Zika Virus affects neurobehavioral development, and causes oxidative stress associated to blood-brain barrier disruption in a rat model of congenital infection.

Zika virus (ZIKV) is a mosquito-borne flavivirus associated with several neurodevelopmental outcomes after in utero infection. Here, we studied a congenital ZIKV infection model with immunocompetent Wistar rats, able to predict disabilities and that could pave the way for proposing new effective therapies. We identified neurodevelopmental milestones disabilities in congenital ZIKV animals. Also, on 22nd postnatal day (PND), blood-brain barrier (BBB) proteins disturbances were detected in the hippocampus with immunocontent reduction of ß_Catenin, Occludin and Conexin-43. Besides, oxidative stress imbalance on hippocampus and cortex were identified, without neuronal reduction in these structures. In conclusion, even without pups' microcephaly-like phenotype, congenital ZIKV infection resulted in neurobehavioral dysfunction associated with BBB and oxidative stress disturbances in young rats. Therefore, our findings highlighted the multiple impact of the congenital ZIKV infection on the neurodevelopment, which reinforces the continuity of studies to understand the spectrum of this impairment and to provide support to future treatment development for patients affected by congenital ZIKV.

Prevalence of sleep disorders in children with Congenital Zika Syndrome.

Studies have reported that children with Congenital Zika Syndrome (CZS) experience changes in their sleep patterns, which can result in mood disturbances, behavioral issues and delays in growth and development. This systematic review synthesized the available evidence on the prevalence of sleep disorders in children with CZS. Eligible studies were those with an observational design that reported sleep disorders in children with CZS using validated questionnaires, polysomnography/electroencephalographic recording or parent/caregiver reports. Searches were conducted in PubMed, Web of Science, SCOPUS and Embase, as well as a gray literature search using Google Scholar. The Freeman-Tukey double-arcsine transformation with a random-effects model was used to estimate the pooled prevalence of sleep disorders with a 95% confidence interval (CI). Five studies were included and data from 340 Brazilian children with CZS were analyzed. The overall prevalence of sleep disorders was 27.4% (95% CI 16.7-39.4), without differences among studies using validated questionnaires (29.4%, 95% CI 21.4-37.8) or report from parents and caregivers (27.4%, 95% CI 11.5-47.0). Sleep disorders are prevalent in children with CZS, impacting their development and quality of life. It is critical to examine the quality of sleep in these children to develop appropriate interventions that can mitigate these issues.

The article discusses a systematic review of studies that have explored the prevalence of sleep disorders in children with Congenital Zika Syndrome (CZS), a condition caused by the Zika virus. The study found that children with CZS often experience changes in their sleep patterns, which can lead to mood disturbances, behavioral issues and delays in growth and development. The review included five studies with a total of 340 Brazilian children with CZS, and the overall prevalence of sleep disorders was found to be 27.4%. This indicates that sleep disorders are prevalent in children with CZS and can significantly impact their development and quality of life. The authors suggest that further research is needed to develop appropriate interventions to mitigate these issues.

Musculoskeletal pain and quality of life in mothers of children with microcephaly, due to congenital Zika virus syndrome.

PURPOSE: The purpose of this study is to observe the prevalence and intensity of musculoskeletal pain and the quality of life in mothers of children with microcephaly and also to compare the scores of the quality of life domains between mothers who had or did not have musculoskeletal pain. METHODS: This is a cross-sectional study that evaluated mothers of children with a clinical diagnosis of microcephaly, due to congenital Zika virus syndrome, in the state of Pernambuco, northeast region, Brazil. To assess musculoskeletal pain, the Nordic Questionnaire of Musculoskeletal Symptoms was used, pain intensity was assessed by the Visual Analogue Scale and quality of life by the SF-36 Questionnaire. RESULTS: Of the 63 mothers evaluated, 59 (93.7%) reported currently experiencing musculoskeletal pain. The lumbar spine was the body region with the highest prevalence of pain (77.8%), followed by the thoracic spine (57.1%) and cervical spine (50.8%). Pain intensity was higher in the lumbar spine (6.00 ± 0.47), thoracic spine (4.44 ± 0.52) and shoulders (3.81 ± 0.51). The domains that presented the lowest scores in the quality of life assessment were general health status (49.0 ± 3.19), emotional aspects (49.7 ± 5.88) and pain (49.7 ± 2.50). Mothers who had musculoskeletal pain had lower scores in all domains of quality of life assessment compared to mothers who did not have pain, demonstrating significant differences for functional capacity (P = 0.035), physical aspects (P = 0.047) and pain (P = 0.002). CONCLUSION: A high prevalence of musculoskeletal pain was observed in mothers of children with microcephaly, with a higher prevalence and intensity in the lumbar spine. The domains related to physical and emotional health presented the worst scores in the quality of life of the evaluated mothers and the presence of musculoskeletal pain reduced the quality of life of the mothers of children with microcephaly in this study.

