. En conclusión, este método brinda una alternativa de bajo costo, alto rendimiento, viabilidad y confiabilidad para el diagnóstico rápido de Zika en instalaciones de atención primaria de salud.

ABSTRACT A Reverse Transcription Loop-mediated Isothermal Amplification (RT-LAMP) method was developed to detect Zika. The primers were designed based on the NS5 region of 64 complete genomes. Lyophilized LAMP reagent was used. Initially, seven different arboviruses were tested and only Zika samples tested positive. Additionally, serial dilutions of one of Zika's RNA were compared using RT-LAMP and qRT-PCR, demonstrating that RT-LAMP is 1,000 times more sensitive. We also evaluated 300 serum samples with RT-LAMP comparing the results with standard qRT-PCR methods, and we obtained a 99.3% sensitivity, 100% specificity, 100% positive predictive value, and 99.3% negative predictive value. In conclusion, this method provides a low-cost, high-performance, viable, and reliable alternative for the rapid diagnosis of Zika in primary health-care facilities.

Clinical and epidemiological aspects of microcephaly in the state of Piauí, northeastern Brazil, 2015-20166 / Aspectos clínicos e epidemiológicos da microcefalia no Estado do Piauí, Nordeste do Brasil, 2015-2016

Abstract Objectives: To describe aspects of the microcephaly epidemic in the state of Piauí. Methods: All cases of congenital microcephaly confirmed in the state between 2015 and 2016 were included (n = 100). Investigation forms of the Regional Reference Center for Microcephaly were reviewed. Discarded cases (n = 63) were used as a comparison group. Results: In October, November, and December 2015 incidence rates reached 4.46, 6.33 and 3.86/1000 live births, respectively; 44 cases were reported in the state capital. Among the mothers of confirmed and discarded cases, the frequency of skin rash during pregnancy was 50/97 (51.5%) and 8/51 (15.7%), respectively (p < 0.001); 33 confirmed cases (35.9%) had a head circumference z-score between −2 and −3, 23 (25%) between −3 and −4, and 8 (8.7%) had a z-score of less than −4. Head computer tomography scans revealed calcifications in 78/95 (82.1%) cases. Lissencephaly, hydrocephalus and agenesis of the corpus callosum were also frequently observed. Ophthalmic findings included retinal pigment epithelium rarefaction and atrophy. Absence of otoacoustic emissions was observed in 21/70 cases. One newborn also presented lower limb muscle atrophy. There were no significant differences in vaccination rates for influenza, diphtheria-tetanus-acellular pertussis, and hepatitis B in either group. Conclusions: The state of Piauí, like others in the northeastern region, faced an epidemic of congenital microcephaly between 2015 and 2016, presumably related to congenital Zika virus infection, more intense in the capital. Current challenges include the improvement of vector control, basic research, scaling-up of diagnostic tools for pre-natal screening of Zika virus, vaccines, and health care for affected children.

Resumo Objetivos: Descrever os aspectos da epidemia de microcefalia no Estado do Piauí. Métodos: Foram incluídos todos os casos de microcefalia congênita confirmados no estado entre 2015-2016 (n = 100). Os formulários de investigação do Centro Regional de Referência em Microcefalia foram analisados. Os casos descartados (n = 63) foram usados como grupo de comparação. Resultados: Em outubro, novembro e dezembro de 2015, as taxas de incidência atingiram 4,46, 6,33 e 3,86/1.000 nascidos vivos, respectivamente; 44 casos foram relatados na capital do estado. Entre as mães de casos confirmados e descartados, a frequência de erupção cutânea durante a gravidez foi 50/97 (51,5%) e 8/51 (15,7%), respectivamente (p < 0,001); 33 casos confirmados (35,9%) apresentaram um escore z de perímetro cefálico entre -2 e -3, 23 (25%) entre -3 e -4 e 8 (8,7%) apresentaram escore z inferior a -4. As tomografias computadorizadas cerebrais revelaram calcificações em 78/95 (82,1%) dos casos. Lisencefalia, hidrocefalia e agenesia do corpo caloso também foram observadas com mais frequência. Os achados oftalmológicos incluíram rarefação e atrofia do epitélio pigmentar da retina. Foram observadas ausência de emissões otoacústicas em 21/70 casos. Um recém-nascido também apresentou atrofia muscular dos membros inferiores. Não houve diferenças significativas nas taxas de vacinação para gripe, vacina difteria tétano e coqueluche acelular e hepatite B em qualquer grupo. Conclusões: O Estado do Piauí, como outros na região Nordeste, enfrentou, entre 2015 e 2016, uma epidemia de microcefalia congênita, supostamente relacionada à infecção congênita pelo vírus Zika, mais intensa na capital. Os desafios atuais incluem melhora do controle de vetores, pesquisa básica, ampliação de ferramentas de diagnóstico para exame pré-natal do vírus Zika, vacinas e cuidados de saúde para crianças afetadas.

