Canada Releases Tamiflu From National Emergency Stockpile

Healthmap Flu Near You – Jan 8th, 2013

# 6836

 

 

It’s no secret that influenza is spreading rapidly across North America.  The latest Flu Near You map (above) shows that both the United States and Canada are feeling the effects of this year’s epidemic.

 

In recent days there have been scattered media  reports of localized, temporary shortages of Tamiflu ® (Oseltamivir). Obviously this is of considerable concern to those who – due to the severity of their illness, or pre-existing conditions – have been prescribed the medication.

 

Today the PHAC has announced the `exceptional action’ of  releasing  some of Canada’s National Emergency Stockpile of Tamiflu, in order to help relieve some of these shortages.

January 8, 2013
For immediate release

Government of Canada to address temporary shortage of flu drug oseltamivir (Tamiflu)

Tamiflu is a drug used to treat the flu; it is not a vaccine.

OTTAWA – The Government of Canada is working with Roche Canada and the provincial and territorial health authorities to address a potential temporary shortage of the antiviral flu drug oseltamivir (Tamiflu).

 

The Public Health Agency of Canada and Health Canada are arranging to immediately release a supply of the drug Tamiflu from the Agency’s National Emergency Stockpile System to the manufacturer for distribution to where it is needed across Canada. This exceptional action will be taken to ensure Tamiflu remains available to those Canadians who need it until the manufacturer replenishes its supply with a new shipment expected in February.

 

The Public Health Agency of Canada and Health Canada will continue to work with the manufacturer and with provincial and territorial health authorities to help ensure the demand for antiviral drugs continues to be met this flu season.

 

Tamiflu is an antiviral medication that is primarily used for the early treatment of individuals infected with the influenza virus – particularly those at high risk of complications due to influenza, such as the elderly, young children, individuals with other medical conditions or pregnant women. Tamiflu can also be prescribed to help reduce the chance of getting the flu following close contact with an infected individual. Tamiflu should not be confused with the seasonal influenza vaccine (flu shot), which remains the best protection against the influenza virus.

The Public Health Agency of Canada is seeing an early spike in flu cases and more severe illness caused by the flu than was seen in the last two years. This year, the flu shot matches the circulating influenza strains very well and therefore offers excellent protection from the virus. Canadians are reminded to get the flu shot to protect themselves and their loved ones. It is not too late to get the flu shot.

It is also important to take the following steps to protect yourself and your family from infection during flu season:

• Wash your hands often with soap and warm water for at least 20 seconds, or use hand sanitizer if soap and water are not available.
• Cough and sneeze into your arm, not your hand.  If you use a tissue, dispose of it as soon as possible and wash your hands.
• Keep doing what you normally do, but if you get sick, stay home.
• Keep your hands away from your face.
• Keep common surface areas – for example, doorknobs, light switches, telephones and keyboards – clean and disinfected.
• Eat healthy foods and stay physically active to keep your immune system strong.

Learn more by getting a copy of Fight Flu: Your Seasonal Flu Guide by contacting
1 800 O-Canada or visiting www.fightflu.ca.

 

 

UPDATED: 1500 hrs EST

 

Shortly after I posted this blog, the following report was released by CTVNews.ca.

 

 

Emergency supply of Tamiflu released amid shortage

CTVNews.ca Staff
Published Tuesday, Jan. 8, 2013 2:40PM EST

The federal government is acknowledging what some doctors have been saying for some time: the country has a shortage of Tamiflu, an antiviral medication often given to those with severe cases of the flu.

 

The Public Health Agency of Canada and Health Canada announced Tuesday they are arranging to immediately release a supply of the drug from the country’s National Emergency Stockpile System.

 

Read more: http://www.ctvnews.ca/health/emergency-supply-of-tamiflu-released-amid-shortage-1.1105596#ixzz2HPquTXHn

»» Read More

Study: The Benefits Of Antiviral Therapy During the 2009 Pandemic

 

Photo Credit – Wikipedia

 

# 6758

 

While the British press continues to excoriate Roche Pharmaceuticals for their refusal to release all of the testing data on their antiviral drug Tamiflu © – and through innuendo, suggest that the drug is ineffective, or worse, even dangerous – we continue to get third party confirmation that oseltamivir does, in fact, have beneficial effects for severe influenza.

 

A quote from an article yesterday in the Daily Mail reads:

 

“And yet for all we know, Tamiflu might be no better than paracetamol: because Roche, the company making it, still withholds vital information on the risks and benefits from researchers, doctors and patients.”

 

Compelling rhetoric, I suppose. And not wrong in its stated goal, which is the full release of all drug testing data.

 

But then again, not precisely true. 

 

We’ve seen many observational studies conducted over the past few years that show pretty clear evidence that the use of oseltamivir in severe influenza reduces morbidity and mortality.

 

The evidence for its benefits for mild, seasonal flu in healthy patients  . . . well, not so much.

 

Although falling short of the `gold standard’ Randomized Controlled Trials (RCTs) preferred by most scientists, we’ve seen a number of observational studies that suggest significant benefits from the drug.

 

In 2010 we saw an observational study that appeared in JAMA  (see Study: Antivirals Saved Lives Of Pregnant Women) that strongly suggested that Tamiflu was life saving for some patients with pandemic flu.

 

And again in 2010, in BMJ: Efficacy of Oseltamivir In Mild H1N1, we saw a study which suggested that the administration of oseltamivir may have significantly reduced the incidence of pneumonia among otherwise healthy pandemic H1N1 patients.

 

And in Study: Antiviral Therapy For H5N1, we saw the largest study to date on the outcomes of H5N1 patients. The bottom line is essentially out of 308 cases studied, the overall survival rate was a dismal 43.5%.

 

But . . . of those who received at least one dose of Tamiflu . . .  60% survived . . .  as opposed to only 24% who received no antivirals.

 

On the safety side of the equation, while all drugs can have adverse effects (AEs), a recent study (see Study: Adverse Events Associated With Oseltamivir Outpatient Treatment) found `no evidence was identified for an increased risk of neuropsychiatric or other AEs following oseltamivir treatment.’

 

We’ve another study published last week in the Journal of Infectious Diseases that conducted a meta-analysis of 90 observational studies during the 2009 H1N1 flu pandemic. Included were nearly 35,000 patients, 85% of whom has laboratory confirmed H1N1.

 

Impact of neuraminidase inhibitor treatment on outcomes of public health importance during the 2009-10 influenza A(H1N1) pandemic: a systematic review and meta-analysis in hospitalized patients

Stella G. Muthuri*, Puja R. Myles*,Sudhir Venkatesan, Jo Leonardi-Bee and Jonathan S. Nguyen-Van-Tam1

Abstract

Background. The impact of neuraminidase inhibitors (NAI) treatment on clinical outcomes of public health importance during the 2009-10 pandemic has not been firmly established.

