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The Zika virus (ZIKV) is a serious global public health crisis. A major control challenge is its multiple transmission modes. This paper aims to simulate the transmission patterns of ZIKV using a dynamic process-based epidemiological model written in ordinary differential equations, which incorporates the human-to-mosquito infection by bites and sewage, mosquito-to-human infection by bites, and human-to-human infection by sex. Mathematical analyses are carried out to calculate the basic reproduction number and backward bifurcation, and prove the existence and stability of the equilibria. The model is validated with infection data by applying it to the 2015–2016 ZIKV epidemic in Brazil. The results indicate that the reproduction number is estimated to be 2.13, in which the contributions by mosquito bite, sex and sewage account for 85.7%, 3.5% and 10.8%, respectively. This number and the morbidity rate are most sensitive to parameters related to mosquito ecology, rather than asymptomatic or human-to-human transmission. Multiple transmission routes and suitable temperature exacerbate ZIKV infection in Brazil, and the vast majority of human infection cases were prevented by the intervention implemented. These findings may provide new insights to improve the risk assessment of ZIKV infection. [ABSTRACT FROM AUTHOR]

Zika Virus (ZIKV) is a positive-strand RNA virus that can lead to Guillain-Barré syndrome or encephalitis in some individuals and hence presents a serious public health risk. Since the first outbreak of ZIKV in Brazil in 2015, no effective clinical inhibitors have been developed, making the development of effective ZIKV drugs an urgent issue that needs to be addressed. ZIKV belongs to the Flaviviridae family, and its structure includes three structural proteins, namely, capsular (C), premembrane (prM), and envelope (E) proteins, as well as seven nonstructural proteins, namely, NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5. To provide a reference for the development of future ZIKV drugs, this paper reviews the structure of the ZIKV based on recent literature reports, analyzes the potential therapeutic targets of various proteins, and proposes feasible drug design strategies. Additionally, this paper reviews and classifies the latest research progress on several protease inhibitors, such as E protein inhibitors, NS2BNS3 inhibitors, and NS5 inhibitors, so that researchers can quickly understand the current status of development and the interconnections among these inhibitors. [ABSTRACT FROM AUTHOR]

Brazil has earned the moniker "arbovirus hotspot", providing an ideal breeding ground for a multitude of arboviruses thriving in various zoonotic and urban cycles. As the planet warms and vectors expand their habitat range, a nuanced understanding of lesser-known arboviruses and the factors that could drive their emergence becomes imperative. Among these viruses is the Iguape virus (IGUV), a member of the Orthoflavivirus aroaense species, which was first isolated in 1979 from a sentinel mouse in the municipality of Iguape, within the Vale do Ribeira region of São Paulo State. While evidence suggests that IGUV circulates among birds, wild rodents, marsupials, bats, and domestic birds, there is no information available on its pathogenesis in both humans and animals. The existing literature on IGUV spans decades, is outdated, and is often challenging to access. In this review, we have curated information from the known literature, clarifying its elusive nature and investigating the factors that may influence its emergence. As an orthoflavivirus, IGUV poses a potential threat, which demands our attention and vigilance, considering the serious outbreaks that the Zika virus, another neglected orthoflavivirus, has unleashed in the recent past. [ABSTRACT FROM AUTHOR]

Objectives Regular quality-assured WGS with antimicrobial resistance (AMR) and epidemiological data of patients is imperative to elucidate the shifting gonorrhoea epidemiology, nationally and internationally. We describe the dynamics of the gonococcal population in 11 cities in Brazil between 2017 and 2020 and elucidate emerging and disappearing gonococcal lineages associated with AMR, compare to Brazilian WGS and AMR data from 2015 to 2016, and explain recent changes in gonococcal AMR and gonorrhoea epidemiology. Methods WGS was performed using Illumina NextSeq 550 and genomes of 623 gonococcal isolates were used for downstream analysis. Molecular typing and AMR determinants were obtained and links between genomic lineages and AMR (determined by agar dilution/Etest) examined. Results Azithromycin resistance (15.6%, 97/623) had substantially increased and was mainly explained by clonal expansions of strains with 23S rRNA C2611T (mostly NG-STAR CC124) and mtr mosaics (mostly NG-STAR CC63, MLST ST9363). Resistance to ceftriaxone and cefixime remained at the same levels as in 2015–16, i.e. at 0% and 0.2% (1/623), respectively. Regarding novel gonorrhoea treatments, no known zoliflodacin-resistance gyrB mutations or gepotidacin-resistance gyrA mutations were found. Genomic lineages and sublineages showed a phylogenomic shift from sublineage A5 to sublineages A1–A4, while isolates within lineage B remained diverse in Brazil. Conclusions Azithromycin resistance, mainly caused by 23S rRNA C2611T and mtrD mosaics/semi-mosaics, had substantially increased in Brazil. This mostly low-level azithromycin resistance may threaten the recommended ceftriaxone-azithromycin therapy, but the lack of ceftriaxone resistance is encouraging. Enhanced gonococcal AMR surveillance, including WGS, is imperative in Brazil and other Latin American and Caribbean countries. [ABSTRACT FROM AUTHOR]

Following the first report of zika virus in March 2015, Brazil experienced its largest sylvatic yellow fever outbreak between 2016 and 2019. This study aimed to investigate the circulation of yellow fever virus (YFV) in non-human primates (NHPs) and mosquitoes collected in urban parks and other metropolitan areas of midwest Brazil between 2017 and 2018. Whole blood samples from 80 NHPs, including 48 black-tailed marmosets (Mico melanurus) and 2332 mosquitoes from six different genera, were collected in the states of Mato Grosso (MT) and Mato Grosso do Sul (MS) and then tested for YFV by RT-qPCR. Additionally, 23 plasma samples of NHPs were tested for neutralizing antibodies for YFV by a plaque reduction neutralization test (PRNT). No YFV RNA or neutralizing antibodies for YFV were detected in NHPs and mosquitoes from MT and MS. The continuous monitoring of YFV circulation in different species of NHPs and vectors in urban areas is instrumental to quickly assess potentially unknown maintenance cycles of yellow fever at the human–animal interface in Brazil. [ABSTRACT FROM AUTHOR]

We generated 238 Zika virus (ZIKV) genomes from 135 persons in Brazil who had samples collected over 1 year to evaluate virus persistence. Phylogenetic inference clustered the genomes together with previously reported ZIKV strains from northern Brazil, showing that ZIKV has been remained relatively stable over time. Temporal phylogenetic analysis revealed limited within-host diversity among most ZIKV-persistent infected associated samples. However, we detected unusual virus temporal diversity from >5 persons, uncovering the existence of divergent genomes within the same patient. All those patients showed an increase in neutralizing antibody levels, followed by a decline at the convalescent phase of ZIKV infection. Of interest, in 3 of those patients, titers of neutralizing antibodies increased again after 6 months of ZIKV infection, concomitantly with real-time reverse transcription PCR re-positivity, supporting ZIKV reinfection events. Altogether, our findings provide evidence for the existence of ZIKV reinfection events. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) is a reemerging flavivirus that is primarily spread through bites from infected mosquitos. It was first discovered in 1947 in sentinel monkeys in Uganda and has since been the cause of several outbreaks, primarily in tropical and subtropical areas. Unlike earlier outbreaks, the 2015–2016 epidemic in Brazil was characterized by the emergence of neurovirulent strains of ZIKV strains that could be sexually and perinatally transmitted, leading to the Congenital Zika Syndrome (CZS) in newborns, and Guillain-Barre Syndrome (GBS) along with encephalitis and meningitis in adults. The immune response elicited by ZIKV infection is highly effective and characterized by the induction of both ZIKV-specific neutralizing antibodies and robust effector CD8+ T cell responses. However, the structural similarities between ZIKV and Dengue virus (DENV) lead to the induction of cross-reactive immune responses that could potentially enhance subsequent DENV infection, which imposes a constraint on the development of a highly efficacious ZIKV vaccine. The isolation and characterization of antibodies capable of cross-neutralizing both ZIKV and DENV along with cross-reactive CD8+ T cell responses suggest that vaccine immunogens can be designed to overcome these constraints. Here we review the structural characteristics of ZIKV along with the evidence of neuropathogenesis associated with ZIKV infection and the complex nature of the immune response that is elicited by ZIKV infection. [ABSTRACT FROM AUTHOR]

