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There is an increasing global burden from chikungunya virus (CHIKV). Bangladesh reported a major epidemic in 2017, but it was unclear whether there had been prior widespread transmission. We conducted a nationally representative seroprevalence survey in 70 randomly selected communities immediately before the epidemic. We found that 69 of 2938 sampled individuals (2.4%) were seropositive to CHIKV. Seropositivity to dengue virus (adjusted odds ratio, 3.13 [95% confidence interval, 1.86–5.27]), male sex (0.59 [.36–.99]), and community presence of Aedes aegypti mosquitoes (1.80 [1.05–3.0]7) were significantly associated with CHIKV seropositivity. Using a spatial prediction model, we estimated that across the country, 4.99 (95% confidence interval, 4.89–5.08) million people had been previously infected. These findings highlight high population susceptibility before the major outbreak and that previous outbreaks must have been spatially isolated. [ABSTRACT FROM AUTHOR]

Aim of Study: The study aims to assess the growing public health threat posed by Oropouche virus (OROV), focusing on its epidemiology, transmission patterns, and the challenges in diagnosis and control. By analyzing the recent spread of OROV to new regions, including Cuba and Colombia, the study seeks to highlight the need for improved surveillance, enhanced diagnostic capabilities, and research into potential treatments and vaccines. Additionally, the study investigates the clinical similarities between Oropouche fever and other arboviruses, which often lead to diagnostic difficulties and mismanagement in affected regions. Results: The virus has caused over 500,000 cases in Brazil alone, with recent outbreaks reporting fatalities, suspected vertical transmission, and potential associations with microcephaly in newborns. Underreporting and limited surveillance have likely led to the underestimation of the true burden of Oropouche fever. Current diagnostic methods, such as serology and RT-PCR, are often inaccessible in low-resource settings, further complicating efforts to control the spread of the virus. The study highlights the importance of improving diagnostic capacity, enhancing surveillance, and conducting further research into vector control, antiviral treatments, and vaccine development. Conclusion: This study emphasizes the urgent need for coordinated international efforts to address the rising threat of Oropouche virus. Considering its rapid spread and potential for global transmission, comprehensive public health measures are necessary to protect vulnerable populations and mitigate the impact of this emerging disease. Enhanced surveillance and the development of accessible diagnostics, vaccines, and treatment options are critical to containing OROV and preventing further outbreaks. [ABSTRACT FROM AUTHOR]

Panama is a country with endemic Dengue virus (DENV) transmission since its reintroduction in 1993. The four serotypes have circulated in the country and the region of the Americas, however, DENV-4 confirmed autochthonous cases have not been identified since 2000, despite its circulation in neighboring countries. Here, we report DENV-4 detection in Panama in the last four-month period of 2023 with cocirculation of the other serotypes, this was associated with a peak of dengue cases during the dry season even thoughmost dengue outbreaks are described in the rainy season. Complete genomes of DENV-4 allowed us to determine that cases were caused by DENV-4 genotype IIb, the same genotype as 23 years ago, with high similarity to DENV-4 sequences circulating in Nicaragua and El Salvador during 2023. This report shows the importance ofmaintaining serotype and genotype surveillance for early detection of new variants circulating in the country. [ABSTRACT FROM AUTHOR]

Simple Summary: Household surveys of communities for potential oviposition containers by mosquito control teams offer effective mechanisms for reducing arbovirus transmission. Here, we combined standard community surveys with GIS mapping to identify premises with Aedes-positive containers and classify container types near the end of the dry season in Trinidad, West Indies. The entomological indices based on key containers (tanks, drums, tubs/basins/buckets) showed that two of the four locations surveyed were already at a high risk for arbovirus transmission going into the wet season. GIS mapping provided inspection teams with specific locations that had Aedes-positive containers and highlighted premises that were not accessible. This information can facilitate the identification of areas within communities that may be at greater risk and should be prioritized for future surveys and control efforts; it also highlights the need to inform and increase community participation. Dengue and other arboviruses remain a global threat, and enhanced efforts to control the mosquitoes that transmit them are urgently needed. A survey of potential manmade Aedes aegypti (L.) and Aedes albopictus (Skuse) oviposition containers was performed in four communities near the end of the typical dry season in 2018 in Trinidad, West Indies. The purpose was to conduct individual premise surveys and use GIS mapping to visualize premises within communities that had Aedes-positive containers, as this information could be used for the prioritization of mosquito control efforts in potential high risk areas as the wet season progressed. Accessible premises were surveyed following standard inspection protocols used by the Insect Vector Control Division (IVCD), Ministry of Health (MOH). The results indicated that two of the four locations would be at high risk for arbovirus transmission going into the wet season. The GIS mapping of premises with Aedes-positive containers facilitated the identification of potential hot spots for arbovirus transmission risk within communities that should be prioritized for enhanced monitoring and vector control efforts, emphasizing the need to increase community participation in standard surveys by IVCD. [ABSTRACT FROM AUTHOR]

On 27 May 2024, the Cuban Ministry of Health reported the first outbreak of Oropouche fever on the island. The etiologic agent, Oropouche virus (OROV), is a poorly understood arbovirus that has been known since the 1960s and represents a public health burden in Latin America. We report the whole-genome characterization of the first European OROV isolate from a returning traveler from Cuba with Oropouche fever-like symptoms. The isolate was obtained from the patient's serum; whole-genome sequencing was performed by next-generation sequencing, followed by phylogenetic analysis and genetic variability studies. The analysis showed that the most closely related sequence was from the French Guiana 2020 outbreak. Interestingly, our isolate is a reassortant virus, included in a highly supported monophyletic clade containing recent OROV cases (Brazil 2015–Colombia 2021), separated from the other four previously known genotypes. More deeply, it was found to be included in a distinct branch containing the sequences of the Brazil 2022–2024 outbreak. The reassortment event involved the S and L segments, which have high similarity with sequences belonging to a new cluster (here defined as OROV_SCDC_2024), while the M segment shows high similarity with older sequences. These results likely describe the viral strain responsible for the current outbreak in Cuba, which may also reflect the ongoing outbreak in Latin America. Further studies are needed to understand how OROV evolves towards traits that facilitate its spread and adaptation outside its original basin, and to track its spread and evolution in the European continent. [ABSTRACT FROM AUTHOR]

Background Over the past 20 years, over 5 million cases of chikungunya, a mosquito-transmitted viral disease, have been reported in over 110 countries. Until recently, preventative strategies for chikungunya were largely ineffective, relying on vector control and individual avoidance of mosquito bites. Methods This review outlines the preclinical and clinical efficacy and safety data that led to the approval of VLA1553 (IXCHIQ®), a live-attenuated vaccine against chikungunya disease. It also describes the innovative development pathway of VLA1553, based on an immunological surrogate of protection, and discusses ongoing and future post-licensure studies. Results In mice and non-human primate models, VLA1553 elicited high titres of neutralizing antibodies, conferred protection against wild-type chikungunya virus challenge and raised no safety concerns. A Phase 1 clinical trial of VLA1553 demonstrated 100% seroconversion among 120 healthy participants, with sustained neutralizing antibody titres after 12 months. These results and determination of a surrogate marker of protection led to advancement of VLA1553 directly into Phase 3 clinical development, as agreed with the US Food and Drug Administration (FDA) and the European Medicines Agency. The pivotal Phase 3 trial met its primary immunogenicity endpoint, achieving seroprotective levels based on immuno-bridging in baseline seronegative participants 28 days post-vaccination. These findings enabled submission of a Biologics Licence Application to the FDA for accelerated approval of VLA1553 in the US for adults aged ≥18 years. Ongoing and planned studies will confirm the clinical efficacy/effectiveness and safety of VLA1553 in adults and younger individuals, and will generate data in chikungunya endemic countries that have the highest unmet need. Conclusion VLA1553 is the first vaccine approved for the prevention of chikungunya disease in adults, following accelerated development based on a serological surrogate marker of protection. VLA1553 adds to strategies to reduce the spread and burden of chikungunya in endemic populations and travellers. [ABSTRACT FROM AUTHOR]

