Search Results (19)

Rabies is a neglected tropical zoonotic disease caused by rabies-virus (RV) infection and is responsible for almost 60,000 annual deaths globally, largely affecting the socio-economically disadvantaged population. Although fatality is preventable by immunization either before or after exposure with therapeutic antibodies, the high cost of prophylaxis or treatment limits their accessibility for the affected population. However, due to the almost 100% fatality rate in symptomatic individuals, almost 29 million annual vaccinations are performed, imposing high financial burden. Human transmission occurs principally through bites from infected dogs and although multiple mammalian species are permissive to RV, transmission from them or from symptomatic humans is rare. To overcome the limitations posed by the requirement of biosafety level-3 (BSL-3) containment for live virus culture, we established a replication-deficient vesicular stomatitis virus (VSV) pseudovirus expressing the Rabies-G (RV-G) protein and a multiplexed Luminex immunoassay for quantifying anti-rabies antibodies in equine sera. The purified pseudovirus exhibited robust luciferase activity and was able to infect multiple mammalian cell lines, although with variable efficiency. Using hyper-immunized equine serum, we observed a strong correlation (ρ > 0.9, p < 0.001) between binding antibody titers measured by the Luminex assay with neutralizing antibody titers determined using the pseudovirus-based neutralization assay. These assays provide a safe, quantitative, and BSL-2-compatible platform for rabies serological evaluation and vaccine testing. Full article

Background and Objectives: Although preventable, rabies represents a significant public health problem. An important part of prevention is the surveillance of people exposed to potentially rabid animals, carried out in the anti-rabies clinics of all public health institutes in Croatia. We aimed to analyze the burden of human animal-bite injuries, patient/biting animal characteristics, and the uptake of anti-rabies post-exposure prophylaxis (PEP). Material and Methods: This retrospective study used medical records data ranging from 2015 to 2024 for all patients in the anti-rabies clinics in Split-Dalmatia County, Croatia. Results: A total of 4105 patients reported contact with a potentially rabid animal. The majority of examined people (52.6%) were working-aged adults (20–60 years). The largest proportion of reported injuries were recorded on the lower limbs (34.9%) and hands/fingers (32.3%). No contact with a proven rabid animal was recorded. PEP was received by 37.7% of those examined. Although dog exposure (68.9%) most frequently led to post-exposure care-seeking, PEP was most common after rodent (91.2%) and bat (87.5%) exposures. Conclusions: Improving public health education is the most effective method of preventing dog bites and thus reducing bite injuries. Promoting responsible dog ownership and behavior around animals, as well as avoiding contact with unfamiliar animals, would likely reduce the need for PEP. The results of this study can also be used in planning health resources, primarily the availability of rabies vaccine and immunoglobulin. In addition, they emphasize the importance of rabies prevention and the continued implementation of all preventive measures in collaboration between the human and animal health sectors. This research may be useful to future public health policies for the control of zoonotic infectious diseases, especially from a “One Health” perspective. Full article

Background/Objectives: Japan is a rabies-free country; therefore, pre-exposure prophylaxis (PrEP) is primarily recommended for travelers to rabies-endemic regions. However, no prior studies in Japan have assessed long-term immunogenicity after PrEP vaccination. Methods: This descriptive study evaluated the long-term persistence of rabies virus-neutralizing antibodies among Japanese adult travelers who had received PrEP. Neutralizing antibody levels were measured using the rabies rapid fluorescent focus inhibition test more than two years post-vaccination. Results: Among 97 participants, 86.6% remained seropositive, with a median interval of 8.5 years since vaccination. Individuals who received three or more doses had significantly higher geometric mean titers than those who received only two doses. A notable proportion of those vaccinated with PCECV-KMB, an older subcutaneous formulation, were seronegative after a long interval. Conclusion: Antibody levels were strongly influenced by the number of vaccine doses, with reduced persistence in those who received only two. If testing confirms sufficient titers, PrEP booster doses may not be needed. However, for individuals with only two doses, older vaccinations, or those given PCECV-KMB, a risk-based assessment is recommended—especially for travelers to rabies-endemic areas. Full article

