Post-exposure rabies prophylaxis in humans exposed to animals in Lublin province (Eastern Poland) in 2012–2015 – A retrospective study

ABSTRACT

Rabies continues to be one of the most important viral diseases and remains a significant threat to public health across the globe. The post-exposure prophylaxis in humans can effectively prevent death after exposure to a potentially infected animal. In Poland, recommendations for rabies PEP followed the national guidelines which recommend that people should receive PEP when bitten by an animal suspected to be infected by rabies. PEP in humans includes cleansing and disinfecting the wound or point of contact, and administering anti-rabies immunization. Rabies vaccine should be given for contacts of category II and category III exposures. RIG should be given for category III contact. The vaccination schedule includes 5 doses given within a 30 day period (the Essen regimen).

The aim. The aim of our study was to determine the frequency of post-exposure prophylaxis among patients exposed to animals and also to assess the animal species suspected as a source of rabies exposure.

Methods. We have retrospectively analyzed medical records from the years 2012–2015 of all adult patients who were exposed to animals and consulted at the Dispensary of Rabies Prophylaxis in the Department of Infectious Diseases at the Medical University in Lublin, Poland. All consulted patients were asked to give an informed consent in case of decision to use collected data for future research work.

Ethical approval was obtained from the Ethics Committee of the Medical University of Lublin, Poland, and all patients included in this study gave an informed consent during consultation after the exposure to animals.

Results. During the studied 4-year period, 511 persons exposed to animals were consulted and prophylactic procedure consisting of active immunization were applied in 54.2% of the total consulted. Dogs and cats were the most common animal species suspected as the source of the rabies exposure. Anti-rabies prophylaxis was applied in 45.8% of all vaccinated patients exposed to dogs, and in 24.2% exposed to cats. All patients with bite wounds were consulted at the Department of Surgery and wound care followed surgical recommendations. In the study group, 45 patients had category III contact. There were 38 patients exposed to dogs, and 7 exposed to cats. There were no people exposed to wildlife in this group. All animals were available for veterinary observation. During and after exposure, none of the animals that serve as a potential source of infection presented with symptoms of rabies. The local epidemiological data indicated that during exposures of our patients, there were no confirmed cases of rabies among animals in Lublin province. Based on the data mentioned above, RIG was not applied.

During the studied period in Lublin province, rabies was confirmed mainly in wildlife, and only in 2 dogs.

Conclusions. In Lublin province, people are still at risk of exposure to rabid animals. The majority of our patients were vaccinated after domestic animals exposure, but rabies was confirmed mainly in wildlife, and since 2013, there were no cases of rabies among domestic animals.

KEYWORDS:

• post-exposure anti-rabies prophylaxis
• rabies
• rabies in animals

Introduction

Rabies is an acute progressive fatal encephalitis caused by a negative stranded RNA virus species of the Lyssavirus genus, family Rhabdoviridae of the Mononegavirales order. The current classification of lyssaviruses defines 14 genetically divergent species include classical Rabies virus (RABV), Lagos bat virus (LBV), Makola virus (MOKV), Duvenhage virus (DUVV), European bat lyssaviruses 1 and 2 (EBLV-1, EBLV-2), Australian bat lyssavirus (ABLV), Irkut virus (IRKV), Aravan virus (ARAV), Khujand virus (KHUV), West Caucasian Bat Virus (WCBV), Shimoni bat virus (SHIBV), Bokeloh bat lyssavirus (BBLV) and Ikoma lyssavirus (IKOV).¹

Two genotypes of rabies viruses have been isolated in Poland – genotype 1 (classic RABV) from terrestrial animals, and genotype 5 (EBLV-1) from bats. Rabies virus (RABV) is the causative agent of the classical rabies and is responsible for the vast majority of all human rabies cases.² Rabies is essentially a fatal viral disease with a total of 19 documented human survivors.³ This infection is still one of the most important viral zoonoses and remains a significant threat to public health across the globe.⁴ The disease is widely distributed on all continents except Antarctica.⁵

Rabies is transmitted from animals to humans through saliva via a bite wound, scratch wound, or licking of a mucous membrane. Although human-to-human transmission has not been proven, some cases of rabies transmission through a corneal transplant from an infected donor have been described.⁶

