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Chinese rice‐field eels rhabdovirus (CrERV) causes haemorrhagic disease in Chinese rice‐field eels (Monopterus albus), leading to significant mortality and economic losses. Sensitive detection of CrERV nucleic acids is essential to control the spread of this pathogen and to treat infected individuals. Herein, we developed an efficient and sensitive droplet digital PCR (ddPCR) method to rapidly detect and quantify CrERV. The ddPCR assay optimal conditions were an annealing temperature of 53°C, and primer and probe concentrations of 0.5 and 0.25 μM, respectively. The assay had a diagnostic sensitivity of 0.23 copies/μL, and was highly specific, showing no cross reactivity with other viruses (infectious haematopoietic necrosis virus, grass carp reovirus, spring viremia of carp virus, largemouth bass ranavirus, carp edema virus, Chinese giant salamander iridovirus, and white spot syndrome virus). Real‐time quantitative PCR testing of 30 Chinese rice‐field eels samples detected CrERV in 7 samples (23.3%), whereas ddPCR detected CrERV in 12 samples (40%), demonstrating its higher sensitivity. Thus, ddPCR represents an advanced method to absolutely quantify CrERV in infected fish with low virus concentrations, providing a valuable tool to manage the spread and impact of CrERV. [ABSTRACT FROM AUTHOR]

Culicoides imicola is the main vector of viral diseases of livestock in Europe such as bluetongue (BT), African horse sickness and epizootic haemorrhagic disease. Climatic factors are the main drivers of C. imicola occurrence and its distribution might be subject to rapid shifts due to climate change. Entomological data, collected during BT surveillance, and climatic/environmental variables were used to analyse ecological niche and to model C. imicola distribution and possible future range shifts in Italy. An ensemble technique was used to weigh the performance of machine learning, linear and profile methods. Updated future climate projections from the latest phase of the Climate Model Intercomparison Project were used to generate future distributions for the next three 20‐year periods, according to combinations of general circulation models and shared socioeconomic pathways and considering different climate change scenarios. Results indicated the minimum temperature of the coldest month (BIO 6) and precipitation of the driest‐warmest months (BIO 14) as the main limiting climatic factors. Indeed, BIO 6 and BIO 14 reported the two highest values of variable importance, respectively, 9.16% (confidence interval [CI] = 7.99%–10.32%), and 2.01% (CI = 1.57%–2.44%). Under the worst‐case scenario of climate change, C. imicola range is expected to expand northward and shift away from the coasts of central Italy, while in some areas of southern Italy, environmental suitability will decrease. Our results provide predictions of C. imicola distribution according to the most up‐to‐date future climate projections and should be of great use to surveillance management at regional and national scales. [ABSTRACT FROM AUTHOR]

The prevalence of hemorrhagic diseases of the central nervous system of dogs and cats is low compared to other diseases such as neoplasia and inflammation. However, the clinical consequences can be devastating. Several etiological and localization-based classification systems have been reported for intracerebral and spinal cord hemorrhage or hematomyelia in humans but similar systems do not exist in veterinary medicine. The authors propose an etiologic classification system for both intraparenchymal hemorrhagic encephalopathy and myelopathy following a review of the literature detailing the presentation, diagnosis, therapy, and prognosis of these diseases. A summary of the investigative and therapeutic approach to these cases is also provided. [ABSTRACT FROM AUTHOR]

Ehrlichia canis is the primary etiologic agent of canine monocytic ehrlichiosis, a serious and sometimes fatal hemorrhagic disease of dogs. Diagnosis of E. canis infection is often retrospectively confirmed by serologic detection of antibodies by immunofluorescent microscopy. Our laboratory previously identified numerous major immunoreactive proteins with species-specific linear antibody epitopes that are useful for immunodiagnosis of CME. More recently, we have defined the entire antibody-reactive immunome of E. canis , substantially increasing the number of major immunoreactive proteins known to exist. In this study, we analyzed and compared seven recently identified antibody reactive E. canis proteins with established diagnostic antigens including tandem repeat proteins TRP19, TRP36 and TRP140 and observed comparable immunoreactivity. Many of these proteins were conserved in different E. canis strains. Multiple linear antibody epitopes were mapped in a highly conserved TRP (Ecaj_0126), including within the tandem repeat domain. Temporal antibody responses were examined, and multiple proteins reacted with antibodies in sera as early as 21 days post experimental infection. Host-specific expression of the proteins was examined which revealed that some proteins exhibited higher expression in mammalian cells, while others in tick cells. This study has identified new immunodiagnostic candidates that exhibit different host expression patterns, information which may be useful for developing ultrasensitive immunodiagnostics and effective vaccines for CME. [ABSTRACT FROM AUTHOR]

Background: African swine fever (ASF) is one of the deadliest swine diseases with haemorrhagic symptoms and a high mortality rate. Plant‐derived additives are potential antiviral agents against viruses due to their environmental and user‐friendly properties. Objectives: This study aims to evaluate the efficacy of plant‐based additives (Phyto.A04 and Phyto.B) compared to an organic acid blend (OAB) in inactivating ASF virus (ASFV) in cell culture and feed. Methods: ASFV‐spiked feed was treated with individual or combined additives such as OAB, Phyto.A04 and Phyto.B. The viability of ASFV after treatment of ASFV‐spiked feed with additives was then confirmed by both methods, real‐time PCR and cell culture. Results: The results of the in vitro test with cell cultures showed that all three additives (OAB, Phyto.A04 and Phyto.B) exerted a strong virucidal effect on ASFV in porcine alveolar macrophage cells. OAB at a concentration of 0.3% reduced the virus concentration from 4.48 log10 HAD50/mL after 1 day of treatment (day 1) to 3.29 log10 HAD50/mL after 3 days of treatment (day 3) and remained undetected after 7 days of treatment (day 7). In Phyto.A04 with 1%, the virus was only detectable on day 1 (3.53 log10 HAD50/mL). Phyto.B with 0.01% and 0.05% both showed good efficacy in completely inhibiting virus presence on days 3 and 7. Conclusions: All additives, OAB, Phyto.A04 and Phyto.B, were able to inactivate ASFV in a dose‐dependent manner, as confirmed by cell culture and PCR methods. The combination of additives at different concentrations consistently improved the virucidal results. [ABSTRACT FROM AUTHOR]

The diversity of South American deer genera during the Quaternary is considered one of the greatest in the world. However, this was established during the beginning of the twentieth century, when the recognition of new extinct deer taxa was based only on differences in antler morphology. Thus, South American extinct deer taxa need a detailed taxonomic revision, and this is the case of the Andean deer genera Agalmaceros and Charitoceros. First, both taxa are diagnosed by the presence of thorns in their antlers. Consequently, by taxonomic priority, Agalmaceros is a senior synonym of Charitoceros. Second, we recognize here that the thorns of the antlers of Agalmaceros are the symptom of a pathology that also affects some extant deer. Excluding the thorns of the antlers, the antler of Agalmaceros is identical to that of Odocoileus virginianus, indicating that Agalmaceros is a junior synonym to this extant deer. The recognition of epizootic hemorrhagic disease as the possible cause for the thorny antlers of Andean O. virginianus and the ample record of this affecting antlers in deer from the tropical Andes suggests that an epidemic occurred in this region in the Late Pleistocene. Before describing a new taxon, taxonomists must exhaust all possibilities to explain morphological variations. In this regard, this contribution provides an interesting, important and weakly explored area in paleontology, namely taxonomic revision under a paleopathology context. With the taxonomic invalidation of Agalmaceros and Charitoceros proposed here, the diversity of South American deer genera during the Pleistocene is poorer than previously established and includes 11 taxa – seven extant and four extinct. [ABSTRACT FROM AUTHOR]