In 2015, the Zika virus (ZIKV) emerged in Brazil, leading to widespread outbreaks in Latin America. Following this, many countries in these regions reported a significant drop in the circulation of dengue virus (DENV), which resurged in 2018-2019. We examine age-specific incidence data to investigate changes in DENV epidemiology before and after the emergence of ZIKV. We observe that incidence of DENV was concentrated in younger individuals during resurgence compared to 2013-2015. This trend was more pronounced in Brazilian states that had experienced larger ZIKV outbreaks. Using a mathematical model, we show that ZIKV-induced cross-protection alone, often invoked to explain DENV decline across Latin America, cannot explain the observed age-shift without also assuming some form of disease enhancement. Our results suggest that a sudden accumulation of population-level immunity to ZIKV could suppress DENV and reduce the mean age of DENV incidence via both protective and disease-enhancing interactions. Dengue virus circulation was unusually low in Brazil in 2015-2018 following the emergence of Zika virus, but subsequently resurged causing large outbreaks with a lower mean age of infection. Here, the authors use mathematical modelling to investigate the links between dengue dynamics and prior Zika infection. [ABSTRACT FROM AUTHOR]

This article deals with the shared impressions of researchers and their experience in fieldwork in Northeast Brazil, within the project's scope: Health promotion in the context of the Zika epidemic: actors and scenarios in decision-making processes (FIOCRUZ/ZIKAlliance). Here, we seek to share field impressions of research on the Zika Virus in two municipalities located in different locations in the Northeast. We highlight the importance of the field notebook in qualitative research and reflect on the results of interviews conducted with women of reproductive age, pregnant women, health professionals, mothers and fathers of children affected by microcephaly, and self-employed workers. From the testimonies, it was possible to observe similarities, identifications, and estrangements between the research subjects and the researchers, constituting a vital thermometer for our perception of the field and the possibilities of producing scientific knowledge about the Zika epidemic in Northeastern Brazil. [ABSTRACT FROM AUTHOR]

In 2015, Brazil was the scene of an event that attracted global attention: the Zika virus epidemic. This pathogen arrived in the tropics, bringing with it something new to the Zika medical literature: the birth of children with changes in fetal development resulting from vertical transmission of the virus to fetuses. The phenomenon, which was classified as a health emergency, began to be widely studied and numerous studies were carried out with children born with changes associated with the Zika virus. This article analyzes a set of interviews conducted in 2022 with scientists who were directly involved in the response to this epidemic in the Metropolitan Region of Recife. As the research was mostly carried out with children, we reflect here on how this characteristic permeated the scientific work of the researchers involved. The main objective is to promote broader discussions about the act of carrying out research in terms of urgency, addressing questions about scientific relationships, especially between researchers and participants (Zika researchers and children diagnosed with the syndrome). A second objective is to think about how Child Anthropology can find fertile ground for dialogue with other areas that focus on children and childhood. [ABSTRACT FROM AUTHOR]

The progressive reappearance of Zika virus (ZIKV) infections since October 2013 and its circulation in >70 countries and territories (from French Polynesia to Brazil and other countries in the Americas, with sporadic spread in Europe and the East) has long been reported as a global public health emergency. ZIKV is a virus transmitted by arthropods (arboviruses), mainly by Aedes mosquitoes. ZIKV can also be transmitted to humans through mechanisms other than vector infection such as sexual intercourse, blood transfusions, and mother-to-child transmission. The latter mode of transmission can give rise to a severe clinical form called congenital Zika syndrome (CZS), which can result in spontaneous abortion or serious pathological alterations in the fetus such as microcephaly or neurological and orofacial anomalies. In this study, beside a succinct overview of the etiological, microbiological, and epidemiological aspects and modes of transmission of Zika virus infections, we have focused our attention on the pathogenetic and histopathological aspects in pregnancy and the pathogenetic and molecular mechanisms that can determine microcephaly, and consequently the clinical alterations, typical of the fetus and newborns, in a subject affected by CZS. [ABSTRACT FROM AUTHOR]

This study aimed to analyze the detection and duration of the Zika virus (ZIKV) in plasma, urine, saliva, sweat, rectal swabs, vaginal secretions, breast milk, and semen and to explore risk factors associated with prolonged viral persistence. A prospective cohort study of symptomatic patients and their household contacts was conducted in Brazil from July 2017 to June 2019. A total of 260 individuals (184 women and 76 men) with confirmed ZIKV infection were enrolled and followed up for 12 months. ZIKV RNA was present in all body fluid specimens and detectable for extended periods in urine, sweat, rectal swabs, and semen. The longest detection duration was found in semen, with high viral loads in the specimens. ZIKV RNA clearance was associated with several factors, including age, sex, education level, body mass index, non-purulent conjunctivitis, joint pain, and whether the participant had a history of yellow fever vaccination. The influence of each of these factors on the low or fast viral clearance varied according to the specific body fluid under investigation. Recurrent ZIKV detection events after total viral clearance were observed in the cohort. Our findings provide valuable insights into the persistence and potential recurrence of ZIKV infection, highlighting the need for continued monitoring and follow-up of individuals infected with ZIKV and for effective prevention measures to reduce the risk of transmission. [ABSTRACT FROM AUTHOR]

Oropharyngeal dysphagia (OD) is a swallowing disorder that involves difficulty in safely passing the food bolus from the oral cavity to the stomach. OD is a common problem in children with congenital Zika virus syndrome (CZS). In this case series, we describe the clinical and acoustic alterations of swallowing in children exposed to the Zika virus during pregnancy in a cohort from Amazonas, Brazil. From July 2019 to January 2020, 22 children were evaluated, 6 with microcephaly and 16 without microcephaly. The mean age among the participants was 35 months (±4.6 months). All children with microcephaly had alterations in oral motricity, mainly in the lips and cheeks. Other alterations were in vocal quality, hard palate, and soft palate. Half of the children with microcephaly showed changes in cervical auscultation during breast milk swallowing. In children without microcephaly, the most frequently observed alteration was in lip motricity, but alterations in auscultation during the swallowing of breast milk were not observed. Regarding swallowing food of a liquid and pasty consistency, the most frequent alterations were incomplete verbal closure, increased oral transit time, inadequacy in capturing the spoon, anterior labial leakage, and increased oral transit time. Although these events are more frequent in microcephalic children, they can also be seen in non-microcephalic children, which points to the need for an indistinct evaluation of children exposed in utero to ZIKV. [ABSTRACT FROM AUTHOR]

The municipality of Salvador, situated in Brazil, distinguished itself as the epicenter of the emergence of microcephaly related to congenital manifestations of Zika syndrome. Despite the anticipated significant developmental setbacks in these children, research has indicated a varied range of outcomes, with certain instances even reflecting minimal developmental delay. Our objective was to pinpoint determinants that could forecast developmental anomalies in children diagnosed with microcephaly associated with congenital Zika syndrome (CZS). Methodology: A forward-looking clinical and neurodevelopmental examination was conducted focusing on neonates diagnosed with microcephaly with CZS, birthed between September 2015 and April 2016 at the Hospital Geral Roberto Santos, in Salvador city. That infants were monitored up to their third year by a multiprofessional team. Child development was assessed using the composite Bayley III score. Undertaken by two blinded experts, cranial CT scan analysis was performed during the neonate period for the detection of brain abnormalities and to quantify ventricle enlargement, measured by Evans' index (EI). Results: Fifty newborns were evaluated with a median head circumference of 28 cm (interquartile range 27–31 cm). EI was associated with neurodevelopmental delay at three years and remained significant after adjustment for head circumference. A 0.1-point increase in EI was associated with a delay of 3.2 months in the receptive language (p = 0.016), 3.4 months in the expressive language (p = 0.016), 3.4 months in the cognitive (p = 0.016), 2.37 months in the gross motor (p = 0.026), and 3.1 months in the fine motor (p = 0.021) domains. Conclusions: EI predicted neurodevelopmental delay in all Bayley domains in children with microcephaly associated with CZS. [ABSTRACT FROM AUTHOR]