Cell adhesion proteins in the cerebrospinal fluid of neonates prenatally exposed to Zika virus: A case-control study.

To compare cell adhesion molecules levels in cerebrospinal fluid (CSF) between Zika virus (ZIKV)-exposed neonates with/without microcephaly (cases) and controls, 16 neonates (cases), 8 (50%) with and 8 (50%) without microcephaly, who underwent lumbar puncture (LP) during the ZIKV epidemic (2015-2016) were included. All mothers reported ZIKV clinical symptoms during gestation, all neonates presented with congenital infection findings, and other congenital infections were ruled out. Fourteen control neonates underwent LP in the same laboratory (2017-2018). Five cell adhesion proteins were measured in the CSF using mass spectrometry. Neurexin-1 (3.50 [2.00-4.00] vs. 7.5 [5.00-10.25], P = 0.001), neurexin-3 (0.00 [0.00-0.00] vs. 3.00 [1.50-4.00], P = 0.001) and neural cell adhesion molecule 2 (NCAM2) (0.00 [0.00-0.75] vs. 1.00 [1.00-2.00], P = 0.001) were significantly lower in microcephalic and non-microcephalic cases than in controls. When these two sub-groups of prenatally ZIKA-exposed children were compared to controls separately, the same results were found. When cases with and without microcephaly were compared, no difference was found. Neurexin-3 (18.8% vs. 78.6%, P = 0.001) and NCAM2 (25.0% vs. 85.7%, P = 0.001) were less frequently found among the cases. A positive correlation was found between cephalic perimeter and levels of these two proteins. Neurexin-2 and neurexin-2b presented no significant differences. Levels of three cell adhesion proteins were significantly lower in CSF of neonates exposed to ZIKV before birth than in controls, irrespective of presence of congenital microcephaly. Moreover, the smaller the cephalic perimeter, the lower CSF cell adhesion protein levels. These findings suggest that low CSF levels of neurexin-1, neurexin-3 and NCAM2 may reflect the effects of ZIKV on foetal brain development.

Gross motor function in children with Congenital Zika Syndrome from Rio de Janeiro, Brazil.

Congenital Zika Syndrome (CZS) is characterized by many impairments especially in the central nervous system, potentially compromising neurodevelopment and causing significant morbidity in affected children. The aim was to assess gross motor function in children with CZS. This was a cross-sectional investigation nested within a prospective cohort study of children with CZS based in a Brazilian referral hospital in Rio de Janeiro. Between March/2017 and February/2018, we performed gross motor function assessments using the Gross Motor Function Classification (GMFCS) and the Gross Motor Function Measure (GMFM), estimating the mean and standard deviation of GMFM scores among GMFCS groups. The study sample included 72 children, with a median age of 13 months (7-25). Of these, 63 (87.5%) had severe motor impairment, 3 (4%) had moderate impairment, and 6 (8%) had mild impairment. The mean GMFM score for each group was respectively 11.6, 26.1, and 81.6, with statistically significant differences (p-value < 0.001). Severely affected children only achieved head control in the sitting posture when supported. Children with milder forms were able to develop walking skills.Conclusion: Most children with CZS have major motor disabilities and a poor prognosis. Better understanding of limitations and functionality in children with CZS can serve as a prognostic guide in their management. What is Known: • Severe motor impairment was present in 63 (87.5%) children with CZS. • The degree of neurological impairment was inversely associated with motor performance. What is New: • Microcephaly was more frequent among children with severe gross motor function impairment. • Children with CZS have major motor disabilities and a poor prognosis.

Fetal central nervous system anomalies according to RT-PCR and trimester of maternal infection with Zika virus: A prospective cohort study.

