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The spread of arboviruses like yellow fever, dengue, chikungunya, and Zika, transmitted by the invasive mosquito Aedes aegypti has led to the development of many strategies to suppress mosquito populations. Given the rapid development of resistance to common chemical larvicides and adulticides in some Ae. aegypti populations, as well as the ever-shrinking chemical options for mosquito control, there is a pressing need for new tools and deployment of those innovative tools as a component of integrative mosquito management programs. Prior to the adoption of any mosquito population intervention, be it conventional or innovative, understanding the baseline population is essential to evaluate the efficacy of the control measure. The Lee County Mosquito Control District in Florida has collected a three-year-long period of baseline entomological surveillance data collection for Ae. aegypti on Captiva and Sanibel Islands as foundational information prior to implementation of a new integrative mosquito management approach. We identified 18 mosquito species and described their population dynamics during the rainy and dry seasons. The two islands had no significant differences in species richness, diversity, dominance, or evenness overall. Yet, there were clear differences between the high rain season and low rain season in the Shannon diversity index, Simpson dominance index, and Pielou species evenness index within each site. Our data suggest that any innovative intervention should begin before mid to late April when the mosquito population is at its lowest and certainly before populations build up to their summer peak between June and September. These data also show the spatial distribution of Ae. aegypti is dynamic in space and time, identifying hotspots of mosquito abundance to focus on for future interventions. Overall, our study emphasizes the importance of entomological data collection to understand the population dynamics of Ae. aegypti mosquitoes, including the impact of environmental factors such as temperature and precipitation. [ABSTRACT FROM AUTHOR]

Background: Yellow fever virus (YFV) and dengue virus (DENV) are among the major re-emerging arboviruses that pose a significant threat to public health. Their associated burden and prevalence can be substantially underestimated due to insufficient surveillance and inadequate diagnosis. This study aimed to determine evidence of dengue, yellow and related flaviviruses circulation among the rural human populations residing in Nguruman (Kajiado County) and Kerio Valley (Baringo County), two dryland ecosystems in the Kenyan Rift Valley. Methods: Serum samples obtained from febrile patients between 5 and 85 years through a hospital-based cross-sectional survey from July 2020 – May 2023, were screened for neutralizing antibodies to YFV, DENV-2 and related flaviviruses, West Nile virus (WNV) and Zika virus (ZIKV) via Plaque reduction neutralization test (PRNT). The study sites and important demographic characteristics were obtained using a structural questionnaire and the data analyzed and seroprevalence compared. A multinomial logistic regression model was done to predict risk for each of the most prevalent viruses with covariates; age, gender, and occupation. Results: Overall, 54.5% (50.1–59.0% 95% confidence interval (CI) of the samples tested positive for at least one of the four Flaviviruses. The percentage was significantly higher in Kerio Valley (64.34%, 184/286) than in Nguruman (40.2%, 78/194) (P<0.0001). YFV had the highest prevalence, followed by WNV (16.25%), ZIKV (5.2%), and DENV-2 (1%). Kerio Valley had a significantly higher YFV seroprevalence (51%) than Nguruman (6%) (P<0.0001), while DENV-2 was observed only in Nguruman with a low seropositivity of 2%. In contrast to Nguruman, where seropositivity rates were higher in males at 47.47% (P=0.049), in Kerio Valley, females showed considerably higher viral seropositivity at 60.82% than males (P<0001). Conclusion: The study suggests that there is significant circulation of Flaviviruses in both regions, posing a public health risk, that could potentially contribute to clinical disease. However, seropositivity rates vary for each specific site. Furthermore, there could be a risk of YFV, WNV, and ZIKV transmission in both sites with DENV transmission specifically noted in Nguruman. The study findings inform direct cost-effective actions (such as YF vaccines) and precise surveillance data of vector populations for improved disease risk prediction. [ABSTRACT FROM AUTHOR]

The Atlantic Forest Biome (AFB) creates an ideal environment for the proliferation of vector mosquitoes, such as Haemagogus and Sabethes species, which transmit the Yellow Fever virus (YFV) to both human and non-human primates (NHP) (particularly Alouatta sp. and Callithrix sp.). From 2016 to 2020, 748 fatal cases of YF in humans and 1,763 in NHPs were reported in this biome, following several years free from the disease. This underscores the imminent risk posed by the YFV. In this study, we examined the spatiotemporal distribution patterns of YF cases in both NHPs and humans across the entire AFB during the outbreak period, using a generalized linear mixed regression model (GLMM) at the municipal level. Our analysis examined factors associated with the spread of YFV, including environmental characteristics, climate conditions, human vaccination coverage, and the presence of two additional YFV-affected NHP species. The occurrence of epizootics has been directly associated with natural forest formations and the presence of species within the Callithrix genus. Additionally, epizootics have been shown to be directly associated with human prevalence. Furthermore, human prevalence showed an inverse correlation with urban areas, temporary croplands, and savannah and grassland areas. Further analyses using Moran's Index to incorporate the neighborhoods of municipalities with cases in each studied host revealed additional variables, such as altitude, which showed a positive correlation. Additionally, the occurrence of the disease in both hosts exhibited a spatio-temporal distribution pattern. To effectively mitigate the spread of the virus, it is necessary to proactively expand vaccination coverage, refine NHP surveillance strategies, and enhance entomological surveillance in both natural and modified environments. [ABSTRACT FROM AUTHOR]

Flavivirus infection is tightly connected to host lipid metabolism. Here, we performed shotgun lipidomics of cells infected with neurotropic Zika, West Nile, and tick-borne encephalitis virus, as well as dengue and yellow fever virus. Early in infection specific lipids accumulate, e.g., neutral lipids in Zika and some lysophospholipids in all infections. Ceramide levels increase following infection with viruses that cause a cytopathic effect. In addition, fatty acid desaturation as well as glycerophospholipid metabolism are significantly altered. Importantly, depletion of enzymes involved in phosphatidylserine metabolism as well as phosphatidylinositol biosynthesis reduce orthoflavivirus titers and cytopathic effects while inhibition of fatty acid monounsaturation only rescues from virus-induced cell death. Interestingly, interfering with ceramide synthesis has opposing effects on virus replication and cytotoxicity depending on the targeted enzyme. Thus, lipid remodeling by orthoflaviviruses includes distinct changes but also common patterns shared by several viruses that are needed for efficient infection and replication. Viruses need host cell lipids for multiplication. Here, the authors use lipidomics to show that lipid remodeling by orthoflaviviruses includes distinct changes but also shared patterns, some of which are needed for efficient viral replication. [ABSTRACT FROM AUTHOR]

