Assessment of respondents' knowledge, attitudes, and practices toward rabies and associated risk factors in Shone Town, Southern Ethiopia.

IMPORTANCE: Rabies is a neglected tropical viral disease most often transmitted through the bite of an infected animal. OBJECTIVE: This study assessed the level of knowledge, attitudes, and practices of the Shone Town community toward rabies. METHODS: A survey-based cross-sectional study was conducted in Shone town, Ethiopia, from November 2022 to April 2023. Woreda was selected purposefully, while Kebeles and the study populations were selected by simple random sampling. Four hundred and sixteen respondents were interviewed using a semi-structured questionnaire. RESULTS: All respondents had heard about rabies from different sources, with the majority hearing from informal sources (62%). Approximately 51.9%, 0.7%, and 47.4% of individuals were aware of saliva contact, rabid animal bites, and both as means of transmission, respectively. The survey showed that 64.4% of participants knew the 100% fatal nature of rabies once the clinical signs developed, and 35.6% did not. Approximately 51.4% of respondents agreed that killing stray dogs was an effective method for rabies prevention. In this study, 72.6% of the respondents had contact with pets, and 36.8% of the interviewees had vaccinated their dogs. Only the educational level (p = 0.03) was associated with knowledge of the transmission route. Age (p = 0.04) and educational level (p = 0.01) had a statistically significant association with knowledge of the risk of not vaccinating dogs. CONCLUSIONS AND RELEVANCE: A lack of formal education in the communities, low levels of education, and the majority of respondents acquiring their knowledge from unofficial sources are important contributors to the low levels of awareness.

Dog ecology and rabies control including canine vaccination coverage: Impacts from a survey in Madagascar.

BACKGROUND: Rabies virus (RABV; species Lyssavirus rabies) is causing one of the oldest zoonotic diseases known to mankind, leading to fatal encephalomyelitis in animals and humans. Despite the existence of safe and effective vaccines to prevent the disease, an estimated 99% of human rabies deaths worldwide are caused by dog-mediated rabies with children at the highest risk of infection. Rabies has been endemic in Madagascar for over a century, yet there has been little research evaluating local knowledge and practices impacting on the rabies control and prevention. Thus, this study was undertaken to better understand the dog ecology including canine vaccine coverage and to assess knowledge and practices of dog owners and veterinarians. METHODOLOGY: A cross-sectional study was conducted among 123 dog-owning households in thirteen fokontanys in Mahajanga from July 4 to September 13, 2016. Single and multi-member dog-owning households in the study area on the day of the interview were eligible for inclusion and purposively selected with the support of a local guide. The survey included a household questionnaire capturing information on the dog's demographics, husbandry practices, knowledge and practices towards rabies and its control measures; the dog ecology questionnaire collected dog characteristics, vaccination status and husbandry practices. All households that reported a dog bite incident, were invited to participate in a dog bite questionnaire. In addition, direct observations of roaming dogs were conducted to assess dog population demographics and to document behavioural characteristics. Two veterinarians were purposively selected and took part in an interview during the survey period, providing information on rabies control activities, including dog-care practices in the area. Descriptive and inferential data analyses were performed using Epi Info version 7.1.5.0 (CDC Atlanta, USA). RESULTS: We recorded a total of 400 dogs, of which 338 (84.5%) were owned amongst 123 households. More than half (67.8%) of owned dogs were between 1 to 5 years old and 95.6% were kept for guarding purposes. 45% of the surveyed dogs had free access to roam outside the premises. The majority (85.4%) of dog owners were knowledgeable that a dog bite could potentially transmit RABV to humans. 19 dog bites were reported and of these 73.6% were caused by the owner's or a neighbour's dog. In 6 of the 19 cases, children between 7 and 15 years of age were the victims. Dog vaccination coverage against rabies was 34% among owned dogs. Of the participants aware of a veterinarian, the majority (55/82) indicated that they accessed veterinarian services at irregular intervals. The main obstacles to vaccinations cited by dog owners were limited financial resources and difficulty accessing veterinary care. CONCLUSION: This study contributes to enhanced understanding of the dog ecology including canine vaccine coverage as well as knowledge and practices of dog owners in Madagascar. Most dogs in the study area were accessible for preventive vaccination through their owners, however only one third of the investigated canine population was vaccinated against rabies. Concerted national efforts towards rabies prevention and control should aim to address financial challenges and access to veterinary services.

