Bat Lyssavirus Research Articles

Frugivorous bats in the Colombian Caribbean region are reservoirs of the rabies virus

BackgroundBats are an important ecological group within ecosystems. The rabies virus is a Lyssavirus, and haematophagous bats are the principal reservoir; however, the virus has also been detected in non-haematophagous bats. The objective was to determine the rabies virus in non-haematophagous bats in the Colombian Caribbean region.MethodsIn 2017, a cross-sectional study was carried out with a base-risk sampling in twelve geographic zones of the Colombian Caribbean area that included the main ecosystems of two departments. 286 bats were captured, which were euthanized with a pharmacological treatment following the ethical protocols of animal experimentation. The taxonomic identification was done with dichotomous keys. The necropsy was carried out at the capture site, and brain samples were kept in liquid nitrogen. The extraction of the RNA was carried out from the frozen brains with Trizol™; a fragment of 914 bp of the glycoprotein G of the rabies virus was amplified with RT-PCR. The amplicons were sequenced with the Sanger method.ResultsTwenty-three genera of bats were identified, and, in two frugivorous, Artibeus lituratus and Artibeus planirostris, amplicons were obtained and sequenced as the rabies virus.ConclusionsThis is the first evidence of natural infection of the rabies virus in frugivorous bats in the Colombian Caribbean area; this result is important for the surveillance and control of rabies.

Enhanced Autophagy Contributes to Reduced Viral Infection in Black Flying Fox Cells.

Bats are increasingly implicated as hosts of highly pathogenic viruses. The underlying virus–host interactions and cellular mechanisms that promote co-existence remain ill-defined, but physiological traits such as flight and longevity are proposed to drive these adaptations. Autophagy is a cellular homeostatic process that regulates ageing, metabolism, and intrinsic immune defense. We quantified basal and stimulated autophagic responses in black flying fox cells, and demonstrated that although black flying fox cells are susceptible to Australian bat lyssavirus (ABLV) infection, viral replication is dampened in these bat cells. Black flying fox cells tolerated prolonged ABLV infection with less cell death relative to comparable human cells, suggesting post-entry mechanisms interference with virus replication. An elevated basal autophagic level was observed and autophagy was induced in response to high virus doses. Pharmacological stimulation of the autophagy pathway reduced virus replication, indicating autophagy acts as an anti-viral mechanism. Enhancement of basal and virus-induced autophagy in bat cells connects related reports that long-lived species possess homeostatic processes that dampen oxidative stress and macromolecule damage. Exemplifying the potential that evolved cellular homeostatic adaptations like autophagy may secondarily act as anti-viral mechanisms, enabling bats to serve as natural hosts to an assortment of pathogenic viruses. Furthermore, our data suggest autophagy-inducing drugs may provide a novel therapeutic strategy for combating lyssavirus infection.

Molecular characterization of the rabies virus' nucleoprotein in dogs from Arequipa, Peru

. To characterize the nucleoprotein (N) and establish the origin of the rabies virus in dogs coming from Arequipa. Thirty samples of nervous tissue from the departments of Arequipa and Puno were analyzed. Total RNA was extracted from the samples and cDNA was synthesized to amplify the nucleoprotein gene, sequence it, and perform bioinformatics analysis. . A defined group was formed with respect to the external group (European bat lyssavirus). This group was classified into two subgroups, one constituted by samples coming from Puno and Arequipa (subgroup A), and another one by samples from Puno (subgroup B), exhibiting a nucleotide identity of 99.9% in subgroup A. This group was classified in two subgroups, one constituted by samples coming from Puno and Arequipa (subgroup A), and another one by samples from Puno (subgroup B), observing a nucleotide identity of 99.9% in subgroup A. The groupings of viral sequences show that the cases of canine rabies reported in Arequipa are the result of the expansion of canine rabies from the endemic region of Puno.

Insights into Australian Bat Lyssavirus in Insectivorous Bats of Western Australia.