The article in the Journal of Travel Medicine discusses new insights into the Oropouche virus (OROV), an arbovirus belonging to the Simbu serogroup. OROV has been associated with outbreaks in various countries in the Americas, causing Oropouche fever characterized by fever, headache, and other symptoms. The virus has been linked to cases of vertical transmission, birth defects, and mortality, with cases reported in pregnant women and newborns. The spread of OROV has been observed in travelers returning from affected regions, highlighting the importance of monitoring and prevention strategies to address this emerging public health concern. [Extracted from the article]

West Nile virus (WNV) and St. Louis encephalitis virus (SLEV) are closely related flaviviruses that can cause encephalitis in humans and related diseases in animals. In nature, both are transmitted by Culex, with wild birds, including jays, sparrows, and robins, serving as vertebrate hosts. WNV and SLEV circulate in the same environments and have recently caused concurrent disease outbreaks in humans. The extent that coinfection of mosquitoes or birds may alter transmission dynamics, however, is not well characterized. We therefore sought to determine if coinfection alters infection kinetics and virus levels in birds and infection rates in mosquitoes. Accordingly, American robins (Turdus migratorius), two species of mosquitoes, and vertebrate and invertebrate cells were infected with WNV and/or SLEV to assess how simultaneous exposure may alter infection outcomes. There was variable impact of coinfection in vertebrate cells, with some evidence that SLEV can suppress WNV replication. However, robins had comparable viremia and antibody responses regardless of coinfection. Conversely, in Culex cells and mosquitoes, we saw a minimal impact of simultaneous exposure to both viruses on replication, with comparable infection, dissemination, and transmission rates in singly infected and coinfected mosquitoes. Importantly, while WNV and SLEV levels in coinfected mosquito midguts were positively correlated, we saw no correlation between them in salivary glands and saliva. These results reveal that while coinfection can occur in both avian and mosquito hosts, the viruses minimally impact one another. The potential for coinfection to alter virus population structure or the likelihood of rare genotypes emerging remains unknown. [ABSTRACT FROM AUTHOR]

Background: Madariaga virus (MADV), a member of the eastern equine encephalitis virus (EEEV) complex, circulates in Latin America and exhibits distinct evolutionary and ecological features compared to the North American EEEV. While published data have shed light on MADV ecology, several key aspects remain unknown. Methods: In this study, we compiled data on virus isolation, vector competence, and animal serology collected over six decades in Latin America to identify critical knowledge gaps on MADV transmission and ecology. Results: Specific vertebrate animals serving as amplifying hosts and the mosquito species acting as enzootic and epizootic vectors have not yet been identified. Other aspects that remain unclear are the virus current geographic distribution, the role of equines as hosts in epizootic cycles, and the full impact of MADV on human health in endemic regions. Conclusions: The numerous knowledge gaps surrounding MADV, its widespread distribution in Latin America, and its potential to cause severe disease in animals and humans emphasize the urgent need for increased research efforts, heightened awareness, and intensified surveillance towards this potential emerging threat. [ABSTRACT FROM AUTHOR]

The Orthobunyavirus oropoucheense species encompasses a group of arthropod‐borne zoonotic viruses transmitted by biting midges to animals including humans. Several large‐scale human outbreaks caused by the prototype member of this species, Oropouche virus (OROV) have been documented since the 1970s and were primarily confined to the Amazon basin. However, since 2022, more widespread OROV outbreaks have been unfolding in Brazil and across South America, with cases exported to Cuba, Italy, Spain, USA and Germany. In Brazil, the virus has reached and established communitary transmission in all geographic areas of the country. We isolated, characterized the cytopathic effect and recovered the full genome of two OROV isolates from the 2022–24 outbreak detected in patients from the Pernambuco state. Phylogenetic data supports a direct introduction from the Amazonas state, the epicenter of the epidemics in the country. As case counts accumulate in the state mounting evidence is supporting the establishiment of sustained transmission chains. Continued studies are critical to understand the transmission cycle in this region, including the most important vectors and reservoirs, to appropriately deploy control measures. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO) has emphasized the urgent need for alternative strategies to chemical insecticides for controlling mosquito populations, particularly the invasive Aedes species, which are known vectors of arboviruses. Among these alternative approaches, the sterile insect technique (SIT) is experiencing rapid development, with numerous pilot trials being conducted worldwide. Main text: This review aims to elucidate the principles of SIT and highlight the significant recent advancements that have facilitated its scalability. I also employ a phased conditional approach to categorize the progression of 39 projects, drawing on peer reviewed studies, press releases and direct communication with project managers. This review indicates that a substantial number of projects illustrate the efficacy of SIT in suppressing Aedes populations, with one project even demonstrating a reduction in dengue incidence. I offer several recommendations to mitigate potential failures and address the challenges of compensation and overcompensation when implementing SIT field trials. Furthermore, I examine the potential implications of male mating harassment on the effectiveness of SIT in reducing disease transmission. Conclusions: This comprehensive assessment underscores the promise of SIT as a viable strategy for mosquito control. The insights gained from these trials not only contribute to the understanding of SIT's effectiveness but also highlight the importance of careful project management and ecological considerations in the pursuit of public health objectives. [ABSTRACT FROM AUTHOR]

More than 75 arboviruses are indigenous to Australia, of which at least 13 are known to cause disease in humans. Alphaviruses are the most common arboviruses, notably including Ross River and Barmah Forest viruses, which contribute a significant public health and economic burden in Australia. Both can cause febrile illness with arthritic symptoms. Each circulates nationally across diverse climates and environments, and has multi-host, multi-vector dynamics. Several medically important flaviviruses also circulate in Australia. Infection with Murray Valley encephalitis or Kunjin viruses is less common but is associated with brain inflammation. Key research priorities for Australian arboviruses aim to understand clinical manifestations, develop timely diagnostics, and identify transmission cycles that permit the maintenance of arboviruses. While these can now be answered for a handful of notifiable alpha- and flaviviruses there are others for which non-human vertebrate hosts and competent arthropod invertebrate vectors are still to be identified and/or whose role in transmission is not well understood. One or more of these 'neglected' arboviruses may be the causative agent of a proportion of the many thousands of fever-related illnesses reported annually in Australia that at present remain undiagnosed. Here, what is known about enzootic cycling of viruses between arthropod vectors and mammalian and avian reservoir hosts is summarised. How and to what extent these interactions influence the epidemiology of arbovirus transmission and infection is discussed. [ABSTRACT FROM AUTHOR]

