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Background: Neurotropic virus infection can cause serious damage to the central nervous system (CNS) in both humans and animals. The complexity of the CNS poses unique challenges to investigate the infection of these viruses in the brain using traditional techniques., Methods: In this study, we explore the use of fluorescence micro-optical sectioning tomography (fMOST) and single-cell RNA sequencing (scRNA-seq) to map the spatial and cellular distribution of a representative neurotropic virus, rabies virus (RABV), in the whole brain. Mice were inoculated with a lethal dose of a recombinant RABV encoding enhanced green fluorescent protein (EGFP) under different infection routes, and a three-dimensional (3D) view of RABV distribution in the whole mouse brain was obtained using fMOST. Meanwhile, we pinpointed the cellular distribution of RABV by utilizing scRNA-seq., Results: Our fMOST data provided the 3D view of a neurotropic virus in the whole mouse brain, which indicated that the spatial distribution of RABV in the brain was influenced by the infection route. Interestingly, we provided evidence that RABV could infect multiple nuclei related to fear independent of different infection routes. More surprisingly, our scRNA-seq data revealed that besides neurons RABV could infect macrophages and the infiltrating macrophages played at least three different antiviral roles during RABV infection., Conclusion: This study draws a comprehensively spatial and cellular map of typical neurotropic virus infection in the mouse brain, providing a novel and insightful strategy to investigate the pathogenesis of RABV and other neurotropic viruses., (© 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Rabies encephalitis is a universally fatal disease. Prolonged survival in children with rabies encephalitis has only been anecdotally reported. Case report: An 11-year-old boy presented with right-handed paraesthesia followed by flaccid weakness, progressive quadriparesis and encephalopathy following an unprovoked, class III dog bite over the right wrist 1 month previously. He received five doses of the rabies vaccine as post exposure prophylaxis. Diagnosis of rabies encephalitis was supported by typical MRI brain and spine findings in addition to marked elevation of anti-rabies neutralizing antibody titers in serum and CSF. He was treated with supportive care, methylprednisolone, dexamethasone and simvastatin and was discharged after 6 weeks of hospital stay in a minimally conscious state, with tracheostomy and naso-gastric feeding tubes. At 9 months follow-up, his neurological status showed minimal improvement. Paralytic rabies with brachial plexitis and encephalomyelitis is an atypical presentation of rabies. Very few surviving cases have been reported from India. Survival from rabies is possible with effective clearing of virus with post exposure prophylaxis, but with severe neurological sequelae., Competing Interests: None

Rabies encephalitis is a fatal zoonotic viral disease transmitted to humans either by domestic animals like dogs and cats or by wild animals like bats, skunks and raccoons. We present the case of a 25-year-old woman admitted due to behavioral disorders, generalized paresthesiasand acute respiratory deterioration compatible with a respiratory distress syndrome (ARDS) requiring orotracheal intubation, mechanical ventilation and empirical initiation of antibiotic and antiviral therapy. Chest tomography showed pneumomediastinum and changes suggestive of pulmonary infection. In the presence of neurological symptoms, a central nervous system (CNS) infection was suspected and the cerebrospinal fluid showed no pleocytosis, hiperproteinorrachy without glucose consumption; cranial CT scan was normal. During hospitalization, the family reported that the patient was bitten by a cat 30-day prior to the onset of rabies-like symptoms, and the animal was sacrificed. The patient had an unfavorable clinical evolution, with electroencephalographic activity dissociation evidenced by video telemetry. The zoonotic exposure led to the suspected diagnosis of rabies infection. The patient died and the suspected diagnosis was confirmed by histopathology, with presence of Negri bodies on cerebellum Purkinje cells and a positive immunofluorescence test for rabies virus. Both, initial extra-neural manifestations and late reporting of rabies exposure led to delayed diagnosis.

