Use of a Modified Preexposure Prophylaxis Vaccination Schedule to Prevent Human Rabies: Recommendations of the Advisory Committee on Immunization Practices - United States, 2022.

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.

Vital Signs: Trends in Human Rabies Deaths and Exposures - United States, 1938-2018.

INTRODUCTION: Each year, rabies causes approximately 59,000 deaths worldwide, including approximately two deaths in the United States. Before 1960, dogs were a common reservoir of rabies in the United States; however, increasingly, species of wildlife (e.g., bats, raccoons) are the main reservoirs. This report characterizes human rabies deaths, summarizes trends in rabies mortality, and highlights current rabies risks in the United States. METHODS: Rabies trends in the United States during 1938-2018 were analyzed using national rabies surveillance data. Data from the Healthcare Cost and Utilization Project for 2006-2014 were used to estimate the number of postexposure prophylaxis (PEP) visits per 100,000 persons during 2017-2018. The Centers for Medicare & Medicaid Services' average sales price data were used to estimate PEP costs. RESULTS: From 1960 to 2018, a total of 125 human rabies cases were reported in the United States; 36 (28%) were attributed to dog bites during international travel. Among the 89 infections acquired in the United States, 62 (70%) were attributed to bats. In 2018, approximately 55,000 persons sought PEP after contact with a potentially rabid animal. CONCLUSIONS AND COMMENTS: In the United States, wildlife rabies, especially in bats, continues to pose a risk to humans. Travelers also might be exposed to canine rabies in countries where the disease is still present; increased awareness of rabies while traveling abroad is needed. Vaccinating pets, avoiding contact with wildlife, and seeking medical care if one is bitten or scratched by an animal are the most effective ways to prevent rabies. Understanding the need for timely administration of PEP to prevent death is critical.

Investigation of Canine-Mediated Human Rabies Death, Haiti, 2015.

In Haiti, an investigation occurred after the death of a 4-year-old girl with suspected rabies. With tips provided by community members, the investigation led to the identification of 2 probable rabies-related deaths and 16 persons bitten by rabid dogs, 75% of which chose postexposure prophylaxis. Community engagement can bolster rabies control.

Tool for Eliminating Dog-Mediated Human Rabies through Mass Dog Vaccination Campaigns.

The World Health Organization and collaborating agencies have set the goal of eliminating dog-mediated human rabies by 2030. Building on experience with rabies endemic countries, we constructed a user-friendly tool to help public health officials plan the resources needed to achieve this goal through mass vaccination of dogs.

Notes from the Field: Assessment of Health Facilities for Control of Canine Rabies - Gondar City, Amhara Region, Ethiopia, 2015.

Rabies is an encephalitic disease that is nearly always fatal after onset of illness. Worldwide, rabies kills an estimated 59,000 humans each year (95% confidence interval [CI] = 25,000-159,000); the majority of the deaths are caused by the rabies virus variant that circulates in dogs (1,2). Canine rabies is endemic in Ethiopia, with an estimated 2,771 human deaths annually (CI = 1,116-12,660) (1-3). Annual rabies-associated livestock losses are estimated at >$50 million (USD), making rabies important to both human and animal health (1).

Animal bite and rabies postexposure prophylaxis reporting--United States, 2013.

CONTEXT: Rabies virus causes a fatal encephalitis and is typically acquired through the bite of an infected mammal. Rabies is preventable through administration of rabies postexposure prophylaxis (PEP), but this must be balanced with the need to avoid unnecessary PEP use. Though not nationally notifiable, some state health departments (SHDs) have made animal bites and use of PEP reportable within their jurisdictions. OBJECTIVE: We evaluated whether animal bites and PEP were reportable to SHDs as of 2013 for every state in the United States. DESIGN: The list of reportable conditions for each SHD as of 2013 was reviewed on the Internet for every state in the United States to determine whether animal bites or PEP were reportable. We then contacted an SHD representative (typically the State Public Health Veterinarian) to confirm data generated through Internet searches. Health departments in states where PEP was reportable were asked to complete a follow-up survey. RESULTS: Animal bites and PEP both were reportable in 9 states (18%). Another 9 states (18%) mandated animal bite reporting but not PEP reporting, while 12 states (24%) mandated PEP reporting but not animal bite reporting. These events were not reportable in 20 states (40%). The benefits reported by personnel from SHDs with PEP reporting systems varied greatly. CONCLUSIONS: Additional investigations focusing on the value of information returned by PEP reporting and identifying best practices for implementation and management are needed. The lack of standardization between current animal bite and PEP reporting systems limits completeness of reporting and comparability of outcomes. National recommendations to standardize case definitions and other data elements might help jurisdictions developing new animal bite or PEP reporting systems.

