Transcript Vaccination - Mercy Family Practice SC

Influenza
Mercy Family Practice SC
Kevin P Rosteing MS MSMI
1500 Heritage Rd Ste A
De Pere WI 54115
920-347-1990
mfprac.com
Size: Metric System
● Meter, average height human 1.7 m = 5'7”;
● 1.0 m = 3.28 feet
Size: Millimeter
1 Millimeter, 10^-3
Size: Microns
7 Microns, 7 x10^-6
Size: Nanometer
80 Nanometers, 80 x 10^-9
Influenza Virus
● Electron Micrography & Diagram showing H:N proteins
Influenza: Transmission
● Spread by a sneeze, or hand to mouth contact
Influenza: Highly Contagious
● Sneeze, can travel 15 feet or more
● Carries 40,000 droplets (25% rate)
● Each droplet carries 390 of virions
● Potential inoculum: 3.9 x10^6 virions
● Duration: 5 minutes on hand; 2 days on
plastic or metal
● Deaths: 30,000 to 48,000 per year in the US
Influenza: History
● Spanish Flu Pandemic: 1918, H1N1
● 500 million infected
● 50-100 million deaths: 15% mortality rate
● In WWI Spain remained neutral
● Death of King Alfonso XIII
Influenza Pandemics
Year
Name
Type
Mortality
1918-1920
Spanish Flu
H1N1
75 x10^6
1957-1958
Asian Flu
H2N2
2.5 x10^6;
69,800 in US
1968-1969
Hong Kong Flu
H3N2
1 x10^6
1977-1978
Russian Flu
H1N1
Small < 23 yo
2008
Bird Flu, Asia
H5N1
379 (59% fatality)
2009-2010
Swine Flu, Mexico
H1N1
284,500
11 subtypes
● Mutation occurs once every 30 years
Bird Flu Cases, Asia
● Initial cases: SE Asia
Influenza: Vectors
2013 in: Shanghai (24), Jiangsu (16), Zhejiang (15)
Vectors: Chickens & Pigs
Bird Flu H5N1; Avian Flu H7N9 & H2N2;
Swine Flu H1N1
Influenza: Seasonal Outbreak
Influenza: Symptoms & Signs
● Rapid course: Incubation period 4-7 days,
Hospitalization 4 days, Death 7 days
● Feverishness & Chills
● Cough & Phlegm production
● Dyspnea (SOB)
● Fatigue & Prostrate: “hit by a Mack Truck”
● VS: Temp 102 P 100 RR 20 BP 110/70 mmHg
● Lungs: Consolidation, Wheezing, Rhonchi
● Labs: ↑WBC, ↑Lymphocytes, ↓Platelets,
↑Creatinine, ↑LFT, pos Nasal swab Influenza A/B
Influenza: Case Hx
Influenza: Cases
Characteristic
Patient 1
Patient 2
Patient 3
Age
27
35
87
Comorbitities
Hepatitis B
Hepatitis B,
Obesity
COPD, HTN
Chickens
Yes
Yes
No
Viral typing
H7N9
H7N9
H7N9
Septic Shock
No
No
No
ARDS
Yes
Yes
Yes
ATN
No
Yes
No
Encephalopathy
No
Yes
Yes
Rhabdomyolysis
Yes
Yes
No
Resp Assist
Ventilator
Ventilator
O2 Mask
Treatment
Ab, Tamiflu,
Amantadine
Ab,Tamiflu
Ab, Tamiflu
Outcome
Died (day 6)
Died (day 19)
Died (day 6)
Ref: Gao, NEJM, 2013, 368 (20), p 1888
Influenza: ARDS
Influenza: ARDS
DNA
DNA vs RNA
DNA Replication
RNA Translation
Influenza Replication
● Error once every 10,000 nucleotides
Influenza Budding
Influenza: Recombination
Influenza: Treatment
● Vaccination: primary prevention
● Less 50% of the population gets vaccinated
● 2009: 78 million doses to 77 countries
● Effectiveness: 62% based on meta-analysis
● H1N1,H5N1 with adjuvant, inactivated
● Influenza A & B, in 2013, 3 subtypes: H1N1,H3N2,H5N1
● Incubated in hen eggs
● Takes about 5-9 months
● Alternatives: Trasdermal, Nasal, Cell Culture
● Anti-viral: oseltamivir (Tamiflu); resistant H1N1 2008
● Start <48 hours from onset of fever
Influenza: Vaccination
•
TLR=Toll-Like Receptor
•
APC=Antigen (Ag) Presenting Cell
•
HLA=Human Leukocyte Antigen
•
TCR=T-Cell antigen Receptor
•
CTL= Cytotoxic T Lymphocyte
•
T-Helper → B-cells, Plasma cells, B-Memory cells
T-Cell-B-cell Interaction
•
Ig-M, immediate response in less than 4 days
•
Ig-G, takes up to 4 weeks, lasts 4 months
T-Cell and B-Cell
Influenza Vaccine
● Two types: Trivalent inactivated and Nasal attenuated
● Each vaccine is grown in hen's eggs
● Duration: 5 months to manufacture
● 1976 Swine Flu and Guillian Barre Syndrome
● Fluzone (Aventis Pasteur), Fluvirin (Evans), and
Fluarix (GlaxoSmithKline), intramuscular injection
● LAIV (FluMist; MedImmune), intranasal spray
