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Over the past decade, there has been a growing interest in ferritin-based vaccines due to their enhanced antigen immunogenicity and favorable safety profiles, with several vaccine candidates targeting various pathogens advancing to phase I clinical trials. Nevertheless, challenges associated with particle heterogeneity, improper assembly and unanticipated immunogenicity due to the bulky protein adaptor have impeded further advancement. To overcome these challenges, we devise a universal ferritin-adaptor delivery platform based on structural insights derived from the natural ferritinophagy complex of the human ferritin heavy chain (FTH1) and the nuclear receptor coactivator 4 (NCOA4). The engineered ferritinophagy (Fagy)-tag peptide demonstrate significantly enhanced binding affinity to the 24-mer ferritin nanoparticle, enabling efficient antigen presentation. Subsequently, we construct a self-assembling rabies virus (RABV) vaccine candidate by noncovalently conjugating the Fagy-tagged glycoprotein domain III (GDIII) of RABV to the ferritin nanoparticle, maintaining superior homogeneity, stability and immunogenicity. This vaccine candidate induces potent, rapid, and durable immune responses, and protects female mice against the authentic RABV challenge after single-dose administration. Furthermore, this universal, ferritin-based antigen conjugating strategy offers significant potential for developing vaccine against diverse pathogens and diseases. The study by Fu and colleagues presents a ferritin-adaptor platform for vaccine development, featuring a rabies virus vaccine candidate that enhances antigen stability and provides potent, durable protection after a single-dose administration. [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]

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]

BackgroundMethodsResultsConclusionRabies 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.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.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.These data demonstrate that K. phaffii produced rRABVG is immunoactive and could be an attractive candidate to develop a low-cost subunit rabies vaccine. [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]

The measurement of rabies-neutralizing antibody is important for monitoring the response to rabies vaccination. For all the purposes of measurement, such as routine monitoring of vaccine response in humans and animals, serosurveys, and biologics qualification, accurate and precise results are necessary. The risks associated with sample handling variation, which may impact the test results, can be overlooked within a laboratory. To determine the robustness of rabies-neutralizing antibodies in human and animal serum, samples were treated to mimic various possible deviations in the sample handling protocols. Potential deviations were designed to investigate common client inquiries and possible sample conditions experienced during shipping, storage, and laboratory processes. The treatments included the duration that sera were kept at a temperature greater than that of a refrigerator (room temperature, zero hours to two weeks), the number and duration of heat inactivation treatments (i.e., heat inactivation directly from freezer storage, etc.), the number of freeze–thaw cycles (zero, four, or six cycles), and the storage duration of sample dilutions in chamber slides before the addition of virus (zero hours to overnight). The results provided evidence for the robustness of rabies antibodies and the antibodies' neutralizing function in uncontaminated, clear human and animal serum. In addition, prolonged heat exposure was identified as exerting the greatest impact on the measurement of rabies antibodies. [ABSTRACT FROM AUTHOR]

Background: Veterinarians, veterinary nurses and veterinary students work and train in a variety of environments and are exposed to a wide range of hazards. Objectives: (1) To compare the rate of health and safety incidents and injuries between veterinarians, veterinary nurses and veterinary students. (2) To investigate the health and safety hazard controls present in Australian veterinary workplaces. Study Design: A cross‐sectional study, using an online questionnaire. Methods: Anonymous links to the questionnaire were disseminated to Australian veterinarians, veterinary nurses and veterinary students. Results: A total of 494 veterinarians, 484 veterinary nurses and 212 veterinary students completed the survey. Incidents and injuries were common, particularly sharps‐related injuries and animal bites. Australian veterinary nurses and veterinarians experienced the studied incidents at similar rates to each other. Veterinary students experienced some incidents and injuries at rates higher than both veterinarians and veterinary nurses, including heatstroke, hypothermia, sunburn, electric shock, loss of consciousness, being rammed or pushed over by an animal and farm equipment injuries. Of the workplace hazard controls reported, first aid boxes were most commonly present, and safety meetings occurred least commonly. Veterinary nurses received Q fever and rabies vaccines much less frequently than veterinarians and veterinary students. Conclusion: This study demonstrated that improvements need to be made to the occupational health and safety standards in the Australian veterinary sector. Veterinarians and veterinary nurses had suboptimal rates of access to many of the required and critical workplace health and safety controls. Improvements to the standard of health and safety training of veterinary students are indicated, given their higher rates of certain incidents and injury. [ABSTRACT FROM AUTHOR]

The first licensed malaria vaccine, RTS,S/AS01 E , confers moderate protection against symptomatic disease. Because many malaria infections are asymptomatic, we conducted a large-scale longitudinal parasite genotyping study of samples from a clinical trial exploring how vaccine dosing regimen affects vaccine efficacy. Between Sept 28, 2017, and Sept 25, 2018, 1500 children aged 5–17 months were randomly assigned (1:1:1:1:1) to receive four different RTS,S/AS01 E regimens or a rabies control vaccine in a phase 2b open-label clinical trial in Ghana and Kenya. Participants in the four RTS,S groups received two full doses at month 0 and month 1 and either full doses at month 2 and month 20 (group R012-20); full doses at month 2, month 14, month 26, and month 38 (group R012-14); fractional doses at month 2, month 14, month 26, and month 38 (group Fx012-14; early fourth dose); or fractional doses at month 7, month 20, and month 32 (group Fx017-20; delayed third dose). We evaluated the time to the first new genotypically detected infection and the total number of new infections during two follow-up periods (12 months and 20 months) in more than 36 000 dried blood spot specimens from 1500 participants. To study vaccine effects on time to the first new infection, we defined vaccine efficacy as one minus the hazard ratio (HR; RTS,S vs control) of the first new infection. We performed a post-hoc analysis of vaccine efficacy based on malaria infection status at first vaccination and force of infection by month 2. This trial (MAL-095) is registered with ClinicalTrials.gov , NCT03281291. We observed significant and similar vaccine efficacy (25–43%; 95% CI union 9–53) against first new infection for all four RTS,S/AS01 E regimens across both follow-up periods (12 months and 20 months). Each RTS,S/AS01 E regimen significantly reduced the mean number of new infections in the 20-month follow-up period by 1·1–1·6 infections (95% CI union 0·6–2·1). Vaccine efficacy against first new infection was significantly higher in participants who were infected with malaria (68%; 95% CI 50–80) than in those who were uninfected (37%; 23–48) at the first vaccination (p=0·0053). All tested dosing regimens blocked some infections to a similar degree. Improved vaccine efficacy in participants infected during vaccination could suggest new strategies for highly efficacious malaria vaccine development and implementation. GlaxoSmithKline Biologicals SA, PATH, Bill & Melinda Gates Foundation, and the German Federal Ministry of Education and Research. [ABSTRACT FROM AUTHOR]

Maternal vaccination is a safe and effective means of preventing infection in pregnant women, their fetuses, and infants after birth. Several vaccines are routinely administered in pregnancy as a valuable part of prenatal care with supporting recommendations from national and international health organizations. Fears concerning vaccine safety in pregnancy are pervasive despite sufficient available safety data to support their use, leading to underutilization of maternal immunization. Despite this hesitancy, the field of maternal vaccination is evolving to include more vaccines in the routine prenatal vaccination schedule, including the new RSV vaccine. This review discusses the currently recommended vaccines in pregnancy, evidence for their use, and an overview of ongoing clinical trials investigating prospective vaccines for pregnant women. [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]