Background: Paralytic form of rabies is frequent in cattle in Latin America, but it is uncommon in goats. There are few clinical reports on furious rabies affecting goats, and the sporadic cases of rabid goats from surveillance programs worldwide lack clinical data. Furthermore, few studies reported the cerebrospinal fluid findings in rabid livestock., Case Presentation: On a farm in Midwestern Brazil, six of 47 Saanen goats died within one week. No vaccination protocols were implemented on the farm and the owner stated bat bites history on the livestock. Although rabies is endemic in Brazil, livestock vaccination is not mandatory. One 1-year-old buck was evaluated and showed non-specific clinical signs evolving within 12-h to nervous signs. Cerebrospinal fluid analysis revealed mononuclear pleocytosis, hyperproteinemia and high glucose levels. At necropsy, no gross lesions were present. Microscopically, discrete to moderate perivascular lymphoplasmacytic cuffing in gray and white matter, neuronal necrosis, neuronophagia, and mononuclear ganglioneuritis was observed in the brainstem and cervical spinal cord. Immunohistochemistry revealed strong anti-rabies virus immunostaining. Fresh central nervous system samples were positive for rabies in direct fluorescent antibody test (dFAT) and mouse intracerebral inoculation test (MIT). Exposed livestock recommendations included immediate vaccination, a strict isolation period of 90 days, and booster vaccinations during the third and eighth weeks., Conclusion: IHC revealed the widespread distribution of rabies virus antigen in the goat's CNS, contrasting the discrete pathological changes. In this goat, definitive diagnosis of paralytic rabies was obtained through the association of epidemiological, clinical, laboratorial, pathological findings (histology and IHC) and gold standard confirmatory tests (dFAT and MIT).

Rabies and canine distemper virus infections in wildlife share similar presenting signs. Canine distemper virus was detected using real-time PCR of conjunctival swabs in rabies positive raccoons (22/32) and skunks (7/34) during a concurrent rabies and canine distemper outbreak in Ontario, Canada in 2015-16. Coinfections with both viruses should be considered, particularly in distemper endemic areas that are at risk of rabies incursion.

Rabies is a life-threatening neglected tropical disease: tens of thousands of cases are reported annually in endemic countries (mainly in Africa and Asia), although the actual numbers are most likely underestimated. Rabies is a zoonotic disease that is caused by infection with viruses of the Lyssavirus genus, which are transmitted via the saliva of an infected animal. Dogs are the most important reservoir for rabies viruses, and dog bites account for >99% of human cases. The virus first infects peripheral motor neurons, and symptoms occur after the virus reaches the central nervous system. Once clinical disease develops, it is almost certainly fatal. Primary prevention involves dog vaccination campaigns to reduce the virus reservoir. If exposure occurs, timely post-exposure prophylaxis can prevent the progression to clinical disease and involves appropriate wound care, the administration of rabies immunoglobulin and vaccination. A multifaceted approach for human rabies eradication that involves government support, disease awareness, vaccination of at-risk human populations and, most importantly, dog rabies control is necessary to achieve the WHO goal of reducing the number of cases of dog-mediated human rabies to zero by 2030.

To review the literature about the use of Rabies Virus-Vaccine (RV-V) as an anticancer immunotherapeutic modality in the light of recent findings. The literature search in relevant databases with the following key words: Rabies virus, cancer, remission. Remissions occured following RV-V injections in patients with cervical cancer and melanoma. Pilot clinical studies showed that RV-V injections enhanced survival in glioblastoma patients, which is supported by findings in GL261 mouse glioma model. If public health studies demonstrate protective role of RV-V against certain types of cancers, it can be benefitted as a novel immune adjuvant in clinic.

A woman aged 77 years was transferred to our neurocritical care unit for evaluation and treatment of rapidly progressive motor weakness and encephalopathy. Examination revealed an ability to follow simple commands only and abnormal movements, including myoclonus, tongue and orofacial dyskinesias, and opsoclonus. Imaging study findings were initially unremarkable, but when repeated, they demonstrated enhancement of the cauda equina nerve roots, trigeminal nerve, and pachymeninges. Cerebrospinal fluid examination revealed mildly elevated white blood cell count and protein levels. Serial electrodiagnostic testing demonstrated a rapidly progressive diffuse sensory motor axonopathy, and electroencephalogram findings progressed from generalized slowing to bilateral periodic lateralized epileptiform discharges. Critical details of her recent history prompted a diagnostic biopsy. Over time, the patient became completely unresponsive with no further abnormal movements and ultimately died. The differential diagnosis, pathological findings, and diagnosis are discussed with a brief review of a well-known yet rare diagnosis.

