1. Influenza Virus Micro401 Case Study #5 Alvaro Gomez Sheila Laqui Jensen Lau November 8, 2007

2. Case Study #5 - Influenza In 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.

3. Influenza virus Background (-)ss RNA virus Orthomyxoviridae family Influenza A & B are Endemic - Winter, peaks Dec - Jan Mc Queen Nancy, micro 401, Lect 5

4. Differential Diagnosis Other Flu-Like Symptoms Respiratory Syncytial Virus (RSV) Meningitis Pneumonia Adenovirus Parainfluenza www.cdc.gov

5. 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

6. Lab Tests - Viral Culture Advantages Disadvantages Whole Virus Measured Virus recoverable Requires Infectious Virus Highly Skilled Technicians Time (3-7days) Cost

7. Lab Tests - IF Advantages Disadvantages Time (2h-1day) Requires Intact Cells Highly Skilled Specialized equip. Cost

8. Lab Tests - EIA Advantages Disadvantages Time (15min-1day) High Throughput Low-Skill No Virus Recoverable

9. Lab Tests - RT-PCR Advantages Disadvantages Sensitive Allows Further Molecular Analysis High Throughput Time (1-2days) Highly Skilled Specialized Equip. Cost

10. Lab Tests - HI Advantages Disadvantages High Throughput Sensitive Specific Time (2 days) Cost Retrospective Paired Samples Needed

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

12. 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

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

14. 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.. 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..

15. 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.. Transmission of Influenza

16. Genetic Variability Antigenic 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

17. 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

18. THANK YOU!!!