Simple Summary: Rabies, a deadly viral disease transmitted mainly through the saliva of infected animals like bats, dogs, and other wildlife, poses significant risks to both livestock and human health, particularly in Brazil. The virus predominantly spreads to herbivores, such as cattle, horses, and goats, through bites from vampire bats. Despite efforts to control the disease through vaccination programs, recent cases in Brazil highlight ongoing challenges. These include sporadic vaccination failures, the presence of vampire bats in some regions, and deforestation, which affects bat habitats and increases disease spread. The economic impact on Brazil's livestock sector is considerable, resulting in losses in meat and milk production and posing public health risks. Effective management strategies involve not only maintaining robust vaccination schedules but also addressing environmental factors that facilitate rabies transmission. Increasing awareness and improving control measures are crucial to reducing the disease's impact. By integrating vaccination efforts with habitat management and ongoing surveillance, Brazil can better protect its livestock and prevent the spread of rabies to humans, ensuring both animal welfare and public health. Rabies, a zoonotic viral disease, poses a significant threat due to its adaptability to diverse environments. Herbivore rabies, predominantly affecting cattle, horses, and goats in Brazil, remains a concern, results in substantial losses in the livestock industry, and poses risks to public health. Rabies virus transmission, primarily through hematophagous bats in Latin America, underscores the need for effective strategies, and vaccination plays a crucial role in controlling herbivorous rabies, with systematic vaccination beingly the primary method. Efforts to control rabies in herbivores include vaccination campaigns, public awareness programs, and the enhancement of surveillance systems. Despite these initiatives, rabies persists and imposes an economic burden and a significant health risk. Economic impacts include losses in the livestock industry, trade restrictions on livestock products, and financial burdens on governments and farmers owing to control measures. Despite the considerable costs of campaigns, surveillance, and control, investing in rabies vaccination and control not only safeguards livestock, but also preserves public health, reduces human cases, and strengthens the sustainability of the livestock industry. Mitigating the impact of herbivorous rabies in Brazil requires integrated approaches and continuous investments in vaccination, surveillance, and control measures to protect public health and ensure the sustainability of the livestock industry, thus contributing to food and economic security. [ABSTRACT FROM AUTHOR]

Background The RTS,S/AS01E (RTS,S) malaria vaccine is recommended for children in malaria endemic areas. This phase 2b trial evaluates RTS,S fractional- and full-dose regimens in Ghana and Kenya. Methods In total, 1500 children aged 5–17 months were randomized (1:1:1:1:1) to receive RTS,S or rabies control vaccine. RTS,S groups received 2 full RTS,S doses at months 0 and 1 and either full (groups R012-20, R012-14-26) or fractional doses (one-fifth; groups Fx012-14-26, Fx017-20-32). Results At month 32 post-dose 1, vaccine efficacy against clinical malaria (all episodes) ranged from 38% (R012-20; 95% confidence interval [CI]: 24%–49%) to 53% (R012-14-26; 95% CI: 42%–62%). Vaccine impact (cumulative number of cases averted/1000 children vaccinated) was 1344 (R012-20), 2450 (R012-14-26), 2273 (Fx012-14-26), and 2112 (Fx017-20-32). To account for differences in vaccine volume (fractional vs full dose; post hoc analysis), we estimated cases averted/1000 RTS,S full-dose equivalents: 336 (R012-20), 490 (R012-14-26), 874 (Fx012-14-26), and 880 (Fx017-20-32). Conclusions Vaccine efficacy was similar across RTS,S groups. Vaccine impact accounting for full-dose equivalence suggests that using fractional-dose regimens could be a viable dose-sparing strategy. If maintained through trial end, these observations underscore the means to reduce cost per regimen thus maximizing impact and optimizing supply. Clinical Trials Registration NCT03276962 (ClinicalTrials.gov). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Rabies virus (RABV) is the etiologic agent of rabies, a fatal brain disease in mammals. Rabies circulation has historically involved the dog has the main source of human rabies worldwide. Nevertheless, in Colombia, cats (Felis catus) have become a relevant species in the epidemiology of rabies. Aims: To characterize rabies cases in humans in Colombia in the last three decades in the context of the epidemiology of the aggressor animal. Materials and Methods: We conducted a retrospective longitudinal epidemiological study of human rabies caused by cats' aggression, collecting primary and secondary information. Variables considered included the demography of the patient, symptoms, information about the aggressor animal as the source of infection and the viral variant identified. Results: We found that the distribution of rabies incidence over the years has been constant in Colombia. Nevertheless, between 2003 and 2012 a peak of cases occurred in rural Colombia where cats were the most frequent aggressor animal reported. Most cats involved in aggression were unvaccinated against rabies. Cat's clinical signs at the time of the report of the human cases included hypersalivation and changes in behaviour. Human patients were mostly children and female and the exposure primarily corresponded to bite and puncture lacerations in hands. The RABV lineage detected in most cases corresponded to variant 3, linked to the common vampire bat (Desmodus rotundus). The geographical presentation of cat borne RABV in humans occurred along the Andes mountains, epidemiologically known as the rabies red Andean corridor. Discussion: By finding cats as the primary source of rabies spillover transmission in Colombia, this report highlights the importance of revising national rabies control and prevention protocol in countries in the Andes region. Conclusion: Our results demonstrate that rabies vaccination for outdoor cats needs to prioritize to reduce the number of rabies‐related human deaths. [ABSTRACT FROM AUTHOR]

Background: Throughout the Americas, Lyssavirus rabies (RV) perpetuates as multiple variants among bat and mesocarnivore species. Interspecific RV spillover occurs on occasion, but clusters and viral host shifts are rare. The spillover and host shift of a big brown bat (Eptesicus fuscus) RV variant Ef-W1 into mesocarnivores was reported previously on several occasions during 2001–2009 in Flagstaff, Arizona, USA, and controlled through rabies vaccination of target wildlife. During autumn 2021, a new cluster of Ef-W1 RV cases infecting striped skunks (Mephitis mephitis) was detected from United States Department of Agriculture enhanced rabies surveillance in Flagstaff. The number of Ef-W1 RV spillover cases within a short timeframe suggested the potential for transmission between skunks and an emerging host shift. Materials and Methods: Whole and partial RV genomic sequencing was performed to evaluate the phylogenetic relationships of the 2021–2023 Ef-W1 cases infecting striped skunks with earlier outbreaks. Additionally, real-time reverse-transcriptase PCR (rtRT-PCR) was used to opportunistically compare viral RNA loads in brain and salivary gland tissues of naturally infected skunks. Results: Genomic RV sequencing revealed that the origin of the 2021–2023 epizootic of Ef-W1 RV was distinct from the multiple outbreaks detected from 2001–2009. Naturally infected skunks with the Ef-W1 RV showed greater viral RNA loads in the brain, but equivalent viral RNA loads in the mandibular salivary glands, compared to an opportunistic sample of skunks naturally infected with a South-Central skunk RV from northern Colorado, USA. Conclusion: Considering a high risk for onward transmission and spread of the Ef-W1 RV in Flagstaff, public outreach, enhanced rabies surveillance, and control efforts, focused on education, sample characterization, and vaccination, have been ongoing since 2021 to mitigate and prevent the spread and establishment of Ef-W1 RV in mesocarnivores. [ABSTRACT FROM AUTHOR]

Children are frequently injured by animal bites, and dog bites account for a large portion of the rabies epidemic worldwide. This case report describes a 3-year-old girl who was bitten by a stray dog and ended up in the emergency room with multiple injuries. The child had extensive bite injuries all over her body. For such injuries, suturing the lesions is the preferred course of action, in conjunction with antibiotic therapy and rabies vaccination. It is essential to administer complete wound care and immediate post-exposure prophylaxis against rabies to guarantee successful treatment and favorable patient results. This report details the child's case, who was followed for 3 months and showed good wound healing and recovery. [ABSTRACT FROM AUTHOR]

