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Objective: To assess the perceptions of mothers and health professionals about the dog-assisted therapy for children with congenital Zika Virus syndrome., Method: Qualitative, descriptive-exploratory research, with six mothers of children with congenital Zika Virus syndrome and six health professionals. Data were obtained at a Brazilian Specialized rehabilitation center in Paraíba, through semi-structured interviews, between February and October 2019. The empirical material was subjected to Inductive Thematic Analysis and interpreted using the Bronfenbrenner's Bioecological Theory., Results: Dog-Assisted Therapy allowed the enhancement of skills that were previously not performed by children, such as: spontaneous hand opening, head control, improved social interaction, reduction of seizure episodes and disruption of spasticity patterns., Final Considerations: Dog-Assisted Therapy was perceived as qualified, humanized and satisfactory support for the evolution of the neuropsychomotor development of children with congenital Zika Virus syndrome.

Purpose: To provide a detailed description of the development of the first case of congenital Zika syndrome (CZS) to be reported in the literature worldwide., Case Description: This report describes the case of a child with CZS monitored from pregnancy until four years of age, with periodic evaluations of head circumference, weight, height, motor function according to the Gross Motor Function Measure (GMFM-88), and the occurrence of comorbidities., Outcomes: The child's birth weight and length were normal (z-score = 1.1 and -1.95, respectively), while head circumference was below the expected value (z-score = -3.15). At 48 months, head circumference reached 43 cm (z-score = -4.48). During daily home physiotherapy sessions, the child achieved developmental milestones, standing unsupported at 17 months, with a GMFM-88x score of 137. With specialist therapy, the child walked independently at 36 months and a total GMFM-66 score of 214 was achieved by 42 months. In the four years of follow-up, the child was hospitalized four times for different reasons. No convulsive seizures occurred., Conclusions: Despite severe neurological impairment, the child's weight and height are adequate for age, with motor and cognitive function improving over the first four years of life.

Background: Paediatric neuroblastoma and brain tumours account for a third of all childhood cancer-related mortality. High-risk neuroblastoma is highly aggressive and survival is poor despite intensive multi-modal therapies with significant toxicity. Novel therapies are desperately needed. The Zika virus (ZIKV) can access the nervous system and there is growing interest in employing ZIKV as a potential therapy against paediatric nervous system tumours, including neuroblastoma., Methods: Here, we perform extensive data mining, integration and re-analysis of ZIKV infection datasets to highlight molecular mechanisms that may govern the oncolytic response in neuroblastoma cells. We collate infection data of multiple neuroblastoma cell lines by different ZIKV strains from a body of published literature to inform the susceptibility of neuroblastoma to the ZIKV oncolytic response. Integrating published transcriptomics, interaction proteomics, dependency factor and compound datasets we propose the involvement of multiple host systems during ZIKV infection., Results: Through data mining of published literature, we observed most paediatric neuroblastoma cell lines to be highly susceptible to ZIKV infection and propose the PRVABC59 ZIKV strain to be the most promising candidate for neuroblastoma oncolytic virotherapy. ZIKV induces TNF signalling, lipid metabolism, the Unfolded Protein Response (UPR), and downregulates cell cycle and DNA replication processes. ZIKV infection is dependent on sterol regulatory element binding protein (SREBP)-regulated lipid metabolism and three protein complexes; V-ATPase, ER Membrane Protein Complex (EMC) and mammalian translocon. We propose ZIKV non-structural protein 4B (NS4B) as a likely mediator of ZIKVs interaction with IRE1-mediated UPR, lipid metabolism and mammalian translocon., Conclusions: Our work provides a significant understanding of ZIKV infection in neuroblastoma cells, which will facilitate the progression of ZIKV-based oncolytic virotherapy through pre-clinical research and clinical trials., Competing Interests: Competing interests: Keith Okamoto declares a competing interest as an advisor of the biotechnology company Vyro. No other competing interests were disclosed., (Copyright: © 2024 Sherwood M et al.)

Here we introduce a first-in-class microRNA-sensitive oncolytic Zika virus (ZIKV) for virotherapy application against central nervous system (CNS) tumors. The described methodology produced two synthetic modified ZIKV strains that are safe in normal cells, including neural stem cells, while preserving brain tropism and oncolytic effects in tumor cells. The microRNA-sensitive ZIKV introduces genetic modifications in two different virus sites: first, in the established 3'UTR region, and secondly, in the ZIKV protein coding sequence, demonstrating for the first time that the miRNA inhibition systems can be functional outside the UTR RNA sites. The total tumor remission in mice bearing human CNS tumors, including metastatic tumor growth, after intraventricular and systemic modified ZIKV administration, confirms the promise of this virotherapy as a novel agent against brain tumors-highly deadly diseases in urgent need of effective advanced therapies., Competing Interests: Declaration of interests C.K. and O.K.O. are co-founders and equity holders of Vyro Bio Inc. From February 1, 2022, C.K. has been the Chief Scientific Officer of Vyro Bio Inc and inventor on patent applications filed by Vyro Bio Inc. related to the ZIKV genetic engineering. From February 1, 2022, O.K.O. has been a member of the Board of Directors of Vyro Bio Inc. From January 31, 2023, H.B. has been a member of the Scientific Advisory Boards of Vyro Bio Inc. From October 18, 2021, G.M.N. has been an employee of Vyro Bio Inc. From January 11, 2022, T.P.S. has been an employee of Vyro Bio Inc. From January 30, 2022, C.Longo has been an employee of Vyro Bio Inc. From February 22, 2022, P.H.M. has been an employee of Vyro Bio Inc. From March 21, 2022, C.Lima has been an employee of Vyro Bio Inc. From May 10, 2022, D.G.M. has been an employee of Vyro Bio Inc. From August 19, 2022, G.G.O.O. has been an employee of Vyro Bio Inc., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Congenital Zika syndrome (CZS) is a health condition that has affected the development of thousands of children in Brazil. Because it is a new condition, its understanding is an ongoing process. Therefore, it is important to know the rehabilitation interventions being delivered to improve the functioning of these children. We aimed to describe the practices of physical therapists (PTs) and occupational therapists (OTs) who provide follow-up care for children with CZS in Brazil., Methods: This cross-sectional study included PTs and OTs who assist children with CZS in Brazil. An online questionnaire was used to verify the participants' personal characteristics and professional work environment, as well as the rehabilitation programs they implemented in Brazil for children with CZS. Data were analyzed using descriptive statistics., Results: A total of 116 professionals (79 PT and 37 OT) who work mainly in public health services (81.9%) participated in the study. Of these, 24.1% plan interventions based on reading scientific articles, 66.4% did not report using the biopsychosocial model, 52.6% do not perform any assessments before starting an intervention, 31.9% use neurodevelopmental treatment, and 22.4% use sensorimotor stimulation interventions. The majority of the interventions are delivered 1 to 2 times a week, lasting up to 1 hour., Conclusions: Professional training and knowledge translation strategies are needed to implement evidence-based practices and improve the quality of rehabilitation programs for Brazilian children with CZS., (© Ayupe et al.)

