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Ping Zhang, Yanan Cai, Fei Ge, Zunmin Zhu, Kai Sun Department of Hematology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Kai Sun, Department of Hematology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, &num;7 Weiwu Road, Zhengzhou, People’s Republic of China, Email sunkai900@163.comIntroduction: This study aims to investigate the incidence, clinical characteristics, and prognosis of thrombosis in Chinese patients with immune thrombocytopenia (ITP).Methods: This was a single-center, retrospective study of adult patients with ITP at the Henan Provincial People’s Hospital from January 2018 to June 2023.Results: A total of 3216 adult patients with primary ITP were included in the study period, with 25 (0.93%) having thrombotic events. The average age of 25 patients with thrombosis is 62.76± 12.79 years, including 11 males and 14 females. In addition, among the 25 thrombotic events, 19 cases were arterial thrombosis (AT), and 6 cases were venous thrombosis (VT). The incidence of AT is higher than that of VT (P=0.009). There was no obvious difference in clinical characteristics between the two groups. The median platelet count at the time of thrombosis in 25 patients was 35 (23, 52) × 109/L. At the onset of thrombosis, 23 patients (92.0%) had a low PLT (< 100× 109/L). One patient with ischemic stroke died in the hospital due to severe infection.Conclusion: ITP may be considered a bleeding disorder with a high risk of thrombosis, and AT is more common than VT in the Chinese population.Keywords: immune thrombocytopenia, arterial thrombosis, venous thrombosis, platelet, hemorrhagic disease

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]

(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]

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.

(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.

Hemorrhagic diseases caused by epizootic hemorrhagic disease virus or by bluetongue virus (BTV) are the most important orbivirus diseases affecting ruminants, including white-tailed deer (WTD). Bluetongue virus is of particular concern for farmed WTD in Florida, given its lethality and its wide distribution throughout the state. This study reports the clinical findings, ancillary diagnostics, and genomic characterization of two BTV serotype 1 strains isolated from two farmed WTD, from two different farms in Florida in 2019 and 2022. Phylogenetic and genetic analyses indicated that these two novel BTV-1 strains were reassortants. In addition, our analyses reveal that most genome segments of these strains were acquired from BTVs previously detected in ruminants in Florida, substantiating their endemism in the Southeastern U.S. Our findings underscore the need for additional research to determine the genetic diversity of BTV strains in Florida, their prevalence, and the potential risk of new BTV strains to WTD and other ruminants. [ABSTRACT FROM AUTHOR]

The Lassa virus is an RNA virus belonging to the Arenaviridae family. It is responsible for Lassa fever, an acute viral zoonosis of the severe hemorrhagic fever type with manifestations of fever, muscle pain, sore throat, nausea, vomiting, and chest and abdominal pain. Lassa fever is endemic in West Africa, where the first case was reported in 1969 in Lassa, a town in Nigeria, more than 50 years ago, and it is estimated that nearly 5000 deaths occur in West Africa each year. Nigeria is one of the endemic hotspots and has experienced numerous recurrent outbreaks of Lassa fever due to the increased multiplication of the host reservoir, Mastomys natalensis. For the Lassa epidemics in 2022 and January 2023 alone, Nigeria accounts for a quarter of the annual deaths from this disease. Poor lifestyle and hygiene, difficulty in diagnosis due to nonspecific symptomatology, lack of effective treatment based on clinical evidence, an ineffective human immunization program combined with a health system that is not adapted or equipped to control and prevent recurrent deadly epidemics, and an outdated regional disease surveillance system in West Africa are some of the challenges that must be overcome to rapidly and effectively eradicate this disease, whose area of spread is constantly expanding as a result of the movement of populations in the context of economic and socio‐cultural activities. [ABSTRACT FROM AUTHOR]

Abstract The Lassa virus is an RNA virus belonging to the Arenaviridae family. It is responsible for Lassa fever, an acute viral zoonosis of the severe hemorrhagic fever type with manifestations of fever, muscle pain, sore throat, nausea, vomiting, and chest and abdominal pain. Lassa fever is endemic in West Africa, where the first case was reported in 1969 in Lassa, a town in Nigeria, more than 50 years ago, and it is estimated that nearly 5000 deaths occur in West Africa each year. Nigeria is one of the endemic hotspots and has experienced numerous recurrent outbreaks of Lassa fever due to the increased multiplication of the host reservoir, Mastomys natalensis. For the Lassa epidemics in 2022 and January 2023 alone, Nigeria accounts for a quarter of the annual deaths from this disease. Poor lifestyle and hygiene, difficulty in diagnosis due to nonspecific symptomatology, lack of effective treatment based on clinical evidence, an ineffective human immunization program combined with a health system that is not adapted or equipped to control and prevent recurrent deadly epidemics, and an outdated regional disease surveillance system in West Africa are some of the challenges that must be overcome to rapidly and effectively eradicate this disease, whose area of spread is constantly expanding as a result of the movement of populations in the context of economic and socio‐cultural activities.

Vector-borne parasites may be transmitted by multiple vector species, resulting in an increased risk of transmission, potentially at larger spatial scales compared to any single vector species. Additionally, the different abilities of patchily distributed vector species to acquire and transmit parasites will lead to varying degrees of transmission risk. Investigation of how vector community composition and parasite transmission change over space due to variation in environmental conditions may help to explain current patterns in diseases but also informs our understanding of how patterns will change under climate and land-use change. We developed a novel statistical approach using a multi-year, spatially extensive case study involving a vector-borne virus affecting white-tailed deer transmitted by Culicoides midges. We characterized the structure of vector communities, established the ecological gradient controlling change in structure, and related the ecology and structure to the amount of disease reporting observed in host populations. We found that vector species largely occur and replace each other as groups, rather than individual species. Moreover, community structure is primarily controlled by temperature ranges, with certain communities being consistently associated with high levels of disease reporting. These communities are essentially composed of species previously undocumented as potential vectors, whereas communities containing putative vector species were largely associated with low levels, or even absence, of disease reporting. We contend that the application of metacommunity ecology to vector-borne infectious disease ecology can greatly aid the identification of transmission hotspots and an understanding of the ecological drivers of parasite transmission risk both now and in the future. [ABSTRACT FROM AUTHOR]

