RESUMO

Zika virus (ZIKV) is a flavivirus of significant epidemiological importance, utilizing various transmission strategies and infecting "immune privileged tissues" during both the pre- and postnatal periods. One such transmission method may involve extracellular vesicles (EVs). EVs can travel long distances without degrading, carrying complex messages that trigger different responses in recipient cells. They can easily cross specialized tissue barriers, such as the placental barrier and the blood-brain barrier, which protects the central nervous system. It is known that some viruses can hijack and exploit the EVs biogenesis machinery to package regulatory elements, viral segments, and even complete viral genomes. This allows them to evade the immune system, amplify their tropism, and enhance their spread. ZIKV likely uses EVs produced by infected cells to insert its genomic RNA or parts of it. This mechanism can ensure viral entry and infection of the nervous tissue, partly explaining its broad viral tropism and silent persistence in various tissues and organs for months. This narrative review summarizes the main features of ZIKV and EVs, highlighting the most recent evidence on the involvement and effects of EVs during ZIKV infection. It also discusses the possibility of EVs acting as carriers of ZIKV through the nervous tissue.

RESUMO

One of the most significant bacteriophage technologies is phage display, in which heterologous peptides are exhibited on the virion surface. This work describes the display of λ decorative protein Dλ linked to the E protein domain III of Zika virus (Dλ-ZEDIII), to the GFP protein (Dλ-GFP), or to different domain III epitopes of the EZIKV protein (Dλ-TD), exhibited on the surface of an in vitro evolved lambda phage (λevo). This phage harbors a gene D deletion and was subjected to directed evolution using Escherichia coli W3110/pDλ-ZEDIII as background. After 20 days (20 cycles of dilution), the λevo phage developed a ~ 22% genome deletion affecting the non-essential λ b region, rendering a more stable phage that exhibited fusion proteins Dλ-ZEDIII or Dλ-GFP but not Dλ-TD. Despite the λevo system was able to decorate itself with the Dλ-ZEDIII protein, the production of viral particles was ~ 1000-fold lower than the λ wild-type, due to the unexpected Dλ-ZEDIII protein aggregation into bacterial inclusion bodies. Decorated phages (106 PFU (plaque forming units)/100 µl) were inoculated into BALB/c mice, and subsequent dot blot and Western blot immunoassays proved the production of murine antibodies against ZIKV (Zika virus). This multipurpose λevo phage display platform may be used interchangeably with other more soluble peptides, providing better yields. KEY POINTS: • λevo platform for displaying recombinant peptides. • Directed evolution to generate λevo with more efficient decoration. • Antigenic reaction in BALB/c mice by inoculating λevo with recombinant peptides.

RESUMO

BACKGROUND: Human activities, such as urbanization and climate change, have facilitated the spread of arbovirus-carrying vectors, disproportionately affecting vulnerable traditional Indigenous communities. OBJECTIVE: To explore the relationships between subclinical myocardial dysfunction, assessed by global longitudinal strain (GLS), and comprehensive arbovirus serology in an Indigenous population, while also describing the serological and epidemiological profile of dengue, chikungunya, and Zika viruses. METHODS: This ancillary study is part of the first phase (2016-2017) of the Project of Atherosclerosis among Indigenous Populations (PAI), a cross-sectional study involving participants from two Indigenous communities with different degrees of urbanization and a highly urbanized city in Northeast Brazil. We assessed the seroprevalence of dengue, chikungunya, and Zika viruses in the Fulni-ô Indigenous community, the less urbanized and most traditional group. Additionally, we explored the relationship between these viruses and subclinical heart disease, assessed by speckle-tracking echocardiography-derived GLS. RESULTS: One hundred seventy-four participants were included, with a median age of 45.0 years (interquartile range 38.0-55.0). The majority were female (58.6%; n = 102). The prevalence of anti-ZIKV IgG was 95.3%; anti-DENV IgG was 85.8%, and anti-CHIKV IgG was 70.9%. GLS abnormalities were detected in nearly half (48.3%) of the cohort. However, no significant association was found between arbovirus serology and GLS. CONCLUSIONS: The findings reveal a high prevalence of positive serology for arboviruses and a significant rate of subclinical cardiac dysfunction. There was no significant association between reduced left ventricular longitudinal strain and positive arbovirus serology, likely due to the limited number of participants with indications of acute contact with the viruses studied. However, the unprecedented and relevant results of this study are noteworthy, as they address critical public health issues, particularly in vulnerable populations. Further research is needed to explore these findings in more depth.

