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Major concerns
- development of drug resistant organisms
- increasing number of immunicompromised populations
- rising number of diseases previously considered rare.
education, surveillance, development of new drugs and vaccines are essential to prevent and treat resurging and emerging neurological infectious diseases.
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Unique aspects of CNS infections
localization of the infection dictates the clinical presentation e.g. whether it is in the CNS or PNS
- The brain is an immune privileged organ
- - blood brain barrier
- - no lymphoid cells--only resident immune cells are innate, during infection, get more (adaptive)
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Emerging neurological infections
- 1. Variant CJD--vairant of mad cow, dementing disease of old people, started showing up more in younger
- 2. Nipah virus encephalitis-- from bats to pics to the food supply to humans
- 3. West Nile virus encephalitis-- RNA virus
- 4. Enterovirus 71 encephalitis--in kids in Taiwian
are usually xenotropic (can grow in a foreign host) and RNA viruses (mutate more readily)
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zooinosis
infections coming from other species
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Determinants of emerging infections
- Providing a pool of susceptible populations--increasing gloab populations and contact between humans
- Altering forms of human or animal contact--e.g. eating animals
- Societal mores--increased sexual contact, day car, agricultural clearing, irrigation (possible mvmt of virus)
- Global movement of animals and animal products
- Medicinal practises--blood transfusions, transplants, drug resistant microbes
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Evolution of west nile
- -isolated in blood of febrile Uganda women
- -endemic in kids in Egypt and Sudan, epidemic in Isreal, S.Africa, India
- -cancer patients experimentally infected in NY
- -some in Franch
- -Algerian epidemic
- -Southeast Romania, 10% fatality
- -Epidemic in Russia, NYC outbreak--spreads to NA
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Clinical principles of neurological infections
- - few infectious pathogens cause neurological disease, but there are the big three: HIV, TB and malaria
- - fever with acute (sudden onset) neurological signs are indicators of neurological infections
- - intra and extra neurological parameters looked at by a team
- - treatment with specific and supportive interventions,
- - prognosis on basis of severity of actue neurological impairment and defined by protracted morbidity (how long till estimated death)
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Principles of infection
neuroinvasion, neurotropism, neurvirulence, neurosusceptibility
neuroinvasion --pathogent specific but does not necessarily lead to disease virulence-- capable of entering the CNS
neurotropism--pathogen specific to anatomical site and cell type (capable of infecting NS, preferential)
neurovirulence--neurological disease related with or without pathogen benefits (capable of causing disease in the NS)
neurosusceptibility--age, immunocompetence, genetically dependent (refers to the host's vulnerability to virus-induced neurological disease and is dictated by host age, species, immune status, and genetic background)
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Common neurological infections (first world)
- viruses--HSV (herpes) VZV (chicken pox), HIV, rabies
- bacteria--N meningiditis, Borreliosis (limes disease)
- fungal--crypto, neoformans,
- parasite--malaria
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Neural cells
CNS--neurons, astrocytes (most abundant, divide all throughout life, limited to NS), oligodendrocytes (make myelin, can regenerate a bit) , endothelial cells (line blood vessels) and microglia(first to respond)/ macrophages (respond to damage, from bone marrow, constantly replenished through circulation)-- BBB
PNS--neurons, Schwann cells, macrophages--BBB
neurons are the targets of disease, the brain is not completely isolated, lymphocytes check NS, macrophages in come from blood
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Human endogenous retroviruses (HERVs)
- --have been entering human genome for millions of years and accumulating, 8% of genome
- --implicated in autoimmune disease like MS
- --can be turned on but can't be submitted.
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Sources of HIV 1 and 2
- Cameroon, Congo, Central African Repulic
- first jump from monkeys to humans about 100 years ago
- jumped by killing and eating non human primates (chimps)
- when virus changes host, behaviour of virus changes
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Course of HIV
Primary infection (4-8 weeks), seroconversion, asymptomatic period (10 years), AIDS (immunosuppression) (1-4 years), treatment phase (>10 years)
lymphocytes decrease during asymptomatic and are very low during AIDS period but increase with treatment
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HIV associated dementia
- Affects 10-20% of HIV patents , usually after development of AIDS and leads to poorer survival rates
- Usually preceeded by minor cognitive motor disorder (MCMD)
- risk factors--extremes of age, mutations in CCR5 and APOE genes , polymorphisms in promoters of TNF and MCP1 genes
AKA AIDS dementia complex, HIV dementia, AIDS encephalopathy
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HIV associated dementia early symptoms/progression
behaviour--apathy, depression, agitation
cognition--memory loss, concentration, mental slowing
motor functioning-- unsteady gait, leg weakness, poor coordination, tremor
some advance quickly, quality of life decreases
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HAD--neuroimaging
- large ventricles, atrophy, white matter chagnes , highly active antiviral retroactive therapy (HAART)
- perivascular cuffing, multinucleated giant cells,
- density of virus highest in subcortical features, huntingtons/parkinsons--subcortical dementias
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Treatment for HIV related neurocognitive disorders
- HAART- dependent on dementia severity
- neuroprotective drugs, NMDA receptor antagonists , growth hormomes, SSRIs etc
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HIV sensory neuropathies
- systematic bilateral burning neuropathic pain, feet>>hands
- bowel/bladder and gait effects
- axonal loss, degeneration
- inflammation within the nerve or dorsal root ganglion
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Herpes Simplex encephalitis (HSE)
- 1-2 infections per 1 million people
- immunocompromised patients not at greater risk
- retinal necrosis
- EEG useful for seizure activity only
- often fatal unless treated
- motrality reduced to 20% with acyclovir
- doesn't tend to reoccur
- lives in trigeminal neuronal cell bodies
- can affect temporal lobe and cause temporal seizure
causes swelling, lymphocytes surround blood vessles, disrupt BBB, let serum in, cause swelling
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