Since emerging in French Polynesia and Brazil in the 2010s, Zika virus (ZIKV) has been associated with fetal congenital disease. Previous studies have compared ancestral and epidemic ZIKV strains to identify strain differences that may contribute to vertical transmission and fetal disease. However, within-host diversity in ZIKV populations during vertical transmission has not been well studied. Here, we used the established anti-interferon treated Rag1-/- mouse model of ZIKV vertical transmission to compare genomic variation within ZIKV populations in matched placentas, fetal bodies, and fetal brains via RNASeq. At early stages of vertical transmission, the ZIKV populations in the matched placentas and fetal bodies were similar. Most ZIKV single nucleotide variants were present in both tissues, indicating little to no restriction in transmission of ZIKV variants from placenta to fetus. In contrast, at later stages of fetal infection there was a sharp reduction in ZIKV diversity in fetal bodies and fetal brains. All fetal brain ZIKV populations were comprised of one of two haplotypes, containing either a single variant or three variants together, as largely homogenous populations. In most cases, the dominant haplotype present in the fetal brain was also the dominant haplotype present in the matched fetal body. However, in two of ten fetal brains the dominant ZIKV haplotype was undetectable or present at low frequencies in the matched placenta and fetal body ZIKV populations, suggesting evidence of a strict selective bottleneck and possible selection for certain variants during neuroinvasion of ZIKV into fetal brains. Author summary: Zika virus (ZIKV) is known to cause congenital disease in humans through vertical transmission of the virus from mothers to fetuses during pregnancy. How the virus populations change during this process is currently not well understood. To evaluate differences in ZIKV populations during vertical transmission, we infected pregnant mice with ZIKV and sequenced the viral populations from matched placentas and fetal bodies at early stages of vertical transmission, and matched placentas, fetal bodies, and fetal brains at late stages of vertical transmission when the virus enters the fetal brain. We determined that there is little restriction of ZIKV diversity during transmission from the placenta to the fetus at early stages. However, there was a sharp decrease in ZIKV diversity in both fetal bodies and fetal brains at late stages. Two predominant viral variants were found across all fetal brains and most fetal bodies at late stages, suggesting there may be possible selection for certain variants during neuroinvasion of ZIKV into fetal brains. [ABSTRACT FROM AUTHOR]

Background: Brazil has a high prevalence of arboviruses, especially Dengue (DENV), Zika (ZKV), and Chikungunya (CHKV). Objectives: To study the risk of DENV, ZKV, and CHKV transmission by blood components in the haematopoietic stem cell transplantation (HSCT) population. Methods: Prospective cohort of HSCT recipients and donors performed at the Hospital das Clinicas da FMUSP, São Paulo‐Brazil. Patients were evaluated by serology and RT‐PCR for DENV, ZKV, and CHKV pre‐transplantation and once a week until neutrophil grafting. In positive cases (positive RT‐PCR and/or serology conversion), an investigation was carried out on the blood components that the patient received to evaluate the possibility of it being transfusion transmitted. Results: A total of 93 patients were included during the study period. The mean age was 52 years with a predominance of males (56.9%). We considered five (5.3%) DENV cases positive by seroconversion in our study. One patient had IgM seroconversion and the other four presented IgG seroconversion to DENV. In the investigation of the blood components, 145 individual samples were analysed. None of the investigated blood components showed a positive RT‐PCR. Conclusion: We observed a low prevalence of DENV, ZKV, and CHKV in HSCT donors and recipients by serology and RT‐PCR, and no case of blood transfusion transmission by RT‐PCR. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) is a flavivirus primarily transmitted by Aedes species mosquitoes, first discovered in Africa in 1947, that disseminated through Southeast Asia and the Pacific Islands in the 2000s. The first ZIKV infections in the Americas were identified in 2014, and infections exploded through populations in Brazil and other countries in 2015/16. ZIKV infection during pregnancy can cause severe brain and eye defects in offspring, and infection in adults has been associated with higher risks of Guillain-Barre syndrome. We initiated a study to describe the natural history of Zika (the disease) and the immune response to infection, for which some results have been reported. In this paper, we identify ZIKV-specific CD4+ and CD8+ T cell epitopes that induce responses during infection. Two screening approaches were utilized: an untargeted approach with overlapping peptide arrays spanning the entire viral genome, and a targeted approach utilizing peptides predicted to bind human MHC molecules. Immunoinformatic tools were used to identify conserved MHC class I supertype binders and promiscuous class II binding peptide clusters predicted to bind 9 common class II alleles. T cell responses were evaluated in overnight IFN-g ELISPOT assays. We found that MHC supertype binding predictions outperformed the bulk overlapping peptide approach. Diverse CD4+ T cell responses were observed in most ZIKV-infected participants, while responses to CD8+ T cell epitopes were more limited. Most individuals developed a robust T cell response against epitopes restricted to a single MHC class I supertype and only a single or few CD8+ T cell epitopes overall, suggesting a strong immunodominance phenomenon. Noteworthy is that many epitopes were commonly immunodominant across persons expressing the same class I supertype. Nearly all of the identified epitopes are unique to ZIKV and are not present in Dengue viruses. Collectively, we identified 31 immunogenic peptides restricted by the 6 major class I supertypes and 27 promiscuous class II epitopes. These sequences are highly relevant for design of T cell-targeted ZIKV vaccines and monitoring T cell responses to Zika virus infection and vaccination. [ABSTRACT FROM AUTHOR]

Microcephaly is a neurological condition characterized by anomalies in the growth of the cranial circumference. This study aims to examine the association between sociodemographic and clinical variables and the occurrence of secondary microcephaly in newborns in Brazil. It also aims to investigate the association between this congenital anomaly and teratogenic infections. This research adopts an observational approach with an ecological, descriptive, and analytical design. The sample includes infants aged ≤28 days and registered in the country's Live Births Information System from January 2015 to December 2021. Newborns were categorized into G1, consisting of newborns with one of the three infections (Zika, toxoplasmosis, or syphilis), and G2, consisting of newborns with two of the three infections. A total of 1513 samples were analyzed and divided into two groups: one infection (syphilis n = 423; toxoplasmosis n = 295; or Zika n = 739) and two infections (n = 56). The northeastern region of Brazil has the highest prevalence of microcephaly. Regarding the population profile, the Zika virus infection is more common among white mothers, while the syphilis infection is more common among black mothers. Among newborns with microcephaly, boys have a lower prevalence of toxoplasmosis infection, while girls have a lower prevalence of Zika virus infection. This study provides pertinent information on each infection and contributes to the epidemiologic understanding of the association between teratogenic infections and microcephaly. [ABSTRACT FROM AUTHOR]

