Influenza: 1) Detail Influenza Epidemics of the the Past, the Present, Past

10/4/2017

Objectives Influenza: 1) Detail influenza epidemics of the The past, the present, past. the (future) pandemic 2) Explain the influenza virus structure, reservoirs, pathogenicity, and vaccination prevention. 3) Discuss future threats of novel Kristin Butler, MLS (ASCP)cm influenza virus strains. Department of Clinical Laboratory Sciences Louisiana Health Sciences Center - Shreveport Fall 2017

A virus as old as time? Influenza Etymology

•As far back as • Italian for “influence”, referring to the 400 BC cause of the disease • Later modified to influenza de freddo •Described by Hippocrates, Of • First used in English by J. Hugger in 1703 the Epidemics • Other archaic terms: “epidemic catarrh” “la grippe” “sweating sickness” “Spanish fever”

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Influenza of the past Influenza of the past

• 1510 pandemic in Europe • “Catarrhal fever” epidemics continue through the 1800s

Influenza of the past Influenza of the past

• European Influenza: Or •1889 Asiatic (Russian) flu the Greatest Disease Epidemic of the Modern Age

by Georg Friedrich Most, 1820

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Pandemics of the past Pandemics of the past

•1918 Spanish flu 1957 1968 1977 Asian flu Hong Kong flu Russian flu

Pandemics of the past Influenza today

2009 H1N1 swine flu •Endemic virus strains • Novel virus strain •Seasonal epidemics • Similar to 1918 virus • First cases seen in children in Mexico •Evolved healthcare and California •Antivirals and antibiotics • Some antiviral •Ongoing threats of future pandemics resistance to novel avian virus strains

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Influenza Virus Influenza Season Three types of flu viruses: • Influenza A – most common, most pathogenic •A flu epidemic every year • Influenza B – less common, less pathogenic • “Flu Season” from October to May • Influenza C – least common, least pathogenic • Peaks in December to March

•Increasing number of virus reservoirs today • Avian, swine, equine, canine, other mammals • Human viruses similar to animal viruses • Unpredictable viral genetics

Influenza Virus Reservoirs Influenza structure

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Influenza virus Influenza antigens binding to host cell • Subtypes are named for surface proteins, ex: H1N1

• Hemagglutinin = binds to epithelial cells • All 15 infect birds, only 6 infect humans • H1, H2, H3 most common

• Neuraminidase = opens host cells to free new virions Influenza virus • All 9 infect birds, only 3 infect humans opening host cell • N1, N2 most common to release newly formed virions

Influenza life cycle Naming influenza strains

1. 5.

4. 2.

1. HA binds to cell 4. Viral replication 2. Endocytosis 5. New virus assembled 3. M2 proteins uncoat 6. NA buds and releases

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Influenza pathology Influenza pathogenicity

• Necrosis of Signs & symptoms Complications epithelial cells • Fever • Dehydration

• Chills • Pneumonia • Severe inflammation in • Muscle aches • Acute bronchitis mucosal glands • Cough, congestion • Sinus infections • Runny nose • Ear infections • Headache • Worsening of • Fatigue chronic conditions

Transmission Why Winter? •Cold air Respiratory Contaminated •Dry air droplets surfaces •More time indoors •Crowded conditions •Decreased immune systems

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Disinfecting surfaces Is it really the flu, or just a cold?

Signs/symptoms Influenza Common cold Onset Abrupt Gradual Fever Usual, 3-4 days Rare Aches, fatigue Usual, severe Slight Chills Common Rare Rhinitis Common Common Sore throat Sometimes Common Cough Usual, severe Mild Headache Common Rare

Diagnosis Diagnosis

Rapid tests PCR • Detect viral • Detect viral RNA antigens • Best sensitivity and • POCT specificity • Better detection in • Flu/RSV combo children than adults • TAT 30 mins • TAT 10-15 mins

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Prevention Flu Vaccine •Vaccinations are a MUST every year • Available in trivalent and quadrivalent •Unpredictable virus formulations •Antibodies form in 2 weeks, remain

constant, then gradually decline • 2017-2018 vaccine: trivalent

A/Michigan/45/2015 (H1N1)pdm09-like virus quadrivalent •Immunity from vaccine ~ 1 year A/Hong Kong/4801/2014 (H3N2)-like virus •All persons 6 months or older should be B/Brisbane/60/2008-like virus vaccinated •2nd booster vaccine when necessary B/Phuket/3073/2013-like virus •High dose shot for elderly

