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Influenza Virus. Micro401 Case Study #5 Alvaro Gomez Sheila Laqui Jensen Lau November 8, 2007. Case Study #5 - Influenza. In late December a 22 year old man suddenly experienced flu-like symptoms. Initial Symptoms Later Symptoms. Headache Myalgia Malaise Dry Cough
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Influenza Virus Micro401 Case Study #5 Alvaro Gomez Sheila Laqui Jensen Lau November 8, 2007
Case Study #5 - Influenza In late December a 22 year old man suddenly experienced flu-like symptoms. Initial Symptoms Later Symptoms • Headache • Myalgia • Malaise • Dry Cough • Fever • Worsened Cough • Nausea • Vomiting 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 - Jan Mc Queen Nancy, micro 401, Lect 5
Differential Diagnosis Other 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 Culture Advantages Disadvantages • Requires Infectious Virus • Highly Skilled Technicians • Time (3-7days) • Cost • Whole Virus Measured • Virus recoverable
Lab Tests - IF Advantages Disadvantages • Time (2h-1day) • Requires Intact Cells • Highly Skilled • Specialized equip. • Cost
Lab Tests - EIA Advantages Disadvantages • No Virus Recoverable • Time (15min-1day) • High Throughput • Low-Skill
Lab Tests - RT-PCR Advantages Disadvantages • Highly Skilled • Specialized Equip. • Cost • Sensitive • Allows Further Molecular Analysis • High Throughput • Time (1-2days)
Lab Tests - HI Advantages Disadvantages • Retrospective • Paired Samples Needed • High Throughput • Sensitive • Specific • Time (2 days) • Cost
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
Amantadine Pre-exposure prophylaxis & treatment of influenza A Blocks M2 proton channel Necessary for uncoating Influenza resistance detected in 2005 Anti-Influenza Drugs 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 Transmission of Influenza 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>.
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
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