Dengue and yellow fever have complex cycles, involving urban and sylvatic mosquitoes, and non‐human primate hosts. To date, efforts to assess the effect of climate change on these diseases have neglected the combination of such crucial factors. Recent studies only considered urban vectors. This is the first study to include them together with sylvatic vectors and the distribution of primates to analyse the effect of climate change on these diseases. We used previously published models, based on machine learning algorithms and fuzzy logic, to identify areas where climatic favourability for the relevant transmission agents could change: 1) favourable areas for the circulation of the viruses due to the environment and to non‐human primate distributions; 2) the favourability for urban and sylvatic vectors. We obtained projections of future transmission risk for two future periods and for each disease, and implemented uncertainty analyses to test for predictions reliability. Areas currently favourable for both diseases could keep being climatically favourable, while global favourability could increase a 7% for yellow fever and a 10% increase for dengue. Areas likely to be more affected in the future for dengue include West Africa, South Asia, the Gulf of Mexico, Central America and the Amazon basin. A possible spread of dengue could take place into Europe, the Mediterranean basin, the UK and Portugal; and, in Asia, into northern China. For yellow fever, climate could become more favourable in Central and Southeast Africa; India; and in north and southeast South America, including Brazil, Paraguay, Bolivia, Peru, Colombia and Venezuela. In Brazil, favourability for yellow fever will probably increase in the south, the west and the east. Areas where the transmission risk spread is consistent to the dispersal of vectors are highlighted in respect of areas where the expected spread is directly attributable to environmental changes. Both scenarios could involve different prevention strategies. [ABSTRACT FROM AUTHOR]

Background: Aedes aegypti, is the primary vector of dengue, Chikungunya, Zika, and yellow fever viruses. Both natural and human-impacted landscapes have selective pressures on Ae. aegypti, resulting in strong genomic structure even within close geographical distances. Materials and Methods: We assess the genetic structure of this medically important mosquito species at the northern leading edge of their distribution in Southwestern USA. Ae. aegypti were collected during 2017 in the urban communities of El Paso and Sparks, Texas (USA) and in the city of Ciudad Juárez, Mexico. Results: Thousands of nuclear loci were sequenced across 260 captured Ae. aegypti. First, we recovered the genetic structure of Ae. aegypti following geography, with all four major collection communities being genetically distinct. Importantly, we found population structure and genetic diversity that suggest rapid expansion through active-short distance dispersals, with Anapra being the likely source for the others. Next, tests of selection recovered eight functional genes across six outliers: calmodulin with olfactory receptor function; the protein superfamily C-type lectin with function in mosquito immune system and development; and TATA box binding protein with function in gene regulation. Conclusion: Despite these populations being documented in the early 2000s, we find that selective pressures on specific genes have already occurred and likely facilitate Ae. aegypti range expansion. [ABSTRACT FROM AUTHOR]

The RNA genome of orthoflaviviruses encodes a methyltransferase within the non-structural protein NS5, which is involved in 2'-O-methylation of the 5'-terminal nucleotide of the viral genome resulting in a cap1 structure. While a 2'-O-unmethylated cap0 structure is recognized in vertebrates by the RNA sensor RIG-I, the cap1 structure allows orthoflaviviruses to evade the vertebrate innate immune system. Here, we analyzed whether the cap0 structure is also recognized in mosquitoes. Replication analyses of 2'-O-methyltransferase deficient yellow fever virus mutants (YFV NS5-E218A) of the vaccine 17D and the wild-type Asibi strain in mosquito cells revealed a distinct downregulation of the cap0 viruses. Interestingly, the level of inhibition differed for various mosquito cells. The most striking difference was found in Aedes albopictus-derived C6/36 cells with YFV-17D cap0 replication being completely blocked. Replication of YFV-Asibi cap0 was also suppressed in mosquito cells but to a lower extent. Analyses using chimeras between YFV-17D and YFV-Asibi suggest that a synergistic effect of several mutations across the viral genome accompanied by a faster initial growth rate of YFV-Asibi cap1 correlates with the lower level of YFV-Asibi cap0 attenuation. Viral growth analyses in Dicer-2 knockout cells demonstrated that Dicer-2 is entirely dispensable for attenuating the YFV cap0 viruses. Translation of a replication-incompetent cap0 reporter YFV-17D genome was reduced in mosquito cells, indicating a cap0 sensing translation regulation mechanism. Further, oral infection of Aedes aegypti mosquitoes resulted in lower infection rates for YFV-Asibi cap0. The latter is related to lower viral loads found in the midguts, which largely diminished dissemination to secondary tissues. After intrathoracic infection, YFV-Asibi cap0 replicated slower and to decreased amounts in secondary tissues compared to YFV-Asibi cap1. These results suggest the existence of an ubiquitously expressed innate antiviral protein recognizing 5'-terminal RNA cap-modifications in mosquitoes, both in the midgut as well as in secondary tissues. Author summary: Arthropod-borne viruses infect both mosquito and vertebrate hosts. One factor influencing the level of viral replication in the host is the ability of the virus to evade or counteract the host's immune system. In vertebrates, it was shown that orthoflaviviruses circumvent the innate immune system by capping their viral genome with a cap1 structure characterized by 2'-O-methylation of the 5'-terminal nucleotide. In contrast, viral genomes lacking 2'-O-methylation (cap0) are recognized as foreign and activate the vertebrate innate immune system. Here, we used yellow fever virus (YFV) strain 17D and Asibi mutants lacking 2'-O-methylation, as well as a cap0 reporter YFV genome, to analyze cap0 recognition in mosquito cells and living mosquitoes. The replication of the YFV cap0 mutants was profoundly impaired in different mosquito cells and cap0 YFV genomes showed reduced translation levels. Based on viral infection experiments in Aedes aegypti mosquitoes, we further demonstrate that these vector mosquitoes recognize the cap0 structure and that a potential recognizing effector protein is localized in the midgut as well as in secondary tissues. Our findings provide the basis for future studies investigating the recognition of foreign RNAs in mosquitoes and should contribute to establish methods to prevent transmission of arboviruses. [ABSTRACT FROM AUTHOR]

