Rabies is a fatal encephalitic disease affecting all mammals. This report describes identification of raccoon rabies virus variant isolated from a stray kitten in an urban Midwestern city that is nonendemic for this virus variant. The kitten originally presented with nonspecific neurologic abnormalities. Astute veterinary, wildlife, and public health professionals played a critical role in the identification of this fatal zoonotic disease and the extensive public health and wildlife management response that ensued. This case serves as an important reminder of the risk of rabies in unvaccinated animals or those without known vaccination status, including stray animals.

In low and middle-income countries, a large proportion of animal rabies investigations end without a conclusive diagnosis leading to epidemiologic interpretations informed by clinical, rather than laboratory data. We compared Extreme Gradient Boosting (XGB) with Logistic Regression (LR) for their ability to estimate the probability of rabies in animals investigated as part of an Integrated Bite Case Management program (IBCM). To balance our training data, we used Random Oversampling (ROS) and Synthetic Minority Oversampling Technique. We developed a risk stratification framework based on predicted rabies probabilities. XGB performed better at predicting rabies cases than LR. Oversampling strategies enhanced the model sensitivity making them the preferred technique to predict rare events like rabies in a biting animal. XGB-ROS classified most of the confirmed rabies cases and only a small proportion of non-cases as either high (confirmed cases = 85.2%, non-cases = 0.01%) or moderate (confirmed cases = 8.4%, non-cases = 4.0%) risk. Model-based risk stratification led to a 3.2-fold increase in epidemiologically useful data compared to a routine surveillance strategy using IBCM case definitions. Our study demonstrates the application of machine learning to strengthen zoonotic disease surveillance under resource-limited settings.

On September 28, 2023, a kitten aged approximately 6 weeks found in Omaha, Nebraska, had test results positive for rabies at the Nebraska Veterinary Diagnostic Center (NVDC) after dying with neurologic signs and having bitten and scratched its caretakers. Preliminary investigation identified 10 exposed persons for whom postexposure prophylaxis (PEP)(†) was recommended. Subsequent variant-typing by NVDC yielded a presumptive positive result for the Eastern raccoon rabies virus variant (RRVV), which CDC confirmed on October 6.

OBJECTIVE: To provide comprehensive epidemiological information about the distribution and occurrence of rabies during 2022 in the US, Canada, and Mexico. METHODS: The US National Rabies Surveillance System collected 2022 animal rabies data from US state and territorial public health departments and USDA Wildlife Services. Temporal and geographic analyses were conducted to evaluate trends in animal rabies cases. RESULTS: During 2022, 54 US jurisdictions reported 3,579 animal rabies cases, reflecting a 2.3% decline from 3,663 cases reported in 2021. Six states collectively reported > 50% of animal rabies cases: Texas (395 [11.0%]), Virginia (337 [9.4%]), Pennsylvania (329 [9.2%]), New York (267 [7.5%]), North Carolina (264 [7.4%]), and California (241 [6.7%]). Out of the total reported rabies animal cases, 3,234 (90.4%) were attributed to wildlife, with bats (1,218 [34.0%]), raccoons (1,014 [28.3%]), skunks (660 [18.4%]), and foxes (269 [7.5%]) representing the primary hosts confirmed with rabies. Rabid cats (222 [6.2%]), cattle (42 [1.2%]), and dogs (50 [1.4%]) constituted > 90% of reported domestic animal rabies cases. CONCLUSIONS: In 2022, there was an increase in the number of animal samples submitted for rabies testing in the US and Canada. A notable geographic expansion of gray fox rabies virus variant was detected in the US. Three human rabies deaths due to vampire bat rabies infection occurred in Mexico; none were reported from the US and Canada. CLINICAL RELEVANCE: Laboratory diagnosis of rabies in animals is critical to ensure judicious use of human rabies postexposure prophylaxis.

