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

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

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

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

A nucleoside-modified mRNA vaccine forming rabies virus-like particle elicits strong cellular and humoral immune responses against rabies virus infection in mice.

Rabies is a lethal zoonotic disease that threatens human health. As the only viral surface protein, the rabies virus (RABV) glycoprotein (G) induces main neutralizing antibody (Nab) responses; however, Nab titre is closely correlated with the conformation of G. Virus-like particles (VLP) formed by the co-expression of RABV G and matrix protein (M) improve retention and antigen presentation, inducing broad, durable immune responses. RABV nucleoprotein (N) can elicit humoral and cellular immune responses. Hence, we developed a series of nucleoside-modified RABV mRNA vaccines encoding wild-type G, soluble trimeric RABV G formed by an artificial trimer motif (tG-MTQ), membrane-anchored prefusion-stabilized G (preG). Furthermore, we also developed RABV VLP mRNA vaccine co-expressing preG and M to generate VLPs, and VLP/N mRNA vaccine co-expressing preG, M, and N. The RABV mRNA vaccines induced higher humoral and cellular responses than inactivated rabies vaccine, and completely protected mice against intracerebral challenge. Additionally, the IgG and Nab titres in RABV preG, VLP and VLP/N mRNA groups were significantly higher than those in G and tG-MTQ groups. A single administration of VLP or VLP/N mRNA vaccines elicited protective Nab responses, the Nab titres were significantly higher than that in inactivated rabies vaccine group at day 7. Moreover, RABV VLP and VLP/N mRNA vaccines showed superior capacities to elicit potent germinal centre, long-lived plasma cell and memory B cell responses, which linked to high titre and durable Nab responses. In summary, our data demonstrated that RABV VLP and VLP/N mRNA vaccines could be promising candidates against rabies.

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

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

Factors associated with the spatiotemporal distribution of dog rabies in Tunisia.

Despite continuous efforts of veterinary services to control rabies in dogs since 1982, rabies remains a cause of death in Tunisia, with more than five reported human cases in 2022. As little is known on the determinants of transmission of rabies in dogs, better understand which factors contribute to its spatial heterogeneity in Tunisia is critical for developing bespoke mitigation activities. In this context, we developed Bayesian Poisson mixed-effect spatio-temporal model upon all cases of rabid dogs reported in each delegation during the period from 2019 to 2021. The best fitting model highlighted the association between the risk of rabies and the mean average monthly temperature, the density of markets and the density of dogs in delegations. Interestingly, no relationship was found between intensity of vaccination in dogs and the risk of rabies. Our results provided insights into the spatio-temporal dynamics of dog rabies transmission and highlighted specific geographic locations where the risk of infection was high despite correction for associated explanatory variables. Such an improved understanding represent key information to design bespoke, cost-efficient, rabies prevention and control strategies to support veterinary services activities and policymaking.

Insights into canine rabies vaccination Disparities in Sierra Leone: A cross-sectional household study.

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 Moyamba, 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 Moyamba to support rabies prevention and control efforts.

Development of mRNA rabies vaccines.

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.

Immunogenicity of 4-dose Essen intramuscular regimen for rabies post-exposure prophylaxis: A multi-center cross-sectional study in China.

BACKGROUND: The 4-dose Essen intramuscular (IM) regimen for rabies post-exposure prophylaxis (PEP) has been recommended by Advisory Committee on Immunization Practices (ACIP) and World Health Organization (WHO), but the large-sample clinical evidence is still limited. METHOD: Rabies virus neutralizing antibodies of 11,752 patients were detected from 409 rabies prevention clinics in 27 provinces in China. Patients with serum collected before or no later than 1 h after injection on the day of the fifth dose (day 28) of 5-dose Essen regimen were included in Group A to observe the immune efficacy of 4-dose Essen IM regimen, and patients with serum collected 14-28 days after injection of the fifth dose were included in Group B to observe the immune efficacy of 5-dose Essen IM regimen. RESULTS: Finally, 2351 cases met the inclusion and exclusion criteria, including 2244 cases in Group A and 107 cases in Group B. The antibody titer of Group A was higher than that of Group B [12.21 (4.15, 32.10) IU/ml vs. 9.41 (3.87, 27.38) IU/ml] (P = 0.002). In Group A, the median antibody titers were 4.01IU/ml, 11.63IU/ml and 29.46IU/ml in patients vaccinated with purified hamster kidney cell vaccine (PHKCV), purified Vero cell vaccine (PVRV), and human diploid cell rabies vaccine (HDCV), respectively, with statistical significance (P < 0.001). CONCLUSIONS: The 4-dose Essen IM regimen could provide satisfactory immune effect, and HDCV induced higher antibody titer than PHKCV or PVRV.