Since its detection in 2015 in Brazil, Zika virus (ZIKV) has remained in the spotlight of international public health and research as an emerging arboviral pathogen. In addition to single infection, ZIKV may occur in co-infection with dengue (DENV) and chikungunya (CHIKV) viruses, with whom ZIKV shares geographic distribution and the mosquito Aedes aegypti as a vector. The main mosquito immune response against arboviruses is RNA interference (RNAi). It is unknown whether or not the dynamics of the RNAi response differ between single arboviral infections and co-infections. In this study, we investigated the interaction of ZIKV and DENV, as well as ZIKV and CHIKV co-infections with the RNAi response in Ae. aegypti. Using small RNA sequencing, we found that the efficiency of small RNA production against ZIKV -a hallmark of antiviral RNAi—was mostly similar when comparing single and co-infections with either DENV or CHIKV. Silencing of key antiviral RNAi proteins, showed no change in effect on ZIKV replication when the cell is co-infected with ZIKV and DENV or CHIKV. Interestingly, we observed a negative effect on ZIKV replication during CHIKV co-infection in the context of Ago2-knockout cells, though his effect was absent during DENV co-infection. Overall, this study provides evidence that ZIKV single or co-infections with CHIKV or DENV are equally controlled by RNAi responses. Thus, Ae. aegypti mosquitoes and derived cells support co-infections of ZIKV with either CHIKV or DENV to a similar level than single infections, as long as the RNAi response is functional. Author summary: Zika virus (ZIKV) is a mosquito-borne human-pathogenic arbovirus of the Flaviviridae family, genus Flavivirus. Other arboviruses, including dengue (DENV) or chikungunya (CHIKV) virus, can occur in the same regions as ZIKV and are also transmitted by Aedes aegypti. Notably, it has been shown that these viruses can co-infect this mosquito, andco-transmission occurs. Such processes may add to the serious public health issues already linked to those pathogens. Arbovirus infections in mosquitoes are controlled through an immune response called RNA interference (RNAi). It is however unknown whether immune responses changs when a mosquito is exposed to a co-infection of ZIKV with either DENV or CHIKV. In this study, we provide evidence that ZIKV co-infections with CHIKV or DENV are similarly well controlled by RNAi as single infections. These findings give new insights into the dynamics of arboviral co-infections in mosquito vectors that increase our understanding of co-infection scenarios during arbovirus outbreaks. [ABSTRACT FROM AUTHOR]

Background: In 2015, an unprecedented epidemic of microcephaly occurred in Brazil. Preliminary observations suggested the involvement of cofactors in the etiopathology of Zika virus-associated microcephaly. Bovine viral diarrhea virus (BVDV) was identified in fetal samples with microcephaly, originating in the state of Paraíba, and two virus sequences, obtained from the amniotic fluid collected from mothers with babies affected by Zika and microcephaly, have been characterized as two different species of BVDV, types 1 and 2. Aim: The involvement of BVDV as a co-factor in the etiopathogenesis of Zika virus-associated microcephaly was explored. Methods: A serological screening using an ELISA test was undertaken to detect antibodies against BVDV among patients referred to the Central Laboratory of Natal, Rio Grande do Norte, encompassing microcephalic babies and their mothers, mothers and pregnants not associated with microcephaly and general patients as a control group. Results: Two samples were positive out of 382 tested (0.52%). No specific relation with birth defects could be established. Conclusions: The study might suggest serological evidence of BVDV in humans. Further studies and the application of improved diagnostic tests adapted to humans are necessary to clarify the epidemiological extent and impact of BVDV. [ABSTRACT FROM AUTHOR]

The state of Ceará, in the Northeast Region of Brazil, presents the simultaneous circulation of Zika (ZIKV), dengue (DENV) and chikungunya (CHIKV) viruses. In 2017 there were a high number of cases of these three arboviruses, especially CHIKV. Here, we detected the presence of arboviruses ZIKV, DENV and CHIKV and their coinfections in women in endemic regions of the city of Fortaleza, Ceará in a post-Zika epidemic year. Sociodemographic and environmental characteristics associated with arbovirus positivity were also analyzed. Women (n = 1289) between 15 and 39 years old were included. RT-qPCR was performed for virus detection and IgM antibody positivity was also analyzed. One hundred and six (8.3%) participants were positive for one or more arboviruses. Monoinfections (76; 5.9%) were distributed between 22 (1.7%) for ZIKV, 39 (3.1%) for DENV and 15 (1.2%) for CHIKV. Co-infections were detected in 30 (2.3%) of the positive participants and one case with triple infection was found. IgM positivity was found in 2.4% of ZIKV RT-qPCR, 9.6% of DENV and 16.3% of CHIKV. RT-qPCR positivity for arboviruses was associated with low socioeconomic class and presence of a water box sealing in the household. A higher positivity to the three viruses occurred in the month with the lowest wind velocity, which was also preceded by the highest peak of rain and humidity. We identified the simultaneous circulation and co-infection of ZIKV, DENV and CHIKV in Fortaleza in a post-Zika epidemic year. We also highlight the need for continuous epidemiological surveillance combined with molecular diagnostic tools. [ABSTRACT FROM AUTHOR]

Introduction: Zika virus (ZIKV) caused an outbreak in Brazil, in 2015, being associated to microcephaly. ZIKV has a strong neurotropism leading to death of infected cells in different brain regions, including the hippocampus, a major site for neurogenesis. The neuronal populations of the brain are affected differently by ZIKV from Asian and African ancestral lineages. However, it remains to be investigated whether subtle variations in the ZIKV genome can impact hippocampus infection dynamics and host response. Objective: This study evaluated how two Brazilian ZIKV isolates, PE243 and SPH2015, that differ in two specific missense amino acid substitutions, one in the NS1 protein and the other in the NS4A protein, affect the hippocampal phenotype and transcriptome. Methods: Organotypic hippocampal cultures (OHC) from infant Wistar rats were infected with PE243 or SPH2015 and analyzed in time series using immunofluorescence, confocal microscopy, RNA-Seq and RT-qPCR. Results: Unique patterns of infection and changes in neuronal density in the OHC were observed for PE243 and SPH2015 between 8 and 48 h post infection (p.i.). Phenotypic analysis of microglia indicated that SPH2015 has a greater capacity for immune evasion. Transcriptome analysis of OHC at 16 h p.i. disclosed 32 and 113 differentially expressed genes (DEGs) in response to infection with PE243 and SPH2015, respectively. Functional enrichment analysis suggested that infection with SPH2015 activates mostly astrocytes rather than microglia. PE243 downregulated biological process of proliferation of brain cells and upregulated those associated with neuron death, while SPH2015 downregulated processes related to neuronal development. Both isolates downregulated cognitive and behavioral development processes. Ten genes were similarly regulated by both isolates. They are putative biomarkers of early hippocampus response to ZIKV infection. At 5, 7, and 10 days p.i., neuronal density of infected OHC remained below controls, and mature neurons of infected OHC showed an increase in the epigenetic mark H3K4me3, which is associated to a transcriptionally active state. This feature is more prominent in response to SPH2015. Conclusion: Subtle genetic diversity of the ZIKV affects the dynamics of viral dissemination in the hippocampus and host response in the early stages of infection, which may lead to different long-term effects in neuronal population. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) is an RNA flavivirus (Flaviviridae family) endemic in tropical and subtropical regions that is transmitted to humans by Aedes (Stegomyia) species mosquitoes. The two main urban vectors of ZIKV are Aedes aegypti and Aedes albopictus, which can be found throughout Brazil. This study investigated ZIKV infection in mosquito species sampled from urban forest fragments in Manaus (Brazilian Amazon). A total of 905 non-engorged female Ae. aegypti (22 specimens) and Ae. albopictus (883 specimens) were collected using BG-Sentinel traps, entomological hand nets, and Prokopack aspirators during the rainy and dry seasons between 2018 and 2021. All pools were macerated and used to inoculate C6/36 culture cells. Overall, 3/20 (15%) Ae. aegypti and 5/241 (2%) Ae. albopictus pools screened using RT-qPCR were positive for ZIKV. No supernatants from Ae. aegypti were positive for ZIKV (0%), and 15 out of 241 (6.2%) Ae. albopictus pools were positive. In this study, we provide the first-ever evidence of Ae. albopictus naturally infected with ZIKV in the Amazon region. [ABSTRACT FROM AUTHOR]