<SNIP>

Results. Regarding mortality we observed a non-significant reduction associated with NAI treatment (at any time) vs none (OR, 0.72 [95% CI, 0.51 - 1.01]). However we observed significant reductions for early treatment (≤48h after symptom onset) vs late (OR, 0.38 [95% CI, 0.27 - 0.53]); and for early treatment vs none (OR, 0.35 [95% CI, 0.18 - 0.71]). NAI treatment (at any time) vs none was associated with an elevated risk of severe outcome (OR, 1.76 [95% CI, 1.22 - 2.54]); but early treatment vs. late reduced the likelihood (OR, 0.41 [95% CI, 0.30 - 0.56]).

Conclusions. During the 2009-10 influenza A(H1N1) pandemic, early initiation of NAI treatment reduced the likelihood of severe outcomes compared with late or no treatment.

 

The full text of the article is available online.

 

For those adverse to navigating the 23-page study, a summary can be found in an accompanying commentary by Fred Y. Aoki, MD, and Frederick G. Hayden, MD.  Although based on observational, often retrospective, studies - Aoki and Hayden praised the large number of studies and patients, and the `methodologic rigor’ of their analysis.

The bottom line?

 

. . . antiviral therapy, principally oseltamivir, initiated within 48 hours of onset, reduced the likelihood of severe outcomes, namely admission to a critical care unit or death, by 49 to 65%.

 

They did find that patients who received oseltamivir were more likely to develop pneumonia, but this is a bit of a red herring, as the most seriously ill patients are more apt to receive antiviral therapy.

 

No, oseltamivir isn’t a panacea against influenza.  It isn’t perfect by any means.

 

But once again we get pretty good data to suggest that it does have significant therapeutic value.  Particularly when administered within the first 48 hours of illness.

 

Last January, in The Tamiflu Controversy Continues  we looked at the debate over the effectiveness of oseltamivir (Tamiflu ®) in the wake of the release of a new Cochrane group analysis that found insufficient evidence to show whether the drug reduces influenza complications and transmission.

Several weeks later in The CDC Responds To The Cochrane Group’s Tamiflu Study we saw that agency’s reaffirmation of their support for the drug.

 

Hopefully, in time we’ll see better antivirals developed.

 

Whether we approve of the data release policy of the parent company or not, oseltamivir remains one of the few pharmacological options we have available to treat severe influenza. 

»» Read More

Study: Adverse Events Associated With Oseltamivir Outpatient Treatment

 

Photo Credit – Wikipedia

 

# 6709

 

 

Oseltamivir (aka Tamiflu ©) is an oral antiviral that was heavily stockpiled by many nations between 2005 and 2088 in anticipation of a  feared `bird flu’ pandemic. 

 

While that particular pathogen remains in the wings (sorry . . . I couldn’t help myself), a pandemic of porcine origin did emerged in 2009 (H1N1), and so these antivirals saw heavy use, particularly in Japan, Great Britain, and in the United States.

 

That said . . . the  stockpiling, and use, of Tamiflu has not been without some controversy.

 

Critics have pointed out a lack of Randomized Controlled Trials (RCTs) to gauge the effectiveness of the drug, and the BMJ has been working along with the Cochrane group to get the manufacturer, Hoffmann-La Roche, to release unpublished trial data.

 

Although falling short of the `gold standard’ RCTs preferred by the Cochrane group for inclusion in their analyses, we’ve seen a number of observational studies that suggest significant benefits from the drug.

 

In 2010 we saw an observational study that appeared in JAMA  (see Study: Antivirals Saved Lives Of Pregnant Women) that strongly suggested that Tamiflu was life saving for some patients with pandemic flu.

 

And again in 2010, in BMJ: Efficacy of Oseltamivir In Mild H1N1, we saw a study which suggested that the administration of oseltamivir may have significantly reduced the incidence of pneumonia among otherwise healthy pandemic H1N1 patients.

 

And lastly, in Study: Antiviral Therapy For H5N1, we saw the largest study to date on the outcomes of H5N1 patients who either received, or did not receive, antiviral treatment.

 

The research appears in the IDSA’s  Journal of Infectious Diseases. The bottom line is essentially out of 308 cases studied, the overall survival rate was a dismal 43.5%.

 

But . . . of those who received at least one dose of Tamiflu . . .  60% survived . . .  as opposed to only 24% who received no antivirals.

 

Efficacy arguments aside, there have also been concerns raised over possible side effects from the drug.

 

It is axiomatic that all drugs have side effects. In fact, in trials with placebos, test subjects have reported adverse reactions (nocebo effect) even though they were taking pills with no active ingredient.

 

Even the most widely used over-the-counter medications can – and sometimes do – cause serious adverse effects.

 

So the mere existence of adverse effects aren’t enough to counsel against a drug’s use. The risks of adverse effects must be weighed against the benefits the drug may provide.

 

Often these AEs are mild, and transitory, and of little concern.

 

 

But in 2006 we began to see reports out of Japan suggesting that a small number of adolescents taking Tamiflu had experienced serious neuropsychiatric symptoms, including delirium, hallucinations, and convulsions.

 

Whether these symptoms were produced by the drug, or by their viral infection, wasn’t known (see Study: Pediatric Neurological Complications With H1N1). But in November of 2006, the FDA posted this safety warning:

 

Tamiflu (oseltamivir phosphate)

Audience: Pediatric and primary care healthcare professionals and patients

[Posted 11/13/2006] Roche and FDA notified healthcare professionals of revisions to the PRECAUTIONS/Neuropsychiatric Events and Patient Information sections of the prescribing information for Tamiflu, indicated for the treatment of uncomplicated acute illness due to influenza infection in patients 1 year and older who have been symptomatic for no more than 2 days and for the prophylaxis of influenza in patients 1 year and older.

There have been postmarketing reports (mostly from Japan) of self-injury and delirium with the use of Tamiflu in patients with influenza. People with the flu, particularly children, may be at an increased risk of self-injury and confusion shortly after taking Tamiflu and should be closely monitored for signs of unusual behavior. A healthcare professional should be contacted immediately if the patient taking Tamiflu shows any signs of unusual behavior.

 

During the 2009 pandemic millions of doses of Tamiflu were prescribed, often to children. While we heard reports of some adverse effects (primarily vomiting & nausea), serious reactions were rare. 

 

In 2010 we saw a review in the journal Eurosurveillance: Adverse Effects of Oseltamivir in Children, that looked at the antiviral treatment of a number of students at a primary school in Sheffield, UK during the 2009 pandemic. 

 

While none of the side effects reported were life-threatening, the nausea, vomiting, abdominal pain and other symptoms were bothersome enough that a minority of those who started the Tamiflu (< 10% ) stopped taking the drug.

 

Today we’ve a new, much larger study, that appears in the journal Pharmacoepidemiology and Drug Safety. It examines the risk of AEs (primarily psychiatric in nature) among more than 27,000 matched pairs (by sex, age, week of illness, and location - where half took the drug & half did not).