Vector-borne infections are a class of human diseases resulting from the transmission of pathogenic microorganisms, including bacteria, viruses, and parasites, through various vectors. Yellow fever, prevalent in both the American and African continents, stands as a prominent example of vector-borne infections. In this paper, we structure the transmission dynamics of yellow fever with vaccine and treatment through non-integer derivative. The fixed point theorem introduced by Banach and Schaefer is utilized to examine the existence and uniqueness of solutions for the proposed yellow fever system. The sufficient conditions of the Ulam-Hyers stability has been established for our system. The solution routes are highlighted using the Laplace Adomian decomposition method to show the influence of input factors on yellow fever. In order to visualise the impacts of fractional-order, vaccine, biting rate, and treatment on the infection level, numerical simulations are performed. We proposed the most attractive parameters of the system for the prevention and control of the infection. Furthermore, it is proposed that the biting rate of mosquitoes is dangerous and can increase the possibility of infection in the community. We suggest that the index of memory, treatment and vaccination are attractive parameters which can reduce the level of infection. [ABSTRACT FROM AUTHOR]

Monitoring yellow fever in non-human primates (NHPs) is an early warning system for sylvatic yellow fever outbreaks, aiding in preventing human cases. However, current diagnostic tests for this disease, primarily relying on RT-qPCR, are complex and costly. Therefore, there is a critical need for simpler and more cost-effective methods to detect yellow fever virus (YFV) infection in NHPs, enabling early identification of viral circulation. In this study, an RT-LAMP assay for detecting YFV in NHP samples was developed and validated. Two sets of RT-LAMP primers targeting the YFV NS5 and E genes were designed and tested together with a third primer set to the NS1 locus using NHP tissue samples from Southern Brazil. The results were visualized by colorimetry and compared to the RT-qPCR test. Standardization and validation of the RT-LAMP assay demonstrated 100% sensitivity and specificity compared to RT-qPCR, with a detection limit of 12 PFU/mL. Additionally, the cross-reactivity test with other flaviviruses confirmed a specificity of 100%. Our newly developed RT-LAMP diagnostic test for YFV in NHP samples will significantly contribute to yellow fever monitoring efforts, providing a simpler and more accessible method for viral early detection. This advancement holds promise for enhancing surveillance and ultimately preventing the spread of yellow fever. [ABSTRACT FROM AUTHOR]

The recent global outbreaks of infectious diseases such as COVID-19, yellow fever, and Ebola have highlighted the critical need for robust health data management systems that can rapidly adapt to and mitigate public health emergencies. In contrast to traditional systems, this study introduces an innovative blockchain-based Electronic Health Record (EHR) access control mechanism that effectively safeguards patient data integrity and privacy. The proposed approach uniquely integrates granular data access control mechanism within a blockchain framework, ensuring that patient data is only accessible to explicitly authorized users and thereby enhancing patient consent and privacy. This system addresses key challenges in healthcare data management, including preventing unauthorized access and overcoming the inefficiencies inherent in traditional access mechanisms. Since the latency is a sensitive factor in healthcare data management, the simulations of the proposed model reveal substantial improvements over existing benchmarks in terms of reduced computing overhead, increased throughput, minimized latency, and strengthened overall security. By demonstrating these advantages, the study contributes significantly to the evolution of health data management, offering a scalable, secure solution that prioritizes patient autonomy and privacy in an increasingly digital healthcare landscape. [ABSTRACT FROM AUTHOR]

Background: Climate change and urbanization will alter the global distribution of disease vectors, changing the disease burden in yet unpredictable ways. Aedes aegypti is a mosquito responsible for transmitting dengue, Zika, chikungunya, and yellow fever viruses that breeds in containers associated with urban environments. We sought to understand how ambient temperature and larval densities in the immature aquatic phases determine adult life history traits and dengue virus loads post-infection. We predicted that larval crowding and high temperatures would both lead to smaller mosquitoes that might struggle to invest in an immune response and, hence, would exhibit high viral loads. Methods: We first examined larval densities from urban and rural areas via a meta-analysis. We then used these data to inform a laboratory-based 2x2 design examining the interacting effects of temperature (21 vs. 26°C) and density (0.2 vs. 0.4 larvae/mL) on adult life history and dengue virus loads. Results: We found that urban areas had an ~8-fold increase in larval densities compared to more rural sites. In the lab, we found that crowding had more impact on mosquito traits than temperature. Crowding led to slower development, smaller mosquitoes, less survival, lower fecundity, and higher viral loads, as predicted. The higher temperature led to faster development, reduced fecundity, and lower viral loads. The virus-reducing effect of higher temperature rearing was, however, overwhelmed by the impact of larval crowding when both factors were present. Conclusions: These data reveal complex interactions between the environmental effects experienced by immature mosquitoes and adult traits. They especially highlight the importance of crowding with respect to adult viral loads. Together, these data suggest that urban environments might enhance dengue virus loads and, therefore, possibly transmission, a concerning result given the increasing rates of urbanization globally. Author summary: The mosquito Aedes aegypti is responsible for transmitting several viruses to humans, including Zika, yellow fever, chikungunya, and dengue. The geographic distribution of this tropical, anthropophilic mosquito vector continues to expand globally due to climate change and increasing urbanization. Ambient temperature and larval densities are two of the most powerful factors in the aquatic juvenile stage in determining adult mosquito traits. Using a meta-analysis, we reveal that urban environments are associated with greater crowding in the larval phase for Ae. aegypti. In the laboratory, we then demonstrate that similar levels of larval crowding also led to increased dengue virus loads in adults following an infectious bloodmeal, which may increase transmission. In contrast, higher temperatures in the larval phase were associated with reduced viral loads in adults, but only when crowding is not present. This is a concerning relationship given that 68% of the world's population will live in urban environments by 2050. [ABSTRACT FROM AUTHOR]

Background: Variations in vaccine responses have been observed between populations. A role for helminth infections has been proposed due to their immunomodulatory properties. In a secondary analysis of data from a randomised trial assessing effects of anthelminthic treatment on vaccine responses, we examined associations between helminth infections at baseline prior to vaccine administration, and vaccine responses among adolescents (9-17 years) in Koome Islands, Lake Victoria, Uganda. Methods: Participants received BCG [week 0], yellow fever (YF-17D), oral typhoid (Ty21a), HPV-prime [week 4], and HPV-boost, tetanus/diphtheria [week 28]. Outcomes were BCG-specific interferon-g ELISpot responses and antibody responses to yellow-fever-, typhoid-, HPV-, tetanus- and diphtheria-specific antigens measured at two time points post vaccination. S. mansoni infection was determined as positive if either the plasma Circulating Anodic Antigen (CAA) assay or stool PCR were positive. Hookworm and Strongyloides were determined by stool PCR. Linear mixed effects regression was used to assess associations. Results: Among 478 adolescents, 70% were Schistosoma mansoni (Sm) infected and 23% hookworm infected at baseline. Sm was associated with lower Salmonella Typhi O:LPS-specific IgG responses (adjusted geometric mean ratio (aGMR) 0.69 (0.57-0.83)), and hookworm with higher diphtheria-specific IgG (aGMR 1.16 (1.02, 1.31)) and lower HPV-16-specific IgG (aGMR 0.70 (0.55, 0.90)) post-vaccination. High Sm intensity was associated with lower BCG-specific interferon-g and S. Typhi O:LPS-specific IgG. Conclusions: We found inverse associations between Sm and responses to two live vaccines, whereas hookworm was positively associated with diphtheriaspecific IgG. These findings support the hypothesis that helminth infections can modulate vaccine responses, while also highlighting potential heterogeneity in the direction of these effects. [ABSTRACT FROM AUTHOR]