Epizootic hemorrhagic disease (EHD) leads to high mortality in white-tailed deer (Odocoileus virginianus) and is caused by a double-stranded RNA (dsRNA) virus. Toll-like receptor 3 (TLR3) plays a role in host immune detection and response to dsRNA viruses. We, therefore, examined the role of genetic variation within the TLR3 gene in EHD among 84 Illinois wild white-tailed deer (26 EHD-positive deer and 58 EHD-negative controls). The entire coding region of the TLR3 gene was sequenced: 2715 base pairs encoding 904 amino acids. We identified 85 haplotypes with 77 single nucleotide polymorphisms (SNPs), of which 45 were synonymous mutations and 32 were non-synonymous. Two non-synonymous SNPs differed significantly in frequency between EHD-positive and EHD-negative deer. In the EHD-positive deer, phenylalanine was relatively less likely to be encoded at codon positions 59 and 116, whereas leucine and serine (respectively) were detected less frequently in EHD-negative deer. Both amino acid substitutions were predicted to impact protein structure or function. Understanding associations between TLR3 polymorphisms and EHD provides insights into the role of host genetics in outbreaks of EHD in deer, which may allow wildlife agencies to better understand the severity of outbreaks. [ABSTRACT FROM AUTHOR]

Elephant endotheliotropic herpesviruses (EEHV) belong to the family Herpesviridae and cause a highly fatal hemorrhagic infection in elephants. EEHV poses a global threat to the already endangered elephant population. Since EEHV is a non-cultivable virus, there is a scarcity of specific diagnostics, therapeutics, and vaccines. In this study, our objective was to develop biologicals for diagnosis and pathological studies against the most prevalent EEHV1A/1B. We expressed two truncated fragments of the DNA polymerase, glycoprotein B (gB), and glycoprotein (gL) of EEHV in the prokaryotic system. Hyperimmune serum against the purified antigens was raised in rabbits and guinea pigs. We validated the reactivity of this hyperimmune serum using western blotting, ELISA, and immune-histochemistry on known positive infected tissues. Samples collected from 270 animals across various states in India were evaluated with these biologicals. The raised antibodies successfully demonstrated virus in immune-cytochemistry. Additionally, all known positive samples consistently exhibited significant inhibition in the OD values when used in the competitive format of ELISA across all four antigens when compared to the serum collected from known negative animals. An apparent sero-prevalence of 10 % was observed in the randomly collected samples. In summary, our study successfully developed and validated biologicals that will be invaluable for EEHV diagnosis and control. • Biologicals for EEHV were developed and evaluated for the purpose of diagnosis and pathogenesis. • Recombinant glycoprotein B, glycoprotein L and DNA polymerase of EEHV were expressed and specific serum were raised. • The developed biologicals were confirmed by Immuno-histochemistry and ELISA methods for diagnosis. [ABSTRACT FROM AUTHOR]

We reviewed case records from the California Animal Health and Food Safety (CAHFS) laboratory and the California Department of Fish and Wildlife (CDFW) spanning 25 years (1990-2014) for all deer accessions submitted to CAHFS for pathology and/or histopathology, with and without a diagnosis of adenoviral hemorrhagic disease (AHD), in order to determine the prevalence of AHD in California. We also examined spatial and temporal distribution, age, and mule deer subspecies in deer that died from AHD. Of 483 deer submitted to CAHFS for diagnostic testing in 1990-2014, 17.2% were diagnosed with confirmed AHD, and 26.5% were confirmed plus suspected cases of AHD. Columbian black-tailed deer ( Odocoileus hemionus columbianus), particularly fawns and juveniles, were most frequently affected. Deer adenovirus ( Odocoileus adenovirus 1; OdAdV-1) was detected by immunohistochemistry in archived CDFW formalin-fixed, paraffin-embedded tissues from deer that died in mortality events in 1981, 1983, and 1986-1987. OdAdV-1 is a common cause of hemorrhagic disease mortality events in California deer, and mortality as a result of AHD is documented as early as 1981.

Abstract Background The crucial role of type I interferon (IFN-I, IFN-α/β) is well known to control central nervous system (CNS) neuroinflammation caused by neurotrophic flaviviruses such as Japanese encephalitis virus (JEV) and West Nile virus. However, an in-depth analysis of IFN-I signal-dependent cellular factors that govern CNS-restricted tropism in JEV infection in vivo remains to be elucidated. Methods Viral dissemination, tissue tropism, and cytokine production were examined in IFN-I signal-competent and -incompetent mice after JEV inoculation in tissues distal from the CNS such as the footpad. Bone marrow (BM) chimeric models were used for defining hematopoietic and tissue-resident cells in viral dissemination and tissue tropism. Results The paradoxical and interesting finding was that IFN-I signaling was essentially required for CNS neuroinflammation following JEV inoculation in distal footpad tissue. IFN-I signal-competent mice died after a prolonged neurological illness, but IFN-I signal-incompetent mice all succumbed without neurological signs. Rather, IFN-I signal-incompetent mice developed hemorrhage-like disease as evidenced by thrombocytopenia, functional injury of the liver and kidney, increased vascular leakage, and excessive cytokine production. This hemorrhage-like disease was closely associated with quick viral dissemination and impaired IFN-I innate responses before invasion of JEV into the CNS. Using bone marrow (BM) chimeric models, we found that intrinsic IFN-I signaling in tissue-resident cells in peripheral organs played a major role in inducing the hemorrhage-like disease because IFN-I signal-incompetent recipients of BM cells from IFN-I signal-competent mice showed enhanced viral dissemination, uncontrolled cytokine production, and increased vascular leakage. IFN-I signal-deficient hepatocytes and enterocytes were permissive to JEV replication with impaired induction of antiviral IFN-stimulated genes, and neuron cells derived from both IFN-I signal-competent and -incompetent mice were vulnerable to JEV replication. Finally, circulating CD11b+Ly-6C+ monocytes infiltrated into the distal tissues inoculated by JEV participated in quick viral dissemination to peripheral organs of IFN-I signal-incompetent mice at an early stage. Conclusion An IFN-I signal-dependent model is proposed to demonstrate how CD11b+Ly-6C+ monocytes are involved in restricting the tissue tropism of JEV to the CNS.

