Inferring the disruption of rabies circulation in vampire bat populations using a betaherpesvirus-vectored transmissible vaccine.

Transmissible vaccines are an emerging biotechnology that hold prospects to eliminate pathogens from wildlife populations. Such vaccines would genetically modify naturally occurring, nonpathogenic viruses ("viral vectors") to express pathogen antigens while retaining their capacity to transmit. The epidemiology of candidate viral vectors within the target wildlife population has been notoriously challenging to resolve but underpins the selection of effective vectors prior to major investments in vaccine development. Here, we used spatiotemporally replicated deep sequencing to parameterize competing epidemiological mechanistic models of Desmodus rotundus betaherpesvirus (DrBHV), a proposed vector for a transmissible vaccine targeting vampire bat-transmitted rabies. Using 36 strain- and location-specific time series of prevalence collected over 6 y, we found that lifelong infections with cycles of latency and reactivation, combined with a high R0 (6.9; CI: 4.39 to 7.85), are necessary to explain patterns of DrBHV infection observed in wild bats. These epidemiological properties suggest that DrBHV may be suited to vector a lifelong, self-boosting, and transmissible vaccine. Simulations showed that inoculating a single bat with a DrBHV-vectored rabies vaccine could immunize >80% of a bat population, reducing the size, frequency, and duration of rabies outbreaks by 50 to 95%. Gradual loss of infectious vaccine from vaccinated individuals is expected but can be countered by inoculating larger but practically achievable proportions of bat populations. Parameterizing epidemiological models using accessible genomic data brings transmissible vaccines one step closer to implementation.

Longitudinal deep sequencing informs vector selection and future deployment strategies for transmissible vaccines.

Vaccination is a powerful tool in combating infectious diseases of humans and companion animals. In most wildlife, including reservoirs of emerging human diseases, achieving sufficient vaccine coverage to mitigate disease burdens remains logistically unattainable. Virally vectored "transmissible" vaccines that deliberately spread among hosts are a potentially transformative, but still theoretical, solution to the challenge of immunising inaccessible wildlife. Progress towards real-world application is frustrated by the absence of frameworks to guide vector selection and vaccine deployment prior to major in vitro and in vivo investments in vaccine engineering and testing. Here, we performed deep sequencing on field-collected samples of Desmodus rotundus betaherpesvirus (DrBHV), a candidate vector for a transmissible vaccine targeting vampire bat-transmitted rabies. We discovered 11 strains of DrBHV that varied in prevalence and geographic distribution across Peru. The phylogeographic structure of DrBHV strains was predictable from both host genetics and landscape topology, informing long-term DrBHV-vectored vaccine deployment strategies and identifying geographic areas for field trials where vaccine spread would be naturally contained. Multistrain infections were observed in 79% of infected bats. Resampling of marked individuals over 4 years showed within-host persistence kinetics characteristic of latency and reactivation, properties that might boost individual immunity and lead to sporadic vaccine transmission over the lifetime of the host. Further, strain acquisitions by already infected individuals implied that preexisting immunity and strain competition are unlikely to inhibit vaccine spread. Our results support the development of a transmissible vaccine targeting a major source of human and animal rabies in Latin America and show how genomics can enlighten vector selection and deployment strategies for transmissible vaccines.

One step closer to a transmissible vaccine for rabies virus.

A recent study in PLOS Biology shows that a betaherpesvirus circulating with the vampire bat, Desmodus rotundus, could serve as an effective vector for a transmissible vaccine capable of reducing the risk of rabies virus spillover in Peru.

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.

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.

Short-Chain Fatty Acids Alleviate Vancomycin-Caused Humoral Immunity Attenuation in Rabies-Vaccinated Mice by Promoting the Generation of Plasma Cells via Akt-mTOR Pathway.

