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The subiculum (SUB), a hippocampal formation structure, is among the earliest brain regions impacted in Alzheimer's disease (AD). Toward a better understanding of AD circuit-based mechanisms, we mapped synaptic circuit inputs to dorsal SUB using monosynaptic rabies tracing in the 5xFAD mouse model by quantitatively comparing the circuit connectivity of SUB excitatory neurons in age-matched controls and 5xFAD mice at different ages for both sexes. Input-mapped brain regions include the hippocampal subregions (CA1, CA2, CA3), medial septum and diagonal band, retrosplenial cortex, SUB, postsubiculum (postSUB), visual cortex, auditory cortex, somatosensory cortex, entorhinal cortex, thalamus, perirhinal cortex (Prh), ectorhinal cortex, and temporal association cortex. We find sex- and age-dependent changes in connectivity strengths and patterns of SUB presynaptic inputs from hippocampal subregions and other brain regions in 5xFAD mice compared with control mice. Significant sex differences for SUB inputs are found in 5xFAD mice for CA1, CA2, CA3, postSUB, Prh, lateral entorhinal cortex, and medial entorhinal cortex: all of these areas are critical for learning and memory. Notably, we find significant changes at different ages for visual cortical inputs to SUB. While the visual function is not ordinarily considered defective in AD, these specific connectivity changes reflect that altered visual circuitry contributes to learning and memory deficits. Our work provides new insights into SUB-directed neural circuit mechanisms during AD progression and supports the idea that neural circuit disruptions are a prominent feature of AD.

Rabies virus (RABV) is among the first recognized viruses of public health concern and has historically contributed to the development of viral vaccines. Despite these significances, the three-dimensional structure of the RABV virion remains unknown due to the challenges in isolating structurally homogenous virion samples in sufficient quantities needed for structural investigation. Here, by combining the capabilities of cryogenic electron tomography (cryoET) and microscopy (cryoEM), we determined the three-dimensional structure of the wild-type RABV virion. Tomograms of RABV virions reveal a high level of structural heterogeneity among the bullet-shaped virion particles encompassing the glycoprotein (G) trimer-decorated envelope and the nucleocapsid composed of RNA, nucleoprotein (N), and matrix protein (M). The structure of the trunk region of the virion was determined by cryoEM helical reconstruction, revealing a one-start N-RNA helix bound by a single layer of M proteins at an N:M ratio of 1. The N-M interaction differs from that in fellow rhabdovirus vesicular stomatitis virus (VSV), which features two layers of M stabilizing the N-RNA helix at an M:N ratio of 2. These differences in both M-N stoichiometry and binding allow RABV to flex its N-RNA helix more freely and point to different mechanisms of viral assembly between these two bullet-shaped rhabdoviruses.

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Background and purpose: Repetitive bloodletting, promoting profuse diarrhoea and vomiting, the formation of artificial ulcers, and other aggressive treatment methods based on humoral theory and Brunonian medicine were used for patients with nervous system (NS) diseases until the end of the 19th century. These methods are also termed "heroic" medicine by modern medical historians. Methods: I analysed doctoral dissertations on the subject of NS diseases, clinical reports from 1806 to 1842 from the Vilnius University clinics, and other primary sources. This study was conducted in the vein of a historical–medical analysis and synthesis of primary sources, using comparative analysis, analogy, descriptive methods, and the method of retrospective diagnosis. Results: Copious bloodletting, purgatives, leeches, cupping therapy, and other potentially harmful methods were frequently employed as habitual treatments for patients with NS diseases. Calomel was used as a purgative and an anti‐inflammatory drug, and acidum borussicum was prescribed for patients with hydrophobia. After analysing three clinical cases, I revealed how principles of desperate, "heroic" medicine were applied to treat severe NS diseases with the "strongest" drugs, described in the scientific literature of the time. Conclusions: My work was not intended to judge or criticize historical treatment methods but to demonstrate on what contemporary scientific theories they were based. We should not rule out the idea that some aggressive treatment methods used nowadays, although they eradicate or reduce the burden of a NS disease, or even prolong patients' lives, may offer exceptional examples of 21st century "heroic" medicine for future generations. [ABSTRACT FROM AUTHOR]

This art installation centers on then-recent outbreaks of rabies and Nipah viruses in India and Bangladesh, and reveals unexpected connections between vultures, fruit bats, and humans. Using Victorian and Dutch decorative arts from time periods in which England and the Netherlands were connected to these contemporary outbreak sites through colonization, the installation highlights the way climate injustice influences which humans and animals bear the most risk in disease spillovers. Using work by cultural anthropologist Ernest Becker, the installation also considers how culture (particularly art) functions as a psychological mechanism for coping with death anxiety. [ABSTRACT FROM AUTHOR]