Grass carp reovirus genotype Ⅱ (GCRV II) causes severe hemorrhagic disease in grass carp and affects the aquaculture industry in China. GCRV Ⅱ isolates have been collected from different epidemic areas in China, and these isolates can lead to different degrees of hemorrhagic symptoms in grass carp. Rare minnow (Gobiocypris rarus) is widely used as a model fish to study the mechanism of hemorrhagic disease because of its high sensitivity to GCRV. In this study, the protein levels in the spleen of rare minnow after infection with GCRV virulent isolate JZ809 and attenuated isolate XT422 were investigated using isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics. 109 and 50 differentially expressed proteins (DEPs) in the virulent and attenuated infection groups were obtained, respectively, among which 40 DEPs were identified in both groups. Combining protein expression profiling with gene ontology (GO) annotation, the responses of rare minnow to the two genotypes GCRV Ⅱ in terms of upregulated proteins were similar, focusing on ATP synthesis, in which ATP can serve as a "danger" signal to activate an immunoreaction in eukaryotes. Meanwhile, the virulent genotype JZ809 induced more immunoproteins and increased the levels of ubiquitin-proteasome system members to adapt to virus infection. However, together with a persistent and excessive inflammatory response and declining carbon metabolism, rare minnow presented more severe hemorrhagic disease and mortality after infection with virulent JZ809 than with attenuated XT422. The results provide a valuable information that will increase our understanding of the pathogenesis of viruses with different levels of virulence and the mechanism of interaction between the virus and host. Furthermore, the 6 proteins that were only significantly upregulated in the XT422 infection group all belonged to cluster 2, and 28 of 30 proteins that were only upregulated in JZ809 infection group were clustered into cluster 1. For the downregulated proteins, all DEPs in the XT422 infection group were clustered into cluster 4, and 25 of 39 proteins that were only significantly downregulated in the JZ809 infection group belonged to cluster 3. The results indicated that the DEPs in the attenuated XT422 infection group might be sensitive and their abundance changed more quickly when fish experienced virus infection. • Two isolates of GCRV Ⅱ, XT422 and JZ809, can induce different degrees of hemorrhagic symptoms in rare minnow. • 109 and 50 DEPs in the virulent and attenuated GCRV infection groups were identified by quantitative proteomics. • The differences in XT422 and JZ809 infection groups including ATP synthesis, immune system, UPS and TCA cycle etc. • The virulent JZ809 cause a persistent and excessive inflammatory response and declining carbon metabolism than XT422. [ABSTRACT FROM AUTHOR]

While several lines of evidence suggest a protective role of T cells against disease associated with Dengue virus (DENV) infection, their potential contribution to immunopathology in the acute phase of DENV infection remains controversial, and it has been hypothesized that the more severe form of the disease (dengue hemorrhagic fever, DHF) is associated with altered T cell responses. To address this question, we determined the transcriptomic profiles of DENV-specific CD8+ T cells in a cohort of 40 hospitalized dengue patients with either a milder form of the disease (dengue fever, DF) or a more severe disease form (dengue hemorrhagic fever, DHF). We found multiple transcriptomic signatures, one associated with DENV-specific interferon-gamma responding cells and two other gene signatures, one specifically associated with the acute phase and the other with the early convalescent phase. Additionally, we found no differences in quantity and quality of DENV-specific CD8+ T cells based on disease severity. Taken together with previous findings that did not detect altered DENV-specific CD4 T cell responses, the current analysis argues against alteration in DENV-specific T cell responses as being a correlate of immunopathology. [ABSTRACT FROM AUTHOR]

Introduction: hemorrhagic disease of the newborn can be prevented with prophylactic administration of vitamin K. Case presentation: 33-day-old female patient, without prenatal control, home delivery, and without administration of vitamin K prophylaxis. Her condition was characterized by a clinical picture of intracranial hypertension, in addition, in laboratory tests, prolonged coagulation times and elevated D-dimer were documented. Late hemorrhagic disease of the newborn was diagnosed with subdural hematoma. Treatment consisted of administration of vitamin K, fresh frozen plasma, and surgery. In the short and medium term, her evolution was satisfactory, without neurological sequelae. Conclusion: vitamin K deficiency hemorrhagic disease can occur up to two months of life; in cases where prophylaxis is not given, its identification is important to prevent serious complications. [ABSTRACT FROM AUTHOR]

Background: The crucial role of type I interferon (IFN-I, IFN-α/β) is well known to control central nervous system (CNS) neuroinflammation caused by neurotrophic flaviviruses such as Japanese encephalitis virus (JEV) and West Nile virus. However, an in-depth analysis of IFN-I signal-dependent cellular factors that govern CNS-restricted tropism in JEV infection in vivo remains to be elucidated.Methods: Viral dissemination, tissue tropism, and cytokine production were examined in IFN-I signal-competent and -incompetent mice after JEV inoculation in tissues distal from the CNS such as the footpad. Bone marrow (BM) chimeric models were used for defining hematopoietic and tissue-resident cells in viral dissemination and tissue tropism.Results: The paradoxical and interesting finding was that IFN-I signaling was essentially required for CNS neuroinflammation following JEV inoculation in distal footpad tissue. IFN-I signal-competent mice died after a prolonged neurological illness, but IFN-I signal-incompetent mice all succumbed without neurological signs. Rather, IFN-I signal-incompetent mice developed hemorrhage-like disease as evidenced by thrombocytopenia, functional injury of the liver and kidney, increased vascular leakage, and excessive cytokine production. This hemorrhage-like disease was closely associated with quick viral dissemination and impaired IFN-I innate responses before invasion of JEV into the CNS. Using bone marrow (BM) chimeric models, we found that intrinsic IFN-I signaling in tissue-resident cells in peripheral organs played a major role in inducing the hemorrhage-like disease because IFN-I signal-incompetent recipients of BM cells from IFN-I signal-competent mice showed enhanced viral dissemination, uncontrolled cytokine production, and increased vascular leakage. IFN-I signal-deficient hepatocytes and enterocytes were permissive to JEV replication with impaired induction of antiviral IFN-stimulated genes, and neuron cells derived from both IFN-I signal-competent and -incompetent mice were vulnerable to JEV replication. Finally, circulating CD11b+Ly-6C+ monocytes infiltrated into the distal tissues inoculated by JEV participated in quick viral dissemination to peripheral organs of IFN-I signal-incompetent mice at an early stage.Conclusion: An IFN-I signal-dependent model is proposed to demonstrate how CD11b+Ly-6C+ monocytes are involved in restricting the tissue tropism of JEV to the CNS. [ABSTRACT FROM AUTHOR]

