Risk of adverse outcomes in offspring with RT-PCR confirmed prenatal Zika virus exposure: An individual participant data meta-analysis of 13 cohorts in the Zika Brazilian Cohorts Consortium.

Background: Knowledge regarding the risks associated with Zika virus (ZIKV) infections in pregnancy has relied on individual studies with relatively small sample sizes and variable risk estimates of adverse outcomes, or on surveillance or routinely collected data. Using data from the Zika Brazilian Cohorts Consortium, this study aims, to estimate the risk of adverse outcomes among offspring of women with RT-PCR-confirmed ZIKV infection during pregnancy and to explore heterogeneity between studies. Methods: We performed an individual participant data meta-analysis of the offspring of 1548 pregnant women from 13 studies, using one and two-stage meta-analyses to estimate the absolute risks. Findings: Of the 1548 ZIKV-exposed pregnancies, the risk of miscarriage was 0.9%, while the risk of stillbirth was 0.3%. Among the pregnancies with liveborn children, the risk of prematurity was 10,5%, the risk of low birth weight was 7.7, and the risk of small for gestational age (SGA) was 16.2%. For other abnormalities, the absolute risks were: 2.6% for microcephaly at birth or first evaluation, 4.0% for microcephaly at any time during follow-up, 7.9% for neuroimaging abnormalities, 18.7% for functional neurological abnormalities, 4.0% for ophthalmic abnormalities, 6.4% for auditory abnormalities, 0.6% for arthrogryposis, and 1.5% for dysphagia. This risk was similar in all sites studied and in different socioeconomic conditions, indicating that there are not likely to be other factors modifying this association. Interpretation: This study based on prospectively collected data generates the most robust evidence to date on the risks of congenital ZIKV infections over the early life course. Overall, approximately one-third of liveborn children with prenatal ZIKV exposure presented with at least one abnormality compatible with congenital infection, while the risk to present with at least two abnormalities in combination was less than 1.0%.

Adherence to antiretroviral therapy and factors associated with non-adherence: a cohort study at two referral services in Brazil.

This cohort study evaluated non-adherence to antiretrovirals at referral services in Pernambuco, Brazil, 2016/2017, through self-report. A generalized mixed-effects model for binary outcomewas used. We assessed 542 participants with an adherence rate of 85.50%. A greater chance of non-adherence was associated with:a low/moderate level of nicotine dependence (OR = 2.79, p = 0.00, IC = 1.44-5.41); ≥7 tablets/day (OR = 6.14, p = 0.00, IC = 3.42-11.02); LPV/r (OR = 1.49, p = 0.6, IC = 0.98-2.26), ddI (OR = 3.34, p = 0.03, IC = 1.12-9.97), ABC (OR = 4.02, p = 0.05, IC = 1.01-16.03), RAL (OR = 2.49, p = 0.01, IC = 1.32-4.70) and DTG (OR = 4.65, p = 0.01, IC = 1.42-15.16); 6-10 year seropositive diagnosis (OR = 2.17, p = 0.01, IC = 1.20-3.92) and symptoms of depression (OR = 1.55, p = 0.03, IC = 1.03-2.33). Protective factors for non-adherence weres: ≥50 years (OR = 0.67, p = 0.06, IC = 0.45-1.01), secondary/higher education (OR = 0.48, p = 0.00, IC = 0.34-0.70), embarrassment at health service (OR = 0.49, p = 0.04, IC = 0.24-0.97), good understanding of antiretrovirals (OR = 0.62, p = 0.03, IC = 0.40-0.96), adverse event (OR = 0.74, p = 0,06, IC = 0.54-1.01), use of TDF (OR = 0.62, p = 0.01, IC = 0.43-0.90), NVP (OR = 0.41, p = 0.05, IC = 0.71-1.00) and EFZ (OR = 0.48, p = 0.01, IC = 0.29-0.80) and good knowledge of HIV/AIDS/ART. (OR = 0.67, p = 0.07, IC = 0.43-1.04). Variables with stronger association were those linked to ART. Systematic use of self-report adherence is recommended for priority groups.