Rabies knowledge gaps and risk behaviour in Dutch travellers: An observational cohort study.

BACKGROUND: Travellers visiting rabies-endemic countries are at risk of rabies infection. Assessing travellers' knowledge and risk perception of rabies and risk behaviour during travel can help identify knowledge gaps and improve pre-travel risk education. METHODS: Cohort study in Dutch adult travellers, using two surveys: one before travel to assess knowledge and perception of rabies, and one after return to identify risk behaviour during travel. RESULTS: The pre-travel and post-travel survey were completed by 301 and 276 participants, respectively. 222 participants had travelled to a high-risk rabies-endemic country. 21.6 % of the participants scored their rabies knowledge as poor. Some participants were unaware cats or bats can transmit rabies (26.6 % and 13.6 %, respectively), or that post-exposure prophylaxis (PEP) is required for certain exposures such as skin abrasions without bleeding or licks on damaged skin (35.5 % and 18.9 %, respectively), while 27.9 % of participants did not know PEP needs to be administered within one day. 115 participants (51.8 %) reported any form of contact with any animal during travel. Two participants reported animal exposure, of which one took adequate PEP measures. Risk factors for animal contact abroad were regularly touching cats or dogs at home or abroad, longer travel duration, having pets during childhood and being an animal lover. CONCLUSIONS: Pre-travel rabies risk education currently does not meet travellers' needs, which is reflected in knowledge gaps and engagement in risk behaviour during travel. During pre-travel health advice, avoiding animal contact abroad should be emphasized, and additional education is required about indications for PEP.

Geographic Distribution of Rabies Virus and Genomic Sequence Alignment of Wild and Vaccine Strains, Kenya.

Rabies, a viral disease that causes lethal encephalitis, kills ≈59,000 persons worldwide annually, despite availability of effective countermeasures. Rabies is endemic in Kenya and is mainly transmitted to humans through bites from rabid domestic dogs. We analyzed 164 brain stems collected from rabid animals in western and eastern Kenya and evaluated the phylogenetic relationships of rabies virus (RABV) from the 2 regions. We also analyzed RABV genomes for potential amino acid changes in the vaccine antigenic sites of nucleoprotein and glycoprotein compared with RABV vaccine strains commonly used in Kenya. We found that RABV genomes from eastern Kenya overwhelmingly clustered with the Africa-1b subclade and RABV from western Kenya clustered with Africa-1a. We noted minimal amino acid variances between the wild and vaccine virus strains. These data confirm minimal viral migration between the 2 regions and that rabies endemicity is the result of limited vaccine coverage rather than limited efficacy.

Zoonoses and pet owners: A survey on risk perception in Northern Italy.

Veterinary and human medicine are focused on the issue of emerging and re-emerging diseases, which are especially represented by zoonosis that could be a threat for public health. Zoonotic risk may come from pets: some canine and/or feline viral, bacterial, parasitic, protozoal or mycotic diseases can be transmitted directly to humans. There are several strategies to prevent the transmission of such zoonosis, and among them vaccination plays an important role. Through a survey carried out in Northern Italy aimed to collect information regarding owners' knowledge and perception of the zoonotic risks associated with three zoonoses (rabies, leptospirosis, and dermatophytosis), it was demonstrated that dog owners tend to adhere more consistently to their pets' vaccination schedules and are more receptive to changes in vaccination scheduling compared to cat owners. This study also suggests that cat owners predominantly visit veterinarians for vaccination purposes, whereas dog owners seek veterinary services for a variety of reasons. The survey highlighted the ongoing need to enhance owners' understanding of zoonoses affecting their pets and also the protective role of vaccines. Veterinarians should undertake the responsibility of educating, reassuring, and informing pet owners about the significance of vaccines for their pets and for public health.

Application prospects of the 2BS cell-adapted China fixed rabies virus vaccine strain 2aG4-B40.

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.