In this report, we document and analyze a case in which the Irkut virus (IRKV) (Mononegavirales: Rhabdoviridae) caused a fatal human case following a bat bite in June 2021. Unfortunately, the available data did not permit a detailed taxonomic classification of the carrier bat (Chiroptera). The event occurred in the southwestern part of the Sikhote-Alin mountain region (Russian Far East) covered by the Ussuri taiga forest. The symptoms of the illness began with the following: fever; pronounced psychomotor and motor agitation; tremor of the lower jaw and tongue; aphasia; dyslexia; and dysphagia. These rapidly developed, leading to a severe and fatal encephalitis. The patient was not vaccinated for rabies and did not receive rabies immunoglobulin. Using brain sections prepared from the deceased, molecular diagnostics were performed: immunofluorescence (polyclonal anti-rabies immunoglobulin) indicating the presence of the lyssavirus antigen; and RT-PCR indicating traces of viral RNA. Sectional material (brain) was used for whole-genome sequencing, resulting in a near-complete sequence of the lyssavirus genome. The obtained genomic sequence was identified as the Irkut virus. A comparative analysis of the new sequence and other currently available IRKV sequences (NCBI) revealed differences. Specifically, amino acid differences between antigenic sites in the isolate and those of the rabies vaccine strain used regionally were noted. The patient history and subsequent analysis confirm human IRKV infection following bat contact. Like other fatal cases of IRKV infection described earlier, this case occurred in the southern part of the Russian Far East. Two have occurred in the southwestern part of the Sikhote-Alin mountain region. This indicates the possible existence of an active, natural viral focus. Full article

Rabies is a zoonotic viral disease that is preventable through vaccination. Effective control strategies should follow the “One Health” concept, as targeting zoonotic pathogens at their animal source is the most effective and cost-efficient approach to protecting human health. The aim of this study was to develop and evaluate two third-generation anti-rabies vaccines based on non-replicative viral vectors, MVA and Ad5, both expressing rabies virus (RABV) glycoprotein (MVA-RG and Ad-RG). MVA-RG was produced using a platform developed in our laboratory, while Ad-RG was generated using a commercial kit. Protection against rabies was assessed in a mouse intracerebral (IC) RABV challenge model. Our results demonstrated that both vectors provided protection against RABV. MVA-RG and Ad-RG administered in two homologous doses conferred 60% and 60–100% protection against RABV challenge, respectively. The survival rate was influenced by the viral vector, the dose, and the immunization scheme. Remarkably, to our knowledge, our study is the first to report 100% protection against IC RABV challenge using a non-replicative Ad5 in a homologous immunization scheme. These promising results support future evaluation of this vaccine candidate in target animals. Full article

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. Full article

Rabies is a fatal zoonotic disease affecting all mammalian species. It is caused by the rabies virus and is prevalent worldwide. Horses are not commonly infected with rabies but their vaccination is recommended due to the potential zoonotic risk. This study aimed to evaluate the duration of immunity following rabies vaccination in horses. A total of 126 serum samples were collected from 93 horses, vaccinated 6 to 91 months before sampling. Rabies-virus-neutralizing antibody (RVNA) levels were evaluated using the Rabies Fluorescent Focus Inhibition Test (RFFIT). A protective RVNA titer of above 0.5 IU/mL was found in 112 (88.9%) of the samples and 84 (90.3%) of the horses. Antibody titers declined over time (rho = −0.271, p = 0.002); however, there was no significant difference in antibody titers or the prevalence of unprotected horses between the time intervals following vaccination. Purebred horses had lower antibody titers (p = 0.024). The response to booster vaccination was inspected in ten horses, and increased antibody titers were found in eight of them. The results of this study demonstrate the prolonged persistence of protective immunity in horses following rabies vaccination, in some cases, for up to eight years. Therefore, the current annual vaccination strategy should be re-evaluated. A rate of 9.7% of poor responders should be considered from an epidemiological perspective in order to minimize the risk of emergence of the disease. Full article

The rabies virus is a major zoonosis that causes severe nervous disease in humans, leading to paralysis and death. The world’s second anti-rabies center was established in 1888 by Victor Babeș, in Bucharest, where an eponymous strain of rabies was isolated and used to develop a method for immunization. The Babeș strain of the rabies virus was used for over 100 years in Romania to produce a rabies vaccine for human use, based on animal nerve tissue, thus having a proven history of prophylactic use. The present study aimed to sequence the whole genome of the Babeș strain and to explore its genetic relationships with other vaccine strains as well as to characterize its relevant molecular traits. After being adapted for multiplication in cell lines and designated BAB-TMP, 99% of the viral genome was sequenced. The overall organization of the genome is similar to that of other rabies vaccine strains. Phylogenetic analysis indicated that the BAB-TMP strain is closely related to the Russian RV-97 vaccine strain, and both seem to have a common ancestor. The nucleoprotein gene of the investigated genome was the most conserved, and the glycoprotein showed several unique amino acid substitutions within the major antigenic sites and linear epitopes. Full article