All the Better to Taste You With, My Dear: ED Management of Mammalian Bites.

Mammal bites account for over 5 million visits to Emergency Departments (EDs) annually. Nurse Practitioners (NPs) need to stay abreast of current guidelines, changes to antibiotic regimens that are now most effective, and understand in what circumstances collaboration with other specialists is indicated. It is not enough to care for the wound, itself, but rather understand in what presentations additional care may be needed despite the fact that there is no clear evidence at the time of evaluation of the need for advanced care. Additionally, NPs should understand what resources are available within their community for wound care that may exceed the scope and ability of the facility in which they practice. Health departments may need to be utilized in the care of ED patients who present with wounds that are suspicious for rabies. Finally understanding what constitutes a high, medium, and low risk bite will aide NPs in delivering optimal care within the communities they serve while also minimizing patient morbidity.

Construction of Vero cell-adapted rabies vaccine strain by five amino acid substitutions in HEP-Flury strain.

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.

An assessment of the operationality and factors influencing the effectiveness of rabies surveillance in Gombe State, Nigeria.

Rabies remains a burden in Africa, disproportionately affecting the most vulnerable despite the availability of effective vaccines. Nigeria, the most populous African country, needs rapid disease control actions and commitments to achieve the goal of eliminating dog-mediated rabies by 2030. Surveillance is an essential element of effective disease control strategies. This study examined the current state of operationality of the rabies surveillance system for early case detection and management in Gombe state, Nigeria, through a One Health lens. It further examined the barriers impeding the effectiveness of the surveillance based on the perception of surveillance workers. Qualitative and quantitative methods were used to assess the structure of the system and its functioning. Data on dog bite and rabid cases obtained from the veterinary services in Gombe state were analysed descriptively. A total of 13 key informants were interviewed using a semi-structured interview guide. Qualitative data were analysed using thematic analysis to explore in depth the factors that influenced the operationality of the system. A total of 157 potential human exposures to rabies were identified in this study, out of which two people reportedly died at the health facility after showing symptoms highly suggestive of rabies. In terms of rabies surveillance and control, cross-sectoral collaboration was found between the human health and veterinary sectors for risk assessment of potential rabies exposures and its management. Some identified factors affecting the operations of the surveillance were inadequate funding, lack of infrastructure, lack of feedback from higher authorities and insufficient knowledge of rabies prevention and management. To improve the capacity for case detection and management within the state, the appropriate authorities may focus on increasing awareness about the disease to the populace to increase the number of cases identified by the system, employ more workers and strengthen the surveillance capability of existing workers.

Trends in Animal Bites and Rabies-related Deaths in Northern Iran: Implications for Public Health Interventions.

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 40922 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 33277 (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 100000 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.

One-dose intradermal rabies booster enhances rabies antibody production and avidity maturation.

The incidence of rabies in Thailand reached its peak in 2018 with 18 human deaths. Preexposure prophylaxis (PrEP) vaccination is thus recommended for high-risk populations. WHO has recently recommended that patients who are exposed to a suspected rabid animal and have already been immunized against rabies should receive a 1-site intradermal (ID) injection of 0.1 mL on days 0 and 3 as postexposure prophylaxis (PEP). In Thailand, village health and livestock volunteers tasked with annual dog vaccination typically receive only a single lifetime PrEP dose and subsequent boosters solely upon confirmed animal bites. However, the adequacy of a single PrEP dose for priming and maintaining immunity in this high-risk group has not been evaluated. Therefore, our study was designed to address two key questions: (1) sufficiency of single-dose PrEP-to determine whether a single ID PrEP dose provides adequate long-term immune protection for high-risk individuals exposed to numerous dogs during their vaccination duties. (2) Booster efficacy for immune maturation-to investigate whether one or two additional ID booster doses effectively stimulate a mature and sustained antibody response in this population. The level and persistence of the rabies antibody were determined by comparing the immunogenicity and booster efficacy among the vaccination groups. Our study demonstrated that rabies antibodies persisted for more than 180 days after cost-effective ID PrEP or the 1st or the 2nd single ID booster dose, and adequate antibody levels were detected in more than 95% of participants by CEE-cELISA and 100% by indirect ELISA. Moreover, the avidity maturation of rabies-specific antibodies occurred after the 1st single ID booster dose. This smaller ID booster regimen was sufficient for producing a sufficient immune response and enhancing the maturation of anti-rabies antibodies. This safe and effective PrEP regimen and a single visit involving a one-dose ID booster are recommended, and at least one one-dose ID booster regimen could be equitably implemented in at-risk people in Thailand and other developing countries. However, an adequate antibody level should be monitored before the booster is administered.

