LOs: 13-14 Flashcards Preview

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Flashcards in LOs: 13-14 Deck (26):
1

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)

2

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

3

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

4

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

5

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)

6

13 Valacyclovir:

Mechanism of Action

Drug Bioavailability

Clinical Use

Nucleoside Analogue
- Pro-drug of acyclovir, converted to ACV

Higher bioavailability than acyclovir

- HSV
- VZV

7

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

8

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

9

13 Cidofovir:

Mechanism of Action

Drug Availability

Clinical Use

Side Effects

Nucleotide Analogue
- requires phosphorylation

#IV

Ganciclovir resistant CMV in organ transplant pts

Nephrotoxicity

10

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

11

13 Amantadine & Rimantadine:

Mechanism of Action

Drug Availability

Clinical Use

Side Effects

Resistance

Ion channel blockers

#Capsules & liquid

Influenza A only (pre-exposure prophylaxis & post-exposure preemptive therapy)

- Amantadine: seizures, dizziness, hallucinations
- Rimantadine: dizziness, fatigue

Mutations in M2 protein

12

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

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)

14

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

15

13 Boceprevir:

Mechanism of Action

Drug Availability

Clinical Use

Side Effects

Resistance

1st generation NS3/4A protease inhibitor

#PO

HCV genotype 1 w/ PegIFN & ribavirin

Anemia, fatigue, & dysgeusia

#Low barrier

16

13 Teleprevir:

Mechanism of Action

Drug Availability

Clinical Use

Side Effects

Resistance

NS3/4A protease inhibitor

#PO

HCV genotype 1 w/ PegIFN & ribavirin

Rash, pruritis, & multiple drug-drug interactions

#Low barrier

17

13 Sofosbuvir:

Mechanism of Action

Drug Availability

Clinical Use

Side Effects

Inhibits the NS5B polymerase

#PO

- HCV genotype 1 w/ PegIFN & ribavirin

- HCV genotypes 2 & 3 w/ ribavirin

No significant side effects

18

13 Simeprevir:

Mechanism of Action

Drug Availability

Clinical Use

Side Effects

NS3/4A protease inhibitor

#PO

HCV genotype 1 w/ PegIFN & ribavirin

Transient mild elevations of bilirubin & photosensitivity

Mutations of NS3/4A protease

19

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)

20

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

21

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

22

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

23

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

24

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

25

14 Creutzfeldt Jacob Disease (vCJD):

Type of Disease

Caused by...

Human to Human Transmission

BSE Spread in UK

Variant Creutzfeldt-Jakob Disease (vCJD)

Spongiform encephalopathies

Prions (abnormal/dead proteins)
- Present in all brains w/o harmful effects
- Can take on an abnormal shape & accumulate, killing brain cells

Cannibalism, corneal transplants, contaminated neurosurgical devices, blood transfusions

Left-over bovine carcasses (bone meal) were used as animal feed --> Mad Cow Disease (BSE)

- Sporadic CJD (younger age at onset and causing rapid death)
- Similar symptoms to BSE, fatal
- Linked to consumption of BSE meat contaminated w/ brain tissue or consumption of brain tissue

26

14 Norovirus:

Causes...

Virus Characteristics

Diagnosis

Reservoir

Transmission

Treatment

Preventative Measures

Self-limited gastro-enteritis
- Nausea, vomiting, abdominal pain, & diarrhea
- Very contagious

- Capsid offers the unstable RNA genome inside protection against high temperatures, drying, acid and detergents
- Flourishes in the GI-tract

PCR, EM, ELISA

Humans

Indirect oral-fecal route & airborne w/ fomites (vomiting)

No available treatment or vaccination

Washing hands, chemical cleaning