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The mosquito midgut functions as a key interface between pathogen and vector. However, studies of midgut physiology and virus infection dynamics are scarce, and in Culex tarsalis—an extremely efficient vector of West Nile virus (WNV)—nonexistent. We performed single-cell RNA sequencing on Cx. tarsalis midguts, defined multiple cell types, and determined whether specific cell types are more permissive to WNV infection. We identified 20 cell states comprising 8 distinct cell types, consistent with existing descriptions of Drosophila and Aedes aegypti midgut physiology. Most midgut cell populations were permissive to WNV infection. However, there were higher levels of WNV RNA (vRNA) in enteroendocrine cells, suggesting enhanced replication in this population. In contrast, proliferating intestinal stem cells (ISC) had the lowest levels of vRNA, a finding consistent with studies suggesting ISC proliferation in the midgut is involved in infection control. ISCs were also found to have a strong transcriptional response to WNV infection; genes involved in ribosome structure and biogenesis, and translation were significantly downregulated in WNV-infected ISC populations. Notably, we did not detect significant WNV-infection induced upregulation of canonical mosquito antiviral immune genes (e.g., AGO2, R2D2, etc.) at the whole-midgut level. Rather, we observed a significant positive correlation between immune gene expression levels and vRNA load in individual cells, suggesting that within midgut cells, high levels of vRNA may trigger antiviral responses. Our findings establish a Cx. tarsalis midgut cell atlas, and provide insight into midgut infection dynamics of WNV by characterizing cell-type specific enhancement/restriction of, and immune response to, infection at the single-cell level. Author summary: West Nile virus is the leading cause of mosquito-borne disease in N. America. Cx. tarsalis is a highly competent vector of WNV that plays a central role in the transmission and maintenance of WNV in nature. It is hypothesized that the permissibility of mosquito midgut cells contributes to the midgut infection barrier and thus impacts the ability of pathogens to establish infection in a mosquito. Additionally, it is postulated that the midgut is the most important organ with respect to determining vector competence. The recent publication of the full Cx. tarsalis genome, in conjunction with the growing body of work demonstrating the successful application of single-cell RNA sequencing methodologies in insect models made it possible for us to examine the cellular composition of the Cx. tarsalis midgut, and WNV infection dynamics therein, at single-cell resolution. We found cell-type-specific differences in viral RNA levels suggesting variability in WNV replication efficiency in specific cell types, identified patterns of differential expression associated with WNV infection in specific cell populations, and characterized aspects of the innate immune response to WNV infection at the tissue and cellular level. [ABSTRACT FROM AUTHOR]

Patients with severe West Nile virus and SARS-CoV-2 infections deserve accurate diagnosis of underlying diseases, determining possible anti-interferon autoantibody production, since they must receive antiviral and immunological therapies to enhance antiviral response. The current study aimed to investigate determinants of severity in a previously healthy patient who experienced 2 life-threatening infections, from West Nile Virus (WNV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). During coronavirus disease 2019 (COVID-19) hospitalization he was diagnosed with a thymoma, retrospectively identified as already present at the time of WNV infection. Heterozygosity for p.Pro554Ser in the TLR3 gene, which increases susceptibility to severe COVID-19, and homozygosity for CCR5 c.554_585del, associated with severe WNV infection, were found. Neutralizing anti-interferon (IFN)-α and anti-IFN-ω autoantibodies were detected, likely induced by the underlying thymoma and increasing susceptibility to both severe COVID-19 pneumonia and West Nile encephalitis. [ABSTRACT FROM AUTHOR]

Neuroinvasive West Nile Virus disease (WNND) can cause lasting cognitive and motor impairments, impacting autonomy and quality of life. Given the scarcity of research on the rehabilitative needs of patients with WNV infection, this study aims to fill a critical gap by assessing the rehabilitation needs of a real-world cohort of WNND patients. We retrospectively analyzed WNND patients who received early Physical Medicine and Rehabilitation (PMR) evaluations during the 2022 outbreak in Veneto, Italy. Data included demographics, comorbidities, length of hospital stay, days at PMR evaluation, and rehabilitation duration until discharge or death, alongside objective examination findings and Barthel Index scores. Among 29 confirmed WNND patients, the median hospital stay was 20 days, with rehabilitation starting after a median of 7 days. Motor weakness affected 48.28% of patients, swallowing issues 6.90%, and respiratory issues 24.13%. A tailored rehabilitation protocol was designed for 96.55% of patients to address functional concerns and prevent complications. Barthel Index scores showed no significant change. Discharge settings were home (58.34%), other departments (25%), and rehabilitation facilities (16.67%). This study highlights the rehabilitation needs of WNND patients, particularly regarding neuromuscular deficits, swallowing, and respiratory issues, stressing the importance of a comprehensive rehabilitation strategy for improved outcomes. [ABSTRACT FROM AUTHOR]

Mosquito-borne flaviviruses represent a public health challenge due to the high-rate endemic infections, severe clinical outcomes, and the potential risk of emerging global outbreaks. Flavivirus disease pathogenesis converges on cellular factors from vectors and hosts, and their interactions are still unclear. Exosomes and microparticles are extracellular vesicles released from cells that mediate the intercellular communication necessary for maintaining homeostasis; however, they have been shown to be involved in disease establishment and progression. This review focuses on the roles of extracellular vesicles in the pathogenesis of mosquito-borne flavivirus diseases: how they contribute to viral cycle completion, cell-to-cell transmission, and cellular responses such as inflammation, immune suppression, and evasion, as well as their potential use as biomarkers or therapeutics (antiviral or vaccines). We highlight the current findings concerning the functionality of extracellular vesicles in different models of dengue virus, Zika virus, yellow fever virus, Japanese encephalitis virus, and West Nile virus infections and diseases. The available evidence suggests that extracellular vesicles mediate diverse functions between hosts, constituting novel effectors for understanding the pathogenic mechanisms of flaviviral diseases. [ABSTRACT FROM AUTHOR]

Flaviviruses are a diverse group of viruses primarily transmitted through hematophagous insects like mosquitoes and ticks. Significant expansion in the geographic range, prevalence, and vectors of flavivirus over the last 50 years has led to a dramatic increase in infections that can manifest as hemorrhagic fever or encephalitis, leading to prolonged morbidity and mortality. Millions of infections every year pose a serious threat to worldwide public health, encouraging scientists to develop a better understanding of the pathophysiology and immune evasion mechanisms of these viruses for vaccine development and antiviral therapy. Extensive research has been conducted in developing effective antivirals for flavivirus. Various approaches have been extensively utilized in clinical trials for antiviral development, targeting virus entry, replication, polyprotein synthesis and processing, and egress pathways exploiting virus as well as host proteins. However, to date, no licensed antiviral drug exists to treat the diseases caused by these viruses. Understanding the mechanisms of host–pathogen interaction, host immunity, viral immune evasion, and disease pathogenesis is highly warranted to foster the development of antivirals. This review provides an extensively detailed summary of the most recent advances in the development of antiviral drugs to combat diseases. [ABSTRACT FROM AUTHOR]

Central nervous system (CNS) resident memory CD8 T cells (TRM) that express IFN-γ contribute to neurodegenerative processes, including synapse loss, leading to memory impairment. Here, we show that CCR2 signaling in CD8 TRM that persist within the hippocampus after recovery from CNS infection with West Nile virus (WNV) significantly prevents the development of memory impairments. Using CCR2-deficient mice, we determined that CCR2 expression is not essential for CNS T cell recruitment or virologic control during acute WNV infection. However, transcriptomic analyses of forebrain CCR2+ versus CCR2− CD8 TRM during WNV recovery reveal that CCR2 signaling significantly regulates hippocampal CD8 TRM phenotype and function via extrinsic and intrinsic effects, limiting expression of CD103, granzyme A and IFN-γ, respectively, and increasing the percentages of virus-specific CD8 T cells. Consistent with this, WNV-recovered Cd8acreCcr2fl/fl mice exhibit decreased recognition memory. Overall, these data implicate CCR2 signaling in the regulation of CD8 TRM phenotype, including antiviral specificity and IFN-γ expression, highlighing a neuroprotective role for CCR2 in limiting CD8 T cell-mediated neuroinflammation and cognitive deficits, providing insights into potential therapeutic targets for CNS infections. [ABSTRACT FROM AUTHOR]

