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

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

 

 

# 5815

 

 

Roughly 10 days ago, in Australia Reports Cluster Of Antiviral Resistant H1N1, I wrote of a large clustering of oseltamivir (Tamiflu) resistant H1N1 cases in New South Wales. More than 2 dozen patients – roughly 14% of the isolates tested from that region since May – have shown a genetic mutation that confers resistance.

 

Ever since the novel H1N1 swine flu virus appeared in the spring of 2009, scientists have worried that it would someday develop resistance to oseltamivir as its predecessor - seasonal H1N1 - did in 2008.

 

Overall, however, the news has been encouraging.

 

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))

 

This recent jump in resistance in Australia is concerning as these cases have not been linked to prior antiviral use or occurred in immunocompromised patients, factors commonly associated with the development of spontaneous resistance in the past.

 

Today the ECDC released a 5-page PDF risk assessment on the rise of resistant H1N1 cases in Australia.  It concludes - that at least for now - “the risk of this cluster becoming more widespread and having public health implications remains low.”

 

It goes on to warn, however, that  “only ongoing surveillance will indicate whether this occurrence remains a localised event or whether it has the potential to become widespread.”

You can read the abstract or download the entire document from the link below.

 

 

ECDC assessment on Oseltamivir-resistant influenza A(H1N1)2009 cluster reported in Australia

06 Sep 2011

Australia has reported oseltamivir resistance of A(H1N1)2009 influenza virus in the state of New South Wales, with assumed person-to-person transmission of the resistant strain. The European Centre of Disease Prevention and Control (ECDC) has produced a rapid risk assessment to assess the situation.

 

The oseltamivir-resistant cases had no known link to oseltamivir exposure and were not immunosuppressed, but were closely linked geographically. Samples from the cluster do not currently exhibit any resistance to zanamivir. Although the cluster has remained localised, it cannot be assumed that the variant virus will not spread.

 

ECDC concludes that at present, the risk of this cluster becoming more widespread and having public health implications remains low. However, if spread does occur, there will be implications for the prophylaxis and treatment of influenza patients and the consequences for public health in Europe will need to be considered.

 

Regardless of the outcome, constant antiviral resistance monitoring is vital in Europe and globally. Only ongoing surveillance will indicate whether this occurrence remains a localised event or whether it has the potential to become widespread.

 

Oseltamivir and zanamivir are active ingredients in antiviral drugs (Tamilfu, Relenza). Vaccination, supplemented by personal hygiene measures, remains the primary measure for prevention of seasonal influenza transmission. However, antiviral drugs are important countermeasures for prophylaxis and treatment, especially in vulnerable people and those with severe influenza.

 

Read the full ECDC risk assessment: Oseltamivir-resistant influenza A(H1N1)2009 cluster in Australia

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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.

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