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Neurological manifestations of retroviruses
FIS Abstracts
Neurological Manifestations of Retroviruses
A5
Rabies: An Increasing Risk Professor David Warrell, Oxford
Professor Mike Harrison, London The presentation will be confined to a discussion of the effects of HIV on the human nervous system.
At autopsy up to 90% of patients with AIDS show histological abnormality and in life some 30-40% have symptomatic CNS disease. Whilst much neurological morbidity is due to opportunistic infections and lymphomas related to immuno suppression other conditions appear to be more directly related to the presence of the virus. Of these HIV associated dementia is the most feared and affects patients with a diagnosis of AIDS at about 7% per year. It presents with cognitive or behavioural changes and the diagnosis may be supported by soft neurological signs and MRI evidence of atrophy and diffuse white matter change. The pathological substrate is diverse with macrophage rather than neuronal infection, but neuronal loss. Viral load and genomic structure both appear to have an impact on the severity of pathological change& Evidence from viral studies, neuropsychology, natural history studies and one small trial all suggest that antiretroviral treatment can influence cognitive outcome as well as survival. Some 50% of patients at autopsy have evidence of spinal cord damage with a vacuolar change in pyramidal tracts and dorsal columns akin to those due to B12 deficiency. B12 metabolites appear to be normal however. HIV is sparse if not absent in the tissue and the role of cytokines uncertain. The condition is only occasionally clinically dominant. Peripheral neuropathies affect about a third of patients with AIDS. Demyelinating neuropathy behaves as in non HIV infected subjects and also responds to steroids, plasmapharesis or lgG. Most common is an axonal sensory painful neuropathy of unknown aetiology which can be mimicked by the effects of some antiretrovirals. Only a drug holiday makes the distinction. HIV is rarely found in nerve biopsies which occasionally implicate CMV infection. A myopathy may occur with evidence of inflammatory change and which is responsive to steroids and needs to be distinguished from that due to the prolonged use of high doses of zidovudine. The latter is rare on current therapeutic doses but appears to be due to mitochondrial damage.
Despite the lack of evidence of the other pathogens, it is striking that all these conditions are largely or totally restricted to the HIV infected person who shows at least laboratory evidence of immunosuppression. It is tempting to speculate that immunosuppression is crucial to HIV replication within the CNS, and that much neuronal damage is due to the secondary effects of macrophage and astrocyte infection through cytokines and other metabolites. These ideas have opened up new avenues for treatment.
Further Reading • Aids and Neurology. Harrison MJG & McArthur JC. Chuchill Livingstone Edinburgh 1996 * AIDS and the nervous system. Berger J, Levy R. Lippincott-Raven New York.
More than 99% of all human rabies deaths in the world occur in tropical developing countries. In India alone, 30,000 to 50,000 people may die of rabies each year. The Lyssavirus genus (family Rhabdoviridae) comprises classical rabies virus, Duvenhage virus (South Africa), Mokola virus (Africa), European bat lyssavirus and the recently-identified Australian bat lyssavirus. All can cause fatal encephalitis in humans. Rabies is a zoonosis, principally affecting domestic and stray dogs in most parts of Africa, Asia and Latin America. In North America, southern Africa, parts of the Caribbean and Europe, the principal mammalian reservoir species are wild carnivores but, in the USA, an increasing number of human infections are attributed to bites by insectivorous bats that may not be noticed by the victims. The risk of rabies is increasing in many parts of the world. For example, there are epizootics of domestic dog rabies in Ecuador, Kwazulu Natal and other parts of Africa, and of raccoon rabies in the eastern United States. However, mass immunisation programmes directed at owned dogs have been successful in Latin America and immunisation of wild mammalian vector species, such as foxes, is becoming possible with oral live attenuated or recombinant vaccines. Domestic dog vaccination is the most cost-effective way of reducing human deaths from rabies. In humans, rabies encephalitis remains incurable but developed of cell culture rabies vaccines has made post-exposure prophylaxis more effective and safe. In tropical developing countries, unsatisfactory nervous tissue vaccines are still widely used because of their relatively low cost. Economical multisite intradermal regimens using cell culture vaccines are now approved by WHO, are effective and may be affordable even in developing countries. Centres for Disease Control (1991). Rabies prevention-United States, 1991: recommendations of the Immunization Practices Advisory Committee (ACIP). Morbid Mortal Wkly Rep 40 RR-3. King AA, Turner GS (1993). Rabies: a review. J Comp Path 108: 1-39. Thomson G, King A (1993). Rabies in Southern and Eastern Africa. Proceedings of Workshop. Onderstepoort J Vet Res 60 (4) Special Issue 263-512. Tsiang H (1993). Pathophysiology of rabies virus infection of the nervous system. Advances in Virus Research 42: 375-412. Warrelt MJ et al (1985). Economical multiple site intradermal immunisation with human diploid-cell-strain vaccine is effective for post-exposure rabies prophylaxis. Lancet i: 1059-62. World Health Organization (1997). WHO Recommendations on rabies post-exposure treatment and the correct technique of intradermal immunization against rabies. WHO/EMC/ZOO.96.6
Neurological Manifestations of Retroviruses
A5
Rabies: An Increasing Risk Professor David Warrell, Oxford
Professor Mike Harrison, London The presentation will be confined to a discussion of the effects of HIV on the human nervous system.
