Administration Of Rabies Vaccine Research Articles

Retrospective Analysis of Dog Bite Injuries in Children with Autism Spectrum Disorder.

Children with autism spectrum disorder (ASD) may suffer a dog bite injury, but the frequency and its clinical impact is unknown. We sought to evaluate the (1) subject characteristics; (2) injury type; (3) clinical care provided; and (4) mortality in children with ASD who suffer a dog bite injury. We hypothesized that children with ASD have higher mortality and require more clinical care than children without ASD. This is a retrospective observational cohort study utilizing the TriNetX ® EHR database of subjects aged 0 to 18 years with dog bite diagnostic codes. Data were analyzed for demographics, diagnostic, medication, procedural codes, and mortality. We analyzed 38,337 subjects (n, %) coded for a dog bite injury [619 (1.6%) with ASD and 37718 (98.4%) without ASD]. Children with ASD had a higher odds of a traumatic injury to the head [1.34 (1.15, 1.57), p < 0.0001] compared to those without. There was no difference in critical care services, hospitalization, mechanical ventilation, and rabies vaccine administration. All-cause mortality at 1 year was low with no deaths reported within the ASD cohort and 37 (0.1%) deaths reported within the no ASD cohort. Children with ASD that suffer dog bite injuries have similar clinical needs to children without ASD but are more likely to suffer a traumatic injury to the head. Future studies are needed to better understand inciting factors for injuries in this population.

Does Perioperative Administration of Rabies Vaccine in Dogs Undergoing Surgical Sterilization Induce an Adequate Antibody Response?

High-volume spay/neuter events may facilitate access to free-roaming dogs to admi-nister rabies vaccination, but important questions remain regarding the effect of surgery and anesthesia on the immune response to a vaccine administered in the perioperative period. This study evaluated the immunogenicity of primary rabies vaccination in dogs when administered during the immediate perioperative period at the time of surgical sterilization (ovariohysterectomy/orchidectomy). Healthy dogs of both sexes presenting for surgical sterilization who had never been vaccinated against rabies virus were eligible for enrollment in the study. Fifty dogs ranging in age from 5 to 96 months were enrolled and were vaccinated against rabies virus during the recovery period following anesthesia and surgery. Rabies virus neutralizing antibody (RVNA) titers were measured preoperatively and 28 days postoperatively. This cohort was compared to a historical control cohort of 57 dogs who received primary rabies vaccination for travel purposes and had RVNA titers measured at the same laboratory as the study group 28-35 days post-vaccination. After controlling for age and sex, there was no statistically significant difference in immunogenicity of a rabies vaccine administered to dogs during the perioperative period in comparison to dogs that received the rabies vaccine for travel alone in the absence of surgery. Perioperative administration of a rabies vaccine in dogs under-going surgical sterilization induces an adequate antibody response. We recommend that rabies vaccine be administered perioperatively during spay/neuter campaigns in canine rabies endemic areas if other opportunities to ac-cess veterinary care and rabies vaccination are limited.

Does Perioperative Administration of Rabies Vaccine in Dogs Undergoing Surgical Sterilization Induce an Adequate Antibody Response?

High-volume spay/neuter events may facilitate access to free-roaming dogs to administer rabies vaccination, but important questions remain regarding the effect of surgery and anesthesia on the immune response to a vaccine administered in the perioperative period. This study evaluated the immunogenicity of primary rabies vaccination in dogs when administered during the immediate perioperative period at the time of surgical sterilization (ovariohysterectomy/orchidectomy). Healthy dogs of both sexes presenting for surgical sterilization who had never been vaccinated against rabies virus were eligible for enrollment in the study. Fifty dogs ranging in age from 5 to 96 months were enrolled and were vaccinated against rabies virus during the recovery period following anesthesia and surgery. Rabies virus neutralizing antibody (RVNA) titers were measured preoperatively and 28 days postoperatively. This cohort was compared to a historical control cohort of 57 dogs who received primary rabies vaccination for travel purposes and had RVNA titers measured at the same laboratory as the study group 28-35 days post-vaccination. After controlling for age and sex, there was no statistically significant difference in immunogenicity of a rabies vaccine administered to dogs during the perioperative period in comparison to dogs that received the rabies vaccine for travel alone in the absence of surgery. Perioperative administration of a rabies vaccine in dogs undergoing surgical sterilization induces an adequate antibody response. We recommend that rabies vaccine be administered perioperatively during spay/neuter campaigns in canine rabies endemic areas if other opportunities to access veterinary care and rabies vaccination are limited.

