PULSE

Upper Respiratory Infections

Wednesday, October 31st 2012

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WhatIsAVirus?

Virus Structure-Viral Genome

- Double-stranded DNA- Single-stranded DNA- Double-stranded RNA- Single-stranded RNA

-Protein Coat - Capsid – built from large number of protein subunits

called capsomeres-Envelope

- Derived from membrane of host cell ~ contain host cell phospholipids and membrane proteins

- Also contain proteins and glycoproteins of viral origin- Non-eveloped – ‘Naked Virus’

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Property Parameters

Nucleic Acid -DNA-RNA-Both DNA and RNA

Shape -Linear-Circular -Segmented

Strandedness -Single-stranded-Double-stranded-Double-stranded with regions of single-strandedness

Sense -Positive Sense (+)-Negative Sense (-)-Ambisense (+/-)

Influenza

Orthomyxoviridae Family

Influenza Viruses: A, B, or C

Spherical or Longitudinalaverage diameter of 80 to 120 nanometers

Glycoproteins Hemagglutinin – primary protein responsible for binding to receptor sites on the cell membrane, allowing the virion to enter the cell Neuraminidase – enables the virus to be released from the host cell ~

enzymes that cleave sialic acid groups from glyocoproteins and are required for influenza virus replication

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Avian & SwineH5N1 H1N1

Bird flu you need to seek TWEETMENT, and for swine flu you can just apply OIKMENT!

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Culture and Diagnosis

-Rapid Influenza Diagnostic Test (RIDT)-Direct Fluorescent Antibody Stain (FDA)-Viral Culture-Real-time Polymerase Chain Reaction (RT-PCR)-Influenza A or B Antibody Test

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Treatment

Influenza A-Amantadine-Rimantadine

Influenza A and B -Zanamirvir (Relenza) -Oseltamivir (Tamiflu)

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Vaccination

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Myth: You can get the flu, or a mild case of it, from the flu vaccine.

Myth: Antibiotics can fight the flu if you get it.

Myth: You don’t need to get the flu vaccine if you got it last year – the strains are basically the same.

Myth: The flu vaccine contains thiomerosal, which may be harmful.

Myth: Getting the flu can be a pain, but it’s not really a serious disease, so vaccination isn’t helpful.

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Causative Organisms Influenza A, B, and C viruses

Most Common Modes of Transmission Droplet Contact, direct contact, some indirect contact

Virulence Factors Glycoprotein spikes, overall ability to change genetically

Culture / Diagnosis Viral culture (3-10 days) or rapid antigen-based or PCR tests

Prevention Killed injected vaccine or inhaled live attenuated vaccine – taken annually

Treatment Amantadine, Rimantadine, zanamivir, or oseltamivir

Influenza Summary

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Upper Respiratory Tract

Includes Mouth, Nose, Throat, Nasal Cavity, Sinuses, Larynx

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1 http://health.rush.edu/healthinformation/care%20guides/28/000141.aspx2 http://www.ohiosinus.com/patient-info/sinus-anatomy-and-function

Lower Respiratory Tract

Includes Trachea Bronchi and Bronchioles in Lungs

33 1 http://health.rush.edu/healthinformation/care%20guides/28/000141.aspx

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Respiratory Tract Defenses

341 http://www.thegeminigeek.com/why-do-we-have-nose-hair/2 http://www.sciencephoto.com/media/311125/enlarge

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3 http://pathmicro.med.sc.edu/ghaffar/innate.htm4 http://pathmicro.med.sc.edu/mayer/stru-11.jpg

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Malaise

Nasal Congestion

Runny Nose (rhinorrhea)

Excessive Sneezing

Coughing

Sore Throat

Mild Fever

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Symptoms of the Common Cold… or Rhinitis

How an affected person feels:

http://www.nhs.uk/conditions/Rhinitis---non-allergic/Pages/Introduction.aspx

What a physician notes on examination:

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Symptoms of the Common Cold

http://www.virtualmedicalcentre.com/diseases/perennial-allergic-rhinitis/30

InflammationRedness (erythema)Pain to touchSwelling

Nasal Discharge

Mild Fever

Swollen lymph nodes – less common

Pathogens Responsible for the Common Cold

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>60% Cases Rhinoviruses

Highly variable serotypesNonenveloped, Icosahedrallinear + stranded ssRNA genome

Binds Intercellular Adhesion Molecule -1

CoronavirusesFewer serotypes – Alpha implicate

Enveloped, Sphericallinear + stranded ssRNA genome

Binds Aminopeptidase N/CD13

http://www.nature.com/news/2009/090212/full/news.2009.98.html

http://phil.cdc.gov/phil/details.asp?pid=4814

Aerosolized Droplets – Sneezing/Coughing

Fomites – inanimate objects or substances that can carry the pathogen

Direct Contact – eg. small children

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Transmission of the Common Cold

How?

