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Uneasy Lies the Head That Wears the Flu

Infectious diseases (ID), as those who read my not-so-secret other blog know, is without a doubt the most interesting speciality of medicine. Every interesting disease is infectious in etiology. What is cool about ID is that it has connections into almost every facet of human culture and history.

I note that at some point I have gone from being the young whippersnapper to the Grandpa Simpson at my hospitals and am one of the few who has been around long enough to be a repository of institutional memory. I remember what it was like 20 plus years ago, when no one consistently washed their hands, when all S. aureus (S. aureui?) were sensitive to beta-lactams and we wore an onion on our belt, as was the style of the day. Oh the changes I have seen.

Besides remembering the not so good old days of my professional career, ID keeps me reminded of how the world used to be in the past. Medicine used to be about the epidemics that would routinely sweep across the world. Polio, measles, mumps, scarlet fever, rheumatic fever, tuberculosis and on and on. I occasionally see TB but thanks to modern medicine many of these scourges have mostly faded from medical practice in the US. Not a one, I might add, has faded due to the efforts of alt med practitioners.

Influenza still gives me pause. It is, as infections go, quite the tricky virus and it remains a difficult beast to treat and prevent. Which is a drag as it remains one of the more consistent causes of infectious morbidity and mortality.

Epidemics and pandemics of influenza have been a reliable feature of the human condition since the gasping oppression first hit Europe 500 years ago. But it is never as simple as flu comes, people are sick, flu goes away.

There are three broad issues in how people respond to infections. There is the host and how able they are to deal with infections: genetic, nutritional, immunologic and other comorbidities that increase or decrease the chance that an individual patient may succumb to a given infection. This century has been fascinating in elucidating the increasing number of genetic variations that in part determine the outcome of an infection. There are those who scoff at personalized medicine, but I look forward to the day when I can smear my patient’s DNA out on a slide, point and say ‘look there’. There is the polymorphism that makes you susceptible or resistant to an infection. In part it is the terrain, but not in the manner the germ theory denialists would have us believe.

There is the effectiveness of the antibiotic, an issue of declining importance as increasing microbial resistance slowly pushes us into the post-antibiotic era. It is also the simplest factor in the interplay of forces that determine the outcome of an infection.

And then there is the intrinsic virulence of the infecting organism. Some organisms are relatively simple in their ability to infect and kill, and others, like S. aureus, are much more devious. I think of S. aureus as the Professor Moriarty of infections. Maybe influenza is the Ra’s al Ghul. I don’t know. Stretching for a metaphor. But looking over the history of influenza, you realize it has a nasty habit of coming back, new and improved, to wreak havoc.

On SCAM sites you can often find the opinion that influenza isn’t that bad, or that the medical-industrial complex overstates the morbidity and mortality of influenza to scare people into vaccination. Sometimes the flu season is mild and sometimes it is not. But I remember.

Those who do not remember the past are condemned to underestimate the morbidity and mortality of influenza.

~ George Santayana. Sort of.

Most in ID have the 1918-1919 pandemic in the back of our minds. In a world before jet travel, influenza went around the world three times, killing about 5% of the world. Some died directly from the flu, some from bacterial superinfections, and some, perhaps, from excessive aspirin consumption. The pandemic was also associated with a marked increase in lost pregnancies, perhaps as many as 1 in 10.

The virus in 1918 appears to have had the dreaded combination of both infectivity and virulence. They have reconstructed the influenza from specimens in the Alaskan permafrost and it was particularly virulent.

2013 is not 1919. We have better nutrition, better understanding of disease spread, antibiotics and better health care (no, not the ‘health care system’ in the US but the ability to treat the ill).

But there is always the worry that influenza will return in a form that is both very infectious and extremely virulent. And it is probably not ‘if’ but ‘when’ it will happen.

The last couple of years there have been some worrisome influenzas. First there is the bird flu, H5N1, that has been slowly making its way across the world. It has high mortality rates, with 60% of cases dying of the disease. It is not, however, particularly infectious as it has decreased affinity to human receptors to which it needs to bind to start disease:

The affinity of the influenza virus to different sialyl-sugar structures is an important determinant of range and pathogenicity in the viral host.14,15 Human influenza viruses preferentially bind to α2,6 sialyl glycan, whereas most avian viruses bind to α2,3 sialyl glycan. Q226L in the HA protein, which was first reported in H7 field viruses, as well as H5 subtypes, was expected to bind strongly to α-2,6 human-like receptors.