Antiviral mechanisms of two broad-spectrum monoclonal antibodies for rabies prophylaxis and therapy.

Rabies is an acute and lethal encephalomyelitis caused by lyssaviruses, among which rabies virus (RABV) is the most prevalent and important for public health. Although preventable through the post-exposure administration of rabies vaccine and immunoglobulins (RIGs), the disease is almost invariably fatal since the onset of clinical signs. Two human neutralizing monoclonal antibodies (mAbs), RVC20 and RVC58, have been shown to be effective in treating symptomatic rabies. To better understand how these mAbs work, we conducted structural modeling and in vitro assays to analyze their mechanisms of action, including their ability to mediate Fc-dependent effector functions. Our results indicate that both RVC20 and RVC58 recognize and lock the RABV-G protein in its pre-fusion conformation. RVC58 was shown to neutralize more potently the extra-cellular virus, while RVC20 mainly acts by reducing viral spreading from infected cells. Importantly, RVC20 was more effective in promoting effector functions compared to RVC58 and 17C7-RAB1 mAbs, the latter of which is approved for human rabies post-exposure treatment. These results provide valuable insights into the multiple mechanisms of action of RVC20 and RVC58 mAbs, offering relevant information for the development of these mAbs as treatment for human rabies.

Shoulder injury related to rabies vaccine administration: a case report

Reactions at the vaccine injection site are usually mild and transient. Musculoskeletal symptoms, such as myalgia and arthralgia, are commonly seen following vaccination. Shoulder injury related to vaccine administration (SIRVA), defined as shoulder pain and limited range of motion in the shoulder after intramuscular vaccine administration into the upper arm, may occur due to incorrect vaccine administration. Using the appropriate injection technique in the intramuscular administration of vaccines will reduce the risk of SIRVA. In this paper, we report the clinical and magnetic resonance imaging findings of a 26-year-old female patient presenting with SIRVA after rabies vaccination and discuss this case in light of the current literature.

Correction: Briggs, D.J.; Moore, S.M. The Route of Administration of Rabies Vaccines: Comparing the Data. Viruses 2021, 13, 1252

The authors wish to make the following corrections to this paper [...].

Colloidal Manganese Salt Improves the Efficacy of Rabies Vaccines in Mice, Cats, and Dogs.

Rabies, caused by rabies virus (RABV), remains a serious threat to public health in most countries worldwide. At present, the administration of rabies vaccines has been the most effective strategy to control rabies. Herein, we evaluate the effect of colloidal manganese salt (Mn jelly [MnJ]) as an adjuvant of rabies vaccine in mice, cats, and dogs. The results showed that MnJ promoted type I interferon (IFN-I) and cytokine production in vitro and the maturation of dendritic cells (DCs) in vitro and in vivo. Besides, MnJ serving as an adjuvant for rabies vaccines could significantly facilitate the generation of T follicular helper (Tfh) cells, germinal center (GC) B cells, plasma cells (PCs), and RABV-specific antibody-secreting cells (ASCs), consequently improve the immunogenicity of rabies vaccines, and provide better protection against virulent RABV challenge. Similarly, MnJ enhanced the humoral immune response in cats and dogs as well. Collectively, our results suggest that MnJ can facilitate the maturation of DCs during rabies vaccination, which can be a promising adjuvant candidate for rabies vaccines. IMPORTANCE Extending the humoral immune response by using adjuvants is an important strategy for vaccine development. In this study, a novel adjuvant, MnJ, supplemented in rabies vaccines was evaluated in mice, cats, and dogs. Our results in the mouse model revealed that MnJ increased the numbers of mature DCs, Tfh cells, GC B cells, PCs, and RABV-specific ASCs, resulting in enhanced immunogenicity and protection rate of rabies vaccines. We further found that MnJ had the same stimulative effect in cats and dogs. Our study provides the first evidence that MnJ serving as a novel adjuvant of rabies vaccines can boost the immune response in both a mouse and pet model.

