Rise in rabies cases in Jammu region: A problem that requires urgent attention.

Context: Rabies is a fatal zoonotic disease that is endemic in India. Both forms of rabies, namely, encephalitic and furious, invariably lead to coma and death. Lack of awareness is the most critical barrier in accessing timely post-exposure prophylaxis that can prevent the progression to clinical disease. Aims: To report the case series of fourteen clinically suspected rabies cases. Settings and Design: We followed a retrospective study design. Data were collected from the Anti Rabies Section of Government Medical College, Jammu, which is a tertiary care hospital of Jammu Division. Methods and Material: We collected data of all patients over a period of three years, from 2017 to 2020, who were diagnosed as cases of clinically suspected rabies on the basis of classic signs and symptoms and who finally succumbed to the disease. Statistical Analysis Used: Descriptive statistics was used to describe the results of the study. Results: In the present description, the mean age of the patients was 31 ± 18.6 years. Out of 14 suspected cases, 9 had not received any post-exposure prophylaxis-neither vaccine nor serum-and instead visited spiritual faith healers. The remaining patients had history of either incomplete, unknown, or incorrect vaccination status. Median duration of presentation of symptoms after dog bite was 42 days, with a range of 15-180 days. Mean survival of patients after presentation of symptoms was around 1.8 days. Conclusions: Low level of awareness resulted in non-seeking of health-care services after animal bites.

Analytical Methods for Evaluating the Immunogenicity of Recombinant Rabies Virus Glycoprotein Expressed in the Yeast Komagataella phaffii.

BACKGROUND: Rabies is a fatal viral disease preventable by vaccination. The multiple-dose regimens, along with the high production costs of current rabies vaccines, limit their use in rabies-endemic countries with developing economies and consequently there is a need for new efficacious, low-cost rabies vaccines. This study investigates the immunogenicity of recombinant rabies virus glycoprotein (rRABVG), expressed in the yeast Komagataella phaffii (K. phaffii), as a candidate subunit rabies vaccine. METHODS: Monoclonal antibodies were used to confirm neutralizing epitopes presence on the rRABVG. The rRABVG potency was estimated by antigen quantification methods using ELISA and SRID. Serological methods, specifically ELISA and RFFIT, were applied to investigate the immune response of mice groups immunized with rRABVG varying doses, with or without adjuvant. RESULTS: The potency estimated by antigen quantification was dependent on the method employed. Active immunization assessment using ELISA was effective when the solid-phase antigen is the rRABVG. The RFFIT data indicated that a single adjuvanted dose of 20 µg rRABVG is sufficient for virus-neutralizing antibodies induction at a protective level of 0.5 IU/mL within 10 days post immunization. CONCLUSION: These data demonstrate that K. phaffii produced rRABVG is immunoactive and could be an attractive candidate to develop a low-cost subunit rabies vaccine.

Factors associated with the rabies vaccination status of dogs in households in Beni City, D.R. Congo.

Human rabies transmitted by dogs still kills thousands of people each year worldwide. Dog bites are common in the city of Beni (Democratic Republic of Congo), which shows low rabies vaccination coverage. This study aimed to determine the factors associated with the rabies vaccination status of dogs. A cross-sectional analytical study was conducted in the town of Beni among dog owners, during a household survey selected using a multistage sampling. The information sought concerned the knowledge and characteristics of the dog owners as well as the vaccination status of these dogs. Logistic regression was used to investigate associations between the vaccination status of the dogs and the main independent factors. Rabies vaccination coverage in Beni was 26% (95% confidence interval [CI]: 22% - 30%). The main factors associated with the rabies vaccination status of the dog were primary education level of household head (adjusted odds ratio [aOR]:4.8; 95% CI: 1.2- 19.8); university education level of household head (aOR: 5.9; 95% CI: 1.6-22); perceived rabies severity (aOR: 44. 4; 95% CI: 10.4-188), having more than one dog in the household (aOR: 2.6; 95% CI: 1.6-4.3); age range 7-12 months (aOR: 0.2; 95% CI: 0.1-0.6) and confined dog breeding (aOR: 3.9; 95% CI: 1.1-14.9). The low vaccination coverage in Beni requires mass vaccination campaigns against canine rabies targeting the dog owners with low education levels, those raising more than one dog, with stray dogs or dogs less than 12 months old.