Frequency-Following Response and Auditory Behavior in Children with Prenatal Exposure to the Zika Virus

Abstract Introduction Prenatal exposure to the Zika virus can impair neurodevelopment and cause auditory damage. Objective To analyze the frequency-following response (FFR) and the auditory behavior (with the LittlEars® questionnaire) of children with and without prenatal exposure to Zika virus infection. Methods A total of 30 children participated in the present study, divided into 3 groups: 10 children with microcephaly and prenatal exposure to the Zika virus; 10 normocephalic children with prenatal exposure to the Zika virus; and 10 children with no evidence of prenatal exposure to the virus. The FFR test was performed with the /da/ syllable. The LittlEars® questionnaire was used with parents/guardians. Results For the FFR measurements, there was no difference between the groups. The children with exposure to the Zika virus presented a final score in the questionnaire below what is expected from children with normal hearing. A significant difference was observed for the final, semantic, and expressive scores between the group with microcephaly and the other groups. A strong negative correlation was seen between the LittlEars® questionnaire final score and the FFR measurements for the group with microcephaly when compared with the other groups. Conclusion Children exposed to the Zika virus, with and without microcephaly, presented FFR patterns similar to what was seen in children with no evidence of virus exposure. However, they showed signs of immature auditory behavior, suggesting auditory development delay.

Decline in head circumference growth and associated factors in congenital Zika syndrome.

Little is known about the evolution of head circumference (HC) in children with congenital Zika syndrome (CZS). This study aims to evaluate HC growth in children with CZS in the first three years of life and identify associated factors. HC data obtained at birth and in neuropediatric consultations from 74 children with CZS were collected from the Child's Health Handbook, parents' reports, and medical records. Predictors of HC z-score were investigated using different mixed-effects models; Akaike's information criterion was used for model selection. The HC z-score decreased from -2.7 ± 1.6 at birth to -5.5 ± 2.2 at 3 months of age, remaining relatively stable thereafter. In the selected adjusted model, the presence of severe brain parenchymal atrophy and maternal symptoms of infection in the first trimester of pregnancy were associated with a more pronounced reduction in the HC z-score in the first three years of life. The decrease of HC z-score in CZS children over the first three months demonstrated a reduced potential for growth and development of the central nervous system of these children. The prognosis of head growth in the first 3 years of life is worse when maternal infection occurs in the first gestational trimester and in children who have severe brain parenchymal atrophy.

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.

Co-circulation of Chikungunya Virus during the 2015-2017 Zika Virus Outbreak in Pernambuco, Brazil: An Analysis of the Microcephaly Epidemic Research Group Pregnancy Cohort.

Co-circulation of arthropod-borne viruses, particularly those with shared mosquito vectors like Zika (ZIKV) and Chikungunya (CHIKV), is increasingly reported. An accurate differential diagnosis between ZIKV and CHIKV is of high clinical importance, especially in the context of pregnancy, but remains challenging due to limitations in the availability of specialized laboratory testing facilities. Using data collected from the prospective pregnancy cohort study of the Microcephaly Epidemic Research Group, which followed up pregnant persons with rash during the peak and decline of the 2015-2017 ZIKV epidemic in Recife, Pernambuco, Brazil, this study aims to describe the geographic and temporal distribution of ZIKV and CHIKV infections and to investigate the extent to which ZIKV and CHIKV infections may be clinically differentiable. Between December 2015 and June 2017, we observed evidence of co-circulation with laboratory confirmation of 213 ZIKV mono-infections, 55 CHIKV mono-infections, and 58 sequential ZIKV/CHIKV infections (i.e., cases with evidence of acute ZIKV infection with concomitant serological evidence of recent CHIKV infection). In logistic regressions with adjustment for maternal age, ZIKV mono-infected cases had lower odds than CHIKV mono-infected cases of presenting with arthralgia (aOR, 99% CI: 0.33, 0.15-0.74), arthritis (0.35, 0.14-0.85), fatigue (0.40, 0.17-0.96), and headache (0.44, 0.19-1.90). However, sequential ZIKV/CHIKV infections complicated discrimination, as they did not significantly differ in clinical presentation from CHIKV mono-infections. These findings suggest clinical symptoms alone may be insufficient for differentiating between ZIKV and CHIKV infections during pregnancy and therefore laboratory diagnostics continue to be a valuable tool for tailoring care in the event of arboviral co-circulation.

