Comparison of Oropharyngeal Dysphagia in Brazilian Children with Prenatal Exposure to Zika Virus, With and Without Microcephaly.

Severe brain damage associated with Zika-related microcephaly (ZRM) have been reported to result in oropharyngeal dysphagia (OPD); however, it is unknown if OPD presents in children with prenatal Zika virus (ZIKV) exposure but only mild or undetectable abnormalities. The aims of this study were: to compare the frequency and characteristics of OPD in children with ZRM and in children without microcephaly born to mothers who tested polymerase chain reaction positive (PCR+) for ZIKV during pregnancy; and to investigate the concordance of caregiver reports of OPD with the diagnosis from the clinical swallowing assessment (CSA). Between Mar/2017 and May/2018, we evaluated 116 children (n = 58 with microcephaly, n = 58 children without microcephaly born to ZIKV PCR + mothers) participating in the Microcephaly Epidemic Research Group (MERG) cohort of children born during the 2015-2016 ZIKV epidemic in Pernambuco, Brazil. To assess OPD we used: a CSA; a clinical assessment of the stomatognathic system; and a questionnaire administered to caregivers. The frequency of OPD was markedly higher in children with ZRM (79.3%) than in the exposed but normocephalic group (8.6%). The children with microcephaly also presented more frequently with anatomic and functional abnormalities in the stomatognathic system. There was a high degree of agreement between the caregiver reports of OPD and the CSA (κ = 0.92). In conclusion, our findings confirm that OPD is a feature of Congenital Zika Syndrome that primarily occurs in children with microcephaly and provide support for policies in which children are referred for rehabilitation with an OPD diagnosis based on caregiver report.

Microcephaly epidemic related to the Zika virus and living conditions in Recife, Northeast Brazil.

BACKGROUND: Starting in August 2015, there was an increase in the number of cases of neonatal microcephaly in Northeast Brazil. These findings were identified as being an epidemic of microcephaly related to Zika virus (ZIKV) infection. The present study aims to analyse the spatial distribution of microcephaly cases in Recife (2015-2016), which is in Northeast Brazil, and its association with the living conditions in this city. METHODS: This was an ecological study that used data from reported cases of microcephaly from the State Health Department of Pernambuco (August 2015 to July 2016). The basic spatial unit of analysis was the 94 districts of Recife. The case definition of microcephaly was: neonates with a head circumference of less than the cut-off point of -2 standard deviations below the mean value from the established Fenton growth curve. As an indicator of the living conditions of the 94 districts, the percentage of heads of households with an income of less than twice the minimum wage was calculated. The districts were classified into four homogeneous strata using the K-means clustering algorithm. We plotted the locations of each microcephaly case over a layer of living conditions. RESULTS: During the study period, 347 microcephaly cases were reported, of which 142 (40.9%) fulfilled the definition of a microcephaly case. Stratification of the 94 districts resulted in the identification of four strata. The highest stratum in relation to the living conditions presented the lowest prevalence rate of microcephaly, and the overall difference between this rate and the rates of the other strata was statistically significant. The results of the Kruskal-Wallis test demonstrated that there was a strong association between a higher prevalence of microcephaly and poor living conditions. After the first 6 months of the study period, there were no microcephaly cases recorded within the population living in the richest socio-economic strata. CONCLUSION: This study showed that those residing in areas with precarious living conditions had a higher prevalence of microcephaly compared with populations with better living conditions.

Clinical spectrum of congenital Zika virus infection in Brazil: Update and issues for research development.

This review aimed to provide an update on the morphological and/or functional abnormalities related to congenital Zika virus (ZIKV) infection, based on primary data from studies conducted in Brazil since 2015. During the epidemic years (2015-2016), case series and pediatric cohort studies described several birth defects, including severe and/or disproportionate microcephaly, cranial bone overlap, skull collapse, congenital contractures (arthrogryposis and/or clubfoot), and visual and hearing abnormalities, as part of the spectrum of Congenital Zika Syndrome (CZS). Brain imaging abnormalities, mainly cortical atrophy, ventriculomegaly, and calcifications, serve as structural markers of CZS severity. Most case series and cohorts of microcephaly have reported the co-occurrence of epilepsy, dysphagia, orthopedic deformities, motor function impairment, cerebral palsy, and urological impairment. A previous large meta-analysis conducted in Brazil revealed that a confirmed ZIKV infection during pregnancy was associated with a 4% risk of microcephaly. Additionally, one-third of children showed at least one abnormality, predominantly identified in isolation. Studies examining antenatally ZIKV-exposed children without detectable abnormalities at birth reported conflicting neurodevelopmental results. Therefore, long-term follow-up studies involving pediatric cohorts with appropriate control groups are needed to address this knowledge gap. We recognize the crucial role of a national network of scientists collaborating with international research institutions in understanding the lifelong consequences of congenital ZIKV infection. Additionally, we highlight the need to provide sustainable resources for research and development to reduce the risk of future Zika outbreaks.

Congenital zika syndrome and family impacts: an integrative review. / Síndrome congênita do zika e impactos para as famílias: uma revisão integrativa.

In 2015, a range of congenital anomalies resulting from mother-to-child transmission of the zika virus emerged. Later called congenital zika syndrome (CZS), the condition includes microcephaly. Since then, around 4,000 children have been affected in 27 countries, with Brazil accounting for the largest proportion of cases. Family caregivers have also been affected. This study analyzes the literature on caregivers of children with CZS and how the disease has affected their everyday lives. We conducted an integrative review using the PubMed, Virtual Health Library, and Embase databases. Thirty-one articles were identified for analysis after screening. The findings were grouped into four categories: a) social impacts - changes in family relationships, life projects, and social life; b) subjective impacts - feelings of resilience, loneliness, grief, overburdening, fear, uncertainty, and spirituality and religion; c) economic and material impacts - loss of income, increased household expenses, change of residence, and unemployment; and d) health impacts - service unpreparedness, selflessness, self-care, changes in nutritional and sleep patterns, and mental health problems, including stress, anxiety and depression.