Importance: The wide endemic range of mosquito-vectored flaviviruses-such as Zika virus and dengue virus serotypes 1-4-places hundreds of millions of people at risk of infection every year. Despite this, there are no widely available vaccines, and treatment of severe cases is limited to supportive care. An avenue toward development of more widely applicable vaccines and targeted therapies is the characterization of monoclonal antibodies that broadly neutralize all these viruses. Here, we measure how single amino acid mutations in viral envelope protein affect neutralizing antibodies with both broad and narrow specificities. We find that broadly neutralizing antibodies with potential as vaccine prototypes or biological therapeutics are quantifiably more difficult to escape than narrow, virus-specific neutralizing antibodies., Competing Interests: J.D.B. is on the scientific advisory boards of Apriori Bio, Invivyd, Aerium Therapeutics, and the Vaccine Company and receives royalty payments as an inventor on Fred Hutch licensed patents related to viral deep mutational scanning. J.B.S. is currently an employee of Universal Cells but performed all work included in this manuscript while an employee of Fred Hutch Cancer Center.

Objective: To know the perspective of health professionals working in specialized care regarding the assistance offered to children with Congenital Zika Virus Syndrome in the Health Care Network., Method: Qualitative study carried out in Campo Grande-MS through semi-structured interviews, between September and October 2020, with 12 professionals working in a reference service for people with physical and intellectual disabilities. Minayo's thematic analysis and the theoretical subsidies of the care model for chronic conditions were used for interpretation., Results: Assistance in the network is weakened by aspects related to access, monitoring and integration between different professionals/services. The potential involves the implementation of the referral and counter-referral system, the communication/integration between these services and the training of professionals., Final Considerations: The participants perceive that assistance is influenced by the availability of trained professionals to work in a network and the optimization of access and follow-up at different points of care.

Glioblastoma (GBM) is one of the most aggressive brain tumors and has a high recurrence rate, and effective treatment is urgently needed. GBM stem cells (GSCs) contribute to GBM recurrence as well as therapeutic resistance to radiation and chemotherapy. Several oncolytic viruses (OVs) have been developed and validated in clinical trials with favorable safety profiles and efficacy against GBM. Recently, Zika virus (ZIKV), a mosquito-borne flavivirus, was shown to preferentially target and kill GSCs and showed promising therapeutic effects in treating GBM in preclinical models. In this review, we summarize the known OVs for the treatment of GBM and highlight the major advantages and existing challenges for the clinical development of oncolytic ZIKV.

Gene therapy's entrance into clinical settings has made it an ever more attractive field of study for various diseases. However, relatively little progress has been made in targeting kidney diseases due to poor gene delivery efficiency in renal cells. The development of novel gene therapy vectors for medical intervention to treat kidney diseases is needed. In this study, we designed and produced a pseudotyped lentiviral vector with envelope glycoproteins of Zika virus (ZIKV), and evaluated its potential use in viral vector entry, neutralization assay, and gene delivery especially in the renal context. The lentiviral vector, simplified as ZIKV-E, is pseudotyped with Env/G-TC representing the transmembrane (TM) and cytoplasmic ( C Y) domains of Env replaced with the TM and CY domains of the glycoprotein (G) of the vesicular stomatitis virus. In vivo results show that ZIKV-E induced efficient transduction in tubular epithelial cells in mouse kidneys, demonstrating >100-fold higher expression of exogenous green fluorescent protein gene compared with that achieved by vesicular stomatitis virus G (VSV-G) protein pseudotyped lentiviral vector. The results also showed that the vector ZIKV-E transduced cells in a pH-independent manner and the transduction was inhibited by anti-ZIKV Env domain III antibodies. Results also show that ZIKV-E can be used as a surrogate for studies of ZIKV entry mechanisms and neutralization antibody assay. In all, this study successfully demonstrated a novel pseudotyped lentiviral vector ZIKV-E for inducing high transduction efficiency in renal tubular epithelial cells that could serve as a foundation for gene therapy for the treatment of inherited renal diseases in humans.

Aim: To evaluate the effects of neurodevelopmental treatment (NDT) in children with congenital Zika syndrome (CZS)., Methods: This prospective, interventional cohort study involved children with CZS undergoing follow-up at a specialist centre in northeastern Brazil. The duration of the proposed NDT protocol was 1 year, with 45-min sessions delivered one to five times weekly. Motor function, weight, height, head circumference and the incidence of comorbidities were evaluated in children before protocol initiation and then at 3, 6 and 12 months of treatment., Results: Thirty children were evaluated (age mean 30.1 ± 3 months). Motor function improved from baseline to 6 months (P = 0.001). No difference in weight and head circumference z-score (P = 0.51 and P = 0.29, respectively), but an increase in height z-score (P < 0.001) was observed over the evaluation period. There was a reduction in the incidence of upper respiratory tract infections, pneumonia and urinary tract infections over the follow-up period., Conclusions: NDT proved to be a viable treatment approach that can improve motor function and reduce the incidence of comorbidities in children with CZS, while having no harmful effects on their growth., (© 2022 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Zika virus (ZIKV), a re-emerging arbovirus, causes teratogenic effects on the fetus and normal nerve functions, resulting in harmful autoimmune responses, which call for the development of therapeutics against ZIKV infection. In this review, we introduce the pathogenesis of ZIKV infection and summarize the advancement in the development of therapeutics against ZIKV infection. It provides guidance for the development of effective therapeutics against ZIKV infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Ji, Jiang and Zhang.)

In 2015 the correlation between increasing numbers of cases of microcephaly and a zika virus outbreak led to recognition of an epidemic of congenital zika virus syndrome (CZVS), highlighting well-known weaknesses in health care measures. This article examines the network of virtual information available on health service provision for children suffering from CZVS in Rio de Janeiro. Using social media analysis, data on information about services and care institutions were collected from virtual sources using the Google search engine, so as to assess relations among these actors in 2018. The results revealed a fragmented network centred on virtual sources and secondary and tertiary public care services, with striking proximity of press sources to public services. Also salient was the isolation of private services and the lack of dialogue between philanthropic and public services. Moreover, the information offered was found to be insufficient and superficial, despite the gaps in the formal rehabilitation network. The evidence thus suggested the importance of a well-established health care service network and the necessity of fostering communication through virtual media.