Rabies is still present on the European continent, although some countries have a rabies-free status. During the last decade, more than 90% of rabies cases occurring in Europe were reported in wildlife.⁷ Wild rabies vector species represent a high risk to the human populations. The raccoon dog (Nyctereutes procyonoides) has become a major factor in the epidemiology of rabies in Eastern and Northern Europe, and is now the second most important wildlife species infected with rabies after the red fox. Also, domestic animals may carry and transmit the disease. Dogs were recognized as a source of rabies infection in Europe several centuries ago. Most industrialized countries have eliminated rabies from domestic dog populations. Rabies in dogs is the main cause of rabies-induced morbidity and mortality in humans, putting over 3.3 billion people at risk of being exposed to the disease.⁸ According to the World Health Organization (WHO) data, there are 61 000 human rabies-related deaths worldwide each year and most occur in Asia and Africa as a result of dog-mediated rabies.⁹ In Poland, the main reservoir of rabies virus is the red fox (Vulpes vulpes) and rabies is still present in wild environment. The terrestrial rabies posed a serious problem in Poland in the 20^th century, but within the past decade the epidemiological situation has started to change. The introduction of safe and immunogenic cell culture based vaccine, and the introduction of mass oral immunization of foxes were key factors in the successful strategy for the elimination of rabies. The vaccination of domestic animals (dogs and cats) also plays an important role in preventing this disease, and has improved over time, but the data from literature indicate that in rural areas of Lublin province, vaccination of dogs against rabies is properly realized by only by 64.8% dog owners, and by only 19.8% of cat owners. The situation needs to be improved.¹⁰

The last case of human rabies in Poland was reported in 2002.¹¹

In Poland, recommendations for rabies post exposure prophylaxis (PEP) followed the national and WHO guidelines which recommend that people should receive PEP when bitten by an animal suspected to be infected by rabies. PEP in humans includes cleansing and disinfecting the wound or point of contact, and administering anti-rabies immunization. Rabies vaccine should be given for contacts of category II and category III exposures (single or multiple transdermal bites, scratches or contamination of mucus membrane with saliva and suspected contact with bats). RIG should be given for category III contact. The vaccination schedule includes 5 doses of rabies vaccine given on days 0, 3, 7, 14 and 30 (the Essen regimen).The WHO recommends observation of a suspected animal source for 10 d. Clinicians make an individual risk assessment for each patient exposed to the animal, and decide whether to administer the rabies vaccine with or without immunoglobulins according to the general recommendations, epidemiological data and the category of the bite. The veterinary situation is taken into account in this assessment, namely the species of the biting animal and the possibility of carrying out examination of the animal, if it can be identified. Furthermore, there seems to be large variations in the use of PEP and especially RIG between European countries, with some countries overreacting and others under prescribing (like Poland).^12,13

Results

During the studied 4-year period (2012 to 2015), 511 persons exposed to animals were consulted at the Dispensary of Rabies Prophylaxis in Lublin (Eastern Poland). The study group consisted of 245 females and 266 males, aged 18–78 y of age (median age 48 years). The majority of the exposures occurred in urban areas (65%). There were 332 residents of cities and 179 residents of villages. The mean interval between the bite and consult was 36 hours.

The total number of consulted and vaccinated persons in studied years are presented in Table 1.

Table 1. Total number of consulted and vaccinated persons from 2012 to 2015 at the Dispensary for Rabies Prophylaxis in the Department of Infectious Diseases, Medical University, Lublin, Poland.

Year	Total number of consulted persons	Total number of vaccinated persons	Percentage of all vaccinated persons (%)
2012	107	40	14.4%
2013	126	60	21.7%
2014	158	89	32.1%
2015	120	88	31.8%
Total	511	277	100%

In the study group, 27% of all exposed had category I contact, 60.7% had category II, and 2.3% had category III contact. In all exposed patients, washing of the wound was performed. All patients presenting with category II or III exposures were consulted at the Department of Surgery and wound care followed the surgical recommendations. Among exposed patients, 277 (54.2%) were vaccinated and all received the Essen regimen. The total number of patients vaccinated after exposure to particular species are presented in Table 2. All patients (100%) completed 5 doses of the rabies vaccine. There were 232 people (84% of all vaccinated) with category II contact, and 45 (16%) with category III contact. For each exposed patient, an individual risk assessment was made based on the general recommendations, epidemiological data, category of the bite, and the animal who served as a potential source of infection. In people with category II and category III contact, if the animal was unknown or not available for veterinary observation, the rabies vaccine was administered. Among 45 patients who had category III contact, 38 were exposed to dogs and 7 were exposed to cats. There were no people exposed to wildlife. All animals were available for veterinary observation, and none of them presented with symptoms of rabies. During this period there were no cases of exposure to rabid animals in Lublin province. The data mentioned above was taken into consideration and resulted in the decision to not apply RIG.