Background: Throughout the Americas, Lyssavirus rabies (RV) perpetuates as multiple variants among bat and mesocarnivore species. Interspecific RV spillover occurs on occasion, but clusters and viral host shifts are rare. The spillover and host shift of a big brown bat (Eptesicus fuscus) RV variant Ef-W1 into mesocarnivores was reported previously on several occasions during 2001-2009 in Flagstaff, Arizona, USA, and controlled through rabies vaccination of target wildlife. During autumn 2021, a new cluster of Ef-W1 RV cases infecting striped skunks (Mephitis mephitis) was detected from United States Department of Agriculture enhanced rabies surveillance in Flagstaff. The number of Ef-W1 RV spillover cases within a short timeframe suggested the potential for transmission between skunks and an emerging host shift. Materials and Methods: Whole and partial RV genomic sequencing was performed to evaluate the phylogenetic relationships of the 2021-2023 Ef-W1 cases infecting striped skunks with earlier outbreaks. Additionally, real-time reverse-transcriptase PCR (rtRT-PCR) was used to opportunistically compare viral RNA loads in brain and salivary gland tissues of naturally infected skunks. Results: Genomic RV sequencing revealed that the origin of the 2021-2023 epizootic of Ef-W1 RV was distinct from the multiple outbreaks detected from 2001-2009. Naturally infected skunks with the Ef-W1 RV showed greater viral RNA loads in the brain, but equivalent viral RNA loads in the mandibular salivary glands, compared to an opportunistic sample of skunks naturally infected with a South-Central skunk RV from northern Colorado, USA. Conclusion: Considering a high risk for onward transmission and spread of the Ef-W1 RV in Flagstaff, public outreach, enhanced rabies surveillance, and control efforts, focused on education, sample characterization, and vaccination, have been ongoing since 2021 to mitigate and prevent the spread and establishment of Ef-W1 RV in mesocarnivores.

Like other neglected diseases, surveillance data for rabies is insufficient and incompatible with the need to accurately describe the burden of disease. Multiple modeling studies central to estimating global human rabies deaths have been conducted in the last two decades, with results ranging from 14,000 to 74,000 deaths annually. Yet, uncertainty in model parameters, inconsistency in modeling approaches, and discrepancies in data quality per country included in global burden studies have led to recent skepticism about the magnitude of rabies mortality. Lack of data not only limits the efficiency and monitoring of rabies elimination strategies but also severely diminishes abilities to advocate for support from international funding agencies. Meanwhile, the most vulnerable communities continue to suffer from deaths that could have been prevented through more robust reporting. The Zero by 30 global strategy to eliminate dog-mediated human rabies by 2030 recommends endemic countries adopt the intersectoral approach, Integrated Bite Case Management (IBCM), as a cost-effective method to enhance surveillance. However, effective implementation of IBCM is impeded by challenges such as limited capacity, resources, knowledge, skills, and attitudes toward compliance. To address this, the World Health Organization and United Against Rabies Forum have developed several open-access tools to guide national control programs in strong data collection practices, and online data repositories to pragmatically streamline reporting and encourage data sharing. Here, we discuss how current and future initiatives can be best employed to improve the implementation of existing surveillance tools and prioritization of effective data reporting/sharing to optimize progress toward 2030 elimination. Copyright © 2024 Swedberg, Bote, Gamble, Fénelon, King and Wallace.

The raccoon (Procyon lotor) variant of the rabies virus (RRV) is enzootic in the eastern United States and oral rabies vaccination (ORV) is the primary strategy to prevent and control landscape spread. Breaches of ORV management zones occasionally occur, and emergency "contingency" actions may be implemented to enhance local control. Contingency actions are an integral part of landscape-scale wildlife rabies management but can be very costly and routinely involve enhanced rabies surveillance (ERS) around the index case. We investigated two contingency actions in Ohio (2017-2019 and 2018-2021) and one in Virginia (2017-2019) using a dynamic, multi-method occupancy approach to examine relationships between specific management actions and RRV occurrence, including whether ERS was sufficient around the index case. The RRV occupancy was assessed seasonally at 100-km(2) grids and we examined relationships across three spatial scales (regional management zone, RRV free regions, and local contingency areas). The location of a grid relative to the ORV management zone was the strongest predictor of RRV occupancy at the regional scale. In RRV free regions, the neighbor effect and temporal variability were most important in influencing RRV occupancy. Parenteral (hand) vaccination of raccoons was important across all three contingency action areas, but more influential in the Ohio contingency action areas where more raccoons were hand vaccinated. In the Virginia contingency action area, ORV strategies were as important in reducing RRV occupancy as a hand vaccination strategy. The management action to trap, euthanize, and test (TET) raccoons was an important method to increase ERS, yet the impacts of TET on RRV occupancy are not clear. The probability of detecting additional cases of RRV was exceptionally high (>0.95) during the season the index case occurred. The probability of detecting RRV through ERS declined in the seasons following initial TET efforts but remained higher after the contingency action compared to the ERS detection probabilities prior to index case incidence. Local RRV cases were contained within one year and eliminated within 2-3 years of each contingency action.

