Indications for post-exposure rabies prophylaxis

INTRODUCTION — Rabies is a viral disease primarily acquired from the bite of a rabid animal. There is no known effective treatment for rabies, and virtually all cases are fatal. Survival remains a rare and largely inexplicable phenomenon, which is often associated with severe neurologic sequelae (table 1).

Although the prognosis is poor in patients who develop rabies, the disease is usually preventable with proper wound care and post-exposure prophylaxis, which was first pioneered by Louis Pasteur in 1885. This topic will discuss when to use rabies prophylaxis. Additional information on rabies biologics (vaccine and immunoglobulin), as well as the epidemiology, clinical features, and treatment of human rabies, are presented elsewhere. (See "Rabies immune globulin and vaccine" and "Clinical manifestations and diagnosis of rabies" and "Treatment of rabies".)

GENERAL PRINCIPLES — The decision to initiate rabies post-exposure prophylaxis after a potential exposure should be made following a thorough risk assessment. Post-exposure prophylaxis includes rabies vaccine with or without rabies immune globulin. The specific regimen depends upon the patient's prior rabies vaccine history and other factors. A detailed discussion of the regimens used for post-exposure prophylaxis is found elsewhere. (See "Rabies immune globulin and vaccine".)

To prevent rabies infection, post-exposure prophylaxis should be administered to all patients who have had a known or likely exposure to rabies, including those who received prior pre-exposure prophylaxis.

In general, we consider an exposure to be:

●A bite or saliva-contaminated scratch from an animal with rabies

●An open wound or mucous membrane exposure to saliva, cerebrospinal fluid, or central nervous system (CNS) tissue from an animal with rabies

However, it is not always possible to confirm an exposure to rabies, and prophylaxis is often administered empirically based upon the possibility that an exposure occurred.

Exposure of normal, keratinized skin to potentially infectious material (ie, saliva, neural tissue) or any contact with blood, urine, feces (guano), or skunk spray of a rabid animal does not constitute an exposure.

RISK ASSESSMENT — After a potential exposure to rabies, it is important to decide if rabies post-exposure prophylaxis should be administered. Consultation with the local public health agency can be valuable in assessing the risk of transmission after a potential exposure.

A prospective study of university-affiliated, urban emergency departments suggested that post-exposure prophylaxis was given inappropriately in approximately 40 percent of cases [1]. A more recent study suggests that this is still the case but that health department consultation can reduce inappropriate prophylaxis by 87 percent [2]. Another report described a school incident in which a parent showed a dead bat to multiple students, some of whom touched the carcass [3]. The bat was later tested for rabies virus, and it was confirmed to be positive. Public health authorities from the local and state health departments and the United States Centers for Disease Control and Prevention (CDC) provided recommendations for post-exposure prophylaxis after interviewing 107 students with potential exposures but only recommended prophylaxis for one person who reported putting her finger in the mouth of the bat.

Initial evaluation — Several factors need to be considered when deciding if post-exposure prophylaxis is needed after a potential exposure to rabies. These include [4,5]:

●The epidemiology of animal rabies in the region. (See 'Animal exposures in the United States' below and 'Animal exposures that occur outside the United States' below.)

●The species of the exposing animal. (See 'Domestic animals' below and 'Wild terrestrial mammals' below and 'Livestock' below.)

●The type of contact with the animal (exposures of concern can occur through a bite or saliva or neural tissue contamination of a scratch, an open wound, or mucous membrane).

Additional considerations include an assessment of factors that could indicate an exposing animal is likely to be rabid (eg, absence of appropriate vaccination, unprovoked attack, recent behavioral changes in the animal, recent bites or wounds on the animal), as well as the availability of the animal for observation/testing. These are discussed in detail below. (See 'Additional considerations' below.)

Almost all cases of rabies are transmitted from rabid animals through a bite. The risk of acquisition increases with multiple bites and with bites in close proximity to the CNS (picture 1) [6]. Data from areas with endemic rabies in dogs have found that children are at increased risk of acquiring rabies because they are more likely to be bitten, particularly in the trunk, head, or neck [7-9], and to suffer severe injuries.