Em 2015, um espectro de anomalias congênitas, incluindo microcefalia, acometeu recém-nascidos como resultado da transmissão vertical pelo vírus zika, posteriormente denominada síndrome congênita do zika (SCZ). Desde então, cerca de 4 mil crianças foram afetadas em 27 países, sendo o Brasil o mais atingido. Cuidadores familiares também têm sido impactados. Esse estudo analisa publicações científicas que investigam as maneiras como a doença afetou as dinâmicas de vida de cuidadores familiares de crianças com SCZ. Realizou-se uma revisão integrativa de literatura consultando as bases de dados PubMed, Biblioteca Virtual em Saúde e Embase. Após as etapas de triagem, foram identificados 31 artigos. Os principais resultados foram agrupados em quatro categorias: a) impactos sociais que evidenciaram mudanças nas relações familiares, nos projetos de vida e no convívio social; b) impactos subjetivos - sentimentos de resiliência, solidão, luto, sobrecarga, medo, incerteza e relação com a espiritualidade; c) impactos econômicos e materiais - perda de renda, aumento de despesas, mudança de moradia e desemprego e d) impactos na saúde - despreparo dos serviços, renúncia do cuidado de si, modificações dos padrões nutricionais e de sono, repercussão para a saúde mental e níveis de estresse, ansiedade e depressão.

Access to childbirth care services in the interior of Pernambuco, Northeast region of Brazil.

OBJECTIVE: To analyze the access of women to the public health system network to childbirth care, highlighting the barriers related to the "availability and accommodation" dimension in a health macroregion of Pernambuco. METHODS: Ecological study, conducted based on hospital birth records from the Hospital Information System of the Brazilian Unified Health System (SUS), and information from the state's Hospital Beds Regulation Center, about women residing in health macroregion II, in 2018. Displacements were reviewed considering the geographic distance between the municipality of residence and that of the childbirth; estimated time of displacement of pregnant women; ratio of shifts blocked for admission of pregnant women for delivery; and the reason for unavailability. RESULTS: In 2018, health macroregion II performed 84% of usual risk childbirths, and 46.9% of high-risk childbirths. The remaining high-risk childbirths (51.1%) occurred in macroregion I, especially in Recife. The reference maternity for high-risk childbirths in that macroregion had 30.4% of the days of day shifts and 38.9% of the night shifts blocked for admission of childbirths; the main reason was the difficulty in maintaining the full team in service. CONCLUSIONS: Women residing in the health macroregion II of Pernambuco face great barriers of access in search of hospital care for childbirth, traveling great distances even when pregnant women of usual risk, leading to pilgrimage in search of this care. There is difficulty regarding availability and accommodation in high-risk services and obstetric emergencies, with shortage of physical and human resources. The obstetric care network in macroregion II of Pernambuco is not structured to ensure equitable access to care for pregnant women at the time of childbirth. This highlights the need for restructuring this healthcare services pursuant to what is recommended by the Cegonha Network.

Zika-Related Microcephaly and Its Repercussions for the Urinary Tract: Clinical, Urodynamic, Scintigraphic and Radiological Aspects.

AIMS: Describing the urodynamic parameters of children aged 3 to 5 years with microcephaly related to congenital Zika syndrome and verifying the association with clinical, imaging and neurological characteristics. METHODS: From October 2018 to March 2020, children with Zika-related microcephaly underwent urological, ultrasonographic and urodynamic evaluation. In selected cases, complementary exams such as urethrocystography and scintigraphy were performed. The children also underwent a complete neurological evaluation. To compare frequency between groups, we used Pearson's chi-squared test or Fisher's exact test. RESULTS: This study evaluated 40 children, of whom 85% were 4 years old, and all had abnormalities on the urodynamic study, with low bladder capacity (92.5%) and detrusor overactivity (77.5%) as the most frequent findings. Only three children had ultrasound abnormalities, but no child had cystographic or scintigraphic abnormalities, and the postvoid residual volume was normal in 80% of cases. In spite of a frequency of 67.5% of intestinal constipation, there was no record of febrile urinary tract infection after the first year of life. All children presented severe microcephaly and at least one neurological abnormality in addition to microcephaly. The homogeneity of the children in relation to microcephaly severity and neurological abnormalities limited the study of the association with the urodynamic parameters. CONCLUSIONS: Urodynamic abnormalities in children aged 3 to 5 years with Zika-related microcephaly do not seem to characterize a neurogenic bladder with immediate risks for the upper urinary tract. The satisfactory bladder emptying suggests that the voiding pattern is reflex.

Risk of SARS-CoV-2 infection among front-line healthcare workers in Northeast Brazil: a respondent-driven sampling approach.

