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28 Cards in this Set
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Respiratory syncytial virus
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Family Paramyxoviridae; SS negative-sense RNA genome
Carries RNA-dependent RNA polymerase Important components: F,G glycoproteins mediate attachment to host cells Also mediate fusion of host cells to form *syncytiae* Serious infection when RSV spreads to lower airway; *RSV bronchiolitis* Also can cause pneumonia; No viremia Incubation of 3-6 days; initial URI symptoms (rhinorrhea, congestion) RSV bronchiolitis in 50% most common reason for admission Incomplete immunity Diagnosis by compatible symptms in winter; rapid antigen test/culture available Supportive treatment only (ribavirin can be used in severe cases) Prevent by sanitary measures; also Ig-based prophylaxis for at-risk infants. No vaccine |
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Influenza
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Orthomyxoviridae, negative-sense SS RNA genome
Hemagglutinin (binding), neuraminidase (budding) Infects columnar epithelial cells of respiratory tract Antigenic drift = accumulation of mutations Antigenic shift = mix & match of viral genome in host animal Diagnose by rapid antigen test, PCR Treat uncomplicated w/ support *Amantidine, rimantidine* (adamantanes) influenza A; not vs influenza B Neuraminidase inhibitors *oseltamivir, zanamivir* for treatment/prphylxs Resistance emerging to neur. inhibitors Seasonal flu vaccine 50-80% efficacy |
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Rotavirus
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Large, non-enveloped dsRNA virus; Reoviridae family
Only groups A,B,C cause disease in humans Seasonal disease Significant mortality in developing world Spread fecal -> oral route Voluminous watery diarrhea can lead to dehydration Diagnose by ELISA on stool for rotavirus antigen Treat by correcting dehydration; prevent by careful handwashing/sanitation Vaccine available (Rotateq/Rotarix) |
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Polio
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Enterovirus (member of Picornaviridae)
positive-sense ssRNA genome 90% infections asymptomatic 8-9% abortive poliomyelitis (fvr, headache, sore throat, meningeal symptms?) 1% severe paralytic polio; CNS seeded with virus, replic in ant horn cells Diagnosis by oropharyngeal culture/stool culture Supportive treatment only IPV in US now; oral vaccine can cause VAPP but more effective |
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Coxsackievirus/echovirus
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Enterovirus
Can cause aseptic meningitis Most cases self-limited Diagnosis by CSF PCR Coxsackievirus type B: myocarditis/pericarditis 2:1 male:female viral invasion of cardiomyocytes leads to local necrosis/inflammation Acute hemorrhagic conjunctivitis: enterovirus 70 or coxsackievirus A24 Hand/foot/mouth disease and herpangina: coxsackievirus A24 or enterovirus 71. painful oral lesions |
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Varicella/zoster virus
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Alphaherpesvirus
3 receptors: heparan sulfate proteoglycan, M6PR, insulin degrading enzyme VZV envelope contains M6P; uses this tag for cellular egress Glycoproteins (gB,gC,gD etc) spread infxn cell->cell, also immune targets Slow incubation (2-3 wk) allows immune response Immunocompromised individuals at greater risk for complications Maternal infection during pregnancy 2% congenital varicella Can administer passive immunization (IgG) in immunocompromised Secondary infxn: zoster. 25% of primary varicella sufferers get it. Live attenuated vaccine available (not for preg, vacc allergic, immunocomp) Diagnose by culture, DFA, skin rash PCR |
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Epstein-Barr Virus
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Gamma herpesvirus
Causes infectious mononucleosis Symptoms: fever, lymphdnpthy, exudative phryngtis, hptsplnmgly, Major glycoprotein = gp350 binds CD21 on B lymphocytes Pts with X-linked agammaglobulinemia cannot be infected w/ EBV Carries genes that mimic IL-10, decrease IFN prodn, inhibit apoptosis Antibodies to EBV nuclear antigen (EBNA) persist for life Can cause nasophryngl carcinoma, lymphomas, oral hairy leukoplakia *T lymphocytes* appear as abnormal lymphs during infxn Latent EBV persists in memory B cells |
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HHV-8
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Gamma herpesvirus
Causes Kaposi's Sarcoma in AIDS pts and elderly Also primary-effusion lymphoma and Castleman's disease |
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Cytomegalovirus
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60% seroprevalence in USA
Viral entry via GU epithelium, upper GI or respiratory tract Also hematogenous or organ transplant related Virus can be latent in host bone marrow stem cells and monocytes Clinical: Mononucleosis, congenital CMV (multiorgan), immunocomp. Diagnose by serology (Ig, antigen, PCR) Treat only for immunocomp.: Ganciclovir, Foscarnet, Cidofovir |
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Herpes simplex virus
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Typically oral/facial (HSV-1), genital (HSV-2)
HSV-1 encephalitis, HSV-2 meningitis Diagnose by serology (Ig, Ag, virus, PCR) Treat w/ oral acyclovir, topical acyclovir/penciclovir IV acyclovir for life-threatening encephalitis Neonatal herpes possible; use C-section, antivirals last 4wks of preg |
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Herpes anti-viral medications
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Acyclovir, valacyclovir, famciclovir, etc.