Nanoparticle-based antigen carrier systems have become a significant area of research with the advancement of nanotechnology. Biodegradable polymers have emerged as particularly promising carrier vehicles due to their ability to address the limitations of existing vaccine systems. In this study, we successfully encapsulated the G5-24 linear peptide, located between amino acids 253 and 275 in the primary sequence of the rabies virus G protein, into biodegradable and biocompatible PLGA copolymer using the double emulsion solvent evaporation method. The resulting nanoparticles had a size of approximately 230.9 ± 0.9074 nm, with a PDI value of 0.168 ± 0.017 and a zeta potential value of −9.86 ± 0.132 mV. SEM images confirmed that the synthesized nanoparticles were uniform in size and distribution. Additionally, FTIR spectra indicated successful peptide loading into the nanoparticles. The encapsulation efficiency of the peptide-loaded nanoparticles was 73.3%, with a peptide loading capacity of 48.2% and a reaction yield of 30.4%. Peptide release studies demonstrated that 65.55% of the peptide was released in a controlled manner over 28 d, following a 'biphasic burst release' profile consistent with the degradation profile of PLGA. This controlled release is particularly beneficial for vaccine studies. Cytotoxicity tests revealed that the R-NP formulation did not induce cytotoxicity in fibroblast cells and enhanced NO production in macrophages, indicating its potential for vaccine development. [ABSTRACT FROM AUTHOR]

Introduction: Rabies has significant health and economic consequences for both humans and animals. Annually, India witnesses 17.4 million dog bites, yet only 3 million individuals receive post-exposure prophylaxis (PEP). There is a shortage of anti-rabies vaccine in India as quoted in many news reports. In India, lack of documentation of previous vaccination against animal bites is there, hence resulting in the re-administration of the anti-rabies vaccine, leading to a significant biological loss (anti-rabies vaccine) Material and Methods: A cross-sectional, retrospective study was conducted. Data was collected, and analyzed from June 2021 to June 2023 a period of 2 years. Results: Majority of the patients reported within the first 24 hours after being bitten while approximately one-third reported after 24 hours. Majority were Category 3 bites and unprovoked. Males, lower-middle class, and bites on lower extremities were common among 4291 patients attending the clinic. Out of 217 re-exposure cases, 185 did not have any documentation regarding their previous treatment of animal bites. Conclusion: Among 4291 patients attending the clinic, majority were Category 3 bites on the lower extremities. 85.25% of re-exposure cases had to be administered a full course of treatment due to a lack of documentation leading to rabies as a biological wastage. This avoidable wastage can be a resource for treating more patients.

Annually, Sierra Leone records an estimated 301 human fatalities due to rabies. Canine vaccination is crucial for rabies prevention and control efforts. However, considerable variability exists in vaccination rates. Reasons for this variation remain unclear. We conducted a cross-sectional study across 2,558 dog-owning households (HHs) to provide insights into factors influencing canine vaccination for targeted prevention and control towards elimination by 2030. First, we described dog ownership practices, then built a probabilistic model to understand factors associated with dog vaccination, and finally used a spatial scan statistic to identify spatial clusters where vaccination rates were low. Our results indicated that only 14% (358/2,558) of participating HHs had fully vaccinated their dogs against rabies. The probability of dog vaccination increased when comparing civil servants to private workers/artisans, with an Odds Ratio(OR) of 1.14 (95% credible interval (Crl) of 0.82–1.56), residing in locations with a veterinary establishment vs. none (OR = 6.43, 95% Crl (4.97–8.35), providing care to dogs vs. allowing dogs to roam freely (OR = 2.38, 95% Crl(1.80–3.17) and owning a single dog vs multiple dogs (OR = 1.20, 95 Crl (0.92–1.56). Conversely, there was a decrease in the estimated probability of vaccination when comparing dog owners located in rural vs. urban areas (OR = 0.58, CrI 95% (0.43–0.78). Latent understanding, a measure of overall understanding of rabies virus, which we estimated using participant education levels and responses to questions about rabies epidemiology, was also an important predictor of vaccination probability (OR = 1.44, 95% Crl (1.04, 2.07). The spatial analysis identified high-risk clusters for low vaccination in the cities of Mayamba, with a radius of 40 km, a relative risk (RR) of 1.10, and Bo, with a radius of 19.9 km with RR of 1.11. These data do not support Sierra Leone reaching the 2030 goal of human rabies elimination caused by dogs. Our study highlights a critical need for public outreach and education, improved vaccination rates, increased accessibility to veterinary services, and targeted interventions in Bo and Mayamba to support rabies prevention and control efforts. Author summary: Canine vaccination plays a vital role in rabies prevention and control efforts; however, significant variability exists in vaccination rates across Sierra Leone. To address this issue, we conducted a cross-sectional study involving 2,558 dog-owning households to understand the factors influencing canine vaccination and identify areas with low vaccination rates. Our findings revealed that vaccination probability increased among civil servants compared to private workers/artisans, those residing in areas with veterinary establishments, those providing care to dogs, and those owning a single dog. Conversely, vaccination probability decreased among dog owners in rural areas compared to urban areas. Latent understanding, a measure of overall understanding of rabies virus, which we estimated using participant education levels and responses to questions about rabies epidemiology, was also an important predictor of vaccination probability. Spatial analysis identified high-risk clusters for low vaccination rates in Mayamba and Bo. These findings underscore the urgent need for public outreach, education initiatives, improved vaccination rates, enhanced veterinary accessibility, and targeted interventions in Bo and Mayamba to combat rabies effectively. [ABSTRACT FROM AUTHOR]

Rabies is a lethal disease caused by the rabies virus (RABV), which causes acute neurological infections in mammals, including human beings. We previously reported that an mRNA vaccine (LVRNA001) encoding the rabies virus's glycoprotein induced strong protective immune responses to rabies in mice and dogs. Here, we further evaluate the safety of LVRNA001. First, we performed a confirmative efficacy study in dogs, which showed that LVRNA001 fully protected the animals from the virus, both pre- and post-infection. Moreover, using pre- and post-exposure prophylaxis murine models, we showed that LVRNA001, built from the CTN-1 strain, was able to protect against various representative RABV strains from the China I–VII clades. To evaluate the safety of the vaccine, chronic and reproductive toxicity studies were performed with cynomolgus macaques and rats, respectively. In a repeated-dose chronic toxicity study, vaccinated monkeys displayed no significant alterations in body weight, temperature, or hematological and biochemical markers. Lymphocyte subset measurement and histopathological examination showed that no toxicity was associated with the vaccine. The immunogenicity study in cynomolgus macaques demonstrated that LVRNA001 promoted the generation of neutralizing antibodies and Th1-biased immune response. Evaluation of reproductive toxicity in rats revealed that administration of LVRNA001 had no significant effects on fertility, maternal performance, reproductive processes, and postnatal outcomes. In conclusion, LVRNA001 can provide efficient protection against rabies virus infection in dogs and mice, and toxicity studies showed no significant vaccine-related adverse effects, suggesting that LVRNA001 is a promising and safe vaccine candidate for rabies prophylaxis and therapy. [ABSTRACT FROM AUTHOR]

Background: Rabies is a fatal zoonotic disease whose pathogenesis has not been fully elucidated, and vaccination is the only effective method for protecting against rabies virus infection. Most inactivated vaccines are produced using Vero cells, which are African green monkey kidney cells, to achieve large-scale production. However, there is a potential carcinogenic risk due to nonhuman DNA contamination. Thus, replacing Vero cells with human diploid cells may be a safer strategy. In this study, we developed a novel 2BS cell-adapted rabies virus strain and analysed its sequence, virulence and immunogenicity to determine its application potential as a human diploid cell inactivated vaccine. Methods and results: The 2BS cell-adapted rabies virus strain 2aG4-B40 was established by passage for 40 generations and selection of plaques in 2BS cells. RNA sequence analysis revealed that mutations in 2BS cell-adapted strains were not located at key sites that regulate the production of neutralizing antibodies or virulence in the aG strain (GQ412744.1). The gradual increase in virulence (remaining above 7.0 logLD50/ml from the 40th to 55th generation) and antigen further indicated that these mutations may increase the affinity of the adapted strains for human diploid cells. Identification tests revealed that the 2BS cell-adapted virus strain was neutralized by anti-rabies serum, with a neutralization index of 19,952. PrEP and PEP vaccination and the NIH test further indicated that the vaccine prepared with the 2aG4-B40 strain had high neutralizing antibody levels (2.24 to 46.67 IU/ml), immunogenicity (protection index 270) and potency (average 11.6 IU/ml). Conclusions: In this study, a 2BS cell-adapted strain of the 2aG4 rabies virus was obtained by passage for 40 generations. The results of sequencing analysis and titre determination of the adapted strain showed that the mutations in the adaptive process are not located at key sequence regions of the virus, and these mutations may enhance the affinity of the adapted strain for human diploid cells. Moreover, vaccines made from the adapted strain 2aG4-B40 had high potency and immunogenicity and could be an ideal candidate rabies virus strain for inactivated vaccine preparation. [ABSTRACT FROM AUTHOR]