Moschus chrysogaster viral hemorrhagic disease (McVHD), caused by the Moschus chrysogaster hemorrhagic disease virus (McHDV), is an acute and highly fatal infectious disease of musk deer. At present, there is no prevention or treatment for this disease. In this study, we constructed a recombinant bacmid containing the McHDV VP60 gene and obtained the recombinant baculovirus rBac-McHDV VP60 by transfection into Sf9 (Spodoptera frugiperda) insect cells. The McHDV VP60 protein was successfully expressed in the insect cell-baculovirus expression system; furthermore, it was released in the supernatant of infected insect cells and spontaneously assembled to form virus-like particles (VLPs), which were structurally and immunologically indistinguishable from the Moschus chrysogaster viral hemorrhagic disease virion. Hypodermic vaccination of rabbits with the VLPs conferred complete protection in 14 days; this protection was found to be effective from the seventh day after VLP injection and was accompanied by a strong humoral response. This study is the first attempt to express the VP60 gene of McHDV using an insect baculovirus system, which provides an experimental basis for the virus-like particle vaccine of McVHD. [ABSTRACT FROM AUTHOR]

Marburg virus disease (MVD) is a zoonotic hemorrhagic disease with an estimated case fatality rate of up to 88%. Ghana recorded its first human MVD outbreak in June 2022 and although the outbreak was quickly brought under control, the transmission dynamics of the disease remained unclear. We assessed the presence of Marburg virus (MARV) antibodies in livestock and dogs and identified associated risk factors that increased the risk of these animals being exposed to MARV in five regions of Ghana. Sera collected from 3113 livestock and dogs in 2 climatic seasons (rainy and dry seasons) were tested for MARV antibodies using an indirect ELISA test. The samples were further tested using dot blotting to substantiate the presence of antibodies against MARV glycoprotein (GP). Overall, MARV antibodies were detected in 20.6% of the animals. The species-specific prevalence was 28.7% in cattle, 21.8% in sheep, 19.5% in goats, 15.3% in dogs and 11.2% in pigs. The seropositivity was higher in the rainy season [RR 1.5; 95% CI 1.3–1.8] and in older animals [RR = 2.6; 95% CI 1.9–3.4]. The findings underscore the importance of regular surveillance using the one health approach and future studies into the role of livestock and dogs as potential intermediaries in the circulation of MARV. [ABSTRACT FROM AUTHOR]

Crimean-Congo Hemorrhagic Fever Virus (CCHFV) is a negative-sense RNA virus spread by Hyalomma genus ticks across Europe, Asia, and Africa. CCHF disease begins as a non-specific febrile illness which may progress into a severe hemorrhagic disease with no widely approved or highly efficacious interventions currently available. Recently, we reported a self-replicating, alphavirus-based RNA vaccine that expresses the CCHFV nucleoprotein and is protective against lethal CCHFV disease in mice. This vaccine induces high titers of non-neutralizing anti-NP antibodies and we show here that protection does not require Fc-gamma receptors or complement. Instead, vaccinated mice deficient in the intracellular Fc-receptor TRIM21 were unable to control the infection despite mounting robust CCHFV-specific immunity. We also show that passive transfer of NP-immune sera confers significant TRIM21-dependent protection against lethal CCHFV challenge. Together our data identifies TRIM21-mediated mechanisms as the Fc effector function of protective antibodies against the CCHFV NP and provides mechanistic insight into how vaccines against the CCHFV NP confer protection. Non-neutralizing antibodies against the nucleoprotein (NP) of Crimean-Congo hemorrhagic fever virus are protective against lethal challenge in mice. Here, the authors show that these anti-NP antibodies protect through the intracellular antibody receptor TRIM21 and that protection is independent of T cells. [ABSTRACT FROM AUTHOR]

Background: In September 2022, Uganda experienced an outbreak of Sudan virus disease (SVD), mainly in central Uganda. As a result of enhanced surveillance activities for Ebola disease, samples from several patients with suspected viral hemorrhagic fever (VHF) were sent to the VHF Program at Uganda Virus Research Institute (UVRI), Entebbe, Uganda, and identified with infections caused by other viral etiologies. Herein, we report the epidemiologic and laboratory findings of Crimean-Congo hemorrhagic fever (CCHF) cases that were detected during the SVD outbreak response. Methodology: Whole blood samples from VHF suspected cases were tested for Sudan virus (SUDV) by real-time reverse transcription–polymerase chain reaction (RT-PCR); and if negative, were tested for CCHF virus (CCHFV) by RT-PCR. CCHFV genomic sequences generated by metagenomic next generation sequencing were analyzed to ascertain strain relationships. Principal findings: Between September 2022 and January 2023, a total of 2,626 samples were submitted for VHF testing at UVRI. Overall, 13 CCHF cases (including 7 deaths; case fatality rate of 53.8%), aged 4 to 60 years, were identified from 10 districts, including several districts affected by the SVD outbreak. Four cases were identified within the Ebola Treatment Unit (ETU) at Mubende Hospital. Most CCHF cases were males engaged in livestock farming or had exposure to wildlife (n = 8; 61.5%). Among confirmed cases, the most common clinical symptoms were hemorrhage (n = 12; 92.3%), fever (n = 11; 84.6%), anorexia (n = 10; 76.9%), fatigue (n = 9; 69.2%), abdominal pain (n = 9; 69.2%) and vomiting (n = 9; 69.2%). Sequencing analysis showed that the majority of identified CCHFV strains belonged to the Africa II clade previously identified in Uganda. Two samples, however, were identified with greater similarity to a CCHFV strain that was last reported in Uganda in 1958, suggesting possible reemergence. Conclusions/Significance: Identifying CCHFV from individuals initially suspected to be infected with SUDV emphasizes the need for comprehensive VHF testing during filovirus outbreak responses in VHF endemic countries. Without expanded testing, CCHFV-infected patients would have posed a risk to health care workers and others while receiving treatment after a negative filovirus diagnosis, thereby complicating response dynamics. Additionally, CCHFV-infected cases could acquire an Ebola infection while in the ETU, and upon release because of a negative Ebola virus result, have the potential to spread these infections in the community. Author summary: Crimean-Congo hemorrhagic fever (CCHF) is a severe hemorrhagic disease whose symptoms mimic those of other viral hemorrhagic fevers (VHFs), significantly challenging its differential diagnosis. Herein, we report on CCHF cases that were detected during the nationwide response activities against an outbreak of Sudan virus (SUDV) in Uganda, from September 2022 to January 2023. Confirmed CCHF cases, mainly males presenting with a range of clinical signs and symptoms, were identified in districts with circulating SUDV, including 4 cases identified within an Ebola treatment center at Mubende hospital, thus complicating patient management and treatment. Our findings highlight the need for broad testing for VHFs and other high-consequence pathogens, even during known VHF outbreaks, in order to identify high risk pathogens with outbreak potential, especially in countries with a broad range of endemic zoonotic viral pathogens. This article also adds to the known molecular epidemiology of CCHF virus in Uganda. [ABSTRACT FROM AUTHOR]

Introduction: Immune reconstitution (IR) kinetics of paediatric patients underwent haploidentical haematopoietic stem cell transplantation (HSCT) with post‐transplant cyclophosphamide (PTCy) have not been extensively studied. We compared IR patterns of children receiving HSCT from haploidentical (n = 92) and HLA‐matched donors (n = 36), and analysed risk factors for viral infection in these patients. Methods: We prospectively measured lymphocyte subset numbers before HSCT and at 1, 3, 6 and 12 months after HSCT. Blood cytomegalovirus (CMV), Epstein–Barr virus, adenovirus, BK virus (BKV) and urine adenovirus and BKV viral loads were measured at designated time points. Results: The median numbers of total T and T helper cells at 1 month were significantly lower in the haploidentical group compared with the HLA‐matched group. Haploidentical HSCT recipients had significantly lower median numbers of several T cell subsets and B cells for 1 year after HSCT. The median NK cell count of the haploidentical group was lower at 1 month. BKV haemorrhagic cystitis, blood CMV and urine adenovirus reactivation were more frequently found in the haploidentical group. Post‐haploidentical HSCT patients receiving anti‐T lymphocyte globulin (ATG) had significantly lower median numbers of total T cells (at 1 month) and T helper cells (at 6 and 12 months) and higher rate of blood BKV reactivation compared with those without ATG. Conclusion: Paediatric patients who undergo haploidentical HSCT with PTCy are likely to have delayed IR and an increased risk of viral reactivation/infection compared with HLA‐matched HSCT. The addition of ATG to PTCy delayed T cell recovery and increased risk of BKV reactivation. [ABSTRACT FROM AUTHOR]