 

Encouragingly, they research concludes that `no evidence was identified for an increased risk of neuropsychiatric or other AEs following oseltamivir treatment.’

Original Report

Risk of adverse events following oseltamivir treatment in influenza outpatients, Vaccine Safety Datalink Project, 2007–2010†

Sharon K. Greene^,, Lingling Li, David K. Shay, Alicia M. Fry, Grace M. Lee, Steven J. Jacobsen, Roger Baxter, Stephanie A. Irving, Michael L. Jackson, Allison L. Naleway, James D. Nordin, Komal J. Narwaney, Tracy A. Lieu

Article first published online: 5 NOV 2012

 

While comforting, this study doesn’t mean that oseltamivir is completely without side effects. Only that their research didn’t turn up an statistically significant increases in the AEs they were tracking among those taking the drug.

 

There are other concerns when it comes to use of oseltamivir, including the possibility that overuse will help generate resistant strains of the influenza virus.

 

But for now, oseltamivir remains one of the few pharmacological options we have available to treat severe influenza.

»» Read More

The CDC Responds To The Cochrane Group’s Tamiflu Study

 

Photo Credit – Wikipedia

 

# 6127

 

Three weeks ago, The Tamiflu Controversy Continues  we looked at the ongoing debate over the effectiveness of oseltamivir (Tamiflu ®) in the wake of the release of a new Cochrane group analysis that found insufficient evidence to show whether the drug reduces influenza complications and transmission.

 

Robert Roos of CIDRAP provided a good summation of that Cochrane group analysis in:

 

Review renews questions about oseltamivir benefits

Robert Roos News Editor

Jan 19, 2012 (CIDRAP News) – A lengthy new analysis of unpublished clinical trial data is renewing questions about the effectiveness of the influenza drug oseltamivir (Tamiflu), saying that although the drug shortens flu symptoms by about a day, there is no evidence that it reduces hospital admissions.

(Continue . . .)

 

 

While research purists may applaud their methods, the problem that I (and many others) have with this analysis is that the Cochrane group set the bar very high as to what studies they would consider, and effectively ignored any observational studies.  

 

As few studies met their criteria, they were unable to determine one way or the other, the overall effectiveness of the drug.

 

Despite the fact that their analysis was inconclusive, some aspects of the media immediately latched onto this as `proof’ that Tamiflu was ineffective. 

 

No doubt spurred by this media buzz, yesterday the CDC on their Have You Heard? website published their rationale for continuing to recommend the use of Oseltamivir for severe influenza.

 

CDC Recommendations for Influenza Antiviral Medications Remain Unchanged

February 7, 2012 -- A recent review of randomized clinical trial data for the influenza neuraminidase inhibitor antiviral medications published by the Cochrane Collaboration, and two related commentaries [“Rethinking credible evidence synthesis” and “Questions Remain over safety and effectiveness of oseltamivir”] published in the British Medical Journal, raised questions about the value of antiviral medications for the prevention and treatment of influenza. After careful consideration of all available evidence, CDC guidance on the use of antiviral medications remains unchanged. The Centers for Disease Control and Prevention (CDC) continues to recommend the use of the neuraminidase inhibitor antiviral drugs (oral oseltamivir and inhaled zanamivir) as an important adjunct in the prevention and treatment of influenza.

 

The Cochrane review assessed unpublished and published data from randomized controlled trials (RCTs) of oral oseltamivir or inhaled zanamivir versus placebo for early treatment (within 48 hours after illness onset) or chemoprophylaxis of uncomplicated seasonal influenza in otherwise healthy adults and children. The review concluded that in adults and children with influenza-like illness, early oseltamivir treatment shortens the duration of symptoms by approximately 21 hours compared to placebo. This finding is similar to results in published RCTs which reported a reduction of approximately one day of laboratory-confirmed influenza illness by early oseltamivir treatment. One RCT in children aged 1 to 3 years with influenza found a reduction of 3.5 days when oseltamivir treatment was started within 24 hours after illness onset. The Cochrane review was unable to reach conclusions about the efficacy of oral oseltamivir or inhaled zanamivir treatment to reduce health complications, including those which might result in hospitalization. The review authors reported that they did not have full access to all unpublished data for oseltamivir RCTs as requested from the manufacturer.

 

A systematic review of RCTs should include unpublished and published data, and researchers should have full access to these data. However, such a review may not fully inform the question of whether antiviral treatment reduces severe influenza complications such as those resulting in hospitalization in generally healthy persons because enormous numbers of participants are needed. The burden of influenza disease is greatest among the elderly, persons with underlying medical conditions such as chronic obstructive pulmonary disease, asthma, congestive heart failure, diabetes, pregnant women, and young children. These groups are at highest risk for developing severe complications from influenza resulting in hospitalization or death, and generally have not been studied in RCTs.

 

The Cochrane review did not consider any data from uncontrolled observational studies of oseltamivir treatment. While such studies have inherent design limitations, they can inform clinical practice and public health, especially when data from RCTs are unavailable or have not been conducted among high-risk groups or hospitalized influenza patients, or because having a placebo group would be unethical since antiviral treatment is recommended for these groups. Indeed, many observational studies of antiviral treatment of seasonal influenza or influenza A (H1N1) pdm09 (2009 pandemic H1N1) have been conducted among hospitalized patients, including critically ill children and adults. These observational studies from many countries have consistently found that early oseltamivir treatment of influenza patients reduces the duration of hospitalization and risk of severe outcomes such as intensive care unit admission or death. These studies have reported that clinical benefit is greatest when oseltamivir treatment is started within 48 hours of illness onset; however clinical benefit has still been observed when oseltamivir treatment is started up to less than 5 days after illness onset.

(Continue . . .)

 

 

While falling short of the `gold standard’ employed by the Cochrane group for inclusion into their analysis, we’ve a number of compelling observational studies to look at, including:

 

In 2010 we saw an observational study that appeared in JAMA  (see Study: Antivirals Saved Lives Of Pregnant Women) that strongly suggested that Tamiflu was life saving for some patients with pandemic flu.

 

And again in 2010, in BMJ: Efficacy of Oseltamivir In Mild H1N1, we saw a study which suggested that the administration of oseltamivir may have significantly reduced the incidence of pneumonia among otherwise healthy pandemic H1N1 patients.

 

And lastly, in Study: Antiviral Therapy For H5N1, we saw the largest study to date on the outcomes of H5N1 patients who either received, or did not receive, antiviral treatment.

 

The research appears in the IDSA’s  Journal of Infectious Diseases. The bottom line is essentially out of 308 cases studied, the overall survival rate was a dismal 43.5%.

 

But . . . of those who received at least one dose of Tamiflu . . .  60% survived . . .  as opposed to only 24% who received no antivirals.

 

 

There are other concerns when it comes to use of oseltamivir, of course. Including the possibility inducing side effects and the possibility of generating resistant strains of the influenza virus.

