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Pathogens (Basel, Switzerland) Jan 2024Rabies is a fatal zoonotic disease affecting all mammalian species. It is caused by the rabies virus and is prevalent worldwide. Horses are not commonly infected with...
Rabies is a fatal zoonotic disease affecting all mammalian species. It is caused by the rabies virus and is prevalent worldwide. Horses are not commonly infected with rabies but their vaccination is recommended due to the potential zoonotic risk. This study aimed to evaluate the duration of immunity following rabies vaccination in horses. A total of 126 serum samples were collected from 93 horses, vaccinated 6 to 91 months before sampling. Rabies-virus-neutralizing antibody (RVNA) levels were evaluated using the Rabies Fluorescent Focus Inhibition Test (RFFIT). A protective RVNA titer of above 0.5 IU/mL was found in 112 (88.9%) of the samples and 84 (90.3%) of the horses. Antibody titers declined over time (rho = -0.271, = 0.002); however, there was no significant difference in antibody titers or the prevalence of unprotected horses between the time intervals following vaccination. Purebred horses had lower antibody titers ( = 0.024). The response to booster vaccination was inspected in ten horses, and increased antibody titers were found in eight of them. The results of this study demonstrate the prolonged persistence of protective immunity in horses following rabies vaccination, in some cases, for up to eight years. Therefore, the current annual vaccination strategy should be re-evaluated. A rate of 9.7% of poor responders should be considered from an epidemiological perspective in order to minimize the risk of emergence of the disease.
PubMed: 38392863
DOI: 10.3390/pathogens13020125 -
PLoS Pathogens Feb 2024Smallpox was the most rampant infectious disease killer of the 20th century, yet much remains unknown about the pathogenesis of the variola virus. Using archived tissue...
Smallpox was the most rampant infectious disease killer of the 20th century, yet much remains unknown about the pathogenesis of the variola virus. Using archived tissue from a study conducted at the Centers for Disease Control and Prevention we characterized pathology in 18 cynomolgus macaques intravenously infected with the Harper strain of variola virus. Six macaques were placebo-treated controls, six were tecovirimat-treated beginning at 2 days post-infection, and six were tecovirimat-treated beginning at 4 days post-infection. All macaques were treated daily until day 17. Archived tissues were interrogated using immunohistochemistry, in situ hybridization, immunofluorescence, and electron microscopy. Gross lesions in three placebo-treated animals that succumbed to infection primarily consisted of cutaneous vesicles, pustules, or crusts with lymphadenopathy. The only gross lesions noted at the conclusion of the study in the three surviving placebo-treated and the Day 4 treated animals consisted of resolving cutaneous pox lesions. No gross lesions attributable to poxviral infection were present in the Day 2 treated macaques. Histologic lesions in three placebo-treated macaques that succumbed to infection consisted of proliferative and necrotizing dermatitis with intracytoplasmic inclusion bodies and lymphoid depletion. The only notable histologic lesion in the Day 4 treated macaques was resolving dermatitis; no notable lesions were seen in the Day 2 treated macaques. Variola virus was detected in all three placebo-treated animals that succumbed to infection prior to the study's conclusion by all utilized methods (IHC, ISH, IFA, EM). None of the three placebo-treated animals that survived to the end of the study nor the animals in the two tecovirimat treatment groups showed evidence of variola virus by these methods. Our findings further characterize variola lesions in the macaque model and describe new molecular methods for variola detection.
Topics: Animals; Benzamides; Dermatitis; Isoindoles; Macaca fascicularis; Smallpox; United States; Variola virus
PubMed: 38386661
DOI: 10.1371/journal.ppat.1012007 -
BMC Neuroscience Feb 2024A pseudotyped modified rabies virus lacking the rabies glycoprotein (G-protein), which is crucial for transsynaptic spread, can be used for monosynaptic retrograde...