Australian bat lyssavirus (ABLV) is a known causative agent of neurological disease in bats, humans and horses. It has been isolated from four species of pteropid bats and a single microbat species (Saccolaimus flaviventris). To date, ABLV surveillance has primarily been passive, with active surveillance concentrating on eastern and northern Australian bat populations. As a result, there is scant regional ABLV information for large areas of the country. To better inform the local public health risks associated with human-bat interactions, this study describes the lyssavirus prevalence in microbat communities in the South West Botanical Province of Western Australia. We used targeted real-time PCR assays to detect viral RNA shedding in 839 oral swabs representing 12 species of microbats, which were sampled over two consecutive summers spanning 2016–2018. Additionally, we tested 649 serum samples via Luminex® assay for reactivity to lyssavirus antigens. Active lyssavirus infection was not detected in any of the samples. Lyssavirus antibodies were detected in 19 individuals across six species, with a crude prevalence of 2.9% (95% CI: 1.8–4.5%) over the two years. In addition, we present the first records of lyssavirus exposure in two Nyctophilus species, and Falsistrellus mackenziei.

Unraveling the role of Myotis myotis in the ecology and transmission of rabies-related lyssaviruses (RRLVs)

Purpose: Insectivorous bats have been found to carry a variety of Rabies-Related Lyssaviruses (RRLVs) across Europe, among which European bat Lyssavirus 1 (EBLV-1) is the most widely distributed. Despite the majority of lethal infections are reported from serotine bats, serological data suggest that other species might have a role in the ecology of this pathogen. EBLV-1 has been associated with spillover events to humans, domestic and wildlife animals, causing a neurological disease clinically indistinguishable from classical rabies. Unraveling its ecology would then be crucial in predicting and mitigating associated risks for public health. Methods & Materials: During 2012-2018, we investigated the role of Myotis myotis in the maintenance and transmission of EBLV-1, through the longitudinal screening of roosts for neutralizing antibodies and viral shedding. Five neighboring maternal colonies were investigated in Northern Italy, whose connectivity was assessed using genetic and capture-recapture studies. Results: Antibodies neutralizing EBLV-1 were detected yearly, confirming that M. myotis are constantly exposed to the virus in the area and do survive the infection. In addition, longitudinal data revealed wide oscillations of antibodies during a single reproductive season, suggesting waning of antibodies and waves of infection. All colonies showed similar serological trends over consecutive years. Indeed, we found evidence for genetic panmixia at the nuclear and mitochondrial level and confirmed the movement of adult females between roosts. Conclusion: Altogether, our results support the role of M. myotis as natural host for an EBLV1-like RRLV. While this bat species usually inhabits underground sites in the Mediterranean areas, M. myotis is a strictly house dweller species in northern areas, with all colonies investigated in this study being located in church roofs. Based on both serological and virological findings, we suggest that the risk for human exposure to the virus is limited, with viral excretion restricted to short predictable windows of time. We predict that this study will be useful to secure public health while maintaining a positive relationship between humans and these large vesper bats, whose critical role in the control of pest insects is well recognized in the area.

Mechanisms for lyssavirus persistence in non-synanthropic bats in Europe: insights from a modeling study

Bats are natural reservoirs of the largest proportion of viral zoonoses among mammals, thus understanding the conditions for pathogen persistence in bats is essential to reduce human risk. Focusing on the European Bat Lyssavirus subtype 1 (EBLV-1), causing rabies disease, we develop a data-driven spatially explicit metapopulation model to investigate EBLV-1 persistence in Myotis myotis and Miniopterus schreibersii bat species in Catalonia. We find that persistence relies on host spatial structure through the migratory nature of M. schreibersii, on cross-species mixing with M. myotis, and on survival of infected animals followed by temporary immunity. The virus would not persist in the single colony of M. myotis. Our study provides for the first time epidemiological estimates for EBLV-1 progression in M. schreibersii. Our approach can be readily adapted to other zoonoses of public health concern where long-range migration and habitat sharing may play an important role.