Disease plays a major role in shaping wildlife populations worldwide, and changes in landscape conditions can significantly influence risk of pathogen exposure, a threat to vulnerable wild species. Three viruses that cause hemorrhagic disease affect cervid populations in the USA (Odocoileus hemionus adenovirus, bluetongue virus, and epizootic hemorrhagic disease virus), but little is known of their distribution and prevalence in wild populations. We explored the distribution and co-occurrence of seroprevalence of these three pathogens in southern mule deer (Odocoileus hemionus fuliginatus), a subspecies of conservation concern and a harvested species native to southern California, to evaluate the distribution of exposure to these pathogens relative to landscape attributes. We found that habitat type, level of development, and proximity to livestock may affect hemorrhagic disease seroprevalence in southern mule deer. Continued monitoring of hemorrhagic disease-causing viruses in areas where deer are in proximity to cattle and human development is needed to better understand the implications of future outbreaks in wild populations and to identify opportunities to mitigate disease impacts in southern mule deer and other cervid species. [ABSTRACT FROM AUTHOR]

Résumé: Les afibrinogénémies sont des pathologies héréditaires exceptionnelles dont le risque hémorragique est majeur. Leur prise en charge et les complications peuvent être complexes car le fibrinogène, en dehors de son rôle dans la coagulation, a un rôle dans l'hémostase et la thrombose et a de nombreuses fonctions pléiotropes dans la cicatrisation, l'inflammation, etc. Afibrinogenemias are exceptional hereditary pathologies whose hemorrhagic risk is major. Their management and complications can be complex because fibrinogen, apart from its role in coagulation, has a role in hemostasis and thrombosis and has many pleiotropic functions in healing, inflammation, etc. [ABSTRACT FROM AUTHOR]

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Abstract Background Epizootic hemorrhagic disease virus (EHDV) is an Orbivirus of veterinary importance which is transmitted by biting midges of the genus Culicoides (Diptera: Ceratopogonidae) to ruminants. Culicoides sonorensis Wirth & Jones, the only confirmed vector of EHDV in the USA, is rare in the southeastern states where transmission persists, suggesting that other Culicoides species transmit EHDV in this region. The present study aimed to determine which Culicoides species transmitted EHDV in Florida and Alabama, two states in the southeastern USA. Viral RNA was detected in field-collected midges using molecular methods. These data are presented alongside data on Culicoides blood meal analysis, white-tailed deer (Odocoileus virginianus) aspiration, and seasonality to demonstrate an interaction between potential vector species and EHDV hosts. Results Out of 661 pools tested, 20 pools were positive for EHDV viral RNA, including six pools from Culicoides stellifer (Coquillett) and 14 pools from Culicoides venustus Hoffman. The overall infection rate was 0.06% for C. stellifer and 2.18% for C. venustus. No positive pools were identified for a further 17 species. Serotypes identified in Culicoides included EHDV-2, EHDV-6, and coinfections of EHDV-2 and EHDV-6 and were identified in similar proportions to serotypes in deer at 3 of 4 deer farms. Viral detections conducted in Alabama also identified one positive pool of C. venustus. Blood meal analysis revealed that both Culicoides species fed on white-tailed deer (verified through aspiration), fallow deer, and elk, species for which EHDV viremia has been documented. Seasonality data indicated that both species were present throughout the period in which viral transmission occurred to EHDV hosts in 2016 in addition to the 2017 epizootic. Conclusions Our finding of EHDV positive pools of field-collected C. stellifer and C. venustus and an interaction between these species and EHDV hosts satisfy two of the four criteria for vector incrimination as set by the World Health Organization. Determining the vectors of EHDV is an important step towards developing sound strategies for the control of vector Culicoides and management of EHDV in the southeastern USA.

Our aim was to verify whether genes in the coagulation complement and cytokine interaction pathways are crucial to the resistance to grass carp hemorrhagic disease in grass carps (Ctenopharyngodon idella). To evaluate this, we acquired male grass carps with grass carp reovirus (GCRV) resistance, F1 generation, ordinary male fish, control F1 progenies (hybridized ordinary fish), and barbel chub (Squaliobarbus curriculus) as a positive control. We compared the expression variation of 13 immune factors in different tissues using real-time fluorescent quantitative PCR. Our results showed that the expression of the transforming growth factor-β3, nerve growth factor receptor, coagulation factor D, chemokine receptor XCR1, profibrinolysin, γ-globulin of complement component 1, complement component 2, and complement component 5 in the different tissues of the barbel chub were significantly higher than those in the grass carps populations under normal conditions. Except for a limited number of genes, their expression exhibited significant differences. There was no significant difference in these genes among grass carp populations with different GCRV resistance. These results indicate that the high gene expression in the coagulation complement and cytokine interaction pathways may be the main reason for the strong resistance of barbel chub to GCRV. However, high gene expression was not a factor affecting GCRV resistance between grass carp populations. [ABSTRACT FROM AUTHOR]

While several lines of evidence suggest a protective role of T cells against disease associated with Dengue virus (DENV) infection, their potential contribution to immunopathology in the acute phase of DENV infection remains controversial, and it has been hypothesized that the more severe form of the disease (dengue hemorrhagic fever, DHF) is associated with altered T cell responses. To address this question, we determined the transcriptomic profiles of DENV-specific CD8+ T cells in a cohort of 40 hospitalized dengue patients with either a milder form of the disease (dengue fever, DF) or a more severe disease form (dengue hemorrhagic fever, DHF). We found multiple transcriptomic signatures, one associated with DENV-specific interferon-gamma responding cells and two other gene signatures, one specifically associated with the acute phase and the other with the early convalescent phase. Additionally, we found no differences in quantity and quality of DENV-specific CD8+ T cells based on disease severity. Taken together with previous findings that did not detect altered DENV-specific CD4 T cell responses, the current analysis argues against alteration in DENV-specific T cell responses as being a correlate of immunopathology.