Mounting evidence suggests that gut microbial composition and its metabolites, including short-chain fatty acids (SCFAs), have beneficial effects in regulating host immunogenicity to vaccines. However, it remains unknown whether and how SCFAs improve the immunogenicity of the rabies vaccine. In this study, we investigated the effect of SCFAs on the immune response to rabies vaccine in vancomycin (Vanco)-treated mice and found that oral gavage with butyrate-producing bacteria (C. butyricum) and butyrate supplementation elevated RABV-specific IgM, IgG, and virus-neutralizing antibodies (VNAs) in Vanco-treated mice. Supplementation with butyrate expanded antigen-specific CD4+ T cells and IFN-γ-secreting cells, augmented germinal center (GC) B cell recruitment, promoted plasma cells (PCs) and RABV-specific antibody-secreting cells (ASCs) generation in Vanco-treated mice. Mechanistically, butyrate enhanced mitochondrial function and activated the Akt-mTOR pathway in primary B cells isolated from Vanco-treated mice, ultimately promoting B lymphocyte-induced maturation protein-1 (Blimp-1) expression and CD138+ PCs generation. These results highlight the important role of butyrate in alleviating Vanco-caused humoral immunity attenuation in rabies-vaccinated mice and maintaining host immune homeostasis. IMPORTANCE The gut microbiome plays many crucial roles in the maintenance of immune homeostasis. Alteration of the gut microbiome and metabolites has been shown to impact vaccine efficacy. SCFAs can act as an energy source for B-cells, thereby promoting both mucosal and systemic immunity in the host by inhibiting HDACs and activation of GPR receptors. This study investigates the impact of orally administered butyrate, an SCFA, on the immunogenicity of rabies vaccines in Vanco-treated mice. The results showed that butyrate ameliorated humoral immunity by facilitating the generation of plasma cells via the Akt-mTOR in Vanco-treated mice. These findings unveil the impact of SCFAs on the immune response of the rabies vaccine and confirm the crucial role of butyrate in regulating immunogenicity to rabies vaccines in antibiotic-treated mice. This study provides a fresh insight into the relationship of microbial metabolites and rabies vaccination.

Evaluating the long-term impact of COVID-19-associated public health interventions on zoonotic and vector-borne diseases in China: an interrupted time series analysis.

BACKGROUND: The long-term impact of COVID-19-associated public health interventions on zoonotic and vector-borne infectious diseases (ZVBs) remains uncertain. This study sought to examine the changes in ZVBs in China during the COVID-19 pandemic and predict their future trends. METHODS: Monthly incidents of seven ZVBs (Hemorrhagic fever with renal syndrome [HFRS], Rabies, Dengue fever [DF], Human brucellosis [HB], Leptospirosis, Malaria, and Schistosomiasis) were gathered from January 2004 to July 2023. An autoregressive fractionally integrated moving average (ARFIMA) by incorporating the COVID-19-associated public health intervention variables was developed to evaluate the long-term effectiveness of interventions and forecast ZVBs epidemics from August 2023 to December 2025. RESULTS: Over the study period, there were 1,599,647 ZVBs incidents. HFRS and rabies exhibited declining trends, HB showed an upward trajectory, while the others remained relatively stable. The ARFIMA, incorporating a pulse pattern, estimated the average monthly number of changes of - 83 (95% confidence interval [CI] - 353-189) cases, - 3 (95% CI - 33-29) cases, - 468 (95% CI - 1531-597) cases, 2191 (95% CI 1056-3326) cases, 7 (95% CI - 24-38) cases, - 84 (95% CI - 222-55) cases, and - 214 (95% CI - 1036-608) cases for HFRS, rabies, DF, HB, leptospirosis, malaria, and schistosomiasis, respectively, although these changes were not statistically significant besides HB. ARFIMA predicted a decrease in HB cases between August 2023 and December 2025, while indicating a relative plateau for the others. CONCLUSIONS: China's dynamic zero COVID-19 strategy may have exerted a lasting influence on HFRS, rabies, DF, malaria, and schistosomiasis, beyond immediate consequences, but not affect HB and leptospirosis. ARFIMA emerges as a potent tool for intervention analysis, providing valuable insights into the sustained effectiveness of interventions. Consequently, the application of ARFIMA contributes to informed decision-making, the design of effective interventions, and advancements across various fields.

Mathematical model of rabies vaccination in the United States.

Rabies is one of the oldest viral diseases and it has been present on every continent except Antarctica. Within the U.S. human rabies cases are quite rare. In the eastern USA, raccoons are the main reservoir hosts and pet vaccination serves as an important barrier against human rabies exposure. In this paper, we develop a compartmental model for rabies transmission amongst raccoons and domestic pets. We find the disease-free equilibria, reproduction numbers for the raccoons and domestic pets. We also determine the vaccination coverage/rates, both for raccoons and pets, needed to achieve the elimination of rabies.

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.

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.

Identification of dynamical changes of rabies transmission under quarantine: Community-based measures towards rabies elimination.