In addition to the rabies virus (RABV), 16 more lyssavirus species have been identified worldwide, causing a disease similar to RABV. Non-rabies-related human deaths have been described, but the number of cases is unknown, and the potential of such lyssaviruses causing human disease is unpredictable. The current rabies vaccine does not protect against divergent lyssaviruses such as Mokola virus (MOKV) or Lagos bat virus (LBV). Thus, a more broad pan-lyssavirus vaccine is needed. Here, we evaluate a novel lyssavirus vaccine with an attenuated RABV vector harboring a chimeric RABV glycoprotein (G) in which the antigenic site I of MOKV replaces the authentic site of rabies virus (RABVG-cAS1). The recombinant vaccine was utilized to immunize mice and analyze the immune response compared to homologous vaccines. Our findings indicate that the vaccine RABVG-cAS1 was immunogenic and induced high antibody titers against both RABVG and MOKVG. Challenge studies with different lyssaviruses showed that replacing a single antigenic site of RABV G with the corresponding site of MOKV G provides a significant improvement over the homologous RABV vaccine and protects against RABV, Irkut virus (IRKV), and MOKV. This strategy of epitope chimerization paves the way towards a pan-lyssavirus vaccine to safely combat the diseases caused by these viruses. [ABSTRACT FROM AUTHOR]

Dog bite injuries often present to Emergency Departments (ED), and between 2001 and 2003, approximately 4.5 million adults and children were injured. Injuries may range from puncture wounds to deep tissue lacerations or avulsions. Deaths have been described. Our objective was to describe dog bite injuries, the overall location of injuries, and need for vaccination among children who presented to a Pediatric ED designated as a level III trauma center with a robust facial surgical infrastructure. This was a 6-year retrospective study. Charts were identified by International Classification of Diseases, Tenth Revision (ICD-10) codes for lacerations or injuries secondary to animal bites and accessing the hospital's trauma database. Variables abstracted were age, sex, type of injury, location, need for antibiotics, immunization states and requirement of tetanus or rabies vaccine, disposition from ED to the operating room, home, or any in-patient unit. We excluded children older than 17 years of age and children who had a post-bite injury infection or injury not initially managed in our facility or medical system. The final cohort consisted of 152 children. The median age was 52 months and age ranged from 2 to 215 months. Children with a single bite injury were older when compared with those with numerous injuries, 81 and 62 months of age, respectively. Among young children, 75% of injuries occurred above the neck and 15.1% were managed in the operating room. Twenty-four percent of children required either a tetanus or rabies vaccination. Most dog bite injuries occurred to facial structures. Comprehensive care of dog victims included awareness of both dog and injured child vaccination status. [ABSTRACT FROM AUTHOR]

Animal-bites are the major cause for rabies transmission to humans. A retrospective study was conducted to determine trends in human animal-bites, spatial distribution and rabies vaccination coverage in cats and dogs in Iringa region for years between 2017 and 2021. Records of animalbites were acquired from animal disease surveillance reports of all Iringa region districts. A total of 2,725 animal-bite human victims were recorded over the period of five years. A decreasing trend in human animal-bites incidence was recorded from 74 bites per 100,000 populations in 2017 to 32 bites per 100,000 populations in 2021. Dogs were the main cause of bites recorded (99%), and the most affected group were children aged between one and 15 years (36%). The spatial distribution of animal-bites cases indicated significant difference between district (P<0.001) with Iringa District Council accounting for 30.2%, Mufindi District Council 21%, Mafinga Town Council 20.7%, Iringa Municipal Council 18.5% and Kilolo District Council accounting for 9.6%. The mean annual vaccination coverage in dogs and cats were about 54% and 35%, respectively during the study period. The number of animal-bite cases recorded is significant to indicate potential risks of rabies transmission to human in Iringa region. Therefore, deliberate efforts should be made in Iringa region to increase vaccination coverage in both cats and dogs. Appropriate intervention measures should also be taken to prevent animal-bites with emphasis to responsible animal ownership. [ABSTRACT FROM AUTHOR]

Background A next-generation Vero cell rabies vaccine (PVRV-NG2) was developed using the same Pitman–Moore strain as in the licensed purified Vero cell vaccine (PVRV; Verorab) and the human diploid cell vaccine (HDCV; Imovax Rabies®). Methods This dual-center, modified, double-blind, phase 3 study evaluated the immunogenic non-inferiority and safety of PVRV-NG2 with and without concomitant intramuscular human rabies immunoglobulin (HRIG) versus PVRV + HRIG and HDCV + HRIG in a simulated post-exposure prophylaxis (PEP) regimen. Healthy adults ≥18 years old (N = 640) were randomized 3:1:1:1 to PVRV-NG2 + HRIG, PVRV + HRIG, HDCV + HRIG, or PVRV-NG2 alone (administered as single vaccine injections on days [D] 0, D3, D7, D14, and 28, with HRIG on D0 in applicable groups). Rabies virus neutralizing antibodies (RVNA) titers were assessed pre- (D0) and post-vaccination (D14, D28, and D42) using the rapid fluorescent focus inhibition test. Non-inferiority, based on the proportion of participants achieving RVNA titers ≥0.5 IU/mL (primary objective), was demonstrated if the lower limit of the 95% CI of the difference in proportions between PVRV-NG2 + HRIG and PVRV + HRIG/HDCV + HRIG was >−5% at D28. Safety was assessed up to 6 months after the last injection. Results Non-inferiority of PVRV-NG2 + HRIG compared with PVRV + HRIG and HDCV + HRIG was demonstrated. Nearly all participants (99.6%, PVRV-NG2 + HRIG; 100%, PVRV + HRIG; 98.7%, HDCV + HRIG; 100%, PVRV-NG2 alone) achieved RVNA titers ≥0.5 IU/mL at D28. Geometric mean titers were similar between groups with concomitant HRIG administration at all time points. Safety profiles were similar between PVRV-NG2 and comparator vaccines. Conclusions In a simulated PEP setting, PVRV-NG2 + HRIG showed comparable immunogenicity and safety to current standard-of-care vaccines. Clinical Trials Registration NCT03965962. [ABSTRACT FROM AUTHOR]

Seroprevalence of lyssaviruses in certain bat species has been proven in the Republic of Croatia, but there have been no confirmed positive bat brain isolates or human fatalities associated with bat injuries/bites. The study included a retrospective analysis of bat injuries/bites, post-exposure prophylaxis (PEP) and geographic distribution of bat injuries in persons examined at the Zagreb Antirabies Clinic, the Croatian Reference Centre for Rabies. In the period 1995–2020, we examined a total of 21,910 patients due to animal injuries, of which 71 cases were bat-related (0.32%). Of the above number of patients, 4574 received rabies PEP (20.87%). However, for bat injuries, the proportion of patients receiving PEP was significantly higher: 66 out of 71 patients (92.95%). Of these, 33 received only the rabies vaccine, while the other 33 patients received the vaccine with human rabies immunoglobulin (HRIG). In five cases, PEP was not administered, as there was no indication for treatment. Thirty-five of the injured patients were biologists or biology students (49.29%). The bat species was confirmed in only one of the exposure cases. This was a serotine bat (Eptesicus serotinus), a known carrier of Lyssavirus hamburg. The results showed that the bat bites were rather sporadic compared to other human injuries caused by animal bites. All bat injuries should be treated as if they were caused by a rabid animal, and according to WHO recommendations. People who come into contact with bats should be strongly advised to be vaccinated against rabies. Entering bat habitats should be done with caution and in accordance with current recommendations, and nationwide surveillance should be carried out by competent institutions and in close collaboration between bat experts, epidemiologists and rabies experts. [ABSTRACT FROM AUTHOR]

