Cases Of Congenital Zika Syndrome Research Articles

3D Head Shape Feature Analysis of Zika-Infected Children.

Congenital Zika syndrome (CZS) has been identified a constellation of congenital anomalies caused by Zika Virus (ZKV) infection during pregnancy. The infection with ZKV could lead to microcephaly of the fetus due to a severe decrease in brain volume and reduced brain growth. The preliminary screening of CZS is based on measuring head circumference; the diagnosis is made if this measurement is below two standard deviations below the mean. The analyses of the 3D head features of infected infants are limited. This study analyzed 3D head images of 35 ZKV-positive cases with an average age of 16.8 ± 2 months and 35 controls with an average age of 14.4 ± 5 months. This study focused on identifying potential diagnostic characteristics of CZS. The 3D head images were captured using a 3D imaging system. The averaged images of the two groups were aligned to illustrate the size and shape differences. There were significant differences in centroid size, head circumference (HC), head height (HH), and chin height (CH) between the two groups. We also identified significant differences in the indices of chin height/total facial height (CH/TFH) and head height/head circumference ratio (HH/HC) between the CZS and control cases. An HH/HC of 0.49 showed a sensitivity of 0.86 and a specificity of 0.74 in diagnosing CZS, which is more sensitive than the routinely used HC measurement. The index of HH/HC has potential to be used as the gold standard for the early screening for the detection of CZS cases.

High-Risk Areas for Congenital Zika Syndrome in Rio de Janeiro: Spatial Cluster Detection.

Brazil reported 18,282 suspected congenital Zika syndrome (CZS) cases up to 2018 and accounts for 61.4% of the total reported Zika cases in the Americas in the period. To detect high-risk areas for children with CZS in the city of Rio de Janeiro, we used cluster detection and thematic maps. We analyzed data using a Poisson model in Satscan 10.1.3 software. We also analyzed the records of children with CZS from 2015 to 2016 to describe the clinical and epidemiological maternal and child profile, as well as live births in 2016 and the social development index (SDI) by neighborhood. In 2015 and 2016, the incidence rates of CZS were 8.84 and 46.96 per 100,000 live births in the city, respectively. Severe congenital findings such as microcephaly and brain damage, osteoarticular impairment, ocular abnormalities, and hearing loss were observed in 47 children. The spatial distribution of CZS was concentrated in the north and west zones in heterogeneous neighborhoods. The neighborhoods with the highest occurrence of CZS cases were found to have the worst SDIs. Stascan detected three spatial clusters in the north zone, where the SDI is lower. The clusters presented high relative risks for CZS (7.86, 1.46, and 2.08), although they were not statistically significant. Our findings highlight a higher occurrence of CZS in areas with less favorable socioeconomic conditions.

Decidual production of interferon lambda in response to ZIKV persistence: Clinical evidence and in vitro modelling

Zika virus (ZIKV) infections during pregnancy can result in Congenital Zika Syndrome (CZS), a range of severe neurological outcomes in fetuses that primarily occur during early gestational stages possibly due to placental damage. Although some placentas can maintain ZIKV persistence for weeks or months after the initial infection and diagnosis, the impact of this viral persistence is still unknown. Here, we aimed to investigate the immunological repercussion of ZIKV persistence in term placentas. As such, term placentas from 64 pregnant women diagnosed with Zika in different gestational periods were analyzed by ZIKV RT-qPCR, examination of decidua and placental villous histopathology, and expression of inflammation-related genes and IFNL1-4. Subsequently, we explored primary cultures of term decidual Extravillous Trophoblasts (EVTs) and Term Chorionic Villi (TCV) explants, as in vitro models to access the immunological consequences of placental ZIKV infection. Placenta from CZS cases presented low IFNL1-4 expression, evidencing the critical protective role of theses cytokines in the clinical outcome. Term placentas cleared for ZIKV showed increased levels of IFNL1, 3, and 4, whether viral persistence was related with a proinflammatory profile. Conversely, upon ZIKV persistence placentas with decidual inflammation showed high IFNL1-4 levels. In vitro experiments showed that term EVTs are more permissive, and secreted higher levels of IFN-α2 and IFN-λ1 compared to TCV explants. The results suggest that, upon ZIKV persistence, the maternal-skewed decidua contributes to placental inflammatory and antiviral signature, through chronic deciduitis and IFNL upregulation. Although further studies are needed to elucidate the mechanisms underlying the decidual responses against ZIKV. Hence, this study presents unique insights and valuable in vitro models for evaluating the immunological landscape of placentas upon ZIKV persistence.