Zika como causa de aborto espontáneo en zonas endémicas / Zika as a cause of spontaneous abortion in endemic areas

Resumen Introducción: Aunque en la mayoría de los casos la infección por el virus del Zika (ZIKV) causa enfermedad febril sin complicaciones, en mujeres embarazadas es causa reconocida de alteraciones congénitas y muerte fetal. La microcefalia es la característica descrita con mayor frecuencia en el síndrome congénito por este virus. Caso clínico: Paciente de sexo femenino de 23 años de edad que cursaba la novena semana de gestación (SDG) por la fecha de la última menstruación y la 10.3 SDG por ultrasonido. Acudió a los servicios de salud por presentar un cuadro clínico compatible con infección por el ZIKV, la cual se confirmó por estudios de laboratorio. A las 18.6 SDG se documentó feto único sin movimientos, con datos de microcefalia, tórax con área cardiaca sin actividad, placenta corporal anterior con calcificación en el 30% e imagen probable de lago venoso versus quiste placentario. La paciente ingresó en urgencias por aborto diferido. Se indujo el trabajo de parto y se obtuvo por vía vaginal un producto masculino de 80 g, con perímetro cefálico de 9 cm. El análisis del cordón umbilical por la reacción en cadena de la polimerasa con retrotranscriptasa confirmó el diagnóstico de síndrome congénito por ZIKV. Conclusiones: Durante el embarazo debe sospecharse la infección por ZIKV para realizar un diagnóstico oportuno y ofrecer una atención integral. La pérdida del producto de la concepción en estas pacientes se ha documentado, y se ha encontrado ARN del ZIKV en las biopsias de las vellosidades coriónicas, lo que podría sugerir el aborto espontáneo de manera temprana durante la viremia.

Abstract Background: Although in most cases Zika is an uncomplicated febrile disease, in pregnant women is a recognized cause of congenital disorders. Microcephaly is the characteristic most frequently described in the congenital Zika virus syndrome, and the diagnosis requires laboratory confirmation. Case report: A 23-year-old female on the ninth week of pregnancy by date of last menstrual period and 10.3 weeks by ultrasound, attended to Health Services, presenting clinical manifestations of Zika infection, which was later confirmed by laboratory tests. In her 18.6 weeks of pregnancy, a non-mobile single fetus was documented. Additional findings were microcephaly, lack of thorax with cardiac activity, anterior corporal placenta with 30% calcification, and an image of probable venous lake versus placental cyst. She was admitted to the emergency room for late abortion and labor was induced, obtaining an 80 g male product with head circumference of 9 cm. Reverse transcription polymerase chain reaction analysis on the umbilical cord was positive for Zika virus. Conclusions: Zika infection during pregnancy must be suspected and diagnosed promptly to offer comprehensive care. The loss of conception in these patients has been documented with results of chorionic villus biopsies, finding Zika virus RNA and suggesting spontaneous abortion early during viremia.

Descriptive study of suspected congenital Zika syndrome cases during the 2015-2016 epidemic in Brazil

Abstract INTRODUCTION: Clinical and epidemiological data on suspected congenital Zika syndrome (CZS) cases from southern Mato Grosso (MT) in Brazil during the Zika virus (ZIKV) outbreak in 2015-2016 were evaluated. METHODS: This is a descriptive case series study of newborns whose mothers were suspected cases of ZIKV infections during their pregnancies. The medical records of all the suspected CZS cases (mothers and newborns) treated by the specialized ambulatory service from June 2015 to August 2016 were analyzed. RESULTS: Twenty suspected CZS cases were included in these analyses. They were categorized into four groups based on the clinical and laboratory findings: confirmed cases (n=1), highly probable cases (n=13), moderately probable cases (n=5), and somewhat probable cases (n=1). The mothers tested negative for STORCH (syphilis, toxoplasmosis, other infections, rubella, cytomegalovirus infection, and herpes simplex) and other important congenital infections; however, specific ZIKV tests were not performed during the study period. Microcephaly was observed in the majority of these newborns, and all the patients showed altered cranial computed tomography image findings. Extracranial abnormalities such as arthrogryposis, and otological and ophthalmological manifestations were also observed. CONCLUSIONS: Although ZIKV was not confirmed to cause the congenital malformations, this study demonstrated that the clinical and epidemiological findings associated with a STORCH exclusion strengthened the CZS diagnosis. The suspected cases in MT occurred simultaneously with the first CZS cases reported in Brazil, suggesting ZIKV circulation in the study region during the same period.