Outcomes may also be worse in patients with bites close to the CNS. In a study from Thailand, the risk of dying from rabies in patients who did not receive post-exposure prophylaxis was highest in those who were severely bitten around the face, neck, and arms, compared with those who were bitten around the feet [10].

In rare cases, rabies has resulted from a nonbite exposure, such as a scratch or mucous membrane that has been in contact with saliva or neural tissue from an animal with rabies. There have also been cases of rabies that have occurred after corneal transplantation or of an organ from a human donor with unrecognized rabies. (See 'Transplant recipients' below.)

No transmission of rabies has been documented from rabies-infected patients to health care providers or household contacts, although there is limited surveillance in parts of the world with the greatest number of human rabies cases. In addition, rabies is not transmitted via fomites or environmental surfaces [4,11,12]. The rabies virus does not survive well outside of the host and is affected by desiccation, sunlight, pH, and other environmental factors. In general, if the material containing the virus is dry, it can be considered noninfectious.

Probable aerosol exposure to rabies virus in laboratories resulted in two cases [13-15]. Two other cases in the early 1960s were attributed to possible airborne exposures in a single cave containing millions of free-tailed bats (Tadarida brasiliensis) in the southwestern United States [16]. However, it is difficult to rule out inapparent bites as the route of transmission given the conditions in the cave, and no other potential airborne exposures have been identified in that cave or any others.

Additional considerations — When assessing the risk of an exposure, it is important to evaluate factors that may indicate an exposing animal is likely to be rabid. These include absence of an appropriate vaccination history in a domestic animal, a report by the victim of an unprovoked attack, and/or a report that the exposing animal was displaying neurologic signs or had a recent history of bites or wounds.

Provoked versus unprovoked exposure — Because rabies virus infection can manifest as an increase in aggressive behavior, an unprovoked attack by an animal could represent the first sign that it is rabid. Determining if an attack is provoked or unprovoked should always be done from the point of view of the animal rather than the human. For example, bites that occur when a person is trying to handle or feed an animal should usually be considered provoked attacks (ie, not evidence of abnormal aggressive behavior) assuming the animal is otherwise acting in a normal manner and not likely to be rabid based on any of the additional considerations mentioned (see 'Initial evaluation' above). Local public health authorities can assist in making this determination.

Vaccination status of domestic animals — Domestic animals should receive rabies vaccination; rabies in vaccinated animals is rare [17]. In sub-Saharan African (where most rabies exposures occur through rabid dogs), a cost-effectiveness analysis demonstrated that annual canine rabies vaccination campaigns, compared with no canine vaccination, would be cost effective and lifesaving [18].

Although few cases of rabies have been reported in animals that have previously been vaccinated, guidelines continue to recommend observation of vaccinated dogs, cats, and ferrets after an exposure [17]. (See 'Domestic animals' below.)

Animal observation and testing — In the United States, decisions about prophylaxis can often be delayed if the animal is a healthy dog, cat, or ferret and is able to be confined and observed for 10 days (algorithm 1).

Data from rabies pathogenesis studies in dogs, cats, and ferrets indicate that these animals uniformly begin to sicken and die within 10 days (usually 5 to 7 days) after the rabies has spread from the CNS to the salivary glands [19-21].

●Observed animals that exhibit any sign of illness during the 10-day observation period should be evaluated by a veterinarian and reported to the local health department. If the animal does develop signs of rabies, it should be euthanized and its head shipped overnight under refrigeration to a laboratory certified to perform rabies testing (most often a public health laboratory).

●If the animal remains healthy for the full 10 days, then it did not have rabies virus in its saliva at the time of exposure. The shedding period (ie, the time during which virus might be found in the saliva prior to an animal's death) is not fully documented for species other than dogs, cats, or ferrets.

Immediate prophylaxis is indicated if the animal develops clinical signs of rabies during the 10-day observation period following the exposures. If post-exposure prophylaxis was initiated and the animal remains well for the full 10 days or is tested for rabies and is found negative, prophylaxis can be discontinued.

The approach to prophylaxis for bats and wild terrestrial mammals that are available for testing is discussed below. (See 'Bat exposures' below and 'Wild terrestrial mammals' below.)