Immune thrombocytopenic purpura (ITP) is a blood disorder characterized by a low platelet count of (less than 100 × 109/L). ITP is an organ-specific autoimmune disease in which the platelets and their precursors become targets of a dysfunctional immune system. This interaction leads to a decrease in platelet number and, subsequently, to a bleeding disorder that can become clinically significant with hemorrhages in skin, on the mucous membrane, or even intracranial hemorrhagic events. If ITP was initially considered a hemorrhagic disease, more recent studies suggest that ITP has an increased risk of thrombosis. In this review, we provide current insights into the primary ITP physiopathology and their consequences, with special consideration on hemorrhagic and thrombotic events. The autoimmune response in ITP involves both the innate and adaptive immune systems, comprising both humoral and cell-mediated immune responses. Thrombosis in ITP is related to the pathophysiology of the disease (young hyperactive platelets, platelets microparticles, rebalanced hemostasis, complement activation, endothelial activation, antiphospholipid antibodies, and inhibition of natural anticoagulants), ITP treatment, and other comorbidities that altogether contribute to the occurrence of thrombosis. Physicians need to be vigilant in the early diagnosis of thrombotic events and then institute proper treatment (antiaggregant, anticoagulant) along with ITP-targeted therapy. In this review, we provide current insights into the primary ITP physiopathology and their consequences, with special consideration on hemorrhagic and thrombotic events. The accumulated evidence has identified multiple pathophysiological mechanisms with specific genetic predispositions, particularly associated with environmental conditions.

Abstract Background Outbreaks of deer hemorrhagic disease (HD) have been documented in the USA for many decades. In the year 2012, there was a severe HD outbreak in Missouri with mortalities reaching approximately 6.9 per thousand. Moreover, Missouri accounted for more than 43% of all reported epizootic HD cases in captive white-tailed deer. Using the data of suspected HD occurrence in Missouri, the primary goal of this paper was to determine if HD in Missouri’s white-tailed deer occurs in spatial clusters. Results The main results of the cluster analysis are as follows. First, the spatial clusters of years 1980, 1988, 2005–2007, 2010, 2012, and 2013 suggest patterns of outbreaks every 6–8 years, with a potential outbreak in years 2018–2020. Secondly, these spatial clusters were more frequent in the central and southern counties. Conclusions The clustering analyses employed in this study have potential applications for improving surveillance programs and designing early warning systems for effective deer population management and potentially reducing the number of HD cases.

Abstract Background Many important vector arthropods are known to stratify vertically in forest environments, a phenomenon which has important implications for vector-borne disease transmission and vector control. Culicoides Latreille biting midges (Diptera: Ceratopogonidae) have been documented using the forest canopy; however, studies of this phenomenon are lacking for many Culicoides species found in great abundance in the state of Florida, USA, some of which have been implicated as suspected vectors of hemorrhagic diseases of white-tailed deer. The present study aimed to determine whether common Culicoides species in Florida stratify vertically and to determine whether strata used by midges corresponded to host use. Methods Trapping was conducted at a big game preserve in Gadsden County, FL, USA. Over two summer field seasons in 2016 and 2017, CDC miniature light traps were set at two levels, one set at 1.37 m, designated as the ground trap, and a nearby trap in the forest canopy set at 6 m during 2016 and 9 m during 2017. Species abundance, physiological status, and blood-meal sources were analyzed and compared between trap heights. Results Species abundances for C. haematopotus, C. stellifer and C. venustus were not significantly different between trap heights during the 2016 season; however, canopy traps were found to have significantly higher abundance of C. arboricola, C. biguttatus, C. debilipalpis, C. haematopotus, C. insignis and C. stellifer than ground traps in 2017. Greater numbers of blood-engorged midges were collected in the canopy compared with ground traps during both study years, and 98.6% and 98.7% of blood meals from canopy collected midges were taken from ground-dwelling mammals in 2016 and 2017, respectively. Conclusions Culicoides species in Florida, including species implicated as vectors of hemorrhagic disease viruses, are found in great abundance in the forest canopy. Many midges are feeding on host species that are known reservoirs of hemorrhagic disease and then moving into the forest canopy, which has implications for the calculation of vectorial capacity. These data contribute valuable ecological information on Culicoides species found in Florida and provide a framework for developing effective vector control strategies to target these species.

Abstract Background Biting midges of the genus Culicoides (Diptera: Ceratopogonidae) exert a significant impact on animal agriculture worldwide because they transmit bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV) to ruminants. Without effective vaccines, BTV/EHDV vector management strategies are needed, particularly in commercial white-tailed deer (WTD) facilities. However, detailed information on the ecology of midge immatures in/around cervid operations is currently lacking. Towards filling this knowledge gap, we conducted two-choice oviposition experiments with field-collected Culicoides stellifer Coquillett (a suspected vector of BTV/EHDV in the USA) under laboratory conditions to examine which natural source from the larval habitat is relatively more attractive for midge oviposition. Methods Field-collected C. stellifer females (CDC-UV light traps) were given a blood meal from live chicken and examined for their oviposition preferences for individual (or mixed) potential larval habitat oviposition stimuli in two-choice bioassays. Substrates included mud from C. stellifer habitat, mud from allopatric site, vegetation (Sphagnum spp. mosses), field water, WTD manure and de-ionized water (control). Results The majority of midges (91%) oviposited in only one dish, with few females (9%) ovipositing in both the dishes. Gravid females demonstrated an overall oviposition preference for substrates with mud and vegetation from the larval habitat, depositing a significantly higher proportion of eggs on mud (52.3%) and vegetation (81.8%) than on controls (≤ 18.2%) (P ≤ 0.0320). Moreover, greater number of eggs per female were deposited on mud (29.5–40.7 depending on trial) and vegetation (38.2) than on controls (≤ 5.8). WTD manure, field water and mud from allopatric site were not found to be more attractive than controls for oviposition. Combining individual substrates (mud + WTD manure; mud + moss + WTD manure + field water) did not elicit greater oviposition responses than mud or moss alone. Conclusions Management strategies to discourage C. stellifer oviposition in/around commercial cervid facilities should likely focus on mud and/or vegetation, rather than WTD manure. However, further studies are needed to examine whether the spatial distributions of C. stellifer and Sphagnum spp. moss are correlated, and to determine whether targeting vegetation in/around cervid facilities can contribute to reductions in local midge densities.