West Nile virus (WNV) is a mosquito-borne zoonotic flavivirus which often causes asymptomatic infection in humans but may develop into a deadly neuroinvasive disease. In this study, we aimed to investigate variables potentially associated with human WNV infection using human and mosquito WNV surveillance and monitoring datasets, established over 20 years, from 2003 to 2022, across the province of Ontario, Canada. We combined climatic and geographic data, mosquito surveillance data (n = 3010 sites), blood donation arboviral detection testing data in the human population, and demographic and socio-economic data from Canadian population censuses. We hypothesized that spatio-temporal indices related to mosquito vector habitat and phenology, in addition to human demographic and socio-economic factors, were associated with WNV infection in the human population. Our results show that high habitat suitability of the main WNV vector in southerly locations of this region, Cx. pipiens/restuans (IRR = 2.0), and variables related to lower income (IRR = 2.8), and shelter infrastructure spending (IRR = 0.7), were key risk factors associated with WNV infection among blood donors from 2003 to 2022 across Ontario (R2 = 0.67). These results may inform points of entry for practical intervention aimed at reducing risk of mosquito-borne pathogens in Canada. [ABSTRACT FROM AUTHOR]

Arthropod-borne viruses or arboviruses, including West Nile virus (WNV), dengue virus (DENV), and Zika virus (ZIKV) pose significant threats to public health. It is imperative to develop novel methods to control these mosquito-borne viral infections. We previously showed that insulin/insulin-like growth factor-1 signaling (IIS)-dependent activation of ERK and JAK-STAT signaling has significant antiviral activity in insects and human cells. Continuous immune pressure can lead to adaptive mutations of viruses during infection. We aim to elucidate how IIS-signaling in mosquitoes selects for West Nile virus escape variants, to help formulate future transmission blocking strategies. We hypothesize that passage of WNV under activation of IIS will induce adaptive mutations or escape variants in the infecting virus. To test our hypothesis, WNV was serially passaged through Culex quinquefasciatus Hsu cells in the presence or absence of bovine insulin to activate IIS antiviral pressure. We sequenced WNV genes encoding for E, NS2B, NS3, and NS5 and identified variants in E and NS5 arising from IIS antiviral pressure. In parallel to the genetic analyses, we also report differences in the levels of virus replication and Akt activation in human cells and mosquitoes using virus passaged in the presence or absence of insulin. Finally, using adult Culex quinquefasciatus , we demonstrated the enhancement of immune response gene expression in virus-infected mosquitoes fed on insulin, compared to control. Notably, virus collected from insulin-fed mosquitoes contained a non-synonymous mutation in NS3. These results contribute towards achieving our long-term goal of manipulating mosquito IIS-dependent antiviral immunity to reduce WNV or other flavivirus transmission to mammalian hosts. [ABSTRACT FROM AUTHOR]

Upon researching predictive models related toWest Nile virus disease, it is discovered that there are numerous parameters and extensive information in most models, thus contributing to unnecessary complexity. Another challenge frequently encountered is the lead time, which refers to the period for which predictions are made and often is too short. This paper addresses these issues by introducing a parsimonious method based on ICC curves, offering a logistic distribution model derived from the vector-borne SEIR model. Unlike existing models relying on diverse environmental data, our approach exclusively utilizes historical and present infected human cases (number of new cases). With a yearlong lead time, the predictions extend throughout the 12 months, gaining precision as new data emerge. Theoretical conditions are derived to minimize Bayesian loss, enhancing predictive precision. We construct a Bayesian forecasting probability density function using carefully selected prior distributions. Applying these functions, we predict monthspecific infections nationwide, rigorously evaluating accuracy with probabilistic metrics. Additionally, HPD credible intervals at 90%, 95%, and 99% levels is performed. Precision assessment is conducted for HPD intervals, measuring the proportion of intervals that does not include actual reported cases for 2020e2022. [ABSTRACT FROM AUTHOR]

Background A new strain of West Nile virus lineage 1 (WNV-1) emerged in the Veneto Region, northern Italy, in 2021, 8 years after the last WNV-1 outbreak in Italy. The virus, which co-circulates with West Nile virus lineage 2 (WNV-2), has become endemic in the region, where, in 2022, most human cases of neuroinvasive disease (WNND) reported in Europe have occurred. Methods Comparative analysis of the epidemiology and clinical presentation of WNV-1 and WNV-2 infection in humans, as well as the temporal and geographic distribution of WNV-1 and WNV-2 among wild birds and Culex pipiens mosquitoes in Veneto, from 16 May to 21 August 2022, to determine if the high number of WNND cases was associated with WNV-1. Results 222 human cases of WNV infection were confirmed by molecular testing, including 103 with West Nile fever (WNF) and 119 with WNND. The WNV lineage was determined in 201 (90.5%) cases, comprising 138 WNV-1 and 63 WNV-2 infections. In addition, 35 blood donors tested positive, including 30 in whom WNV lineage was determined (13 WNV-1 and 17 WNV-2). Comparative analysis of the distribution of WNV-1 and WNV-2 infections among WNND cases, WNF cases and WNV-positive blood donors showed that WNND patients were more likely to have WNV-1 infection than blood donors (odds ratio 3.44; 95% confidence interval: 1.54–8.24; P  = 0.0043). As observed in humans, in wild birds, WNV-1 had a higher infection rate (IR) and showed a more rapid expansion than WNV-2. At variance, the distribution of the two lineages was more even in mosquitoes, but with a trend of rapid increase of WNV-1 IR over WNV-2. Conclusions Comparative analysis of WNV-1 vs WNV-2 infection in humans, wild birds and mosquitos showed a rapid expansion of WNV-1 and suggested that WNV-1-infected patients might have an increased risk to develop severe disease. [ABSTRACT FROM AUTHOR]

This report by the European Food Safety Authority and the European Centre for Disease Prevention and Control presents the results of zoonoses monitoring and surveillance activities carried out in 2023 in 27 Member States (MSs), the United Kingdom (Northern Ireland) and 10 non‐MSs. Key statistics on zoonoses and zoonotic agents in humans, food, animals and feed are provided and interpreted historically. In 2023, the first and second most reported zoonoses in humans were campylobacteriosis and salmonellosis, respectively. For both agents, an increase in the absolute number of cases was observed in comparison with 2022. Fifteen MSs and the United Kingdom (Northern Ireland) reached all the established targets in poultry populations with regard to the reduction in Salmonella prevalence for the relevant serovars. Salmonella samples from carcases of various animal species, and samples for Campylobacter quantification from broiler carcases, were more frequently positive when performed by the competent authorities than when own‐checks were conducted. Shiga toxin‐producing Escherichia coli (STEC) was the third most reported zoonotic agent in humans, followed by Yersinia enterocolitica and Listeria monocytogenes. L. monocytogenes and West Nile virus infections were the most severe zoonotic diseases, with the highest percentage of hospitalisations among cases and the highest case fatality rates. Twenty‐seven MSs and the United Kingdom (Northern Ireland) reported a slight decrease in food‐borne outbreaks in 2023 overall in comparison with 2022, although the overall number of reported human cases and hospitalisations increased. Salmonella Enteritidis remained the most frequently reported causative agent for reported cases and food‐borne outbreaks. Salmonella in 'eggs and egg products' was the agent/food pair of most concern. In 2023 this combination caused the largest number of outbreaks and cases among all agent/food combination and ranked second in number of hospitalisations. Salmonella was also the causative agent associated with the majority of multi‐country outbreaks reported in the EU in 2023. This report also provides updates on brucellosis, echinococcosis, Q fever, rabies, toxoplasmosis, trichinellosis, tuberculosis due to Mycobacterium bovis or M. caprae, and tularaemia. [ABSTRACT FROM AUTHOR]