EVALUATING THE SOURCE OF EXPOSURE — The approach to post-exposure prophylaxis described below is based upon the recommendations of the Advisory Committee on Immunization Practices (ACIP) for rabies post-exposure (algorithm 1) [4,22]. Other guidelines panels, such as the World Health Organization (WHO), have also made recommendations on the use of post-exposure prophylaxis [23,24]. Compared with United States guidelines, which recommend administration of immune globulin and vaccination following an exposure for anyone who has not previously received pre- or post-exposure prophylaxis, the WHO recommends immune globulin only for select exposure situations (table 2). The WHO guidelines are discussed in greater detail below. (See 'Special considerations in resource-limited settings' below.)

In many scenarios, the decision to initiate post-exposure can be complex. Clinicians should seek the help of local or state public health authorities for further advice regarding the need for post-exposure prophylaxis. In the United States, contacts can be found on the CDC website. Clinicians can also check the CDC website for rabies updates.

Bat exposures — Classic rabies virus in bats has only been identified in the Americas. However, rabies-like lyssaviruses have been identified in bats globally, and any interaction with bats should be considered to have the potential for a lyssavirus exposure with the possibility of a fatal outcome [25,26]. In the United States, bat rabies has been found in all states except Hawaii. Between 1990 and 2018, 51 (91 percent) of the 56 human cases of rabies acquired in the United States were due to rabies acquired from bats [27,28].

Post-exposure prophylaxis should be considered when there has been a potential contact between a human and a bat. This includes individuals who have been in a room with a bat if they are unable to rule out any physical contact. Our approach to post-exposure prophylaxis is as follows:

●If the bat is available for testing, prophylaxis can be delayed if the results will be available promptly (eg, several days), since more than 90 percent of bats submitted for testing are negative for rabies. Bats should not be picked up or handled by anyone except trained and vaccinated persons unless the layperson can safely capture and confine the bat. A video demonstration of how to safely capture a bat is available on the New York State Department of Health website.

●If testing is not available or if the bat tests positive for rabies, post-exposure prophylaxis should be administered in the following settings:

•To all individuals who have had a bite, scratch, or mucous membrane exposure from a bat.

•When direct contact with a bat occurred and the individual is unable to rule out a bite or scratch.

•If an individual has been in a room with a bat and is unable to rule out any physical contact. Such individuals include a sleeping person who awakens to find a bat in the room, an unattended child, a mentally disabled person, and an intoxicated person. This approach is consistent with the recommendations of the ACIP for rabies post-exposure prophylaxis [4,22]; however, some guideline panels do not advocate this approach [29].

●Post-exposure prophylaxis is not necessary if the person was aware of the bat at all times while in an enclosed or open space and is certain that there was no bite, scratch, or mucous membrane exposure. Household members who were not in a room with the bat do not require post-exposure prophylaxis. A clustering of human cases associated with bat exposures has never been reported (eg, within the same household or among campers at an outside camp).

The risk for rabies resulting from an encounter with a bat is often difficult to assess because bites by bats may be too small to be routinely detected or may occur at night during sleep (picture 1) [30]. From 1990 to 2007, a total of 34 naturally acquired bat-associated human cases of rabies were reported. In 15 cases, physical contact was reported but no bite was documented, and, in 11 cases, no known bat encounter was reported at all [4]. However, by the time rabies is diagnosed, getting an accurate history is usually precluded.

In a study that evaluated this approach by estimating bedroom exposure to bats in a population survey of 14,453 households, the number of individuals who would need to be treated to prevent a single case of bat rabies related to bedroom exposure without recognized contact ranged from 314,000 to 2.7 million persons, at a cost of USD $228 million to $2 billion [31]. In this study, the incidence of rabies was based on reported cases in the United States and Canada over a 17-year period. Given these findings, the recommendations in Canada changed in 2009 so that prophylaxis is only recommended if there is both direct contact with a bat and a bite, scratch, or saliva exposure into a wound or mucous membrane cannot be ruled out [29].

