tag:theconversation.com,2011:/id/topics/facts-about-flu-5767/articlesFacts about flu – The Conversation2015-09-29T20:08:36Ztag:theconversation.com,2011:article/382872015-09-29T20:08:36Z2015-09-29T20:08:36ZControversies in medicine: the rise and fall of the challenge to Tamiflu<figure><img src="https://images.theconversation.com/files/96412/original/image-20150928-21366-d740kn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">As part of pandemic preparation, in the early 2000s many countries amassed large stockpiles of the influenza neuraminidase inhibitor Tamiflu.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/hisgett/3641376785/">Tony Hisgett/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>One of the biggest recent controversies in medicine involves the effectiveness – or otherwise – of the antiviral drug Tamiflu. Governments around the world have stockpiled the drug for use in severe influenza pandemics, but many have raised doubts about its effectiveness.</p>
<p>Influenza causes annual “seasonal” epidemics in temperate countries and circulates year-round in the tropics. Pandemics occur when there’s a relatively new flu virus containing components of bird or swine flu viruses, against which the human population has little protection. </p>
<p>Global pandemic preparedness efforts were spurred in the early 2000s by the emergence of SARS, and highly pathogenic H5N1 influenza in birds, which was associated with rare but often fatal infection in humans. The problem is that the severity of pandemics can vary markedly; from the Spanish flu of 1918-19, which is estimated to have killed 20-50 million people worldwide, to the much milder 2009 swine flu, which <a href="http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001558">resulted in between</a> 150,000 and 250,000 deaths (a similar number to the annual mortality of seasonal epidemics). </p>
<h2>Reviewing evidence</h2>
<p>Governments tend to prepare for the worst because there’s no way of knowing the impact a flu pandemic will have on the population. And, as pandemics are rare, the evidence base for public health responses has to be largely taken from studies of seasonal influenza.</p>
<p>As part of pandemic preparation, in the early 2000s many countries amassed large stockpiles of the influenza neuraminidase inhibitor Tamiflu. A 2000 clinical trial had <a href="http://jama.jamanetwork.com/article.aspx?articleid=192425">indicated modest benefits</a> from this drug, but its ability to <a href="http://jama.jamanetwork.com/article.aspx?articleid=193547">reduce disease severity and limit onward spread</a> had potential for much greater benefits in reducing death and disease at the population level.</p>
<p>In 2006 the <a href="http://www.cochrane.org/about-us">Cochrane Neuraminidase Inhibitors Review Team</a> published a review on behalf of the Cochrane Collaboration, an independent network of researchers who review evidence for medical interventions to help improve health-care decision-making. <a href="http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001265.pub2/abstract;jsessionid=DAAC348A24E621BF48DEDF728C522519.f01t02">Its overall conclusion</a> was that the drug shouldn’t be used for treating seasonal flu, but was suitable for use as part of a suite of public health measures in pandemics.</p>
<p>But in the aftermath of the – fortunately – mild 2009 pandemic, the social and economic costs of the global public health response to this event were widely questioned. In particular, given the large amounts of money spent on Tamiflu, claims of <a href="http://www.bbc.com/news/10235558">conflict of interest</a> and <a href="http://ahrcanum.com/2009/07/01/tamiflu-linked-to-origins-of-ah1n1-swine-flu-pandemic/">conspiracy theories</a>, some <a href="http://www.dailymail.co.uk/news/article-1176743/Donald-Rumsfelds-controversial-links-drug-company-Tamiflu.html">more credible than others</a>, abounded. </p>
<p>Then, in the process of updating their 2006 Cochrane review, and in response to <a href="http://www.bmj.com/content/339/bmj.b5106.long">questions raised</a> through the Cochrane review’s feedback mechanism regarding prevention of complications and drug safety, the reviewing team requested access to Roche Tamiflu trials data in 2009. They were refused. In the years that followed, Roche came under particular scrutiny with claims that <a href="http://www.bmj.com/content/345/bmj.e7303">critical clinical trial information</a> had been withheld from publication. </p>
<p>In 2012, the <a href="http://www.bmj.com/tamiflu">BMJ launched a website</a> devoted to a public campaign, lobbying the company to release full clinical reports on all relevant studies conducted in support of the drug’s licence. The campaign was successful when, in 2013, Roche provided all the requested documentation. </p>
<h2>The question mark</h2>
<p>For the first time, full clinical study reports, which include tables of all study outcomes rather than those selected for publication, were made available. In addition, submissions to and correspondence with drug regulatory authorities were included. These reports, often many hundreds of pages long, formed the basis of a new meta-analysis conducted by the <a href="http://bmjopen.bmj.com/content/4/9/e005253.full">Cochrane Neuraminidase Inhibitors Review Team</a>. </p>
<p>With the new information to hand, the authors concluded the <a href="http://bmjopen.bmj.com/content/4/9/e005253.full">risk of bias</a> in several published studies was higher than had been previously assessed. This was due to missing or incomplete information, or deficiencies in study design. </p>
<p>Roche provided data on 83 studies, and regulatory authorities provided information on more than 200 trials. But only 46 studies (20 of Tamiflu and 26 of Relenza) were included in <a href="http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008965.pub4/abstract;jsessionid=76F622C5B03F0FF262E8B76396219022.f03t01">the final analysis</a> as eligible and unbiased. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/96413/original/image-20150928-21366-19hmcgm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/96413/original/image-20150928-21366-19hmcgm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=420&fit=crop&dpr=1 600w, https://images.theconversation.com/files/96413/original/image-20150928-21366-19hmcgm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=420&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/96413/original/image-20150928-21366-19hmcgm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=420&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/96413/original/image-20150928-21366-19hmcgm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=528&fit=crop&dpr=1 754w, https://images.theconversation.com/files/96413/original/image-20150928-21366-19hmcgm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=528&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/96413/original/image-20150928-21366-19hmcgm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=528&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A 2014 review found giving the drug to family members of an infected person prevented infections in about 15% of people.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/k790i/3852576091/">Anil Jadhav/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<p>Still, the <a href="http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008965.pub4/abstract;jsessionid=76F622C5B03F0FF262E8B76396219022.f03t01">findings of this 2014 review</a> were remarkably similar to the group’s previous reports. The review showed Tamiflu hastened flu recovery by about 17 hours in adults and 29 hours in kids. Anticipated side effects of nausea and vomiting were reported in less than 5% of treated people. And giving the drug to family members of an infected person prevented infections in about 15%.</p>
<p>The meta-analysis also looked at the risk of hospitalisations and secondary infections following flu. It concluded that antivirals were ineffective for reducing these adverse outcomes. But because the trials under consideration were mostly in generally healthy people with seasonal influenza infections, the <a href="http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008965.pub4/abstract;jsessionid=76F622C5B03F0FF262E8B76396219022.f03t01">number of hospitalisations</a> was very small, affecting only 71 of 4,400 study participants. And while the main review finding was of a 1% absolute reduction in self-reported pneumonia, this figure represented a 56% relative risk reduction in the Tamiflu-treated group.</p>
<p><a href="http://community.cochrane.org/features/tamiflu-relenza-how-effective-are-they?">Based on this evidence</a>, BMJ and Cochrane Collaboration questioned the usefulness of neuraminidase inhibitors in pandemics and called for governments to review their guidance for the drug’s use.</p>
<h2>A different view</h2>
<p>Meanwhile, another independent group, the <a href="http://www.mugas.net">Multiparty Group for Advice on Science</a>, brought together four leading academics in the field of influenza to review and oversee re-analysis of Tamiflu trials data. To support this work, they obtained an unrestricted grant from Roche. Their aim was to resolve uncertainties regarding appropriate public health use of this drug. </p>
<p>The group negotiated with Roche to gain access to not just summary reports of treatment group outcomes (as previously analysed), but individually listed patient data from nine adult Tamiflu trials involving 4,328 participants. These provided much greater statistical power to assess differences. The trials, selected on the basis they assessed the currently recommended treatment dose, would have been included among those provided to the Cochrane reviewers.</p>
<p>This <a href="http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2962449-1/abstract">new analysis found</a>, similarly to the Cochrane review, that the drugs hastened recovery from influenza infection by about a day, with the side effects of nausea and vomiting in a minority of patients. It said that in people with confirmed flu, Tamiflu <a href="http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2962449-1/abstract">reduced the risk of secondary respiratory infections</a> requiring antibiotics by 44%. Hospitalisations in the Tamiflu group were down by 63%. </p>
<p>These findings were more in keeping with observational studies of “real world” Tamiflu use among patients hospitalised with a clinical or laboratory diagnosis of influenza during the 2009 pandemic. While this broader clinical definition of flu is less specific than in a randomised trial, it does represent the basis on which doctors make treatment decisions in everyday practice. </p>
<h2>Other research</h2>
<p>A <a href="http://www.ncbi.nlm.nih.gov/pubmed/23204175">meta-analysis of published data from 90 such studies</a> published in 2012 demonstrated a 60% reduction in the odds of intensive care unit admission and death among hospitalised influenza patients who received prompt antiviral therapy. This study was also funded by an unrestricted grant from Roche. </p>
<p>And <a href="http://www.thelancet.com/journals/lanres/article/PIIS2213-2600%2814%2970041-4/abstract">a follow-up 2014 analysis</a> of individual patient data from nearly 30,000 participants who took part in studies identified through the 2012 meta-analysis found a 50% reduction in the odds of death among those treated within 48 hours of symptom onset, compared with no treatment. It was also funded by Roche.</p>
<p>Given that randomised controlled trials are logistically and ethically challenging to conduct in pandemic events, it’s <a href="http://www.nature.com/news/analysis-of-trial-data-revives-flu-drug-row-1.16820">unlikely there will ever be a consensus</a> on Tamiflu’s effectiveness for use in pandemics. But observational studies conducted during the 2009 pandemic seem to reinforce the initial clinical trials evidence base on which Tamiflu was recommended for stockpiling against pandemic threats. </p>
<p>Indeed, <a href="http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2815%2960074-5/abstract">the drug’s benefits</a> appear to be greatest in severe influenza seasons and pandemics.</p><img src="https://counter.theconversation.com/content/38287/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jodie McVernon is a member of the Australian Technical Advisory Group on Immunisation and has provided advice to the Australian Government Office of Health Protection on pandemic planning, including on antiviral stockpiling and distribution; she is also a Director of the Influenza Specialist Group. </span></em></p>One of the biggest recent controversies in medicine involves the effectiveness of the antiviral drug Tamiflu. Governments have stockpiled the drug but many have raised doubts about its usefulness.Jodie McVernon, Associate Professor, Population Health, The University of MelbourneLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/304052014-08-12T07:23:37Z2014-08-12T07:23:37ZWorried about the flu season? Here’s the story behind the figures<figure><img src="https://images.theconversation.com/files/56266/original/yd5dy9n7-1407825251.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Influenza can be a serious and even life-threatening illness, but most infections are mild and self-limiting.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/triciawang/3596943233">HI TRICIA! 王 圣 捷/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-sa/4.0/">CC BY-NC-SA</a></span></figcaption></figure><p><a href="http://www.theguardian.com/society/2014/aug/11/flu-cases-in-australia-more-than-double-last-years-number">Today’s reports</a> suggesting a particularly severe flu season could easily be overstating the case. The figures, <a href="http://www.isg.org.au/assets/assets/FLU-IS-HERE-Embargoerd-Media-Relase-11-08-14.pdf?">released by Influenza Specialist Group</a> say there have been more than 20,000 cases of flu nationally so far this year, double last year’s number. </p>
<p>The release highlights the fundamental problem with trying to get a picture of the flu’s impact. This 20,979 figure comes from labs confirming the presence of the virus in samples sent to them by doctors working in hospitals or in the community.</p>
<p>This is known as notification data and placing too much reliance on these data can lead to an exaggeration of seasonal severity because testing has become more widespread and frequent.</p>
<p>Testing increased after the 2009 swine flu pandemic, with increased flu awareness among doctors and more labs performing tests. Increased testing has meant increased notifications, but not necessarily increased disease or severity. </p>
<p>This graph of nationally notified cases puts 2014 in perspective:</p>
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<img alt="" src="https://images.theconversation.com/files/56254/original/k2zzqydw-1407818581.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/56254/original/k2zzqydw-1407818581.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=453&fit=crop&dpr=1 600w, https://images.theconversation.com/files/56254/original/k2zzqydw-1407818581.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=453&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/56254/original/k2zzqydw-1407818581.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=453&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/56254/original/k2zzqydw-1407818581.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=569&fit=crop&dpr=1 754w, https://images.theconversation.com/files/56254/original/k2zzqydw-1407818581.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=569&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/56254/original/k2zzqydw-1407818581.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=569&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="attribution"><span class="source">National Notifiable Diseases Database</span></span>
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<p>While influenza can be a serious and even life-threatening illness, most infections are mild and self-limiting, and the 2014 season is unlikely to be any different.</p>
<p>There’s certainly been a rise in cases this year but we don’t yet know how high it will go. As the table above shows, it’s now a bit higher than 2013, but we don’t know whether the 2014 season is just starting to rise or has already peaked.</p>