The incidence of dengue virus disease has increased globally across the past half-century, with highest number of cases ever reported in 2019 and again in 2023. We analyzed climatological, epidemiological, and phylogenomic data to investigate drivers of two decades of dengue in Cambodia, an understudied endemic setting. Using epidemiological models fit to a 19-y dataset, we first demonstrate that climate-driven transmission alone is insufficient to explain three epidemics across the time series. We then use wavelet decomposition to highlight enhanced annual and multiannual synchronicity in dengue cycles between provinces in epidemic years, suggesting a role for climate in homogenizing dynamics across space and time. Assuming reported cases correspond to symptomatic secondary infections, we next use an age-structured catalytic model to estimate a declining force of infection for dengue through time, which elevates the mean age of reported cases in Cambodia. Reported cases in >70-y-old individuals in the 2019 epidemic are best explained when also allowing for waning multitypic immunity and repeat symptomatic infections in older patients. We support this work with phylogenetic analysis of 192 dengue virus (DENV) genomes that we sequenced between 2019 and 2022, which document emergence of DENV-2 Cosmopolitan Genotype-II into Cambodia. This lineage demonstrates phylogenetic homogeneity across wide geographic areas, consistent with invasion behavior and in contrast to high phylogenetic diversity exhibited by endemic DENV-1. Finally, we simulate an age-structured, mechanistic model of dengue dynamics to demonstrate how expansion of an antigenically distinct lineage that evades preexisting multitypic immunity effectively reproduces the older-age infections witnessed in our data. [ABSTRACT FROM AUTHOR]

Our knowledge of alphavirus genetic diversity is mainly based on viruses isolated from anthropophilic mosquito species, humans, and livestock during outbreaks. Studies on alphaviruses from sylvatic amplification cycles in sub-Saharan Africa have been conducted less often than from epizootic environments. To gain insight into alphavirus diversity in enzootic transmission cycles, we collected over 23,000 mosquitoes in lowland rainforest and savannah gallery forest in southwestern Uganda and tested them for alphavirus infections. We detected Sindbis virus (SINV) in a Culex Culex sp. mosquito and Middelburg virus (MIDV) in Eretmapodites intermedius and Mansonia africana. MIDV is a mosquito-borne alphavirus that causes febrile illness in sheep, goats, and horses and was previously not known to occur in Uganda. SINV, also a mosquito-borne alphavirus, causes mild infections in humans. Full genomes of SINV and MIDV were sequenced, showing a nucleotide identity of 99% to related strains. Both isolates replicated to high titres in a wide variety of vertebrate cells. Our data suggest endemic circulation of SINV and MIDV in Uganda. [ABSTRACT FROM AUTHOR]

Introduction: Armenia's favorable geographical and climatic conditions support mosquitoes, sandflies, and ticks that can transmit various diseases. This study aimed to determine the prevalence of these vectors and circulating arboviruses in Armenia and assess healthcare workers' knowledge of arboviral diseases. Methodology: In 2021, we conducted fieldwork, combining morphological identification of vectors with polymerase chain reaction (PCR) analysis of pathogens to map the distribution of potential arbovirus vectors across Armenia. Results: Our entomological surveys identified four mosquito genera--Anopheles, Aedes, Culex, and Culiseta--comprising 20 species; and 11 species of Ixodidae ticks. Culex pipiens was found in all 11 regions, while Culiseta spp. was absent in Ararat Province. PCR testing of mosquito and tick samples revealed Crimean-Congo hemorrhagic fever virus (CCHFV) in 13 tick samples, but West Nile virus (WNV) was not detected in mosquitoes. Specifically, 13 out of 525 Ixodes tick pools tested positive for CCHFV; the positive samples originated from Hyalomma marginatum ticks in Syunik's Sisian region. None of the 11 pools that contained 473 Cx. pipiens mosquitoes tested positive for WNV. Analysis of questionnaires from 499 healthcare workers showed that epidemiologists, infectious disease specialists, and family doctors had greater awareness of arboviral diseases than other specialists. However, there was a low rate of sample submission for laboratory diagnosis and confirmation. Conclusions: The extensive presence of vectors combined with limited knowledge of arboviral diseases complicates disease understanding in Armenia. Strengthening the surveillance system through training and improved sample collection is essential for disease monitoring and public health interventions. [ABSTRACT FROM AUTHOR]

Insect-specific viruses (ISVs) include viruses that are restricted to the infection of mosquitoes and are spread mostly through transovarial transmission. Despite using a distinct mode of transmission, ISVs are often phylogenetically related to arthropod-borne viruses (arboviruses) that are responsible for human diseases and able to infect both mosquitoes and vertebrates. ISVs can also induce a phenomenon called "superinfection exclusion", whereby a primary ISV infection in an insect inhibits subsequent viral infections of the insect. This has sparked interest in the use of ISVs for the control of pathogenic arboviruses transmitted by mosquitoes. In particular, insect-specific flaviviruses (ISFs) have been shown to inhibit infection of vertebrate-infecting flaviviruses (VIFs) both in vitro and in vivo. This has shown potential as a new and ecologically friendly biological approach to the control of arboviral disease. For this intervention to have lasting impacts for biological control, it is imperative that ISFs are maintained in mosquito populations with high rates of vertical transmission. Therefore, these strategies will need to optimise vertical transmission of ISFs in order to establish persistently infected mosquito lines for sustainable arbovirus control. This review compares recent observations of vertical transmission of arboviral and insect-specific flaviviruses and potential determinants of transovarial transmission rates to understand how the vertical transmission of ISFs may be optimised for effective arboviral control. [ABSTRACT FROM AUTHOR]

Oropouche Virus (OROV; genus of Orthobunyavirus) is the causal agent of Oropouche Fever (OF). Due to the lack of specific signs and symptoms and the limited availability of diagnostic tests, the actual epidemiology of OROV infections and OF has been extensively disputed. In this systematic review with meta-analysis, a literature search was carried out in PubMed, Scopus, EMBASE, and MedRxiv in order to retrieve relevant articles on the documented occurrence of OROV infections. Pooled detection rates were then calculated for anti-OROV antibodies and virus detection (i.e., viral RNA detected by viral cultures and/or real-time polymerase chain reaction [RT-qPCR]). Where available, detection rates for other arboviruses (i.e., Dengue [DENV], Chikungunya [CHKV], and Zika Virus [ZIKV]) were calculated and compared to those for OROV. A total of 47 studies from South America and the Caribbean were retrieved. In individuals affected by febrile illness during OROV outbreaks, a documented prevalence of 0.45% (95% confidence interval [95%CI] 0.16 to 1.12) for virus isolation, 12.21% (95%CI 4.96 to 27.09) for seroprevalence (including both IgM and IgG class antibodies), and 12.45% (95%CI 3.28 to 37.39) for the detection of OROV-targeting IgM class antibodies were eventually documented. In the general population, seroprevalence was estimated to be 24.45% (95%CI 7.83 to 55.21) for IgG class antibodies. The OROV detection rate from the cerebrospinal fluids of suspected cases of viral encephalitis was estimated to be 2.40% (95%CI 1.17 to 5.03). The occurrence of OROV infections was consistently lower than that of DENV, CHKV, and ZIKV during outbreaks (Risk Ratio [RR] 24.82, 95%CI 21.12 to 29.16; RR 2.207, 95%CI 1.427 to 3.412; and RR 7.900, 95%CI 5.386 to 11.578, respectively) and in the general population (RR 23.614, 95%CI 20.584 to 27.129; RR 3.103, 95%CI 2.056 to 4.685; and RR 49.500, 95%CI 12.256 to 199.921, respectively). In conclusion, our study stresses the possibly high underestimation of OROV prevalence in the general population of South America, the potential global threat represented by this arbovirus infection, and the potential preventive role of a comprehensive "One Health approach". [ABSTRACT FROM AUTHOR]

