Rabies in Europe

Epidemiology, Clinical Management, and Prevention

Background: Rabies is one of the oldest known zoonoses. In Europe, because cases are rare and medical experience is limited, there is often uncertainty about the indications and modalities of pre- and post-exposure prophylaxis (PrEP, PEP).

Methods: This review is based on studies of the epidemiology, diagnosis, treatment, and prophylaxis of rabies that were published from January 2000 to October 2025 and retrieved by a selective search in PubMed, supplemented by data from the WHO, CDC, ECDC, RKI, and FLI and the current recommendations of the German Standing Committee on Vaccination (STIKO).

Results: The WHO reports that approximately 60 000 persons die of rabies each year around the world, mainly in southern Asia and Africa, and that dogs are the source of the infection in more than 99% of cases. Once the disease has become manifest, its lethality is nearly 100%. Terrestrial rabies is considered to have been largely eliminated in the member states of the European Union (EU) since 2008, although zoonotically relevant bat lyssaviruses are still being regularly documented. As a result, even in Germany, a low risk of infection remains through contact with bats and through importation of infected animals from endemic areas abroad. The use of modern cell-culture vaccines for PrEP yields protection rates of 96–100%, with rare severe side effects (<1:10 000). PEP is highly effective: after its administration in more than 29 million cases per year around the world from 1980 to 2022, only 122 breakthrough infections were registered, mainly because of faulty administration of rabies immunoglobulin, inadequate wound cleansing, and a late start of PEP. The main preventive measures are PrEP, avoidance of exposure, rapid wound disinfection, early PEP, and counseling by specialists in travel medicine.

Conclusion: Despite the favorable epidemiological situation, the possibility of rabies should be considered early on for anyone in Europe who has had an unclear animal exposure—especially to bats—or a potential rabies exposure abroad. When questions remain about the indication or modalities of PEP, expert advice should be obtained from an infectious disease unit or a rabies information center.

Cite this as: Reinhardt F, Wendt S, Pfeffer M, Freuling C, Müller T, Lübbert C: Rabies in Europe: Epidemiology, clinical management, and prevention. Dtsch Arztebl Int 2026; 123: 108–114. DOI: 10.3238/arztebl.m2025.0220

Rabies is one of the oldest known zoonoses and is almost always fatal once clinical symptoms appear. According to WHO data, approximately 60 000 people worldwide die of rabies each year, mainly in South Asia and Africa (1, 2). In the countries of the European Union (EU), terrestrial rabies has largely been eradicated by comprehensive vaccination programs in wild animals (3, 4); there remains a low risk of infection in Germany through contact with bats and animals imported from endemic areas (5, 6). Moreover, unvaccinated travelers to endemic areas are subject to a relevant risk of rabies exposure (the probability of contact with a potentially rabid animal is 0.5–2% per month of travel) and must be treated on return to Germany (6, 7, 8). The last case of fox rabies in Germany occurred in 2006, the last autochthonous case in humans after a dog bite in 1981 and after a fox bite in 1990, and the last imported infection (from Morocco) in 2007 (4, 6, 9). The complete worldwide eradication of rabies would require the elimination of all existing wild animal reservoirs by comprehensive vaccination programs. This can only be regarded as unrealistic.

The limited clinical experience in Europe, owing to the rarity of the disease, contributes to existing uncertainty about the indication and implementation of life-saving post-exposure prophylaxis (PEP) or pre-exposure prophylaxis (PrEP) by vaccination (protective effect after basic immunization: at least 10 years) (10). In view of increasing global mobility, persistent animal reservoirs, and the possibility of imported cases, awareness of these issues needs to be raised among medical professionals.

In this review, we survey the current epidemiological situation and summarize clinical aspects and evidence-based prevention strategies.

Methods

A selective search was conducted in PubMed for pertinent articles dealing rabies in humans that were published in German or English from January 2000 to October 2025. Data from the World Health Organization (WHO), the US Centers for Disease Control and Prevention (CDC), the European Centre for Disease Prevention and Control (ECDC), the Robert Koch Institute (RKI), and the Friedrich Loeffler Institute (FLI) were considered as well, as were the current recommendations of the German Standing Committee on Vaccination (STIKO).