Rabies is a neglected viral zoonotic disease with an almost 100% fatality rate. A pilot project was initiated by the National Institute of Health (NIH), Islamabad, in collaboration with Health Security Partners (HSP) to establish a real-time dog bite surveillance in humans in public sector secondary care hospitals of Islamabad. The main objective of this study was to analyze different characteristics of dog bite cases, identify gaps in surveillance, and recommend suggestions to improve and strengthen real-time dog bite surveillance systems. An observational cross-sectional study was conducted in two major public sector hospitals in Islamabad from December 2019 to July 2020. Data on demographic information, site of the dog bite, category of the dog bite, and treatment was collected via a WVS mobile-based application. Descriptive analysis was carried out for different variables at a p-value of <0.05. A total of 338 dog bite cases were captured in the World Veterinary Service (WVS) application, and most cases (n = 226, 85.6%) were reported in December 2019 with a male-to-female ratio of 2:1. Most cases were reported from the age group of 22 to 31 years (n = 178, 53%). Out of the total number of cases, 263 (78%) presented with a single anatomical location, and 174 (51%) had Category II wounds. All dog bite patients were given only the first dose of the anti-rabies vaccine at the hospital level. Real-time dog bite surveillance via a mobile-based application proved to be effective for the timely recording and management of dog bite cases. Young people were reported to be mostly affected by dog bites, and nearly half of the cases were managed in hospitals. Refresher training was conducted for medics and paramedics for mobile-based applications, dog bite management, and proper referral of cases to tertiary care hospitals. Full article

Seven brands of veterinary rabies vaccines are commercially available in Sri Lanka, but there is no established procedure to test the potency of the vaccines at the local level, especially prior to their release. The aim of this study was to test the potency of these vaccines using a mouse challenge test in collaboration with the EU/WOAH/WHO Reference Laboratory for Rabies, ANSES-Nancy, France. Based on the European Pharmacopoeia, the inactivated rabies vaccines complied with the mouse potency test if the estimated potency is ≥1.0 IU in the smallest prescribed dose. Among the eight tested vaccines, four single-dose preparations (Rabisin™, Raksharab™, Nobivac™ RL, and Nobivac™ Rabies) were compliant, with potencies of 12 IU/dose, 7.2 IU/dose, 4.4 IU/dose, and 3.4 IU/dose, respectively. Three of the single-dose preparations (Canvac™ R, Defensor™ 3, and Rabies killed vaccine) were not compliant, with potency values <1.0 IU/dose. One multidose preparation (Raksharab™ multidose) had a potency of 1.3 IU/dose, even though the test was not validated. Based on these results, it appears that some rabies vaccine batches that are currently available in the local market do not comply with the mouse potency test. Testing the vaccines’ potency before registration and release to the market appears to be an important step to allow good immunization to animals during pre-exposure vaccination programs. Full article

Infection with the rabies virus (RABV) results in a 100% lethal neurological disease once symptoms develop. Post-exposure prophylaxis (PEP) consists of a combination of vaccination and anti-rabies immunoglobulins (RIGs); it is 100% effective if administered early after exposure. Because of its limited availability, alternatives for RIGs are needed. To that end, we evaluated a panel of 33 different lectins for their effect on RABV infection in cell culture. Several lectins, with either mannose or GlcNAc specificity, elicited anti-RABV activity, of which the GlcNAc-specific Urtica dioica agglutinin (UDA) was selected for further studies. UDA was found to prevent the entry of the virus into the host cell. To further assess the potential of UDA, a physiologically relevant RABV infection muscle explant model was developed. Strips of dissected swine skeletal muscle that were kept in a culture medium could be productively infected with the RABV. When the infection of the muscle strips was carried out in the presence of UDA, RABV replication was completely prevented. Thus, we developed a physiologically relevant RABV muscle infection model. UDA (i) may serve as a reference for further studies and (ii) holds promise as a cheap and simple-to-produce alternative for RIGs in PEP. Full article