Hemorrhagic moyamoya disease (HMMD) can result in poor outcomes. Serum biomarkers may play a significant role in predicting HMMD outcomes. This study retrospectively analyzed the correlation between serum biomarkers at the time of admission and outcomes for patients with HMMD. We evaluated 270 patients with HMMD admitted to Yijishan Hopital of Wannan Medical College between July 2017 and April 2023. The patients were categorized into 2 groups according to their modified Rankin Scale scores at 3 months after discharge. Univariate and multivariate analyses were used to identify the associations between biomarkers and clinical outcomes. Receiver operating characteristic curves were obtained to investigate the potential of the biomarkers for predicting prognosis. Of the 270 patients analyzed, 96 (35.6%) had unfavorable outcomes. The potential predictors were identified using the univariate analysis. The subsequent multivariate logistic regression analysis showed that the systemic inflammatory response index (SIRI) (odds ratio 0.86, 95% confidence interval 0.75–0.98, P = 0.028] and serum glucose to potassium ratio (GPR) (odds ratio 0.53, 95% confidence interval 0.38–0.76, P < 0.001) were independent risk factors of poor outcomes. The receiver operating characteristic analysis indicated that patients with a higher SIRI (≥2.12) and GPR (≥1.75) levels were more likely to have unfavorable outcomes. An elevated GPR and SIRI at admission were associated with a poor clinical outcome at the 3-month follow-up for patients with HMMD. Therefore, these biomarkers could be considered in future management decisions for these patients. [ABSTRACT FROM AUTHOR]

Hemophilia B is an inherited hemorrhagic disorder characterized by a deficiency of blood coagulation factor IX (FIX) that results in abnormal blood coagulation. The blood coagulation is already evident in hemophiliacs at the fetal stage, and thus intracranial hemorrhage and other bleeding complications can occur at birth, leading to sequelae. Therefore, it is important to develop effective treatments for hemophiliacs in utero. In this study, in order to transplacentally deliver FIX from pregnant mice to their fetuses, an improved adenovirus (Ad) vector expressing human FIX fused with the IgG Fc domain (FIX Fc fusion protein), which plays a crucial role in neonatal Fc receptor (FcRn)-mediated transcytosis across the placenta, was intravenously administered to E13.5 pregnant mice. Significant levels of FIX Fc fusion protein were detected in 0-day-old newborn mice whose mothers were administered an Ad vector expressing FIX Fc fusion protein. Wild-type FIX overexpressed in the pregnant mice was not delivered to the fetuses. Plasma FIX levels in the newborn mice were relatively well correlated with those in their mothers, although transplacental delivery efficiencies of FIX Fc fusion protein were slightly reduced when the FIX Fc fusion protein was highly expressed in the mother mice. Plasma FIX levels in the newborn mice were about 3.6–6.4% of those in their mothers, Transplacental delivery of FIX Fc fusion protein to their fetuses successfully improved the blood clotting ability in the newborn mice. [Display omitted] • An improved adenovirus vector mediated efficient expression of FIX Fc fusion protein. • FIX Fc fusion protein, not wild-type FIX, was delivered from pregnant mice to fetuses. • Transplacental delivery of FIX to fetuses improved blood clotting ability in neonates. [ABSTRACT FROM AUTHOR]

This study was important to improve proper biosecurity measures and controlling the spread of Aeromonas to prevent future outbreaks. This research sought to determine whether virulent Aeromans species were present in morbid rainbow trout, their resistance and their genetic relatedness. A total number of 542 tissue lesion specimens were collected from gill, liver, heart and kidneys in morbid domesticated fish in Duhok province, Iraq. The gyrB DNA sequence analysis was used to determine the species classification. Drug susceptibility testing was conducted for all isolated strains using disc diffusion technique. The genotyping analysis was carried out using enterobacterial repetitive intergenic consensus-polymerase chain reaction. Thirty-four isolates were found and they were classified into three species (Aeromonas veronii, Aeromonas sorbia, and Aeromonas allosaccharophila), where A. veronii stand as one of the most prevalent species. The most frequently affected organ by Aeromonas was the gills among four different organs. The detection frequencies of the virulence genes aerolysin, outer membrane protein, glycerophospholipid-cholesterol acyltransferase, elastase, flagella, serine protease, cytotonic heat-labile, and hemolysin were 100%, 100%, 79.41%, 64.70%, 76.47%, 67.64%, 70.58%, and 41.17, respectively. None of the strains possessed all of the virulence markers. All isolates were completely resistant to ceftazidime, amoxicillin and doxycycline. All isolates were found to be multi-drug-resistant. Regardless of the nearest geographic source area of samples and the same Aeromonas species, there was a high genetic diversity. The results of this study could help farmers and researchers make informed decisions about measures of biosecurity and proper therapeutic drugs to apply to prevent current outbreaks and prevent them from recurring again. [ABSTRACT FROM AUTHOR]

African swine fever (ASF) is a highly fatal hemorrhagic disease affecting domestic pigs caused by African swine fever virus (ASFV). Genetic analysis of ASFV isolates to date has identified 24 geographically related genotypes with various subgroups, but only genotype I and II ASFVs have been reported outside Africa. ASFV genotype II and genotype I viruses were reported in China in 2018 and 2021, respectively. In this study, unique and highly conserved noncoding regions were found between MGF_505-9R and MGF_505-10R in the 188 genomes of ASFV genotypes I and II. A pair of primers was designed on the basis of this region. By optimizing the reaction system and conditions, a SYBR Green I fluorescence PCR assay that can distinguish between ASFV genotypes I and II was established, and the sensitivity, reproducibility and specificity were evaluated. The detection limit was 1 TCID50/0.1 mL for both genotypes, with no cross-reactivity observed with other common pig pathogens. The intra- and interbatch variation coefficients were both less than 1.2%. Clinical sample detection analysis revealed 47 positive cases out of 100, including 3 for genotype I and 44 for genotype II, aligning with results from the WOAH-recommended and national standard methods. The method developed in this study allows for the differentiation of ASFV genotypes I and II without the need for genome sequencing, offering a convenient and rapid approach for ASFV detection and genotype identification. [ABSTRACT FROM AUTHOR]

Background: Elephant endotheliotropic herpesvirus (EEHV) infection is the most common cause for lethal hemorrhagic disease in captive juvenile Asian elephants (Elephas maximus). Although EEHV1 is known as the most likely cause of fatal haemorrhagic disease in Asian elephants, EEHV5 was lately involved in lethal cases of haemorrhagic disease in captive elephants. Case presentation: Here we report the first death of a four-year old Asian elephant diagnosed with EEHV5 in Germany. Molecular diagnosis yielded detection of EEHV5 DNA in all tested tissues. Histopathological examination revealed typical features of hemorrhagic disease in all examined organs. EEHV5 was sequenced from total DNA isolated from heart tissue by Illumina and Nanopore sequencing. Sequencing data showed 3,881 variants, distributed across the entire genome, compared to the published EEHV5 sequence. Conclusions: We have detected EEHV5 in a fatal disease case of a male Asian elephant. Whole genome sequencing revealed substantial differences of our DNA isolate compared to available EEHV5 sequences. This report of fatal haemorrhagic disease associated with EEHV5 infection should raise awareness for EEHV5 as an important elephant pathogen. Genome sequencing and downstream SNPs analysis will further encourage future research to understand genetic diversity, pathogenesis and virulence of EEHVs with respect to developing new diagnostic methods, prophylactic strategies, and implementation of surveillance and control measures. [ABSTRACT FROM AUTHOR]

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The African swine fever virus (ASFV) is a large enveloped DNA virus that causes a highly pathogenic hemorrhagic disease in both domestic pigs and wild boars. The ASFV genome contains a double-stranded DNA encoding more than 150 proteins. The ASFV possesses only one protease, pS273R, which is important for virion assembly and host immune evasion. Therefore, the specific monoclonal antibody (mAb) against pS273R is useful for ASFV research. Here, we generated two specific anti-pS273R mAbs named 2F3 and 3C2, both of which were successfully applied for ELISA, Western blotting, and immunofluorescence assays. Further, we showed that both 2F3 and 3C2 mAbs recognize a new epitope of N terminal 1–25 amino acids of pS273R protein, which is highly conserved across different ASFV strains including all genotype I and II strains. Based on the recognized epitope, an indirect ELISA was established and was effective in detecting antibodies during ASFV infection. To conclude, the specific pS273R mAbs and corresponding epitope identified will strongly promote ASFV serological diagnosis and vaccine research. [ABSTRACT FROM AUTHOR]