BACKGROUND: Rabies expert on demand (REOD) telehealth service is provided by the U.S. Centers for Disease Control and Prevention (CDC) to assist public health practitioners, health providers, and the public to interpret national and international rabies prevention guidelines. REOD is staffed by subject matter experts of the CDC Poxvirus and Rabies Branch to assess each unique situation and provide evidence-based guidance to stakeholders. This study aims to describe the utilization of a rabies telehealth system and provide insight into common consultations. METHODS: A cross-sectional study of the nature of inquiries to REOD was done using the data collected from September 1, 2017 to September 30, 2021. An inquiry tracking form and Microsoft Access database were developed to document all inquiries received. Inquired ones were summarized to determine the frequency of inquiries by month, category, and location. RESULTS: Over a 49-month period, REOD received 5228 inquiries. Peak inquiries (n = 108) occurred during August 2019. The most frequent inquiries received pertained to risk assessment and management of rabies exposures (n = 1109), requests for testing assistance (n = 912), consultation for suspected human rabies (n = 746), rabies exposures and post-bite treatment occurring internationally (n = 310), and consultation for deviations in the recommended pre- and postexposure prophylaxis regimen (n = 300). CONCLUSION: REOD is a global resource for consultation related to managing rabies exposures, diagnostic issues, and rabies control strategies. REOD is a regularly utilized CDC service, as the demand for up-to-date rabies guidance remains high. REOD fulfills a critical role for the interpretation and consultation on rabies prevention guidelines to stakeholder.

The re-introduction of rabies into susceptible animal populations can have dire human and animal health impacts, in addition to substantial financial implications for re-elimination [1], [2]. In the late 1970s and early 1980s the canine rabies virus variant was reintroduced into the southern United States, resulting in 2 human and over 500 animal deaths and over $40m USD to re-eliminate the disease over the following 20 years [3], [4]. In 2015, canine rabies was introduced into Sarawak, Malaysia [5], where it has resulted in over 30 human deaths and control efforts are still ongoing to control the outbreak. Clearly, the introduction of canine rabies is no trivial matter, and global standards, such as those from the World Organization for Animal Health’s (WOAH) Terrestrial Animal Health Code [6], have been developed to support countries to prevent such occurrences. Current-day importation of rabies-infected dogs into North America and Europe are driven entirely be the illegal movement of dogs; that is, dogs that did not comply with national and international requirements for movement [7], [8], [9]. | | WOAH’s current standards for dog movement from countries endemic with rabies virus include criteria that the dog is healthy at the time of travel, is up-to-date on rabies vaccination, is permanently identified (e.g. microchip), has an adequate rabies virus neutralizing antibody (RVNA) titer (defined as >0.5 IU/ml), and has served a waiting period of at least 90 days (and not more than 365 days) after the date of which the adequate serum sample was collected – referred to as the “waiting period” [6]. Given the fact that nearly all modern-day rabies importation events have been associated with intentional or unintentional non-compliance with the WOAH waiting period, several peer-reviewed scientific publications have re-examined the rationale for the 90-day waiting period (Table 1), with particular interest in compromising between the scientific evidence and alleviating long-waiting periods that may be encouraging dog owners and importers to undermine the waiting period requirement [9], [10], [11]. This against the background that people are increasingly unsatisfied with the 90 day waiting period based on our experience and furthermore, that fraudulent documents can run rampant in the current system [12], [13].

Dog importation data from 2018-2020 were evaluated to ascertain whether the dog importation patterns in the United States changed during the COVID-19 pandemic, specifically with regard to denial of entry. Dog denial of entry reports from January 1, 2018, to December 31, 2020, stored within the Centers for Disease Control and Prevention (CDC) Quarantine Activity Reporting System, were reviewed. Basic descriptive statistics were used to analyze the data. Reason for denial, country of origin, and month of importation were all examined to determine which countries of origin resulted in the largest number of denials, and whether there was a seasonal change in importations during the COVID-19 pandemic (2020), compared to previous years (2018 and 2019). During 2020, CDC denied entry to 458 dogs. This represents a 52% increase in dogs denied entry compared to the averages in 2018 and 2019. Dogs were primarily denied entry for falsified rabies vaccination certificates (56%). Three countries exported 74% of all dogs denied entry into the United States, suggesting that targeted interventions may be needed for certain countries. Increased attempts to import inadequately vaccinated dogs from countries with canine rabies in 2020 may have been due to the increased demand for domestic pets during the COVID-19 pandemic. Educational messaging should highlight the risk of rabies and the importance of making informed pet purchases from foreign entities to protect pet owners, their families, and the public.Competing Interest StatementThe authors have declared no competing interest.CBPCustoms and Border ProtectionCDCCenters for Disease Control and PreventionCFRCode of Federal RegulationsCOVID-19coronavirus disease 2019CRVVcanine rabies virus variantQARSQuarantine Activity Reporting SystemRVCrabies vaccination certificate