Rabies viral encephalitis, though one of the oldest recognized infectious disease of humans, remains an incurable, fatal encephalomyelitis, despite advances in understanding of its pathobiology. Advances in science have led us on the trail of the virus in the host, but the sanctuaries in which the virus remains hidden for its survival are unknown. Insights into host-pathogen interactions have facilitated evolving immunologic therapeutic strategies, though we are far from a cure. Most of the present-day knowledge has evolved from in vitro studies using fixed (attenuated) laboratory strains that may not be applicable in the clinical setting. Much remains to be unraveled about this elusive virus. This review attempts to re-examine the current advances in understanding of the pathobiology of the rabies virus that modulate the diagnosis, treatment, and prevention of this fatal disease.

Although limited publications address clinical management of symptomatic patients with rabies in intensive care units, the overwhelming majority of human rabies cases occur in the rural setting of developing countries where healthcare workers are few, lack training and drugs. Based on our experience, we suggest how clinicians in resource-limited settings can make best use of essential drugs to provide assistance to patients with rabies and their families, at no risk to themselves. Comprehensive and compassionate patient management of furious rabies should aim to alleviate thirst, anxiety and epileptic fits using infusions, diazepam or midazolam and antipyretic drugs via intravenous or intrarectal routes. Although the patient is dying, respiratory failure must be avoided especially if the family, after being informed, wish to take the patient home alive for funereal rites to be observed. Healthcare staff should be trained and clinical guidelines should be updated to include palliative care for rabies in endemic countries., (© 2016 John Wiley & Sons Ltd.)

The Milwaukee protocol has been attributed to survival in rabies encephalitis despite a lack of scientific evidence supporting its therapeutic measures. We have reviewed the literature with reference to specific treatment recommendations made within the protocol. Current literature fails to support an important role for excitotoxicity and cerebral vasospasm in rabies encephalitis. Therapies suggested in the Milwaukee protocol include therapeutic coma, ketamine infusion, amantadine, and the screening/prophylaxis/management of cerebral vasospasm. None of these therapies can be substantiated in rabies or other forms of acute viral encephalitis. Serious concerns over the current protocol recommendations are warranted. The recommendations made by the Milwaukee protocol warrant serious reconsideration before any future use of this failed protocol.

We report a patient with an unusual initial metabolic presentation of imported human rabies who became symptomatic within 2 weeks of returning from Mali to France. This is the single case of imported human rabies identified in France within the past 11 years and the first report of viral RNA in bronchial secretions., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Cardiomyopathies have been rarely described in rabbits. Here we report myocardial necrosis of the ventricular wall in rabbits with experimentally induced rabies. Myocardial lesions were found only in rabbits with brain lesions, and the severity of the cardiac lesions was proportional to that of the brain lesions. Neither the frequency nor the cumulative dose of anesthesia was related to the incidence or the severity of the myocardial lesions. The myocardial lesions were characterized by degeneration and/or necrosis of myocardial cells and were accompanied by contraction band necrosis, interstitial fibrosis, and infiltration of inflammatory cells. The brain lesions due to rabies virus infection were most prominent in the cerebral cortex, thalamus, hypothalamus, brainstem, and medulla. Rabies virus antigen was not found in the hearts of any rabbits. Based on these findings, the myocardial lesions were classified as neurogenic cardiomyopathy., (© The Author(s) 2014.)

Paralytic rabies closely simulates Guillain-Barre syndrome or ascending myelitis often causing clinical dilemma. Two such patients were managed in our hospital whose magnetic resonance imaging (MRI) revealed characteristic findings revealing T2 hyper intensity in central spinal cord and in posterior brainstem and hypothalamus. These MRI findings are helpful in the diagnosis of rabies in appropriate setting. We also review the literature on MRI changes in paralytic rabies.

