What Is the Optimal Therapy for Patients with H5N1 Influenza? - PLoS Med.

[Giuseppe]

PLoS Medicine: What Is the Optimal Therapy for Patients with H5N1 Influenza?

What Is the Optimal Therapy for Patients with H5N1 Influenza?

Nicholas J. White1*, Robert G. Webster2*, Elena A. Govorkova2, Timothy M. Uyeki3*
1 Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand,
2 Department of Infectious Diseases, Division of Virology, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America,
3 Epidemiology and Prevention Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America


Background to the debate

In a 2007 article in PLoS Medicine [10], Holger J. Sch?nemann and colleagues described a new process used by the World Health Organization for rapidly developing clinical management guidelines in emergency situations. These situations include outbreaks of emerging infectious diseases.

The authors discussed how they developed such a ?rapid advice? guideline for the pharmacological management of avian influenza A (H5N1) virus infection. The guideline recommends giving the antiviral drug oseltamivir at a dose of 75 mg twice daily for five days.

In this Debate, Nicholas White argues that such dosing is inadequate, Robert Webster and Elena Govorkova say that combination antiviral therapy should be used, and Tim Uyeki reminds us that clinical care of patients with H5N1 entails much more than antiviral treatment.

These issues may also apply to therapy of patients hospitalized with severe disease due to novel swine-origin influenza A (H1N1) virus infection.


Citation:

White NJ, Webster RG, Govorkova EA, Uyeki TM (2009) What Is the Optimal Therapy for Patients with H5N1 Influenza? PLoS Med 6(6): e1000091. doi:10.1371/journal.pmed.1000091
Published: June 23, 2009
Copyright: ? 2009 White et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Funding:

NJW is a Wellcome Trust Principal Fellow. RGW and EAG are funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN266200700005C; and by the American Lebanese Syrian Associated Charities (ALSAC). The funders had no role in the decision to publish or preparation of the manuscript. TMU received no specific funding.


Competing interests:

NJW is the co-chairman of the World Health Organization antimalarial treatment guidelines committee. RGW reports receiving research funding from Hoffmann-La Roche and BioCryst Pharmaceuticals and receiving consulting fees from GlaxoSmithKline. EAG reports receiving research funding from Hoffmann-La Roche and BioCryst Pharmaceuticals.


Abbreviations:

HPAI, highly pathogenic avian influenza A; RCT, randomised clinical trial; SARS, severe acute respiratory syndrome; SARS-CoV, SARS-associated coronavirus; WHO, World Health Organization

* E-mail: nickwdt@tropmedres.ac (NJW); robert.webster@stjude.org (RGW); tuyeki@cdc.gov (TMU)
? The findings and conclusions are those of the author and do not necessarily represent the official position of the Centers for Disease Control and Prevention.Provenance: Nicholas White's Viewpoint was originally submitted as an Essay, and was externally peer reviewed. The other two Viewpoints were commissioned and were not peer reviewed.
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<cite cite="http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000091">PLoS Medicine: What Is the Optimal Therapy for Patients with H5N1 Influenza?</cite>

 

[Sally Furniss]

Re: PLoS Med. What Is the Optimal Therapy for Patients with H5N1 Influenza?

Re: PLoS Med. What Is the Optimal Therapy for Patients with H5N1 Influenza?

Best Clinical Management For H5N1 Infection Debated



The best ways of managing patients with H5N1 infection (avian influenza) are debated by experts in this week's open access journal PLoS Medicine.

Higher than recommended doses of the antiviral drug oseltamivir Tamiflu should be used to fight H5N1 influenza, argues Nicholas White (Mahidol University, Bangkok, Thailand). In contrast to the current WHO guidelines recommending that oseltamivir be given at a dose of 75 mg twice daily for five days, Dr. White argues that higher doses should be given for H5N1 infection to avoid any possibility of under-dosing those patients with unusual pharmacokinetics and more resistant organisms. This will come at the expense of increased toxicity, he says, but is necessary given the mortality burden of H5N1 infection and the fact that H5N1 replicates more rapidly than seasonal influenza viruses, reaches much greater viral burdens than do other human influenza viruses, and resistance develops swiftly.