INTRODUCTION: In October 2015, an epidemic of Zika began in Colombia's geographic areas with a high population of mosquitoes of the genus Aedes. We aimed to describe the fetal brain ultrasound findings in pregnant women with active symptoms or a history of symptoms suggestive of Zika virus (ZIKV) infection. MATERIAL AND METHODS: Eligible pregnant women were tested with reverse transcriptase-polymerase chain reaction (RT-PCR) for ZIKV and followed prospectively using detailed anatomic ultrasound and transvaginal neurosonography to detect structural anomalies of the fetal central nervous system (CNS). RESULTS: A total of 115 symptomatic women with a positive ZIKV RT-PCR and 55 with a negative ZIKV RT-PCR were enrolled in the study; CNS compromise of the fetus occurred in 22% and 17%, respectively (p = 0.255). Callosal dysgenesis (14.5%) was the most frequent anomaly of the CNS, followed by microcephaly (13.6%) and neuronal migration disorders (8.3%). When symptomatic ZIKV RT-PCR-positive women were categorized by trimester of infection, CNS anomalies were present in 40% of first-trimester infections, compared with 21% and 7% in second- and third-trimester infections (p = 0.002). CNS anomalies were also more severe in first-trimester-infected fetuses than in second- and third-trimester-infected fetuses. The high prevalence of CNS anomalies in fetuses of symptomatic ZIKV RT-PCR negative women suggests a high rate of false-negative cases and an even higher prevalence of CNS anomalies than observed in this study. CONCLUSIONS: The prevalence of fetal CNS anomalies was higher than previously reported in the literature for both symptomatic RT-PCR-positive and -negative pregnant women. Corpus callosum anomalies, microcephaly, neuronal migration disorders, and brain parenchymal hyperechogenicities were the most frequent CNS anomalies detected. In addition, CNS anomalies were more frequent and severe in infected fetuses during the first trimester of pregnancy than during the second or third trimester.

Orofacial features in children with microcephaly associated with Zika virus: A scoping review.

OBJECTIVE: To analyze published scientific evidence about the most common orofacial disorders in children with microcephaly associated with ZIKV infection. METHODS: Through a scoping review, we respond to the search question was formulated: "What are the orofacial alterations in children with microcephaly associated with ZIKV?" It was performed a search in PubMed, EMBASE, Scopus, and Health Virtual Library. It was selected papers wrote in English, Portuguese, or Spanish. An evidence quality analysis was performed using the Agency for Healthcare Research and Quality classification. RESULTS: It was included 11 studies performed in the Brazilian Northeast region. The studies were carried out between 2018 and 2020. The main related alterations were delay in the tooth-eruption and deformation in the oral structures. CONCLUSION: The results observed in our work show moderate scientific evidence regarding the association of ZIKV with orofacial alterations in children with microcephaly due to the classifications of the quality of evidence of each one of the included studies. The main changes reported were in the chronology of tooth eruption, alteration in teeth, and oral structures.

Neurological and neuropsychological sequelae of Zika virus infection in children in León, Nicaragua.

Objectives: To describe the presence and persistence of neurological and neuropsychological sequelae among children with acquired Zika virus infection and assess whether those sequelae were more common in children infected with Zika virus compared to uninfected children. Methods: We conducted a prospective cohort study of children with and without Zika virus infection in León, Nicaragua, using a standard clinical assessment tool and questionnaire to collect data on symptoms at three visits, about 6 months apart, and a battery of standardized instruments to evaluate neurocognitive function, behavior, depression, and anxiety at the last two visits. Results: Sixty-two children were enrolled, with no significant differences in demographics by infection group. Children infected with Zika virus had a range of neurological symptoms, some of which persisted for 6 to 12 months; however, no consistent pattern of symptoms was observed. At baseline a small percentage of children infected with Zika virus had an abnormal finger-to-nose test (13%), cold touch response (13%), and vibration response (15%) versus 0% in the uninfected group. Neurocognitive deficits and behavioral problems were common in both groups, with no significant differences between the groups. Children infected with Zika virus had lower cognitive efficiency scores at the 6-month visit. Anxiety and depression were infrequent in both groups. Conclusions: Larger studies are needed to definitively investigate the relationship between Zika virus infection and neurological symptoms and neurocognitive problems, with adjustment for factors affecting cognition and behavior, including mood and sleep disorders, home learning environment, history of neuroinvasive infections, and detailed family history of neuropsychological problems.

[Evidence synthesis: guidelines for diagnosis and treatment of dengue, chikungunya, and zika in the Region of the AmericasSíntese de evidências: diretrizes para o diagnóstico e o tratamento da dengue, chikungunya e zika na Região das Américas]. / Síntesis de evidencia: Directrices para el diagnóstico y el tratamiento del dengue, el chikunguña y el zika en la Región de las Américas.

