A Pandemic Disease that Should Really Scare You!

Somewhere lurking out there, there is a virus that can suddenly put you into a coma. When you awaken, if you ever do awaken, you may be surprised to find that you have Parkinson’s disease, even if you’re in the prime of your life, a movement disorder that can accurately be described as a healthy mind that is trapped in a prison of a body. This disease is called encephalitis lethargica and no one really knows for sure what causes it, much less how to cure it, although an undiscovered virus is the likely culprit. Striking in 1917, encephalitis lethargica caused an epidemic that lasted for a decade before suddenly disappearing as mysteriously as it had arrived. But not before leaving a wake of incapacitated victims in its wake. And all of this raises the question, why the hell haven’t you ever heard of this horrible disease? The answer is pandemic influenza, a disease that was far worse than encephalitis lethargica by many orders of magnitude.

Awakenings

“Awakenings” is based on the work of neurologist Oliver Sacks with patients with encephalitis lethargica in the 1960’s in a long term care facility (yeah, 45 years after most of them contracted the disease). The film stars Robin Williams and Robert DeNiro.

A YouTube video clip of a Diane Sawyer interview with Oliver Sacks with images of encephalitis lethargica patients. The quality isn’t the greatest due to degradation of the original film, but it is still very much worth your time to watch it. Encephalitis lethargica isn’t completely a thing of the past. There still are sporadic cases that pop up from time to time.

There are two main types of influenza that infect humans, influenza A and influenza B. In 1918 a particularly nasty strain of influenza A called H1N1, aka: Spanish Flu, killed between 50-100 million people worldwide. To put that into perspective, all deaths (military and civilian, including the Holocaust) in World War II, the bloodiest war in history, only totaled about 50 million. And World War II lasted from 1939-1945, six years compared to the two measly years (1918-1919) that Spanish Flu was in circulation. To make matters worse, Spanish Flu was particularly deadly to young adults, mowing down many of the healthiest and most productive citizens with its bloody reaper.

CampFunstonKS-InfluenzaHospital

The makeshift influenza wards at Fort Riley, Kansas during the 1918 influenza pandemic.

One hypothesis for the increased mortality in what is generally the healthiest cohort of people, people who are in their prime, is based on the fact that only a small portion of the damage from influenza is actually caused by the virus itself. The inflammatory response of the body to the influenza virus is the real killer and a particularly virulent strain of influenza induces a more potent immune response, possibly resulting in young people (who have very strong immune systems) suffering from increased damage compared to people who have a weaker immune systems.

W_curve

The dotted line is the typical pattern of mortality (death) during an influenza outbreak. It is U-shaped, with the highest mortality seen in the very young and the very old. The solid line is the W-shaped pattern of influenza fatalities that was seen during the 1918 flu pandemic. It was highly fatal to three groups of people: the very young, people in the primes of their lives (teenage years to mid 30’s), and the very old. The increased mortality in very young and very old people in both pandemic flu situations and in a more typical flu season is due to a generally fragile state of the body during very early childhood and in the elderly.

The reason that we are discussing influenza today is twofold. First, the United States is presently in the midst of a flu pandemic that is arguably the worst to strike it in decades. Second, there is a disturbing amount of ignorance out there regarding this very important disease. Part of this ignorance is due to Americans’ unfortunate use of the term “flu” to refer to run-of-the-mill viral illnesses, such as the common cold. I often joke with my colleagues that if we called the common cold the “stomach AIDS” or “the 24 hour AIDS” no one would worry about using a condom when they visited a brothel. True influenza is a serious disease that kills around 20,000 Americans per year, and that’s during an average flu season. Your chance of getting the flu in any given year is around 1:15 (but the rate is much higher during pandemic years), so if you think that you get “the flu” every year and you’re “only sick for a day or two” then influenza probably isn’t the culprit of the illness that you are referring to. True flu makes your whole body hurt, makes you spike high fevers, causes snot to pour out of your nose, elicits a nonproductive cough that can be strong enough to make you vomit, and generally makes you sick as hell. Another issue is that the influenza virus changes every year and some strains make folks much sicker than other strains do, the problem being that it is hard to predict in advance which strains are going to be really nasty and which are going to be milder.

usmap2

A map of the current influenza burden in the United States (2nd week of January 2015). This year there are at least two major strains of influenza circulating. The H3N2 strain of influenza A is the most prevalent strain. H3N2 has historically caused some of the worst influenza pandemics in terms of mortality (death). Influenza B is also circulating — fortunately influenza B tends to be a milder disease than influenza A in otherwise healthy people. Unfortunately, this isn’t necessarily true in susceptible populations (the very young, the very old, people with severe chronic diseases, people on immunosuppressant drugs, etc.). It also unfortunately means that you can get the flu more than once this season.

