Dr Jack Lambert writes on the dangers of rabies — which is no longer endemic in Europe. However, global travel patterns mean that the disease always poses a threat.

Rabies is one of the oldest zoonotic diseases affecting humans. It has historically been recognised as far back as 2000 BC from genetic evidence in Babylon. It is a single stranded RNA virus (rhaboviridiae) of the genus lyssavirus. There are several genotypes with human disease being caused primarily by genotype.

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1. It remains an important public health issue as it is invariably fatal in humans once symptoms have occurred; however, it is preventable so long as adequate post exposure prophylaxis (PEP) has been provided.

h4. Ireland

Ireland is considered rabies free and practises strict quarantine of imported animals. In Ireland there have been no indigenous rabies cases reported since 1903, and in Northern Ireland since 1923. However, we are a global community and travellers come and leave Ireland with increasing frequency.

The case of the young 38 year old lady who tragically died in Royal Victoria hospital in Belfast from rabies in January 2009 highlights this issue. It is believed she contracted the disease during a working holiday in South Africa, where she was bitten whilst trying to separate two fighting dogs, one of which was apparently foaming at the mouth.

She remained well upon her return for over a year until she began to manifest central nervous system (CNS) symptoms at which point the best supportive treatment was all that could be offered. She had been vaccinated with rabies vaccine two years previously.

Recently four people in Dublin had to receive rabies PEP after an illegally imported kitten started acting very strangely and bit them. The illegal importation of animals is an ongoing problem and causes a potential risk to outbreak and re-emergence of rabies in our wildlife population.

There is additionally an increasing prevalence of a rabies-like virus in our bat population. European bat lyssavirus (EBLV) is similar to the rabies virus and causes classical rabies in humans. It was found to be the culprit in a Scottish man who succumbed to rabies in 2002, prompting surveillance of the incidence and prevalence of the virus in both the UK and Ireland since then.

Scottish figures would suggest an approximate 2 per cent prevalence of EBLV among the Daubenton species of bat, but this would appear to be rising. There were three other cases of EBLV-related cases in Europe — all of which were fatal.

Recommendation in the UK and Ireland is therefore, that any person bitten by a bat should be treated with PEP, and any individual handling bats should have pre-exposure prophylaxis.

h4. Incubation and manifestation

The incubation period for rabies virus is highly variable, it is usually between 9-12 weeks but it may be up to two years or more. It is thought to depend on location of inoculation, with decreased incubation times related to bites which are located on highly innervated areas or those which are more severe as the potential for delivery of increased viral load into the system. The virus is highly neurotropic and travels by axoplasmic flow to the CNS. There is passive secretion to glands such as the salivary glands where virus is abundantly excreted. Saliva is generally infectious from three to five days before onset of clinical signs until death of the animal.

The spectra of clinical manifestations of human disease usually begin with pain and paraesthesia at the inoculation site, low grade fevers, general malaise, nausea and vomiting — which progresses on to excitability of the CNS with increasing paralysis and progressive encephalomyelitis. The characteristic hydrophobia of rabies is usually a combination of hypoglossal spasm and generalised jaw paralysis which make the patient apprehensive and fearful when confronted with fluids despite the fact that they have an unquenchable thirst.

The sign of foaming at the mouth occurs as the body produces huge amounts of saliva in an attempt to quench the dehydration in a patient who is unable to swallow. Death usually occurs from respiratory paralysis. The disease is invariably fatal once the onset of neurological manifestation occurs. Pre- exposure and post exposure prophylaxis is the best treatment.

h4. Diagnosis

Diagnosis of rabies antemortem is generally based on history and clinical grounds as the reliability of antemortem tests tends to be variable.

The general standard is fluorescent antibody testing for viral antigen in corneal smear or nuchal skin biopsy. Isolation from saliva/CSF or body fluid with reverse transcription polymerase chain reaction (RT PCR) is also possible.

Post mortem diagnosis, made from human and animal CNS tissues includes fluorescent antibody testing on cerebellum, medulla and hippocampus. Pathognomic is the presence of Negri bodies in the cerebrum; however these are only seen in about 20 per cent of cases. Rabies tissue culture Inhibitory test can also be used.

Ireland uses the Health Protection Authority in the UK for Rabies diagnosis. Most cases, unfortunately, are made post-mortem with identification of rabies by histopathology or viral specific tests on CNS tissues.

h4. Vaccination

Pre-exposure vaccination is recommended for those at high risk, including laboratory workers, healthcare workers who have or are about to come into contact with a patient with probable or confirmed rabies, those who are in direct contact with imported animals, zoo staff, veterinarians, food safety inspection staff, dog wardens, those who handle exotic animals, and those who may be exposed to a high-risk animal.

There are two vaccine products in Ireland. They can be used interchangeably and are readily available through general practitioners and pharmacists. Those who are travelling — and will be living in an endemic country for greater than a month — should be considered for vaccination. If the risk is assessed as low, the vaccine schedule is 0, 7, 28 days, with two further boosters if significant exposure is anticipated (i.e. laboratory workers in a high risk setting).

h4. Booster vaccinations

Booster vaccinations are necessary and can be evaluated by testing post vaccine antibody levels similar to what is done with hepatitis B.

Post-exposure vaccination recommendations include cleaning the wound with copious soap and water and then iodine, seeking specialist advice and contacting the local health department. The risk assessment should include questions about country of exposure, the severity and site of the wound, the circumstances of the bite, species and the behaviour of the animal, the immune status of the individual and the vaccination status of the animal.

If the risk is assessed as low, the vaccine schedule is 0, 3, 7, 14 and 30 days. If the risk is high then human rabies immunoglobulin should be given into and around the wound to neutralise the virus and the vaccine given at a separate site to induce active immunity. Tetanus toxoid should also be given as indicated. A supply of human rabies immunoglobulin (HRIg) is maintained at Cherry Orchard Hospital in Dublin.

General guidelines would advise that any animal which is observed for up to ten days following the exposure and remains well is unlikely to be rabid and one can await post mortem testing on the animal before having to proceed with treatment of the affected patient.

However, more often than not, the animal may not be known, or it may not be feasible to follow up as such with the animal as would often be the case with a traveller who has returned home with a history of such a contact.

Patients deemed to be at high risk such as those who have a received a bite in an endemic country (India, Asia, Africa, and parts of Eastern Europe) from a usual animal which acts as a reservoir should receive PEP and the HRIg. Anyone bitten by a bat, regardless of country, should be treated with PEP and HRIg.

h4. Summary

While rabies is no longer an endemic disease in much of Europe, global travel patterns should alert practitioners that the threat is still there. Options include pre and post exposure prophylaxis, with two vaccine products being available in Ireland as well as a rabies specific immunoglobulin. The diagnosis of rabies disease is a clinical one, and the absence of confirmatory laboratory results should not change the presumptive diagnosis in the proper clinical setting.

References are available on request.