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Does treating fever spread influenza?

Influenza

One of these things is not like the other

Treating a fever with medication like Advil or Tylenol is reflex action when we come down with colds and influenza. But could treating fevers actually worsen an illness and contribute to its spread in the population? That’s the impression you may have gained from the headlines and press last week, where antipyretics (fever-reducing medications) were described as some type of “anti-vaccine”:

Fever-reducing meds encourage spread of flu: McMaster report

Taking over-the-counter flu medication to cut your fever might help you feel better, but it might not be so good for the people you come into contact with.

When it comes to fever, your mother really did know what’s best

Who would have thought that the simple giving of a fever reducing agent, to either one of our family members or ourselves before we go off to school or work, may inadvertently lead to the death of someone that we see that day?

Use of fever-reducing drugs may lead to tens of thousands more influenza cases

The bottom line is that fever suppression increases the number of annual cases by approximately five per cent, corresponding to more than 1,000 additional deaths from influenza in a typical year across North America.

The paper, published in Proceedings of the Royal Society B, entitled “Population-level effects of suppressing fever“, got a lot of press: Google says 116+ news articles. And it’s not surprising. Who can resist an “Everything you know is wrong” story? It’s a great hook and it seems to call into question one of the most frequent reasons we take medication. Treating fever, especially in children, has been the norm for decades. I can still recall some of my childhood cold- and flu-related feverish nights, 30+ years on. The vivid dreams that felt like hallucinations, the sweating and shivering, and tossing and turning for hours. I’d lie awake waiting for the next dose of Tylenol so I could sleep. Influenza infections can be miserable and exhausting, and have the potential to do serious harm, killing thousands each year. Analgesics that reduce fever, aches and pains may help people get to sleep and to stay asleep – something you covet when you’re bedridden and ill, or caring for your sick child who’s radiating heat.

David Earn, the lead author of the paper, is a professor of mathematics at McMaster University in Hamilton, Ontario. The analysis considers the impact of treating the fever of influenza infections and the population-level consequences. (It’s not available free online, unfortunately.) There is no new medical data in this paper. It is, in the authors’ own words, a “theoretical argument” – a mathematical model based on a series of assumptions:

  • Fever is beneficial, not harmful
  • Suppressing fever with antipyretics may increase the extent and duration to which the virus is shed
  • Treating fever with antipyretics (drugs that reduce fever) increases the probability that the sick will interact with the well
  • Sick people using antipyretics will therefore shed more viruses to more people, causing larger epidemics, and more deaths from influenza

Let’s look at these assertions sequentially to assess their validity.

Fever – is it beneficial?

While reaching for analgesics to treat a fever is a reflex action for many, there is some evidence to suggest that fever is a beneficial adaptive response in the infected. Clay Jones discussed fever phobia in 2012 and while he argues that it’s often unnecessarily over-treated, he’s not convinced there’s a sound medical basis for leaving it untreated.

There is merit to the idea that fever has a beneficial purpose but it remains somewhat controversial. Elevating our core body temperature in response to infection is a primitive and almost universal response, seen even in cold-blooded species. Lizards have been observed staying in the sun longer and fish seeking out warmer water when ill for example. This implies at least that there is some degree of survival advantage in being able to develop a fever. Some bacteria and viruses do grow poorly when exposed to higher temperatures. Iron is required for growth by many pathogenic bacteria, and it appears that fever decreases availability of it in the blood. Test tube studies have shown that elevated temperatures may increase the activity of various components of the immune system. There are a few non-primate experiments, particularly in rats and rabbits, that have shown improved outcomes with fever and even some human studies showing prolonged symptoms when fever is treated aggressively. But everything seems to increase the activity of various components of the immune system in test tubes, and those studies were small and difficult to extrapolate to all humans or to all specific fever causing infections. Plus there is also data showing that the immune system may actually become impaired during high fevers above 104-105 degrees. And there is also evidence in animals and human patients that raises concerns of poorer outcomes from some illnesses, particularly in critically ill patients, with very high fever. It is a mixed picture essentially and the jury is still out. Regardless, any benefit of fever is likely so minimal that it would not preclude treatment of a miserable toddler with a temperature of 102.

Mark Crislip has written about the merits of fever as well:

There are numerous beneficial physiologic effects that occur as part of the febrile response. Virtually all aspects of the physiologic response to infection are, dare I say it, boosted, and many wings of the immune system function better at higher temperatures. I feel the naturalistic fallacy creeping over me: fever is an almost universal response to infection that evolved millions of years ago and helps enhance the response to infection. So suppressing a fever during infection should be bad. Right? This becomes a little less clear cut. There are issues as to how the fever is suppressed: mechanical, such as ice or alcohol baths. Pharmacologic: acetaminophen, steroids, aspirin or nonsteroidal anti-inflammatories, all of which have effects that go beyond suppressing fevers. What infection is occurring? A response that has evolved as a response to the infections found on the plains of East Africa could be counter productive against diseases of modernity like Pseudomonas sepsis in the ICU or MRSA endocarditis in a heroin user.