Animal exposures in the United States — When deciding if a specific animal exposure is likely to transmit rabies, it is important to take into account the type of animal and the location where the exposure occurred. As an example, in developing countries, dogs continue to account for 90 percent or more of reported cases in humans [32]. By contrast, bat-variant rabies viruses have emerged as the dominant source associated with indigenously acquired human rabies in the United States; other animal reservoirs include raccoons, skunks, and foxes [27,28].

The approach to rabies post-exposure prophylaxis after a bite or a mucosal exposure to a mammal in the United States is described in the algorithm (algorithm 1) and is summarized below.

Domestic animals — After an exposure to a domestic animal (dog, cat, or ferret) in the United States, the decision to initiate post-exposure prophylaxis can typically be delayed if the animal is healthy and can be quarantined for 10 days of observation (algorithm 1). This approach should be used even if the animal is vaccinated. (See 'Animal observation and testing' above and 'Vaccination status of domestic animals' above.)

If these conditions cannot be met, providers should contact public health authorities to determine the need for post-exposure prophylaxis. The probability of human exposure to rabies by a domestic animal in the United States is low as the number of rabies cases among domestic animals, such as dogs or cats, has declined markedly in the United States [4]. However, rabid dogs and cats are sporadically reported from areas with enzootic wildlife rabies. In addition, domestic animals that are incubating rabies have been imported from regions of the world where canine rabies is still enzootic [17,33].

More cats than dogs are currently reported rabid in the United States [27]. This is related to fewer cat vaccination laws, which results in a smaller percentage of cats vaccinated against rabies compared with dogs. Cats are also more often allowed to be free roaming than dogs and are therefore more likely to encounter rabid wildlife.

Wild terrestrial mammals — In the United States, terrestrial carnivores, such as raccoons, skunks, and foxes, are the animals most likely to be infected with rabies, after bats (figure 1) [34]. Rabies has also been reported in large rodents (woodchucks and beavers) in areas of the United States where raccoon rabies is prevalent.

Direct human and domestic animal contact with wild terrestrial mammals should be avoided. However, if an exposure does occur, we use the following approach to determine if post-exposure prophylaxis is needed (algorithm 1):

●Raccoons, foxes, and skunks should be regarded as rabid until proven otherwise. Larger carnivores, such as coyotes, bobcats, mountain lions, wolves, bears, woodchucks, and beavers, should also be considered rabid (unless proven otherwise) if they are involved in an unprovoked attack on a person.

•Post-exposure prophylaxis should be initiated immediately in response to any severe exposure (eg, multiple bites or a bite on the head, neck, or trunk) from an animal likely to be rabid. If the animal can be safely captured by someone who is trained and vaccinated, it should be euthanized and tested as soon as possible. The vaccination series may be discontinued if the animal tests negative for rabies.

•If the type of exposure to one of these animals is of lower risk (eg, minimal bite wound to extremity, nonbite exposure), post-exposure prophylaxis can be delayed temporarily if the animal can be tested promptly (eg, a few days). (See 'Animal observation and testing' above.)

●Post-exposure prophylaxis for bites involving small, wild rodents, such as squirrels, chipmunks, rats, hamsters, gerbils, guinea pigs, mice, and lagomorphs (rabbits and hares), is generally not indicated. There has never been a case of transmission to a human from one of these animals, and these animals are likely to die from an exposing incident rather than survive to develop rabies.

However, the need for post-exposure prophylaxis in this situation should be evaluated on a case-by-case basis, in consultation with public health authorities [35]. Rabies has been identified in pet rabbits and guinea pigs caged outdoors (caging may sufficiently protect them from severe injury or death during encounters with infected wildlife to allow them to develop rabies later) [36], and this must be considered when evaluating the risk of rabies transmission from lagomorph and rodent bites.

Livestock — No human cases of rabies following exposure to livestock have been documented in the United States. However, cases of rabies in livestock infected by wild animals are reported [27]. Thus, the need for post-exposure prophylaxis after a bite or nonbite exposure from livestock should be managed individually in consultation with local public health authorities.

Animal exposures that occur outside the United States — If a patient is bitten by a mammal or is otherwise potentially exposed to rabies outside the United States, every attempt should be made to ascertain the relevant rabies epidemiology in the geographic area of exposure as part of a thorough rabies exposure risk evaluation. Information on rabies risks by country can be located on the CDC travel website.