A 3-yr-old male Komodo dragon (Varanus komodoensis) presented acutely in early October 2021 with an abnormal posture and asymmetric tetraparesis. The subadult lizard had spent the previous 4 months either in an outdoor space or in an indoor space with open windows. Physical examination, radiographs, and complete blood count and chemistry panel failed to reveal the cause of the neurologic signs. West Nile virus (WNV) plaque reduction serum neutralization on presentation was negative (1:20), as was WNV polymerase chain reaction (PCR) testing and viral isolation on whole blood. Empirical treatment with a daily corticosteroid, course of antibiotics, and encouragement of mild exercise was initiated. Magnetic resonance imaging of the brain and spinal cord was unremarkable, and a lumbar cerebrospinal fluid (CSF) tap revealed a mononuclear pleocytosis and protein elevation. Follow-up WNV serology revealed a rising titer and seroconversion 13 days after presentation (1:80) and 32 days after presentation (1:640); however, WNV PCR testing of CSF was negative. This Komodo dragon gradually improved over 6 wk before being put back on public display 74 days after presentation. The WNV titer remained high (1:640) through the winter of 2021–22, and an anamnestic response was observed following a vaccination series with a killed equine vaccine in the spring of 2022. There is a previous brief report of WNV infection in a captive crocodile monitor (Varanus salvadorii) and an unpublished case in the same species at the first author's institution. This is the first report of neurologic disease from presumptive WNV infection in a Komodo dragon. We recommend that WNV infection be a differential diagnosis if a varanid lizard presents with acute neurologic signs with a history of arthropod vector exposure, particularly in the summer or fall. [ABSTRACT FROM AUTHOR]

West Nile Virus (WNV) is a zoonotic, vector-borne pathogen affecting humans and animals, particularly in Europe. The virus is primarily transmitted through mosquitoes that infect birds, which serve as the main reservoirs. Humans and horses are incidental hosts. This review focuses on the epidemiology of WNV in southern Europe, particularly its increasing prevalence. Methods included an extensive literature review and analysis of recent outbreaks. WNV is largely asymptomatic in humans, but a small percentage can develop West Nile neuroinvasive disease (WNND), leading to severe neurological symptoms and fatalities. Horses can also suffer from neurological complications, with high mortality rates. Climate change, migratory birds, and mosquito population dynamics contribute to the virus spread across Europe. Control efforts focus on vector management, and while vaccines are available for horses, none has been approved for humans. Surveillance, particularly of bird and mosquito populations, and further research into the virus molecular structure are crucial for understanding and mitigating future outbreaks. [ABSTRACT FROM AUTHOR]

Background: West Nile virus (WNV) is a rapidly growing problem worldwide. The lack of emergency treatment and a safe licensed vaccine against WNV allows the virus to cause sporadic outbreaks of human disease, including fatal cases. Formalin-inactivated vaccines have been used for a long time and have been shown to be very safe and effective, especially in susceptible populations. Methods: By adapting tick-borne encephalitis vaccine production technology, we produced a laboratory-inactivated vaccine against WNV based on the strain SHUA, isolated from humans with a lethal WNV infection in the year 2021. Results: The potential vaccine was tested for safety in vitro and in vivo in outbred SHK mice of different ages, including PCR analysis of the brains of these mice to test for the absence of viral RNA after intracerebral injection. Conclusions: The inactivated whole-virion laboratory vaccine showed 100% seroconversion and immunogenicity against WNV strain SHUA-1, isolated from a lethal human case, and provided the mice with 100% protection from disease and death. [ABSTRACT FROM AUTHOR]

Background: Algeria like other North African countries is experiencing recurrent episodes of West Nile Virus (WNV) emergences and new health threats associated with the introduction of Aedes albopictus in 2010 are to be feared. To improve the surveillance of mosquito-borne pathogens, we performed a study using innovative tools based on multiplex molecular methods. Methods: We combined two approaches: a high-throughput chip based on the BioMark Dynamic array system to detect arboviruses in mosquitoes, and a set of immunologic methods (ELISA, microsphere immunoassays (MIA) and virus microneutralization tests (MNT)) for serological surveys in animal hosts. We investigated two distinct regions: a first zone located in the coastal humid region and a second one in the Saharan desert region. Principal findings: We collected a total of 1,658 mosquitoes belonging to nine different species and found predominantly Culex pipienss. l. (56.5%) and Cx. perexiguus (27.5%). From 180 pools of 10 mosquitoes, we detected four arboviruses: Banna virus (BAV), chikungunya virus (CHIKV), Sindbis virus (SINV), and Usutu virus (USUV). Moreover, we examined 389 blood samples from equids and poultry and found that 52.4% were positive for flavivirus antibodies in ELISA, while 30.8% were positive for WNV and two chickens and two equids were positive for USUV by MNT and MIA respectively. Conclusions: To our knowledge, this is the first report of five arboviruses circulating in Algeria, with three reported for the first time (CHIKV, BAV, and USUV). Our study brings evidence that reinforcing surveillance using more discriminant tools may help in anticipating future emergences and propose adapted control measures. Author summary: Arboviruses are a significant threat to public health because of their epidemic and zoonotic potential. The geographical distribution of mosquito-borne diseases such as West Nile Fever has expanded over the last decades. Countries of the Mediterranean region are not spared. In this context, surveillance of the circulation of such viruses needs to be achieved before the appearing of human or animal cases. The aim of our study was to use innovative and highly efficient tools to highlight the circulation of arboviruses in mosquito vectors, animal reservoirs or exposed animals in Algeria. A total of 1,658 mosquitoes belonging to nine different species were collected and screened for arboviruses usinghighthroughput chips based on the BioMark Dynamic arrays system, capable of screening various arboviruses in a single experiment. Moreover, we analyzed 389 blood samples from equids and poultry using 3 different serologic methods. Our results bring, for the first time in Algeria, evidence of the cryptic circulation of 5 arboviruses: West Nile virus, chikungunya virus, Usutu virus, Sindbis virus and for the first time out of the Asian region, Banna virus. This approach, as an early warning system, is enabling for an early detection of pathogens circulation above-threshold before disease appearance in humans. [ABSTRACT FROM AUTHOR]

The diversity and abundance of vectors are essential parameters in the transmission dynamics of West Nile virus (WNV) between its avian reservoirs and clinically susceptible mammalian species. Knowing the determinants of vector abundance could be thus useful in preventing West Nile fever (WNF) cases and associated socio‐economic impact. We designed a survey at the wildlife–livestock interface to test the hypothesis that variations in environmental favourability between anthropized and wild scenarios modulate WNV vector abundance and transmission risk. In a continental Mediterranean region where WNF has recently emerged, we selected nine sampling sites and allocated three areas to every site with a decreasing gradient of wildlife–livestock interaction: A1—a horse farm where interaction is maximal; A2—a zone of intermediate interaction 500–1000 m from the farm; and A3—an entirely wild zone of low interaction 1–5 km from the farm. At a fortnightly frequency, we estimated mosquito abundance at each of the 27 study sites in May–December 2018 and April–July 2019. We estimated bird and mammal abundance, collected meteorological information and characterised mosquito habitat at the site scale. Thereafter, we studied the determinants of Culex spp., Culex pipiens sensu lato (s.l.) Linnaeus, 1758 (Diptera: Culicidae) and Culex theileri  Theobald, 1903 abundance by constructing negative binomial generalised linear mixed models. We identified 20 mosquito species, with a notable predominance of Culex spp. and, particularly, of Cx. pipiens s.l. We found differences in the spatiotemporal distribution of Culex spp. abundance and confirmed our hypothesis by finding important effects of local environmental variations in abundance. The accumulated rainfall in fortnights 4–14 and the mean temperature of the two fortnights before sampling were positively and statistically significantly associated with the abundance of Cx. pipiens s.l. (Z = 13.09, p < 0.001, and Z = 9.91, p < 0. 001, respectively) and Culex spp. (Z = 13.35, p < 0.001, and Z = 6.99, p < 0.001, respectively), while the mean temperature of the two previous fortnights was a positive statistically significant predictor (Z = 14.69, p < 0.001) of the abundance of Cx. theileri. The farm environment was the most conducive predictor to hosting Culex spp. compared with wild settings. Our results indicate that continental Mediterranean environments are favourable for WNV circulation and maintenance, especially the environment of anthropized rural settings such as farms. These results will have an impact on the spatiotemporal risk prediction of WNF emergence in continental Mediterranean environments. [ABSTRACT FROM AUTHOR]