Quarantine has been long used as a public health response to emerging infectious diseases, particularly at the onset of an epidemic when the infected proportion of a population remains identifiable and logistically tractable. In theory, the same logic should apply to low-incidence infections; however, the application and impact of quarantine in low prevalence settings appears less common and lacks a formal analysis. Here, we present a quantitative framework using a series of progressively more biologically realistic models of canine rabies in domestic dogs and from dogs to humans, a suitable example system to characterize dynamical changes under varying levels of dog quarantine. We explicitly incorporate health-seeking behaviour data to inform the modelling of contact-tracing and exclusion of rabies suspect and probable dogs that can be identified through bite-histories of patients presenting at anti-rabies clinics. We find that a temporary quarantine of rabies suspect and probable dogs provides a powerful tool to curtail rabies transmission, especially in settings where optimal vaccination coverage is yet to be achieved, providing a critical stopgap to reduce the number of human and animal deaths due to rabid bites. We conclude that whilst comprehensive measures including sensitive surveillance and large-scale vaccination of dogs will be required to achieve disease elimination and sustained freedom given the persistent risk of rabies re-introductions, quarantine offers a low-cost community driven solution to intersectoral health burden.

Rabies vaccination adherence and associated factors among rabies-exposed patients in Shenzhen, China: a hospital-based cross-sectional study.

Adherence to post-exposure prophylaxis and post-exposure vaccination (PEV) is an important measure to prevent rabies. The purpose of this study was to explore the adherence to the vaccination protocol and its influencing factors among rabies-exposed patients in Shenzhen, China. A cross-sectional survey was conducted in a tertiary hospital in Shenzhen, China, to obtain epidemiological characteristics of patients; knowledge, attitude, and practice scores of rabies prevention; and medical records. A total of 326 patients requiring full rabies PEV were included in this study, and only 62% (202) completed the full course of vaccination according to the norms of the vaccination guidelines. After multifactor logistic regression, the factors influencing adherence to vaccination were as follows: age 31 to 40 years, time spent to reach the nearest rabies prevention clinic was >60 min, the time of injury was at night to early morning, the place of injury was a school/laboratory, the animal causing injury was a cat, the health status of the animal causing injury could not be determined, and patients with higher practice scores (all p<0.05). Understanding the factors influencing rabies vaccination adherence among rabies-exposed patients in urban areas of China and promote changes in patients' practice toward rabies prevention is essential for rabies elimination by 2030.

Spatial accessibility and inequality analysis of rabies-exposed patients to rabies post-exposure prophylaxis clinics in Guangzhou City, China.

BACKGROUND: The incidence of rabies exposure is high and increasing in China, leading to an urgent demand of rabies post-exposure prophylaxis (PEP) clinics for the injured. However, the spatial accessibility and inequality of rabies-exposed patients to rabies PEP clinics is less known in China. METHODS: Based on rabies exposure data, PEP clinic data, and resident travel origin-destination (OD) matrix data in Guangzhou City, China, we first described the incidence of rabies exposure in Guangzhou from 2020 to 2022. Then, the Gaussian two-step floating catchment area method (2SFCA) was used to analyze the spatial accessibility of rabies-exposed patients to rabies PEP clinics in Guangzhou, and the Gini coefficient and Moran's I statistics were utilized to evaluate the inequality and clustering of accessibility scores. RESULTS: From 2020 to 2022, a total of 524,160 cases of rabies exposure were reported in Guangzhou, and the incidence showed a significant increasing trend, with an average annual incidence of 932.0/100,000. Spatial accessibility analysis revealed that the overall spatial accessibility scores for three scenarios (threshold of driving duration [d0] = 30 min, 45 min, and 60 min) were 0.30 (95% CI: 0.07, 0.87), 0.28 (95% CI: 0.11, 0.53) and 0.28 (95% CI: 0.14, 0.44), respectively. Conghua, Huangpu, Zengcheng and Nansha districts had the higher accessibility scores, while Haizhu, Liwan, and Yuexiu districts exhibited lower spatial accessibility scores. The Gini coefficient and Moran's I statistics showed that there were certain inequality and clustering in the accessibility to rabies PEP clinics in Guangzhou. CONCLUSIONS: This study clarifies the heterogeneity of spatial accessibility to rabies PEP clinics, and provide valuable insights for resource allocation to achieve the WHO target of zero human dog-mediated rabies deaths 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.

Rabies post-exposure prophylaxis in the emergency department.