Identification of Zika virus in immature phases of Aedes aegypti and Aedes albopictus: a surveillance strategy for outbreak anticipation

A progressive increase in the circulation of arboviruses in tropical countries has been observed, accounting for 700,000 yearly deaths in the world. The main objective of this article was to identify the presence of Zika (ZIKV), dengue (DENV), and Chikungunya (CHIKV) viruses in immature stages of Aedes aegypti and Ae. albopictus. Household collections of immature phases of the vectors were carried out in the years 2015 and 2016. A total of 2902 dwellings were visited and the rate of infestation with larvae and pupae of Aedes mosquitoes was 283/1462 (19.4%) in March 2015 and 55/1440 (3.8%) in June 2015. In March 2015, 907 larvae/pupae were collected (583 or 64.3% of Ae. aegypti and 324 or 35.7% of Ae. albopictus) while in June 2015 there was a reduction in the number of immature forms found: 197 larvae/pupae (121 or 61.4% of Ae. aegypti and 76 or 38.6% of Ae. albopictus). This reduction was accompanied by a decrease in suspected human ZIKV cases from March to June 2015. The RT-qPCR performed in 18 pools identified that three (two of Ae. aegypti and one of Ae. albopictus) were positive for ZIKV, and none were positive for DENV or CHIKV. Our findings demonstrated that ZIKV was present in immature stages of insect vectors in the study region at least five months prior to the peak of ZIKV associated cases. Xenomonitoring of immature phases of the vectors may prove useful for predicting outbreaks.

Relationship between microcephaly and Zika virus during pregnancy: a review

SUMMARY AIM: the present study analysed the association between Zika-virus and microcephaly during the gestational period of women in Brazil. Methodology: Systematic reviews of intervention research, current publications of clinical investigations were used systematic search strategies in three electronic databases PubMed, SciELO and Google academic. The following keywords were used: Microcephaly, gestation, Zika-virus to perform the search, and 1020 articles were obtained after exclusion, 45 were left and 35 were eligible. The collection period was from 2004 to 2017. Results: Epidemiological data suggest a temporal association between the quantitative increase and the Zika-virus epidemic, especially in Northeast Brazil. It is not consensual to measure the cephalic perimeter curve to be considered. Conclusion: Given this, the application of techniques to accurately diagnose the relationship between causes and effects in the pathogenesis of Zika virus infection in the central nervous system should be prioritized.

RESUMO OBJETIVO: O presente estudo analisou a associação entre Zika vírus e microcefalia durante o período gestacional de mulheres no Brasil. METODOLOGIA: Revisões sistemáticas de pesquisas de intervenção, publicações atuais de investigações clínicas. Foram utilizadas estratégias de buscas sistemáticas em três bases de dados eletrônicos: PubMed, SciELO e Google acadêmico. Utilizaram-se as palavras-chave microcefalia, gestação e Zika vírus para realizar a busca, sendo obtidos 1.020 artigos. Após a exclusão, restaram 45 e na elegibilidade, 35. O período da coleta foi de 2004 a 2017. Resultados: Os dados epidemiológicos preconizam uma associação temporal entre a ampliação do quantitativo e epidemia de Zika vírus, especialmente no Nordeste do Brasil. Não é consensual a mensuração da curva de perímetro cefálico a ser considerada. CONCLUSÃO: Visto isso, deve ser priorizada a aplicação de técnicas para diagnosticar com precisão as relações entre causas e efeitos na patogênese da infecção pelo Zika vírus no sistema nervoso central.

Encephalitis associated with Zika virus infection and reactivation of the varicella-zoster virus in a Brazilian child

Abstract We report a case of encephalitis associated with Zika virus infection and reactivation of varicella-zoster virus in the central nervous system of a Brazilian child. This case raises the possibility that reactivation of the latent varicella-zoster virus may be a mechanism of neurological impairment induced by acquired Zika virus infection.