We present the case of a 19-year-old who developed psychotic symptoms after exposure to a potentially rabid animal and post-exposure prophylactic treatment. This case serves to remind physicians to fully explore the possibility of a nonpsychiatric origin of de novo psychotic symptoms and provides indirect evidence in favor of the possible involvement of the immune system in the development of psychotic disorders.

On 16 March 2012 a rabid eastern red bat (Lasiurus borealis) was found attached to an evening bat (Nycticeius humeralis) in Randolph County, Arkansas, USA. This appears to be the first confirmed case of a rabid bat attacking a bat of another species.

The developing world is still endemic to rabies, tetanus, leprosy, and malaria. Globally more than 55000 people die of rabies each year, about 95% in Asia and Africa. Annually, more than 10 million people, mostly in Asia, receive postexposure vaccination against the disease. World Health Organization estimated tetanus-related deaths at 163000 in 2004 worldwide. Globally, the annual detection of new cases of leprosy continues to decline and the global case detection declined by 3.54% during 2008 compared to 2007. Malaria is endemic in most countries, except the US, Canada, Europe, and Russia. Malaria accounts for 1.5-2.7 million deaths annually. Much of the disease burden related to these four infections is preventable., (© 2014 Elsevier B.V. All rights reserved.)

A 9-year-old boy died of rabies complications. We report the unusual combination between rabies, coronary dilatation on echocardiography and coronary vasculitis documented upon autopsy. In the search for the etiological agent of Kawasaki disease, we suggest that a viral infection with potential antigenic similarities to rabies virus should be entertained., (© 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.)

Rabies is a fatal disease resulting from rabies virus infection, causing severe neurological symptoms and ultimately death by destroying the nervous system. In general, a patient tends to see a neurologist or an infectious diseases physician, with very common and typical discipline-related signs and symptoms, such as hydrophobia, aerophobia, and mental disorders. However, we reported a rabies patient who was first admitted to see a thoracic surgeon with spontaneous pneumomediastinum., (Copyright © 2013 Elsevier Editora Ltda. All rights reserved.)

In May 2011, a girl aged 8 years from a rural county in California was brought to a local emergency department (ED) with a 1-week history of progressive sore throat, difficulty swallowing, and weakness. After she developed flaccid paralysis and encephalitis, rabies was diagnosed based on 1) detection of rabies virus-specific antibodies in serum and cerebrospinal fluid (CSF), 2) a compatible clinical syndrome in the patient, and 3) absence of a likely alternative diagnosis. The patient received advanced supportive care, including treatment with therapeutic coma. She was successfully extubated after 15 days and discharged from the hospital 37 days later to continue rehabilitation therapy as an outpatient. The public health investigation identified contact with free-roaming, unvaccinated cats at the patient's school as a possible source of infection. Several of these cats were collected from the school and remained healthy while under observation, but at least one was lost to follow-up. A total of 27 persons received rabies postexposure prophylaxis (PEP) for potential exposures to the patient's saliva. No further cases of rabies associated with this case have been identified. Rabies prevention efforts should highlight the importance of domestic animal vaccination, avoidance of wildlife and unvaccinated animals, and prompt PEP after an exposure.

On July 8, 2011, the New Jersey Department of Health and Senior Services (NJDHSS) contacted CDC about possible rabies in a hospitalized Haitian woman aged 73 years. Rabies was included in the differential diagnosis because she had acute, progressive encephalitis of unknown etiology. No history of animal exposure had been reported at the time of hospitalization. On July 18, CDC confirmed rabies virus infection, later identified as a canine rabies virus variant present in Haiti. The patient's neurologic status continued to deteriorate, leading to her death on July 20. This report summarizes the patient's clinical course and the associated public health investigation. This is the third report of human rabies in the United States acquired in Haiti since 2000 and highlights the importance of obtaining a detailed history for patients who have traveled from a rabies-endemic country and the value of consultation with medical and public health professionals regarding any animal bites.