Decline in head circumference growth and associated factors in congenital Zika syndrome / Declínio no crescimento do perímetro cefálico e fatores associados à síndrome congênita associada à infecção pelo vírus Zika / Disminución del crecimiento del perímetro cefálico y factores asociados en el síndrome congénito del Zika

Little is known about the evolution of head circumference (HC) in children with congenital Zika syndrome (CZS). This study aims to evaluate HC growth in children with CZS in the first three years of life and identify associated factors. HC data obtained at birth and in neuropediatric consultations from 74 children with CZS were collected from the Child's Health Handbook, parents' reports, and medical records. Predictors of HC z-score were investigated using different mixed-effects models; Akaike's information criterion was used for model selection. The HC z-score decreased from -2.7 ± 1.6 at birth to -5.5 ± 2.2 at 3 months of age, remaining relatively stable thereafter. In the selected adjusted model, the presence of severe brain parenchymal atrophy and maternal symptoms of infection in the first trimester of pregnancy were associated with a more pronounced reduction in the HC z-score in the first three years of life. The decrease of HC z-score in CZS children over the first three months demonstrated a reduced potential for growth and development of the central nervous system of these children. The prognosis of head growth in the first 3 years of life is worse when maternal infection occurs in the first gestational trimester and in children who have severe brain parenchymal atrophy.

Pouco se sabe sobre a evolução do perímetro cefálico (PC) em crianças com síndrome congênita associada à infecção pelo vírus Zika (SCZ) em acompanhamentos contínuos. Este estudo buscou avaliar o crescimento do PC em crianças com SCZ nos primeiros três anos de suas vidas e identificar os fatores associados a ele. Os dados do PC ao nascimento e obtidos em consultas neuropediátricas de 74 crianças com SCZ foram coletados no Cartão da Criança, nos laudos paternos e em seus prontuários. Os preditores de escore-z para PC foram investigados utilizando-se diferentes modelos de efeitos mistos. O critério de informação de Akaike foi utilizado para selecionar os modelos usados. O escore-z de PC diminuiu de -2,7 ± 1,6 ao nascimento para -5,5 ± 2,2 aos 3 meses de idade, mas permaneceu relativamente estável desde então. No modelo ajustado selecionado, a presença de atrofia parênquimal cerebral grave e sintomas maternos de infecção no primeiro trimestre de sua gravidez estiveram associados a uma redução mais acentuada no escore-z de PC nos primeiros três anos de vida dos participantes. A diminuição do escore-z de PC em crianças com SCZ nos primeiros 3 meses de sua vida monstra o potencial reduzido de crescimento e desenvolvimento do sistema nervoso central dessas crianças. O prognóstico de crescimento do perímetro cefálico nos primeiros 3 anos de vida é pior quando a infecção materna ocorreu no primeiro trimestre gestacional e em crianças que tiveram atrofia parênquimal grave.

Se conoce poco sobre la evolución del perímetro cefálico (PC) en niños con síndrome de Zika congénito (SZC) en los seguimientos continuos. El objetivo del estudio fue evaluar el crecimiento del PC en niños con SZC en los primeros 3 años de vida e identificar los factores asociados. Se recogieron datos del PC al nacimiento y obtenidos en las consultas de neuropediatría de 74 niños con SZC a partir de la Tarjeta del Niño, los informes de los padres y los registros médicos. Se investigaron los predictores de la puntuación Z del PC mediante diferentes modelos de efectos mixtos; se utilizó el criterio de información de Akaike para la selección del modelo. La puntuación Z del PC disminuyó de -2,7 ± 1,6 al nacer a -5,5 ± 2,2 a los 3 meses de edad, pero a partir de entonces se mantuvo relativamente estable. En el modelo ajustado seleccionado, la presencia de atrofia grave del parénquima cerebral y los síntomas maternos de infección en el primer trimestre del embarazo se asociaron con una reducción más pronunciada de la puntuación Z del PC en los primeros 3 años de vida. La disminución de la puntuación Z del PC en los niños con SZC durante los primeros 3 meses demuestra el menor potencial de crecimiento y desarrollo del sistema nervioso central de estos niños. El pronóstico del crecimiento de la cabeza en los primeros 3 años de vida es peor cuando la infección materna se produjo en el primer trimestre gestacional y en los niños que tenían una atrofia grave del parénquima cerebral.

Neighbourhood-level income and Zika virus infection during pregnancy in Recife, Pernambuco, Brazil: an ecological perspective, 2015-2017.