Zika detection: comparison of methodologies

ABSTRACT Many countries in the Americas have detected local transmission of multiple arboviruses that cause febrile illnesses. Therefore, laboratory testing has become an important tool for confirming the etiology of these diseases. The present study aimed to compare the sensitivity and specificity of three different Zika virus detection assays. One hundred serum samples from patients presenting with acute febrile symptoms were tested using a previously reported TaqMan® RT-qPCR assay. We used a SYBR® Green RT-qPCR and a conventional PCR methodologies to compare the results. Of the samples that were determined to be negative by the TaqMan® RT-qPCR assay, 100% (Kappa = 0.670) were also found to be negative by SYBR® Green RT-qPCR based on Tm comparison; however, 14% (Kappa = 0.035) were found to be positive by conventional PCR followed by agarose gel electrophoresis. The differences between the ZIKV strains circulating worldwide and the low viremia period can compromise diagnostic accuracy and thereby the accuracy of outbreak data. Therefore, improved assays are required to improve the diagnosis and surveillance of arbovirus.

Prevalence of Guillain-Barré syndrome among Zika virus infected cases: a systematic review and meta-analysis

ABSTRACT Zika virus (ZIKV) is an emergent flavivirus transmitted mainly through Aedes spp. mosquitoes that is posing challenge to healthcare services in countries experiencing an outbreak. Usually ZIKV infection is mild, but in some cases it has been reported to progress into neurological diseases such as microcephaly in infants and Guillain-Barré syndrome (GBS) in adults. GBS is a debilitating autoimmune disorder that affects peripheral nerves. Since ZIKV caused massive outbreaks in South America in the past few years, we aimed to systematically review the literature and perform a meta-analysis to estimate the prevalence of GBS among ZIKV-infected individuals. We searched PubMed and Cochrane databases and selected three studies for a meta-analysis. We estimated the prevalence of ZIKV-associated GBS to be 1.23% (95% CI = 1.17-1.29%). Limitations include paucity of data regarding previous flavivirus infections and ZIKV-infection confirmation issues. Our estimate seems to be low, but cannot be ignored, since ZIKV outbreaks affects an overwhelming number of individuals and GBS is a life-threatening debilitating condition, especially in pregnant women. ZIKV infection cases must be closely followed to assure prompt care to reduce the impact of GBS associated-sequelae on the quality of life of those affected.

First evidence of Zika virus venereal transmission in Aedes aegypti mosquitoes

BACKGROUND Aedes aegypti is considered the main Zika virus (ZIKV) vector, and is thought to be responsible for the 2015-2016 outbreak in Brazil. Zika positive Ae. aegypti males collected in the field suggest that vertical and/or venereal transmission of ZIKV may occur. OBJECTIVES In this study, we aimed to demonstrate that venereal transmission of ZIKV by Ae. aegypti can occur under laboratory conditions. METHODS Ae. aegypti collected in the city of Manaus, confirmed as negative for Zika, Dengue and Chikungunya virus by reverse transcription real-time polymerase chain reaction (RT-qPCR) (AaM3V- strain), were reared under laboratory conditions and used for the experiments. The ZIKV used in this study was isolated from a patient presenting with symptoms; ZIKV was confirmed by RT-qPCR. Experiment 1: virgin male mosquitoes of AaM3V- strain were intrathoracically inoculated with a ZIKV suspension; four days after injection, they were transferred to a cage containing virgin females of AaM3V- strain and left to copulate for five days. Experiment 2: virgin female mosquitoes of AaM3V- strain were orally infected with a ZIKV suspension by blood feeding membrane assay; nine days after blood feeding, they were placed in cages with Ae. aegypti AaM3V- virgin males and left to copulate for four days. After copulation, all mosquitoes were individually evaluated for viral infection by RT-qPCR. FINDINGS The mean infection rate in Experiment 1 and Experiment 2 was 45% and 35%, respectively. In both experiments, cycle threshold values ranged from 13 to 35, indicating the presence of viral genomes. MAIN CONCLUSION Ae. aegypti males intrathoracically inoculated with a ZIKV suspension are infected and can transmit the virus to uninfected females by mating. Moreover, Ae. aegypti females orally infected with a ZIKV suspension can transmit the virus to uninfected males by copulation. This study shows that ZIKV infection of Ae. aegypti mosquitoes occurs not only during blood feeding, but also during copulation.