Vaccination Timeline
Vaccine Trivalence
Season
H1N1
H3N2
B-Strain
2010-2011
A/ California/
7/2009
A/ Perth/ 16/2009
B/ Brisbane/ 60/
2008
2011-2012
A/ California/
7/2009
A/ Perth/ 16/2009
B/ Brisbane/ 60/
2008
2012-2013
A/ California/
7/2009 pdm09
A/ Victoria/ 361/
2011
B/ Wisconsin/ 1/
2010, B/ Brisbane/
60/ 2008
2013-2014
A/ California/
7/2009 pdm09
A/ Victoria/ 361/
2011 variant
B/ Massachusetts/
2/ 2012, B/
Brisbane/ 60/ 2008
2014-2015
A/ California/
7/2009 pdm09
A/ Texas/ 50/ 2012
B/Massachusetts/
2/ 2012
Influenza Vaccine Indications
● Children ages 6 to 59 months
● Pregnant women
● Adults older than 50 years of age
● Asthma & COPD
● CAD, CHF, cardiac disease
● Diabetes mellitus
● Blood dyscrasias
● Renal insufficiency
● Immunosuppression (including
HIV)
Influenza Vaccine Contraindications
● Trivalent inactive virus (Injection)
– Egg Allergy
– Prior allergic reaction
– Prior Guillian Barre syndrome
● Live attenuated virus (Nasal)
– Children younger than 5 years
– Children or adolescents taking aspirin
– Adults older than 50
– Immunocompromised persons
– Adults with chronic heart, lung, or kidney
disease
Vaccine: is there a better way?
● Cell Culture: $20 to $80 per dose
● Production time drops from 20 (5 mo) to 10 weeks (2.5 mo)
● Available on short notice during any season
● Maintained in aseptic environment (avoids bacterial
contamination in eggs)
● Might provide broader immunity to influenza variants such as
H3N2
● Safe for individuals with allergy to eggs
Vaccine Production
Influenza A Antivirals
M2 Channel Inhibitors;
Amantadine (Symmetrel) & rimantadine (Flumadine)
Influenza A&B Antivirals
Neuraminidase Inhibitors (NAI):
oseltamivir (Tamiflu) & zanamivir (Relenza)
References
●
1918 Flu Pandemic, Wikipedia, www [http://en.wikipedia.org/wiki/1918_flu_pandemic],
accessed 4/25/2014.
●
Anonymous, – Pandemic Influenza Vaccine Manufacturing Process and Timeline-WHO,
Saturday, 8, August, 2009, www [http://gozonews.com/10190/pandemic- influenza- vaccinemanufacturing- process- and- timeline- who], accessed 5/4/2014.
●
Breesee, Joseph, Epidemic Influenza—Responding to the Expected but Unpredictable,
NEJM, 2/14/2013, 368(7), pp 589-592.
●
Fineberg, Harvey, Pandemic Preparedness and Response—Lessons from the H1N1
Influenza of 2009, 4/3/14, NEJM, 370 (14), pp 1335-1342.
●
Gao, R, et al, Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus, 5/16/13,
NEJM, 368 (20), pp 1888-1897.
●
Glezen, WP, Cell-Culture-Derived Influenza Vaccine Production, 2011-02-26, Lancet, Vol 377
(9767), pp 698-700.
●
Influenza Pandemic, Wikipedia, www [http://en.wikipedia.org/wiki/Influenza_pandemic],
accessed 4/25/2014.
References
●
Madsen, John, Utilization of Single-Use Technology for Production of Virus-Like Particle
(VLP)-based Influenza Vaccines, Novavax, Inc, www [http://www.novavax.com/ download/
file/ anaheim_dispo_conf_9_08.pdf], accessed 5/4/2014.
●
Qun Li, et al, Epidemiology of Human Infections withAvian Influenza A(H7N9) Virus in China,
2/6/14, NEJM, 370 (6), pp 520-532.
●
Sanchez, TMC, Development of an in Vitro Mimic of the In Vivo Deposition of VirusContaining Particulate Matter onto the Bronchial Epithelium, Thesis Paper, Simon Fraser
University, Summer 2010.
●
Szymczakiewicz-Multanowska, et al, A New Mammalian Cell Culture-Derived Influenza
Vaccine is as Safe as, and Immunogenically Non-Inferior to, an Egg-Based Influenza
Vaccine, International Journal of Infectious Diseases, 2008-12-01 Vol 12 ( Supp 1), pp e155e155.
●
White, Jason, Influenza, Medical Ecology, www
[http://www.medicalecology.org/diseases/influenza/influenza.htm], accessed 4/27/2014.
●
Waldman, SA, et al, Pharmacology and Therapeutics: Principles to Practice , First Edition,
Chapter 91, Vaccines, 2009 by Saunders, an imprint of Elsevier Inc., pp 1247-1268.