The Americas, particularly Brazil, were greatly impacted by the widespread Zika virus (ZIKV) outbreak in 2015 and 2016. Efforts were made to implement genomic surveillance of ZIKV as part of the public health responses. The accuracy of spatiotemporal reconstructions of the epidemic spread relies on the unbiased sampling of the transmission process. In the early stages of the outbreak, we recruited patients exhibiting clinical symptoms of arbovirus-like infection from Salvador and Campo Formoso, Bahia, in Northeast Brazil. Between May 2015 and June 2016, we identified 21 cases of acute ZIKV infection and subsequently recovered 14 near full-length sequences using the amplicon tiling multiplex approach with nanopore sequencing. We performed a time-calibrated discrete phylogeographic analysis to trace the spread and migration history of the ZIKV. Our phylogenetic analysis supports a consistent relationship between ZIKV migration from Northeast to Southeast Brazil and its subsequent dissemination beyond Brazil. Additionally, our analysis provides insights into the migration of ZIKV from Brazil to Haiti and the role Brazil played in the spread of ZIKV to other countries, such as Singapore, the USA, and the Dominican Republic. The data generated by this study enhances our understanding of ZIKV dynamics and supports the existing knowledge, which can aid in future surveillance efforts against the virus. [ABSTRACT FROM AUTHOR]

Purpose: Aedes aegypti mosquito-borne diseases have a significant impact on public health in Brazil. In this study, we investigated the presence of the Zika virus (ZIKV) and dengue virus (DENV) in serum and urine samples from symptomatic participants who attended an Emergency Care Unit located in a city in the northwestern region of São Paulo between February 2018 and April 2019. Methods: Serum and urine samples were collected from participants suspected of having arbovirus infection. After the extraction of viral RNA, viral detection was performed by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) (One-Step RT-qPCR). Results: A total of 305 participants participated in this study. A total of 283 blood and 270 urine samples were collected. Of 305 patients, 36.4% (111/305) were positive for ZIKV, 43.3% (132/305) for DENV2, and 0.3% (1/305) for DENV1. Coinfection with ZIKV/DENV2 was observed in 13.1% of participants. If only serum samples were used, ZIKV detection would have decreased to 23.3% (71/305). Of all the participants included in the study, only one was suspected of having ZIKV infection based on clinical diagnosis, and the remaining participants were suspected of having DENV. Conclusion: By testing serum and urine samples, we increased the detection of both viruses and detected considerable levels of ZIKV and DENV-2 coinfection when compared to other studies. Additionally, we detected an unnoticed ZIKV outbreak in the city. These findings highlight the importance of the molecular diagnosis of arboviruses to aid public health surveillance and management strategies. [ABSTRACT FROM AUTHOR]

During times of crisis, media coverage increases significantly, shaping public opinion and creating images of the places where these events occur. In this context, this paper analyses the Zika virus epidemic in Brazil, a past crisis that gained increased media attention during the months leading up to the 2016 Olympic Games in Rio, to identify the cognitive and affective components of published information. To this end, we subjected 1034 headlines (from digital editions of leading Spanish daily newspapers) related to tourism security at the Olympic Games to content analysis and employed a series of attributes to approach the cognitive and affective components of the information analysed. The results reveal that alarmist and negative headlines are more frequent when security issues, particularly citizen security, are reported. News headlines about the Olympic Games are generally descriptive and more positive. In the field of health security, citation-type headlines—those citing information provided by experts or authorities—are used more frequently. By analysing a past crisis, this study has several implications for Destination Management Organisations (DMOs) dealing with such events. In this context, we highlight some good practices to maximise informative news and minimise alarmist ones. [ABSTRACT FROM AUTHOR]

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

The C-terminal portion of the E protein, known as stem, is conserved among flaviviruses and is an important target to peptide-based antiviral strategies. Since the dengue (DENV) and Zika (ZIKV) viruses share sequences in the stem region, in this study we evaluated the cross-inhibition of ZIKV by the stem-based DV2 peptide (419–447), which was previously described to inhibit all DENV serotypes. Thus, the anti-ZIKV effects induced by treatments with the DV2 peptide were tested in both in vitro and in vivo conditions. Molecular modeling approaches have demonstrated that the DV2 peptide interacts with amino acid residues exposed on the surface of pre- and postfusion forms of the ZIKA envelope (E) protein. The peptide did not have any significant cytotoxic effects on eukaryotic cells but efficiently inhibited ZIKV infectivity in cultivated Vero cells. In addition, the DV2 peptide reduced morbidity and mortality in mice subjected to lethal challenges with a ZIKV strain isolated in Brazil. Taken together, the present results support the therapeutic potential of the DV2 peptide against ZIKV infections and open perspectives for the development and clinical testing of anti-flavivirus treatments based on synthetic stem-based peptides. [ABSTRACT FROM AUTHOR]

Introduction: Zika virus (ZIKV) is an arbovirus (arthropod-borne virus) in the genus Flavivirus and Flaviviridae family. In November 2015, several cases of microcephaly in Northeastern of Brazil suggested ZIKV involvement. Case Report: A 33-year-old primigravida developed fever and cutaneous rash at 7th week of gestation (WGA). The ultrasound and MRI examination showed head circumference < 5th centile and enlargement of lateral ventricles. The infant was delivered at 39th WGA with microcephaly. Microscopy of the placenta showed chronic villitis and intervillitis, nodular stromal fibrosis in the stem villi, and vascular thickening. Postnatal CT showed collapsed cranium due to growth impairment of the suprathalamic brain, multiple cerebral calcifications, parenchymal atrophy, and ventricular dilatation. Now, at 6 years old, the child suffers from severe neurologic symptoms, including seizures. Conclusion: This case gathers images of prenatal and postnatal period, and placental histopathology. The long-term follow-up highlights the dramatic neurological sequelae induced by ZIKV. [ABSTRACT FROM AUTHOR]

Background: The severity and distribution of dengue virus (DENV) infections have been attributed to a complex interaction among viral, host and environmental factors. Herein, we investigated the influence of chikungunya (CHIKV) and Zika (ZIKV) viruses on the epidemiological profile of dengue cases, using Recife, Pernambuco state, Brazil, as a study model. In addition, we described and compared the epidemiological profile related to each arbovirus (DENV vs. CHIKV vs. ZIKV). Methods: All cases of dengue, chikungunya and Zika reported to the Pernambuco Health Department in 2011–2013 (DENV circulation) and 2016–2018 (DENV, CHIKV and ZIKV co-circulation) were included in our study. The cases were classified by sex, age and race/color and their distribution was analyzed by the χ2 test. Furthermore, the data were also analyzed for co-infections. Temperature, humidity and rainfall data were analyzed using one-way ANOVA and paired t-test. Results: During 2011–2013, 15,315 dengue cases were diagnosed, most of them female, brown and 20–29 age group. Between 2016 and 2018, 15,870 dengue cases were described, which presented the same profile described above. In the two triennia, the female/male dengue ratio fluctuated significantly, ranging from 1.07 to 1.52. Regarding chikungunya, 7076 cases were reported, most of them female and brown. The female/male ratio also fluctuated significantly, ranging from 1.62 to 2.1. Two main age groups were observed in chikungunya: ≤ 19 years (minority of diagnoses) and ≥ 20 years (majority of diagnoses). In the same triennium, 266 Zika cases were reported to the Pernambuco Health Department, mainly in females and in the 0–9 and 20–39 age groups. In general, 119 co-infections were identified: 117 DENV-CHIKV, 1 CHIKV-ZIKV and 1 DENV-CHIKV-ZIKV. Concerning climate data, only the humidity in 2011 was significantly different from the other years. Conclusion: The epidemiological profile of dengue cases did not change after the introduction of CHIKV and ZIKV. Females were the most diagnosed with dengue, chikungunya or Zika, however we found important differences in the age profile of these arboviruses, which should be considered by public health policies, as well as investigated in future studies of virus-host interaction. Highlights: The introduction of chikungunya and Zika viruses did not change the epidemiological profile of dengue cases in our study population. Most cases of dengue, chikungunya and Zika have been described in women. Dengue, chikungunya and/or Zika cases had different age profiles. The female/male ratio in chikungunya was higher than that observed in dengue cases. The epidemiological differences among dengue, chikungunya and Zika must be considered by public health policies. [ABSTRACT FROM AUTHOR]

