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Article Released Fri-14th-October-2005 15:11 GMT
Contact: Ruth Institution: Nature Publishing Group
 Virology: A patient with an oseltamivir-resistant strain of bird flu

The paper raises the possibility that the current prophylactic regimen for Tamiflu (oseltamivir) may have contributed to the emergence of partial resistance to the drug in a Vietnamese patient.

[3] Virology: A patient with an oseltamivir-resistant strain of bird flu virus (p1107)

This paper is freely available before print publication on 20 October 2005 in view of
current concern about avian flu. We have also included additional context below.

FOR FURTHER CLARIFICATION AND RELEVANT BACKGROUND PLEASE READ:

This paper provides an analysis of an H5N1 virus -- isolated from a patient
in Vietnam earlier this year (1) - that is partially resistant to
oseltamivir.

The potential emergence of a resistant virus is a continuing concern of
health agencies, although evidence to date suggests that viruses with
mutations giving rise to resistance have reduced fitness, making them less
transmissible and of lower pathogenicity.

The paper's findings highlight the fact that the current recommended
prophylactic treatment regimen (2) may involve suboptimal doses and
durations of oseltamivir treatment that could contribute to the emergence of
resistant virus. It also raises the possibility that a larger arsenal of
influenza antivirals may need to be developed. Stockpiling zanamivir (sold
as Relenza) in addition to oseltamivir may be warranted.

Although the case described in this paper was part of a family cluster, the
paper does not directly address the issue of human-to-human transmission of
H5N1. For journalists interested in this issue, the most recent update on
the significance of familial clusters has just been released in advance of
publication by the US Centres for Disease Control, the World Health
Organization, and the Thai government (3).

Endnotes/links:
1. WHO Inter-country Consultation Influenza A/H5N1 in Humans in Asia Manila
May 6th-7th 2005.
http://www.who.int/csr/disease/avian_influenza/H5N1IntercountryAssessment.pdf

2. http://www.cdc.gov/flu/professionals/treatment/dosage.htm

3. Family Clustering of Avian Influenza A (H5N1) Emerging Infectious
Diseases, Volume 11, Number 11-November 2005
http://www.cdc.gov/ncidod/EID/vol11no11/05-0646.htm

[3] Virology: A patient with an oseltamivir-resistant strain of bird flu
virus (p1107)

For immediate release
(Please note corrected author email address)

An H5N1 strain of bird influenza virus that infected a Vietnamese girl in
February is resistant to the antiviral drug oseltamivir (sold as Tamiflu),
Yoshihiro Kawaoka and colleagues report in a Brief Communication in this
week's Nature. The girl recovered, but the finding raises the concern that
oseltamivir may not be sufficient to fight a potential H5N1 pandemic.
Circumstances indicate that the girl could have been infected by her brother
rather than directly by birds, the authors say. However, more such cases of
suspected transmission of the virus from human to human need to be
investigated and verified before the implications can be assessed.
The researchers identified a mutation in the virus strain's neuraminidase
protein that rendered it resistant to oseltamivir, a drug which is designed
to inhibit neuraminidase. However, when they used the resistant virus to
infect ferrets, they found that it was still sensitive to zanamivir (sold as
Relenza), another drug that inhibits the neuraminidase protein. "It could be
useful to stockpile zanamivir as well as oseltamivir in the event of an H5N1
influenza pandemic", the authors conclude.

CONTACT:
Yoshihiro Kawaoka (University of Tokyo, Japan and University of Wisconsin,
Madison, USA. Also at: Japan Science and Technology Agency, Kawaguchi,
Saitama, Japan)
Tel: +81 3 5449 5310 (Tokyo, Japan) and +1 608 265 4925 (Wisconsin, USA);
E-mail: kawaoka@ims.u-tokyo.ac.jp and kawaoka@svm.vetmed.wisc.edu

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