<p>The 2013 season was late and mild, so it’s not really surprising that there are more cases this year than at the corresponding time last year. </p>
<h2>The 2014 flu season so far</h2>
<p>This is what we know about this year’s flu season: outbreaks have been reported in aged-care residential facilities, even where staff and resident vaccination coverage have been high. And in the community, younger people are seeing doctors with influenza-like illnesses. </p>
<p>Sounds pretty bad, right? It is but it’s also a little more complex than is usually acknowledged. And that’s often because acknowledging complexity can make public health messaging and vaccine marketing more difficult. So this is what you need to know. </p>
<p>First, influenza is a common infection that has a very wide clinical spectrum; infection can occur without any symptoms, without fever, or with a few mild respiratory symptoms. A <a href="http://www.thelancet.com/journals/lanres/article/PIIS2213-2600(14)70034-7/abstract">recent five-year study</a> from England, for instance, found less than half of all laboratory confirmed flu infections were associated with symptoms.</p>
<p>But it may also be associated with serious respiratory and other symptoms requiring intensive care admission.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/56267/original/t9gwhhwr-1407825545.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/56267/original/t9gwhhwr-1407825545.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/56267/original/t9gwhhwr-1407825545.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/56267/original/t9gwhhwr-1407825545.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/56267/original/t9gwhhwr-1407825545.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/56267/original/t9gwhhwr-1407825545.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/56267/original/t9gwhhwr-1407825545.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A recent UK study found less than half of all laboratory confirmed flu infections were associated with symptoms.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/thelotuscarroll/11421138033">Lotus Carroll/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-sa/4.0/">CC BY-NC-SA</a></span>
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<p>So, most infections are mild and resolve on their own but we obviously want to prevent serious infections. Vaccination is the best prevention measure but it is by no means perfect. </p>
<h2>The flu vaccine</h2>
<p>The important thing here is that vaccines aren’t all created equal. Rubella and measles vaccines are about 90% effective at preventing disease but the type of flu vaccines we have in Australia (inactivated vaccines) are only <a href="http://onlinelibrary.wiley.com/doi/10.1111/irv.12018/abstract">about 50% to 70% effective</a>.</p>
<p>Some years, they don’t even make this grade: an <a href="https://www.mja.com.au/journal/2014/201/2/influenza-vaccine-effectiveness-australia-results-australian-sentinel-practices">estimate for the 2012 vaccine in Australia</a> suggested it was only 23% effective. </p>
<p>What this means is that people should not expect to be protected from influenza just because they have been vaccinated. What they should expect is a decrease in their risk of infection. Most years that overall risk should be halved.</p>
<p>Another thing to keep in mind is that when we estimate the effectiveness of the influenza vaccine, we’re only estimating protection against disease we can identify. </p>
<p>We don’t know, for instance, whether the vaccine has a beneficial effect on mild disease. And because the circulating strains and the vaccine usually change every year, the effectiveness of the vaccine varies by year.</p>
<h2>It gets more complicated</h2>
<p>Although we can all get flu from any type of the influenza virus, people of different ages are likely to suffer adverse outcomes from different types. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/56268/original/cqmfb4g7-1407825672.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/56268/original/cqmfb4g7-1407825672.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=328&fit=crop&dpr=1 600w, https://images.theconversation.com/files/56268/original/cqmfb4g7-1407825672.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=328&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/56268/original/cqmfb4g7-1407825672.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=328&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/56268/original/cqmfb4g7-1407825672.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=412&fit=crop&dpr=1 754w, https://images.theconversation.com/files/56268/original/cqmfb4g7-1407825672.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=412&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/56268/original/cqmfb4g7-1407825672.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=412&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The type of flu vaccines we have in Australia (inactivated vaccines) are only about 50% to 70% effective.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/mccord/295079027">Lance McCord/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-sa/4.0/">CC BY-NC-SA</a></span>
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<p>The virus known as swine flu, which is the influenza subtype H1N1, for instance, is more likely to infect younger people, but the consequences of infection are still worse for older people if they’re infected. </p>
<p>But the aged-care facility outbreaks reported this season have mostly been caused by a different subtype of influenza virus, H3N2. This is the subtype generally associated with more severe influenza seasons. Although H1N1 dominated the season early, we’re now seeing the emergence of H3N2 viruses.</p>
<p>The influenza vaccines available in Australia are made of the components of three flu viruses – H1N1, H3N2 and B. As I said above, they’re changed every year in an attempt to provide protection against the right strain of the virus.</p>
<p>But here’s the rub. For a number of years now, inactivated influenza vaccines have <a href="https://www.mja.com.au/insight/2014/26/flu-vax-needs-mature-debate">not worked as well</a> against H3 as they have against H1.</p>
<p>In older people, in particular, effectiveness against H3 has been very poor; that’s why we’re seeing outbreaks in aged-care facilities despite high vaccine coverage in those places.</p>
<h2>What this means for you</h2>
<p>So, let’s put this all into perspective.</p>
<p>Influenza is common. It presents with a wide clinical spectrum, from infection without any symptoms to infection leading to death. You might be bedridden or you might not even notice you’ve got it.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/56270/original/r5s9dnnt-1407825911.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/56270/original/r5s9dnnt-1407825911.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=402&fit=crop&dpr=1 600w, https://images.theconversation.com/files/56270/original/r5s9dnnt-1407825911.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=402&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/56270/original/r5s9dnnt-1407825911.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=402&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/56270/original/r5s9dnnt-1407825911.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=505&fit=crop&dpr=1 754w, https://images.theconversation.com/files/56270/original/r5s9dnnt-1407825911.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=505&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/56270/original/r5s9dnnt-1407825911.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=505&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">You could end up in bed when you have the flu or you could not even notice you’ve got it, or fall somewhere in between.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/williambrawley/4195919691">William Brawley/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<p>Despite the usual messages, influenza symptoms can resemble the common cold. But unlike the common cold, flu can kill some people. </p>
<p>Death is more common in older adults with other medical problems, but also occurs – rarely – in otherwise healthy children. Serious outcomes, like hospital admission, are uncommon for healthy adults and death in this age group is exceedingly rare.</p>
<p>Although vaccination remains the best option for prevention, influenza vaccines don’t offer the sort of protection we’ve come to expect from the best childhood vaccines. </p>
<p>Finally, we are in the midst of this year’s influenza season. Over the next few weeks, many of us will be infected without even knowing it. And a small number of us will become seriously ill. Those who are at <a href="http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20850">serious risk of an adverse outcome</a> from infection should be vaccinated but realise that vaccination will not guarantee protection against influenza.</p><img src="https://counter.theconversation.com/content/30405/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Heath Kelly has accepted airfares and accommodation (but no honorarium) from Sanofi Pasteur to present at a one day Master class on influenza in Singapore in June 2014.</span></em></p>Today’s reports suggesting a particularly severe flu season could easily be overstating the case. The figures, released by Influenza Specialist Group say there have been more than 20,000 cases of flu nationally…Heath Kelly, Professor (Adjunct) in Infectious Diseases Epidemiology, Australian National UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/140482013-06-07T01:06:23Z2013-06-07T01:06:23ZThe heart of the matter: how effective is the flu jab really?<figure><img src="https://images.theconversation.com/files/25128/original/ht2xvdwm-1370487393.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">At the heart of debates about whether to get the flu shot is the question of its effectiveness.</span> <span class="attribution"><span class="source">Rachel Strum</span></span></figcaption></figure><p><em><strong>Facts about Flu</strong> - We’ve considered all kinds of matters related to influenza this week. Now to the heart of the matter.</em></p>
<p>People who think influenza vaccines are highly effective may have been surprised at <a href="http://www.usatoday.com/story/news/health/2013/02/21/flu-vaccine-doesnt-work-over-65/1934651/">recent news stories</a> saying they’re <a href="http://www.cidrap.umn.edu/cidrap/content/influenza/general/news/feb2113vaccine.html">only moderately so</a>. Although vaccines are still the best tool available to combat this seasonal scourge, their ability to protect lies well below that of other vaccines, such as those given in childhood.</p>
<p>The inactivated influenza vaccine (flu jab) is the only one licensed for use in Australia. To determine how well these vaccines protect people from the flu, scientists use results from two different types of studies. </p>
<p>The gold standard study is called a randomised controlled trial (RCT). The second type is the observational study.</p>
<h2>Randomised controlled trial</h2>
<p>In an RCT, about half of the subjects get the vaccine and the other half receive a placebo (a shot that contains only saline or some other safe, inert material). Those participating in the study don’t know which one they’ve received until the study has concluded.</p>
<p>Researchers design the study so that people recruited to participate are very similar in terms of age, health status, and gender. It’s important that both the groups are as alike as possible to ensure their bodies’ response to the shots are directly comparable.</p>
<p>The design of randomised controlled trials also allows for more control over variables that can affect how well a vaccine works under ideal conditions. </p>
<p>Participants are checked each week to see if they have any symptoms of an influenza-like illness. If they do, they’re tested. This allows researchers to know with more certainty that they have tested everyone with symptoms in their study. </p>
<p>After a time, researchers determine the frequency of influenza in both groups and determine how well the vaccine works. This is called vaccine efficacy.</p>
<h2>Observational studies</h2>
<p>The most commonly used observational study is known as a case-control study. This type of study helps estimate how well influenza vaccines work in a real-world setting, which is different to lab conditions for a number of reasons. </p>
<p>In a real-world setting, people unwell enough to seek out care and those with risk factors for complications become your primary study population. This tends to reduce the impact of the vaccine when compared to RCTs (although improvements in study design have minimised this reduction significantly), but reflects how influenza vaccines are actually used. </p>
<p>With this study type, people seeking care for an acute respiratory illness (known as an influenza-like illness) at a doctor’s office or medical clinic are voluntarily enrolled in the study. They’re identified as a case if they test positive for the influenza virus – meaning they were actually infected – and are designated a control if they test negative.</p>
<p>In the analysis, researchers compare the frequency of recent influenza vaccination among the cases and the controls, taking into account the same factors considered with the RCT. This estimate of how well the vaccine protects is known as vaccine effectiveness.</p>
<h2>So, how effective is it?</h2>
<p>During the 2008 and 2009 influenza seasons, an RCT was conducted in <a href="http://clinicaltrials.gov/ct2/show/NCT00562484">Australia</a> and New Zealand in healthy non-elderly adults. Vaccine efficacy against all three influenza strains included in the vaccine was 60%.</p>
<p>Case-control studies conducted in Australia found similar results. While the estimates of how well the vaccine works each year varies (because the formula of the vaccine changes), the <a href="http://onlinelibrary.wiley.com/doi/10.1111/irv.12018/abstract">average effectiveness</a> from 2007 to 2011 was 62% in healthy adults under the age of 65. </p>
<p>How well the vaccine works in a given year also depends on the <a href="https://theconversation.com/h1n1-h5n1-h7n9-what-on-earth-does-it-all-mean-14815">dominant strain of the virus</a> in circulation and the population group that’s most impacted by it. </p>
<p>All this means that, on average, healthy non-elderly adults in Australia can expect the vaccine to prevent an influenza infection serious enough to require medical care about 60% of the time. Based on data from clinical trials, up to 10% of adults and up to 20% of young children will be diagnosed with seasonal influenza in a given year. </p>
<p>In children aged between six to 59 months, results from an <a href="http://journals.lww.com/pidj/Abstract/2011/02000/Vaccine_Effectiveness_Against_Laboratory_confirmed.4.aspx">observational study</a> showed the vaccine works about 70% of the time in preventing influenza that requires medical attention. </p>
<p>Influenza vaccine efficacy and effectiveness studies including both observational and RCTs take place around the world. The results of these Australian studies are similar to a recently conducted review of influenza vaccine <a href="http://www.sciencedirect.com/science/article/pii/S147330991170295X">efficacy and effectiveness</a> from multiple countries.</p>
<h2>The vulnerable</h2>
<p>But data are limited on how well influenza vaccines work in adults over age 65 and in people with chronic health conditions and other risk factors that increase the likelihood of complications from influenza. </p>
<p>Yet these are the populations for which the influenza vaccine is strongly recommended and actively promoted in Australia and around the world.</p>
<p>What the data shows is that the influenza vaccine doesn’t work as well in these populations as it does in healthy adults of working age. Indeed, during the <a href="http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6207a2.htm">past influenza season</a>, vaccine effectiveness in people over 65 in the United States was 27%, while overall effectiveness for all ages was 56%. </p>
<p>While influenza vaccines don’t provide the level of protection desired by public health, they are still the best way to <a href="https://www.mja.com.au/journal/2013/198/7/evidence-based-policies-control-influenza">prevent influenza</a> for most people. They should continue to be used while <a href="http://www.cidrap.umn.edu/cidrap/center/mission/articles/ccivi-landing.html">better vaccines are developed</a>. </p>