Post-exposure prophylaxis should generally be initiated immediately after a dog bite in areas where canine rabies is endemic (eg, Asia and Africa); prophylaxis can then be discontinued if testing or observation proves the animal is not rabid [24]. In such settings, observation without prophylaxis is reasonable if the biting animal is a healthy dog or cat that has previously been vaccinated against rabies, is reliably reported not to have any possible exposures to rabies in the last six months, and is readily accessible for monitoring for the 10-day period. These situations are highly variable, and the risk of rabies from a dog bite varies even within an endemic country. In general, patients should be managed in consultation with the local or state health department.

Among 43 cases of human rabies diagnosed in the United States between 2003 and 2016, 10 were attributed to exposure to dogs outside the United States [27]. The incubation period for such imported cases has been reported to be as long as eight years [37].

Dogs remain the primary rabies reservoir species in most of the developing world, including Africa, Asia, the Middle East, Mexico, and Central and South America, as well as Eastern Europe [38,39]. In some of those areas, various wild carnivores act as rabies reservoir species as well. By contrast, a few areas have managed to control canine and wildlife rabies (or never had any), including most of Western Europe, Australia, and New Zealand, and pose a limited risk for rabies from terrestrial animals [40].

Bat rabies, or other bat lyssaviruses that can cause encephalitic disease indistinguishable from rabies, has been identified globally, and interaction with bats should be considered to have the potential for exposure. (See 'Bat exposures' above.)

Human exposures — Human-to-human transmission of rabies can theoretically result from bite and nonbite exposures, but reports are very rare, poorly documented, and occur in places where it is difficult to rule out potential animal exposures. No transmission of rabies has been documented from rabies-infected patients to health care providers or to household contacts in the United States. However, human-to-human transmission arising from transplantation (corneas, organs, tissues) is well documented.

Health care workers — Routine delivery of health care to a patient with rabies is only considered to constitute a rabies exposure if mucous membranes or nonintact skin come in contact with potentially infectious body fluids or tissues (such as saliva, cerebrospinal fluid, and neural tissue) [12]. Standard infection control precautions would minimize the risk of any such exposure and should be routinely employed [41-43]. As an example, staff should wear gowns, masks, gloves, and eye/face protection, particularly when there is risk of aerosols and splashes from respiratory secretions, such as those that can occur during intubation and suctioning [24]. Because the rabies virus is inactivated by desiccation and ultraviolet irradiation, a dry surface or object should be considered noninfectious.

Transplant recipients — Several cornea transplant recipients have died of rabies [44-49]. Cases have occurred in Thailand, India, Iran, France, and the United States. In all these cases, the donor was later found to have died of an illness that was either proved to be, or was compatible with, rabies. Guidelines for corneal transplantation have since been implemented, which reject corneas from those dying of unexplained encephalitis.

In 2004, rabies transmission was also documented from a solid organ/tissue donor to transplant recipients [50]. The organ donor died from a subarachnoid hemorrhage following an illness characterized by severe mental status changes and a low-grade fever. The death was attributed to noninfectious causes, and organs and tissues were recovered and transplanted. Three recipients of organs and one recipient of vascular tissue subsequently died of laboratory-confirmed rabies. A follow-up public health investigation found that the donor had reported being bitten by a bat, and bat strain rabies was identified [51]. Since that time, rabies transmission in solid organ transplant recipients has been reported in Germany, the United States, and China [52-55].

If a patient is discovered to have received a transplant from a donor with rabies before the recipient develops symptoms consistent with rabies, post-exposure prophylaxis should be administered.

Bite and nonbite exposures — Bite and nonbite exposures from humans with rabies could theoretically transmit the virus. Two cases of purported human-to-human transmission were reported in 1996 in Ethiopia (one through a bite and the other through kissing) [56]; however, there have been no laboratory-confirmed cases of human-to-human rabies transmission.

Although human-to-human transmission, if it occurs, is extremely rare, contact of mucous membranes or nonintact skin with potentially infectious body fluids or tissues (such as saliva, cerebrospinal fluid, and CNS tissue) from a patient diagnosed with rabies should be considered to constitute a rabies exposure, and post-exposure prophylaxis should be administered.

