Influenza VirusMicro401 Case Study #5

Alvaro Gomez

Sheila Laqui

Jensen Lau

November 8, 2007

Case Study #5 - InfluenzaIn late December a 22 year old man suddenly experienced

flu-like symptoms.

Headache Myalgia Malaise Dry Cough Fever

Worsened Cough Nausea Vomiting

Initial Symptoms Later Symptoms

His family had experienced similar symptoms two weeks prior.

Influenza virus Background

(-)ss RNA virus Orthomyxoviridae family Influenza A & B are

Endemic - Winter,

peaks Dec - JanMc Queen Nancy, micro 401, Lect 5

Differential DiagnosisOther Flu-Like Symptoms

Respiratory Syncytial Virus (RSV) Meningitis Pneumonia Adenovirus Parainfluenza

www.cdc.gov

Molecular Lab Tests Viral Culture

Immunofluorescence (IF)

Enzyme Immunoassay (EIA)

Real-Time PCR (RT-PCR)

Hemagglutination inhibition (HI)Ellis, J, S. Rev, Med. Virol. Vol 12, 375-389 2002

Lab Tests - Viral CultureAdvantages

Disadvantages Whole Virus

Measured Virus recoverable

Requires Infectious Virus

Highly Skilled Technicians

Time (3-7days) Cost

Lab Tests - IFAdvantages

Disadvantages Time (2h-1day) Requires Intact

Cells Highly Skilled Specialized

equip. Cost

Lab Tests - EIAAdvantages

Disadvantages Time (15min-1day) High Throughput Low-Skill

No Virus Recoverable

Lab Tests - RT-PCRAdvantages

Disadvantages Sensitive Allows Further

Molecular Analysis High Throughput Time (1-2days)

Highly Skilled Specialized

Equip. Cost

Lab Tests - HIAdvantages

Disadvantages High Throughput Sensitive Specific Time (2 days) Cost

Retrospective Paired Samples

Needed

Tissue Test

Nasopharyngeal (Swab or Aspirate) Bronchoalveolar Lavage Serum (HI) Chest Radiography (Pneumonia) Lumbar Puncture (Meningitis)

Final Diagnosis Viral Culture (6 days results) IF (1 day) EIA (1 day) Lumbar Puncture negative for Meningitis X-ray scan negative for Pneumonia

Patient’s results came back positive for Influenza B antigens

Anti-Influenza Drugs Amantadine

Pre-exposure prophylaxis & treatment of influenza A

Blocks M2 proton channel Necessary for

uncoating

Influenza resistance detected in 2005

Zhuang, Xiaowei. “Zhuang Group – Cell Entry Project.” Cellular entry of viruses and non-viral gene delivery vectors. 18 October 2007. Harvard University. 6 November 2007. <http://zhuang.harvard.edu/cellentry.html>.

Bright, Rick, et. al. Adamantane Resistance Among Influenza A Viruses Isolated Early During the 2005-2006 Influenza Season in the United States . The Journal of the American Medical Association. 2006;295:(doi:10.1001/jama.295.8.joc60020). 6 November 2007. <jama.ama-assn.org/cgi/content/full/295.8.joc60020v1>.

Dimmock, N.J., et. al. Introduction to Modern Virology – 6th ed. Blackwell Publishing. Malden, MA. 2007.

Anti-Influenza Drugs NA Inhibitors

Zanamivir (Relenza®) & Oseltamivir (Tamiflu®) Pre-exposure prophylaxis & treatment of influenza A & B

“Flu Wiki.” Neuraminidase Inhibitors. 19 December 2006. Melanie Matson. 6 November 2007. <http://www.fluwikie.com/pmwiki.php?n=Consequences.NeuraminidaseInhibitors>.

Fiore, Anthony, et. al. “Morbidity and Mortality Weekly Report.” Prevention and Control of Influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2007 . 13 July 2007. Centers for Disease Control and Prevention. 1 November 2007. <http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5606a1.htm>.

Spread through large particle respiratory droplets & airborne transmission

Incubation period 1-4 days Adults infectious up to 5

days after illness onset Children infectious up to

10 days after illness onset

People at Risk People 65 years or older Children in general Adults & children with

chronic heart or lung diseases, diabetes, kidney disease or anemia

Immunocompromised individuals

Fiore, Anthony, et. al. “Morbidity and Mortality Weekly Report.” Prevention and Control of Influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2007. 13 July 2007. Centers for Disease Control and Prevention. 1 November 2007. <http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5606a1.htm>.

Transmission of Influenza

Genetic VariabilityAntigenic shift:Major change in the influenza

A virus subtypes HA and NA protein changes –

population has little immunity for mutant virus

Two Patterns of influenza A: Annual epidemics in most

countries Every 10-12 years-

extensive pandemics http://virology-online.com/viruses/Influenza.htm

Mc Queen NANCY, micro 401, Lec 5

How does the virus change?Antigenic Drift Produces new virus strains

not recognized by the body’s immune system

Occurs continuously over time

This “drift” creates new virus strains that the immune system does not recognize or has little or no resistance for

http://virology-online.com/viruses/Influenza.htm

Mc Queen Nancy, micro 401, Lect 5

THANK YOU!!!