Complete Recovery from Clinical Rabies: Case Report

Karahocagil, Mustafa Kasım; Akdeniz, Hayrettin; Aylan, O.; Sünnetçioğlu, Mahmut; Ün, Hikmet; Yapici, Kubilay; Baran, Ali İrfan

doi:10.5336/medsci.2011-24811

Cited by 25 publications

(11 citation statements)

References 12 publications

(13 reference statements)

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“…Prior to the Milwaukee Protocol, few human cases of rabies survival received post-exposure prophylaxis only with administration of the vaccine [15, 16, 17, 18]. Complete recovery or with sequels in rabies patients is limited to a few cases in the literature linked to the history of immunization with the combination of vaccines and passive immunization of antibodies at the onset of symptoms [19, 20, 21]. Studies with B cell-deficient mice, which underwent CNS virus inhibition after peripheral administration of RABV-specific antibodies at 5 d.p.i, support these results.…”

Section: Discussionmentioning

confidence: 99%

Intracerebral transfection of anti-rabies virus antibodies is an effective therapy for rabies

Agostinho

Brandão

2019

Preprint

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27Rabies is a zoonotic neurological disease with 100% lethality. Some of the rare human 28 patients who survived after multiple drug treatment have inherited severe sequelae. The 29 objective of this study was to investigate the action of the transfection of antibodies against 30 rabies in the central nervous system of mice as target therapy for rabies. 32Author summary 33 The present study showed that after 48 h of RABV inoculation, mice injected by the 34 intracerebral route with anti-RABV F(ab')₂ complexed with Bioporter® Protein Delivery 35 Reagent (Genlantis) as a transfection agent, showing a morbidity/mortality rate of 30% with a 36 minimum incubation period of seven days, while in the control group a significantly higher 37 (p<0.0198) 90% morbidity/mortality was reached in thirteen days after a maximum 5-day 38 incubation period, suggesting that the transfection of anti-RABV antibodies into the brain might 39 prevent or delay RABV dissemination in an early stage of rabies infection. For the first time, a 40 single compound was able to inhibit replication of the virus in the nervous system with high 41 efficiency. This result can provide important results for the planning of protocols to prevent the 42 fatal outcome of the disease in advanced stages. New studies focusing on the optimization of 43 intracellular antibody delivery may be one of the main bases for more effective anti-rabies 44 therapy. 45 46 47 48Rabies is a zoonotic neurological disease with 100% lethality; some of the few human 49 patients who survived after a multi-drug treatment developed severe motor impairment due to 50 ischaemic encephalopathy followed by necrosis of the hippocampus, cerebellum and cortex [1-51 2]. The use of immunomodulators and antivirals has not been shown to be effective in inhibiting 52 the progression of the disease when tested in mice and humans [3][4]. Circa 59,000 human 53 deaths occur worldwide yearly due to rabies, and although it is preventable with pre and post-54 exposure prophylaxis, the logistics and costs involved in rabies treatments are a limiting factor 55 to saving lives [5]. 56 Rabies lyssavirus RABV (Mononegavirales: Rhabdoviridae: Lyssavirus) is a 57 neurotropic virus with a circa 11 Kb negative-sense single-stranded RNA as a genome that 58 codes for the nucleoprotein (N), phosphoprotein (P), matrix protein (M), envelope glycoprotein 59 (G) and the RNA-dependent RNA-polymerase L protein [6], and it is most often transmitted 60 amongst mammals via saliva after an initial local replication in muscle cells that follows to the 61 central nervous system (CNS) via axons [7]. Within a variable period of time after infection, 62 signs of hyperactivity, hypersalivation and hydrophobia are detectable. The virus causes enough 63damage to the brain in a few days that the infection invariably leads to coma and death by 64 cardio-respiratory arrest [8]. 65 Here, we show that the use of intracerebral transfection of anti-RABV antibodies to treat 66 mice inoculated with RABV reduces mortality and extends t...