The Zika epidemic brought to the fore the birth of children with unknown and unexpected needs that demand longitudinal follow-up, strengthening the bond, comprehensiveness and coordination of care in health, which are essential attributes of primary health care (PHC). This article aims to evaluate the orientation of PHC care, using the PCATool-Brasil. The data were collected between 2016 and 2019, by means of interviews with parents of children who were born in a public maternity hospital in Recife (state of Pernambuco) between October 2015 and February 2016, a critical period of the microcephaly outbreak, especially in the Northeast of Brazil. The parents of 109 children participated in the survey, 15.6% of which had a confirmed microcephaly diagnosis. The degree of affiliation and access was sufficient, but the aspects of coordination of care, longitudinality, comprehensiveness, family and community orientation were insufficient. In the context of congenital Zika syndrome, these attributes are essential for the care of children and families. The fostering of health from these domains depends on the orientation of the models of care and their management with state and federal investments. The defense of life depends on the ability to place life above all other rationalities.

Arboviral infections such as Chikungunya (CHIKV), Dengue (DENV) and Zika (ZIKV) are a major disease burden in tropical and sub-tropical countries, and there are no effective vaccinations or therapeutic drugs available at this time. Understanding the role of the T cell response is very important when designing effective vaccines. Currently, comprehensive identification of T cell epitopes during a DENV infection shows that CD8 and CD4 T cells and their specific phenotypes play protective and pathogenic roles. The protective role of CD8 T cells in DENV is carried out through the killing of infected cells and the production of proinflammatory cytokines, as CD4 T cells enhance B cell and CD8 T cell activities. A limited number of studies attempted to identify the involvement of T cells in CHIKV and ZIKV infection. The identification of human immunodominant ZIKV viral epitopes responsive to specific T cells is scarce, and none have been identified for CHIKV. In CHIKV infection, CD8 T cells are activated during the acute phase in the lymph nodes/blood, and CD4 T cells are activated during the chronic phase in the joints/muscles. Studies on the role of T cells in ZIKV-neuropathogenesis are limited and need to be explored. Many studies have shown the modulating actions of T cells due to cross-reactivity between DENV-ZIKV co-infections and have repeated heterologous/homologous DENV infection, which is an important factor to consider when developing an effective vaccine.

Background: During the 2015 Zika virus infection (ZVI) epidemic swiping through the Americas, few cases of ZVI with severe, potentially life-threatening thrombocytopenia were reported. Platelet transfusion, corticosteroids and intravenous immunoglobulins (IVIG) were in most cases applied as therapeutic options, predominantly with success. We present a comprehensive overview concerning the pathophysiology, treatment strategies and outcomes of patients with ZVI and severe thrombocytopenia (platelet count <50 × 10 9 /L)., Method: A literature search was performed., Results: Eleven case reports and case series with a total of 28 patients met the inclusion criteria; including five cases with lethal outcome. Therapeutic strategies, including platelet transfusion, administration of steroids and/or IVIG were described in 24 cases., Conclusions: Severe thrombocytopenia is a rare, but potentially life-threatening complication of ZVI. The principal pathophysiological mechanism appears to immune-induced thrombocytopenia. Due to a paucity of cases, the optimal treatment strategy remains to be elucidated., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Zika virus (ZIKV) is transmitted primarily through infected Aedes aegypti or Aedes albopictus mosquitoes. ZIKV infection during pregnancy was linked to adverse fetal/infant outcomes, including microcephaly, brain anomalies, ocular disorders, intrauterine growth restriction, and other congenital malformations. Human anti-Zika virus immunoglobulin (ZIKV-Ig) is being developed for prophylaxis of ZIKV in at-risk populations, including women of childbearing potential and pregnant women. A phase 1 single-center, double-blind, randomized, placebo-controlled study was conducted to assess the safety and pharmacokinetics (PK) of a single 50.0-mL ZIKV-Ig intravenous dose in healthy adult male or non-pregnant female subjects 18 to 55 years of age. Subjects received either ZIKV-Ig (n = 19) or saline placebo (n = 11). Safety was evaluated based on adverse events (AEs), laboratory test results, physical examinations, and vital signs. Overall, there were 11 subjects (36.7%) with treatment-related AEs including eight subjects (42.1%) in the ZIKV-Ig group and three subjects (27.3%) in the placebo group. Of the AEs considered treatment related, three subjects (15.8%) experienced headache (mild). There were no serious AEs, no deaths, and no discontinuations resulting from AEs. Overall, the safety profile of ZIKV-Ig in this study population of healthy adult subjects appeared to be safe and well tolerated. The results of the pharmacokinetic analysis determined that ZIKV-Ig had a maximum observed concentration of 182.3 U/mL (coefficient of variation, 21.3%), the time at which Cmax occurred of 2.3 hours ± 1.0 (SD), an area under the concentration-time curve0-∞ of 77,224 h × U/mL (coefficient of variation, 17.9%), and a half-life of 28.1 days, which is similar to other human-derived commercial Ig intravenous products.

Objective: to know health professionals' perceptions about care actions provided to children with Congenital Zika Virus Syndrome and their families., Methods: this is a qualitative study, carried out in a capital of center-western Brazil, based on the Unified Health System theoretical precepts. Data were collected in September and October 2020, through audio-recorded interviews with 12 health professionals from a specialized service and submitted to analysis of content, thematic modality., Results: the implementation of care actions with these children occurs through multidimensional assessment of children and their families, use of the Unique Therapeutic Project, therapeutic interventions for the development of children and the communication and exchange of interprofessional and family experiences, in addition to considering professionals' prior knowledge and their search for it., Final Considerations: children with CZS and their families need individualized, frequent, integrated and continuous care.

Purpose of Review: This article provides an overview of congenital infections affecting the central nervous system (CNS), discussing the epidemiology, clinical features, diagnostic tools, and preventive and treatment measures for a variety of pathogens with the potential to infect the developing fetal brain., Recent Findings: Contrary to popular belief, many congenital CNS infections are preventable and treatable. Treatment options exist for congenital cytomegalovirus, human immunodeficiency virus (HIV), herpes simplex virus, toxoplasmosis, and syphilis, although the efficacy of these treatments and the populations that may benefit from treatment are variable. Zika virus has recently emerged as a pathogen affecting the fetal brain, and new data suggest that the pathogenesis of Zika virus involves direct infection of neuronal progenitor cells leading to destruction of CNS tissue. The incidence of congenital syphilis has been increasing in the United States over the past decade as a direct result of new syphilis cases among adults and poor access to adequate maternal health care., Summary: Congenital CNS infections often result in significant neurologic morbidity in pediatric patients. Therefore, early identification of maternal illness and implementation of preventive measures are important in improving developmental outcomes and quality of life., (Copyright © 2021 American Academy of Neurology.)