<p><em>This is the final article in our series <strong>Facts about Flu</strong>. Click on the links below to read other instalments in the series.</em></p>
<p><strong>Part one</strong>: <a href="https://theconversation.com/of-influenza-flu-potions-and-key-opinion-leaders-14003">Of influenza, flu, potions and key opinion leaders</a></p>
<p><strong>Part two</strong>: <a href="https://theconversation.com/influenza-vaccine-for-2013-who-what-why-and-when-14050">Influenza vaccine for 2013: who, what, why and when?</a></p>
<p><strong>Part three</strong>: <a href="https://theconversation.com/h1n1-h5n1-h7n9-what-on-earth-does-it-all-mean-14815">H1N1, H5N1, H7N9? What on earth does it all mean</a></p>
<p><strong>Part four</strong>: <a href="https://theconversation.com/the-tamiflu-saga-shows-why-all-research-data-should-be-public-13951">The Tamiflu saga shows why all research data should be public</a></p>
<p><strong>Part five</strong>: <a href="https://theconversation.com/csls-flu-vaccine-leaves-a-hole-in-australias-pandemic-plan-14359">CSL’s flu vaccine leaves a hole in Australia’s pandemic plan</a></p>
<p><strong>Part six</strong>: <a href="https://theconversation.com/should-flu-shots-be-mandatory-for-health-care-workers-14039">Should flu shots be mandatory for health-care workers?</a></p>
<p><strong>Part seven</strong>: <a href="https://theconversation.com/the-holy-grail-of-influenza-research-a-universal-flu-vaccine-14046">The Holy Grail of influenza research: a universal flu vaccine</a></p>
<p><strong>Part eight</strong>: <a href="https://theconversation.com/is-it-really-the-flu-the-other-viruses-making-you-ill-in-winter-14895">Is it really the flu? The other viruses making you ill in winter</a> </p><img src="https://counter.theconversation.com/content/14048/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Nick Kelley does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Facts about Flu - We’ve considered all kinds of matters related to influenza this week. Now to the heart of the matter. People who think influenza vaccines are highly effective may have been surprised…Nick Kelley, Research Associate at the Center for Infectious Disease Research and Policy, University of MinnesotaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/148952013-06-06T20:43:17Z2013-06-06T20:43:17ZIs it really the flu? The other viruses making you ill in winter<figure><img src="https://images.theconversation.com/files/25126/original/twhtm8gd-1370486454.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A lot of the illness we think of being caused by the 'flu' is actually due to other viruses.</span> <span class="attribution"><span class="source">Kim Keegan</span></span></figcaption></figure><p><em><strong>Facts about Flu</strong> - Perhaps the misery you feel when ill in winter isn’t the fault of the much-maligned influenza virus after all.</em></p>
<p>RSV, hMPV, CoV… these may all sound like random acronyms, but they are influenza’s less well-known viral cousins. In fact, studies have shown that a lot of illness that we think of being caused by the “flu” is actually due to these <a href="http://www.ncbi.nlm.nih.gov/pubmed/15227858">other viruses</a>. </p>
<p>Some of them are seasonal, such as respiratory syncytial virus (RSV) and parainfluenza virus. While others, such as coronaviruses (CoV) and rhinoviruses, are found all year around. </p>
<p>And others still are found living in your nose, throat or windpipe, but it isn’t clear whether they do much. These include respiratory <a href="http://www.ncbi.nlm.nih.gov/pubmed/20357093">polyomaviruses</a> WU and KI (known to those in the field as the “Wookie” viruses). But why is all this important?</p>
<h2>Complications of respiratory viruses</h2>
<p>For most of us, respiratory viral infections are an annoyance that, at worst, require us to take a day or so off work. Occasionally, complications ensue in otherwise healthy people for reasons that aren’t entirely clear to doctors. </p>
<p>In recent years, we’ve found that around a quarter of the people are admitted to hospital with <a href="https://www.mja.com.au/journal/2012/197/4/hospitalisation-confirmed-influenza-sentinel-surveillance-system-2010-and-2011?0=ip_login_no_cache=d7a6556e77276ee17283715da91d6f21">influenza</a> don’t have an obvious reason for ending up there (that is, they don’t have an identifiable medical risk factor). </p>
<p>In addition to secondary bacterial pneumonia, which is known as a complication of the flu, some studies suggest that influenza might <a href="http://jid.oxfordjournals.org/content/early/2012/10/09/infdis.jis598.full">trigger</a> heart attacks and strokes.</p>
<p>In some people, “ordinary” respiratory viruses are known to be dangerous. These include asthmatics, those whose underlying severe medical problems, and those with impaired immune systems. </p>
<p>In young children, viral infections can cause diseases such as croup, which sometimes requires hospitalisation. In Indigenous children, we think that there’s an <a href="http://www.biomedcentral.com/1471-2334/11/161">interplay</a> between viral infections and more serious bacterial infections such as middle ear disease, an important cause of impaired hearing.</p>
<p>So, there’s clearly a real need for effective vaccines and treatments for some of these other viruses.</p>
<p>Indeed, some of these respiratory viruses are really nasty. <a href="http://www.who.int/csr/sars/country/table2004_04_21/en/index.html">SARS</a>, a coronavirus that emerged in China, was known to have affected 8,096 people and resulted in the deaths of at least 775 (including many health-care workers caring for infected patients). It was estimated to <a href="http://www.ncbi.nlm.nih.gov/books/NBK92473/">cost</a> around A$40 billion. </p>
<p>On a different scale, a related <a href="http://www.who.int/csr/disease/coronavirus_infections/en/index.html">novel coronavirus</a> is currently the focus on attention in the Middle East, where a hospital outbreak in Saudi Arabia has been known to involve 13 patients. Seven of these people have died and over 50 cases have been reported in total.</p>
<h2>What ails thee</h2>
<p>For most of us, what we think of as “the flu” (fever, with a runny nose, sore throat or cough, and body aches and pains) is actually not due to influenza virus infections. In fact, <a href="http://www.ncbi.nlm.nih.gov/pubmed/15227858">studies</a> have shown that of those with this syndrome, only about 40% have influenza – even in the middle of winter.</p>
<p>There don’t appear to be any <a href="http://www.ncbi.nlm.nih.gov/pubmed/22712880">simple ways</a> to tell what’s due to the influenza virus and what’s due to other viral infections. The currently available tests aren’t that useful because they’re relatively expensive and the results aren’t available for at least a day or so.</p>
<p>This is important for our perception of the effectiveness of influenza vaccines and treatment. While this vaccine is <a href="http://www.ncbi.nlm.nih.gov/pubmed/19333374">reasonably effective</a> in preventing influenza, it isn’t anywhere as good at preventing flu-like symptoms generally (because it only prevents those due to influenza).</p>
<p>The flu vaccine may <a href="https://www.mja.com.au/journal/2013/198/7/evidence-based-policies-control-influenza">not be quite as good</a> as we had first thought, but it’s still better than nothing. It has been shown to reduce the need to take <a href="http://cid.oxfordjournals.org/content/48/3/292.full">days off work</a> and <a href="http://www.ncbi.nlm.nih.gov/pubmed/21810450">prevent hospitalisation</a>. </p>
<p>There is some evidence that the protection of influenza vaccines may be <a href="http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=4699592">inferior</a> to that produced by natural infection. This is the rationale for a new generation of “live attenuated” vaccines that provide protection but without causing significant illness. </p>
<p>Although these new vaccines, which are not yet available in Australia, seem to be effective in <a href="http://www.nejm.org/doi/full/10.1056/NEJMoa065368">children</a>, results in <a href="http://www.nejm.org/doi/full/10.1056/NEJMoa0808652">adults</a> have been disappointing. </p>
<p>Antivirals are also only <a href="http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008965.pub3/abstract;jsessionid=49246D9AB89436FC1FC95068FD0D770A.d02t04">effective</a> for influenza and some would say that even this is <a href="http://theconversation.com/tamiflu-effectiveness-questioned-as-drug-company-refuses-to-release-data-10733">debatable</a>. To have any effect, they need to be started soon after the onset of symptoms – both these factors dilute out the effectiveness of treatment.</p>
<p>Other than influenza, there’s no proven effective treatment against respiratory viruses, although there are some expensive <a href="http://pediatrics.aappublications.org/content/102/3/531">preventative agents</a> and <a href="http://bloodjournal.hematologylibrary.org/content/117/10/2755.long">antivirals</a> we often try for patients who are critically ill or who are at very high risk of getting really ill.</p>
<p>Remarkably, respiratory viruses, which are essentially little particles of genetic material that arguably aren’t even alive, continue to cause all this misery.</p>
<p><em>This is the eighth article in our series <strong>Facts about Flu</strong>. Click on the links below to read other instalments in the series.</em></p>
<p><strong>Part one</strong>: <a href="https://theconversation.com/of-influenza-flu-potions-and-key-opinion-leaders-14003">Of influenza, flu, potions and key opinion leaders</a></p>
<p><strong>Part two</strong>: <a href="https://theconversation.com/influenza-vaccine-for-2013-who-what-why-and-when-14050">Influenza vaccine for 2013: who, what, why and when?</a></p>
<p><strong>Part three</strong>: <a href="https://theconversation.com/h1n1-h5n1-h7n9-what-on-earth-does-it-all-mean-14815">H1N1, H5N1, H7N9? What on earth does it all mean</a></p>
<p><strong>Part four</strong>: <a href="https://theconversation.com/the-tamiflu-saga-shows-why-all-research-data-should-be-public-13951">The Tamiflu saga shows why all research data should be public</a></p>
<p><strong>Part five</strong>: <a href="https://theconversation.com/csls-flu-vaccine-leaves-a-hole-in-australias-pandemic-plan-14359">CSL’s flu vaccine leaves a hole in Australia’s pandemic plan</a></p>
<p><strong>Part six</strong>: <a href="https://theconversation.com/should-flu-shots-be-mandatory-for-health-care-workers-14039">Should flu shots be mandatory for health-care workers?</a></p>
<p><strong>Part seven</strong>: <a href="https://theconversation.com/the-holy-grail-of-influenza-research-a-universal-flu-vaccine-14046">The Holy Grail of influenza research: a universal flu vaccine</a></p>
<p><strong>Part nine</strong>: <a href="https://theconversation.com/the-heart-of-the-matter-how-effective-is-the-flu-jab-really-14048">The heart of the matter: how effective is the flu jab really?</a></p><img src="https://counter.theconversation.com/content/14895/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Allen Cheng receives funding from the Department of Health and Ageing to perform surveillance for influenza. His employer has received funding from CSL Ltd for a study of influenza vaccine side effects. He is a member of the Advisory Committee on Prescription Medicines that advises the Therapeutic Goods Administration on the regulation of drugs and vaccines - the views expressed here may not necessarily reflect the views of the Committee or the TGA.</span></em></p>Facts about Flu - Perhaps the misery you feel when ill in winter isn’t the fault of the much-maligned influenza virus after all. RSV, hMPV, CoV… these may all sound like random acronyms, but they are influenza’s…Allen Cheng, Associate Professor in Infectious Diseases Epidemiology, Monash UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/140462013-06-06T02:13:12Z2013-06-06T02:13:12ZThe Holy Grail of influenza research: a universal flu vaccine<figure><img src="https://images.theconversation.com/files/25085/original/45hz76nb-1370411538.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Creating the universal flu vaccine will require more than innovation in science.</span> <span class="attribution"><span class="source">Joel Kramer</span></span></figcaption></figure><p><em><strong>Facts about Flu</strong> - What if you needed just one flu shot to protect you from pandemic as well as the yearly seasonal flu viruses in circulation?</em></p>
<p>Imagine you could only identify people by their jackets. Once someone took off their jacket and put a new one on, you would have no idea who they were. Sound frustrating? </p>
<p>No, this is not a pitch for a new sci-fi movie – it’s how your immune system and the influenza virus interact.</p>
<p>Your immune system uses clues from intruders, such as viruses and bacteria, to figure out how to respond (or not respond). In the case of influenza, the clues most easily and quickly available are the outer coat proteins of the virus, which are dominated by two called hemagglutinin (HA) and neuraminidase (NA).</p>
<p>Unfortunately, these proteins change or mutate more often than do other influenza proteins. This means that every time your body encounters an influenza virus with slightly different coat proteins, it can’t immediately recognise the virus. </p>
<p>And, in the worst-case scenario, this means you will get ill before your immune system can work out what happened and mount a defence.</p>
<p>These mutations in viral coat proteins are the main reason influenza vaccine formulations are changed frequently and vaccination is recommended every year.</p>
<h2>Better targets</h2>
<p>The idea behind a “universal” influenza vaccine is to devise a way of educating your immune system to be less easily fooled by small changes in the virus’ coat. Ideally, a universal vaccine would protect you from all types of influenza viruses for a lifetime.</p>
<p>Two <a href="https://theconversation.com/h1n1-h5n1-h7n9-what-on-earth-does-it-all-mean-14815">main types of influenza</a> infect humans, type A and type B (seasonal influenza vaccines comprise both types). They’re quite different and likely require different vaccine strategies. </p>
<p>Influenza A is more complex, being further subdivided into subtypes based on their reactivity in specific tests (called antigenicity) and the genetic similarity of their hemagglutinin and neuraminidase. </p>
<p>Two examples of A strains are 2009 H1N1 pandemic influenza and the H7N9 strain currently infecting people in China.</p>
<p>In the short term, it’s likely that when someone talks about a universal influenza vaccine, she’s really talking about a more broadly cross-protective vaccine against more than one strain of influenza A.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/25084/original/6jysdrfd-1370411526.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/25084/original/6jysdrfd-1370411526.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=352&fit=crop&dpr=1 600w, https://images.theconversation.com/files/25084/original/6jysdrfd-1370411526.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=352&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/25084/original/6jysdrfd-1370411526.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=352&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/25084/original/6jysdrfd-1370411526.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=443&fit=crop&dpr=1 754w, https://images.theconversation.com/files/25084/original/6jysdrfd-1370411526.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=443&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/25084/original/6jysdrfd-1370411526.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=443&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Our immune system identifies influenza viruses by their coats.</span>
<span class="attribution"><span class="source">Guy H/Flickr</span></span>
</figcaption>
</figure>
<p>A broadly cross-protective vaccine would be required to create a response that your immune system hasn’t figured out how to trigger naturally, which is a difficult task. Scientists believe that the key to such a vaccine is in the antigen (the active ingredient) in vaccines. </p>
<p>Viral coat proteins are generally the easiest antigens or parts of the influenza virus for the immune system to access.