IMPORTANCE: In the US, rabies postexposure prophylaxis (PEP) is often administered without a comprehensive and regionally appropriate rabies risk assessment. For low-risk exposures, this can result in patients incurring out-of-pocket expenses or experiencing adverse effects of PEP unnecessarily. OBJECTIVE: To use a model to estimate (1) the probability that an animal would test positive for rabies virus (RABV) given that a person was exposed, and (2) the probability that a person would die from rabies given that they were exposed to a suspect rabid animal and did not receive PEP, and to propose a risk threshold for recommending PEP according to model estimates and a survey. DESIGN, SETTING, AND PARTICIPANTS: In this decision analytical modeling study, positivity rates were calculated using more than 900 000 animal samples tested for RABV between 2011 and 2020. Other parameters were estimated from a subset of the surveillance data and the literature. Probabilities were estimated using Bayes' rule. A survey was administered among a convenience sample of state public health officials in all US states (excluding Hawaii) plus Washington, DC and Puerto Rico to determine a risk threshold for PEP recommendation. Respondents were asked whether they would recommend PEP given 24 standardized exposure scenarios while accounting for local rabies epidemiology. MAIN OUTCOMES AND MEASURES: A quantitative and regionally appropriate approach for helping health care practitioners and public health professionals determine whether to recommend and/or administer rabies PEP. RESULTS: A total of 1728 unique observations were obtained from the model for the probability that an animal would test positive for RABV given that a person was exposed, and 41 472 for ) the probability that a person would die from rabies given that they were exposed to a suspect rabid animal and did not receive PEP. The median probability that an animal would test positive for RABV given that a person was exposed ranged from 3 × 10-7 to 0.97, while the probability that a person would die from rabies given that they were exposed to a suspect rabid animal and did not receive PEP ranged from 1 × 10-10 to 0.55. Fifty public health officials out of a target sample size of 102 responded to the survey. Using logistic regression, a risk threshold was estimated for PEP recommendation of 0.0004; PEP may not be recommended for exposures with probabilities below this threshold. CONCLUSIONS AND RELEVANCE: In this modeling study of rabies in the US, the risk of death|exposure was quantified and a risk threshold was estimated. These results could be used to inform the decision-making process as to the appropriateness of recommending rabies PEP.

BACKGROUND: Rabies is a neglected disease, primarily due to poor detection stemming from limited surveillance and diagnostic capabilities in most countries. As a result, there is limited ability to monitor and evaluate country, regional, and global progress towards the WHO goal of eliminating human rabies deaths by 2030. There is a need for a low-cost, readily reproducible method of estimating rabies burden and elimination capacity in endemic countries. METHODS: Publicly available economic, environmental, political, social, public health, and One Health indicators were evaluated to identify variables with strong correlation to country-level rabies burden estimates. A novel index was developed to estimate infrastructural rabies elimination capacity and annual case-burden for dog-mediated rabies virus variant (DMRVV) endemic countries. FINDINGS: Five country-level indicators with superior explanatory value represent the novel "STOP-R index:" (1) literacy rate, (2) infant mortality rate, (3) electricity access, (4) political stability, and (5) presence/severity of natural hazards. Based on the STOP-R index, 40,111 (95% CI 25,854-74,344) global human rabies deaths are estimated to occur in 2022 among DMRVV-endemic countries and are projected to decrease to 32,349 (95% CI 21,110-57,019) in 2030. INTERPRETATION: The STOP-R index offers a unique means of addressing the data gap and monitoring progress towards eliminating dog-mediated human rabies deaths. Results presented here suggest that factors external to rabies programs influence the successes of rabies elimination, and it is now possible to identify countries exceeding or lagging in expected rabies control and elimination progress based on country infrastructure.

BACKGROUND: Rabies is a deadly zoonotic disease with nearly 100% fatality rate. In the United States, rabies virus persists in wildlife reservoirs, with occasional spillover into humans and domestic animals. The distribution of reservoir hosts in US counties plays an important role in public health decision-making, including the recommendation of lifesaving postexposure prophylaxis upon suspected rabies exposures. Furthermore, in surveillance data, it is difficult to discern whether counties have no cases reported because rabies was not present or because counties have an unreported rabies presence. These epizootics are monitored by the National Rabies Surveillance System (NRSS), to which approximately 130 state public health, agriculture, and academic laboratories report animal rabies testing statistics. Historically, the NRSS classifies US counties as free from terrestrial rabies if, over the previous 5 years, they and any adjacent counties did not report any rabies cases and they tested ≥15 reservoir animals or 30 domestic animals. OBJECTIVE: This study aimed to describe and evaluate the historical NRSS rabies-free county definition, review possibilities for improving this definition, and develop a model to achieve more precise estimates of the probability of terrestrial rabies freedom and the number of reported county-level terrestrial rabies cases. METHODS: Data submitted to the NRSS by state and territorial public health departments and the US Department of Agriculture Wildlife Services were analyzed to evaluate the historical rabies-free definition. A zero-inflated negative binomial model created county-level predictions of the probability of rabies freedom and the expected number of rabies cases reported. Data analyzed were from all animals submitted for laboratory diagnosis of rabies in the United States from 1995 to 2020 in skunk and raccoon reservoir territories, excluding bats and bat variants. RESULTS: We analyzed data from 14,642 and 30,120 county-years in the raccoon and skunk reservoir territories, respectively. Only 0.85% (9/1065) raccoon county-years and 0.79% (27/3411) skunk county-years that met the historical rabies-free criteria reported a case in the following year (99.2% negative predictive value for each), of which 2 were attributed to unreported bat variants. County-level model predictions displayed excellent discrimination for detecting zero cases and good estimates of reported cases in the following year. Counties classified as rabies free rarely (36/4476, 0.8%) detected cases in the following year. CONCLUSIONS: This study concludes that the historical rabies freedom definition is a reasonable approach for identifying counties that are truly free from terrestrial raccoon and skunk rabies virus transmission. Gradations of risk can be measured using the rabies prediction model presented in this study. However, even counties with a high probability of rabies freedom should maintain rabies testing capacity, as there are numerous examples of translocations of rabies-infected animals that can cause major changes in the epidemiology of rabies.