It is why those who have developed H5N1 have had to had close and prolonged contact with birds before getting the disease. They had to suck in a lot of influenza before it could cause disease.

However it would only take a couple of mutations or acquisition of a new chunk of DNA for the H5N1 strain to become far more infectious, although as a consequence it could lose some virulence. The two do not always go hand in hand, since it may not pay for the virus to be too virulent. There is, as an aside, some information to suggest that HIV, perhaps due to declining opportunity for spread due to safe sex etc, is becoming more infectious/virulent.

But for now H5N1 is a low grade uneasy worry in the back of the mind. Is it going to acquire new DNA? Mutate? Both? Neither? Fade away like an old soldier? Got me. If I could predict the future I would not be writing for this blog

Then there was H1N1.

Getting in the wayback machine I can see my first response to H1N1, published Tuesday, 28 Apr 2009 on my other blog:

I had five days off with my youngest for his spring break, and we spent the time at the Oregon Coast. Great time. No TV, only dial up internet, no newspaper, no contact with the real world. So I get back on Sunday and my wife tells me we are in a State of Emergency.

What?

We have closed the borders with Mexico

No way. Why?

Because of Swine Flu.

Huh? Flu season is over. Where in the hell did that come from?

Whether or not this is going to be a pandemic strain, and whether it is going to kill off 2% of the world like the 1919 pandemic, I can’t say. It may just dribble off the court and be a false alarm. I hope so.

However, people seem to be in panic mode real soon. As I write this there are 40 cases in the US, no deaths. People are wearing masks around town and asking for oseltamivir. Some people are keeping there kids home from school, even though no cases reported in Oregon.

We are just finishing the flu season. There were about 30,000 documented cases of flu, 55 deaths documented in kids, and thousands of extra deaths in adults. And it was a slow year.

There is a Cinco de Mayo party coming up (what day is that?) and concern was expressed about having the kids attend. Maybe 30,000 people die each year in car accidents. If you really want to protect you kids you would make sure they got a flu shot and not let them in a car. And don’t get me started on deaths from guns.

Swine flu? We will see. “Prediction is very hard, especially when it’s about the future” – Yogi Berra” Or perhaps it was “I predict the future to be full of pic-a-nic baskets, Boo-Boo.” Ask a psychic, not me.

I would prefer the government to over-react than under-react with infections. They (infections not government. Or did I get it backwards?) can spread to fast and kill too quickly. It is better safe than sorry. One of these days, be it avian flu, or this swine flu, or another strain, flu will come out of nowhere and kill a boatload of people. If it is going to kill lots of people, there is not much we can do for now except not inhale. Worked for President Clinton.

H1N1 turned out to be better than it could have been but worse than I would have wanted. An amazing thing about the H1N1 epidemic was that in Portland it was just severe enough to hit our peak capacity: every ICU bed full, all ventilators in use and if another patient came through the door needing advanced care we had nothing. They would die. Instead, the pandemic faded. There were also deaths I am not accustomed to seeing: the young, the pregnant, and we had two deaths from H1N1 encephalitis.

World wide H1N1

resulted in an estimated range of deaths from between 151,700 and 575,400 people who perished worldwide from 2009 H1N1 virus infection during the first year the virus circulated. A disproportionate number of deaths occurred in Southeast Asia and Africa, where access to prevention and treatment resources are more likely to be limited.

Mortality not as awful as prior pandemics at least in terms of numbers killed, unless you were the one who died. It was more remarkable as to who died and it was the worst flu season of my career.

It will be interesting to see what the epidemiology of this year’s flu season will be. It was a busy year with a lot of influenza in the outpatient setting but my sense is that there was little impact on my hospitals. There was not the surge of the critically ill in the ICU we saw with H1N1.

And now? There is H7N9 in China, a new bird flu.

Virulent? Seems to be. About 17 of 87 cases have died, about 20%, a number that is a moving target. Infectious? Best I can tell human to human transmission is perhaps possible, although most cases are from poultry. It apparently has low virulence in birds but kills humans, so it has the potential to spread widely by way of migratory birds, a worry with H5N1 as well. And the entire human population is at risk; with no prior H7N9 infections in humans no one is immune.