OBJECTIVES: We assessed the prevalence of SARS-CoV-2 infection, personal protective equipment (PPE) shortages and occurrence of biological accidents among front-line healthcare workers (HCW). DESIGN, SETTING AND PARTICIPANTS: Using respondent-driven sampling, the study recruited distinct categories of HCW attending suspected or confirmed patients with COVID-19 from May 2020 to February 2021, in the Recife metropolitan area, Northeast Brazil. OUTCOME MEASURES: The criterion to assess SARS-CoV-2 infection among HCW was a positive self-reported PCR test. RESULTS: We analysed 1525 HCW: 527 physicians, 471 registered nurses, 263 nursing assistants and 264 physical therapists. Women predominated in all categories (81.1%; 95% CI: 77.8% to 84.1%). Nurses were older with more comorbidities (hypertension and overweight/obesity) than the other staff. The overall prevalence of SARS-CoV-2 infection was 61.8% (95% CI: 55.7% to 67.5%) after adjustment for the cluster random effect, weighted by network, and the reference population size. Risk factors for a positive RT-PCR test were being a nursing assistant (OR adjusted: 2.56; 95% CI: 1.42 to 4.61), not always using all recommended PPE while assisting patients with COVID-19 (OR adj: 2.15; 95% CI: 1.02 to 4.53) and reporting a splash of biological fluid/respiratory secretion in the eyes (OR adj: 3.37; 95% CI: 1.10 to 10.34). CONCLUSIONS: This study shows the high frequency of SARS-CoV2 infection among HCW presumably due to workplace exposures. In our setting, nursing assistant comprised the most vulnerable category. Our findings highlight the need for improving healthcare facility environments, specific training and supervision to cope with public health emergencies.

Neurodevelopment in Children Exposed to Zika Virus: What Are the Consequences for Children Who Do Not Present with Microcephaly at Birth?

The relation of Zika virus (ZIKV) with microcephaly is well established. However, knowledge is lacking on later developmental outcomes in children with evidence of maternal ZIKV infection during pregnancy born without microcephaly. The objective of this analysis is to investigate the impact of prenatal exposure to ZIKV on neuropsychomotor development in children without microcephaly. We evaluated 274 children including 235 ZIKV exposed and 39 controls using the Bayley-III Scales of Infant and Toddler Development (BSIDIII) and neurological examination. We observed a difference in cognition with a borderline p-value (p = 0.052): 9.4% of exposed children and none of the unexposed control group had mild to moderate delays. The prevalence of delays in the language and motor domains did not differ significantly between ZIKV-exposed and unexposed children (language: 12.3% versus 12.8%; motor: 4.7% versus 2.6%). Notably, neurological examination results were predictive of neurodevelopmental delays in the BSIDIII assessments for exposed children: 46.7% of children with abnormalities on clinical neurological examination presented with delay in contrast to 17.8% among exposed children without apparent neurological abnormalities (p = 0.001). Overall, our findings suggest that relative to their unexposed peers, ZIKV-exposed children without microcephaly are not at considerably increased risk of neurodevelopmental impairment in the first 42 months of life, although a small group of children demonstrated higher frequencies of cognitive delay. It is important to highlight that in the group of exposed children, an abnormal neuroclinical examination may be a predictor of developmental delay. The article contributes to practical guidance and advances our knowledge about congenital Zika.

Zika-related adverse outcomes in a cohort of pregnant women with rash in Pernambuco, Brazil.

BACKGROUND: While Zika virus (ZIKV) is now widely recognized as a teratogen, the frequency and full spectrum of adverse outcomes of congenital ZIKV infection remains incompletely understood. METHODS: Participants in the MERG cohort of pregnant women with rash, recruited from the surveillance system from December/2015-June/2017. Exposure definition was based on a combination of longitudinal data from molecular, serologic (IgM and IgG3) and plaque reduction neutralization tests for ZIKV. Children were evaluated by a team of clinical specialists and by transfontanelle ultrasound and were classified as having microcephaly and/or other signs/symptoms consistent with congenital Zika syndrome (CZS). Risks of adverse outcomes were quantified according to the relative evidence of a ZIKV infection in pregnancy. FINDINGS: 376 women had confirmed and suspected exposure to ZIKV. Among evaluable children born to these mothers, 20% presented with an adverse outcome compatible with exposure to ZIKV during pregnancy. The absolute risk of microcephaly was 2.9% (11/376), of calcifications and/or ventriculomegaly was 7.2% (13/180), of additional neurologic alterations was 5.3% (13/245), of ophthalmologic abnormalities was 7% (15/214), and of dysphagia was 1.8% (4/226). Less than 1% of the children experienced abnormalities across all of the domains simultaneously. Interpretation: Although approximately one-fifth of children with confirmed and suspected exposure to ZIKV in pregnancy presented with at least one abnormality compatible with CZS, the manifestations presented more frequently in isolation than in combination. Due to the rare nature of some outcomes and the possibility of later manifestations, large scale individual participant data meta-analysis and the long-term evaluation of children are imperative to identify the full spectrum of this syndrome and to plan actions to reduce damages.

[Covid-19 in the Northeast of Brazil: from lockdown to the relaxation of social distancing measures]. / Covid-19 no nordeste do Brasil: entre o lockdown e o relaxamento das medidas de distanciamento social.

Even in the period when the Covid-19 pandemic was on the rise in the Northeast of Brazil, the relaxation of social distancing measures was introduced. The scope of the study is to assess, in the light of the epidemiological-sanitary situation in the region, the suitability of relaxation of social distancing measures. Based on the WHO guidelines for relaxation of social distancing, operational indicators were created and analyzed for each guideline in the context of the Northeast. To analyze the behavior of the epidemic, according to selected indicators, Joinpoint trend analysis techniques, heat maps, rate ratios and time trends between capitals and the state interior were compared. The weekly growth peak of the epidemic occurred in May-July 2020 (epidemiological weeks 19 to 31). In most capitals, there was no simultaneous downward trend in the number of cases and deaths in the 14 days prior to flexibilization. In all states the number of tests performed was insufficient. In epidemiological week 24, the state percentages of ICU/Covid-19 bed occupancy were close to or above 70%. The epidemiological situation of the nine Northeastern state capitals analyzed here did not meet criteria and parameters recommended by the World Health Organization for the relaxation of social distancing measures.