 

But for now, it remains one of the few pharmacological options we have available to treat severe influenza.

»» Read More

The Tamiflu Controversy Continues

 

 

Photo Credit – Wikipedia  

# 6085

 

 

The debate over the effectiveness of oseltamivir (Tamiflu ®) is back in the news once more with the release of a new Cochrane group analysis that finds insufficient evidence to prove that the drug reduces flu complications and transmission.

 

If it seems we’ve been here before, you are right (see Effect Measure’s The Tamiflu doesn't work non-story from 2009).

 

Many researchers point out anecdotal and observational data showing that early administration of oseltamivir does reduce complications from influenza, and can be lifesaving.

 

As an example, In 2010 we saw an observational study that appeared in JAMA  (see Study: Antivirals Saved Lives Of Pregnant Women) that strongly suggested that Tamiflu was life saving for some patients with pandemic flu.

 

And again in 2010, in BMJ: Efficacy of Oseltamivir In Mild H1N1, we saw a study which suggested that the administration of oseltamivir may have significantly reduced the incidence of pneumonia among otherwise healthy pandemic H1N1 patients.

 

And lastly, in Study: Antiviral Therapy For H5N1, we saw the largest study to date on the outcomes of H5N1 patients who either received, or did not receive, antiviral treatment.

 

The research appears in the IDSA’s  Journal of Infectious Diseases. The bottom line is essentially out of 308 cases studied, the overall survival rate was a dismal 43.5%.

 

But . . . of those who received at least one dose of Tamiflu . . .  60% survived . . .  as opposed to only 24% who received no antivirals.

 

 

Alas, these are observational studies, which are not considered the `best evidence’ by most scientists.

 

Ideally what researchers want are a series of well mounted Randomized controlled trials (RCTs) – long considered the `gold standard’ for drug research. But these are expensive, and difficult to conduct ethically when trying to evaluate a potentially life saving drug.

 

So we are left with is a choice that reminds one of the one offered by Chico Marx in the 1933 classic Duck Soup (“Who you gonna believe, me or your own eyes?”).

 

Choosing between observational data that suggests a clinical benefit verses a lack of well mounted studies that actually prove a benefit.

 

Complicating matters, there are ongoing charges that Roche Laboratories has not been forthcoming with all of the data that has been requested by the Cochrane group.

 

Admittedly, there are other concerns when it comes to use of oseltamivir, including the possibility of incurring side effects and the (potential, at least) of generating resistant strains of the influenza virus.

 

Robert Roos of CIDRAP News takes us on a detailed journey down this rabbit hole, with as good a summary of the issues as you are apt to find anywhere.

 

Review renews questions about oseltamivir benefits

Robert Roos News Editor

Jan 19, 2012 (CIDRAP News) – A lengthy new analysis of unpublished clinical trial data is renewing questions about the effectiveness of the influenza drug oseltamivir (Tamiflu), saying that although the drug shortens flu symptoms by about a day, there is no evidence that it reduces hospital admissions.

(Continue . . .)

 

Despite a lot of unanswered questions, for now at least, oseltamivir remains one of the few pharmacological options likely to be available during a pandemic.

»» Read More

NEJM: Oseltamivir Resistant H1N1 in Australia

 

 

# 6042

 

A correspondence appears in today’s NEJM that provides some detailed information on a story we began to follow last August (see Australia Reports Cluster Of Antiviral Resistant H1N1); the detection of an unusual number of oseltamivir (Tamiflu ®) resistant H1N1 viruses in and around the Newcastle area of New South Wales.

 

First, a little background.

 

During 2008 and early 2009 -prior to the emergence of the 2009 H1N1 pandemic virus - the old seasonal H1N1 virus developed nearly complete resistance to the antiviral drug oseltamivir.  

 

The H1N1pdm09 virus which replaced the old H1N1 – while resistant to the older amantadines – has remained largely sensitive to oseltamivir. The concern is, that over time, this newer strain might one day develop resistance as well.

 

During the first two years, only 1%-2% of samples tested have shown the most common mutation known to convey oseltamivir resistance; H275Y, where a single amino acid substitution (histidine (H) to tyrosine (Y)) occurs at the neuraminidase position 275.

 

(Note: some scientists use 'N2 numbering' (H274Y) and some use 'N1 numbering' (H275Y))

 

Most of the resistant cases we’ve seen reported have been isolated and sporadic, with no apparent epidemiological links. They have  often occurred in patients under therapeutic or prophylactic treatment with oseltamivir, and are assumed to have been the result of spontaneous resistance. 

 

 

Which brings us to today’s report in the NEJM that looks at the:

 

Community Transmission of Oseltamivir-Resistant A(H1N1)pdm09 Influenza

N Engl J Med 2011; 365:2541-2542 December 29, 2011

 

 

What the authors found was evidence for the sustained community transmission of a resistant strain of the H1N1pdm09 virus. 

 

After analyzing viral samples pulled from 182 patients seen in emergency departments, intensive care units, and doctor’s offices in New South Wales between May and August of 2011, they found 29 (16%) carried the H275Y resistance mutation.

 

Most of the patients lived within 50km of Newcastle, and while 10 of the cases could be epidemiologically linked (2 in 4 households, 2 in a shared car trip), the rest could not.

 

Only one had been treated with oseltamivir prior to testing.

 

The good news is that while 7 of these cases were hospitalized (24%), none ended up in the Intensive care unit, and none died. This resistant strain also appears to be antigenically similar to the vaccine strain.

 

The authors recommend:

 

As winter approaches in the Northern Hemisphere, it remains important to ensure that A(H1N1)pdm09 strains from early in the season are analyzed rapidly for any indication that this transmissible oseltamivir-resistant variant has spread.

 

 

So far, this appears to be regional phenomenon, and numbers like these have not been reported in other parts of the world.

 

For more on this evolving story, you may wish to revisit:

 

WER: Update On Anti-Viral Resistant Influenza

ECDC: Risk Assessment On Australia’s Antiviral Resistant H1N1 Cluster

»» Read More

CIDRAP News: Signs Of Tamiflu Resistant H1N1 Spreading

 

 

# 6020

 

 

Lisa Schnirring, writing last night for CIDRAP News, has a terrific piece on the slow, but still worrisome spread of Tamiflu resistant H1N1 influenza strains over the past couple of years.

 

This is a topic this blog has covered a couple of times in recent months (see WER: Update On Anti-Viral Resistant Influenza and ECDC: Risk Assessment On Australia’s Antiviral Resistant H1N1 Cluster), but Lisa brings us details of two new studies, one in the EID Journal and the other in the Lancet.

 

So I’ll just step aside and invite you to read:

 

 

Signs of Tamiflu-resistant 2009 H1N1 flu transmission cited

Lisa Schnirring Staff Writer

Dec 19, 2011 (CIDRAP News) – An analysis of 2009 H1N1 influenza virus isolates from the 2010-11 flu season suggests that low-level community transmission of an oseltamivir-resistant strain took place, a development that bears close watching, researchers reported today.

