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the flu today ALEX JAKLE self deception, or: “i’m pretty sure this is the best nerd nite talk you’ll ever hear” JAMES MANN h.h. holmes: a devil born in his soul
or over a very wide area, crossing international boundaries and usually affecting a large number of people • 1918 Influenza Data: – Upwards of 500 million infected worldwide – ~50-100 million deaths worldwide – ~2.5% death rate in the US • Variable some places worse than others. • What made the 1918 influenza so deadly? – Unique historical context – Unique viral qualities
• The world descends into the trenches • War conditions are great for spreading infections: – Close quarters – Injuries – Fatigue and stress – Poor Sanitation – Limited food supply
the morning of March 11, 1918, a young private reported to the Army hospital at Fort Riley, Kansas, complaining of fever, sore throat, and headache. • By noon, the hospital had more than one hundred cases; in a week, there were five hundred. Forty-eight soldiers died at Fort Riley. – 1% fatality rate compared to 0.025-0.5% mortality rate associated with common influenza • Soldiers infected with the virus both symptomatic and asymptomatic were shipped overseas to fight in WWI
Riley October: Japan September: US, India China, Russia May 1918 Spain February: Third Wave of influenza hit all second wave places + Australia August 1918 Europe-Africa
Surgeon General) after visiting camp Devon near Boston – "Every bed is full, yet others crowd in…the faces wear a bluish cast; a cough brings up the blood-stained sputum. In the morning, the dead bodies are stacked about the morgue like cordwood.” • Speed of Influenza – People would complain of flu-like symptoms (headache, soar throat) and be dead in 1-2 days – The spread of the disease was incredibly quick • September 1918: 12,000 died in the US • October 1918: 165,000 died in the US
died; 50-100 million people worldwide – 1918 flu killed more people in 25 weeks than HIV has killed in 25 years – It killed more people than the plagues of the middle ages killed in a century – Seven times as many people died from 1918 flu as were killed in WWI – 50% of the Alaskan Inuit population died – 20% of South Pacific Islanders died • What made this Influenza so deadly?
embedded in paraffin from 1918 flu victims • To obtain a source of unmodified 1918 virus, researchers got permission from Eskimo tribes in Alaska to exhume the bodies of 1918 flu victims buried in 1918 in areas of Alaskan permafrost – Lung tissue was removed from 3 victims and the total viral sequence was obtained • Now—what to do with that info? – Dual use research – Nature wanted to publish it, the US government was a bit skiddish
needs to be tightly controlled to allow gas exchange to occur • Viral or bacterial infections can disrupt normal oxygen uptake, but are cleared by immune responses • Overactive immune responses can be detrimental – Cytokine storm can cause fluid exit the blood stream and enter tissue • Severe fluid build up in the lungs restricts oxygen absorption into the blood stream – This is what caused cyanosis in 1918 pandemic patients, they had heavily disrupted oxygen absorption in the blood
• Increased virulence in the lung: infected more cells and copied itself faster than other influenza viruses much more infectious than typical influenza – The H protein determines what cell types the virus can get into • The pandemic influenza virus H protein allowed it to infect many more cells in the lung and trachea • Increased viral load in the lung caused a dangerously strong immune response – Cytokine TNFα makes endothelial cells leaky – Fluid came into the lungs through blood flow and patients would suffocate – If you survived that, you had mucus build up in your lungs and secondary bacterial pneumonia would kill you
are people still freaking out about Influenza today (H1N1 2009)? – “A useful way to think about influenza A events of the past 91 years is to recognize that we are living in a pandemic era that began around 1918.” –David Morens et al. NEJM (2009) • Each year the flu infects a billion people around the world, killing 250,000–500,000 of them. (.025-.05%) • 10-20% of US residents get the flu • Viruses have the ability to change rapidly into something much more deadly – Quick generation time
Influenza A produces 10 proteins from the 8 genome segments – Humans have ~20,000-25,000 protein coding genes • ~100 times smaller than than a cell • Smaller size means less material, making copies is much simpler than it is for our cells • We lose the evolutionary arms race because viruses change faster – Viral generation times are on the minute, hour, scale – Human generation times measured in decades
to mutations • When viruses copy themselves they make a lot of mistakes • Replication errors accumulate in the virus as they make copies. We call them mutations. • Influenza viruses mutate a lot over the course of the year – The flu can re-infect people who have encountered the virus the previous year
new H or N gene. Antigenic Shift=Viral mix and match Bird Flu and Human or Swine Flu in the same host -End up in the same cell -Replicate in that cell -Viral genomes rearranged and released from cell Get brand new form of the virus with limited protection Almost always happens when we get new pandemics. This is what happened in 1918 and again in 2009.
H5N1 • H1N1: scare of 2009 “swine flu” – Quadruple re-assortment virus: elements of 2 Swine, 1 Avian and 1 Human flu viruses recombined themselves (antigenic shift) – Like 1918 virus, seemed to be killing healthy adults as well as the very old and very young – Hasn’t been as widely spread or as dangerous as 1918 influenza • Not out of the woods yet. still worried because 2009 could be the first wave • Our vaccinations will hopefully help, our containment efforts helped • H5N1: avian flu in Asia (not SARS) – Highly pathogenic strains in birds can wipe out 90-100% of colony in 48hrs • 1997 Hong Kong – Very little crossover to humans but… • Has happened and it’s not pretty (598 cases, 348 deaths ~60% mortality rate) • Virus can’t spread quickly in humans yet…
H5N1 • If you had an H5N1 virus infect the same cell as a common human influenza virus and recombine…. – H5N1 virus kills 60% of people it infects – Annual human influenza A virus (H1N1) can be transmitted from person to person, infects about 1 billion people per year – yikes –….but like…how likely is that really….