Introduction: Dengue, chikungunya, and Zika are viral diseases that pose a constant threat to public health. These three arboviruses can produce very similar clinical pictures, which represents a challenge to achieving an accurate clinical diagnosis and can lead to inadequate management and even fatal outcomes. Guidelines for the Clinical Diagnosis and Treatment of Dengue, Chikungunya, and Zika is part of the effort by the Pan American Health Organization and the countries of the Region of the Americas to prevent severe cases and death from these diseases, in a complex epidemiological context in which multiple factors favor transmission dynamics and lead to outbreaks and epidemics in the countries of the Region. Objectives: Synthesize the recommendations in the PAHO guidelines, published in 2022, in order to present appropriate diagnosis and treatment of these arboviruses, and to address aspects of implementation of the recommendations. Methods: The guidelines and their recommendations were synthesized. In addition, a systematic search was conducted in PubMed, Lilacs, Health Systems Evidence, Epistemonikos, and gray literature for studies done in the Region of the Americas, in order to identify barriers, facilitators, and implementation strategies. Process and outcome indicators for implementation of the recommendations were identified and formulated. Results: We present 12 recommendations applicable to adult and pediatric patients with suspected or confirmed dengue, chikungunya, or Zika, along with barriers, facilitators, and strategies for their implementation. Conclusions: The recommendations provide strategies for timely diagnosis and treatment of acute cases of dengue, chikungunya, and Zika, as well as considerations for implementation of the strategies.

Introdução: Dengue, chikungunya e zika são doenças virais que representam uma ameaça constante à saúde pública. As três arboviroses podem produzir um quadro clínico muito semelhante, o que representa um desafio para se obter um diagnóstico clínico adequado, podendo levar a um manejo inadequado e eventos fatais. O documento Diretrizes para o diagnóstico e o tratamento da dengue, chikungunya e zika faz parte do esforço da Organização Pan-Americana da Saúde e dos países da Região das Américas para prevenir casos graves e mortes por essas doenças, em meio a um complexo panorama epidemiológico onde a presença de múltiplos fatores favorece a dinâmica de transmissão e causa surtos e epidemias nos países da Região. Objetivos: Sintetizar as recomendações do documento mencionado, publicado pela OPAS em 2022, a fim de apresentar o diagnóstico e o tratamento adequados dessas arboviroses e abordar aspectos da implementação das recomendações. Métodos: Foi realizada uma síntese do documento e suas recomendações. Além disso, foi feita uma busca sistemática nas bases de dados PubMed, LILACS, Health Systems Evidence, Epistemonikos e na literatura cinzenta de estudos realizados na América Latina e no Caribe para identificar barreiras, facilitadores e estratégias de implementação. Foram identificados e construídos indicadores de processo e de resultado da implementação das recomendações. Resultados: Apresentam-se 12 recomendações aplicáveis a pacientes adultos e pediátricos com suspeita ou confirmação de dengue, chikungunya ou zika. Apresentam-se, ainda, barreiras, facilitadores e estratégias para sua implementação. Conclusões: As recomendações fornecem estratégias para o diagnóstico e o tratamento oportunos de casos agudos de dengue, chikungunya e zika, bem como considerações para sua implementação.

Defining dysmorphic facial features in congenital Zika syndrome.

Congenital Zika syndrome (CZS) constitutes a recently identified malformation caused by Zika virus infection during pregnancy. Limited data is available to date on the facial dysmorphic features of these patients. This study evaluated the facial dysmorphisms of children with CZS, compared with clinically healthy children, using clinical examination and standardized photographic images. Sixty-three children with CZS (9.70 ± 3.2 months-age), and 31 Controls (8.67 ± 6.2 months-age) joined the study. Seven out of 15 indices differed between groups: midfacial height (MFH)/horizontal facial reference (HFR) (p = .0003), interalar distance/HFR (p = .0027), nasal root depth/MFH (p = .0030), posterior nasal length/MFH (p = .0002), vertical position of the ear/MFH (p <.0001), ear length/MFH (p = .0005), chin height/total facial height (CH/TFH) (p <.0001). A CH/TFH of 0.229 showed 93.9% sensitivity and 80.6% specificity in diagnosing CZS. Children with CZS had broad, short faces, decreased intercanthal distance, short posterior nasal length, prominent nasal root, broad nasal wings, and high-set and long ears. Increased chin height index provided the most accurate diagnostic potential.

