NEJM -- Prevention and Treatment of Seasonal Influenza

[Giuseppe]

NEJM -- Prevention and Treatment of Seasonal Influenza

Prevention and Treatment of Seasonal Influenza

W. Paul Glezen, M.D.

This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author's clinical recommendations.


In February 2007, fever developed in a previously healthy 15-year-old girl, with a peak temperature of 102?F (38.9?C) and mild upper respiratory congestion.

The next day she was seen by her primary care physician.

A rapid screening test for group A streptococcus was negative, and oseltamivir was prescribed.

After two doses, she continued to have fever and also had nausea and emesis, malaise, and restlessness but could not get out of bed.

Two days later, she was taken to the local emergency room, where she was found to be hypotensive.

Despite intensive resuscitative efforts, she died 12 hours later; the postmortem examination showed necrotizing pneumonia and extensive alveolar hemorrhage.

A viral culture confirmed an influenza A (H1N1) infection, and methicillin-resistant Staphylococcus aureus was isolated from a tracheal aspirate.

Could this death have been prevented?

[Free full text available following below link. IOH]

<cite cite="http://content.nejm.org/cgi/content/full/359/24/2579?query=TOC">NEJM -- Prevention and Treatment of Seasonal Influenza</cite>

[HenryN]

Re: NEJM -- Prevention and Treatment of Seasonal Influenza

NEJM site appears to be down. Did the H1N1 have H274Y?

[Giuseppe]

Re: NEJM -- Prevention and Treatment of Seasonal Influenza

It isn't indicated by paper.

Enclosed: PDF article.

[HenryN]

Re: NEJM -- Prevention and Treatment of Seasonal Influenza

It isn't indicated by paper.

Enclosed: PDF article.

That speaks volumes since H274Y in New Caledonia H1N1 was definitely circulating in Texas at the time the patient died:

organism="Influenza A virus (A/Texas/31/2007(H1N1))"
/mol_type="viral cRNA"
/strain="A/Texas/31/2007"
/serotype="H1N1"
/isolate="2007728928"
/host="Homo sapiens"
/db_xref="taxon:505576"
/segment="6"
/country="USA"
/collection_date="28-Mar-2007"
/note="passage details: M1/C1
A/NEW CALEDONIA/20/99-like (H1N1); adamantane-sensitive;
oseltamivir-resistant"

[HenryN]

Re: NEJM -- Prevention and Treatment of Seasonal Influenza

It isn't indicated by paper.

Enclosed: PDF article.

The paper cites the following for guidance on treatment with anti-virals

http://www.cdc.gov/mmwr/preview/mmwrhtml/rr57e717a1.htm

Recommendations for Using Antiviral Agents for Seasonal Influenza

Annual vaccination is the primary strategy for preventing complications of influenza virus infections. Antiviral medications with activity against influenza viruses are useful adjuncts in the prevention of influenza, and effective when used early in the course of illness for treatment. Four influenza antiviral agents are licensed in the United States: amantadine, rimantadine, zanamivir, and oseltamivir. Influenza A virus resistance to amantadine and rimantadine can emerge rapidly during treatment. Because antiviral testing results indicated high levels of resistance (413--416), neither amantadine nor rimantadine should be used for the treatment or chemoprophylaxis of influenza A in the United States during the 2007--08 influenza season. Surveillance demonstrating that susceptibility to these antiviral medications has been reestablished among circulating influenza A viruses will be needed before amantadine or rimantadine can be used for the treatment or chemoprophylaxis of influenza A. Oseltamivir or zanamivir can be prescribed if antiviral chemoprophylaxis or treatment of influenza is indicated. Oseltamivir is licensed for treatment of influenza in persons aged >1 year, and zanamivir is licensed for treating influenza in persons aged >7 years. Oseltamivir and zanamivir can be used for chemoprophylaxis of influenza; oseltamivir is licensed for use as chemoprophylaxis in persons aged >1 year, and zanamivir is licensed for use in persons aged >5 years.
During the 2007--08 influenza season, influenza A (H1N1) viruses with a mutation that confers resistance to oseltamivir were identified in the United States and other countries. As of June 27, 2008, in the United States, 111 (7.6%) of 1,464 influenza A viruses tested, and none of 305 influenza B viruses tested have been found to be resistant to oseltamivir. All of the resistant viruses identified in the United States and elsewhere are influenza A (H1N1) viruses. Of 1020 influenza A (H1N1) viruses isolated from patients in the United States, 111 (10.9%) exhibited a specific genetic mutation that confers oseltamivir resistance (417). Influenza A (H1N1) virus strains that are resistant to oseltamivir remain sensitive to zanamivir. Neuraminidase inhibitor medications continue to be the recommended agents for treatment and chemoprophylaxis of influenza in the United States. However, clinicians should be alert to changes in antiviral recommendations that might occur as additional antiviral resistance data becomes available during the 2008--09 influenza season (http://www.cdc.gov/flu/professionals/antivirals/index.htm).

