Start Spreading the Flus

Photo Credit –CDC PHIL

 

# 8203

 

A new study that appeared in the Proceedings of the Royal Society B yesterday, provides a fresh look at a topic I’ve written about several times in the past; the potential downsides of using antipyretic meds (ibuprofen, acetaminophen or paracetamol, etc) for flu-related fever.

 

While earlier studies have concentrated on the affects of these meds on the individuals taking them, this new study looks at the population-level impact of taking these fever-reducing meds during an influenza outbreak.

 

Fever is the body’s natural reaction to infection, and since most viruses have a narrow `comfort zone’, a spike in temperature can lower the amount of virus the host is carrying  . ..  and shedding.  Another side effect of fever is that it makes you feel miserable, and so people with a fever are more likely to stay home, rather than go to work or school.

 

When you artificially reduce the fever, you not only give the virus a better environment in which to replicate, you are also more likely to go out and infect others.  A double whammy.

 

While neither of these concepts is new, this study attempts to quantify the impact in terms of the virus’s R₀ (R naught) or Basic Reproductive Number, and they calculate the use of fever suppression meds increases the number of annual cases by approximately 5%, resulting in more  than 1,000 additional flu deaths each year in North America.

 

First, a link to the study, then some excerpts from the press release from McMaster University, after which I’ll be back with more.

 

Population-level effects of suppressing fever

David J. D. Earn,  Paul W. Andrews and Benjamin M. Bolker

Abstract

Fever is commonly attenuated with antipyretic medication as a means to treat unpleasant symptoms of infectious diseases. We highlight a potentially important negative effect of fever suppression that becomes evident at the population level: reducing fever may increase transmission of associated infections. 

(Continue . . . )

 

McMaster University researchers find fever-reducing medications may aid spread of influenza

Hamilton, ON (Jan. 21, 2014) -- Contrary to popular belief, fever-reducing medication may inadvertently cause more harm than good.

New research from McMaster University has discovered that the widespread use of medications that contain fever-reducing drugs may lead to tens of thousands more influenza cases, and more than a thousand deaths attributable to influenza, each year across North America. These drugs include ibuprofen, acetaminophen and acetylsalicylic acid.

"When they have flu, people often take medication that reduces their fever. No-one likes to feel miserable, but it turns out that our comfort might be at the cost of infecting others," said lead author David Earn, an investigator with the Michael G. DeGroote Institute for Infectious Disease Research (IIDR) and professor of mathematics at McMaster University.

"Because fever can actually help lower the amount of virus in a sick person's body and reduce the chance of transmitting disease to others, taking drugs that reduce fever can increase transmission. We've discovered that this increase has significant effects when we scale up to the level of the whole population."

The study, published in the Proceedings of the Royal Society B today, was co-authored with McMaster professors Ben Bolker, of the departments of mathematics & statistics and biology and the IIDR, and Paul Andrews of the Department of Psychology, Neuroscience and Behaviour.

(Continue . .. )

 

The authors caution that this work is preliminary, the data is incomplete and heterogeneous, and that more work needs to be done before concrete proposals regarding the use of these drugs can be made.

 

In a real world example of how fever-reducers can increase the public’s exposure to an influenza virus, in  Vietnam Discovers Passengers Beating Thermal Scanners we looked at reports of people using fever reducing meds to evade airline passenger screening during the 2009 H1N1 pandemic.

 

I’ve also written about studies that suggest that the concurrent use of antipyretics may inhibit the immune response when receiving vaccines. In fact, it has even been theorized that one of the reasons that the elderly often develop less-than-robust immunity from the flu vaccine may be due to their frequent consumption of NSAIDs.

 

Several past blogs on this phenomenon include:

 

Anti-Inflammatory Meds And Vaccines

Common Pain Relievers May Dampen Vaccination Benefits

A Few Inflammatory Remarks

 

In a another story  from 2011 - the American Academy of Pediatrics (AAP) released a report on the use of antipyretics in children, suggesting that we ought not over-treat fevers.

