Administration Of Rabies Post-exposure Prophylaxis Research Articles

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

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

Rabies in an imported dog, Ontario, Canada, 2022.

Importation of rabies-infected dogs results in significant and costly public and animal health risks. In January 2022, a dog in Ontario, Canada, which was imported from Iran in June 2021, developed rabies, leading to an extensive public health investigation and administration of rabies post-exposure prophylaxis to 37 individuals. The dog was infected with a rabies virus variant known to circulate in Iran. This is the second reported case of a rabies-infected dog imported into Canada in 2021 from a high-risk country for canine mediated rabies. This case emphasizes the need for public education regarding the risks associated with importing dogs from high-risk countries for canine-mediated rabies and the benefits of establishing a public health team specializing in rabies exposure investigations.

Human Rabies — Texas, 2021

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.

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

BackgroundAn 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 findingsTo 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.ConclusionsOur 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.

Inappropriate Administration of Rabies Postexposure Prophylaxis, Cook County, Illinois, USA.

Administration of rabies postexposure prophylaxis (PEP) is expensive and time-consuming. In suburban Cook County, Illinois, USA, administration of 55.5% of PEP treatments did not follow Advisory Committee on Immunization Practices guidelines. Health department consultation lowered the odds of inappropriate PEP administration by 87%. Providers should consult their health department before prescribing PEP.

Rabies post-exposure prophylaxis started during or after travel: A GeoSentinel analysis.

BackgroundRecent studies demonstrate that rabies post-exposure prophylaxis (RPEP) in international travelers is suboptimal, with only 5–20% of travelers receiving rabies immune globulin (RIG) in the country of exposure when indicated. We hypothesized that travelers may not be receiving RIG appropriately, and practices may vary between countries. We aim to describe the characteristics of travelers who received RIG and/or RPEP during travel.Methodology/Principal findingsWe conducted a multi-center review of international travelers exposed to potentially rabid animals, collecting information on RPEP administration. Travelers who started RPEP before (Group A) and at (Group B) presentation to a GeoSentinel clinic during September 2014–July 2017 were included. We included 920 travelers who started RPEP. About two-thirds of Group A travelers with an indication for rabies immunoglobulin (RIG) did not receive it. Travelers exposed in Indonesia were less likely to receive RIG in the country of exposure (relative risk: 0.30; 95% confidence interval: 0.12–0.73; P = 0.01). Travelers exposed in Thailand [Relative risk (RR) 1.38, 95% Confidence Interval (95% CI): 1.0–1.8; P = 0.02], Sri Lanka (RR 3.99, 95% CI: 3.99–11.9; P = 0.013), and the Philippines (RR 19.95, 95% CI: 2.5–157.2; P = 0.01), were more likely to receive RIG in the country of exposure.Conclusions/SignificanceThis analysis highlights gaps in early delivery of RIG to travelers and identifies specific countries where travelers may be more or less likely to receive RIG. More detailed country-level information helps inform risk education of international travelers regarding appropriate rabies prevention.

Surveillance of Rabies Postexposure Prophylaxis in Greece: 4 Years Experience.

Rabies reemerged in Greek fauna during October 2012, 25 years after the last report in animals and 42 after the last human case. This study examined the administration of rabies postexposure prophylaxis (PEP) in humans over the period 2012-2016. A total of 1,454 individuals (62.6% males) received PEP. The vast majority (92.3%) of regimens was initiated in high risk for animal rabies areas (11.1 PEP per 100,000 residents per year). Among the exposed, 77.0% presented at a healthcare setting during the first 24 h after the incident; more severe injuries were associated with faster presentation (p < 0.05). A vaccine series was administered in 54.5% of exposed persons whereas 43.7% received both vaccine and immunoglobulin and 1.7% immunoglobulin only. Exposure to stray dogs represented 68.4% of all incidents. In exposures occurring in nonhigh risk for rabies areas, bat was the second most frequently involved animal (13.4% of incidents). All dogs and cats evaluated by a veterinarian and laboratory-confirmed rabid were initially deemed suspect for rabies during clinical examination or according to history. No human rabies cases were recorded during the period of the study. Surveillance of PEP represents a valuable tool for aiding assessment of present and future demands in prophylaxis biologicals, outlining the epidemiological profile of exposures and planning effective policies for the management of exposure incidents.