Rabies is one of the oldest viral diseases and it has been present on every continent except Antarctica. Within the U.S. human rabies cases are quite rare. In the eastern USA, raccoons are the main reservoir hosts and pet vaccination serves as an important barrier against human rabies exposure. In this paper, we develop a compartmental model for rabies transmission amongst raccoons and domestic pets. We find the disease-free equilibria, reproduction numbers for the raccoons and domestic pets. We also determine the vaccination coverage/rates, both for raccoons and pets, needed to achieve the elimination of rabies. [ABSTRACT FROM AUTHOR]

Rabies virus (RABV) causes fatal neurological disease. Pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) using inactivated-virus vaccines are the most effective measures to prevent rabies. In Japan, HEP-Flury, the viral strain, used as a human rabies vaccine, has historically been propagated in primary fibroblast cells derived from chicken embryos. In the present study, to reduce the cost and labor of vaccine production, we sought to adapt the original HEP-Flury (HEP) to Vero cells. HEP was repeatedly passaged in Vero cells to generate ten- (HEP-10V) and thirty-passaged (HEP-30V) strains. Both HEP-10V and HEP-30V grew significantly better than HEP in Vero cells, with virulence and antigenicity similar to HEP. Comparison of the complete genomes with HEP revealed three non-synonymous mutations in HEP-10V and four additional non-synonymous mutations in HEP-30V. Comparison among 18 recombinant HEP strains constructed by reverse genetics and vesicular stomatitis viruses pseudotyped with RABV glycoproteins indicated that the substitution P(L115H) in the phosphoprotein and G(S15R) in the glycoprotein improved viral propagation in HEP-10V, while in HEP-30V, G(V164E), G(L183P), and G(A286V) in the glycoprotein enhanced entry into Vero cells. The obtained recombinant RABV strain, rHEP-PG4 strain, with these five substitutions, is a strong candidate for production of human rabies vaccine. [ABSTRACT FROM AUTHOR]

Background: Rabies is a neglected tropical disease endemic in 150 countries, including India where it is present in all states and union territories except Andaman and Nicobar Islands Lakshadweep. Kerala reports high incidence of animal bites. This article discusses the preventable death of a 17-year-old tribal girl due to rabies in Kerala and the equity concerns it raises. Methods: The case study was conducted using qualitative methods such as rapid key informant interviews, interactions in tribal assembly meetings, unstructured participant observations, and document verification. Thematic analysis was used, and the results are presented as an ethnographic summary with the use of quotes to substantiate the observations. Results: The girl had gone to a town with her sister for a few days when she developed difficulty in eating, behavioral abnormalities, and injuries on her body. She subsequently died, and a post-mortem revealed Negri bodies in her brain, confirming rabies as the cause of death. The girl had been bitten by a puppy from the forest eight months prior, but she did not receive post-exposure prophylaxis. Multiple dogs are kept in each household in the settlement, and the community takes good care of them since they protect them from wild animals. However, awareness about the need for post-exposure prophylaxis is low, and access to it is difficult for this population. The social problems in the settlement affect their quality of life and their interactions with the outside world. Conclusions: To prevent such deaths, it is essential to increase awareness and ensure equitable access to life-saving vaccines and immunoglobulin in hard-to-reach tribal areas. The cost-effectiveness of pre-exposure prophylaxis for children in high-risk areas such as this tribal settlement should be evaluated and compared with the WHO-recommended strategies of mass canine vaccination and One Health. [ABSTRACT FROM AUTHOR]

In developing countries, it is imperative to implement cost-effective strategies for animal humoral response development in the production of antiserum. This study compared the effect of immunization regimens on the humoral immune response of New Zealand White (NZW) rabbits (N = 24) using cell culture rabies vaccine (CCRV) through intradermal (ID) and traditional intramuscular (IM) routes. The rabbits were divided into three experimental groups: (a) IPC-R2 with a two-site one-week regimen; (b) TRC-R3 with a two-site twenty-eight-day regimen; and (c) Alternate-R4 with a four-site one-week regimen. These regimens were then compared to the standard IM schedule of five doses of rabies vaccine administered at days 0, 3, 7, 14, and 28 in control group R-1. The results were evaluated at days 14 and 35 postvaccination using rabies-specific Platelia II™ ELISA kit method. The results showed a better response to the ID regimen than the IM route regarding immunogenicity and volume consumption of the vaccine. The three selected ID regimes showed significantly higher mean titer values than the control IM regimen group R-1 (p < 0.001). The study aims to explore simple immunization strategies to enhance the RV-specific antibody titers for immunization donor animals. This method would produce polyclonal antibodies and strengthen local production of polyclonal antibodies in Pakistan to deal with vaccine and rabies immunoglobulin (RIG) shortage, thus providing effective postexposure prophylaxis (PEP) for better control of rabies in developing countries. [ABSTRACT FROM AUTHOR]

Simple Summary: This study examined patterns of dog ownership in three different states in India. The main aim was to understand who owns dogs, their reasons for owning them, and how these patterns vary in different areas. We conducted quantitative surveys to gather information on the number of people who own dogs, their backgrounds, and their attitudes towards their pets. Our findings show that there are significant differences in dog ownership depending on where people live and their economic status. In particular, we found settlements in Gujarat state to possess significantly fewer privately owned dogs that Tamil Nadu and Uttarakhand. These results are important because they help us understand the needs of dog owners and their pets in different parts of India. This information can be used by those making decisions about public health and animal welfare, such as how to manage stray dogs or prevent diseases that can spread from dogs to humans. This study is valuable as it provides a clearer picture of dog ownership in India, which can help improve the lives of both people and animals. This paper presents the demographics, dynamics, and attitudes of dog ownership across three states in India. The background of this research is set against the increasing significance of pet ownership in urban Indian contexts, with a particular focus on understanding the variations in dog-ownership patterns and their implications for public health and animal welfare. We employed a survey-based approach, gathering quantitative survey data from dog owners (n = 563) and non-dog-owners (n = 9282) across different socioeconomic and geographic backgrounds in seven Indian settlements. The results reveal notable differences in dog-ownership patterns, influenced by regional state. In particular, settlements in Gujarat were found to have significantly fewer dog-owning households than those in Tamil Nadu, with no differences found according to settlement size. Dog ownership was found to be more common in households of higher socioeconomic standing, and settlements in Uttarakhand were found more frequently to possess dogs for reasons other than companionship. Data from Ahmedabad and Vadodara, specifically, also indicate rapidly increasing rates of pet ownership. Sterilisation and rabies vaccination proportions were typically low and high, respectively, across all settlements, with few significant differences found among settlements. Confinement of owned dogs at night was significantly lower in Nainital than all other settlements. Differences in attitudes towards roaming dogs between dog owners and non-dog-owners were also examined, with the results indicating both positive and negative trends accordingly. Our results emphasise the need for region-specific strategies in public health and animal welfare policies, acknowledging the diverse nature of pet ownership in India. This research provides valuable insight for policymakers and animal welfare organisations, underlining the importance of tailored approaches to address the unique challenges and opportunities in the Indian context. [ABSTRACT FROM AUTHOR]