Spatiotemporal distribution of a non-haematophagous bat community and rabies virus circulation: a proposal for urban rabies surveillance in Brazil.

In Brazil, rabies surveillance is based on monitoring domestic and wild animals, although the most prevalent lineage of the rabies virus (RABV) currently diagnosed in Brazil is associated with bats, particularly non-haematophagous bats. Disease control is based on the mass vaccination of dogs and cats. We used data collected by the passive surveillance system of the city of Campinas from 2011 to 2015, to describe the temporal and geographic distributions of the bat specimens and RABV and discuss the current rabies surveillance with the advent of the declaration of canine and feline rabies-free areas in Brazil. We described the species, locations and health statuses of the collected bat specimens. Moreover, all samples were submitted for RABV diagnosis. Then, we performed a time series decomposition for each bat family. Additionally, we determined the spatiotemporal relative risk for RABV infection using the ratio of the kernel-smoothed estimates of spatiotemporal densities of RABV-positive and RABV-negative bats. From the 2537 bat specimens, the most numerous family was Molossidae (72%), followed by Vespertilionidae (14%) and Phyllostomidae (13%). The bat families behaved differently in terms of seasonal and spatial patterns. The distribution of bats varied geographically in the urban environment, with Molossidae and Phyllostomidae being observed downtown and Vespertilionidae being observed in peripheral zones. Concurrently, a significant relative risk of RABV infection was observed downtown for Vespertilionidae and in peripheral zones for Molossidae. No RABV-positive sample clusters were observed. As a result of the official declaration of RABV-free areas in southern Brazil, mass dog and cat vaccinations are expected to halt in the near future. This stoppage would make most dog and cat populations susceptible to other RABV lineages, such as those maintained by non-haematophagous bats. In this scenario, all information available on bats and RABV distribution in urban areas is essential. Currently, few studies have been conducted. Some local health authorities, such as that in Campinas, are spontaneously basing their surveillance efforts on bat rabies, which is the alternative in reality scenario of increased susceptibility to bat-associated RABV that is developing in Brazil.

Lyssavirus Spp. – Rabies Viruses As A Still-Present Problem

Abstract The genus Lyssavirus spp. currently includes 14 species that are responsible for causing rabies, rabies-like and rabies-related diseases. The first symptoms of infection are similar to a cold and mainly include fever, headache and general fatigue. Then comes brain dysfunction and acute neurological symptoms, and ultimately – in most cases – death. Lyssaviruses are spread mainly through direct contact with the carrier that contains the viral reservoir. The gold standard in diagnostics is the method of direct immunofluorescence, through which viral antigens are detected – mainly in the saliva of a patient. Currently, rabies treatment is an experimental form of therapy according to the Milwaukee protocol. 1. Introduction. 2. Systematics. 2.1. Lagos bat virus. 2.2. Mokola virus. 2.3 Duvenhage virus. 2.4. European bat 1 lyssavirus. 2.5. European bat 2 lyssavirus. 2.6. Australian bat lyssavirus. 3. Characteristics. 3.1. Molecular structure. 3.2. Genome and gene expression. 3.3. Life cycle. 4. Pathogenicity. 4.1. Pathogenesis. 4.2. Rabies symptoms. 5. Prevention, prophylaxis, diagnostics, treatment. 5.1. Vaccinations. 5.2. Postexposure prophylaxis. 5.3. Diagnostics. 5.4. Experimental treatment. 6. Summary

Active and passive surveillance for bat lyssaviruses in Italy revealed serological evidence for their circulation in three bat species.