Acyclovir is guanosine analogue Active vs HSV, VZV, limited vs CMV Needs to triphosph intracellularly by viral thymidine kinase & cell. kinases Acyclovir-triphosphate is comp. inhibitor of viral DNA polymerase Affinity for viral DNApol >> cellular DNApol; viral DNA chain terminator Resistance by mutations in viral thymidine kinase, viral DNApol Major acv toxicities: headache, nausea, renal dysfxn, neurologic |
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Anti-influenza medications
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Amantidine, rimantidine: anti-influ A only. Act vs viral M2 protn. Amantidine more neurotoxic
Zanamivir, oseltamivir: anti-influ A/B. Inhibits neuraminidase Zan. is administered by inhalation (tox: airway complications) Oseltamivir administered orally (tox: nausea, vom) Use Zan/Osel to treat flu w/in 24-48hr of symptoms, also prophylxs Resistance vs oseltamivir recently |
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Ribavirin
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Effective vs broad range of viruses
Vs. flu inhibits capping/elongation of mRNA Vs. others depletes intracellular nucleotides, esp. GTP Aerosol or oral route Major toxicity = anemia Used orally vs. HCV, also aerosol treatment for RSV |
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Anti-hepatitis
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Lamivudine (HBV)
Adefovir dipivoxil (HBV) Entecavir (HBV nucleoside analogue) Telbivudine(HBV) Treat HCV w/ ribavirin + INF-alpha |
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Passive immunization
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Immune globulin for prophylaxis/post-exposure proph.
CMV (organ transpl., pneumonia) rabies RSV HBV VZV (immunocomp. children/adults) |
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NucleoSide Reverse Transcriptase Inhibitors
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NsRTI: Zidovudine (AZT), Didaonsine
Absence of 3' -OH group means chain termination Side effects: lactic acidosis, nausea, headache, neuropathy, pancreatitis |
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NucleoTide Reverse Transcriptase Inhibitors
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TDF
nephrotoxicity, Fanconi syndrome, bone mineralization disorder |
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Non-Nucleoside Reverse Transcriptase Inhibitors
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NNRTIs
Bind reverse transcriptase close to active site Lock RT in inactive configuration Only active vs HIV-1 Can either induce or inhibit CYP3A4 Efavirenz: teratogenic, neurocognitive impairment |
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Protease inhibitors
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Bind HIV protease at active site
Prevent cleavage of gag, gag-pol precursor proteins Incomplete virions produced Side effects: abdominal, diarrhea, All CYP3A4 inhibitors; Ritonavir is especially potent inhibitor |
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Entry inhibitors
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Fusion inhibitor: Enfurvitide - binds gp41 on viral envelope
CCR5 antagonist: Maraviroc binds CCR5 on CD4+ cells |
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Integrase inhibitor
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Raltegravir prevents integration of viral DNA into host cell genome
Works synergistically with all ART |
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First live antiretroviral therapy
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Two NRTIs
plus one NNRTI or one PI/ritonavir |
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Passive vaccination
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administration of EXOGENOUS antibody to provide TEMPORARY protection from disease
ex. maternal IgG transfer to fetus, VZV/HBV/HAV/ rabies prophylaxis |
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Determinants of response to immunization
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1) genetic host characteristics
2) age/immune status of the host 3) whether vaccine is live or inactivated 4) vaccine dosage 5) route of administration (e.g. admin via mucosa leads to IgA production) 6) Adjuvants modulate immune response |
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Live attenuated vaccines
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Measles/Mumps/Rubella
Oral polio (doses @ 2,4,6 mo.) VZV |
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Whole killed vaccines
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Hepatitis A (two doses 6-12 mo apart confer protection for 10 yr)
Influenza Inactivated polio Pertussis |
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Subunit vaccines
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Hepatitis B (for all adults, though some individuals never seroconvert)
Haemophilus influenzae (infants) Meningococcal polysaccharide (A,C,Y,W135) Pneumococcal polysaccharide (>65yr, adults/children >2yr at hi risk) Conjugated pneumococcal polysaccharide (<2yr) |
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Toxoid vaccines
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Diptheria
Tetanus |