 

Though the conclusion was based on a small number of patients, the authors said a higher prevalence of the resistant strain last year in people who weren't exposed to oseltamivir (Tamiflu) compared to the pandemic months is a notable difference. Researchers from the US Centers for Disease Control and Prevention (CDC) and their state partners reported their findings in an early online release from Emerging Infectious Diseases.

(Continue . . .)

»» Read More

Australia Reports Cluster Of Antiviral Resistant H1N1

 

 

# 5786

 

 

Since it first appeared in the spring of 2009, scientists have worried that the H1N1 swine flu would someday develop resistance to the antiviral medication oseltamivir (Roche’s Tamiflu ®) as its predecessor - seasonal H1N1 - did in 2008.

 

Overall, however, the news has been generally good.

 

During the first two years, only 1%-2% of samples tested have shown the most common mutation known to convey oseltamivir resistance; H275Y, where a single amino acid substitution (histidine (H) to tyrosine (Y)) occurs at the neuraminidase position 275.

 

(Note: some scientists use 'N2 numbering' (H274Y) and some use 'N1 numbering' (H275Y))

 

Most of these cases of antiviral resistance occurred spontaneously in people after being treated with the drug, and quite often involved immunocompromised individuals.

 

Yesterday, ProMed Mail published a report from Australia on an unusual and worrisome cluster of oseltamivir resistance in New South Wales.  More than 2 dozen patients – roughly 14% of the isolates tested from that region since May – have shown the H275Y mutation.

 

INFLUENZA (50): AUSTRALIA (NEW SOUTH WALES), H275Y MUTATION CLUSTER

********************************************************
A ProMED-mail post
http://www.promedmail.org
ProMED-mail is a program of the
International Society for Infectious Diseases
http://www.isid.org
Date: Thu 24 Aug 2011
From: Kate Hardie

A cluster of oseltamivir-resistant A(H1N1)2009 influenza cases with onset between May and August 2011 has been detected in the Hunter region of New South Wales (NSW), Australia.

 

Viruses from 25 of 184 (14 percent) A(H1N1)2009 cases from the Hunter New England region exhibited highly reduced oseltamivir sensitivity due to the H275Y substitution in the neuraminidase. The H275Y mutation is a well-established substitution previously reported to confer oseltamivir resistance in N1 neuraminidases and was present in the widespread oseltamivir resistant pre-pandemic seasonal A(H1N1) virus.

(Continue . . . )

 

Significantly, none of the cases reportedly took the antiviral prior to their flu test, and in follow up interviews with 16 of these cases, none have a history of being immunocompromised.

 

Jason Gale, writing for Bloomberg News, has more details, including some quotes from World Health Organization officials on this finding.

 

Tamiflu-Resistant Flu Outbreak Reported in Australia’s Newcastle, WHO Says

By Jason Gale - Aug 25, 2011 9:25 PM ET

 

For now, the H1N1 virus remains overwhelmingly sensitive to oseltamivir, even in the New South Wales region where all of these cases are located. And the H1N1 virus with the H275Y mutation remains sensitive to GSK’s Relenza, an alternative antiviral.

 

The concern is that this appears to be a biologically fit, easily transmitted strain of H1N1 and that it might eventually spread beyond this region.

 

Which is exactly what we saw happen with the old seasonal H1N1 virus, when in early 2008 Norway began to report a rise in resistant samples, and less than a year later the resistant strain was the predominant strain around the world.

 

It’s a crowded viral field out there, and whether this resistant strain can compete with the numerous non-resistant strains of H1N1 on the global stage is something we will have to wait to see.

 

This is a compelling enough reason, however, to get that seasonal flu shot this year. It is better to try to prevent the flu, than to have to treat it. 

 

Photo Credit PHIL

 

Particularly if treatment options should become more limited in the future.

»» Read More

The WHO’s Flu Review

 

 

# 5582

 

 

 

With the 2010-2011 northern hemisphere flu season at its end, the World Health Organization has released a summary of global influenza trends over the past six months.

 

This summary appears in the latest Weekly Epidemiological Record 2011, 86, 221–232 and on the WHO’s Global Alert and Response (GAR) page.

 

I’ve excerpted a few passages (and reformatted for readability), but the entire report is worth reading.  I’ll return with some brief comments:

 

 

 

Summary review of the 2010-2011 northern hemisphere winter influenza season

This review summarizes the chronology, epidemiology, and virology of the northern hemisphere temperate regions' winter influenza season encompassing the time period from October 2010 through the end of April 2011.

 

It is an expanded version of the WHO Weekly Epidemiological Record (WER) 27 May 2011, vol. 86 (pp 221-232).

 

Summary points

• The winter influenza season in the temperate countries of the northern hemisphere began in late October in Asia, a month later in Europe and North America, but was largely over by the end of April.

 
• The most commonly detected virus was different in North America, where influenza A(H3N2) and influenza type B co-circulated with influenza A(H1N1)2009, and Europe, where influenza A(H1N1)2009 was by far the most commonly detected virus.

• Although it was no longer the predominant influenza virus circulating in many parts of the world, H1N1 (2009) otherwise behaved much the same way as it had during the pandemic in terms of the age group most affect and the clinical pattern of illness.

• The impact of the influenza season in some areas where H1N1 (2009) was the predominant virus was more than in the previous year, most notably in the United Kingdom (UK) where intensive care units were stressed by large numbers of cases requiring ventilatory support.

• More than 90% of viruses detected around the world were similar antigenically to those found in the seasonal trivalent influenza vaccine.

 
• Antiviral resistance in influenza A(H1N1)2009 remained at a very low level. There were case reports with no history of exposure to antiviral medications, consistent with some community transmission of resistant virus.

<SNIP>

Conclusions

Influenza A(H1N1)2009 continues to circulate widely. However in contrast to the pattern observed during the pandemic, the virus is now co-circulating with other influenza viruses and was not the predominant influenza A virus in many countries.

 

Circulation this season occurred during the expected influenza seasonal time frame with no out-of-season community transmission reported in temperate northern countries. The pattern of association between severe disease and age was similar to that observed previously.

 

Influenza A(H1N1)2009 continues to be more of a problem for young and middle-aged adults, while influenza A(H3N2) causes more severe disease in adults over the age of 65 years. Influenza type B appears to disproportionately affect young children.

 

A few countries appeared to have a higher number of severe cases compared to last year for reasons that are unclear. This was most notable in the UK though this observation may well be a surveillance artefact related to the active surveillance for severe disease that was carried out there.

 

All three circulating viruses demonstrated very little antigenic drift over the last year and were closely related to the three strains contained in the seasonal influenza vaccine. In addition, all but a very small percentage of viruses tested remain sensitive to neuraminidase inhibitors.

 

This reemphasises the need to continue to vaccinate and to treat early patients at high risk for developing severe disease, including those at the extremes of age, those with certain chronic medical illness, and pregnant women.

