Hunt’s Learning Objectives Block 5 – Flashcards
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| acute viral encephalitis |
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| encephalitic arbovirus-->mc type, patient recovers or dies |
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| Sporadic Necrotizing Viral encephalitis |
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| herpes simplex=emergency b/c affects temporal lobes and can be treated with acyclovir |
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| Subacute encephalitis |
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| measles and SSPE this is very rare and occurs years after the acute viral syndrome |
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| Post-infectious viral encephalitis |
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| measles This is rare it occurs about one week after the acute infection |
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| viral meningitis in summer and fall |
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| non-polio enteroviruses like echo, coxsackie A and B, enterovirueses |
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| Viral meningitis in the pre vaccine era in the winter and spring |
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| mumps |
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| Meningoencephalitis in the summer and fall in the US |
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| arboviruses |
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| Major cause pf non-arboviral zoonotic agent of encephalitis globally |
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| Rabies |
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| Herepesviral encephalitis |
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| the only serious viral CNS syndrome for which specific antiviral therapy is effective in reducing morbitity and mortality when promptly administered -about 70% are fatal ifuntreated -diagnose with RT-PCR which is more rapid than cell culture |
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| lymphocytic choriomeningitis |
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| -a virus harbored in mice and pet rodents -member of arena virus family - and can cause meningitis or meniningoencephalitis -in US and Eurupe |
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| Lassa virus |
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| west africa hemorrhagic fever and macupo and Junin viruses in South America (hemorrhagic fever) |
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| Filoviridae responsible for hemorrhagic fever with high fatality rates in humans and primates |
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| -Ebola and Marburg virus -fruit eating bats have been proposed as a reservoir, but not yet proven for Ebola virus, as a natural reservoir |
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| Major route of human to human transmission of ebola virus in sub saharan africa |
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| Contact with blood or blood-contaminated body fluids |
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| Common properties of zoonotic agents in the genus hantavirus of the family bunyaviridae |
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| natural hosts=rodents shedding of virus in rodent excreta, human infection by inhalation of virus and generalized infections with high morbidity and mortality |
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| Hantaan virus |
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| in Korea a hemorrhagic fever with renal syndrome versus Sin Nombre virus from deer mice and related rodent hantaviruses in the U.S. and Latin America (Hantavirus pulmonary Syndrome) |
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| Assays for Sin Nombre virus and related viruses in suspected cases of HPS |
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| RT-PCR or immunohistochemistry of lung tissue, and ELISA to dect anti-hantavirus IgM or IgM in serum |
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| What is ribavirin specifically good for, which zoonotic infections? |
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| Lassa virus, Hantaan virus and LCM Virus |
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| What are the important human viruses in the enterovirus family in the picornaviridae family? |
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| (+) SS non segmented naked icosahedral nucleocapsid -Poliovirus 1-3 -Coxsakie A and B viruses Echoviruses -Enteroviruses 68-71 |
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| epidemiology and pathogenesis common to all enteroviruses? |
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| -Contagious -Fecal-oral transmission -Peak incidence in late summer and early fall subclinical or mild infections in majority -long-term acquired imunity to specific serotype |
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| herpangina and hand foot and mouth disease |
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| Coxsackie A, entero 71 |
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| Acute hemorrhagic conjunctivitis |
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| AHC; coxsackie A or entero 70 |
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| non-vesicular exanthems |
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| echo |
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| pleurodynia |
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| coxsackie B |
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| aseptic meningitis |
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| echo and coxsackie A and B |
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| Encephalitis |
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| entero 71 |
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| myocarditis and pericarditis |
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| coxsacie B |
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| acute-flaccid paralysis |
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| polio, entero 71 |
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| acute respiratory disease |
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| entero 68 |
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| laboratory diagnosis of serious human enteroviral infections |
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| cell culture more rapid RT-PCR of CSF |
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| Poliovirus and paralytic polio epidemics in the US |
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| -Salk =trivalent inactivated polio vaccine-injected IM -Sabin trivalent live attenuated polio vaccine (OBV)-so protected secretory -IPV is only one recommended in the US -Both protect against poliovirus typess 1-3 -risk of vaccine-associated paralytic poliomyelitis (VAPP) -OPV in developing countries in the WHO global polio Eradication Initiative- the oral was easiest to administer so it was a huge tool in attempting to erradicate it with National Immunization days in developing countries -Goal is to have eradicated by 2013.. -There is a risk of post-polio syndrom: approximately 1/3 of survivors of mild and severe paralytic polio from the middle of 20th century have been experiencing syndrome of fatigue, muscle weakness/atrophy and difficulty breathing, believe to be due to nerve attrition as they age, with no evidence for latency/reactivation of poliovirus - - |