Human rabies is a prevalent issue in China, posing a significant public health concern in the country. This study fitted the Bayesian model of separable in spatial and temporal variation and inseparable spatiotemporal variation in disease risk respectively based on Integrated Nested Laplace Approximation (INLA) to investigate the spatiotemporal characteristics of human rabies across 31 provinces in China from 2004 to 2020. It also investigated the influence of natural and socio-environmental factors on the incidence of the disease. Within the study period, a total of 26,807 cases of human rabies were reported, with the highest risk of incidence occurring in 2007, followed by a steady annual decline to the lowest risk in 2020. Guangxi Province exhibited the highest risk, while Jilin Province had the lowest, with the southern, central, and eastern regions reporting higher risks than the northern and western areas. By 2020, most provinces such as Guangxi and Guizhou had significantly reduced their relative risk (RR) of human rabies from historical highs. However, some provinces like Hunan, Henan, and Jiangsu experienced an increase in RR compared to previous years. As the annual average temperature increases, the risk of human rabies incidence in China correspondingly rises. Conversely, with increases in the annual average daily sunshine duration, per capita disposable income of urban residents, and local government healthcare expenditures, the risk of human rabies incidence declines. We conclude that the risk of human rabies in China initially increased and then decreased annually from 2004 to 2020. Future efforts should continuously increase financial investments in rabies prevention and control, focusing particularly on Hunan, Henan, Jiangsu, and provinces characterized by higher temperatures, shorter sunshine durations, and lower economic levels. Author summary: Rabies is a Neglected Tropical Disease (NTD), predominantly prevalent in Africa and Asia, with a nearly 100% fatality rate upon onset. China is striving to achieve the WHO's global goal of zero deaths from dog-mediated human rabies by 2030. Therefore, exploring the spatial and temporal evolution of human rabies in China and the possible influencing factors can provide a scientific basis for the development of more effective human rabies prevention and control programs in China. The results of the study showed that from 2004 to 2020, the overall relative risk of human rabies incidence in China showed an increasing and then decreasing trend. The relative risk of most provinces, such as Guangxi and Guizhou, declined significantly, but there were still some provinces, such as Hunan and Henan, where the relative risk showed a rising trend year by year. The results of the analysis of influencing factors indicate that lower per capita disposable income of urban residents, local government healthcare expenditures and sunshine hours, higher temperatures are associated with a higher risk of human rabies. [ABSTRACT FROM AUTHOR]

Background: This case report describes the treatment of a 12-year-old indigenous Brazilian girl from the Maxakali group with rabies using the adapted Milwaukee Protocol. Case presentation: The patient suffered a superficial bat bite on her right elbow, reported on April 5, 2022. Despite receiving immunoglobulin, a vaccine, and antiviral medications such as amantadine and sapropterin, the patient succumbed to the disease 25 days after hospital admission. The report highlights the inherent challenges in treating rabies due to the virus's neurotropic nature and the difficulties in delivering antiviral drugs to the central nervous system. The case underscores the need for early antiviral intervention and calls for more studies to validate and improve treatment protocols for rabies in vulnerable populations, particularly those with genetic and immunological susceptibilities like the Maxakali indigenous group. Conclusion: The findings suggest that while the Milwaukee Protocol offers some hope, significant obstacles remain in achieving successful outcomes in rabies cases. [ABSTRACT FROM AUTHOR]

Objective: MVN GABAergic neurons is involved in the rebalance of commissural system contributing to alleviating acute peripheral vestibular dysfunction syndrome. This study aims to depict monosynaptic inputs to MVN GABAergic neurons. Methods: The modified rabies virus-based retrogradation method combined with the VGAT-IRES-Cre mice was used in this study. Moreover, the commissural connections with MVN GABAergic neurons were analyzed. Results: We identified 60 nuclei projecting to MVN GABAergic neurons primarily distributed in the cerebellum and the medulla. The uvula-nodulus, gigantocellular reticular nucleus, prepositus nucleus, intermediate reticular nucleus, and three other nuclei sent dense inputs to MVN GABAergic neurons. The medial (fastigial) cerebellar nucleus, dorsal paragigantocellular nucleus, lateral paragigantocellular nucleus and 10 other nuclei sent moderate inputs to MVN GABAergic neurons. Sparse inputs to MVN GABAergic neurons originated from the nucleus of the solitary tract, lateral reticular nucleus, pedunculopontine tegmental nucleus and 37 other nuclei. The MVN GABAergic neurons were regulated by the contralateral MVN, lateral vestibular nucleus, superior vestibular nucleus, and inferior vestibular nucleus. Conclusion: Our study contributes to further understanding of the vestibular dysfunction in terms of neural circuits and search for new strategies to facilitate vestibular compensation. [ABSTRACT FROM AUTHOR]

Rabies is a lethal viral animal disease that assaults the central nervous system. Its glycoprotein is a viral protein that is essential for viral pathogenicity. Initially, the rabies vaccine was produced from nerve tissue, but it is no longer recommended since it causes adverse effects and is less effective. The anti-idiotype antibody vaccination is one option that functions as homologous artificial antigens to the glycoprotein of the rabies virus. The CDR is the structure of anti-idiotypic antibodies that play a role in mimicking epitopes. It may resemble or be identical to epitopes seen in rabies virus glycoproteins. The objective of this study is to determine the affinity of the CDR anti-idiotype antibody for the rabies virus glycoprotein epitope by studying the CDR electrostatic value. This electrostatic value was analyzed by bioinformatics approaches using a webPIPSA server. The findings revealed an electrostatic resemblance between the structure of anti-idiotype antibodies and the rabies virus glycoprotein. Further study will be aimed at collecting electrostatic values from each structure to create an anti-rabies vaccine. [ABSTRACT FROM AUTHOR]