The Route of Administration of Rabies Vaccines: Comparing the Data

Cell culture rabies vaccines were initially licensed in the 1980s and are essential in the prevention of human rabies. The first post-exposure prophylaxis (PEP) vaccination regimen recommended by the World Health Organization (WHO) was administered intramuscularly over a lengthy three-month period. In efforts to reduce the cost of PEP without impinging on safety, additional research on two strategies was encouraged by the WHO including the development of less expensive production methods for CCVs and the administration of reduced volumes of CCVs via the intradermal (ID) route. Numerous clinical trials have provided sufficient data to support a reduction in the number of doses, a shorter timeline required for PEP, and the approval of the intradermal route of administration for PEP and pre-exposure prophylaxis (PreP). However, the plethora of data that have been published since the development of CCVs can be overwhelming for public health officials wishing to review and make a decision as to the most appropriate PEP and PreP regimen for their region. In this review, we examine three critical benchmarks that can serve as guidance for health officials when reviewing data to implement new PEP and PreP regimens for their region including: evidence of immunogenicity after vaccination; proof of efficacy against development of disease; and confirmation that the regimen being considered elicits a rapid anamnestic response after booster vaccination.

Rabies vaccination and multiple sclerosis relapse: A retrospective cohort study

BackgroundNo studies assessing rabies vaccine (RV) tolerability in persons with multiple sclerosis (MS) have been conducted. Given the lack of safety data, RV is recommended essentially only for post-exposure prophylaxis, which is difficult to administer effectively in many rabies-endemic countries. We sought to determine whether RV administration as pre-exposure prophylaxis was associated with MS relapse. MethodsThis retrospective cohort study compared the clinical courses of MS patients in the year before and after rabies vaccination. The year before vaccination was defined as the pre-exposure risk period, the three months thereafter as the exposure-risk period, and the following nine months as the post-risk period. All adult MS patients immunized with RV between 2014 and 2018 and with available medical records in the two-year window were included. The primary outcome was the incidence of symptomatic MS relapse in the exposure-risk period versus the pre-exposure period. ResultsFifty-five patients received at least one dose of RV. Most (38/55, 69%) were female; mean age was 38.5 years (SD ±9.2). While 21 (38%) patients experienced 24 relapses in the year before vaccination, only three (5%) experienced one relapse each in the post-vaccination exposure-risk period; three others (5%) experienced a total of four relapses in the subsequent post-risk period. The annualized relapse rates in the pre-exposure, exposure-risk, and post-risk periods were 0.44, 0.22, and 0.10, respectively (rate ratio for exposure-risk to pre-exposure periods, 0.509 [95% CI 0.098–1.677]). ConclusionsIn this cohort, rabies vaccination was not associated with clinical MS relapse. Larger, prospective studies are needed to confirm these results.

Rabies vaccination strategies in the Netherlands in 2018: a cost evaluation.