Analysis of congenital Zika syndrome clinicopathologic findings reported in the 8 years since the Brazilian outbreak

Aim: A Zika virus outbreak that began in Brazil, developed into an international public health emergency that extended from February 2015 until November 2016. Zika-infected pregnant women gave birth to a cohort of infants with congenital Zika syndrome (CZS) originally defined by severe microcephaly, retinal scarring, joint deformities, and hypertonia. This study examines the nature, extent, and severity of all CZS clinicopathologic findings described to date, compiled and analyzed by system. It reviews studies monitoring disease progression and proposing classification schemes for CZS stages. The teratogenic cellular and molecular mechanisms implicated in CZS pathogenesis are also discussed. Methods: A systematic review was conducted by literature search through WorldCat.org and ProQuest Central databases to identify studies on case series from the 2015–2016 CZS outbreak. Results: Twenty-six reports were included describing radiologic, ophthalmologic, audiologic, orthopedic, and laboratory test results in CZS cases including stillborns between 2016 and 2023. CZS neuropathology included prenatal and postnatal microcephaly, cerebral calcifications, quadriparesis, epilepsy, ventriculomegaly, reduced cerebral parenchyma, malformation of cortical development, and sleep electroencephalogram disturbances. Visual deficits were due to retinal and optic nerve lesions. Conductive and sensorineural hearing deficits were stable. Hypertonia, hypotonia, and spasticity with foot, hip, knee, and shoulder deformities resulted in arthrogryposis and restricted joint mobility. There was enlargement of immune organs, increased leukocyte counts, and cytokine dysregulation. Oro-craniofacial deformities affected the midface and caused dental eruption delay. Additional studies proposed that these systemic teratogenic effects could be attributable to transplacental Zika virus infection of multiple fetal progenitor cell lineages. Conclusions: The CZS-associated impairments in brain, eye, musculoskeletal, and immunologic functions caused disabilities that varied from moderate to severe, and significantly increased age-specific mortality rates. Further research is warranted to assess progression, classify stages, elucidate the precise molecular mechanisms mediating Zika teratogenicity, develop suitable therapeutic strategies, and design supportive social policies.

Serious Concern of Congenital Zika Syndrome (CZS) in India: A Narrative Review.

Congenital Zika syndrome (CZS) is a major concern in India and highlights the multifaceted challenges posed by the Zika virus (ZIKV). The alarming increase in CZS cases in India, a condition that has serious effects on both public health and newborns, has raised concerns. This review highlights the importance of raising concern and awareness and taking preventive measures by studying the epidemiology, clinical symptoms, and potential long-term consequences of CZS. The review also contributes to worldwide research and information sharing to improve the understanding and prevention of CZS. As India deals with the changing nature of CZS, this thorough review is an important tool for policymakers, health workers, and researchers to understand what is happening now, plan for what to do in the future, and work together as a team, using medical knowledge, community involvement, and study projects to protect newborns' health and reduce the public health impact of these syndromes.

Craniofacial and dental features in children aged 3-5years with congenital Zika syndrome.