Lassa fever virus (LASV), a member of the Arenavirus family, is the etiological agent of Lassa fever, a severe hemorrhagic disease that causes considerable morbidity and mortality in the endemic areas of West Africa. LASV is a rodent-borne CDC Tier One biological threat agent and is on the World Health Organization's (WHO) Priority Pathogen list. Currently, no FDA-licensed vaccines or specific therapeutics are available. Here, we describe the efficacy of a deactivated rabies virus (RABV)-based vaccine encoding the glycoprotein precursor (GPC) of LASV (LASSARAB). Nonhuman primates (NHPs) were administered a two-dose regimen of LASSARAB or an irrelevant RABV-based vaccine to serve as a negative control. NHPs immunized with LASSARAB developed strong humoral responses to LASV-GPC. Upon challenge, NHPs vaccinated with LASSARAB survived to the study endpoint, whereas NHPs in the control group did not. This study demonstrates that LASSARAB is a worthy candidate for continued development. [ABSTRACT FROM AUTHOR]

Introduction: Bleeding in neonates is a significant cause of morbidity and mortality in the neonatal period. The early identification of bleeding and its cause (bleeding or clotting disorder) is very important for the appropriate management and for prognostication. Material & Methods: After obtaining institutional ethics committee approval, 21 patients with diagnosis of onset of hemorrhagic disorder were recruited from 550 patients admitted to the Neonatal Intensive Care Unit (NICU) after obtaining written informed consent from their parents/guardians. A detailed history including family history, maternal history and perinatal history was recorded. Thorough assessment and relevant investigations were done for all 21 patients diagnosed with bleeding disorder out of 550 patients. Duration of hospital stay and immediate outcome i.e.-Morbidity and mortality in such neonates were noted. Results: The incidence of bleeding in neonates was 3.8%. Thrombocytopenia was major cause for bleeding [8(38.1%)] followed by VKDB [5 (24%)]. VLBW babies (19.04%) and preterm babies (11.1%) had a statistically significant risk of bleeding. 71.4% (15/21) of neonates had bleeding in the first week of life. 14.3% (3/21) of NICU deaths were in the neonates with bleeding which indicates that bleeding constituted a significant risk factor for mortality in NICU. The outcome in the VKDB was dismal (67% mortality and 33% neurologic sequelae) A statistically significant correlation was found between maternal factors such as Gestational Age<34 weeks, History of Instrumental delivery, history of maternal fever and Anaemia Conclusion: Early and prompt diagnosis of hemorrhagic disease of the newborn can alleviate the devastating consequences. [ABSTRACT FROM AUTHOR]

Most mathematical models that assess the vectorial capacity of disease-transmitting insects typically focus on the influence of climatic factors to predict variations across different times and locations, or examine the impact of vector control interventions to forecast their potential effectiveness. We combine features of existing models to develop a novel model for vectorial capacity that considers both climate and vector control. This model considers how vector control tools affect vectors at each stage of their feeding cycle, and incorporates host availability and preference. Applying this model to arboviruses of veterinary importance in Europe, we show that African horse sickness virus (AHSV) has a higher peak predicted vectorial capacity than bluetongue virus (BTV), Schmallenberg virus (SBV), and epizootic haemorrhagic disease virus (EHDV). However, AHSV has a shorter average infectious period due to high mortality; therefore, the overall basic reproduction number of AHSV is similar to BTV. A comparable relationship exists between SBV and EHDV, with both viruses showing similar basic reproduction numbers. Focusing on AHSV transmission in the UK, insecticide-treated stable netting is shown to significantly reduce vectorial capacity of Culicoides, even at low coverage levels. However, untreated stable netting is likely to have limited impact. Overall, this model can be used to consider both climate and vector control interventions either currently utilised or for potential use in an outbreak, and could help guide policy makers seeking to mitigate the impact of climate change on disease control. [ABSTRACT FROM AUTHOR]

African swine fever (ASF) is a deadly hemorrhagic disease of domestic and wild swine that was first described in the early 20th century after the introduction of European pigs to Kenya. The etiological agent, the African swine fever virus (ASFV), is a large DNA virus within the Asfarviridae family that is broadly categorized epidemiologically into genotypes based on the nucleotide sequence of B646L, the gene encoding the major capsid protein p72. ASF outbreaks in Africa have been linked historically to 25 genotypes by p72 nucleotide analysis and, recently, to 6 genotypes by amino acid comparison, whereas global outbreaks of ASF outside of Africa have only been linked to 2 genotypes: genotype I, which led to an outbreak in Europe during the 1960s that later spread to South America, and genotype II, responsible for the current pandemic that began in Georgia in 2007 and has since spread to Europe, Asia, and Hispaniola. Here, we present an analysis of the genome of ASFV Spencer, an isolate that was collected in 1951 near Johannesburg, South Africa. While nucleotide analysis of Spencer indicates the p72 coding sequence is unique, differentiating from the closest reference by five nucleotides, the predicted amino acid sequence indicates that it is 100% homologous to contemporary genotype 1. Full genome analysis reveals it is more similar to Mkuzi1979 and encodes genes that share similarity with either genotype 1 or genotype 2 outbreak strains. [ABSTRACT FROM AUTHOR]

Rift Valley fever virus (RVFV) causes disease outbreaks in livestock and humans; however, its inter-epidemic circulation is poorly understood, similar to other arboviruses affecting cattle such as bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV). Serum samples were collected in Baringo County, Kenya from 400 cattle, accompanied by a risk factor questionnaire. Serological tests were then conducted to determine the exposure of cattle to RVFV, BTV, and EHDV. RVFV, BTV, and EHDV IgG seroprevalence rates were 15.5%, 91.5%, and 91%, respectively. Seropositivity for RVFV, BTV, and EHDV was significantly higher in adult cattle, as well as in females for RVFV. Cattle with herd owners aged between 30–39 years were less likely to be seropositive for RVFV compared to those with owners over the age of 60 years. High seroprevalence of BTV and EHDV in cattle indicates significant exposure and the subclinical circulation of these viruses, presenting a risk of outbreaks to sheep and naïve cattle. Moreover, the detection of RVFV-seropositive young cattle born after the last reported outbreak suggests inter-epidemic circulation of the virus. Overall, monitoring these arboviruses in cattle is crucial in understanding their distribution and seroprevalence during inter-epidemic periods. [ABSTRACT FROM AUTHOR]