Mesmo no período em que a pandemia de Covid-19 encontrava-se em crescimento no Nordeste do Brasil, iniciou-se a adoção de medidas de flexibilização do distanciamento social. O objetivo do estudo é o de avaliar a pertinência das propostas de flexibilização, tomando-se em conta a situação da pandemia em cada local e o momento em que foram adotadas. Tendo como referência as diretrizes da OMS, foram construídos e analisados indicadores operacionais para cada diretriz, no contexto da região Nordeste. Para análise do comportamento da epidemia, conforme indicadores selecionados, foram usadas técnicas de Joinpoint Trend Analysis, mapas de calor, razão de taxas e comparação da tendência temporal entre capitais e interior dos estados. O pico do crescimento semanal ocorreu em maio-julho/2020 (semanas epidemiológicas 19 a 31). Na maioria das capitais não se observou tendência decrescente simultânea do número de casos e óbitos nos 14 dias prévios à flexibilização. Em todos os estados o quantitativo de testes realizados foi insuficiente. Na semana epidemiológica 24 os percentuais estaduais de ocupação de leitos de UTI/Covid-19 foram próximos ou superiores 70%. A situação epidemiológica das nove capitais dos estados do Nordeste, no momento em que a decisão de flexibilização foi tomada, mostra que nenhuma delas atendia aos critérios e parâmetros recomendados pela OMS.

Zika Brazilian Cohorts (ZBC) Consortium: Protocol for an Individual Participant Data Meta-Analysis of Congenital Zika Syndrome after Maternal Exposure during Pregnancy.

Despite great advances in our knowledge of the consequences of Zika virus to human health, many questions remain unanswered, and results are often inconsistent. The small sample size of individual studies has limited inference about the spectrum of congenital Zika manifestations and the prognosis of affected children. The Brazilian Zika Cohorts Consortium addresses these limitations by bringing together and harmonizing epidemiological data from a series of prospective cohort studies of pregnant women with rash and of children with microcephaly and/or other manifestations of congenital Zika. The objective is to estimate the absolute risk of congenital Zika manifestations and to characterize the full spectrum and natural history of the manifestations of congenital Zika in children with and without microcephaly. This protocol describes the assembly of the Consortium and protocol for the Individual Participant Data Meta-analyses (IPD Meta-analyses). The findings will address knowledge gaps and inform public policies related to Zika virus. The large harmonized dataset and joint analyses will facilitate more precise estimates of the absolute risk of congenital Zika manifestations among Zika virus-infected pregnancies and more complete descriptions of its full spectrum, including rare manifestations. It will enable sensitivity analyses using different definitions of exposure and outcomes, and the investigation of the sources of heterogeneity between studies and regions.

Racial vulnerability and individual barriers for Brazilian women seeking first care following abortion. / Vulnerabilidade racial e barreiras individuais de mulheres em busca do primeiro atendimento pós-aborto.

Social inequalities in Brazil are reflected in women's search for abortion care, when they face individual, social, and structural barriers and are exposed to situations of vulnerability. Black women are the most heavily exposed to these barriers, from the search for the service to the care itself. The study aimed to analyze factors related to individual barriers in the search for first post-abortion care according to race/color. The study was conducted in Salvador (Bahia State), Recife, (Pernambuco State) and São Luís (Maranhão State), Brazil, with 2,640 patients admitted to public hospitals. Logistic regression was performed to analyze differences according to race/color (white, brown, and black), with "no individual barriers in the search for first care" as the reference category in the dependent variable. Of the women interviewed, 35.7% were black, 53.3% brown, and 11% white. Black women had less schooling, fewer children, and reported more induced abortions (31.1%) and more second-trimester abortions (15.4%). Black women reported more individual barriers in the search for first care (32% vs. 28% in brown women and 20.3% in whites), such as fear of being mistreated and lack of money for transportation. Regression analysis confirmed the association between black and brown race/color and individual barriers in the search for post-abortion care, even after adjusting for all the selected variables. The results confirmed the situation of vulnerability for black women and brown women in Brazil. Racial discrimination in health services and abortion-related stigma can act simultaneously, delaying women's access to health services, a limitation that can further complicate their post-abortion condition.

As desigualdades sociais no Brasil se refletem na busca por atenção pelas mulheres com abortamento, as quais enfrentam barreiras individuais, sociais e estruturais, expondo-as a situações de vulnerabilidades. São as negras as mais expostas a essas barreiras, desde a procura pelo serviço até o atendimento. O estudo objetivou analisar os fatores relacionados às barreiras individuais na busca do primeiro atendimento pós-aborto segundo raça/cor. A pesquisa foi realizada em Salvador (Bahia), Recife (Pernambuco) e São Luís (Maranhão), Brasil, com 2.640 usuárias internadas em hospitais públicos. Foi realizada regressão logística para análise das diferenças segundo raça/cor (branca, parda e preta), considerando-se "não houve barreiras individuais na busca pelo primeiro atendimento" como categoria de referência da variável dependente. Das entrevistadas, 35,7% eram pretas, 53,3% pardas e 11% brancas. Mulheres pretas tinham menor escolaridade, menos filhos e declararam mais o aborto como provocado (31,1%), após 12 semanas de gestação (15,4%). Relataram mais barreiras individuais na busca pelo primeiro atendimento (32% vs. 28% entre pardas e 20,3% entre brancas), tais como o medo de ser maltratada e não ter dinheiro para o transporte. Na regressão, confirmou-se a associação entre raça/cor preta e parda e barreiras individuais na busca de cuidados pós-aborto, mesmo após o ajuste por todas as variáveis selecionadas. Os resultados confirmam a situação de vulnerabilidade das pretas e pardas. A discriminação racial nos serviços de saúde e o estigma em relação ao aborto podem atuar simultaneamente, retardando a ida das mulheres ao serviço, o que pode configurar uma situação limite de maior agravamento do quadro pós-abortamento.