Let’s pause for a moment and step back to the basics of virology. Influenza is a virus, which means it is genetic material that is surrounded by a protein capsule. A virus is neither living nor dead. Like living things, viruses reproduce and change over time as they adapt to their environment. Unlike living things, viruses are incapable of reproducing on their own or of producing energy to power a metabolism. Instead viruses such as influenza must hijack the cells of living organisms to make more copies of the virus. A virus unable to do this goes extinct. In the simplest terms, a virus is a parasite that survives by infiltrating living cells (like mine and yours) and then transforming those cells into virus-making slave machines. The virus-infected cells crank out new viruses until either their energy is exhausted and the cell dies or until the cell is so filled with new viruses that it bursts open.

226px-EM_of_influenza_virus

Influenza magnified 100,000x by an electron microscope.

There are two main classes of viruses. DNA viruses use the same genetic material that our human cells use to encode the “blueprints” for making new cells and for running those cells after they’ve been made. The smallpox virus is a good example of a DNA virus. Influenza on the other hand is an RNA virus. RNA is similar, but not identical, to DNA. A major difference is that RNA is significantly less stable than DNA. This lack of stability actually works in influenza’s advantage because it allows the virus to mutate extremely quickly. Most mutations result in a defective virus but some result in a functional virus that is different enough not to be recognized by the body’s immune system. This is called “genetic drift” and it is why there is a new influenza epidemic every year, and the reason why you can get the flu this year even if you have had it in the past. Influenza is also capable of another genetic trick whereby it can swap large portions of its genome (genetic material) with another similar, yet substantially different, strain of influenza. The proteins that are swapped are called hemaglutinin and neuraminidase and they are the “H” and the “N” of the common nomenclature for flu. In 2009, H1N1 caused a pandemic (fortunately the 2009 strain of H1N1 was fairly wimpy) whereas this year it is H3N2 that is the major problem. This swapping of H and N proteins often occur in birds and pigs before the virus hops back into a human host again. This is called “genetic shift” (aka: antigenic shift) and it is the cause of the flu pandemics that sweep the globe every few decades.

Smallpox_virus_virions_TEM_PHIL_1849

The smallpox virus magnified 370,000x by an electron microscope. The loop in the middle of the virus is its DNA genome.

Influenza is a seasonal disease in the temperate regions of the world, annually occurring during the winter in both the Northern and the Southern Hemispheres (remember that January is winter in the Northern Hemisphere whereas June is winter below the equator). No one really knows why this seasonality occurs, but a lot of researchers suspect that it has to do with people spending more time indoors and crowded next to one another when it is cold outside. Flu is spread both by droplets that are aerosolized when someone who is infected with influenza coughs or sneezes, and spread when an uninfected person touches something that a person with influenza has inadvertently deposited virus on by direct contact. The seasonality of influenza is not true in the tropics. At equatorial latitudes it is a year round disease and there can be multiple influenza outbreaks in a single year.

1024px-Sneeze

It isn’t very surprising that most strains of influenza are bred in the tropical and subtropical latitudes where poverty and poor hygiene often exist side-by-side subsistence farming on lands that humans share with hogs and birds (namely chickens). Flu loves to infect pigs, birds, and humans and its trans-species hopscotch is historically a prime culprit in the breeding of new pandemic strains of influenza. The 2009 H1N1 pandemic was a great example of this phenomena, producing a strain that fortunately turned out to be very mild but which very easily could have been a major killer. There is currently an extremely deadly form of avian flu in China called H7N9. The most recent mortality rate for H7N9 is 25% in people who are treated with modern medical care, including mechanical ventilation (aka: life support). In comparison, the mortality of the 1918 Spanish Flu was about 2.5%. Most people infected with this truly awful H7N9 strain of influenza have had direct contact with infected birds, usually chickens, but there have been sporadic cases of human-to-human transmission. Whenever this nasty virus mutates into a form that is readily spread from human-to-human a lot of people are probably going to die.

joni ernst 2

Skipping your flu shot before castrating hogs, a bad idea.