Holistic application of the one health approach in the prevention and control of rabies: plausible steps towards achieving the 2030 vision in Africa.

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.

Cross-border surveillance of sheep and goat rabies in Brazil.

Since Brazil has the largest territory in South America and borders 10 other countries, rabies control is strategic to prevent cross-border spread. However, prevention and control of rabies in small ruminants is neglected. The present study evaluated the spatiotemporal distribution and temporal trends of rabies in small ruminants in Brazil between 2005 and 2023. Official data on rabies case notifications and the population density of goats and sheep from the Brazilian states were used. Descriptive epidemiology and temporal analyses of high-risk clusters and trends were conducted. Rabies cases were reported in all states, except for the Federal District, Roraima, Amapá, Amazonas, and Rondônia. In sheep, 174 cases were reported, with an emphasis on Paraná (25.29 %), being highest. There were 64 cases in goats, with a highlight on Bahia (37.50 %) and Maranhão (18.75 %). However, Espírito Santo presented the highest incidence risk (IR) for goats and sheep. The highest peaks in IR occurred in 2005, 2006 and 2013. A temporal trend of decreasing goat cases was observed in northeastern Brazil from 2005 to 2023. In sheep, the Northeast region showed a downward trend in rabies cases. Three high-risk clusters were identified: the primary cluster for goats occurred in 2006, and for sheep, between 2005 and 2013. Rabies in small ruminants occurs across all Brazilian regions, with high-risk areas in the Northeast, Southeast, and South, as well as a risk of cross-border transmission. These findings support animal health authorities in strengthening rabies control for small ruminants and reducing the risk of transboundary spread.

The roles of rabies virus structural proteins in immune evasion and implications for vaccine development.

Rabies is a zoonotic infectious disease that targets the nervous system of human and animals and has about 100% fatality rate without treatment. Rabies virus is a bullet-like viral particle composed of five structural proteins, including nucleoprotein (N), phosphorylated protein (P), matrix protein (M), glycoprotein (G), and large subunit (L) of RNA-dependent RNA polymerase. These multifunctional viral proteins also play critical roles in the immune escape by inhibiting specific immune responses in the host, resulting in massive replication of the virus in the nervous system and abnormal behaviors of patients such as brain dysfunction and hydrophobia, which ultimately lead to the death of patients. Herein, the role of five structural proteins of rabies virus in the viral replication and immune escape and its implication for the development of vaccines were systemically reviewed, so as to shed light on the understanding of pathogenic mechanism of rabies virus.

Epidemiological characteristics of human rabies cases reported by sites in China from 2006 to 2022.

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.

Rabies Virus Regulates Inflammatory Response in BV-2 Cells through Activation of Myd88 and NF-κB Signaling Pathways via TLR7.

Rabies is a fatal neurological infectious disease caused by rabies virus (RABV), which invades the central nervous system (CNS). RABV with varying virulence regulates chemokine expression, and the mechanisms of signaling pathway activation remains to be elucidated. The relationship between Toll-like receptors (TLRs) and immune response induced by RABV has not been fully clarified. Here, we investigated the role of TLR7 in the immune response induced by RABV, and one-way analysis of variance (ANOVA) was employed to evaluate the data. We found that different RABV strains (SC16, HN10, CVS-11) significantly increased CCL2, CXCL10 and IL-6 production. Blocking assays indicated that the TLR7 inhibitor reduced the expression of CCL2, CXCL10 and IL-6 (p < 0.01). The activation of the Myd88 pathway in BV-2 cells stimulated by RABV was TLR7-dependent, whereas the inhibition of Myd88 activity reduced the expression of CCL2, CXCL10 and IL-6 (p < 0.01). Meanwhile, the RABV stimulation of BV-2 cells resulted in TRL7-mediated activation of NF-κB and induced the nuclear translocation of NF-κB p65. CCL2, CXCL10 and IL-6 release was attenuated by the specific NF-κB inhibitor used (p < 0.01). The findings above demonstrate that RABV-induced expression of CCL2, CXCL10 and IL-6 involves Myd88 and NF-κB pathways via the TLR7 signal.

A single dose of recombinant adenoviral vector rabies vaccine expressing two copies of glycoprotein protects mice from lethal virus challenge.