BACKGROUND
A pseudotyped modified rabies virus lacking the rabies glycoprotein (G-protein), which is crucial for transsynaptic spread, can be used for monosynaptic retrograde tracing. By coupling the pseudotyped virus with transgene expression of the G-protein and the avian leukosis and sarcoma virus subgroup A receptor (TVA), which is necessary for cell entry of the virus, researchers can investigate specific neuronal populations. Responder mouse lines, like the RΦGT mouse line, carry the genes encoding the G-protein and TVA under Cre-dependent expression. These mouse lines are valuable tools because they reduce the number of viral injections needed compared to when using helper viruses. Since RΦGT mice do not express Cre themselves, introducing the pseudotyped rabies virus into their brain should not result in viral cell entry or spread.
RESULTS
We present a straightforward flowchart for adequate controls in tracing experiments, which we employed to demonstrate Cre-independent expression of TVA in RΦGT mice.
CONCLUSIONS
Our observations revealed TVA leakage, indicating that RΦGT mice should be used with caution for transgene expression of TVA. Inaccurate tracing outcomes may occur if TVA is expressed in the absence of Cre since background leakage leads to nonspecific cell entry. Moreover, conducting appropriate control experiments can identify the source of potential caveats in virus-based neuronal tracing experiments.
Topics: Mice; Animals; Software Design; Receptors, Virus; Avian Proteins; Rabies virus; GTP-Binding Proteins
PubMed: 38383317
DOI: 10.1186/s12868-024-00848-1 -
Frontiers in Microbiology 2024Rabies is a fatal zoonotic disease that poses a threat to public health. Rabies virus (RABV) is excreted in the saliva of infected animals, and is primarily transmitted...
Rabies is a fatal zoonotic disease that poses a threat to public health. Rabies virus (RABV) is excreted in the saliva of infected animals, and is primarily transmitted by bite. The role of the salivary glands in virus propagation is significant, but has been less studied in the pathogenic mechanisms of RABV. To identify functionally important genes in the salivary glands, we used RNA sequencing (RNA-seq) to establish and analyze mRNA expression profiles in parotid tissue infected with two RABV strains, CVS-11 and PB4. The biological functions of differentially expressed genes (DEGs) were determined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, which revealed 3,764 DEGs (678 up-regulated and 3,086 down-regulated) in the CVS-11 infected group and 4,557 DEGs (874 up-regulated and 3,683 down-regulated) in the PB4 infected group. Various biological processes are involved, including the salivary secretion pathway and the phosphatidylinositol 3-kinase-Akt (PI3K-Akt) signaling pathway. This study provides the first mapping of the transcriptome changes in response to RABV infection in parotid tissue, offering new insights into the study of RABV-affected salivary gland function and RABV pathogenic mechanisms in parotid tissue. The salivary gland-enriched transcripts may be potential targets of interest for rabies disease control.
PubMed: 38380102
DOI: 10.3389/fmicb.2024.1354936 -
The Indian Journal of Medical Research Jan 2024Rabies is a lethal viral disease transmitted through the bite of rabid animals. India has a high burden of rabies, contributing to a significant proportion of the global... (Review)
Review
Rabies is a lethal viral disease transmitted through the bite of rabid animals. India has a high burden of rabies, contributing to a significant proportion of the global deaths. However, under-reporting of the disease is prevalent due to lack of laboratory confirmation. Laboratory diagnosis of rabies plays a crucial role in differentiating the disease from clinical mimics, initiation of appropriate care, implementing infection control measures and informing disease surveillance. This review provides an overview of the recent advancements in laboratory diagnosis of rabies, aimed at updating physicians involved in diagnosis and management of rabies cases in India.
Topics: Animals; Rabies; Rabies virus; Laboratories; India; Clinical Laboratory Techniques; Bites and Stings
PubMed: 38376376
DOI: 10.4103/ijmr.ijmr_131_23 -
Antiviral Research Apr 2024Rabies, a viral zoonosis, is responsible for almost 59,000 deaths each year, despite the existence of an effective post-exposure prophylaxis. Indeed, rabies causes acute...