The role of the emergency provider lies at the forefront of recognition and treatment of novel and re-emerging infectious diseases in children. Familiarity with disease presentations that might be considered rare, such as vaccine-preventable and non-endemic illnesses, is essential in identifying and controlling outbreaks. As we have seen thus far in the novel coronavirus pandemic, susceptibility, severity, transmission, and disease presentation can all have unique patterns in children. Emergency providers also have the potential to play a public health role by using lessons learned from the phenomena of vaccine hesitancy and refusal., Competing Interests: Disclosure C.C. Chen has no commercial or financial conflicts of interest. A. Whitehead has no commercial or financial conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: We have previously reported on neurogenic bladder dysfunction among Congenital Zika Vírus Syndrome (CZS) patients, but it is unknown how they will respond to treatment., Objective: To assess whether children with neurological lower urinary tract dysfunction and CZS will respond to Standard therapies., Methodology: A prospective observational cohort study of children with CZS referred for urological assessment between 2016 and 2020 to our quaternary center in Brazil. Urological protocol included clinical history, urinalysis and culture, renal and bladder ultrasonography and urodynamic study. Patients were treated based on findings from the first evaluation, with oxybutynin chloride for overactive bladder and low bladder compliance, clean intermittent catheterization for ineffective bladder emptying, or dual therapy when both were observed. Urological outcomes were evaluated between the first and second visits considering patient's adherence. Outcomes measured included clinical, imaging, and urodynamic variables. Data was analyzed using the IBM SPSS 22 software., Results: From the cohort of 90 patients, 56 completed the second urodynamic assessment and were included. One presented underactive bladder and 55 overactive bladder. Among these 55, 39 were adherent and 16 non-adherents to the prescribed treatment. Among the 39 adherents, 8 adhered regularly to oxybutynin and clean intermittent catheterization (CIC), 29 to oxybutynin alone, and two to catheterization alone. During follow-up, the number of patients with urinary tract infection and postvoid residual increased, but all other parameters had improved. Renal and bladder ultrasonography improved in 10, maximum bladder pressure decreased in 22 and maximum cystometric capacity and compliance increased in 14 patients. Sixteen patients did not adhere regularly to the prescribed treatment and although the number of patients with urinary tract infection reduced with antibiotic therapy, their bladder capacity and compliance did not improve during follow-up., Discussion: Ultrasonographic and urodynamic improvements were observed after 10.8 ± 7.5 months of treatment, including one patient with ureterohydronephrosis that resolved. Adherence to CIC remains a challenge and reflected in the number of patients presenting urinary tract infection and postvoid residual. The immediate clinical relevance is the major study strength, given the previously uncharacterized therapy options for this patient population. The number of patients remains one of the study limitations, reducing our ability to perform more advanced statistical analyses., Conclusion: Patients with Zika-related neurological lower urinary tract dysfunction may benefit from conventional therapies. Results confirmed ultrasonographic and urodynamic improvements after treatment, although not statically significant. Adherence to treatment, specifically to CIC, remains a challenge., Competing Interests: Conflicts of interest None., (Copyright © 2021 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background: The co-circulation of types of arbovirus in areas where they are endemic increased the risk of outbreaks and limited the diagnostic methods available. Here, we analyze the epidemiological profile of DENV, CHIKV and ZIKV at the serological and molecular level in patients with suspected infection with these arboviruses in the city of Juazeiro do Norte, Ceará, Brazil., Methods: In 2016, the Central Public Health Laboratory (LACEN) of Juazeiro do Norte received 182 plasma samples from patients who visited health facilities with symptoms compatible with arbovirus infection. The LACEN performed serological tests for detection of IgM/IgG to DENV and CHIKV. They then sent these samples to the Retrovirology Laboratory of the Federal University of São Paulo and Faculty of Medical of the ABC where molecular analyses to confirm the infection by DENV, ZIKV and CHIKV were performed. The prevalence of IgM/IgG antibodies and of infections confirmed by RT-qPCR were presented with 95% confidence interval., Results: In serologic analysis, 125 samples were positive for antibodies against CHIKV and all were positive for antibodies against DENV. A higher prevalence of IgG against CHIKV (63.20% with 95% CI: 45.76-70.56) than against DENV (95.05% with 95% CI: 78.09-98.12) was observed. When the samples were submitted to analysis by RT-qPCR, we observed the following prevalence: mono-infection by ZIKV of 19.23% (95% CI: 14.29-34.82) patients, mono-infection by CHIKV of 3.84% (95% CI: 2.01-5.44) and co-infection with ZIKV and CHIKV of 1.09% (95% CI: 0.89-4.56)., Conclusion: The serologic and molecular tests performed in this study were effective in analyzing the epidemiological profile of DENV, CHIKV and ZIKV in patients with suspected infection by these arboviruses in the city of Juazeiro do Norte, Ceará/Brazil., (© 2021. The Author(s).)

Objective: To identify scientific knowledge about the attention to health surveillance and development of Brazilian children under the age of three years involving the Congenital Zika virus (ZIKV) Syndrome., Data Sources: This is an integrative literature review of primary studies with Brazilian children under three years of age from 2015 to 2019. The searches were carried out in the databases Latin American and Caribbean Literature in Health Sciences (LILACS), US National Library of Medicine (PubMed), Cumulative Index to Nursing and Allied Health Literature (CINAHL), SCOPUS and Web of Science. It was carried out by crossing the keywords in English (child, child development and Zika virus) and in Portuguese (criança, desenvolvimento infantil e Zika vírus), with the combination of the Boolean operator "AND"., Data Synthesis: The knowledge produced is related to the specific health and development problems of children affected by the Congenital ZIKV Syndrome, with clinical characteristics, care demands, multiprofessional performance, health monitoring and surveillance needs., Conclusions: This integrative review synthesized scientific knowledge by adding aspects that reinforce the relevance of appropriate approaches to assess and care for children, linked to the engagement of caregivers, the need to document, evaluate and track the situations of children in early childhood and long-term, management coordination of care and its challenges in the context of primary health care.