 

Clinical Report—Fever and Antipyretic Use in Children

Janice E. Sullivan, MD, Henry C. Farrar, MD,

ABSTRACT EXCERPTS

Fever in a child is one of the most common clinical symptoms managed by pediatricians and other health care providers and a frequent cause of parental concern. Many parents administer antipyretics even when there is minimal or no fever, because they are concerned that the child must maintain a “normal” temperature.

Fever, however, is not the primary illness but is a physiologic mechanism that has beneficial effects in fighting infection. There is no evidence that fever itself worsens the course of an illness or that it causes long-term neurologic complications.

(Continue . . . .)

 

And in early 2013, in Adding To A Feverish Debate, we looked at another study appearing in the Journal of Pediatrics on another possible (albeit, rare) adverse effect seen in a small number of young children with fever and dehydration at a hospital in Indiana who received treatment with NSAIDs.

 

A accompanying press release from Indiana University that warned the administration of NSAIDs to reduce fever may result in AKI - Acute kidney Injury – in young children.

 

Common anti-fever medications pose kidney injury risk for children

Sick children, especially those with some dehydration from flu or other illnesses, risk significant kidney injury if given drugs such as ibuprofen and naproxen, Indiana University School of Medicine researchers said Friday.

In an article published online Jan. 25 by the Journal of Pediatrics, Jason Misurac, M.D., and colleagues from IU and Butler University reported that nearly 3 percent of cases of pediatric acute kidney injury over a decade could be traced directly to having taken the common nonsteroidal anti-inflammatory drugs, or NSAIDs

(Continue . . .).

 

None of this is designed to demonize a useful, and ubiquitous, class of drugs.  But it is axiomatic that there is no such thing as a 100% safe, 100% benign drug – even those you can buy over the counter.

 

If there is a health benefit to be had, we must weigh that against the (usually very slight) risks of taking the these meds.

 

Although the jury is still out on most of these concerns, and more research is needed, there is an increasing body of evidence that suggests we might want to think twice before automatically reaching for fever reducers in the medicine cabinet.

Adding To A Feverish Debate

Photo Credit –CDC PHIL

#6881

 

Long time readers may recall that during the summer of 2011 we looked at a study (see A Feverish Debate) that questioned the conventional wisdom of using antipyretic meds (ibuprofen, acetaminophen or paracetamol, etc) to reduce influenza-related fever.

 

This contrarian view made headlines when researchers from the Wellington based Medical Research Institute of New Zealand, published a paper (Antipyretic therapy for influenza infection—benefit or harm?) in the New Zealand Medical Journal.

 

You can read the entire paper, but their conclusion read:

 

We conclude that there is an insufficient evidence base to support the use of antipyretics in the treatment of fever from influenza infection.

 

The limited evidence that does exist suggests that the administration of antipyretics may have the potential to increase the severity of influenza illness and the risk of mortality.

 

We suggest that randomised controlled trials of the effect of antipyretics in the treatment of influenza are undertaken as an urgent priority.

 

We are still waiting for results from RCTs to support their concerns, but the idea of letting a fever run its course (at least, up to a point) as part of the body’s natural immune system’s defense isn’t new.

 

In a another story - also from 2011 - the American Academy of Pediatrics (AAP) released a report on the use of antipyretics in children, suggesting that we ought not over-treat fevers.

 

Clinical Report—Fever and Antipyretic Use in Children

Janice E. Sullivan, MD, Henry C. Farrar, MD,

ABSTRACT EXCERPTS

Fever in a child is one of the most common clinical symptoms managed by pediatricians and other health care providers and a frequent cause of parental concern. Many parents administer antipyretics even when there is minimal or no fever, because they are concerned that the child must maintain a “normal” temperature.

 

Fever, however, is not the primary illness but is a physiologic mechanism that has beneficial effects in fighting infection. There is no evidence that fever itself worsens the course of an illness or that it causes long-term neurologic complications.

(Continue . . . .)

 

 

Today, a study appears in the Journal of Pediatrics on another possible (albeit, rare) adverse effect seen in a small number of young children with fever and dehydration at a hospital in Indiana who received treatment with NSAIDs.

 

We’ve a press release from Indiana University that warns the administration of NSAIDs to reduce fever may result in AKI - Acute kidney Injury – in young children.