The wide geographical distribution and genetic diversity of bat-associated lyssaviruses (LYSVs) across Europe suggest that similar viruses may also be harboured in Italian insectivorous bats. Indeed, bats were first included within the passive national surveillance programme for rabies in wildlife in the 1980s, while active surveillance has been performed since 2008. The active surveillance strategies implemented allowed us to detect neutralizing antibodies directed towards European bat 1 lyssavirus in six out of the nine maternity colonies object of the study across the whole country. Seropositive bats were Myotis myotis, M. blythii and Tadarida teniotis. On the contrary, the virus was neither detected through passive nor active surveillance, suggesting that fatal neurological infection is rare also in seropositive colonies. Although the number of tested samples has steadily increased in recent years, submission turned out to be rather sporadic and did not include carcasses from bat species that account for the majority of LYSVs cases in Europe, such as Eptesicus serotinus, M. daubentonii, M. dasycneme and M. nattereri. A closer collaboration with bat handlers is therefore mandatory to improve passive surveillance and decrypt the significance of serological data obtained up to now.

Active sero-survey for European bat lyssavirus type-1 circulation in North African insectivorous bats

Bats have specific biological and ecological characteristics that make them suitable hosts for viruses; some of these viruses have the ability to infect humans and other domestic and wild mammals1....

Street rabies virus strains associated with insectivorous bats are less pathogenic than strains isolated from other reservoirs

Rabies is a fatal and viral zoonosis that causes acute, progressive encephalitis and remains an important concern in public health. In the last few years, there has been a change in the epidemiological profile of rabies after implementing canine rabies control in the Americas, which has led to a significant increase in both human and pet cases of rabies associated with insectivorous bats. Thus, it is important to understand the pathogenesis caused by Rabies virus (RABV) isolates from insectivorous bats. Viral growth kinetics, cell-to-cell spread and virus uptake in vitro were analyzed for RABV isolates from Eptesicus furiralis and Myotis nigricans. For pathogenesis evaluation, mice were inoculated with RABV isolates from Eptesicus furiralis and Myotis nigricans, and clinical signs were observed for 40 days. We observed that the insectivorous bat strains showed a higher replication rate, faster cell-to-cell spread and delayed virus uptake in N2a cells. Furthermore, after the first sign of a clinical infection, mice infected with Myotis nigricans and Eptesicus furiralis isolates succumbed rapidly (6 ± 9 days) compared with RABV strains associated with other reservoirs. Our results show that the insectivorous bat RABV strains are less pathogenic for mice than strains associated with other reservoirs. In addition, this study also indicates that the differences in the biological characteristics of the RABV strains are important to their pathogenicity. An enhanced understanding of rabies pathogenesis may be important for the development of novel therapies for humans and in the implementation of rabies control strategies.

Bat rabies in Washington State: Temporal-spatial trends and risk factors for zoonotic transmission (2000-2017).

BackgroundRabies is a zoonotic viral disease that can affect all mammals. In the United States, the majority of human rabies cases are caused by bats, which are the only known reservoirs for rabies virus (RABV) in Washington State. We sought to characterize bat RABV epidemiology in Washington among bats submitted by the public for RABV testing.MethodsWe examined temporal and spatial trends in RABV positivity (% positive) for taxonomically identified bats submitted to diagnostic laboratories during 2006–2017. For a subset of Myotis species, we evaluated sensitivity and predictive value positive (PPV) of morphological identification keys, using mitochondrial markers (cytochrome b) as a reference. For bats tested during 2000–2016, we analyzed RABV positivity by circumstances of encounters with humans, cats, and dogs.ResultsDuring 2006–2017, RABV positivity for all bat species was 6.0% (176/2,928). Among species with ≥100 submissions, RABV positivity was 2.0%–11.7% and highest among big brown bats (Eptesicus fuscus). An increasing trend in annual positivity was significant only for big brown bats (P = 0.02), and was circumstantially linked to a geographic cluster. Sensitivity and PPV of morphological identification keys was high for M. evotis but varied for M. lucifugus, M. californicus, M. yumanensis, and M. septentrionalis. A positive RABV result was significantly associated with nonsynanthropic species, abnormal behavior, abnormal hiding, injury, biting, found in a body of water, found alive, found outdoors, and caught by a dog.ConclusionMonitoring passive RABV surveillance trends enables public health authorities to perform more accurate risk assessments. Differences in temporal and spatial trends in RABV positivity by bat species indicate the importance of collecting taxonomic data, although morphological identification can be unreliable for certain Myotis species. Current public health practices for RABV exposures should be maintained as RABV infection in bats can never be excluded without diagnostic testing.