Rabies continues to kill an estimated 59,000 people annually, with up to 99% of human cases transmitted by domestic dogs. The elimination of human deaths from dog-mediated rabies is achievable by applying a One Health approach, and the framework to do this is outlined in Zero by 30: the Global Strategic Plan to end human deaths from dog-mediated rabies by 2030. To build on this global goal, and implement the approaches set out in Zero by 30, the United Against Rabies Forum was launched in 2020. This paper gives a review of the objectives, governance, activities and achievements of the United Against Rabies Forum to date. It also outlines ongoing work, and next steps as the United Against Rabies Forum reviews its first 2 years of activities and identifies priority areas for the coming 12 months.

BACKGROUND: Integrated bite case management (IBCM) is a multi-sectoral response to animal-bites which reduces human and canine rabies mortality through animal quarantine, bite-victim counseling, and vaccination tracking. Haiti's national rabies surveillance program was established in 2013 using paper-based IBCM (pIBCM) with adoption of an electronic smartphone application (eIBCM) in 2018. METHODS: We evaluated the feasibility of implementing the electronic app in Haiti and compared pIBCM and eIBCM data quality collected January 2013-August 2019. Deaths prevented, cost-per-death averted, and cost-per-investigation during use of pIBCM and eIBCM were estimated using a previously validated rabies cost-effectiveness tool that accounted for bite-victim demographics; probability of acquiring rabies; post-exposure prophylaxis; and costs including training, supplies, and salaries. We compared pIBCM and eIBCM based on data comprehensiveness, completeness, and reporting efficiency. Surveys were administered to IBCM staff to evaluate the usefulness, simplicity, flexibility, and acceptability of eIBCM. RESULTS: Of 15,526 investigations, 79% were paper-based and 21% electronic. IBCM prevented 241 (estimated) human rabies deaths. Using pIBCM, cost-per-death averted was $2,692 and the cost-per-investigation was $21.02; up to 55 data variables were collected per investigation; data transmission took 26 days to reach national staff, and 180 days until analysis. Using eIBCM, the cost-per-death averted was $1,247 and the cost-per-investigation was $22.70; up to 174 data variables were collected per investigation; data transmission took 3 days to reach national staff, and 30 days until analysis. Among 12,194 pIBCM investigations, 55% were mappable by commune, compared to 100% of eIBCM investigations mappable by GPS. Animal case definitions were incorrectly ascribed by investigators in 5.5% of pIBCM investigations and zero for eIBCM; typically, errors were in determining probable vs. suspect case assignments. Overall, eIBCM was well-accepted by staff, who reported the app is easy-to-use, facilitates investigations, and compared to pIBCM hastens data reporting. DISCUSSION: In Haiti, eIBCM showed improved data completeness, data quality, and shorter notification times with minimal increase in operational cost. The electronic app is simple-to-use and facilitates IBCM investigations. Rabies endemic countries could refer to eIBCM in Haiti as a cost-effective means to reduce human rabies mortality and improve surveillance capacity.

OBJECTIVE: To characterize clinical and epidemiologic features of SARS-CoV-2 in companion animals detected through both passive and active surveillance in the US. ANIMALS: 204 companion animals (109 cats, 95 dogs) across 33 states with confirmed SARS-CoV-2 infections between March 2020 and December 2021. PROCEDURES: Public health officials, animal health officials, and academic researchers investigating zoonotic SARS-CoV-2 transmission events reported clinical, laboratory, and epidemiologic information through a standardized One Health surveillance process developed by the CDC and partners. RESULTS: Among dogs and cats identified through passive surveillance, 94% (n = 87) had reported exposure to a person with COVID-19 before infection. Clinical signs of illness were present in 74% of pets identified through passive surveillance and 27% of pets identified through active surveillance. Duration of illness in pets averaged 15 days in cats and 12 days in dogs. The average time between human and pet onset of illness was 10 days. Viral nucleic acid was first detected at 3 days after exposure in both cats and dogs. Antibodies were detected starting 5 days after exposure, and titers were highest at 9 days in cats and 14 days in dogs. CLINICAL RELEVANCE: Results of the present study supported that cats and dogs primarily become infected with SARS-CoV-2 following exposure to a person with COVID-19, most often their owners. Case investigation and surveillance that include both people and animals are necessary to understand transmission dynamics and viral evolution of zoonotic diseases like SARS-CoV-2.