Las desigualdades sociales en Brasil se reflejan en la búsqueda de atención sanitaria por parte de las mujeres que abortan, que enfrentan barreras individuales, sociales y estructurales, exponiéndolas a situaciones de vulnerabilidad. Las negras son las más expuestas a estas barreras, desde la búsqueda del servicio hasta la atención. El estudio tuvo como objetivo analizar los factores relacionados con las barreras individuales en la búsqueda de la primera atención post-aborto según raza/color. La investigación se realizó en Salvador (Bahia), Recife (Pernambuco) y São Luis (Maranhão), Brasil, con 2.640 pacientes internadas en hospitales públicos. Se realizó una regresión logística para el análisis de las diferencias según raza/color (blanca, mulata/mestiza y negra), considerándose "no tuvo barreras individuales en la búsqueda de la primera atención" como categoría de referencia de la variable dependiente. De las entrevistadas 35,7% eran negras, 53,3% mulatas/mestizas y 11% blancas. Las mujeres negras tenían menor escolaridad, menos hijos y declararon más el aborto como provocado (31,1%), tras 12 semanas de gestación (15,4%). Informaron más barreras individuales en la búsqueda de la primera atención (32% vs. 28% entre multas/mestizas y un 20,3% entre las blancas), tales como el miedo de ser maltratada y no tener dinero para el transporte. En la regresión se confirmó la asociación entre raza/color negro y mulato/mestizo y barreras individuales en la búsqueda de cuidados post-aborto, incluso tras el ajuste por todas las variables seleccionadas. Los resultados confirman la situación de vulnerabilidad de las negras y mulatas/mestizas. La discriminación racial en los servicios de salud y el estigma en relación con el aborto pueden actuar simultáneamente, retardando la ida de las mujeres al servicio de salud, lo que puede constituir una situación límite de mayor gravedad en el cuadro post-aborto.

Quality assessment of abortion care from the users' perspective: dimensional structure of the QualiAborto-Pt questionnaire. / Avaliação da qualidade da atenção ao aborto na perspectiva das usuárias: estrutura dimensional do instrumento QualiAborto-Pt.

Abortion complications are a major public health problem, and studies to assess the quality of abortion care require adequate measurement tools. This study is a continuation of such an instrument's refinement, the QualiAborto-Pt questionnaire. Using data from a survey of 2,336 women hospitalized for abortion complications in 19 hospitals in three state capitals in Northeast Brazil (Salvador - Bahia, Recife - Pernambuco, and São Luís - Maranhão), we implemented a series of exploratory and confirmatory factor analyses based on a 55-item prototype. The analyses indicate a structure with 17 items in five dimensions: reception, orientation, inputs/physical environment, technical quality, and continuity of care. All the items in the final model displayed acceptable reliability, absence of content redundancy, and factor specificity, as well as theoretical consistency with the respective dimensions. The solution also shows discriminant factor validity. Despite some persistent issues for further analysis and clarification, this version merits recommendation for use in Brazil.

As complicações do aborto são um importante problema de saúde pública e pesquisas para avaliar a qualidade da atenção requerem ferramentas de aferição adequadas. Este estudo dá sequência ao processo de refinamento de um instrumento para esse fim - QualiAborto-Pt. Utilizando-se dados de um inquérito com 2.336 mulheres internadas por complicações do aborto em 19 hospitais de três capitais do Nordeste brasileiro (Salvador - Bahia, Recife - Pernambuco e São Luís - Maranhão), implementou-se uma sequência de análises fatoriais exploratórias e confirmatórias com base em um protótipo de 55 itens. As análises apontam para uma estrutura de 17 itens em cinco dimensões: acolhimento, orientação, insumos/ambiente físico, qualidade técnica e continuidade do cuidado. Todos os itens do modelo final evidenciam confiabilidade aceitável, ausência de redundância de conteúdo, especificidade fatorial, e guardam coerência teórica com as respectivas dimensões. A solução também mostra validade fatorial discriminante. Ainda que persistam algumas questões a aprofundar e acertar, esta versão merece ser recomendada para uso no Brasil.

Las complicaciones del aborto son un importante problema de salud pública y las investigaciones para evaluar la calidad de la atención requieren herramientas de medición adecuadas. Este estudio da continuación al proceso de perfeccionamiento de un instrumento para este fin - QualiAborto-Pt. Se utilizaron datos de una encuesta con 2.336 mujeres internadas por complicaciones con el aborto en 19 hospitales de tres capitales del nordeste brasileño (Salvador - Bahia, Recife - Pernambuco e São Luís - Maranhão), se implementó una secuencia de análisis factoriales exploratorios y confirmatorios, a partir de un prototipo de 55 ítems. Los análisis apuntan una estructura de 17 ítems en cinco dimensiones: acogida, orientación, insumos/ambiente físico, calidad técnica y continuidad del cuidado. Todos los ítems del modelo final evidencian confiabilidad aceptable, ausencia de redundancia de contenido, especificidad factorial, y guardan coherencia teórica con sus respectivas dimensiones. La solución también muestra validez factorial discriminante. A pesar de que persistan algunas cuestiones por profundizar y acertar, esta versión merece ser recomendada para su uso en Brasil.

The first hundred days of COVID-19 in Pernambuco State, Brazil: epidemiology in historical context. / Cem dias de COVID-19 em Pernambuco, Brasil: a epidemiologia em contexto histórico.