INTRODUCTION: Rabies is a fatal infectious disease, that poses a major public health threat in developing countries. With an annual death toll of approximately 59,000, more than half of which are children, an urgent need exists for a safe, affordable, and effective preventive measure against rabies virus infection. METHODOLOGY: A recombinant rabies vaccine called Ad5-dRVG was constructed by introducing two copies of the rabies virus glycoprotein into a human adenoviral vector. Virus-neutralizing assays and virus challenge experiments were employed to evaluate the Ad5-dRVG vaccine. RESULTS: Our findings demonstrate that a single dose of Ad5-dRVG, administered either intramuscularly or orally, elicited significantly stronger immune responses than Ad5-RVG. Moreover, both vaccines provided complete protection in mice. Notably, the vaccine exhibited remarkable efficacy even at low doses, suggesting potential cost reduction in production. CONCLUSIONS: The development of the Ad5-dRVG recombinant rabies vaccine represents a significant advancement in rabies prevention. Its enhanced immunogenicity, demonstrated efficacy and potential cost savings make it a promising candidate for widespread use.

Rabies epidemiology in Malaysia (2015-2023): A cross-sectional insights and strategies for control.

BACKGROUND: Malaysia currently faces significant challenges in controlling the spread of dog-mediated human rabies, as evidenced by recurrent outbreaks in newly affected areas and increasing human fatalities. MATERIALS AND METHODS: A cross-sectional study was conducted to analyse surveillance data from 2015 to 2023 to examine the epidemiological characteristics of rabies in Malaysia. Data from multiple sources were used, and descriptive statistics, incidence rates, and reproductive numbers were calculated. QGIS software was used to map the distribution of rabies cases, and statistical methods were employed to evaluate associations between rabies incidence, vaccination coverage, and risk factors. We further explored the effectiveness of vaccination campaigns and public health interventions in reducing rabies transmission. RESULTS: Our findings revealed 995 confirmed rabies cases in animals. Sarawak reported the highest proportion of rabies cases at 97.99 %, showing a significant correlation between location and rabies cases (p < .001). Dogs comprised 89.35 % of confirmed cases, while the average annual vaccination rate was only 16.66 %, far below the 59.05 % needed for herd immunity. Moreover, human rabies cases reported in Sarawak had an alarmingly high fatality rate of 90.28 %, highlighting the urgent need for improved public health measures and surveillance. CONCLUSION: This research provides critical insights for policymakers and health officials to improve rabies control strategies in Malaysia.

A single dose of an ALVAC vector-based RABV virus-like particle candidate vaccine induces a potent immune response in mice, cats and dogs.

Rabies, caused by the Rabies virus (RABV), is a highly fatal zoonotic disease. Existing rabies vaccines have demonstrated good immune efficacy, but the complexity of immunization procedures and high cost has impeded the elimination of RABV, particularly in the post-COVID-19 era. There is a pressing need for safer and more effective rabies vaccines that streamline vaccination protocols and reduce expense. To meet this need, we have developed a potential rabies vaccine candidate called ALVAC-RABV-VLP, utilizing CRISPR/Cas9 gene editing technology. This vaccine employs a canarypox virus vector (ALVAC) to generate RABV virus-like particles (VLPs). In mice, a single dose of ALVAC-RABV-VLP effectively activated dendritic cells (DCs), follicular helper T cells (Tfh), and the germinal center (GC)/plasma cell axis, resulting in durable and effective humoral immune responses. The survival rate of mice challenged with lethal RABV was 100%. Similarly, in dogs and cats, a single immunization with ALVAC-RABV-VLP elicited a stronger and longer-lasting antibody response. ALVAC-RABV-VLP induced superior cellular and humoral immunity in both mice and beagles compared to the commercial inactivated rabies vaccine. In conclusion, ALVAC-RABV-VLP induced robust protective immune responses in mice, dogs and cats, offering a novel, cost-effective, efficient, and promising approach for herd prevention of rabies.

Contribution of artificial intelligence for understanding animal rabies epidemiology in Morocco: What are the perspectives of an innovative and predictive approaches?