RESUMO

BACKGROUND: Urban arboviruses pose a significant global burden, particularly in tropical regions like Brazil. São Sebastião, a lower-middle-class urban area just 26 km from the Brazilian capital, is an endemic area for dengue. However, asymptomatic cases may obscure the actual extent of the disease. In this study, we measured the seroprevalence of dengue, Zika virus, and chikungunya, and compared these findings with surveillance data. METHODS: A cross-sectional study was conducted involving 1,535 households. ELISA serological tests were performed to detect IgM and IgG antibodies against dengue, Zika virus, and chikungunya. History of previous exposure to arboviruses, data on age, gender, and education level were collected through a questionnaire. Participants who tested positive for IgM and/or IgG were classified as soropositive. Statistical analyses included tests for normality, associations, mean comparisons, and correlations. Positive serological results were compared with cases captured by local epidemiological surveillance. RESULTS: The study included 1,405 individuals, divided into two groups related to pre-pandemic and pandemic COVID-19 phases. Among participants, 0.7% to 28.8% self-reported history of dengue, Zika, or chikungunya. However, the estimated overall seroprevalence was 64.3% (95% CI: 61.8-66.7) for dengue virus, 51.4% (95% CI: 48.8-53.9) for Zika virus, and 5.4% (95% CI: 4.4-6.7) for chikungunya virus. Multiple arboviruses were noted at 4.0% (95% CI: 3.1-5.1). Advancing age and lower education were associated with higher exposure to arboviruses (p < 0.05). The estimated number of urban arboviral infections was 84 times higher than reported cases. CONCLUSIONS: The large gap between seroprevalence estimates and cases captured by epidemiological surveillance suggests a silent circulation of arboviruses, highlighting the need for comprehensive serological surveys in endemic regions. Addressing these discrepancies is crucial for effective resource allocation and implementation of public health interventions.

RESUMO

BACKGROUND: Gestational Zika virus (ZIKV) infection is associated with the development of congenital Zika syndrome (CZS), which includes microcephaly and fetal demise. The magnitude and quality of orthoflavivirus-specific humoral immunity have been previously linked to the development of CZS. However, the role of ZIKV NS1-specific humoral immunity in mothers and children with prenatal ZIKV exposure and CZS remains undefined. In addition, considering that most of the at-risk population lives in dengue virus (DENV)-endemic areas, it is not clear what is the association between pre-existing DENV NS1-specific humoral immunity and CZS. METHODS: Here, we studied 328 mothers and children with a clinical diagnosis and seropositivity for ZIKV infection during pregnancy, included during the 2015-2016 ZIKV epidemic in Colombia. We also performed clinical evaluation and pediatric neurological follow-up. The relative levels of circulating NS1-specific IgM and IgG against ZIKV and DENV were evaluated in mothers and children, and the association with the development of microcephaly was analyzed. RESULTS: DENV and ZIKV IgG-NS1 antibodies in pregnant women were placentally transferred, and this passage and its duration in children depended on the maternal levels of the antibodies. We reported that higher concentrations of pre-existing DENV, but not ZIKV IgG-NS1 antibodies, were associated with a reduced risk of CZS-related microcephaly. Also, we observed that the IgM-NS1 response in infants is long-term and has a minor association with poor outcomes. CONCLUSIONS: The development of microcephaly in children prenatally exposed to ZIKV is associated with low plasma levels of placentally transferred, pre-existing DENV IgG-NS1 antibodies. These data are compatible with a protective role of anti-NS1 IgG antibodies against ZIKV infection during pregnancy and highlight the promising role of NS1 as an orthoflavivirus vaccine target in high-risk populations.

