LOs: 13-14 Flashcards
13 Viral Diseases:
Immediately Lethal Viral infections
Self-Limited Viral Infections
Contained Viral Infections
Rare, vascular inflammation
- Ebola, Yellow fever, Hanta viruses
Most infections, host develops immunity & eradicates the virus through cytotoxic T cells & B cells
- Life-long: Hepatitis A
- Short duration: RSV
- Overcome acquired immunity: Influenza
Contained by immune system but not eradicated
- Chronic persistent infection: ongoing replication (Hepatitis C, HIV)
- Latent infection: replicate during stress or immunosuppressive states (Varicella, VZV & Shingles)
13 Immunization:
Active Immunization
- Live Attenuated Vaccines
- Inactivated Viruses or Recombinant Proteins
Passive Immunization
Elicits an immune response by T-cells (cytotoxic T-cells) and/or neutralizing antibodies by B- cells
- Elicit an immune response but they are too weak to cause disease, not safe in immunocompromised
- Safe in immunocompromised
Immunoglobulins derived from human serum neutralize the virus and block its infectivity by prohibiting viral entry into cells
- Doesn’t elicit immune response
- Short half-life, protection not long lasting
- Shortages, expensive
13 Treatments of Viral Infections:
Virucides
Imunomodulation
Antivirals
Directly inactivate intact viral particles
- Ex. detergents, organic solvents, UV light, photodynamic inactivation
Stimulate the host immune response to better contain or eradicate the virus infection
- Inducing host factors with antiviral properties: interferon (cytokine) degrades viral RNA, inhibits viral protein synthesis, & enhances CTLs & NK cells
- Restoring host immunity: decrease immunosuppressant medications or treat the cause of the immunosuppressed state (ex. decrease immunosuppressants in renal transplant pt to contain EBV) (ex. AIDS pt on antiretrovirals to increase CD4 count to treat Kaposi sarcoma)
Inhibit viral replication by targeting virus-specific proteins
- Only act on replicating viruses early in infection
- Rapid development of drug resistance
13 Antivirals:
Polymerase Inhibitors
- Nucleoside Analogues (4)
- Nucleotide Analogues (1)
- Pyrophosphage Analogues (1)
For Influenza
- Ion Channel Blockers (2)
- Sialic Acid Analogues (2)
Hepatitis C
- Cytokines (1)
- Viral RNA Synthesis Inhibitors (1)
- Protease Inhibitors (4)
Hepatitis B
- Nucleoside Analogues (4)
- Nucleotide Analogues (2)
- Inhibit viral polymerase w/ faulty nucleoside: acyclovir, valacyclovir, ganciclovir, valganciclovir
- Inhibit viral polymerase w/ faulty nucleotide: cidofovir
- Inhibit viral polymerase: foscarnet
- Block M2 channels to block protons from entering virion so pH can’t be maintained: amantadine, rimantadine
- Block release of new virions by inhibiting viral neuraminidase: oseltamivir, zanamivir
- Interferon-alpha
- Ribavirin
- Polyprotein cleaved to NS3/4A & NS5B to inhibit polymerase & HCV replication: telaprevir, boceprevir, sofosbuvir, simeprevir
- Lamivudine, emtricitabine, entecavir, telbivudine
- Tenofovir, adefovir
13 Acyclovir:
Mechanism of Action
Spectrum of Activity
Clinical Use
Product Availability
Adverse Effects
Resistance
Nucleoside Analogue
- Requires intracellular phosphorylation & a viral thymidine kinase (TK) to inhibit viral DNA polymerase
HSV-1 > HSV-2 > VZV (requires higher doses)
- Orolabial herpes
- Genital herpes
- Neonatal herpes
- Herpes encephalitis
IV for serious HSV (ex. encephalitis)
- Renal failure
- Neurologic side effects
- Reduced or absent TK (active drug not produced)
- Viral DNA polymerase decreases affinity for ACV-TP (after prolonged treatment)