A descriptive analysis of rabies post-exposure prophylaxis data: 2013, Ontario, Canada.

By 2013, the number of confirmed rabid animals in Ontario had decreased to unprecedented low numbers, yet the expected decrease in the number of courses of rabies post-exposure prophylaxis (RPEP) administered did not occur consistent with the decrease in animal rabies cases (Figure ). This prompted a review of the reasons that RPEP was administered in Ontario. This study provides a descriptive analysis of the exposure incidents resulting in RPEP administration in Ontario during 2013 using data obtained from the integrated Public Health Information System, a Web-based disease surveillance system. Findings from the study revealed that the number of RPEP courses administered could be reduced, without increased risk of rabies, through the following strategies: (i) Education and resources for public health staff and healthcare providers who assess animal exposures to improve interpretation of guidelines for RPEP administration. (ii) Refinement of guidelines for public health staff and healthcare providers to ensure that they support detailed consideration of the circumstances of the exposure in order to assist with the risk assessment. Guidelines should also support completion of a risk assessment when exposures to skunks, foxes, raccoons and other wild carnivores are provoked by the victim, as opposed to automatically providing RPEP as recommended by current guidelines. (iii) Public education strategies to prevent exposures to animals (e.g., do not touch unattended animals, bat proofing your house, proper removal of bats from the house). (iv) Defining the criteria to declare a jurisdiction rabies-free. (v) Exploring strategies to improve surveillance for rabid animals.

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

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. We evaluated whether animal bites and PEP were reportable to SHDs as of 2013 for every state in the United States. 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. 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. 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.

Human Rabies Post-Exposure Prophylaxis and Animal Rabies in Ontario, Canada, 2001-2012.

In Ontario, Canada, the implementation of an annual rabies control programme in wildlife that began in 1989 resulted in a marked, steady decrease in the number of animal rabies cases. The number of animal rabies cases decreased from 1870 in 1989 to 183 in 2000 (Nunan et al., 2002 Emerg Infect Dis 8, 214). In our study period, the number of animal rabies cases continued to decrease from 210 in 2001 to 28 in 2012. The marked decrease in animal rabies cases since 1989 has resulted in a decrease in the risk of human infection. A concomitant decrease in the number of rabies post-exposure prophylaxis (RPEP) administered was anticipated but failed to occur. The mean rate of RPEP, 13.9 RPEP administered per 100,000 persons, from 2001-2012 was approximately the same as the rate in the 1990 s. Two possible reasons that the rate of RPEP administration has not decreased include strict adherence to RPEP recommendations and administration of RPEP when it is not recommended. A reduction in the number of RPEP administered, consistent with the decrease in the animal rabies cases, would provide some financial savings for the government. Ideally, an increased use of the risk assessment approach in keeping with recent guidelines, rather than adhering to previous prescriptive recommendations for RPEP administration, coupled with a continuing low incidence of animal rabies cases will result in decreased, and yet appropriate, use of RPEP. Consideration should be given to identify how guidelines could be revised to more effectively target high-risk exposures and reduce the administration of RPEP for instances in which the risk of rabies virus exposure is exceedingly low.

Clinician outreach to improve the quality of rabies postexposure prophylaxis administration: Maryland's experience, 2010-2011.

Errors in the administration of rabies postexposure prophylaxis (PEP) are known to occur despite guidelines promulgated by the Advisory Committee on Immunization Practices (ACIP). In addition to elevating a patient's PEP failure risk, errors in administration increase medical expenses. A record review conducted at a local health department in Maryland revealed that ∼8% of reported PEPs deviated from ACIP guidelines. Physicians surveyed at a local hospital also demonstrated knowledge gaps concerning use of rabies immune globulin and special indications for the five-dose PEP series. In response, we implemented an intervention to raise clinician awareness and adherence to recommended protocols. Activities included development of a patient fact sheet, hospital-based poster, and online training course targeted to a diverse group of healthcare providers. We also explored the use of hospital informatics in delivering PEP guidance. Clinician outreach by using a multipronged approach might increase adherence to recommended protocols.