Early detection of Zika virus (ZIKV) transmission within geographic regions informs implementation of community mitigation measures such as vector reduction strategies, travel advisories, enhanced surveillance among pregnant women, and possible implementation of blood and organ donor screening or deferral. Standardized, comparative assessments of ZIKV assay and testing lab performance are important to develop optimal approaches to ZIKV diagnostic testing and surveillance. We conducted an expanded blinded panel study to characterize and compare the analytical performance of fifteen diagnostic and blood screening ZIKV NAT assays, including detection among single- and multiplex assays detecting ZIKV, dengue virus (DENV) and chikungunya virus (CHIKV). A 300 member blinded panel was constructed, consisting of 11 serial half-log dilutions ranging from ~104 to 10−1 genome equivalents/mL in 25 replicates each of the Tahitian Asian ZIKV isolate in ZIKV-negative human serum. Additionally, clinical samples from individuals with DENV-like syndrome or suspected ZIKV infection in Brazil were evaluated. The majority of assays demonstrated good specificity. Analytical sensitivities varied 1–2 logs, with a substantially higher limit of detection (LOD) in one outlier. Similar analytical sensitivity for ZIKV RNA detection in singleplex and multiplex assays of the Grifols and ThermoFisher tests were observed. Coefficient of Assay Efficiency (CE), calculated to characterize assays' RNA extraction and amplification efficiency, ranged from 0.13 for the Certest VIASURE multiplex and 0.75 for the Grifols multiplex assays. In general, assays using transcription mediated amplification (TMA) technology had greater CE compared to assays using conventional PCR technology. Donor screening NAT assays were significantly more sensitive than diagnostic RT-qPCR assays, primarily attributable to higher sample input volumes. However, ideal assays to maximize sensitivity and throughput may not be a viable option in all contexts, with other factors such as cost, instrumentation, and regulatory approval status influencing assay availability and selection, particularly in resource constrained settings. Author summary: Having standardized, comparative studies of Zika virus (ZIKV) tests are important for implementing optimal diagnostic testing and disease surveillance. Detection of ZIKV nucleic acid is ideal for confirming infection; however, knowing the sensitivity and specificity of a test is needed for selecting the right test in a given laboratory. We looked at the analytical performance of 15 diagnostic and blood screening ZIKV molecular tests, including tests that detect ZIKV only and tests that detect ZIKV plus other arboviruses. We found donor screening NAT assays were significantly more sensitive than diagnostic RT-qPCR assays, mostly due to the higher sample input volumes. We also found no difference in analytical sensitivity between tests that only detected ZIKV compared to tests that detected ZIKV and related viruses. The ideal molecular test will depend on the testing context, with other factors such as cost, instrumentation, and regulatory approval status influencing assay availability and selection. [ABSTRACT FROM AUTHOR]

The high incidence of Zika virus (ZIKV) infection in the period of 2015–2016 in Brazil may have affected linear height growth velocity (GV) in children exposed in utero to ZIKV. This study describes the growth velocity and nutritional status based on the World Organization (WHO) standards of children exposed to ZIKV during pregnancy and followed up in a tertiary unit, a reference for tropical and infectious diseases in the Amazon. Seventy-one children born between March 2016 and June 2018 were monitored for anthropometric indices: z-score for body mass index (BMI/A); weight (W/A); height (H/A) and head circumference (HC/A); and growth velocity. The mean age at the last assessment was 21.1 months (SD ± 8.93). Four children had congenital microcephaly and severe neurological impairment. The other 67 were non-microcephalic children (60 normocephalic and 7 macrocephalic); of these; 24.2% (16 children) had neurological alterations, and 28.8% (19 children) had altered neuropsychomotor development. Seventeen (24.2%) children had inadequate GV (low growth velocity). The frequencies of low growth among microcephalic and non-microcephalic patients are 25% (1 of 4 children) and 23.9% (16 of 67 children); respectively. Most children had normal BMI/A values during follow-up. Microcephalic patients showed low H/A and HC/A throughout the follow-up, with a significant reduction in the HC/A z-score. Non-microcephalic individuals are within the regular ranges for H/A; HC/A; and W/A, except for the H/A score for boys. This study showed low growth velocity in children with and without microcephaly, highlighting the need for continuous evaluation of all children born to mothers exposed to ZIKV during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Early child development is a critical stage of life that influences social, educational and health outcomes worldwide. A few years after Zika epidemic, families of children born with congenital Zika syndrome (CZS) continue to face uncertainties when it comes to the development of their children. The present study sought to analyse the developmental trajectories of a subset of children born with CZS in the first 24 months of life. Methods: Thirty‐five children with CZS were assessed with the Bayley‐III Scales at 12 and 24 months of age from November 2016 to December 2018 in a rehabilitation centre in Brazil. Inclusion criteria included children with established diagnosis of CZS. Exclusion criteria included the presence of arthrogryposis, prematurity, irregular follow‐up, clinical complications or other causes of microcephaly. Children born with CZS who evolved with cerebral palsy (CP) were classified according to the Gross Motor Function Classification System (GMFCS) at 2 years of age. Results: At 12 months of age mean composite scores on the Bayley cognitive, communication and motor scores were 57.71 (SD 7.11), 57.94 (SD 14.34) and 49.26 (7.20), respectively. At 24 months of age, composite scores were 57.43 (SD 7.11), 53.60 (SD 12.29) and 48.83 (7.76). In addition, 31 (88.57%) out of 34 children diagnosed with CP were classified as GMFCS levels IV and V. Conclusion: Zika virus congenital infection is a risk factor for functional impairments across all developmental domains having a direct and substantial negative impact in early child development. [ABSTRACT FROM AUTHOR]

First isolated in 1947, the Zika virus was initially connected only to limited or sporadic human infections. In late 2015, the temporal clustering of a Zika outbreak and microcephaly in newborn babies from northeastern Brazil, and the identification of a causal link between the two, led to the characterization of the congenital Zika syndrome. In the wake of the epidemic, several countries from Latin America advised women to postpone pregnancies for periods ranging from six months to two years. These recommendations initiated critical conversations about the challenges of implementing them in societies with limited access to contraception, widespread socioeconomic inequalities, and high rates of unplanned and adolescent pregnancies. The messaging targeted exclusively women, despite a high prevalence of imbalances in the relationship power, and addressed all women as a group, failing to recognize that the decision to postpone pregnancies will impact different women in different ways, depending on their age at the time. Finally, in several countries affected by the Zika epidemic, due to restrictive reproductive policies, legally terminating a pregnancy is no longer an option even at the earliest time when brain malformations as part of the congenital Zika syndrome can be detected by ultrasonography. The virus continued to circulate after 2016 in several countries. Climate change models predict an expansion of the geographical area where local Zika transmission may occur, indicating that the interface between the virus, teratogenesis, and reproductive rights is a topic of considerable interest for medicine, social sciences, and public health for years to come. [ABSTRACT FROM AUTHOR]

