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.

Towards rabies elimination in the Asia-Pacific region: From theory to practice.

Rabies is a major neglected zoonotic disease and causes a substantial burden in the Asian region. Currently, Pacific Oceania is free of rabies but enzootic areas throughout southeast Asia represent a major risk of disease introduction to this region. On September 25-26, 2019, researchers, government officials and related stakeholders met at an IABS conference in Bangkok, Thailand to engage on the topic of human rabies mediated by dogs. The objective of the meeting was focused upon snowballing efforts towards achieving substantial progress in rabies prevention, control and elimination within Asia by 2030, and thereby to safeguard the Pacific region. Individual sessions focused upon domestic animal, wildlife and human vaccination; the production and evaluation of quality, safety and efficacy of existing rabies biologics; and the future development of new products. Participants reviewed the progress to date in eliminating canine rabies by mass vaccination, described supportive methods to parenteral administration by oral vaccine application, considered updated global and local approaches at human prophylaxis and discussed the considerable challenges ahead. Such opportunities provide continuous engagement on disease management among professionals at a trans-disciplinary level and promote new applied research collaborations in a modern One Health context.

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.

Human Rabies - Virginia, 2017.

On May 9, 2017, the Virginia Department of Health was notified regarding a patient with suspected rabies. The patient had sustained a dog bite 6 weeks before symptom onset while traveling in India. On May 11, CDC confirmed that the patient was infected with a rabies virus that circulates in dogs in India. Despite aggressive treatment, the patient died, becoming the ninth person exposed to rabies abroad who has died from rabies in the United States since 2008. A total of 250 health care workers were assessed for exposure to the patient, 72 (29%) of whom were advised to initiate postexposure prophylaxis (PEP). The total pharmaceutical cost for PEP (rabies immunoglobulin and rabies vaccine) was approximately $235,000. International travelers should consider a pretravel consultation with travel health specialists; rabies preexposure prophylaxis is warranted for travelers who will be in rabies endemic countries for long durations, in remote areas, or who plan activities that might put them at risk for a rabies exposures.

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.

Dog-Mediated Human Rabies Death, Haiti, 2016.

Haiti has experienced numerous barriers to rabies control over the past decades and is one of the remaining Western Hemisphere countries to report dog-mediated human rabies deaths. We describe the circumstances surrounding a reported human rabies death in 2016 as well as barriers to treatment and surveillance reporting.

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 death attributed to exposure in Central America with symptom onset in a U.S. detention facility - Texas, 2013.

On June 7, 2013, a man was diagnosed in a Texas hospital with rabies. He had been detained in a U.S. detention facility during his infectious period. To identify persons exposed to rabies who might require rabies postexposure prophylaxis (PEP), CDC and the Texas Department of State Health Services (DSHS) conducted investigations at four detention facilities, one medical clinic, and two hospitals. In all, 25 of 742 persons assessed for rabies exposure were advised to receive PEP. Early diagnosis of rabies is essential for implementation of appropriate hospital infection control measures and for rapid assessment of potential contacts for PEP recommendations.

Raccoon rabies virus variant transmission through solid organ transplantation.

IMPORTANCE: The rabies virus causes a fatal encephalitis and can be transmitted through tissue or organ transplantation. In February 2013, a kidney recipient with no reported exposures to potentially rabid animals died from rabies 18 months after transplantation. OBJECTIVES: To investigate whether organ transplantation was the source of rabies virus exposure in the kidney recipient, and to evaluate for and prevent rabies in other transplant recipients from the same donor. DESIGN: Organ donor and all transplant recipient medical records were reviewed. Laboratory tests to detect rabies virus-specific binding antibodies, rabies virus neutralizing antibodies, and rabies virus antigens were conducted on available specimens, including serum, cerebrospinal fluid, and tissues from the donor and the recipients. Viral ribonucleic acid was extracted from tissues and amplified for nucleoprotein gene sequencing for phylogenetic comparisons. MAIN OUTCOMES AND MEASURES: Determination of whether the donor died from undiagnosed rabies and whether other organ recipients developed rabies. RESULTS: In retrospect, the donor's clinical presentation (which began with vomiting and upper extremity paresthesias and progressed to fever, seizures, dysphagia, autonomic dysfunction, and brain death) was consistent with rabies. Rabies virus antigen was detected in archived autopsy brain tissue collected from the donor. The rabies viruses infecting the donor and the deceased kidney recipient were consistent with the raccoon rabies virus variant and were more than 99.9% identical across the entire N gene (1349/1350 nucleotides), thus confirming organ transplantation as the route of transmission. The 3 other organ recipients remained asymptomatic, with rabies virus neutralizing antibodies detected in their serum after completion of postexposure prophylaxis (range, 0.3-40.8 IU/mL). CONCLUSIONS AND RELEVANCE: Unlike the 2 previous clusters of rabies virus transmission through solid organ transplantation, there was a long incubation period in the recipient who developed rabies, and survival of 3 other recipients without pretransplant rabies vaccination. Rabies should be considered in patients with acute progressive encephalitis of unexplained etiology, especially for potential organ donors. A standard evaluation of potential donors who meet screening criteria for infectious encephalitis should be considered, and risks and benefits for recipients of organs from these donors should be evaluated.

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.

Every Dog Has Its Data: Evaluation of a Technology-Aided Canine Rabies Vaccination Campaign to Implement a Microplanning Approach.

Background: Robust dog vaccination coverage is the primary way to eliminate canine rabies. Haiti conducts annual canine mass vaccination campaigns, but still has the most human deaths in the Latin American and Caribbean region. We conducted an evaluation of dog vaccination methods in Haiti to determine if more intensive, data-driven vaccination methods, using smartphones for data reporting and geo-communication, could increase vaccination coverage to a level capable of disrupting rabies virus transmission. Methods: Two cities were designated into "Traditional" and "Technology-aided" vaccination areas. Traditional areas utilized historical methods of vaccination staff management, whereas Technology-aided areas used smartphone-supported spatial coordination and management of vaccination teams. Smartphones enabled real time two-way geo-communication between campaign managers and vaccinators. Campaign managers provided geographic instruction to vaccinators by assigning mapped daily vaccination boundaries displayed on phone handsets, whilst vaccinators uploaded spatial data of dogs vaccinated for review by the campaign manager to inform assignment of subsequent vaccination zones. The methods were evaluated for vaccination effort, coverage, and cost. Results: A total of 11,420 dogs were vaccinated during the 14-day campaign. The technology-aided approach achieved 80% estimated vaccination coverage as compared to 44% in traditional areas. Daily vaccination rate was higher in Traditional areas (41.7 vaccinations per team-day) compared to in technology-aided areas (26.8) but resulted in significantly lower vaccination coverages. The cost per dog vaccinated increased exponentially with the associated vaccination coverage, with a cost of $1.86 to achieve 25%, $2.51 for 50% coverage, and $3.19 for 70% coverage. Conclusions: Traditional vaccination methods failed to achieve sufficiently high vaccination coverages needed to interrupt sustained rabies virus transmission, whilst the technology-aided approach increased coverage above this critical threshold. Over successive campaigns, this difference is likely to represent the success or failure of the intervention in eliminating the rabies virus. Technology-aided vaccination should be considered in resource limited settings where rabies has not been controlled by Traditional vaccination methods. The use of technology to direct health care workers based on near-real-time spatial data from the field has myriad potential applications in other vaccination and public health initiatives.