An estimated 2.5 million people have been internally and externally displaced in the Tigray region of northern Ethiopia in conflict and post-conflict settings. This induced a loss of access to basic and essential healthcare services. The situation was overwhelming, causing service inaccessibility, inadequate health facilities, unstable security to access the services, shortage of supplies and drugs, and medical equipment's in the region. The regional public health emergency management is one service delivery set up for the critically ill. It is characterized by weak emergency management capacities, poor coordination and integration. In addition, the system falls in to two independent sectors in the Tigray Health Bureau (THB), Tigray Health Research Institute (THRI). This leads to a fragmented system, an unclear leadership and governance role and a poor service delivery setup and tracking mechanism. The situation leads to resource duplication and poor business practice. Indeed, this type of service delivery setup secures personal and professional interest more than community interest. The situation exacerbated the occurrence of recurrent outbreaks in the region, with, for instance, zoonotic diseases (anthrax and rabies), acute watery diarrhoea, measles, malaria, yellow fever, and coronavirus disease 2019 (COVID-19) approaching to their level of epidemic. Moreover, they will spike as an epidemic in the future. All these circumstances made it evident that the system need reform to adhere with legal global, national, and regional frameworks, guidelines and proclamations. The system should have one service delivery set up at regional level. It must fall into regional public health institutes (PHIs) to adhere its service packages to the current advancements. Furthermore, integrated effort need from program implementers, relevant stakeholders and policy-makers should be committed and work together in the review and reform process. [ABSTRACT FROM AUTHOR]

Over the past decades, the number of arthropod-borne virus (arbovirus) outbreaks has increased worldwide. Knowledge regarding the sylvatic cycle (i.e., non-human hosts/environment) of arboviruses is limited, particularly in Africa, and the main hosts for virus maintenance are unknown. Previous studies have shown the presence of antibodies against certain arboviruses (i.e., chikungunya-, dengue-, and zika virus) in African non-human primates and bats. We hypothesize that small mammals, specifically rodents, may function as amplifying hosts in anthropogenic environments. The detection of RNA of most arboviruses is complicated by the viruses' short viremic period within their hosts. An alternative to determine arbovirus hosts is by detecting antibodies, which can persist several months. Therefore, we developed a high-throughput multiplex immunoassay to detect antibodies against 15 medically relevant arboviruses. We used this assay to assess approximately 1,300 blood samples of the multimammate mouse, Mastomys natalensis from Tanzania. In 24% of the samples, we detected antibodies against at least one of the tested arboviruses, with high seroprevalences of antibodies reacting against dengue virus serotype one (7.6%) and two (8.4%), and chikungunya virus (6%). Seroprevalence was higher in females and increased with age, which could be explained by inherent immunity and behavioral differences between sexes, and the increased chance of exposure to an arbovirus with age. We evaluated whether antibodies against multiple arboviruses co-occur more often than randomly and found that this may be true for some members of the Flaviviridae and Togaviridae. In conclusion, the development of an assay against a wide diversity of medically relevant arboviruses enabled the analysis of a large sample collection of one of the most abundant African small mammals. Our findings highlight that Mastomys natalensis is involved in the transmission cycle of multiple arboviruses and provide a solid foundation to better understand the role of this ubiquitous rodent in arbovirus outbreaks. Author summary: One of the main causes of zoonotic related human morbidity and mortality is the transmission of arthropod-borne viruses such as dengue virus, Yellow Fever virus, and chikungunya virus. These viruses cannot only infect humans but also livestock, pets, and wildlife, though our understanding of their non-human hosts remains limited. Rodents are thought to be an important host for these viruses because they can be abundant, often live near humans, and some are already known to be viral hosts. However, research has focused mostly on non-human primates, neglecting other potential wild hosts. To address this gap, we have developed a high-throughput antibody test to screen rodent blood against 15 different arboviruses. Our findings reveal that Mastomys natalensis, a common African rodent species, carries antibodies that (cross-)react against these viruses. We hypothesize that immunologically naïve juveniles may drive transmission, particularly during population outbreaks. These outbreaks coincide with environmental conditions that are favorable for mosquitoes, thus increasing the risk of spillover to humans, livestock, and wildlife. Understanding the role of rodents in arbovirus transmission dynamics is crucial for mitigating zoonotic disease risks. [ABSTRACT FROM AUTHOR]

Viral diseases like yellow fever, dengue, and Zika have an alarming impact on public health. These diseases can be transmitted by Aedes mosquito species, such as Ae. albopictus, which is now found in many countries outside its original range. Xenorhabdus and Photorhabdus spp. are enteric bacterial symbionts of insect-preying nematodes and are known to produce an array of natural products with various activities including larvicidal activity. In this study, the effects of natural products produced by four Xenorhabdus and one Photorhabdus bacteria on the ovipositional behavior of Ae. albopictus mosquitoes were assessed. Utilizing a binary choice assay in insect cages, gravid female mosquitoes were presented with two oviposition cups containing water supplemented with varying concentrations of bacterial supernatants (50–1% concentrations) versus control medium. After 72 h, the eggs deposited on filter papers were counted. The oviposition attractant index (OAI) feature of the bacterial supernatant was evaluated using the number of eggs laid in the cups. Notably, all tested supernatants exhibited concentration-dependent deterrence of oviposition. Xenorhabdus cabanillasii displayed the strongest deterrent effect, inhibiting egg-laying at 50–5% concentrations (OAI: − 0.87 to − 0.35), followed by X. nematophila (50–10%, OAI: − 0.82 to − 0.52). Xenorhabdus szentirmaii, X. doucetiae, and P. kayaii showed significant deterrence at ≥ 20% concentrations. Using promoter exchange mutants generated by the easyPACId approach, fabclavine from X. szentirmaii was identified as the bioactive compound with evident deterrent effects. Such deterrents targeting egg-laying could be valuable for controlling populations by disrupting their breeding in suitable habitats. [ABSTRACT FROM AUTHOR]