Background Except for public health case reports, the incidence of Zika virus (ZIKV), chikungunya virus (CHIKV), and dengue virus (DENV) infection are not available to assess the potential blood transfusion safety threat in Brazil. Methods Pools of 6 donation samples (MP6) left over from human immunodeficiency virus, hepatitis B virus, and hepatitis C virus nucleic acid testing were combined to create MP18 pools (3 MP6 pools). Samples were tested using the Grifols triplex ZIKV, CHIKV, and DENV real-time transcription mediated amplification assay to estimate prevalence of RNAemia and incidence, and to compare these results to case reports in São Paulo, Belo Horizonte, Recife, and Rio de Janeiro, from April 2016 through June 2019. Results ZIKV, CHIKV, and DENV RNAemia were found from donors who donated without overt symptoms of infection that would have led to deferral. The highest RNAemic donation prevalence was 1.2% (95% CI,.8%–1.9%) for DENV in Belo Horizonte in May 2019. Arbovirus infections varied by location and time of year, and were not always aligned with annual arbovirus outbreak seasons in different regions of the country. Conclusions Testing donations for arboviruses in Brazil can contribute to public health. Transfusion recipients were likely exposed to ZIKV, CHIKV, and DENV viremic blood components during the study period. [ABSTRACT FROM AUTHOR]

Brazil has experienced an increase in outbreaks caused by flaviviruses. The high incidence of dengue fever, the morbidity of Zika in children, and the high mortality of yellow fever have affected millions in recent years. Deciphering host-virus interactions is important for treating viral infections, and the mitogen-activated protein kinases (MAPK) are an interesting target because of their role in flavivirus replication. In particular, mitogen-activated protein kinase kinase (MEK), which targets extracellular-signal-regulated kinase (ERK), is necessary for dengue and yellow fever infections. In this study, we evaluated the role of the MEK/ERK pathway and the effect of the MEK inhibitor trametinib on the Asian ZIKV strain PE243 and the prototype African ZIKV strain MR766, addressing genome replication, morphogenesis, and viral release. ZIKV infection stimulated ERK phosphorylation in Vero cells at 12 and 18 hours postinfection (hpi). Trametinib showed sustained antiviral activity, inhibiting both ZIKV strains for at least four days, and electron microscopy showed probable inhibition of ZIKV morphogenesis. ZIKV PE243 can complete one cycle in Vero cells in 14 hours; genome replication was detected around 8 hpi, intracellular viral particles at 12 hpi, and extracellular progeny at 14 hpi. Treatments at 6-hour intervals showed that trametinib inhibited late stages of viral replication, and the titration of intra- or extracellular virions showed that the treatment especially affected viral morphogenesis and release. Thus, ZIKV stimulated ERK phosphorylation during viral morphogenesis and release, which correlated with trametinib inhibiting both the signaling pathway and viral replication. [ABSTRACT FROM AUTHOR]

Obesity is increasing in incidence worldwide, especially in women, which can affect the outcome of pregnancy. During this period, viral infections represent a risk to the mother, the placental unit, and the fetus. The Zika virus (ZIKV) outbreak in Brazil has been the cause of congenital Zika syndrome (CZS), with devastating consequences such as microcephaly in newborns. Herein, we analyzed the impact of maternal overweight/obesity on the antiviral factors' expression in the placental tissue of Zika-infected mothers. We accessed placentas from women with and without obesity from 34 public health units (São Paulo) and from Zika-infected mothers with and without obesity from the Clinical Cohort Study of ZIKV pregnant women (Rio de Janeiro, Brazil). We first verified that obesity, without infection, did not alter the constitutive transcriptional expression of antiviral factors or IFN type I/III expression. Interestingly, obesity, when associated with ZIKV infection, showed a decreased transcriptional expression of RIG-I and IFIH1 (MDA-5 protein precursor gene). At the protein level, we also verified a decreased RIG-I and IRF-3 expression in the decidual placenta from the Zika-infected obese group, regardless of microcephaly. This finding shows, for the first time, that obesity associated with ZIKV infection leads to an impaired type I IFN downstream signaling pathway in the maternal–fetal interface. [ABSTRACT FROM AUTHOR]

Objectives. To characterize the distribution profile of dengue, chikungunya, and Zika virus infections in Latin America and the Caribbean and to identify possible factors associated with the risk of dissemination and severity of these arboviruses. Methods. The protocol of this review was registered on the PROSPERO platform. Searches were carried out in the following databases: Virtual Health Library, MEDLINE/PubMed, and Embase. The search terms were: Zika virus, Zika virus infection, dengue, dengue virus, chikungunya virus, chikungunya fever, epidemiology, observational study, Latin America, and Caribbean region. Studies that addressed the distribution of these arboviruses and the risk factors associated with dengue, Zika virus disease, and chikungunya, published between January 2000 and August 2020 in English, Portuguese, and Spanish, were included. Results. Of 95 studies included, 70 identified risk factors, clinical manifestations, and outcomes for arbovirus infections and 25 described complications and/or deaths. The highest frequency of confirmed cases was for dengue. Brazil reported most cases of the three arboviruses in the period analyzed. Environmental and socioeconomic factors facilitated the proliferation and adaptation of vectors, and host-related factors were reported to aggravate dengue. Most deaths were due to chikungunya, Zika virus disease caused most neurological alterations, and dengue resulted in greater morbidity leading to more frequent hospitalization. Conclusions. The review provides a broad view of the three arboviruses and the intrinsic aspects of infections, and highlights the factors that influence the spread of these viruses in the populations studied. [ABSTRACT FROM AUTHOR]

Objective: To analyze the relationship between microcephaly and social inequality indicators in the state of Paraíba during the biennium January 2015 and December 2016. Methods: Ecological study with data from newborn microcephaly records and municipal socioeconomic, environmental, and demographic indicators was conducted using two health information systems from the Brazilian Ministry of Health (SINASC and SINAN) and the Brazilian Institute of Geography and Statistics. A Poisson multiple regression model was applied with a significance level of 5%. Results: Among 223 municipalities in Paraíba, 74 registered new cases of microcephaly. The number of Zika virus cases, number of inhabitants, number of households without adequate water supply, and household income were predictor variables of the number of new cases of microcephaly in Paraíba. Conclusion: Microcephaly is associated with indicators of social inequality in Paraíba. Zika virus cases, water supply, and family income are the indicators that best explain the increase in microcephaly cases. Therefore, these variables must be monitored by health professionals and authorities. [ABSTRACT FROM AUTHOR]

In this paper, we developed a multi-patch model for the spread of Zika virus infection taking, into account direct and indirect transmissions along with vertical transmission. The model was analyzed to gain insights into the disease's spread. The model was fitted to a data set collected from two neighboring countries, Brazil and Colombia, to estimate some of its parameters and use it for calculating ℜ0 and sensitivity analysis. Our results show that ℜ0 is less than one in both countries, which indicates that the disease will die out. Also, our results show that direct transmission is the most important route for spreading the disease; hence, it has to gain more focus in any controlling strategy. [ABSTRACT FROM AUTHOR]

The strain of Zika virus (ZIKV) that circulated during the 2015 epidemic in Brazil has been associated with more than 2000 cases of microcephaly from September 2015 through November 2016. The viral genome determines the biology and pathogenesis of a virus and the virus employs its own gene products to evade host immune surveillance, manipulate cellular machineries, and establish efficient replication. Therefore, understanding the functions of virus‐encoded protein not only aids the knowledge of ZIKV biology but also guides the development of anti‐ZIKV drugs. In this review, we focus on 10 proteins encoded by ZIKV and summarize their functions in ZIKV replication and pathogenesis according to studies published in the past 6 years. [ABSTRACT FROM AUTHOR]

