H1N1 Virus Mutation and Oseltamivir (Tamiflu) Resistance; Duke University Medical Center Patient Cluster Raises Questions

In its Weekly Epidemiological Report (WER), the World Health Organization (WHO) confirmed a worldwide count of 225 cases of H1N1 that were resistant to oseltamivir (Tamiflu). The “225 cases came from 20 countries and included 65 cases in the Americas, 77 in Europe, 1 in Africa, and 82 in the Western Pacific region. All cases had the H275Y mutation that confers resistance to oseltamivir
… but not to the other antiviral medication in general use, zanamivir (Relenza).

In 142 cases for which data was available, the plurality (56 cases or 40%) involved severely immunocompromised patients, 38% were linked to flu treatment, 11% were associated with chemoprophylaxis (preventative) treatment.

WHO further looked at two clusters of oseltamivir-resistant H1N1 treated at Duke University Medical Center (four cases), and University Hospital in Cardiff, Wales (eight cases). The report underscored “that severely immunocompromised patients are at a higher risk of developing oseltamivirresistant virus during treatment.”

WHO also examined a cluster of previously unreported oseltamivir-resistant H1N1 cases in Vietnam among seven healthy adults who were traveling together by train.

Editor’s Comment: Three of the four cases were fatal at Duke University Med Center and WHO concluded… “the role of H1N1 infection in contributing to the deaths is uncertain.” The Recombinomics blog finds this curious, since the patients were isolated “in the same ward, infected with the same virus, at the same time.”

Somewhat more disquieting was the revelation… “In 3 of the 4 cases, the H275Y mutation was identified before oseltamivir was administered.” This raises the question of why these patients were treated with oseltamivir? Press releases from the medical center have not shed any light on the matter, but would only confirm the underlying conditions in the patients, and that an assessment was in progress.

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CIDRAP: Global Tamiflu-resistant H1N1 cases reach 225
Duke UMC: CDC Confirms Four New Cases of Oseltamivir (Tamiflu)-Resistant H1N1
Duke UMC: Tests Show No Further Cases of Oseltamivir-Resistant H1N1 at Duke University Hospital
Recombinomics: Recombinomics Commentary 15:58 February 09, 2010
WHO: Weekly epidemiological record No. 6, 2010, 85, 37–48, Update on oseltamivirresistant pandemic A (H1N1) 2009 influenza virus: January 2010 (PDF)

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  1. […] Oseltamivir (Tamiflu) resistance in pandemic A(H1N1) 2009 viruses has been limited. However, WHO also noted “the majority of seasonal A(H1N1) viruses were oseltamivir resistant.” This resistance developed during the 2008-2009 flu season. […]

  2. […] the Norwegian data needs to control for covarying factors, such as underlying patient conditions. The three fatalities in the USA that had the mutation were patients treated at Duke University, all …; this association had not been highlighted in reporting. At most, the Norwegian data suggests an […]

  3. […] Available data indicates severely immunocompromised patients make up the plurality of oseltamivir-re… It is not clear from this abstract exactly when Duke University Medical Center staff confirmed the […]