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80 result(s) for "Freuling, Conrad M."
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Susceptibility of Raccoon Dogs for Experimental SARS-CoV-2 Infection
Raccoon dogs might have been intermediate hosts for severe acute respiratory syndrome-associated coronavirus in 2002-2004. We demonstrated susceptibility of raccoon dogs to severe acute respiratory syndrome coronavirus 2 infection and transmission to in-contact animals. Infected animals had no signs of illness. Virus replication and tissue lesions occurred in the nasal conchae.
Comparative pathogenesis of different phylogroup I bat lyssaviruses in a standardized mouse model
A plethora of bat-associated lyssaviruses potentially capable of causing the fatal disease rabies are known today. Transmitted via infectious saliva, occasionally-reported spillover infections from bats to other mammals demonstrate the permeability of the species-barrier and highlight the zoonotic potential of bat-related lyssaviruses. However, it is still unknown whether and, if so, to what extent, viruses from different lyssavirus species vary in their pathogenic potential. In order to characterize and systematically compare a broader group of lyssavirus isolates for their viral replication kinetics, pathogenicity, and virus release through saliva-associated virus shedding, we used a mouse infection model comprising a low (10 2 TCID 50 ) and a high (10 5 TCID 50 ) inoculation dose as well as three different inoculation routes (intramuscular, intranasal, intracranial). Clinical signs, incubation periods, and survival were investigated. Based on the latter two parameters, a novel pathogenicity matrix was introduced to classify lyssavirus isolates. Using a total of 13 isolates from ten different virus species, this pathogenicity index varied within and between virus species. Interestingly, Irkut virus (IRKV) and Bokeloh bat lyssavirus (BBLV) obtained higher pathogenicity scores (1.14 for IRKV and 1.06 for BBLV) compared to rabies virus (RABV) isolates ranging between 0.19 and 0.85. Also, clinical signs differed significantly between RABV and other bat lyssaviruses. Altogether, our findings suggest a high diversity among lyssavirus isolates concerning survival, incubation period, and clinical signs. Virus shedding significantly differed between RABVs and other lyssaviruses. Our results demonstrated that active shedding of infectious virus was exclusively associated with two RABV isolates (92% for RABV-DogA and 67% for RABV-Insectbat), thus providing a potential explanation as to why sustained spillovers are solely attributed to RABVs. Interestingly, 3D imaging of a selected panel of brain samples from bat-associated lyssaviruses demonstrated a significantly increased percentage of infected astrocytes in mice inoculated with IRKV (10.03%; SD±7.39) compared to RABV-Vampbat (2.23%; SD±2.4), and BBLV (0.78%; SD±1.51), while only individual infected cells were identified in mice infected with Duvenhage virus (DUVV). These results corroborate previous studies on RABV that suggest a role of astrocyte infection in the pathogenicity of lyssaviruses.
Role of Oral Rabies Vaccines in the Elimination of Dog-Mediated Human Rabies Deaths
Domestic dogs are responsible for nearly all the »59,000 global human rabies deaths that occur annually. Numerous control measures have been successful at eliminating dog-mediated human rabies deaths in upper-income countries, including dog population management, parenteral dog vaccination programs, access to human rabies vaccines, and education programs for bite prevention and wound treatment. Implementing these techniques in resource-poor settings can be challenging; perhaps the greatest challenge is maintaining adequate herd immunity in free-roaming dog populations. Oral rabies vaccines have been a cornerstone in rabies virus elimination from wildlife populations; however, oral vaccines have never been effectively used to control dog-mediated rabies. Here, we convey the perspectives of the World Organisation for Animal Health Rabies Reference Laboratory Directors, the World Organisation for Animal Health expert committee on dog rabies control, and World Health Organization regarding the role of oral vaccines for dogs. We also issue recommendations for overcoming hesitations to expedited field use of appropriate oral vaccines.