RECENT CHANGES IN INFECTIOUS DISEASES IN EUROPEAN WILDLIFE

Many infectious diseases originating from, or carried by, wildlife affect wildlife conservation and biodiversity, livestock health, or human health. We provide an update on changes in the epidemiology of 25 selected infectious, wildlife-related diseases in Europe (from 2010-16) that had an impact, or may have a future impact, on the health of wildlife, livestock, and humans. These pathogens were selected based on their: 1) identification in recent Europe-wide projects as important surveillance targets, 2) inclusion in European Union legislation as pathogens requiring obligatory surveillance, 3) presence in recent literature on wildlife-related diseases in Europe since 2010, 4) inclusion in key pathogen lists released by the Office International des Epizooties, 5) identification in conference presentations and informal discussions on a group email list by a European network of wildlife disease scientists from the European Wildlife Disease Association, or 6) identification as pathogens with changes in their epidemiology during 2010-16. The wildlife pathogens or diseases included in this review are: avian influenza virus, seal influenza virus, lagoviruses, rabies virus, bat lyssaviruses, filoviruses, canine distemper virus, morbilliviruses in aquatic mammals, bluetongue virus, West Nile virus, hantaviruses, Schmallenberg virus, Crimean-Congo hemorrhagic fever virus, African swine fever virus, amphibian ranavirus, hepatitis E virus, bovine tuberculosis ( Mycobacterium bovis), tularemia ( Francisella tularensis), brucellosis ( Brucella spp.), salmonellosis ( Salmonella spp.), Coxiella burnetii, chytridiomycosis, Echinococcus multilocularis, Leishmania infantum, and chronic wasting disease. Further work is needed to identify all of the key drivers of disease change and emergence, as they appear to be influencing the incidence and spread of these pathogens in Europe. We present a summary of these recent changes during 2010-16 to discuss possible commonalities and drivers of disease change and to identify directions for future work on wildlife-related diseases in Europe. Many of the pathogens are entering Europe from other continents while others are expanding their ranges inside and beyond Europe. Surveillance for these wildlife-related diseases at a continental scale is therefore important for planet-wide assessment, awareness of, and preparedness for the risks they may pose to wildlife, domestic animal, and human health.

Assessment of a Rabies Virus Rapid Diagnostic Test for the Detection of Australian Bat Lyssavirus.

Australian bat lyssavirus (ABLV) is closely related to the classical rabies virus and has been associated with three human fatalities and two equine fatalities in Australia. ABLV infection in humans causes encephalomyelitis, resulting in fatal disease, but has no effective therapy. The virus is maintained in enzootic circulation within fruit bats (Pteropid spp.) and at least one insectivorous bat variety (Saccolaimus flaviventris). Most frequently, laboratory testing is conducted on pteropodid bat brains, either following a potential human exposure through bites, scratches and other direct contacts with bats, or as opportunistic assessment of sick or dead bats. The level of medical intervention and post-exposure prophylaxis is largely determined on laboratory testing for antigen/virus as the demonstrable infection status of the in-contact bat. This study evaluates the comparative diagnostic performance of a lateral flow test, Anigen Rabies Ag detection rapid test (RDT), in pteropodid variant of ABLV-infected bat brain tissues. The RDT demonstrated 100% agreement with the reference standard fluorescent antibody test on 43 clinical samples suggesting a potential application in rapid diagnosis of pteropodid variant of ABLV infection. A weighted Kappa value of 0.95 confirmed a high level of agreement between both tests.