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| What animal has the highest reported incidence of rabies in the US? |
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| raccoon- epizootic spreading from the southeast to the north and west over the last three decades -Skunks and bats are the next most common -bats are the animal associated with the vast majority of rare human cases where exposure occurred within the U/S in the last 2 decades, in contrast to dogs for imported human rabies cases |
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| Pathogenesis of rabies in humans and other animals |
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| initial replication in striated muscle near the site of bite or mucosal exposure, infection of nerve ending and centripetal spread via motor and sensory axons to the spinal cord and brain, infection of the brain and spread to salivary gland, and overwhelming encephalitis resulting in coma and death. |
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| Post-exposure prophylaxis for non-immune humans potentially exposed to a rabid animal by bite, scratch or mucosal exposure |
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| -active immunization with inactivated virus vaccine (4 doses instead of previous 5 dose) -passime immunization with high-titer human IgG [RIG] |
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| -Who should have prexposure immunization to rabies? |
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| -forest rangers -vets -laboratory researches -active immunization, 3 dose primary, and boosters every 1-2 years |
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| Public health programs for the prevention of rabies in animal |
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| -annual vaccination of dogs and cats in all states -vaccination of wildlife on a more limited scale with a live-recombinant vaccinia virus vaccine (vaccinia-rabies glycoprotein=V-RG) |
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| Unique feateure of abnormal prion proteins which are responsible for slowing-developing but ultimately fatal neurological syndromes known as spongiform encephalopathies including |
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| -extreme resistance to physical and chemical treatments -abnormal conformational change with increased beta sheet -less alpha-helical structure in abnormal compared to normal prion protein -genetic alterations which are associated with familial/genetic diseases rather than sporadic.... -genetic forms of human TSE's are char. by mutant genes which encode PrP which spon. misfolds into a distinct pathogenic form at a much higher rate and younger age than with sCJD: mutation in codons #102 for GSS and#178 for fatal familial insomnia -polymorphism at aa #129 of the human prion/PRP (methionine or valine) is important in susceptibility to BSE-induced vCJD with essentially all of the UK cases involving #129 Met/Met homozygosity present in ~40% of UK population, whereas humans with #129 Val/Val homozygosity appear to have sig. higher risk for iatrogenic CJD |
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| SSporadic Prion |
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| CJD |
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| Exogenous prion |
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| kuru, vCJD |
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| familial/genetic prion diseases |
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| Gerstmann-Straussler-Scheinker syndrom, fatal familial insomnia and familial CJD in humans |
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| 2 prion diseases in domestic animals -and etiological rel of them to the others |
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| -Scrapie in sheep -Vobine Spongiform encephalopathy (BSE) -Scrapie and BSE-scrapie has never been transmitted to humans -BSE is the presumed source for vCJD in humans and also for TSE's in many other mammals |
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| Two concepts of recombinant viral vectors |
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| infectious but replication-defective virus and packaging cell lines |
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| major advantage of retroviral vectors |
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| efficient integration of proviral DNA into chromosomal DNA |
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| Essential viral sequences which must be present in plasmids used in construction of these vectors |
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| -upstream and downstreame LTR sequences -psi=psi genome-RNA packaging sequence -must be devoid of all other retroviral sequences |
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| advantage of newer lentivirus vectors as compared to murine retrovirus-derived vectors |
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| -integration of proviral DNA in non-dividing and dividing cells for lentivirus versus only in dividing cels for murine viruses |
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| advantage of newer "pseudotyped" retroviruses as compared to murine viruses with amphotropic Env protein |
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| -increased virion stability and extended host range with the VSV-G rhabdovirus envelope glycoprotein replacing the retrovirus Env protein |
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| What is major biosafety risk of retro/lenti virus vectors? |
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| insertional mutagenesis, based upon limited experience of retroviral vectors in humans as gene therapy for X-linked SCID |
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| major diff. between adenoviral and retroviral/lentiviral vectors for gene therapy, inc |
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| -lack of integration of adenoviral DNA into chromosomes -increased capacity for larger cDNA/transgene sequences in recombinant adenoviral genomes |
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| clinical disadvantage of firs-generation, E1 gene-adenoviral vectors: |
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| -leakiness of viral gene expression which allows development of cellular immune responses (anti-viral CTLs), thereby eliminating cells containing the rcombinant adenoviral genomes) |
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| Recombinant parvovirus vectors derived from adeno-associated viruses (AAVs), what is the major advantage? |
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| -viral DNA persistence in nucleus and/or integration into chromosomal DNA in abscence of adenoviral helper -mjr disadvantage= small size of genome limits size of cDNA/transgene |