Reports on tropical infections among kidney transplant (KT) recipients have increased in recent years, mainly because of the growing number of KT programs located in tropical and subtropical areas, and greater mobility or migration between different areas of the world. Endemic in emerging and developing regions, like most countries in Latin America, tropical infections are an important cause of morbidity and mortality in this population. Tropical infections in KT recipients may exhibit different pathways for acquisition compared with those in nonrecipients, such as transmission through a graft and reactivation of a latent infection triggered by immunosuppression. Clinical presentation may differ compared with that in immunocompetent patients, and there are also particularities in diagnostic aspects, treatment, and prognosis. KT patients must be screened for latent infections and immunized properly. Last, drug-drug interactions between immunosuppressive agents and drugs used to treat tropical infections are an additional challenge in KT patients. In this review, we summarize the management of tropical infections in KT patients.

Background: Pandemic events often trigger a surge of clinical trial activity aimed at rapidly evaluating therapeutic or preventative interventions. Ensuring rapid public access to the complete and unbiased trial record is particularly critical for pandemic research given the urgent associated public health needs. The World Health Organization (WHO) established standards requiring posting of results to a registry within 12 months of trial completion and publication in a peer reviewed journal within 24 months of completion, though compliance with these requirements among pandemic trials is unknown., Methods: This cross-sectional analysis characterizes availability of results in trial registries and publications among registered trials performed during the 2009 H1N1 influenza, 2014 Ebola, and 2016 Zika pandemics. We searched trial registries to identify clinical trials testing interventions related to these pandemics, and determined the time elapsed between trial completion and availability of results in the registry. We also performed a comprehensive search of MEDLINE via PubMed, Google Scholar, and EMBASE to identify corresponding peer reviewed publications. The primary outcome was the compliance with either of the WHO's established standards for sharing clinical trial results. Secondary outcomes included compliance with both standards, and assessing the time elapsed between trial completion and public availability of results., Results: Three hundred thirty-three trials met eligibility criteria, including 261 H1N1 influenza trials, 60 Ebola trials, and 12 Zika trials. Of these, 139 (42%) either had results available in the trial registry within 12 months of study completion or had results available in a peer-reviewed publication within 24 months. Five trials (2%) met both standards. No results were available in either a registry or publication for 59 trials (18%). Among trials with registered results, a median of 42 months (IQR 16-76 months) elapsed between trial completion and results posting. For published trials, the median elapsed time between completion and publication was 21 months (IQR 9-34 months). Results were available within 24 months of study completion in either the trial registry or a peer reviewed publication for 166 trials (50%)., Conclusions: Very few trials performed during prior pandemic events met established standards for the timely public dissemination of trial results.

Beginning in 2015, Brazil witnessed the births of thousands of children with neurological abnormalities linked to the Zika virus. Drawing on ethnographic fieldwork conducted between 2016 and 2018 with parents of children with congenital Zika syndrome in Salvador da Bahia, this article attends to how one of Brazil's most overused obstetric technologies-cesarean section-was mobilized to mitigate the uncertainties of Zika's reproductive consequences. I argue that during the epidemic, C-section constituted a form of what I call interventive care, in which others interceded on behalf of pregnant women to secure surgical delivery. In dialogue with scholarship problematizing autonomy in reproductive decision making, I show how my Bahian interlocutors understood such intercessions, and the C-sections themselves, as forms of appropriate, concerned care. I suggest, furthermore, that interventive care highlights the ways in which reproductive decisions are distributed among people rather than autonomous, particularly in contexts of heightened uncertainty., (© 2020 by the American Anthropological Association.)

Objective: To comprehend the daily rites of child-mothers with congenital Zika virus syndrome for the prevention of COVID-19 during the pandemic., Method: Study with a qualitative-exploratory approach, in the light on the comprehensive sociology of Michel Maffesoli, carried out in WhatsApp groups of associations of families of children with the syndrome. 44 mothers answered the online questionnaire between April and May 2020. Lexical and similarity analyzes were used through IRaMuTeQ., Results: Mothers encourage exercises for child development and help the children's school activities, watch television, sew, cook, support other mothers on social networks and find satisfaction in not meeting previously established schedules. To prevent COVID-19, mothers adopt physical distance, try to consume healthy foods and intensify hygiene measures., Final Considerations: Child-mothers experience, in physical distance being closer to their children and other mothers through the networks, and adopt preventive care to COVID-19, with care overload.

What Is Known and Objective: The sudden and extensive outbreak of coronavirus (SARS-CoV-2) has overshadowed another developing viral threat: the Zika flavivirus. Of particular concern is that pregnant women can pass Zika virus to the foetus, and there is a strong implication of an association between Zika virus infection and foetal microcephaly. Currently, there is no vaccine, and there is no cure., Methods: Published literature and Internet sources were searched for information related to Zika virus, its transmission, its clinical presentation and sequalae, prevention and implications (practice and regulatory) for healthcare providers. The identified English sources were reviewed, assessed and synthesized. Emphasis was placed on providing an overview of the problem, and identification of unmet needs and future directions., Results and Discussion: Zika virus poses a major challenge for healthcare providers, particularly in areas unaccustomed to it, since it is transmitted to humans by the vector Aedes aegypti mosquito. The outbreak impacts every healthcare provider, because every provider is required to report cases of Zika infection to their state or local health agencies--whether the infection is confirmed or merely suspected. Since the virus has become a worldwide crisis, healthcare providers will need to work across national boundaries and medical disciplines in order to educate patients about Zika symptoms and the mosquito vector. Until further information is known, infected patients (male and female) are being advised to avoid conceiving a child., What Is New and Conclusion: Until a vaccine is developed or effective treatment for Zika virus is discovered, healthcare providers must be AVP (aware, vigilant and proactive) in order to lessen the spread and impact of the implicated devastating birth defects (microcephaly) and other neurological disorders (eg Guillain-Barré Syndrome) of this infection. Unfortunately, many knowledge gaps exist. There is an urgent need for a reliable, inexpensive diagnostic test, an effective treatment and an approved and readily available vaccine., (© 2020 John Wiley & Sons Ltd.)

Due to migration and international travels, obstetricians are increasingly faced with a globalized obstetric setting and should adapt their daily clinical and diagnostic approach to the modifications of tropical and subtropical infections epidemiology. This paper is focused on five emerging infectious diseases, namely Chagas disease, HTLV-1 infection, malaria, schistosomiasis and Zika virus infection, having a high prevalence in migrant populations and which can affect international travelers. These diseases frequently pass unrecognized since they are characterized by few or no symptoms during pregnancy, however they may cause a relevant maternal, fetal and neonatal impact. Specific and reliable diagnostic and treatment options are available but are rarely used during routine obstetrical practice., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Prenatal infections have long been recognized as important, preventable causes of developmental disabilities. The list of pathogens that are recognized to have deleterious effects on fetal brain development continues to grow, most recently with the association between Zika virus (ZIKV) and microcephaly. To answer clinical questions in real time about the impact of a novel infection on developmental disabilities, an historical framework is key. The lessons learned from three historically important pathogens: rubella, cytomegalovirus, and ZIKV, and how these lessons are useful to approach emerging congenital infections are discussed in this review. Congenital infections are preventable causes of developmental disabilities and several public health approaches may be used to prevent prenatal infection. When they cannot be prevented, the sequelae of prenatal infection may be treatable. WHAT THIS PAPER ADDS: The list of prenatal infections associated with developmental disabilities continues to increase. Lessons learned from rubella, cytomegalovirus, and Zika virus have implications for new pathogens. Severity of illness in the mother does not correlate with severity of sequelae in the infant., (© 2020 Mac Keith Press.)

