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      Rabies

      Latest update: - Authors: Nele Alders, Ula Maniewski

      Rabies is a fatal but preventable disease. It is caused by an RNA virus belonging to the Rhabdoviridae family, genus Lyssavirus. 

      Transmission

      Rabies virus is transmitted through direct contact with saliva or brain/nervous system tissue from an infected animal. People usually get rabies from the bite of a rabid animal, but transmission is also possible after scratches, abrasions, or open wounds that are exposed to saliva or other potentially infectious material from a rabid animal. Human- to- human transmission does not generally occur, but has been described after organ transplantation. 

      Reservoirs

      All mammals are believed to be susceptible to rabies, but the major reservoirs are terrestrial carnivores and bats. 

      The following groups of animals bear an increased risk:

      • Cats and dogs. In developing countries, dogs are the major reservoir. Occasionally imported rabid cats or dogs are detected in countries where canine rabies has been eradicated. 
      • Wild land mammals (such as fox, wolf, monkey, raccoon,...) can be rabid in some areas in where canine rabies was eradicated, such as North America and eastern Europe. 
      • The risk of rabies transmission in monkeys is relatively low, but not non-existent.
      • Bats from endemic and non-endemic countries.
      •  In principle, there is virtually no risk of rabies in rodents.

      Life cycle

      When the rabies virus is introduced into a muscle through a bite from an infected animal it travels from the site of the bite to the brain by moving within the nerves. The animal does not appear ill during this time. Late in the disease the virus reaches the brain and causes inflammation. It moves from the brain to the salivary glands and saliva. After the virus has multiplied in the brain almost all animals begin to show the first signs of rabies although the virus can be excreted in the saliva of infected animals several days before illness is apparent. The infected animal usually dies within seven days of becoming sick.

      Incubation period     

      The incubation period is typically two to three months but may vary from one week to one year, depending on factors as the location of the virus entry and the viral load.

      Symptoms

      The first symptoms might be similar to flu, including weakness, fever or headache. There may be a discomfort, prickling, or an itching sensation at the site of the bite. Symptoms than progress to cerebral dysfunction, anxiety, confusion and agitations. As the disease progresses, the person may experience delirium, abnormal behaviour, hallucinations, hydrophobia and insomnia. The acute period of disease typically ends after two to ten days. Once clinical signs of rabies appear, the disease is nearly always fatal, and treatment is typically supportive. 
      In animals, agitation is not always present and some animals are lethargic. 

      Risk areas

      Rabies is present on all continents, except Antarctica, with over 95% of human deaths occurring in Asia and Africa. In Belgium rabies only occurs in bats and - exceptionally - in (illegally) imported mammals. 

      While dog mediated rabies is a major burden in many countries in Asia and Africa, it is close to extinction in most Latin American countries.

      Wildlife rabies is present in North America and some east-European countries.

      In Western Europe including Belgium, Scandinavia, Australia, New-Zealand and Japan, rabies only occurs in bats and exceptionally in (illegally) imported mammals.

      The dashboard of the WHO gives an overview of the risk of rabies in dogs per country:

      View the map

      Prevention

      Introduction

      Rabies is a preventable disease. It is important to counsel travellers:

      1. To avoid contact with animals.
      2. Pre- exposure vaccination (PrEP).
      3. First aid treatment of the lesion.
      4. To always consult a doctor after a scratch or a bite as soon as possible (even if they have been vaccinated) to see if they require specific anti-rabies immunoglobulins and a series of rabies vaccinations.
      5. A scratch or (possible) bite from a bat should always be treated as high risk (category III according to WHO) all over the world.

      Travellers can call the travel assistance insurance for advice on reliable medical facilities. The vaccines and anti-rabies immunoglobulins are not always available in tropical and subtropical countries, meaning that urgent repatriation is sometimes required. The International Society of Travel Medicine (ISTM) publishes a list of travel clinics offering rabies vaccination and anti-rabies immunoglobulins.

      Treating the lesion

      1. Thoroughly clean the lesion (however small or superficial it might be) with plenty of soap and water (since the virus is very sensitive to detergents) for 15 minutes. Rinse abundantly.
      2. Debridement of the lesion and careful disinfection (iodine (e.g., iso-Betadine®) or ethanol 60-80%).
      3. If possible, delay stitching the wound.
      4. Repeat tetanus vaccine and start antibiotics (of the amoxicillin-clavulanic acid type) if necessary.
      5. For monkey bites (risk of herpes virus B in macaques), start antiviral therapy (Valacyclovir 5x 800 mg per day for seven to fourteen days).
      6. No indication for special hygienic measures when caring for the patient during the
        incubation period.