With respect to data on influenza and fevers, Crislip points to this review which notes the following:

In animal models, treatment with antipyretics for influenza infection increases the risk of mortality. There are no randomized placebo-controlled trials of antipyretic use in influenza infection in humans that reported data on mortality and a paucity of clinical data by which to assess their efficacy. We suggest that randomized placebo-controlled trials of antipyretic use in human influenza infection are urgently required, and that these are sufficiently powered to investigate a potential effect on mortality.

The bottom line in the medical literature, nicely summarized by these two SBM authors, is that fevers may offer beneficial effects, but there is no clear evidence of harm from treating them. So it seems premature to conclude that fevers in influenza confer meaningful beneficial effects.

Does suppressing a fever lead to more virus shedding?

The authors make the following statement to support their claim that treating fevers lead to more virus shedding:

To our knowledge, the only published experiment concerning the effects of antipyretic treatment on influenza viral shedding was conducted in ferrets (considered the best animal model for human influenza).

And they’re absolutely correct. There is no published evidence in humans to demonstrate that treating the fevers of influenza leads to more virus shedding. The authors cite what they believe to be supporting evidence in colds and chicken pox infections, but their relevance to influenza is unclear. The only other indirect evidence that seems relevant is a paper that they state shows a correlation between antipyretics and influenza A, but the abstract notes this was due to a second, bacterial infection, so it’s not relevant to this argument. I’m not a fan of relying on animal models to make conclusions about human outcomes, especially when I can easily find contradictory information, such as mice models that find acetaminophen reduces the morbidity associated with influenza without compromising immune responses. On balance it seems reasonable to conclude that there’s no convincing evidence to suggest that treating fevers will lead to more virus shedding.

Does treating a fever increase the likelihood that the sick will interact with the well?

The authors argue that a proportion of infected individuals will treat their fever. This proportion (“p”) will therefore increase their probability of infecting others to some extent (“fp“). The reproduction number (“R”) is the number of secondary infections caused by a primary infection. (In short, how many people does each sick person infect?) R is therefore proposed to increase by a factor of fp because of antipyretic use. The net effect is that treating fevers will increase that reproduction number, and therefore the overall size of the influenza pandemic (“Z”). These calculations are described in detail in a free supplement to the paper.

Are those with influenza infections more likely to interact with the well? The authors offer no justification for this assumption, perhaps believing it to be self-evident. They simply state:

An individual whose fever has been reduced is likely to feel better and is therefore more likely to interact with others.

But there’s no evidence provided to support this statement. It’s a hypothesis that’s completely unsubstantiated. It’s possible, yes. But it’s also speculation. It could be that those with treated infections don’t change their habits enough to increase their contact with others. There is no evidence to answer the question.

Will more viral shedding lead to larger epidemics, and deaths from influenza?

The authors try to establish a relationship between the illness, viral shedding, and transmission of the influenza virus. Their approach is as follows:

In order to infer the overall transmission implications, we need an estimate of the natural infectivity of influenza, i.e. the probability that a susceptible contacted by an (nonantipyretic-using) infectious individual will become infected. We are not aware of direct measurements of this probability, so we use published estimates [42] of the household secondary attack rate (SAR) as a proxy.

Yet another estimate in the absence of direct evidence. It’s not clear that infections within a household are a relevant comparator to the broader population. So this another assumption based on indirect data of questionable relevance. There is some research in this area which is somewhat supportive of the idea that virus shedding is generally correlated with the severity of the infection. However, it’s been established that virus shedding starts before symptoms like fever appear, and children start shedding earlier than adults. In addition, shedding can continue for days or even weeks after the symptoms have disappeared. It’s also important to note that 30-50% of influenza infection may not cause illness. And if they don’t cause illness, there’s no need to treat a fever. On balance, there’s no substantive or persuasive evidence to demonstrate that the antipyretics will have any meaningful influence on the degree to which influenza is spread in a population.

The remainder of the paper is the description of a population-based model estimating the negative consequences of treating the fevers of influenza. The authors estimate that most influenza fevers are treated with antipyretics (and again, don’t provide any direct evidence), ultimately concluding that treating fevers with antipyretics increases the spread of influenza by “at least 1%”, and suggesting that “at least 700 deaths per year” could be prevented in the United States alone by avoiding antipyretic medication when treating influenza. To the authors’ credit, they use a range of probabilities for each of their estimates. But in the absence of establishing cause-and-effect to any meaningful degree, this reminded me more of tooth fairy science than of a serious discussion of epidemiology. The authors paint a correlation between the harms of antipyretic use with the indiscriminate use of antibiotics, a comparison that falls flat given the good evidence of harms with antibiotic use, and the speculation throughout this analysis.

Conclusion

The idea that treating the fever of influenza with medication leads to more deaths in a population is a hypothesis. Critically, the authors fail to provide adequate scientific justification for their approach, nor do they substantiate any of their key assumptions with real world data. While successful in gaining media impressions and potentially frightening people away from treating the fevers associated with influenza, the paper fails to offer any credible evidence to support their claim that antipyretics have serious, negative population-level consequences. While it’s perfectly fine not to treat a fever, there is no convincing evidence to suggest that you’re putting others in the population at risk if you choose to do so.

