A case report of rabies in a striped hyena (Hyaena hyaena) in Qazvin Province of Iran.

Rabies is a fatal and zoonotic disease that remains endemic in Iran. In this article, rabies in a striped hyena (Hyaena hyaena) in Qazvin Province, Iran, was found when being hunted for using the genitals for traditional thoughts of the people. The fluorescent antibody technique confirmed rabies infection in the brain sample, and vaccination was done for injured hunter.

Enhancement of immune responses by co-stimulation of TLR3 - TLR7 agonists as a potential therapeutics against rabies in mouse model.

Rabies is always fatal, when post-exposure prophylaxis is administered after the onset of clinical symptoms. To date, there is no effective treatment of rabies once clinical symptoms has initiated. Therefore, we aimed to provide evidences which indicate the promising effects of combination treatment with TLR agonists following rabies infection. Four groups of rabies infected-mice (10-mice/group) were treated with PolyI:C 50 µg (a TLR3 agonist), Imiquimod50 µg (a TLR7 agonist), (Poly + Imi)25 µg and (Poly + Imi)50 µg respectively. The immune responses in each experimental groups were investigated in the brain through evaluation of GFAP, MAP2, CD4, HSP70, TLR3, TLR7 and apoptotic cell expression as well as determination of IFN-γ, TNF-α and IL-4, levels. The treatment with combination of agonists (Poly + Imi)50 µg/mouse resulted a 75% decrease of mortality rate and better extended survival time following street rabies virus infection. Higher number of CD4+T cells, TLR3 and TLR7 expression in the brain parenchyma observed in the groups receiving both combined agonist therapies at the levels of 25 µg and 50 µg. In spite of decreased number of neuronal cell, significant higher number of astrocytes was shown in the group given (Poly + Imi)25 µg. The obtained results also pointed to the dramatic decrease of HSP70 expression in all groups of infected mice whereas higher number of apoptotic cells and Caspase 8 expression were recorded in (Poly + Imi)25 µg treated group. Furthermore, the cytokine profile consisting the increased levels of TNF-α, IFN-γ and IL-4 revealed that both humoral and cellular responses were highly modulated in combination therapy of 50 µg of Imiquimod and Poly I:C. Reduced viral load as quantified by real-time PCR of rabies N gene expression in the brain also correlated with the better survival of agonist-treated groups of mice. Based on obtained results, we have presented evidences of beneficial utilization of combined agonist therapy composed of TLR3/TLR7 ligands. This treatment regimen extended survival of infected mice and decreased significantly their mortality rate. We believe that the results of synergy-inducing protection of both TLR3/TLR7 agonists lead to the enhancement of innate immune responses cells residing in the CNS which warrant the studies to further understanding of crosstalk mechanisms in cellular immunity against rabies in the future.

Seroconversion after three doses of intramuscular rabies vaccine as a post-exposure treatment.

Rabies is still threatening half of the world's population with the global burden of canine rabies being estimated as 59,000 human deaths, annually. With no cure existing for clinical rabies, post-exposure prophylaxis (PEP) is the only certain means to save lives of the exposed people. In Iran, bite incidences exceed 180,000 per year, where all victims receive 5 vaccine doses for PEP, conforming to the Essen regimen. More than two-thirds of the exposed individuals stop receiving treatments after day 7, for the reason of being exposed to a non-rabid dog or cat. According to the national standard protocols, these individuals should re-start a complete 5-dose PEP course upon the re-exposure. New WHO recommendations based on scientific data is encouraging revisions to the existing prophylaxis programs. In order to know if an incomplete Essen regimen can provide adequate immunity, in the present study, 5 groups of individuals who had only received 3 first doses of the Essen regimen within the previous 1, 3, 6, 12 and 24 months were examined for immunity against rabies. Our results indicated sufficient anti-rabies neutralizing antibody in all individuals, before and after receiving two standard booster doses (i.e. days 0 and 3). This might also suggest the adequacy of the 3 first doses of vaccination, as a one-week long post-exposure vaccination program.