      Pre-exposure vaccination

      The preventive vaccination cannot guarantee complete protection, but creates an immunological memory. This ensures that protective antibodies are quickly produced after revaccination.

      Indication

      1. Occupational risk (veterinarian, biologist, lab technician or on a military mission).
      2. Volunteers or students who come into contact with animals that may be infected with rabies, for example bats.
      3. When travelling to a country where rabies occurs in dogs (map), and the following risk factors:
        ⦁ Long or frequent stay.
        ⦁ Staying in remote areas where medical help is not readily available.
        ⦁ Risky activities (for example cycling, jogging or visiting a monkey park).
        ⦁ Children and adolescents.

      To evaluate if a traveller should be advised to have a preventive rabies vaccination the Risk score for rabies PrEP vaccination in travellers can be used. 

      Vaccine: Rabipur® is currently the only available vaccine in Belgium. 
      Schedule: In May 2018 the PrEP schedule was adjusted to 2 doses with a minimal 7-day interval. For immunocompromised patients a three-dose schedule is advised on day 0,7 and 28. (see table below)
      Route of administration: intramuscular or intradermal (off-label). An intradermal dose consists of 2 smaller doses  (2x 0.1ml) in the lower arm, this can be administered according to the WHO guideline.
      Duration of protection: After two doses the immunological memory is considered lifelong. Measurement of antibodies is not necessary in travellers or expats and but might be useful in immunocompromised patients, this is done via Sciensano preferably after 4-6 weeks but can be done starting from 10 days after the 3th injection.
      In case of possible exposure to rabies, revaccination should be started as soon as possible, but the administration of antibodies (MARIG or HRIG) is never necessary, except in case of immunosuppression. 
      Children: it can be used in children of all age. They should receive the same dose as adults (Rabipur® 1ml per intramuscular injection). In children <2 year it should be administered in the anterolateral thigh muscle. 
      Contra- indications: history of serious hypersensitivity to components of rabies vaccine. (In view of the almost invariably fatal outcome of rabies, there is no contraindication to PEP vaccination).
      Side effects: 35–45% of vaccinees report minor and transient erythema, pain or swelling at the site of injection. Mild systemic adverse events following immunization, such as transient fever, headache, dizziness and gastrointestinal symptoms, have been observed in 5–15% of vaccinees. Serious adverse events following immunization seldom occur.

      Day of vaccination Route
      Routine schedule Day 0 and day 7 (or later)

      Intradermal dose: 2x 0.1ml in 2 different sites in anterior lower arm (= 4 injections in total)

      Intramuscular dose: 1x 1ml in deltoid (or <2 year of age: anterolateral thigh)

      Last minute schedule

      (Individuals who receive only a single dose of PrEP should be managed with full PEP in the case of potential rabies exposure prior to the 2nd dose)

      Day 0 and day X

      (Day X after returning or on departure for the next trip)

      Intradermal dose: 2x 0.1ml in 2 different sites in anterior lower arm (= 4 injections in total)

      Intramuscular dose: 1x 1ml in deltoid (or <2 year of age: anterolateral thigh)
      Immunocompromised Day 0, day 7 and day 28

      Intramuscular dose: 1x 1ml in deltoid (or <2 year of age: anterolateral thigh)

      Measurement of antibodies after 4-6 weeks

      Post exposure prophylaxis 

      After a potential exposure, the risk for rabies and the need for post exposure prophylaxis should be evaluated by a doctor. This should be based on:

      1. The probability that the animal is infected depending on the epidemiological risk factors.
      2. The risk category of the patient based on the WHO exposure risk categories (animal, region and type of contact).
      3. The patient’s history (e.g., PrEP, immunocompromised).

      More information, including the different post exposure schedules, can be found in the guideline for Post-exposure prophylaxis against rabies. 

      The treatment is best administered between 24 and 48 hours after the risk exposure. If no medical treatment was given within this timeframe, the treatment should always be carried out regardless of the timing of the exposure to the risk.

      The ideal administration of the post exposure prophylaxis is:

      • Vaccination within 24 hours.
      • Human anti-rabies immunoglobulins (MARIG) within 48 hours and, at the latest, within 7 days of the start of post-exposure vaccination. No more immunoglobulins are given seven days after the start of the vaccination series. In contrast, MARIG is always administered if the vaccination sequence has yet to be started (e.g., more than 10 days after the risk bite).

      Additional information

      References

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