Introduction: Screening and postoperative intervention of breast tumors are critical for the effective diagnosis and treatment of disease development, and reliable diagnostic/screening methods become a key link. Objective: Thromboelastogram (TEG), routine platelet (PLT) count, and the coagulation function indicators in patients with different breast diseases were determined and analyzed to explore their predictive value in secondary bleeding disorders. Methods: A total of 131 patients with breast diseases, admitted to Jiangsu University Affiliated Hospital from January 2019 to December 2022, were selected as the research subjects. The detection items were analyzed using the receiver operating curve (ROC) after grouping for secondary bleeding disorders of patients with breast cancer. Results: The reaction (R) and the coagulation (K) times were lower in the malignant breast disease group, while the coagulation angle (a), maximum amplitude (MA), coagulation index (CI), fibrinogen (FIB), and D-dimer (D-D) were higher than those in the benign breast disease group. The t-tests proved that the MA and FIB values were statistically significant (p < 0.05) in the benign and malignant breast disease groups. The R and K in patients with breast diseases were positively correlated with the activated partial thromboplastin time (aPTT) and D-D, but were negatively correlated with PLT. The a angle was negatively correlated with aPTT and D-D, but was positively correlated with PLT. The MA for PLT function was positively correlated with FIB and PLT. CI was negatively correlated with aPTT, thrombin time (TT), and D-D, but was positively correlated with PLT. ROC curve analysis showed that the CI and a angle had a significant predictive value, whereas the correlation of the other indicators was relatively low. Conclusion: Coagulation tests showed significant differences in patients with breast cancer, differing from those with benign breast diseases. TEG combined with conventional coagulation indicators is potentially valuable for the prediction of secondary bleeding disorders in patients with breast cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: High-dose post-transplant cyclophosphamide is effective in preventing graft-versus-host disease (GVHD) but is associated with adverse outcomes such as delayed engraftment, infections, and cardiac issues. This pilot study evaluated the efficacy and toxicity of reduced-dose PTCY (40 mg/kg/day) in patients undergoing HLA-matched allogeneic hematopoietic stem cell transplantation (alloHSCT). Neutrophil and platelet engraftment occurred at medians of 15 and 16 days, respectively. At day 100, the incidences of grade II–IV and III–IV acute GVHD were 18.2% and 4.5%, respectively, with no cases of grade IV acute GVHD or steroid-refractory disease. One-year incidence of moderate-severe chronic GVHD was 6.4%. Both incidences, acute GVHD and chronic GVHD, are similar to our previous experience with higher doses of PTCY. Two-year overall survival and relapse-free survival were 77.1% and 58.3%. There were low incidences of infections and only one early cardiac event. These results suggest that reduced-dose PTCY provides adequate immunosuppression with a low toxicity profile. PTCY 50 mg/kg/day on days +3/+4 is an excellent strategy to prevent GVHD. However, its use is associated with adverse outcomes such as delayed engraftment, increased risk of infection, and cardiac complications. This pilot study evaluates the efficacy and toxicity of a reduced dose of PTCY (40 mg/kg/day) combined with tacrolimus in 22 peripheral blood HLA-matched alloHSCT patients. At day +100, the cumulative incidences of grade II–IV and III–IV acute GVHD were 18.2% and 4.5%, respectively. No grade IV acute GVHD or steroid-refractory disease was observed. The cumulative incidences of all-grade and moderate-severe chronic GVHD at 1-year were 11.4% and 6.4%, respectively. No patient died from transplant-related complications. Two-year OS and RFS were 77.1% and 58.3%, respectively. All patients engrafted, with neutrophil and platelet recovery occurring at a median of 15 (IQR 14–16) and 16 days (IQR 12–23), respectively. The cumulative incidences of bloodstream bacterial infections, polyomavirus BK hemorrhagic cystitis, HHV6 reactivation, CMV reactivation, and fungal infections were 13.6%, 9.1%, 9.1%, 4.6%, and 6%, respectively. Only one early cardiac event was observed. These results suggest that PTCY 40 mg/kg/day on a +3/+4 schedule provides adequate immunosuppression to allow for engraftment and prevent clinically significant GVHD with a low toxicity profile. [ABSTRACT FROM AUTHOR]

Background: The Government of India allowed the State of Haryana to go for the 27th round of FMD and HS combined oil adjuvant vaccine for mass vaccination of eligible bovine population, at a six monthly interval under FMD-CP. This was the second phase of the combined vaccination. Haryana is the only state in India where a single FMD and HS combined vaccine was used in bovines as a pilot project for protection against two most economically important diseases i.e. Hemorrhagic Septicemia (HS) and Foot and Mouth (FMD) diseases. The aim of this study is to describe the current uptake and usage of FMD and HS dual vaccine on the basis of a questionnaire-based survey of livestock owners in Haryana. Methods: Randomly selected livestock owners from 6 district namely Karnal, Panipat, Kurukshetra, Ambala, Panchkula and Yamunanagar of Haryana State were contacted and a questionnaire, made available in paper format, was distributed to them to participate in this study. Appropriate, answers to open questions were categorised into themes using thematic analysis methodology (Attride-Stirling, 2001). Result: Total of 96.81 (ninety six point eight one) percent of respondents (n=942/973) had their cattle vaccinated. Of the 31 respondents who excluded their animals from the vaccination, 58.06 percent pregnant (18/31), 16.12 percent lactating (5/31), 12.9 percent calves (4/31) and 6.45 percent sick (2/31) animals were indicated. The respondents who excluded their animals further expressed their desire to get their animals vaccinated during later stages of life. [ABSTRACT FROM AUTHOR]

Disease co-occurrence in wildlife populations is common yet understudied. In the case of disease-caused mortality, the mortality attributed to one disease has the potential to buffer populations against subsequent alternative disease outbreaks by reducing populations and thus contacts needed to sustain disease transmission. However, substantial disease-driven population declines may also prevent populations from recovering, leading to localized extinctions. Hemorrhagic disease (HD), a vector-transmitted, viral disease in white-tailed deer (WTD), similar to chronic wasting disease (CWD), a prion disease, has increased in frequency and distribution in the United States. However, unlike CWD, which progresses slowly, HD can cause mortality only days after infection. Hemorrhagic disease outbreaks can result in substantial localized mortality events in WTD near vector habitats such as wetlands and may reduce local deer densities and consequent CWD transmission. The objective of our study was to evaluate the potential for HD outbreaks to buffer CWD risk where the diseases co-occur. Using an agent-based modeling approach, we found that frequent, intense HD outbreaks have the potential to mitigate CWD risk, especially if those outbreaks occur shortly after CWD introduction. However, HD outbreaks that do not result in substantial WTD mortality are unlikely to impact CWD or WTD population dynamics. Severe HD outbreaks may reduce CWD cases and could present an opportunity for managers to boost CWD control initiatives in a post-HD outbreak year. [ABSTRACT FROM AUTHOR]

The epizootic hemorrhagic disease virus (EHDV) is a novel emerging threat for the European livestock sector. First detected in Sardinia and southern Spain at the end of 2022, this transboundary disease emerged in France in September 2023 despite restrictions on animal movement and enhanced surveillance protocols. Although virus spread is believed to be mediated by the dispersal of Culicoides vectors by the wind, prediction is difficult due to the large number of meteorological parameters that must be considered. Using simulations of atmospheric trajectories, we developed a model to investigate the long‐distance dispersal risk zone of Culicoides in Europe, starting from different source zones. Our model predicted with good sensitivity the newly EHDV‐infected areas in France over a period of 5 weeks after its first introduction in the country. Prospectively, we predicted that the midge dispersal zone of early 2024 could expand toward most of the western half of France and could sporadically reach new countries under favorable spring conditions. The wind dispersal risk maps provided are intended to support better preparedness and response to Culicoides‐borne diseases. [ABSTRACT FROM AUTHOR]

Background: Factor XI (FXI) deficiency is an autosomal hemorrhagic disorder characterized by reduced plasma FXI levels. Multiple ancestral variants in the F11 gene have been identified in Ashkenazi Jews and other selected European populations. However, there are few reports of predominant variants in Chinese and/or East Asian populations. The aim of this study is to characterize the genotypes and phenotypes of FXI deficiency and identify the predominant variants. Results: Of the 41 FXI-deficient patients, 39 exhibited severe FXI defects, considerably more than those with partial defects. The APTT levels showed a negative correlation with FXI activity levels (coefficient=-0.584, P <.001). Only nine patients experienced mild bleeding, including one partially defective patient and eight severely defective patients. The majority of patients were referred for preoperative screenings (n = 22) and checkups (n = 14). Genetic analysis revealed that 90% of the patients had genetic defects, with 2, 16, and 19 cases of heterozygous, homozygous, and compound heterozygous patients, respectively. Seventeen variants were detected in the F11 gene (6 novel), including eleven missense variants, four nonsense variants, and two small deletions scattered throughout the F11. Of the 11 missense variants, six have not yet been studied for in vitro expression. Protein modeling analyses indicated that all of these variants disrupted local structural stability by altering side-chain orientation and hydrogen bonds. Nine variants, consisting of three missense and six null variants, were detected with a frequency of two or more. The highest allele frequency was observed in p.Q281* (21.25%), p.W246* (17.50%), p.Y369* (12.50%), and p.L442Cfs*8 (12.50%). The former two were variants specific to East Asia, while the remaining two were southeast China-specific variants. Conclusion: Our population-based cohort demonstrated that no correlation between the level of FXI activity and the bleeding severity in FXI deficiency. Additionally, the prevalence of FXI deficiency may have been underestimated. The nonsense p.Q281* was the most common variant in southeast China, suggesting a possible founder effect. [ABSTRACT FROM AUTHOR]