Jaundice is one of the most frequent metabolic disorders detected in the newborn period. Neonatal jaundice is most likely to be physiological, it is a transient condition and does not require treatment, at the same time it can be a symptom of a serious disease which requires diagnosis and therapy. It is presented a clinical case of conjugational jaundice in newborn from mother with diabetes, with manifestations of hemorrhagic disease. The peculiarity of this case is a complicated course of this disease with hypoxic lesions of the central nervous system and partial intestinal obstruction. In this observation it is shown the effectiveness of the therapy with early diagnosis of the disease and the complications before the appearance of the developed clinical picture.

A wild population of white-tailed deer (Odocoileus virginianus) was surveyed for evidence of past or current epizootic hemorrhagic disease virus (EHDV) and current bluetongue virus (BTV) infections. We collected 121 blood samples from hunter-harvested or live-captured deer from two state-managed properties in northwest Florida, US; live captures were in support of a movement ecology study. Blood samples were tested for antibodies against titers to three EHDV serotypes (EHDV-1, EHDV-2, and EHDV-6), and multiplex quantitative reverse transcription PCR was used to identify the presence of EHDV or BTV viral RNA. Of these samples, 81% (98/121) tested seropositive for at least one of three serotypes of EHDV. Of those testing seropositive, 33% (40/121) contained antibodies for two serotypes, and 19% (24/121) contained antibodies for all three EHDV serotypes. Furthermore, results of generalized linear models indicated that the probability of infection by EHDV serotypes 1 and 6 increased with an animal's age. Our findings indicate that seroprevalence may be high for multiple serotypes in regions where these orbiviruses are endemic. These results could prove useful for managing disease risk in naïve deer populations. [ABSTRACT FROM AUTHOR]

Bluetongue virus and epizootic hemorrhagic disease (HD) virus are globally distributed, vector‐borne viruses that infect and cause disease in domestic and wild ruminant species. The forces driving increases in resulting HD may be linked to weather conditions and increasing severity has been noted in northerly latitudes. We evaluated the role of drought severity in both space and time on changes in HD reports across the eastern United States for a recent 15 year period. The objectives of this study were to: (a) develop a spatiotemporal model to evaluate if drought severity explains changing patterns of HD presence; and (b) determine whether this potential risk factor varies in importance over the present range of HD in the eastern United States. Historic data (2000–2014) from an annual HD presence–absence survey conducted by the Southeastern Cooperative Wildlife Disease Study and from the United States Drought Monitor were used for this analysis. For every county in 23 states and for each of 15 years, data were based on reported drought status for August, wetland cover, the physiographic region, and the status of HD in the previous year. We used a generalized linear mixed model to explain HD presence and evaluated spatiotemporal predictors across the region. We found that drought severity was a significant predictor of HD presence and the significance of this relationship was dependent on latitude. In more northerly latitudes, where immunological naivety is most likely, we demonstrated the increasing strength of drought severity as a determinant of reported HD and established the importance of variation in drought severity as a risk factor over the present range of HD in the eastern United States. Our research provides spatially explicit evidence for the link between climate forces and emerging disease patterns across latitude for a globally distributed disease. [ABSTRACT FROM AUTHOR]

Adult female survival is an important component to population models and management programs for white‐tailed deer (Odocoileus virginianus), but short‐term survival studies (1–3 yrs) may not accurately reflect the variation in interannual survival, which could alter management decisions. We monitored annual survival and cause‐specific mortality rates of adult female white‐tailed deer (n = 158) for 6 years (2010–2012, 2016–2018) in southern Delaware, USA. Annual survival rate differed among years. Survival rates (±SE) and mortality causes were similar in 3 years (2011 = 0.72 ± 0.08, 2017 = 0.68 ± 0.08, 2018 = 0.74 ± 0.09) and comparable to previous research from mixed forest‐agricultural landscapes. A relatively low survival rate in 2010 (0.48 ± 0.11) was influenced by hunter harvest and potentially compounded by abnormally severe winter conditions in the prior year. A peracute outbreak of hemorrhagic disease occurred during summer 2012, resulting in an annual survival rate of 0.38 ± 0.11, and to our knowledge is the first reported case of a hemorrhagic disease outbreak in a monitored wild population with known fates. In 2016, we did not observe any harvest mortality, resulting in high annual survival (0.96 ± 0.04). Our results demonstrate the degree of variability in annual survival and cause‐specific mortality rates within a population. We caution against the use of short‐term survival studies to inform management decisions, particularly when incorporating survival data into population models or when setting harvest objectives. © 2020 The Wildlife Society. We monitored annual survival of adult female white‐tailed deer for 6 years. Variability among years was high because of mortality associated with uncommon climatic conditions, mortality from a hemorrhagic disease outbreak, and a year with no harvest mortality. Short‐term studies may not accurately represent the long‐term variability in annual white‐tailed deer survival rates. [ABSTRACT FROM AUTHOR]

This study presents the gross and histopathological findings of adenoviral hemorrhagic disease (AHD) in two yearling and one adult mule deer (Odocoileus hemionus). These cases represent the first known outbreak of deer adenovirus (Odocoileus adenovirus 1) in Arizona. Over the span of a month, three female captive mule deer were submitted to Midwestern University's Animal Health Institute for postmortem examination. All of these deer were from the same deer farm and historical findings were similar, consisting of acute presentation of hemorrhagic diarrhea and sudden death. Grossly and histopathologically, all cases had severe pulmonary edema and hemorrhagic enteritis. Additionally, two of the three cases had low numbers of large amphophilic intranuclear inclusions expanding endothelial cells within the small intestine and lungs. Viral PCR of pooled small intestine, lung, and spleen from each of the three cases were positive for deer adenovirus and negative for blue tongue and epizootic hemorrhagic disease. [ABSTRACT FROM AUTHOR]