Zika virus infection has been associated to congenital zika syndrome (CZS) in newborns and is characterized by microcephaly, central/axial motor and sensory dysfunction, dysphagia among other previously described severe health complications. CZS is usually diagnosed postpartum by evident/apparent neural development problems. Although there are some reports of craniofacial/dentition development in CZS, several clinical oral aspects are still unknown. This study describes some structural and functional characteristics of facial and cranial growth and deciduous dentition in CZS-affected children. Some cranial, facial and dental characteristics were determined in 14 children with CZS aged 3-5years and compared them against 12 apparently healthy children paired by age and gender. Fourteen CZS cases presented microcephaly, maxillary prognathism, altered facial thirds, asymmetric pupillary line, bruxism (p = 0.006), deep and anterior open bite and distal step decidual molar relationship (p = 0.031). CZS children cannot feed by themselves and most cannot walk and have not develop coordinated and intelligible language according to their chronological age. In contrast, controls presented normal skull features, have autonomous locomotion skills, speak intelligible language, feed by themselves, presented a harmonic intermaxillary relationship and have symmetrical facial thirds. Microcephaly, dysphagia, bruxism, mandibular retrognathia, altered facial proportions and malocclusion are the main craniofacial and oral features at CZS. The complications of CZS including those related with the face and the oral cavity are still being identified. This study revealed some cranial, facial and oral features in children affected by CSZ. Interdisciplinary rehabilitation protocols must address these syndromic features that could improve children and parents living conditions.

Causes of death in children with congenital Zika syndrome in Brazil, 2015 to 2018: A nationwide record linkage study.

Children with congenital Zika syndrome (CZS) have severe damage to the peripheral and central nervous system (CNS), greatly increasing the risk of death. However, there is no information on the sequence of the underlying, intermediate, immediate, and contributing causes of deaths among these children. The aims of this study are describe the sequence of events leading to death of children with CZS up to 36 months of age and their probability of dying from a given cause, 2015 to 2018. In a population-based study, we linked administrative data on live births, deaths, and cases of children with CZS from the SINASC (Live Birth Information System), the SIM (Mortality Information System), and the RESP (Public Health Event Records), respectively. Confirmed and probable cases of CZS were those that met the criteria established by the Brazilian Ministry of Health. The information on causes of death was collected from death certificates (DCs) using the World Health Organization (WHO) DC template. We estimated proportional mortality (PM%) among children with CZS and among children with non-Zika CNS congenital anomalies (CA) by 36 months of age and proportional mortality ratio by cause (PMRc). A total of 403 children with confirmed and probable CZS who died up to 36 months of age were included in the study; 81.9% were younger than 12 months of age. Multiple congenital malformations not classified elsewhere, and septicemia unspecified, with 18 (PM = 4.5%) and 17 (PM = 4.2%) deaths, respectively, were the most attested underlying causes of death. Unspecified septicemia (29 deaths and PM = 11.2%) and newborn respiratory failure (40 deaths and PM = 12.1%) were, respectively, the predominant intermediate and immediate causes of death. Fetuses and newborns affected by the mother's infectious and parasitic diseases, unspecified cerebral palsy, and unspecified severe protein-caloric malnutrition were the underlying causes with the greatest probability of death in children with CZS (PMRc from 10.0 to 17.0) when compared to the group born with non-Zika CNS anomalies. Among the intermediate and immediate causes of death, pneumonitis due to food or vomiting and unspecified seizures (PMRc = 9.5, each) and unspecified bronchopneumonia (PMRc = 5.0) were notable. As contributing causes, fetus and newborn affected by the mother's infectious and parasitic diseases (PMRc = 7.3), unspecified cerebral palsy, and newborn seizures (PMRc = 4.5, each) were more likely to lead to death in children with CZS than in the comparison group. The main limitations of this study were the use of a secondary database without additional clinical information and potential misclassification of cases and controls. The sequence of causes and circumstances involved in the deaths of the children with CZS highlights the greater vulnerability of these children to infectious and respiratory conditions compared to children with abnormalities of the CNS not related to Zika.

Microcephaly in South Brazil: Are cases of Congenital Zika Syndrome increasing in recent years?

Northeast Brazil was the first region to detect a significant increase in babies born with microcephaly associated with prenatal zika virus infection in 2015. Rio Grande do Sul (RS) state was less impacted due to the temperate climate preventing the spread of the vector. This study investigated the prevalence and etiology of congenital microcephaly in RS in two different periods. This cross-sectional descriptive study included all live births with congenital microcephaly in RS from 2015 to 2022. Cases were divided into two groups: P1 "outbreak" (2015-16); and P2 "endemic" (2017-22). There were 58 cases of microcephaly (3.8/10,000) in P1 and 148 (1.97/10,000) in P2. Congenital Zika Virus infection was the etiology in 5.2% (n=3) in P1 and 6.7% (n=10) in P2. In conclusion, although the ZIKV outbreak in Brazil has receded, RS remains an area of concern, with a possible slight increase of live births with microcephaly secondary to ZIKV prenatal infection relative to the number of cases due to congenital infections. The broader distribution of the vector Aedes aegypti with warmer temperatures in our state might be linked to the increase in recent years. This study can be an alert to other regions of temperate or subtropical climates.