BackgroundThe risk of contracting rabies is low for travellers. However, the number of Dutch travellers potentially exposed abroad following an animal-associated injury and needing post-exposure prophylaxis (PEP) has increased, resulting in increased costs.AimHere, we evaluated the costs and the cost-effectiveness of different pre- and post-exposure interventions in the Netherlands, taking into account the 2018 World Health Organization (WHO) recommendations for the prevention of rabies.MethodsA decision tree-based economic model was constructed. We calculated and compared the cost of different WHO pre-exposure prophylaxis (PrEP) recommendations, intramuscular vs intradermal vaccination and PEP subsequent to increased vaccination coverage in risk groups. We estimated cost-effectiveness, expressed as incremental costs per rabies immunoglobulin (RIG) administration averted, using a societal perspective. Statistical uncertainty regarding number of travellers and vaccination coverage was assessed.ResultsTotal costs at the national level were highest using previous WHO recommendations from 2012, estimated at EUR 15.4 million annually. Intradermal vaccinations in combination with the current recommendations led to the lowest costs, estimated at EUR 10.3 million. Higher vaccination uptake resulted in higher overall costs. The incremental costs per RIG administration averted varied from EUR 21,300-46,800.ConclusionsThe change in rabies PrEP and PEP recommendations in 2018 reduced total costs. Strategies with increased pre-travel vaccination uptake led to fewer RIG administrations and fewer vaccinations after exposure but also to higher total costs. Although larger scale intradermal administration of rabies vaccine can reduce total costs of PrEP and can positively influence vaccination uptake, it remains a costly intervention.

Behavioral and structural barriers to accessing human post-exposure prophylaxis and other preventive practices in Arequipa, Peru, during a canine rabies epidemic.

A canine rabies epidemic started in early 2015 in Arequipa, Peru and the rabies virus continues to circulate in the dog population. Some city residents who suffer dog bites do not seek care or do not complete indicated post-exposure prophylaxis (PEP) regimens, increasing the risk of human rabies. The objectives of our study are to qualitatively assess knowledge about rabies, and preventive practices, such as rabies vaccine administration, following a dog bite. We conduct eight focus group discussions in peri-urban and urban communities with 70 total participants. In our results, we observe low awareness of rabies severity and fatality, and different practices following a dog bite, depending on the community type: for example, whereas participants in the urban communities report cleaning the wound with hydrogen peroxide rather than soap and water, participants in peri-urban areas cover the wound with herbs and hair from the dog that bit them. Misconceptions about rabies vaccines and mistreatment at health centers also commonly prevent initiating or completing PEP. We identify important behavioral and structural barriers and knowledge gaps that limit evidence-based preventive strategies against rabies and may threaten successful prevention of dog-mediated human rabies in this setting.

Knowledge of students about rabies and its post exposure prophylaxis and health seeking behaviour in University of Western UP.

Introduction: Rabies is a major public health problem in Asia. Of the estimated 55,000 human cases that occur annually worldwide, more than half occur in Asian countries. Rabies is exceptionally fatal encephalitis but can be prevented by appropriate post exposure prophylaxis. Objectives: To assess the knowledge of students about rabies and its causes, reservoir , mode of transmission , symptoms, wound management , post exposure prophylaxis , seeking behaviour, site for anti rabies vaccine administration after dog bite. Methodology: This cross-sectional study was conducted among 375 college students in various colleges under Swami Vivekananda Subharti University Meerut UP. Results: (55%) of students knew that rabies is caused by a virus. 18.66% students knew correct first aid measures such as wash with soap and water. Conclusion: The findings of the study indicated lack of knowledge on various aspects of the rabies &amp; its prevention. There are many misconceptions and lack of awareness about rabies. There is strong need to organize awareness programme using educational session.

Equine Rabies Immunoglobulin: A Review

Rabies is a major cause of human death in many developing countries. There is a worldwide shortage of human and equine rabies immune globulin. The WHO recommends combined administration of rabies vaccine and rabies immune globulin to patients after exposure. The implementation of post exposure prophylaxis by vaccination and specific immunoglobulin therapy are largely hampered by its high cost. The equine rabies immunoglobulin is less expensive than human rabies immunoglobulin, and is used for rabies post-exposure prophylaxis in developing countries.&#x0D; Equine rabies immunoglobulin is a F(ab)2 with high specific activity, purity, and safety. Healthy horses are immunized with a rabies vaccine. Crude plasma is collected and immunoglobulin is converted into F(ab)2 fragments by pepsin digestion. The F(ab)2 fragments are purified using caprylic acid precipitation followed by ultrafiltration.&#x0D; Keywords: Rabies, Equine rabies immunoglobulin (ERIG), Human rabies immunoglobulin (HRIG), IgG, Caprylic acid, Pepsin.