And it apparently has good potential:

The gene sequences also indicate that these viruses may be better adapted than other avian influenza viruses to infecting mammals. For example, the presence of Q226L in the HA protein has been associated with reduced binding to avian-like receptors bearing sialic acids linked to galactose by α-2,3 linkages found in the human lower respiratory tract,1 and potentially an enhanced ability to bind to mammalian-like receptors bearing sialic acids linked to galactose by α-2,6 linkages located in the human upper airway.

It would appear that H7N9 is not to be the next pandemic strain to repeat the disaster of 1918. Not quite there genetically. One of these days, though, it will happen. Infectious, virulent and a susceptible population and influenza will kill a lot of people.

Only the dead have seen the end of influenza.

~ George Santayana. Sort of.

Posted in: Basic Science, Epidemiology, History, Science and Medicine

Leave a Comment (7) ↓

7 thoughts on “Uneasy Lies the Head That Wears the Flu

  1. norrisL says:

    In 2002 I very nearly saw “the end of influenza.” I would wake up in a hot sweat and barely get myself 3 metres to the toilet. Then I would wake up with massive cold shivers. I was delirious. My wife was barely better than I, but my daughter was 8 weeks old. I cannot believe that she did not get it. If she did get it, I have little doubt that she would have died without an enormous amount of medical intervention. We have flu vacc every year. Even if the now almost 11 year old Charlotte doesn’t want the vaccine.

  2. windriven says:

    “The two do not always go hand in hand, since it may not pay for the virus to be too virulent. There is, as an aside, some information to suggest that HIV, perhaps due to declining opportunity for spread due to safe sex etc, is becoming more infectious/virulent.”

    Hmmm… I wonder if someone can clarify this for me. It seems to have a Lamarckian cast that runs counter to my (admittedly imperfect) understanding of evolutionary theory. I do not understand how declining opportunity to spread would preferentially bias survival of more virulent strains or, moreover, how broad opportunity to spread would bias survival of less virulent strains.

  3. FulfilledDeer says:

    Windriven

    This is sort of a guess, but the quicker you kill the host, or even if you do kill the host, the less chance you have to spread. Herpes simplex is everywhere because it doesn’t usually kill the host. Ebola…not so much.

  4. BillyJoe7 says:

    windriven:

    “I do not understand how…broad opportunity to spread would bias survival of less virulent strains”

    All else being equal, for a virus to survive to reproduce, it would be an advantage to be both virulent and infectious. But it’s all a matter of degree. If the virus is not sufficiently virulent, the host’s defences are more likely to kill the virus. No advantage there. As the virulence of the virus increases, the virus becomes capable of killing the host. If the virus dies along with the host, again no advantage. But if, simultaneously as it’s virulence increases, it’s infectivity also increases, the virus can survive the killing of its host by spreading to another host. Of course, there is no advantage if the virus is so virulent that it kills off all hosts. Unless, of course, the virus has a “reservoir” in another animal species.

    “I do not understand how…declining opportunity to spread [by the hosts' us of condoms] would preferentially bias survival of more virulent strains”

    All else being equal, for a virus to survive to reproduce, it would be an advantage to be both virulent and infectious. But, despite increasing infectivity, the hosts’ use of condoms could still reduce the opportunity of the virus to spread. But no defence is perfect so, occasionally, a small number of viruses will break through the defences. In this situation, it would be an advantage for them to have increased virulence.

  5. Alia says:

    A few years ago I went to a panel entitled “What will kill off humankind?” It was a kind of interdisciplinary meeting, with some sci-fi writers and some scientists. There was also a professor of microbiology who said something along the line “The next flu pandemic is just a question of time. Get your shots”. And so I do.

  6. windriven says:

    @BillyJoe and FD

    Thank you both. I’m still struggling to accept the virulence argument – though the infectiousness argument is clear. But I’ll write that off to a personal failing on my part. Thanks again.

  7. chrismo says:

    “Those who do not remember that influenza has an RNA genome (*ahem. paging Dr. Crislip) are condemned to have trouble interpreting the data.”

    –This persnickety virologist

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