Virological classification and pathophysiology

The rabies virus (RABV) is the most important of the 18 currently recognized viruses (eTable 1) belonging to the genus Lyssavirus within the family Rhabdoviridae (11). It is an enveloped virus that is shaped like a bullet (12). The genome consists of a single strand of RNA of negative polarity, 12 kilobases long, encoding five viral proteins: nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G), and RNA-dependent RNA polymerase (L) (12). The G protein plays a key role in the entry of the virion into the host cell. It binds to several receptors, including the nicotinic acetylcholine receptor (nAChR), the neural cell adhesion molecule (NCAM) and the p75 neurotrophin receptor (p75NTR), as well as to gangliosides (13). After receptor binding, the virus is taken up into the cell by clathrin-mediated endocytosis. Low pH triggers fusion of the viral envelope with the endosome membrane, resulting in the release of the ribonucleoprotein (RNP) complex into the cytoplasm (12, 13).

eTable 1

Synopsis of currently known lyssaviruses

Viral replication initially occurs locally in muscle cells at motor end plates. Assembly takes place in the cytoplasm and leads to the formation of inclusion bodies (“Negri bodies”) in the CNS, especially in the hippocampus and cerebellar cortex (12). A key feature of RABV is retrograde, purely transsynaptic axonal transport at speeds of up to 100 mm/day (13, 14), which allows the virus to reach the central nervous system (CNS). From there, it spreads anterograde to visceral organs and salivary glands (12, 14). Cytopathic effects are usually not observed (15). Neurological manifestations result from neuronal dysfunction and from mitochondrial dysfunction, which causes axonal edema (14, 15, 16, 17). Phosphoprotein (P) makes a major contribution to immune evasion by inhibiting the host cell’s interferon signaling pathways (18).

Epidemiology

The global situation

There is a risk of rabies on most of the world’s continents. According to the WHO, rabies causes approximately 60 000 deaths per year around the world; 95% are in Asia and Africa, with children under age 15 accounting for about 40% of cases (1, 19). The economic cost of rabies is estimated at US$8.6 billion per year. Dogs are the main carriers of the disease worldwide, causing more than 99% of all human infections. High-risk regions (Figure) include, in particular (1, 19):

• India, with ca. 20 000 deaths per year, is the most affected country in the world, accounting for nearly a third of global rabies mortality.
• other Asian countries: Bangladesh, Pakistan, Nepal, Philippines, Vietnam, Cambodia, the People’s Republic of China
• Africa
• South and Central America: Haiti, Guatemala, Bolivia.

Figure

The presence and risk of canine rabies worldwide

Only a few regions of the world are officially considered rabies-free. The definition refers primarily to terrestrial rabies, i.e., rabies transmitted by wild carnivores and dogs, and does not include rabies transmitted by bats. Antarctica, Australia, and Western Europe, along with the Oceanic countries, are rabies-free in this sense, with a possible low risk of infection from bat lyssaviruses (eFigure 1) (20). The Tripartite (WHO, WOAH, FAO) is pursuing the goal of eradicating canine rabies by 2030 with its “Zero by 30” strategy (21). World Rabies Day takes place annually on September 28 to draw attention to the significance of the disease and the effort to eliminate rabies worldwide.

Europe

Almost all EU countries are considered free of terrestrial rabies or rabies-controlled. Nevertheless, lyssaviruses are still present in the animal kingdom. Human cases have become rare in Europe thanks to effective control programs and efficient medical infrastructures with widespread availability of rabies vaccines (2019: four travel-associated cases and one autochthonous case in France; 2025: one autochthonous case in Romania, one travel-associated case in Spain, and one in the United Kingdom) (9, 22, 23). Various human-pathogenic lyssaviruses are endemic in European bat populations (eFigure 1, eTable 1). They are also very rarely detected in other animal species, such as cats (France, Italy, Netherlands), stone martens (Germany), and sheep (Denmark) (23, 24, 25). A total of five human deaths caused by bat lyssaviruses have been documented in Europe to date (Ukraine 1977, Russia 1985, Finland 1985, Great Britain 2002, France 2019). Imported animals pose a potential risk of infection, as demonstrated by the introduction of a rabid dog from Algeria to France in 2015 (22). Fox rabies remains endemic in parts of Eastern Europe (Belarus, Russia, Moldova, Ukraine) and in neighboring regions in Poland, Slovakia, Hungary, and Romania (25) (eFigure 1).

