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 VirusesIdentified by 2 Surface Protein StructuresCombinations

“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 20th Century

A(H1N1)A(H2N2) A(H3N2)

1918: “Spanish Flu” 1957: “Asian Flu” 1968: “Hong Kong Flu”

20-40 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