STUDY OBJECTIVES: Rabies is a zoonotic single-stranded RNA lyssavirus that can cause acute infections of the central nervous system (CNS) including encephalomyelitis, encephalitis, and meningoencephalitis that is progressively fatal. Rabies is more common in developing countries, but approximately 23,000 people in the United States (US) are estimated to have been exposed or to have received post exposure prophylaxis (PEP) yearly. Nebraska Medicine follows the Advisory Committee on Immunization Practices (ACIP) guidelines for the vaccination series, as well as the 20 units/kg administration of immunoglobulin (RIG). Nebraska Medicine Medical Center (NMC) and Bellevue Medical Center (BMC) treat the scheduling of the complete rabies vaccine series differently. At both campuses, patients receive their immunoglobulin and first vaccine in the Emergency Department (ED). At NMC, patients are scheduled to receive the remainder of their vaccination series at the outpatient infusion center by the ED pharmacist. At BMC, the subsequent vaccinations are given as "Nurse Only" return visits to the ED. The objective of this study was to compare patient compliance of two different processes for follow-up rabies vaccine series completion. This project's primary aim was to determine the rate of patient compliance for follow up rabies vaccine doses. The secondary aims of this project were to determine if there was a difference in patient follow-up compliance between the two campuses, patient specific factors that impact compliance, and potential cost savings if a dose rounding protocol for RIG was utilized. METHODS: This retrospective chart review was completed as a quality improvement project. Data from patients who had received either rabies immunoglobulin and/or a rabies vaccine, were >18 years of age, and were not admitted were collected for a 3-year period from July 1, 2019, to June 30, 2022. Data were abstracted from the patient's EMR (electronic medical records) using a SQL (Structured query language) query of pre-identified data elements. When unable to abstract with SQL query, data elements were manually abstracted. All data abstracted was collated and descriptive analysis performed. RESULTS: A total of 723 individual encounters were identified during the study period. After combining rabies series for each individual patient, 173 unique patients remained. After exclusions were applied, 143 patients were included: 104 patients from NMC, and 39 from BMC. For the primary outcome, appropriate completion between the two campuses was 78.3%. When comparing the two campuses, completion rates were higher at NMC (82% vs. 69%), although not statistically significant (p = 0.12). Appropriate completion of vaccine series was statistically significant for both payor and exposure type. Application of a dose rounding policy with those >45 kg, rounding to the nearest vial, as well as rounding down if at the midpoint interval, 56 fewer vials would have been used between the two campuses. This would have resulted in a potential cost savings of $57,928.64 over the study period.

Exposure History, Post-Exposure Prophylaxis Use, and Clinical Characteristics of Human Rabies Cases: A Twelve-Year Retrospective Review at a Tertiary Facility in Ghana.

BACKGROUND: Robust monitoring and reporting systems for rabies are lacking thus increasing the risk of underreporting. Highlighting the rabies cases brings to bear the needed urgent attention for more efforts at preventing and controlling the disease. OBJECTIVE: To describe the epidemiological characteristics of patients managed for clinical rabies at the largest referral facility in Ghana. METHODS: A retrospective single-center hospital-based chart review and data extraction were conducted for persons managed for clinical rabies infection at the Korle-Bu Teaching Hospital from January 2008 to December 2019. Data analysis was done using STATA. Descriptive statistics were used to summarize the epidemiological and clinical characteristics. Fisher's exact test, the Kruskal-Wallis test, and Spearman's correlation coefficient were used to explore significant associations. RESULTS: A total of 28 cases were recorded over the period of review. All of them died and most (68%) of them were males. Twenty-one percent of them were less than 15 years old. Their median age interquartile range (IQR) was 31 years (25.5 years) and the median incubation period for rabies (IQR) was 60 days (60 days). The source of rabies for cases was mainly dog bites. The vaccination status of all the animals could not be ascertained. Majority (80%) of the patients took neither anti-rabies vaccine nor immunoglobulin as post-exposure prophylaxis after the dog bite. The median time of admission before death (interquartile range) was 2 days (2 days). Majority (82%) of the cases were furious rabies. CONCLUSION: Attention should be directed at mass vaccination of dogs as dog bites are common. Ensuring availability and access to post-exposure prophylaxis (PEP) is also critical in averting rabies-related deaths.