Reference

Earn D.J.D., Andrews P.W. & Bolker B.M. (2014). Population-level effects of suppressing fever, Proceedings of the Royal Society B: Biological Sciences, 281 (1778) 20132570-20132570. DOI:

Posted in: Epidemiology, Pharmaceuticals, Science and Medicine

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55 thoughts on “Does treating fever spread influenza?

  1. windriven says:

    “[T]he paper fails to offer any credible evidence to support their claim that antipyretics have serious, negative population-level consequences. While it’s perfectly fine not to treat a fever, there is no convincing evidence to suggest that you’re putting others in the population at risk if you choose to do so.”

    Then again, there is no compelling evidence that treating moderate fever due to influenza does any particular good. And there is, if nothing else, plausibility to the notion that those whose symptoms are treated will be more likely to engage with other members of the community.

    Perhaps the real story should be along the lines of: don’t be a Typhoid Mary – if you’ve got influenza, take two Tylenol but stay the hell away from me.

    1. WilliamLawrenceUtridge says:

      Assuming the lack of visible symptoms while shedding is an evolutionary response to intra-group pressure (i.e. people who were visibly sick right away got stabbed or abandoned so they wouldn’t infect the group, thank you Sheldon Cooper), here is yet another opportunity for human reason to overcome the blind cruelty of unguided evolution. Control the fever, and prevent transmission through isolation.

      I wish that we could simply stop the world for a month. Everybody stocks up enough food and stays home for 30 days. We could probably eliminate a significant proportion of lethal diseases this way.

      Plus, I could get through my netflix list.

      1. tmac57 says:

        WLU- I find your statement completely unfounded…there is no way you are getting through your Netflix queue in only 30 days!

        ;)

    2. Greg says:

      …stay the hell away from me.

      Couldn’t agree more – especially in the workplace! Many people seem to feel some kind of obligation to work while sick, not considering the fact they could be infecting others, which impacts the health of other employees and their families and costs employers in lost productivity. Even worse for me is I am a contractor so I don’t get paid for days I am off. Whenever anyone at work says they’re feeling ill, I avoid them like the plague. I’m also careful when riding public transit – I never touch anything barehanded and if any riders are coughing uncontrollably, I move away from them.

      Thankfully I have a pretty good immune system – in recent years I’ve seldom been ill for more than 24 hours and very often I will feel better after 6 – 8 hours when I feel like I’ve come down with a cold. I can’t say if I’ve ever had the flu – certainly not as an adult.

    3. alexd says:

      It’s important to remember that “feeling better” is definitely a “particular good” and absolutely deserves weight when justifying a treatment plan. It may not reduce the course or severity of the illness, but relieving uncomfortable symptoms is a valid reason to take a medication. The burden of evidence falls heavier on the anti-pyretic side because of the subjective benefit to the patient of increasing comfort.

  2. windriven says:

    30 days isn’t long enough. I have books stacked up that I haven’t had time to read that will soon start yellowing.

    1. Chris says:

      Oh my! Yes! I have a stack in my bedroom, plus I actually had to return two large tomes to the library because other books I had to check out other books I had on hold. Plus I have some DVDs I’d like to watch.

      In the last five or so years I have not had any kind of serious fever. The last time I felt very sick I was able to watch DVDs of the most of the Farscape series.

      The thing that has changed is that I get a flu shot every year. This year the “flu” manifested itself as a mildly scratchy throat and a couple of nights of needing ten hours of sleep. Apparently lots of folks are down and out with some kind of illness, I guess I may have been exposed to one of the flu strains. But I suffered very little because my immune system had been “educated.”

      (oh, rats! I just thought of something. When I went to the library today to pick up some holds I noticed near mine a book on “superimmunity” waiting for someone else. I should have put a wee note inside saying: get a flu vaccine!)

      1. Chris says:

        Bad grammar: “books I had to check out other books that I had on hold.”

        It is still a clumsy sentence.

        1. windriven says:

          It’s the thought that counts ;-)

  3. daedalus2u says:

    I need to ask what is the null hypothesis, and what data is there that addresses that null hypothesis.

    Everyone always wants to feel “good”. If medicines were to be chosen based on what made people feel “good”, the combination of heroin and cocaine would be a best seller.

    How you feel is not always a good indication of how well you are doing.

    People who feel well, usually go about their daily lives as “normal”, interacting with the people they normally interact with. Children go to school, parents go to work, people go shopping, ride mass transit, go to meetings, go to movies, ride on planes.

    It is disingenuous to claim “there is no evidence”.

    “Are those with influenza infections more likely to interact with the well? The authors offer no justification for this assumption, perhaps believing it to be self-evident. They simply state:
    ‘An individual whose fever has been reduced is likely to feel better and is therefore more likely to interact with others.’ [duh]
    But there’s no evidence provided to support this statement. It’s a hypothesis that’s completely unsubstantiated. It’s possible, yes. But it’s also speculation. It could be that those with treated infections don’t change their habits enough to increase their contact with others. There is no evidence to answer the question.”

    When people feel sick and stay home in bed, they reduce their contact with others. When those sick feelings are masked with drugs and people go about their normal lives, they maintain their contact with other, normally healthy people.