The timeline of the COVID-19 pandemic began on December 31, 2019, in China, with SARS-CoV-2 identified as the etiological agent. This article aims to describe the COVID-19 epidemic's spatial and temporal dynamics in the first hundred days in the State of Pernambuco, Brazil. We present the evolution in cases and deaths according to epidemiological weeks. We analyzed the series of accumulated daily confirmed COVID-19 cases, with projections for the subsequent 15 days, using the JoinPoint app. This software allows identifying turning points, testing their statistical significance. We also analyze the trend in the spread of COVID-19 to the interior of the state, considering the percent distribution of cases in the state capital, Recife, municipalities in Greater Metropolitan Recife, and the state's interior, by sets of three weeks, constructing thematic maps. The first hundred days of the COVID-19 epidemic resulted in 52,213 cases and 4,235 deaths from March 12, or epidemiological week 11, until June 20, 2020 (epidemiological week 25). The peak in the epidemic curve occurred in epidemiological week 21 (May 23), followed by deceleration in the number of cases. We initially detected the spread of cases from the city center to the periphery of the state capital and Metropolitan Area, followed by rapid spread to the state's interior. There was a decrease in the mean daily growth starting in April, but with an average threshold of more than 6,000 weekly cases of COVID-19. At the end of the period, the state's case series indicates the persistence of SARS-CoV-2 circulation and community transmission. Finally, paraphrasing Gabriel Garcia Marques in One Hundred Years of Solitude, we ask whether we are facing "a pause in the storm or a sign of redoubled rain".

A pandemia de COVID-19 iniciou sua linha do tempo em 31 de dezembro de 2019 na China e o SARS-CoV-2 identificado como agente etiológico. O objetivo deste manuscrito é descrever a dinâmica espacial e temporal da epidemia de COVID-19 nos primeiros cem dias, no Estado de Pernambuco, Brasil. Apresentamos a evolução de casos e óbitos segundo semana epidemiológica. Realizamos a análise da série do acumulado diário de casos da COVID-19 confirmados, com projeções para os 15 dias subsequentes, utilizando o aplicativo JoinPoint. Esse programa possibilita identificar pontos de inflexão testando sua significância estatística. Analisamos também a tendência de interiorização da COVID-19 no estado, considerando a distribuição percentual de casos ocorridos no Recife, municípios da Região Metropolitana de Recife e do interior, por conjuntos de três semanas, com construção de mapas temáticos. Os 100 dias da epidemia de COVID-19 resultaram em 52.213 casos e 4.235 óbitos entre 12 de março, correspondendo se 11, até 20 de junho de 2020 (semana epidemiológica 25). O pico da curva epidêmica ocorreu na semana epidemiológica 21 (23 de maio), seguido por desaceleração do número de casos. Detectou-se, inicialmente, a periferização dos casos na capital e região metropolitana, seguida por rápida disseminação para o interior do estado. Houve redução das taxas de crescimento médio diário a partir de abril, mas com patamar de mais de 6.000 casos semanais de COVID-19, em média. Ao final do período, a série de casos do estado indica persistência da circulação e transmissão comunitária do SARS-CoV-2. Finalmente, questiona-se parafraseando Garcia Marques em Cem Anos de Solidão, se estaríamos diante de "uma estiagem ou prenúncio de recrudescimento".

La pandemia de COVID-19 inicia su línea del tiempo el 31 de dicembre de 2019 en China y el SARS-CoV-2 identificado como agente etiológico. El objetivo de este trabajo original es describir la dinámica espacial y temporal de la epidemia de COVID-19 en los primeros cien días de epidemia, en el estado de Pernambuco, Brasil. Presentamos la evolución de casos y óbitos según las semanas epidemiológicas. Realizamos el análisis de la serie del acumulado diario de casos de COVID-19 confirmados, con proyecciones para los 15 días subsiguientes, utilizándose la aplicación JoinPoint. Este programa posibilita identificar puntos de inflexión, probando su significancia estadística. Analizamos también la tendencia de interiorización de la COVID-19 en el estado, considerándose la distribución porcentual de casos ocurridos en Recife, municipios de la Región Metropolitana de Recife y del interior, por conjuntos de tres semanas, con unas construcciones de mapas temáticos. Los cien días de la epidemia de COVID-19 resultaron en 52.213 casos y 4.235 óbitos entre el 12 de marzo, correspondiendo a la semana epidemiológica 11, hasta el 20 de juno de 2020 (semana epidemiológica 25). El pico de la curva epidémica ocurrió en la semana epidemiológica 21 (23 de mayo), seguido de una desaceleración en el número de casos. Se detectó, inicialmente, la periferización de los casos en la capital y región metropolitana, seguido por la rápida diseminación hacia el interior del estado. Hubo una reducción de las tasas de crecimiento medio diario a partir de abril, pero con un nivel de más de 6.000 casos semanales de COVID-19 de media. Al final del período la serie de casos del estado indica la persistencia de la circulación y transmisión comunitaria del SARS-CoV-2. Finalmente, se cuestiona, parafraseando a García Márquez en Cien Años de Soledad, si estamos ante "un periodo de remisión o la antesala de un recrudecimiento".

COVID-19 in Northeast Brazil: achievements and limitations in the responses of the state governments. / COVID-19 no Nordeste brasileiro: sucessos e limitações nas respostas dos governos dos estados.

