Syrian Hamsters Model Does Not Reflect Human-like Disease after Aerosol Exposure to Encephalitic Alphaviruses.

Venezuelan (VEE), eastern (EEE), and western (WEE) equine encephalitis viruses are encephalitic New World alphaviruses that cause periodic epizootic and epidemic outbreaks in horses and humans that may cause severe morbidity and mortality. Currently there are no FDA-licensed vaccines or effective antiviral therapies. Each year, there are a limited number of human cases of encephalitic alphaviruses; thus, licensure of a vaccine or therapeutic would require approval under the FDA animal rule. Approval under the FDA animal rule requires the disease observed in the animal model to recapitulate what is observed in humans. Currently, initial testing of vaccines and therapeutics is performed in the mouse model. Unfortunately, alphavirus disease manifestations in a mouse do not faithfully recapitulate human disease; the VEEV mouse model is lethal whereas in humans VEEV is rarely lethal. In an effort to identify a more appropriate small animal model, we evaluated hamsters in an aerosol exposure model of encephalitic alphavirus infection. The pathology, lethality, and viremia observed in the infected hamsters was inconsistent with what is observed in NHP models and humans. These data suggest that hamsters are not an appropriate model for encephalitic alphaviruses to test vaccines or potential antiviral therapies.

Safety and immunogenicity of a novel trivalent recombinant MVA-based equine encephalitis virus vaccine: A Phase 1 clinical trial.

BACKGROUND: Three encephalitic alphaviruses-western, eastern, and Venezuelan equine encephalitis virus (WEEV, EEEV and VEEV)-can cause severe disease and have the potential to be used as biological weapons. There are no approved vaccines for human use. A novel multivalent MVA-BN-WEV vaccine encodes the envelope surface proteins of the 3 viruses and is thereby potentially able to protect against them all, as previously demonstrated in animal models. This first-in-human study assessed the safety, tolerability, and immunogenicity of MVA-BN-WEV vaccine in healthy adult participants. METHODS: Forty-five participants were enrolled into 3 dose groups (1 × 10E7 Inf.U, 1 × 10E8 Inf.U, and 2 × 10E8 Inf.U), received 2 doses 4 weeks apart, and were then monitored for 6 months. RESULTS: The safety profile of MVA-BN-WEV was acceptable at all administered doses, with incidence of local solicited AEs increased with increasing dose and no other clinically meaningful differences between dose groups. One SAE (Grade 2 pleural effusion) was reported in the lowest dose group and assessed as possibly related. No AEs resulted in death or led to withdrawal from the second vaccination or from the trial. The most common local solicited AE was injection site pain, and general solicited AEs were headache, fatigue, and myalgia. MVA-BN-WEV induced humoral immune responses; WEEV-, EEEV- and VEEV-specific neutralizing antibody responses peaked 2 weeks following the second vaccination, and the magnitude of these responses increased with dose escalation. The highest dose resulted in seroconversion of all (100 %) participants for WEEV and VEEV and 92.9 % for EEEV, 2 weeks following second vaccination, and durability was observed for 6 months. MVA-BN-WEV induced cellular immune responses to VEEV E1 and E2 (EEEV and WEEV not tested) and a dose effect for peptide pool E2. CONCLUSION: The study demonstrated that MVA-BN-WEV is well tolerated, induces immune responses, and is suitable for further development. CLINICAL TRIAL REGISTRY NUMBER: NCT04131595.

Current and future potential distribution of Culex (Melanoconion) (Diptera: Culicidae) of public health interest in the Neotropics.