BACKGROUND: No rabies post-exposure prophylaxis (PEP) failure has been documented in humans in the United States using modern cell-culture vaccines. In January 2021, an 84-year-old male died from rabies six months after being bitten by a rabid bat despite receiving timely rabies post-exposure prophylaxis (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 contacts of the patient. RESULTS: Rabies virus antibodies present in serum and cerebrospinal fluid were non-neutralizing. Antemortem blood testing revealed 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, three (0.9%) warranted PEP. CONCLUSION: This is the first reported failure of rabies PEP in the Western Hemisphere using a cell culture 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.

Historical targets for country-level animal rabies testing volumes were abandoned due to ethical and welfare concerns, and interpretation challenges of testing healthy animals. To-date, no quantitative threshold has been established for evaluating adequate surveillance capacity specific to suspected rabid animals. The purpose here is to establish quantitative testing thresholds for rabies suspected animals to assess a country's rabies surveillance capacity. Animal rabies testing data was obtained from official and unofficial rabies surveillance platforms from 2010 to 2019 and supplemented with official country reports and published literature. Testing rates were determined for all-animal and domestic animals, and standardized per 100,000 estimated human population; the domestic animal rate was also standardized per 100,000 estimated dog population. There were 113 countries that reported surveillance data eligible for analysis. Countries reporting the most data were under WHO categories as having endemic human rabies or no dog rabies. The annual median all-animal testing rate for all countries was 1.53 animals/100,000 human population (IQR 0.27-8.78). Three proposed testing rate thresholds are an all-animal rate of 1.9 animals/100,000 humans, a domestic animal per human rate of 0.8 animals/100,000 humans, and a domestic animal per dog rate of 6.6 animals/100,000 dogs. These three peer-derived rabies testing thresholds for passive surveillance can be used to facilitate assessment of a country's rabies surveillance capacity.

OBJECTIVE: To provide epidemiological information on the occurrence of animal and human rabies in the US during 2021 and summaries of 2021 rabies surveillance for Canada and Mexico. PROCEDURES: State and territorial public health departments and USDA Wildlife Services provided data on animals submitted for rabies testing in 2021. Data were analyzed temporally and geographically to assess trends in domestic animal and wildlife rabies cases. RESULTS: During 2021, 54 US jurisdictions reported 3,663 rabid animals, representing an 18.2% decrease from the 4,479 cases reported in 2020. Texas (n = 456 [12.4%]), Virginia (297 [8.1%]), Pennsylvania (287 [7.8%]), North Carolina (248 [6.8%]), New York (237 [6.5%]), California (220 [6.0%]), and New Jersey (201 [5.5%]) together accounted for > 50% of all animal rabies cases reported in 2021. Of the total reported rabid animals, 3,352 (91.5%) involved wildlife, with bats (n = 1,241 [33.9%]), raccoons (1,030 [28.1%]), skunks (691 [18.9%]), and foxes (314 [8.6%]) representing the primary hosts confirmed with rabies. Rabid cats (216 [5.9%]), cattle (40 [1.1%]), and dogs (36 [1.0%]) accounted for 94% of rabies cases involving domestic animals in 2021. Five human rabies deaths were reported in 2021. CLINICAL RELEVANCE: The number of animal rabies cases reported in the US decreased significantly during 2021; this is thought to be due to factors related to the COVID-19 pandemic.

In late August 2021, a boy aged 7 years was bitten by a bat while he was playing outside his apartment home in Medina County, Texas. He informed his parents; however, no rabies postexposure prophylaxis (PEP) was sought because there were no visible bite marks, and the family was unaware that contact with a bat, including in the absence of visible bite marks, might cause rabies. Approximately 2 months later, the child was hospitalized for altered mental status, seizures, and hypersalivation and ultimately received a diagnosis of rabies. Experimental therapies were attempted; however, the child died 22 days after symptom onset. Fifty-seven persons who met criteria for suspected or known exposure to infectious secretions in this case were advised to consult with a medical provider about the need for rabies PEP in accordance with Advisory Committee on Immunization Practices (ACIP) guidelines (1). Rabies, an acute, progressive neuroencephalitis, is nearly always fatal. Although dogs are the most common source of human rabies deaths worldwide and account for an estimated 59,000 annual cases of human rabies globally (2), bats are the most common source of domestically acquired rabies in the United States and have been implicated in 31 (81.6%) of 38 human infections since 2000 (3). Attempts to prevent death or poor neurologic outcomes once rabies symptoms develop have been largely unsuccessful (4). Administration of rabies PEP, comprising rabies immunoglobulin and a series of doses of rabies vaccine, is critical to preventing rabies after an exposure; enhanced public education about the risk posed by bats, and the availability of PEP to prevent rabies, is needed.