Robert Webster and Elena Govorkova from St. Jude Children's Research Hospital in Memphis, USA, writing in response to Nicholas White's article, disagree. They argue that we must instead consider a multidrug approach to managing patients with H5N1, an approach that is supported by animal data and "can guard against the emergence of resistant strains." Tim Uyeki from the Centers for Disease Control and Prevention in Atlanta, USA, emphasizes theneed for more data to help inform clinical management of patients with H5N1 infections. In the absence of these data, he argues, we need a multipronged strategy: pharmacological strategies including combination antiviral treatment, anti-inflammatory agents, and immunotherapy, and non-pharmacological strategies such as the standardization of optimal ventilator and fluid management, especially for acute respiratory distress syndrome, and management of other complications.

In a 2007 article in PLoS Medicine (PLoS Med 4(5): e119), Holger J. Sch?nemann and colleagues described a new process used by the World Health Organization for rapidly developing clinical management guidelines in emergency situations. These situations include outbreaks of emerging infectious diseases. The authors discussed how they developed such a "rapid advice" guideline for the pharmacological management of avian influenza A (H5N1) virus infection. The guideline recommends giving the antiviral drug oseltamivir at a dose of 75 mg twice daily for five days.

Funding: NJW is a Wellcome Trust Principal Fellow. RGW and EAG are funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN266200700005C; and by the American Lebanese Syrian Associated Charities (ALSAC). The funders had no role in the decision to publish or preparation of the manuscript. TMU received no specific funding.

Competing Interests: NJW is the co-chairman of the World Health Organization antimalarial treatment guidelines committee. RGW reports receiving research funding from Hoffmann-La Roche and BioCryst Pharmaceuticals and receiving consulting fees from GlaxoSmithKline. EAG reports receiving research funding from Hoffmann-La Roche and BioCryst Pharmaceuticals.

Citation:
"What Is the Optimal Therapy for Patients with H5N1 Influenza?"
White NJ, Webster RG, Govorkova EA, Uyeki TM (2009)
PLoS Med 6(6): e1000091.

Source
PLoS Medicine

http://www.medicalnewstoday.com/articles/155052.php

 

[St Michael]

Re: PLoS Med. What Is the Optimal Therapy for Patients with H5N1 Influenza?

Re: PLoS Med. What Is the Optimal Therapy for Patients with H5N1 Influenza?

In the absence of these data, he argues, we need a multipronged strategy: pharmacological strategies including combination antiviral treatment, anti-inflammatory agents, and immunotherapy, and non-pharmacological strategies such as the standardization of optimal ventilator and fluid management, especially for acute respiratory distress syndrome, and management of other complications.

:applause:

 

[St Michael]

Re: What Is the Optimal Therapy for Patients with H5N1 Influenza? - PLoS Med.

The combination of oseltamivir and ribavirin is far from optimal, but many approaches to combination therapy for influenza are in the pipeline: (1) development of additional neuraminidase inhibitors or parenteral drug formulations; (2) new antiviral targets, including the polymerase and hemagglutinin molecule and attachment inhibition; (3) modulation of overexuberant innate host response; (4) antibody-mediated therapy; and (5) combined antiviral and vaccine strategies. Currently under development is the neuraminidase inhibitor peramivir, which has three chemical groups that interact with the active-site residues of neuraminidase, resulting in tight binding and a slow rate of dissociation.

...

Combination chemotherapy consisting of anti-influenza drugs and inflammation inhibitors (e.g., celecoxib and mesalazine) was recently reported as a promising approach to control H5N1 infection in mice [25]. Another exciting recent discovery is the ability of the type II diabetes drug pioglitazone to modulate tissue-damaging compounds of the innate immune response without compromising T cell-mediated viral clearance [26].

Yes!!!:applause: