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Yuli virus was isolated by intracerebral (i.c.) inoculation of suckling mice with a 10% brain suspension from 11-year-old patient who died under signs of atypical hydrophobia after a bat bite into lower lip. Identification with a panel of monoclonal antibodies (MoAb) to nucleocapsid protein (NP) confirmed that Yuli virus belongs to Lyssavirus genus, as an antigenic variant of the European Duvenhage virus.

A Cryptococcus neoformans strain which in 1983 caused an infection of the central nervous system (CNS) in a wildlife fox with rabies-like symptoms was tested for its strain-specific brown colour effect (BCE) on Guizotia abyssinica creatinine agar and for its ability to assimilate creatinine. Both reactions were found to be positive. These results were found to be largely identical with those of 2 out of 3 strains having caused fatal cryptococcosis in 1970, 1979 and 1983 in persons living in the area where the fox had been found (radius 40-100 km). Some theoretical aspects of the epidemiology and pathogenesis of cryptococcosis in the wildlife fox and rodents are discussed. For further epidemiological investigations into the prevalence of Cr. neoformans in man and animals in this area, the two reactions for detecting and typing, i.e. the BCE on Guizotia abyssinica creatinine agar and the creatinine assimilation are proposed.

A case of human rabies is reported showing a peculiar course in some respects. The lack of a satisfactory history concerning an animal bite 5 months earlier as well as a misleading psychiatric history led to difficulty and delay in reaching a diagnosis. Under intensive care, including mechanical ventilation and cardiac pacing, the disease reached a final stage, which is rarely seen. The clinical course and the pathological findings are described in detail and the etiology and prognosis of the disease are discussed. The latter remains rather hopeless de spite modern intensive care.

After an incubation period of one to two months rabies presents with non-specific prodromal symptoms and often with paraesthesiae of the bitten area. As in canine rabies there are furious and dumb forms of the disease. In man, furious rabies is characterised by hydrophobia: terror and excitation with spasms of inspiratory muscles, larynx and pharynx precipitated by attempts to drink and by a variety of other stimuli. Hydrophobia may represent an exaggerated respiratory tract irritant reflex with associated arousal potentiated by the selective destruction of brain stem inhibitory systmes. Also typical of furious rabies are intermittent episodes of excitement, hallucinations and maniacal behaviour. Focal neurological abnormalities are surprisingly uncommon. Other signs include hypersalivation, tachycardia and hyperpyrexia. Paralysis and coma supervene after a few days: survival rarely exceeds seven days. Dumb or paralytic rabies is an ascending flaccid paralysis with sphincter involvement and sensory disturbances. Death from respiratory and bulbar paralysis occurs after a longer illness than furious rabies. In a minority of cases hydrophobia develops before the terminal coma. Complications include respiratory arrest, pneumonitis, cardiac arrhythmias and interstitial myocarditis, posterior pituitary disorders, and gastrointestinal bleeding. Differential diagnoses of furious rabies include hysterical pseudo hydrophobia, tetanus, other encephalitides, delirium tremens and various other intoxications. Paralytic rabies may have to be distinguished from postvaccinal encephalomyelitis, poliomyelitis and other causes of Landry-type ascending paralysis. Intensive care has produced some promising results: life-threatening complications can be prevented but there is some evidence that the severity of the encephalitis is the ultimate barrier to survival.

Objective: To test the effect of interferon alfa and tribavirin (ribavirin) in patients with rabies encephalitis., Design: An open trial of chemotherapy and intensive care in patients with early rabies., Setting: The intensive care unit of a Bangkok hospital., Patients: Four conscious men with clinical rabies encephalitis., Interventions: Rapid virological diagnosis of rabies. Treatment with intravenous and intraventricular injections of high doses of lymphoblastoid interferon alfa in three patients and tribavirin in one patient. Intensive care was given throughout., Main Outcome Measures: Rabies infection confirmed by antigen detection and virus isolation. Rabies neutralising antibody and specific IgM sought in serum and cerebrospinal fluid. Interferon concentrations monitored before and during treatment in three patients., Results: Interferon alfa treatment produced high concentrations in serum and cerebrospinal fluid. All four patients died after 5 1/2 to 12 1/2 days of treatment with no evidence of virostatic or clinically beneficial effects from either treatment., Conclusion: Interferon alfa treatment is not effective in rabies encephalitis. The use of tribavirin warrants further study, possibly combined with new therapeutic methods.

Seven weeks after he was bitten on the lip by a puppy in the Gambia a patient showed symptons of rabies. Passive and active immunisation was begun three days after the onset of symptons. The evidence indicated that death was a direct consequence of the central nervous system disease rather than any associated complication. Our inability to alter the course of the illness appreciably emphasises the importance of immediate postexposure immunisation in rabies and draws attention to the present lack of effective means of preventing virus replication within the central nervous system.