    No evidence? Please, this is SBM. That is EBM plus critical thinking. We are not idiots. “Completely unsubstantiated”? No. There is substantial prior plausibility to this hypothesis. Fever is a highly conserved infection response; even insects upregulate their temperature to counter infections.

    Sickness behaviors are universally experienced. Why? Presumably because organisms that exhibited sickness behaviors out reproduced organisms that did not. “Flu-like symptoms” are observed in many disorders, not just flu. “Flu-like symptoms” are conserved sickness feelings which physiology triggers so as to promote certain sickness behaviors. “Flu-like-symptoms” can be triggered in the absence of infectious agents. Presumably such symptoms are not a necessary part of an infection, but are part of a triggered response to an infection.

    My own hypothesis is that physiology triggers sickness feelings (feeling weak and crappy), so that one doesn’t run around using resources such as ATP. The capacity to produce ATP is limited, and a just-in-time ATP production allows more ATP to be used for reproduction. The only way that physiology can induce resting behaviors is by making the organism feel weak and crappy; a “feature”, not a “bug”.

    What the proper null hypothesis should be:

    “Sickness behaviors are universally observed and so very likely evolved because they are adaptive. Interfering with highly conserved sickness behaviors will likely have adverse effects. Is it demonstrated that interfering with sickness feelings and sickness behaviors does not have adverse effect?”

    The default is “first do no harm”.

    1. Hakainokami says:

      People who don’t have sick days are going to go to work sick, tylenol or no tylenol. Ditto for people who have no one else to go grocery shopping run errands etc. If it has to be done it will be done while sick regardless of tylenol. So you would have to show that people substantially increased their contact with well people past what they would have done without antipyretic use. You can’t just assume that.

      1. Greg says:

        Many employers tell people to stay home when they are ill and will at times send people home out of concern for the other employees. I agree that many will probably go to work anyhow as they don’t bother to consider the ramifications of their actions. I am likely an exception, though I won’t get paid, I will stay home to take care of myself, in the hope that by doing so, I will recover more quickly. A little bed-rest at the right time can work wonders. In my own experience, when I’ve come down with flu-like (or cold-like) symptoms and gone to bed immediately I’ve been well again in as little as 4 hours. It makes sense to seek rest when warranted to allow your body to mount an optimal defense.

      2. Beth says:

        I think it’s a reasonable assumption that people who feel better will have more contact with others than people who are suffering the effects of a flu like illness. Sure, they will still go grocery shopping, run errands, etc. but, my experience is that when I don’t feel well, I reduce such excursions to the whatever extent that I can and ask others to do errands and shopping when possible.

    2. Andrey Pavlov says:

      I’m going to disagree with you D2u. There is much more nuance here and it sides well with Scott on this one.

      The first major assumption is that anti-pyretic treatment will change subsequent behavior and that said change will be enough to cross a threshold such that more people become infected.

      You rightly state that improvement of symptoms is likely to increase mobility and get people out of the house. But you then make the equally unsubstantiated claim that they would return to normal behavior. I’m sorry, but that fails my critical thinking test.

      So the baseline assumption is that you are homebound (or otherwise have your range of mobility diminished) and that treating with an antipyretic will make you feel better to the point where it will significantly alter your behavior. This neglects the people that will remain at the same restricted mobility and range and just be happy to feel a bit better. It also neglects the fact that an anti-pyretic will not make you feel normal it will only make you feel better from the fever and some myalgias. The rest of the disease process is still in play. So the second implicit assumption is that an anti-pyretic will actually lead to a significant change in behavior, and that is far from established.

      Next, you infer that once the anti-pyretic makes you feel better that you will then act normally. This is patently absurd. You don’t have the flu (and note this is flu not flu-like illness) and take a Tylenol and suddenly feel 100% fine such that you completely forget you have the flu. People will still take extra precautions, you will still warn others that you feel better but still have the flu, you will wash your hands more, touch less things, use hand sanitizers, and so will others around you. In other words, the idea that you will return to normal behavior is just absurd. Yes, there will be some rather inconsiderate people that do not take any additional precautions or warn others that they are ill at all (and be in such a state that others somehow won’t notice anyways), but those must be a small percentage of the population.

      So I agree with Scott here – there is no evidence to substantiate that the sort of necessary behavioral changes actually happen and enough confounders and reason to believe that they wouldn’t – or if they did be mitigated by secondary illness behaviors – that this sort of analysis is just a random stab at some possible outcome. Sure, given all the assumptions made by the authors we will have that outcome. But there is little justification – even on prior plausibility and SBM standards – to think that this would happen. It is arguing how many angels can dance on the head of a pin.

      1. windriven says:

        “The first major assumption is that anti-pyretic treatment will change subsequent behavior and that said change will be enough to cross a threshold such that more people become infected.”

        Andrey, I’m with Daedalus on this one. I readily accept that the available evidence doesn’t break hard in any particular direction. But based on simple observation those who feel better interact more. Further, the general community is less likely to avoid contact with someone who appears relatively well than someone who is clearly ill.