To Where?

Infection initiates in uppermost throat & nasal cavityhttp://www.sos03.com/Diseases/Lung/Common_Cold

No cure actually targets the virus

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Treatment of the Common Cold

Instead, treat the symptoms:

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Immune Response to the Common Cold

And let your immune system do the rest …

Innate Immune ResponseMacrophages

Eosinophils

Adaptive Immune Response

Cytotoxic & Natural Killer T Cells

B Cells

http://www.cancer.gov/cancertopics/understandingcancer/immunesystem/AllPages

What is Pneumonia?

An anatomical diagnosis –

inflammatory condition of lung where fluid fills the alveoli

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http://www.britannica.com/EBchecked/media/107200/The-alveoli-and-capillaries-in-the-lungs-exchange-oxygen-for

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Symptoms of Pneumonia

How an affected person might feel:Short of Breath - dyspnea

Frequent Cough

Fever

Chills

Chest Pain

Fatigued

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Symptoms of Pneumonia

LRhttp://www.uptodate.com.medjournal.hmc.psu.edu:2048/contents/image?imageKey=PEDS/86360&topicKey=PEDS%2F5986&source=preview&rank=undefined

What a physician notes on examination:Fever

Rapid shallow breathing – tachypnea

Reduced breath sounds

Crackling

Pleural rub against chest wall

Chest X-ray infiltrate

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Pathogens Responsible for Pneumonia

Bacterial:

Streptococcus Pneumoniae Legionella Pneumophilia

Mycoplasma Pneumophilia

Viral:

Hantavirus Betacoronavirus

Influenzavirus

Rhinovirus

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Pathogens Responsible for Pneumonia

Streptococcus Pneumoniae

- small, paired, gram + cocci

- about 2/3 of community acquired cases

- more common among immuno-compromised

- binds monosaccharide - sialic acid - upper throat

- binds disaccharide - N-acetylgalactosamine b1-4 galactose- in lower respiratory tract

http://textbookofbacteriology.net/S.pneumoniae.html

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http://phil.cdc.gov/phil/details.asp?pid=11150

Pathogens Responsible for Pneumonia

Legionella Pneumophilia

- gram -, rod-like

- aerobic

- more common in aqueous habitats in association with amoeba

- infects macrophages in alveoli

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Mycoplasma Pneumophilia- genus lacks cell walls

- smallest free-living organism

- variable shape

- binds to carbohydrate antigen on respiratory epithelium

- aerobic & anaerobic

http://www.nejm.org/doi/full/10.1056/NEJM199411243312105

Pathogens Responsible for Pneumonia

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Pathogens Responsible for Pneumonia

Hantavirus- negative sense ssRNA

- composed of 4 proteins Nucleocapsid G1 & G2 – envelope RNA polymerase

- envelope glycoproteins may attach to integrin cell-surface molecule, which is found on endothelial cells and platelets throughout the body

http://www.nlm.nih.gov/medlineplus/ency/imagepages/17201.htm

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Pathogens Responsible for Pneumonia

SARS - Coronavirus

Enveloped, Spherical

linear + stranded ssRNA genome

Binds Angiotensin-Converting Enzyme-2 as a receptor/mode of entry into cells

no new cases since 2004

http://www.cdc.gov/sars/lab/images.html

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Transmission of Pneumonia

Commonly as Aerosolized Droplets – Sneezing/Coughing

Less common as Fomites – although S. pneumoniae may survive dessication

Rarely during casual contact

How?Bacterial:

Viral:

Commonly as Aerosolized Droplets – Sneezing/Coughing

Hantavirus is spread via airborne dust contaminated by excretory products of infected rodents

How?

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Treatment of Pneumonia

Bacterial:

Streptococcus Pneumoniaeβ-Lactam antibiotics

Penicillin Cephalosporin

Legionella PneumophiliaMacrolides

AzythromycinErythromycin

QuinolonesCiproflaxin

Mycoplasma PneumoniaeQuinolonesMacrolides

Viral:

Again, no cure. SARS in vitro studies

If severe respiratory distress, may be intubated & given oxygen therapy