Introduction This analysis evaluates potential reporting discrepancies of the DD2341 Form (Report of Animal Bite—Potential Rabies Exposure) submitted to a forward-deployed Rabies Advisory Board to the Theater Medical Data Store (TMDS) and Reportable Medical Event (RME) systems to identify reporting gaps that can lead to improved best practices that ensure documentation of Post Exposure Prophylaxis (PEP) of potential rabies exposures into service members (SMs) electronic medical records. Materials and Methods The project compares the number of Service Member animal exposure DD2341 reports submitted to the Camp Arifjan, Kuwait Rabies Advisory Board to in-theater treatment electronic records at the same forward deployed locations from January 1, 2018 to December 31, 2019 recorded in the TMDS and RME databases. Records included active duty and reserve SM deployed to six countries in the United States Central Command (USCENTCOM) area of responsibility. The analysis compared some demographic information, type of potential rabies exposure (e.g. whether a bite or scratch), and PEP to rabies with Human Rabies Immune Globulin (HRIG), Human Rabies Vaccine (HRV), or both between the reporting systems. Results There were 44 fewer records of PEP from the TMDS data records than reported from in theater written reports. Electronic record data showed 85 coded rabies exposure diagnoses. Twenty-two received HRV and no HRIG, while four received HRIG and HRV for PEP. Only seven of the 26 SM receiving rabies PEP had a confirmed RME associated with the electronic record. There were 116 SM animal exposure written reports, with 70 reporting PEP. There were 41 records indicating the SM received HRIG and HRV as part of PEP, while 29 reports indicated that the patient received only HRV PEP. Of the 41 SM receiving HRIG, 32 of the exposures were from cat scratches or bites. Seven records specified HRIG was indicated for treatment but not available at the location; therefore, HRV was the only treatment available. The most common reason indicated on the written report for not receiving rabies PEP was that treatment was not indicated based on the risk category of animal exposure. Conclusions This study is the first to compare the electronic medical record data to in theater reports for potential rabies exposure in a theater of operations. The analysis suggests that some written forms generated in the USCENTCOM theater are not entered into SM Military Health System electronic medical records, indicating that electronic medical records may be a less sensitive method than in-theatre reports for rabies program surveillance in a deployed setting. There is under-reporting in electronic medical records of rabies PEP in both TMDS and RME databases. Rabies PEP is an RME according to the Armed Forces Health Surveillance Division guidelines and case definitions. There needs to be better integration of the DD2341 into the electronic medical records system. [ABSTRACT FROM AUTHOR]

Introduction: Rabies has significant health and economic consequences for both humans and animals. Annually, India witnesses 17.4 million dog bites, yet only 3 million individuals receive post‑exposure prophylaxis (PEP). There is a shortage of anti‑rabies vaccine in India as quoted in many news reports. In India, lack of documentation of previous vaccination against animal bites is there, hence resulting in the re‑administration of the anti‑rabies vaccine, leading to a significant biological loss (anti‑rabies vaccine), Material and Methods: A cross‑sectional, retrospective study was conducted. Data was collected, and analyzed from June 2021 to June 2023 a period of 2 years. Results: Majority of the patients reported within the first 24 hours after being bitten while approximately one‑third reported after 24 hours. Majority were Category 3 bites and unprovoked. Males, lower‑middle class, and bites on lower extremities were common among 4291 patients attending the clinic. Out of 217 re‑exposure cases, 185 did not have any documentation regarding their previous treatment of animal bites. Conclusion: Among 4291 patients attending the clinic, majority were Category 3 bites on the lower extremities. 85.25% of re‑exposure cases had to be administered a full course of treatment due to a lack of documentation leading to rabies as a biological wastage. This avoidable wastage can be a resource for treating more patients. [ABSTRACT FROM AUTHOR]

Background: Rabies remains a public health problem in middle-income countries like Iran, despite being preventable. This study aimed to evaluate the six-year incidence of animal bites in the southern Caspian Sea region from 2016 to 2022, and focus on estimating the direct costs of animal bite cases using the incidence-based method. Methods: A multicenter, registry-based study was conducted using surveillance data of animal bites. Results: Of the 40 922 cases reported during the study period, 65.9% were male and 34.1% were female. Animal bites were most frequent among individuals over 50 years of age (23.5%), while children under 10 years of age had the lowest frequency of animal bites (2.3%). Animal bites were most common in June. Dogs were responsible for 33 277 (81%) cases, cats for 5,624 (13.7%) cases, cows for 1054 (2.5%) cases, and other animals for the remaining cases. During the six-year study period, four deaths due to rabies were reported in the study area. The annual bite incidence rate was 386.3 per 100 000 people in northern Iran. The males-to-female ratio was highest in 2019 (M/F ratio = 2.4, 95% CI = 1.2-3.4). Conclusion: The elderly are at higher risk of animal bites, especially in rural areas. It is important to emphasize the use of protective clothing, washing wounds with soap water and rabies vaccination as initial treatment. Targeted vaccination efforts for eligible animals should be prioritized to minimize unnecessary financial burden. Educating farmers about rabies prevention programs, especially in cases of cow bites, is also important. [ABSTRACT FROM AUTHOR]

Pemphigus is a rare autoimmune bullous disease, with pemphigus vulgaris (PV) and pemphigus foliaceous (PF) being its most common forms. This report presents a case of PF triggered by vaccinations. A previously healthy 38-year-old Caucasian man developed skin lesions six months after receiving vaccinations for hepatitis A, rabies, cholera, typhoid fever, and yellow fever before travelling to Sudan. Exami- nation revealed pruritic erosions, crusts, and flaccid blisters primarily on the trunk and limbs. Histopathology was nonspecific, but direct immunofluorescence showed intercellular IgG, C3c, and C1q deposits. Elevated autoantibodies against desmoglein 1 (DSG1) confirmed the PF diagnosis. The patient responded well to oral prednisone and topical treatments, with complete resolution of symptoms within six months. The aetiology of pemphigus remains unclear, but vaccines can nonspecifically activate the immune system, potentially triggering pemphigus in predisposed individuals. This case highlights the need to consider pemphigus as a potential adverse effect of vaccination. [ABSTRACT FROM AUTHOR]

Rabies, primarily transmitted to humans by dogs (accounting for 99% of cases). Once rabies occurs, its mortality rate is approximately 100%. Post-exposure prophylaxis (PEP) is critical for preventing the onset of rabies after exposure to rabid animals, and vaccination is a pivotal element of PEP. However, high costs and complex immunization protocols have led to poor adherence to rabies vaccinations. Consequently, there is an urgent need to develop new rabies vaccines that are safe, highly immunogenic, and cost-effective to improve compliance and effectively prevent rabies. In recent years, mRNA vaccines have made significant progress in the structural modification and optimization of delivery systems. Various mRNA vaccines are currently undergoing clinical trials, positioning them as viable alternatives to the traditional rabies vaccines. In this article, we discuss a novel mRNA rabies vaccine currently undergoing clinical and preclinical testing, and evaluate its potential to replace existing vaccines.

Rabies control remains challenging in low and middle-income countries, mostly due to lack of financial resources, rapid turnover of dog populations and poor accessibility to dogs. Rabies is endemic in Cambodia, where no national rabies vaccination program is implemented. The objective of this study was to assess the short and long-term vaccination-induced immunity in Cambodian dogs under field conditions, and to propose optimized vaccination strategies. A cohort of 351 dogs was followed at regular time points following primary vaccination only (PV) or PV plus single booster (BV). Fluorescent antibody virus neutralization test (FAVNT) was implemented to determine the neutralizing antibody titer against rabies and an individual titer ≥0·5 IU/mL indicated protection. Bayesian modeling was used to evaluate the individual duration of protection against rabies and the efficacy of two different vaccination strategies. Overall, 61% of dogs had a protective immunity one year after PV. In dogs receiving a BV, this protective immunity remained for up to one year after the BV in 95% of dogs. According to the best Bayesian model, a PV conferred a protective immunity in 82% of dogs (95% CI: 75–91%) for a mean duration of 4.7 years, and BV induced a lifelong protective immunity. Annual PV of dogs less than one year old and systematic BV solely of dogs vaccinated the year before would allow to achieve the 70% World Health Organization recommended threshold to control rabies circulation in a dog population in three to five years of implementation depending on dog population dynamics. This vaccination strategy would save up to about a third of vaccine doses, reducing cost and time efforts of mass dog vaccination campaigns. These results can contribute to optimize rabies control measures in Cambodia moving towards the global goal of ending human death from dog-mediated rabies by 2030. Author summary: Rabies is a fatal zoonotic viral disease. Dog vaccination is recognized as the most cost-effective and sustainable solution to rabies prevention. Cambodia is endemic with canine mediated rabies, that would cause to around 800 human death each year. This country also has a large owned but mostly free-roaming dog population that makes efficient massive vaccination hard to achieve. In this study, we vaccinated 351 dogs with or without booster one year later. We then used serological assessed the short and long-term vaccination-induced immunity in these dogs, and Bayesian modeling to identify a vaccination strategy adapted to the Cambodian dog population characteristics. Yearly primary vaccinations for young dogs, supplemented with a single booster injection of these dogs promises to achieve 70% dog vaccination coverage effectively and efficiently, and control rabies circulation in dog populations. Applying this new strategy running for five more years after the vaccination coverage of at least 70% is achieved, this implies per 1,000 dogs between 2000 and 5 000 saved vaccine doses depending on dog population characteristics. Our results could help controlling rabies in Cambodia and potentially be adopted by other countries facing similar challenges. [ABSTRACT FROM AUTHOR]