CONTEXTE: Des systèmes de surveillance et de déclaration robustes pour la rage font défaut, augmentant ainsi le risque de sousdéclaration. Mettre en lumière les cas de rage suscite l'attention urgente nécessaire pour redoubler d'efforts dans la prévention et le contrôle de la maladie. OBJECTIF: Décrire les caractéristiques épidémiologiques des patients traités pour une rage clinique dans le plus grand établissement de référence au Ghana. MÉTHODES: Une revue rétrospective des dossiers médicaux et une extraction de données basées à l'hôpital ont été réalisées pour les personnes traitées pour une infection à la rage clinique à l'Hôpital d'Enseignement Korle-Bu de janvier 2008 à décembre 2019. L'analyse des données a été effectuée à l'aide de STATA. Des statistiques descriptives ont été utilisées pour résumer les caractéristiques épidémiologiques et cliniques. Le test exact de Fisher, le test de Kruskal-Wallis et le coefficient de corrélation de Spearman ont été utilisés pour explorer les associations significatives. RÉSULTATS: Un total de 28 cas ont été enregistrés sur la période examinée. Tous sont décédés et la plupart d'entre eux (68%) étaient des hommes. Vingt et un pour cent d'entre eux avaient moins de 15 ans. Leur âge médian (plage interquartile) était de 31 ans (25,5 ans) et la période d'incubation médiane de la rage (plage interquartile) était de 60 jours (60 jours). La principale source de rage pour les cas était principalement les morsures de chiens. Le statut vaccinal de tous les animaux n'a pas pu être déterminé. La majorité (80%) des patients n'ont pris ni vaccin antirabique ni immunoglobuline en prophylaxie post-exposition après la morsure de chien. Le délai médian d'admission avant le décès (plage interquartile) était de 2 jours (2 jours). La majorité (82%) des cas étaient atteints de rage furieuse. CONCLUSION: L'attention devrait être dirigée vers la vaccination de masse des chiens car les morsures de chien sont courantes. Assurer la disponibilité et l'accès à la prophylaxie post-exposition (PPE) est également crucial pour éviter les décès liés à la rage. MOTS-CLÉS: Rage, morsure de chien, post-exposition, prophylaxie, vaccination de masse.

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.

Side-by-side Comparative Study of the Immunogenicity of the Intramuscular and Intradermal Rabies Post-exposure Prophylaxis Regimens in a Cohort of Suspected Rabies Virus Exposed Individuals.

All World Health Organization (WHO) pre-qualified rabies vaccines for humans are inactivated tissue culture rabies virus formulations produced for intramuscular (IM) administration. Due to costs and vaccine shortage, dose-saving intradermal (ID) administration of rabies post-exposure prophylaxis (PEP) is encouraged by WHO. This study compared the immunogenicity of the ID 2-site, 3-visit Institut Pasteur Cambodge (IPC) PEP regimen to the IM 1-site, 4-visit 4-dose Essen regimen using Verorab vaccine (Sanofi). The development of neutralizing antibodies (nAbs) and T cell response was assessed in 210 patients with a category II or III animal exposure in a rabies-endemic country. At day 28, all participants developed nAbs (≥0.5 IU/mL), irrespective of PEP scheme, age, or administration of rabies immunoglobulin. T cell response and nAb titers were similar for both PEP schemes. This study demonstrated that the 1-week ID IPC regimen is as effective as the 2-week IM 4-dose Essen regimen in inducing an anti-rabies immune response under real-life PEP.

Fatal Human Rabies Infection With Suspected Host-Mediated Failure of Post-Exposure Prophylaxis Following a Recognized Zoonotic Exposure-Minnesota, 2021.

BACKGROUND: No human rabies post-exposure prophylaxis (PEP) failure has been documented in the United States using modern cell culture-based vaccines. In January 2021, an 84-year-old male died from rabies 6 months after being bitten by a rabid bat despite receiving timely rabies PEP. We investigated the cause of breakthrough infection. METHODS: We reviewed medical records, laboratory results, and autopsy findings and performed whole-genome sequencing (WGS) to compare patient and bat virus sequences. Storage, administration, and integrity of PEP biologics administered to the patient were assessed; samples from leftover rabies immunoglobulin were evaluated for potency. We conducted risk assessments for persons potentially exposed to the bat and for close patient contacts. RESULTS: Rabies virus antibodies present in serum and cerebrospinal fluid were nonneutralizing. Antemortem blood testing revealed that the patient had unrecognized monoclonal gammopathy of unknown significance. Autopsy findings showed rabies meningoencephalitis and metastatic prostatic adenocarcinoma. Rabies virus sequences from the patient and the offending bat were identical by WGS. No deviations were identified in potency, quality control, administration, or storage of administered PEP. Of 332 persons assessed for potential rabies exposure to the case patient, 3 (0.9%) warranted PEP. CONCLUSIONS: This is the first reported failure of rabies PEP in the Western Hemisphere using a cell culture-based vaccine. Host-mediated primary vaccine failure attributed to previously unrecognized impaired immunity is the most likely explanation for this breakthrough infection. Clinicians should consider measuring rabies neutralizing antibody titers after completion of PEP if there is any suspicion for immunocompromise.