RESUMO

Immunological memory, a fundamental immune system mechanism, is instrumental in long-term protection. Successful vaccines can elicit and sustain immunological memory against pathogens for the long term. Memory B cells (MBC) are key players in secondary responses due to their longevity and rapid differentiation into high-affinity antibody-secreting cells upon second antigen exposure. However, the availability of circulating MBCs is limited. Here we describe a protocol, which presents a straightforward and practical method for activating and expanding Zika virus (ZIKV) specific MBC. PBMCs collected from individuals who had been infected with ZIKV two years prior were cultured by supplementing with IL-2 and R848, a TLR-7/8 agonist, and then pulsed with inactivated virus. After seven days, this stimulation led to a notable rise in virus-specific functional MBC, as evidenced by a significant increase in the production of anti-ZIKV IgG. Importantly, the ZIKV pulse did not induce changes in the PBMC culture of individuals without a history of ZIKV infection. These findings demonstrate that virus-specific MBC can be expanded in vitro, even using PBMC cultures from individuals infected years before. Therefore, our protocol is a practical and effective tool for studies that require a larger number of human MBCs from previously infected individuals that are functional and specific to the pathogen under investigation.

RESUMO

Objetivo: apresentar uma análise da distribuição de casos de dengue, Zika vírus e Chikungunya nos municípios de Goiás, buscando identificar padrões de distribuição geográfica e possíveis correlações com variáveis socioambientais, como população, distância da capital e infraestrutura de saneamento básico. Método: estudo de natureza transversal e descritiva, conduzido por meio de dados coletados através do Tabnet de 2017 a 2022. Resultados: fatores como o clima, o bioma Cerrado, a alta mobilidade e a falta de infraestrutura, como rede de esgoto, favorecem a proliferação do mosquito Aedes aegypti e a disseminação de arboviroses em Goiás, especialmente em áreas densamente povoadas, como Goiânia e Aparecida de Goiânia. Conclusão: a promoção da educação em Saúde Planetária nos serviços de Atenção Primária à Saúde (APS) é essencial para mitigar esses problemas, pois capacita a população a entender as relações entre meio ambiente, saúde e sociedade, ressaltando que a desarmonia gera doenças, como as arboviroses.

Objective: present an analysis of the distribution of dengue, Zika virus, and Chikungunya cases in the municipalities of Goiás, aiming to identify patterns of geographic distribution and possible correlations with socio-environmental variables, such as population, distance from the capital, and basic sanitation infrastructure. Method: across-sectional and descriptive study based on data collected through Tabnet from 2017 to 2022. Results: factors such as climate, the Cerrado biome, high mobility, and lack of infrastructure, such as sewage systems, contribute to the proliferation of the Aedes aegypti mosquito and the spread of arboviruses in Goiás, especially in densely populated areas like Goiânia and Aparecida de Goiânia. Conclusion: promoting Planetary Health education in Primary Health Care (PHC) services is essential to address these issues, as it empowers the population to understand the relationships between the environment, health, and society, emphasizing that disharmony leads todiseases like arboviruses.

Objetivo: presentar un análisis de la distribución de casos de dengue, virus del Zika y chikungunya en los municipios de Goiás, con el objetivo de identificar patrones de distribución geográfica y posibles correlaciones con variables socioambientales, como población, distancia a la capital e infraestructura de saneamiento básico. Método: estudio transversal y descriptivo basado en datos recopilados a través de Tabnet de 2017 a 2022. Resultados: factores como el clima, el bioma Cerrado, la alta movilidad y la falta de infraestructura, como redes de alcantarillado, favorecen la proliferación del mosquito Aedes aegypti y la propagación de arbovirus en Goiás, especialmente en áreas densamente pobladas, como Goiânia y Aparecida de Goiânia. Conclusión: la promoción de la educación en Salud Planetaria en los servicios de Atención Primaria de Salud (APS) es esencial para mitigar estos problemas, ya que capacita a la población para comprender las relaciones entre el medio ambiente, la salud y la sociedad, enfatizando que la desarmonía genera enfermedades, como los arbovirus.