This paper briefly discusses the history of European rabbit biocontrol attempts by intentionally inducing epidemics in Australia. Feral rabbits in Australia pose a significant threat to biodiversity, affecting 304 endangered plant and animal species. Several epidemics were produced in feral rabbit populations, successively, in 1937-1950, 1996 and 2017. Studies for testing viruses obtained from feral rabbits carried out in the 2000's showed that the majority of these viruses were more virulent than the viruses used to initiate the epidemic. A new recovery of the feral rabbit population is expected to follow this episode. The production in the laboratory of several viral strains in addition to the strains appeared by spontaneous mutation predisposes to risks the domestic rabbits from farms, which belong to the same species, Oryctolagus cuniculus. [ABSTRACT FROM AUTHOR]

In recent years, an alarming number of cases of lethal acute hemorrhagic disease have occurred in Asian elephant calves raised in logging camps in Myanmar. To determine whether these deaths were associated with infection by elephant endotheliotropic herpesvirus (EEHV), we conducted diagnostic PCR subtype DNA sequencing analysis on necropsy tissue samples collected from 3 locations. We found that EEHV DNA from 7 PCR loci was present at high levels in all 3 calves and was the same EEHV1A virus type that has been described in North America, Europe, and other parts of Asia. However, when analyzed over 5,610 bp, the strains showed major differences from each other and from all previously characterized EEHV1A strains. We conclude that these 3 elephant calves in Myanmar died from the same herpesvirus disease that has afflicted young Asian elephants in other countries over the past 20 years. [ABSTRACT FROM AUTHOR]

The transmission of multiple serotypes of epizootic hemorrhagic disease virus (EHDV) between farmed and free-ranging wildlife is of interest to livestock industries and natural resource agencies. We compared the seroprevalence of EHDV-1, -2, and -6 in wild and farmed white-tailed deer (Odocoileus virginianus) herds in Florida, US. We compared serological prevalence, circulating serotypes, antibody titers, and viremia with the use of 171 whole-blood samples from 150 unvaccinated white-tailed deer from farm pens, a farm preserve, and wild deer on adjacent public lands between March 2016 and May 2017. Despite aggressive chemical vector control on the farm, we found higher seroprevalence and titers against the predominant EHDV serotype in farmed deer (in pens and the preserve) than in wild deer. The higher exposure to EHDV of farmed vs. wild deer may have been because of the higher densities of farmed vs. wild deer, the presence of exotic amplifying hosts such as elk (Cervus canadensis) in the preserve, or genetic factors that predisposed farmed deer to disease. [ABSTRACT FROM AUTHOR]

EEHV is a ubiquitous virus, which most likely has co-evolved with elephants and is shed by healthy individuals and maintained in the herds. Yet, the factors determining calf susceptibility to the virus remain unknown. Here, we explored the impact of EEHV-HD in the European captive Asian elephant population in a retrospective statistical study spanning the last 35 years. We show that EEHV-HD was implicated in more than half of all deaths recorded in calves older than one months old. Moreover, the median age across EEHV-HD fatalities was significantly lower compared to other death causes. Finally, we investigated if heredity and zoo-associated factors could be linked to a higher susceptibility of calves to this disease. We used a univariable logistic regression model to evaluate if either fathers, mothers, or zoos could, separately, be considered as risk factors to the development of the disease. Afterwards, we used a two multivariable model, combining: (1) fathers and zoos, and (2) mothers and zoos. Overall, we found that two fathers, one mother, and four zoos had three or more times higher risk of their calves becoming sick when compared to all others, pointing us to the presence of a management or environmental element, which can have paternal and maternal influence and leads to calf susceptibility or resistance to EEHV-HD.

Bluetongue (BT) and epizootic hemorrhagic disease (EHD) cases have increased worldwide, causing significant economic loss to ruminant livestock production and detrimental effects to susceptible wildlife populations. In recent decades, hemorrhagic disease cases have been reported over expanding geographic areas in the United States. Effective BT and EHD prevention and control strategies for livestock and monitoring of these diseases in wildlife populations depend on an accurate understanding of the distribution of BT and EHD viruses in domestic and wild ruminants and their vectors, the Culicoides biting midges that transmit them. However, national maps showing the distribution of BT and EHD viruses and the presence of Culicoides vectors are incomplete or not available at all. Thus, efforts to accurately describe the potential risk of these viruses on ruminant populations are obstructed by the lack of systematic and routine surveillance of their hosts and vectors. In this review, we: (1) outline animal health impacts of BT and EHD in the USA; (2) describe current knowledge of the distribution and abundance of BT and EHD and their vectors in the USA; and (3) highlight the importance of disease (BT and EHD) and vector surveillance for ruminant populations.

Hemorrhagic disease (HD) is considered one of the most significant infectious diseases of white-tailed deer in North America. Investigations into environmental conditions associated with outbreaks suggest drought conditions are strongly correlated with outbreaks in some regions of the United States. However, during 2017, an HD outbreak occurred in the Eastern United States which appeared to be associated with a specific physiographic region, the Appalachian Plateau, and not drought conditions. The objective of this study was to determine if reported HD in white-tailed deer in 2017 was correlated with physiographic region. There were 456 reports of HD from 1605 counties across 26 states and 12 physiographic regions. Of the 93 HD reports confirmed by virus isolation, 76.3% (71/93) were identified as EHDV-2 and 66.2% (47/71) were from the Appalachian Plateau. A report of HD was 4.4 times more likely to occur in the Appalachian Plateau than not in 2017. Autologistic regression models suggested a statistically significant spatial dependence. The underlying factors explaining this correlation are unknown, but may be related to a variety of host, vector, or environmental factors. This unique outbreak and its implications for HD epidemiology highlight the importance for increased surveillance and reporting efforts in the future.