Rabies is one of the most lethal infectious diseases, with those living in Asia and Africa having the highest risk of dying from rabies. We conducted a knowledge, attitudes and practices survey in urban and peri-urban areas of Bangladesh to describe canine bite rates, rabies knowledge, and healthcare seeking behaviors and barriers to human and dog vaccination. A bite risk assessment score (BRAS) and healthcare-seeking behavior score (HSBS) was calculated for each bite victim. Respondents were given two hypothetical situations to assess potential behaviors after a bite and willingness to pay for rabies vaccine and immunoglobulin. In total, 2,447 households participated in the survey and 85 bite victims were identified. The BRAS identified that 31% of bites posed no risk of rabies transmission. Multivariate analyses showed that living in Chittagong (β = 1.4; 95% CI: 0.1, 2.7) was associated with a higher HSBS. Findings presented here provide useful information regarding bite occurrences, healthcare-seeking behaviors, and a need for strategies to increase rabies awareness.

Zoonotic diseases represent a heavy global burden, causing important economic losses, impacting animal health and production, and costing millions of human lives. The vaccination of animals and humans to prevent inter-species zoonotic disease transmission is an important intervention. However, efforts to develop and implement vaccine interventions to reduce zoonotic disease impacts are often limited to the veterinary and agricultural sectors and do not reflect the shared burden of disease. Multisectoral collaboration, including co-development opportunities for human and animal vaccines, expanding vaccine use to include animal reservoirs such as wildlife, and strategically using vaccines to interrupt complex transmission cycles is needed. Addressing zoonoses requires a multi-faceted One Health approach, wherein vaccinating people and animals plays a critical role.

Guatemala has held dog rabies mass vaccination campaigns countrywide since 1984, yet the virus remains endemic. To eliminate dog-mediated human rabies, dog vaccination coverage must reach at least 70%. The Guatemala rabies program uses a 5:1 human:dog ratio (HDR) to estimate the vaccination coverage; however, this method may not accurately reflect the heterogeneity of dog ownership practices in Guatemalan communities. We conducted 16 field-based dog population estimates in urban, semi-urban and rural areas of Guatemala to determine HDR and evaluate the standard 5:1. Our study-derived HDR estimates varied from 1.7-11.4:1 (average 4.0:1), being higher in densely populated sites and lowest in rural communities. The community-to-community heterogeneity observed in dog populations could explain the persistence of rabies in certain communities. To date, this is the most extensive dog-population evaluation conducted in Guatemala, and can be used to inform future rabies vaccination campaigns needed to meet the global 2030 rabies elimination targets.

Dog-mediated rabies kills tens of thousands of people each year in India, representing one third of the estimated global rabies burden. Whilst the World Health Organization (WHO), World Organization for Animal Health (OIE) and the Food and Agriculture Organization of the United Nations (FAO) have set a target for global dog-mediated human rabies elimination by 2030, examples of large-scale dog vaccination programs demonstrating elimination remain limited in Africa and Asia. We describe the development of a data-driven rabies elimination program from 2013 to 2019 in Goa State, India, culminating in human rabies elimination and a 92% reduction in monthly canine rabies cases. Smartphone technology enabled systematic spatial direction of remote teams to vaccinate over 95,000 dogs at 70% vaccination coverage, and rabies education teams to reach 150,000 children annually. An estimated 2249 disability-adjusted life years (DALYs) were averted over the program period at 526 USD per DALY, making the intervention 'very cost-effective' by WHO definitions. This One Health program demonstrates that human rabies elimination is achievable at the state level in India.

On June 16, 2021, rabies virus infection was confirmed in a dog included in a shipment of rescue animals imported into the United States from Azerbaijan. A multistate investigation was conducted to prevent secondary rabies cases, avoid reintroduction of a dog-maintained rabies virus variant (DMRVV), identify persons who might have been exposed and would be recommended to receive rabies postexposure prophylaxis, and investigate the cause of importation control failures. Results of a prospective serologic monitoring (PSM) protocol suggested that seven of 32 (22%) animals from the same shipment as the dog with confirmed rabies virus infection and who had available titer results after rabies vaccine booster had not been adequately vaccinated against rabies before importation. A requirement for rabies vaccination certificates alone will not adequately identify improper vaccination practices or fraudulent paperwork and are insufficient as a stand-alone rabies importation prevention measure. Serologic titers before importation would mitigate the risk for importing DMRVV.