Systematic review: fetal death reporting and risk in Zika-affected pregnancies.

OBJECTIVES: Zika virus is linked to several adverse pregnancy outcomes. We assessed whether Zika infection during pregnancy is associated with increased risk of foetal death (miscarriage, stillbirth, abortion) and whether there is incomplete reporting of such deaths. METHODS: We searched PubMed, Embase, CINAHL, Web of Science and LILACS for studies reporting Zika-affected completed pregnancies (ending in foetal death or live birth), excluding studies whose aim required live birth. Studies 'allowed' foetal death if their populations were defined to encompass both live births and foetal deaths, regardless of whether deaths were actually found. Two authors independently extracted data and assessed study quality. Foetal death absolute and relative risks in Zika-affected vs. unaffected pregnancies were calculated. RESULTS: We found 108 reports including 24 699 completed, Zika-affected pregnancies. The median absolute risk in 37 studies of completed, Zika-affected pregnancies was 6.3% (IQR 3.2%, 10.6%) for foetal death and 5.9% (IQR 0%, 29.1%) for non-fatal adverse outcomes (e.g. microcephaly). More studies allowed non-fatal adverse outcomes (95%) than foetal death (58%). Of studies which allowed them, 94% found at least one foetal death. In 37% of reports, it was unknown whether foetal deaths were allowed. Only one study had sufficient data to estimate a foetal death relative risk (11.05, 95% CI 3.43, 35.55). CONCLUSIONS: Evidence was insufficient to determine whether foetal death risk is higher in Zika-affected pregnancies, but suggests quality of foetal death reporting should be improved, including stating whether foetal deaths were found, how many, and at what gestational ages, or justifying their exclusion.

OBJECTIFS: Le virus Zika est lié à plusieurs issues défavorables de la grossesse. Nous avons évalué si l'infection à Zika pendant la grossesse était associée à un risque accru de mort fœtale (fausse couche, mortinaissance, avortement) et s'il y avait une déclaration incomplète de ces décès. MÉTHODES: Nous avons recherché dans PubMed, EMBASE, Cinahl, Web of Science et LILACS des études rapportant des grossesses terminées touchées par le virus Zika (se terminant par une mort fœtale ou une naissance vivante), à l'exclusion des études dont l'objectif nécessitait une naissance vivante. Les études «autorisaient¼ la mort fœtale si leur population était définie comme englobant à la fois les naissances vivantes et les décès fœtaux, indépendamment du fait que des décès aient été effectivement constatés. Deux auteurs ont indépendamment extrait les données et évalué la qualité des études. Les risques absolus et relatifs de mortalité fœtale dans les grossesses affectées par Zika par rapport aux grossesses non affectées ont été calculés. RÉSULTATS: Nous avons trouvé 108 reports dont 24.699 grossesses terminées et affectées par le virus Zika. Le risque médian absolu dans 37 études portant sur des grossesses terminées affectées par Zika était de 6,3% (IQR 3,2%, 10,6%) pour la mort fœtale et de 5,9% (IQR 0%, 29,1%) pour les issues indésirables non mortelles (par exemple microcéphalie). Plus d'études ont «autorisé¼ des résultats indésirables non mortels (95%) que la mort fœtale (58%). Parmi les études qui les ont «autorisé¼, 94% ont trouvé au moins un décès fœtal. Dans 37% des rapports, il n'est pas indiqué si la mort fœtale avait été «autorisée¼. Une seule étude contenait des données suffisantes pour estimer un risque relatif de mort fœtale (11,05 ; IC95%: 3,43, 35,55). CONCLUSIONS: Les données étaient insuffisantes pour déterminer si le risque de mort fœtale est plus élevé dans les grossesses touchées par le virus Zika, mais suggèrent que la qualité des reports sur les décès fœtaux devrait être améliorée, notamment en indiquant si des décès fœtaux ont été constatés, combien et à quel âge gestationnel, ou justifiant leur exclusion.

Educational behaviors of pregnant women in the Bronx during Zika's International emerging epidemic: "First mom and then I'd Google. And then my doctor".