The European rabbit (Oryctolagus cuniculus) is a key species of great ecological and economical interest in the Mediterranean ecosystem. During the last decades important changes in the land use have transformed part of its natural habitat, a problem that has been aggravated by the incidence of two viral diseases, myxomatosis and hemorrhagic disease (RHD) causing a major decline in the populations of Mallorca. The conservation of the species has been based on certain occasions in the realization of repopulations. This paper shows the results of a study initiated in Mallorca whose ultimate purpose is to minimize the risks associated with this management measure, and establish the methodological basis for a correct recovery of the species. Therefore, a sampling of the rabbit populations susceptible of being donors has been carried out, analyzing their genetic and sanitary characteristics, at the same time that a survey of the situation of the wild rabbit populations of Mallorca has been carried out. In this way, the hunting administration of Mallorca has developed during the years 2016 and 2019 the field rabbit experimental breeding from six donor populations in controlled conditions of semi-freedom in the Center Cinegètic de Mallorca. The rabbits obtained have served to repopulate areas in which rabbit density was low or zero. The losses caused by the new variant of the RHD (virus RHDV-2) in the breeding nuclei, and the predation in the areas of repopulation, have been the most important causes of mortality. Subsequently, lower mortality rates have been observed, suggesting a greater natural immune response capacity to the RHD, and the following repopulations carried out on the island until now have shown high rates of survival and adaptation of the specimens. [ABSTRACT FROM AUTHOR]

Bluetongue virus serotype 3 (BTV-3) has been found in the US since 1999 and was recently identified in white-tailed deer (WTD; Odocoileus virginianus) found dead in Virginia, US and West Virginia, US in 2016. Bluetongue viruses are known to cause pathologic changes in WTD; however, the relative virulence and pathogenicity of BTV-3 in WTD is unknown. In our study, eight WTD fawns, 6–12 wk old, were needle inoculated subcutaneously with a field isolate of BTV-3, with one fawn shaminoculated as a control during July 2017; all were monitored to determine the pathogenicity of BTV-3 in WTD. All inoculated fawns developed viremias that were first detected on postinoculation day (PID), 3 with peak titers on PID 5 by both quantitative reverse-transcription PCR (qRT-PCR) and virus isolation. The sham-inoculated control fawn also became viremic on PID 12, presumably through contact with infected fawns. Mild clinical signs, including periorbital edema and hyperemia, were first seen on PID 5. None of the fawns developed a significant febrile response, clinical pathology changes, or BTV-3 neutralizing antibodies. The cytokines TNF-α, IL-1β, and IFN-α were not detected by commercial enzyme-linked immunosorbent assays developed for bovids. The absence of severe clinical disease, fibrinogenemia, thrombocytopenia, and leukopenia, along with the lack of seroconversion and a detectable cytokine response during the study period, is atypical when compared to previous experimental BTV serotype infections in WTD but may be related to the young age of these deer, possible attenuation of the BTV-3 strain used, innate resistance or, in some cases to maternally derived antibody to other BTV serotypes. [ABSTRACT FROM AUTHOR]

During summer and early fall of 2012, the US experienced the largest outbreak of hemorrhagic disease (HD) on record; deer (both Odocoileus virginianus and Odocoileus hemionus) in 35 states were affected, including many northern states where HD typically does not occur. Epizootic hemorrhagic disease virus (EHDV) was the predominant virus isolated, with serotype 2 (EHDV-2) representing 66% (135/205) of all isolated viruses. Viruses within the EHDV serogroup are genetically similar, but we hypothesized that subtle genetic distinctions between viruses would exist across the geographic range of the outbreak if multiple EHDV-2 strains were responsible. We examined viral relatedness and molecular epidemiology of the outbreak by sequencing the mammalian binding protein (VP2) gene and the insect vector binding protein (VP7) gene of 34 EHDV-2 isolates from 2012 across 21 states. Nucleotide sequences of VP2 had 99.0% pairwise identity; VP7 nucleotide sequences had 99.1% pairwise identity. Very few changes were observed in either protein at the amino acid level. Despite the high genetic similarity between isolates, subtle nucleotide differences existed. Both VP2 and VP7 gene sequences separated into two distinct clades based on patterns of single-nucleotide polymorphisms after phylogenetic analysis. The clades were divided geographically into eastern and western clades, although those divisions were not identical between VP2 and VP7. There was also an association between percent sequence identity and geographic distance between isolates. We concluded that multiple EHDV-2 strains contributed to this outbreak. [ABSTRACT FROM AUTHOR]

Highlights • Five different BTV serotypes were detected in Brazilian dwarf brocket deer (Mazama nana). • Serotypes 3, 14, 18, 19, 22 were isolated from animals with hemorrhagic disease. • Brazilian dwarf brocket deer (Mazama nana) is highly susceptible to BTV infection. Abstract Bela Vista Biological Sanctuary (RBV) is a protected area of Itaipu Binacional, a hydroelectric power company located on the border of Brazil and Paraguay. A captive population of Brazilian dwarf brocket deer (Mazama nana , Cervidae, Artiodactyla) is maintained for conservation purposes. Despite the reproductive success of the animals, outbreaks of a fatal hemorrhagic disease have been registered over the years, compromising conservation efforts. In order to identify the etiological agents of these hemorrhagic diseases, 32 captive Brazilian dwarf brockets were sampled to investigate bluetongue virus (BTV), epizootic hemorrhagic disease (EHD), and adenovirus hemorrhagic disease (AHD), in 2015. Only one deer (1/32; 3.12%) was seropositive for BTV. After this survey, five animals died in the early autumn of 2015 and 2016, again presenting clinical signs of hemorrhagic disease. Using RT-qPCR, RT-PCR and DNA sequencing, five BTV serotypes (3, 14, 18, 19, and 22) were identified in blood and tissues collected during necropsies. These BTV serotypes had not been previously described or isolated in Brazil, either in wild or domestic ruminants. Additionally, differential diagnosis was performed for EHD and AHD, but all samples were negative for both diseases. The multiple distinct BTV serotypes identified in these outbreaks resulted in a high lethality (100%) of Brazilian dwarf brockets and indicated that various BTV serotypes are circulating in the area. [ABSTRACT FROM AUTHOR]

Ebola virus disease (EVD) is a severe, fatal, zoonotic, hemorrhagic disease. The current outbreak is the largest in history and has spread across continents. Consequently, it has made the WHO to declare it as a public health emergency of international concern. To the best of our knowledge, it is the first comprehensive review of EVD and its implications for the dental fraternity.