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Arboviruses have been reported over the years as constant threats to blood transfusion recipients, given the high occurrence of asymptomatic cases and the fact that the presence of viremia precedes the onset of symptoms, making it possible that infected blood from donors act as a source of dissemination. This work aims to identify the prevalence of dengue virus (DENV), Zika virus (ZIKV) and Chikungunya virus (CHIKV) infection in blood donors during epidemic and non-epidemic periods; classify the donor as symptomatic or asymptomatic; and verify the need to include DENV, CHIKV and ZIKV in the nucleic acid test (NAT) platform in northern Brazil. We investigated 36,133 thousand donations in two years of collection in Northern Brazil. One donor was positive for DENV and one for CHIKV (0.002% prevalence). As the prevalence for arboviruses was low in this study, it would not justify the individual screening of samples from donors in a blood bank. Thus, DENV- and CHIKV-positive samples were simulated in different amounts of sample pools, and both were safely detected by molecular biology even in a pool of 14 samples, which would meet the need to include these three viruses in the routine of blood centers in endemic countries such as Brazil. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) is a widespread flavivirus transmitted to humans through the bite of Aedes mosquitoes. The number of ZIKV cases increased significantly between 2015 and 2016, and Brazil was the first to report autochthonous transmission of infection. The main neurological disorder related to ZIKV infection is microcephaly. Fetal magnetic resonance imaging (MRI) is the gold standard examination for the analysis of fetal brain infection, followed by obstetric ultrasonography. Cerebral atrophy, intracranial calcifications, ventriculomegaly, cerebellar, and brain gyrus abnormalities are some of the most common findings. Postnatal MRI shows high sensitivity and specificity. Corpus callosum abnormalities, cerebellar hypoplasia, and choroid plexus dilation can be also observed. We present a review of congenital ZIKV infection with emphasis on pre and postnatal brain findings using ultrasonography, MRI, computed tomography, and three-dimensional reconstruction models. [ABSTRACT FROM AUTHOR]

Infections with Flavivirus in pregnant women are not associated with vertical transmission. However, in 2015, severe cases of congenital infection were reported during the Zika virus outbreak in Brazil. More subtle infections in children born to mothers with ZIKV still remain uncertain and the spectrum of this new congenital syndrome is still under construction. This study describes outcomes regarding neurodevelopment and neurological examination in the first years of life, of a cohort of 77 children born to pregnant women with ZIKV infection in Manaus, Brazil, from 2017 to 2020. In the group of normocephalic children (92.2%), most showed satisfactory performance in neuropsychomotor development, with a delay in 29.6% and changes in neurological examination in 27.1%, with two children showing muscle-strength deficits. All microcephalic children (5.2%) evolved with severe neuropsychomotor-development delay, spastic tetraparesis, and alterations in the imaging exam. In this cohort, 10.5% of the children had macrocephaly at birth, but only 2.6% remained in this classification. Although microcephaly has been considered as the main marker of congenital-Zika-virus syndrome in previous studies, its absence does not exclude the possibility of the syndrome. This highlights the importance of clinical follow-up, regardless of the classification of head circumference at birth. [ABSTRACT FROM AUTHOR]

First isolated in 1947, the Zika virus was initially connected only to limited or sporadic human infections. In late 2015, the temporal clustering of a Zika outbreak and microcephaly in newborn babies from northeastern Brazil, and the identification of a causal link between the two, led to the characterization of the congenital Zika syndrome. In the wake of the epidemic, several countries from Latin America advised women to postpone pregnancies for periods ranging from six months to two years. These recommendations initiated critical conversations about the challenges of implementing them in societies with limited access to contraception, widespread socioeconomic inequalities, and high rates of unplanned and adolescent pregnancies. The messaging targeted exclusively women, despite a high prevalence of imbalances in the relationship power, and addressed all women as a group, failing to recognize that the decision to postpone pregnancies will impact different women in different ways, depending on their age at the time. Finally, in several countries affected by the Zika epidemic, due to restrictive reproductive policies, legally terminating a pregnancy is no longer an option even at the earliest time when brain malformations as part of the congenital Zika syndrome can be detected by ultrasonography. The virus continued to circulate after 2016 in several countries. Climate change models predict an expansion of the geographical area where local Zika transmission may occur, indicating that the interface between the virus, teratogenesis, and reproductive rights is a topic of considerable interest for medicine, social sciences, and public health for years to come. [ABSTRACT FROM AUTHOR]

Background: Since 1952 when Zika Virus (ZIKV): a Flavivirus, was first discovered in humans, it has not received enough scientific research compared to some of the other members of the family Flaviviridae; like Dengue Virus (DENV). However, this has not stopped the virus from infecting the human population globally. In particular, the global spread of ZIKV has led to a surge in observational studies. Methods: Regarding recently published ZIKV-related literature, we are not aware of any reviews strictly focusing on ZIKV from the perspective of observational studies. Therefore, we reviewed recently published observational studies exploring the global spread of ZIKV and its association with Congenital ZIKV Infection (CZI) and clinical manifestations in adults. Online databases including google scholar, PubMed and Elsevier were used for retrieving relevant studies. Results: ZIKV cases have been reported in different parts of the world, with certain regions reporting more cases than the rest, like Brazil. ZIKV causes a wide spectrum of diseases and disorders including microcephaly, developmental disorders, and Guillain-Barre syndrome to name a few. Furthermore, CZI in neonates mainly manifests into neurological disorders and diseases, whereas ZIKV in adults’ targets various organs. Conclusion: ZIKV poses a serious threat to human population and observational studies provide a different perspective on the damaging capabilities of ZIKV in real-life settings. Moreover, there are gaps in the literature regarding ZIKVrelated-complications that future experimental studies need to address. These complications include in-utero transmission, Guillain-Barre syndrome, cross-reactivity, sexual transmission, along with its persistence in the male reproductive tract. [ABSTRACT FROM AUTHOR]

Background: Congenital anomalies are associated with several clinical and epidemiological complications. Following the Zika epidemic onset in Latin America, the incidence of congenital anomalies increased in Brazil. This study aimed to determine the frequency of congenital anomalies in one Brazilian state and assess potential factors associated with them.Methods: This cross-sectional descriptive study was based on data concerning congenital anomalies recorded in the Brazilian Live-Born Information System during the Zika epidemic in Mato Grosso do Sul state from 2015 to 2018. Congenital anomalies were stratified according to year of birth and classified using ICD-10 categories.Results: In total, 1,473 (0.85%) anomalies were registered. Within the number of cases recorded, microcephaly showed the greatest frequency and variations, with a 420% increase observed in the number of cases from 2015 to 2016. We identified an increase in the incidence of central nervous system anomalies, with the highest peak observed in 2016 followed by a subsequent decrease. Musculoskeletal, nervous, and cardiovascular system anomalies, and eye, ear, face, and neck anomalies represented 73.9% of all recorded anomalies. There was an increased chance of congenital anomalies in uneducated (odds ratio [OR] 5.56, 95% confidence interval [CI] 2.61-11.84) and Indigenous (OR 1.32, 95% CI 1.03-1.69) women, as well as among premature births (OR 2.74, 95% CI 2.39-3.13).Conclusions: We estimated the incidence of congenital anomalies during the Zika epidemic. Our findings could help to support future research and intervention strategies in health facilities to better identify and assist children born with congenital anomalies. [ABSTRACT FROM AUTHOR]

The study of global health agenda-setting and issue-prioritization has been one of the key aspects of a critical literature that, in recent years, has aimed to identify the political dimensions of global health governance and to shed light on points of tension, exclusion, and inequality. This essay speaks to this critical global health literature, focusing on the construction of the category of emergencies of international concern. Considering the case of the outbreak of zika and congenital syndrome in Brazil in 2016, it explores the conditions enabling the construction of an emergency. We question the factors and conditions around this public health event that were considered during the decision-making process and that transcended material, more objective data regardingzika's epidemiology, its morbimortality, or its association with congenital malformations. We conclude that the securitized context and the growing relevance of risk to global health are important conditions for understanding emergency declarations. [ABSTRACT FROM AUTHOR]