The COVID-19 pandemic has been most severe in the poorest regions of Brazil, such as the states of the Northeast Region. The lack of national policies for pandemic control forced state and municipal authorities to implement public health measures. The aim of this study is to show the effect of these measures on the epidemic. The highest incidence of COVID-19 among the nine states in the Northeast was recorded in Sergipe, Paraíba and Ceará. Piauí, Paraíba and Ceará were the states that most tested. Factors associated with transmission included the high proportion of people in informal work. States with international airports played an important role in the entry of the virus and the initial spread, especially Ceará. All states applied social distancing measures, banned public events and closed schools. The response was a significant increase in social distancing, especially in Ceará and Pernambuco, a decline in the reproduction rate (Rt), and a separation of the curve of observed cases versus expected cases if the non-pharmacological interventions had not been implemented in all states. Poverty, inequality, and the high rates of informal work provide clues to the intensity of COVID-19 in the region. On the other hand, the measures taken early by the governments mitigated the effects of the pandemic.

No Brasil, a pandemia da COVID-19 tem sido severa nos estados das regiões mais pobres, como o Nordeste. A falta de políticas nacionais para controle da pandemia levou as autoridades estaduais e municipais a implementarem medidas de saúde pública. O objetivo deste estudo é mostrar o efeito dessas medidas na epidemia. A maior incidência da COVID-19 entre os nove estados do Nordeste foi registrada em Sergipe, Paraíba e Ceará. O Piauí, a Paraíba e Ceará foram os que mais testaram. Muitos estados apresentavam alta proporção de pessoas em trabalho informal. Estados com aeroportos internacionais tiveram importante papel na entrada e disseminação inicial do vírus, em especial o Ceará. Todos os estados aplicaram medidas de distanciamento social, proibição de eventos públicos e fechamento de unidades de ensino. As respostas foram o aumento significativo de distanciamento social, em especial Ceará e Pernambuco, a queda do número de reprodução (Rt) e a separação da curva dos casos observados da curva dos casos esperados sem as intervenções não medicamentosas em todos os estados. A pobreza, a desigualdade e as altas taxas de trabalho informal fornecem pistas do porquê da intensidade da COVID-19 na região. Por outro lado, as medidas de mitigação tomadas precocemente pelos governantes amenizaram os efeitos da pandemia.

Clinical spectrum of congenital Zika virus infection in Brazil: Update and issues for research development

ABSTRACT This review aimed to provide an update on the morphological and/or functional abnormalities related to congenital Zika virus (ZIKV) infection, based on primary data from studies conducted in Brazil since 2015. During the epidemic years (2015-2016), case series and pediatric cohort studies described several birth defects, including severe and/or disproportionate microcephaly, cranial bone overlap, skull collapse, congenital contractures (arthrogryposis and/or clubfoot), and visual and hearing abnormalities, as part of the spectrum of Congenital Zika Syndrome (CZS). Brain imaging abnormalities, mainly cortical atrophy, ventriculomegaly, and calcifications, serve as structural markers of CZS severity. Most case series and cohorts of microcephaly have reported the co-occurrence of epilepsy, dysphagia, orthopedic deformities, motor function impairment, cerebral palsy, and urological impairment. A previous large meta-analysis conducted in Brazil revealed that a confirmed ZIKV infection during pregnancy was associated with a 4% risk of microcephaly. Additionally, one-third of children showed at least one abnormality, predominantly identified in isolation. Studies examining antenatally ZIKV-exposed children without detectable abnormalities at birth reported conflicting neurodevelopmental results. Therefore, long-term follow-up studies involving pediatric cohorts with appropriate control groups are needed to address this knowledge gap. We recognize the crucial role of a national network of scientists collaborating with international research institutions in understanding the lifelong consequences of congenital ZIKV infection. Additionally, we highlight the need to provide sustainable resources for research and development to reduce the risk of future Zika outbreaks.

Perinatal analyses of Zika- and dengue virus-specific neutralizing antibodies: A microcephaly case-control study in an area of high dengue endemicity in Brazil.

Laboratory confirmation of Zika virus (ZIKV) infection during pregnancy is challenging due to cross-reactivity with dengue virus (DENV) and limited knowledge about the kinetics of anti-Zika antibody responses during pregnancy. We described ZIKV and DENV serological markers and the maternal-fetal transfer of antibodies among mothers and neonates after the ZIKV microcephaly outbreak in Northeast Brazil (2016). We included 89 microcephaly cases and 173 neonate controls at time of birth and their mothers. Microcephaly cases were defined as newborns with a particular head circumference (2 SD below the mean). Two controls without microcephaly were matched by the expected date of delivery and area of residence. We tested maternal serum for recent (ZIKV genome, IgM and IgG3 anti-NS1) and previous (ZIKV and DENV neutralizing antibodies [NAbs]) markers of infection. Multiple markers of recent or previous ZIKV and DENV infection in mothers were analyzed using principal component analysis (PCA). At delivery, 5.6% of microcephaly case mothers and 1.7% of control mothers were positive for ZIKV IgM. Positivity for ZIKV IgG3 anti-NS1 was 8.0% for case mothers and 3.5% for control mothers. ZIKV NAbs was slightly higher among mothers of cases (69.6%) than that of mothers of controls (57.2%; p = 0.054). DENV exposure was detected in 85.8% of all mothers. PCA discriminated two distinct components related to recent or previous ZIKV infection and DENV exposure. ZIKV NAbs were higher in newborns than in their corresponding mothers (p<0.001). We detected a high frequency of ZIKV exposure among mothers after the first wave of the ZIKV outbreak in Northeast Brazil. However, we found low sensitivity of the serological markers to recent infection (IgM and IgG3 anti-NS1) in perinatal samples of mothers of microcephaly cases. Since the neutralization test cannot precisely determine the time of infection, testing for ZIKV immune status should be performed as early as possible and throughout pregnancy to monitor acute Zika infection in endemic areas.

Zika virus infection in pregnancy: Establishing a case definition for clinical research on pregnant women with rash in an active transmission setting.