Immunity from rabies depends on rabies virus neutralizing antibodies (RVNA) induced after immunization; however, the influence of antibody isotype switching has not been extensively investigated. This has become particularly relevant with changes in World Health Organization (WHO) recommended rabies vaccine regimens that may influence RVNA isotype kinetics, potentially affecting the peak, and longevity, of RVNA immunoglobulin (IgG) levels. We developed rapid and reliable assays for quantifying the anti-rabies IgM/IgG class switch in human serum based on an indirect ELISA technique. The immune response was tracked in ten individuals naïve to the rabies vaccine by quantifying serum titers weekly, from day seven to day 42 post-immunization, using a serum neutralization assay and the ELISA IgM/IgG assays. The average RVNA IU/mL levels were at D0 ≤ 0.1, D7 0.24, D14 8.36, D21 12.84, D28 25.74 and D42 28.68. Levels of specific IgM antibodies to rabies glycoprotein (EU/mL) were higher, on average, at D7, 1.37, and from D14, 5.49, to D21, 6.59. In contrast, average IgG antibodies (EU/mL) predominated from D28, 10.03, to D42, 14.45. We conclude that levels of anti-rabies IgM/IgG at D28 characterize the isotype class switch. These assays, combined with serum neutralization assays, distinguished the RVNA levels in terms of the IgM/IgG responses and are expected to add to the diagnostic repertoire, provide additional information in establishing rabies vaccine regimens, both post- and pre-exposure prophylaxis, and contribute to research efforts. Full article

Rabies is one of the oldest known zoonotic diseases. Rhabdovirus, an RNA virus belonging to the genus Lyssavirus and family Rhabdoviridae, causes rabies. Rabies diagnosis is challenging as the rabies virus remains confined to neurons after the initial animal bite. It largely remains immune-evasive until the infection reaches the central nervous system. The bottleneck in rabies diagnosis remains the non-availability of technical expertise and failure to collect an appropriate sample. The laboratory confirmation of rabies in both antemortem and postmortem samples is important. The samples were tested for anti-rabies antibodies using quantitative ELISA. In this report, two case studies are presented to demonstrate the suitability of ELISA for the intra vitam diagnosis of rabies using cerebrospinal fluid (CSF) as a diagnostic sample. The interpretation of serology results for both vaccinated and unvaccinated individuals has been discussed in detail, which has helped to confirm the antemortem diagnosis of rabies. In this report, we observed that ELISA can be a viable alternative for anti-rabies antibody detection in CSF and can be used as a viable alternative to more technically challenging tests, such as Rapid Fluorescent Focus Inhibition Test (RFFFIT) and Immunofluorescence Assays (IFA). Full article

Ormutivimab is the first recombinant human anti-rabies monoclonal antibody (rhRIG) approved for clinical application in China. In this study, a population pharmacodynamic (PPD) model was established to compare the neutralizing antibody activities of Ormutivimab and human rabies immunoglobulin (HRIG), alone or combined with human rabies vaccine (Vero), in a phase II clinical trial, and to recommend a target dose for the phase III trial. The model was verified to fit the PPD data well. The stability of the model was verified by the bootstrap method. The level of neutralizing antibodies in vivo increased rapidly after administration of Ormutivimab or HRIG. Neutralizing antibodies with a strong activity were produced at 7 days (Ormutivimab + vaccine) or 10 days (HRIG + vaccine) after induction by the vaccine in vivo. Compared to that induced by HRIG + vaccine, the level of the neutralizing antibodies induced by Ormutivimab + vaccine peaked higher and faster. The levels of neutralizing antibodies induced by Ormutivimab + vaccine and HRIG + vaccine were similar within 21 days after administration. According to these results and the safety data, 20 IU·kg⁻¹ was recommended as the target dose in the confirmatory study of Ormutivimab. Registration: ClinicalTrials.gov #NCT02559921. Full article

Understanding dog population dynamics plays a vital role in planning both rabies and dog management interventions. Establishing a human to dog ratio and an understanding how the urban/rural nature of the community might affect the overall dog population estimate provides an easy-to-use reference to estimate approximate dog populations in a range of communities. A total of 10,664 households were interviewed in 10 locations in the Philippines (2017 and 2018) to understand the dog population variations among the urban, semi-urban and rural areas. Epicollect5 and OSM tracker applications were used to conduct household interviews using a predesigned fixed set of questions. All answers were recorded directly using mobile phone applications. The survey results showed that for every 1000 humans, there are 256.3 dogs in rural areas, 213.8 dogs in semi-rural areas, 208.7 dogs in urban areas and 170.0 dogs on small islands of the Philippines. We estimate a total dog population in the Philippines of 23.29 million dogs (CI 95%, 22.51–24.07 million). Based on the survey findings from Quezon City and Cebu City, targets, resources allocations and vaccination approach were adjusted for the anti-rabies vaccination program at two locations in 2018, which lead to a 3- to 4-fold increase in the total number of dogs vaccinated in each city compared to previous years. Full article