BACKGROUND: The objective of the study was to understand how pregnant women learned about Zika infection and to identify what sources of information were likely to influence them during their pregnancy. METHODS: We conducted 13 semi-structed interviews in English and Spanish with women receiving prenatal care who were tested for Zika virus infection. We analyzed the qualitative data using descriptive approach. RESULTS: Pregnant women in the Bronx learned about Zika from family, television, the internet and their doctor. Informational sources played different roles. Television, specifically Spanish language networks, was often the initial source of information. Women searched the internet for additional information about Zika. Later, they engaged in further discussions with their healthcare providers. CONCLUSIONS: Television played an important role in providing awareness about Zika to pregnant women in the Bronx, but that information was incomplete. The internet and healthcare providers were sources of more complete information and are likely the most influential. Efforts to educate pregnant women about emerging infectious diseases will benefit from using a variety of approaches including television messages that promote public awareness followed up by reliable information via the internet and healthcare providers.

Effect of Intensive Physiotherapy Training for Children With Congenital Zika Syndrome: A Retrospective Cohort Study.

OBJECTIVE: To investigate the effect of intensive physiotherapy training on the motor function of children with congenital Zika syndrome (CZS). DESIGN: A retrospective cohort study. SETTING: A support center for children with microcephaly. PARTICIPANTS: Children (N=7) aged 14 to 18 months old who were diagnosed with CZS and previously monitored more than 1 year. INTERVENTIONS: A 2-stage protocol repeated uninterruptedly for 1 year. In the first stage, the children were submitted to 1 hour of conventional physiotherapy and 1 hour of suit therapy 5 times a week for 4 weeks. The second stage consisted of 1 hour of suit therapy 3 times a week for 2 weeks. MAIN OUTCOME MEASURES: Gross motor function measure (GMFM) and body weight. RESULTS: Six evaluations were conducted approximately 3 months apart. An increase in the overall GMFM score was observed between the first and second (P=.046), first and third (P=.018), first and fourth (P=.018), first and fifth (P=.043), and first and sixth evaluations (P=.018). Differences in the scores of the individual GMFM dimensions were found only for dimension A (lying and rolling) between the first and fourth evaluations (P=.027) and for dimension B (sitting) between the first and third (P=.018), first and fourth (P=.046), and first and sixth evaluations (P=.027). No difference was found in body weight between the first and sixth evaluations (P=.009). During follow-up, only 1 child required hospitalization, and another had increased irritability. CONCLUSIONS: Children with CZS were able to perform 2 hours of motor physiotherapy daily with no serious complications, resulting in an increase or stabilization in GMFM scores.

Parental Stress in Primary Caregivers of Children with Evidence of Congenital Zika Virus Infection in Northeastern Brazil.

BACKGROUND: Despite the well-known role of parents as caregivers, few studies have addressed their health outcomes related to the Zika virus epidemic. METHODS: A cross-sectional study was carried out with 146 primary caregivers of children 15-26 months of age, with laboratory and/or clinical evidence of Zika infection between August and October 2017 in three Brazilian municipalities: João Pessoa and Campina Grande in the state of Paraíba and Fortaleza in the state of Ceará. Caregivers reported on their child's life and health, family circumstances and underwent screening for stress using the Parenting Stress Index-Short Form. Children were evaluated for developmental delays and clinical outcomes. Differences in the prevalence of risk factors between caregivers with high or clinically relevant stress and those with normal stress were evaluated. RESULTS: Of the 146 participants, 13% (n = 19) were classified as having high or clinically relevant stress, all of them mothers. The two risk factors significantly and independently associated with high levels of stress, compared with individuals with normal stress levels, were "reporting difficulty in covering basic expenses" (adjusted OR 3.6 (95% CI 1.1-11.8; p = 0.034)) and "having a child with sleep problems" (adjusted OR 10.4 (95% CI 1.3-81.7; p = 0.026)). CONCLUSIONS: Some factors seem to contribute significantly more than others to the level of stress experienced by caregivers of children with evidence of Zika virus congenital infection. Interventions and preventive strategies should also target caregivers, who in turn will be able to respond to the unique characteristics of their child.

Long-Term Outcomes of Infants with Congenital Zika Virus Infection in Ecuador: A Retrospective Longitudinal Study.