Flu Vaccine How Flu Vaccines are made

2017-2018 Vaccine 2016-2017 Vaccine 1) Egg based flu vaccines A/Michigan/45/2015 A/California/7/2009 •Grown in chicken eggs (H1N1)pdm09-like virus (H1N1)pdm09-like virus •70+ years

A/Hong A/Hong Kong/4801/2014 Kong/4801/2014 (H3N2)- 2) Cell based flu vaccines (H3N2)-like virus like virus •Grown in mammalian cells •FDA approval August 2016 B/Brisbane/60/2008-like B/Brisbane/60/2008-like virus virus 3) Recombinant flu vaccines

•Grown in insect eggs B/Phuket/3073/2013-like B/Phuket/3073/2013-like virus virus •Since 2013

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How are vaccine viruses Viral evolution selected? • Year-round surveillance of influenza •Antigenic drift: minor genetic changes to HA/NA antigens • WHO Centers for Reference & Research on •Gradual, continuous change over time Influenza •Lack of proofreading in replication • Atlanta, Georgia, USA (Centers for Disease Control •Silent mutations in HA/NA proteins and Prevention, CDC) •Occurs in A and B virus types • London, United Kingdom (The Francis Crick Institute) • Melbourne, Australia (Victoria Infectious Diseases •Cause of yearly epidemics Reference Laboratory) •Cause of infection even after vaccine • Tokyo, Japan (National Institute for Infectious Diseases) • Beijing, China (National Institute for Viral Disease Control and Prevention)

Flu Vaccine options Antibody protection

•Standard-dose shot •High-dose trivalent shot •Recombinant trivalent shot •Trivalent shot w/adjuvant •Standard-dose quadrivalent shot •Intradermal quadrivalent shot 36

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Antibody protection against influenza CDC recommendations

High risk pop. Options • Adults over 65 • Only injectable • Children under 2 vaccines recommended • Pregnant women • Nasal spray vax is • Nursing home and NOT recommended LTAC residents • Egg-free options • Immuno- compromised • High dose for elderly persons • Generic Tamiflu now available

Herd Immunity Threat of a future pandemic HOW IT WORKS: Percent vaccinated: 0% Percent vaccinated: 25% Percent vaccinated: 50%

Percent vaccinated: 75% Percent vaccinated: 90% Percent vaccinated: 95%

Blue = unvaccinated Black = infected Yellow = vaccinated

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Influenza Virus Reassortment Viral evolution • How antigenic shift •Antigenic shift: major change to virus occurs •Reassortment of viral genes • Domestic pigs and •Sudden change birds are mixing vessel •Rapid infection in population for new combination •Occurs in type A virus only of influenza viral •Origin of novel viruses genes •Cause of pandemics • 2009 H1N1 pandemic •Limited to no protection from vaccine virus contained avian, swine, and human flu genes

Pandemic potential Deadly Avian flu? H5N1 H7N9 • Highly pathogenic avian •Animal is co- influenza (HPAI) infected with genetically • Wild aquatic waterfowl and domestic different viruses poultry are reservoirs for influenza type A •Reassortment • Genetically different from viruses that cause occurs human infection…for now… •Novel virus emerges • Ability to directly infect humans • Human-to-human transmission

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Threat of a future pandemic Threat of a future pandemic HPAI Asian H5N1 HPAI Asian H7N9 • Endemic in poultry • Endemic in poultry in China • 700 human infections since 2003 • 5th epidemic in China currently • Most cases from direct or close contact • 1562 human infections since 2013 with sick or dead poultry • Most cases from direct or close contact • Person-to-person transmission is rare, with sick or dead poultry limited, and not sustained • Person-to-person transmission is limited and not sustained • Pandemic potential if genetic reassortment of avian H5N1 and human influenza A • Greater pandemic potential than H5N1

https://gis.cdc.gov/grasp/fluview/ma in.html Additional Info

•WHO Influenza http://www.who.int/influenza/en/

•CDC Seasonal Influenza Resource https://www.cdc.gov/flu/index.htm

•Louisiana DHH http://ldh.louisiana.gov/index.cfm/pag e/1591

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Thank you for listening!

Kristin Butler, MLS (ASCP)cm Department of Clinical Laboratory Science School of Allied Health Professions LSU Health Sciences Center (318) 813-2919 [email protected]