In late December 2010, a male resident of Wisconsin, aged 70 years, sought treatment for progressive right shoulder pain, tremors, abnormal behavior, and dysphagia at an emergency department (ED). He was admitted for observation and treated with benzodiazepines and haloperidol, a neuroleptic, for presumed alcohol withdrawal syndrome. The next day, he had rhabdomyolysis, fever, and rigidity, and neuroleptic malignant syndrome was diagnosed. The neuroleptic was discontinued, but the patient's clinical status worsened, with encephalopathy, respiratory failure, acute renal failure requiring hemodialysis, and episodes of cardiac arrest. With continued clinical deterioration, additional causes were considered, including rabies. On hospital day 12, rabies virus antigens and nucleic acid were detected in the nuchal skin biopsy and rabies virus nucleic acid in saliva specimens sent to CDC. A rabies virus variant associated with silver-haired bats (Lasionycteris noctivagans) was identified. The patient died on hospital day 13. His spouse reported that they had been selling firewood, and bats had been present in the woodpile; however, the man had not reported a bat bite. Two relatives and five health-care workers potentially exposed to the man's saliva received postexposure prophylaxis. This case highlights the variable presentations of rabies and the ease with which a diagnosis of rabies can be missed in a clinically challenging patient with comorbidities. Clinicians should consider rabies in the differential diagnosis for patients with progressive encephalitis or neurologic illness of unknown etiology and caregivers should take precautions to avoid exposure to body fluids. Continued public education regarding risks for rabies virus exposure during interactions with wildlife, particularly bats, is important.

In August 2010, CDC confirmed a case of rabies in a migrant farm worker, aged 19 years, hospitalized in Louisiana with encephalitis. The man developed acute neurologic symptoms at the end of July, shortly after arriving in the United States from Michoacán, Mexico. Despite supportive care, his condition deteriorated, and he died on August 21. Antemortem diagnostic testing confirmed the diagnosis of rabies, and samples collected at autopsy were positive for a vampire bat rabies virus variant. The patient's mother reported that he had been bitten by a bat in July in Mexico but had not sought medical care. Postexposure prophylaxis (PEP) was offered to 27 of the patient's contacts in Louisiana and to 68 health-care workers involved in his care. Although bats have become the primary source of human rabies in the United States, this is the first reported death from a vampire bat rabies virus variant in the United States. Clinicians caring for patients with acute progressive encephalitis should consider rabies in the differential diagnosis and implement early infection control measures.

On November 9, 2009, a Michigan hospital informed CDC of suspected rabies in a man aged 55 years. The patient reportedly had awakened with a bat on his arm 9 months earlier but had not sought medical evaluation. He went to a local emergency department (ED) on October 30 and soon after was hospitalized; he died 12 days later. On November 14, CDC confirmed infection with a rabies virus variant that commonly infects the silver-haired bat (Lasionycteris noctivagans). This report summarizes the patient's clinical course and the associated public health investigation. The report highlights the importance of public awareness of rabies, particularly among persons who might be at risk for wildlife exposures. Persons who experience contact with a bat and cannot confidently rule out a bite or scratch should seek prompt medical attention.

