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.

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.

Knowledge, attitudes, and practices of healthcare professionals regarding rabies in tertiary care hospitals: A cross-sectional study in Peshawar, Pakistan.

BACKGROUND: Rabies, caused by the rhabdovirus, is a fatal zoonotic disease with over 59,000 annual deaths globally. Asia and Africa account for 95%, with India leading, followed by China. In Pakistan, where it's endemic, over 50,000 cases are reported yearly. Controlling rabid dog populations through vaccination is crucial in curbing mortality. This research aimed to evaluate healthcare professionals' knowledge, attitudes, and practices concerning rabies in Peshawar, Pakistan. METHODS: The study was conducted at different tertiary care hospitals in Peshawar, Pakistan from 16 August 2021 to 15 February 2022. Cross-sectional research was conducted to gather data from a total of 100 healthcare workers representing different sections within the healthcare field, including Medical Officers, House Officers, Faculty Staff, Nurses, and Paramedics. Data on knowledge, attitudes, and practices about rabies were collected using a standardized questionnaire. The data analysis included using descriptive statistics and chi-square testing to ascertain potential correlations. RESULTS: Among the healthcare professionals, 68 (68%) were males, and 32 (32%) were females. Profession-wise, the included professionals were Nurses 31 (31%), Medical Officers 27 (27%), House officers 26 (26%), paramedical staff 13 (13%), and faculty staff 3 (3%). 91 (91%) and 9 (9%) healthcare professionals responded that dogs and cats are responsible for rabies transmission, respectively. Moreover, 82 (82%) individuals responded that animal bite plays a vital role in the transmission of rabies, whilst 76 (76%) individuals responded that rabies transferred from human to human. 82 (82%) individuals replied that the anti-rabies vaccine (ARV) is the treatment of choice for rabies. Furthermore, 78 (78%) individuals responded that ARV is safe in pregnancy and lactation. Moreover, after being asked about the perception of the health care professionals about the failure in controlling rabies, their responses were unavailability of ARV/RIG 41 (41%), lack of control of stray dogs 34 (34%), lack of awareness 20 (20%). The study revealed statistically significant correlations between healthcare occupations and variables: knowledge of animals responsible for transmitting rabies (p = 0.024) and awareness of human-to-human transmission (p = 0.007). Significant disparities were noted in understanding rabies transmission through contaminated water (p = 0.002). There were variations in attitudes and practices seen across different positions, particularly about views about home treatments (p = 0.033) and the perceived effectiveness of cleansing bite wounds (p = 0.010). Disparities in perceptions of rabies treatment and the accessibility of anti-rabies vaccines and immunoglobulin were observed, with variations based on individual roles. CONCLUSION: The present research elucidates variations in rabies knowledge, attitudes, and practices among healthcare workers, specifically concerning their respective roles. Tailored training programs and standardized practices play a crucial role in mitigating these discrepancies, fostering a greater understanding of rabies, and enhancing the quality of patient treatment. It is recommended that future studies undertake an assessment of the efficacy of therapies and advocate for the adoption of collaborative One Health strategies in the realm of rabies management.

Bat Bites and Rabies PEP in the Croatian Reference Centre for Rabies 1995-2020.

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.

Identification of risk factors on rabies vaccine efficacy from censored data: Pre-travel tests for dogs and cats from Yaoundé (2005-2015).

Little research is available on acquired immunity to rabies in dogs and cats from Central Africa, particularly regarding the legal movements of pets. Movement of domestic animals from rabies-endemic countries like Cameroon to rabies free areas poses one of the main risks for rabies introduction into rabies-free areas. Thus, the aim of this study was to assess the effect of various risk factors on rabies vaccine efficacy in Cameroonian. Since the dependent variable, rabies neutralizing titres, were censored from above (right-censoring), Generalized Additive Model for Location, Scale and Shape (GAMLSS) was used in the analysis. Overall, 85.7% of dogs and 100% of cats had titres greater than or equal to 0.5 IU/mL, which is considered protective. Additionally, compared to cats, the value of the rabies-neutralizing serum titres in dogs was on average smaller by 2.3 IU/mL. For each additional year of age, the value of the rabies-neutralizing serum titre, on average, increased by approximately 0.14 IU/mL. Finally, for each 30 additional days between the date of the last rabies vaccination and the date of the sampling, the value the rabies neutralizing titre, on average, decreased by approximately 0.10 IU/mL, given the species and age at sampling were equivalent. These results are useful for assessing risk and improving surveillance to prevent the introduction of rabies into a country via the international movement of animals.