Purpose: To provide an overview of pre-selected emerging arboviruses (arthropod-borne viruses) that cause ocular inflammation in humans. Methods: A comprehensive review of the literature published between 1997 and 2023 was conducted in PubMed database. We describe current insights into epidemiology, systemic and ocular manifestations, diagnosis, treatment, and prognosis of arboviral diseases including West Nile fever, Dengue fever, Chikungunya, Rift Valley fever, Zika, and Yellow fever. Results: Arboviruses refer to a group of ribonucleic acid viruses transmitted to humans by the bite of hematophagous arthropods, mainly mosquitoes. They mostly circulate in tropical and subtropical zones and pose important public health challenges worldwide because of rising incidence, expanding geographic range, and occurrence of prominent outbreaks as a result of climate change, travel, and globalization. The clinical signs associated with infection from these arboviruses are often inapparent, mild, or non-specific, but they may include serious, potentially disabling or life-threatening complications. A wide spectrum of ophthalmic manifestations has been described including conjunctival involvement, anterior uveitis, intermediate uveitis, various forms of posterior uveitis, maculopathy, optic neuropathy, and other neuro-ophthalmic manifestations. Diagnosis of arboviral diseases is confirmed with either real time polymerase chain reaction or serology. Management involves supportive care as there are currently no specific antiviral drug options. Corticosteroids are often used for the treatment of associated ocular inflammation. Most patients have a good visual prognosis, but there may be permanent visual impairment due to ocular structural complications in some. Community-based integrated mosquito management programs and personal protection measures against mosquito bites are the best ways to prevent human infection and disease. Conclusion: Emerging arboviral diseases should be considered in the differential diagnosis of ocular inflammatory conditions in patients living in or returning from endemic regions. Early clinical consideration followed by confirmatory testing can limit or prevent unnecessary treatments for non-arboviral causes of ocular inflammation. Prevention of these infections is crucial. [ABSTRACT FROM AUTHOR]

The incidence of arbovirus infections has increased in recent decades. Other than dengue, chikungunya, and West Nile viruses, the data on arbovirus in solid organ transplant (SOT) are limited to case reports, and infections in renal transplant recipients account for most of the reported cases. Dengue and West Nile infections seem to be more severe with higher mortality in SOT patients than in the general population. Acute kidney injury is more frequent in patients with dengue and chikungunya although persistent arthralgia with the latter is less frequent. There is no clear relationship between arboviral infection and acute cellular rejection. Pre-transplant screening of donors should be implemented during increased arboviral activity but, despite donor screening and negative donor nucleic acid amplification test (NAT), donor derived infection can occur. NAT may be transiently positive. IgM tests lack specificity, and neutralizing antibody assays are more specific but not readily available. Other tests, such as immunohistochemistry, antigen tests, PCR, metagenomic assays, and viral culture, can also be performed. There are a few vaccines available against some arboviruses, but live vaccines should be avoided. Treatment is largely supportive. More data on arboviral infection in SOT are needed to understand its epidemiology and clinical course. [ABSTRACT FROM AUTHOR]

In this review, recent advances in the combination of CRISPR–Cas systems with graphene-based electrolyte-gated transistors are discussed in detail. In the first part, the functioning of CRISPR–Cas systems is briefly explained, as well as the most common ways to convert their molecular activity into measurable signals. Other than optical means, conventional electrochemical transducers are also developed. However, it seems that the incorporation of CRISPR/Cas systems into transistor devices could be extremely powerful, as the former provides molecular amplification, while the latter provides electrical amplification; combined, the two could help to advance in terms of sensitivity and compete with conventional PCR assays. Today, organic transistors suffer from poor stability in biological media, whereas graphene materials perform better by being extremely sensitive to their chemical environment and being stable. The need for fast and inexpensive sensors to detect viral RNA arose on the occasion of the COVID-19 crisis, but many other RNA viruses are of interest, such as dengue, hepatitis C, hepatitis E, West Nile fever, Ebola, and polio, for which detection means are needed. [ABSTRACT FROM AUTHOR]

The article discusses the need for enhanced surveillance and response strategies for arbovirus outbreaks in Italy. It highlights factors contributing to the reemergence of arboviruses, such as viral adaptation, climate change, and increased population mobility. The article introduces ArboItaly, a centralized repository that consolidates epidemiological data and integrates information on different hosts to facilitate the identification of trends and improve control measures. It emphasizes the importance of international collaboration, genomic surveillance, and proactive approaches in managing the evolving threat of arboviruses. The document is a list of references for scientific articles related to arboviral diseases, providing a range of perspectives and research findings on topics such as transmission dynamics, surveillance systems, control methods, and the impact of environmental factors on disease spread. [Extracted from the article]

West Nile virus (WNV) and Usutu virus (USUV) are closely related flaviviruses with differing capacities to cause neurological disease in humans. WNV is thought to use a transneural route of neuroinvasion along motor neurons and causes severe motor deficits. The potential for use of transneural routes of neuroinvasion by USUV has not been investigated experimentally, and evidence from the few clinical case reports of USUV-associated neuroinvasive disease is lacking. We hypothesised that, compared with WNV, USUV is less able to infect motor neurons, and therefore determined the susceptibility of human induced pluripotent stem cell (iPSC)-derived spinal cord motor neurons to infection. Both viruses could grow to high titres in iPSC-derived neural cultures. However, USUV could not productively infect motor neurons due to restriction by the antiviral response, which was not induced upon WNV infection. Inhibition of the antiviral response allowed for widespread infection and transportation of USUV along motor neurons within a compartmented culture system. These results show a stark difference in the ability of these two viruses to evade initiation of intrinsic antiviral immunity. Our data suggests that USUV cannot infect motor neurons in healthy individuals but in case of immunodeficiency may pose a risk for motor-related neurological disease and transneural invasion. Brief summary: West Nile virus, but not Usutu virus, can productively infect human motor neurons as a possible route of neuroinvasion. [ABSTRACT FROM AUTHOR]

Objective: Unknown etiology Background: West Nile virus (WNV) is a vector-borne flavivirus that is typically transmitted by Aedes and Anopheles mosquitos. WNV infection typically presents with symptoms consistent with viral meningitis, which include fever, headache, and meningeal signs. WNV infections are typically self-resolving, with symptoms lasting 3-10 days. Although uncommon, patients with WNV infection can be afflicted with hyponatremia, although the etiology is unclear. Because of encephalitis, neuroinflammation may be involved in the deterioration of adrenal signaling, leading to salt wasting. Case Report: We present the case of a 75-year-old man who presented with headache, neck pain, photophobia, and viral illness symptoms. He was found to be profoundly hyponatremic, concerning for SIADH. He had a sodium drop to 117 mmol/L, leading to further lethargy and confusion. He received 3% saline, fluid restriction, and salt tablets, and more common causes of SIADH were ruled out. MRI revealed the absence of the posterior pituitary bright spot. He was subsequently found to have positive WNV titers and improved with continued supportive treatment. Conclusions: WNV presents a unique challenge to providers due to its difficult diagnosis and association with hyponatremia. There is no clear role for specific medical treatment such as corticosteroids vs IV immunoglobulins. Supportive care is recommended for those testing positive for WNV. Clinicians should consider the possibility of viral infections, such as WNV, in patients living in endemic areas who present with unexplained hyponatremia, cognitive symptoms, and relevant history. [ABSTRACT FROM AUTHOR]

