Adverse events following rabies vaccine

The vaccine


There are three main types of rabies vaccine:


Vaccines containing animal brain tissues


Avian vaccines using as a substrate duck embryo, are inactivated by b propiolactone, and purification is done by ultracentrifugation. This vaccine is used in Europe.


Cell-cultured vaccines


Mild adverse events


Vaccines containing animal brain tissues (Wiktor, 1980)


General systemic reactions 

The various minor disorders that may develop during and after a course of antirabies treatment includes fever, headache, insomnia, palpitations, and diarrhoea. Sensitization to proteins contained in older vaccines can cause a sudden shock-like collapse, usually toward the end of the course of treatment.


Local reactions

Erythematous patches may develop approximately 7 to 10 days after the beginning of anti-rabies treatment. Lesions appear on the skin a few hours after administration and fade in 6 to 8 hours, reappearing after the next dose.

Cell-cultured vaccines

Cell-cultured vaccines are widely accepted as well-tolerated rabies vaccines, although reported reaction rates to primary immunization have varied with the monitoring system. In a large-scale testing of the safety and immunogenicity of human diploid cell vaccine performed on American veterinary students, adverse reaction rates observed in more than 1770 volunteers are shown in table 6.

Table 6. Adverse events following HDC rabies vaccine (Plotkin 1980)

Adverse event


Significant sore arm




Malaise, nausea or both


Allergic edema



In another study of post-exposure vaccination, 21% had local reactions, 3.6% had fever, 7% had headache, and 5% had nausea. The most common local reactions are erythema, pain and induration (Anderson et al., 1980). A comparative study of HDCV and PVRV vaccines in 144 volunteers did not show serious adverse event with either vaccine, although some vaccinees complained of redness, induration or local pain and exceptionally, fever (Ajjan & Pilet, 1989)


Allergic reactions

Allergic reactions are reported mostly after booster doses of HDCV vaccines (CDC, 1984; Dreesen et al., 1986). The overall incidence was 11 per 10,000 vaccinees (0,11%), but rose to 6% after boosters (Fishbein et al., 1993). These reactions have been attributed to antigenicity conferred on the stabilizer - human albumin - by the b -propiolactone used to inactivate the virus. The b -propiolactone increases the capacity of albumin to form an immune complexes (CDC, 1984; Anderson et al., 1987; Swanson et al., 1987). Respiratory symptoms are mild, there have been no fatalities. Epinephrine, antihistamines and occasionally steroids have been used in successful treatment of these reactions, which have resolved in 2 to 3 days.


Severe adverse events


Vaccines containing animal brain tissues

Severe and fatal reactions

A patient may suffer from serious and often fatal illness after nerve tissue vaccine. These accidents are of two types: (1) vaccine-induced rabies, a disease induced by the living "fixed virus" present in the Ferme or Pasteur vaccines, and (2) neuroparalytic accidents, which present the greatest danger from rabies vaccination. All types of vaccines containing adult mammalian nervous tissues exhibit similar capacities for inducing neuroparalytic reactions. The neuroparalytic reactions usually develops between the 13th and the 15th days of treatment and may assume one of the following three forms:

  1. Landry type. In this type of accident, the patient rapidly becomes pyrexial and suffers pain in the back. Flaccid paralysis of legs begins and within one day, the arms become paralyzed. Later, the paralysis spreads to the face, tongue, and other muscles. The fatality rate is about 30%; in the remaining 70%, recovery usually occurs rapidly.
  2. Dorsolumbar type. Less severe than Landry type, this is the most common form of neuroparalytic accident. Clinical features are explicable by the presence of dorsolumbar myelitis. The patient may be febrile and feel weak, with paralysis of the lower limbs, diminished sensation and sphincter disturbances. The fatality rate does not exceed 5%.
  3. Neuritis type. In this type of accident, the patient may be pyrexial and usually shows a temporary paralysis of the facial, oculomotor, glossopharyngeal or vagus nerves.

Neuroparalytic accidents are caused by allergic "encephalomyelitis", attributable to sensitization to adult nerve tissue antigen (myelin based protein). The incidence of these reactions varies widely from 0.0017% to 0.44% and is definitely lower in people receiving DEV and in people receiving properly manufactured vaccine of newborn rodent brain.


Cell-cultured vaccines

Neurological reactions

Although five cases of central nervous system disease, including transient neuroparlytic illness of Guillain-Barré type, have been reported among the millions of individuals given human diploid cell vaccines (Bernard et al., 1982; Boe & Nyland, 1980; Knittel et al., 1989; Tornatore & Richert, 1990; Moulignier et al., 1991). This rate is too low to be positively related to vaccination, because the background incidence of such diseases is about 1 per 100,000 per year. This low incidence after human diploid cell vaccine compares well with a neurological complication rate of 1:1600 people for nerve tissue vaccine, 1:8000 for suckling mouse brain vaccine and 1:32,000 for duck embryo vaccine.



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