Microcephaly caused by congenital Zika virus infection and viral detection in maternal urine during pregnancy / Microcefalia causada por infecção congênita pelo Zika virus e detecção viral na urina materna durante a gestação

Summary Currently Latin America is undergoing a major epidemic of Zika virus, which is transmitted by Aedes mosquitoes. Concern for Zika virus infection has been increasing as it is suspected of causing brain defects in newborns such as microcephaly and, more recently, potential neurological and autoimmune complications including Guillian-Barré syndrome and acute disseminated encephalomyelitis. We describe a case of virus infection in a 25-year-old woman during the first trimester of her pregnancy, confirmed by laboratory tests only for the detection of viral particles in maternal urine, with imaging studies demonstrating the progression of cranial and encephalic changes in the fetus and later in the newborn, such as head circumference reduction, cerebral calcifications and ventriculomegaly.

Resumo Atualmente, a América Latina está passando por uma grande epidemia de Zika vírus, transmitido por mosquitos Aedes. A preocupação pela infecção pelo Zika vírus vem aumentando, uma vez que é suspeita de causar defeitos cerebrais em recém-nascidos, como a microcefalia e, mais recentemente, potenciais complicações neurológicas e autoimunes, como síndrome de Guillian-Barré e encefalomielite disseminada aguda. Descrevemos um caso de infecção pelo vírus em uma mulher de 25 anos durante o primeiro trimestre de gestação, confirmado dentre os exames laboratoriais apenas pela detecção de partículas virais na urina materna, com estudos de imagens demonstrando a evolução das alterações cranianas e encefálicas no feto e no recém-nascido, como redução do perímetro cefálico, calcificações cerebrais e ventriculomegalia.

Zika: an ongoing threat to women and infants / Zika: uma ameaça permanente para mulheres e crianças / Zika: una amenaza permanente para mujeres y niños

Recent data from the municipality of Rio de Janeiro, Brazil, shows a sharp drop in the number of reported occurrences of Zika during the summer of 2016/2017, compared to the previous summer. There is still a much higher incidence among women than men, almost certainly due to sexual transmission. An unexpected feature of the new data is that there are proportionally far more cases affecting children under 15 months than older age classes. By comparing incidence rates in 2016/2017 and 2015/2016, we were able to deduce the proportion of reported cases affecting men and women, and verify that gender disparity is still present. Women and children are still risk groups for Zika infection, even during non-epidemic seasons.

Dados recentes do Município de Rio de Janeiro, Brasil, mostram uma queda importante na notificação de casos de Zika no verão de 2016/2017, comparado ao verão anterior. A incidência ainda é muito mais alta em mulheres do que em homens, quase certamente em função da transmissão sexual. Uma característica inesperada dos novos dados é que, proporcionalmente, há muito mais casos em crianças abaixo dos 15 meses de idade, quando comparadas àquelas das faixas mais velhas. Ao comparar as taxas de incidência em 2016/2017 e 2015/2016, conseguimos deduzir a proporção de casos notificados em homens e mulheres e confirmar que a disparidade de gênero ainda existe. As mulheres e crianças ainda são grupos de risco para a infecção pelo vírus Zika, mesmo durante períodos não epidêmicos.

Datos recientes del municipio de Río de Janeiro, Brasil, muestran un descenso importante en la notificación de casos de Zika durante el verano de 2016/2017, comparado con el verano anterior. La incidencia todavía es mucho más alta en mujeres que en hombres, casi con seguridad debido a la transmisión sexual. Una característica inesperada de los nuevos datos es que, proporcionalmente, hay muchos más casos en niños por debajo de los 15 meses de edad, cuando se comparan con aquellas franjas con edad superior. Al comparar las tasas de incidencia en 2016/2017 y 2015/2016, conseguimos deducir la proporción de casos notificados en hombres y mujeres y confirmar que la disparidad de género todavía existe. Las mujeres y niños todavía son grupos de riesgo para la infección por el virus Zika, incluso durante períodos no epidémicos.