RESUMO

Dengue is the most prevalent arboviral disease globally, with Brazil currently experiencing a significant rise in cases. Dengue virus (DENV) typically co-circulates with other clinically and antigenically similar flaviviruses, such as Zika virus (ZIKV). The clinical diagnosis is difficult and accurate serological analysis represents an unmet challenge. Traditionally, serological analysis of DENV infection focuses on the acute phase via detection of NS1 or IgM. Developing IgG DENV-specific assays has been defiant due to the co-circulation of four antigenically distinct serotypes and a strong cross-reactivity with other arboviruses, particularly with ZIKV. The goal of this study was to produce recombinant domain III of the Envelope (EDIII) proteins of each DENV serotype and ZIKV and evaluate the ability to detect specific IgG antibodies. The antigens were tested on the ELISA platform to measure DENV-specific IgG in mice and patients infected with ZIKV and DENV. The assay differentiated serotype-specific IgG responses in susceptible mice (AG129) experimentally infected with DENV or ZIKV. In addition, the test demonstrated a robust performance achieving 87.8% sensitivity and 91.4% specificity when tested against 648 well-characterized sera collected from humans infected with DENV and/or ZIKV. The test was further applied to serum samples collected from 318 healthy individuals from an endemic region in Northwest/Central Brazil, without a previous diagnosis of DENV, and revealed that 65% of the samples reacted with at least one DENV serotype antigen, including 123 monotypic samples (88 for DENV-1) and 90 samples reacting with multiple antigens. Collectively, these results indicate that the IgG DENV-EDIII ELISA is a valuable tool for assessing the serological status of populations in endemic areas, particularly in regions where other flaviviruses, particularly ZIKV, co-circulate and offer support to establish public health policies against the disease.

RESUMO

This study aimed to evaluate the association between microcephaly and hearing disorders in children with exposed or suspected exposure to Zika virus (ZIKV) during the intrauterine period. In this cross-sectional study, we enrolled children exposed or suspected of being exposed to ZIKV during intrauterine period, admitted to the hospital between April 2016 and July 2018, and followed up until September 2021. All children underwent at least one automated auditory brainstem response (AABR) test. For analysis, the patients were divided into four groups: those with microcephaly, without microcephaly, suspected ZIKV infection, and controls. Other causes of microcephaly were excluded. Hearing impairment was assessed using the AABR to determine associations with microcephaly or central nervous system (CNS) abnormalities. Of the 134 children included, 34 (25.4%) were diagnosed with congenital Zika syndrome (CZS), of whom 28 (82.4%) had microcephaly, and the remaining six (17.6%) without microcephaly. Among the 28 children with microcephaly, 3 (10.7%) had abnormal AABR. Among CZS children without microcephaly (n = 6), 1 (16.7%) had abnormal AABR (Fisher's exact test p = 0.56).Conclusion: In our study population, that hearing impairment assessed using the AABR test was not associated with microcephaly or severe CNS alterations.

RESUMO

El documento contiene las disposiciones para la atención integral de salud de las personas con la enfermedad de Zika

RESUMO

Health communication has proven to play a crucial role in addressing diseases such as dengue, Zika and chikungunya, for which there are no definitive or easily accessible vaccines. In this context, this discipline becomes a fundamental tool to promote the change behavior and promote preventive practices that reduce the transmission of these diseases. By not having a definitive medical solution, accurate and timely information, effectively disseminated through educational campaigns, media and communication channels public health, can significantly influence individual and community actions to control the spread of these mosquito-borne viruses. The accumulated research around the threat of the aforementioned arboviral diseases brings together a series of recommendations around specific communication activities, such as disseminating timely and accurate information that integrates public health concerns and the needs of information of the population, especially vulnerable groups such as women of childbearing age, pregnant women and health workers. Furthermore, his proposal involves continuing with the initiatives to encourage behavioral changes, as well as social mobilization and participation community, with a view to controlling the vector and eliminating its breeding sites, while keeping the public informed about the risks of infection, ongoing public health processes and investigations in development. This work proposes to adopt a unified and coherent government approach to communication strategic and operational, involving partners and allies from the non-governmental sector. This involves defining and implement a system that guarantees the coherence of messages between the national government and the local health authorities, as well as developing content guides aimed at obtaining messages unified and define protocols for the release of public information in emergency situations health, such as the spread of dengue and other diseases caused by arboviruses. In summary, we are looking for comprehensive, coordinated and evidence-based communication to effectively confront the emergency of public health represented by arboviral diseases.