Anthropogenic activities are altering ecosystem stability and climate worldwide, which is disturbing and shifting arbovirus vector distributions. Although the overall geographic range of some epidemiologically important species is recognized, the spatiotemporal variation for other species in the context of climate change remains poorly understood. Here we predict the current potential distribution of 9 species of Culex (Melanoconion) based on an ecological niche modeling (ENM) approach and assess spatiotemporal variation in future climate change in the Neotropics. The most important environmental predictors were the mean temperature of the warmest season (27 °C), precipitation during the driest month (50 mm), and precipitation during the warmest season (>200 mm). The best current model for each species was transferred to the future general circulation model IPSL-CM6A-LR, using 2 shared socioeconomic pathway scenarios (ssp1-2.6, ssp5-8.5). Under both scenarios of climatic change, an expansion of suitable areas can be observed followed by a strong reduction for the medium-long future under the worst scenario. The multivariate environmental similarity surface analysis indicated future novel climates outside the current range. However, none of the species would occur in those areas. Even if many challenges remain in improving methods for forecasting species responses to global climate change and arbovirus transmission, ENM has strong potential to be applied to the geographic characterization of these systems. Our study can be used for the monitoring of Culex (Melanoconion) species populations and their associated arboviruses, contributing to develop region-specific public health surveillance programs.

Clinical and epidemiological characteristics of Madariaga and Venezuelan equine encephalitis virus infections.

Madariaga virus (MADV) and Venezuelan equine encephalitis virus (VEEV) are emerging arboviruses affecting rural and remote areas of Latin America. However, there are limited clinical and epidemiological reports available, and outbreaks are occurring at an increasing frequency. We addressed this gap by analyzing all the available clinical and epidemiological data of MADV and VEEV infections recorded since 1961 in Panama. A total of 168 of human alphavirus encephalitis cases were detected in Panama from 1961 to 2023. Here we describe the clinical signs and symptoms and epidemiological characteristics of these cases, and also explored signs and symptoms as potential predictors of encephalitic alphavirus infection when compared to those of other arbovirus infections occurring in the region. Our results highlight the challenges clinical diagnosis of alphavirus disease in endemic regions with overlapping circulation of multiple arboviruses.

Measuring Anxiety Among Latino Immigrant Populations: Within-Country and Between-Country Comparisons.

Anxiety is the most prevalent mental health disorder among adults worldwide. Given its increased prevalence among migrants due to their marginalized position in the societies where they reside, psychometric evaluations of anxiety measures such as the Generalized Anxiety Disorder-7 (GAD-7) are needed for use with migrants. The present study is the first attempt to compare the structure of GAD-7 scores for (a) different Latino groups in the same country and (b) the same Latino group in two different countries. Using three samples of Mexican and Venezuelan migrants (total N = 933), we provide reliability and validity evidence of the GAD-7 for use with adult Latino migrants. Utilizing confirmatory factor analysis and item response theory, we demonstrate that the GAD-7 is internally consistent, possesses a strong single-factor structure, and generates scores with equivalent psychometric properties. GAD-7 is appropriate for use with Mexican and Venezuelan migrants across differing gender groups and education levels.

Therapeutic efficacy of a potent anti-Venezuelan equine encephalitis virus antibody is contingent on Fc effector function.

The development of specific, safe, and potent monoclonal antibodies (Abs) has led to novel therapeutic options for infectious disease. In addition to preventing viral infection through neutralization, Abs can clear infected cells and induce immunomodulatory functions through engagement of their crystallizable fragment (Fc) with complement proteins and Fc receptors on immune cells. Little is known about the role of Fc effector functions of neutralizing Abs in the context of encephalitic alphavirus infection. To determine the role of Fc effector function in therapeutic efficacy against Venezuelan equine encephalitis virus (VEEV), we compared the potently neutralizing anti-VEEV human IgG F5 (hF5) Ab with intact Fc function (hF5-WT) or containing the loss of function Fc mutations L234A and L235A (hF5-LALA) in the context of VEEV infection. We observed significantly reduced binding to complement and Fc receptors, as well as differential in vitro kinetics of Fc-mediated cytotoxicity for hF5-LALA compared to hF5-WT. The in vivo efficacy of hF5-LALA was comparable to hF5-WT at -24 and + 24 h post infection, with both Abs providing high levels of protection. However, when hF5-WT and hF5-LALA were administered + 48 h post infection, there was a significant decrease in the therapeutic efficacy of hF5-LALA. Together these results demonstrate that optimal therapeutic Ab treatment of VEEV, and possibly other encephalitic alphaviruses, requires neutralization paired with engagement of immune effectors via the Fc region.