Molecular and serological survey of lyssaviruses in Croatian bat populations

BackgroundRabies is the only known zoonotic disease of bat origin in Europe. The disease is caused by species belonging to the genus Lyssavirus. Five Lyssavirus species, i.e., European bat lyssavirus (EBLV)-1, EBLV-2, Bokeloh bat lyssavirus, Lleida bat lyssavirus, and West Caucasian bat virus, have been identified in European bats. More recently, a proposed sixth species, Kotalahti bat lyssavirus, was detected. Thus, in this study, active surveillance was initiated in order to obtain insights into the prevalence of lyssaviruses in Croatian bat populations and to improve our understanding of the public health threat of infected bats.ResultsIn total, 455 bats were caught throughout Continental and Mediterranean Croatia. Antibodies were found in 20 of 350 bats (5.71%, 95% confidence interval 3.73–8.66). The majority of seropositive bats were found in Trbušnjak cave (Continental Croatia, Eastern part), and most seropositive bats belonged to Myotis myotis (13/20). All oropharyngeal swabs were negative for the presence of Lyssavirus.ConclusionsThe presence of lyssaviruses in bat populations was confirmed for the first time in Croatia and Southeastern Europe. The results of this study suggest the need for further comprehensive analyses of lyssaviruses in bats in this part of Europe.

Establishing research priorities to improve the One Health efficacy of Australian general practitioners and veterinarians with regard to zoonoses: A modified Delphi survey

While general medical practitioners (GPs) and veterinarians are often the first line responders in the face of a disease outbreak, pathways to improving the One Health efficacy of these clinicians remain unclear. A two-phase modified Delphi survey of professionals with known expertise in One Health (‘expert panel’) was used to 1) identify key knowledge, attitudes and practices (KAPs) of GPs and veterinarians that would be consistent with a One Health approach to zoonoses; and 2) determine priorities for future surveys with Australian GPs and veterinarians to identify important gaps that impede effective diagnosis and management of zoonoses. A list of 13 topics/sub-topics, as well as a list of 25 specific zoonotic diseases/agents emerged from the first phase of the survey. In the second phase the expert panel identified general knowledge of the clinical aspects and epidemiological aspects of zoonoses, as well as risk management practices, as the most important KAPs and research priorities for both GPs and veterinarians. In terms of diseases, the expert panel regarded knowledge of Hendra virus, Q fever, Australian bat lyssavirus (ABLV), anthrax and Brucella suis most important for veterinarians, whilst for GPs, Q fever, gastrointestinal/foodborne diseases, influenza, ABLV and local vector-borne diseases were found to be most important by the expert panel. Some differences were noted in terms of prioritization of topics/sub-topics and diseases/agents according to expert background (veterinary and non-veterinary). The Delphi survey technique enabled efficient collection of data from a diverse range of One Health ‘experts’/specialists and provided clear priorities for proposed future research, and potentially for educational interventions to improve One Health efficacy of clinicians.

Rabies virus vectors and reservoir species.

Rabies is an ancient zoonotic disease caused by infection with the rabies virus (RABV). While the circulation of RABV in domestic dogs has been appreciated for centuries, the recognition of bat and wild carnivore reservoirs began in the early part of the 20th century. Bats are the ancestral reservoir of RABV and a remarkable diversity of species perpetuate distinct lineages of the virus, despite the fact that circulation in bats is geographically limited to the New World fauna. The circulation of RABV in domestic dogs likely represents a historic shift from a bat reservoir, although the timing and details of such an ancient event have been difficult to resolve from the virus genetic evidence. Since becoming established in the domestic dog population, RABV has undergone repeated host shifts to wild carnivores globally. These shifts have most frequently been to species within families of the Caniformia suborder of carnivores. The circulation of RABV in bats has been linked to host shifts to wild carnivore reservoirs in North and South America. It is clear that RABV has been incredibly successful at exploiting diverse chiropteran and carnivore hosts. With improved control of circulation in domestic dogs, surveillance is likely to yield additional discoveries regarding the diversity of wildlife reservoirs and vectors of RABV.

