It’s Just Not the Flu Anymore Rick Hong, MD Associate Chairman CCHS EMC Medical Director, PHPS

The “Flu” Contagious respiratory illness Caused by influenza viruses Can cause mild to severe illness, even death In US (yearly): –5% to 20% incidence –more than 200,000 hospitalized –about 36,000 deaths High risk population –the elderly –young children –co-morbidities

Influenza Viruses 3 Types “A” – Various Animals (Pandemic) “B” – Human (Epidemic) “C” – Human (Mild Infection)

Type “A” Influenza Viruses Identified by 2 Surface Protein Structures Combinations “H” - Hemagglutinin (1 – 16) Entry into Cell “N” - Neuraminidase ( 1- 9) Exit from Cell 144 Possible combinations Current Avian or Bird Flu Strain: A (H5N1) High Pathogenic and Low Pathogenic

Viral Replication

What’s the Problem?

Antigenic Drift Variants from frequent point mutations during replication Less frequently in Influenza B Antibody against one influenza virus type/subtype confers limited or no protection against another type/subtype Antibody to one antigenic variant may not protect against a new antigenic variant of the same type/subtype Virologic basis for seasonal epidemics and the incorporation of one or more new strains in each year's influenza vaccine

Antigenic Shift More dangerous, less frequent mutations Emergence of a novel influenza virus Not “recognized” by immune system Can cause epidemics/pandemics

Definitions Seasonal Flu –respiratory illness transmitted person to person –some human immunity; vaccine available Pandemic Flu –virulent human flu that causes a global outbreak –easily spread from person to person –little natural immunity; no vaccine –no pandemic flu currently Avian Flu –influenza viruses occurring naturally among wild birds –H5N1 variant lethal to domestic fowl –transmitted from birds to humans (human-to-human?) –no human immunity; no vaccine

Influenza Pandemics 20 th Century A(H1N1) A(H2N2)A(H3N2) 1918: “Spanish Flu” 1957: “Asian Flu”1968: “Hong Kong Flu” Million deaths 675,000 U.S. deaths 1-4 Million deaths 70,000 U.S. deaths 1-4 Million deaths 34,000 U.S. deaths

Abrupt onset of constitutional and respiratory signs and symptoms –fever (3-5 d) –myalgias (3-5 d) –headache –malaise (2 w) Typically resolves after 3-7 days Cough and malaise can persist for >2 weeks Secondary bacterial pneumonia or primary influenza viral pneumonia Difficult to distinguish from other respiratory illnesses (70% accurate) Case Definition –nonproductive cough (2 w) –sore throat –rhinitis – otitis media, nausea, vomiting

Transmission Incubation period of 1-4 days Via respiratory droplet (e.g., cough, sneeze) Viral shedding from the day before symptoms through 5-10 days after illness onset (longer in children and the immunocompromised)

Lab Testing Preferred specimen: nasopharyngeal/nasal swab, wash, aspirate Rapid influenza tests –Results within 30 minutes –May determine type (A vs. B) –High false negative results (30%) Viral culture –Results in 3-10 days –Determine specific subtype or strain –reference standard of diagnosis Not necessary to test all patients –May not affect clinical decision-making –Expensive –Labor intensive –Cohort hospitalized patients –Outbreaks

Prevention Vaccination –two types of vaccines: "flu shot” –an inactivated vaccine (containing killed virus) –people older than 6 months, including healthy people and people with chronic medical conditions. nasal-spray flu vaccine (LAIV for “Live Attenuated Influenza Vaccine”) –live, weakened flu viruses –approved in healthy people 5 years to 49 years of age who are not pregnant. –contains three influenza viruses-one A (H3N2) virus, one A (H1N1) virus, and one B virus strains based on surveillance and estimations about which types and strains of viruses will circulate in a given year –development of antibodies after 2 weeks

Prevention “Health Habits” –avoid close contact –stay home when you are sick –cover your mouth and nose with a tissue –wash your hands –avoid touching your eyes, nose, or mouth

Antivirals NOT a substitute for vaccination Must be taken each day for the duration of influenza activity in the community (8 weeks) 4 licensed influenza antiviral agents available –M2 ion channel inhibitors (amantadine, rimantadine) only protects against Influenza A high levels of resistance not recommended by CDC and ACIP –neuraminidase inhibitors (Influenza A & B) oseltamivir (Tamiflu): ages > 1 year zanamivir (Relenza): ages >5 years.

Treatment In general, supportive care only Antivirals –Influenza A virus resistance to amantadine and rimantadine –neuraminidase inhibitors for both influenza A and B viruses oseltamivir for treatment of persons aged >1 year zanamivir for treatment of persons aged >7 years