 

Common anti-fever medications pose kidney injury risk for children

Sick children, especially those with some dehydration from flu or other illnesses, risk significant kidney injury if given drugs such as ibuprofen and naproxen, Indiana University School of Medicine researchers said Friday.

 

In an article published online Jan. 25 by the Journal of Pediatrics, Jason Misurac, M.D., and colleagues from IU and Butler University reported that nearly 3 percent of cases of pediatric acute kidney injury over a decade could be traced directly to having taken the common nonsteroidal anti-inflammatory drugs, or NSAIDs.

 

Although relatively few in terms of percentage of total kidney damage cases, the children with problems associated with NSAIDs included four young patients who needed dialysis, and at least seven who may have suffered permanent kidney damage, the researchers said.

 

"These cases, including some in which patients' kidney function will need to be monitored for years, as well as the cost of treatment, are quite significant, especially when you consider that alternatives are available and acute kidney injury from NSAIDs is avoidable," Dr. Misurac, a fellow in pediatric nephrology, said.

 

Although such drugs have been linked to kidney damage in small, anecdotal reports, the study reported Thursday is believed to be the first large-scale study of the incidence and impact of acute kidney injury caused by NSAIDs.

 

The research team evaluated medical records at Riley Hospital for Children at IU Health in Indianapolis from January 1999 through June 2010 and found 1,015 cases in which patients had been treated for acute kidney injury from any cause.

 

After excluding cases in which the acute kidney injuries could possibly be explained by other factors, such as diseases affecting kidney function, the researchers found 27 cases, or 2.7 percent, in which the only factors were the administration of NSAIDs. In nearly all cases, the NSAIDs were administered before the children were admitted to the hospital. Because many of the 1,015 cases involved multiple potential causes of acute kidney injury, the researchers said the 27 cases are likely an underestimate of the number of cases in which NSAIDs contributed to the kidney damage.

 

Among the researchers' findings:

• Most of the children had been treated with recommended dosages.
• All of the children under the age of 5 needed to undergo dialysis temporarily, were more likely than the older children to be placed in an intensive care unit and needed longer hospital stays.
• The average cost for hospital and kidney specialist fees in the 27 cases was nearly $13,500, and the costs were much higher for younger children. At least $375,000 was spent on the NSAID-associated kidney injury cases at Riley Hospital over the study period, the researchers said, but billing data for other specialists were not available in the database, suggesting that the actual costs were likely much higher.

NSAIDs affect kidney function by restricting blood flow to the blood-filtering components of the kidneys, which suggests the risks from the drugs are greater among children who are dehydrated due to the effects of their illness, such as vomiting or diarrhea, Dr. Misurac said.

 

Fever is normal during an infection and not in itself dangerous, he noted, so "one alternative to NSAIDs would be acetaminophen, but another alternative would be no medication at all, at least for a while, to let the body fight the infection."

 

 

In a somewhat related story, I’ve written about studies that suggest that the concurrent use of antipyretics may inhibit the immune response when receiving vaccines.

 

In fact, it has even been theorized that one of the reasons that the elderly often develop less-than-robust immunity from the flu vaccine may be due to their frequent consumption of NSAIDs.

 

Several past blogs on this phenomenon include:

 

Anti-Inflammatory Meds And Vaccines

Common Pain Relievers May Dampen Vaccination Benefits

A Few Inflammatory Remarks

 

For now the evidence against the use of antipyretics (particularly NSAIDs) for fevers and influenza-like illness is very limited.

 

But these reports do show that - even after decades of use by hundreds of millions of people – our understanding of the effects of many commonly used over-the-counter medications remains less than complete.

A Feverish Debate

 

 

 

# 5687

 

Photo Credit –CDC PHIL

 

A topic I’ve written about several times in the past is back in the news again; the advisability of using antipyretic meds (ibuprofen, acetaminophen or paracetamol, etc) for flu-related fever.

 

The eye-catching headline and lede in yesterday’s New Zealand Herald reads:

 

'Don't use paracetamol for fever'

By Martin Johnston

5:30 AM Monday Jul 11, 2011

A respected scientific group has recommended not using paracetamol and several other drugs to reduce flu-related fever, saying they may increase the risk of death.