BACKGROUND: Few congenital Zika syndrome (CZS) cases have been notified in Ecuador and, to our knowledge, there are no significant published studies dealing with their clinical evolution. We present a detailed clinical characterization of 21 children with congenital Zika virus (ZIKV) infection born in Ecuador who were followed up until September 2019. METHODS: We did a retrospective longitudinal study of children attended by the infectious disease specialists of Francisco Icaza Bustamante Children's Hospital (Guayaquil) due to congenital ZIKV infection suspicion. The inclusion criteria consisted of laboratory confirmed diagnosis of congenital ZIKV infection. RESULTS: Sixteen of these 21 cases of congenital ZIKV infection showed clinical, neuroimaging and laboratory findings strongly suggestive of CZS and 5 children showed laboratory findings compatible with congenital ZIKV infection without congenital manifestations associated to CZS. All children with CZS showed neurodevelopmental delay, spasticity and hyperreflexia during follow-up, whereas the majority of them (14/15) experienced recurrent epileptic seizures and dysphagia (12/13). Two CZS cases died during follow-up. Visual evoked potential and hearing screening with acoustically evoked auditory brainstem response were abnormal in 50% and 37.5% of CZS cases, respectively. Congenital ZIKV infection without findings consistent with CZS at birth was not clinically relevant at 23 months of age in the five cases of our cohort. CONCLUSIONS: Severe neurodevelopmental delay, severe microcephaly, epileptic seizures and dysphagia were present at 2 years of age in most CZS cases of our cohort.

First aid intervention with mothers/caregivers of children affected by the Zika virus in Brazil.

BACKGROUND: Children with microcephaly associated with the Zika virus are more likely to develop choking and apnea, so it is necessary that mothers of this population receive first aid training to cope with emergency situations that their children may experience. OBJECTIVE: To understand how an educational first aid intervention with mothers/caregivers of Brazilian children with congenital Zika virus syndrome impacts their management of seizures and choking. METHOD: A qualitative study conducted in a philanthropic institution with ten mothers/caregivers of children with congenital Zika virus syndrome. Data were collected between August and November 2018 through four focus groups with two meetings for intervention/educational workshops in first aid on situations of choking and seizure. After one month, two more meetings were held to evaluate the effectiveness of this action performed at home. The empirical material was submitted to Content Analysis, and discussed in the light of Paulo Freire's Pedagogy of Autonomy. RESULTS: The mothers/caregivers performed ineffective and harmful behaviors to the children in situations of choking and seizure before the intervention. Thus, the intervention empowered these caregivers through an exchange of experiences which began to present discernment, autonomy, resolving capacity and confidence to act in these experienced situations. They also became knowledge disseminators for family members and neighbors. CONCLUSION: The educational intervention can have satisfactory results in training mothers/caregivers in first aid, highlighting the importance of this initiative to reduce the morbidity and mortality of children who experience choking and seizures.

Prevalence of Zika virus neutralizing antibodies in healthy adults in Vietnam during and after the Zika virus epidemic season: a longitudinal population-based survey.

BACKGROUND: Between 2016 and 2019, 265 cases of Zika virus (ZIKV) infection were reported in Vietnam, predominantly in southern Vietnam. In 2016, a case of ZIKV-associated microcephaly was confirmed in the Central Highlands, and several members of the infant's family were confirmed to be infected with ZIKV. The study aims to determine the level of immunity to ZIKV in the general population of the ZIKV epidemic region. METHODS: A total of 879 serum samples were collected from 801 participants between January 2017 and July 2018, during and after the ZIKV epidemic in Vietnam. The samples were tested for anti-ZIKV immunoglobulin M (IgM) and immunoglobulin G (IgG), and anti-dengue virus (DENV) IgG antibodies using enzyme-linked immunosorbent assays (ELISA). Plaque-reduction neutralization test (PRNT) for ZIKV was performed on all samples, and for DENV on the samples that ZIKV neutralizing antibody positive. RESULTS: A total of 83 (10.3%) participants had anti-ZIKV IgM. Of the 83, 6 were confirmed to be ZIKV antibodies positive using PRNT and anti-ZIKV IgG ELISA. Of the 718 participants who were anti-ZIKV IgM negative, a further 3 cases were confirmed as positive for antibodies against ZIKV. Of the 9 participants with ZIKV infection, 5 lived in the same village as the infant with ZIKV-associated microcephaly and the other 4 lived in 2 neighboring communes. Repeat samples were collected from the 83 ZIKV IgM positive participants 1.5 years after the first collection. No new cases of ZIKV infection were detected. In addition, 2 of 3 participants with anti-ZIKV NS1 IgG demonstrated a 4- to 8-fold increase in ZIKV neutralizing antibody titer. CONCLUSIONS: ZIKV was present in the area around Krong Buk, with the rate of ZIKV-specific antibodies was 1.1% in the community since at least 2016. While the low levels of circulation together with low seroprevalence suggests a limited outbreak in the region, the results also reflect on low levels of protective immunity to Zika within the population. These results provide a better understanding of the current ZIKV epidemic status in the region and demonstrate a need for implementation of more effective ZIKV infection control measures.