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.

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.

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.

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.

Effect of Rabies Booster Vaccination on Antibody Levels in African Wild Dogs (Lycaon pictus).

Rabies is a highly virulent viral disease that has been associated with large-scale population declines of the endangered African wild dog (Lycaon pictus). Rabies vaccination may be a valuable conservation tool in this species, but studies indicate that a single dose does not always confer protective immunity. We examined 47 serum samples from 22 captive African wild dogs (sampled opportunistically for other purposes) to assess whether serum antibody levels after vaccination correlated with the number of doses received and whether other factors affected outcomes. Results of the fluorescent antibody virus neutralization test showed that median antibody titers were 0.085 IU/mL prevaccination, 0.660 IU/mL after a single vaccination, and 22.150 IU/mL after a booster vaccination. Antibody titers above 0.5 IU/mL, internationally accepted as the threshold for seroconversion, were found in none of the samples taken prevaccination, 66.67% of samples taken after primary vaccination, and 90.90% of samples collected after booster vaccination. This study illustrates the probable protective benefit a rabies booster vaccination may provide in African wild dogs and serves as a basis for future research to improve vaccination protocols contributing to the conservation of this endangered species.

Immunogenicity and Safety of a Purified Vero Rabies Vaccine-Serum Free, Compared With 2 Licensed Vaccines, in a Simulated Rabies Post-Exposure Regimen in Healthy Adults in France: A Randomized, Controlled, Phase 3 Trial.

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.

Comparative analysis of rabies pathogenic and vaccine strains detection by RIG-I-like receptors.

Rabies virus (RABV) is a lethal neurotropic virus that causes 60,000 human deaths every year globally. RABV infection is characterized by the suppression of the interferon (IFN)-mediated antiviral response. However, molecular mechanisms leading to RABV sensing by RIG-I-like receptors (RLR) that initiates IFN signaling currently remain elusive. Here, we showed that RABV RNAs are primarily recognized by the RIG-I RLR, resulting in an IFN response in the infected cells, but this response varied according to the type of RABV used. Pathogenic RABV strain RNAs, Tha, were poorly detected in the cytosol by RIG-I and therefore caused a weak antiviral response. However, we revealed a strong IFN activity triggered by the attenuated RABV vaccine strain RNAs, SAD, mediated by RIG-I. We characterized two major 5' copy-back defective interfering (5'cb DI) genomes generated during SAD replication. Furthermore, we identified an interaction between 5'cb DI genomes, and RIG-I correlated with a high stimulation of the type I IFN signaling. This study indicates that wild-type RABV RNAs poorly activate the RIG-I pathway, while the presence of 5'cb DIs in the live-attenuated vaccine strain serves as an intrinsic adjuvant that strengthens its efficiency by enhancing RIG-I detection thus strongly stimulates the IFN response.

What would be the impact on the rabies risk of reducing the waiting period before dogs are imported? A modelling study based on the European Union legislation.

AIMS: Lyssavirus rabies (RABV) is responsible for a major zoonotic infection that is almost always lethal once clinical signs appear. Rabies can be (re)introduced into rabies-free areas through transboundary dog movements, thus compromising animal and human health. A number of measures have been implemented to prevent this happening, one of which is the waiting period (WP) after anti-rabies vaccination and serological testing. This WP ensures that antibodies assessed through the serological test are due to the vaccine, not to infection. Indeed, if antibodies are due to RABV infection, the dog should display clinical signs within this WP and would not therefore be imported. METHODS AND RESULTS: Within a framework of quantitative risk assessment, we used modelling approaches to evaluate the impact of this WP and its duration on the risk of introducing rabies via the importation of dogs into the European Union. Two types of models were used, a classical stochastic scenario tree model and an individual-based model, both parameterised using scientific literature or data specifically applicable to the EU. Results showed that, assuming perfect compliance, the current 3-month waiting period was associated with a median annual number of 0.04 infected dogs imported into the EU. When the WP was reduced, the risk increased. For example, for a 1-month WP, the median annual number of infected dogs imported was 0.17 or 0.15 depending on the model, which corresponds to a four-fold increase. CONCLUSION: This in silico study, particularly suitable for evaluating rare events such as rabies infections in rabies-free areas, provided results that can directly inform policymakers in order to adapt regulations linked to rabies and animal movements.