Defining the Cynomolgus Macaque (Macaca fascicularis) Animal Model for Aerosolized Venezuelan Equine Encephalitis: Importance of Challenge Dose and Viral Subtype.

Venezuelan equine encephalitis virus (VEEV) outbreaks occur sporadically. Additionally, VEEV has a history of development as a biothreat agent. Yet, no FDA-approved vaccine or therapeutic exists for VEEV disease. The sporadic outbreaks present a challenge for testing medical countermeasures (MCMs) in humans; therefore, well-defined animal models are needed for FDA Animal Rule licensure. The cynomolgus macaque (CM) model has been studied extensively at high challenge doses of the VEEV Trinidad donkey strain (>1.0 × 108 plaque-forming units [PFU]), doses that are too high to be a representative human dose. Based on viremia of two subtypes of VEEV, IC, and IAB, we found the CM infectious dose fifty (ID50) to be low, 12 PFU, and 6.7 PFU, respectively. Additionally, we characterized the pattern of three clinical parameters (viremia, temperature, and lymphopenia) across a range of doses to identify a challenge dose producing consistent signs of infection. Based on these studies, we propose a shift to using a lower challenge dose of 1.0 × 103 PFU in the aerosol CM model of VEEV disease. At this dose, NHPs had the highest viremia, demonstrated a fever response, and had a measurable reduction in complete lymphocyte counts-biomarkers that can demonstrate MCM efficacy.

Real-time RT-PCR for Venezuelan equine encephalitis complex, Madariaga, and Eastern equine encephalitis viruses: application in human and mosquito public health surveillance in Panama.

Eastern equine encephalitis virus (EEEV), Madariaga virus (MADV), and Venezuelan equine encephalitis virus complex (VEEV) are New World alphaviruses transmitted by mosquitoes. They cause febrile and sometimes severe neurological diseases in human and equine hosts. Detecting them during the acute phase is hindered by non-specific symptoms and limited diagnostic tools. We designed and clinically assessed real-time reverse transcription polymerase chain reaction assays (rRT-PCRs) for VEEV complex, MADV, and EEEV using whole-genome sequences. Validation involved 15 retrospective serum samples from 2015 to 2017 outbreaks, 150 mosquito pools from 2015, and 118 prospective samples from 2021 to 2022 surveillance in Panama. The rRT-PCRs detected VEEV complex RNA in 10 samples (66.7%) from outbreaks, with one having both VEEV complex and MADV RNAs. VEEV complex RNA was found in five suspected dengue cases from disease surveillance. The rRT-PCR assays identified VEEV complex RNA in three Culex (Melanoconion) vomerifer pools, leading to VEEV isolates in two. Phylogenetic analysis revealed the VEEV ID subtype in positive samples. Notably, 11.9% of dengue-like disease patients showed VEEV infections. Together, our rRT-PCR validation in human and mosquito samples suggests that this method can be incorporated into mosquito and human encephalitic alphavirus surveillance programs in endemic regions.

Alphavirus-based replicons demonstrate different interactions with host cells and can be optimized to increase protein expression.

IMPORTANCE: Alphavirus replicons are being developed as self-amplifying RNAs aimed at improving the efficacy of mRNA vaccines. These replicons are convenient for genetic manipulations and can express heterologous genetic information more efficiently and for a longer time than standard mRNAs. However, replicons mimic many aspects of viral replication in terms of induction of innate immune response, modification of cellular transcription and translation, and expression of nonstructural viral genes. Moreover, all replicons used in this study demonstrated expression of heterologous genes in cell- and replicon's origin-specific modes. Thus, many aspects of the interactions between replicons and the host remain insufficiently investigated, and further studies are needed to understand the biology of the replicons and their applicability for designing a new generation of mRNA vaccines. On the other hand, our data show that replicons are very flexible expression systems, and additional modifications may have strong positive impacts on protein expression.

Examining healthcare needs and decisions to seek health services among Venezuelan migrants living in Trinidad and Tobago using Andersen's Behavioral Model.