There are no approved flaviviral therapies and the development of vaccines against flaviruses has the potential of being undermined by antibody-dependent enhancement (ADE). The flavivirus nonstructural protein 1 (NS1) is a promising vaccine antigen with low ADE risk but has yet to be explored as a broad-spectrum therapeutic antibody target. Here, we provide the structural basis of NS1 antibody cross-reactivity through cocrystallization of the antibody 1G5.3 with NS1 proteins from dengue and Zika viruses. The 1G5.3 antibody blocks multi-flavivirus NS1-mediated cell permeability in disease-relevant cell lines, and therapeutic application of 1G5.3 reduces viremia and improves survival in dengue, Zika, and West Nile virus murine models. Finally, we demonstrate that 1G5.3 protection is independent of effector function, identifying the 1G5.3 epitope as a key site for broad-spectrum antiviral development., (Copyright © 2021, American Association for the Advancement of Science.)

Medically important flaviviruses cause diverse disease pathologies and collectively are responsible for a major global disease burden. A contributing factor to pathogenesis is secreted flavivirus nonstructural protein 1 (NS1). Despite demonstrated protection by NS1-specific antibodies against lethal flavivirus challenge, the structural and mechanistic basis remains unknown. Here, we present three crystal structures of full-length dengue virus NS1 complexed with a flavivirus-cross-reactive, NS1-specific monoclonal antibody, 2B7, at resolutions between 2.89 and 3.96 angstroms. These structures reveal a protective mechanism by which two domains of NS1 are antagonized simultaneously. The NS1 wing domain mediates cell binding, whereas the β-ladder triggers downstream events, both of which are required for dengue, Zika, and West Nile virus NS1-mediated endothelial dysfunction. These observations provide a mechanistic explanation for 2B7 protection against NS1-induced pathology and demonstrate the potential of one antibody to treat infections by multiple flaviviruses., (Copyright © 2021, American Association for the Advancement of Science.)

Guillain-Barré syndrome (GBS) is a rare, but potentially fatal, immune-mediated disease of the peripheral nerves and nerve roots that is usually triggered by infections. The incidence of GBS can therefore increase during outbreaks of infectious diseases, as was seen during the Zika virus epidemics in 2013 in French Polynesia and in 2015 in Latin America. Diagnosis and management of GBS can be complicated as its clinical presentation and disease course are heterogeneous, and no international clinical guidelines are currently available. To support clinicians, especially in the context of an outbreak, we have developed a globally applicable guideline for the diagnosis and management of GBS. The guideline is based on current literature and expert consensus, and has a ten-step structure to facilitate its use in clinical practice. We first provide an introduction to the diagnostic criteria, clinical variants and differential diagnoses of GBS. The ten steps then cover early recognition and diagnosis of GBS, admission to the intensive care unit, treatment indication and selection, monitoring and treatment of disease progression, prediction of clinical course and outcome, and management of complications and sequelae.

Importance: Acute anterior uveitis has been reported to be associated with Zika virus (ZIKV) infection in case reports and retrospective studies based on systemic clinical signs of ZIKV and positive serologic tests., Objective: To describe the ophthalmic findings associated with systemic ZIKV infection during the 2016 ZIKV outbreak in Guadeloupe in the French West Indies., Design, Setting, and Participants: This cohort study assessed adult patients with red eye and virologic or serologic confirmation of acute ZIKV infection who were admitted to the Pointe-à-Pitre University Hospital from January 1, 2016, to January 1, 2017, for a systematic ophthalmologic examination. All patients with anterior uveitis also underwent a complete uveitis workup to rule out other causes of uveitis. Patients were excluded from the study if they had active uveitis and a history of uveitis or positive serology for other infectious diseases including dengue fever virus and chikungunya virus. Data were analyzed from January 1, 2016, to January 1, 2017., Exposures: Patients with confirmed ZIKV infection underwent full ophthalmic examination at study inception and 3, 6, and 12 months., Main Outcomes and Measures: Description of the presenting ocular characteristics, management, and outcome., Results: Of 62 total patients with a red eye, 32 (51.6%) had no uveitis (mean [SD] age, 27.8 [3.7] years; 26 women [81.3%]) and 30 (48.4%) had anterior uveitis (mean [SD] age, 27.5 [3.8] years; 26 women [86.7%]), which was bilateral in all cases. Acute anterior uveitis was nongranulomatous and without synechiae, exhibiting mild anterior chamber reaction with small keratic precipitates. Ocular hypertension occurred in 25 patients (83.3%) with uveitis at presentation and persisted in 15 patients (50%) at 1 year despite antiglaucoma therapy and control of uveitis. Uveitis responded to topical steroids in all cases. Intraocular pressure was within normal limits for all patients without uveitis throughout the follow-up period., Conclusions and Relevance: Anterior uveitis was present in almost half of patients with a red eye and acute systemic ZIKV infection; the uveitis was usually bilateral and often associated with increased intraocular pressure. These results suggest that ophthalmic evaluation should be performed in patients with red eye and acute ZIKV infection to potentially detect and manage hypertensive anterior uveitis.

Understanding the pathophysiology, management, and prevention of emerging infectious diseases among pregnant women is imperative to achieve a successful response from the medical community. Ebola and Zika viruses represent infections with profound public health implications. In particular, Ebola virus is associated with high case fatality and pregnancy and neonatal loss rates, while Zika virus has been associated with multiple congenital anomalies; these features present critical clinical dilemmas for management of pregnant and reproductive aged women. The objective of this article is to summarize key background information and best practices for management of Ebola and Zika virus in pregnancy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives. To provide a comprehensive workflow to identify top influential health misinformation about Zika on Twitter in 2016, reconstruct information dissemination networks of retweeting, contrast mis- from real information on various metrics, and investigate how Zika misinformation proliferated on social media during the Zika epidemic. Methods. We systematically reviewed the top 5000 English-language Zika tweets, established an evidence-based definition of "misinformation," identified misinformation tweets, and matched a comparable group of real-information tweets. We developed an algorithm to reconstruct retweeting networks for 266 misinformation and 458 comparable real-information tweets. We computed and compared 9 network metrics characterizing network structure across various levels between the 2 groups. Results. There were statistically significant differences in all 9 network metrics between real and misinformation groups. Misinformation network structures were generally more sophisticated than those in the real-information group. There was substantial within-group variability, too. Conclusions. Dissemination networks of Zika misinformation differed substantially from real information on Twitter, indicating that misinformation utilized distinct dissemination mechanisms from real information. Our study will lead to a more holistic understanding of health misinformation challenges on social media.