(Continue . . . )

 

 

The respected scientific group referenced in the article above is Wellington based Medical Research Institute of New Zealand. And their advice runs contrary to what we usually hear from our doctors, the CDC, and the World Health Organization.

 

Constant readers will recall that last May I wrote (see It Gives You Fever) about about a clinical trial this research group was about begin that would examine the merits and risks of taking antipyretics with influenza.

 

The concern is that when we take fever reducers, we lower the body’s temperature to provide symptomatic relief – but we also create a more favorable environment for the virus to replicate.

 

Essentially trading comfort for circumventing the body’s natural defense mechanism.

 

Last year, in A Hot Topic For Further Research I wrote about new research that suggested (but fell short of proving) that we may be better off carrying a bit of a fever – rather than reaching for the pill bottle -  when we have the flu.

 

And while that isn’t exactly a new idea, the evidence to support it has been limited.

 

The study – again conducted by the Medical Research Institute of New Zealand -  appeared in the Journal of the Royal Society of Medicine (registration required for access) – and provided a retrospective analysis of previous animal (not human) studies on the outcomes of the treatment of bacterial and viral infections with antipyretics.

 

The effect on mortality of antipyretics in the treatment of influenza infection: systematic review and meta-analysis

Sally Eyers, Mark Weatherall, Philippa Shirtcliffe, Kyle Perrin, and Richard Beasley

v.103(10); Oct 1, 2010

 

In a review of the existing literature, researchers at the Medical Research Institute of New Zealand and Capital & Coast District Health Board, identified 8 (non-human animal) studies that met their inclusion criteria.

 

They found that the risk of mortality increased by roughly 33% when antipyretics were used in influenza infected animals.  This risk was observed with aspirin, paracetamol, and diclofenac.

 

As I pointed out at the time, there were a lot of limitations to this study, not the least of which is that research on mice, chickens, and ferrets isn’t always applicable to humans.

 

Hence the need for the clinical trial on humans underway in New Zealand.

 

From the Medical Research Institute’s website, a description of goals of the clinical trial.

 

The effect on mortality of antipyretics in the treatment of influenza

Antipyretics are recommended for the symptomatic treatment of influenza infection.  However there is evidence that fever is a protective physiological response, that treating fever secondary to infections may be harmful and that human tropic influenza viruses are variable temperature-sensitive.

In a systematic review and meta-analysis we have identified that in animal models treatment with antipyretics for influenza infection increases the risk of mortality.  There are no randomised controlled 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.

In response to these findings the MRINZ is now undertaking a placebo-controlled randomised trial of paracetamol use in influenza infection. This study is funded by the Health Research Council of New Zealand.

 

The results of that trial are not yet available, and so while the Medical Research Institute is publicly questioning the value of reducing fevers with influenza, they are not yet calling for health authorities to change their existing stance on the use of antipyretics.

 

They also state that using these meds as a pain reliever for muscle aches and headaches when you have influenza, is a reasonable practice.

 

And to round out this debate, the New Zealand Self Medication Industry Association (who have a vested interest in the sale of these products) has weighed in with the following press release.

 

Tuesday 12 July 2011, 12:13pm

Media release from New Zealand Self-Medication Industry Association

The New Zealand Self-Medication Industry Association (SMI), the industry body representing non-prescription consumer healthcare products, said today it was aware of a recommendation by the Wellington-based Medical Research Institute that antipyretics, such as paracetamol, ibuprofen and aspirin, not be used to reduce flu-related fever.

 

"We have only just received this information and, as the Institute itself said, there was insufficient evidence for the Ministry of Health to change its current position on these products. It's important people do not overreact and stop using antipyretics altogether.

 

Paracetamol and ibuprofen, for example, are well recognized for the relief of pain," commented SMI executive director Tim Roper.

"Fever management guidelines highlight that it is important to treat the patient and not the thermometer - SMI and its members endorse this approach. We are confident that if this approach is used, that these medicines can be used safely.

"Nevertheless, our members welcome the opportunity to work with Medsafe to discuss any matters that may arise, after the Ministry has reviewed the new information."

 

 

Although the jury is still out on all of this (and I’ve not discarded the Tylenol from my medicine cabinet), the American Academy of Pediatrics (AAP) released a report earlier this year on the use of antipyretics in children, suggesting that we ought not over-treat fevers.