Introduction: Beginning in 2016, Trinidad and Tobago experienced increasing flows of migrants and refugees from Venezuela. Through a Government Registration Exercise in 2019, followed by a Re-registration Exercise in 2020, migrants and refugees benefitted from access to publicly available primary care and emergency medical services. By applying Andersen's Behavioral Model for Health Service Use, our study examined the non-communicable disease care needs of migrants, and factors influencing their decision to seek public and private health services. Method: Between September and December 2020, a health questionnaire was administered via telephone to n = 250 migrants from Venezuela. Descriptive statistics summarized the constructs of Andersen's Behavioral Model. The model comprised of predisposing factors including migrants' social characteristics; enabling factors namely monthly earnings, education level and most trusted source of information on medical needs; need for care factors such as migrants self-reported health status, presence of non-communicable health conditions and having visited a doctor in the past 12 months; and the outcome variables which were migrants' decisions to seek public and private health services. Pearson χ2 tests, odds ratios and multivariable logistic regression with backward elimination examined the factors influencing a migrant's decision to seek health services. Results: Overall, 66.8% of migrants reported they would seek public health services, while 22.4% indicated they would seek private health services. Predisposing factors namely length of time residing in Trinidad and Tobago (p = 0.031) and living with family/friends (p = 0.049); the enabling factor of receiving information from publicly available sources (p = 0.037); and the need for care factor of visiting a doctor for a physical health problem (p = 0.010) were significant correlates of their decision to seek care in the public sector. Predisposing factors namely living with family/friends (p = 0.020) and the enabling factor of having difficulty accessing healthcare services (p = 0.045) were significant correlates of their decision to seek care from private providers. Discussion: Our findings demonstrated the positive association between social networks and a migrant's decision to use public and private health services, thus underscoring the importance of family and friends in facilitating health service use, promoting proper health practices and preventing diseases. Overall, the use of Andersen's Behavioral Model aided in identifying the factors associated with the use of health services by Venezuelan migrants in Trinidad and Tobago. However, further studies are needed to better understand their need for ongoing care, to inform policy, and to plan targeted health interventions for addressing the gaps in health service access, barriers and use.

Migration Status and Utilization of Healthcare Services Among Venezuelan Immigrants in Peru.

BACKGROUND: In general, migrants in illegal situations encounter a greater barrier to accessing medical care because of their migration status due to not having the required documentation to be able to obtain insurance in the receiving country. OBJECTIVE: To evaluate the association between migration status and the use of health services in the Venezuelan population residing in Peru. METHODS: Data from the second Survey Directed to the Venezuelan Population Residing in Peru (ENPOVE) of 2022 were analyzed. The dependent variable was use of health services in the last month. The exposure variable was migration status (legal/illegal). Generalized linear models of the Poisson family with link log function were used to obtain crude and adjusted prevalence ratios (aPR), for potential confounding variables. Additionally, we evaluated the association of interest, stratified by gender. FINDINGS: Data from 1569 migrants were analyzed. Participants with illegal migration status represented 32.4% (men: 24.3%; women: 36.7%); likewise, 58.1% did not use health services. Illegal migration status was associated with lower health care use (aPR: 0.75; 95%CI: 0.61-0.92). Likewise, after stratifying by sex, the association was maintained only in male migrants (aPR: 0.53; 95%CI: 0.39-0.82) but not in women (aPR: 0.84; 95%CI: 0.67-1.05). CONCLUSION: 58.1% of Venezuelan migrants in Peru did not seek medical attention despite having health problems. Having an illegal immigration status leads to a lower probability of using these services, especially in men.

Deep spatial profiling of Venezuelan equine encephalitis virus reveals increased genetic diversity amidst neuroinflammation and cell death during brain infection.