Background: Rabies is an important public health problem in developing countries such as India where an alarmingly high incidence of the infection is reported every year despite the availability of highly effective, potent and safe vaccines. In clinical practice, diagnosis of the furious (encephalitic) form of rabies poses little difficulty. In contrast, the paralytic form poses a diagnostic dilemma, to distinguish it from Guillain-Barré syndrome. The problem is further compounded in the absence of a history of dog bite, clinical features resembling a psychiatric syndrome., Method: The present study analysed the spectrum of neurological manifestations in 47 cases of rabies encephalitis (34 paralytic, six encephalitic, and seven psychiatric manifestations) from two hospitals in south India, confirmed at post-mortem by demonstration of a viral antigen in the brain. A history of dog bite was elicited in 33 patients and fox bite in one. Twenty-two patients received postexposure prophylaxis. The incubation period ranged from 7 days to 4 years. Clinical features were analysed, looking for any clinical pointers that provide clues to a diagnosis of paralytic rabies., Results and Discussion: Fever, distal paresthaesias, fasciculation, alteration in sensorium, rapid progression of symptoms and pleocytosis in cerebrospinal fluid should alert the neurologist to consider rabies encephalomyelitis. Detection of the viral antigen in the corneal smear and a skin biopsy from the nape of the neck had limited usefulness in the ante-mortem diagnosis. Although a few clinical signs may help indicate rabies encephalomyelitis antemortem, confirmation requires neuropathological/neurovirological assistance. The preponderance of atypical/paralytic cases in this series suggests that neurologists and psychiatrists need to have a high index of clinical suspicion, particularly in the absence of a history of dog bite.

Rabies is a serious zoonotic disease. Recovery has been well documented in only six human patients worldwide. Five of those patients had received rabies vaccinations before illness; one had not received rabies vaccination but survived infection after prolonged intensive care. In most of these survivors, moderate to profound neurologic sequelae occurred. In all six survivors, rabies was diagnosed based on exposure history, compatible clinical symptoms, and detection of rabies virus-neutralizing antibodies (VNA). This report describes the clinical course and laboratory findings of an adolescent girl with encephalitis who had not had rabies vaccination and who had been exposed to bats 2 months before illness. Antibodies to rabies virus were detected in specimens of the girl's serum and cerebrospinal fluid (CSF) by indirect fluorescent antibody test (IFA). However, the presence of rabies VNA was not detected until after she had received single doses of rabies vaccine and human rabies immune globulin (HRIG). Although the patient required multiple hospitalizations and follow-up visits for recurrent neurologic symptoms, she survived without intensive care. No alternate etiology was determined, and abortive human rabies (defined in this report as recovery from rabies without intensive care) was diagnosed. Public education should emphasize avoiding exposure to bats and other potentially rabid wildlife and seeking prompt medical attention after exposure to such animals. Rabies is preventable if rabies immune globulin and vaccine are administered soon after an exposure; however, this case also suggests the rare possibility that abortive rabies can occur in humans and might go unrecognized.

Rabies is a fatal viral encephalitis characterized by a clinically acute and progressive course. With rare exceptions, there is a discrepancy between clinical outcome and frank histological alterations in rabies. Investigators have postulated that rabies virus may modify neurotransmission through occupancy of cellular receptors or alteration of ion channels. We took advantage of these observations to improvise a successful therapy for rabies. The Milwaukee protocol ( www.mcw.edu/rabies ) was further modified to treat two German patients. We measured pterins and monoamine neurotransmitter metabolites in the CSF of patients with rabies by HPLC with electrochemical or fluorescent detection. We report loss of tetrahydrobiopterin (BH(4)) and associated pathological decrease of dopaminergic and serotoninergic neurotransmission in three successive patients with rabies. CSF levels of BH(4) and neurotransmitter metabolites increased in two patients who were supplemented. Our findings support the long-standing speculation of modified neurotransmission in the pathogenesis of rabies, but by another mechanism. Brain turnover of dopamine and serotonin is reduced following rabies-acquired BH(4) deficiency. Neuronal nitric oxide synthase is BH(4)-dependent and may also be involved, possibly causing cerebrovascular insufficiency in one patient. This work must be carefully replicated in animal models and future patients. We are cautiously optimistic at the prospect of readily available, metabolically specific, enteral therapy for rabies.

It is generally accepted that there are not prominent features of neuronal cell death in rabies encephalitis. However, Hemachudha and coworkers recently reported widespread apoptosis in the central nervous system of several human rabies cases (BMC Infect Dis 5: 104, 2005). In this study we have evaluated morphological features and markers of neuronal apoptosis in postmortem brain tissue from 12 cases of human rabies who died in four different countries. Histopathological analysis, TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling) staining, and immunostaining for cleaved (activated) caspase-3 were performed on paraffin-embedded tissues from the cerebral cortex, hippocampus, and brainstem, and additional regional areas from one of the cases. We did not find morphological evidence of neuronal apoptosis or TUNEL staining in any of the cases of rabies encephalitis. Similarly, immunostained cleaved caspase-3 was not seen in neurons, but prominent staining was observed in microglial processes. We conclude that neuronal apoptosis does not play an important pathogenetic role in human rabies encephalitis.