In 2015-2016, the little known Zika virus (ZIKV) caused an epidemic, in which it became recognized as a unique human pathogen associated with a range of devastating congenital abnormalities collectively categorized as congenital Zika syndrome (CZS). In adults, the virus can trigger the autoimmune disorder Guillain-Barré syndrome (GBS), characterized by ascending paralysis. In February 2016, the World Health Organization (WHO) declared ZIKV to be a Public Health Emergency of International Concern. The global public health problem prompted academia, industry, and governments worldwide to initiate development of an effective vaccine to prevent another ZIKV epidemic that would put millions at risk. The development of reverse genetic systems for the study and manipulation of RNA viral genomes has revolutionized the field of virology, providing platforms for vaccine and antiviral development. In this review, we discuss the impact of reverse genetic systems on the rapid progress of ZIKV vaccines and antiviral therapeutics., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Congenital Zika virus (ZIKV) infection can cause lifelong medical and developmental conditions and management needs. There is limited information on the strengths and weaknesses of the systems of care for addressing ZIKV and other neurodevelopmental disabilities (NRD) in the United States (US) Affiliated Pacific Island Territories. Therefore, the purpose of the study was to assess the quality of the chronic illness systems of care for children with congenital ZIKV and other NRD in the US Pacific Island Territories. A cross-sectional study was conducted among health professionals from American Samoa, Guam, and Commonwealth of the Northern Mariana Islands. Participants completed an adapted version of the Assessment of Chronic Illness Care 3.5 (ACIC), which is based on the Chronic Care Model. The median Total Program Score was calculated, which ranged from limited support (0-2), basic support (3-5), reasonably good support (6-8), to fully developed support for care (9-11). Among the 17 health professionals who completed the survey, 47% were Guamanian/Chamorro, 24% were Samoan, 12% were Filipino, and 6% were Other Pacific Islanders. The median (25th percentile, 75th percentile [interquartile range]) Total Program Score was 5 (3, 6 [3]), indicating basic support for ZIKV and other NRD care for children. As more is learned about the full spectrum of clinical findings related to ZIKV, it is critical to continue to build an interdisciplinary maternal and child health workforce with the capacity and preparation to adequately address the special needs of children with ZIKV and other NRD., (©Copyright 2020 by University Health Partners of Hawai‘i (UHP Hawai‘i).)

Since 2015 Brazil has experienced the social repercussions of the Zika virus epidemic, thus raising a debate about: difficulties of diagnosis; healthcare access for children with Zika Congenital Syndrome (ZCS); the search for benefits by affected families; social and gender inequalities; and a discussion on reproductive rights, among others. The objective of this article is to analyse access to specialized health services for the care of children born with ZCS in three North-eastern states of Brazil. This is an exploratory cross-sectional study which analyses recorded cases of microcephaly at the municipal level between 2015 and 2017. Most of the cases of ZCS were concentrated on the Northeast coast. Rio Grande do Norte and Paraiba had the highest incidence of microcephaly in the study period. The states of Bahia, Paraiba and Rio Grande do Norte were selected for their high incidence of microcephaly due to the Zika Virus. Socio-territorial vulnerability was stratified using access to microcephaly diagnosis and treatment indicators. The specialized care network was mapped according to State Health Secretaries Protocols. A threshold radius of 100 km was stablished as the maximum distance from municipalities centroids to specialised health care for children with microcephaly. Prenatal coverage was satisfactory in most of the study area, although availability of ultrasound equipment was uneven within states and health regions. Western Bahia had the lowest coverage of ultrasound equipment and lacked health rehabilitation services. ZCS's specialized health services were spread out over large areas, some of which were outside the affected patients' home municipalities, so displacements were expensive and very time consuming, representing an extra burden for the affected families. This study is the first to address accessibility of children with microcephaly to specialised health care services and points to the urgent need to expand coverage of these services in Brazil, especially in the northeastern states, which are most affected by the epidemic., Competing Interests: The authors have declared that no competing interests exist.

Rooted in the dialogic public relations model, the aim of this paper was to analyze the way in which hospital organizations use Facebook to communicate and build relationships with their patients and followers. Using a content analysis of Facebook profiles, there is a reflection on how dialogic principles are applied in the management of Facebook by hospitals in Portugal. Special attention will be paid to communication regarding the Zika virus, which was of public interest at the time the empirical analysis was carried out. The study demonstrates that Portuguese hospitals are present on Facebook but do not use the social network dialogically or to communicate about topical themes of public interest.

Rapid spread of ZIKA virus (ZIKV) and its association with severe birth defects have raised worldwide concern. Recent studies have shown that ZIKV retains its infectivity and remains structurally stable at temperatures up to 40 °C, unlike dengue and other flaviviruses. In spite of recent cryo-EM structures that showed similar architecture of ZIKA and dengue virus (DENV) E protein shells, little is known that makes ZIKV so temperature insensitive. Here, we attempt to unravel the molecular basis of greater thermal stability of ZIKV over DENV2 by executing atomistic molecular dynamics (MD) simulations on the viral E protein shells at 37 °C. Our results suggest that ZIKA E protein shell retains its structural integrity through stronger inter-raft communications facilitated by a series of electrostatic and H-bonding interactions among multiple inter-raft residues. In comparison, the DENV2 E protein shell surface was loosly packed that exhibited holes at all 3-fold vertices, in close agreement with another EM structure solved at 37 °C. The residue-level information obtained from our study could pave way for designing small molecule inhibitors and specific antibodies to inhibit ZIKV E protein assembly and membrane fusion.