RESUMO

The Zika virus epidemic of 2015-16, which caused over 1 million confirmed or suspected human cases in the Caribbean and Latin America, was driven by a combination of movement of infected humans and availability of suitable habitat for mosquito species that are key disease vectors. Both human mobility and mosquito vector abundances vary seasonally, and the goal of our research was to analyze the interacting effects of disease vector densities and human movement across metapopulations on disease transmission intensity and the probability of super-spreader events. Our research uses the novel approach of combining geographical modeling of mosquito presence with network modeling of human mobility to offer a comprehensive simulation environment for Zika virus epidemics that considers a substantial number of spatial and temporal factors compared to the literature. Specifically, we tested the hypotheses that 1) regions with the highest probability of mosquito presence will have more super-spreader events during dry months, when mosquitoes are predicted to be more abundant, 2) regions reliant on tourism industries will have more super-spreader events during wet months, when they are more likely to contribute to network-level pathogen spread due to increased travel. We used the case study of Colombia, a country with a population of about 50 million people, with an annual calendar that can be partitioned into overlapping cycles of wet and dry seasons and peak tourism and off tourism seasons that drive distinct cyclical patterns of mosquito abundance and human movement. Our results show that whether the first infected human was introduced to the network during the wet versus dry season and during the tourism versus off tourism season profoundly affects the severity and trajectory of the epidemic. For example, Zika virus was first detected in Colombia in October of 2015. Had it originated in January, a dry season month with high rates of tourism, it likely could have infected up to 60% more individuals and up to 40% more super-spreader events may have occurred. In addition, popular tourism destinations such as Barranquilla and Cartagena have the highest risk of super-spreader events during the winter, whereas densely populated areas such as Medellín and Bogotá are at higher risk of sustained transmission during dry months in the summer. Our research demonstrates that public health planning and response to vector-borne disease outbreaks requires a thorough understanding of how vector and host patterns vary due to seasonality in environmental conditions and human mobility dynamics. This research also has strong implications for tourism policy and the potential response strategies in case of an emergent epidemic.

RESUMO

The epidemiologic effects of Zika virus (ZIKV) sexual transmission in virus-endemic countries remain unclear. We conducted a 2-level, linear mixed-effects logistic regression analysis by using a recently acquired population-based ZIKV and chikungunya virus (CHIKV) serologic dataset obtained from persons residing in Northeast Brazil (n = 2,070 participants). We adjusted mathematical models for housing type and age of participants; the models indicated a significantly higher likelihood of ZIKV seropositivity among persons engaged in a sexual relationship within the same household (odds ratio 1.25 [95% CI 1.00-1.55]; p = 0.047), regardless of their partner's ZIKV serostatus, and among participants with a ZIKV-seropositive sex partner within the same household (odds ratio 1.54 [95% CI 1.18-2.01]; p = 0.002). CHIKV was also modeled as a control; no sex-associated effects were observed for CHIKV serology. Inclusion of ZIKV sexual transmission in prevention and control strategies is urgently needed, particularly in ZIKV-endemic regions.