Adherence to guideline recommendations for human rabies immune globulin patient selection, dosing, timing, and anatomical site of administration in rabies postexposure prophylaxis

ABSTRACTRabies is a fatal disease that mandates proper prophylaxis after a rabies virus exposure to prevent death. This study evaluated adherence to Centers of Disease Control and Prevention (CDC) recommendations for rabies immune globulin (IG) patient selection, dosing, timing of administration, and anatomical site of administration for rabies postexposure prophylaxis. This retrospective, cross-sectional study included patients who received at least one dose of rabies IG or rabies vaccine at a multi-hospital health system from January 2015 through June 2018. This study included 246 patients, and all of them received at least one dose of rabies vaccine. Two patients had a history of rabies vaccination, did not have an indication for rabies IG, and appropriately did not receive additional rabies IG. Rabies IG was administered to 91% (223 of 244) of patients with an indication. Of 223 patients who received rabies IG, 219 (98%) received doses within 10% of 20 IU/kg of body weight, and all 223 (100%) received rabies IG within 7 days of the first rabies vaccine administration. Only 56% (96 of 170) of patients with a wound that could be infiltrated with rabies IG actually received rabies IG via infiltration into and around the wound. This multi-hospital health system study demonstrated high adherence to guideline recommendations for rabies IG patient selection (91%), dosing (98%), and timing (100%). However, only 56% of eligible patients received rabies IG infiltration at wound sites as recommended by guidelines.

Compatibility between a rabies vaccine and a combined vaccine against canine distemper, adenovirosis, parvovirosis, parainfluenza virus and leptospirosis

In many cicumstances, veterinarians are requiring to be able to administer rabies vaccine in dogs at the same time as vaccinating against canine distemper, adenovirus, parvovirus, parainfluenza virus and leptospirosis. The aim of this study was to assess the compatibility between a multivalent vaccine and a rabies vaccine when injected at two separate sites. Lack of interference was assessed by comparing serological response to viral components during one year following primary vaccination with vaccines administered alone or concomitantly. Antibody response to all tested components was comparable, irrespective of whether vaccines were administered individually or concurrently. Notably, the rabies vaccine induced very strong and protective seroconversion in dogs, whether it was administered concomitantly with the combo vaccine or not. This facilitates administration of rabies vaccine, which is a key factor for controlling the disease.

Intradermal administration of Rabies Vaccine at an affordable cost: Experience from tertiary care hospital in Jammu

Background: Rabies continue to be a major public health challenge in India. It can certainly be prevented by timely and appropriate administration of WHO recommended pre and post exposure prophylaxis. Intradermal regimen is running successfully and beneficial both in monetary as well as non-monetary terms. Aim&amp; Objective:To evaluate the reduction in direct cost incurred with the use of intradermal regimen as compared to intramuscular regimen. Settings and Design: The present cross-sectional study was conducted in Government Medical College Jammu, a tertiary care centre. Methods and Material: A total of 17535 patients attending Anti Rabies Section of GMC Jammu were studied from Jan 2015 to September 2017.The patients belonging to Category II and III received 0.1 ml 2 site ID purified vero cell culture vaccine (PVCCV) on days 0, 3, 7 and 28 (2-2-2-0-2) and Rabies Immunoglobulin (RIG)(Category III only). Cost borne per patient receiving intradermal regimen was calculated and compared with cost borne in case Intramuscular regimen would have been used. Statistical analysis: Results were presented in descriptive manner using percentages and proportions. Conclusions: Intradermal regimen reduces the direct cost as compared to intramuscular regimen.

Staphylococcal enterotoxin C2 as an adjuvant for rabies vaccine induces specific immune responses in mice.