Rabies is a major zoonotic disease legally notifiable in Morocco and elsewhere. Given the burden of rabies and its impact on public health, several national control programs have been implemented since 1986, without achieving their expected objectives. The aim of this study was to design a predictive analysis of rabies in Morocco. The expected outcome was the construction of probabilistic diagrams that can guide actions for the integrated control of this disease, involving all stakeholders, in the country. Such modeling is an essential step in operational epidemiology to optimize expenditure of public funds allocated to the integrated strategy for fighting this disease. The methodology employed combined the use of geospatial analysis tools (kriging) and artificial intelligence models (Machine Learning). In order to investigate the link between the risk of rabies within a territorial municipality (commune) and its socio-economic situation, the following data were analyzed: (1) health data: reported animal cases of rabies between 2004 and 2021 and data obtained through the ArcGIS kriging tool (Geospatial data); (2) demographic and socio-economic data. We compared several Machine Learning models. Of these, the "Imbalanced-Xgboost" model associated with kriging yielded the best results. After optimizing this model, we mapped our results for better visualization. The obtained results complement and consolidate previous study in this field with greater accuracy, showing a strong correlation between a commune's socio-economic status, its geographical location and its risk level of rabies. From this, 399 out of the 1546 communes have been identified as high-risk areas, accounting for 25.8% of the total number of communes. Under this risk-based approach, the results of these analyses make it practical to take targeted decisions for rabies prevention and control, as well as canine population control, in a territorial commune according to its risk level. Such an approach allows obvious optimized distribution of financial resources and adaptation of the control actions to be taken. The study highlights also the importance of using innovative technologies to refine epidemiological approaches and fill gaps in field data. Through this study, we hope to contribute to eradication of rabies in Morocco by providing reliable data and practical recommendations for control actions against rabies.

Study of dog population dynamics and rabies awareness in Thailand using a school-based participatory research approach.

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.

Rabies post-exposure prophylaxis: A retrospective analysis of timing of initiation and antibody responses in a Belgian cohort.

BACKGROUND: We aimed to determine the timeliness of rabies post-exposure prophylaxis (PEP) and the proportion of individuals with an adequate antibody response post-PEP among those attending the Belgian national reference center. METHODS: Retrospective analysis of patient records who attended our center from 2018 to 2023. Delay was defined as rabies immunoglobulin (RIG) and vaccine initiation beyond 2 calendar days after exposure. Antibodies were measured by rapid fluorescent focus inhibition test (RFFIT) after PEP in high-risk exposures. A titer ≥0.5 IU/ml was considered adequate. RESULTS: We reviewed 317 patient records. Among individuals with inland exposure (n = 103), 85 % timely received PEP. Among travelers exposed abroad (n = 214), administration of RIG and vaccine initiation were timely in 30 % and 50 % of cases, respectively. An adequate antibody response was detected in 99.5 % (195/196) individuals. CONCLUSION: Substantial PEP delays among travelers were observed. The robust antibody responses suggest that routine serological follow-up is not necessary for all patients.

Assessing the Safety of a Novel Monoclonal Antibody Cocktail for Postexposure Prophylaxis in Category III Animal Exposures.

Background: TwinRab™ is a novel life-saving biological containing two monoclonal antibodies (docaravimab and miromavimab) essential for all age victims of category III animal exposures. It effectively neutralizes rabies and similar viruses at the exposure site until the body generates vaccine-induced antibodies. This postmarketing surveillance study assesses the safety of TwinRab™ in current postexposure prophylaxis (PEP) use and aims to reinforce its safety data for future applications. Methods: The prospective, open-label observational study was conducted on patients with the World Health Organization category III animal exposures at a government hospital in a northern region of India, by a suspected rabid animal. The study protocol included administering TwinRab™ (40 IU/kg) and a full course of anti-rabies vaccination as PEP. Results: Out of 405 participants, 404 completed the study as per the protocol. Adverse events (AEs) occurred in 12.35% of cases, with 9.88% local AEs (primarily pain and tenderness) and 2.47% systemic AEs (fever, malaise, and myalgia). All AEs were mild and resolved without complications. Most participants (88.9%) and investigators (89.1%) rated TwinRab™'s tolerability as excellent. Conclusion: The present study demonstrates the evidence of a satisfactory safety profile along with better tolerability of TwinRab™ (40 IU/kg) for category III animal exposures and supports its continued usage.

Oral rabies vaccination of foxes in Türkiye, 2019-2022.