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.

Human rabies in Iran.

BACKGROUND: Like most Asian and African countries, Iran is highly endemic for rabies, which is a preventable disease with the timely utilisation of post-exposure prophylaxis (PEP). With the availability of affordable vaccination in Iran, there are still several rabies deaths which are assumed misdiagnosed or received ineffective PEP. METHODS: We reviewed the files of 16 human rabies deaths, consisting of two groups: 1, ineffective treatment; and 2, erroneous PEP. RESULTS: Most of the studied cases were male and were from rural areas. Stray dogs were found to be the common biting animal (68.75%). Of the patients, 10/16 (62.5%) who had injuries on their head and/or face demonstrated shorter incubation periods. The incubation period was longer in a 4-year-old boy who sustained injuries in his abdomen and back. All the patients in group 1 received four doses of vaccine and administration of human rabies immune globulin (HRIG), and death occurred with the mean of 49 days after the bite. This mean was 27 days in three patients in group 2, who received vaccine without administration of HRIG. CONCLUSION: In a total of 1,188,579 cases of PEP given in Iran during: 2002-2011, it is not known whether all PEPs were correctly administered by World Health Organization standards. Extending rabies awareness programmes and timely PEP education in the community in accordance with the implementation of rabies control measures might lead to a decrease in these unfortunate scenarios and heavy financial burden of vaccination required due to the prevalence of rabies.

Proteomics analysis of human brain tissue infected by street rabies virus.

In order to extend the knowledge of rabies pathogenesis, a two-dimensional electrophoresis/mass spectrometry based postmortem comparative proteomics analysis was carried out on human brain samples. Alteration in expression profile of several proteins was detected. Proteins related to cytoskeleton, metabolism, proteasome and immune regulatory systems showed the most changes in expression levels. Among these groups, the cytoskeleton related proteins (dynein light chain, ß-centractin, tubulin alpha-1C chain and destrin) and metabolism associated proteins (fatty acid-binding protein, macrophage migration inhibitory factor, glutamine synthetase and alpha enolase) were the main altered proteins. These alterations may be considered as an evidence of disturbances in neuronal key processes including axonal transport, synaptic activity, signaling and metabolic pathways in rabies virus infected human brain.

Report of the first meeting of the middle East and eastern europe rabies expert bureau, istanbul, Turkey (june 8-9, 2010).

Rabies is a threat in all parts of the world where animal reservoirs persists, including Eastern Europe and the Middle East. Rabies experts from seven Middle East and Eastern European countries (Croatia, Egypt, Georgia, Iran, Serbia, Turkey, and Ukraine) met for two days in Istanbul, Turkey (June 8-9, 2010), to exchange information on the epidemiological situation concerning human and animal rabies in their respective countries and to discuss strategies for rabies elimination and control. They decided to establish a regional network, the Middle East and Eastern Europe Rabies Expert Bureau (MEEREB), a regional network of experts, to increase collaboration in rabies prevention and control at the local, regional, and global levels.

Antibody persistence, 32 years after post-exposure prophylaxis with human diploid cell rabies vaccine (HDCV).

In 1975-1976 forty-five persons severely bitten by rabid wolves and dogs in Iran were treated successfully against rabies with HDCV. In this study contact was made with 26 of 45 above persons, 32 years after their initial treatment and all had rabies neutralizing antibody ranging from 0.3 to 2.69 IU/ml of serum. Of the 26 persons, 17 had received a booster dose of HDCV, 28 years ago and the remaining 9 persons, who had not received any booster since the initial treatment, were given one booster dose of HDCV. All 9 of these patients developed an anamnestic response after their booster inoculation. This study confirms the persistence of rabies neutralizing antibody in persons that received post-exposure vaccination with HDCV, 32 years previously. Furthermore, a single booster inoculation with HDCV resulted in anamnestic response in all individuals.