Rabies remains a serious public health problem in many developing countries. A case in the West received media attention with the recovery of an American teenager who had not received rabies post-exposure prophylaxis. This case confirmed that rabies is not an invariably fatal disease. Review of the literature revealed only two survivors with good neurological status in nearly 40 years. Both had neutralizing antibodies in cerebrospinal fluid at or shortly after presentation, but the usual diagnostic tests for rabies were negative, a rather unique finding. It is highly probable that these two children managed to mount an unusually effective early immune response to the infection that contributed to, or was responsible for, recovery. Curative efforts for human rabies using critical care resources should especially target patients who show early neutralizing antibody. More basic research is needed to develop effective therapies for human rabies.

This column discusses the etiology and clinical manifestation of and postexposure prophylaxis for rabies in humans.

Purpose of Review: Increased awareness of the long-neglected rabies virus could promote the highly effective methods of preventing human deaths. Rabies and rabies-related lyssaviruses have recently been appearing in unexpected places, sometimes with dire consequences. Although rabies of canine origin remains 100% fatal in human beings, should the surprising recovery of a single unvaccinated child influence treatment now?, Recent Findings: Evidence of rabies-related lyssavirus infection of bats is increasing across continents and with new virus types. Human rabies has been misdiagnosed as cerebral malaria, or even drug abuse. Organ transplant recipients have been infected. The first unvaccinated patient, a teenager, bitten by a bat, recovered from rabies encephalitis, but why might this be? Highly effective control and prevention of infection is possible. Preexposure prophylaxis for schoolchildren could now become routine. Improved economical intradermal postexposure vaccine regimens could increase the availability of affordable treatment in developing countries. Controlling dog rabies could prevent 95% of human deaths, but education and resources are lacking., Summary: The risks and problems of rabies and other lyssaviruses vary greatly across the world. Knowledge of epidemiology and prevention could save the lives of victims of animal bites and promote efforts to control and even eliminate dog rabies.

Rabies, being a major zoonotic disease, significantly impacts global public health. It is invariably fatal once clinical signs are apparent. The majority of human rabies deaths occur in developing countries. India alone reports more than 50% of the global rabies deaths. Although it is a vaccine-preventable disease, effective rabies prevention in humans with category III bites requires the combined administration of rabies immunoglobulin (RIG) and vaccine. Cell culture rabies vaccines have become widely available in developing countries, virtually replacing the inferior and unsafe nerve tissue vaccines. Limitations inherent to the conventional RIG of either equine or human origin have prompted scientists to look for monoclonal antibody-based human RIG as an alternative. Fully human monoclonal antibodies have been found to be safer and equally efficacious than conventional RIG when tested in mice and hamsters. In this chapter, rabies epidemiology, reservoir control measures, post-exposure prophylaxis of human rabies, and combination therapy for rabies are discussed. Novel human monoclonal antibodies, their production, and the significance of plants as expression platforms are emphasized.

Objectives: The present study was undertaken to standardize skin testing and to develop a safe and effective premedication protocol for administration of ERIG in those with skin test positivity/hypersensitivity., Methods: A method of grading of skin testing was developed using injection histamine as a positive control. This was evaluated by using it on 517 subjects who had severe (WHO category III) exposure to rabies. A premedication protocol consisting of injections pheniramine, ranitidine, hydrocortisone and adrenaline was evaluated by using it on fifty one subjects who were skin test positive/hypersensitive to ERIG., Results: The premedication protocol was safe and effective as all the S1 subjects could be administered the full dose of ERIG despite being skin test positive/hypersensitive to ERIG. Besides the premedication drugs/protocol did not affect the immune response to vaccine and ERIG therapy.