Rabies, a viral zoonosis, is responsible for almost 59,000 deaths each year, despite the existence of an effective post-exposure prophylaxis. Indeed, rabies causes acute encephalomyelitis, with a case-fatality rate of 100 % after the onset of neurological clinical signs. Therefore, the development of therapies to inhibit the rabies virus (RABV) is crucial. Here, we identified, from a 30,000 compound library screening, phthalazinone derivative compounds as potent inhibitors of RABV infection and more broadly of Lyssavirus and even Mononegavirales infections. Combining in vitro experiments, structural modelling, in silico docking and in vivo assays, we demonstrated that phthalazinone derivatives display a strong inhibition of lyssaviruses infection by acting directly on the replication complex of the virus, and with noticeable effects in delaying the onset of the clinical signs in our mouse model.
Topics: Animals; Mice; Rabies virus; Rabies; Lyssavirus; Gene Library; Disease Models, Animal
PubMed: 38373533
DOI: 10.1016/j.antiviral.2024.105838 -
International Journal of Circumpolar... Dec 2024Rabies is often described as the quintessential One Health problem, linking especially animal health to human health. I examined how rabies is managed in the circumpolar...
Rabies is often described as the quintessential One Health problem, linking especially animal health to human health. I examined how rabies is managed in the circumpolar North through semi-structured interviews of key informants in three cases: Alaska, Northwest Territories, and Svalbard. While rabies is controlled at the territorial or state level in the Northwest Territories and Alaska, respectively, the perception of where authority lies in rabies management is less evident in Norway concerning Svalbard than in the other two cases. Respondents generally characterised the working relationship between sectors and scales of governments as positive. However, coordination remains one of the main challenges to rabies management, with harsh environmental conditions and small remote communities adding additional challenges in all three cases. Rabies managers in Svalbard also face unique conditions, such as risks associated with hunting and the particular administrative structure of Svalbard. Due to limited veterinary services in dispersed small and remote communities, dogs present challenges to rabies management in Alaska and the Northwest Territories. Personal relationships are important in disease management across agencies, and the unique challenges in the far North will likely pose challenges in adopting approaches to disease management from temperate climates.
Topics: Animals; Humans; Dogs; Rabies; Rabies virus; One Health; Alaska; Norway
PubMed: 38369781
DOI: 10.1080/22423982.2024.2318059 -
Travel Medicine and Infectious Disease 2024Rabies remains a deadly zoonotic disease, primarily prevalent in Eastern European countries, with a significant global burden in Asia and Africa. Post-exposure... (Observational Study)
Observational Study
BACKGROUND
Rabies remains a deadly zoonotic disease, primarily prevalent in Eastern European countries, with a significant global burden in Asia and Africa. Post-exposure prophylaxis (PEP) is critical to prevent clinical rabies. Serbia, a country with a relatively low animal rabies incidence, has been implementing a 4-dose Essen PEP regimen for 13 years. This real-world study aimed to assess the effectiveness of the 4-dose Essen regimen, considering demographic and clinical factors, after WHO Category III exposure.
METHOD
The study included 601 patients who received the 4-dose Essen PEP and 79 who received an additional 5th dose.
RESULTS
Age emerged as a critical factor influencing seroconversion rates after the 4-dose regimen, with older individuals exhibiting lower RVNA titers. Logistic regression indicated a 3.18% decrease in seroconversion odds for each added year of age. The Cox proportional hazards mixed model highlighted age-related risks, with age groups 45-60 and 75-92 at the highest risk of non-seroconversion. Human Rabies Immune Globulin (HRIG) administration was associated with lower RVNA values after the 4-dose regimen, suggesting interference with vaccine immunogenicity among people who received larger doses of HRIG.