TIMING OF PROPHYLAXIS — Once it has been determined that the patient should receive rabies post-exposure prophylaxis, prophylaxis should begin as soon as possible after the exposure. However, post-exposure prophylaxis should be administered even if there is a delay, given the long latency period between exposure and onset of disease (the average incubation period is 45 days) [37]. Specific information regarding dosing regimens is presented elsewhere. (See "Rabies immune globulin and vaccine".)

TRAVELERS

Pretravel counseling — Discussions of pre-exposure prophylaxis are part of proper counseling for travelers to rabies enzootic/endemic regions of the world (including most of Asia, Africa, the Middle East, Mexico, and Latin America) who are visiting areas where the danger of an exposure may be high and post-exposure care may be difficult to access (eg, rural, remote, nontouristic). (See "Rabies pre-exposure prophylaxis", section on 'Risk-stratification and indications'.)

All patients should be advised to avoid exposure to stray and wild animals and should be educated about appropriate wound cleaning. In addition, children should be closely supervised when traveling, since they are more likely to inadvertently provoke animals and be injured; they are also less likely to report exposures [16]. In a case-control study, increased likelihood of exposure to a potentially rabid animal among travelers correlates with youth, male sex, travel to western or southeastern Asia, visiting a monkey park, previous travel to the area, and considering oneself to be an experienced traveler to an area [57].

If an exposure occurs, exposed individuals should seek prompt medical care, regardless of whether they have received rabies vaccination in the past. The American consulates abroad can often provide information on accessing these products. In some situations, it may be prudent to recommend that the traveler return home immediately to receive appropriate care.

Returning travelers — Some travelers may have initiated post-exposure prophylaxis after an exposure while traveling. Travel medicine advisors should be aware that post-exposure prophylaxis measures undertaken in resource-limited countries may differ from the Advisory Committee on Immunization Practices (ACIP) guidelines, which are followed within the United States [4,22]. This includes differences in both the suggested regimens and the biologic products [23,24,58,59]. (See 'Special considerations in resource-limited settings' below and "Rabies immune globulin and vaccine".)

There are certain questions that may arise when the traveler returns. State or local health departments should be contacted for specific advice in these cases; however, our general approach is as follows:

●If a traveler returns home before completing a regimen in a resource-limited setting, it is not known whether completion of the immunization series with intramuscularly administered rabies vaccine (rather than the intradermal vaccine that is often administered in resource-limited settings) is effective or whether the entire series should be given de novo.

•In patients who have already completed most of the series abroad, completion of the immunization series with intramuscularly administered rabies vaccine and documentation of a protective rapid fluorescent focus inhibition test (RFFIT) antibody titer as defined by ACIP is recommended [4]. (See "Rabies immune globulin and vaccine", section on 'Post-exposure immunization' and "Rabies immune globulin and vaccine", section on 'Postvaccination serologic testing'.)

•In patients where the immunogenicity of the particular product is uncertain or if a vaccine was administered in a geographic location where proper vaccine storage and handling may be questionable, it is reasonable to administer the full series with a vaccine licensed in the United States, especially if there is any question about the vaccine product, vaccine handling and storage, administration route, or completeness of the regimen they have received (see "Rabies immune globulin and vaccine", section on 'Post-exposure immunization'). State or local health departments should be contacted for specific advice in these cases.

●If a traveler sustained scratches or abrasions, World Health Organization guidelines recommend only vaccine, which differs from the ACIP guidelines that recommend both vaccine and rabies immune globulin (RIG) for this type of exposure. In this setting, RIG can be administered upon return if it is no later than seven days after the start of an immunization series; RIG should not be administered after because it may suppress the immune response to rabies vaccine [60].

●If a traveler completes the entire post-exposure regimen in a resource-limited setting, with or without administration of RIG, documentation of a protective RFFIT antibody titer as defined by the ACIP is generally recommended, and additional doses of vaccine are reasonable if the titer is below the recommended threshold. (See "Rabies immune globulin and vaccine", section on 'Postvaccination serologic testing'.)