Rabies is controlled by mass animal vaccination campaigns. Cats, dogs, and wild animals (e.g., bats) are large reservoirs of this virus and can pose a significant threat to the human health, especially in the developing countries. The nucleoprotein of the rabies virus is of great scientific interest since it has the potential to generate immunity in animals and can be used as for immunochemical diagnostics. The study aimed to test a large-scale expression of the rabies N protein in a prokaryotic system. The recombinant N protein was successfully expressed and purified. It was immunologically recognized by specific antibodies and was able to induce the production of specific antibodies in a mouse immunization assay. These encouraging results indicate that the recombinant N protein can be evaluated as an antigen for the development of a subunit vaccine or for a diagnostic assay. [ABSTRACT FROM AUTHOR]

Human rabies cases today are predominantly associated with infection from rabid domestic dogs. Unlike dogs, a common global reservoir species that perpetuates rabies viruses (RABV) within their populations, domestic cats are much less frequently reported or vaccinated. Epidemiologically, cats are important vectors of lyssaviruses but are not viral reservoirs. Typically, cats are incidental hosts only, infected with the predominant lyssavirus in their geographic locale. Human cases associated with rabid cats have occurred in Africa, Asia, Europe and throughout the Americas. As adept, solitary hunters, wild and domestic felids are at risk of lyssavirus infection based upon interactions with infected prey, such as bats, or from transmission by other mesocarnivores, such as rabid dogs, foxes, jackals, raccoons, and skunks. Current veterinary vaccines provide safe and effective immunity in cats against phylogroup I lyssaviruses, such as RABV, but not against divergent lyssaviruses in phylogroups II-IV. With the focus upon the global elimination of canine rabies, the emergence of rabies in cats represents a concerning trend. Clearly, education about the occurrence of rabies in cats needs to be improved, as well as the routine vaccination of cats to reduce the associated risks to public health, agriculture, and conservation biology from a One Health perspective. [ABSTRACT FROM AUTHOR]

Bat‐borne pathogens are a threat to global health and in recent history have had major impacts on human morbidity and mortality. Examples include diseases such as rabies, Nipah virus encephalitis, and severe acute respiratory syndrome (SARS). Climate change may exacerbate the emergence of bat‐borne pathogens by affecting the ecology of bats in tropical ecosystems. Here, we report the impacts of climate change on the distributional ecology of the common vampire bat Desmodus rotundus across the last century. Our retrospective analysis revealed a positive relationship between changes in climate and the northern expansion of the distribution of D. rotundus in North America. Furthermore, we also found a reduction in the standard deviation of temperatures at D. rotundus capture locations during the last century, expressed as more consistent, less‐seasonal climate in recent years. These results elucidate an association between D. rotundus range expansion and a continental‐level rise in rabies virus spillover transmission from D. rotundus to cattle in the last 50 years of the 120‐year study period. This correlative study, based on field observations, offers empirical evidence supporting previous statistical and mathematical simulation‐based studies reporting a likely increase of bat‐borne diseases in response to climate change. We conclude that the D. rotundus rabies system exemplifies the consequences of climate change augmentation at the wildlife–livestock–human interface, demonstrating how global change acts upon these complex and interconnected systems to drive increased disease emergence. [ABSTRACT FROM AUTHOR]

Animal rabies is a potentially fatal infectious disease in mammals, especially dogs. Currently, the number of rabies cases in pet dogs is increasing in several regions of Thailand. However, no passive postexposure prophylaxis (PEP) has been developed to combat rabies infection in animals. As monoclonal antibodies (MAbs) are promising biological therapies for postinfection, we developed a canine-neutralizing MAb against rabies virus (RABV) via the single-chain variable fragment (scFv) platform. Immunized phage-displaying scFv libraries were constructed from PBMCs via the pComb3XSS system. Diverse canine VHVLκ and VHVLλ libraries containing 2.4 × 108 and 1.3 × 106 clones, respectively, were constructed. Five unique clones that show binding affinity with the RABV glycoprotein were then selected, of which K9RABVscFv1 and K9RABVscFv16 showed rapid fluorescent foci inhibition test (RFFIT) neutralizing titers above the human protective level of 0.5 IU/ml. Finally, in silico docking predictions revealed that the residues on the CDRs of these neutralizing clones interact mainly with similar antigenic sites II and III on the RABV glycoprotein. These candidates may be used to develop complete anti-RABV MAbs as a novel PEP protocol in pet dogs and other animals. [ABSTRACT FROM AUTHOR]

Rabies is an invariably fatal infectious-contagious viral disease caused by viruses in the genus Lyssavirus, which affects the central nervous system of domestic and wild mammals. This study draw attention to the importance of insectivorous bats and domestic cats in the epidemiology of rabies. For this, two cases of rabies registered in domestic cats in the southeast region of Rio Grande do Sul were analyzed. Diagnoses were based on histological alterations and positive staining for the virus in direct immunofluorescence with confirmation by biological test, immunohistochemical evaluation and identification of the rabies virus variant by polymerase chain reaction. In Brazil, a change in the epidemiological profile of rabies has been observed, in which bats play a major role in the current chain of transmission of the disease. It is noteworthy, that the antigenic viral variant AgV-4, typical of the insectivorous bat Tadarida brasiliensis, was identified in the domestic cats affected in this study [ABSTRACT FROM AUTHOR]