Background: Rabies in Turkey is maintained by dogs, but following a sustained spill-over, red fox mediated rabies had spread from the Aegean region to the central part of Türkiye. During the past four years from 2019 to 2023 large scale efforts used oral rabies vaccination (ORV) to control rabies in red foxes. Here, we present the results of the largest ORV campaign on the Asian continent. Methods: ORV campaigns were carried out twice a year in spring and autumn with a targeted bait density of 20-23 baits/km2. Monitoring of ORV campaigns included the GIS-based analyses of bait distribution, the assessment of bait uptake through biomarker detection and the determination of seroconversion (sero-positivity in ELISA) in the target species collected within the vaccination area. For determination of fox rabies incidence in vaccination areas as the main indicator of the performance of the ORV campaigns, epidemiological data was obtained from the national passive surveillance program. Results: Aerial bait distribution was highly accurate, with >99 % of baits being recorded from targeted zones, thus meeting the desired bait densities. Although the overall bait uptake (28.1 %; 95 %CI: 23.2-32.8) and seroprevalance (36.3 %; 95 %CI: 30.0-43.2) were low, rabies incidence drastically decreased in ORV areas and rabies was eliminated from western and central parts of Turkey, with no reported cases in foxes from ORV areas in 2022 and 2023. Conclusions: A large-scale ORV campaign against fox rabies using high quality vaccine baits and the GIS-aided and monitored bait distribution was able to control fox mediated rabies in the western and central parts of Türkiye. Rabies control both in dogs and foxes should be expanded to cover also the eastern parts of Türkiye, to become eventually rabies free.

Resveratrol inhibits rabies virus infection in N2a cells by activating the SIRT1/Nrf2/HO-1 pathway.

Rabies is a highly lethal infectious disease with no existing treatment available, thus investigating effective antiviral compounds to control rabies virus (RABV) infection is of utmost importance. Resveratrol is a natural phenolic compound that, as a phytoalexin, exhibits several biological activities, including antiviral activity. In this study, we evaluated the inhibitory effect of resveratrol on RABV infection and investigated its molecular antiviral mechanism. We found that resveratrol significantly inhibited RABV infection, including the phases of adsorption, replication, and release, and also directly inactivated RABV and inhibited its infectivity. However, resveratrol had no significant effect on RABV internalization. Resveratrol also reduced RABV-induced oxidative stress, specifically reactive oxygen species and malondialdehyde levels. Western blotting analysis revealed that resveratrol enhanced antioxidant signaling via the SIRT1/Nrf2/HO-1 pathway and inhibited viral replication. Viral infection was enhanced after SIRT1 knockdown, which inhibited the SIRT1/Nrf2/HO-1 antioxidant signaling pathway, suggesting that this pathway plays an important role in RABV replication. Overall, resveratrol prevented the adsorption, replication, and release of RABV and directly inactivated RABV, but failed to inhibit RABV internalization. Furthermore, resveratrol activated the SIRT1/Nrf2/HO-1 pathway to inhibit RABV replication and suppressed RABV-induced oxidative stress. These findings highlight the therapeutic potential of resveratrol for fighting RABV infections.

Dog Bite to the Hand: Infectious Disease Considerations.

We present the case of a 27-year-old man who sustained a bite wound from a stray dog found on the side of a highway. He had cleaned the wound well, hoping to avoid infection, but when it swelled and became red, he sought medical attention. The authors describe the management of cellulitis and prophylaxis for rabies and tetanus.

Factors affecting the outcome of primary rabies vaccination in young cats.

Limited data exist on the factors affecting feline rabies vaccination outcomes during primary immunization. This study aimed to assess if specific factors (signalment, vaccination count, vaccine brand, and time since last vaccination) correlated with meeting global antibody titer standards and absolute titers in young cats given monovalent inactivated rabies vaccines. Analyzing a dataset from cats tested before their first annual booster using the FAVN test, logistic and linear regression models were applied. Among 379 cats, 94.2 % achieved titers meeting or exceeding the standard threshold (≥0.5 IU/ml). Time since last vaccination proved to be the primary predictor of vaccination success. Cats receiving two vaccinations tended toward higher titers. Age, sex, breed, and vaccine type showed no impact on outcomes. The present study indicates that vaccination failure in young cats is uncommon, and that the time interval from the latest vaccination is the single most important predictor of successful rabies vaccination.