Congenital Zika Virus Infection: a Review with Emphasis on the Spectrum of Brain Abnormalities.

PURPOSE OF REVIEW: In 2016, the World Health Organization declared the Zika virus (ZIKV) outbreak a Public Health Emergency of International Concern following a cluster of associated neurological disorders and neonatal malformations. Our aim is to review the clinical and neuroimaging findings seen in congenital Zika syndrome. RECENT FINDINGS: ZIKV injures neural progenitor cells in the hippocampus, a brain region important for learning, memory, cognition, and emotion/stress response. Positron emission tomography has revealed global neuroinflammation in ZIKV infection in animal models. Congenital Zika syndrome is associated with a spectrum of brain abnormalities, including microcephaly, parenchymal calcifications, malformations of cortical development and defective neuronal migration, corpus callosum abnormalities, ventriculomegaly, and brainstem and cerebellar abnormalities.

Simultaneous diagnosis of dengue virus, Chikungunya virus, and Zika virus infection using a new point-of-care testing (POCT) system based on the loop-mediated isothermal amplification (LAMP) method.

INTRODUCTION: Dengue fever, Chikungunya fever, and Zika virus infection have similar symptoms and overlapping areas of endemicity and so cannot be distinguished clinically. Rapid diagnosis tests are available for each infection but each test covers only single target. There are PCR-based methods available that test for all three infections simultaneously, not applicable for in-vitro diagnostic use. The aim of this study was to evaluate the diagnostic accuracy of a new point-of-care testing (LAMP POCT) based on loop-mediated isothermal amplification method that tests for all three viruses simultaneously, using serum or urine samples, and takes about 45 min. METHODS: LAMP POCT was evaluated as the comparator on 67 individuals, of whom 56 had dengue, three had Chikungunya, two had Zika virus infection and six did not have any kind of these infections confirmed by RT-PCR. RESULTS: Among individuals with dengue, the sensitivity of LAMP POCT was 100% in samples collected in the first 3 days after illness onset, all three patients with Chikungunya were LAMP POCT positive, and both patients with Zika virus infection were LAMP POCT negative. There were no false-positive test results. CONCLUSIONS: LAMP POCT has potential utility as a point-of-care combination test for dengue and Chikungunya viruses, but further prospective studies are needed among individuals with Chikungunya virus and Zika virus infection, using serum and urine samples.

Health demands and care of children with congenital Zika syndrome and their mothers in a Brazilian state.

BACKGROUND: A Zika virus (ZIKV) infection outbreak occurred in Brazil in 2015, accompanied by a marked increase in the number of newborns presenting with microcephaly and other neurological disorders. This characteristic set of birth defects was later termed congenital Zika syndrome (CZS). The therapeutic itinerary of mothers and children infected by ZIKV can be determined by several factors, including the relationship established with existing healthcare services. Here, we aimed to describe and analyze the extent to which children with CZS, born from 2015 to 2018 in the state of Mato Grosso do Sul, Brazil, and their mothers were treated according to the guidelines established by the Brazilian Ministry of Health. METHODS: This was a descriptive cross-sectional study that considered all children (and respective mothers) with confirmed or suspected CZS born in Mato Grosso do Sul. Children and their mothers were identified based on all suspected or confirmed cases of congenital anomalies in Mato Grosso do Sul that were reported to the Registry of Public Health Events. We analyzed data on the epidemiological profile of mother-child pairs and the care received by them. Data were summarized using statistical descriptive analysis. RESULTS: We showed that most mothers were white women (57%) with low income. Among pregnant women, 73% had a diagnosis of fever caused by ZIKV infection at a primary health care institution (PHCI), but only 36% received the necessary information regarding the risk of CZS. Over a third (36%) of the mothers did not receive guidance about childcare follow-up and 73% did not receive guidance regarding the availability of social support after childbirth. Gaps in medical care were observed mainly in pregnant women treated at a PHCI. Specialized assistance for children was adequate in most cases. Psychosocial support was not made available to women throughout their therapeutic itineraries. CONCLUSIONS: Here, we identified gaps in the care of families and children with disabilities, which can have an important impact on their quality of life. Beyond protocols, practical interventions must cover all the needs that arise throughout the therapeutic itineraries not only of children but also of pregnant women and mothers.