Clinical and epidemiological characteristics of probable cases of congenital Zika syndrome and dengue antibody levels, Tuxtla Gutierrez, Chiapas, Mexico.

A case series of suspected cases of congenital Zika syndrome in a maternity hospital in Tuxtla Gutierrez, Chiapas, Mexico was assembled to assess why they were not reported and explore the hypothesis of dengue antibody dependent Zika disease. Clinical and imaging records, and interviews of a total of 13 of the cases revealed that only one of them was laboratory confirmed because appropriate specimens were not collected from the newborns as required by the case definition. 1) Microcephaly, 2) hypoplasia/hypogeneses, thinning or absence of brain structures, 3) multiple birth defects, 4) calcifications, and cysts, 5) meningocele/encephalocele and 6) hydrocephalus were found in 100%, 76.9%, 38.5%, 38.5%, 30.8%, and 23.1%, respectively. They clustered geographically, and 77% occurred within May 2016 to March 2017, and recalled or were told by a doctor they Zika fever. Using as referent a group of mothers who delivered normal newborns in the same hospital, and an 80% plaque reduction neutralization test for dengue virus 1 and 2, there was a four-fold increased risk of congenital Zika syndrome among those with dengue 1 antibody as compared to those with dengue 2 antibody (odds ratio = 3.6; 95% confidence interval: 0.7, 20.5), reaching only borderline statistical significance. The case definitions of congenital Zika syndrome used during the pandemic probably needed to be simpler to gain sensitivity.

The economic burden of congenital Zika Syndrome in Brazil: an overview at 5 years and 10 years

BackgroundThe aim of this paper is to estimate the economic burden of children with congenital Zika Syndrome (CZS) in Brazil over 5–10 years.MethodsWe conducted a modelling study based on data...

Population-based surveillance for congenital zika virus syndrome: a latent class analysis of recorded cases from 2015–2018

ObjectiveThis study aims to describe clinical findings and determine the medium-term survival of congenital zika syndrome (CZS) suspected cases.MethodsA retrospective cohort study using routine register-based linked data. It included all suspected cases of CZS born in Brazil from January 1, 2015, to December 31, 2018, and followed up from birth until death, 36 months, or December 31, 2018, whichever came first. Latent class analysis was used to cluster unconfirmed cases into classes with similar combinations of anthropometry at birth, imaging findings, maternally reported rash, region, and year of birth. Kaplan–Meier curves were plotted, and Cox proportional hazards models were fitted to determine mortality up to 36 months.ResultsWe followed 11,850 suspected cases of CZS, of which 28.3% were confirmed, 9.3% inconclusive and 62.4% unconfirmed. Confirmed cases had almost two times higher mortality when compared with unconfirmed cases. Among unconfirmed cases, we identified three distinct clusters with different mortality trajectories. The highest mortality risk was observed in those with abnormal imaging findings compatible with congenital infections (HR = 12.6; IC95%8.8–18.0) and other abnormalities (HR = 11.6; IC95%8.6–15.6) compared with those with normal imaging findings. The risk was high in those with severe microcephaly (HR = 8.2; IC95%6.4–10.6) and macrocephaly (HR = 6.6; IC95%4.5–9.7) compared with normal head size.ConclusionAbnormal imaging and head circumference appear to be the main drivers of the increased mortality among suspected cases of CZS. We suggest identifying children who are more likely to die and have a greater need to optimise interventions and resource allocation regardless of the final diagnoses.