Prevenção é a melhor forma de evitar infecção por raiva em humanos

Problema de saúde pública que pode afetar seres humanos, rebanhos e animais domésticos, a raiva é uma doença infecciosa viral aguda e grave, com letalidade próxima a 100%.

Safety and immunogenicity of a serum-free purified Vero rabies vaccine in healthy adults: A randomised phase II pre-exposure prophylaxis study.

A serum-free, highly purified Vero cell rabies vaccine (PVRV-NG) is under development. We previously demonstrated that pre-exposure prophylaxis (PrEP) with PVRV-NG had a satisfactory safety profile and was immunogenically non-inferior to the licensed purified Vero cell rabies vaccine in adults. Here, we evaluated the safety and immunogenic non-inferiority of PrEP with PVRV-NG compared to the licensed human diploid cell vaccine (HDCV) in healthy adults (NCT01784874). Participants received three vaccinations (days 0, 7, and 28) as PrEP with or without a booster injection after 12 months. Rabies virus neutralising antibodies (RVNA) were evaluated on days 0, 28 (subgroup only), and 42, and Months 6, 12, and 12 + 14 days (booster group only). Non-inferiority (first primary objective) was based on the proportion of participants with RVNA titres ≥ 0.5 IU/mL (World Health Organization criteria for seroconversion) on day 42, expected to be ≥ 99% (second primary objective). Safety was evaluated after each dose and monitored throughout the study. At day 42, PVRV-NG was non-inferior to HDCV and the first primary objective was met; seroconversion was observed for 98.3% of PVRV-NG recipients and 99.1% of HDCV recipients. As < 99% of participants in the PVRV-NG group had RVNA titres ≥ 0.5 IU/mL, the second primary objective was not met. Booster vaccination produced a strong increase in RVNA titres for all groups, primed with PVRV-NG or HDCV. RVNA geometric mean titres tended to be higher for HDCV than PVRV-NG primary vaccine recipients. In a complementary evaluation using alternative criteria for seroconversion (complete virus neutralization at 1:5 serum dilution), 99.6% and 100% of participants in the PVRV-NG and HDCV groups, respectively, achieved seroconversion across the vaccine groups. No major safety concerns were observed during the study. PVRV-NG was well tolerated, with a similar safety profile to HDCV in terms of incidence, duration, and severity of adverse events after primary and booster vaccinations. ClinicalTrials.gov number: NCT01784874.

Inhibitory effect of concomitantly administered rabies immunoglobulins on the immunogenicity of commercial and candidate human rabies vaccines in hamsters.

The World Health Organization protocol for rabies post-exposure prophylaxis (PEP) recommends extensive wound washing, immediate vaccination, and administration of rabies immunoglobulin (RIG) in severe category III exposures. Some studies have shown that RIG can interfere with rabies vaccine immunogenicity to some extent. We investigated the interference of RIG on a next generation highly purified Vero cell rabies vaccine candidate (PVRV-NG) versus standard-of-care vaccines in a previously described hamster model. The interference of either human (h) or equine (e) RIG on the immune response elicited by PVRV-NG, Verorab® (purified Vero cell rabies vaccine, PVRV), and Imovax® Rabies (human diploid cell rabies vaccine; HDCV) was evaluated using the 4-dose Essen PEP regimen. The anti-rabies seroneutralizing titers and specific serum IgM titers were measured by fluorescent antibody virus neutralization test and enzyme-linked immunosorbent assay, respectively, for the vaccines administered with or without RIG. The RIG interference on PVRV-NG, observed transiently at Day 7, was similar to that on PVRV and tended to be lower than that on HDCV using both read-outs. In summary, the results generated in the hamster model showed that RIG induced similar or less interference on PVRV-NG than the standard-of-care vaccines.

Review of Oral Rabies Vaccination of Dogs and Its Application in India.

Oral rabies vaccines (ORVs) have been in use to successfully control rabies in wildlife since 1978 across Europe and the USA. This review focuses on the potential and need for the use of ORVs in free-roaming dogs to control dog-transmitted rabies in India. Iterative work to improve ORVs over the past four decades has resulted in vaccines that have high safety profiles whilst generating a consistent protective immune response to the rabies virus. The available evidence for safety and efficacy of modern ORVs in dogs and the broad and outspoken support from prominent global public health institutions for their use provides confidence to national authorities considering their use in rabies-endemic regions. India is estimated to have the largest rabies burden of any country and, whilst considerable progress has been made to increase access to human rabies prophylaxis, examples of high-output mass dog vaccination campaigns to eliminate the virus at the source remain limited. Efficiently accessing a large proportion of the dog population through parenteral methods is a considerable challenge due to the large, evasive stray dog population in many settings. Existing parenteral approaches require large skilled dog-catching teams to reach these dogs, which present financial, operational and logistical limitations to achieve 70% dog vaccination coverage in urban settings in a short duration. ORV presents the potential to accelerate the development of approaches to eliminate rabies across large areas of the South Asia region. Here we review the use of ORVs in wildlife and dogs, with specific consideration of the India setting. We also present the results of a risk analysis for a hypothetical campaign using ORV for the vaccination of dogs in an Indian state.