Defining cases of Zika virus (ZIKV) infection is a critical challenge for epidemiological research. Due to ZIKV's overlapping clinical features and potential immunologic cross-reactivity with other flaviviruses and the current lack of an optimal ZIKV-specific diagnostic assay, varying approaches for identifying ZIKV infections have been employed to date. This paper presents the laboratory results and diagnostic criteria developed by the Microcephaly Epidemic Research Group for defining cases of maternal ZIKV infection in a cohort of pregnant women with rash (N = 694) recruited during the declining 2015-2017 epidemic in northeast Brazil. For this investigation, we tested maternal sera for ZIKV by quantitative reverse transcription polymerase chain reaction (qRT-PCR), Immunoglobulin (Ig) M and IgG3 enzyme-linked immunosorbent assays (ELISAs), and Plaque Reduction Neutralization Test (PRNT50). Overall, 23.8% of participants tested positive by qRT-PCR during pregnancy (range of detection: 0-72 days after rash onset). However, the inter-assay concordance was lower than expected. Among women with qRT-PCR-confirmed ZIKV and further testing, only 10.1% had positive IgM tests within 90 days of rash, and only 48.5% had ZIKV-specific PRNT50 titers ≥20 within 1 year of rash. Given the complexity of these data, we convened a panel of experts to propose an algorithm for identifying ZIKV infections in pregnancy based on all available lines of evidence. When the diagnostic algorithm was applied to the cohort, 26.9% of participants were classified as having robust evidence of a ZIKV infection during pregnancy, 4.0% as having moderate evidence, 13.3% as having limited evidence of a ZIKV infection but with uncertain timing, and 19.5% as having evidence of an unspecified flavivirus infection before or during pregnancy. Our findings suggest that integrating longitudinal data from nucleic acid and serologic testing may enhance diagnostic sensitivity and underscore the need for an on-going dialogue regarding the optimization of strategies for defining cases of ZIKV in research.

Understanding the relation between Zika virus infection during pregnancy and adverse fetal, infant and child outcomes: a protocol for a systematic review and individual participant data meta-analysis of longitudinal studies of pregnant women and their infants and children.

INTRODUCTION: Zika virus (ZIKV) infection during pregnancy is a known cause of microcephaly and other congenital and developmental anomalies. In the absence of a ZIKV vaccine or prophylactics, principal investigators (PIs) and international leaders in ZIKV research have formed the ZIKV Individual Participant Data (IPD) Consortium to identify, collect and synthesise IPD from longitudinal studies of pregnant women that measure ZIKV infection during pregnancy and fetal, infant or child outcomes. METHODS AND ANALYSIS: We will identify eligible studies through the ZIKV IPD Consortium membership and a systematic review and invite study PIs to participate in the IPD meta-analysis (IPD-MA). We will use the combined dataset to estimate the relative and absolute risk of congenital Zika syndrome (CZS), including microcephaly and late symptomatic congenital infections; identify and explore sources of heterogeneity in those estimates and develop and validate a risk prediction model to identify the pregnancies at the highest risk of CZS or adverse developmental outcomes. The variable accuracy of diagnostic assays and differences in exposure and outcome definitions means that included studies will have a higher level of systematic variability, a component of measurement error, than an IPD-MA of studies of an established pathogen. We will use expert testimony, existing internal and external diagnostic accuracy validation studies and laboratory external quality assessments to inform the distribution of measurement error in our models. We will apply both Bayesian and frequentist methods to directly account for these and other sources of uncertainty. ETHICS AND DISSEMINATION: The IPD-MA was deemed exempt from ethical review. We will convene a group of patient advocates to evaluate the ethical implications and utility of the risk stratification tool. Findings from these analyses will be shared via national and international conferences and through publication in open access, peer-reviewed journals. TRIAL REGISTRATION NUMBER: PROSPERO International prospective register of systematic reviews (CRD42017068915).

ZikaPLAN: addressing the knowledge gaps and working towards a research preparedness network in the Americas.

Zika Preparedness Latin American Network (ZikaPLAN) is a research consortium funded by the European Commission to address the research gaps in combating Zika and to establish a sustainable network with research capacity building in the Americas. Here we present a report on ZikaPLAN`s mid-term achievements since its initiation in October 2016 to June 2019, illustrating the research objectives of the 15 work packages ranging from virology, diagnostics, entomology and vector control, modelling to clinical cohort studies in pregnant women and neonates, as well as studies on the neurological complications of Zika infections in adolescents and adults. For example, the Neuroviruses Emerging in the Americas Study (NEAS) has set up more than 10 clinical sites in Colombia. Through the Butantan Phase 3 dengue vaccine trial, we have access to samples of 17,000 subjects in 14 different geographic locations in Brazil. To address the lack of access to clinical samples for diagnostic evaluation, ZikaPLAN set up a network of quality sites with access to well-characterized clinical specimens and capacity for independent evaluations. The International Committee for Congenital Anomaly Surveillance Tools was formed with global representation from regional networks conducting birth defects surveillance. We have collated a comprehensive inventory of resources and tools for birth defects surveillance, and developed an App for low resource regions facilitating the coding and description of all major externally visible congenital anomalies including congenital Zika syndrome. Research Capacity Network (REDe) is a shared and open resource centre where researchers and health workers can access tools, resources and support, enabling better and more research in the region. Addressing the gap in research capacity in LMICs is pivotal in ensuring broad-based systems to be prepared for the next outbreak. Our shared and open research space through REDe will be used to maximize the transfer of research into practice by summarizing the research output and by hosting the tools, resources, guidance and recommendations generated by these studies. Leveraging on the research from this consortium, we are working towards a research preparedness network.