But vaccines don’t have to be constrained by normal influenza biology because scientists can design vaccines using methods, strategies or ingredients not available in nature. </p>
<p>The influenza virus contains internal proteins, such as the matrix protein and the nucleoprotein, that don’t mutate frequently. And even the ever-changing hemagglutinin and neuraminidase proteins have parts (called either domains or epitopes, depending on their size) that don’t frequently mutate. But these are normally hidden from the immune system. </p>
<p>These protein parts are all possible targets for a universal vaccine. Couple these novel antigens with advances in vaccine manufacturing and delivery, and the scientific prospects for universal or broadly protective influenza vaccines are bright.</p>
<h2>Hurdles on the horizon</h2>
<p>But sadly, clever ideas alone don’t bring a vaccine to market. A new kind of vaccine would face a number of barriers before it could ever be administered to the general public. These include regulation, financial incentives for its creation, and policy.</p>
<p>Influenza vaccines are approved by regulatory authorities based on the response the vaccine generates toward the frequently changing portion of hemagglutinin. If a vaccine doesn’t rely on that particular portion of the viral coat, it doesn’t have a clear or inexpensive path to regulatory approval.</p>
<p>Also, a broadly protective vaccine may not need to be administered every year, which would cause a pricing conundrum. A universal vaccine would need to command a much higher price or it wouldn’t be as commercially viable as current flu vaccines, which are administered every year.</p>
<p>But to get to even that point, the vaccine must overcome current policy barriers. Many countries recommend current influenza vaccines for large portions of their populations – <em>as is</em> – with no improvements. This is clearly a disincentive for investment in influenza vaccine innovation.</p>
<p>Clearly, this is one puzzle that cannot be solved with brilliant science alone. If we want to solve a problem that even nature can’t, we’ll need much more than clever science. </p>
<p>We will need smart innovations in regulation as well as market incentives to make universal influenza vaccines a reality. Are we up for the challenge?</p>
<p><strong>Click on the links below for:</strong></p>
<ul>
<li><p><a href="http://www.cidrap.umn.edu/cidrap/files/80/ccivi%20report.pdf">A report I co-authored</a> on all the aspects of vaccine manufacturing to identify the barriers to a novel influenza vaccine</p></li>
<li><p><a href="http://www.cell.com/trends/microbiology/abstract/S0966-842X%2813%2900074-7">A review</a> describing the current options for cross-protective or universal influenza vaccines</p></li>
<li><p>A <a href="http://www.nature.com/nm/journal/v16/n12/full/nm1210-1389.html">review and commentary</a> on the host-response necessary to obtain universal protection from influenza vaccines</p></li>
</ul>
<p><em>This is the seventh article in our series <strong>Facts about Flu</strong>. Click on the links below to read other instalments in the series.</em></p>
<p><strong>Part one</strong>: <a href="https://theconversation.com/of-influenza-flu-potions-and-key-opinion-leaders-14003">Of influenza, flu, potions and key opinion leaders</a></p>
<p><strong>Part two</strong>: <a href="https://theconversation.com/influenza-vaccine-for-2013-who-what-why-and-when-14050">Influenza vaccine for 2013: who, what, why and when?</a></p>
<p><strong>Part three</strong>: <a href="https://theconversation.com/h1n1-h5n1-h7n9-what-on-earth-does-it-all-mean-14815">H1N1, H5N1, H7N9? What on earth does it all mean</a></p>
<p><strong>Part four</strong>: <a href="https://theconversation.com/the-tamiflu-saga-shows-why-all-research-data-should-be-public-13951">The Tamiflu saga shows why all research data should be public</a></p>
<p><strong>Part five</strong>: <a href="https://theconversation.com/csls-flu-vaccine-leaves-a-hole-in-australias-pandemic-plan-14359">CSL’s flu vaccine leaves a hole in Australia’s pandemic plan</a></p>
<p><strong>Part six</strong>: <a href="https://theconversation.com/should-flu-shots-be-mandatory-for-health-care-workers-14039">Should flu shots be mandatory for health-care workers?</a></p>
<p><strong>Part eight</strong>: <a href="https://theconversation.com/is-it-really-the-flu-the-other-viruses-making-you-ill-in-winter-14895">Is it really the flu? The other viruses making you ill in winter</a> </p>
<p><strong>Part nine</strong>: <a href="https://theconversation.com/the-heart-of-the-matter-how-effective-is-the-flu-jab-really-14048">The heart of the matter: how effective is the flu jab really?</a></p><img src="https://counter.theconversation.com/content/14046/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Katie Ballering does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Facts about Flu - What if you needed just one flu shot to protect you from pandemic as well as the yearly seasonal flu viruses in circulation? Imagine you could only identify people by their jackets. Once…Katie Ballering, Research Associate at the Center for Infectious Disease Research and Policy, University of MinnesotaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/140392013-06-05T20:41:51Z2013-06-05T20:41:51ZShould flu shots be mandatory for health-care workers?<figure><img src="https://images.theconversation.com/files/25079/original/qysw7qjf-1370409168.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The idea of vulnerable patients becoming infected by their health-care practitioner has spawned mandatory vaccination policies in many places.</span> <span class="attribution"><span class="source">Thompson Rivers University</span></span></figcaption></figure><p><em><strong>Facts about Flu</strong> – Today we consider the ethics of requiring one group of people to have the flu shot as a condition of employment.</em></p>
<p>We’re still looking for ways of preventing and treating influenza, and several vaccines are available. But there’s a growing controversy about whether some populations should be forced to vaccinate for the health of others. </p>
<p>Health-care workers are prime targets for mandatory influenza vaccination because they must maintain good health while they assist the ill. The idea of vulnerable patients, including the elderly, becoming infected by their health-care practitioner has spawned mandatory vaccination policies in many places, but are they clinically and ethically sound?</p>
<h2>Making rules</h2>
<p>The 10th edition of the Australian Immunisation Handbook <a href="http://www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/B5D5093F77D77F07CA257B2600816A05/$File/NIPS1.pdf">recommends influenza vaccination</a> for all health-care workers, staff of nursing homes and long-term care facilities (including students). </p>
<p>And around the world, <a href="http://www.immunize.org/honor-roll/influenza-mandates.asp">hospitals and health systems</a> are creating policies requiring their health-care workers to be vaccinated against influenza. </p>
<p>Some require it as a condition of employment unless there’s a medical reason (for instance <a href="http://www.immunize.org/honor-roll/influenza-mandates.asp#dc">Capital Hill Nursing Center, Washington DC</a>), while others impose work restrictions on those who refuse (such as requiring them to <a href="http://www.shea-online.org/View/ArticleId/113/Strict-Policy-Raises-Hospital-s-Worker-Flu-Vaccination-Rate-Above-90-Percent.aspx">wear face masks</a>). </p>
<p>In between are places such as the <a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=23163679">Peter MacCallum Cancer Centre</a> in Melbourne, which, since 2009, has had a “mandatory” influenza vaccination program. But there are no punitive consequences for staff who refuse to participate. </p>
<p>According to the <a href="http://www.preventinfluenza.org/profs_workers.asp">Immunization Action Coalition (IAC)</a>, a non-profit organisation led by four family physicians and a paediatrician:</p>
<blockquote>
<p>Vaccination of health-care workers (HCWs) has been shown to reduce influenza infection and absenteeism among HCWs, prevent mortality in their patients, and result in financial savings to sponsoring health institutions. </p>
</blockquote>
<p>But is there data to support this statement and therefore, mandatory vaccination measures?</p>
<h2>Show us your data</h2>
<p>The Cochrane Collaboration, an international research review organisation, insists there isn’t.</p>
<p>In their report, <a href="http://onlinelibrary.wiley.com/store/10.1002/14651858.CD005187.pub3/asset/CD005187.pdf?v=1&t=hhhb3cbt&s=cf4a1a4b5c10803ca9e5cefab029e730d8f5a899">Influenza vaccination for health care workers who work with the elderly</a>, they performed a meta-analysis, exploring data from five published research studies on the matter. </p>
<p>The report concluded that vaccination didn’t show any effect on laboratory-proven influenza, pneumonia or deaths from pneumonia. The Cochrane review also noted that there was “no accurate data on rates of laboratory-proven influenza in healthcare workers.” </p>
<p>Another <a href="http://www.ncbi.nlm.nih.gov/pubmed/21978606">study</a> (by researchers based in Hong Kong) performed a similar meta-analysis of the effectiveness of seasonal influenza vaccination in health-care workers. It said:</p>
<blockquote>
<p>No evidence can be found of influenza vaccinations significantly reducing the incidence of influenza, number of influenza-like-illness episodes, or days with influenza-like illness. </p>
</blockquote>
<p>With this constellation of information, it’s difficult to see how the IAC and the Australian Technical Advisory Group on Immunisation (authors of the Australian Immunisation Handbook) draw their conclusions.</p>
<p>Given the lack of evidence supporting mandated influenza vaccination for health-care workers, what are the harms of initiating and enforcing such policies?</p>
<h2>Ethical considerations</h2>
<p>Health-care worker vaccination mandates are potentially harmful without evidence of the benefits they aim to produce. In terms of ethics, policies that lack supporting data can spread public fear; namely, that risks to patients are high unless mandates are in place. </p>
<p>Mandates could also result in a false sense of safety and less care with common-sense protections, such as hand-washing and drying, and covering the mouth and nose when sneezing and coughing. </p>
<p>And people who experience serious (even if not life-threatening) vaccination reactions will be unnecessarily burdened.</p>
<p>Mandates with harsh consequences, such as employment termination or hiring blockade, violate health-care workers’ autonomy because of their inherent coerciveness. </p>
<p>On the other hand, vaccine manufacturers will benefit; sales from the top 10 vaccine manufacturers were estimated at <a href="http://www.fiercevaccines.com/special-reports/top-10-selling-flu-vaccines-2012">US$2.65 billion in 2012</a>. And employers and health systems will perceive risk-management benefit – and <a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=23415931">legal teams</a> will stand by ready to defend the vaccine mandates. </p>
<p>But the ethical principle of non-maleficence (the goal of avoiding or minimising harm) requires policy bodies, employers, health systems and legal teams, to take a second look at such mandates because there’s no clinical evidence for this vaccination scheme to become standard care. </p>
<p>The notion of “protecting patients” creates a duty of care propped up by the vaccination mandate. But given the lack of evidence for benefits, there can be no imposed duty to make health-care workers get an influenza vaccination.</p>
<p><em>This is the sixth article in our series <strong>Facts about Flu</strong>. Click on the links below to read other instalments in the series.</em></p>
<p><strong>Part one</strong>: <a href="https://theconversation.com/of-influenza-flu-potions-and-key-opinion-leaders-14003">Of influenza, flu, potions and key opinion leaders</a></p>
<p><strong>Part two</strong>: <a href="https://theconversation.com/influenza-vaccine-for-2013-who-what-why-and-when-14050">Influenza vaccine for 2013: who, what, why and when?</a></p>
<p><strong>Part three</strong>: <a href="https://theconversation.com/h1n1-h5n1-h7n9-what-on-earth-does-it-all-mean-14815">H1N1, H5N1, H7N9? What on earth does it all mean</a></p>
<p><strong>Part four</strong>: <a href="https://theconversation.com/the-tamiflu-saga-shows-why-all-research-data-should-be-public-13951">The Tamiflu saga shows why all research data should be public</a></p>
<p><strong>Part five</strong>: <a href="https://theconversation.com/csls-flu-vaccine-leaves-a-hole-in-australias-pandemic-plan-14359">CSL’s flu vaccine leaves a hole in Australia’s pandemic plan</a></p>
<p><strong>Part seven</strong>: <a href="https://theconversation.com/the-holy-grail-of-influenza-research-a-universal-flu-vaccine-14046">The Holy Grail of influenza research: a universal flu vaccine</a></p>
<p><strong>Part eight</strong>: <a href="https://theconversation.com/is-it-really-the-flu-the-other-viruses-making-you-ill-in-winter-14895">Is it really the flu? The other viruses making you ill in winter</a> </p>