Background: In India, over 35% of global human Rabies deaths occur, primarily from dog bites which are responsible for over 95% of cases. Objective of this study was to assess the epidemiological profile and practices regarding animal bite, among animal bite victims attending the OPD of Rural Health and Training Centre affiliated to a Tertiary Care Centre in Rewa. Methods: This was a facility based cross-sectional study. Sample size was 150. New animal bite victims were interviewed using a semi-structured questionnaire after obtaining informed verbal consent. The questionnaire consisted of demographic profile and questions regarding victims’ awareness about rabies, anti-rabies vaccine and their practices following the animal bite. Conclusion: Younger age group (persons of 0-30 years age group) are more commonly affected. Awareness among participants may be raised by utilising school health programs Major biting animals were dogs. Very few people are aware of the need for observing animals post bite. Wound care practices need to be improved. Pet dog rabies vaccination rate is very low, which needs to be focused upon for achieving rabies control. [ABSTRACT FROM AUTHOR]

The growing population in Yucatan has led to the expansion of construction in the Mayan jungle for tourist spaces, residential areas, and agriculture. Recently, rabies cases in cats (Felis catus) have increased in the state. This study aimed to perform antigenic and genetic characterization of the rabies viruses in felines and to present the spatial distribution and environmental features of the areas where these cases were reported. The ArcGIS software and R were employed to generate maps depicting the geographic locations of rabies cases in cats. A total of nine feline rabies cases occurred during the period 2003–2022. Three antigenic variants were detected: dog-related RVV1 (n = 1); vampire bat variant RVV3 (n = 1); and the canine-originated atypical variant (n = 7). Cases reported in Merida (n = 4) and Muna (n = 4) were localized to urban areas, while Cuncunul (n = 1) was rural. This study highlights the concerning resurgence of rabies infections in cats, emphasizing the looming threat of its reintroduction in dogs should vaccination rates diminish. The genetic affinity between the atypical variant and the canine virus underscores the urgent need for vigilance in maintaining high vaccination coverage across all susceptible species. [ABSTRACT FROM AUTHOR]

Simple Summary: To advance the national rabies control effort in Cambodia, a coalition comprising government and non-government organizations spearheaded a short-duration canine rabies vaccination campaign in the capital province of Cambodia, Phnom Penh, and the neighboring Kandal Province. The campaign was conducted over 10 days to establish significant herd immunity to stop dog-mediated rabies transmission. The campaign deployed 120 vaccination teams, each consisting of two vaccinators and one tuk-tuk driver. Parenteral rabies vaccines were delivered using a door-to-door method. Utilizing the mobile application, the teams received spatial guidance during the campaign and performed data collection. The campaign vaccinated 74,983 dogs in just 10 days, achieving the district mean coverage of 70.7% among the owned dog population in Phnom Penh Province. The implementation of such a large-scale campaign in a short space of time created a blueprint for mass dog vaccination in urban areas, contributing to upscaling rabies control strategies across Cambodia. Background: WHO and WOAH advocate for annual high-coverage canine rabies vaccination campaigns as the most sustainable approach to eliminate the risk of dog rabies transmission to humans. It is estimated that Cambodia has one of the highest human rabies deaths per capita of any country (5.8 human deaths per 100,000 people), highlighting the urgent need to implement an effective canine rabies vaccination program. To this end, a coalition of government and non-government organizations conducted a pioneering short-duration dog rabies vaccination campaign over 10 days across Phnom Penh and Kandal Provinces in May 2023. Methods: Over 10 working days, 120 vaccination teams, each consisting of two vaccinators and one tuk-tuk driver, traveled door-to-door to deliver parenteral rabies vaccines to all dogs that could be held by the teams or members of the community. Spatial team management and data collection were conducted through the WVS Data Collection Application. Results: A total of 74,983 dogs were vaccinated, giving a mean vaccination rate of 62.5 dogs per team per day. An additional 2145 cats were vaccinated. Of all dogs encountered by the teams, 84.0% could be vaccinated, with 99.1% of those being identified as owned. Post-vaccination surveys of 4356 households estimated a mean vaccination coverage of 70.7% in owned dogs across the districts of Phnom Penh Province. Conclusion: Short-duration, large-scale canine rabies vaccination campaigns can achieve high vaccination coverage using a door-to-door approach in urban centers of Cambodia. Data gathered through the campaign yielded insights to support the refinement and planning of a wider rabies control strategy and is anticipated to drive further support for subsequent campaigns in Cambodia. [ABSTRACT FROM AUTHOR]

Background: Rabies is an incessant public health threat in China. The Ministry of Health implemented the Central Payment for Rabies Prevention and Control Project to assist with rabies prevention and control in a few representative provinces in 2006. Methods: Data on human rabies cases reported by the National Infectious Disease Reporting Information Management System and national surveillance sites from 2006 to 2022 were collected, and statistical and multivariate analyses were then used to assess the effectiveness of current prevention and control efforts. Results: During 2006–2022, a total of 2025 human rabies cases were collected by the national surveillance sites, with incidence rates far above the national average, but the incidence rate was consistent with the national trend. Human rabies cases demonstrated a dual peak distribution in terms of exposure and onset dates, with the peak exposure dates falling mostly in the spring and summer and the peak onset dates occurring mostly in the summer and autumn. Three danger categories are shown by the geographical distribution: high, medium and low. Dogs had a high infection rate (86.93%), with own domesticated dogs accounting for the majority of infections. The rates of post-exposure prophylaxis are not constant. The median incubation period was 71 days. Conclusions: Various measures and policies implemented by the government have played a key role in reducing the incidence of rabies. To effectively prevent and control the resurgence of epidemics and halt the spread of the virus among host animals, it is imperative to prioritize and implement a robust dog management system, accelerate research and development of animal vaccines and improve the level of post-exposure prophylaxis. [ABSTRACT FROM AUTHOR]

