Natural Infection with Rabies Virus: A Histopathological and Immunohistochemical Study of Human Brains

OBJECTIVES: Despite all the efforts and increased knowledge of rabies, the exact mechanisms of infection and mortality from the rabies virus are not well understood. To understand the mechanisms underlying the pathogenicity of rabies virus infection, it is crucial to study the tissue that the rabies virus naturally infects in humans. METHODS: Cerebellum brain tissue from 9 human post mortem cases from Iran, who had been infected with rabies virus, were examined histopathologically and immunohistochemically to evaluate the innate immune responses against the rabies virus. RESULTS: Histopathological examination revealed inflammation of the infected cerebellum and immunohistochemical analyses showed an increased immunoreactivity of heat shock protein 70, interleukin-6, interleukin-1, tumor necrosis factor-alpha, caspase-3, caspase-9, toll-like receptor3 and toll-like receptor4 in the infected brain tissue. CONCLUSION: These results indicated the involvement of innate immunity in rabies infected human brain tissue, which may aggravate the progression of this deadly disease.

[Study on lasting immunity in previously treated persons against rabies and investigation of booster effect of Vero rabies vaccine]

Human rabies is preventable by prompt post-exposure prophylaxis. The total number of rabies vaccine doses administered during post-exposure prophylaxis is 5; given on days 0, 3, 7, 14 and 30. The aim of this study was to measure the durability of rabies neutralizing antibody in exposed persons treated 14-17 years ago and to investigate the effect of 2 boosters of rabies vaccine. This study was conducted in 2 phases. In phase 1 blood samples were taken from 100 rabies vaccine recipients 14-17 years after they had received the vaccine. In the 2nd stage of the studies 30 volunteers from the first phase of the study were divided into 2 groups of 15 subjects each; the first group was given 2 booster doses of the vaccine intra-dermally on days 0 and 3. In the 2[nd] group the 2 doses were administered through the intramuscular route; blood samples were collected 10 days after the booster doses. Rapid Focus Fluorescent Inhibition Test [RFFIT] was used for measuring the antibodies in both phases. The rabies neutralizing antibody was detected in the sera of all 100 individuals who had received the rabies vaccine, 85% of whom demonstrated titers ?0.5 IU/ml. In the groups who received the booster doses, serology results demonstrated higher rabies neutralizing antibody titers in persons who had received the two booster injections intradermally. This study confirms the persistence of rabies neutralizing antibody for at least 14 years after a full course of primary post-exposure prophylaxis; furthermore two booster inoculations of Vero rabies vaccine on days 0 and 3, given intradermally resulted in a sharp increase in the level of antibodies, indicating that two boosters could protect against rabies after a repeat exposure