Trends in encephalitis-associated deaths in the United States, 1999-2008.

BACKGROUND: While encephalitis may be caused by numerous infectious, immune and toxic processes, the etiology often remains unknown. METHODS: We analyzed multiple cause-of-death mortality data during 1999-2008 for the USA, using the 10th revision of International Classification of Diseases codes for encephalitis, listed anywhere on the death record, including 'specified' and 'unspecified' encephalitis. Annual and average annual age-adjusted and age-specific death rates were calculated. RESULTS: For 1999-2008, 12,526 encephalitis-associated deaths were reported with 68.5% as unspecified encephalitis. The average annual age-adjusted encephalitis-associated death rate was 4.3 per 1 million persons, 1.3 for specified and 2.9 for unspecified encephalitis. Annual encephalitis-associated death rates had a significant downward trend (p < 0.01). The most common specified encephalitis deaths were herpesviral encephalitis (36.7%), Toxoplasma meningoencephalitis (27.8%) and Listeria meningitis/meningoencephaltis (6.8%). HIV was colisted with 15.0% of encephalitis-associated deaths, 58.4% of these with a specified code. CONCLUSION: Encephalitis-associated death rates decreased during 1999-2008, and herpesvirus was the most commonly identified infectious agent associated with encephalitis deaths. The high proportion of unspecified encephalitis deaths highlights the continued challenge of laboratory confirmation for causes of encephalitis and the importance of monitoring trends to assess the impact of new diagnostics and guide potential interventions.

Rabies in captive deer, Pennsylvania, USA, 2007-2010.

Since January 2007, a total of 11 rabid deer from 4 deer farms have been identified in 2 neighboring Pennsylvania counties. Vaccination of deer against rabies, decreasing wildlife animal contact with deer, and education of deer farmers may prevent further cases of rabies in captive deer and exposures to humans.

Community survey after rabies outbreaks, Flagstaff, Arizona, USA.

Flagstaff, Arizona, USA, experienced notable outbreaks of rabies caused by a bat rabies virus variant in carnivore species in 2001, 2004, 2005, 2008, and 2009. The most recent epizootic involved transmission among skunk and fox populations and human exposures. Multiple, wide-ranging control efforts and health communications outreach were instituted in 2009, including a household survey given to community members. Although the Flagstaff community is knowledgeable about rabies and the ongoing outbreaks in general, gaps in knowledge about routes of exposure and potential hosts remain. Future educational efforts should include messages on the dangers of animal translocation and a focus on veterinarians and physicians as valuable sources for outreach. These results will be useful to communities experiencing rabies outbreaks as well as those at current risk.

A country classification system to inform rabies prevention guidelines and regulations.

BACKGROUND: Assessing the global risk of rabies exposure is a complicated task requiring individual risk assessments, knowledge of rabies epidemiology, surveillance capacity and accessibility of rabies biologics on a national and regional scale. In many parts of the world, availability of this information is limited and when available is often dispersed across multiple sources. This hinders the process of making evidence-based health and policy recommendations to prevent the introduction and spread of rabies. METHODS: CDC conducted a country-by-country qualitative assessment of risk and protective factors for rabies to develop an open-access database of core metrics consisting of the presence of lyssaviruses (specifically canine or wildlife rabies virus variants or other bat lyssaviruses), access to rabies immunoglobulins and vaccines, rabies surveillance capacity and canine rabies control capacity. Using these metrics, we developed separate risk scoring systems to inform rabies prevention guidance for travelers and regulations for the importation of dogs. Both scoring systems assigned higher risk to countries with enzootic rabies (particularly canine rabies), and the risk scoring system for travelers also considered protective factors such as the accessibility of rabies biologics for post-exposure prophylaxis. Cumulative scores were calculated across the assessed metrics to assign a risk value of low, moderate or high. RESULTS: A total of 240 countries, territories and dependencies were assessed, for travelers, 116 were identified as moderate to high risk and 124 were low or no risk; for canine rabies virus variant importation, 111 were identified as high-risk and 129 were low or no risk. CONCLUSIONS: We developed a comprehensive and easily accessible source of information for assessing the rabies risk for individual countries that included a database of rabies risk and protective factors based on enzootic status and availability of biologics, provided a resource that categorizes risk by country and provided guidance based on these risk categories for travelers and importers of dogs into the United States.