Rabies vaccine administration is the most effective method to prevent the occurrence of rabies disease. However, administration of rabies vaccine without adjuvant always shows low efficiency. As a member of superantigen, staphylococcal enterotoxin C2 (SEC2) non-specifically activates T-cells at extremely low concentration. It enlightens us that SEC2 may be used as an adjuvant. We carried out the experiment that the mice received twice immunization with rabies vaccine in the presence or absence of SEC2 at 1-week interval. Serum and splenocytes from immunized mice were collected to measure the level of rabies-specific-IgG and the cell that secretes IFN-γ or IL-4. The promotion of antigen-specific splenocytes proliferation was also detected. Besides, a challenge test was performed to evaluate the protective efficiency of SEC2. It was shown that mice immunized with vaccine combined with SEC2 generated more specific anti-rabies-antibodies. The results for production of IFN-γ and IL-4, as well as the proliferation of splenocytes from immunized mice indicated SEC2 promoted the specific immune responses induced by rabies vaccine. Moreover, immunization of mice with vaccine combined with SEC2 provided efficient protection against the lethal rabies exposure. Taken together, our findings indicated that SEC2 can be served as an adjuvant for rabies vaccines.

Knowledge Regarding Visits for Health Services, Number of Doses of ARV, Site for Anti Rabies Vaccine Administration among College Students

Knowledge Regarding Visits for Health Services, Number of Doses of ARV, Site for Anti Rabies Vaccine Administration among College Students

Clinical management and humoral immune responses to rabies post-exposure prophylaxis among three patients who received solid organs from a donor with rabies.

The rabies virus causes a fatal encephalitis and can be transmitted through organ transplantation. In 2013, a man developed rabies 18 months after receiving a kidney from a donor with rabies, who was not known to have been infected when the organs were procured. Three additional persons who received organs from the same donor (liver, kidney, heart), all of whom were not vaccinated for rabies before transplantation, received rabies post-exposure prophylaxis (PEP) with rabies immune globulin and 5 doses of rabies vaccine as soon as the diagnosis of rabies was made in the donor (18 months after their transplant surgeries). We describe their clinical management. As the 3 recipients were all on immunosuppressive medications, post-vaccination serologic testing was performed using the rapid fluorescent focus inhibition test to measure rabies virus neutralizing antibodies (RVNAs). An acceptable antibody response to administration of rabies vaccine was defined as detection of RVNAs at a concentration ≥0.1 IU/mL from a serum specimen collected ≥7 days after the fifth vaccine dose. All 3 recipients demonstrated an acceptable antibody response despite their immunosuppressed states. More than 36 months have passed since their transplant surgeries, and all 3 recipients have no evidence of rabies. The survival of 3 previously unvaccinated recipients of solid organs from a donor with rabies is unexpected. Although the precise factors that led to their survival remain unclear, our data suggest that PEP can possibly enhance transplant safety in settings in which donors are retrospectively diagnosed with rabies.

Generation and characterization of neutralizing human recombinant antibodies against antigenic site II of rabies virus glycoprotein (VAC11P.1106)

Abstract Currently recommended treatment for individuals exposed to rabies virus (RV) is post-exposure prophylaxis (PEP) through the combined administration of rabies vaccine and rabies immune globulin (RIG). Human monoclonal antibodies (mAbs) that neutralize RV offer an opportunity to replace RIG for rabies PEP. Here a combinatorial human Fab library was constructed using antibody genes derived from the blood of RV-vaccinated donors. Selections of this library against purified RV virions resulted in the identification of 11 unique Fab antibodies specific for RV glycoprotein. Of the Fab antibodies, five were converted to full human IgG1 format. The human IgG antibodies revealed high binding affinity and neutralizing activities against RV fixed strains through a rapid fluorescent focus inhibition test (RFFIT) in vitro as well as the early stage protective function after exposure to RV infection in vivo. Furthermore, epitope mapping and binding competition analysis showed that all of obtained human neutralizing and protective antibodies were directed to the antigenic site Ⅱ of RV glycoprotein. Our results provide not only important insight into the protective immune response to RV in humans, but also more candidates eligible for use in a mAb cocktail aimed at replacing RIG for rabies post-exposure prophylaxis.