        Mark Crislip advocates strenuously for influenza vaccination of health care workers every autumn. Influenza is transmitted by contact and by aerosol. One might argue that hospitalized populations are at increased risk. But that does not suggest that non-hospitalized populations are at no risk.

        The evidence is weak. But absence of evidence is not evidence of absence. In the absence of evidence isn’t prudent exercise of common sense reasonable?

        1. Andrey Pavlov says:

          But based on simple observation those who feel better interact more

          Yes, except that is an assumption itself. How much more? Is it enough to make a difference in and of itself? Does it overcome the equally valid and general observation that people who are sick – regardless of how they feel – still act differently than if they were not sick, in manners that decrease the likelihood of spreading infection? Do people around them who are not sick not also have altered behaviors?

          Further, the general community is less likely to avoid contact with someone who appears relatively well than someone who is clearly ill.

          Correct, but implicit here is the assumption that taking an anti-pyretic will make you appear well to others. I don’t think that is a reasonable assumption. You don’t have influenza, take an anti-pyretic, and suddenly nobody can tell you are ill. Unless you have some sort of magical Tylenol that I should be taking? You still sniffle, have body aches, have a cough – yes, you appear less ill, but certainly identifiably ill.

          I accept that feeling better will – on the whole – lead to more interaction. The question is how much more and to what extent is it mitigated by secondary illness behaviors? Is that balance enough to tip a threshold in order to make any sort of clinically significant change in influenza transmission? There are way too many assumptions in this model, some of which I find unreasonable, to really say anything.

          But absence of evidence is not evidence of absence. In the absence of evidence isn’t prudent exercise of common sense reasonable?

          Absolutely agreed. But the prudent exercise here is not to advocate we don’t take anti-pyretics, but that we do so and advocate for the responsible minimization of transmission regardless of how we feel. And that is assuming that, on a population level, taking an anti-pyretic will really increase the transmission of the flu by any appreciable amount. I’m simply not convinced that we can do anything more than weave just-so stories about it. Making a model based on a lot of simplifications and assumptions is just a fancy way of doing exactly that.

      2. daedalus2u says:

        Treating fever sufficient to make people feel better doesn’t need to restore them such that they resume 100.000% of their normal activities in order to increase the spread of disease. Most instances of flu are not diagnosed (you really need a test to differentiate flu from the many flu-like illnesses).

        The analysis in the supplement doesn’t even posit increased contact, the results are based solely on increased shedding due to exposure to anti-pyretics. Their analysis doesn’t use human data, they use ferrets, which is a better model for flu than are mice.

        It is not appropriate to cherry-pick the model you use because it gives you the results you want (choosing mouse data because it doesn’t show increased virus shedding and rejecting the ferret data because it does).

        The comment by Rork below is completely appropriate. They propose a model, assign values to the various parameters based on the limited data that is available. What parameter values would be needed to have no effect on the transmission and what data and/or theory supports those particular values?

        In some ways the analysis is like the analysis done to demonstrate “herd immunity” following community-scale vaccinations. You don’t need to decrease transmission to zero to prevent epidemics, you only need to reduce the transmission to less then 1. Is there any data to demonstrate “herd immunity”? Was their data to demonstrate the vaccination strategy that eventually eradicated smallpox? What would the public health implications of waiting until there was such data have been?

        No data or arguments were presented to suggest there are effects that counter this, only that “there is no human data” so “I will assume what ever I want to assume”, and “I will assume virus shedding doesn’t increase”, “if people feel better they won’t spend more time out and about” and “blunting the normal fever response doesn’t prolong the infectious period.”

        Those could be true, but there is no data or plausible physiology based arguments on them either.

        This is the type of experiment that can’t be done. There will never be the kind of data on differential human virus shedding, and differential transmissibility due to anti-pyretic use that would allow these questions to be unambiguously answered.

        1. daedalus2u says:

          You are making the nirvana fallacy. Because there isn’t perfect data to support the idea, the idea can be rejected. That isn’t how SBM works. You have to use Bayesian analysis, and when you do that, the prior probability that widespread use of anti-pyretics increases transmission of fever causing infectious diseases is very high, even in the absence of data. With no data that addresses the issue, the prior probability does not get modified by the absence of data.

          Dr Crislip (in the link cited) reports that:

          “This is by no means a comprehensive review of the risk and benefits of treating fever. Outside of comfort to the patient I cannot find a consistant benefit of treating infectious fevers. The preponderance of information suggests treating infectious fevers is almost always detrimental.”

          As reported by Dr Crislip, what we have is data suggesting increases in transmission and virulence, and the absence of data suggesting decreases in transmission, or decreases in virulence. You can’t take “zero data suggesting decreases in transmission” and via Bayesian analysis come up with a decrease, or even with the absence of an increase.

          The absolute number of deaths is likely small, but it is likely not zero. It is likely too small to measure except with an extremely large prospective study (which can’t be done because it would be unethical and extremely expensive, and the manufacturers of anti-pyretics would fight you all the way), and maybe not even then.