Congenital Zika syndrome and living conditions in the largest city of northeastern Brazil

BackgroundThe Zika virus (ZIKV) epidemic hit Brazil in 2015 and resulted in a generation of children at risk of congenital Zika syndrome (CZS). The social vulnerability of certain segments of the population contributed to the disproportional occurrence of CZS in the Brazilian Northeast, the poorest region in the country. Living conditions are essential factors in understanding the social determination of CZS, which is embedded in a complex interaction between biological, environmental, and social factors. Salvador, the biggest city in the region, played a central role in the context of the epidemic and was a pioneer in reporting the ZIKV infection and registering a high number of cases of CZS. The aim of the study was identifying the incidence and spatial distribution pattern of children with CZS in the municipality of Salvador, according to living conditions.MethodsThis is an ecological study that uses the reported cases of ZIKV and CZS registered in the epidemiological surveillance database of the Municipal Secretariat of Health of the city of Salvador between August of 2015 and July of 2016. The neighborhoods formed the analysis units and the thematic maps were built based on the reported cases. Associations between CZS and living conditions were assessed using the Kernel ratio and a spatial autoregressive linear regression model.ResultsSeven hundred twenty-six live births were reported, of which 236 (32.5%) were confirmed for CZS. Despite the reports of ZIKV infection being widely distributed, the cases of CZS were concentrated in poor areas of the city. A positive spatial association was observed between living in places with poorer living conditions and births of children with CZS.ConclusionsThis study shows the role of living conditions in the occurrence of births of children with CZS and indicates the need for approaches that recognize the part played by social inequalities in determining CZS and in caring for the children affected.

Peculiarities of Zika Immunity and Vaccine Development: Lessons from Dengue and the Contribution from Controlled Human Infection Model.

The Zika virus (ZIKV) was first isolated from a rhesus macaque in the Zika forest of Uganda in 1947. Isolated cases were reported until 2007, when the first major outbreaks of Zika infection were reported from the Island of Yap in Micronesia and from French Polynesia in 2013. In 2015, ZIKV started to circulate in Latin America, and in 2016, ZIKV was considered by WHO to be a Public Health Emergency of International Concern due to cases of Congenital Zika Syndrome (CZS), a ZIKV-associated complication never observed before. After a peak of cases in 2016, the infection incidence dropped dramatically but still causes concern because of the associated microcephaly cases, especially in regions where the dengue virus (DENV) is endemic and co-circulates with ZIKV. A vaccine could be an important tool to mitigate CZS in endemic countries. However, the immunological relationship between ZIKV and other flaviviruses, especially DENV, and the low numbers of ZIKV infections are potential challenges for developing and testing a vaccine against ZIKV. Here, we discuss ZIKV vaccine development with the perspective of the immunological concerns implicated by DENV-ZIKV cross-reactivity and the use of a controlled human infection model (CHIM) as a tool to accelerate vaccine development.

Congenital Zika Syndrome Is Associated With Interferon Alfa Receptor 1.

Host factors that influence Congenital Zika Syndrome (CZS) outcome remain elusive. Interferons have been reported as the main antiviral factor in Zika and other flavivirus infections. Here, we accessed samples from 153 pregnant women (77 without and 76 with CZS) and 143 newborns (77 without and 66 with CZS) exposed to ZIKV conducted a case-control study to verify whether interferon alfa receptor 1 (IFNAR1) and interferon lambda 2 and 4 (IFNL2/4) single nucleotide polymorphisms (SNPs) contribute to CZS outcome, and characterized placenta gene expression profile at term. Newborns carrying CG/CC genotypes of rs2257167 in IFNAR1 presented higher risk of developing CZS (OR=3.41; IC=1.35-8.60; Pcorrected=0.032). No association between IFNL SNPs and CZS was observed. Placenta from CZS cases displayed lower levels of IFNL2 and ISG15 along with higher IFIT5. The rs2257167 CG/CC placentas also demonstrated high levels of IFIT5 and inflammation-related genes. We found CZS to be related with exacerbated type I IFN and insufficient type III IFN in placenta at term, forming an unbalanced response modulated by the IFNAR1 rs2257167 genotype. Despite of the low sample size se findings shed light on the host-pathogen interaction focusing on the genetically regulated type I/type III IFN axis that could lead to better management of Zika and other TORCH (Toxoplasma, Others, Rubella, Cytomegalovirus, Herpes) congenital infections.