Estimating the risk of rabies transmission to humans in the U.S.: a delphi analysis

BackgroundIn the United States, the risk of rabies transmission to humans in most situations of possible exposure is unknown. Controlled studies on rabies are clearly not possible. Thus, the limited data on risk has led to the frequent administration of rabies post-exposure prophylaxis (PEP), often in inappropriate circumstances.MethodsWe used the Delphi method to obtain an expert group consensus estimate of the risk of rabies transmission to humans in seven scenarios of potential rabies exposure. We also surveyed and discussed the merits of recommending rabies PEP for each scenario.ResultsThe median risk of rabies transmission without rabies PEP for a bite exposure by a skunk, bat, cat, and dog was estimated to be 0.05, 0.001, 0.001, and 0.00001, respectively. Rabies PEP was unanimously recommended in these scenarios. However, rabies PEP was overwhelmingly not recommended for non-bite exposures (e.g. dog licking hand but unavailable for subsequent testing), estimated to have less than 1 in 1,000,000 (0.000001) risk of transmission.ConclusionsOur results suggest that there are many common situations in which the risk of rabies transmission is so low that rabies PEP should not be recommended. These risk estimates also provide a key parameter for cost-effective models of human rabies prevention and can be used to educate health professionals about situation-specific administration of rabies PEP.

The cost of preventing rabies at any cost: Post-exposure prophylaxis for occult bat contact

Investigations conducted by public health in Quebec, Canada, following report of human exposure to a bat were reviewed to evaluate the implementation of the recommendation for rabies post-exposure prophylaxis (RPEP) for household bat exposure (without documented direct contact). Of all RPEP recommended, 12% was for direct bat contact with bite, 7% for direct bat contact without known bite and 81% for household exposure. When bat was not available for testing, RPEP was almost always recommended. Household bat exposure has become the most frequent reason for RPEP administration. Given the rarity of rabies, RPEP recommendations related to household bat exposure may warrant review.

Risk factors for human exposure to raccoon rabies during an epizootic in Connecticut.

The emergence of rabies among terrestrial wildlife poses increasing but poorly defined risks to people. In particular, events leading to human exposure to rabies virus via mammalian reservoirs remain elusive. Thus, we determined those risk factors associated with human exposure to rabies-positive animals during a raccoon rabies epizootic in Connecticut. Existing passive surveillance data on animal rabies tests in Connecticut from 1991 through 1994 were evaluated for demographic, ecological, and behavioral characteristics of human exposure. Of 2,525 rabies-positive terrestrial animals identified, human contact was reported on 556 occasions (22%) and involved at least 939 individuals. The annual incidence of exposure rose from none during 1985-1990 to 66 in 1991 and then averaged 291 during 1992-1994. Exposure was most often indirect in nature, involved a rabies-positive raccoon, was mediated through a domestic animal, and occurred most frequently either near or inside the home. These results suggest that human exposure to rabid animals represents a significant, reemerging public health concern in the United States. Analysis of the epizootiology of rabies infection and of individual exposure risks could reduce inappropriate administration of rabies postexposure prophylaxis, as well as inform other proposed interventions.

Human exposure to rabies from pet wild raccoons in South Carolina and West Virginia, 1987 through 1988.

During 1987 and 1988, exposures to eight pet wild raccoons in South Carolina and West Virginia resulted in administration of rabies post-exposure prophylaxis to 19 children and 26 adults. All eight raccoons appeared normal at the time of capture, and three had no signs of illness when sacrificed. The direct medical cost resulting from these exposures was $23,714 ($527 per person). Regulations and public education may help decrease this type of rabies exposure.