A new generation, serum-free, antibiotic-free, purified Vero rabies vaccine (PVRV-NG; Sanofi) has been developed based on the same Pitman-Moore viral strain used for the currently licensed purified Vero cell rabies vaccine (PVRV; Verorab®, Sanofi) and human diploid cell vaccine (HDCV; Imovax® Rabies, Sanofi). PVRV-NG has demonstrated a satisfactory safety profile and induces robust immune responses, with non-inferiority demonstrated versus PVRV when given as a three-dose pre-exposure prophylaxis (PrEP) regimen in healthy children and adults. Here, we evaluated the safety and immunogenic non-inferiority of PVRV-NG compared to HDCV when administered as simulated post-exposure prophylaxis (PEP), with concomitant administration of human rabies immunoglobulin (HRIG), in healthy adults in the USA. Participants were vaccinated according to the 5-dose Essen intramuscular regimen (4-week, 1-injection site regimen, with a single dose given on days 0, 3, 7, 14 and 28) for PEP, with concomitant HRIG administered on day 0. Rabies virus neutralising antibodies (RVNA) were evaluated on days 0, 14, 28 and 42. Non-inferiority of PVRV-NG compared with HDCV was shown if the lower limit of the 95 % confidence interval (CI) for the difference in seroconversion rates (RVNA titers ≥ 0.5 IU/mL on day 14) between PVRV-NG and HDCV was above the non-inferiority margin of –5 %. Safety was evaluated after each vaccination and monitored throughout the study. The difference in seroconversion rate between the PVRV-NG and HDCV groups was –2.8 % (95 % CI, –8.08 to 4.20), indicating that non-inferiority was not demonstrated. The seroconversion rate was < 99 % in both study groups on day 14. There were no major safety concerns identified, and PVRV-NG demonstrated a similar safety profile to HDCV. [ABSTRACT FROM AUTHOR]

• Overview of the mass rabies vaccination carried out in an indigenous Brazilian population. • Technical, operational and logistical adaptations adapted to the local demographic reality. • The benefits of vaccination in response to a rabies outbreak outweigh the risks. • Only serological control will determine the effectiveness of mass rabies vaccination. [ABSTRACT FROM AUTHOR]

The 'One Health' (OH) approach is the most promising idea in realising the global goal of eliminating canine-mediated human rabies by 2030. However, taking an OH approach to rabies elimination can mean many different things to different people. We conducted a systematic review scrutinizing economic evaluations (EEs) retrieved from MEDLINE OVID, Embase OVID, Global Health OVID, CINAHL EBSCO and ECONLIT EBSCO that used the OH approach with the intent of identifying cost-effective sets of interventions that can be combined to implement an optimal OH-based rabies elimination program and highlight key gaps in the knowledge base. Our review suggests that an optimal OH program to tackle rabies should incorporate mass dog vaccination and integrated bite case management in combination with efficient use of post-exposure prophylaxis along with a shift to a 1-week abbreviated intradermal rabies vaccine regimen in humans. We recommend that future EEs of OH interventions for rabies elimination should be performed alongside implementation research to ensure proposed interventions are feasible and adopt a wider societal perspective taking into account costs and outcomes across both the human health and animal welfare sectors. The systematic review has been registered with PROSPERO. [ABSTRACT FROM AUTHOR]

Control of dog-mediated rabies relies on raising awareness, access to post-exposure prophylaxis (PEP) and mass dog vaccination. To assess rabies awareness in Moramanga district, Madagascar, where rabies is endemic, two complementary quantitative and qualitative approaches were carried out in 2018. In the quantitative approach, a standardized questionnaire was administered to 334 randomized participants living in 170 households located less than 5 km from the anti-rabies treatment center (ARTC) located in Moramanga city (thereafter called the central area), and in 164 households located more than 15 km away from the ARTC in two rural communes (thereafter called the remote area). Logistic regression models were fitted to identify factors influencing knowledge and practice scores. The qualitative approach consisted in semi-structured interviews conducted with 28 bite victims who had consulted the ARTC, three owners of biting dogs, three ARTC staff and two local authorities. Overall, 15.6% (52/334) of households owned at least one dog. The dog-to-human ratio was 1:17.6. The central area had a significantly higher dog bite incidence (0.52 per 100 person-years, 95% CI: 0.31–0.84) compared to the remote area (0.22 per 100 person-years, 95% CI: 0.09–0.43) (p = 0.03). The care pathway following a bite depended on wound severity, how the dog was perceived and its owner's willingness to cover costs. Rabies vaccination coverage in dogs in the remote area was extremely low (2.4%). Respondents knew that vaccination prevented animal rabies but owners considered that their own dogs were harmless and cited access and cost of vaccine as main barriers. Most respondents were not aware of the existence of the ARTC (85.3%), did not know the importance of timely access to PEP (92.2%) or that biting dogs should be isolated (11.1%) and monitored. Good knowledge scores were significantly associated with having a higher socio-economic status (OR = 2.08, CI = 1.33–3.26) and living in central area (OR = 1.91, CI = 1.22–3.00). Good practice scores were significantly associated with living in central area (OR = 4.78, CI = 2.98–7.77) and being aware of the ARTC's existence (OR = 2.29, CI = 1.14–4.80). In Madagascar, knowledge on rabies was disparate with important gaps on PEP and animal management. Awareness campaigns should inform communities (i) on the importance of seeking PEP as soon as possible after an exposure, whatever the severity of the wound and the type of biting dog who caused it, and (ii) on the existence and location of ARTCs where free-of-charge PEP is available. They should also encourage owners to isolate and monitor the health of biting dogs. Above all, awareness and dog vaccination campaigns should be designed so as to reach the more vulnerable remote rural populations as knowledge, good practices and vaccination coverage were lower in these areas. They should also target households with a lower socio-economic status. If awareness campaigns are likely to succeed in improving access to ARTCs in Madagascar, their impact on prompting dog owners to vaccinate their own dogs seems more uncertain given the financial and access barriers. Therefore, to reach the 70% dog vaccination coverage goal targeted in rabies elimination programs, awareness campaigns must be combined with free-of-charge mass dog vaccination. Author summary: Despite effective animal and human vaccines, rabies causes over 59,000 human deaths annually, mainly in children and in poor rural communities in Asia and Africa. World Health Organization and partners have recently launched the "Zero by 30" global plan which aims to end human deaths by dog-mediated rabies by 2030 by raising awareness, increasing access to post-exposure prophylaxis (PEP) and mass dog vaccination. In Madagascar, where rabies is endemic, a network of anti-rabies treatment centers (ARTC) delivers free-of-charge vaccines to exposed patients. As little is known on rabies awareness in Malagasy communities, we set up quantitative and qualitative surveys on rabies knowledge, attitudes and practices (KAP). Results showed that major hosts, main transmission routes, clinical signs and outcomes were known by most respondents. Yet knowledge on the existence of ARTC, the usefulness and availability of PEP, usefulness of confining and monitoring biting dogs was very low. Although bite incidence was lower, remote rural areas had more limited knowledge, poorer practices on rabies and extremely low dog vaccination coverage, so awareness campaigns should make sure remote rural populations are reached. If these campaigns are likely to succeed in improving access to ARTCs, their impact on dog vaccination seems more uncertain. Therefore, to reach dog vaccination coverage goals, the center-piece of rabies elimination strategies, awareness campaigns must be combined with free-of-charge mass dog vaccination. [ABSTRACT FROM AUTHOR]