EXPOSURES IN INDIVIDUALS WHO HAVE RECEIVED PRIOR RABIES VACCINATION — For individuals exposed to rabies who have a history of receiving pre-exposure prophylaxis or have previously received a full post-exposure prophylaxis regimen, fewer post-exposure vaccinations may be necessary and rabies immune globulin may not be required, depending upon whether certain criteria are met. Details for management of these patients are found elsewhere. (See "Rabies immune globulin and vaccine", section on 'Regimens for previously vaccinated individuals'.)

SPECIAL CONSIDERATIONS IN RESOURCE-LIMITED SETTINGS — Because of a combination of limited resources and a high incidence of canine rabies, many resource-limited countries have adopted the World Health Organization (WHO) recommendations, in which post-exposure prophylaxis depends upon the type of contact with the confirmed or suspected rabid animal [23,24]. The WHO classifies rabies exposure into three categories and recommends the use of rabies immune globulin only to the extent that it can be infiltrated into and around the wound (table 2).

A discussion of the vaccine formulations and dosing schedules used in resource-limited settings is presented elsewhere. (See "Rabies immune globulin and vaccine", section on 'Rabies biologics' and "Rabies immune globulin and vaccine", section on 'Resource-limited settings'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Rabies" and "Society guideline links: Travel medicine".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Rabies (The Basics)")

●Beyond the Basics topics (see "Patient education: Animal and human bites (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Post-exposure management – For patients who have had an exposure to rabies, we recommend proper wound care and post-exposure prophylaxis (Grade 1A). Because post-exposure prophylaxis is highly effective and rabies is a fatal infection, we give post-exposure prophylaxis to any patient who is deemed to have had a potential exposure. (See 'General principles' above.)

•Risk assessment – The decision to initiate rabies post-exposure prophylaxis should be made following a thorough risk assessment. The risk assessment should include consideration of the type of exposure, local rabies epidemiology in animals, vaccination history of the animal, circumstances of the exposure incident, and the availability of the animal for observation or rabies testing. Consultation with the local public health agency can be valuable in assessing the risk of transmission after a potential exposure. (See 'Risk assessment' above.)

-Bat exposures – Rabid bats are the dominant source associated with indigenously acquired human rabies in the United States. Post-exposure prophylaxis should be considered when there has been a potential contact between a human and a bat. This includes individuals who have been in a room with a bat if they are unable to rule out any physical contact. If the bat is available for testing, prophylaxis may be delayed if the results will be available promptly. (See 'Bat exposures' above.)

-Exposures to animals other than bats – The approach to rabies post-exposure prophylaxis after a bite or a mucosal exposure to mammals other than bats depends upon the likelihood the animal is infected with rabies (algorithm 1). In the United States, terrestrial carnivores, such as raccoons, skunks, and foxes, are most likely to be infected. By contrast, in developing countries, dogs continue to account for 90 percent or more of reported rabies cases in humans. (See 'Animal exposures in the United States' above and 'Animal exposures that occur outside the United States' above.)

-Exposures to humans with rabies – Transmission of rabies from rabies-infected patients to health care providers or to household contacts has not been documented, although there is limited surveillance in parts of the world with the greatest number of human rabies cases. Human-to-human transmission arising from transplantation (corneas, organs, tissues) is well described. (See 'Human exposures' above.)

●Pre-exposure prophylaxis – In individuals who have received pre-exposure prophylaxis, post-exposure prophylaxis is still required after an exposure. Pre-exposure prophylaxis is particularly important in areas where rabies immune globulin may be unavailable and may afford some protection when post-exposure prophylaxis administration is delayed. (See "Rabies pre-exposure prophylaxis".)

●Travelers – If an exposure occurs in a traveler, prompt medical care should be sought. However, clinicians should be aware that post-exposure prophylaxis vaccines and immune globulins, as well as schedules received abroad, may differ from regimens offered in the United States. (See 'Travelers' above and "Rabies immune globulin and vaccine", section on 'Rabies biologics' and "Rabies immune globulin and vaccine", section on 'Resource-limited settings'.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Wichai Techasathit, MD, MPH, who contributed to earlier versions of this topic review.