Comparative Study on the Immunogenicity and Efficacy of Different Post-exposure Intramuscular Rabies Vaccination Regimens in China.

Objective: This study aimed to compare the current Essen rabies post-exposure immunization schedule (0-3-7-14-28) in China and the simple 4-dose schedule (0-3-7-14) newly recommended by the World Health Organization in terms of their safety, efficacy, and protection. Methods: Mice were vaccinated according to different immunization schedules, and blood was collected for detection of rabies virus neutralizing antibodies (RVNAs) on days 14, 21, 28, 35, and 120 after the first immunization. Additionally, different groups of mice were injected with lethal doses of the CVS-11 virus on day 0, subjected to different rabies immunization schedules, and assessed for morbidity and death status. In a clinical trial, 185 rabies-exposed individuals were selected for post-exposure vaccination according to the Essen schedule, and blood was collected for RVNAs detection on days 28 and 42 after the first immunization. Results: A statistically significant difference in RVNAs between mice in the Essen and 0-3-7-14 schedule groups was observed on the 35th day ( P < 0.05). The groups 0-3-7-14, 0-3-7-21, and 0-3-7-28 showed no statistically significant difference ( P > 0.05) in RVNAs levels at any time point. The post-exposure immune protective test showed that the survival rate of mice in the control group was 20%, whereas that in the immunization groups was 40%. In the clinical trial, the RVNAs positive conversion rates on days 28 (14 days after 4 doses) and 42 (14 days after 5 doses) were both 100%, and no significant difference in RVNAs levels was observed ( P > 0.05). Conclusion: The simple 4-dose schedule can produce sufficient RVNAs levels, with no significant effect of a delayed fourth vaccine dose (14-28 d) on the immunization potential.

Protective Activity of Inactivated Rabies Vaccine Using Flagellin-Based Adjuvant.

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.

Bayesian modeling of post-vaccination serological data suggests that yearly vaccination of dog aged <2 years old is efficient to stop rabies circulation in Cambodia.

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.

Mixed methods to evaluate knowledge, attitudes and practices (KAP) towards rabies in central and remote communities of Moramanga district, Madagascar.

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 (0.53 per 100 person-years, 95% CI: 0.31-0.85) 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 (89.5%) 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.

Bovine rabies cases in Ecuador: a retrospective cross-sectional observational study (2007 to 2020).

The hematophagous bats are usually the main reservoir of sylvatic rabies, being one of the most important viral zoonoses affecting humans and livestock in Latin America. Despite the most countries have already studied spatio-temporal distribution of bovine rabies, however, in Ecuador, little has been reported about the state of rabies in the country. Aiming to this objective, a descriptive observational study was realized from 2007 to 2020 based on the formal reports by WAHI-OIE and surveillance of bovine rabies retrieved from its official website. During the study period in Ecuador, some 895 cases of rabies were confirmed in cattle. In addition, in the total of bovine rabies cases seen in Andean and Coast regions (185 effected bovines), Loja and Esmeraldas had 95 (6.16% cases per 10,000 animals) and 51 (1.7% cases per 10,000 animals), respectively. Furthermore, the Amazon region indicated higher rabies cases in cattle than to the observed in other regions (710 rabies cases) while it was highly fluctuating with respect to the years (9.74 to 42.82% cases per 10,000 animals). However, Zamora (292 rabies cases), Orellana (115 rabies cases) and Sucumbíos (113 rabies cases) yielded the highest incidence rates than other provinces (9 to 42% cases per 10,000 animals). Based on this evidence, it has been fundamental to assess the current national program for preventing and control of the sylvatic rabies, being also necessary to include concept of the ecology of the vampire bat. Regardless of these results, vaccination is vital for control programs to prevent rabies in livestock and need to be widely increased for limiting their geographic and temporal spread.