Venezuelan equine encephalitis virus (VEEV) causes a febrile illness that can progress to neurological disease with the possibility of death in human cases. The evaluation and optimization of therapeutics that target brain infections demands knowledge of the host's response to VEEV, the dynamics of infection, and the potential for within-host evolution of the virus. We hypothesized that selective pressures during infection of the brain may differ temporally and spatially and so we investigated the dynamics of the host response, viral transcript levels, and genetic variation of VEEV TC-83 in eight areas of the brain in mice over 7 days post-infection (dpi). Viral replication increased throughout the brain until 5-6 dpi and decreased thereafter with neurons as the main site of viral replication. Low levels of genetic diversity were noted on 1 dpi and were followed by an expansion in the genetic diversity of VEEV and nonsynonymous (Ns) mutations that peaked by 5 dpi. The pro-inflammatory response and the influx of immune cells mirrored the levels of virus and correlated with substantial damage to neurons by 5 dpi and increased activation of microglial cells and astrocytes. The prevalence and dynamics of Ns mutations suggest that the VEEV is under selection within the brain and that progressive neuroinflammation may play a role in acting as a selective pressure. IMPORTANCE Treatment of encephalitis in humans caused by Venezuelan equine encephalitis virus (VEEV) from natural or aerosol exposure is not available, and hence, there is a great interest to address this gap. In contrast to natural infections, therapeutic treatment of infections from aerosol exposure will require fast-acting drugs that rapidly penetrate the blood-brain barrier, engage sites of infection in the brain and mitigate the emergence of drug resistance. Therefore, it is important to understand not only VEEV pathogenesis, but the trafficking of the viral population within the brain, the potential for within-host evolution of the virus, and how VEEV might evolve resistance.

Polimorfismo de proteína 5, 10-metilentetrahidrofolatoreductasa en población venezolana / Polymorphisms proteína 5, 10-metilentetrahidrofolatoreductasa in venezuelan people

El folato es un miembro del grupo de la vitamina B y está relacionado con enfermedades crónicas como anemia megaloblástica, enfermedad cardiovascular, cáncer, disfunción cognitiva y riesgo de defectos del tubo neural. La proteína 5,10-metilentetrahidrofolato reductasa (MTHFR) juega un papel clave en el metabolismo del folato mediante la síntesis de nucleótidos y reacciones de metilación. El gen MTHFR se encuentra en el cromosoma 1 (1p36.3), y se han descrito dos alelos comunes, el alelo C677T (termolábil) y el alelo A1298C.El objetivo de este estudio es evaluar la distribución de los polimorfismos genéticos en MTHFR C677T y A1298C en la población venezolana. METODOS: estudio de tipo transversal, descriptivo, experimental y correlacional Las muestras de sangre se colectaron en 314 donantes no emparentados y sanos de la población. Los polimorfismos de un solo nucleótido(SNP) MTHFR 677C>T y 1298A>C se analizaron mediante polimorfismo de longitud de fragmento de restricción de reacción en cadena de polimerasa (PCR-RFLP). El desequilibrio de ligamiento (LD) entre pares de SNP se calculó mediante la prueba X. usando Prism 5 (GraphPad software, Inc). RESULTADOS: Encontramos mayor frecuencia genotípica de heterocigotos para el polimorfismo MTHFR C677T en la población general venezolana, con excepción del grupo caucásico. El polimorfismo MTHFR A1298C en el 70%de la población de estudio es homocigoto de tipo salvaje, encontrándose una baja frecuencia de homocigoto mutado. CONCLUSIONES: Se encontraron diferencias significativas entre grupos étnicos, destacando la importancia del genotipado racial de estos polimorfismos en la población venezolana(AU)

Folate is a member of the vitamin B and it has also been indicated that may be related to chronic diseases such as megaloblastic anemia, cardiovascular disease, cognitive dysfunction and risk of neural tube. Methylenetetrahydro folatereductase (MTHFR) is a key enzyme of folate pathway by nucleotide synthesis and methylation reactions. Several polymorphisms were reported in MTHFR gene but C677Tand A1298 polymorphism are most studied and these have been reported to be risk factor for several diseases/disorders. The present study was designed to determine the frequency of MTHFR polymorphisms in Venezuelan healthy population. METHODS: The blood samples were collected from 314 unrelated and healthy donors from population. Both the MTHFR 677C>T and 1298A>C single nucleotide polymorphisms (SNPs) were analyzed by Polymerase chainreaction-restriction fragment length polymorphism (PCR-RFLP). Linkage disequilibrium (LD) between pair of SNPs was calculated through the .. test using Prism 5 (GraphPad sftoware, Inc). RESULTS: We find higher genotypic frequency of heterozygotes for the MTHFR C677T polymorphism in the Venezuelan general population, with the exception of the Caucasian group. MTHFR A1298C polymorphism in 70%of the study population is homozygous wild type, finding alow frequency of homozygous mutated. CONCLUSIONS: Significant differences between ethnic groups were found,highlighting the importance of racial genotyping of these polymorphisms in the Venezuelan population(AU)

Interferon inhibits a model RNA virus via a limited set of inducible effector genes.