Evaluation of bladder and bowel functions in children with microcephaly and congenital zika syndrome

Children with Congenital Zika Syndrome (CZS) present structural cortical changes that may compromise the integrity of their connections with urinary and digestive systems, causing bowel and bladder dysfunctions. To evaluate bladder and bowel dysfunction (BBD) in children with CZS. This is an observational cross-sectional study of a series of CZS cases. Urinary tracts were investigated using a bladder function protocol consisting of clinical history, detailed physical examination, laboratory tests, ultrasound of the lower and upper urinary tracts, and urodynamic evaluation. The bowel function protocol expanded anamnesis with questions related to signs and symptoms of functional disorders, Bristol scale, and ultrasound of the rectal ampoule. Forty children with CZS, aged between one and five years were included. The majority (80%) had bladder and bowel dysfunction (BBD), 12.5% had bladder dysfunction only, and 7.5% only bowel dysfunction. A reduced bladder capacity was confirmed in 36 patients (90%), while 15 (40%) presented postvoid residual greater than 20% of their cystometric capacity. Thirty-five patients (87.5%) presented four signs/symptoms of functional bowel disorders and the rectal ampoule ultrasound was >2.9cm in 21 (52.5%). Moreover, 19 (47.5%) presented urinary tract infection, while 5 (12.5%) developed pyelonephritis and required hospitalization. Renal ultrasound showed nephrolithiasis in three (7.5%), one (2.5%) presented horseshoe kidney, and a duplicated collecting system was found in three patients. Cryptorchidism was presented in eight (34%). Our study confirmed the presence of BBD in 80% of the children with CZS studied in this series. This is the first time that bowel dysfunction is confirmed in the settings of CZS. This recognition will facilitate early identification and appropriate therapies in an attempt to reduce complications. One limitation of the study is the absence of a control group. Due to the new aspects of CZS, it has been difficult to find a suitable group of patients with neurological disorders to compare and performing urodynamic studies in children without neurological or non-neurological voiding dysfunction is unethical. Appropriate control groups for future studies may be children with microcephaly due to other causes or older children with CZS who were not yet investigated or treated. Another limitation is the lack of a standard quantitative evaluation of bowel dysfunction in children with neurological disorders. Bladder and bowel dysfunction was confirmed in 80% of the children with CZS. This is a new Zika virus-associated neuromuscular disorder that needs to be further investigated.

Whole-exome sequencing reveals insights into genetic susceptibility to Congenital Zika Syndrome.

Congenital Zika Syndrome (CZS) is a critical illness with a wide range of severity caused by Zika virus (ZIKV) infection during pregnancy. Life-threatening neurodevelopmental dysfunctions are among the most common phenotypes observed in affected newborns. Risk factors that contribute to susceptibility and response to ZIKV infection may be related to the virus itself, the environment, and maternal genetic background. Nevertheless, the newborn’s genetic contribution to the critical illness is still not elucidated. Here, we aimed to identify possible genetic variants as well as relevant biological pathways that might be associated with CZS phenotypes. For this purpose, we performed a whole-exome sequencing in 40 children born to women with confirmed exposure to ZIKV during pregnancy. We investigated the occurrence of rare harmful single-nucleotide variants (SNVs) possibly associated with inborn errors in genes ontologically related to CZS phenotypes. Moreover, an exome-wide association analysis was also performed using a case-control design (29 CZS cases and 11 controls), for both common and rare variants. Five out of the 29 CZS patients harbored known pathogenic variants likely to contribute to mild to severe manifestations observed. Approximately, 30% of affected individuals carried at least one pathogenic or likely pathogenic SNV in genes candidates to play a role in CZS. Our common variant association analysis detected a suggestive protective effect of the rs2076469 in DISP3 gene (p-value: 1.39 x 10−5). The IL12RB2 gene (p-value: 2.18x10-11) also showed an unusual distribution of nonsynonymous rare SNVs in control samples. Finally, genes harboring harmful variants are involved in processes related to CZS phenotypes such as neurological development and immunity. Therefore, both rare and common variations may be likely to contribute as the underlying genetic cause of CZS susceptibility. The variations and pathways identified in this study may also have implications for the development of therapeutic strategies in the future.