<p><strong>Part nine</strong>: <a href="https://theconversation.com/the-heart-of-the-matter-how-effective-is-the-flu-jab-really-14048">The heart of the matter: how effective is the flu jab really?</a></p><img src="https://counter.theconversation.com/content/14039/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Katrina Bramstedt does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Facts about Flu – Today we consider the ethics of requiring one group of people to have the flu shot as a condition of employment. We’re still looking for ways of preventing and treating influenza, and…Katrina Bramstedt, Associate Professor, Medical Ethics, Bond UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/143592013-06-05T01:57:00Z2013-06-05T01:57:00ZCSL’s flu vaccine leaves a hole in Australia’s pandemic plan<figure><img src="https://images.theconversation.com/files/25044/original/6f35stqd-1370391118.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Not being able to give children the locally-manufactured vaccine leaves a hole in our pandemic preparations.</span> <span class="attribution"><span class="source">Julian Smith/AAP</span></span></figcaption></figure><p><em><strong>Facts about Flu</strong> - We often hear of an expected pandemic and had a scare in 2009 with the swine flu, but how well are we prepared?</em></p>
<p>Although no longer considered an immediate risk, the <a href="http://www.who.int/csr/don/2013_05_29/en/index.html">recent outbreak of bird flu</a> (H7N9) in China means pandemic planning is back on national agendas. A cornerstone of these plans is the early availability of vaccines - and Australia may have a problem. </p>
<p>Depending on when it becomes available, a pandemic vaccine should be targeted at those most at risk of a severe outcome from infection or at those who amplify its spread. </p>
<p>For both the seasonal and pandemic flu, the main spreaders are children. So a pandemic vaccine should be safe to give to children. Indeed, children, especially the very young, are one of the groups most at risk of <a href="http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5810a1.htm">severe outcomes</a>.</p>
<p>During the 2009 flu pandemic, Australia relied on local manufacturer CSL to produce a vaccine. After China, Australia was the second country in the world to have a pandemic vaccine available. It was given to both adults and children.</p>
<p>But CSL’s influenza vaccines are no longer recommended for children younger than five years and doubt exists about their safe use in children up to ten years old. </p>
<p>The change in recommendation by Australia’s <a href="http://www.nhmrc.gov.au/guidelines/publications/nic0043a">National Health and Medical Research Council</a> followed events in 2010, which had their genesis three years earlier.</p>
<h2>Questions about safety</h2>
<p>In 2007, a number of children in Western Australia died of influenza-related causes. So, the state government <a href="http://onlinelibrary.wiley.com/doi/10.1111/j.1750-2659.2010.00167.x/abstract">started a campaign</a> to provide free flu vaccines to children under the age of five. </p>
<p>CSL and other vaccine manufacturers provided vaccines at no cost. The first year of the campaign (2008) went well and the <a href="http://journals.lww.com/pidj/Abstract/2011/02000/Vaccine_Effectiveness_Against_Laboratory_confirmed.4.aspx">vaccine was assessed</a> as being about 60% effective, which is pretty much as expected. </p>
<p>No safety problems were recognised in 2008 or 2009, but things went horribly wrong in 2010.</p>
<p>In that year, the CSL flu vaccine – but not other registered vaccines – were found to have caused an unusually large number of high fevers. Some of these fevers were so severe that they <a href="http://bmjopen.bmj.com/content/1/1/e000016.abstract">led to fits</a>.</p>
<p>What’s more, some of the fits were prolonged and at least one resulted in <a href="http://www.theaustralian.com.au/news/features/virus-in-the-system/story-e6frg8h6-1226063484330">ongoing disability</a> in a previously healthy child. Following extensive investigation, the CSL vaccines are no longer recommended for children younger than five years old in Australia, the United Kingdom or the United States.</p>
<p>The events of 2010 probably couldn’t have been foreseen because the Fluvax seems to have been safe for children in some years but not others. It’s a problem CSL has yet to fully understand but, in retrospect, it <a href="http://www.sciencedirect.com/science/article/pii/S0264410X13004076">does not appear</a> to be isolated to 2010. </p>
<h2>Fevers and children</h2>
<p>CSL’s Fluvax was <a href="https://www.ebs.tga.gov.au/servlet/xmlmillr6?dbid=ebs%2FPublicHTML%2FpdfStore.nsf&docid=CDB8FE0FC46396A2CA257AF0003CBA98&agid=(PrintDetailsPublic)&actionid=1">first registered in Australia</a> for adults and children in 1991, at a time when formal studies of efficacy and safety were not routinely required. The vaccine was re-licensed for children in 2002, in a formulation that did not contain the preservative thiomersal, but was otherwise largely unchanged from the vaccine registered 11 years previously. </p>
<p>The regulator, Australia’s <a href="http://www.tga.gov.au/">Therapeutic Goods Administration</a>, refers to this method of registration as “grandfathering”. This implies the registration is based on confidence arising from widespread use or experience, but it’s not necessarily supported by formal evidence. </p>
<p>But grandfathering of Fluvax for children was done with almost no grandfatherly experience of its use in children. Although used widely in adults for many years, Fluvax was little used in children before the Western Australian campaign. </p>
<p>Because Fluvax was registered for children in Australia, it was <a href="https://www.mja.com.au/journal/2013/198/7/challenges-regulating-influenza-vaccines-children?0=ip_login_no_cache%3Da88ef0f843dc86ae09984d97357b1e83">registered for use in children</a> in a number of other countries – even though the Australian registration was not based on efficacy or safety data. </p>
<p>The <a href="http://www.lakemedelsverket.se/SPC_PIL/Pdf/par/Afluria,%20suspension%20for%20injection.pdf">international practice</a> of registering in one country when the vaccine was registered in another country was followed. It was only when Sweden requested safety data on the vaccine formulation without the thiomersal preservative that CSL conducted a safety and efficacy trial in children. This was done over two years in 2005 and 2006.</p>
<p>The <a href="http://onlinelibrary.wiley.com/doi/10.1111/j.1750-2659.2009.00108.x/abstract">results of this trial</a> were not published until 2009. And although not recognised at the time, they foreshadowed the problems of increased fever and related fits that were detected the following year. </p>
<p>At the request of US regulators, in 2009 CSL conducted a <a href="http://clinicaltrials.gov/ct2/show/NCT00959049?term=CSLCT-USF-07-36&rank=1">head-to-head comparison</a> of Fluvax with another US-registered influenza vaccine in children. Fluvax produced significantly more fevers than the other vaccine.</p>
<p>In another CSL-sponsored trial in Australia <a href="http://onlinelibrary.wiley.com/doi/10.1111/irv.12107/abstract">published this year</a>, the company’s 2009 southern hemisphere vaccine was found to be associated with high fever in children.</p>
<h2>A hole in the plan</h2>
<p>Fluvax was no longer recommended for young children after 2010, but it has been inadvertently given to children in Australia since. There was a <a href="http://www.news.com.au/breaking-news/banned-flu-vaccine-given-to-wa-children/story-e6frfkp9-1226335228864">serious adverse outcome</a> documented in the ACT only last year.</p>
<p>Given these ongoing problems, there may be reluctance to give any future pandemic influenza vaccine manufactured by CSL to children, unless it’s shown that benefits outweighed risks. And this leaves a potentially large hole in Australia’s pandemic plans.</p>
<p>To fill this hole, CSL would need to show it understood why its seasonal vaccines cause high fevers in children, at least in some years. The US Food and Drug Administration <a href="http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm259888.htm">has suggested the problem</a> is related, at least in part, to the CSL manufacturing process, and <a href="http://www.sciencedirect.com/science/article/pii/S0264410X12014272">CSL agrees</a>. </p>
<p>Even when the problem (known in the trade as the “root cause”) is identified, understood and fixed, CSL would need to conduct a very large trial of the improved vaccine to demonstrate its safety and efficacy. Only then could Australians once again feel confident about giving Fluvax to children. </p>
<p>Failing that, the nation will need to turn to other vaccine manufacturers to fill the hole in our pandemic plans. But this may mean there are insufficient doses available when the vaccine is most needed.</p>
<p><em>This is the fifth article in our series <strong>Facts about Flu</strong>. Click on the links below to read other instalments in the series.</em></p>
<p><strong>Part one</strong>: <a href="https://theconversation.com/of-influenza-flu-potions-and-key-opinion-leaders-14003">Of influenza, flu, potions and key opinion leaders</a></p>
<p><strong>Part two</strong>: <a href="https://theconversation.com/influenza-vaccine-for-2013-who-what-why-and-when-14050">Influenza vaccine for 2013: who, what, why and when?</a></p>
<p><strong>Part three</strong>: <a href="https://theconversation.com/h1n1-h5n1-h7n9-what-on-earth-does-it-all-mean-14815">H1N1, H5N1, H7N9? What on earth does it all mean</a></p>
<p><strong>Part four</strong>: <a href="https://theconversation.com/the-tamiflu-saga-shows-why-all-research-data-should-be-public-13951">The Tamiflu saga shows why all research data should be public</a></p>
<p><strong>Part six</strong>: <a href="https://theconversation.com/should-flu-shots-be-mandatory-for-health-care-workers-14039">Should flu shots be mandatory for health-care workers?</a></p>
<p><strong>Part seven</strong>: <a href="https://theconversation.com/the-holy-grail-of-influenza-research-a-universal-flu-vaccine-14046">The Holy Grail of influenza research: a universal flu vaccine</a></p>
<p><strong>Part eight</strong>: <a href="https://theconversation.com/is-it-really-the-flu-the-other-viruses-making-you-ill-in-winter-14895">Is it really the flu? The other viruses making you ill in winter</a> </p>
<p><strong>Part nine</strong>: <a href="https://theconversation.com/the-heart-of-the-matter-how-effective-is-the-flu-jab-really-14048">The heart of the matter: how effective is the flu jab really?</a></p><img src="https://counter.theconversation.com/content/14359/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Heath Kelly once attended a CSL vaccine meeting to discuss study design and will be attending a meeting in Valencia, Spain in June sponsored by Sanofi Pasteur. </span></em></p>Facts about Flu - We often hear of an expected pandemic and had a scare in 2009 with the swine flu, but how well are we prepared? Although no longer considered an immediate risk, the recent outbreak of…Heath Kelly, Professor (Adjunct) in Infectious Diseases Epidemiology, Australian National UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/139512013-06-04T20:44:02Z2013-06-04T20:44:02ZThe Tamiflu saga shows why all research data should be public<figure><img src="https://images.theconversation.com/files/25006/original/bxfpp6yd-1370324296.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Roche has repeatedly refused to hand over trial data so researchers can evaluate whether Tamiflu reduces the symptoms of influenza.</span> <span class="attribution"><span class="source">kiyong2/Flickr</span></span></figcaption></figure><p><em><strong>Facts about Flu</strong> - Today, we consider the long-running attempt to evaluate whether the antiviral drug Tamiflu works.</em></p>
<p>There’s a dispute going on at the moment, a war of words with lots of public relations manoeuvring. It’s all about the disclosure of trials undertaken in the past. And it is between Cochrane reviewers (of which I am one) and Big Pharma (in this case, Hoffman-La-Roche of Switzerland).</p>
<p>To understand the dispute, it’s necessary to go back a bit in history. </p>
<p>Tamiflu (oseltamivir) is a drug, cleverly-designed in 2000 to attack a molecule in the influenza virus. It prevents the influenza virus bursting infected human cells to spread more virus in the body. </p>
<p>It works rather like antibiotics on bacteria, except that it’s very specific to viruses or, rather, one virus exclusively – the one that causes influenza. It looked as if this class of drug was going to revolutionise treating this virus’ infections, in much the same way that antibiotics have made treatment of once-dreaded bacterial infections routine.</p>
<p>Roche performed trials and the results were used to get approval from different regulatory authorities for it to be used routinely. The agencies include the US FDA (Federal Drug Administration), Europe’s EMA (European Medicines Authority), and Australia’s TGA (Therapeutic Drug Administration). </p>
<p>The trial reports supplied to regulatory authorities are called clinical study reports, and they are massive documents with added volumes of appendices, which set out every important detail of the trial. </p>
<p>The FDA approved Tamiflu for shortening the illness, but not for preventing complications. “Complications” means secondary (bacterial) infections, such as pneumonia. The EMA and TGA approved it for both indications. </p>
<p>This difference in approval is important. </p>
<p>The approval process is secret, ostensibly for “commercial interests”, although what these are at this stage of the drug’s development (testing how effective the drug is) remains unclear. Still, we often don’t know outside the closed doors what issues are raised in the clinical study reports. </p>
