Rabies Immunoglobulin Vaccination : Indication, dosage, side effect, precaution

Vaccination against rabies is used in two distinct situations:

  • to protect those who are at risk of exposure to rabies, i.e. preexposure vaccination;
  • to prevent the development of clinical rabies after exposure has occurred, usually following the bite of an animal suspected of having rabies, i.e. post-exposure prophylaxis.

The vaccines used for pre-exposure and post-exposure vaccination are the same, but the immunization schedule differs. Rabies immunoglobulin is used only for post-exposure prophylaxis. Modern vaccines of cell-culture or embryonated-egg origin are safer and more effective than the older vaccines, which were produced in brain tissue. These modern rabies vaccines are now available in major urban centres of most countries of the developing world. Rabies immunoglobulin, on the other hand, is in short supply worldwide and may not be available, even in major urban centres, in many dog rabies-infected countries.


Pre-exposure vaccination should be offered to people at high risk of exposure to rabies, such as laboratory staff working with rabies virus, veterinarians, animal handlers and wildlife officers, and other individuals living in or travelling to countries or areas at risk. Travellers with extensive outdoor exposure in rural areas – such as might occur while running, bicycling, hiking, camping, backpacking, etc. – may be at risk, even if the duration of travel is short. Preexposure vaccination is advisable for children living in or visiting countries or areas at risk, where they provide an easy target for rabid animals.

Pre-exposure vaccination is also recommended for individuals travelling to isolated areas or to areas where immediate access to appropriate medical care is limited or to countries where modern rabies vaccines are in short supply and locally available rabies vaccines might be unsafe and/or ineffective.

Pre-exposure rabies vaccination consists of three full intramuscular (i.m.) doses of cell-culture- or embryonated-egg-based vaccine given on days 0, 7 and 21 or 28 (a few days’ variation in the timing is not important). For adults, the vaccine should always be administered in the deltoid area of the arm; for young children (under 1 year of age), the anterolateral area of the thigh is recommended. Rabies vaccine should never be administered in the gluteal area: administration in this manner will result in lower neutralizing antibody titres.

To reduce the cost of cell-derived vaccines for pre-exposure rabies vaccination, intradermal (i.d.) vaccination in 0.1-ml volumes on days 0, 7 and either 21 or 28 may be considered. This method of administration is an acceptable alternative to the standard intramuscular administration, but it is technically more demanding and requires appropriate staff training and qualified medical supervision.

Concurrent use of chloroquine can reduce the antibody response to intradermal application of cell-culture rabies vaccines. People who are currently receiving malaria prophylaxis or who are unable to complete the entire three-dose pre-exposure series before starting malarial prophylaxis should therefore receive pre-exposure vaccination by the intramuscular route.

Periodic booster injections are not recommended for general travellers. However, in the event of exposure through the bite or scratch of an animal known or suspected to be rabid, individuals who have previously received a complete series of pre- or post-exposure rabies vaccine (with cell-culture or embryonated-egg vaccine) should receive two booster doses of vaccine. Ideally, the first dose should be administered on the day of exposure and the second 3 days later. This should be combined with thorough wound treatment (see “Post-exposure prophylaxis”, below). Rabies immunoglobulin is not required for patients who have previously received a complete vaccination series.

The incubation period for rabies in some cases lasts very long (20-90 days after being bitten) so that this disease is classified into slow virus disease. Incubation period the shortest is about 10 days. The incubation period will be longer if the bite is located on lower limbs, compared to the face. Rabies in children usually has an incubation period short ones.

The first symptoms that arise are malaise, anxiety, sometimes fever or nausea. In the bite area itching, pain or burning sensation, sometimes taste tingling sensation. The prodromal period lasts from 2-10 days, then enters the phase neurologic.

The symptoms of this second phase can be divided into 2 parts, namely raging and paralysis, both of these forms can occur both in humans and in animals. In ferocious rabies seen rebellious, hyperactive, wild and stiff neck behavior.