Rabies remains a significant public health challenge in Africa, primarily burdening impoverished rural communities, with children and young adults being the most vulnerable. Achieving complete elimination in the continent by 2030 requires a coordinated effort hinged on the One Health concept, external support from international organizations like the World Health Organization (WHO) and the national governments of endemic countries. Here, we reviewed the various socio-economic and ecological factors influencing the spatial distribution and molecular epidemiology of the disease. To mitigate the transmission of rabies on a global scale, and specifically in Africa, we proposed a multi-pronged approach including enhanced access to healthcare resources, cultural sensitization and massive health promotion with efforts geared towards promoting responsible dog and pet ownership and population management, effective monitoring, and mitigation of environmental changes. [ABSTRACT FROM AUTHOR]

Rabies is a neglected disease primarily related to dog-mediated transmission to humans. Accurate dog demographic and dynamic data are essential for effectively planning and evaluating population management strategies when designing interventions to prevent rabies. However, in Thailand, longitudinal survey data regarding dog population size are scarce. A school-based participatory research (SBPR) approach was conducted to survey owned dogs for one year in four high-risk provinces (Chiang Rai, Surin, Chonburi, and Songkhla) of Thailand, aiming to understand dog population dynamics and raise awareness about rabies. 'Pupify' mobile application was developed to collect data on dog population and observe the long-term population dynamics in this study. At the end of the data collection period, telephone interviews were conducted to gain insight into contextual perceptions and awareness regarding both animal and human rabies, as well as the social responsibility of dog owners in disease prevention and control. Among 303 high school students who registered in our study, 218 students reported at least one update of their dog information throughout the one-year period. Of 322 owned dogs from our survey, the updates of dog status over one year showed approximately 7.5 newborns per 100-dog-year, while deaths and missing dogs were 6.2 and 2.7 per 100-dog-year, respectively. The male to female ratio was approximately 1.8:1. Twenty-three students (10%) voluntarily participated and were interviewed in the qualitative study. The levels of rabies awareness and precautions among high-school students were relatively low. The high dropout rate of the survey was due to discontinuity in communication between the researcher and the students over the year. In conclusion, this study focused on using the SBPR approach via mobile application to collect data informing dog population dynamics and raising awareness regarding rabies in Thailand Other engaging platforms (e.g. Facebook, Instagram, Twitter, and other popular applications) is necessary to enhance communication and engagement, thereby sustaining and maintaining data collection. Further health education on rabies vaccination and animal-care practices via social media platforms would be highly beneficial. For sustainable disease control, engaging communities to raise awareness of rabies and increase dog owners' understanding of their responsibilities should be encouraged. [ABSTRACT FROM AUTHOR]

After the COVID-19 pandemic, efforts have gradually been focused on medical care, epidemiological surveillance, and preventive health programs. An example of this is the identification during 2023 by the Epidemiological Surveillance System [of Mexico] of the increase in dengue cases and the presence of serotype 3, as well as cases of measles (imported and related to importation) and, at the same time, cases of human rabies with transmission from pet animals. Mexico's health system has been characterized by achievements in vaccine-preventable pathologies, as well as the robust epidemiological surveillance system for febrile exanthematous illness and vector-transmitted diseases. In this essay, the previous and current situation of selected diseases in Mexico in the post-pandemic stage of COVID-19 is presented. [ABSTRACT FROM AUTHOR]

Background: Dog‐mediated rabies virus variant (DMRVV), a zoonotic pathogen that causes a deadly disease in animals and humans, is present in more than 100 countries worldwide but has been eliminated from the United States since 2007. In the United States, the U.S. Centers for Disease Control and Prevention has recorded four instances of rabies in dogs imported from DMRVV‐enzootic countries since 2015. However, it remains uncertain whether the incidence of DMRVV among imported dogs from these countries significantly surpasses that of domestically acquired variants among domestic U.S. dogs. Aim: This evaluation aimed to estimate the number of dogs imported from DMRVV‐enzootic countries and compare the risk of rabies between imported dogs and the U.S. domestic dog population. Materials and Methods: Data from the CDC's dog import permit system (implemented during 2021 under a temporary suspension of dog importation from DMRVV‐enzootic countries) and U.S. Customs and Border Protection's Automated Commercial Environment system, each of which records a segment of dogs entering the U.S. from DMRVV‐enzootic countries, was analysed. Additionally, we estimated the incidence rate of rabies in dogs imported from DMRVV‐enzootic countries and compared it to the incidence rate within the general U.S. dog population, due to domestically acquired rabies variants, over the eight‐year period (2015–2022). Results: An estimated 72,589 (range, 62,660–86,258) dogs were imported into the United States annually between 2015 and 2022 from DMRVV‐enzootic countries. The estimated incidence rate of rabies was 16 times higher (range, 13.2–19.4) in dogs imported from DMRVV‐enzootic countries than that estimated for domestically acquired rabies in the general U.S. dog population. Conclusions: Preventing human exposure to dogs with DMRVV is a public health priority. The higher risk of rabies in dogs imported from DMRVV‐enzootic countries supports the need for importation requirements aimed at preventing the reintroduction of DMRVV into the United States. [ABSTRACT FROM AUTHOR]