 

 

 

While admittedly a convoluted flu season, with four flu strains (five if you count the few remnants of seasonal H1N1) in circulation, and widely varying impacts around the world – some `good news’ stands out.

 

First, the feared rise in antiviral resistance for the 2009 H1N1 virus has not yet happened, with 98% of the samples testing still sensitive to oseltamivir.

 

However, since there were a few cases of oseltamivir resistance with no known exposure to the drug, concerns over possible limited community transmission of a resistant virus remain.

 

 

Second, while scattered mutations in the 2009 H1N1 virus have been detected, the vast majority of viruses tested remain antigenically similar to the current tri-valent influenza vaccine.

 

 

The chart below illustrates 99% of the H1N1 (2009) and 96% of the  H3N2 viruses tested were antigenically similar to the current vaccine.

 

 

With two main lineages of B viruses that co-circulate each year, scientists must decide which strain to include in the vaccine. Some years they guess wrong, but this year nearly 91% of B viruses tested were a match (B Victoria) for vaccine strain.

 

 

While no guarantees can be made for what these influenza viruses will do in the next 6 to 12 months, for now they are behaving pretty much as scientists predicted.

 

The best news is that the vaccine being produced for the 2011-2012 flu season (Southern & Northern Hemisphere) appears to be an excellent match for 90% of the flu viruses currently circulating.

 

Of course, the only constant with influenza viruses is change.  

 

And so we will watch the progress of the upcoming flu season south of the equator with great interest. What happens in Australia, New Zealand, South American, and South Africa can often tell us a lot about the kind of flu season we may see in the fall.

 

Stay tuned.

»» Read More

CIDRAP: UK Findings Hint At Resistant Flu Strain

 

 

 

# 5286

 

 

Robert Roos, news editor of CIDRAP, has a summary tonight of a Rapid Communications report that appears in today’s Eurosurveillance Journal regarding a small number of oseltamivir resistant H1N1 flu strains recently detected in the UK.

 

The report is called:

 

Eurosurveillance, Volume 16, Issue 5, 03 February 2011

Rapid communications

Continued emergence and changing epidemiology of oseltamivir-resistant influenza A(H1N1)2009 virus, United Kingdom, winter 2010/11

A Lackenby , J Moran Gilad, R Pebody, S Miah, L Calatayud, S Bolotin, I Vipond, P Muir, M Guiver, J McMenamin, A Reynolds, C Moore, R Gunson, CI Thompson, M Galiano, A Bermingham, J Ellis, M Zambon

 

Rather than squandering valuable electrons by needlessly summarizing this report myself, I’ll simply direct you to CIDRAP’s excellent  summary.

 

 

UK findings hint at spread of resistant H1N1 strain

Robert Roos News Editor

Feb 3, 2011 (CIDRAP News) – British researchers say 3 of 27 cases of oseltamivir (Tamiflu)-resistant 2009 H1N1 influenza detected in Britain so far this season were in outpatients who had no known exposure to the drug, suggesting that resistant strains may be spreading at a low level in the community.

 

Writing in Eurosurveillance today, the authors say the finding "suggests possible onward transmission of resistant strains and could be an indication of a possibility of changing epidemiology of oseltamivir-resistant influenza A(H1N1) virus." However, no transmission has been confirmed so far, they report.

(Continue . . .)

»» Read More

Study: Oseltamivir-Resistant Pandemic Flu Cases In The US

 

 

 

# 5191

 

 

Unlike its seasonal cousin (which has all but vanished), the 2009 novel H1N1 virus remains largely susceptible to the antiviral medication oseltamivir (Tamiflu).

 

During a 14-month period (April 2009-June 2010) 6,740 H1N1 samples were submitted to US surveillance systems for testing, and of those, only 37 (.5%) proved resistant to oseltamivir.

 

That’s the encouraging news from a study, published yesterday, in the CDC’s  EID Journal.

 

The link, and an excerpt describing the patient profile follow.  Go ahead and read it. 

 

I’ll be back with a bit more when you return.

 

 

Characteristics of Patients with Oseltamivir-Resistant Pandemic (H1N1) 2009, United States

Graitcer SB, Gubareva L, Kamimoto L, Doshi S, Vandermeer M, Louie J, et al. Characteristics of patients with oseltamivir-resistant pandemic (H1N1) 2009, United States. Emerg Infect Dis. 2011 Feb; [Epub ahead of print]

 

(EXCERPT)

 

Most patients infected with oseltamivir-resistant pandemic (H1N1) 2009 viruses were hospitalized (81%), had a severe immunocompromising condition (76%), and had been exposed to oseltamivir before collection of the specimen tested for antiviral resistance (89%) (Table); 9 (30%) had received oseltamivir as chemoprophylaxis, and 21 (70%) had received oseltamivir as treatment.

 

Four patients with oseltamivir-resistant pandemic (H1N1) 2009 virus infection had no documented exposure to oseltamivir before collection of the specimen for testing, including exposure to family members receiving oseltamivir.

 

No epidemiologic links were found between the 4 patients.

 

For now, the good news is that the 2009 H1N1 virus remains overwhelmingly sensitive to Tamiflu.

 

But of course, the same could have been said about the old seasonal H1N1 virus back in 2006-2007, when 99% of isolates tested showed good sensitivity to oseltamivir.

 

Resistance is usually caused by a mutation, known as H275Y, where a single amino acid substitution (histidine (H) to tyrosine (Y)) occurs at the neuraminidase position 275

 

(Note: some scientists use 'N2 numbering' (H274Y) and some use 'N1 numbering' (H275Y)).

 

Back in 2007, the belief was that the mutation that made the virus resistant to Tamiflu (H275Y), also reduced its biological fitness – suggesting that mutated versions of the viruses were unlikely to spread widely.

 

 

But those hopes were dimmed when, by the end of the 2007-2008 flu season, nearly 13% of H1N1 isolates tested the United States were resistant to the drug.

 

By December of 2008 nearly all seasonal H1N1 isolates tested around the world carried the H275Y mutation that conferred Tamiflu resistance.

 

Thus far, it appears that most of these resistant 2009 H1N1 strains have developed in immuno-compromised patients as so-called `spontaneous mutations’ – not as the result of contracting a circulating and already-resistant virus.

 

 

Human-to-human transmission of an oseltamivir-resistant novel H1N1 virus has only rarely been demonstrated.  A couple of reports on those include:

 

NEJM: Community Cluster Of Tamiflu Resistant H1N1

WER Review: Oseltamivir Resistance In Pandemic H1N1

 

 

Today, the news is good; resistance in novel H1N1 is rare.  But pharmacological victories over constantly evolving viruses (and bacteria) tend to be fleeting, and so the need for new classes of antivirals is great.  

 

The authors sum of their report this way:

 

Although the number of patients with oseltamivir-resistant pandemic (H1N1) 2009 virus infections was small in the United States during this period, this is the largest case-series published and confirms findings from reports with smaller samples (8–10).