Interferons control viral infection by inducing the expression of antiviral effector proteins encoded by interferon-stimulated genes (ISGs). The field has mostly focused on identifying individual antiviral ISG effectors and defining their mechanisms of action. However, fundamental gaps in knowledge about the interferon response remain. For example, it is not known how many ISGs are required to protect cells from a particular virus, though it is theorized that numerous ISGs act in concert to achieve viral inhibition. Here, we used CRISPR-based loss-of-function screens to identify a markedly limited set of ISGs that confer interferon-mediated suppression of a model alphavirus, Venezuelan equine encephalitis virus (VEEV). We show via combinatorial gene targeting that three antiviral effectors-ZAP, IFIT3, and IFIT1-together constitute the majority of interferon-mediated restriction of VEEV, while accounting for < 0.5% of the interferon-induced transcriptome. Together, our data suggest a refined model of the antiviral interferon response in which a small subset of "dominant" ISGs may confer the bulk of the inhibition of a given virus.

Mutations in the non-structural protein coding region regulate gene expression from replicon RNAs derived from Venezuelan equine encephalitis virus.

Self-replicating RNA (repRNA) derived from Venezuelan equine encephalitis (VEE) virus is a promising platform for gene therapy and confers prolonged gene expression due to its self-replicating capability, but repRNA suffers from a suboptimal transgene expression level due to its induction of intracellular innate response which may result in inhibition of translation. To improve transgene expression of repRNA, we introduced point mutations in the non-structural protein 1-4 (nsP1-4) coding region of VEE replicon vectors. As a proof of concept, inflammatory cytokines served as genes of interest and were cloned in their wild type and several mutant replicon vectors, followed by transfection in mammalian cells. Our data show that VEE replicons bearing nsP1GGAC-nsP2T or nsP1GGAC-nsP2AT mutations in the nsP1-4 coding region could significantly reduce the recognition by innate immunity as evidenced by the decreased production of type I interferon, and enhance transgene expression in host cells. Thus, the newly discovered mutant VEE replicon vectors could serve as promising gene expression platforms to advance VEE-derived repRNA-based gene therapies.

Tumour Necrosis Factor-α, Chemokines, and Leukocyte Infiltrate Are Biomarkers for Pathology in the Brains of Venezuelan Equine Encephalitis (VEEV)-Infected Mice.

Venezuelan equine encephalitis virus (VEEV) is a disease typically confined to South and Central America, whereby human disease is characterised by a transient systemic infection and occasionally severe encephalitis, which is associated with lethality. Using an established mouse model of VEEV infection, the encephalitic aspects of the disease were analysed to identify biomarkers associated with inflammation. Sequential sampling of lethally challenged mice (infected subcutaneously) confirmed a rapid onset systemic infection with subsequent spread to the brain within 24 h of the challenge. Changes in inflammatory biomarkers (TNF-α, CCL-2, and CCL-5) and CD45+ cell counts were found to correlate strongly to pathology (R>0.9) and present previously unproven biomarkers for disease severity in the model, more so than viral titre. The greatest level of pathology was observed within the olfactory bulb and midbrain/thalamus. The virus was distributed throughout the brain/encephalon, often in areas not associated with pathology. The principal component analysis identified five principal factors across two independent experiments, with the first two describing almost half of the data: (1) confirmation of a systemic Th1-biased inflammatory response to VEEV infection, and (2) a clear correlation between specific inflammation of the brain and clinical signs of disease. Targeting strongly associated biomarkers of deleterious inflammation may ameliorate or even eliminate the encephalitic syndrome of this disease.