Breakthrough infection of rabies is rarely reported. And it is difficult to make a definite diagnosis of rabies for patients with atypical clinical manifestations. Here we report a rabies breakthrough infection who presented atypical clinical manifestations. The diagnosis of rabies was confirmed by the detection of rabies virus in cerebrospinal fluid by metagenomics next-generation sequencing (mNGS). [ABSTRACT FROM AUTHOR]

Background: Rabies is an acute and 100% fatal viral disease transmitted to humans through the bite or lick of an infected animal. It can be successfully prevented if a complete course of anti-rabies vaccine (ARV) is taken following an animal bite. The present study reveals the compliance of animal bite victims to post-exposure prophylaxis (PEP). Aims and Objectives: The objectives of the study are as follows:(1) To determine the adherence to PEP among animal bite victims and factors influencing it. Materials and Methods: A retrospective record-based cross-sectional study was conducted at the anti-rabies clinic of VIMS Hospital Ballari. Information regarding sociodemographic variables, animal bite history, category of bite, treatment received, and completion of ARV schedule of all the animal bite cases were collected from the animal bite register and treatment card during the period from July 2023 to December 2023. Results: Out of the total 350 animal bite victims, all of them received the first dose of vaccine, 86.28% completed two doses, 72% completed three doses, and only 51.14% completed the schedule by taking all four doses, 37% of them completed the schedule without any delay, 14% delayed one or more doses, and the rest 49% did not complete the schedule. Conclusion: Adherence to PEP is a dire necessity as rabies is a fatal disease. Counseling the animal bite victims about the importance of adhering to the complete PEP schedule at the time of administering the first dose of vaccine is crucial. [ABSTRACT FROM AUTHOR]

This case investigates and documents the occurrence of rabies in an unvaccinated 4-month-old Boerboel dog in Ebonyi State, Nigeria, emphasising the ethical considerations and implications for existing animal welfare policies. Despite Nigeria enacting the Animal Diseases (Control)Act, 2022, cases of rabies persist, contributing to thousands of human rabies cases annually. The legal framework highlights the ethical responsibilities of pet owners, mandating annual rabies vaccinations and holding owners accountable for their pets' actions. This case report details the dog's behavioural changes, subsequent euthanasia and laboratory confirmation of rabies. Investigations reveal gaps in vaccination compliance with challenges in community cooperation for free vaccination initiatives. The case highlights the global significance of rabies control, highlighting the ethical responsibilities of pet owners, emphasises the consequences of rabies, and advocates for strengthened policies and improved compliance to effectively combat rabies and protect both animal and human welfare in Nigeria. [ABSTRACT FROM AUTHOR]

Identifying spatial clusters of rabies in animals aids policymakers in allocating resources for rabies prevention and control. This study aimed to investigate spatial patterns and hotspots of rabies in different animal species at the county level in New Jersey. Data on animal rabies cases from January 1989 to December 2023 were obtained from the New Jersey Department of Health and aggregated by county. Global Moran's index (I) statistics were computed for each species to detect global spatial clustering (GeoDa version 1.22). Local Moran's indicators of spatial association (LISA) were computed to identify local clusters of rabies. The results from the LISA analysis were mapped using ArcGIS Pro to pinpoint cluster locations. A total of 9637 rabies cases were analyzed among raccoons (n = 6308), skunks (n = 1225), bats (n = 1072), cats (n = 597), foxes (n = 225), and groundhogs (n = 210). A global Moran's test indicated significant global spatial clustering in raccoons (I = 0.32, p = 0.012), foxes (I = 0.29, p = 0.011), and groundhogs (I = 0.37, p = 0.005). The LISA results revealed significant spatial clustering of rabies in raccoons and foxes in southeastern New Jersey and in groundhogs in northern New Jersey. These findings could guide the development of targeted oral rabies vaccination programs in high-risk New Jersey counties, reducing rabies exposure among domestic animals and humans. [ABSTRACT FROM AUTHOR]

On Friday June 16, 2023 at 4:00 pm, Niagara Region Public Health & Emergency Services (NRPH&ES) received notification of a rabies positive result for a cat that they had submitted for rabies testing earlier that week. The investigation revealed that it was a domestic cat from an urban area in St. Catharines that had been around numerous people and other animals during its infectious period. As part of the follow-up, NRPH&ES contacted all potential exposures, coordinated vaccination for those that required it and collaborated with other agencies to ensure the safety of all those involved. In addition, NRPH&ES navigated working with vaccine hesitant clients who were uncooperative in providing details pertaining to people who may have been in contact with the rabid cat, other animals living in the household, and ultimately reluctant to receive rabies post exposure prophylaxis (rPEP). Through innovation, unconventional methods and deviation from standard practice, NRPH&ES was able to build a trusting relationship with all clients, gather the information they required to conduct a fulsome investigation, and vaccinate and confine the other animal exposed to the rabid cat. [ABSTRACT FROM AUTHOR]