Abundance and seasonal composition of adult indoor resting Culicine mosquitoes in Dutse were studied between April to September 2021. Culex pipiens complex and Aedes species has been proven as the potential vectors of public health importance. However, their abundance and seasonal composition has not been adequately studied in Dutse, Northwest Nigeria to document their vectorial profile. This study was designed to fill the gap. Adult indoor resting mosquitoes were collected using Pyrethrum Spray catch (PSC) from April - September 2021 and were morphologically and molecularly identified using keys and polymerase chain reaction (PCR). Data generated were analysed using Statistical Package for Social Sciences (SPSS). 2656 mosquitoes, comprising Culex quinquefasciatus (2507) and Aedes species (149) were collected. Culex quinquefasciatus was the most abundant species (94.4%) collected while the least were Aedes species (5.6%). The results revealed that in Jidawa, more Culex quinquefasciatus (80) were collected in August while the least were collected in June (25). For Aedes mosquitoes, higher collection (75) was realised in April while July recorded zero collection. The monthly variation of the mosquitoes showed the peak in the month of April (690) and May (300) in Jidawa when compared to Kargo (430) and (100) respectively. In the dry season, more mosquitoes were collected In Jidawa while in Kargo more were collected during the wet seasons. The result of the molecular identification of the Culex pipiens complex reveals Culex quinquefasciatus as the only sibling species in both Jigawa and Kargo. The occurrence of Culex quinquefasciatus and Aedes species is an indication of the signal against lymphatic filariasis, dengue fever, arbovirus and yellow fever in the area. Therefore, there is need for vector control programmes and public orientation on the drivers of mosquito abundance in the study area, taking into cognisance the seasonality variation of the mosquitoes. [ABSTRACT FROM AUTHOR]

The article focuses on the 1793 outbreak of yellow fever in the early American republic and Atlantic world and how it impacted the origins of the democratic movement. The author discusses how Philadelphia, Pennsylvania’s Democratic Republicans worked to form the Democratic Society of Pennsylvania and how it was impacted by the pandemic outbreak.

• Essential oils from Cerrado plants are active against Aedes aegypti. • Alpinia zerumbet and E. langsdorffii oils show larvicide potential for Ae. aegypti. • Eugenia langsdorffii exhibits new larvicidal properties against mosquitos. The Aedes aegypti mosquito serves as the primary vector for transmitting viral diseases such as dengue, Zika, chikungunya, and urban yellow fever. Essential oils comprising volatile organic compounds derived from a single plant species have demonstrated repellent activity against various mosquito species, including Ae. aegypti. Despite their potential therapeutic benefits, only limited studies have explored the larvicidal activity of essential oil from plants occurring in Cerrado. To address this gap, the present study evaluated the larvicidal efficacy of different essential oils (EO) sourced from native and cultivated plants in the Cerrado biome against Ae. aegypti larvae. Essential oils were extracted from Alpinia zerumbet (Pers.) B.L.Burtt & R.M.Sm., Baccharis retusa DC., Blepharocalyx salicifolius (Kunth) O. Berg, Cymbopogon densiflorus (Steud.) Stapf , Eugenia langsdorffii O. Berg , Myracrodruon urundeuva Allemão. Notably, B. retusa is dioecious; hence, it was categorized into male and female plants each with a separated extraction of leaves and flowers. Among the essential oils tested, those derived from A. zerumbet and E. langsdorffii exhibited the highest activity, resulting in 100 % mortality of Ae. aegypti larvae at a 100 mg/L concentration. The calculated LC 50 values were 36.6 mg/L and 53.5 mg/L for A. zerumbet and E. langsdorffii, respectively, with the corresponding LC 90 values of 66.3 mg/L and 103.9 mg/L. Analysis of the major components revealed the presence of 1,8-cineole, sabinene, terpinen-4-ol, and γ-terpinene in A. zerumbet essential oil, while limonene, δ-cadinol, myrcene, and spathulenol were predominant in E. langsdorffii essential oil. However, further studies are required to identify the active components responsible for the observed larvicidal activity and elucidate their mode of action. [ABSTRACT FROM AUTHOR]

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Arthropod‐borne viruses, such as dengue virus (DENV), pose significant global health threats, with DENV alone infecting around 400 million people annually and causing outbreaks beyond endemic regions. This study aimed to enhance serological diagnosis and discover new drugs by identifying immunogenic protein regions of DENV. Utilizing a comprehensive approach, the study focused on peptides capable of distinguishing DENV from other flavivirus infections through serological analyses. Over 200 patients with confirmed arbovirus infection were profiled using high‐density pan flavivirus peptide arrays comprising 6253 peptides and the computational method matrix of local coupling energy (MLCE). Twenty‐four peptides from nonstructural and structural viral proteins were identified as specifically recognized by individuals with DENV infection. Six peptides were confirmed to distinguish DENV from Zika virus (ZIKV), West Nile virus (WNV), Yellow Fever virus (YFV), Usutu virus (USUV), and Chikungunya virus (CHIKV) infections, as well as healthy controls. Moreover, the combination of two immunogenic peptides emerged as a potential serum biomarker for DENV infection. These peptides, mapping to highly accessible regions on protein structures, show promise for diagnostic and prophylactic strategies against flavivirus infections. The described methodology holds broader applicability in the serodiagnosis of infectious diseases. [ABSTRACT FROM AUTHOR]

Purpose : Aedes aegypti (L.,1762) is a primary vector of arboviral infections like dengue, yellow fever, Zika. Female mosquitoes are influenced by various physical and chemical cues from host when blood feeding, e.g., they find some individuals with certain blood types or certain conditions more attractive than others. This study determined whether Ae. aegypti shows a preference when offered blood from a patient with diabetes mellitus (DM), an endocrine disorder associated with abnormal glucose metabolism, compared to healthy blood from non-DMs. Methods: In the dual feeding experiments, forty newly emerged female mosquitoes were provided with two blood feeding systems with blood from a non-diabetic (healthy) and diabetic patient using artificial feeders. Blood from 12 diabetic and 12 non-diabetic patients was matched by ABO blood type (e.g., diabetic type O blood was compared with non-diabetic type O blood). The number of mosquitoes that landed and fed from each membrane was counted every 2 min for thirty minutes. Results: Ae. aegypti species significantly preferred for blood from non-diabetic individuals (50–65% among the different blood type groups) compared to blood from diabetic individuals. Using multiplex allele-specific PCR it was also determined that, Ae. aegypti significantly preferred the O blood group regardless of blood sugar level compared to others. Conclusion: Ae. aegypti has less preference for diabetic blood to non-diabetics. Regardless people affected with this condition need to take preventive measures to reduce mosquito bites as they tend to have weaker immune systems and can experience more severe cases of dengue. [ABSTRACT FROM AUTHOR]