13 Valacyclovir:
Mechanism of Action
Drug Bioavailability
Clinical Use
Nucleoside Analogue
- Pro-drug of acyclovir, converted to ACV
Higher bioavailability than acyclovir
- HSV
- VZV
13 Ganciclovir:
Mechanism of Action
Drug Availability
Clinical Use
Side Effects
Resistance
Nucleoside Analogue
- Requires intracellular phosphorylation by UL97 to inhibit viral polymerase & DNA synthesis
PO, IV, & intraocular
CMV in immunocompromised (AIDS, organ/bone marrow transplant)
Bone marrow suppression
Mutations on UL97 CMV kinase
13 Valganciclovir:
Mechanism of Action
Drug Availability
Clinical Use
Side Effects
Resistance
Nucleoside Analogue
- Requires intracellular phosphorylation by UL97 to inhibit viral polymerase & DNA synthesis
- Prodrug of ganciclovir
PO
CMV in immunocompromised (AIDS, organ/bone marrow transplant), especially post transplantation & CMV prophylaxis
Bone marrow suppression
Mutations on UL97 CMV kinase
13 Cidofovir:
Mechanism of Action
Drug Availability
Clinical Use
Side Effects
IV
Nucleotide Analogue
- requires phosphorylation
Ganciclovir resistant CMV in organ transplant pts
Nephrotoxicity
13 Foscarnet:
Mechanism of Action
Drug Availability
Clinical Use
Side Effects
Pyrophosphage Analogue
- Inhibits DNA polymerase
- Not dependent on viral TK
IV
Broad
- HSV resistant to acyclovir
- CMV resistant to ganciclovir (UL97 mutation)
- Nephrotoxicity
- Electrolyte abnormalities
- Penile ulcers
13 Amantadine & Rimantadine:
Mechanism of Action
Drug Availability
Clinical Use
Side Effects
Resistance
Capsules & liquid
Ion channel blockers
Influenza A only (pre-exposure prophylaxis & post-exposure preemptive therapy)
- Amantadine: seizures, dizziness, hallucinations
- Rimantadine: dizziness, fatigue
Mutations in M2 protein
13 Oseltamivir & Zanamivir:
Mechanism of Action
Drug Availability
Clinical Use
Side Effects
Resistance
Sialic Acid Analogues (neuraminidase Inhibitors)
- Oseltamivir: PO
- Zanamavir: powder
Influenza A (including H1N1) & Influenza B
- Prophylaxis & preemptive therapy
- Strains resistant to adamantanes
- Oseltamivir: nausea & vomiting
- Zanamivir: bronchospasm & cough (caution in pts w/ asthma or COPD), nausea & vomiting
Zanamavir usually still active in oseltamivir resistant strains
13 Interferon-alpha:
Mechanism of Action
Drug Availability
Clinical Use
Side Effects
Cytokine leads to cellular responses
- Pegylated formulations (PegIFN) have longer half-life & are more effective
Subcutaneous injections
HCV w/ ribavirin
- Flue like symptoms
- Neuropsychiatric symptoms (depression)
13 Ribavirin:
Mechanism of Action
Drug Availability
Clinical Use
Side Effects
Viral mRNA synthesis nhibitor
- Decreases nucleotide pool
PO, IV, & inhaled
many RNA viruses
- HCV
- RSV
- Lassa virus
Hemolytic anemia
13 Boceprevir:
Mechanism of Action
Drug Availability
Clinical Use
Side Effects
Resistance
PO
1st generation NS3/4A protease inhibitor
HCV genotype 1 w/ PegIFN & ribavirin
Anemia, fatigue, & dysgeusia
13 Teleprevir:
Mechanism of Action
Drug Availability
Clinical Use
Side Effects
Resistance
PO
NS3/4A protease inhibitor
HCV genotype 1 w/ PegIFN & ribavirin
Rash, pruritis, & multiple drug-drug interactions
13 Sofosbuvir:
Mechanism of Action
Drug Availability
Clinical Use
Side Effects
PO
Inhibits the NS5B polymerase
- HCV genotype 1 w/ PegIFN & ribavirin
- HCV genotypes 2 & 3 w/ ribavirin
No significant side effects
13 Simeprevir:
Mechanism of Action
Drug Availability
Clinical Use
Side Effects
PO
NS3/4A protease inhibitor
HCV genotype 1 w/ PegIFN & ribavirin
Transient mild elevations of bilirubin & photosensitivity