Combination drug treatment prolongs survival of experimentally infected mice with silver-haired bat rabies virus

Rabies is a lethal disease in humans and animals, killing approximately 60,000 people every year. Currently, there is no treatment available, except post-exposure prophylaxis (PEP) that can be administered whenever exposure to a rabid animal took place. Here we describe the beneficial effects of a combination treatment initiated at day 4 post infection, containing anti-viral drugs and immune modulators in infected mice. Combination therapy resulted in significant increase in survival time (P < 0.05) and significantly lowers viral RNA in the brain and spinal cord (P < 0.05). Furthermore, treatment influenced markers of pyroptosis and apoptosis and early inflammatory response as measured by the levels of TNF-α. Morphological lesions were absent in rabies virus infected mice with few signs of inflammation. However, these were not significant between the different groups.

Combination therapy of rabies-infected mice with inhibitors of pro-inflammatory host response, antiviral compounds and human rabies immunoglobulin

Recent studies demonstrated that inhibitors of pro-inflammatory molecular cascades triggered by rabies infection in the central nervous system (CNS) can enhance survival in mouse model and that certain antiviral compounds interfere with rabies virus replication in vitro. In this study different combinations of therapeutics were tested to evaluate their effect on survival in rabies-infected mice, as well as on viral load in the CNS. C57Bl/6 mice were infected with Silver-haired bat rabies virus (SHBRV)-18 at virus dose approaching LD50 and LD100. In one experimental group daily treatments were initiated 4 h before-, in other groups 48 or 96 h after challenge. In the first experiment therapeutic combination contained inhibitors of tumour necrosis factor-α (infliximab), caspase-1 (Ac-YVAD-cmk), and a multikinase inhibitor (sorafenib). In the treated groups there was a notable but not significant increase of survival compared to the virus infected, non-treated mice. The addition of human rabies immunoglobulins (HRIG) to the combination in the second experiment almost completely prevented mortality in the pre-exposure treatment group along with a significant reduction of viral titres in the CNS. Post-exposure treatments also greatly improved survival rates. As part of the combination with immunomodulatory compounds, HRIG had a higher impact on survival than alone. In the third experiment the combination was further supplemented with type-I interferons, ribavirin and favipiravir (T-705). As a blood-brain barrier opener, mannitol was also administered. This treatment was unable to prevent lethal consequences of SHBRV-18 infection; furthermore, it caused toxicity in treated mice, presumably due to interaction among the components. In all experiments, viral loads in the CNS were similar in mice that succumbed to rabies regardless of treatment. According to the findings, inhibitors of detrimental host response to rabies combined with antibodies can be considered among the possible therapeutic and post-exposure options in human rabies cases.

Evidence of Australian bat lyssavirus infection in diverse Australian bat taxa.

Historically, Australia was considered free of rabies and rabieslike viruses. Thus, the identification of Australian bat lyssavirus (ABLV) in 1996 in a debilitated bat found by a member of the public precipitated both public health consternation and a revision of lyssavirus taxonomy. Subsequent observational studies sought to elaborate the occurrence and frequency of ABLV infection in Australian bats. This paper describes the taxonomic diversity of bat species showing evidence of ABLV infection to better inform public health considerations. Blood and/or brain samples were collected from two cohorts of bats (wild‐caught and diagnostic submissions) from four Australian states or territories between April 1996 and October 2002. Fresh brain impression smears were tested for ABLV antigen using fluorescein‐labelled anti‐rabies monoclonal globulin (CENTOCOR) in a direct fluorescent antibody test; sera were tested for the presence of neutralising antibodies using a rapid fluorescent focus inhibition test. A total of 3,217 samples from 2,633 bats were collected and screened: brain samples from 1,461 wild‐caught bats and 1,086 submitted bats from at least 16 genera and seven families, and blood samples from 656 wild‐caught bats and 14 submitted bats from 14 genera and seven families. Evidence of ABLV infection was found in five of the six families of bats occurring in Australia, and in three of the four Australian states/territories surveyed, supporting the historic presence of the virus in Australia. While the infection prevalence in the wild‐caught cohort is evidently low, the significantly higher infection prevalence in rescued bats in urban settings represents a clear and present public health significance because of the higher risk of human exposure.