Oral infection of mosquitoes by arboviruses often results in a large degree of variation in the amount of infectious virus between individual mosquitoes, even when the mosquitoes are from inbred laboratory strains. This variability in arbovirus load has been shown to affect virus transmissibility. Previously, our group described population genetic and specific infectivity differences between the virus populations found in high and low titer Aedes aegypti mosquitoes that had been orally infected with Sindbis virus (SINV). In this study, we sought to investigate whether there were also differences in transcriptomic response between these high and low titer mosquitoes. Results from the transcriptomic data analysis showed that more genes involved in antiviral activity, endopeptidase activity, and methyltransferase activity were upregulated in low titer mosquitoes than in high titer mosquitoes, relative to blood-fed controls. Meanwhile, genes involved in ion transport, energy metabolism, acetylation, glycosylation, lipid metabolism, and transport tended to be upregulated in high titer mosquitoes more than in low titer mosquitoes, relative to blood-fed mosquitoes. Overall, genes involved in antiviral activities tended to be upregulated in low titer mosquitoes while genes involved in proviral activities were mostly upregulated in high titer mosquitoes. This study has identified a number of candidate mosquito genes that are putatively associated with SINV titer variability after oral infection of Ae. aegypti, and these can now be investigated in order to ascertain their roles in virus replication and their contributions to determining vector competence. [ABSTRACT FROM AUTHOR]

Oropouche virus (OROV) is an emerging arbovirus endemic in Latin America and the Caribbean that causes Oropouche fever, a febrile illness that clinically resembles some other arboviral infections. It is currently spreading through Brazil and surrounding countries, where, from 1 January to 1 August 2024, more than 8000 cases have been identified in Bolivia, Brazil, Columbia, and Peru and for the first time in Cuba. Travelers with Oropouche fever have been identified in the United States and Europe. A significant occurrence during this epidemic has been the report of pregnant women infected with OROV who have had miscarriages and stillborn fetuses with placental, umbilical blood and fetal somatic organ samples that were RT-PCR positive for OROV and negative for other arboviruses. In addition, there have been four cases of newborn infants having microcephaly, in which the cerebrospinal fluid tested positive for IgM antibodies to OROV and negative for other arboviruses. This communication examines the biology, epidemiology, and clinical features of OROV, summarizes the 2023–2024 Oropouche virus epidemic, and describes the reported cases of vertical transmission and congenital infection, fetal death, and microcephaly in pregnant women with Oropouche fever, addresses experimental animal infections and potential placental pathology findings of OROV, and reviews other bunyavirus agents that can cause vertical transmission. Recommendations are made for pregnant women travelling to the regions affected by the epidemic. [ABSTRACT FROM AUTHOR]

Systemic viral infection of insects typically begins with the primary infection of midgut epithelial cells (enterocytes) and subsequent transit of the progeny virus in an apical-to-basal orientation into the hemocoel. For insect-vectored viruses, an oppositely oriented process (basal-to-apical transit) occurs upon secondary infection of salivary glands and is necessary for virus transmission to non-insect hosts. To examine this inversely oriented virus transit in these polarized tissues, we assessed the intracellular trafficking of two model viral envelope proteins (baculovirus GP64 and vesicular stomatitis virus G) in the midgut and salivary gland cells of the model insect, Drosophila melanogaster. Using fly lines that inducibly express either GP64 or VSV G, we found that each protein, expressed alone, was trafficked basally in midgut enterocytes. In salivary gland cells, VSV G was trafficked apically in most but not all cells, whereas GP64 was consistently trafficked basally. We demonstrated that a YxxØ motif present in both proteins was critical for basal trafficking in midgut enterocytes but dispensable for trafficking in salivary gland cells. Using RNAi, we found that clathrin adaptor protein complexes AP-1 and AP-3, as well as seven Rab GTPases, were involved in polarized VSV G trafficking in midgut enterocytes. Our results indicate that these viral envelope proteins encode the requisite information and require no other viral factors for appropriately polarized trafficking. In addition, they exploit tissue-specific differences in protein trafficking pathways to facilitate virus egress in the appropriate orientation for establishing systemic infections and vectoring infection to other hosts. IMPORTANCE Viruses that use insects as hosts must navigate specific routes through different insect tissues to complete their life cycles. The routes may differ substantially depending on the life cycle of the virus. Both insect pathogenic viruses and insect-vectored viruses must navigate through the polarized cells of the midgut epithelium to establish a systemic infection. In addition, insect-vectored viruses must also navigate through the polarized salivary gland epithelium for transmission. Thus, insect-vectored viruses appear to traffic in opposite directions in these two tissues. In this study, we asked whether two viral envelope proteins (VSV G and baculovirus GP64) alone encode the signals necessary for the polarized trafficking associated with their respective life cycles. Using Drosophila as a model to examine tissue-specific polarized trafficking of these viral envelope proteins, we identified one of the virus-encoded signals and several host proteins associated with regulating the polarized trafficking in the midgut epithelium. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to characterise long-term neurological and neurocognitive sequelae after tick-borne encephalitis (TBE) in adults. Methods: 98 prospective consecutive TBE patients, classified by disease severity, were included. Immediate outcomes were evaluated with Glasgow Outcome Scale (GOS) and Rankin Scale (RS). After 6 and 18 months, long-term disability was evaluated using Modified Rankin Scale (MRS) and neurocognitive assessment was performed with Matrics Consensus Cognitive Battery (MCCB), measuring processing speed, attention/vigilance, working memory, verbal learning, visual learning, reasoning/problem solving and social cognition. The MCCB results were compared to healthy age, gender and education-matched controls. Results: Mild, moderate, and severe TBE was diagnosed in 53.1%, 38.8%, and 8.2% of cases, respectively. At discharge, 25.5% of the patients had major or moderate impairments (GOS) and various levels of disability in 34.7% (RS). Up to 18 months from the onset of TBE, over 20% remained with slight to moderate disability (MRS). GOS, RS and MRS scores correlated with disease severity. At 6 months after the onset, TBE patients scored significantly lower than controls in processing speed, verbal, and visual learning. Two latter domains were significantly more impaired in patients with mild TBE. Patients aged 18-39 performed significantly worse in attention/vigilance and working memory, whereas aged 60+ in verbal learning. A year later, significant improvement was observed in six of seven cognitive domains. Conclusions: Long-term neurological sequelae persist in a substantial proportion of TBE patients with significant impairment in several cognitive domains, especially in younger patients and even after mild TBE. [ABSTRACT FROM AUTHOR]

Cervus nippon (sika deer) are widely distributed throughout eastern Asia. Deer possess a variety of antibodies against several zoonotic pathogens, indicating that they act as reservoir of zoonoses. In this study, we reported the characterization of cultured cells derived from sika deer and evaluated their susceptibility to arthropod-borne viruses to clarify their usefulness in virological studies. Cells derived from testicular tissue in Dulbecco's modified eagle medium with 16% fetal bovine serum started growing as primary cultured cells. The diploid cells consisted of 68 chromosomes, consistent with those of Japanese sika deer previously reported. The phylogenetic analysis showed the cells formed a robust clade with Japanese population of C. nippon, indicating that the cultured cells established in this study were originated from the Japanese sika deer. The cells immortalized by the simian virus 40 T-antigen were predominantly spindle-shaped cells exhibiting adhesive properties, and cultivated at 37°C and 5% CO2, which are common culture conditions for many mammalian cell lines. Western blotting analysis indicated that the cultured cells were multiple types of cells that coexist, including at least epithelial, fibroblast, and also Leydig cells. We confirmed that the cells have susceptibility to several arboviruses distributed in Japan: Getah virus, Japanese encephalitis virus, Oz virus, and severe fever with thrombocytopenia syndrome virus, but not to Tarumiz tick virus. From these results, the cells contribute to clarify the role of sika deer as a reservoir of zoonoses in nature and deer-associated experimental research at the cellular and molecular levels. [ABSTRACT FROM AUTHOR]