Mutations of NS3/4A protease
13 Lamivudine, Adefovir, Entecavir, Telbivudine, Emtricitabine and Tenofovir:
Mechanism of Action
Clinical Use
Resistance
Nucleoside/Nucleotide analogues
Chronic active Hepatitis B infection
Common in lamivudine (stopping this drug can cause a flare-up of hepatitis)
14 Epidemiology Definitions:
Incubation Period
Infectious Period
Latent Period
Epidemic
Endemic
Pandemic
Incidence
Incidence Rate
Prevalence
time from exposure to development of disease
length of time a person can transmit disease
period of infection without being infectious
occurrence of cases of illness in excess of expectancy
epidemic whose incidence remains stable
global outbreak
number of new cases in a given time period in a given population (ex. 93 new cases in 2008)
number of new cases per population at risk for the disease over time (ex. 0.5 cases / pt-day or ventilator-days or central-line days)
total number of disease cases / # individuals in the population
14 Epidemiology Definitions:
Attack rate (infectivity)
Primary/secondary cases
Case fatality
Virulence
Reservoir
Vector
Zoonosis
proportion of exposed individuals who become ill
person who infects a population (primary) & those who subsequently contract the infection (secondary)
proportion of infected individuals who die of the infection
the degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates (CFR) and/or the ability of the organism to
invade the tissues of the host
ecological niche of the pathogen
any organism (usually an arthropod like a mosquito or tick) which harbors infectious agent and transmits it to susceptible individuals
infections that can spread from vertebrate animals to man
14 Ro:
Formula: Ro = b x k x D
If Ro < 1
If Ro = 1
If Ro > 1
Herd immunity threshold
Ro (basic reproductive rate) = number of secondary cases following a single introduction into a fully susceptible population
b = attack rate (how infectious)
k = number of potentially infectious contacts the average person in the population has per unit time
D = duration of infectivity of an infected person
If Ro < 1, then every new generation of infection will affect fewer individuals and the disease will die out (vaccinated population)
If Ro = 1, then approximately the same number of individuals are infected with every new generation causing endemicity (West Nile Virus)
If Ro > 1, then there is an ever increasing number of infected individuals causing epidemic or pandemic (Influenza)
Fraction of a population that must be immune to a given microorganism to prevent an outbreak beyond one index case
- Higher the Ro, larger the number of immune people is required to confer herd immunity
14 Avian Influenza:
Pathogenicity
Predominant Strain
Transmission
Conditions for a Pandemic
Resistance
- Low: respiratory & GI tract
- High: disseminated disease
H5N1: causes illness & death in birds & humans
- Expanding host range, new reservoirs excrete virus w/o becoming ill
- Endemic in Asian domestic fowl (migrating birds, illegal fowl trading)
No efficient transmission to humans due to tropism (interspecies barrier)
- Reassortment: genetic material exchanged b/n human & avian viruses
- Adaptive mutation: increases ability to bind human cells in subsequent infections
- Amantadine & rimantadine (birdfeed)
- Oseltamivir also reported
14 West Nile Virus:
Causes…
Location
Reservoir
Transmission
Preventative Measures
Encephalitis
Africa, Middle East, Eastern Europe, & now US
Birds
Mosquitoes
- Mosquito control by spraying and eliminating water pools (tires)
- Personal protection
- Screening of organ and blood donations