Household survey on owned dog population and rabies knowledge in selected municipalities in Bulacan, Philippines: A cross-sectional study.

BACKGROUND: Despite the effort to eradicate rabies in the Philippines, human rabies cases have not decreased in the past decade. Rabid dogs pose the most significant hazard in the countries with the highest burden of rabies, and 70% rabies vaccine coverage is recommended for dogs in high-risk areas. Ascertaining the owned dog population and community knowledge on rabies can help improve vaccine coverage and information campaigns. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cross-sectional survey in six randomly selected communities (five urban, one rural) in Central Luzon, Philippines. We first conducted the complete mapping of 9,173 households and then randomly selected 727 households. More than half (54.1%) of the households owned dogs (1.21 dogs/household). In the 727 households, we identified 878 owned dogs and 3256 humans. According to these results, the dog-to-human ratio was approximately 1:3.7. Only 8.8% of households reported a history of dog bite in 2019. Among dog-owning households, 31% reported that they allow their dogs to roam freely. Of the recorded dogs, 35.9% have never been vaccinated, and only 3.5% were spayed or castrated. Factors associated with lower rabies knowledge include (1) no education aOR: 0.30 (0.16-0.59), and (2) only primary school education aOR: 0.33 (0.22-0.49). In contrast, factors associated with higher knowledge include (1) owning a dog and not allowing them to roam freely aOR: 2.01 (1.41-2.87) and (2) owning a dog and allowing them to roam freely aOR: 1.84 (1.17-2.92), when compared to those with no dogs. CONCLUSIONS/SIGNIFICANCE: We identified a larger dog population in the community than the usual estimates (1:10), suggesting that annual vaccine needs in the Philippines must be reassessed. Our survey shows a relatively good understanding of rabies; however, awareness of the concept of rabies as a disease, and how animals and humans can acquire it, is lacking.

Current characteristics of animal rabies cases in Thailand and relevant risk factors identified by a spatial modeling approach.

The situation of human rabies in Thailand has gradually declined over the past four decades. However, the number of animal rabies cases has slightly increased in the last ten years. This study thus aimed to describe the characteristics of animal rabies between 2017 and 2018 in Thailand in which the prevalence was fairly high and to quantify the association between monthly rabies occurrences and explainable variables using the generalized additive models (GAMs) to predict the spatial risk areas for rabies spread. Our results indicate that the majority of animals affected by rabies in Thailand are dogs. Most of the affected dogs were owned, free or semi-free roaming, and unvaccinated. Clusters of rabies were highly distributed in the northeast, followed by the central and the south of the country. Temporally, the number of cases gradually increased after June and reached a peak in January. Based on our spatial models, human and cattle population density as well as the spatio-temporal history of rabies occurrences, and the distances from the cases to the secondary roads and country borders are identified as the risk factors. Our predictive maps are applicable for strengthening the surveillance system in high-risk areas. Nevertheless, the identified risk factors should be rigorously considered and integrated into the strategic plans for the prevention and control of animal rabies in Thailand.

Research Advances on the Interactions between Rabies Virus Structural Proteins and Host Target Cells: Accrued Knowledge from the Application of Reverse Genetics Systems.

Rabies is a lethal zoonotic disease caused by lyssaviruses, such as rabies virus (RABV), that results in nearly 100% mortality once clinical symptoms appear. There are no curable drugs available yet. RABV contains five structural proteins that play an important role in viral replication, transcription, infection, and immune escape mechanisms. In the past decade, progress has been made in research on the pathogenicity of RABV, which plays an important role in the creation of new recombinant RABV vaccines by reverse genetic manipulation. Here, we review the latest advances on the interaction between RABV proteins in the infected host and the applied development of rabies vaccines by using a fully operational RABV reverse genetics system. This article provides a background for more in-depth research on the pathogenic mechanism of RABV and the development of therapeutic drugs and new biologics.