Background: Climate change is likely to increase the risk of human transmission of arboviruses endemic to Canada, including West Nile virus (WNV), Eastern equine encephalitis virus (EEEV) and California serogroup virus (CSV), calling for enhanced surveillance, including entomological surveillance targeting mosquito vectors. A scoping review was carried out to document the public health contributions of entomological surveillance of arboviruses of importance in Canada. Methods: The Ovid® and EBSCO platforms and the grey literature were searched to identify documents published between 2009 and 2023, in English or French, dealing with entomological surveillance of arboviruses of interest, conducted annually for human health purposes under the aegis of a government authority, with specified public health objectives and actions. Results: The 42 selected publications mainly reported two public health objectives of adult mosquito surveillance: early warning of viral circulation and assessment of the level of risk of human transmission. Recommended actions included clinical preparedness, risk communication, promotion of personal protection measures and vector control. The main objectives of immature mosquito surveillance were to identify sites with high larval densities, in order to reduce/eliminate them and target the application of larvicides. Conclusion: In a context of climate change favouring the spread of arboviruses, this study highlights the potential public health contributions of regular entomological surveillance of endemic arboviruses of importance in Canada. It helps support concrete actions to protect the health of the population from the risks of arboviral transmission. [ABSTRACT FROM AUTHOR]

Temperature is a determining factor for the viral cycle. In this study, we investigate the effect of different temperatures on the cycles of two important arboviruses—Zika (ZIKV) and Chikungunya (CHIKV)—in Vero (mammalian) and C6/36 (mosquito) cells. We compare genome quantification to infectivity at 28 °C and 37 °C in both cell types. Virus–cell interaction was also examined by transmission electron microscopy, allowing the observation of phenomena such as virus-surfing and giant forms for CHIKV, as well as the the scarcity of ZIKV in C6/36 cells compared to its cycle in mammalian cells. [ABSTRACT FROM AUTHOR]

Objetivos. Evaluar la frecuencia de los síntomas en pacientes con oropouche y compararlos con los observados en el dengue y otras arbovirosis. Métodos. Se realizó una revisión sistemática basada en MOOSE y PRISMA; se incluyeron estudios sobre manifestaciones clínicas agudas en pacientes con oropouche. La búsqueda incluyó las bases de datos PubMed, Biblioteca Virtual en Salud, Cochrane Library y Google Scholar hasta septiembre de 2024. Se compararon los síntomas del oropouche con los del dengue y otras arbovirosis, y se valoró la certeza con el enfoque GRADE. Resultados. Se incluyeron 23 estudios con 3 648 pacientes con oropouche. Los síntomas más frecuentes en pacientes con oropouche fueron fiebre (97%) y cefaleas (86%). No hubo diferencias en la frecuencia de fiebre ni cefaleas entre pacientes con oropouche y dengue. Sin embargo, la odinofagia (28%) y el dolor abdominal (15%) fueron más frecuentes en el oropouche que en el dengue (OR 3,20 y 2,50, respectivamente). Las mialgias (69%) y las artralgias (57%) fueron menos frecuentes en los pacientes con oropouche en comparación con el dengue. Conclusiones. La fiebre y las cefaleas son frecuentes en la fiebre de Oropouche, pero no ayudan a diferenciarlo del dengue. En cambio, la odinofagia y el dolor abdominal son más frecuentes en los pacientes con oropouche, mientras que las mialgias, las artralgias y el exantema prevalecen más en el dengue. Estos hallazgos pueden ayudar en el diagnóstico diferencial en áreas de cocirculación arboviral. Se requieren estudios adicionales sobre la recurrencia y la duración de los síntomas para mejorar las estrategias diagnósticas.

Abstract Vector‐borne diseases caused by arthropod‐borne viruses (arboviruses) are a considerable challenge to public health globally. Mosquito‐borne arboviruses, such as Chikungunya, Dengue, and Zika viruses, cause a range of human illnesses and may be fatal. Currently, efforts to control these diseases still face challenges due to growing vector resistance towards insecticides, urbanization, and limited effective antiviral treatments and vaccines. Animal models are crucial in antiviral research on mosquito‐borne arboviruses, playing a role in understanding disease mechanisms, vaccine development, and toxicity testing, but the application of animal models still faces the challenges of ethical considerations and animal‐to‐human translational success. Genetically engineered mouse models, hamster models and non‐human primate (NHP) are currently used in arbovirus research, but new models such as tree shrews and novel humanized mice are emerging. In the context of Malaysian research, the use of long‐tailed macaques as potential NHP models for arbovirus research is possible; however, it faces the ethical dilemma of using an endangered species for scientific purposes. Overall, animal models play a crucial role in advancing infectious disease research, but a balance between medical research and species conservation must be upheld.

Objetivo. Identificar e sintetizar evidências sobre efetividade e custo-efetividade da metodologia Aedes com Wolbachia para redução dos casos de arboviroses. Método. Revisão sistemática rápida, com busca realizada em fevereiro de 2022 em cinco portais de busca e bases de dados bibliográficas online. As etapas de seleção foram conduzidas por dois revisores, com resolução de conflitos por um terceiro. A extração dos dados foi feita por um revisor e conferida posteriormente por outro. Os critérios de inclusão foram estudos com descrição de custo-efetividade e efetividade da metodologia Aedes com Wolbachia, a partir de intervenções em campo, publicados nos idiomas português, inglês e espanhol, sem restrição de data de publicação. Resultados. Foram incluídos quatro estudos, sendo um ensaio randomizado em cluster, dois quase- experimental e um antes-depois, publicados entre 2019 e 2021 em quatro países. Os estudos encontrados tiveram resultados efetivos em alguns dos desfechos avaliados, como na diminuição da incidência de casos de dengue, Zika e chikungunya. Apesar de não terem sido identificados estudos experimentais abordando custo-efetividade da estratégia Aedes com Wolbachia, alguns estudos de modelagem demonstraram um potencial custo-benefício desta estratégia. Conclusão. Considerando os resultados apresentados, conclui-se que a Wolbachia apresenta potencial para ser uma estratégia economicamente efetiva e que leva à redução da incidência de casos de dengue, Zika e chikungunya. Apesar disso, não é possível, todavia, recomendar a estratégia como política pública, pois ainda são necessários mais estudos de grande porte e de alta qualidade metodológica para subsidiar a tomada de decisão política.

Fort Sherman virus (FSV) was isolated in Panama in 1985 from a US soldier. We report a case of human FSV infection in a febrile patient from northern coastal Peru in 2020. FSV infections spanning ≈35 years and a distance of 2,000 km warrant diagnostics, genomic surveillance, and investigation of transmission cycles.

Western equine encephalitis virus (WEEV) is a mosquitoborne virus that reemerged in December 2023 in Argentina and Uruguay, causing a major outbreak. We investigated the outbreak using epidemiologic, entomological, and genomic analyses, focusing on WEEV circulation near the Argentina‒Uruguay border in Rio Grande do Sul state, Brazil. During November 2023‒April 2024, the outbreak in Argentina and Uruguay resulted in 217 human cases, 12 of which were fatal, and 2,548 equine cases. We determined cases on the basis of laboratory and clinical epidemiologic criteria. We characterized 3 fatal equine cases caused by a novel WEEV lineage identified through a nearly complete coding sequence analysis, which we propose as lineage C. Our findings highlight the importance of continued surveillance and equine vaccination to control future WEEV outbreaks in South America.