Effects of high ambient temperatures on various stages of rabies virus infection have been studied. Ambient temperature increased within the tolerated range was found to have little effect upon body temperature of normal mice, but caused marked elevation of temperature during illness. Temperatures at onset of patent illness in mice were lower than normal. Increased body temperature in the higher thermic ambience during the incubation period was associated with decreased mortality and frequent abortive infections. Exposure to high ambient temperature late in the incubation period delayed onset of illness, decreased mortality, and increased frequency of abortive infections, but exposure to high ambient temperature after onset of patent illness did not affect the course of the disease.

Two atypical cases of rabies, mimicking respectively schizophrenic psychosis and acute manic excitement, are reported along with autopsy data. The importance to recognize these variants, particularly in rabies prevalent areas, is emphasized. The potential sources of diagnostic confusion are discussed, along with a review of the relevant literature.

Six patients with proved rabies were studied with a combination of clinical, physiologic and pathologic technics. Three were given a type of intensive care but died with evidence of respiratory failure. Although circulatory failure did not develop in any of the six patients, three had supraventricular arrhythmias: interstitial myocarditis was found in one of these and rabies virus was isolated from the myocardium of another. Inspiratory muscle spasm was the dominant clinical feature in all cases. This occurred as part of the hydrophobic response and followed stimulation of the upper respiratory tract and skin. Hydrophobia may represent an exaggerated respiratory tract irritant reflex with associated arousal. Later in the course of the disease, various patterns of periodic and ataxic breathing were observed. Widespread brain stem encephalitis was discovered at autopsy, with particular involvement of the neighborhood of the nucleus ambiguous in two of three patients examined. In one patient cerebral metabolism was grossly abnormal, with greatly reduced cerebral oxygen consumption suggesting irreversible brain damage. Respiratory and circulatory disturbances may well be immediate causes of death in patients with rabies, but the present studies reemphasize the severity of the encephalitis which remains the ultimate barrier to survival. In the developing countries in which rabies is still a major problem and in which the cost precludes intensive care, the clinical management of rabies can aim only to reduce suffering by heavy sedation.

Recovery from rabies was studied in an experimental model. Young adult mice were inoculated in a hindlimb footpad with street rabies virus (fox salivary gland isolate). In a group of 62 mice, 97% developed clinical rabies with paresis of the extremities and spasticity, and 37% recovered with neurological sequelae. There was an acute inflammatory reaction in the brainstem and grey matter of the spinal cord, and degeneration of myelinated axons in the white matter of the cord and in the dorsal roots. Rabies virus antigen was found in the central nervous system of all mice examined between day 5 and 13, and also in trigeminal and dorsal root ganglia. Surviving mice had neutralizing antibodies in serum and brain tissue, and 90% survived an intracerebral challenge with the CVS strain of fixed rabies virus. Spontaneous recovery from rabies encephalomyelitis was demonstrated with evidence of viral replication and pathological changes in the central nervous system.

A patient with rabies presented with penile hypersensitivity and recurrent ejaculation. This preceded the more classical manifestations such as hydrophobia and aerophobia by approximately 8 hours. A review of the literature reveals that a variety of urogenital symptoms may rarely occur in rabies. Ours is however the first report documenting the occurrence of these symptoms at the onset of the disease in an autopsy proven case of rabies. Damage to the amygdaloid nucleus has been postulated to be the basis of these urogenital symptoms. This correlates well with our autopsy findings of extensive neuronal damage and Negri bodies in the temporal poles.

Lymphocyte proliferation tests to rabies antigen and myelin basic protein were performed on peripheral blood lymphocytes from nine patients with the encephalitic form and on seven with the paralytic form of human rabies. Six of the nine patients with encephalitis had proliferative responses to rabies antigen, whereas all of the patients with paralysis had no response. Two patients in each group also had a proliferative response to myelin basic protein. The myelin basic protein-reactive patients had a more rapidly fatal disease than the non-reactive patients. This preliminary study suggests that host immune responses may influence the clinical manifestations and course in human rabies.

Rabies virus belong to the family Rhabdoviridae; it has a coiled RNA core surrounded by a bullet-shaped envelop, covered with glycoproteins surface projections. After entry into a new host in the bite site, the virus multiplies in muscle cells and it spreads through neural pathways, without stimulating a protective host immune-response. Transmission depends on simultaneous delivery of virus to the salivary gland and the limbic system of the brain, which is the cause of the animal fury and biting tendency. In México, rabies continues to be a serious health and economic problem, and urban rabies still predominates with a large number of human and animal cases recorded yearly. A total of 426 human deaths were reported between 1978 and 1983. Over 9,069 cases of animal rabies were reported in 1986 and 50,000 patients required antirabies postexposure vaccinations. Infected animals can be identified by demonstration of specific fluorescence in brain tissue. A dog or cat which has bitten a human should be captured and observed by a veterinarian for 15 days. The immediate objective of postexposure treatment is to prevent virus from entering and damaging neural tissue, therefore, promptness is essential. All wounds should be thoroughly cleared with soap and water concurrent use of both passive and active immunization provides optimal therapy. Wherever possible, human rather than equine products should be used for passive immunization, and Fuenzalida's nerve tissue rabies vaccine should be used for active protection. Paediatricians should urge parents to caution children attempting to get stray or wild animals as pets. Domestic dogs and cats should be thoroughly vaccinated.