Effectively preventing and controlling zoonotic diseases requires a One Health approach that involves collaboration across sectors responsible for human health, animal health (both domestic and wildlife), and the environment, as well as other partners. Here we describe the Generalizable One Health Framework (GOHF), a five-step framework that provides structure for using a One Health approach in zoonotic disease programs being implemented at the local, sub-national, national, regional, or international level. Part of the framework is a toolkit that compiles existing resources and presents them following a stepwise schematic, allowing users to identify relevant resources as they are required. Coupled with recommendations for implementing a One Health approach for zoonotic disease prevention and control in technical domains including laboratory, surveillance, preparedness and response, this framework can mobilize One Health and thereby enhance and guide capacity building to combat zoonotic disease threats at the human-animal-environment interface.

Rabies is an ancient lethal scourge that has plagued humankind for centuries [...].

OBJECTIVE: To provide epidemiological information on animal and human cases of rabies in the US during 2020 and summaries of 2020 rabies surveillance for Canada and Mexico. ANIMALS: All animals submitted for laboratory diagnosis of rabies in the US during 2020. PROCEDURES: State and territorial public health departments and USDA Wildlife Services provided 2020 rabies surveillance data. Data were analyzed temporally and geographically to assess trends in domestic and wildlife rabies cases. RESULTS: During 2020, 54 jurisdictions submitted 87,895 animal samples for rabies testing, of which 85,483 (97.3%) had a conclusive (positive or negative) test result. Of these, 4,479 (5.2%) tested positive for rabies, representing a 4.5% decrease from the 4,690 cases reported in 2019. Texas (n = 580 [12.9%]), Pennsylvania (371 [8.3%]), Virginia (351 [7.8%]), New York (346 [7.7%]), North Carolina (301 [6.7%]), New Jersey (257 [5.7%]), Maryland (256 [5.7%]), and California (248 [5.5%]) together accounted for > 60% of all animal rabies cases reported in 2020. Of the total reported rabid animals, 4,090 (91.3%) involved wildlife, with raccoons (n = 1,403 [31.3%]), bats (1,400 [31.3%]), skunks (846 [18.9%]), and foxes (338 [7.5%]) representing the primary hosts confirmed with rabies. Rabid cats (288 [6.4%]), cattle (43 [1.0%]), and dogs (37 [0.8%]) accounted for 95% of rabies cases involving domestic animals in 2020. No human rabies cases were reported in 2020. CONCLUSIONS AND CLINICAL RELEVANCE: For the first time since 2006, the number of samples submitted for rabies testing in the US was < 90,000; this is thought to be due to factors related to the COVID-19 pandemic, as similar decreases in sample submission were also reported by Canada and Mexico.

Human rabies is an acute, progressive encephalomyelitis that is nearly always fatal once symptoms begin. Several measures have been implemented to prevent human rabies in the United States, including vaccination of targeted domesticated and wild animals, avoidance of behaviors that might precipitate an exposure (e.g., provoking high-risk animals), awareness of the types of animal contact that require postexposure prophylaxis (PEP), and use of proper personal protective equipment when handling animals or laboratory specimens. PEP is widely available in the United States and highly effective if administered after an exposure occurs. A small subset of persons has a higher level of risk for being exposed to rabies virus than does the general U.S. population; these persons are recommended to receive preexposure prophylaxis (PrEP), a series of human rabies vaccine doses administered before an exposure occurs, in addition to PEP after an exposure. PrEP does not eliminate the need for PEP; however, it does simplify the rabies PEP schedule (i.e., eliminates the need for rabies immunoglobulin and decreases the number of vaccine doses required for PEP). As rabies epidemiology has evolved and vaccine safety and efficacy have improved, Advisory Committee on Immunization Practices (ACIP) recommendations to prevent human rabies have changed. During September 2019-November 2021, the ACIP Rabies Work Group considered updates to the 2008 ACIP recommendations by evaluating newly published data, reviewing frequently asked questions, and identifying barriers to adherence to previous ACIP rabies vaccination recommendations. Topics were presented and discussed during six ACIP meetings. The following modifications to PrEP are summarized in this report: 1) redefined risk categories; 2) fewer vaccine doses in the primary vaccination schedule; 3) flexible options for ensuring long-term protection, or immunogenicity; 4) less frequent or no antibody titer checks for some risk groups; 5) a new minimum rabies antibody titer (0.5 international units [IUs]) per mL); and 6) clinical guidance, including for ensuring effective vaccination of certain special populations.