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Medical Microbiology > Influenza > Flashcards

Flashcards in Influenza Deck (30):
1

Most common symptoms of uncomplicated influenza

Fever, cough, malaise. Self-limited.

2

How to distinguish influenza from the common cold (rhino, adeno, corona)?

Systemic symptoms like fever + chills, headaches and myalgias, anorexia and malaise. Abrupt onset with duration ~ 3 days.

3

What other symptoms, aside from systemic symptoms, are caused by influenza?

Respiratory symptoms= dry cough, sore throat, rhinorrhea, sneezing is more frequent with adeno/corona/rhinoviruses than the flu. Duration ~7-8 days, usually persist/worsen after resolution of systemic symptoms.

4

Complications of influenza

Primary viral pneumonia, secondary bacterial pneumonia, myositis, myoglobinuria, myocarditis, toxic shock syndrome, guillain barre syndrome.

5

Primary viral pneumonia

Extension of the URI into the LRT, begins like uncomplicated influenza, but gets progressively worse, can cause diffuse bilateral/multilobar opacities.

6

Secondary bacterial pneumonia

Follows seemingly uncomplicated flu, biphasic illness = initial improvement, but 4-14 days later, bacterial pneumonia sets in. Focal consolidation. Generally caused by strep pneumo or s aureus, rather than h. influenzae.

7

Influenza family

Orthomyxoviridae, groups ABC

8

Structure of the flu virus

Negative-sense (genome is complementary to mRNA, segmented (7 or 8 RNAs per genome), nucleoprotein, which binds genomic viral RNA

9

NP + vRNA

Ribonucleoprotein complex, a stable complex that remains similar across many virus strains, the target of most diagnostic tests.

10

How to make clinical diagnosis:

flu season + fever + cough = flu

11

RIDT

Rapid influenza diagnostic testing, an enzyme immunoassay that looks for NP. Very specific (98%), only 62% sensitive (some false negatives).

12

DFA test for flu

Direct fluorescent antigen, best test. Epithelial cells from nasopharynx put on slide, stained with fluorescently labeled flu specific antibodies.

13

Neuraminidase

NA for short, receptor destroying glycoprotein that is expressed on the viral surface, enhances the efficiency of progeny virus release from infected cells, target of protective antibody responses (but less so than hemagluttinin)

14

Osteltamivir and Zanamivir

two antivirals that target neuraminidase, allow sialic acid to be cleaved before galactose to cause efficient egress of progeny virus.

15

M2

Matrix 2, ion channel in the viral envelope, proton flux acidifies endosomes for fusion and uncoating, target of a non-neutralizing antibody response

16

Amantadine and Rimantadine

Two antivirals that target M2. Orally administrated, inhibits pH-dependent virus endosome fusion and genome uncoating. Active only against influenza A. Side effects = CNS, N/V, loss of appetite.

17

Influenza life cycle

Attachment with HA binding to sialic acid, entry via endocytosis, fusion with endosome and uncoating (this step is blocked by amantidine and rimantidine), viral genome is imported into the nucleus where mRNA is synthesized, exported, translated and modified, packaged and exported. To enable release, NA must destroy sialic acid to let the virus go. Osteltamivir and zanamivir block this step, preventing release.

18

Oseltamivir

Oral, standard adult dose 75mg 2x/day x 5 days. Prodrug that is cleaved by hepatic esterases to create a carboxylate. Renally cleared, can cause N/V.

19

Zanamivir

Inhaled 10mg 2x/day for direct delivery to respiratory tract. Contraindicated in reactive airway disease (asthma/COPD) due to bronchospasm.

20

Adamantane resistance

Very easy, a single point mutation in the M2 ion channel is sufficient to confer resistance. This mutation doesn't affect viral function, just antiviral function. All influenza A viruses circulating currently have adamantane resistance.

21

Target of the majority of the neutralizing antibody response?

Hemagglutinin, receptior binding glycoprotein expressed on the viral surface.

22

Antigenic drift

Over time, accumulating amino acid mutations in HA eventually enable escape from antibody recognition. Enables reinfection of previously infected hosts.

23

Antigenic shift

Novel HA genes from the animal reservoir can result in a virus to which the human population in immunologically naive.

24

Polymerase complex (PA, PB1 and PB2)

RNA-dependent RNA polymerase, transcribes (-)sense genomic viral RNA into + sense mRNA for translation of viral proteins by host cell machinery, AND complementary RNA. No proofreading, so very error prone, 1 misincorporation per 10^3-10^5 nts. These mutations can be advantageous! For example, mutation in HA helps evade antibodies (antigenic drift), mutation in M2 to NA confers drug resistance.

25

Influenza vaccine primary immunogen

HA! Body creates anti-HA antibodies to neutralize (prevent infection by preseting receptor binding) or non-neutralize (preventing endosome fusion).

26

Trivalence

Prevents against 2 types of influenza A (H1N1, H3N2) and B.

27

Split Virus Vaccine

Egg-grown viruses are distrupted with a detergine to solubilize the viral membrane, releasing surface glycoproteins HA and NA.

28

Subunit Vaccine

After detergent treatment, the surface proteins are separated out from the rest of the virus components.

29

Attenuated Vaccine

Backbone is an influenza virus that grows poorly above 35 degrees C.

30

Recombinated HA influenza vaccine

(RIV), antigens are grown in culture (HA), rapid production, shorter shelf life, similar immunogenicity and efficacy.