Spatio-temporal Use of Oral Rabies Vaccines in Fox Rabies Elimination Programmes in Europe
In Europe, the elimination of wildlife rabies using oral rabies vaccination [ORV] of foxes for more than 30 years has been a success story. Since a comprehensive review on the scope of the different oral rabies vaccine baits distributed across Europe has not been available yet, we evaluated the use of different vaccine baits over the entire period of ORV [1978-2014]. Our findings provide valuable insights into the complexity of ORV programs in terms of vaccine related issues. More than 10 oral vaccines against rabies were used over the past four decades. Depending on many factors, the extent to which oral rabies virus vaccines were used varied considerably resulting in huge differences in the number of vaccine doses disseminated in ORV campaigns as well as in large spatial and temporal overlaps. Although vaccine virus strains derived from the SAD rabies virus isolate were the most widely used, the success of ORV campaigns in Europe cannot be assigned to a single oral rabies virus vaccine alone. Rather, the successful elimination of fox rabies is the result of an interaction of different key components of ORV campaigns, i.e. vaccine strain, vaccine bait and strategy of distribution.
Ecology and epidemiology of rabies in humans, domestic animals and wildlife in Namibia, 2011-2017
Rabies is a fatal zoonotic disease that causes a heavy burden on societies. Namibia, a country in southern Africa, is aiming at controlling the disease in its main reservoir, the domestic dog. To facilitate the implementation comprehensive information on the ecology and epidemiology of the disease and surveillance is of utmost importance. The study presented assesses the baseline data for both human and animal rabies surveillance in Namibia in recent times and establishes correlations with ecological and socio-economic data in order to provide an up-to-date picture on the epidemiology of rabies in Namibia. For instance, it was important to identify the main drivers in the epidemiology, and whether the control strategy by mass vaccination of dogs is undermined by cycles of rabies in wildlife. Rabies in humans was reported mainly from the Northern Communal Areas (NCAs), with a total of 113 cases from 2011 to 2017, representing an incidence of between 1.0 and 2.4 annual human rabies deaths per 100,000 inhabitants. Kavango, the region with the highest human rabies incidence was also the region with the lowest animal rabies surveillance intensity. Generally, the vast majority (77%) of dog samples originated from communal farm land, followed by urban areas (17%), while only a small fraction (3%) was submitted from freehold farm areas. In contrast, kudu and eland submissions were almost exclusively from freehold farmland (76%) and urban areas (19%), whereas the submission of cattle samples was evenly distributed among freehold farms (46%) and communal farm land (46%). The likelihood of sample submission decreased exponentially with distance to one of the two laboratories. Overall, 67% (N = 1,907) of all samples submitted tested rabies-positive, with the highest positivity rate observed in kudus (89%) and jackals (87%). The transmission cycle of rabies in dogs appears restricted to the northern communal areas of Namibia, whilst rabies in wildlife species is predominately reported from farmland in central Namibia, mostly affecting kudu (Tragelaphus strepsiceros) and livestock with a likely reservoir in wildlife canids such as jackals or bat-eared foxes. The analysis confirms the presence of two independent transmission cycles in Namibia with little geographic overlap, thus allowing for a sustainable control of rabies in dogs in the NCAs.
Evaluation of Six Commercially Available Rapid Immunochromatographic Tests for the Diagnosis of Rabies in Brain Material
Rabies is a neglected zoonotic disease that causes an estimated 60,000 human deaths annually. The main burden lies on developing countries in Asia and Africa, where surveillance and disease detection is hampered by absence of adequate laboratory facilities and/or the difficulties of submitting samples from remote areas to laboratories. Under these conditions, easy-to-use tests such as immunochromatographic assays, i.e. lateral flow devices (LFD), may increase surveillance and improve control efforts. Several LFDs for rabies diagnosis are available but, except for one, there are no data regarding their performance. Therefore, we compared six commercially available LFDs for diagnostic and analytical sensitivity, as well as their specificity and their diagnostic agreement with standard rabies diagnostic techniques using different sample sets, including experimentally infected animals and several sets of field samples. Using field samples the sensitivities ranged between 0% up to 100% depending on the LFD and the samples, while for experimentally infected animals the maximum sensitivity was 32%. Positive results in LFD could be further validated using RT-qPCR and sequencing. In summary, in our study none of the tests investigated proved to be satisfactory, although the results somewhat contradict previous studies, indicating batch to batch variation. The high number of false negative results reiterates the necessity to perform a proper test validation before being marketed and used in the field. In this respect, marketing authorization and batch release control could secure a sufficient quality for these alternative tests, which could then fulfil their potential.