Abstract Monitoring yellow fever in non-human primates (NHPs) is an early warning system for sylvatic yellow fever outbreaks, aiding in preventing human cases. However, current diagnostic tests for this disease, primarily relying on RT-qPCR, are complex and costly. Therefore, there is a critical need for simpler and more cost-effective methods to detect yellow fever virus (YFV) infection in NHPs, enabling early identification of viral circulation. In this study, an RT-LAMP assay for detecting YFV in NHP samples was developed and validated. Two sets of RT-LAMP primers targeting the YFV NS5 and E genes were designed and tested together with a third primer set to the NS1 locus using NHP tissue samples from Southern Brazil. The results were visualized by colorimetry and compared to the RT-qPCR test. Standardization and validation of the RT-LAMP assay demonstrated 100% sensitivity and specificity compared to RT-qPCR, with a detection limit of 12 PFU/mL. Additionally, the cross-reactivity test with other flaviviruses confirmed a specificity of 100%. Our newly developed RT-LAMP diagnostic test for YFV in NHP samples will significantly contribute to yellow fever monitoring efforts, providing a simpler and more accessible method for viral early detection. This advancement holds promise for enhancing surveillance and ultimately preventing the spread of yellow fever.

Since the characterization of the CRISPR-Cas9 system in prokaryotes, it has become the prime choice in gene editing because of its exceptional flexibility, ease of use, high efficiency, and superior specificity. As a result, CRISPR-Cas9-mediated gene-editing technologies have enabled researchers not only to engineer transgenic animal strains with site-directed insertions more efficiently but also to generate desired mutants for previously intractable species. One such species is the invasive yellow fever mosquito, Aedes aegypti, which is notorious for its ability to transmit many blood-borne human pathogens. Methods for developing new transgenic strains of the yellow fever mosquito may aid in the effort to control its populations and provide significant benefits for the public. Here, we provide an overview of injection and noninjection methods for generating transgenic mosquitoes and also highlight important experimental design features.

Abstract Background In late 2021, Ghana was hit by a Yellow Fever outbreak that started in two districts in the Savannah region and spread to several other Districts in three regions. Yellow fever is endemic in Ghana. However, there is currently no structured vector control programme for Aedes the arboviral vector in Ghana. Knowledge of Aedes bionomics and insecticide susceptibility status is important to control the vectors. This study therefore sought to determine Aedes vector bionomics and their insecticide resistance status during a yellow fever outbreak. Methods The study was performed in two yellow fever outbreak sites (Wenchi, Larabanga) and two non-outbreak sites (Kpalsogu, Pagaza) in Ghana. Immature Aedes mosquitoes were sampled from water-holding containers in and around human habitations. The risk of disease transmission was determined in each site using stegomyia indices. Adult Aedes mosquitoes were sampled using Biogents Sentinel (BG) traps, Human Landing Catch (HLC), and Prokopack (PPK) aspirators. Phenotypic resistance to permethrin, deltamethrin and pirimiphos-methyl was determined with WHO susceptibility tests using Aedes mosquitoes collected as larvae and reared into adults. Knockdown resistance (kdr) mutations were detected using allele-specific multiplex PCR. Results Among the 2,664 immature Aedes sampled, more than 60% were found in car tyres. Larabanga, an outbreak site, was classified as a high-risk zone for the Yellow Fever outbreak (BI: 84%, CI: 26.4%). Out of 1,507 adult Aedes mosquitoes collected, Aedes aegypti was the predominant vector species (92%). A significantly high abundance of Aedes mosquitoes was observed during the dry season (61.2%) and outdoors (60.6%) (P

Abstract Background Uganda has a sentinel surveillance system in seven high-risk sites to monitor yellow fever (YF) patterns and detect outbreaks. We evaluated the performance of this system from 2017 to 2022. Methods We evaluated selected attributes, including timeliness (lags between different critical time points), external completeness (proportion of expected sentinel sites reporting ≥ 1 suspect case in the system annually), and internal completeness (proportion of reports with the minimum required data elements filled), using secondary data in the YF surveillance database from January 2017–July 2022. We conducted key informant interviews with stakeholders at health facility and national level to assess usefulness, flexibility, simplicity, and acceptability of the surveillance system. Results In total, 3,073 suspected and 15 confirmed YF cases were reported. The median time lag from sample collection to laboratory shipment was 37 days (IQR:21–54). External completeness was 76%; internal completeness was 65%. Stakeholders felt that the surveillance system was simple and acceptable, but were uncertain about flexibility. Most (71%) YF cases in previous outbreaks were detected through the sentinel surveillance system; data were used to inform interventions such as intensified YF vaccination. Conclusion The YF sentinel surveillance system was useful in detecting outbreaks and informing public health action. Delays in case confirmation and incomplete data compromised its overall effectiveness and efficiency.

Background: Flavivirus pose a continued threat to global health, yet their worldwide burden and trends remain poorly quantified. We aimed to evaluate the global, regional, and national incidence of three common flavivirus infections (Dengue, yellow fever, and Zika) from 2011 to 2021. Methods: Data on the number and rate of incidence for the three common flavivirus infection in 204 countries and territories were retrieved from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021. The estimated annual percent change (EAPC) was calculated to quantify the temporal trend during 2011-2016, 2016-2019, and 2019-2021, respectively. Results: In 2021, an estimated 59,220,428 individuals were infected globally, comprising 58,964,185 cases of dengue, 86,509 cases of yellow fever, and 169,734 cases of Zika virus infection. The age-standardized incidence rate (ASIR) of the three common flavivirus infections increased by an annual average of 5.08% (95% CI 4.12 to 6.05) globally from 2011 to 2016, whereas decreased by an annual average of -8.37% (95% CI -12.46 to -4.08) per year between 2016 to 2019. The ASIR remained stable during 2019-2021, with an average change of 0.69% (95% CI -0.96 to 2.37) per year globally for the three common flavivirus infections. Regionally, the burden of the three common flavivirus infections was primarily concentrated in those regions with middle income, such as South Asia, Southeast Asia, and Tropical Latin America. Additionally, at the country level, there was an inverted "U" relationship between the SDI level and the ASI. Notably, an increase in the average age of infected cases has been observed worldwide, particularly in higher-income regions. Conclusion: Flavivirus infections are an expanding public health concern worldwide, with considerable regional and demographic variation in the incidence. Policymakers and healthcare providers must stay vigilant regarding the impact of COVID-19 and other environmental factors on the risk of flavivirus infection and be prepared for potential future outbreaks. [ABSTRACT FROM AUTHOR]