Rabies healthcare-seeking behaviors of urban and peri-urban residents: Results from a rabies knowledge, attitudes, and practices survey, Bangladesh, 2018.

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 (ß = 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.

Evaluating Surveillance for and Estimating Administration of Rabies Postexposure Prophylaxis in the United States, 2012-2018.

BACKGROUND: An evaluation of postexposure prophylaxis (PEP) surveillance has not been conducted in over 10 years in the United States. An accurate assessment would be important to understand current rabies trends and inform public health preparedness and response to human rabies. METHODOLOGY/PRINCIPLE FINDINGS: To understand PEP surveillance, we sent a survey to public health leads for rabies in 50 U.S. states, Puerto Rico, Washington DC, Philadelphia, and New York City. Of leads from 54 jurisdictions, 39 (72%) responded to the survey; 12 reported having PEP-specific surveillance, five had animal bite surveillance that included data about PEP, four had animal bite surveillance without data about PEP, and 18 (46%) had neither. Although 12 jurisdictions provided data about PEP use, poor data quality and lack of national representativeness prevented use of this data to derive a national-level PEP estimate. We used national-level and state specific data from the Healthcare Cost & Utilization Project (HCUP) to estimate the number of people who received PEP based on emergency department (ED) visits. The estimated annual average of initial ED visits for PEP administration during 2012-2017 in the United States was 46,814 (SE: 1,697), costing upwards of 165 million USD. State-level ED data for initial visits for administration of PEP for rabies exposure using HCUP data was compared to state-level surveillance data from Maryland, Vermont, and Georgia between 2012-2017. In all states, state-level surveillance data was consistently lower than estimates of initial ED visits, suggesting even states with robust PEP surveillance may not adequately capture individuals who receive PEP. CONCLUSIONS: Our findings suggest that making PEP a nationally reportable condition may not be feasible. Other methods of tracking administration of PEP such as syndromic surveillance or identification of sentinel states should be considered to obtain an accurate assessment.

Rabies surveillance in the United States during 2009.

During 2009, 49 states and Puerto Rico reported 6,690 rabid animals and 4 human rabies cases to the CDC, representing a 2.2% decrease from the 6,841 rabid animals and 2 human cases reported in 2008. Approximately 92% of reported rabid animals were wildlife. Relative contributions by the major animal groups were as follows: 2,327 (34.8%) raccoons, 1,625 (24.3%) bats, 1,603 (24.0%) skunks, 504 (75%) foxes, 300 (4.5%) cats, 81 (1.2%) dogs, and 74 (1.1%) cattle. Compared with 2008, numbers of rabid raccoons and bats that were reported decreased, whereas numbers of rabid skunks, foxes, cats, cattle, dogs, and horses that were reported increased. Fewer rabid raccoons, compared with 2008, were reported by 12 of the 20 eastern states where raccoon rabies is enzootic, and number of rabid raccoons decreased by 2.6% overall nationally. Despite a 10% decrease in the number of rabid bats that were reported and a decrease in the total number of bats submitted for testing, bats were the second most commonly submitted animal, behind cats, during 2009. The number of rabid skunks that were reported increased by 0.9% overall. The proportion of rabid skunks in which infection was attributed to the raccoon rabies virus variant decreased from 473% in 2008 to 40.9% in 2009, resulting in a 12.7% increase in the number of rabid skunks infected with a skunk rabies virus variant. The number of rabid foxes increased 11.0% overall from the previous year. Four cases of rabies involving humans were reported from Texas, Indiana, Virginia, and Michigan. The Texas case represented the first presumptive abortive human rabies case, with the patient recovering after the onset of symptoms without intensive care. The Indiana and Michigan cases were associated with bat rabies virus variants. The human rabies case in Virginia was associated with a canine rabies virus variant acquired during the patient's travel to India.

Quantifying the risk of rabies in biting dogs in Haiti.