eFigure 1

Rabies in Europe: a) terrestrial rabies in Europe, 2020-2025 b) rabies in bats in Europe, 1977-2025

Germany

Germany has been officially free of terrestrial rabies since 2008. This was achieved mainly through systematic vaccination programs employing vaccine baits for foxes (26). No human cases of rabies have been documented since 2007 (as of 2025). Nevertheless, bat lyssaviruses (especially EBLV-1 and –2) are regularly detected in Germany (eFigure 1), e.g., in 2023 in an injured serotine bat (Eptesicus serotinus) in Leipzig that had bitten a 59-year-old woman (27). Approximately 95% of bat rabies cases involve serotine bats. Spillover events, such as virus transmission to a stone marten, have shown that mammalian species other than bats can also be infected (28).

Sources of infection

Lyssaviruses only infect mammals, so only these are considered potential sources of infection under natural conditions (12). Human epidemiological significance is usually limited to a few species and varies depending on the region. Dogs are the most important reservoir and the most important transmitter to humans worldwide, especially in Asia and Africa (1, 19). In Europe, red foxes (Vulpes vulpes) are a reservoir, while in Eastern Europe the raccoon dog (Nyctereutes procyonoides) also plays an important role (19).

In North America, on the other hand, raccoons (Procyon lotor) and striped skunks (Mephitis mephitis) are the main reservoirs, while in Arctic regions, arctic foxes (Vulpes lagopus) are responsible for the spread of rabies (19). Bats are the actual virus reservoirs and presumably the original source of terrestrial rabies (12, 28), although they also contract rabies themselves. Bat species are considered natural reservoir hosts for 16 of the 18 lyssaviruses that have been described (eTable 1) (19).

Biological and ecological characteristics such as high life expectancy, low reproduction rate, life in social colonies with virus transmission, and long-distance migration favor long-term virus persistence in these populations (12, 19).

Depending on the region and species, 0.1–5% of bats in a population are considered to be infected with lyssaviruses, and the percentage may be even higher in South American vampire bats (19, 24). In 2024, an outbreak among marine mammals (Cape fur seals, Arctocephalus pusillus) was reported for the first time in South Africa‘s Western Cape Province, with several cases of human bites (29). According to the WHO, however, seals have not played any relevant role in rabies epidemiology to date. Rodents are also considered epidemiologically insignificant (19).

Rabies can also be transmitted via solid organ or tissue allografts, with transplant recipients being particularly vulnerable to viral manifestation because of the associated immunosuppression. Since 1978, 16 transplant-associated cases have been reported worldwide, including in Germany in 2005, in the People‘s Republic of China in 2015/2016, and in the USA in 2025 (30, 31).

This underscores the need for consistent screening of donor organs in or from endemic areas and in risk constellations (travel history, animal contact).

Risk assessment for travelers

The risk assessment for lyssavirus infection depends largely on

• whether terrestrial or bat-associated lyssaviruses circulate in the country (eFigure 1),
• the local risk of animal contact and animal bites, and
• the local availability of rabies vaccines and additional specific immunoglobulins (eFigure 2) (32).

eFigure 2

The geographic distribution of preventive factors against rabies (access to rabies vaccine, surveillance, and canine rabies control capacity). Modified from (32).

eFigure 3

Algorithm for practical procedures in the event of exposure to rabies in Germany

Animal bites are the main risk of exposure. The WHO estimates that 0.1–5% of the population in rabies-endemic regions are bitten by an animal each year, with dogs being by far the most important cause (19). In a Thai cohort study, the risk of being bitten was estimated at 1.1/100 travelers per month, while the risk of being licked or scratched was estimated at 3.1/100 travelers per month (33). In a German study of 2,915 travelers returning from abroad, 2% had potential exposure to rabies through contact with animals, with 31% of the contacts being unprovoked; 19% of those exposed sought medical help and 38% received appropriate treatment before returning to Germany (8). In a recent French study of 2,916 exposed returnees, 91% had not received a rabies vaccination prior to their trip (34).