<p>Some of Roche’s trials were subsequently published in journals, and the drug was marketed reasonably successfully. It was extremely successful in Japan, where half of the world’s production was sold. </p>
<p>Enter the <a href="http://www.cochrane.org/">Cochrane Collaboration</a>. This is a non-profit organisation that sets out to help clinicians and their patients decide which treatments are effective, and how effective. </p>
<p>It does this by systematically collecting all the trials done that answer a clinical question (such as “does Tamiflu reduce the symptoms of influenza?”), and then seeing if the results can be combined statistically to provide an overall answer. </p>
<p>Cochrane reviews are helpful to clinicians, especially when different trials on the same topic provide different answers. They help clinicians decide whether a treatment is likely to be effective for a particular patient. They also help health administrators decide whether to promote, or even subsidise that treatment. </p>
<p>This is called a “<a href="https://theconversation.com/how-do-we-know-what-works-systematic-research-reviews-5979">systematic review</a>” and Cochrane reviews have the most rigorous process. It includes feedback, enabling anyone to critically comment on the review and how it was conducted. </p>
<p>A Cochrane review of neuraminidase inhibitors (the class of drugs that Tamiflu sits in) was <a href="http://espace.library.uq.edu.au/view/UQ:82084">conducted and published in 2006</a>. It concluded that Tamiflu was effective at shortening influenza symptoms, and reducing complications.</p>
<p>But feedback from a Japanese paediatrician in 2009 highlighted the review’s <a href="http://www.ncbi.nlm.nih.gov/pubmed/12885681">uncritical acceptance</a> of some published data incorporated in the process. </p>
<p>This led to a re-evaluation of the recommendations and the conclusion of the review. It <a href="http://www.thecochranelibrary.com/userfiles/ccoch/file/CD001265.pdf">now said</a> that whether Tamiflu reduced or prevented complications of influenza was “uncertain”. </p>
<p>This was concordant with the FDA’s refusal to approve the drug for reducing complications. </p>
<p>We (the updated international team of Cochrane reviewers) wrote to the manufacturer to obtain the necessary data to resolve the issue. Long and complex interchanges that have <a href="http://www.bmj.com/tamiflu">now been made public</a> took place.</p>
<p>We still haven’t received all the data we need, and in our next update, have <a href="http://www.bmj.com/content/339/bmj.b5164">resorted to information</a> from the FDA and EMA obtained in a variety of ways. But inconsistencies in what was published and what we have, suggest there are still more data needed for answers to these questions. </p>
<p>The whole rigmarole has two implications. </p>
<p>First, we still remain in some doubt about the effectiveness of Tamiflu for preventing influenza complications. This matters because it was the prime reason the world armed itself with warehouses of Tamiflu under the threat of pandemic influenza in 2009. </p>
<p>Roche sold literally billions of dollars worth of Tamiflu for this singular reason. But has the world been sold a pup? Until the trials are openly released for scrutiny, it’s impossible for us, the world, the purchasers of this drug, to know. </p>
<p>Second, the implications are far beyond just Tamiflu. Until recently, the world had adopted the randomised controlled trial as the benchmark test for treatments. But there are clearly some problems with this. </p>
<p>One of these problems is the partial release of trial data (effected by selective publishing) that will help the sales of a commercial drug or device. </p>
<p>We’re concerned that this might have happened in this instance, even though the drug company in question has declared (several times, including originally in 2009) that it will provide all the data we need. </p>
<p><a href="http://www.plosmedicine.org/article/info:doi%2F10.1371%2Fjournal.pmed.1001201">This kind of thing</a> has happened before: drugs have had dangerous side effects suppressed by the manufacturers resulting in hundreds of patient deaths. </p>
<p>There are two ways this can be fixed. </p>
<p>Registering clinical trials needs to be made mandatory so we know they exist. This has progressed and there are many registers available for registering trials that can be searched. </p>
<p>And that all trial data is published needs to be made mandatory. That trials can be conducted on patients as guinea pigs – who sign up to them in the belief that this will somehow advance medical science and their fellow humans – but never see the light of day, seems to verge on the unethical. (Most patient trial data on Tamiflu have never been published). </p>
<p>There’s a campaign for this called <a href="http://www.alltrials.net/">Alltrials</a>. Sign up as an individual. Get your institution to sign as well. This is important. </p>
<p>In the meantime, we’re still working on unravelling the Tamiflu mystery using sub-optimal information… Watch this space. </p>
<p><em>This is the fourth article in our series <strong>Facts about Flu</strong>. Click on the links below to read other instalments in the series.</em></p>
<p><strong>Part one</strong>: <a href="https://theconversation.com/of-influenza-flu-potions-and-key-opinion-leaders-14003">Of influenza, flu, potions and key opinion leaders</a></p>
<p><strong>Part two</strong>: <a href="https://theconversation.com/influenza-vaccine-for-2013-who-what-why-and-when-14050">Influenza vaccine for 2013: who, what, why and when?</a></p>
<p><strong>Part three</strong>: <a href="https://theconversation.com/h1n1-h5n1-h7n9-what-on-earth-does-it-all-mean-14815">H1N1, H5N1, H7N9? What on earth does it all mean</a></p>
<p><strong>Part five</strong>: <a href="https://theconversation.com/csls-flu-vaccine-leaves-a-hole-in-australias-pandemic-plan-14359">CSL’s flu vaccine leaves a hole in Australia’s pandemic plan</a></p>
<p><strong>Part six</strong>: <a href="https://theconversation.com/should-flu-shots-be-mandatory-for-health-care-workers-14039">Should flu shots be mandatory for health-care workers?</a></p>
<p><strong>Part seven</strong>: <a href="https://theconversation.com/the-holy-grail-of-influenza-research-a-universal-flu-vaccine-14046">The Holy Grail of influenza research: a universal flu vaccine</a></p>
<p><strong>Part eight</strong>: <a href="https://theconversation.com/is-it-really-the-flu-the-other-viruses-making-you-ill-in-winter-14895">Is it really the flu? The other viruses making you ill in winter</a> </p>
<p><strong>Part nine</strong>: <a href="https://theconversation.com/the-heart-of-the-matter-how-effective-is-the-flu-jab-really-14048">The heart of the matter: how effective is the flu jab really?</a></p><img src="https://counter.theconversation.com/content/13951/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Chris Del Mar receives funding from the NHMRC (funding the "Acute Respiratory Infection" Cochrane Review Group), and for updating the Cochrane review "Neuraminidase Inhibitors for influenza in children and adults", as well as the UK's National Institute of Health Research for this review. </span></em></p>Facts about Flu - Today, we consider the long-running attempt to evaluate whether the antiviral drug Tamiflu works. There’s a dispute going on at the moment, a war of words with lots of public relations…Chris Del Mar, Professor of Public Health, Bond UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/148152013-06-04T01:19:54Z2013-06-04T01:19:54ZH1N1, H5N1, H7N9? What on earth does it all mean<figure><img src="https://images.theconversation.com/files/24970/original/jhyvpc9t-1370302448.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">One of three major types of the flu viruses that infect people, influenza A ranges from H1 to H17 and from N1 to N9.</span> <span class="attribution"><span class="source">Señor Codo</span></span></figcaption></figure><p><em><strong>Facts about Flu</strong> - Ever wondered what flu classifications mean? Read on.</em></p>
<p>The pandemic influenza strain, or swine flu, that spread globally in 2009 was referred to as H1N1 and the <a href="http://www.who.int/csr/don/2013_05_29/en/index.html">new bird flu</a> currently spreading in China is A H7N9. Most of us can probably understand what is meant by bird or swine in this context but what do the letters and numbers mean?</p>
<p>There are three major types of influenza that infect humans, known as influenza A, B and C. Influenza A and B can both cause serious infections, and are the cause of what we call the flu. Influenza C viruses differ from influenza A and B, and only cause a mild infection, so they don’t appear in vaccines. </p>
<p>A pandemic influenza strain is one that humans have not been previously exposed to, so people do not have immunity to it. It also spreads rapidly in the community. </p>
<p>When it has been around for a while and there’s widespread immunity to it, the virus will cause less serious illness, becoming one of the annual seasonal strains. But these seasonal strains continue to change all the time, never going back to the original strain.</p>
<h2>Hs and Ns</h2>
<p>Influenza A and B viruses have two types of spikes that cover their surface – the haemagglutinin (H) and the neuraminidase (N). </p>
<p>Viruses attach by their haemagglutinin onto receptors on the surface of cells in order to infect them, like a grappling hook. And the neuraminidase removes these receptors from infected cells at the right time to allow newly synthesised viruses to escape and spread.</p>
<p>Among influenza A viruses there are 17 different types of haemagglutinin, from H1 to H17 and nine different types of neuraminidase, from N1 to N9. Each virus has one type of H (such as H1) and one type of N (such as N1).</p>
<p>While most strains of influenza A viruses infect multiple types of birds, including poultry, ducks and geese, some strains also infect pigs. Indeed, avian influenza strains are endemic in wild birds, especially in Asia. But, interestingly, most birds don’t get ill from the flu.</p>
<p>The new H7N9 strain emerging in China does not make birds ill, for instance, but has been killing about a third of infected humans. The H5N1 strain, on the other, has evolved to kill birds and some humans who are infected from these birds. </p>
<p>So, while there are many combinations of H and N seen in birds, widespread human infection has only been caused by a few. H1N1, which was responsible for the 1918 pandemic virus and the recent swine flu pandemic, H2N2, the 1957 Asian flu pandemic strain, and the H3N2 Hong Kong pandemic strain in 1968, which displaced the Asian flu.</p>
<p>The seasonal influenza A strains currently circulating in humans are H1N1 and H3N2, but they have changed a lot since their first introduction into humans. </p>
<p>Influenza B strains do not circulate in animals, so they cannot cause a pandemic. But, like influenza A viruses, they continually change, so we will never become immune to every strain. These are the other component of the flu vaccine.</p>
<h2>Immune responses</h2>
<p>When we are infected with a virus, or given an influenza vaccine (the flu shot), we mount an immune response. Antibodies against this virus will continue to circulate in our bodies, and will help prevent future infection with the same strain of virus if we are exposed to it again.</p>
<p>Although seasonal “flu shots” contain H1N1, H3N2 and influenza B viruses, the strains are selected from the viruses circulating at the end of the spring the previous year. But there are continual changes (from year to year) within each strain.</p>
<p>This means that even if you were infected or vaccinated with the strains of flu circulating last year, when the virus comes around this year, it may have changed sufficiently so your antibodies no longer recognise it. So you can still get flu, even if you have been vaccinated.</p>
<p>While H5N1 and H7N9 strains can directly infect humans from birds, these viruses have not yet adapted sufficiently to spread from human to human. They could adapt either through random mutations, or by generating a mixed or “reassortant” virus.</p>
<p>This happens if two different strains of influenza infect the one host. They can swap and mix their genes, and may generate a virus that can now spread from human to human.</p>
<p>Vaccines can be used to prevent flu, but it’s critical to have the matching H and N to provide immunity. When a new pandemic strain arises, such as the H5N1 or H7N9, we don’t have vaccines against that unique combination of H and N.</p>
<p>It can take more than six months to make a vaccine against a virus with new combination of H and N types, so those of us who work on influenza hold our breath when there are reports of numerous people being infected with a new bird or animal strain. Who knows what numbers of the dice will be our next pandemic strain?</p>
<p><em>This is the third article in our series <strong>Facts about Flu</strong>. Click on the links below to read other instalments in the series.</em></p>
<p><strong>Part one</strong>: <a href="https://theconversation.com/of-influenza-flu-potions-and-key-opinion-leaders-14003">Of influenza, flu, potions and key opinion leaders</a></p>
<p><strong>Part two</strong>: <a href="https://theconversation.com/influenza-vaccine-for-2013-who-what-why-and-when-14050">Influenza vaccine for 2013: who, what, why and when?</a></p>