Rabies is a fatal viral disease typically transmitted through the bite of rabid animal. Domestic dogs cause over 99% of human rabies deaths. Over half of the world's population lives in a country where the canine rabies virus variant is endemic and dog bites are common. An estimated 29 million people worldwide receive post-bite vaccination after being exposed to animals suspected of rabies. Accurate and timely risk assessment of rabies in biting dogs is critical to ensure that rabies PEP is administered to all persons with a suspected rabies exposure, while avoiding PEP administration in situations where rabies can be definitively ruled out. In this study, a logistic regression model was developed to quantify the risk of rabies in biting dogs, using data from Haiti's animal rabies surveillance program. Significant risk factors identified in the model were used to quantify the probability of rabies in biting dogs. The risk of rabies in a biting dog as assessed through Haiti's rabies surveillance program was highly elevated when the dog displayed hypersalivation (OR = 34.6, 95% CI 11.3-106.5) or paralysis (OR = 19.0, 95% CI 4.8-74.8) and when the dog was dead at the time of the assessment (OR = 20.7, 95% CI 6.7-63.7). Lack of prior rabies vaccination, biting 2 or more people, and if the dog was a puppy also increased the probability that a biting dog would have rabies. The model showed high sensitivity (100%) and specificity (97%) when examined using validation data. This model enables us to project the risk of rabies in biting dogs in Haiti shortly after the bite event and make provisional PEP recommendations prior to laboratory testing or dog quarantine results. Application of this model may improve adherence to PEP for bite victims who can be educated on the quantitative risk of the exposure event. This model can also be used to reduce unnecessary PEP costs when the risk of rabies is determined as sufficiently low and the animal is available for observation.

Barriers to attendance of canine rabies vaccination campaigns in Haiti, 2017.

We conducted a cross-sectional survey to better understand the barriers to attendance at canine rabies vaccination campaigns in Haiti. A structured community-based questionnaire was conducted over a 15-day period during May-June 2017, focused on socio-economic status correlated with participation at canine rabies vaccination campaigns. Questions phrased as a bidding game were asked to determine individuals' willingness to pay (WTP) for dog rabies vaccination and willingness to walk (WTW) to fixed-point vaccination campaigns. The Kaplan-Meier estimator was applied to determine relationships between survey variables. Logistic regression was used to examine factors associated with participants' WTP and WTW. A total of 748 households from eight communities were surveyed. Respondents were predominantly female (54.4%) and had a median age of 45 years. The total number of owned dogs reported from households was 926, yielding a human-to-dog ratio in dog-owning households of 5.2:1. The majority of dogs (87.2%) were acquired for security, and 49% were allowed to roam freely; 42.0% of dog owners reported that they were unable to manage (or restrain) their dogs using a leash. Seventy per cent of dog owners were willing to pay up to 15.9 gourdes (0.25 USD) and/or walk up to 75 m to vaccinate their dogs. Households that owned free-roaming dogs, owned dogs for the purpose of companionship and owned dogs that they were unable to walk on a leash were associated with a higher WTP for vaccination. Living in Artibonite Department, having a middle or higher household income, and owning a dog for security purpose were associated with a higher WTW for vaccination. Low leash use and propensity for dogs to roam freely are barriers to successful fixed-point vaccination methods in Haiti, and alternative methods such as door to door (DD), capture-vaccinate-release (CVR) or oral vaccination should be explored. There may be some prospect for fee-for-service vaccination in Haiti; however, this programme should be introduced as a supplement, rather than a replacement for free rabies vaccination programmes so that mass dog vaccination is not discouraged.

Evaluation of species identification and rabies virus characterization among bat rabies cases in the United States.

OBJECTIVE: To evaluate species identification and rabies virus (RABV) characterization among samples from bats submitted for rabies testing in the United States and assess whether a standardized approach to specimen selection for RABV characterization could enhance detection of a sentinel event in virus dissemination among bats. SAMPLE: United States public health rabies surveillance system data collected in January 2010 through December 2015. PROCEDURES: The number of rabies-tested bats for which species was reported and the number of RABV-positive samples for which virus characterization would likely provide information regarding introduction of novel RABV variants and translocation and host-shift events were calculated. These specimens were designated as specimens of epizootiological importance (SEIs). Additionally, the estimated test load that public health laboratories could expect if all SEIs underwent RABV characterization was determined. RESULTS: Species was reported for 74,928 of 160,017 (47%) bats submitted for rabies testing. Identified SEIs were grouped in 3 subcategories, namely nonindigenous bats; bats in southern border states, Florida, Puerto Rico, and the US Virgin Islands; and bats of species that are not commonly found to be inflected with RABV. Annually, 692 (95% CI, 600 to 784) SEIs were identified, of which only 295 (95% CI, 148 to 442) underwent virus characterization. Virus characterization of all SEIs would be expected to increase public health laboratories' overall test load by 397 (95% CI, 287 to 506) samples each year. CONCLUSIONS AND CLINICAL RELEVANCE: Species identification and RABV characterization may aid detection of a sentinel event in bat RABV dissemination. With additional resources, RABV characterization of all SEIs as a standardized approach to testing could contribute to knowledge of circulating bat RABV variants.

Evaluation of rabies virus characterization to enhance early detection of important rabies epizootic events in the United States.

OBJECTIVE: To evaluate rabies virus (RABV) characterization data obtained from animal specimens submitted to the US public health rabies surveillance system and propose a standardized approach to sample selection for RABV characterization that could enhance early detection of important rabies epizootic events in the United States. SAMPLE: United States public health rabies surveillance system data collected from January 1, 2010, through December 31, 2015. PROCEDURES: Data were reviewed to identify RABV-positive specimens for which virus characterization would likely provide information regarding any of 4 overarching events (discovery of novel variants, translocation of RABV variants, host-shift events, and any unusual rabies-related event) that could substantially alter animal rabies epizootiology in the United States. These specimens were designated as specimens of epizootiological importance (SEIs). Estimates of the additional number of specimens that public health laboratories could expect to process each year if all SEIs underwent RABV characterization were calculated. RESULTS: During the 6-year period, the mean annual number of SEIs was 855 (95% CI, 739 to 971); the mean number of SEIs that underwent virus characterization was 270 (95% CI, 187 to 353). Virus characterization of all SEIs would be expected to increase the public health laboratories' test load by approximately 585 (95% CI, 543 to 625) specimens/y. CONCLUSIONS AND CLINICAL RELEVANCE: Prioritization of RABV characterization of SEIs may improve early detection of rabies events associated with RABV host shifts, variant translocations, and importation. Characterization of SEIs may help refine wildlife rabies management practices. Each public health laboratory should evaluate testing of SEIs to ensure diagnostic laboratory capacity is not overstretched.

Rabies surveillance in the United States during 2008.

During 2008, 49 states and Puerto Rico reported 6,841 cases of rabies in animals and 2 cases in humans to the CDC, representing a 3.1% decrease from the 7,060 cases in animals and 1 case in a human reported in 2007. Approximately 93% of the cases were in wildlife, and 7% were in domestic animals. Relative contributions by the major animal groups were as follows: 2,389 (34.9%) raccoons, 1,806 (26.4%) bats, 1,589 (23.2%) skunks, 454 (6.6%) foxes, 294 (4.3%) cats, 75 (1.1%) dogs, and 59 (0.9%) cattle. Compared with numbers of cases reported in 2007, numbers of cases reported in 2008 increased among cats, cattle, and skunks and decreased among dogs, raccoons, bats, and foxes. Numbers of rabid raccoons reported during 2008 decreased in 11 of the 20 eastern states where raccoon rabies was enzootic; overall number of rabid raccoons reported decreased by 8.6% during 2008, compared with 2007. On a national level, the number of rabies cases involving skunks increased by 7.7% during 2008, compared with the number reported in 2007; this was the first increase in the number of reported rabid skunks since 2006. The total number of cases of rabies reported nationally in foxes decreased 1.7% in 2008, compared with 2007. The 1,806 cases of rabies reported in bats represented a 6.7% decrease, compared with the number reported in 2007. One case of rabies in a dog imported from Iraq was reported at a quarantine station in New Jersey during 2008. Follow-up of potentially exposed animals in the same shipment did not reveal any secondary transmission. The United States remained free from dog-to-dog transmission of canine rabies virus variants. Total number of rabid dogs reported decreased 19.4% in 2008, compared with 2007. Two human rabies cases were reported from California and Missouri during 2008. The California case involved a recent immigrant from Mexico and was attributed to a newly identified rabies virus variant most likely associated with Mexican free-tailed bats. The case in Missouri was attributed to a rabies virus variant associated with eastern pipistrelle and silver-haired bats.