Use of infectious disease surveillance reports to monitor the Zika virus epidemic in Latin America and the Caribbean from 2015 to 2017: strengths and deficiencies

ObjectivesTo summarise the occurrence of congenital Zika syndrome (CZS) in Latin America and the Caribbean from 2015 to 2017 using two outcome measures derived from infectious disease surveillance reports and...

Zika Syndrome: Assessing the fatality rate since the 2015 Zika outbreak

Background: Many studies have demonstrated a causal link between Zika virus (ZIKV) infection, microcephaly (MCP) and other congenital abnormalities (CA). We aimed to determine the perinatal case fatality rate in cases of Congenital Zika Syndrome (CZS) in the Rio Grande do Norte State (RN), a Brazilian Northeast State highly impacted by the Zika outbreak. Methods and materials: A cross-sectional study was conducted using data obtained through the State Health Department (SHD) for cases of MCP and CA in RN from April 2015 to December 31, 2017. Definition of perinatal period: commences at 22 completed weeks (154 days) of gestation and ends seven completed days after birth. Perinatal case fatality rate is defined as the number of deaths as a fraction of the number of sick persons with a specific disease (×100). Results: During the study period, there were 519 cases of MCP and others CA notified in RN, of which 150 were confirmed and 126 remain under investigation. The remaining 243 cases have been ruled out by presenting normal exams or due to presenting microcephaly by non-infectious causes. Of the total confirmed cases, 30.0% (45/150) died after birth or during pregnancy. 64.4% (29/45) of confirmed deaths had ZIKV infection during pregnancy and 4.4% (02/45) had a positive TORCH blood test. The deaths related to Zika were confirmed using either clinical/epidemiological/radiological (the presence of typical and indicative alterations of congenital ZIKV infection) or clinical/epidemiological/serological (RT-PCR and/or IgM/IgG antibodies against ZIKV). Eleven cases remain under investigation and five were ruled out. Conclusion: This study highlights a high rate of perinatal lethality (64.4%) in cases of CZS. Despite the growing number of CZS cases, the real incidence and prevalence might be higher due to the underreporting and lack of resources for confirmatory diagnostic tests (laboratory and imaging). Due to the high rate of lethality, our findings predict an increase in the infant mortality rate in areas endemic for arboviruses. Because the severe neurological complications caused by CZS, it is likely to pose a substantial burden on public spending on healthcare. This study may be used to better describe the CZS, its prognosis and natural history.

Plaque Reduction Neutralization Test (PRNT) in the Congenital Zika Syndrome: Positivity and Associations with Laboratory, Clinical, and Imaging Characteristics.

The short duration of viremia, low blood viral load, inaccessibility to timely specific diagnostic tests, and cross-reactions with other flaviviruses have hindered laboratory confirmation of Congenital Zika Syndrome (CZS). This study analyzes the positivity of the plaque reduction neutralization test (PRNT) in children with clinical or imaging characteristics of CZS and its association with laboratory, clinical, and imaging characteristics. The 94 clinical cases of CZS submitted to the ZIKV PRNT90 test were followed from 2016 to 2018. The mean age of children at PRNT90 collection was 22 ± 6 months Standard Deviation. The ZIKV PRNT90 was positive (titer ≥ 10) in 40 (42.5%) children. ZIKV PRNT90 positivity was associated with severe microcephaly in newborns (p = 0.016), lower head circumference z-score at birth (p = 0.043) and 24 months of age (p = 0.031), and severe reduction of the cerebral parenchyma volume (p = 0.021), expressing greater disease severity. Negative PRNT90 in children with characteristic signs of CZS may be due to false-negative results, indicating that the diagnosis of CZS should be primarily syndromic.

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

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. 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. 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. Severe neurodevelopmental delay, severe microcephaly, epileptic seizures and dysphagia were present at 2 years of age in most CZS cases of our cohort.