Immunogenicity evaluation of a bivalent vaccine based on a recombinant rabies virus expressing gB protein of FHV-1 in mice and cats.

Feline viral rhinotracheitis (FVR) is caused by the feline herpesvirus-1 (FHV-1), which commonly results in upper respiratory symptoms, and can result in death in the kittens and weak cats. Rabies is an infectious disease with zoonotic characteristics highly relevant to public health and also poses a serious threat to cats. Vaccines are the most effective method to control the spread of both FHV-1 and RABV and have the advantage that they produce long-term specific immune responses. In this study, we constructed a bivalent vaccine against FHV-1 and rabies virus (RABV) simultaneously. The vaccine was constructed by cloning FHV-1 gB into a RABV based vector, and the recombinant RABV (SRV9-FHV-gB) expressing the FHV-1 gB protein was rescued. The growth characteristics of SRV9-FHV-gB were analyzed on NA and BSR cells. To assess the immunogenicity of the vaccine, mice and cats were immunized with SRV9-FHV-gB supplemented with Gel02 adjuvant. The SRV9-FHV-gB exhibited the same growth characteristics as the parent virus SRV9 in both BSR cells and NA cells. The safety of SRV9-FHV-gB was evaluated using 5-day-old and 14-day-old suckling mice. The results showed that mice infected with the SRV9-FHV-gB survived for longer than those in the SRV9 group. Mice immunized with inactivated SRV9-FHV-gB produced high titers of specific antibodies against FHV-1 and neutralizing antibodies against RABV. Cats that received three immunizations with SRV9-FHV-gB also produced neutralizing antibodies against both FHV-1 and RABV. This study represents the first time that a bivalent vaccine targeting FHV-1 and RABV has been constructed, laying the foundations and providing inspiration for the development of other multivalent vaccines.

Mathematical model of rabies vaccination in the United States.

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.

Spatial clusters, temporal behavior, and risk factors analysis of rabies in livestock in Ecuador.

Rabies, a globally distributed and highly lethal zoonotic neglected tropical disease, has a significant impact in South America. In Ecuador, animal rabies cases are primarily linked to livestock, and hematophagous bats play a crucial role in disease transmission. This study aims to identify temporal trends, spatial patterns, and risk factors for animal rabies in Ecuador between 2014 and 2019. Epidemiological survey reports from the official Animal Rabies Surveillance Program of the Phyto and Zoosanitary Regulation and Control Agency of Ecuador (AGROCALIDAD) were used. The Animal Rabies Surveillance Program from AGROCALIDAD consists of an official passive surveillance program that receives reports from farmers or individuals (both trained or untrained) who have observed animals with neurological clinical signs and lesions compatible with bat bites, or who have seen or captured bats on their farms or houses. Once this report is made, AGROCALIDAD personnel is sent for field inspection, having to confirm the suspicion of rabies based on farm conditions and compatibility of signs. AGROCALIDAD personnel collect samples from all suspicious animals, which are further processed and analyzed using the Direct Fluorescent Antibody (DFA) test for rabies confirmatory diagnosis. In this case, study data comprised 846 bovine farms (with intra-farm sample sizes ranging from 1 to 16 samples) located in different ecoregions of Ecuador; out of these, 397 (46.93%) farms tested positive for animal rabies, revealing six statistically significant spatial clusters. Among these clusters, three high-risk areas were identified in the southeast of Ecuador. Seasonality was confirmed by the Ljung-Box test for both the number of cases (p < 0.001) and the positivity rate (p < 0.001). The Pacific Coastal lowlands and Sierra regions showed a lower risk of positivity compared to Amazonia (OR = 0.529; 95% CI = 0.318 - 0.883; p = 0.015 and OR = 0.633; 95% CI = 0.410 - 0.977; p = 0.039, respectively). The breeding of non-bovine animal species demonstrated a lower risk of positivity to animal rabies when compared to bovine (OR = 0.145; 95% CI = 0.062 - 0.339; p < 0.001). Similarly, older animals exhibited a lower risk (OR = 0.974; 95% CI = 0.967 - 0.981; p < 0.001). Rainfall during the rainy season was also found to decrease the risk of positivity to animal rabies (OR = 0.996; 95% CI = 0.995 - 0.998; p < 0.001). This study underscores the significance of strengthening the national surveillance program for the prevention and control of animal rabies in Ecuador and other countries facing similar epidemiological, social, and geographical circumstances.