Mosquito-borne viral diseases such as dengue fever, chikungunya, and yellow fever have been documented in Ethiopia since the 1960s. However, the efficacy of public health insecticides against Aedes aegypti that transmits these viruses remains poorly understood in the country, particularly in the Afar Region. Thus, the aim of the study was to assess the susceptibility status of Ae. aegypti to deltamethrin, permethrin, alpha-cypermethrin, pirimiphos-methyl, bendiocarb, and propoxur insecticides. Larvae and pupae of Aedes species were collected from Awash Arba, Awash Sebat, and Werer towns of the Afar Region of Ethiopia during July-October 2022, brought to the Aklilu Lemma Institute of Pathobiology, insectary and reared to adults. Non-blood-fed, 3–5 days-old females Ae. aegypti were exposed to pyrethroid, carbamate, and organophosphate insecticide impregnated papers in tube test following the standard guidelines. Knockdown rates were noted at 10 minutes interval until one hour. The mortality in mosquitoes was recorded 24 hours after 60 minutes of exposure. The mortality rates of Ae. aegypti exposed to propoxur were 87% in all the study towns. Similarly, 88% mortality in Ae. aegypti was recorded when tested with bendiocarb in Awash Sebat and Awash Arba towns. Suspected resistance of Ae. aegypti (95% mortality) to alpha-cypermethrin was observed in Awash Arba town. However, Ae. aegypti collected from all the three sites was observed to be susceptible to deltamethrin, permethrin, and pirimiphos-methyl. Ae. aegypti was resistant to 0.1% bendiocarb and 0.1% propoxur and possibly resistant to 0.05% alpha-cypermethrin. On the other hand, it was susceptible to 0.05% deltamethrin, 0.75% permethrin, and 0.25% pirimiphos-methyl. Thus, vector control products with deltamethrin, permethrin, and pirimiphos-methyl can be used in the control of adult Ae. aegypti in the Afar Region of Ethiopia. However, further studies should be carried out to evaluate the susceptibility status of Ae. aegypti to alpha-cypermethrin in the Awash Arba area. [ABSTRACT FROM AUTHOR]

Introduction: Egg allergy usually manifests during the initial 2 years of life, a period in which most vaccinations are administered. This often leads to delays in the application of some vaccines in patients with egg allergies, exposing them to a risk of contracting preventable infections. The aim of the study was to describe the frequency of reactions after applying the yellow fever vaccine (YFV) within a population with egg allergy. Methods: This was a cohort study with retrospective, multicenter data (2014–2023). Patient records diagnosed with egg allergy were gathered from their initial egg-related reactions until their YFV administration. Information was also collected about hypersensitivity tests conducted for egg and YFV such as the skin prick test (SPT) and intradermal test (IDT). Results: Among the 171 records analyzed, 23.9% of patients had a history of egg anaphylaxis. Out of these, 5 patients had a positive SPT and 21 IDT with the YFV. All patients tolerated the application of YFV without developing hypersensitivity reactions, regardless of the results of the YFV tests, the severity of egg reactions, the number of egg reactions, or the time since the last egg reaction. Out of the total patient cohort, 46.1% (79 individuals) encountered delays in receiving the YFV, and in this subset, 14% faced delays lasting longer than 12 months. Conclusion: The risk of allergic reactions with the YFV remains low. YFV tests generate delays in the vaccine application without providing high diagnostic accuracy. YFV should not be deferred even in patients with a history of severe egg reactions. [ABSTRACT FROM AUTHOR]

Background: Aedes aegypti (L.) is the main vector of dengue, yellow fever, Zika, and chikungunya viruses in many parts of the world, impacting millions of people worldwide each year. Insecticide-based interventions have been effective in controlling Aedes mosquito populations for several years, but in recent times, resistance to these compounds has developed, posing a global threat to the control of this mosquito. Methods: Ovitraps were used to collect A. aegypti eggs in the cities of Tartagal and San Ramón de la Nueva Orán (Salta), Puerto Iguazú (Misiones), and Clorinda (Formosa). World Health Organization (WHO)-impregnated papers with the discriminating concentration (DC) of permethrin, 5X, 10X and pirimiphos methyl were used for the toxicological bioassays. We also genotyped each sample for the three kdr single nucleotide polymorphisms (SNP): V410L, V1016I, and F1534C in individual TaqMan quantitative PCR (qPCR) reactions. Results: All investigated A. aegypti populations were highly resistant to permethrin, as the mortality percentage with the permethrin 10×DC remained below 98%. However, all populations were 100% susceptible to pirimiphos-methyl. Kdr genotyping demonstrated the presence of the V410L mutation for the first time in Argentina in all the populations studied. A prevalence of the triple mutant genotype (LL + II + CC) was observed in the northeastern cities of Clorinda (83.3%) and Puerto Iguazú (55.6%). Conclusions: This study demonstrates for the first time the presence and intensity of resistance to permethrin in different populations from Argentina, and correlates the observed phenotype with the presence of kdr mutations (genotype). [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]

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]

The tiny bloodsucker Aedes aegypti is the primary vector of some fatal diseases like dengue, zika and yellow fever which presents a significant concern for the healthcare sector of Bangladesh. To manage this insect vector, the feasibility of Sterile Insect Technique (SIT) in Bangladesh is being investigated for which quality radio-sterilized males are indispensable. Typically, the sterile males are chilled at low temperature to facilitate their transportation from rear-out-facility to the release site, concurrently to minimize the metabolism, stress and physical damage. In this study, the impact of chilling temperatures (4, 7 and 10 °C) and exposure periods (1, 4, 8 and 24 h) have been studied on the survival, chill-coma recovery rate (CCRR), induced sterility and flight ability of lab-reared local A. aegypti strain. Different chilling temperatures had insignificant effect on CCRR except the 24 h exposure duration. Log-rank test of Kaplan-Meier survival curve showed the significant effect of chilling temperature and duration on the survival. Notably, the chilling temperature of 7 °C exposed for 1 h was found to be optimum in terms of survival. Hence, the induced sterility and flight ability were studied only for this specific temperature and duration, revealing the insignificant effects between the sterile-chilled and sterile but non-chilled A. aegypti. This study underscores the recommendation to chill the mosquitoes at 7 °C for 1 h which will be helpful for the implementation of SIT in Bangladesh. [ABSTRACT FROM AUTHOR]