Abstract Schmallenberg virus (SBV) and bluetongue virus (BTV) are both transmitted by Culicoides biting midges and infect predominantly ruminants. To investigate the extent of virus spread in the 2022 and 2023 vector seasons, we serologically tested wild ruminants from western Germany. While antibodies against BTV were not detected in any animal, regardless of age or sampling time, numerous wild ruminants tested positive for antibodies to SBV. In 2022, a low seroprevalence of 4.92% was measured. In sharp contrast, 40.15% of the animals tested positive in 2023. Of the young animals, about 31.82% were seropositive, clearly indicating large-scale SBV circulation in summer and autumn 2023.

Introduction Dengue disease represents a large and growing global threat to public health, accounting for a significant burden to health systems of endemic countries. The World Health Organization’s (WHO) Strategic Advisory Group of Experts (SAGE) and the European Medicines Agency (EMA) currently recommend the use of TAK-003 dengue vaccine in high dengue burden and transmission settings for countries considering vaccination as part of their integrated management strategy for prevention and control of Dengue.Areas covered This paper describes the main conclusions of a workshop held by the Arbovirus Committee of the Latin American Society of Pediatric Infectious Diseases (SLIPE) in November 2023, to generate consensus recommendations on the introduction of this new vaccine in the region. Considerations were made regarding the molecular epidemiology of dengue infection in the Americas and the need for more precise phylogenetic classification and correlation with clinical outcome and disease severity.Expert opinion Introduction of dengue vaccine should be considered as an strategy for health entities in the region, with participation of social sectors, scientific societies, and ministries of health that could be able to create a successful vaccination program.

Abstract Background Rift Valley fever virus (RVFV) is a zoonotic mosquito-borne virus with serious implications for livestock health, human health, and the economy in Africa, and is suspected to be endemic in north-eastern KwaZulu-Natal (KZN), South Africa. The vectors of RVFV in this area are poorly known, although several species, such as Aedes (Neomelaniconion) mcintoshi, Aedes (Neomelaniconion) circumluteolus, Aedes (Aedimorphus) durbanensis, and Culex (Lasioconops) poicilipes may be involved. The aim of the study was to determine the vertebrate blood meal sources of potential RVFV mosquito vectors in north-eastern KZN and to characterize the host-biting network. Methods Blood-fed mosquitoes were collected monthly from November 2019 to February 2023 using a backpack aspirator, CO2-baited Centers for Disease Control and Prevention (CDC) miniature light traps and tent traps, in the vicinity of water bodies and livestock farming households. The mosquitoes were morphologically identified. DNA was extracted from individual mosquitoes and used as templates to amplify the vertebrate cytochrome c oxidase I (COI) and cytochrome b (cytb) genes using conventional polymerase chain reaction (PCR). Amplicons were sequenced and queried in GenBank and the Barcode of Life Data systems to identify the vertebrate blood meal sources and confirm mosquito identifications. All mosquitoes were screened for RVFV using real time reverse transcription (RT)-PCR. Results We identified the mammalian (88.8%) and avian (11.3%) blood meal sources from 409 blood-fed mosquitoes. Aedes circumluteolus (n = 128) made up the largest proportion of collected mosquitoes. Cattle (n = 195) and nyala (n = 61) were the most frequent domestic and wild hosts, respectively. Bipartite network analysis showed that the rural network consisted of more host-biting interactions than the reserve network. All mosquitoes tested negative for RVFV. Conclusions Several mosquito species, including Ae. circumluteolus, and vertebrate host species, including cattle and nyala, could play a central role in RVFV transmission. Future research in this region should focus on these species to better understand RVFV amplification. Graphical Abstract

Abstract Oropouche and Mayaro viruses are enzootic arboviruses of public health concern throughout Latin America. Recent outbreaks of OROV in northern region and sporadic autochthonous cases in western region of Brazil, suggest a silent circulation of these neglected viruses. Aiming to investigate the exposure of different species of domestic animals to MAYV and OROV in urban and peri-urban areas of West-Central Brazil, we performed a cross-sectional serosurvey by plaque reduction neutralization test (PRNT). Our findings included neutralizing antibodies for both arboviruses in cattle, dogs and horses, suggesting eventual role of domestic animals in enzootic arbovirus surveillance in Brazil.

Dengue fever (DF) is the most frequent arboviral disease globally. Deforestation, armed conflicts, and climate change have caused an unprecedented global spread of DF, raising concerns in healthcare systems worldwide. Systemic manifestations of the disease range from mild to severe and, in some cases, can lead to death. Although neurological complications have been reported over the last few decades, they are often neglected or underreported. The present narrative review aims to describe the most important central and peripheral nervous system complications and provide guidance to neurologists in terms of diagnosis and management.

Abstract Background Culex pipiens L. is a principal vector of zoonotic arboviruses in Europe, acting in both an amplification role in enzootic transmission between avian hosts and as a bridge vector between avian hosts and mammals. The species consists of two forms which are indistinguishable using morphological methods but possess varying ecological and physiological traits that influence their vector capacity. In this study we validate methods that can be used to extract trace DNA from single pupal exuviae of Cx. pipiens for use in molecular speciation of samples. These DNA extraction methods are compared using measurement of the total yield and successful identification using a real-time polymerase chain reaction (PCR) assay. Results Genomic DNA was initially extracted from colony-derived individuals using an ethanol precipitation method, two commercially available DNA extraction kits: DNeasy® Blood & Tissue Kit (Qiagen, UK) and Wizard® SV Genomic DNA Purification System (Promega, UK) and a direct real-time PCR method. Time elapsed between eclosion and processing of pupae significantly influenced Cx. pipiens form identification as nucleic acid concentration and PCR amplification success decreased with increased time elapsed. Real-time PCR amplification success, however, was not shown to vary significantly between the three extraction methods, with all methods successfully identifying all samples, but the direct real-time PCR method achieved a lesser amplification success rate of 70% (n = 20 for each treatment). More variable results were produced when field-derived exuviae were used, with no significant difference in real-time PCR amplification success found across the four methods and a lower overall rate of successful identification of 55–80%. Conclusions This study shows that both colony and field derived Cx. pipiens pupal exuviae can be a useful non-invasive source of trace DNA permitting accurate biotype differentiation for at least twenty-four hours post-eclosion. The significance and utility of this technique in ecological and behavioural studies of Cx. pipiens is discussed and recommendations made for use according to experimental scenario.