CONCLUSIONS
This study provides valuable real-world evidence for rabies PEP in a non-homogeneous population with potential comorbidities. The results underscore the importance of optimizing PEP strategies, particularly in older individuals, and reconsidering HRIG dosing to improve seroconversion rates.
Topics: Animals; Humans; Aged; Rabies; Post-Exposure Prophylaxis; Serbia; Antibodies, Viral; Rabies Vaccines; Rabies virus
PubMed: 38369074
DOI: 10.1016/j.tmaid.2024.102697 -
Revista Da Sociedade Brasileira de... 2024Human Rabies (HR) is a fatal zoonotic disease caused by lyssaviruses, with the rabies virus (RABV) identified as the causative agent. While the incidence of HR... (Review)
Review
Human Rabies (HR) is a fatal zoonotic disease caused by lyssaviruses, with the rabies virus (RABV) identified as the causative agent. While the incidence of HR transmitted by dogs has decreased in Latin America, there has been a corresponding rise in transmission via wild animals. Given the lack of effective treatments and specific therapies, the management of HR relies on the availability of post-exposure prophylaxis and animal control measures. This review examines the dynamics and spread of HR during the global pandemic.
Topics: Humans; Animals; Dogs; Rabies; Pandemics; Brazil; COVID-19; Rabies virus
PubMed: 38359308
DOI: 10.1590/0037-8682-0520-2023 -
Journal of Feline Medicine and Surgery Feb 2024Some expert groups recommend that cats should be vaccinated with non-adjuvanted feline leukaemia virus (FeLV) and rabies vector vaccines, which, in the European Union,...
OBJECTIVES
Some expert groups recommend that cats should be vaccinated with non-adjuvanted feline leukaemia virus (FeLV) and rabies vector vaccines, which, in the European Union, are currently not licensed for concurrent use and have to be administered at least 14 days apart (different from the USA) and thus at separate visits, which is associated with more stress for cats and owners. The aim of this study was to assess the anti-rabies antibody response in cats after vaccination against rabies and FeLV at concurrent vs separate (4 weeks apart) visits using two canarypox-vectored vaccines (Purevax Rabies and Purevax FeLV; Boehringer Ingelheim) and to evaluate the occurrence of vaccine-associated adverse events (VAAEs).
METHODS
Healthy FeLV antigen-negative client-owned kittens (n = 106) were prospectively included in this randomised study. All kittens received primary vaccinations against rabies (week 0) and FeLV (weeks 4 and 8). After 1 year, the study group (n = 52) received booster vaccinations against rabies and FeLV concurrently at the same visit (weeks 50-52). The control group (n = 54) received booster vaccinations against rabies (weeks 50-52) and FeLV (weeks 54-56) separately. Anti-rabies virus antibodies (anti-RAV Ab) were determined by fluorescent antibody virus neutralisation assay at weeks 4, 50-52 and 54-56, and compared between both groups using a Mann-Whitney U-test.
RESULTS
Four weeks after the first rabies vaccination, 87/106 (82.1%) kittens had a titre ⩾0.5 IU/ml and 19/106 (17.9%) had a titre <0.5 IU/ml. Four weeks after the 1-year rabies booster, all cats had adequate anti-RAV Ab according to the World Organisation for Animal Health (⩾0.5 IU/ml), and the titres of the study group (median = 14.30 IU/ml) and the control group (median = 21.39 IU/ml) did not differ significantly ( = 0.141). VAAEs were observed in 7/106 (6.6%) cats.
CONCLUSIONS AND RELEVANCE
Concurrent administration of Purevax FeLV and Purevax Rabies vector vaccines at the 1-year booster does not interfere with the development of anti-RAV Ab or cause more adverse effects and thus represents a better option than separate vaccination visits for cats and owners.
Topics: Animals; Cats; Antibodies, Viral; Cat Diseases; Immunity, Humoral; Leukemia Virus, Feline; Rabies; Vaccination; Viral Vaccines
PubMed: 38358295
DOI: 10.1177/1098612X231218643