A group of self-limiting and frequently neglected diseases exist in the literature like Rickettsial disease, Malaria, Dengue fever, Chikungunya, West Nile virus infection, Rift Valley fever, Bartonellosis, or Lyme disease which are poorly understood due to lack of proper diagnostic testing. Currently, multimodal imaging has become a critical modality in the diagnosis and management of ocular diseases. Optical coherence tomography (OCT) is one such remarkable imaging modality in the field of ophthalmology providing high-resolution, cross-sectional images of the retina and choroid with the recent advances such as enhanced depth imaging and swept source OCT. Additionally, OCT angiography (OCTA) has further revolutionised dynamic imaging of retinal and choroidal vasculature non-invasively. This review article highlights the OCT and OCTA biomarkers in the diagnosis and prognosis of the aforementioned neglected diseases. [ABSTRACT FROM AUTHOR]

Ivermectin (IVM)-treated birds provide the potential for targeted control of Culex mosquitoes to reduce West Nile virus (WNV) transmission. Ingestion of IVM increases mosquito mortality, which could reduce WNV transmission from birds to humans and in enzootic maintenance cycles affecting predominantly bird-feeding mosquitoes and from birds to humans. This strategy might also provide an alternative method for WNV control that is less hampered by insecticide resistance and the logistics of large-scale pesticide applications. Through a combination of field studies and modeling, we assessed the feasibility and impact of deploying IVM-treated birdfeed in residential neighborhoods to reduce WNV transmission. We first tracked 105 birds using radio telemetry and radio frequency identification to monitor their feeder usage and locations of nocturnal roosts in relation to five feeder sites in a neighborhood in Fort Collins, Colorado. Using these results, we then modified a compartmental model of WNV transmission to account for the impact of IVM on mosquito mortality and spatial movement of birds and mosquitoes on the neighborhood level. We found that, while the number of treated lots in a neighborhood strongly influenced the total transmission potential, the arrangement of treated lots in a neighborhood had little effect. Increasing the proportion of treated birds, regardless of the WNV competency status, resulted in a larger reduction in infection dynamics than only treating competent birds. Taken together, model results indicate that deployment of IVM-treated feeders could reduce local transmission throughout the WNV season, including reducing the enzootic transmission prior to the onset of human infections, with high spatial coverage and rates of IVM-induced mortality in mosquitoes. To improve predictions, more work is needed to refine estimates of daily mosquito movement in urban areas and rates of IVM-induced mortality. Our results can guide future field trials of this control strategy.

OBJECTIVES: The objective of this study was to report on the development of neuroinvasive West Nile virus (WNV) infection in the context of anti-CD20 monotherapy for multiple sclerosis (MS). METHODS: This is a case series study. RESULTS: In 2021-2022, we observed 4 cases of neuroinvasive WNV infection in our patient population of 2009 patients with MS on ocrelizumab, compared with a total of 46 cases of neuroinvasive WNV infection reported in Pennsylvania and 40 in New Jersey. Odds were 258 times that of the general population (95% confidence interval 97-691), χ2 p < 0.0001). All were women aged 41-61 years with variable disease duration, level of disability, and duration of anti-CD20 therapy. All presented in summer/early fall with fever, headache, and encephalopathy consistent with meningoencephalitis. Three patients had acute cerebellitis. Two had anterior nerve root involvement progressing to quadriparesis, and 1 developed refractory nonconvulsive status epilepticus. All required intubation and experienced significant morbidity. All had CSF pleocytosis. Two patients were WNV IgM positive in both the serum and CSF, 1 patient had positive serum IgM and CSF metagenomic next-generation sequencing (mNGS), while 1 had positive CSF mNGS with negative serum and CSF antibodies. DISCUSSION: Neuroinvasive WNV infection can develop with anti-CD20 monotherapy in the absence of additional immunosuppression. WNV serologies may be negative in the setting of anti-CD20 treatment; in the appropriate clinical context, one should consider direct detection methods such as PCR or mNGS-based testing.

West Nile virus is a mosquito-borne illness that usually presents as asymptomatic or with a viral syndrome, and normally is treated with supportive care or immunotherapy. However, some patients can develop neurologic symptoms of viral meningoencephalitis. This article describes a patient who developed opsomyoclonus, a rare complication of West Nile virus meningoencephalitis. She was treated with immunotherapy with no resolution of her symptoms. Symptom improvement occurred with subsequent treatment with clonazepam and dexamethasone. [ABSTRACT FROM AUTHOR]

The aim of the work was to study the epidemiological situation on West Nile fever (WNF) in the Republic of Tatarstan in 2023.Materials and methods. An operational epidemiological analysis of WNF cases registered in the Republic of Tatarstan in 2023 was performed. In order to establish sources and risk factors for infection of the population, 987 samples of zoo-entomological material were examined for the presence of West Nile virus (WNV) markers. A set of laboratory diagnostic methods was used: ELISA, RT-PCR, sequencing.Results and discussion. It has been established that all cases of WNF were registered in the region in the summer-autumn period of 2023, mainly in August, among residents of the city of Kazan who had not traveled outside the Russian Federation and the Republic of Tatarstan over the past six months. The incidence rate of WNF in the Republic of Tatarstan was 0.20 per 100 thousand population, the mortality rate reached 12.5 %. Signs of damage to the central nervous system were present in 6 out of 8 (75 %) patients. The majority of people with severe clinical symptoms belonged to older age groups and had concomitant diseases. Cases of the infection were reported in all age groups, with the exception of children and adolescents. The spatial characteristics of morbidity have been investigated, indicating the diffuse nature of the distribution of cases. The integrated use of methods, consisting in the concurrent use of polymerase chain reaction and enzyme-linked immunosorbent assay, made it possible to laboratory confirm cases of WNF in patients at different stages of the disease. The circulation of a subvariant of the WNV of the second genotype in the Republic of Tatarstan, currently dominant in the southern and central regions of Russia, has been established. A set of measures has been proposed to optimize epidemiological surveillance and control of WNF in the Republic of Tatarstan.

Background. Annual studies of West Nile virus (WNV) circulating in endemic areas are necessary to characterize its properties and track them over time. Given the lack of specific antiviral therapy for West Nile fever (WNF), it is of interest to study sensitivity to drugs widely used in modern practice. The aim of the study is to study the sensitivity of West Nile virus strains circulating in the Russian Federation in 2018–2021 to drugs used to treat viral infections.Material and methods. The sensitivity of WNV strains to ribavirin, riamilovir, and umifenovir was determined using Vero cell culture.Results and discussion. A study of the sensitivity of WNV strains circulating in the Russian Federation in 2018–2021 to therapeutic drugs used to treat viral infections showed their heterogeneity in this regard. Thus, 5 strains (WNV_Volgograd_601/18, Volgograd_723/18, Volgograd_830/18, Voronezh_794/21, Astrachan_962/21) out of 10 studied were characterized by some differences in resistance to ribavirin and riamilovir. No statistically significant differences were revealed when comparing drug resistance indicators of the group of WNV strains of the «old» genovariant with those of the «new» group.Conclusion. Further analysis of the genome of the studied WNV strains will allow us to establish genetic characteristics, which may contribute to the establishment of molecular mechanisms of resistance to ribavirin, riamilovir, and umifenovir.