Swallowing pain and hoarseness is caused by laryngospasm. Pathognomonic symptoms are hydrophobia, the desire to swallow fluid resulting in spasm of the pharyngeal and laryngeal muscle aches can cause aspiration of fluid into the trachea. Fear also causes spasm. Some experts hypothesize that the presence of encephalitis in the brain stem causes the occurrence of inspiring motor neuron inhibitors.

The respiratory path reflex is immediately aroused, followed by spasm of inspiration, so that aerophobia can arise. Neurological examination can found meningism, palatal muscle paralysis and vocal cords so that the voice is hoarse and arises severe coughing, involuntary movements, and reflexes vary from hyperactivity to absent. Cerebrospinal fluid can show mild pleiocytosis, especially mononuclear.

Blood the edge shows an increase in mononuclear cells. Deaths in rabies in the acute phase arise by due to heart or respiratory problems. Cardiac arrhythmias are often found because of them myocarditis. Shortness of breath caused by laryngospasm or aspiration. The acute neurologic phase lasts 2-10 days, with the possibility of worsening the status mentally into a coma. Patients can survive in this phase for 2 weeks, especially on rabies silent. Usually death comes immediately after the arrival of a coma, except if intubated and mechanically ventilated, can last for months. During times coma, many problems will arise, including brain edema, SIADH, and diabetes insipidus other manifestations such as hypothalamic dysfunction, hypotension or arrhythmias and pneumonia.

The diagnosis can be made based on a history of animal bites, tingling bitten areas and hydrophobia. Laboratory diagnosis is carried out by finding the virus through the fluorescence antibody test on a smear corneal epithelial cell smear or skin incision from the skin at the hairline. Serologic diagnostics can be established if the patient is not given preventative treatment after being bitten, a rapid rise in neutralizing virus titers will appear antibodies that will appear 6-10 days after the onset of symptoms.

This kind of antibody can detected in-vitro quickly by using the fluorescent rapid fluorescent focus inhibition test (RFIT) or plaque-reduction neutralization test (PRNT). Rabies can too diagnosed in patients who are immune to rabies and is characterized by an increase in titer after the onset arises and is strengthened with a titer level of> 1: 5,000, a value which is usually cannot be achieved with immunization. The rabies virus can be isolated on days 4 and 24 after the onset of the disease. Virus isolation can be obtained from cerebrospinal fluid, tissue brain and urine sediment in the first 2 weeks of the disease.

A post mortem diagnosis can be made in the presence of cytoplasmic inclusions (Negri bodies) in brain tissue.

Human rabies immune globulin (HRIG) is administered only once, at the beginning of anti-rabies prophylaxis, to previously unvaccinated persons. This will provide immediate antibodies until the body can respond to the vaccine by actively producing antibodies of its own. If possible, the full dose of HRIG should be thoroughly infiltrated in the area around and into the wounds.

Any remaining volume should be injected intramuscularly at a site distant from vaccine administration. HRIG should never be administered in the same syringe or in the same anatomical site as the first vaccine dose.

However, subsequent doses of vaccine in the four-dose series can be administered in the same anatomic location where the HRIG dose was administered. If HRIG was not administered when vaccination was begun, it can be administered up to seven days after the administration of the first dose of vaccine. Beyond the seventh day, HRIG is not recommended since an antibody response to the vaccine is presumed to have occurred.

Because HRIG can partially suppress active production of antibody, no more than the recommended dose should be administered. The recommended dose of HRIG is 20 IU/kg body weight. This formula is applicable to all age groups, including children.

The most common side effects are pain at the injection site, fever, and headache. Severe bad reactions (such as anaphylaxis) are rare.

If given while pregnant, this drug will not need a baby. This drug works by binding to the rabies virus before it can enter the nerve tissue. After the virus enters the central nervous system, rabies immunoglobulin is no longer useful. Rabies immunoglobulin was first used as a blood serum obtained from 1891.

Rabies immunoglobulin began to be used frequently in the medical field in the 1950s. This drug is included in the World Health Organization’s Essential Medication List. Immunoglobulin is expensive and difficult to obtain in developing countries. In the United States, prices can reach 1,000 US dollars per dose.

Rabies immunoglobulin is made from human plasma or horses that have high levels of antibodies in their bodies. The horse version is not as expensive as the human version, but side effects occur more often.