Zika virus (ZIKV) infections during pregnancy can lead to adverse neurodevelopmental and clinical outcomes in congenitally infected offspring. As the city of Recife in Pernambuco State, Brazil-the epicentre of the Brazilian microcephaly epidemic-has considerable disparities in living conditions, this study used an ecological approach to investigate the association between income at the neighbourhood level and the risk of ZIKV infections in pregnant individuals between December 2015 and April 2017. The spatial distribution of pregnant individuals with ZIKV infection was plotted on a map of Recife stratified into four categories based on mean monthly income of household heads. Additionally, a Poisson regression model with robust variance was fitted to compare proportions of ZIKV infections among pregnant individuals in relation to the mean monthly income of household heads, based on the 2010 census data, across 94 neighbourhoods in Recife. The results provide evidence that the risk of ZIKV infection to pregnant individuals was higher among those residing in lower-income neighbourhoods: relative to neighbourhoods that had a mean monthly income of ≥5 times minimum wage, neighbourhoods with <1 and 1 to <2 times minimum wage had more than four times the risk (incidence rate ratio, 95% CI 4.08, 1.88 to 8.85 and 4.30, 2.00 to 9.20, respectively). This study provides evidence of a strong association between neighbourhood-level income and ZIKV infection risks in the pregnant population of Recife. In settings prone to arboviral outbreaks, locally targeted interventions to improve living conditions, sanitation, and mosquito control should be a key focus of governmental interventions to reduce risks associated with ZIKV infections during pregnancy.

A new insight into the definition of microcephaly in Zika congenital syndrome era.

This study aimed to compare the anthropometric measurements and body proportionalities of neonates born before the Zika virus epidemic with those born during this period. We compared 958 neonates born during the pre-Zika epidemic with 264 neonates born during the epidemic period. The newborns had their head circumference, weight, and length classified according to the Fenton & Kim growth chart. We considered disproportionate those individuals that presented microcephaly and adequate weight or length for sex and gestational age, and those whose head circumferences were lower than the ratio ((length / 2) + 9.5) - 2.5cm. We estimated the frequencies of Zika positivity and brain imaging findings among neonates with microcephaly born during the epidemic period, concerning the anthropometric and body proportionality parameters. Low weight and proportionate microcephaly were similar among newborns from both periods. However, the frequencies of newborns with microcephaly with a very low length and disproportionate microcephaly were higher among the neonates of the epidemic period with brain abnormalities and positive for Zika virus. We conclude that, at birth, the disproportion between head circumference and length can be an indicator of the severity of microcephaly caused by congenital Zika.

[Evaluation of implementation of the response to the public health emergency of microcephaly in Pernambuco State, Brazil]. / Avaliação da implantação da resposta à emergência de saúde pública de microcefalia no Estado de Pernambuco, Brasil.

This study aimed to assess the degree of implementation of the response to the emergency of microcephaly associated with Zika virus in Pernambuco State, Brazil. This was a normative evaluative study conducted in the initial epicenter of the public health emergency of international concern, from October 2015 to July 2017. A logical model was produced for the intervention under analysis, with the components of Management, Surveillance, and Care in the dimensions of structure, process, and result, based on technical publications and institutional guidelines, in addition to a corresponding log frame of indicators for assessment. Data were collected through a questionnaire, direct observation, and consultation of official documents. The results showed partial implementation (74.9%) of the response to the microcephaly emergency by the Pernambuco State Health Department, with the process dimension reaching 75% of the expected level and the structure dimension, 74.5%. Surveillance was the only component that was assessed as implemented (81%), although with a shortage of regional and laboratory investments, while Management (74.2%) and Care (68.8%) were partially implemented, with insufficiencies in items related to human resources and physical structure, planning, and evaluation. In conclusion, the response to the public health emergency of international concern involving microcephaly associated with the Zika virus was assessed as partially implemented, with different levels between the intervention´s components, especially surveillance when compared to management and care. The shortcomings signal the need for investments to deal with future public health emergencies, with a view towards more timely and adequate interventions.