          It may be that anti-pyretics have other effects that need to be considered, but that is a broader question. Aspirin may reduce clotting sufficiently that there is a reduction in ischemic events. Or the increase in domestic chaos from fever-addled children administered anti-pyretics may overwhelm caretaker capacity. However, as in Dr Crislip’s anecdote, this depends upon the caretaker.

          1. Andrey Pavlov says:

            You are making the nirvana fallacy. Because there isn’t perfect data to support the idea, the idea can be rejected.

            That is not at all what I am doing. I am saying that there are too many conflicting Bayesian priors whose actual effect size we have no real idea of, in an extremely complicated system, such that any prediction cannot be reasonably made. It isn’t that this model isn’t plausible or that I am discounting some evidence over others – I am saying that there is too little relevant evidence to come to any conclusion with certainty. I am saying that the model that shows anti-pyretic use does not affect transmission at all is just as valid as the one that says it increases or decreases transmission.

            I agree that there are rational reasons to suspect it may increase transmission. I am saying that there is no rational way to defend the conclusion against arguments otherwise. Which is precisely why I called it a fancy “just-so” story, because that is what it is. You can’t possible argue with solid evidence that in this particular case the ferret model of influenza virus shedding is closer to humans than the murine model. So by what basis can you choose either? And if I choose murine, the model is drastically different.

            So no, there is no nirvana fallacy here. There is a recognition that while indeed quite plausible there is a distinct paucity of evidence to actually answer the question in anything more than a conjecture (no matter how well informed and expert that conjecture is) and that no matter what it is, at best, a very small effect size.

            1. daedalus2u says:

              Where is the conflicting data? There is data showing that (in some circumstances) anti-pyretics increase virus shedding and prolong disease duration.

              Is there any data showing that anti-pyretics decrease virus shedding and shorten disease duration (as measured by virus shedding)?

              If there isn’t data showing that anti-pyretics decrease virus shedding, then there is not clinical equipoise (in a SBM sense) between the two positions.

              It most certainly can be argued that the ferret model is closer to human than the mouse model. Mice don’t get fevers from flu, ferrets do.

    3. windriven says:

      ” the combination of heroin and cocaine would be a best seller.”

      In some quarters it is :-)

    4. goodnightirene says:

      “When people feel sick and stay home in bed, they reduce their contact with others.”

      Depends–on a lot of things:

      How important is it for sick person to work that day ?
      Maybe she’s out of fever-reducer and has to go to Walgreen’s?
      There’s no bread for the kids’ lunch, so off to the store in spite of flu.

      Another factor is the severity of the illness causing the fever–which would affect the above scenarios.

      I’m sure there are many more variables along these lines, and so I must agree with SG–there isn’t enough evidence to confirm what may seem obvious IF you make certain assumptions (such as the person is too sick to get out of bed and will take the day off even if it means getting fired.

      When “critically-thinking people” start making assumptions without evidence they cease to be good thinkers–at least that’s what I’ve been learning here for some years now.

  4. rork says:

    Good article about the details, but let me tone troll:
    “The idea that treating the fever of influenza with medication leads to more deaths in a population is a hypothesis. Critically, the authors fail to provide adequate scientific justification for their approach”
    Hypothesis: I think it is the conclusion of a model with certain values for the parameters of interest – and you can stick other values in to that same model. It’s the point. Maybe we need better values for the parameter estimates is the work to be done.
    Approach: Their approach is a model. You never complained about the model, only that the parameter estimates they used have insufficient data behind them. We have uncertainty, so on to the usual dictum: more data is good.
    (I haven’t read the lay press about this, but can imagine I’ll be as horrified as usual.)

  5. Calli Arcale says:

    I have to admit there is a certain common-sense appeal to the idea that people who treat their fevers are more likely to go out in public and share their germs. But I also have to agree that it hasn’t been demonstrated how significant this problem is. I think it’s a very interesting question, though, and I think it’s an important enough one that somebody ought to take a stab and studying it to try to answer it. To what extent does antipyretic use affect people’s interaction with others while sick? I very much want to know now. ;-)

  6. Kiiri says:

    Have to agree more with Andrey here than some others. I hate models. I am an epidemiologist and I hate models. Models run based on what you put into them as the assumptions of the model. When I see the word ‘model’ I automatically flip to the methods and find out what they put in as the basic assumptions. I totally agree with Scott’s takedown, this was a model with some pretty shaky assumptions. They also had to know that the lay press was about to demonize Tylenol. First, if you are ill and have sick days, and you are a reasonable person, you stay home. However, I work in outbreak investigations and I will tell you that many people HAVE to go to work while ill. Many jobs (most in service!) don’t have paid sick time, so any time not at work is coming out of your paycheck. For a lot of people living paycheck to paycheck this can translate into homelessness really quickly. Also if you are ill and a mom the kids still have to come first (unless you have a fine understanding husband like mine) so what they need means you have to do it regardless of how you feel. I also agree with Andrey, Tylenol is good, but not liquid gold. Granted for the toddler if I can give him an hours relief that translates into the ability for him to sleep for a few hours I will dose him every four hours like clockwork. I disagree with the assumption that only Tylenol leads to significantly more social interaction liable to spread flu. Some people will go out because they have to (Tylenol or not) and some people are just inconsiderate. Paid sick time and public education on social distancing are probably the best bets we have.