Microcefalia e dinâmica familiar: a percepção do pai frente à deficiência do filho / Microcefalia y dinámica familiar: la percepción del padre frente a la discapacidad del hijo / Microcephaly and family dynamics: fathers' perceptions of their children's disability

Resumo: A família é um dos pilares da vida psicológica dos indivíduos, influenciando os padrões de comportamento, o sentimento de pertencimento social e a saúde psíquica. Tal estrutura pode ser abalada quando há um membro com microcefalia associada ao Zika vírus, que ocorre quando o menino apresenta perímetro cefálico igual ou inferior a 31,9cm, e a menina, igual ou inferior a 31,5cm. Esta pesquisa visa analisar o impacto do diagnóstico de microcefalia do bebê na função paterna. Para tanto, foram realizadas entrevistas com cinco pais de crianças com microcefalia em três municípios do interior da Paraíba, Brasil. Os instrumentos foram questionário e entrevista semiestruturada gravada, submetida à análise temático-categorial. Todos os pais entrevistados participam da rotina dos filhos, sendo esse envolvimento "condicionado" pelo trabalho, bem como pela severidade da deficiência. Alguns aspectos são comuns, como reação ao diagnóstico e preocupações.

Resumen: La familia es uno de los pilares de la vida psicológica de los individuos, influenciando patrones de comportamiento, sentimiento de pertenencia social y salud psíquica. Esta estructura puede desmoronarse cuando existe un miembro con microcefalia, asociada al virus Zika, que se produce cuando el niño presenta un perímetro cefálico igual o inferior a 31,9cm, y la niña, igual o inferior a 31,5cm. El objetivo de esta investigación es analizar el impacto del diagnóstico de microcefalia del bebé en el desempeño paterno. Para tal fin, se realizaron entrevistas a cinco padres de niños con microcefalia en tres municipios del interior de Paraíba, Brasil. Los instrumentos fueron: cuestionario y entrevista semiestructurada grabada, sometida a un análisis categorial temático. Todos los padres entrevistados participaron en la rutina de los hijos, encontrándose su implicación "condicionada" por el trabajo, así como por el grado de severidad de la discapacidad. Algunos aspectos son comunes como la reacción al diagnóstico y las preocupaciones.

Abstract: The family is a key pillar in an individual's psychological life, influencing behavior patterns, feelings of social belonging, and emotional health. The family structure can be shaken by the arrival of an infant with microcephaly associated with the Zika virus, defined in newborn boys as head circumference less than or equal to 31.9cm and in newborn girls as less than or equal to 31.5cm. The study analyzes the impact of an infant's diagnosis of microcephaly on the paternal function. Interviews were held with five fathers of children with microcephaly from three communities in rural Paraíba State, Brazil. The instruments were a questionnaire and semi-structured interview that was taped and submitted to thematic and categorial analysis. All five fathers were participating in the routine care of their children, with this involvement "conditioned" by their work as well as by the disability's severity. Some aspects were common to all five fathers, such as their reaction to the diagnosis and their concerns.

Follow up of a robust meta-signature to identify Zika virus infection in Aedes aegypti: another brick in the wall

The mosquito Aedes aegypti is the main vector of several arthropod-borne diseases that have global impacts. In a previous meta-analysis, our group identified a vector gene set containing 110 genes strongly associated with infections of dengue, West Nile and yellow fever viruses. Of these 110 genes, four genes allowed a highly accurate classification of infected status. More recently, a new study of Ae. aegypti infected with Zika virus (ZIKV) was published, providing new data to investigate whether this "infection" gene set is also altered during a ZIKV infection. Our hypothesis is that the infection-associated signature may also serve as a proxy to classify the ZIKV infection in the vector. Raw data associated with the NCBI/BioProject were downloaded and re-analysed. A total of 18 paired-end replicates corresponding to three ZIKV-infected samples and three controls were included in this study. The nMDS technique with a logistic regression was used to obtain the probabilities of belonging to a given class. Thus, to compare both gene sets, we used the area under the curve and performed a comparison using the bootstrap method. Our meta-signature was able to separate the infected mosquitoes from the controls with good predictive power to classify the Zika-infected mosquitoes.

Low seroprevalence of Zika virus in Cameroonian blood donors

Abstract A Zika virus seroepidemiology study was performed in 1084 blood donors collected from August to October 2015 in six sites of Cameroon representing a large panel of eco-environments. Samples were tested using an anti-NS1 IgG ELISA detection kit and positives were further confirmed by seroneutralization. The observed global seroprevalence was low (around 5%, peaking at 10% and 7.7% in Douala and Bertoua, respectively) with risk factors associated with seropositivity pointing to the existence of a local (peri-)sylvatic cycle of transmission. These results call attention to the potential introduction and subsequent spread in African urban areas of Asian genotype Zika virus currently circulating in the Americas and adapted to transmission by peri-domestic mosquitoes. They should leverage reinforced surveillance efforts in Africa.