<p><strong>Part four</strong>: <a href="https://theconversation.com/the-tamiflu-saga-shows-why-all-research-data-should-be-public-13951">The Tamiflu saga shows why all research data should be public</a></p>
<p><strong>Part five</strong>: <a href="https://theconversation.com/csls-flu-vaccine-leaves-a-hole-in-australias-pandemic-plan-14359">CSL’s flu vaccine leaves a hole in Australia’s pandemic plan</a></p>
<p><strong>Part six</strong>: <a href="https://theconversation.com/should-flu-shots-be-mandatory-for-health-care-workers-14039">Should flu shots be mandatory for health-care workers?</a></p>
<p><strong>Part seven</strong>: <a href="https://theconversation.com/the-holy-grail-of-influenza-research-a-universal-flu-vaccine-14046">The Holy Grail of influenza research: a universal flu vaccine</a></p>
<p><strong>Part eight</strong>: <a href="https://theconversation.com/is-it-really-the-flu-the-other-viruses-making-you-ill-in-winter-14895">Is it really the flu? The other viruses making you ill in winter</a> </p>
<p><strong>Part nine</strong>: <a href="https://theconversation.com/the-heart-of-the-matter-how-effective-is-the-flu-jab-really-14048">The heart of the matter: how effective is the flu jab really?</a></p><img src="https://counter.theconversation.com/content/14815/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jennifer McKimm-Breschkin does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Facts about Flu - Ever wondered what flu classifications mean? Read on. The pandemic influenza strain, or swine flu, that spread globally in 2009 was referred to as H1N1 and the new bird flu currently…Jennifer McKimm-Breschkin, Chief Research Scientist, Virology Project Leader, CSIROLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/140502013-06-03T20:38:13Z2013-06-03T20:38:13ZInfluenza vaccine for 2013: who, what, why and when?<figure><img src="https://images.theconversation.com/files/24935/original/6cg5m27c-1370240209.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">There's still much confusion about the use of flu vaccines and their effectiveness.</span> <span class="attribution"><span class="source">Lance McCord</span></span></figcaption></figure><p><em><strong>Facts about Flu</strong> - Today, Ian Barr considers advice about who should get a flu shot.</em></p>
<p>Questions about who should be vaccinated against influenza are asked each year as the winter (and influenza) season approaches. Even though influenza vaccines have been used since the 1940s, there’s still much confusion about their use and effectiveness. </p>
<p>In most Western countries, vaccines are widely used by public health authorities, workplaces and individuals to reduce the risk of contracting the flu.</p>
<p>So what is the risk of being infected with influenza each year? This figure is variable and can be as low as one in 100 or as high as one in three. </p>
<p>It depends on many factors such as: </p>
<ul>
<li>if you have young children, </li>
<li>if your children attend daycare or school, </li>
<li>if you use public transport, </li>
<li>if you live in an institution such as a nursing home or boarding school, </li>
<li>your vaccination status, and </li>
<li>the (constantly-changing) virus itself.<br></li>
</ul>
<p>Try working out your odds (it’s a difficult task, let me assure you). And assuming your risk of infection is relatively low, what will be the outcome if you do become infected? Again, the answer is: “it depends”.</p>
<h2>The pyramid of illness</h2>
<p>Influenza is generally a mild disease. Many people, especially children, won’t even know they’ve been infected with the flu. We call these people asymptomatic. Other healthy children and adults might be somewhat indisposed by a seasonal influenza infection, missing a week’s school or work. </p>
<p>But some other people and groups run a higher risk of a more serious illness following an influenza infection. These include very young children, the elderly, pregnant women, asthmatics and, cancer and organ transplantation patients. A small proportion of these people will be hospitalised, and some will die. </p>
<p>In the most recent <a href="http://www.cdc.gov/flu/weekly/">2012-3 US influenza season</a>, for instance, some 12,343 people were hospitalised with about half of these being elderly (65 years or older) along with 217 pregnant women. There were also 146 children (18 years old or younger) and thousands of adults and elderly who died from influenza or its complications. These findings are likely to be proportionally similar in Australia (that is, about one-tenth of these numbers).</p>
<p>So a reasonable case can be made for avoiding infection from influenza for a number of people. But short of becoming a hermit, living in a remote location and avoiding people or taking drugs (Tamiflu or Relenza) every day for months on end, vaccination is the most viable option currently available.</p>
<h2>From the experts</h2>
<p>Various groups have considered the question of who should get the influenza vaccine. In April 2012, the World Health Oganization’s (WHO) <a href="http://www.who.int/influenza/vaccines/SAGE_information/en/">Strategic Advisory Group of Experts (SAGE)</a> on immunisation <a href="http://www.who.int/wer/2012/wer8721.pdf">recommended</a> that pregnant women were the most important risk group for seasonal influenza vaccination. </p>
<p>It also supported the recommendation – in no particular order of priority – for vaccination of:</p>
<ul>
<li>health-care workers, </li>
<li>children six months to 59 months of age, </li>
<li>the elderly, and </li>
<li>those with high-risk conditions.</li>
</ul>
<p>The <a href="http://www.health.gov.au/internet/immunise/publishing.nsf/Content/handbook10-4-7">10th Edition of the Australian Immunisation Handbook (2013) says</a>:</p>
<blockquote>
<p>Annual influenza vaccination is recommended for any person ≥6 months of age for whom it is desired to reduce the likelihood of becoming ill with influenza. </p>
</blockquote>
<p>It also strongly recommends vaccination for similar groups to SAGE with some additions such as Aboriginal and Torres Strait Islander people aged 15 years or older.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/24932/original/q6pykgkj-1370239981.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/24932/original/q6pykgkj-1370239981.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/24932/original/q6pykgkj-1370239981.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/24932/original/q6pykgkj-1370239981.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/24932/original/q6pykgkj-1370239981.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/24932/original/q6pykgkj-1370239981.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/24932/original/q6pykgkj-1370239981.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The flu virus.</span>
<span class="attribution"><span class="source">ben dalton</span></span>
</figcaption>
</figure>
<p>Other groups such as the <a href="http://www.cdc.gov/flu/professionals/acip/">US-based Advisory Committee on Immunisation Practices</a> (ACIP) have, since 2010, continued to recommend annual influenza vaccine for all children aged six months or older.</p>
<h2>Vaccine safety and effectiveness</h2>
<p>Unfortunately, the performance of influenza vaccines in achieving robust protection is far from perfect, especially among the elderly. This age group has a deteriorating immune system due to ageing, which results in reduced responses to vaccinations, including the influenza vaccine. </p>
<p>For many years, scientists have tried to find the Holy Grail of influenza vaccines – a vaccine that is long lasting, works well in all age groups, fully protects against all circulating viruses, and provides protection from influenza viruses that don’t normally circulate in people. </p>
<p>Not one of these aims has been achieved despite around 80 years of effort, experimentation and clinical trials. While <a href="http://www.landesbioscience.com/journals/vaccines/article/18859/2011HV0077R.pdf">some progress has been made</a>, they are relatively minor and are yet to replace or substantially improve the current practice of annual vaccination. </p>
<p>The good news is that while the protection offered by current flu vaccines could be improved, their safety profile is generally very good, with very few serious adverse reactions. There have been a few exceptions to this, such as with the <a href="http://www.ncbi.nlm.nih.gov/pubmed/21929484">CSL’s vaccine</a> for children in 2010. </p>
<p>This brand is <a href="http://www.ncbi.nlm.nih.gov/pubmed/22094632">no longer approved</a> or given to children under ten years of age and has been successfully replaced with non-CSL brands by other influenza vaccine manufacturers.</p>
<h2>What to do?</h2>
<p>The range of influenza vaccines available overseas currently is larger than Australia. In the United States, for example, they have the choice of inactivated virus vaccines, live attenuated (or crippled) virus vaccines and recombinant protein vaccines (made by modern molecular techniques). </p>
<p>In Australia, only the inactivated influenza vaccines, delivered by injection, are currently available. These vaccines are made by growing influenza viruses in embryonated hens eggs, which are then purified, inactivated and formulated into the finished vaccine. </p>
<p>That’s a bit of background (there is a lot more available, for example, on the US <a href="http://www.cdc.gov/flu/protect/vaccine/index.htm">Centers for Disease Control website</a>), but the question for you is – do I get the influenza vaccine this winter? </p>
<p>It’s not too late as the peak time for influenza in Australia is usually in August. But like many things to do with the flu we can’t be sure of this. So if you do decide to get vaccinated, the sooner you do it, the better. And remember, it will take approximately two weeks before your body will reach its maximum level of protection following vaccination. </p>
<p>As for me, given that I work with influenza viruses continually, I have chosen to get the influenza vaccine each year for the past 13 years. But the chances of me running into an influenza virus is a daily possibility, a somewhat higher risk than most of you!</p>
<p><em>This is the second article in our series <strong>Facts about Flu</strong>. Click on the links below to read other instalments in the series.</em></p>
<p><strong>Part one</strong>: <a href="https://theconversation.com/of-influenza-flu-potions-and-key-opinion-leaders-14003">Of influenza, flu, potions and key opinion leaders</a></p>
<p><strong>Part three</strong>: <a href="https://theconversation.com/h1n1-h5n1-h7n9-what-on-earth-does-it-all-mean-14815">H1N1, H5N1, H7N9? What on earth does it all mean</a></p>
<p><strong>Part four</strong>: <a href="https://theconversation.com/the-tamiflu-saga-shows-why-all-research-data-should-be-public-13951">The Tamiflu saga shows why all research data should be public</a></p>
<p><strong>Part five</strong>: <a href="https://theconversation.com/csls-flu-vaccine-leaves-a-hole-in-australias-pandemic-plan-14359">CSL’s flu vaccine leaves a hole in Australia’s pandemic plan</a></p>
<p><strong>Part six</strong>: <a href="https://theconversation.com/should-flu-shots-be-mandatory-for-health-care-workers-14039">Should flu shots be mandatory for health-care workers?</a></p>
<p><strong>Part seven</strong>: <a href="https://theconversation.com/the-holy-grail-of-influenza-research-a-universal-flu-vaccine-14046">The Holy Grail of influenza research: a universal flu vaccine</a></p>
<p><strong>Part eight</strong>: <a href="https://theconversation.com/is-it-really-the-flu-the-other-viruses-making-you-ill-in-winter-14895">Is it really the flu? The other viruses making you ill in winter</a> </p>
<p><strong>Part nine</strong>: <a href="https://theconversation.com/the-heart-of-the-matter-how-effective-is-the-flu-jab-really-14048">The heart of the matter: how effective is the flu jab really?</a></p><img src="https://counter.theconversation.com/content/14050/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ian Barr is the Deputy Director of the WHO Collaborating Centre for Reference and Research on Influenza based at VIDRL in North Melbourne. The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health and Ageing and also receives funding from the IFPMA (International Federation of Pharmaceutical Manufacturers & Associations). IB holds shares in CSL Limited, a manufacturer of influenza vaccines.</span></em></p>Facts about Flu - Today, Ian Barr considers advice about who should get a flu shot. Questions about who should be vaccinated against influenza are asked each year as the winter (and influenza) season approaches…Ian Barr, Deputy Director, WHO Collaborating Centre for Reference and Research on InfluenzaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/140032013-06-02T20:30:08Z2013-06-02T20:30:08ZOf influenza, flu, potions and key opinion leaders<figure><img src="https://images.theconversation.com/files/24754/original/zyk6twjt-1369974487.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The flu is not a disease, it is what's known as a syndrome – a series of signs and symptoms caused by a variety of agents.</span> <span class="attribution"><span class="source">sunnyUK/Flickr</span></span></figcaption></figure><p><em><strong>Welcome to Facts about Flu</strong> - Our week-long series of articles about influenza.</em></p>
<p>Ever wonder why the flu, coughs and colds that you suffered from in your youth have become a monster killer that rolls out every autumn, putting the lives of scores of law-abiding folks at risk?</p>