 

Although all patients in our comparison group of patients with oseltamivir-susceptible pandemic (H1N1) 2009 were hospitalized, most patients in the oseltamivir-resistant group were also hospitalized. Finally, we do not have a comparison group of patients with immunocompromising conditions and oseltamivir-susceptible pandemic (H1N1) 2009 virus infections; thus, risk factors for infection with oseltamivir-resistant infection among patients with immunocompromising conditions cannot be determined.

 

The finding of oseltamivir-resistant pandemic (H1N1) 2009 viruses associated with oseltamivir treatment highlights the need for new antiviral agents and new treatment strategies.

»» Read More

PLoS Medicine: Mono or Combo Antiviral Therapy?

 

 

# 5028

 

 

Pharmacological victories over continually evolving pathogens are often fleeting at best. 

 

No sooner do researchers release a new generation of antibiotics or antivirals, than these organisms begin to find ways to work around them.  

 

History shows that if we create a better mousetrap, nature immediately goes to work building a better mouse.

 

Amantadine managed to remain an effective treatment and/or prophylaxis against influenza A for four decades, although it was used only sparingly for the first 30 years or so.

 

Overuse of Amantadine, particularly its inclusion into chicken feed during the late 1990s to combat bird flu in Asia – has been credited with a dramatic rise in influenza’s resistance to the drug by 2005.

 

Tamiflu (oseltamivir), released in 1999 proved extremely effective against influenza until 2008, when a resistant version of seasonal H1N1 appeared and quickly spread around the world.

 

Seasonal H3N2, along with the pandemic strain of H1N1, remain largely susceptible to the drug.  As does H5N1.

 

At least for now. 

 

We’ve a new study in Plos Medicine that takes a look at the best use (monotherapy or as a combination) of two well known antivirals used for treating seasonal (and by extension, pandemic) influenza.

 

The two antivirals in question are both neuraminidase inhibitors; Roche Laboratories  Tamiflu (oseltamivir) and GlaxoSmithKline’s Relenza (zanamivir). 

 

The study, which comes up with a somewhat surprising answer, is called:

 

Efficacy of Oseltamivir-Zanamivir Combination Compared to Each Monotherapy for Seasonal Influenza: A Randomized Placebo-Controlled Trial

Duval X, van der Werf S, Blanchon T, Mosnier A, Bouscambert-Duchamp M, et al. 2010 Efficacy of Oseltamivir-Zanamivir Combination Compared to Each Monotherapy for Seasonal Influenza: A Randomized Placebo-Controlled Trial. PLoS Med 7(11): e1000362. doi:10.1371/journal.pmed.1000362

 

 

Over the 2008-2009 (pre-pandemic) influenza season, researchers enlisted the aid of 145 general practitioners across France, and conducted a randomized placebo-controlled study on adult patients with a positive influenza A rapid test and reporting flu-like symptoms for less than 36 hours. 

 

Those that fell into that criteria were randomized into one of 3 groups who received either:

 

(1) oral oseltamivir 75 mg twice daily plus zanamivir 10 mg by inhalation twice daily

(2) oral oseltamivir 75 mg twice daily plus inhaled placebo, or

(3) zanamivir 10 mg by inhalation twice daily plus oral placebo.

 

The assessment of each treatment regimen was evaluated virologically and clinically.  The participants in this study were all blinded to the individual treatment protocols. 

 

Using reverse transcription (RT)-PCR testing, they monitored nasal viral shedding levels, while clinical evaluation included the amount of time to resolution of illness and the incidence of secondary complications of influenza. 

 

Most (85%) of these patients were assumed to have had H3N2 seasonal influenza, which predominated that year.  The study was supposed to involve 900 patients, but was cut short by the emergence of the novel H1N1 virus in the spring of 2009, and so only 541 patients were enrolled.

 

The goal was to determine what worked best.

 

Tamiflu alone

Relenza alone

Or a combination of the two.

 

While a more expensive treatment option, many scientists have suggested that a combination of antivirals – instead of using a single drug - might help prevent the creation of new antiviral resistant strains.

 

It has also been assumed that a combination of two antivirals might prove more effective as well.

 

Today’s study – while limited in scope and size – seems to call both of those ideas into question.

 

When the blinds were removed researchers discovered that by the 2nd day of treatment, 62.5% of those receiving Tamiflu alone saw a significant reduction in viral load compared to just 40.5% of those receiving Relenza. 

 

Additionally, the study found:

 

(reparagraphed from the study):

 

Overall the oseltamivir-zanamivir combination was both virologically and clinically significantly less effective than the oseltamivir monotherapy.

 

In addition, the clinical effects of the oseltamivir-zanamivir combination on time to resolution of symptoms were not significantly different from that of zanamivir monotherapy, suggesting that oseltamivir does not add clinical benefit to zanamivir monotherapy.

 

The combination of antivirals was also linked to a slightly increased incidence of side effects.

 

For ethical reasons, there was not a double-placebo arm to this study.

 

In other words, we have no comparison of outcomes between those who received no antivirals and those who received one of the protocols above.

 

The authors sum up their study this way:

 

 

Despite the theoretical potential for the reduction of the emergence of antiviral resistance, the lower efficiency of the oseltamivir-zanamivir combination found in this study calls for caution in its use in clinical practice.

 

Thus, also considering the superiority of oseltamivir monotherapy over zanamivir monotherapy observed in this trial, oseltamivir should be the recommended primary anti-influenza treatment during influenza seasons with predominant H3N2 viruses naturally susceptible to oseltamivir.

 

These results would need to be confirmed for the 2009 H1N1 pandemic virus and in the coming years, for future circulating influenza viruses.

 

The entire open access study is available here.

 

Interesting findings that will need to be analyzed (and repeated)  by others, particularly since the strain of H3N2 in circulation in 2008 is no longer with us. 

 

The results may not be the same with other virus strains.

 

This study also doesn’t resolve ongoing questions over whether single-antiviral drug treatment exacerbates the development of resistant strains.  

 

Given the limited number of influenza antivirals available now or in the pipeline, finding ways to protect the ones we have remains a serious consideration.

»» Read More

BMJ: Efficacy of Oseltamivir In Mild H1N1

 

 

# 4948

 

 

One of the ongoing debates in the world of influenza has been over the efficacy of administering oseltamivir (Tamiflu) in the treatment of mild influenza in otherwise healthy individuals.

 

You may recall that last December a cluster of articles appeared in the BMJ which seriously questioned the lack of supportive scientific evidence in this matter (see BMJ: A Review Of Tamiflu’s Efficacy Against Seasonal Influenza).

 

Published 8 December 2009, doi:10.1136/bmj.b5106
Cite this as: BMJ 2009;339:b5106
Research

Neuraminidase inhibitors for preventing and treating influenza in healthy adults: systematic review and meta-analysis

 

 

While the entire study is worth reading, the bottom line was there is insufficient evidence, according to the authors, to conclude either for or against Tamiflu for use in healthy adults with seasonal influenza.