[HenryN]

Re: NEJM -- Prevention and Treatment of Seasonal Influenza

That speaks volumes since H274Y in New Caledonia H1N1 was definitely circulating in Texas at the time the patient died:

organism="Influenza A virus (A/Texas/31/2007(H1N1))"
/mol_type="viral cRNA"
/strain="A/Texas/31/2007"
/serotype="H1N1"
/isolate="2007728928"
/host="Homo sapiens"
/db_xref="taxon:505576"
/segment="6"
/country="USA"
/collection_date="28-Mar-2007"
/note="passage details: M1/C1
A/NEW CALEDONIA/20/99-like (H1N1); adamantane-sensitive;
oseltamivir-resistant"

From the H1N1 paper on neuraminidase inhibitors which included the above isolate:

Based on the available information, two of the seven oseltamivir-resistant viruses from the 2006 to 2007 influenza season analyzed in the present study were recovered from patients following oseltamivir treatment, namely A/Texas/12/2007(H3N2), with the E119V mutation, and A/Massachusetts/5/2007 (H1N1), with the H274Y mutation.

Thus, the Texas isolate (with H274Y) was from a patient who was NOT treated with Tamiflu.

[HenryN]

Re: NEJM -- Prevention and Treatment of Seasonal Influenza

Commentary

http://www.recombinomics.com/News/12110803/H1N1_Texas_15F.html

[AlaskaDenise]

Re: NEJM -- Prevention and Treatment of Seasonal Influenza

Commentary

http://www.recombinomics.com/News/12...Texas_15F.html

Commentary

Fatal H1N1 Infection In Healthy Child In Texas
Recombinomics Commentary 11:45
December 11, 2008

In February 2007, fever developed in a previously healthy 15-year-old girl, with a peak temperature of 102?F (38.9?C) and mild upper respiratory congestion. The next day she was seen by her primary care physician. A rapid screening test for group A streptococcus was negative, and oseltamivir was prescribed.

Two days later, she was taken to the local emergency room, where she
was found to be hypotensive. Despite intensive resuscitative efforts, she died 12 hours later; the postmortem examination showed necrotizing pneumonia and extensive alveolar hemorrhage. A viral culture confirmed an influenza A (H1N1) infection, and methicillin-resistant Staphylococcus aureus was isolated from a tracheal aspirate.

The major influenza virus that was prevalent during that season was
influenza A/New Caledonia (H1N1), a strain that was included in the available vaccine.

This girl was one of 12 children who were reported to have died in Texas during the 2006?2007 influenza season.

The above comments are from a paper in today?s New England Journal of Medicine entitled ?Prevention and Treatment if Seasonal Influenza.? It details the fatal H1N1 infection of the 15F described above and discusses oseltamivir resistance in general terms, with a reference to the current recommendations for anti-virals which cite the level of 7.6% overall and 10.9% for H1N1 in the United States last season, which keeps the prior recommendations which discourage treatment with adamantidines and recommend treatment with oseltamivir. The recommendations also include the reminder to check for changes in recommendations for the 2008/2009 season, but at this time the recommendations are unchanged even though they represent a mismatch with the influenza circulation in the United States this season.

During the 2006/2007 it was still assumed that oseltamivir resistance would be limited to treated patients and H274Y would be associated with a fitness penalty. However, last season the widespread levels of H274Y, including frequencies of 67% in Norway clearly indicated that there was no fitness penalty. Moreover, it was also clear that H274Y had been identified on a number of seasonal flu backgrounds, including New Caledonia isolates from the 2006/2007 and in fact one isolate, collected on March 28, 2007 was in Texas. The sequence from the isolate, A/Texas/31/2007(H1N1), was public, and the lack of treatment in the host was also published.

The author of the paper disclosed ?receiving consulting fees from Sanofi Pasteur, GlaxoSmithKline, Roche, Novartis, MedImmune, and Merck and research support from MedImmune? so he should have been familiar with recent developments, including levels of 100% resistance in H1N1 in multiple countries in the summer hemisphere this year.

In the United States and Europe this season H274Y has become fixed in H1N1 and in the United States 85-90% of influenza A tested to date has H274Y, yet the current antiviral recommendations remain mismatched with the influenza in circulation and the paper in today?s NEJM on treating seasonal flu glaringly avoids the current situation, which was quite predictable when the paper was written and reviewed.


.

[AlaskaDenise]

Re: NEJM -- Prevention and Treatment of Seasonal Influenza

As a treatment option, would it be appropriate to give both antivirals concurrently, should it be difficult to have timely serotype testing?

.