Animal bites are a frequent reason for primary care and emergency department visits by children. Rabies is endemic in Iran, with 5 to 11 deaths reported annually. Over 90% of rabies cases in the country are caused by dog bites, and more than 50% of the victims are children under 15 years old. The mortality rate of rabies is 100%. A 4-year-old girl, who had been bitten by a dog and sustained facial lacerations 16 days prior to admission, presented with fever and loss of consciousness. Despite wound washing, receiving four doses of the rabies vaccine and immunoglobulin, and taking cephalexin on the fifth day after the bite, she developed rabies encephalitis. Rabies was confirmed through a skin biopsy and saliva PCR. Treatment included vancomycin, meropenem, and acyclovir in addition to favipiravir. The patient was intubated due to impaired consciousness and respiratory issues, and her hypertension was managed with medication. A brain CT scan showed normal findings. Cerebrospinal fluid analysis revealed protein at 52, glucose at 63, and no cellular presence. Vancomycin and acyclovir were discontinued when blood culture, wound culture, cerebrospinal fluid, and PCR results returned negative. Echocardiography results were acceptable, and the patient’s lab tests showed no other abnormalities except for leukocytosis at admission, an ESR of 60, and a CRP of 40. The patient remained intubated for two weeks and continued to receive supportive measures, ongoing drug therapy, ventilator adjustments, and water and electrolyte balance management. During hospitalization, she showed no response to the apnea test, oculovestibular reflex, or doll's eye maneuver. Two weeks later, she developed bradycardia and subsequently died, with a final diagnosis of furious rabies. Despite receiving the rabies vaccine and immunoglobulin, the patient died within a month of the bite, which may be attributed to the location of the bite on her face, the timing of her treatment, or the quality of the vaccine.

Background Rabies, a zoonotic disease, poses a significant global public health challenge, and post-exposure prophylaxis (PEP) is crucial for prevention. Monoclonal antibodies (mAbs) have emerged as a promising alternative to rabies immunoglobulins due to their high efficacy and standardized manufacturing process. Materials and Methods A prospective, open-label post-marketing surveillance study was conducted with patients of WHO category-III suspected rabid animal bites. TwinRab™, a novel cocktail of docaravimab and miromavimab, was administered at a dosage of 40 IU/kg in and around the wound, along with the anti-rabies vaccine, which was administered intradermal as per Thai Red Cross regimen. Results In this study, 200 subjects received TwinRab™ with a 100% completion rate. Three (1.5%) patients showed solicited local AEs, and two (1%) patients showed solicited systemic AEs, which were resolved after appropriate treatment intervention. The overall tolerability assessment showed positive ratings from doctors (94%) and patients (74%). Conclusion The post-marketing surveillance study demonstrated the safety of TwinRab™ in patients who experienced category-III suspected rabid animal bites, thereby supporting its potential as an alternative option for PEP in the management of animal bite for the prevention of rabies.

Background.The rabies virus neutralizing antibodies titers is a public health problem in the world, including Indonesia. Rabies is zoonotic and causes death in humans with a case fatality rate of 100%. Anti-idiotype antibody (Ab2) from chicken immunoglobulin (IgY) can be a substitute antigen for the rabies virus. This research aims to study the potential of rabies vaccine based on anti-idiotype antibody (Ab2) with nano-chitosan as an adjuvant.Materials and methods.The production of Ab2 is derived from purified and characterized chicken immunoglobulins. Nano-chitosan is made from chitosan from shrimp shell waste. Vaccination tests were carried out on rats compared with commercial vaccines as a positive control and physiological solutions as a negative control. The characterization results of IgY Ab2 were IgY rabies with BM ~180 kDa, heavy chains (BM ~60 kDa), and light chains (BM ~30 kDa) of IgY. Nano-chitosan is less than 100 nm in size, can dissolve well, and does not cause side effects in experimental animals.Results.The vaccine formula uses a concentration of 0.5%, where the ratio of nano-chitosan and Ab2 is 1:1. The Ab2 concentration used was about 1000 units per mL of the Ab2 suspension.Conclusion.This study concludes that anti-idiotype antibodies dissolved in nano-chitosan adjuvant can induce the formation of antibodies with titers that are not statistically different from the antibody titers induced by commercial rabies vaccines. Nano-chitosan has a potential vaccine adjuvant candidate, safe to use, and can enhance the immunogenicity of an antigen applied subcutaneously. According to the results of this study, it is recommended that post-vaccination antibody titers be measured regularly: for example, every one week for six weeks after vaccination. This measurement determines the time of the peak of the antibody titer so that the time for revaccination can be determined.

Background and Aim: Rabies is a zoonotic disease that persists endemic in numerous countries worldwide. In Vietnam, the main sources of rabies are dogs and cats, and they caused 76 human deaths annually by 2017–2021. Long An province has recently experienced an increasing burden of rabies, with seven fatal cases reported in the past 5 years. Various rabies control measures have been implemented in this province, including mass vaccination of the animal population, post-vaccination monitoring, diagnostic testing of suspected rabid dogs, dog bite investigation, animal management, pre-exposure treatment, post-exposure treatment (PET), and awareness programs. This study aimed to estimate the cost of rabies control measures for animals and humans in Long An province in 2022. Materials and Methods: An economic model was developed to estimate the costs of rabies control under two scenarios, with and without external financial support from the private sector. Inputs for the model included data from published literature, publicly available reports on rabies, government data, expert opinions, and a pilot study conducted in Vietnam. Results: The total annual costs of rabies control, with or without external support, were estimated to be VND 62.62 and 62.77 billion (equivalent to USD 2.67 and 2.68 million), respectively. The highest proportion of costs was related to PET in humans (84.50% and 84.30%), followed by the cost of mass vaccination paid by animal owners (14.28% and 13.90%). Most of the expenses were paid by the private sector (98.87% and 98.98%) rather than the public sector (1.14% and 1.20%). Conclusion: This study described a transparent and reproducible method for estimating the economic costs of rabies control at the provincial level. The economic model developed showed that control of rabies by mass vaccination is more cost-effective than using PET to prevent human death. The model can be applied to future economic analyses of rabies control in other provinces of Vietnam and other rabies-endemic countries.