Background: Rift Valley fever virus (RVFV) is a zoonotic mosquito-borne virus with serious implications for livestock health, human health, and the economy in Africa, and is suspected to be endemic in north-eastern KwaZulu-Natal (KZN), South Africa. The vectors of RVFV in this area are poorly known, although several species, such as Aedes (Neomelaniconion) mcintoshi, Aedes (Neomelaniconion) circumluteolus, Aedes (Aedimorphus) durbanensis, and Culex (Lasioconops) poicilipes may be involved. The aim of the study was to determine the vertebrate blood meal sources of potential RVFV mosquito vectors in north-eastern KZN and to characterize the host-biting network. Methods: Blood-fed mosquitoes were collected monthly from November 2019 to February 2023 using a backpack aspirator, CO2-baited Centers for Disease Control and Prevention (CDC) miniature light traps and tent traps, in the vicinity of water bodies and livestock farming households. The mosquitoes were morphologically identified. DNA was extracted from individual mosquitoes and used as templates to amplify the vertebrate cytochrome c oxidase I (COI) and cytochrome b (cytb) genes using conventional polymerase chain reaction (PCR). Amplicons were sequenced and queried in GenBank and the Barcode of Life Data systems to identify the vertebrate blood meal sources and confirm mosquito identifications. All mosquitoes were screened for RVFV using real time reverse transcription (RT)-PCR. Results: We identified the mammalian (88.8%) and avian (11.3%) blood meal sources from 409 blood-fed mosquitoes. Aedes circumluteolus (n = 128) made up the largest proportion of collected mosquitoes. Cattle (n = 195) and nyala (n = 61) were the most frequent domestic and wild hosts, respectively. Bipartite network analysis showed that the rural network consisted of more host-biting interactions than the reserve network. All mosquitoes tested negative for RVFV. Conclusions: Several mosquito species, including Ae. circumluteolus, and vertebrate host species, including cattle and nyala, could play a central role in RVFV transmission. Future research in this region should focus on these species to better understand RVFV amplification. [ABSTRACT FROM AUTHOR]

Due to several epizootic events between 2020 and 2021 in the south of Brazil near the border with Argentina, we performed mosquito surveys in areas of epidemiological risk in northeast Argentina to evaluate abundance and distributions of mosquito vectors from the yellow fever virus (YFV) (Diptera: Culicidae). For the most abundant species, the number of individuals captured per collector was evaluated based on the capturing time range. With a total sampling effort of 191 collector-hours, we captured 676 mosquitoes belonging to 6 genera and 16 species. The most abundant species were Aedes (Ochlerotatus) scapularis (Rondani) (33.58%), Sabethes (Sabethes) albiprivus Theobald (20.27%), Aedes (Stegomyia) albopictus (Skuse) (17.75%) and Haemagogus (Conopostegus) leucocelaenus (Dyar and Shannon) (15.86%). Sabethes albiprivus and Ae. albopictus showed activity peaks at noon and morning, respectively, while other species showed no important time differences between 10:00AM and 15:00PM. Our results show that the most abundant mosquito species in those environments with epidemiological risk in northern Corrientes and southern Misiones are categorized as important in the transmission of the YFV. Moreover, we report an expansion of Ae. albopictus distribution and the first record of Aedes (Ochlerotatus) patersoni Shannon and Del Ponte in Corrientes and Misiones provinces. [ABSTRACT FROM AUTHOR]

Mayaro virus (MAYV) is an arbovirus first isolated in Trinidad and Tobago in 1954. MAYV is the causative agent of Mayaro fever, which is characterised by high fever, maculopapular rash, myalgia and arthralgia. The potential for chronic arthralgia is of particular clinical concern. Currently, MAYV outbreaks are restricted to South and Central America, with some cases reported in Africa as well as several imported cases in Europe. However, in recent years, MAYV has become a growing global concern due to its potential to emerge into urban transmission cycles. Challenges faced with diagnostics, as well as a lack of specific antivirals or licensed vaccines further exacerbate the potential global health threat posed by MAYV. In this review, we discuss this emerging arboviral threat with a particular focus on the current treatment and vaccine development efforts. Overall, MAYV remains a neglected arbovirus due to its limited area of transmission. However, with the potential of its urbanisation and expanding circulation, the threat MAYV poses to global health cannot be overlooked. Further research into the improvement of current diagnostics, as well as the development of efficacious antivirals and vaccines will be crucial to help prevent and manage potential MAYV outbreaks. [ABSTRACT FROM AUTHOR]

The emergence and re-emergence of arthropod-borne viruses is a public health threat. For routine surveillance in public health laboratories, cost-effective and reproducible methods are essential. In this review, we address the technical considerations of high-throughput sequencing methods (HTS) for arbovirus surveillance in national health laboratories, focusing on pre-sequencing, sequencing, and post-sequencing approaches, underlining the importance of robust wet and dry laboratory workflows for reproducible analysis. We aim to provide insights for researchers and clinicians interested in arbovirus, diagnosis, and surveillance by discussing current advances in sequencing methods and bioinformatics pipelines applied to arboviruses. [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]

Advancing climate change increases the risk of future infectious disease outbreaks, particularly of zoonotic diseases, by affecting the abundance and spread of viral vectors. Concerningly, there are currently no approved drugs for some relevant diseases, such as the arboviral diseases chikungunya, dengue or zika. The development of novel inhibitors takes 10–15 years to reach the market and faces critical challenges in preclinical and clinical trials, with approximately 30% of trials failing due to side effects. As an early response to emerging infectious diseases, CavitOmiX allows for a rapid computational screening of databases containing 3D point-clouds representing binding sites of approved drugs to identify candidates for off-label use. This process, known as drug repurposing, reduces the time and cost of regulatory approval. Here, we present potential approved drug candidates for off-label use, targeting the ADP-ribose binding site of Alphavirus chikungunya non-structural protein 3. Additionally, we demonstrate a novel in silico drug design approach, considering potential side effects at the earliest stages of drug development. We use a genetic algorithm to iteratively refine potential inhibitors for (i) reduced off-target activity and (ii) improved binding to different viral variants or across related viral species, to provide broad-spectrum and safe antivirals for the future. [ABSTRACT FROM AUTHOR]

Aedes mosquitoes play a pivotal role as vectors of several arboviral diseases, presenting significant public health challenges worldwide. Their invasive success in tropical regions has raised substantial medical concerns. In Guatemala, Aedes mosquitoes are widely distributed and are the primary vectors of the dengue virus. Efforts to control and monitor Aedes populations have evolved over time, incorporating strategies such as spatial repellents, larvicides, genetic modifications, and targeted interventions. Previous research has shown the heterogeneous spatial-temporal distribution of these mosquitoes within each season, influenced by temperature variations and favorable environmental conditions for breeding. This study analyzed hot-spot patterns of spatiotemporal egg density in Santa Elena de la Cruz, Petén, Guatemala, from March to September 2022. The aim was to determine whether these patterns were influenced by non-residential larval habitats with plant cover that are not treated by healthcare entities, as well as the proximity between such habitats. Our findings include the collection and registration of over 16,000 Aedes eggs during the study period. Local analyses revealed hot-spot patterns in egg densities associated with non-residential larval habitats and their proximity. These insights highlight critical focal points where targeted interventions could be implemented more effectively, resulting in cost-efficient mosquito vector control. [ABSTRACT FROM AUTHOR]

Ticks can transmit many pathogens, including arboviruses, to their vertebrate hosts. Arboviruses must overcome or evade defense mechanisms during their passage from the tick gut to the hemolymph, salivary glands, and the feeding site in the host skin. This review summarizes current knowledge of defense mechanisms in specific tick tissues and at the feeding site in the host skin. We discuss the possible roles of these defense mechanisms in viral infection and transmission. The responses of tick salivary proteins to arbovirus infection are also discussed. This review provides information that may help accelerate research on virus–tick interactions. [ABSTRACT FROM AUTHOR]