At autopsy up to 90% of patients with AIDS show histological abnormality and in life some 30-40% have symptomatic CNS disease. Whilst much neurological morbidity is due to opportunistic infections and lymphomas related to immuno suppression other conditions appear to be more directly related to the presence of the virus. Of these HIV associated dementia is the most feared and affects patients with a diagnosis of AIDS at about 7% per year. It presents with cognitive or behavioural changes and the diagnosis may be supported by soft neurological signs and MRI evidence of atrophy and diffuse white matter change. The pathological substrate is diverse with macrophage rather than neuronal infection, but neuronal loss. Viral load and genomic structure both appear to have an impact on the severity of pathological change& Evidence from viral studies, neuropsychology, natural history studies and one small trial all suggest that antiretroviral treatment can influence cognitive outcome as well as survival. Some 50% of patients at autopsy have evidence of spinal cord damage with a vacuolar change in pyramidal tracts and dorsal columns akin to those due to B12 deficiency. B12 metabolites appear to be normal however. HIV is sparse if not absent in the tissue and the role of cytokines uncertain. The condition is only occasionally clinically dominant. Peripheral neuropathies affect about a third of patients with AIDS. Demyelinating neuropathy behaves as in non HIV infected subjects and also responds to steroids, plasmapharesis or lgG. Most common is an axonal sensory painful neuropathy of unknown aetiology which can be mimicked by the effects of some antiretrovirals. Only a drug holiday makes the distinction. HIV is rarely found in nerve biopsies which occasionally implicate CMV infection. A myopathy may occur with evidence of inflammatory change and which is responsive to steroids and needs to be distinguished from that due to the prolonged use of high doses of zidovudine. The latter is rare on current therapeutic doses but appears to be due to mitochondrial damage.
Despite the lack of evidence of the other pathogens, it is striking that all these conditions are largely or totally restricted to the HIV infected person who shows at least laboratory evidence of immunosuppression. It is tempting to speculate that immunosuppression is crucial to HIV replication within the CNS, and that much neuronal damage is due to the secondary effects of macrophage and astrocyte infection through cytokines and other metabolites. These ideas have opened up new avenues for treatment.
Further Reading • Aids and Neurology. Harrison MJG & McArthur JC. Chuchill Livingstone Edinburgh 1996 * AIDS and the nervous system. Berger J, Levy R. Lippincott-Raven New York.
More than 99% of all human rabies deaths in the world occur in tropical developing countries. In India alone, 30,000 to 50,000 people may die of rabies each year. The Lyssavirus genus (family Rhabdoviridae) comprises classical rabies virus, Duvenhage virus (South Africa), Mokola virus (Africa), European bat lyssavirus and the recently-identified Australian bat lyssavirus. All can cause fatal encephalitis in humans. Rabies is a zoonosis, principally affecting domestic and stray dogs in most parts of Africa, Asia and Latin America. In North America, southern Africa, parts of the Caribbean and Europe, the principal mammalian reservoir species are wild carnivores but, in the USA, an increasing number of human infections are attributed to bites by insectivorous bats that may not be noticed by the victims. The risk of rabies is increasing in many parts of the world. For example, there are epizootics of domestic dog rabies in Ecuador, Kwazulu Natal and other parts of Africa, and of raccoon rabies in the eastern United States. However, mass immunisation programmes directed at owned dogs have been successful in Latin America and immunisation of wild mammalian vector species, such as foxes, is becoming possible with oral live attenuated or recombinant vaccines. Domestic dog vaccination is the most cost-effective way of reducing human deaths from rabies. In humans, rabies encephalitis remains incurable but developed of cell culture rabies vaccines has made post-exposure prophylaxis more effective and safe. In tropical developing countries, unsatisfactory nervous tissue vaccines are still widely used because of their relatively low cost. Economical multisite intradermal regimens using cell culture vaccines are now approved by WHO, are effective and may be affordable even in developing countries. Centres for Disease Control (1991). Rabies prevention-United States, 1991: recommendations of the Immunization Practices Advisory Committee (ACIP). Morbid Mortal Wkly Rep 40 RR-3. King AA, Turner GS (1993). Rabies: a review. J Comp Path 108: 1-39. Thomson G, King A (1993). Rabies in Southern and Eastern Africa. Proceedings of Workshop. Onderstepoort J Vet Res 60 (4) Special Issue 263-512. Tsiang H (1993). Pathophysiology of rabies virus infection of the nervous system. Advances in Virus Research 42: 375-412. Warrelt MJ et al (1985). Economical multiple site intradermal immunisation with human diploid-cell-strain vaccine is effective for post-exposure rabies prophylaxis. Lancet i: 1059-62. World Health Organization (1997). WHO Recommendations on rabies post-exposure treatment and the correct technique of intradermal immunization against rabies. WHO/EMC/ZOO.96.6