It is now understood that the flatfish farming industry faces significant threats from Chinook salmon bafinivirus (CSBV) induced hemorrhagic disease. Developing a prompt and efficient diagnostic method is crucial for effective disease control and minimizing losses in aquaculture production. This research assessed the loop-mediated isothermal amplification (LAMP) technique, using a specific primer set, for rapid and precise detection of CSBV. The primer set for LAMP detection was selected based on its demonstrated high specificity and sensitivity, as confirmed through visualization and gel electrophoresis. The CSBV-LAMP reaction system operated at an effective temperature of 63–67°C for 60 min. Importantly, the LAMP assay could identify viral genomic cDNA at an extremely low concentration of 10 pg/μL within 60 min at 65°C. Moreover, this reaction system accurately detected CSBV in naturally infected flatfish samples, yielding a 100% positive detection rate. [ABSTRACT FROM AUTHOR]

Crimean-Congo hemorrhagic fever virus (CCHFV) is a life-threatening arthropod-borne virus transmitted by tick bites or contact with blood or tissues of viraemic individuals and animals. CCHFV continues its existence in a broad region with sporadic cases or outbreaks. CCHFV infection is observed frequently as an asymptomatic, but sudden severe disease characterised by haemorrhagic can occur. Diagnostic methods employ enzyme-linked immunosorbent assay (ELISA) and real-time reverse transcription-polymerase chain reaction (RT-PCR). Although ribavirin has been recommended in treatment besides supportive therapy approaches, no antiviral or vaccine for CCHF is currently approved. This review demonstrates general knowledge of CCHFV, summarising its molecular biology, pathogenesis, diagnosis, epidemiology, sustaining and transmission, treatment and prevention strategies, including vaccine candidates. [ABSTRACT FROM AUTHOR]

Retrospective serological and case diagnostic data of endemic bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV) provide evidence of viral transmission among livestock and wildlife from 2016 in Kansas and Nebraska. Serological testing of mature cattle in nine distinct regional zones of Kansas revealed 76% to 100% had detectable antibodies to BTV and/or EHDV. Specimens tested in the Kansas Veterinary Diagnostic Laboratory (55 submissions) were 51% test positive for antibodies to BTV and/or EHDV. Specimens tested in the Nebraska Veterinary Diagnostic Center (283 submissions) were 25% test positive for antibodies to BTV and/or EHDV. Low disease incidence in white-tailed deer and other susceptible wild ungulates was observed during 2016. However, there were no confirmed reports of disease in livestock in either state. The reasons for emergence of significant clinical disease in livestock and wildlife populations remain undefined. [ABSTRACT FROM AUTHOR]

The mammarenavirus Lassa virus (LASV) causes the life-threatening hemorrhagic fever disease, Lassa fever. The lack of licensed medical countermeasures against LASV underscores the urgent need for the development of novel LASV vaccines, which has been hampered by the requirement for a biosafety level 4 facility to handle live LASV. Here, we investigated the efficacy of mRNA-lipid nanoparticle (mRNA-LNP)- based vaccines expressing the LASV glycoprotein precursor (LASgpc) or nucleoprotein (LCMnp) of the prototypic mammarenavirus, lymphocytic choriomeningitis virus (LCMV), in mice. Two doses of LASgpc- or LCMnp-mRNA-LNP administered intravenously (i.v.) protected C57BL/6 mice from a lethal challenge with a recombinant (r) LCMV expressing a modified LASgpc (rLCMV/LASgpc2m) inoculated intracranially. Intramuscular (i.m.) immunization with two doses of LASgpc- or LCMnp-mRNA-LNP significantly reduced the viral load in C57BL/6 mice inoculated i.v. with rLCMV/LASgpc2m. High levels of viremia and lethality were observed in CBA mice inoculated i.v. with rLCMV/LASgpc2m, which were abrogated by i.m. immunization with two doses of LASgpc-mRNA-LNP. The protective efficacy of two i.m. doses of LCMnp-mRNA-LNP was confirmed in a lethal hemorrhagic disease model of FVB mice i.v. inoculated with wild-type rLCMV. In all conditions tested, negligible and high levels of LASgpc- and LCMnp-specific antibodies were detected in mRNA-LNP-immunized mice, respectively, but robust LASgpc- and LCMnp-specific CD8+ T cell responses were induced. Accordingly, plasma from LASgpcmRNA-LNP-immunized mice did not exhibit neutralizing activity. Our findings and surrogate mouse models of LASV infection, which can be studied at a reduced biocontainment level, provide a critical foundation for the rapid development of mRNA-LNPbased LASV vaccines. IMPORTANCE Lassa virus (LASV) is a highly pathogenic mammarenavirus responsible for several hundred thousand infections annually in West African countries, causing a high number of lethal Lassa fever (LF) cases. Despite its significant impact on human health, clinically approved, safe, and effective medical countermeasures against LF are not available. The requirement of a biosafety level 4 facility to handle live LASV has been one of the main obstacles to the research and development of LASV countermeasures. Here, we report that two doses of mRNA-lipid nanoparticle-based vaccines expressing the LASV glycoprotein precursor (LASgpc) or nucleoprotein (LCMnp) of lymphocytic choriomeningitis virus (LCMV), a mammarenavirus genetically closely related to LASV, conferred protection to recombinant LCMV-based surrogate mouse models of lethal LASV infection. Notably, robust LASgpc- and LCMnp-specific CD8+ T cell responses were detected in mRNA-LNP-immunized mice, whereas no virus-neutralizing activity was observed. [ABSTRACT FROM AUTHOR]

The Ebola virus (EBOV) is a member of the Orthoebolavirus genus, Filoviridae family, which causes severe hemorrhagic diseases in humans and non-human primates (NHPs), with a case fatality rate of up to 90%. The development of countermeasures against EBOV has been hindered by the lack of ideal animal models, as EBOV requires handling in biosafety level (BSL)-4 facilities. Therefore, accessible and convenient animal models are urgently needed to promote prophylactic and therapeutic approaches against EBOV. In this study, a recombinant vesicular stomatitis virus expressing Ebola virus glycoprotein (VSV-EBOV/GP) was constructed and applied as a surrogate virus, establishing a lethal infection in hamsters. Following infection with VSV-EBOV/GP, 3-week-old female Syrian hamsters exhibited disease signs such as weight loss, multi-organ failure, severe uveitis, high viral loads, and developed severe systemic diseases similar to those observed in human EBOV patients. All animals succumbed at 2-3 days post-infection (dpi). Histopathological changes indicated that VSV-EBOV/GP targeted liver cells, suggesting that the tissue tropism of VSV-EBOV/GP was comparable to wild-type EBOV (WT EBOV). Notably, the pathogenicity of the VSV-EBOV/GP was found to be species-specific, age-related, gender-associated, and challenge route-dependent. Subsequently, equine anti-EBOV immunoglobulins and a subunit vaccine were validated using this model. Overall, this surrogate model represents a safe, effective, and economical tool for rapid preclinical evaluation of medical countermeasures against EBOV under BSL-2 conditions, which would accelerate technological advances and breakthroughs in confronting Ebola virus disease. [ABSTRACT FROM AUTHOR]

The Crimean-Congo hemorrhagic fever virus (CCHFV) is an emerging pathogen of the Orthonairovirus genus that can cause severe and often lethal hemorrhagic diseases in humans. CCHFV has a broad tropism and can infect a variety of species and tissues. Here, by using gene silencing, blocking antibodies or soluble receptor fragments, we identify the low-density lipoprotein receptor (LDL-R) as a CCHFV entry factor. The LDL-R facilitates binding of CCHFV particles but does not allow entry of Hazara virus (HAZV), another member of the genus. In addition, we show that apolipoprotein E (apoE), an exchangeable protein that mediates LDL/LDL-R interaction, is incorporated on CCHFV particles, though not on HAZV particles, and enhances their specific infectivity by promoting an LDL-R dependent entry. Finally, we show that molecules that decrease LDL-R from the surface of target cells could inhibit CCHFV infection. Our study highlights that CCHFV takes advantage of a lipoprotein receptor and recruits its natural ligand to promote entry into cells. This study shows that Crimean-Congo hemorrhagic fever virus (CCHFV) recruits apoE, an exchangeable apolipoprotein that mediates LDL/LDL-R interaction, to promote virion entry via the LDLR. Molecules that down-regulate LDL-R inhibit CCHFV infection. [ABSTRACT FROM AUTHOR]