Table 2. Vaccinated persons after exposure to particular species.

Animal species suspected of being a source of infection	2012	2013	2014	2015	Total number of vaccinated persons	Total number of people exposed to particular species
Dog (Canis familiaris)	22	32	37	36	127	312
Cat (Felis catus)	10	16	22	19	67	104
Bat (Myotis myotis)	3	—	18	11	32	35
Red fox (Vulpes vulpes)	2	2	1	1	4	14
Squirrel (Sciurus vulgaris)	—	2	1	5	8	8
Chimpanzee (Pan paniscus)	—	3	2	2	7	7
Rat (Rattus norvegicus)	2	4	4	6	16	21
Hamster (Mesocricetus auratus )	1	1	—	—	2	2
Mole (Talpa europaea)	—	—	—	2	2	2
Ferret (Mustela putorius furo)	—	—	1	1	2	2
Doe (Capreolus capreolus)	—	—	—	1	1	2
Marten (Martes martes)	—	—	—	1	1	1
Otter (Lutra lutra)	—	—	1	—	1	1

Not all of the exposed people were vaccinated. Of 511 exposed persons, PEP was not applied in 45.8%. In these cases, no risk factors were detected. Patients from this group had no direct contact with animals, or the contact was through intact skin with no bites or scratches (category I). PEP was also not applied in people exposed to domestic animals with no symptoms of the disease under veterinary observation. In the study group, there were no persons re-exposed to animal bites. For rabies-exposed patients who have previously undergone complete pre-exposure vaccination or post-exposure treatment with cell-derived rabies vaccines, 2 intramuscular doses of a cell-derived vaccine separated by 3 d are sufficient. RIG treatment is not necessary in such cases.⁹

We have not observed any case of rabies in our exposed and vaccinated patients. It is obligatory in Poland to collect and report data of all vaccinated patients to Sanitary Inspection Services who are responsible for future procedures. Reporting of human rabies cases is also obligatory in Poland.

The total number of rabid animals both in Poland and in Lublin province in 2012–2015 are presented in Table 3.

Table 3. Total number of rabid animals in Poland and in Lublin province in 2012–2015.

	2012	2013	2014	2015	Total
Poland	667	410	206	101	1384
Wildlife species	530	314	160	78	1082
Bats	22	19	11	4	56
Domestic animals	115	77	35	19	246
Lublin province	4	20	2	4	30
Wildlife species	4	16	2	4	26
Bat	—	2	—	—	2
Domestic animals	—	2	—	—	2

Discussion

Rabies is a lethal disease and human cases are preventable by prompt administration of post-exposure prophylaxis. Human rabies prevention relies largely on vaccination. Cell-based rabies vaccines have a well-established safety and efficacy profile. In Poland the incidence of human rabies is low and reflects the success of a vaccination program based on the implementation of the oral vaccination of wild animals. It is estimated that each year over 15 million people receive PEP regimen worldwide, which prevents an estimated 327 000 annual deaths from rabies. Post-exposure prophylaxis is recommended depending on the type of exposure and the vaccination status of the patient.¹⁴

Our data indicate an increase in the number of vaccinated patients each year, during the studied 4- year period. The epidemiological data based on the reported rabies surveillance data to the WHO (Rabies Bulletin Europe) indicate decrease in total number of rabid animals in Poland during studied 4-year period from 667 cases in 2012 to 101 cases in 2015 ¹⁵ (Data presented in Table 3). Our study demonstrated that PEP was applied inappropriately in a majority of the cases. Most vaccinated patients from the studied group were exposed to domestic animals. Followed the epidemiological data during the study period in Lublin province, rabies was confirmed only in 2 dogs in 2013, which indicates that people vaccinated after exposure to domestic animals were vaccinated inappropriately because in fact, they were not exposed to rabid animals. The most common reason for inappropriate PEP was exposure from an animal unavailable for observation or testing. In Poland, post-exposure prophylaxis is administered to approximately 7000 people annually, and in most cases, immunization followed exposure to animals in which rabies could neither be ruled out nor confirmed.¹⁶ Data from literature also indicate that PEP was frequently misused. The results presented by Moran GJ. et al. suggest that the use of PEP was inappropriate in 40% of vaccinated patients.¹⁷

In our study, PEP was given to a majority of patients with dog or cat exposures, and these animals accounted for 70% of all vaccinated cases. Since domestic animals can serve as a link for rabies virus between wildlife and humans, vaccination of dogs and cats continues to be an extremely effective public health measure in preventing rabies in humans. Data from literature indicate that rabies is uncommon in vaccinated dogs and cats but can occur. Veterinarians should include rabies in the differential diagnosis for any dog or cat with clinical signs compatible with rabies, regardless of vaccination history. Continued surveillance is imperative to document vaccination failure and identify trends related to vaccination failure.¹⁸ In our study, dogs were the most common animal species suspected as a source of rabies exposure, and PEP was applied in 45.85% of all vaccinated patients. The number of reported cases of rabies in domestic dogs in Poland has decreased substantially, primarily because of improved canine vaccination and stray animal control programmes.¹⁶ In Lublin province, among domestic animals, rabies was confirmed only in 2 dogs in 2013. There were no cases of rabies in cats.