    1. Andrey Pavlov says:

      Well said Kiiri. And that is my entire point – just like that ridiculous Monte Carlo sim of the acupuncture in UTI, a model is only as good as the variables you do or don’t put in. We can spin all sorts of stories about what may or may not actually happen in the real world and make a model. We could argue about how many people would really feel better enough after some tylenol that they would go out and risk spreading infection to others vs how many are out there anyways and just using the tylenol to get by and so on ad nauseum. This model demonstrates only that we can make models. It tells us nothing at all interesting about the real world and what really may happen. The fact that we can all agree that it is very conceivable that people who are ill may take tylenol and feel better and thus be more active outside the home means nothing more than we can agree on that. I can’t possibly begin to weigh that against the number of people already going out and the number who would still stay in and just use the relief to sleep, all of which we must also agree are equally plausible. It is the totality of all those factors, combined with exogenous environmental factors (did you get sick right before a deadline? did your boss say you would get fired if you missed one more day of school? did your SO get stuck somewhere so you are forced to go get the kids?) is what will dictate the actual effect of taking an anti pyretic on the epidemiology of influenza.

      This study is nothing more than a fancy argument over a beer at the pub.

  7. mousethatroared says:

    Reading and typing after a martini here, but aren’t dehydration and confusion any concern (from the fever, not the martini – which is not contagious, unfortunately) when leaving a fever to nature? Occasionally, when the kids are sick, the only time I can get them to take any liquids is when they have had a dose of Tylenol to help them feel a bit better.

    For people living alone, isn’t it better to stay in your right mind and have the presence of mind to go to urgent care, than descend into the delirium that is severe fever? I don’t know, just throwing out hypothesis…since that seems to be what the paper was about. The last time I had a real fever and no tylenol on hand, I decide to make a pact with God that I would marry my (then) boyfriend if I lived. You would have to know my then boyfriend to understand the dangers here, but REALLY nor good! It seems fever really can do weird things to your thinking, is that safe, if you are alone?

    The only concern I can see here, that I can give any credence too, is that people might have more social contact when they are controlling their symptoms through medication. Yeah, I can see that. In fact, if I had to bet, I’d bet that people DO get more social contact when they take tylenol for the flu. BUT, heck, what Andrey Pavlov said, take the tylenol and stay home…or heck how about give hourly worker SICK TIME (!!!) and don’t pressure salaried workers to go to work to attend endless meetings that are pointless anyway (yeah, you know what I’m talking about) or encourage workers to work remotely when they are ill. That’s what tele-conferencing and the internet is for!

    Not that I want an engineer who is ill writing the code for my ignition system…but that’s another story.

    And, hey even if you DO give your kids tylenol, don’t send them to school, knowing they have a fever before the tylenol…it’s in the damned handbook. You know who you are.

    1. Andrey Pavlov says:

      Glad you enjoyed your martini, Mouse. ;-)

      I was enjoying $7 pitchers at trivia night in the local pub last night as you were posting this.

  8. mousethatroared says:

    And what’s up with the ferret…did I miss the part about the ferret?

    1. windriven says:

      Ummm … you might want to slow down on the martinis mouse ;-) You DID miss the part about ferrets – they are a preferred animal model for influenza transmission. Scott mentioned this in his post.

      1. mousethatroared says:

        One martini and a small one at that…I’m a lightwieght. I figured there must be ferrets in there somewhere – wouldn’t thing that Scott Garuva would include the picture just because ferrets are cute.

    2. Chris says:

      A clue:
      http://www.virology.ws/?s=ferret

      I chose the search because some of the podcast titles are hilarious. Like “The Second Ferret of the Apocalypse.”

      1. windriven says:

        “One flu over the ferrets’ nest” :-) !

        1. weing says:

          TWIV and SGU are a must every week.

          1. Chris says:

            Much of the really deep biological stuff just flies over my head, but I still learn lots. Plus the banter is really fun.

          2. Chris says:

            Go back several episodes ago and you will find a picture of my garden. They actually read an email a couple of years ago from me about the aphid borne virus that causes color breaks in tulips, and how it affected the Dutch tulip mania.

          3. windriven says:

            TWIV? This Week in the Vatican?

            But seriously, I hadn’t heard of it. I guessed This Week in Virology and indeed there is such a podcast. I’ll check it out.

            1. weing says:

              Yes, this week in virology.

      2. mousethatroared says:

        wow – ( what is the emoticon for awe struck) gotta love the internet.

    3. Jeff Rubinoff says:

      The Ferrets of Old England? http://www.youtube.com/watch?v=0h-VCYn_4O4

      1. angorarabbit says:

        Coming late to the party.

        I.S.I.R.T.A.!!! YouTube has redeemed itself.
        I owe you big time, Jeff.