Crimean-Congo haemorrhagic fever virus (CCHFV) is a globally significant tick-borne zoonotic pathogen that causes fatal haemorrhagic disease in humans. Despite constituting an ongoing public health threat, limited research exists on the presence of CCHFV among herdsmen, an occupationally exposed population that has prolonged contact with ruminants and ticks. This cross-sectional study, conducted between October 2018 and February 2020 in Kwara State, Nigeria, was aimed at assessing CCHFV seroprevalence among herdsmen and non-herdsmen febrile patients, and identifying the associated risk factors. Blood samples from herdsmen (n = 91) and febrile patients in hospitals (n = 646) were analyzed for anti-CCHFV IgG antibodies and CCHFV S-segment RNA using ELISA and RT-PCR, respectively. Results revealed a remarkably high CCHFV seroprevalence of 92.3% (84/91) among herdsmen compared to 7.1% (46/646) in febrile patients. Occupational risk factors like animal and tick contact, tick bites, and hand crushing of ticks significantly contributed to higher seroprevalence in the herdsmen (p<0.0001). Herdsmen were 156.5 times more likely (p<0.0001) to be exposed to CCHFV than febrile patients. Notably, the odds of exposure were significantly higher (OR = 191.3; p<0.0001) in herdsmen with a history of tick bites. Although CCHFV genome was not detectable in the tested sera, our findings reveal that the virus is endemic among herdsmen in Kwara State, Nigeria. CCHFV should be considered as a probable cause of febrile illness among humans in the study area. Given the nomadic lifestyle of herdsmen, further investigations into CCHF epidemiology in this neglected population are crucial. This study enhances our understanding of CCHFV dynamics and emphasizes the need for targeted interventions in at-risk communities. [ABSTRACT FROM AUTHOR]

(1) Background: Epizootic hemorrhagic disease virus (EHDV) and bluetongue virus (BTV) are orbiviruses that cause hemorrhagic disease (HD) with significant economic and population health impacts on domestic livestock and wildlife. In the United States, white-tailed deer (Odocoileus virginianus) are particularly susceptible to these viruses and are a frequent blood meal host for various species of Culicoides biting midges (Diptera: Ceratopogonidae) that transmit orbiviruses. The species of Culicoides that transmit EHDV and BTV vary between regions, and larval habitats can differ widely between vector species. Understanding how midges are distributed across landscapes can inform HD virus transmission risk on a local scale, allowing for improved animal management plans to avoid suspected high-risk areas or target these areas for insecticide control. (2) Methods: We used occupancy modeling to estimate the abundance of gravid (egg-laden) and parous (most likely to transmit the virus) females of two putative vector species, C. stellifer and C. venustus, and one species, C. haematopotus, that was not considered a putative vector. We developed a universal model to determine habitat preferences, then mapped a predicted weekly midge abundance during the HD transmission seasons in 2015 (July–October) and 2016 (May–October) in Florida. (3) Results: We found differences in habitat preferences and spatial distribution between the parous and gravid states for C. haematopotus and C. stellifer. Gravid midges preferred areas close to water on the border of well and poorly drained soil. They also preferred mixed bottomland hardwood habitats, whereas parous midges appeared less selective of habitat. (4) Conclusions: If C. stellifer is confirmed as an EHDV vector in this region, the distinct spatial and abundance patterns between species and physiological states suggest that the HD risk is non-random across the study area. [ABSTRACT FROM AUTHOR]

Introduction: Moyamoya disease (MMD) is a vascular disease with significant risk of mortality due to ischemia or hemorrhage in the brain. The goal of the study was to explore three-dimensional arterial spin labeling (3D-ASL) to improve evaluation of cerebral hemodynamics in patients with MMD. Methods: Our study included 54 cases of ischemic MMD and 42 cases of hemorrhagic MMD. Dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI) and 3D-ASL were performed at 3.0 T. Based on these scans, cerebral blood flow (CBF), mean transit time (MTT), and time to peak (TTP) were calculated and compared between patients with different disease subtypes. Receiver operating characteristics analysis was used to assess the diagnostic sensitivity and specificity of different imaging procedures and parameters. Results: Our data suggested that CBF in the lesion area was more severely reduced in patients with hemorrhagic MMD than in those with ischemic MMD. The CBF parameter in 3D-ASL diagnosed hemorrhagic and ischemic MMD with a significant sensitivity and specificity of 80.59% and 57.41%, respectively, with an area under the curve (AUC) of 0.75. We also found that the relative CBF of 3D-ASL was more pronounced decreased and the relative MTT and TTP of DSC-PWI were significantly increased in patients with hemorrhagic MMD than those with ischemic MMD. Specificity and sensitivity and AUC of 3D-ASL were better than the comparison of absolute values from DSC-PWI scans. Conclusion: Our study indicated that 3D-ASL is powerful in differentiating patients with cerebral ischemic or hemorrhagic MMD, providing another diagnostic tool that could potentially improve precision medicine to monitoring MMD patients. [ABSTRACT FROM AUTHOR]

Simple Summary: African swine fever (ASF) is a lethal hemorrhagic disease of Suidae, i.e., domestic pigs and wild boars, caused by African swine fever virus (ASFV). The development of cross-protective vaccines against ASF is imperative for effective disease control, particularly in regions where ASF is endemic, potentially featuring multiple circulating ASFV isolates. It was shown that the intranasal administration of a low dose of ASFV-PSA-1NH (immunotype IV, genotype I) to pigs led to minimal manifestation of clinical signs of ASF and the formation of a high level of protection against the heterologous strain ASFV-Stavropol 01/08 (seroimmunotype VIII, genotype II). African swine fever (ASF) is a lethal hemorrhagic disease of Suidae, i.e., domestic pigs and wild boars, caused by African swine fever virus (ASFV). The development of cross-protective vaccines against ASF is imperative for effective disease control, particularly in regions where ASF is endemic, potentially featuring multiple circulating ASFV isolates. The investigation of non-hemadsorbing naturally attenuated isolates and laboratory recombinant strains with a deletion in the EP402R gene has attracted interest. Our study aimed to assess the impacts of various administration routes and doses of the naturally attenuated ASFV-PSA-1NH (immunotype IV, genotype I) isolate on the manifestation of clinical signs of ASF and the level of protection against the heterologous ASFV-Stavropol 01/08 strain (seroimmunotype VIII, genotype II). The results demonstrated that the intranasal administration of a low dose of ASFV-PSA-1NH to pigs minimized the clinical signs of ASF and established a high level of protection against the heterologous strain ASFV-Stavropol 01/08. Despite the challenges in standardizing the dosage for intranasal administration, this approach appears as a viable alternative in ASF vaccination. [ABSTRACT FROM AUTHOR]

Objectives: Contrast‐enhanced ultrasound (CEUS) is increasingly utilized for the noninvasive assessment of renal cystic lesions, using the Bosniak grading system. Bosniak 3–4 lesions require surgical referral, which allows correlation with the histopathological outcome. Methods: In this single‐center, retrospective study we evaluated renal CEUS exams conducted with SonoVue® with a diagnosis of a Bosniak 3 or 4 lesion between 2019 and 2022. A total of 49 patients and 50 lesions met the inclusion criteria, 31 lesions had available histopathological results. Patient demographics, cyst morphology, and dominant imaging features were registered. The histopathological diagnosis was considered a reference standard. Results: Positive predictive power (PPV) for neoplastic lesions was comparable in the Bosniak 3 and 4 categories (75 vs 93.3%, P =.33), while PPV for histopathologically malignant lesion was considerably higher in the latter group (25 vs 93.33%, P =.0002). None of the lesions which had vividly enhancing thin septa as their dominant CEUS feature were malignant. Oncocytoma, multilocular cystic renal neoplasm of low malignant potential, and cystic nephroma were the major benign entities among Bosniak 3 lesions. Localized cystic kidney disease and hemorrhagic cysts were found to be the primary mimickers leading to false positive imaging findings. Conclusions: CEUS has a high predictive power for malignancy in the Bosniak 4 category, which is not maintained in the Bosniak 3 group due to the large proportion of benign lesions. Adherence to rigorous rule‐in criteria and active surveillance strategies need to be considered for equivocal CEUS Bosniak 3 lesions. Access the CME test here and search by article title. [ABSTRACT FROM AUTHOR]