Recombinant transmissible vaccines will be intrinsically contained despite the ability to superinfect.

INTRODUCTION: Transmissible vaccines offer a novel approach to suppressing viruses in wildlife populations, with possible applications against viruses that infect humans as zoonoses - Lassa, Ebola, rabies. To ensure safety, current designs propose a recombinant vector platform in which the vector is isolated from the target wildlife population. Because using an endemic vector creates the potential for preexisting immunity to block vaccine transmission, these designs focus on vector viruses capable of superinfection, spreading throughout the host population following vaccination of few individuals. AREAS COVERED: We present original theoretical arguments that, regardless of its R0 value, a recombinant vaccine using a superinfecting vector is not expected to expand its active infection coverage when released into a wildlife population that already carries the vector. However, if superinfection occurs at a high rate such that individuals are repeatedly infected throughout their lives, the immunity footprint in the population can be high despite a low incidence of active vaccine infections. Yet we provide reasons that the above expectation is optimistic. EXPERT OPINION: High vaccine coverage will typically require repeated releases or release into a population lacking the vector, but careful attention to vector choice and vaccine engineering should also help improve transmissible vaccine utility.

Real-world evidence of rabies post-exposure prophylaxis in Serbia: Nation-wide observational study (2017-2019).

BACKGROUND: Rabies remains a deadly zoonotic disease, primarily prevalent in Eastern European countries, with a significant global burden in Asia and Africa. Post-exposure prophylaxis (PEP) is critical to prevent clinical rabies. Serbia, a country with a relatively low animal rabies incidence, has been implementing a 4-dose Essen PEP regimen for 13 years. This real-world study aimed to assess the effectiveness of the 4-dose Essen regimen, considering demographic and clinical factors, after WHO Category III exposure. METHOD: The study included 601 patients who received the 4-dose Essen PEP and 79 who received an additional 5th dose. RESULTS: Age emerged as a critical factor influencing seroconversion rates after the 4-dose regimen, with older individuals exhibiting lower RVNA titers. Logistic regression indicated a 3.18% decrease in seroconversion odds for each added year of age. The Cox proportional hazards mixed model highlighted age-related risks, with age groups 45-60 and 75-92 at the highest risk of non-seroconversion. Human Rabies Immune Globulin (HRIG) administration was associated with lower RVNA values after the 4-dose regimen, suggesting interference with vaccine immunogenicity among people who received larger doses of HRIG. CONCLUSIONS: This study provides valuable real-world evidence for rabies PEP in a non-homogeneous population with potential comorbidities. The results underscore the importance of optimizing PEP strategies, particularly in older individuals, and reconsidering HRIG dosing to improve seroconversion rates.

Mechanism of action of phthalazinone derivatives against rabies virus.

Rabies, a viral zoonosis, is responsible for almost 59,000 deaths each year, despite the existence of an effective post-exposure prophylaxis. Indeed, rabies causes acute encephalomyelitis, with a case-fatality rate of 100 % after the onset of neurological clinical signs. Therefore, the development of therapies to inhibit the rabies virus (RABV) is crucial. Here, we identified, from a 30,000 compound library screening, phthalazinone derivative compounds as potent inhibitors of RABV infection and more broadly of Lyssavirus and even Mononegavirales infections. Combining in vitro experiments, structural modelling, in silico docking and in vivo assays, we demonstrated that phthalazinone derivatives display a strong inhibition of lyssaviruses infection by acting directly on the replication complex of the virus, and with noticeable effects in delaying the onset of the clinical signs in our mouse model.