BackgroundWest Nile virus (WNV) is the leading cause of mosquito-borne disease in humans in the United States. Since the introduction of the disease in 1999, incidence levels have stabilized in many regions, allowing for analysis of climate conditions that shape the spatial structure of disease incidence.ObjectivesOur goal was to identify the seasonal climate variables that influence the spatial extent and magnitude of WNV incidence in humans.MethodsWe developed a predictive model of contemporary mean annual WNV incidence using U.S. county-level case reports from 2005 to 2019 and seasonally averaged climate variables. We used a random forest model that had an out-of-sample model performance of R2=0.61.ResultsOur model accurately captured the V-shaped area of higher WNV incidence that extends from states on the Canadian border south through the middle of the Great Plains. It also captured a region of moderate WNV incidence in the southern Mississippi Valley. The highest levels of WNV incidence were in regions with dry and cold winters and wet and mild summers. The random forest model classified counties with average winter precipitation levels

The distribution, epidemiology, and socioeconomic impact of Rift Valley fever (RVF) and West Nile (WN) viruses are poorly known in areas of sub‐Saharan countries like Ethiopian pastoral region. The human and livestock density in the area has increased greatly in recent years, but little work has been done on arboviral diseases and their potential impact on human and livestock health. The aim of this study was to detect the circulation of zoonotic arboviruses such as Rift Valley fever virus and West Nile viruses in the livestock population and to estimate seroprevalence in Afar pastoral area northeast Ethiopia. Cross‐sectional serological survey was carried out in 736 serum samples from which cattle (224), camel (155), goats (121), sheep (144), and donkeys (92) were tested for the presence of anti‐RVFV and anti‐WNV IgG using a competitive enzyme‐linked immunosorbent assay (c‐ELISA) in two purposively selected districts of the Afar region. The present study revealed a 9.1% (95% CI = 8.86–9.29) seroprevalence of co‐circulation of RVF and WNV. High 32/155 (20.7%) seroprevalence of co‐circulation was seen in camels, followed by goat 14/121 (11.6%), cattle 16/224 (7.14%), and sheep 5/144 (3.5%), respectively, and higher 41/421 (9.7%) seroprevalence of co‐circulation was observed in Amibara district than Haruka district. Camels were seven times (OR: 7.016, 95% CI = 2.639–18.653) more likely to be seropositive for the co‐circulation than sheep (p ≤ 0.001). Livestock herds found in Amibara district were 1.2 times (OR: 1.165, 95% CI = 0.680–1.996) more likely to be seropositive for RVFV infection than those in Haruka areas. Given the co‐occurrence of RVFV and WNV circulations, along with often suboptimal human and animal health surveillance in many similar areas' attention should be given. Investigation of the potential socioeconomic and health impacts of zoonotic arbovirus infections in such areas is crucial. Since both RVFV and WNFV are transmitted through a mosquito vector, avoiding mosquito bites is the primary method of prevention. [ABSTRACT FROM AUTHOR]

Background and purpose: Culicidae plays a crucial role in the spread of diseases like Malaria and arboviral diseases such as Japanese Encephalitis, Zika virus, Chikungunya, Dengue fever, Yellow fever, and West Nile fever. Different mosquito species have different abundance and distribution due to a variety of factors, such as physicochemical factors, weather conditions, vegetation, and human activities. The characteristics of larval habitats are among the factors affecting the population, and diversity, and determining the preferred breeding places of the species. For this reason, a study was conducted to examine the species diversity of Culicidae and their larval habitats in Shushtar County. Materials and methods: This cross-sectional study was conducted in Shushtar County from the central, Mian Ab and Shuaibiya districts, 2021. Larvae were collected from the breeding places in the sampling areas including Noormohammadi, Konarpir, Saheli, Abu Gerva, and Pirdalu by using the dipping technique in spring and summer and kept in lactophenol solution. Then, a microscopic slide was prepared from the samples using licidophor, which were identified with valid diagnostic keys. Characteristics of larval habitat such as habitat type, water condition, vegetation, substrate type, water quality, and light condition were also recorded. To analyze the data and determine the relationship between the frequency and characteristics of larval habitats, SPSS version 16 software and a chi-square statistical test were used. Qualitative variables were also reported as numbers (percentages). Abundance and distribution maps of samples were prepared using ArcGIS software version 10.5. Results: In this study, a total of 527 larvae were identified, including five species of Anopheles stephensi, Culex pusillus, and Cx. sinaiticus, Cx. theileri and, Cx. Perexiguus. Anopheles stephensi with the lowest frequency (8.48%) was reported only from the Saheli area. This species was collected from temporary, stationary, without vegetation, mud substrate, cloudy water, sunny, and natural habitats. Culex theileri, one of the important vectors of arboviral diseases, was observed in temporary and natural habitats, stagnant waters without vegetation, and cloudy and sunny waters habitates. Culex pusillus was the only species observed in Pirdalo and Abu Gerva. By examining the larval habitats of Culicidae in Shushtar County, Cx. pusillus was the most abundant collected species, from temporary habitat (82.7%), stagnant waters (73.6%), mud substrate (100%), turbid waters (78.6%), natural (95%), and sunny (82.7%). Also, the abundance of collected larvae in temporary habitats, stagnant waters, in areas with vegetation, and mud substrate was high. Besides, it was more abundant in turbid waters and sunny areas, and these differences were statistically significant (P<0.0001). Conclusion: In this study, Cx.pusillus was the most common species, while An. stephensi was the least common abundance among collected species. It was observed significant difference between this species and the type of habitat, water flow, vegetation, water quality, and light conditions. Conducting more comprehensive studies in this field, especially regarding the possible role of different species of Culicidae, helped to solve the health and medical problems of humans and veterinary medicine in the future. [ABSTRACT FROM AUTHOR]

The emerging zoonotic West Nile virus (WNV) has serious impact on public health. Thus, understanding the molecular basis of WNV infections in mammalian hosts is important to develop improved diagnostic and treatment strategies. In this context, the role of microRNAs (miRNAs) has been analyzed by several studies under different conditions and with different outcomes. A systematic comparison is therefore necessary. Furthermore, additional information from mRNA target expression data has rarely been taken into account to understand miRNA expression profiles under WNV infections. We conducted a meta-analysis of publicly available miRNA expression data from multiple independent studies, and analyzed them in a harmonized way to increase comparability. In addition, we used gene-set tests on mRNA target expression data to further gain evidence about differentially expressed miRNAs. For this purpose, we also studied the use of target information from different databases. We detected a substantial number of miRNA that emerged as differentially expressed from several miRNA datasets, and from the mRNA target data analysis as well. When using mRNA target data, we found that the targetscan databases provided the most useful information. We demonstrated improved miRNA detection through research synthesis of multiple independent miRNA datasets coupled with mRNA target set testing, leading to the discovery of multiple miRNAs which should be taken into account for further research on the molecular mechanism of WNV infections. [ABSTRACT FROM AUTHOR]

The common house mosquito (Culex pipiens) is a native vector for West Nile virus (WNV). Invasive species like the tiger mosquito (Aedes albopictus) and Asian bush mosquito (Aedes japonicus) are rapidly spreading through Europe, posing a major threat as vectors for dengue, chikungunya (CHIKV), and Japanese encephalitis virus (JEV). These mosquitoes share a similar ecological niche as larvae, but the carry-over effects of aquatic larval interactions to the terrestrial adult stage remain largely unknown and their medical relevance requires further investigation. This study examines the context dependency of larval interactions among Aedes albopictus, Aedes japonicus, and Culex pipiens. The survival, development time, growth, and energetic storage were measured in different European populations within density-response (intraspecific) experiments and replacement (interspecific) experiments at 20 °C and 26 °C. Overall, Ae. japonicus was the weakest competitor, while competition between Ae. albopictus and Cx. pipiens varied with temperature. Adults emerging from this larval competition were infected as follows: Culex pipiens with WNV, Ae. albopictus with CHIKV, and Ae. japonicus with JEV. While no JEV infection was observed, mosquitoes experiencing interspecific interactions during their larval stages exhibited higher infection rates and viral RNA titers for CHIKV and WNV. This increased susceptibility to viral infection after larval competition suggests a higher risk of arbovirus transmission in co-occurring populations. [ABSTRACT FROM AUTHOR]

This article explores the role of microglia, a type of immune cell in the central nervous system, in viral-induced neuroinflammation. It discusses the different types of viruses that can cause central nervous system infections and how they infiltrate the CNS. The article highlights the responses of glial cells, particularly astrocytes and microglia, to viral infections and suggests that microglia play a crucial role in regulating the immune response and neuroinflammation associated with viral infections. It also mentions the potential implications of viral infections, such as COVID-19, on the function and activation of microglia and astrocytes. [Extracted from the article]