The main reservoir for rabies in Poland are foxes, and in our study, exposure to foxes was the reason for vaccination in 9 people (3.25%). All of those exposed to foxes did not meet the criteria for RIG. The indication for RIG included the kind of exposure (category III contact), the unavailability of the animal for veterinary examination, and also epidemiological information about cases of rabid animals in the environment where the exposition occurred. In Lublin province, rabies was confirmed in 25 foxes (86.7% of all rabid animals). Oral vaccination (ORV) is the only efficient method of rabies eradication in wildlife. To control rabies in wildlife, oral immunization of foxes was introduced in Poland in 1993. The vaccine is effective when it confers immunity against the virus circulating in the environment. Monitoring of the effect of ORV in Poland has shown that, e.g., in 2013 around 77% of foxes submitted for testing were seropositive. Epidemiological data showed a decrease in the number of rabies cases in foxes, from 3084 in 1992 (before the start of ORV in Poland) to 101 in 2015, confirming the efficacy and stability of the vaccine strains. Also other factors, such as bait integrity or the system of vaccine distribution (aerial distribution not reaching the urban foxes) have failed, playing an important role in rabies outbreaks in Southern Poland in 2010–2013.¹⁹ In 2010, an increase in rabies incidence was observed in Poland with 151 rabies cases recorded. Twenty-two cases were recorded in domestic animals (in 8 cats, 7 dogs, 4 cattle, in 2 sheep, and in one horse). In wildlife, rabies was diagnosed in 117 foxes, 2 martens, 1 racoon dog, one badger, and in one deer. The reason for such change in the rabies distribution was an outbreak of rabies in Krakow voivodeship. Rabies was diagnosed in 118 animals (94 foxes, 6 cats, 6 dogs, 4 cattle, 3 martens, 1 badger, 2 sheep, and in 1 horse). Phylogenetic analysis of isolates from the outbreak showed their high similarity with the strains circulating in Ukraine and Romania, which may suggest the possible source of origin of the rabies virus in the outbreak. This could have been caused by illegal import of pet animals.²⁰ In 2015, Poland recorded a lower number of rabies cases compared with the previous 3 y period (2012–2014).¹⁵

Although the red fox remains the main rabies reservoir in Europe, the cases of rabies in raccoon dogs (Nyctereutes procyonides) has increased in North-Eastern Europe and in Baltic countries.²¹ In Lublin province, rabies was confirmed in one raccoon dog in 2015, but there were no known cases of exposure to raccoon dogs among our patients.

Bats have been shown to be an important reservoir of rabies virus. Bat rabies has been laboratory confirmed in different parts of the world. In Europe, bat rabies in humans is very rare but in some other parts of the world, it is more frequently observed. Four different lyssavirus species have been isolated from European bats, and the majority of isolates were characterized as EBLV-1.²² Exposure to bats or their secretions should be considered as a potential rabies risk regardless of the world region in which the exposure occurs. In our study, PEP was applied in 32 of the 35 people exposed to bats. In Lublin province, rabies was confirmed only in 2 bats in 2013, but in Poland from 2012–2015, there were 56 bats with confirmed rabies (4% of all rabid animals).

We also noted human exposure to rodents. PEP was applied in 16 people exposed to rats (5.8%), in 8 (2.9%) exposed to squirrels, and in 2 exposed to hamsters. Rabies remained rare in rodents and lagomorphs, however, transmission of rabies virus via exposure to a rabid rodent may be possible. Small rodents (e.g., squirrels, chipmunks, rats, mice, hamsters, guinea pigs, and gerbils) and lagomorphs (including rabbits and hares) are rarely infected with rabies, but can transmit rabies to humans. During studied period, there were no cases of rabies among rodents, but data from literature reported cases in this group of animals.²⁴ Based on the data mentioned above and due to the fact that rabies still exists in wildlife, we decided to apply PEP in people exposed to rodents unavailable for observation or testing.