We have several ways to protect ourselves, and perhaps more importantly, our fellow humans, particularly infants, the elderly, and the chronically ill, against influenza. The first proven group of methods are staying home if you are sick, practicing good hand hygiene (hand sanitizer is probably best because most folks don’t wash their hands for the 15 seconds that you really need to to get them clean), and covering your mouth when you cough/sneeze. The proper way to cough/sneeze is into the crook of your elbow, not onto your hand, because your hand touches things and influenza can be spread by direct contact. Second, the seasonality of influenza in the temperate regions of the world is a blessing because it has allowed scientists to predict the strain of flu that will cause problems next year enough in advance to target the annual flu shot to the anticipated problem strain. Actually the flu shot contains the three most likely candidates for the next influenza outbreak and usually the scientists are correct and one of these three strains turns out to be the one that causes the outbreak. Most years the flu shot is 80-90% effective. This year it is only about 35% effective according to the CDC because influenza mutated (change) at the last minute, but 35% effective is still millions of cases of flu prevented and likely thousands of vulnerable lives saved. The flu shot, but not the nasal spray, contains DEAD flu virus and it cannot give you influenza. Some folks can get some mild flu-like symptoms for a day or two, usually the first year that they get the shot, due to their bodies’ immune response (which is what we want) to the dead flu antigens that are present in the vaccine (because they are the reason that it works). The only really common side-effect of the flu shot in my experience is a day or two of slight discomfort at the injection site. The intranasal influenza vaccine contains weakened live flu virus and it commonly does cause upper respiratory symptoms, especially a runny nose but also sometimes a dry cough, that are generally mild but that can be severe enough that it is recommended that asthmatics and other people with chronic lung diseases should not be vaccinated with the intranasal vaccine.

The_Devil

The Devil.

250px-Fluzone_vaccine_extracting

The Flu Shot. Not the same as the devil. Evidently this is a controversial distinction in some circles.

Our final line of defense against influenza is the anti-influenzal drugs, of which oseltamivir (Tamiflu) and zanamivir are the most effective. Unfortunately, the efficacy (how well they work) ranges wildly from year-to-year depending on the strain of influenza that is in circulation. Some years these drugs are >90% effective in decreasing the severity and duration of an influenza infection if taken within the first 48 hours of becoming symptomatic. Other years these drugs are completely worthless because the circulating strain of influenza is resistant to them. Fortunately, the H3N2 strain of influenza that is causing such trouble this year is very sensitive to oseltamivir (Tamiflu), which is why I have been writing prescriptions for it left and right for the past month. And speaking of my day job, that’s all for now folks. Stay well!

 

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Dr. Leonardo Noto

Author Bio: Dr. Leonardo Noto is the nom de plume of a former airborne battalion surgeon who is now in civilian practice. Dr. Noto is the author of four books and he also writes for a medical education corporation that assists medical students, interns, and residents as they prepare for the medical board examinations. Dr. Noto is the proud father of an extremely spoiled 16-month-old American Bulldog who enjoys slobbering everywhere and tearing up things that he is not supposed to! Dr. Noto is an amateur practitioner of muay Thai and Brazilian jiu jitsu and he recently began learning to play the guitar (but he is currently a quite terrible musician, as his neighbors will readily attest).

Remember to discuss all health concerns with your personal physician (I don’t count!) before making any medical decisions. www.leonardonoto.com is intended to present general medical information for entertainment purposes and not as specific guide to any medical treatment. The author has made every effort to present accurate information; however, due to the ever-changing nature of medicine and the intrinsic caveats that are inherent in any particular case, no medical decisions should ever be made based on information gleaned from the internet (duh!). The internet and self-education are great, but they don’t replace your Doc!