Necesidades en salud sexual y reproductiva en mujeres migrantes venezolanas

Objetivo . Conocer las necesidades en salud sexual y reproductiva de la población venezolana migrante residente en Lima y Trujillo. Métodos . La muestra estuvo constituida por 1,616 mujeres, de ellas 1,114 mujeres del cono sur de Lima y 502 mujeres de la provincia de Trujillo, a quienes se les aplicó una encuesta para evaluar las siguientes dimensiones: características poblacionales, requerimientos de servicios de salud, salud materna, planificación familiar, prevención del cáncer de cuello uterino y mama e infecciones de transmisión sexual. Resultados . La mayoría de las mujeres venezolanas tenía entre 20 y 34 años. Contaban con cédula de identidad en un 66,8%; sin embargo, en 60% el documento no se encontraba vigente y más del 80% no tenía regularizada su condición migratoria. El estado conviviente correspondía a 46% y soltera a 40,8%. El 56,7% de las encuestadas indicó tener estudios secundarios; el 82,2% tenía un ingreso mensual familiar menor de 900 soles; el 75,1% en Lima y el 94% en Trujillo refirió no contar con algún tipo de seguro. Solo el 48% usaba algún método anticonceptivo, preferentemente los métodos anticonceptivos reversibles de larga duración. Entre 78% y 85,1% no hacía uso de servicios de prevención del cáncer de cuello uterino y más del 90% no lo hacía para prevención de cáncer de mama. Las infecciones de transmisión sexual estuvieron presentes en 2 y 5% de la población encuestada, respectivamente. Conclusión . El perfil de salud sexual y reproductiva (SSR) de la población migrante venezolana de las zonas de estudio tuvieron sus características propias no comparables con la vulnerabilidad de la población peruana, y revela que en ellas existen necesidades en SSR que requieren ser atendidas.

Objective : To determine the sexual and reproductive health needs of the Venezuelan migrant population residing in Lima and Trujillo. Methods : The sample consisted of 1,616 women, including 1,114 women from the southern cone of Lima and 502 women from the province of Trujillo. A survey was applied to evaluate the following dimensions: population characteristics, health service requirements, maternal health, family planning, cervical and breast cancer prevention, and sexually transmitted infections. Results : Most of the Venezuelan women were between 20-34 years old. They had an identity card in 66.8%; however, 60% of them did not have a valid document and more than 80% did not have their migratory status regularized. 46% were cohabiters and 40.8% were single. 56.7% reported having secondary education. 82.2% had a monthly family income of less than 900 soles; 75.1% in Lima and 94% in Trujillo reported not having any type of insurance. Only 48% used any contraceptive method, preferably long-acting reversible contraceptive methods. Between 78%85.1% did not use cervical cancer prevention services and more than 90% did not use breast cancer prevention services. Sexually transmitted infections were present in 2 and 5% of the surveyed population. Conclusion : The sexual and reproductive health (SRH) profile of the Venezuelan migrant population in the study areas had its own characteristics that was not comparable with the vulnerability of the Peruvian population, and reveals that they have SRH needs that require attention.

Inhibitors of the Ubiquitin-Mediated Signaling Pathway Exhibit Broad-Spectrum Antiviral Activities against New World Alphaviruses.

New World alphaviruses including Venezuelan Equine Encephalitis Virus (VEEV) and Eastern Equine Encephalitis Virus (EEEV) are mosquito-transmitted viruses that cause disease in humans and equines. There are currently no FDA-approved therapeutics or vaccines to treat or prevent exposure-associated encephalitic disease. The ubiquitin proteasome system (UPS)-associated signaling events are known to play an important role in the establishment of a productive infection for several acutely infectious viruses. The critical engagement of the UPS-associated signaling mechanisms by many viruses as host-pathogen interaction hubs led us to hypothesize that small molecule inhibitors that interfere with these signaling pathways will exert broad-spectrum inhibitory activity against alphaviruses. We queried eight inhibitors of the UPS signaling pathway for antiviral outcomes against VEEV. Three of the tested inhibitors, namely NSC697923 (NSC), bardoxolone methyl (BARM) and omaveloxolone (OMA) demonstrated broad-spectrum antiviral activity against VEEV and EEEV. Dose dependency and time of addition studies suggest that BARM and OMA exhibit intracellular and post-entry viral inhibition. Cumulatively, our studies indicate that inhibitors of the UPS-associated signaling pathways exert broad-spectrum antiviral outcomes in the context of VEEV and EEEV infection, supporting their translational application as therapeutic candidates to treat alphavirus infections.