The Indian Grey Wolf Canis lupus pallipes is an iconic species of grassland in India. It is a Schedule 1 species according to the Wildlife Protection Act, 1972 and CITES Appendix 1 species. In the absence of parental care, five wolf pups were rescued from Baavarla on 26 November 2020 and brought into Machia Biological Park for hand rearing. In the absence of colostrum, a milk replacer formula (PetLac) was provided to the pups. The pups were kept at an ambient room temperature of 101°F as an adjustment to their natural surroundings. Gripe water, Vitamin A, and multivitamins were administered orally. The temperature and body growth parameters were measured and recorded weekly. Rabies vaccine was administered in the 26th week from the date of rescue. The diet of the wolf was gradually changed and from the 37th week, raw meat was included in their diet. Antibiotics Ciplox-TZ (ciprofloxacin and tinidazole tablet) Brand-Cipla and SPORLAC-DS (lactic acid bacillus tablets 120M) Brand-sanzyme Ltd. were given periodically to restore the gut fauna of the pups. [ABSTRACT FROM AUTHOR]

Rabies is a zoonotic disease with high lethality. Most human deaths are associated with the bites received from dogs and cats. Vaccination is the most effective method of preventing rabies disease in both animals and humans. In this study, the ability of an adjuvant based on recombinant Salmonella typhimurium flagellin to increase protective activity of the inactivated rabies vaccine in mice was evaluated. A series of inactivated dry culture vaccine for dogs and cats "Rabikan" (strain Shchelkovo-51) with addition of an adjuvant at various dilutions were used. The control preparation was a similar series of inactivated dry culture vaccine without an adjuvant. Protective activity of the vaccine preparations was evaluated by the NIH potency test, which is the most widely used and internationally recommended method for testing effectiveness of the inactivated rabies vaccines. The value of specific activity of the tested rabies vaccine when co-administered with the adjuvant was significantly higher (48.69 IU/ml) than that of the vaccine without the adjuvant (3.75 IU/ml). Thus, recombinant flagellin could be considered as an effective adjuvant in the composition of future vaccine preparations against rabies virus. [ABSTRACT FROM AUTHOR]

Wildlife rabies has been well controlled in Israel due to regular oral rabies vaccine (ORV) campaigns targeting the primary rabies reservoirs, red foxes (Vulpes vulpes) and golden jackals (Canis aureus). During 2017, a rabies outbreak was detected in golden jackals in the Jezreel and Hama'ayanot Valleys covering approximately 500 km2 area in Israel's Northern District. From October 2017 to March 2018, 68 of 93 (73%) reported rabies cases were golden jackals and the majority were juveniles of less than 1 year of age. Unusually high jackal population densities in the region (>80 animals/km2), with a large proportion of juveniles born after the autumn ORV campaign, fueled the outbreak to a peak of 19 reported cases during January 2018. Two high-density ORV campaigns (one during October 2017 and another during March 2018) targeted jackal habitat with bait densities up to 200 baits/km2. In addition to routine November and January baiting cycles, additional ORV baits were deployed during the summer months (July-October) to increase bait uptake by the unvaccinated juveniles. Due to an abundance of aquaculture in the area, bait acceptance studies were performed to confirm sufficient vaccine uptake. As high ambient temperatures conditions are common in the outbreak area, thermostability studies were conducted prior to these campaigns to determine whether the vaccinia-vectored recombinant oral vaccine was suitable for use under extreme weather conditions. Geographically and demographically targeted ORV distribution, paired with population control through focused culling, followed by enhanced rabies surveillance and rapid laboratory testing of suspect wildlife cases, contributed to rapid outbreak control by late March 2018. [ABSTRACT FROM AUTHOR]

Introduction: Rabies is a zoonotic disease that can be fatal and continues to impose a significant financial burden on developing countries. Recently, there have been advancements in the introduction of cell culture vaccines and immunoglobulin, as well as the approval of Intradermal (ID) schedules for vaccine administration. Aim: To assess the knowledge of doctors in Rewa District regarding the National Guidelines for Rabies Prophylaxis in 2019. Materials and Methods: A cross-sectional study was conducted, involving doctors from tertiary healthcare centres, district hospitals, and private practices. Data were collected over a period of one month from 206 doctors using a Google form, which included information about their field of practice and their knowledge of recent guidelines on Rabies prophylaxis. Data analysis was performed using the Chi-square test. Results: Out of the 206 doctors surveyed, 92 (44.7%) were male. A 56.7% of the doctors were aware of the regimen and dosage for ID administration of the Anti Rabies Vaccine, (ARV) and 44.6% were knowledgeable about the modification of Post-Exposure Prophylaxis (PEP) to Pre-Exposure Prophylaxis (PrEP) in the Essen regimen. Furthermore, 70.9% of the doctors were familiar with the dosage of Human Rabies Immunoglobulin (HRIG), while 42.7% knew how to manage animal bites in immunocompromised patients. Conclusion: The study revealed a lack of sufficient knowledge on various aspects of rabies management among the doctors surveyed. This underscores the need for reorientation programs and Continuing Medical Education (CMEs) training to be provided to doctors to enhance their knowledge of rabies and improve the effective management of animal bites. [ABSTRACT FROM AUTHOR]

Echolocating big brown bats (Eptesicus fuscus) broadcast downward frequency-modulated sweeps covering the ultrasonic range from 100–23 kHz in two harmonics. They perceive target range from the time delay between each broadcast and its returning echo. Previous experiments indicated that the bat's discrimination acuity for broadcast-echo delay declines when the lowest frequencies (23–35 kHz) in the first harmonic of an echo are removed. This experiment examined whether echo detection is similarly impaired. Results show that detection thresholds for echoes missing these lowest frequencies are raised. Increased thresholds for echoes differing in spectra facilitates the bat's ability to discriminate against clutter. [ABSTRACT FROM AUTHOR]

BACKGROUND: This study aimed to establish chemometric models using Raman spectroscopy data for biochemical monitoring of rabies Virus‐Like Particles (VLP) production based on baculovirus/insect cell system. The models were developed using fresh and stored samples from the initial development stages (Schott culture flasks). The following modeling techniques were assessed: partial least squares (PLS) and artificial neural networks (ANN). The effects of spectral filtering approaches, spectral ranges (400–1850 cm−1; 100–3425 cm−1), and sample cryopreservation were also considered. The applicability of the models was evaluated using experimental data from assays carried out in a benchtop bioreactor. RESULTS: The results showed that the prediction capacity of the chemometric models was negatively impacted when samples from rabies VLP production were cryopreserved. Further studies are needed to confirm the maximum storage time for samples (< 4 months) without a significant difference in model predictions compared to those from an in line database. The dilution of the sample should be kept constant throughout the rabies VLP development stages. A nonlinear correlation was observed between dilution and the predicted values of biochemical parameters from Raman spectral data. The choice of spectral filtering has a major impact on the prediction accuracy of chemometric models. CONCLUSION: The optimal filtering approach should be individually optimized for each biochemical parameter. The ANN models were significantly more suitable for biochemical monitoring than the PLS approach. The 400–1850 cm−1 Raman shift range is recommended for biochemical monitoring of rabies VLP using a baculovirus/insect cell platform when samples are cell‐free. © 2023 Society of Chemical Industry (SCI). [ABSTRACT FROM AUTHOR]