 

Clinical Report—Fever and Antipyretic Use in Children

Janice E. Sullivan, MD, Henry C. Farrar, MD,

 

ABSTRACT EXCERPTS

 

Fever in a child is one of the most common clinical symptoms managed by pediatricians and other health care providers and a frequent cause of parental concern. Many parents administer antipyretics even when there is minimal or no fever, because they are concerned that the child must maintain a “normal” temperature.

 

Fever, however, is not the primary illness but is a physiologic mechanism that has beneficial effects in fighting infection. There is no evidence that fever itself worsens the course of an illness or that it causes long-term neurologic complications.

 

Thus, the primary goal of treating the febrile child should be to improve the child's overall comfort rather than focus on the normalization of body temperature.

 

(Continue . . . .)

 

 

And lastly, I would mention that in 2009 I wrote about some of the downsides to taking anti-inflammatory drugs like Aspirin, Tylenol, and Ibuprofen in a blog called  A Few Inflammatory Remarks.

 

It concerned a Lancet study that suggested giving babies acetaminophen (Tylenol) right before or immediately after getting a vaccination may inhibit or lower their immune response.

 

It also discussed several studies from the University of Rochester, that indicate the use of NSAIDs could lower the body’s antibody response.

 

It is axiomatic that there is no such thing as a 100% safe, 100% benign drug – even those you can buy over the counter.  

 

If there is a health benefit to be had, we must weigh that against the (usually very slight) risks of taking the these meds.

 

While the overall risks of taking these drugs are likely exceedingly small, hopefully we’ll soon have research that will help quantify the risks and rewards of using these common fever reducing medicines.

It Gives You Fever

 

 

# 5534

 

 

Photo Credit – PHIL

 

An interesting study is about to get underway in New Zealand which will look at the potential downside to taking antipyretics – fever reducers – when you have influenza.

 

When we take antipyretics, we lower the body’s temperature to provide symptomatic relief – but we also create a more favorable environment for the virus to replicate.

 

Last year, in A Hot Topic For Further Research I wrote:

 

Today we have some new research that suggests (but falls far short of proving) that we may be better off carrying a bit of a fever – rather than reaching for the pill bottle -  when we have the flu.

 

And while that isn’t exactly a new idea, the evidence to support it has been limited.

 

It makes sense, of course.

 

A fever is the body’s way of combating an infection.  And we know human adapted flu viruses replicate in a narrow temperature range, and that replication is inhibited by fever.

 

If we reduce the fever, we are (theoretically, anyway) undermining our body’s own protective immune response.

 

And that in turn could increase the amount of time we remain ill, and shed the flu virus.

 

First the study in the Journal of the Royal Society of Medicine (registration required for access) – which is a retrospective analysis of previous animal (not human) studies on the outcomes of the treatment of bacterial and viral infections with antipyretics.

 

The effect on mortality of antipyretics in the treatment of influenza infection: systematic review and meta-analysis

Sally Eyers, Mark Weatherall, Philippa Shirtcliffe, Kyle Perrin, and Richard Beasley

v.103(10); Oct 1, 2010

In a review of the existing literature, researchers at the Medical Research Institute of New Zealand and Capital & Coast District Health Board, identified 8 (non-human animal) studies that met their inclusion criteria.

 

They found that the risk of mortality increased by roughly 33% when antipyretics were used in influenza infected animals.  This risk was observed with aspirin, paracetamol, and diclofenac.

 

 

This retrospective study was on animals, not humans, and so the question remains; Is it desirable to carry a low fever when battling influenza?

 

Over the next few months a clinical trial at special ward at Wellington Hospital in New Zealand may help answer that question. It will be used to monitor the progress of 80 influenza patients who will receive either paracetamol (acetaminophen) or a placebo for fever.

 

The story from Stuff.nz.co, then I’ll return with a bit more.

 

 

Flu study kicks off clinical trials unit

KATE NEWTON

A new clinical trials unit at Wellington Hospital will let researchers carry out studies that have not been possible in New Zealand before.

 

The first trial will be to study if giving paracetamol to people with influenza makes it worse.

 

The 14-bed unit is the first in a New Zealand public hospital.