Clinical features

The incubation period varies and is usually in the range of two weeks to several months. Rarely, incubation periods of over a year (up to eight years) have been documented (1, 12, 17, 24). Factors such as the location and depth of the bite wound and the viral load affect the duration: bites to the head or near the head (close to the CNS) have shorter incubation periods (17, 24). The course of rabies can be divided into different stages (Table 1). In some cases, those affected first show psychiatric symptoms (14, 35). The main pathognomonic symptoms are hydrophobia and aerophobia, which are due to pathophysiological viral effects on the CNS (14, 15, 17). Hydrophobia manifests itself in convulsive pharyngeal muscle spasms and panic reactions at the mere sight or attempt to drink, while aerophobia is characterized by spastic reactions to drafts of air or slight tactile stimuli. Both are almost specific to the encephalitic form of rabies and are found in combination with hypersalivation (“furious rabies”). In contrast, the rarer “dumb rabies” is mainly characterized by paralysis; its recognition as a manifestation of rabies is often delayed because it is not associated with typical signs, such as aggression.

Table 1

Clinical studies of human rabies

Treatment concepts and prognosis

Once clinical symptoms appear, rabies is almost always fatal (as of 2025: fewer than 35 documented cases that survived for at least six months, some with severe neurological sequelae) (36, 37, 38). Prognostic factors for survival may include individually pronounced immune responses at the onset of symptoms and bat-derived lyssavirus infections with lower virulence (38). Most persons survive no more than a few days to weeks.

The Milwaukee Protocol, published in 2004 and associated with the survival of a 15-year-old US rabies patient, is based on a ketamine-induced coma and antiviral therapy with ribavirin and amantadine (39). Despite this single success story, reliable evidence of efficacy is lacking, and at least 64 cases of treatment failure have been documented to date (40). Studies show that the underlying concepts—such as N-methyl-D-aspartate receptor antagonism by ketamine—are neither scientifically sound nor effective (37, 40). Current reviews and treatment recommendations therefore give priority to purely palliative care (14, 19, 38, 40).

Diagnostic evaluation

The diagnosis of rabies is made by a combination of clinical assessment, laboratory testing, and, if necessary, the time-limited observation of suspect animals. The German National Reference Laboratory for Rabies (eBox 1) offers consultation and laboratory services.

eBox 1

Contact addresses

Antemortem diagnosis

Rabies is clinically suspected in patients with indicative manifestations (hydrophobia, aerophobia, hypersalivation) and a positive exposure history, but confirmation by laboratory testing is essential, especially in atypical cases (19, e1). Molecular biological methods (e.g., reverse transcriptase polymerase chain reaction [RT-PCR]) are the method of choice for detecting viral RNA in saliva, neck skin biopsies, and cerebrospinal fluid. The parallel submission of multiple tissue samples is recommended (19, e2, e3). The detection of neutralizing antibodies in cerebrospinal fluid can also confirm a CNS infection in vaccinated individuals (19, e4).

Postmortem Diagnosis

The gold standard is the detection of viral RNA by RT-PCR or direct virus detection in a fluorescence antibody test (FAT) in brain stem and cerebellar tissue (19, e2). Alternatively, direct immunohistochemical virus detection or virus isolation in cell culture can be used (19, e3, e4). Histopathological methods such as the microscopic detection of Negri bodies are only of auxiliary value because of their inadequate sensitivity (e5).

Animal observation and rabies monitoring

In the event of exposure to a bite in endemic areas, the WHO recommends that the dog in question be professionally observed (e.g., by a veterinarian) for at least ten days. If no symptoms of rabies appear during this period, PEP can be discontinued for the person or persons who have been exposed. In practice, however, animal observation is often impractical or impossible; in the event of well-founded suspicion in an outbreak situation, the killing of the suspect animal with subsequent histopathological examination and testing can be ordered as a public health measure. Wild animals should always be examined by laboratory testing (19, e1). In Bavaria, for instance, 934 foxes, 250 other wild animals, and 279 domestic and farm animals were examined as part of terrestrial rabies monitoring between 2015 and 2024, along with 1620 bats, six of which tested positive (e6).