Monkey bites are an important risk among travelers, being the second most common animal bite risk to travelers after dog bites. PEP after monkey bites was applied in 9 patients (3.25%) exposed to monkeys and all were travelers to South-Eastern Asia.

Cumulative data from one study from Poland indicate that total numbers of vaccinated persons differ from particular voivodeships and among 7243 vaccinated persons in one year period, PEP was applied in 1180 persons in Małopolskie voivodeship, in 889 in Mazowieckie, in 700 persons in Łódzkie, in 263 in Lublin province, and in 167 in Świetokrzyskie. This data reflects both the epidemiological situation of rabies in different parts of Poland and the relative overall area of each province. Rabies was confirmed in 60 animals (in 45 in Małopolskie, in 5 in Podkarpackie, in 3 animals in Mazowieckie, in 3 in Lublin province, in 3 animals in Podlaskie, and in single animals in Mazowieckie, Warmińsko-Mazurskie, Wielkopolskie, and Zachodnio-Pomorskie.²⁵

As a result of the ongoing implementation of ORV, the number of rabies cases reported annually in Europe steadily declined from 17 202 in 1978 to 7581 in 2010. During this period, 9 countries successfully eliminated fox rabies from their territory. Finland and the Netherlands achieved rabies-free status in 1991, Switzerland in 1998, Belgium and Luxembourg in 2001, the Czech Republic in 2004, and Germany and Austria in 2008. An imported dog rabies case with limited secondary transmission caused France to lose its rabies-free status in 2008, but rabies freedom was regained in 2010. Italy became rabies-free in 1997, although fox rabies re-emerged  most recently in 2008. Slovakia reported its last case in 2006 and could be regarded as rabies-free. Other countries now close to eliminating rabies include Hungary, where the last reported case was in 2010 and Lithuania, Estonia and Italy, where only single cases were reported in 2011.²⁶

Although the rabies situation in Europe is reasonably good, Poland has not achieved a rabies free status yet. Cases of animal rabies in Poland and in Lublin province as mentioned above are still noted and people are still at risk of exposure to rabid animals. It should be pointed that the rabies situation in Lublin voivodeship is, among others, caused by a cross-border problem. The increasing rabies incidence in the neighboring regions of Ukraine resulted in reinfection of the Polish side along the common borders. This situation forced the veterinary authority to safeguard territory by maintaining a vaccination belt in those border areas. Also, animals movement from other parts of Poland to our voivodeship may result in spread of rabies virus. To minimize the risk of rabies ORV for foxes, mass vaccination of domestic animals, proper pre- and post- exposure prophylaxis in humans followed by public information campaigns should be continued in all parts of Poland.²⁰

It should also be pointed that even rabies-free European countries regularly report imported cases of rabies, mainly in pets. Illegal importation of infected animals poses a threat of rabies introduction into rabies-free areas.

Our study is a retrospective review of medical records, which is not ideal to provide comprehensive information about PEP. As this is a limitation of current study, new prospective research about PEP in Poland should be performed.

Patients and methods

We have retrospectively analyzed medical records from the years 2012–2015 of all adult patients who were exposed to animals and consulted at the Dispensary for Rabies Prophylaxis in the Department of Infectious Diseases at the Medical University in Lublin, Poland. Children under 18 y of age exposed to animals are consulted at the Department of Infectious Diseases for Children in Lublin (data are not available for us). A standard case report form was completed for each exposed patient and, based on the included data, analysis was performed. For the stud,y medical records of all patients exposed to animals and consulted at the Dispensary for Rabies Prophylaxis were reviewed, and nobody was excluded from the study. The descriptive statistics were used and the data were not analyzed electronically. The aim of our study was to determine the frequency of PEP among consulted patients and also to assess the animal species suspected as a source of rabies exposure.

The diagnosis of rabies in animals in Poland is based on techniques recommended by WHO. In our country, the unified fluorescent antibody test (FAT) procedure is applied in veterinary regional laboratories authorized for rabies diagnosis. This involves impressions from different parts of the brain on microscope slides. Positive and negative controls are prepared for each FAT run. In case of negative FAT and human exposure, virus isolation in cell culture in mouse inoculation test is performed to verify the result of antigen detection.²³

Conclusion

In Lublin province, people are still at risk of exposure to rabid animals. Although total number of rabid animals decreased every year during the studied period, cases of animal rabies were still noted. The majority of our patients were vaccinated after domestic animals exposure, but rabies was confirmed mainly in wildlife and since 2013, there were no cases of rabies among dogs.

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.