<p>The answer is complex but, strangely, it hasn’t much to do with viruses, bugs and other nasty things lurking in dark cupboards.</p>
<p>Here are a few facts.</p>
<p>The surest way to create a market for lotions and potions is to create a need for them. You do that by either ramping up an existing problem or manufacturing a brand new one that fits the indications for use of your lotions and potions. In our case, there’s a bit of both.</p>
<h2>Syndrome or disease?</h2>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/24749/original/6x74fgdq-1369973753.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/24749/original/6x74fgdq-1369973753.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=973&fit=crop&dpr=1 600w, https://images.theconversation.com/files/24749/original/6x74fgdq-1369973753.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=973&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/24749/original/6x74fgdq-1369973753.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=973&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/24749/original/6x74fgdq-1369973753.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1223&fit=crop&dpr=1 754w, https://images.theconversation.com/files/24749/original/6x74fgdq-1369973753.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1223&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/24749/original/6x74fgdq-1369973753.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1223&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
<span class="attribution"><span class="source">Mike Licht, NotionsCapital.com</span></span>
</figcaption>
</figure>
<p>The flu, as its commonly known, is not a disease: it is what is known as a syndrome. A syndrome is a series of signs (like cough) and symptoms (like feeling knackered, or having aches and pains) caused by a variety of agents. </p>
<p>The flu comes around every year but only a small proportion of flu episodes can actually be ascribed to influenza viruses. Around 7% to 10% of flu episodes are influenza “on average” i.e. averaged over a six-month period. </p>
<p>The vast majority of flu episodes are either caused by other viruses (you’ve probably never heard of them but here’s a selection: metapneumovirus, rhinovirus, respiratory syncytial virus) or have no recognised cause. You can’t tell what is causing what, when, where without lab tests, which are expensive. </p>
<p>These lab test are also, by and large, useless for practical purposes because even if you wanted to know what is going on, by the time you get the answer you are feeling a lot better, thank you.</p>
<p>And here’s the trick: the public don’t know this. To them, all flu is influenza and vice versa. So the easiest way to create a need is to blur the distinction between the two, making folk around the world believe that when they’re watching Google’s flu tracker, they’re watching the progress of influenza. </p>
<p>They are not.</p>
<p>Great public health bodies, such as the <a href="http://www.cdc.gov/flu/">US Centers for Disease Control and Prevention</a> (CDC), are very good at doing this as their abuse of this f-word shows.</p>
<h2>Claiming the deaths</h2>
<p>Next come models. If you were to ask how many certified influenza deaths took place in Walkabout Creek in, say 2010, you would get one of two answers: don’t know, or a very low number. </p>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/24751/original/w6jntc5x-1369973925.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/24751/original/w6jntc5x-1369973925.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=1011&fit=crop&dpr=1 600w, https://images.theconversation.com/files/24751/original/w6jntc5x-1369973925.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=1011&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/24751/original/w6jntc5x-1369973925.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=1011&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/24751/original/w6jntc5x-1369973925.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1270&fit=crop&dpr=1 754w, https://images.theconversation.com/files/24751/original/w6jntc5x-1369973925.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1270&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/24751/original/w6jntc5x-1369973925.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1270&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
<span class="attribution"><span class="source">Mike Licht, NotionsCapital.com</span></span>
</figcaption>
</figure>
<p>Influenza-related deaths are extremely difficult to ascertain for a complex series of reasons, including the impossibility of distinguishing flu-related from influenza-related deaths. Like with all forms of flu, to be able to tell them apart you need tests or, if you’re dead, a post-mortem. That’s probably not something you agree your grandad’s body should be subjected to in order to please people like me. </p>
<p>So enter models, a complex alchemy of bits of data on the circulation of certain viruses (never mind the others), past certain influenza-deaths figures, and all sorts of deaths from different causes (now even heart attacks), which are deemed by the modeller to possibly be influenza related. </p>
<p>This is why when death figures are quoted in official documents, a range of estimates is always reported. With models, only one thing is certain – that the modeller can prove or disprove anything you want.</p>
<p>Now you’d think that, like packets of cigarettes, all these warnings from the World Health Organization (WHO), CDC and other such worthies and all the recommendations for lotions and potions would come with a warning about the validity of the data on which they are supposedly based. Think again.</p>
<h2>The icing on the cake</h2>
<p>The finishing touch for creating our market is to get academia, public health agencies and the media so involved in the issue that they are unable (and, in some cases, unwilling) to look critically at what is going on, to think outside the box.</p>
<p>An even better move is to get decision makers to make policy and police it. This guarantees unsolvable conflicts and a passport to no change of policy, even in the absence of any valid data to support it.</p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/24750/original/3nh5kktk-1369973859.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/24750/original/3nh5kktk-1369973859.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=990&fit=crop&dpr=1 600w, https://images.theconversation.com/files/24750/original/3nh5kktk-1369973859.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=990&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/24750/original/3nh5kktk-1369973859.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=990&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/24750/original/3nh5kktk-1369973859.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1244&fit=crop&dpr=1 754w, https://images.theconversation.com/files/24750/original/3nh5kktk-1369973859.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1244&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/24750/original/3nh5kktk-1369973859.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1244&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
<span class="attribution"><span class="source">Mike Licht, NotionsCapital.com</span></span>
</figcaption>
</figure>
<p>In the early 2000s, WHO’s policies were written by a selected group of outside influenza experts. These had and still have very close ties with industry. They are known as key opinion leaders. There’s loads down under, too. </p>
<p>Not all key opinion leaders are pharma creatures; some actually believe what they say. But what they do consciously or unconsciously is spin the message as I have described.</p>
<p>In Canada, very powerful key opinion leaders introduced a policy in late 2012 for health-care workers to get vaccinated against influenza, or wear a mask with a badge declaring their status of hazards to the community, or be sacked. Attempts at coercion may be on the way down under, too, and you should be vigilant.</p>
<h2>Slice of disbelief</h2>
<p>I am sure you’ve found all this absolutely extraordinary and probably unbelievable. If you did, go ask your local public health body what the influenza casualty rate in Walkabout Creek was in a period of your choice.</p>
<p>If they answer, and answer with a range of figures, ask them why there’s a need for a range. And if the answer is I don’t know or it’s very difficult, ask them how they know influenza is a threat.</p>
<p>I’ll leave you with one more fact. </p>
<p>The best scientific evidence on whether influenza vaccines work comes from healthy adults, the group that least needs protection and that can mount the best antibody response to the virus without help. </p>
<p>Here’s what happens in the most-optimistic-possible scenario when the ever-changing influenza viral configuration closely matches that contained in the vaccine (which happens one year out of two, on average):</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/23313/original/nsq5vjvp-1367905976.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/23313/original/nsq5vjvp-1367905976.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/23313/original/nsq5vjvp-1367905976.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=361&fit=crop&dpr=1 600w, https://images.theconversation.com/files/23313/original/nsq5vjvp-1367905976.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=361&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/23313/original/nsq5vjvp-1367905976.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=361&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/23313/original/nsq5vjvp-1367905976.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=453&fit=crop&dpr=1 754w, https://images.theconversation.com/files/23313/original/nsq5vjvp-1367905976.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=453&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/23313/original/nsq5vjvp-1367905976.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=453&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption"></span>
<span class="attribution"><span class="source">Tom Jefferson</span></span>
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</figure>
<p>You need to vaccinate 100 health adults to prevent three cases. That means cases with sets of symptoms, not death or pneumonia, and there’s no good evidence that they do that.</p>
<p>Other pictures and the complete relevant evidence reviews can be <a href="http://www.cochranejournalclub.com/vaccines-for-preventing-influenza-clinical/">here</a>.</p>
<p><em>This is the first article in our series <strong>Facts about Flu</strong>. Click on the links below to read other instalments in the series.</em></p>
<p><strong>Part two</strong>: <a href="https://theconversation.com/influenza-vaccine-for-2013-who-what-why-and-when-14050">Influenza vaccine for 2013: who, what, why and when?</a></p>
<p><strong>Part three</strong>: <a href="https://theconversation.com/h1n1-h5n1-h7n9-what-on-earth-does-it-all-mean-14815">H1N1, H5N1, H7N9? What on earth does it all mean</a></p>
<p><strong>Part four</strong>: <a href="https://theconversation.com/the-tamiflu-saga-shows-why-all-research-data-should-be-public-13951">The Tamiflu saga shows why all research data should be public</a></p>
<p><strong>Part five</strong>: <a href="https://theconversation.com/csls-flu-vaccine-leaves-a-hole-in-australias-pandemic-plan-14359">CSL’s flu vaccine leaves a hole in Australia’s pandemic plan</a></p>
<p><strong>Part six</strong>: <a href="https://theconversation.com/should-flu-shots-be-mandatory-for-health-care-workers-14039">Should flu shots be mandatory for health-care workers?</a></p>
<p><strong>Part seven</strong>: <a href="https://theconversation.com/the-holy-grail-of-influenza-research-a-universal-flu-vaccine-14046">The Holy Grail of influenza research: a universal flu vaccine</a></p>
<p><strong>Part eight</strong>: <a href="https://theconversation.com/is-it-really-the-flu-the-other-viruses-making-you-ill-in-winter-14895">Is it really the flu? The other viruses making you ill in winter</a> </p>
<p><strong>Part nine</strong>: <a href="https://theconversation.com/the-heart-of-the-matter-how-effective-is-the-flu-jab-really-14048">The heart of the matter: how effective is the flu jab really?</a></p><img src="https://counter.theconversation.com/content/14003/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>TJ has published on influenza antivirals and received a UK National Institute of Health Research Grant funding for the update and amalgamation of two Cochrane Reviews: neuraminidase inhibitors for preventing and treating influenza in healthy adults and children.
TJ receives royalties from his books published by Blackwell and Il Pensiero Scientifico Editore, none of which are on influenza. He is occasionally interviewed by market research companies for anonymous interviews about Phase 1 or 2 products. He was a consultant in a legal case regarding oseltamivir and is a now acting in a legal case on influenza vaccination on behalf of healthcare workers' unions in Canada.
TJ consulted for Roche 1997-1999 and Sanofi Synthelabo in 2004.</span></em></p>Welcome to Facts about Flu - Our week-long series of articles about influenza. Ever wonder why the flu, coughs and colds that you suffered from in your youth have become a monster killer that rolls out…Tom Jefferson, Epidemiologist, CochraneLicensed as Creative Commons – attribution, no derivatives.