In a malaria-endemic area of Africa, rabies was an important cause of fatal central nervous system infection, responsible for 14 (10.5%) of 133 cases. Four patients had unusual clinical manifestations, and rabies was only diagnosed postmortem. Three (11.5%) of 26 fatal cases originally attributed to cerebral malaria were due to rabies.

Acute respiratory distress syndrome (ARDS) is the first potentially lethal complication in rabies virus infection, although its occurrence is rare. We report on a fatal case of rabies virus infection in a 45-year-old woman from Hu-Nan Province, China. The neurologic signs of limb numbness and water phobia occurred from 61 days after the dog bite; the clinical course was progressive, with the most severe clinical manifestations being fever, encephalitis, and ARDS. The woman expired 12 days after admission to the hospital. An autopsy proved rabies encephalitis, mainly involving the medulla oblongata, the thalamus, part of the pons, the cerebellum, and the hippocampus. The lung pathologic examination revealed the organizing phase of ARDS with diffuse alveolar damage, hyaline membrane formation, type II alveolar cell hyperplasia accompanied by proliferation of fibroblasts and infiltration of mononuclear cells into the interstitial space. Immunohistochemistry stain and reverse transcription-polymerase chain reaction for rabies virus failed to demonstrate the organism in the lung tissue. Strong expression of inducible nitric oxide synthase (iNOS) was detected in the alveolar macrophages. An immunologic mechanism with iNOS expression in the absence of direct invasion of the organism may participate in the pathogenesis of ARDS associated with rabies.

A retrospective study was conducted in nine patients with rabies admitted to a hospital of Fortaleza, Brazil. Autopsy was performed in all cases. The ages ranged from three to 81 years and six were males. They all were bitten by dogs. The time between the accident and the hospital admission ranged from 20 to 120 days (mean 45 +/- 34 days). The time until death ranged from one to nine days (mean 3.3 +/- 5.5 days). The signs and symptoms presented were fever, hydrophobia, aerophobia, agitation, disorientation, dyspnea, sialorrhea, vomiting, oliguria, sore throat, pain and hypoesthesia in the site of the bite, headache, syncope, cough, hematemesis, mydriasis, hematuria, constipation, cervical pain and priapism. In three out of six patients, there was evidence of acute renal failure, defined as serum creatinine > or = 1.4 mg/dL. The post-mortem findings in the kidneys were mild to moderate glomerular congestion and mild to intense peritubular capillary congestion. Acute tubular necrosis was seen in only two cases. This study shows some evidence of renal involvement in rabies. Histopathologic findings are nonspecific, so hemodynamic instability, caused by autonomic dysfunction, hydrophobia and dehydration must be responsible for acute renal failure in rabies.

Background: Rabies is readily diagnosed when it presents as the classic furious form. Paralytic and atypical forms can pose significant problems in diagnosis. Catastrophic incidents included 7 organ transplant recipients who died of rabies recently in United States and Germany. Although rabies remains top in the lists of differential diagnosis of encephalitis in rabies endemic area, its complication may divert physicians from making a relevant management. We encountered an unusual case of paralytic rabies who presented with spontaneous pneumomediastinum., Case Presentation: A young male presented with fever and dysphagia. There was a history of fluctuating consciousness and aerophobia but they were absent or could not be demonstrated at the time of admission. He exhibited subcutaneous chest wall emphysema and was found to have pneumomediastinum which resulted in surgical intervention. He developed paralysis followed by seizures during postoperative period. Diagnosis was confirmed by demonstration of rabies RNA in saliva during the preterminal phase and by the autopsy. Over 200 hospital staff subsequently received rabies postexposure prophylaxis., Conclusion: Spontaneous pneumomediastinum can be a rare complication of rabies. It may lead clinicians to perform inappropriate treatment, particularly when phobic spasms are not present and agitation is not prominent. High level of awareness of rabies in any patient with confusion albeit subtle or with any obscure neurological presentations such as difficulty swallowing with no identifiable causes must be borne in mind.