RESUMO

Central nervous system (CNS) cancers are responsible for high rates of morbidity and mortality worldwide. Malignant CNS tumors such as adult Glioblastoma (GBM) and pediatric embryonal CNS tumors such as medulloblastoma (MED) and atypical teratoid rhabdoid tumors (ATRT) present relevant therapeutic challenges due to the lack of response to classic treatment regimens with radio and chemotherapy. Recent findings on the Zika virus' (ZIKV) ability to infect and kill CNS neoplastic cells draw attention to the virus' oncolytic potential. Studies demonstrating the safety of using ZIKV for treating malignant CNS tumors, enabling the translation of this approach to clinical trials, are scarce in the literature. Here we developed a co-culture model of mature human cerebral organoids assembled with GBM, MED or ATRT tumor cells and used these assembloids to test ZIKV oncolytic effect, replication potential and preferential targeting between normal and cancer cells. Our hybrid co-culture models allowed the tracking of tumor cell growth and invasion in cerebral organoids. ZIKV replication and ensuing accumulation in the culture medium was higher in organoids co-cultured with tumor cells than in isolated control organoids without tumor cells. ZIKV infection led to a significant reduction in tumor cell proportion in organoids with GBM and MED cells, but not with ATRT. Tumoroids (3D cultures of tumor cells alone) were efficiently infected by ZIKV. Interestingly, ZIKV rapidly replicated in GBM, MED, and ATRT tumoroids reaching significantly higher viral RNA accumulation levels than co-cultures. Moreover, ZIKV infection reduced viable cells number in MED and ATRT tumoroids but not in GBM tumoroids. Altogether, our findings indicate that ZIKV has greater replication rates in aggressive CNS tumor cells than in normal human cells comprising cerebral organoids. However, such higher ZIKV replication in tumor cells does not necessarily parallels oncolytic effects, suggesting cellular intrinsic and extrinsic factors mediating tumor cell death by ZIKV.

RESUMO

Flaviviruses are vector-borne RNA viruses that seriously threaten global public health due to their high transmission index in humans, mainly in endemic areas. They spread infectious diseases that affect approximately 400 million people globally, primarily in developing countries struggling with persistent epidemic diseases. Viral infections manifest as hemorrhagic fever, encephalitis, congenital abnormalities, and fatalities. Despite nearly two decades of drug discovery campaigns, researchers have not identified promising lead compounds for clinical trials to treat or prevent flavivirus infections. Although scientists have made substantial progress through drug discovery approaches and vaccine development, resolving this complex issue might need some time. New therapeutic agents that can safely and effectively target key components of flaviviruses need to be identified. NS2B-NS3pro is an extensively studied pharmacological target among viral proteases. It plays a key role in the viral replication cycle by cleaving the polyprotein of flaviviruses and triggering the formation of structural and non-structural proteins. In this review, studies published from 2014 to 2023 were examined, and the specificity profile of compounds targeting NS2B-NS3 pro proteases for treating flavivirus infections was focused on. Additionally, the latest advancements in clinical trials were discussed. This article might provide information on the prospects of this promising pharmacological target.

RESUMO

Major clusters of Guillain-Barré Syndrome (GBS) emerged during the Zika virus (ZIKV) outbreaks in the South Pacific and the Americas from 2014 to 2016. The factors contributing to GBS susceptibility in ZIKV infection remain unclear, although considerations of viral variation, patient susceptibility, environmental influences, and other potential factors have been hypothesized. Studying the role of viral genetic factors has been challenging due to the low viral load and rapid viral clearance from the blood after the onset of Zika symptoms. The prolonged excretion of ZIKV in urine by the time of GBS onset, when the virus is no longer present in the blood, provides an opportunity to unravel whether specific ZIKV mutations are related to the development of GBS in certain individuals. This study aimed to investigate the association between specific ZIKV genotypes and the development of GBS, taking advantage of a unique collection of ZIKV-positive urine samples obtained from GBS cases and controls during the 2016 ZIKV outbreak in Colombia. Utilizing Oxford-Nanopore technology, we conducted complete genome sequencing of ZIKV in biological samples from 15 patients with GBS associated with ZIKV and 17 with ZIKV infection without neurological complications. ZIKV genotypes in Colombia exhibited distribution across three clades (average bootstrap of 90.9±14.9%), with two clades dominating the landscape. A comparative analysis of ZIKV genomes from GBS and non-neurological complications, alongside 1368 previously reported genomes, revealed no significant distinctions between the two groups. Both genotypes were similarly distributed among observed clades in Colombia. Furthermore, no variations were identified in the amino acid composition of the viral genome between the two groups. Our findings suggest that GBS in ZIKV infection is perhaps associated with patient susceptibility and/or other para- or post-infectious immune-mediated mechanisms rather than with specific ZIKV genome variations.