In other words, the authors stated that more studies were needed.

 

Although it certainly won’t end the debate, we’ve a new open access retrospective study appearing this week in the BMJ  which suggests that administration of oseltamivir may have significantly reduced the incidence of pneumonia among otherwise healthy pandemic H1N1 patients.

 

BMJ 2010; 341:c4779 doi: 10.1136/bmj.c4779 (Published 28 September 2010)

Cite this as: BMJ 2010; 341:c4779

• Research

Effectiveness of oseltamivir on disease progression and viral RNA shedding in patients with mild pandemic 2009 influenza A H1N1: opportunistic retrospective study of medical charts in China

 

Hongjie Yu, Qiaohong Liao,Yuan Yuan,Lei Zhou, Nijuan Xiang, Yang Huai, Xiuhua Guo, Yingdong Zheng, H Rogier van Doorn, Jeremy Farrar, Zhancheng Gao, Zijian Feng, Yu Wang, Weizhong Yang

Conclusions Chinese patients with 2009 H1N1 infection predominantly presented with features of uncomplicated, self limiting acute respiratory illness. 2009 H1N1 might be shed longer than seasonal influenza virus.

Treatment with oseltamivir was associated with a significantly reduced development of radiographically confirmed pneumonia and a shorter duration of fever and viral RNA shedding.

Though these patients benefited from treatment, the findings should be interpreted with caution as the study was retrospective and not all patients underwent chest radiography.

 

 

For those who would like the short version, there is a press release covering the highlights.  I’ve excerpted a few paragraphs.  Follow the link to read it in its entirety.

 

Swine flu patients benefited from taking Tamiflu, says study

Research: Effectiveness of oseltamivir on disease progression and viral RNA shedding in patients with mild pandemic 2009 influenza A H1N1: opportunistic retrospective study of medical charts in China

Healthy people who caught swine flu during the 2009 pandemic may have been protected against developing radiographically (x-ray) confirmed pneumonia by taking the antiviral drug oseltamivir (Tamiflu), concludes a study of cases in China published on bmj.com today.

 

The researchers also show that oseltamivir treatment was associated with shorter duration of fever and viral RNA shedding (the period when a virus is contagious), although they stress that their findings should be interpreted with caution.

(Continue . . .)

 

While the  lack of peer-reviewed RCTs (Randomized Controlled Trials) on oseltamivir – which can provide genuine ethical dilemmas to mount – will continue to leave some questioning the efficacy of Tamiflu in mild influenza, anecdotal reports and retrospective analysis continues to show the drug to be beneficial, particularly in cases of severe influenza.

 

Today’s study adds a new dimension to the debate, by strongly suggesting that it may reduce morbidity in healthy adults with mild influenza symptoms.

 

Additionally, the researchers reported that:

 

Our study suggests that 2009 H1N1 is shed from one day before the onset of symptoms to eight days after onset for most (91%) patients and can be shed up to 21 days.

The BMJ’s summary reads, in part:

 

What this study adds

• In patients with mild pandemic 2009 H1N1 infection, oseltamivir can protect against subsequent development of radiographic pneumonia, even in those who start treatment more than two days after the onset of symptoms

• Early oseltamivir treatment within two days of symptom onset can reduce the duration of fever and viral RNA shedding

• Pandemic 2009 H1N1 virus is shed from one day before the onset of clinical symptoms to up to eight days after onset for most patients and is shed for longer than seasonal influenza virus

 

There are other concerns when it comes to the routine use of oseltamivir with mild influenza, including the possibility of causing side effects and the (potential, at least) of generating resistant strains of the influenza virus.

 

Both matters to be taken up by other studies and on another day.

»» Read More

Study: Antiviral Therapy For H5N1

 

# 4896

 

 

One of the ongoing debates in the world of pandemic influenza has been on the value of Oseltamivir (Tamiflu) for pandemic influenza.

 

Critics point out that the drug can have (rare) side effects and that it only reduces the duration of seasonal flu symptoms by an average of 1.3 days.    A modest but measureable benefit.

 

Where Tamiflu – and other antivirals – appear to make a bigger difference is in reducing symptoms in those who have pre-existing risk factors or conditions – including pregnancy – or those who are experiencing serious influenza complications.

 

And among H5N1 bird flu cases around the world, those that have survived (40%) were likely to have received early antiviral intervention.

 

Granted, most of the `evidence’ for the effectiveness of antivirals comes from observational studies, which some researchers find wanting (see BMJ: A Review Of Tamiflu’s Efficacy Against Seasonal Influenza).

 

Randomized controlled trials (RCTs) – while considered the `gold standard’ for drug research – are almost impossible to conduct ethically when trying to evaluate a potentially life saving drug.

 

We would all like medicine to be based on treatments and drugs proved – beyond a shadow of a doubt – to be safe and effective . . . but sometimes we must accept a lower burden of proof -the preponderance of evidence - instead.

 

 

Earlier this year, another observational study appeared in JAMA  (see Study: Antivirals Saved Lives Of Pregnant Women) that strongly suggested that Tamiflu was life saving for some patients with pandemic flu.

 

Today we’ve the largest study yet on the outcomes of H5N1 patients who either received, or did not receive, antiviral treatment.  

 

The research appears in the IDSA’s  Journal of Infectious Diseases along with a companion editorial (h/t Tetano on FluTrackers for the link)

 

 

DOI: 10.1086/656316

Effectiveness of Antiviral Treatment in Human Influenza A(H5N1) Infections: Analysis of a Global Patient Registry

Wiku Adisasmito,Paul K. S Chan,Nelson Lee, Ahmet Faik Oner,Viktor Gasimov,Faik Aghayev, Mukhtiar Zaman, Ebun Bamgboye, Nazim Dogan, Richard Coker, Kathryn Starzyk, Nancy A. Dreyer, and Stephen Toovey

 

 

While I would encourage you to read the entire study (and editorial) the bottom line is essentially out of 308 cases studied, the overall survival rate was a dismal 43.5%.

But . . . of those who received at least one dose of Tamiflu . . .  60% survived . . .  as opposed to only 24% who received no antivirals.

 

 

 

The greatest benefit was derived when treatment was started within 48 hours of falling ill, but even delayed treatment was seen to have some value.

 

Treatment with oseltamivir was linked to a 49% reduction in mortality.

 

As this study, and the editorial comment point out, longer courses of antivirals and at higher doses may be needed to improve survival these rates. 

 

The `Double the Dose for Double The Duration’ option is something that we’ve discussed many times in the past ( see Hong Kong Finds Success With Higher Tamiflu Doses and How Much Tamiflu Is Enough?)

 

 

Today’s study, however, gives us the best evidence to date that antivirals can, and do, save lives when used in the treatment of H5N1 infections. 

»» Read More