Background: Launaea nudicaulis (L.) Hook. f. is a glabrous perennial herb having simple, sessile leaf and yellow flower. In Ayurveda it is used as a botanical source of Gojihva. The herb is said to be useful as a Shaka (vegetable) and medicine for various diseases like Raktapitta (hemorrhagic disorders), Shwaasa (breathing problems), Kasa (cough), Kushtha (skin diseases), Vrana (wounds), Visarpa (erysipelas), Prameha (diabetes mellitus), and Aruchi (anorexia). Few researches have also been published on its analgesic, anti-inflammatory activity, anti-diabetic and wound healing but its micromorphology, pharmacognosy, physiochemical and bio-element analysis is not reported yet. Objectives: The present study was carried out to study the micromorphology, pharmacognosy, physiochemical and bio-element analysis for proper identification and authentication of the herb. Materials and Methods: The macroscopy, microscopy, physicochemical, phytochemical parameters and bio-element analysis were done using different chemicals and reagents with standard procedures. Results: The presence of golden yellow latex in the root of the herb is identification characteristic. Calcium oxalate crystals and stone cells were seen in powder study. The GC-MS analysis identified 25 metabolites which comprised of fatty acids, sugars, amino acids etc. HPLC analysis revealed presence of 10 metabolites among which Cichoric acid was found in maximum concentration. Conclusion: The results of the study will help for the proper identification and authentication of the herb. [ABSTRACT FROM AUTHOR]

Genetically diverse simian arteriviruses (simarteriviruses) naturally infect geographically and phylogenetically diverse monkeys, and cross-species transmission and emergence are of considerable concern. Characterization of most simarteriviruses beyond sequence analysis has not been possible because the viruses fail to propagate in the laboratory. We attempted to isolate 4 simarteriviruses, Kibale red colobus virus 1, Pebjah virus, simian hemorrhagic fever virus, and Southwest baboon virus 1, by inoculating an immortalized grivet cell line (known to replicate simian hemorrhagic fever virus), primary macaque cells, macrophages derived from macaque induced pluripotent stem cells, and mice engrafted with macaque CD34+- enriched hematopoietic stem cells. The combined effort resulted in successful virus isolation; however, no single approach was successful for all 4 simarteriviruses. We describe several approaches that might be used to isolate additional simarteriviruses for phenotypic characterization. Our results will expedite laboratory studies of simarteriviruses to elucidate virus-host interactions, assess zoonotic risk, and develop medical countermeasures. [ABSTRACT FROM AUTHOR]

Eel (Anguilla sp.) is an important freshwater‐cultured species with high economic value in China. Anguillid herpesvirus 1 (AngHV‐1) has been proven to be the pathogen of "mucus sloughing and haemorrhagic septicaemia disease" in eels, resulting in significant mortality and substantial losses to the eel industry. Current diagnostic methods for detecting AngHV‐1 are limited to laboratory‐based tests, for example, conventional end‐point PCR and qPCR. Therefore, there is an urgent need to develop an accurate, rapid, and simple detection method for on‐site diagnosis of AngHV‐1. In this study, we developed a recombinase‐aided amplification combined lateral flow dipstick (RAA‐LFD) assay for the detection of AngHV‐1. The RAA‐LFD assay can be performed within a temperature range of 18–45°C, with a reaction time of just 10 min for amplification. Importantly, the established RAA‐LFD assay exhibited no reactivity with other common aquatic viral pathogens, indicating its high specificity. The limit of detection for this method is 102 copies of AngHV‐1, which is more sensitive than the established conventional end‐point PCR method similarly targeting ORF95. Clinical detection of the diseased samples demonstrated that the accuracy of RAA‐LFD was significantly higher than that of the conventional end‐point PCR. In conclusion, the developed RAA‐LFD assay has proven to be a convenient, rapid, sensitive, and reliable tool for on‐site diagnosis of AngHV‐1. This advancement will be invaluable for the prevention and control of AngHV‐1 in the eel farming industry. [ABSTRACT FROM AUTHOR]

Viral hemorrhagic fever poses a significant public health challenge due to its severe clinical presentation and high mortality rate. The diagnostic process is hindered by similarity of symptoms across different diseases and the broad spectrum of pathogens that can cause hemorrhagic fever. In this study, we applied viral metagenomic analysis to 43 serum samples collected by the Public Health Laboratory (Fundação Ezequiel Dias, FUNED) in Minas Gerais State, Brazil, from patients diagnosed with hemorrhagic fever who had tested negative for the standard local hemorrhagic disease testing panel. This panel includes tests for Dengue virus (DENV) IgM, Zika virus IgM, Chikungunya virus IgM, yellow fever IgM, Hantavirus IgM, Rickettsia rickettsii IgM/IgG, and Leptospira interrogans IgM, in addition to respective molecular tests for these infectious agents. The samples were grouped into 18 pools according to geographic origin and analyzed through next-generation sequencing on the NextSeq 2000 platform. Bioinformatic analysis revealed a prevalent occurrence of commensal viruses across all pools, but, notably, a significant number of reads corresponding to the DENV serotype 2 were identified in one specific pool. Further verification via real-time PCR confirmed the presence of DENV-2 RNA in an index case involving an oncology patient with hemorrhagic fever who had initially tested negative for anti-DENV IgM antibodies, thereby excluding this sample from initial molecular testing. The complete DENV-2 genome isolated from this patient was taxonomically classified within the cosmopolitan genotype that was recently introduced into Brazil. These findings highlight the critical role of considering the patient's clinical condition when deciding upon the most appropriate testing procedures. Additionally, this study showcases the potential of viral metagenomics in pinpointing the viral agents behind hemorrhagic diseases. Future research is needed to assess the practicality of incorporating metagenomics into standard viral diagnostic protocols. [ABSTRACT FROM AUTHOR]

Simple Summary: Elephant endotheliotropic herpesvirus (EEHV) represents a significant viral infection in young Asian elephants (Elephas maximus). The EEHV1A genotype predominantly induces EEHV hemorrhagic disease, while the EEHV4 genotype also contributes to hemorrhagic symptoms affecting the gastrointestinal and cardiovascular systems, often leading to fatality in young Asian elephants. Recently, instances of co-infection involving EEHV1A and -4 in Asian elephants have been documented. The present study aims to further elucidate the clinical and pathological lesions in these EEHV1A and -4 co-infection cases, as well as refine treatment protocols. Three cases of double infection with elephant endotheliotropic herpesvirus (EEHV) types 1A and 4 in captive Asian elephants are presented. The first calf was a 4-year-old female that showed initial signs of lethargy and depression. The second calf was a 6-year-old female that displayed signs of depression and diarrhea and died within 48 h of the start of supportive treatment. The third was a 2-year-old male that died suddenly while living with the herd. Necropsies were performed in the first and second elephants, while only a tongue sample was collected from the third calf. EEHV infection was confirmed via quantitative PCR (qPCR) and gene sequencing, revealing double subtypes of EEHV1A and -4 infections. This study describes the hematological and pathological characteristics within the host following double EEHV infection. [ABSTRACT FROM AUTHOR]

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Lassa fever (LF) is a zoonotic viral hemorrhagic disease endemic to several West African countries. Approximately 300–500,000 cases occur annually across all ages with 10–20% case fatality rates. A LF vaccine is a recognized public health priority, with several candidates entering clinical trials. However, the perspectives of regional experts regarding critical vaccine properties, ideal delivery methods, and priority target populations remain unclear. Using a mixed methods approach with a standardized questionnaire, we individually interviewed 8 West African stakeholders, each with extensive knowledge and experience of LF. They strongly favored the use of a mass, proactive campaign strategy to immunize a wide age range of people in high-risk areas, including pregnant women and health care workers. We estimated that these and other plausible delivery scenarios could result in an initial demand of anywhere from 1 to 100 million doses, with most demand coming from Nigeria. These findings may help inform LF vaccine development and deployment efforts. [ABSTRACT FROM AUTHOR]