Microglia, the resident macrophages of the central nervous system, exhibit altered gene expression in response to various neurological conditions. This study investigates the relationship between West Nile Virus infection and microglial senescence, focusing on the role of LGALS3BP, a protein implicated in both antiviral responses and aging. Using spatial transcriptomics, RNA sequencing and flow cytometry, we characterized changes in microglial gene signatures in adult and aged mice following recovery from WNV encephalitis. Additionally, we analyzed Lgals3bp expression and generated Lgals3bp-deficient mice to assess the impact on neuroinflammation and microglial phenotypes. Our results show that WNV-activated microglia share transcriptional signatures with aged microglia, including upregulation of genes involved in interferon response and inflammation. Lgals3bp was broadly expressed in the CNS and robustly upregulated during WNV infection and aging. Lgals3bp-deficient mice exhibited reduced neuroinflammation, increased homeostatic microglial numbers, and altered T cell populations without differences in virologic control or survival. These data indicate that LGALS3BP has a role in regulating neuroinflammation and microglial activation and suggest that targeting LGALS3BP might provide a potential route for mitigating neuroinflammation-related cognitive decline in aging and post-viral infections. [ABSTRACT FROM AUTHOR]

Emerging infectious diseases (EIDs) are newly emerging and reemerging infectious diseases. The National Institute of Allergy and Infectious Diseases identifies the following as emerging infectious diseases: SARS, MERS, COVID-19, influenza, fungal diseases, plague, schistosomiasis, smallpox, tick-borne diseases, and West Nile fever. The factors that should be taken into consideration are the genetic adaptation of microbial agents and the characteristics of the human host or environment. The new approach to identifying new possible pathogens will have to go through the One Health approach and omics integration data, which are capable of identifying high-priority microorganisms in a short period of time. New bioinformatics technologies enable global integration and sharing of surveillance data for rapid public health decision-making to detect and prevent epidemics and pandemics, ensuring timely response and effective prevention measures. Machine learning tools are being more frequently utilized in the realm of infectious diseases to predict sepsis in patients, diagnose infectious diseases early, and forecast the effectiveness of treatment or the appropriate choice of antibiotic regimen based on clinical data. We will discuss emerging microorganisms, omics techniques applied to infectious diseases, new computational solutions to evaluate biomarkers, and innovative tools that are useful for integrating omics data and electronic medical records data for the clinical management of emerging infectious diseases. [ABSTRACT FROM AUTHOR]

Mosquitoes of the Culex genus are responsible for a large burden of zoonotic virus transmission globally. Collectively, they play a significant role in the transmission of medically significant diseases such as Japanese encephalitis virus and West Nile virus. Climate change, global trade, habitat transformation and increased urbanisation are leading to the establishment of Culex mosquitoes in new geographical regions. These novel mosquito incursions are intensifying concerns about the emergence of Culex-transmitted diseases and outbreaks in previously unaffected areas. New mosquito control methods are currently being developed and deployed globally. Understanding the complex interaction between pathogens and mosquitoes is essential for developing new control strategies for Culex species mosquitoes. This article reviews the role of Culex mosquitos as vectors of zoonotic disease, discussing the transmission of viruses across different species, and the potential use of Wolbachia technologies to control disease spread. By leveraging the insights gained from recent successful field trials of Wolbachia against Aedes-borne diseases, we comprehensively discuss the feasibility of using this technique to control Culex mosquitoes and the potential for the development of next generational Wolbachia-based control methods. [ABSTRACT FROM AUTHOR]

Vector-borne pathogens impact both humans and animals; once established in a specific region, vector-borne diseases are considerably more challenging to control, particularly when wild animals serve as the natural reservoir. Prevention and control of vector-borne diseases are significantly affected by global warming. Therefore, rising temperatures will lead to a higher incidence of vector-borne diseases as well as the distribution of vectors. The processed data were taken from the National Institute of Public Health - National Centre for Communicable Diseases Surveillance and Control of, as well as from the national literature. Therefore, 5 diseases of medical importance were introduced into the study. According to INSP-CNSCBT data, from 2009 to 2023, the most confirmed cases were for: Lyme Disease - 5.654, West Nile Encephalitis - 827, Malaria - 369, Dengue Fever - 80 and Tick-borne Encephalitis (TBE) - 22. West Nile encephalitis entered into the national surveillance program in 1997. However, the highest prevalence was reported in 2018, when 277 cases of West Nile encephalitis were confirmed in humans in Romania. Cases of West Nile Encephalitis, as well as those of Dengue Fever, were increasing during 2018-2019, followed by a decrease, possibly related to the COVID-19 pandemic. Assessing the risk of the most significant vector-borne diseases should be a priority, because climate is a crucial factor in their spread. Understanding the dynamics of the vector-borne diseases and preventing epidemics in the upcoming years require the support of local multidisciplinary research programs for integrated human, animal, and vector epidemiologic surveillance. [ABSTRACT FROM AUTHOR]

West Nile virus (WNV) is the most common mosquito-borne disease in the United States, resulting in hundreds of reported cases yearly in California alone. The transmission cycle occurs mostly in birds and mosquitoes, making meteorological conditions, such as temperature, especially important to transmission characteristics. Given that future increases in temperature are all but inevitable due to worldwide climate change, determining associations between temperature and WNV incidence in humans, as well as making predictions on future cases, are important to public health agencies in California. Using surveillance data from the California Department of Public Health (CDPH), meteorological data from the National Oceanic and Atmospheric Administration (NOAA), and vector and host data from VectorSurv, we created GEE autoregressive and zero-inflated regression models to determine the role of temperature and other environmental factors in WNV incidence and predictions. An increase in temperature was found to be associated with an increase in incidence in 11 high-burden Californian counties between 2017–2022 (IRR = 1.06), holding location, time of year, and rainfall constant. A hypothetical increase of two degrees Fahrenheit—predicted for California by 2040—would have resulted in upwards of 20 excess cases per year during our study period. Using 2017–2021 as a training set, meteorological and host/vector data were able to closely predict 2022 incidence, though the models did overestimate the peak number of cases. The zero-inflated model closely predicted the low number of cases in winter months but performed worse than the GEE model during high-transmission periods. These findings suggests that climate change will, and may be already, altering transmission dynamics and incidence of WNV in California, and provides tools to help predict incidence into the future. Author summary: West Nile Virus is a disease that is spread by mosquitoes. Though it commonly infects birds, transmission to humans is possible and can lead to severe health effects. Temperature is known to affect the transmission cycle of West Nile virus, but it is unclear how global warming might change who, or how many people, may get infected with the virus. In this study, the researchers looked at how climate change may affect West Nile virus in California, and how health officials may better be able to predict future cases. The study found that there could be an increase in West Nile virus cases in humans due to increases in temperature in the next 20 years, but that we already have many tools and sources of data to predict cases. These findings reinforce the possible consequences of climate change on human health, and aid in the understanding in the complex relationship between climate and infectious diseases. [ABSTRACT FROM AUTHOR]

Aedes albopictus, also known as the Asian tiger mosquito, is indigenous to the tropical forests of Southeast Asia. Ae. albopictus is expanding across the globe at alarming rates, raising concern over the transmission of mosquito-borne diseases, such as dengue, West Nile fever, yellow fever, and chikungunya fever. Since Ae. albopictus was reported in Houston (Harris County, Texas) in 1985, this species has rapidly expanded to at least 32 states across the United States. Public health efforts aimed at controlling Ae. albopictus, including surveillance and adulticide spraying operations, occur regularly in Harris County. Despite rotation of insecticides to mitigate the development of resistance, multiple mosquito species including Culex quinquefasciatus and Aedes aegypti in Harris County show organophosphate and pyrethroid resistance. Aedes albopictus shows relatively low resistance levels as compared to Ae. aegypti, but kdr-mutation and the expression of detoxification genes have been reported in Ae. albopictus populations elsewhere. To identify potential candidate detoxification genes contributing to metabolic resistance, we used RNA sequencing of field-collected malathion-resistant and malathion-susceptible, and laboratory-maintained susceptible colonies of Ae. albopictus by comparing the relative expression of transcripts from three major detoxification superfamilies involved in malathion resistance due to metabolic detoxification. Between these groups, we identified 12 candidate malathion resistance genes and among these, most genes correlated with metabolic detoxification of malathion, including four P450 and one alpha esterase. Our results reveal the metabolic detoxification and potential cuticular-based resistance mechanisms associated with malathion resistance in Ae. albopictus in Harris County, Texas. Author summary: The Asian tiger mosquito, Aedes albopictus, is an invasive species rapidly expanding worldwide. It is the main vector for several arboviruses, including dengue virus, Zika virus, and chikungunya virus. These viral diseases pose a substantial threat to global public health. Ae. albopictus has developed resistance to insecticides such as malathion, making its control more challenging. To uncover the genetic basis of this resistance, we conducted a study using RNA sequencing-based transcriptome profiling. In this study, we obtained gene expression patterns in malathion-resistant and susceptible mosquitoes. The transcriptomic information allowed us to identify potential key genes in detoxification gene families associated with metabolic resistance to malathion. Our discovery provides insights into the molecular mechanisms behind malathion resistance in Ae. albopictus. Our research not only contributes to the understanding of mosquito biology and control but also highlights the future direction for continued efforts in developing innovative strategies to mitigate rapid development of insecticide resistance in Ae. albopictus. [ABSTRACT FROM AUTHOR]