 

It will let researchers keep participants in medical studies overnight for close monitoring – significantly widening the scope of what trials can be done.

(Continue . . .)

 

 

In a somewhat related story, I’ve written about studies that suggest that the concurrent use of antipyretics may inhibit the immune response when receiving vaccines.

 

In fact, it has even been theorized that one of the reasons that the elderly often develop less-than-robust immunity from the flu vaccine may be due to their frequent consumption of NSAIDs.

 

Several past blogs on this phenomenon include:

 

Anti-Inflammatory Meds And Vaccines

Common Pain Relievers May Dampen Vaccination Benefits

A Few Inflammatory Remarks

 

For now the evidence against the human use of antipyretics (and NSAIDs) in these situations is faint (at best).

 

But these reports do show that the effects of many over-the-counter medicines – even those used for decades by hundreds of millions of people - remain incompletely understood.

A Hot Topic For Further Research

 

 

 

# 5055

 

 

Look into just about any modern medicine cabinet and you are likely to find the workhorse of over-the-counter medications – antipyretics; fever reducers, that also reduce pain and/or inflammation.

 

Aspirin, paracetamol (acetaminophen), and ibuprofen are often the first (and sometimes only) medicine we reach for when we have the flu.  

 

Today we have some new research that suggests (but falls far short of proving) that we may be better off carrying a bit of a fever – rather than reaching for the pill bottle -  when we have the flu. 

 

And while that isn’t exactly a new idea, the evidence to support it has been limited.

 

It makes sense, of course.  

 

A fever is the body’s way of combating an infection.  And we know human adapted flu viruses replicate in a narrow temperature range, and that replication is inhibited by fever.

 

If we reduce the fever, we are (theoretically, anyway) undermining our body’s own protective immune response. 

 

And that in turn could increase the amount of time we remain ill, and shed the flu virus.

 

First the study in the Journal of the Royal Society of Medicine (registration required for access) – which is a retrospective analysis of previous animal (not human) studies on the outcomes of the treatment of bacterial and viral infections with antipyretics.

 

 

The effect on mortality of antipyretics in the treatment of influenza infection: systematic review and meta-analysis

Sally Eyers, Mark Weatherall, Philippa Shirtcliffe, Kyle Perrin, and Richard Beasley

v.103(10); Oct 1, 2010

In a review of the existing literature, researchers at the Medical Research Institute of New Zealand and Capital & Coast District Health Board, identified 8 (non-human animal) studies that met their inclusion criteria.

 

They found that the risk of mortality increased by roughly 33% when antipyretics were used in influenza infected animals.  This risk was observed with aspirin, paracetamol, and diclofenac.

Abstract (Excerpt)

Conclusion

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.

 

 

There were a lot of limitations to this study, not the least of which is that research on mice, chickens, and ferrets isn’t always applicable to humans.

 

Particularly since mice (used in many of these studies) can exhibit a fall in body temperature when infected with the influenza virus (Behavioral thermoregulation in mice inoculated with influenza virus), which could skew some of these results.

 

But these findings certainly do invite further study, particularly considering how often use of antipyretics are recommended in the treatment of influenza.

 

In a somewhat related story, over the past couple of years I’ve written about studies that suggest the administration of antipyretics may inhibit the immune response from vaccines.

 

In fact, it has even been theorized that one of the reasons that the elderly often develop less-than-robust immunity from the flu vaccine may be due to their frequent consumption of NSAIDs.

 

Several past blogs on this phenomenon include:

 

Anti-Inflammatory Meds And Vaccines

Common Pain Relievers May Dampen Vaccination Benefits

A Few Inflammatory Remarks

 

 

None of this is offered as medical advice, of course.  For that, I would refer you to your healthcare provider and to the recommendations of your public health departments. 

 

For now, the evidence against the human use of antipyretics (and NSAIDs) in these situations is faint (at best). And so I’m not about to weed out my medicine cabinet over this.  

 

Not yet, anyway.

 

But these reports do illustrate that the complex physiological effects of many over-the-counter medicines – even those used for decades by hundreds of millions of people - remain incompletely understood.

 

A little humility-inspiring lack of certitude with which to start your week.