A prospective study on health seeking behaviour and post exposure prophylaxis received by animal bite victims at the anti-rabies clinic in a tertiary care centre of urban Bangalore.

Background: Rabies is 100% preventable by administering early and complete post exposure prophylaxis (PEP). Animal bite victims must have the knowledge and attitude necessary to seek appropriate medical care at the earliest to receive the required PEP. Objectives: The present study sought to ascertain the health-seeking behavior of animal bite victims, their knowledge and attitude regarding rabies prophylaxis, the PEP they received, and their level of compliance with the full course of anti-rabies vaccination. Methods: The study included animal bite cases that presented to the anti-rabies clinic and matched the eligibility criteria. All the required details were recorded using an internally validated structured questionnaire. All participants were followed up for six months to ensure their health conditions and compliance with the vaccination schedule. Results: Out of 1058 respondents, 57.9% were adults, with 46.6% belonging to middle socioeconomic class. 91.1% of them were informed biting animals as dogs. Before arriving at the anti-rabies clinic, 93.3% of the study subjects washed their wounds, and 62.4% visited to another health facility. Rabies knowledge was inadequate among the study participants, only 54.8% being mindful about the disease and its prevention. The compliance with the full course of antirabies vaccination was found to be 77.9%. All subjects were healthy, confirming that PEP is safe and effective. Conclusion: Regular social and behavioral change communication (SBCC) needs to be implemented with regard to health-seeking behavior.

Using remote technology to count dogs.

Georgina Mills discusses how Google Street View could help in counting dogs in Peru to support approaches to rabies management.

Profile and Geospatial Analysis of Dog Bite Cases Attending the Antirabies Vaccine Outpatient Department at the Tertiary Level Hospital of Mumbai.

BACKGROUND: Dog bites pose a significant public health concern in India, necessitating an understanding of their epidemiological profile and spatial distribution. Adopting the One Health approach, which considers the interconnection of human, animal, and environmental health, is vital for developing effective interventions. OBJECTIVES: The study aimed to assess the epidemiological profile and geospatial trends of dog bite cases in an urban area, focusing on the age and gender distribution of victims, severity of bites, and spatial distribution of cases to inform prevention strategies. MATERIALS AND METHODS: A retrospective secondary data analysis was conducted on dog bite cases reported in 2022 at a tertiary care hospital in Mumbai. The epidemiological profile, including age, gender, and severity of bites, was examined. Quantum Geographic Information System (QGIS) was utilized for spatial distribution analysis, identifying hotspots within the urban area. RESULTS: Of the 3350 cases, 70.7% were below 40 years old, 81.6% were male, and 78.18% had Category III bites indicating severe injuries. Most cases (74%) were caused by stray dogs. QGIS analysis revealed five hotspots within the urban area. CONCLUSION: The study highlights the predominance of dog bites among younger males and the severity of injuries. Spatial analysis identified specific hotspots, underscoring the need for targeted interventions. Implementing a comprehensive surveillance system incorporating GIS technology and adopting a One Health approach can enhance the control and prevention of dog bite cases and reduce the risk of rabies outbreaks.

Optimizing the location of vaccination sites to stop a zoonotic epidemic.

Mass vaccinations are crucial public health interventions for curbing infectious diseases. Canine rabies control relies on mass dog vaccination campaigns (MDVCs) that are held annually across the globe. Dog owners must bring their pets to fixed vaccination sites, but sometimes target coverage is not achieved due to low participation. Travel distance to vaccination sites is an important barrier to participation. We aimed to increase MDVC participation in silico by optimally placing fixed-point vaccination locations. We quantified participation probability based on walking distance to the nearest vaccination site using regression models fit to participation data collected over 4 years. We used computational recursive interchange techniques to optimally place fixed-point vaccination sites and compared predicted participation with these optimally placed vaccination sites to actual locations used in previous campaigns. Algorithms that minimized average walking distance or maximized expected participation provided the best solutions. Optimal vaccination placement is expected to increase participation by 7% and improve spatial evenness of coverage, resulting in fewer under-vaccinated pockets. However, unevenness in workload across sites remained. Our data-driven algorithm optimally places limited resources to increase overall vaccination participation and equity. Field evaluations are essential to assess effectiveness and evaluate potentially longer waiting queues resulting from increased participation.

Toward the Development of a Pan-Lyssavirus Vaccine.

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.

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.