The opinions voiced on this medical blog are solely the author’s own and they do not reflect the opinions or values of Dr. Noto’s employers, past or present. Dr. Noto’s medical blogs should never be used as supporting evidence for legal testimony — this is of course obvious to anyone who isn’t a complete moron, but some people are rather stupid.

 

REFERENCES

1. Encephalitis Lethargica: http://nervous-system.emedtv.com/encephalitis-lethargica/encephalitis-lethargica.html

2. Dolin, Raphael. Epidemiology of Influenza. Jul 17, 2014. www.uptodate.com.

3. Dolin, Raphael. Diagnosis of Seasonal Influenza in Adults. Aug 15, 2013. www.uptodate.com.

4. Flu Map of the United States. http://www.cdc.gov/flu/weekly/usmap.htm.

5. What You Should Know for the 2014-2015 Influenza Season. http://www.cdc.gov/flu/about/season/flu-season-2014-2015.htm.

6. Smallpox Virus Electronmicrograph. http://en.wikipedia.org/wiki/Smallpox. Photo Credit: Content Providers(s): CDC/ Dr. Fred Murphy; Sylvia Whitfield.

7. Influenza Virus Electronmicrograph. http://en.wikipedia.org/wiki/Influenza. Photo Credit: Cynthia Goldsmith Content Providers(s): CDC/ Dr. Terrence Tumpey.

8. Fort Riley, Kansas Influenza Ward. http://en.wikipedia.org/wiki/1918_flu_pandemic#mediaviewer/File:CampFunstonKS-InfluenzaHospital.jpg. Courtesy of Wikipedia and the United States Government.

9. 1918 Influenza Mortality Chart. http://en.wikipedia.org/wiki/1918_flu_pandemic#mediaviewer/File:W_curve.png. Courtesy of Wikipedia and the CDC.

10. Awakenings Movie Poster. http://en.wikipedia.org/wiki/Awakenings#mediaviewer/File:Awakenings.jpg.

11.Encephalitis Lethargica Awakenings Oliver Sacks with text. Diane Sawyer interview. www.youtube.com. 

12. H7N9: Severe Illness, High Death Rate. http://www.medscape.com/viewarticle/804596.

13. The Influenza Pandemic of 1918. https://virus.stanford.edu/uda/.

14. Joni Ernst Campaign Image. http://www.blogforchoice.com/archives/2015/01/that-time-joni.html.

15. Guy Sneezing. http://en.wikipedia.org/wiki/Sneeze#mediaviewer/File:Sneeze.JPG. Courtesy of the CDC.

16. The Devil. http://en.wikipedia.org/wiki/File:The_Devil.jpg.

17. List of Vaccine Topics (Flu Shot Image). http://en.wikipedia.org/wiki/List_of_vaccine_topics

The Next Worldwide Pandemic? H7N9 Influenza – New Strain of Flu With A 100% Mortality Rate!

Update: Hot off the press. The Centers for Disease Control now reports 126 confirmed cases of H7N9 in China. 1 person in 5 infected with this new strain of influenza have died of the infection, with the virus seeming to have a higher mortality in older persons (some flu viruses actually have higher mortality in the young, but this is rare). Person-to-person transmission has not been definitively shown but it is suspected in a minority of the cases — a troubling finding for a strain of influenza that now seems to have a 20% mortality rate. In a way viruses with a lower (but still high) mortality rate can actually be more dangerous than viruses with an extremely high mortality rate. Ebola has an 80-90% mortality rate; however, because the virus kills virtually all of it’s victims and kills them rapidly the disease has, fortunately, never caused more than a local outbreak. An influenza virus with a 20% mortality rate, if confirmed, that could spread from person-to-person (still unproven and hopefully not the case with H7N9) is a scary thought indeed.