  9. Bruce Lindgren says:

    The article referred to in this post is helpful in establishing a question suitable for further research. It does not credibly lead to firm treatment (or non-treatment) guidelines. Having had the flu in the past year (even with a flu shot) I found that treating it with a fever reducer made me fell a little better, but not so well that I was ready to re-join the human race. On the other hand, I did re-join my travel group sooner than I would have because I did not want to be stranded in a small town with no transportation. This anecdote suggests that there are many issues that can be studied, but there is no clear evidence regarding treatment at the present time. We can guess, but we don’t really know. It’s like a lot in life.

    1. Beth says:

      Did the article actually propose firm treatment (or non-treatment) guidelines. I inferred that it was more about asking whether or not our current approach may lead to some unintended negative consequences.

  10. Ramon Smith says:

    This article discusses influenza types A and B. check this out! http://www.nytimes.com/health/guides/disease/the-flu/overview.html

  11. schawking says:

    If reducing fever increases the length of time an infected person is ill and doing nothing allows the fever to thwart the virus quicker, causing the infected person to feel better sooner then I would think a homeopath would jump all over this phenomena and claim that their treatments work better then pharmaceuticals.

    example one: Sick person takes fever reducer and illness lingers for 7-8 days.

    example two: Sick person takes homeopathic remedy and illness subsides in 5-6 days.

    Presto, homeopathy “works” better.

    1. WilliamLawrenceUtridge says:

      That’s exactly how the alleged higher rates of survival in homeopathic hospitals at the turn of the century are explained – “real” medicine (which was prescientific and essentially no better than the magical invocations of homeopaths) was actively harmful compared to doing nothing. Hence, “nothing” was superior. I mean, it was a matter of degree, people still died in droves, but slightly smaller (slower?) droves than in a “real” hospital.

  12. schawking says:

    If reducing fever increases the length of time an infected person is ill and doing nothing allows the fever to thwart the virus quicker, causing the infected person to feel better sooner, then I would think a homeopath would jump all over this phenomena and claim that their treatments work better then pharmaceuticals.

    example one: Sick person takes fever reducer and illness lingers for 7-8 days.

    example two: Sick person takes homeopathic remedy and illness subsides in 5-6 days.

    Presto, homeopathy “works” better.

  13. Aditi says:

    I discovered your site while researching anti-vaccine propaganda. Very good collections of articles based on facts! In India there is a LOT of ignorance, but most people who went to primary school “believe” in vaccines. It’s just that they don’t have access to hospitals and doctors so a lot of people miss out. Just eradicating Polio took years and years – we are now Polio free for 3 years straight. Recently discovered that some Americans don’t “believe” in vaccines. It is very surprising if you consider that almost everyone went to primary school in America.

    Keep Writing!!

    Cheers.

  14. Ronald L Cook says:

    When I was a Ph.D. student at Utah State University I attended several presented by Prof. Thomas Emery. Prof Emery was a leader in the field of microbial siderophores. Bacteria release siderophores to scrounge for iron in order to grow. For many bacteria (mabe most) the effectiveness of the siderophores decreases with increasing temperature. A quote from the link below

    Without iron, the bacteria cannot grow within the body. We have seen that during infection the body restricts the levels of blood plasma iron in order to make it more difficult for the microbes to grow. It may be possible that one of the reasons that fever is produced is to inhibit the ability of the microorganism to produce siderophores, which might other wise effectively compete for the last traces of iron in the blood plasma. Thus, normal body temperature and adequate iron nutrition may be just fine for people in good health, but may actually be detrimental at the onset of infection

    http://digitalcommons.usu.edu/cgi/viewcontent.cgi?article=1067&context=honor_lectures

    Thus, one needs to let the fever go if the fever is caused by bacterial infection because bacteria need iron to grow whereas virus don’t need iron so the biological reasons to shut down a viral fever are not as yet clear

  15. Max says:

    Ummm…. Drugs come with side effects. Fevers are beneficial at effectively ridding the system of pathogens as long as they aren’t toppling 104 degrees or so AND are virtually always self limiting. Why anyone would try to support taking needless (and sometimes harmful) fever reducers can only stem from true ignorance of fevers and physiology or owning stock in Tylenol. So sad that you’ve even entertained the notion of defending this ridiculous practice.

    1. WilliamLawrenceUtridge says:

      Fevers come with side effects too – notably convulsions, brain damage and death. And there’s not really any crystal-clear evidence that they are of universal benefit. Claiming that fevers have been shown to be universally beneficial rather demonstrates that your understanding of them is based more on charicature than reality.

      1. Max says:

        Those side effects virtually never come before 105 degrees. Read my post again before trying to sound like you know what you’re talking about. If you’re arguing that fevers don’t serve the best interest of a human in the defense of pathogens… I really shouldn’t even dignify your comment with a response. I’m not going to teach you basic biology, physiology, and pathology. Go back to school!

        1. Sawyer says:

          After listening to a few medical podcasts on the topic I’ve come to the conclusion that fevers are way more complicated than I thought they were. I imagine a lot of people here are in the same boat.

          Offering the proverbial “F*$k you, you’re all morons” is probably not the most fruitful way to start a conversation, Max.

    2. weing says:

      “Why anyone would try to support taking needless (and sometimes harmful) fever reducers can only stem from true ignorance of fevers and physiology or owning stock in Tylenol.”
      Malaria? FCAS?

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