RESUMO

La comunicación en salud ha demostrado desempeñar un papel crucial en el abordaje de enfermedades como el dengue, el zika y la chikunguña, para las cuales no existen vacunas definitivas o de fácil acceso. En este contexto, dicha disciplina se convierte en una herramienta fundamental para fomentar el cambio de comportamiento y promover prácticas preventivas que reduzcan la transmisión de estas enfermedades. Al no contar con una solución médica definitiva, la información precisa y oportuna, difundida de manera eficaz a través de campañas educativas, medios de comunicación y canales de salud pública, puede influir significativamente en las acciones individuales y comunitarias para controlar la propagación de estos virus transmitidos por mosquitos. La investigación acumulada en torno a la amenaza de las enfermedades arbovirales mencionadas reúne una serie de recomendaciones en torno a actividades de comunicación específicas, tales como difundir información oportuna y precisa que integre las preocupaciones de salud pública y las necesidades de información de la población, especialmente de los grupos vulnerables como las mujeres en edad fértil, las embarazadas y los trabajadores de la salud. Además, su propuesta pasa por continuar con las iniciativas para fomentar cambios de comportamiento, así como la movilización social y la participación comunitaria, con miras a controlar el vector y eliminar sus criaderos, al tiempo que se mantiene al público informado sobre los riesgos de la infección, los procesos de salud pública en curso y las investigaciones en desarrollo. El presente trabajo propone adoptar un enfoque gubernamental unificado y coherente de la comunicación estratégica y operativa, involucrando a socios y aliados del sector no gubernamental. Esto implica definir e instrumentar un sistema que garantice la coherencia de los mensajes entre el gobierno nacional y las autoridades sanitarias locales, así como desarrollar guías de contenido dirigidas a obtener mensajes unificados y definir protocolos para la liberación de información pública en situaciones de emergencias de salud, como la propagación del dengue y otras enfermedades causadas por arbovirus. En resumen, se busca una comunicación integral, coordinada y basada en evidencia para enfrentar eficazmente la emergencia de salud pública que representan las enfermedades arbovirales.

RESUMO

In this study, we synthesized and characterized a series of coumarin-imidazopyridine hybrid ligands (HL1-HL4) and their corresponding Zn(II) complexes (C1-C4). The ligands were synthesized via a two-step process in 56-90 % yields. The resulting ligands, were utilized to form Zn(II) complexes, characterized by conductivity measurements, HRMS, IR, 1H NMR spectroscopy and X-ray diffractions. Biological evaluations revealed that these compounds exhibited potent antiviral activity against Zika virus (ZIKV), with EC50 values ranging from 0.55 to 4.8 µM and SI of up to 1490. Notably, the complexes (the first-in-class Zn(II) anti-ZIKV complexes) generally displayed enhanced activity compared to their respective ligands, with some compounds outperforming the reference antiviral, ribavirin. The Time of Addition assay suggested that while some compounds interfere with both viral entry (with a virucidal component) and replication phases, other only acted in replication phases. These results together with molecular modeling studies on ZIKV Envelope protein and ZIKV NS2B-NS3 offered insights for their mode of actions and further optimizations.

RESUMO

The Zika virus (ZIKV) epidemic declared in Brazil between 2015 and 2016 was associated with an increased prevalence of severe congenital malformations, including microcephaly. The distribution of microcephaly cases was not uniform across the country, with a disproportionately higher incidence in the Northeast region (NE). Our previous work demonstrated that saxitoxin (STX), a toxin present in the drinking water reservoirs of the NE, exacerbated the damaging effects of ZIKV on the developing brain. We hypothesized that the impact of STX might vary among different neural cell types. While ZIKV infection caused severe damages on astrocytes and neural stem cells (NSCs), the addition of STX did not exacerbate these effects. We observed that neurons subjected to STX exposure were more prone to apoptosis and displayed higher ZIKV infection rate. These findings suggest that STX exacerbates the harmful effects of ZIKV on neurons, thereby providing a plausible explanation for the heightened severity of ZIKV-induced congenital malformations observed in Brazil's NE. This study highlights the importance of understanding the interactive effects of environmental toxins and infectious pathogens on neural development, with potential implications for public health policies.