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Section: Discussionmentioning

confidence: 99%

Intracerebral transfection of anti-rabies virus antibodies is an effective therapy for rabies

Agostinho

Brandão

2019

Preprint

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“…Rabies antibody was present when first tested within a week of the onset of symptoms. He had had supportive treatment but no specialised intensive care and returned to normal life as a shepherd [ 3 ].…”

Section: The Likelihood Of Recovery Will Vary According To the Orimentioning

confidence: 99%

“…Two children bitten by bats in the USA, only one of whom had received rabies post-exposure vaccination, have recovered from rabies encephalomyelitis to live independent lives [ 1 , 2 ]. Another person, who was bitten by a dog in Turkey and was incompletely vaccinated, also recovered [ 3 ]. However, most rabies patients given expert intensive care have either died in the acute phase or have survived for varying periods of time, but with incapacitating neurological impairment.…”

Section: Introductionmentioning

confidence: 99%

The Imperative of Palliation in the Management of Rabies Encephalomyelitis

Warrell

Tarantola

2017

TropicalMed

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The aim of this review is to guide clinicians in the practical management of patients suffering from rabies encephalomyelitis. This condition is eminently preventable by modern post-exposure vaccination, but is virtually always fatal in unvaccinated people. In the absence of any proven effective antiviral or other treatment, palliative care is an imperative to minimise suffering. Suspicion of rabies encephalomyelitis depends on recognising the classic symptomatology and eliciting a history of exposure to a possibly rabid mammal. Potentially treatable differential diagnoses must be eliminated, notably other infective encephalopathies. Laboratory confirmation of suspected rabies is not usually possible in many endemic areas, but is essential for public health surveillance. In a disease as agonising and terrifying as rabies encephalomyelitis, alleviation of distressing symptoms is the primary concern and overriding responsibility of medical staff. Calm, quiet conditions should be created, allowing relatives to communicate with the dying patient in safety and privacy. Palliative management must address thirst and dehydration, fever, anxiety, fear, restlessness, agitation, seizures, hypersecretion, and pain. As the infection progresses, coma and respiratory, cardiovascular, neurological, endocrine, or gastrointestinal complications will eventually ensue. When the facilities exist, the possibility of intensive care may arise, but although some patients may survive, they will be left with severe neurological sequelae. Recovery from rabies is extremely rare, and heroic measures with intensive care should be considered only in patients who have been previously vaccinated, develop rabies antibody within the first week of illness, or were infected by an American bat rabies virus. However, in most cases, clinicians must have the courage to offer compassionate palliation whenever the diagnosis of rabies encephalomyelitis is inescapable.

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“…There are only ten reported cases of rabies cure in the literature that do not lack scientific evidence, and only three of them had completely recovered or suffered mild sequelae [4][5][6][7][8][9][10][11][12][13][14]. There is constant research on new, more effective and less expensive agents displaying potential antiviral activities on rabies [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Bufotenine, a tryptophan-derived alkaloid, suppresses the symptoms and increases the survival rate of rabies-infected mice: the development of a pharmacological approach for rabies treatment

Vigerelli

Sciani

Pereira

et al. 2020

J. Venom. Anim. Toxins incl. Trop. Dis

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Background: Between 40,000-70,000 people die yearly of rabies, an incurable disease. Besides post-bite vaccination, no treatment is available for it. Methods: First, virus dilution for antiviral effects in mice was determined. Then, animals were treated as follows: control (NaCl 250 µL/animal/day); bufotenine (0.63, 1.05 and 2.1 mg in 250 µL of NaCl/animal/day); rabies (10-6,82 CVS dilution); and test (10-6,82 CVS dilution and bufotenine, in the above-mentioned doses). Animals were observed daily for 21 days or until the 3 rd stage of rabies infection. Twitch-tension and liposome studies were applied to understand the possible interaction of bufotenine with receptors, particularly acetylcholine. Results: Bufotenine was able to increase the survival rate of intracerebrally virus-infected mice from 15 to 40%. Bufotenine did not seem to interfere with the acetylcholine response in the skeletal muscle, indicating that its mechanism of action is not blocking the virus entrance due to nAChR antagonism. By analyzing liposomes, we could observe that bufotenine did not passively penetrates cell membranes, indicating the necessity of complementary structures to cell penetration. Conclusions: Bufotenine is a promising candidate for drug development. After further chemical modification, it might be possible to dissociate minor side effects, increase efficiency, efficacy and pharmacokinetics, yielding a true anti-rabies drug.

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Complete Recovery from Clinical Rabies: Case Report

Cited by 25 publications

References 12 publications

Intracerebral transfection of anti-rabies virus antibodies is an effective therapy for rabies

Intracerebral transfection of anti-rabies virus antibodies is an effective therapy for rabies

The Imperative of Palliation in the Management of Rabies Encephalomyelitis

Bufotenine, a tryptophan-derived alkaloid, suppresses the symptoms and increases the survival rate of rabies-infected mice: the development of a pharmacological approach for rabies treatment

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