Este estudo teve por objetivo avaliar o grau de implantação da resposta à emergência da microcefalia associada ao vírus Zika em Pernambuco, Brasil. Trata-se de um estudo avaliativo normativo realizado no epicentro inicial da emergência em saúde pública internacional, ocorrida entre outubro de 2015 e julho de 2017. Elaborou-se um modelo lógico da intervenção sob análise, contendo os componentes Gestão, Vigilância e Assistência em suas dimensões de estrutura, processo e resultado, a partir de publicações técnicas e normativas institucionais, além de uma matriz de indicadores correspondente para julgamento. Coletaram-se dados a partir da aplicação de questionário, observação direta e consulta a documentos oficiais. Os resultados mostraram implantação parcial (74,9%) da resposta à emergência de microcefalia pela Secretaria Estadual de Saúde, com a dimensão processo atingindo 75% do esperado, e a estrutura, 74,5%. A Vigilância foi o único componente avaliado como implantado (81%), ainda que com carência de investimentos regionais e laboratorial, e a Gestão (74,2%) e a Assistência (68,8%), parcialmente implantadas, com insuficiências nos quesitos referentes a recursos humanos e estrutura física, planejamento e avaliação. Conclui-se que o grau de implantação da resposta à emergência em saúde pública internacional de microcefalia associada ao vírus Zika foi avaliado como implantação parcial, com diferentes níveis entre os componentes da intervenção, sobressaindo-se a Vigilância em comparação à Gestão e Assistência. As inconformidades sinalizam a necessidade de investimentos para o enfrentamento de futuras emergências em saúde pública, com vistas a intervenções mais oportunas e adequadas.

El objetivo de este estudio fue evaluar el grado de implantación de la respuesta a la emergencia de microcefalia, asociada al virus Zika, en Pernambuco, Brasil. Se trata de un estudio evaluativo normativo, realizado en el epicentro inicial de la emergencia en salud pública internacional, ocurrida entre octubre de 2015 y julio de 2017. Se elaboró un modelo lógico de la intervención, bajo el análisis que contenía los componentes Gestión, Vigilancia y Asistencia, en sus dimensiones de estructura, proceso y resultado, a partir de publicaciones técnicas y normativas institucionales, y una matriz de indicadores correspondiente para el juicio. Se recogieron datos a partir de la aplicación del cuestionario, observación directa y consulta de documentos oficiales. Los resultados mostraron una implantación parcial (74,9%) de la respuesta a la emergencia de microcefalia por la Secretaría Estatal de Salud, con la dimensión proceso alcanzando a un 75% de lo esperado y la estructura, un 74,5%. La Vigilancia fue el único componente evaluado como implantado (81%), aunque con carencia de inversiones regionales y de laboratorio, y la Gestión (74,2%) y Asistencia (68,8%), parcialmente implantadas, con insuficiencias en los requisitos referentes a recursos humanos y estructura física, planificación y evaluación. Se concluye que el grado de implantación de la respuesta a la emergencia en salud pública internacional de microcefalia, asociada al virus Zika, fue evaluado como implantación parcial, con diferentes niveles entre los componentes de la intervención, sobresaliendo la Vigilancia, en comparación con la Gestión y la Asistencia. Las inconformidades indican la necesidad de inversiones para enfrentar futuras emergencias en salud pública, con vista a intervenciones más oportunas y adecuadas.

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.

Epidemic preparedness: Prenatal Zika virus screening during the next epidemic.

Zika virus (ZIKV) is a vectorborne infectious agent of global public health significance due to its potential to cause severe teratogenic outcomes. The question of whether health systems should consider adopting screening programmes for ZIKV infections during pregnancy warrants consideration. In this analysis, we apply the Wilson-Jungner framework to appraise the potential utility of a prenatal ZIKV screening programme, outline potential screening strategies within the case-finding pathway, and consider other epidemiological factors that may influence the planning of such a screening programme. Our evaluation of a potential prenatal ZIKV screening programme highlights factors affirming its usefulness, including the importance of Congenital Zika Syndrome as a public health problem and the existence of analogous congenital prenatal screening programmes for STORCH agents (syphilis, toxoplasmosis, others (eg, human immunodeficiency virus, varicella-zoster virus, parvovirus B19), rubella, cytomegalovirus, and herpes simplex virus). However, our assessment also reveals key barriers to implementation, such as the need for more accurate diagnostic tests, effective antiviral treatments, increased social service capacity, and surveillance. Given that the reemergence of ZIKV is likely, we provide a guiding framework for policymakers and public health leaders that can be further elaborated and adapted to different contexts in order to reduce the burden of adverse ZIKV-related birth outcomes during future outbreaks.

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.

[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.

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

Resumo 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.

Abstract 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.

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.