Humoral immunity is an essential component of the protective immune response to flavivirus infection. Typically, primary infection generates a robust neutralizing antibody response that mediates viral control and protection. It is becoming increasingly apparent that secondary infection with a closely related flavivirus strain can result in immunological cross-reactivity; however, the consequences to infection outcome remain controversial. Since its introduction to Brazil in 2015, Zika virus (ZIKV) has caused an epidemic of fetal congenital malformations within the Americas. Because ZIKV is a mosquito-borne flavivirus with a high degree of sequence and structural homology to Dengue virus (DENV), the role of immunological cross-reactivity in ZIKV and DENV infections has become a great concern. In this review, we highlight contemporary findings that implicate a role for flavivirus antibodies in mediating protection, contributing to pathogenesis, and seeding the human placenta., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: To describe the mechanisms of implementation of Zika virus diagnosis, prevention, and management guidelines in Colombia, and to characterize their influence on efforts to defend sexual and reproductive rights., Methods: A qualitative study performed between February and April 2018 in three municipalities in Colombia. We conducted 30 semistructured interviews and five focus groups with key informants who played a role during the epidemic. These included decision-makers, program coordinators, healthcare providers, pregnant women diagnosed with Zika virus, and members of affected communities., Results: We identified barriers to and facilitators for the implementation of the national Zika virus response plan. Barriers included a lack of coordination between vector control efforts and in the realms of sexual and reproductive rights. Facilitators included healthcare providers' response to the epidemic, the development of technical skills, and the establishment of coordination and referral networks across different institutions., Conclusion: A multidimensional approach that considers healthcare services, gender issues, and the environment is crucial. We highlight the epidemic's effects on women's sexual and reproductive rights, mainly related to inequalities in sexual and reproductive health such as the increased risk of sexually transmitted infections experienced by the poorest and most vulnerable women., (© 2020 World Health Organization; licensed by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Objective: To explore the perceptions and experiences of pregnant women in accessing healthcare services during the epidemic in Colombia during 2015-2016., Methods: A qualitative study using semistructured interviews was conducted in Villavicencio. Six women who had been diagnosed with Zika virus infection during their pregnancies and whose fetus had suspected microcephaly participated in the investigation. Grounded theory was used and thematic content analysis was made for each category identified., Results: Three main themes affecting access to healthcare services were identified: (1) women knew basic information about the virus, but it was limited; (2) access to services was delayed due to their lack of availability or limited supply in the municipality; and (3) most of the participants made out-of-pocket payments to get access to services that were not provided., Conclusions: Several gaps were identified in the provision of healthcare services to pregnant women during the Zika epidemic. Policy makers need to utilize the results from affected communities to develop and implement public policies that adapt and respond to their priorities and needs., (© 2020 World Health Organization; licensed by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Objectives: To analyze the initial healthcare response to the Zika virus in Piura, Peru, and assess the perceptions of midwives and nurses regarding their role in prevention of Zika virus and management of congenital Zika syndrome (CZS)., Methods: This ethnographic study used a rapid qualitative assessment design. Data were collected through a focus group with midwives and in-depth interviews with midwives (n=11) and nurses (n=5)., Results: The focus of the early Zika virus response in Piura was on pregnant women and vector control. Midwives received some training on Zika-related care during the early response. Nurses did not receive any Zika-specific training. Neither nurses nor midwives were trained in neonatal CZS surveillance. Midwives were clear about the value and feasibility of incorporating Zika virus surveillance in their daily work, however nurses were not. They referred to lack of training and appropriate tools as limitations. Confusion about Zika virus and CZS symptomatology and effects persisted in both groups. Concerns about their own personal risk influenced the ways they engaged with Zika virus prevention in the community., Conclusion: Long-term management of endemic Zika virus in Piura will require the engagement of both nurses and midwives as primary care providers., (© 2020 World Health Organization; licensed by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Human challenge trials (HCTs) deliberately infect participants in order to test vaccines and treatments in a controlled setting, rather than enrolling individuals with natural exposure to a disease. HCTs are therefore potentially powerful tools to prepare for future outbreaks of emerging infectious diseases. Yet when an infectious disease is emerging, there is often substantial risk and uncertainty about its complications, and few available interventions, making an HCT ethically complex. In light of the need to consider ethical issues proactively as a part of epidemic preparedness, we use the case of a Zika virus HCT to explore whether and when HCTs might be ethically justified to combat emerging infectious diseases. We conclude that emerging infectious diseases could be appropriate candidates for HCTs and we identify relevant considerations and provide a case example to illustrate when they might be ethically acceptable.

Guillain-Barré syndrome (GBS) is a rare, but potentially fatal, immune-mediated disease of the peripheral nerves and nerve roots that is usually triggered by infections. The incidence of GBS can therefore increase during outbreaks of infectious diseases, as was seen during the Zika virus epidemics in 2013 in French Polynesia and 2015 in Latin America. Diagnosis and management of GBS can be complicated as its clinical presentation and disease course are heterogeneous, and no international clinical guidelines are currently available. To support clinicians, especially in the context of an outbreak, we have developed a globally applicable guideline for the diagnosis and management of GBS. The guideline is based on current literature and expert consensus, and has a ten-step structure to facilitate its use in clinical practice. We first provide an introduction to the diagnostic criteria, clinical variants and differential diagnoses of GBS. The ten steps then cover early recognition and diagnosis of GBS, admission to the intensive care unit, treatment indication and selection, monitoring and treatment of disease progression, prediction of clinical course and outcome, and management of complications and sequelae.

The Congenital Zika Syndrome (CZS) epidemic took place in Brazil between 2015 and 2017 and led to the emergence of at least 3194 children born with CZS. We explored access to healthcare services and activities in the Unified Health Service (Sistema Único de Saúde: SUS) from the perspective of mothers of children with CZS and professionals in the Public Healthcare Network. We carried out a qualitative, exploratory study, using semi-structured interviews, in two Brazilian states-Pernambuco, which was the epicentre of the epidemic in Brazil, and Rio de Janeiro, where the epidemic was less intense. The mothers and health professionals reported that healthcare provision was insufficient and fragmented and there were problems with follow-up care. There was a lack of co-ordination and an absence of communication between the various specialized services and between different levels of the health system. We also noted a public-private mixture in access to healthcare services, resulting from a segmented system and related to inequality of access. High reported household expenditure is an expression of the phenomenon of underfunding of the public system. The challenges that mothers and health professionals reported exposes contradictions in the health system which, although universal, does not guarantee equitable and comprehensive care. Other gaps were revealed through the outbreak. The epidemic provided visibility regarding difficulties of access for other children with disabilities determined by other causes. It also made explicit the gender inequalities that had an impact on the lives of mothers and other female caregivers, as well as an absence of the provision of care for these groups. In the face of an epidemic, the Brazilian State reproduced old fashioned forms of action-activities related to the transmitting mosquito and to prevention with an emphasis on the individual and no action related to social determinants., (© The Author(s) 2019. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.)