Simple Summary: Arboviruses, such as Ross River virus, Barmah Forest virus, and dengue virus, have the potential to pose a public health threat in Australia. Certain arboviruses pose significant concerns due to their potential impact on the safety and supply of blood transfusion products, necessitating a greater in-depth understanding of spatiotemporal patterns. This study analyzed the spatiotemporal distribution of eight arboviruses of public health significance in Australia from 2002 to 2017, using Geographic Information System mapping and space–time scan statistics. Key weather variables, including rainfall, temperature, and humidity, were found to influence arbovirus incidence rates and blood donation counts. The findings highlight regions at risk and offer insights for improving public health interventions. Arboviruses pose a significant global public health threat, with Ross River virus (RRV), Barmah Forest virus (BFV), and dengue virus (DENV) being among the most common and clinically significant in Australia. Some arboviruses, including those prevalent in Australia, have been reported to cause transfusion-transmitted infections. This study examined the spatiotemporal variation of these arboviruses and their potential impact on blood donation numbers across Australia. Using data from the Australian Department of Health on eight arboviruses from 2002 to 2017, we retrospectively assessed the distribution and clustering of incidence rates in space and time using Geographic Information System mapping and space–time scan statistics. Regression models were used to investigate how weather variables, their lag months, space, and time affect case and blood donation counts. The predictors' importance varied with the spatial scale of analysis. Key predictors were average rainfall, minimum temperature, daily temperature variation, and relative humidity. Blood donation number was significantly associated with the incidence rate of all viruses and its interaction with local transmission of DENV, overall. This study, the first to cover eight clinically relevant arboviruses at a fine geographical level in Australia, identifies regions at risk for transmission and provides valuable insights for public health intervention. [ABSTRACT FROM AUTHOR]

Mosquito-borne arboviruses include several pathogens that are responsible for many diseases of significant public health burden. Mosquitoes also host many insect-specific viruses that cannot replicate in vertebrate cells. These insect-specific viruses persist in nature predominantly via vertical transmission (VT), and they exhibit high VT rates (VTRs). Cell-fusing agent virus (CFAV), an insect-specific orthoflavivirus, shows high VTRs in naturally infected mosquitoes but not in artificially infected mosquitoes. To determine whether the high VTRs are due to transovarial transmission, we investigated VT and ovary infection patterns in naturally CFAV-infected Aedes aegypti (Bangkok) mosquitoes. VT was monitored by detecting CFAV among the progeny by reverse-transcription polymerase chain reaction and ovary infection was determined by in situ hybridization using a virus-specific probe. We showed that in CFAV-positive mosquitoes, ovarian follicles were infected, suggesting that VT occurs by transovarial transmission in naturally infected mosquitoes. Additionally, mosquitoes harbored dormant, non-replicative CFAV that remained below the detection level. These results suggested that CFAV persists via VT in nature and has the potential to remain dormant in diapausing mosquitoes during unfavorable conditions. Understanding this VT mechanism is crucial for comprehending the persistence of insect-specific viruses (and potentially dual-host arboviruses) in their natural environment. [ABSTRACT FROM AUTHOR]

Dengue (DENV) and Chikungunya (CHIKV) viruses can be transmitted simultaneously by Aedes mosquitoes, and there may be co-infections in humans. However, how the adaptive immune response is modified in the host has yet to be known entirely. In this study, we analyzed the cross-reactivity and neutralizing activity of IgG antibodies against DENV and CHIKV in sera of patients from the Mexican Institute of Social Security in Veracruz, Mexico, collected in 2013 and 2015 and using IgG antibodies of BALB/c mice inoculated with DENV and/or CHIKV. Mice first inoculated with DENV and then with CHIKV produced IgG antibodies that neutralized both viruses. Mice were inoculated with CHIKV, and then with DENV; they had IgG antibodies with more significant anti-CHIKV IgG antibody neutralizing activity. However, the inoculation only with CHIKV resulted in better neutralization of DENV2. In sera obtained from patients in 2013, significant cross-reactivity and low anti-CHIKV IgG antibody neutralizing activity were observed. In CHIKV-positive 2015 sera, the anti-DENV IgG antibody neutralizing activity was high. These results suggest that CHIKV stimulates DENV2-induced memory responses and vice versa. Furthermore, cross-reactivity between the two viruses generated neutralizing antibodies, but exchanging CHIKV for DENV2 generated a better anti-CHIKV neutralizing response. [ABSTRACT FROM AUTHOR]

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Oropouche and Mayaro viruses are enzootic arboviruses of public health concern throughout Latin America. Recent outbreaks of OROV in northern region and sporadic autochthonous cases in western region of Brazil, suggest a silent circulation of these neglected viruses. Aiming to investigate the exposure of different species of domestic animals to MAYV and OROV in urban and peri-urban areas of West-Central Brazil, we performed a cross-sectional serosurvey by plaque reduction neutralization test (PRNT). Our findings included neutralizing antibodies for both arboviruses in cattle, dogs and horses, suggesting eventual role of domestic animals in enzootic arbovirus surveillance in Brazil. [ABSTRACT FROM AUTHOR]

Bluetongue virus (BTV, Sedoreoviridae: Orbivirus) causes an economically important disease, namely, bluetongue (BT), in domestic and wild ruminants worldwide. BTV is endemic to South India and has occurred with varying severity every year since the virus was first reported in 1963. BT can cause high morbidity and mortality to sheep flocks in this region, resulting in serious economic losses to subsistence farmers, with impacts on food security. The epidemiology of BTV in South India is complex, characterized by an unusually wide diversity of susceptible ruminant hosts, multiple vector species biting midges (Culicoides spp., Diptera: Ceratopogonidae), which have been implicated in the transmission of BTV and numerous co-circulating virus serotypes and strains. BT presence data (1997–2011) for South India were obtained from multiple sources to develop a presence/absence model for the disease. A non-linear discriminant analysis (NLDA) was carried out using temporal Fourier transformed variables that were remotely sensed as potential predictors of BT distribution. Predictive performance was then characterized using a range of different accuracy statistics (sensitivity, specificity, and Kappa). The top ten variables selected to explain BT distribution were primarily thermal metrics (land surface temperature, i.e., LST, and middle infrared, i.e., MIR) and a measure of plant photosynthetic activity (the Normalized Difference Vegetation Index, i.e., NDVI). A model that used pseudo-absence points, with three presence and absence clusters each, outperformed the model that used only the recorded absence points and showed high correspondence with past BTV outbreaks. The resulting risk maps may be suitable for informing disease managers concerned with vaccination, prevention, and control of BT in high-risk areas and for planning future state-wide vector and virus surveillance activities. [ABSTRACT FROM AUTHOR]

We performed whole genome sequencing (WGS) of 15 Palyam serogroup virus (PALV) strains isolated from cattle or Culicoides biting midges in Japan from 1984 to 2018. We found that the PALV strains consisted of Chuzan (Kasba) virus (CHUV), D'Aguilar virus (DAGV), Bunyip Creek virus, and another PALV, Marrakai virus (MARV). The Japanese MARV strains isolated in 1997 were closely related to Australian PALV strains isolated in 1968–1976 in genome segments 2 and 10, but they were most closely related to other Japanese PALV strains in the other genome segments. Our data suggest that the Japanese MARV strains were reassortant viruses between Asian and Australian PALVs. In addition to the WGS, we developed a real-time reverse-transcription polymerase chain reaction assay that can broadly detect PALV and specifically detect CHUV and DAGV, utilizing the data obtained by the WGS in this study. We detected the DAGV gene in bovine stillborn fetuses and congenitally abnormal calves in 2019 using the newly developed assay. To our knowledge, this is the first report of isolation of MARV outside of Australia and the first report of detection of PALV in bovine fetuses or calves with congenital abnormality outside of Africa. [ABSTRACT FROM AUTHOR]