Simple Summary: Insect-borne viruses, such as those of the Flaviviridae family, pose a serious risk to global health. WNV, a mosquito-borne flavivirus, is transmitted primarily by the Culex mosquito. Despite the increasing exposure of populations to mosquito-borne flaviviruses and the expanding range of the vector mosquito, there are limited resources available to prevent or treat flavivirus infections. Using the model organism Drosophila melanogaster, commonly known as the fruit fly, we previously found that insulin signaling reduces WNV infection. We translated these finding to mosquitoes and human cells and showed similar mechanisms of insulin-mediated antiviral activity. However, insect and mammalian hormones can regulate insulin signaling. Specifically, decretin hormones suppress insulin secretion, especially during periods of starvation and low glucose intake. In this study, we show that the insect decretin, Limostatin, and its mammalian ortholog, Neuromedin U, can promote WNV infection. These results suggest that the inhibition of decretin signaling may be a novel therapeutic target to control WNV infection. The arbovirus West Nile virus (WNV) is a danger to global health. Spread primarily by mosquitoes, WNV causes about 2000 cases per year in the United States. The natural mosquito immune response controls viral replication so that the host survives but can still transmit the virus. Using the genetically malleable Drosophila melanogaster model, we previously dissected innate immune pathways used to control WNV infection. Specifically, we showed that insulin/IGF-1 signaling (IIS) activates a JAK/STAT-mediated immune response that reduces WNV. However, how factors that regulate IIS in insects control infection has not been identified. D. melanogaster Limostatin (Lst) encodes a peptide hormone that suppresses insulin secretion. Its mammalian ortholog, Neuromedin U (NMU), is a peptide that regulates the production and secretion of insulin from pancreatic beta cells. In this study, we used D. melanogaster and human cell culture models to investigate the roles of these insulin regulators in immune signaling. We found that D. melanogaster Lst mutants, which have elevated insulin-like peptide expression, are less susceptible to WNV infection. Increased levels of insulin-like peptides in these flies result in upregulated JAK/STAT activity, leading to protection from infection. Treatment of human cells with the insulin regulator NMU results in increased WNV replication. Further investigation of methods to target Lst in mosquitoes or NMU in mammals can improve vector control methods and may lead to improved therapeutics for human and animal infection. [ABSTRACT FROM AUTHOR]

Background: Autochthonous human West Nile virus (WNV) infections were notified in the infectious disease surveillance system in Germany in 2018 for the first time and every year since then. Since clinically apparent infections are infrequent, we conducted two studies to investigate subclinical infections of this emerging disease in Germany in 2019 to detect infections not visible to surveillance based on symptomatic infections: limited-scope blood donor testing and a serosurvey among employees at two Berlin zoos with a history of demonstrated WNV infections in animals. Methods: For the zoo study, employees of the two zoos in Berlin were invited to participate in the study in late 2019. Blood samples were drawn and tested for the presence of antibodies (immunoglobulin M [IgM] and immunoglobulin G [IgG]) against WNV, and two other flaviviruses present in Germany: Usutu virus and Tick-borne encephalitis virus (TBEV). For the study in blood donors, four blood establishments with collection sites in regions with documented WNV-infected animals in 2018 and 2019 participated in the study. All donations in these regions were tested for WNV genome from July to November 2019. Results: In the enzyme-linked immunosorbent assay, none of the 70 tested zoo employees were WNV IgM-positive, 8 were WNV IgG-positive, additional 2 participants had equivocal results. All 10 were negative in the virus neutralization test (VNT) for WNV, but positive in the VNT for TBEV. None of the 4273 samples from blood donors tested in areas with WNV-infected animals was positive for WNV-RNA. Conclusion: Our results indicate that WNV circulation in Germany, though clearly documented in animals in 2019, apparently affected very few humans. Still areas with WNV-positive animals remain risk areas for human infection as well. [ABSTRACT FROM AUTHOR]

An analysis of the epidemiological situation on West Nile fever (WNF) in the Russian Federation in 2023 has revealed an increase in the number of cases (210) relative to the year 2022 by 6.3 times, the long-term average value by 1.2 times. Manifestations of the epidemic process were characterized by a significant expansion in the number of territories, where cases of the disease were confirmed (24 constituent entities, including in 13 – for the first time); a long epidemic season; an increase in the proportion of cases with a severe clinical course and fatality rate, which significantly exceeded the long-term average across Russia (8.5 and 1.2 %, respectively). Patients with fever and other similar manifestations of WNF were examined for the presence of the disease markers in 50 entities of the Russian Federation. Continued trend towards a decrease in the volume of diagnostic studies carried out by medical organizations and an increase in the time required for the etiological deciphering of disease cases has been established. Serological examination of sample groups of healthy population was performed in 65 entities. Epizootiological monitoring was carried out in 74 entities, rate of infection of carriers and vectors with West Nile virus (WNV) was confirmed in 14 entities. In the territory of the European part of Russia and the North Caucasus, the circulation of WNV lineages 1, 2 and 4 with the dominance of WNV lineage 2 has been established. Data on the genetic heterogeneity of WNV lineage 2 strains that circulated in Russia in 2023 have been obtained. Based on an analysis of climatic factors, a forecast of WNF incidence in the Russian Federation for 2024 was prepared.

Introduction. The relevance of the study is due to the need to assess the real expansion of West Nile fever (WNF) in Russia, analyze the manifestations of epizootic and epidemic processes and study the population structure of West Nile virus (WNV). Aim. To obtain objective data on the intensity of WNV circulation in certain territories of Russia and study the properties of the isolated strains of the pathogen. Materials and methods. 4564 samples of field material from 23 subjects of the Russian Federation and 1547 samples of clinical material from 12 subjects of the Russian Federation were examined. A set of laboratory diagnostic methods was used: ELISA, RT-PCR, virological, sequencing. Results. In 20 out of 1331 (1.5%) examined febrile patients, IgM antibodies to WNV were detected, including positive cases identified for the first time in the Karachay-Cherkess Republic, Tver and Vladimir regions. The presence of immunity to WNV was found on average in 8.6% of 11 federal subjects' population with high seroprevalence rates in Zaporozhye (24,5%), Tula (15,4%) and Kursk (11,1%) regions. Low-avidity IgG antibodies were detected in 44 (33,1%) samples from a population of 9 federal subjects. Intensive circulation of WNV lineage 2 in the epizootic cycle in the southern part of European Russia was confirmed. 12 WNV isolates were obtained, including those isolated for the first time in the Republic of Crimea, the Karachay-Cherkess Republic and the Stavropol Territory. The heterogeneity of circulating WNF causative agent's strains related to the two clades of the WNV lineage 2 formed in 2021 and 2022 was established. Conclusion. In the course of comprehensive monitoring studies, a new northern border of the WNF range was established, which as of 2022 passes through the territory of the Tver region. Data from seroepidemiological studies, including the detection of low-avidity IgG antibodies, confirm fairly intense, but undiagnosed contact of the population of the European part of Russia with the WNF pathogen. In the southern region of the European part of Russia, WNV genotype 2 predominantly circulates, belonging to at least two clades formed in 2021 and 2022.