Abstract Background This case report describes the treatment of a 12-year-old indigenous Brazilian girl from the Maxakali group with rabies using the adapted Milwaukee Protocol. Case presentation The patient suffered a superficial bat bite on her right elbow, reported on April 5, 2022. Despite receiving immunoglobulin, a vaccine, and antiviral medications such as amantadine and sapropterin, the patient succumbed to the disease 25 days after hospital admission. The report highlights the inherent challenges in treating rabies due to the virus’s neurotropic nature and the difficulties in delivering antiviral drugs to the central nervous system. The case underscores the need for early antiviral intervention and calls for more studies to validate and improve treatment protocols for rabies in vulnerable populations, particularly those with genetic and immunological susceptibilities like the Maxakali indigenous group. Conclusion The findings suggest that while the Milwaukee Protocol offers some hope, significant obstacles remain in achieving successful outcomes in rabies cases.

Abstract Breakthrough infection of rabies is rarely reported. And it is difficult to make a definite diagnosis of rabies for patients with atypical clinical manifestations. Here we report a rabies breakthrough infection who presented atypical clinical manifestations. The diagnosis of rabies was confirmed by the detection of rabies virus in cerebrospinal fluid by metagenomics next-generation sequencing (mNGS).

Abstract Background Rabies is an incessant public health threat in China. The Ministry of Health implemented the Central Payment for Rabies Prevention and Control Project to assist with rabies prevention and control in a few representative provinces in 2006. Methods Data on human rabies cases reported by the National Infectious Disease Reporting Information Management System and national surveillance sites from 2006 to 2022 were collected, and statistical and multivariate analyses were then used to assess the effectiveness of current prevention and control efforts. Results During 2006–2022, a total of 2025 human rabies cases were collected by the national surveillance sites, with incidence rates far above the national average, but the incidence rate was consistent with the national trend. Human rabies cases demonstrated a dual peak distribution in terms of exposure and onset dates, with the peak exposure dates falling mostly in the spring and summer and the peak onset dates occurring mostly in the summer and autumn. Three danger categories are shown by the geographical distribution: high, medium and low. Dogs had a high infection rate (86.93%), with own domesticated dogs accounting for the majority of infections. The rates of post-exposure prophylaxis are not constant. The median incubation period was 71 days. Conclusions Various measures and policies implemented by the government have played a key role in reducing the incidence of rabies. To effectively prevent and control the resurgence of epidemics and halt the spread of the virus among host animals, it is imperative to prioritize and implement a robust dog management system, accelerate research and development of animal vaccines and improve the level of post-exposure prophylaxis.

Abstract Rabies remains a significant public health challenge in Africa, primarily burdening impoverished rural communities, with children and young adults being the most vulnerable. Achieving complete elimination in the continent by 2030 requires a coordinated effort hinged on the One Health concept, external support from international organizations like the World Health Organization (WHO) and the national governments of endemic countries. Here, we reviewed the various socio-economic and ecological factors influencing the spatial distribution and molecular epidemiology of the disease. To mitigate the transmission of rabies on a global scale, and specifically in Africa, we proposed a multi-pronged approach including enhanced access to healthcare resources, cultural sensitization and massive health promotion with efforts geared towards promoting responsible dog and pet ownership and population management, effective monitoring, and mitigation of environmental changes.

The intercalated cells of the amygdala (ITCs) are a fundamental processing structure in the amygdala that remain relatively understudied. They are phylogenetically conserved from insectivores through primates, inhibitory, and project to several of the main processing and output stations of the amygdala and basal forebrain. Through these connections, the ITCs are best known for their role in conditioned fear, where they are required for fear extinction learning and recall. Prior work on ITC connectivity is limited, and thus holistic characterization of their afferent and efferent connectivity in a genetically defined manner is incomplete. The ITCs express the FoxP2 transcription factor, affording genetic access to these neurons for viral input-output mapping. To fully characterize the anatomic connectivity of the ITCs, we used cre-dependent viral strategies in FoxP2-cre mice to reveal the projections of the main (mITC), caudal (cITC), and lateral (lITC) clusters along with their presynaptic sources of innervation. Broadly, the results confirm many known pathways, reveal previously unknown ones, and demonstrate important novel insights about each nucleuss unique connectivity profile and relative distributions. We show that the ITCs receive information from a wide range of cortical, subcortical, basal, amygdalar, hippocampal, and thalamic structures, and project broadly to areas of the basal forebrain, hypothalamus, and entire extent of the amygdala. The results provide a comprehensive map of their connectivity and suggest that the ITCs could potentially influence a broad range of behaviors by integrating information from a wide array of sources throughout the brain.

Rabies is one of the oldest known diseases, caused by the virus belonging to Rhabdoviridae family. It primarily spreads through the saliva of infected animals, most commonly via bites, leading to viral encephalitis, which is often fatal without prompt treatment. Historically, rabies was a uniformly fatal disease. With evelopment of Pasteur rabies vaccine in 1885, fatalities were drastically reduced especially in developed countries. In contrast, less developed regions continue to face significant challenges due to inadequate access to prevention and treatment.