Mapping Eastern (EEE) and Venezuelan Equine Encephalitides (VEE) among Equines Using Geographical Information Systems, Colombia, 2008-2019.

INTRODUCTION: Eastern equine encephalitis virus (EEEV) and Venezuelan equine encephalitis virus (VEEV) viruses are zoonotic pathogens affecting humans, particularly equines. These neuroarboviruses compromise the central nervous system and can be fatal in different hosts. Both have significantly influenced Colombia; however, few studies analyse its behaviour, and none develop maps using geographic information systems to characterise it. OBJECTIVE: To describe the temporal-spatial distribution of those viruses in Colombia between 2008 and 2019. METHODS: Retrospective cross-sectional descriptive study, based on weekly reports by municipalities of the ICA, of the surveillance of both arboviruses in equines, in Colombia, from 2008 to 2019. The data were converted into databases in Microsoft Access 365®, and multiple epidemiological maps were generated with the Kosmo RC1®3.0 software coupled to shape files of all municipalities in the country. RESULTS: In the study period, 96 cases of EEE and 70 of VEE were reported, with 58% of EEE cases occurring in 2016 and 20% of EEV cases in 2013. The most affected municipalities for EEE corresponded to the department of Casanare: Yopal (20), Aguazul (16), and Tauramena (10). In total, 40 municipalities in the country reported ≥1 case of EEE. CONCLUSIONS: The maps allow a quick appreciation of groups of neighbouring municipalities in different departments (1° political division) and regions of the country affected by those viruses, which helps consider the expansion of the disease associated with mobility and transport of equines between other municipalities, also including international borders, such as is the case with Venezuela. In that country, especially for EEV, municipalities in the department of Cesar are bordering and at risk for that arboviral infection. there is a high risk of equine encephalitis outbreaks, especially for VEE. This poses a risk also, for municipalities in the department of Cesar, bordering with Venezuela.

Arboviruses in Mammals in the Neotropics: A Systematic Review to Strengthen Epidemiological Monitoring Strategies and Conservation Medicine.

Arthropod-borne viruses (arboviruses) are a diverse group of ribonucleic acid (RNA) viruses, with the exception of African swine fever virus, that are transmitted by hematophagous arthropods to a vertebrate host. They are the important cause of many diseases due to their ability to spread in different environments and their diversity of vectors. Currently, there is no information on the geographical distribution of the diseases because the routes of transmission and the mammals (wild or domestic) that act as potential hosts are poorly documented or unknown. We conducted a systematic review from 1967 to 2021 to identify the diversity of arboviruses, the areas, and taxonomic groups that have been monitored, the prevalence of positive records, and the associated risk factors. We identified forty-three arboviruses in nine mammalian orders distributed in eleven countries. In Brazil, the order primates harbor the highest number of arbovirus records. The three most recorded arboviruses were Venezuelan equine encephalitis, Saint Louis encephalitis and West Nile virus. Serum is the most used sample to obtain arbovirus records. Deforestation is identified as the main risk factor for arbovirus transmission between different species and environments (an odds ratio of 1.46 with a 95% confidence interval: 1.34-1.59). The results show an increase in the sampling effort over the years in the neotropical region. Despite the importance of arboviruses for public health, little is known about the interaction of arboviruses, their hosts, and vectors, as some countries and mammalian orders have not yet been monitored. Long-term and constant monitoring allows focusing research on the analysis of the interrelationships and characteristics of each component animal, human, and their environment to understand the dynamics of the diseases and guide epidemiological surveillance and vector control programs. The biodiversity of the Neotropics should be considered to support epidemiological monitoring strategies.