The duty to report

An overview of the reporting of human cases, as required in Germany by the Infection Protection Act (IfSG), and of animal cases in Germany, as required by the Animal Health Act and the Rabies Ordinance, can be found in eBox 2.

eBox 2

The duty to report, according to the German Infection Protection Act (Infektionsschutzgesetz, IfSG)

Prevention

Pre-exposure prophylaxis (PrEP)

The most effective preventive measures are exposure avoidance (eTable 2) and immunization (Table 2). The STIKO recommends rabies PrEP before travel to countries with a high risk of rabies and an unreliable health care system, for longer or repeated stays outside Western Europe, Australia, and Oceania, and for expected contact with wild animals, including contact with bats in any country (e7, e8). Modern cell-culture vaccines (Table 2) are well tolerated, with serious side effects in less than 1 per 10,000 cases according to the EMA classification (anaphylaxis, Guillain-Barré syndrome, encephalitis), as well as highly immunogenic (seroconversion rate with antibody titer ≥ 0.5 IU/mL after at least two vaccine doses: 96–100%) (e9, e10, e11).

Table 2

Pre-exposure prophylaxis against rabies (PrEP) with the vaccines that have been approved in Germany, according to (e7, e8, e14)

eTable 2

Overview of the main measures for avoidance of rabies exposure, based on the recommendations of the WHO, CDC, and WOAH/FAO (19, e15, e17).

Professional advice from the field of travel medicine should be sought before travel abroad (e12). The rare side effects of the rabies vaccine must be carefully weighed against the risk of rabies exposure, which depends on the destination, travel style, and duration of travel. As rabies is always fatal if left untreated, the risk of infection clearly outweighs the risk of side effects in the event of possible virus contact.

Post-exposure prophylaxis (PEP)

After relevant animal contact with a risk of rabies (bite injuries, mucosal exposure, Table 3), the general principles of wound treatment apply (Box) (e13). The relevant recommendations emphasize rinsing with water and alkaline soap in order to inactivate and reduce lyssaviruses (e14, e15). After exposure to rabies (Table 3), PEP (rabies vaccination series plus human rabies immunoglobulin) should be started on the day of exposure if possible (eFigure 3), without waiting for the findings of the veterinary examination.

Box

General measures for post-exposure prophylaxis after contact with an animal at risk for having rabies

Table 3

Post-exposure prophylaxis against rabies (PEP) depending on the degree of exposure (according to the STIKO and the DTG, 2025).

The aim of PEP is to neutralize the virus before it reaches the CNS. If the animal test results are later negative, the vaccination series can be discontinued, or continued as PrEP.

Because of the wide variation of the incubation period, PEP may still be useful months after exposure (e15). Its overall efficacy is high, provided that it is used correctly and early enough (systematic review: 122 breakthrough infections [1980–2022] in 29 million PEP treatments annually worldwide) (e16). Breakthrough infections usually have identifiable causes (eTable 3) (e15, e16).

eTable 3

Risk factors for breakthrough infection despite rabies PEP, from (e16)

Pregnancy is not a contraindication for PEP. In the event of a vaccine shortage, updated information from the Paul Ehrlich Institute (PEI) on the supply situation and the recommendations of the STIKO concerning alternative vaccination strategies should be considered. As part of PEP, qualified professional advice should be sought whenever possible, e.g., from specialized rabies counseling centers, whose contact details are usually available from coordinating centers or the local public health authorities.

Conflict of interest statement
CL has received honoraria for lectures about rabies vaccination from the Bavarian Nordic and Sanofi-Aventis companies.

The remaining authors state that they have no conflict of interest.

Manuscript submitted on 7 August 2025, revised version accepted on 20 Novemver 2025.

Translated from the original German by Ethan Taub, M.D.

Corresponding author
Prof. Dr. med. Christoph Lübbert, DTM&H

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