Infections with Flaviviridae viruses, such as hepatitis C (HCV), dengue (DENV), and yellow fever (YFV) viruses, are major public health problems worldwide. In the case of HCV, treatment is associated with drug resistance and high costs, while there is no clinically approved therapy for DENV and YFV. Consequently, there is still a need for new chemotherapies with alternative modes of action. We have previously identified novel 2-hydroxypyrazino[1,2-a]indole-1,3(2H,4H)-diones as metal-chelating inhibitors targeting HCV RNA replication. Here, by utilizing a structure-based approach, we rationally designed a second series of compounds by introducing various substituents at the indole core structure and at the imidic nitrogen, to improve specificity against the RNA-dependent RNA polymerase (RdRp). The resulting derivatives were evaluated for their potency against HCV genotype 1b, DENV2, and YFV-17D using stable replicon cell lines. The most favorable substitution was nitro at position 6 of the indole ring (compound 36), conferring EC50 1.6 μM against HCV 1b and 2.57 μΜ against HCV 1a, with a high selectivity index. Compound 52, carrying the acetohydroxamic acid functionality (-CH2CONHOH) on the imidic nitrogen, and compound 78, the methyl-substituted molecule at the position 4 indolediketopiperazine counterpart, were the most effective against DENV and YFV, respectively. Interestingly, compound 36 had a high genetic barrier to resistance and only one resistance mutation was detected, T181I in NS5B, suggesting that the compound target HCV RdRp is in accordance with our predicted model. [ABSTRACT FROM AUTHOR]

Yellow fever virus (YFV) infections can cause severe diseases in humans, resulting in mass casualties in Africa and the Americas each year. Secretory NS1 (sNS1) is thought to be used as a diagnostic marker of flavivirus infections, playing an essential role in the flavivirus life cycle, but little is known about the composition and structure of YFV sNS1. Here, we present that the recombinant YFV sNS1 exists in a heterogeneous mixture of oligomerizations, predominantly in the tetrameric form. The cryoEM structures show that the YFV tetramer of sNS1 is stacked by the hydrophobic interaction between β-roll domains and greasy fingers. According to the 3D variability analysis, the tetramer is in a semi-stable state that may contain multiple conformations with dynamic changes. We believe that our study provides critical insights into the oligomerization of NS1 and will aid the development of NS1-based diagnoses and therapies. [ABSTRACT FROM AUTHOR]

Epidemics have significant impacts on primate populations. In 2016, yellow fever spread rapidly to the most densely populated states of Brazil, resulting in the death of hundreds of humans and thousands of nonhuman primates. The Yellow Fever Surveillance Program (Programa de Vigilância da Febre Amarela) implemented by the Brazilian government was designed to prevent and control yellow fever outbreaks. In 2020, the regional reference laboratory at the Oswaldo Cruz Institute in Rio de Janeiro state in Brazil, responsible for yellow fever diagnosis, gave us access to 24 DNA samples from capuchin monkeys, which had tested negative for yellow fever virus. The samples were all from sites in Brazil where Sapajus nigritus is the only species of capuchin monkey present. We attempted to sequence two mitochondrial molecular markers commonly used for Cebidae, but five samples did not amplify. In this study, we performed additional DNA amplification and the Basic Local Alignment Search Tool (BLAST) to confirm the species identity of the 19 samples, which amplified and identify the taxon of the five samples that had failed to amplify. Among the 19 samples correctly identified as Sapajus, one was not Sapajus nigritus but another Sapajus species. Of the five samples that previously failed to amplify, three were similar to Callicebus nigrifrons, one was similar to Alouatta guariba clamitans, and one failed to amplify successfully for any marker. These findings show an error rate of 5/24 (21%) in the original taxonomic identification. Misidentification occurred at the genus level as well as the species level. Our findings highlight the importance of precise taxonomic classification in obtaining reliable data on the consequences of the yellow fever epidemic for primates. [ABSTRACT FROM AUTHOR]

Many viruses have evolved structured RNA elements that can influence transcript abundance and translational efficiency, and help evade host immune factors by hijacking cellular machinery during replication. Here, we evaluated the functional impact of sub-genomic flaviviral RNAs (sfRNAs) known to stall exoribonuclease activity, by incorporating these elements into recombinant adeno-associated viral (AAV) genome cassettes. Specifically, sfRNAs from Dengue, Zika, Japanese Encephalitis, Yellow Fever, Murray Valley Encephalitis, and West Nile viruses increased transcript stability and transgene expression compared to a conventional woodchuck hepatitis virus element (WPRE). Further dissection of engineered transcripts revealed that sfRNA elements (i) require incorporation in cis within the 3′ untranslated region (UTR) of AAV genomes, (ii) require minimal dumbbell structures to exert the observed effects, and (iii) can stabilize AAV transcripts independent of 5′−3′ exoribonuclease 1 (XRN1)-mediated decay. Additionally, preliminary in vivo assessment of AAV vectors bearing sfRNA elements in mice achieved increased transcript abundance and expression in cardiac tissue. Leveraging the functional versatility of engineered viral RNA elements may help improve the potency of AAV vector-based gene therapies. IMPORTANCE Viral RNA elements can hijack host cell machinery to control stability of transcripts and consequently, infection. Studies that help better understand such viral elements can provide insights into antiviral strategies and also potentially leverage these features for therapeutic applications. In this study, by incorporating structured flaviviral RNA elements into recombinant adeno-associated viral (AAV) vector genomes, we show improved AAV transcript stability and transgene expression can be achieved, with implications for gene transfer. [ABSTRACT FROM AUTHOR]

Background: Yellow fever (YF) remains a significant public health concern in Nigeria, with sporadic outbreaks causing considerable morbidity and mortality. This zoonotic viral disease is transmitted primarily by Aedes mosquitoes, posing a constant threat to human populations. Although vaccination efforts have been ongoing for years, outbreaks still occur, underscoring the need for a comprehensive approach to combat YF. In Nigeria, adopting a One Health approach is imperative for effective yellow fever control. This approach recognizes the intricate interplay between human health, animal health, and the environment. Key strategies include the implementation of travel advisories, widespread vaccination campaigns, and early detection and reporting of cases. Surveillance efforts extend to both human and non-human primate populations to monitor the circulation of the virus accurately. Community engagement plays a vital role in this approach, with local communities actively participating in efforts to eliminate mosquito breeding sites. Integrated mosquito management techniques, such as the use of insecticides and repellents, are promoted alongside community-led interventions to reduce breeding grounds, such as removing stagnant water. By embracing the principles of One Health and implementing coordinated efforts across regions within Nigeria, we can strive towards the eradication of yellow fever. This holistic approach holds the potential to mitigate the burden of disease and pave the way for a future free from the threat of yellow fever outbreaks in Nigeria. [ABSTRACT FROM AUTHOR]