The H1N1 “Spanish Flu” pandemic of 1918 killed more people than The First World War, so fears about influenza are not just media hype. Influenza usually causes you to feel lousy with fever, chills, myalgias (muscle pains), cough, and gastrointestinal symptoms (especially diarrhea). But a particularly nasty strain can be deadly and not just for the very young and the very old, but for adults in the primes of their lives too. One of the problems with the flu is that many people toss around the term “flu” to describe just about any viral illness. “24 hour flu” and “stomach flu” are common illnesses and nothing to get too worked-up about, but the problem is that neither of these illnesses are actually caused by the influenza virus. Instead, they are examples of people inappropriately tossing out the term “flu” to describe illnesses that are caused by other, less pathogenic viruses. Real influenza virus, especially when a nasty strain is in circulation, can be a really big deal and if you don’t believe me then visit the graves of one of the 30 million people who were killed by the Spanish Flu of 1918! As such, the emergence in China of a new and unique strain of flu, H7N9, that infected and killed three people in February and March of this year has perked up the ears of epidemiologist worldwide and for good reason – it may be the next global pandemic. While H7N9 is currently thought to pass only from birds to people, and not from people to people, that may not remain true for much longer and I’m going to explain why (hold on to your seats young Padawans, it’s going to be a bumpy ride!).

There are three main types of Influenza, conveniently named Influenza A, B, and C. Influenza B is primarily a human disease and it pops up from time-to-time and occasionally causes epidemics (localized outbreaks). Influenza C is almost entirely confined to animals. The type of influenza that causes pandemics (pandemic = a worldwide outbreaks of a disease) is influenza A and this tricky viruses lives in pigs, birds, and humans, loving to wreak havoc in the bodies of all of the above. Influenza A has two especially important viral proteins called hemagluttinin and neuraminidase and these two proteins are responsible for the naming of the different STRAINS of influenza A. There are 16 known types of the hemagluttinin protein and 9 known types of the neuraminidase protein. H1N1, the strain of influenza A responsible for the 2009 flu pandemic, has type-1 hemagluttinin and type-1 neuraminidase whereas H7N9 has type-7 hemaglutinin and type-9 neuraminidase. The combination of H7 and N9 has never been seen before and this means that nobody, including you, has acquired immunity to it — not a good situation!

So what’s the deal with these influenza viral proteins and why the heck do they matter? Hemagluttinin works by anchoring the flu virus to one of your body’s cells, a cell in your nose or in your lungs for instance, allowing the flu virus to penetrate into that cell. Once influenza is inside it hijacks the cell and forces it to make more influenza viruses, essentially turning your otherwise normal and well-behaving nose or lung cell into an influenza factory! Fresh off of the assembly line, these newly produced “baby” viruses then exit the hijacked factory cell using neuraminidase, breaking free to find new cells to infect and then repeating the cycle until before long your body is harboring a raging influenza infection.

 flu

Image: An artist’s rendition of an influenza virus. Viruses exist in the gray area between living and dead. They are capable of reproducing but only with the assistance (generally the involuntary assistance) of true cellular organisms. Viruses infect all forms of life from bacteria, to plants, to animals and humans.                        

The white blood cells of your body’s immune system use hemagluttinin and neuraminidase as a way to recognize the influenza virus and to destroy both the virus particles and the hijacked factory-cells that are producing new “baby” viruses. The problem is that influenza is constantly changing through both antigenic drift and antigenic shift into new forms that your body can’t recognize and that are therefore capable of causing a new infection, even if you’ve been infected with another strain of influenza before, even recently! Antigenic drift is the accumulation over time of minor mutations in preexisting subtypes of hemagluttinin and neuraminidase and this process is responsible for slowly producing new subtypes of these viral proteins over a period of years and decades. For example, originally there was probably only one type of hemagluttinin protein, H1 (let’s just assume it was H1, although H1 is actually just the first one that scientists discovered and it probably wasn’t really the first). Over years-to-decades H1 acquired enough mutations to form a hemaglutinin molecule that was different enough to deserve a new name, H2. This has happened at least 16 times since science has become advanced enough to monitor the process and that is the reason why there are 16 different subtypes of hemaglutinin, all of them potentially capable of producing a new pandemic strain of influenza.