established a National Pandemic Planning Committee • The 4 coordinating centers are in Atlanta, London, Melbourne and Tokyo • They all have biosecurity level 4 sophisticated labs for early diagnosis • Essential since influenza symptoms are essentially similar to anthrax and SARS symptoms • Anti-viral drugs are being stockpiled and manufacturers have been identified who could immediately begin vaccine production • Physician scientists like Nathan Wolfe are trying to track dangerous viruses across the planet to stay ahead of a potential pandemic – Find his book ‘The Viral Storm’
guidance • Trilla, A., Trilla, G. & Daer, C. The 1918 ‘Spanish Flu’ in Spain. CLIN INFECT DIS 47, 668–673 (2008). • Taubenberger, J. K. & Morens, D. M. 1918 Influenza: the mother of all pandemics. Emerging Infect. Dis. 12, 15– 22 (2006). • RICHARD, S. A., SUGAYA, N., SIMONSEN, L., MILLER, M. A. & VIBOUD, C. A comparative study of the 1918–1920 influenza pandemic in Japan, USA and UK: mortality impact and implications for pandemic planning. Epidemiol. Infect. 137, 1062 (2009). • Sun, Y. et al. Cutting Edge: Negative Regulation of Dendritic Cells through Acetylation of the Nonhistone Protein STAT-3. The Journal of Immunology 182, 5899– 5903 (2009). • Nguyen-Van-Tam, J. The epidemiology and clinical impact of pandemic influenza. Vaccine 21, 1762–1768 (2003).
sentence Try to mess with your minds a little bit Torture, mangle, or otherwise disfigure the meaning of “cynical” Consume 2 oz. of rye whiskey Compare you to a baseball player
able to get a hit off me. No one’s going to be able to touch me.... When you start to doubt yourself, you’ve already lost.” “‘I know this hitter can’t hit me. I’m gonna beat this guy. I’m better than him.’ If he beats you, tip your cap to him. But he won’t.”
able to get a hit off me. No one’s going to be able to touch me.... When you start to doubt yourself, you’ve already lost.” “I know this hitter can’t hit me. I’m gonna beat this guy. I’m better than him.’ If he beats you, tip your cap to him. But he won’t.” “Confidence is everything. If you don’t truly, truly, truly, believe you’re the best on the field, it’s gonna show up.”
it ‘til you make it. Even if you’re not succeeding like you’d like to, you have to have that mindset that you’re still the best.” “Confidence is everything, in my opinion. Especially in this game. You obviously know that it’s a game of failure. I really do believe that baseball is 100% confidence. It’s a game where you have to kinda trick your mind, and believe in yourself even when you’re doing bad.”
making big money - especially if you break their income down to an hourly wage. But they’re getting rewarded in ways that go beyond dollars and cents. The kid on the streets is getting a shot at a dream. The dream is the he will be the one to make this hustling thing pay off in a big way. He sees the guy who gets rich and drives the nice car and thinks, yep, that’ll be me. He ignores the other stories going around, about dudes who get shot or beaten to death with bricks and chains”
sentence Try to mess with your minds a little bit Torture, mangle, or otherwise disfigure the meaning of “cynical” Consume 2 oz. of rye whiskey Compare you to a baseball player
sentence Try to mess with your minds a little bit Torture, mangle, or otherwise disfigure the meaning of “cynical” Consume 2 oz. of rye whiskey Compare you to a baseball player
Auschwitz]. During those few seconds, while Hanke was warning me, the whole responsibility had become a reality... from that moment on, I was inescapably contaminated morally; from fear of discovering something which might have made me turn from my course, I had closed my eyes. This deliberate blindness outweighs whatever good I may have done or tried to do in the last period of the war”
sentence Try to mess with your minds a little bit Torture, mangle, or otherwise disfigure the meaning of “cynical” Consume 2 oz. of rye whiskey Compare you to a baseball player
sentence Try to mess with your minds a little bit Torture, mangle, or otherwise disfigure the meaning of “cynical” Consume 2 oz. of rye whiskey Compare you to a baseball player
sentence Try to mess with your minds a little bit Torture, mangle, or otherwise disfigure the meaning of “cynical” Consume 2 oz. of rye whiskey Compare you to a baseball player
sentence Try to mess with your minds a little bit Torture, mangle, or otherwise disfigure the meaning of “cynical” Consume 2 oz. of rye whiskey Compare you to a baseball player
sentence Try to mess with your minds a little bit Torture, mangle, or otherwise disfigure the meaning of “cynical” Consume 2 oz. of rye whiskey Compare you to a baseball player
sentence Try to mess with your minds a little bit Torture, mangle, or otherwise disfigure the meaning of “cynical” Consume 2 oz. of rye whiskey Compare you to a baseball player
sentence Try to mess with your minds a little bit Torture, mangle, or otherwise disfigure the meaning of “cynical” Consume 2 oz. of rye whiskey Compare you to a baseball player
sentence Try to mess with your minds a little bit Torture, mangle, or otherwise disfigure the meaning of “cynical” Consume 2 oz. of rye whiskey Compare you to a baseball player
Event 7-9:30 pm Great Lakes Coffee Roasting Company in Midtown Detroit in fact, it’s next week! if you’re going to be anywhere near midtown thursday (3/28), come see us for circus, drunken history, and spiders!
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