Renewed Public Health Threat from Emerging Lyssaviruses
Pathogen discovery contributes to our knowledge of bat-borne viruses and is linked to the heightened interest globally in bats as recognised reservoirs of zoonotic agents. The transmission of lyssaviruses from bats-to-humans, domestic animals, or other wildlife species is uncommon, but interest in these pathogens remains due to their ability to cause an acute, progressive, invariably fatal encephalitis in humans. Consequently, the detection and characterisation of bat lyssaviruses continues to expand our knowledge of their phylogroup definition, viral diversity, host species association, geographical distribution, evolution, mechanisms for perpetuation, and the potential routes of transmission. Although the opportunity for lyssavirus cross-species transmission seems rare, adaptation in a new host and the possibility of onward transmission to humans requires continued investigation. Considering the limited efficacy of available rabies biologicals it is important to further our understanding of protective immunity to minimize the threat from these pathogens to public health. Hence, in addition to increased surveillance, the development of a niche pan-lyssavirus vaccine or therapeutic biologics for post-exposure prophylaxis for use against genetically divergent lyssaviruses should be an international priority as these emerging lyssaviruses remain a concern for global public health.
Evaluating the 2024 dog oral rabies vaccination campaign in the Zambezi region, Namibia using GIS and household surveys
The 2024 oral rabies vaccination (ORV) campaign in Namibia’s Zambezi region aimed to address persistent rabies transmission through a large-scale effort combining direct dog vaccination and owner-assisted distribution. A total of 9,393 baits were distributed, and the campaign demonstrated feasibility and operational efficiency, achieving an estimated vaccination coverage of 47.9% of dogs in just four days, increasing to 56.8% when accounting for prior parenteral vaccination efforts. Spatial analysis revealed an average vaccination coverage of 60% across 10 × 10 km grid cells, and encompassed 81% of the human population of the Zambezi region within the vaccination coverage area. Post-vaccination surveys indicated a rise in vaccination rates (54.5% of dogs vaccinated, up from 18.9%) and lower presence of rabies. Improved education and awareness campaigns, targeted interventions in low-coverage areas, and enhanced surveillance are recommended to further reduce rabies incidence. The findings highlight the promise and proficiency of ORV campaigns in resource-constrained settings and demonstrate that its application can be key for sustained rabies control efforts in Namibia.
Dog ecology and rabies knowledge, attitude and practice (KAP) in the Northern Communal Areas of Namibia
In 2021, a comprehensive dog demographic questionnaire combined with a KAP survey were conducted in the northern communal areas (NCAs) of Namibia with the aim of gaining a better understanding of dog populations, owner behaviour, and knowledge, attitudes and practices (KAP) relating to rabies. The survey of 3,726 households across the eight regions of the NCAs provided insights that will inform interventions in order to improve human rabies prevention and Namibia’s dog rabies control strategy. The results showed a relatively low average human/dog ratio (HDR) of 5.4:1 indicating a surprisingly high dog population of at least 272,000 dogs in the NCAs, 93% of which appear to be owned but are free-roaming. Data analysis revealed opportunities but also highlighted needs for improvements in rabies surveillance and mass dog vaccinations. Although knowledge, attitude, and practice scores towards epidemiologic and clinical aspects, human rabies prevention, and dog rabies vaccination were deemed to be acceptable, the survey nevertheless revealed deficiencies in certain aspects in some of the population. Interestingly, data seemed to indicate relatively high dog bite incidences per 100,000 people, ranging between 262 and 1,369 and a certain number of unreported human rabies cases. Despite the very high number of dogs, only 50% of dog-owning households reported having vaccinated their dogs. In order to address these issues, the planning, announcement, and implementation of mass dog vaccination campaigns needs to be adapted to achieve adequate vaccination coverage. Another focus needs to be on rabies awareness and education if Namibia is to be significantly contributing to the global goal of “Zero by 30”.
From Field Tests to Molecular Tools—Evaluating Diagnostic Tests to Improve Rabies Surveillance in Namibia
Rabies is endemic in Namibia and is present both in wildlife carnivores and domestic free-roaming dogs. The disease thus represents a challenge for public human and veterinary disease control. Namibia has implemented a national strategic plan to control rabies and the country’s activities are supported by international organizations. To this end, rabies diagnosis at the Central Veterinary Laboratory (CVL) was improved in the frame of a World Organization for Animal Health (WOAH) laboratory twinning program: from practical sampling techniques and the use of lateral flow devices to a novel universal and discriminatory quantitative real-time Reverse transcription polymerase chain reaction (RT-qPCR), which easily identify dog-associated rabies viruses. The procedures applied and the results can be used as a template to improve rabies laboratory diagnosis.