While antigenic drift is a relatively lethargic process, antigenic shift is responsible for rapidly producing novel strains of influenza A and it is the process that produces the strains that are responsible for most influenza pandemics. Antigenic shift occurs when two strains of influenza – say H1N1 and H7N9 – both infect the same cell in, for example, a chicken. The protein subunits and the genetic material that code for them (the “blueprints” for the proteins) sometimes get mixed up and you end up with a cell that might produce H1N9 or H7N1, a novel strain of flu that no one has ever been exposed to. Because domestic pigs and chickens tend to live cramped and unsanitary conditions on farms, especially in developing countries, these animals are breeding factories for new strains of influenza. And since domestic pigs and chickens also live in close proximity to humans (farm workers), it doesn’t take much for a new strain of influenza to be born.

chickenpigs

Images: Domestic Chickens and Pigs in China: The source of most of history’s influenza pandemics. Note that the 2009 H1N1 pandemic was an exception in that it likely originated from a pig farm in Mexico.

Not all strains of influenza A infect are equally good at infecting birds, pigs, or humans – some prefer birds, some prefer pigs, and some prefer good ole’ mankind. But the problem is that influenza mutates (changes) rapidly so that a virus that only infects birds today may hop to humans tomorrow. Similarly, not all strains of influenza are terribly virulent (virulent essentially means capable of causing a nasty disease), some are  actually quite mild whereas others are truly horrible. Luckily the H1N1 strain of influenza A that caused the 2009 outbreak was mild (unless you were a pregnant woman, in which case it was highly fatal), but we won’t always be so lucky. Interestingly, most of the damage caused by influenza infection probably isn’t caused by the virus itself but rather by your body’s inflammatory response to it. When triggered by a particularly nasty strain of influenza, this inflammatory damage is a set up for acute respiratory distress syndrome – a disorder in which inflammatory damage to the lungs causes them to become flooded with fluid and generally dysfunctional. To add insult to the injury, widespread inflammatory lung damage provides an excellent “petri dish” for bacteria to grow in, making influenza victims highly susceptible to developing atypical pneumonias from bacteria that normally don’t grow in the lungs. Staph aureus pneumonia is particularly notorious for killing flu victims – staph aureus is the same bug that causes skin abscesses and it doesn’t take much of an imagination to picture what it would do to your fragile lungs!

Fortunately H7N9 doesn’t appear to pass from humans-to-humans, at least for now. All of the known cases of this disease have been attributed to humans being in close contact with infected animals, and thank goodness for that because all three of the people who are known to have been infected with H7N9 died of the disease. But like all strains of influenza H7N9 is constantly mutating, probably even as you read this article. No one can predict with certainty whether H7N9 will fully make the leap to humans and become a human-to-human transmissible disease. Yet history shows that the question is not when we will have another deadly flu pandemic, but when.

Dr. Leonardo Noto

Physician and Author of Medical School 101, Intrusive Memory, The Life of a Colonial Fugitive, and The Cannabinoid Hypothesis –> (Click on the book covers on the right to check out my books!).

Author Bio: Dr. Leonardo Noto is the nom de plume of a former airborne battalion surgeon who is now in civilian practice. Dr. Noto is the author of four books and he also writes for a medical education corporation that assists medical students, interns, and residents as they prepare for the medical board examinations. Dr. Noto is the proud father of an extremely spoiled 12-month-old American Bulldog who enjoys slobbering everywhere and tearing up things that he is not supposed to! Dr. Noto is an amateur practitioner of muay Thai and Brazilian jiu jitsu and he recently began learning to play the guitar (but he is currently a quite terrible musician, as his neighbors will readily attest).

Remember to discuss all health concerns with your personal physician (I don’t count!) before making any medical decisions. www.leonardonoto.com is intended to present general medical information for entertainment purposes and not as specific guide to any medical treatment. The author has made every effort to present accurate information; however, due to the ever-changing nature of medicine and the intrinsic caveats that are inherent in any particular case, no medical decisions should ever be made based on information gleaned from the internet (duh!). The internet and self-education are great, but they don’t replace your Doc!

The Life of a Colonial FugitiveIntrusive Memory E-CoverMedical School 101The Cannabinoid Hypothesis

References

How the Influenza Virus Changes. http://www.cdc.gov/flu/about/viruses/change.htm. Accessed 23 MAY 2013.

Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus. The New England Journal of Medicine. Vol. 368 No. 20. 16 MAY 2013.

Images Courtesy of Wikipedia/Wikimedia Commons and Google Images.