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Summary: Rabies is an almost invariably fatal disease that can present as classic furious rabies or paralytic rabies. Recovery has been reported in only a few patients, most of whom were infected with bat rabies virus variants, and has been associated with promptness of host immune response and spontaneous (immune) virus clearance. Viral mechanisms that have evolved to minimise damage to the CNS but enable the virus to spread might explain why survivors have overall good functional recovery. The shorter survival of patients with furious rabies compared with those with paralytic rabies closely corresponds to the greater amount of virus and lower immune response in the CNS of patients with the furious form. Rabies virus is present in the CNS long before symptom onset: subclinical anterior horn cell dysfunction and abnormal brain MRI in patients with furious rabies are evident days before brain symptoms develop. How the virus produces its devastating effects and how it selectively impairs behaviour in patients with furious rabies and the peripheral nerves of patients with paralytic rabies is beginning to be understood. However, to develop a pragmatic treatment strategy, a thorough understanding of the neuropathogenetic mechanisms is needed. [Copyright &y& Elsevier]

Rabies is inevitably fatal and presents a horrifying clinical picture. Human rabies can manifest in either encephalitic (furious) or paralytic (dumb) forms. The brainstem is preferentially involved in both clinical forms, though there are no clinical signs of brainstem dysfunction. Differences in tropism at the inoculation site or the CNS, in the route of spread, or in the triggering of immune cascades in the brainstem may account for clinical variation. Rabies still poses diagnostic problems, particularly the paralytic form, which closely resembles Guillain-Barre´ syndrome, or when a patient is comatose and cardinal signs may be lacking. Molecular methods allow reliable detection of rabies-virus RNA in biological fluids or tissue before death. Deviations from the recommendations on prophylaxis of the World Health Organization lead to unnecessary loss of life. To date, attempts to treat human rabies have been unsuccessful. [Copyright &y& Elsevier]

Presents a clinical case of a 26-year-old female patient admitted to a hospital with a history of dog bite to the right leg 2 moths previously. Diagnosis on the patient; Development of total limb and facial paralysis of the patient soon after receiving intravenous human rabies immune globulin; Treatment to the patient.

Pre- as well as post-exposure prophylaxis plays an important role in controlling the number of deaths associated with human rabies. Rabies vaccines, classically injected intramuscularly, are now also administered by intradermal (ID) route. Vaccines to be administered by the ID route should meet the same quality, safety and efficacy specifications as vaccines for intramuscular (IM) use. The aim of this paper is to provide information based on publicly available data regarding the ID use of rabies vaccines and to identify potential needs for further analysis of the potency, immunogenicity and effectiveness of rabies vaccines administered by this route. A first literature search, focused on the immunogenicity of rabies vaccines given by ID route, identified 338 publications in the period 1997–2018, 40 of which were included in our analyses. A second search investigating the effectiveness of ID vaccination resulted in 371 hits for the period 2007–2018, of which 13 suitable publications were retained. The immunogenicity of current rabies vaccines was analyzed in 3 ways: proportion of subjects reaching the antibody threshold of 0.5 IU/ml after ID vaccination, relationship between potency and immunogenicity of the vaccine given intradermally, and comparison of antibody responses after IM or ID vaccination. Overall, vaccines administered intradermally were found immunogenic. Post-exposure prophylaxis by ID route appeared at least as immunogenic as by IM regimens. By contrast, ID pre-exposure prophylaxis trended towards lower antibody titers than IM vaccination, but the observation was not associated with any clinical relevance. Vaccine effectiveness was assessed by investigating survival after exposure. Data from more than 30,000 patients who sought rabies post-exposure prophylaxis did not indicate that current vaccines administered by ID route lack efficacy. These results support current recommendations for ID vaccination against rabies. However, published data on ID performance were associated with significant weaknesses that future research should better address. [ABSTRACT FROM AUTHOR]

Abstract: Plasma from 10 patients who had received rabies vaccine either intradermally (ID) or intramuscularly (IM) was examined for 20 chemo- and cytokines. Plasma samples were withdrawn on days 0, 3 and 7 after vaccination. These chemo- and cytokines and sampling days were chosen based on data collected from a protein array analysis of 122 cytokines conducted on one recipient of vaccine administered IM and one recipient of vaccine administered ID. Although eotaxin, interleukin (IL)-5 in the ID and IL-1 beta in the IM group were the only chemo- and cytokines that reached statistical significance (p <0.05), the overall trends may suggest bias on Th1 or Th2 according to vaccination routes. IL-1 alpha, -2, and -6, hemofiltrate cysteine–cysteine chemokine (HCC-4), glucocorticoid induced tumor necrosis factor receptor (GITR), tumor necrosis factor (TNF) related apoptosis inducing ligand-receptor (TRAIL-R3) had some degree of elevation in the ID group. TNF-alpha, gamma-interferon, granulocytes/macrophages – colony stimulating factor (GM-CSF), transforming growth factor (TGF)-beta, lymphotactin and pulmonary and activation-regulated chemokine (PARC) were elevated, although not to a significant level, in the IM group. IL-12, interferon-inducible T cell alpha chemoattractrant (I-TAC) and sertoli cell factor (SCF) were not significantly elevated in both groups whereas IL-4 and -10 were unchanged. Further studies are required to determine whether the presence of specific chemokines, such as eotaxin, is responsible for the production of high levels of rabies virus neutralizing antibody after administration of the dose-sparing ID regimen. [Copyright &y& Elsevier]

The World Health Organization reports that over 60,000 humans die of rabies annually, worldwide. Most occur in remote regions of developing countries. Almost all victims received no postexposure rabies prophylaxis (PEP). There are no facilities or health personnel able to provide it in many areas where the disease is prevalent. A first approach to correct this problem would be by extending provision of modern PEP to areas where human rabies is most prevalent. [ABSTRACT FROM AUTHOR]

We report the case of a 7-year-old Thai girl that was bitten by a dog. She received prompt wound care followed by eight-site intradermal post-exposure rabies schedule using purified chick embryo vaccine. Treatment followed WHO recommendations for desperate situations where no rabies immune globulin (RIG) is available. The patient died 15 days later with classical symptoms and signs of encephalitic rabies. [Copyright &y& Elsevier]