Oseltamivir-Resistant Pandemic (H1N1) 2009 Virus Infection in England and Scotland, 2009–2010

Laurence Calatayud , Angie Lackenby, Arlene Reynolds, Jim McMenamin, Nick F. Phin, Maria Zambon, and Richard Pebody

Author affiliations: Health Protection Agency, London, UK (L. Calatayud, A. Lackenby, N.F. Phin, M.C. Zambon, R. Pebody); Health Protection Scotland, Glasgow, Scotland, UK (A. Reynolds, J. McMenamin)

Abstract

Oseltamivir has been widely used for pandemic (H1N1) 2009 virus infection, and by April 30, 2010, a total of 285 resistant cases were reported worldwide, including 45 in the United Kingdom. To determine risk factors for emergence of oseltamivir resistance and severe infection, a case–control study was conducted in the United Kingdom. Study participants were hospitalized in England or Scotland during January 4, 2009–April 30, 2010. Controls had confirmed oseltamivir-sensitive pandemic (H1N1) 2009 virus infections, and case-patients had confirmed oseltamivir-resistant infections. Of 28 case-patients with available information, 21 (75%) were immunocompromised; 31 of 33 case-patients (94%) received antiviral drugs before a sample was obtained. After adjusting for confounders, case-patients remained significantly more likely than controls to be immunocompromised and at higher risk for showing development of respiratory complications.

Selective drug pressure likely explains the development of oseltamivir resistance, especially among immunocompromised patients. Monitoring of antiviral resistance is strongly recommended in this group.

Neuraminidase inhibitors, antiviral drugs that limit replication of influenza A and B viruses (1), are recommended in the United Kingdom for treatment and prophylaxis of patients at higher risk for severe or complicated influenza virus infection (2). During the initial containment phase of the 2009 influenza pandemic, antiviral drugs were prescribed for all patients with confirmed infections and their close contacts. During the subsequent treatment phase of the pandemic, the drugs were recommended for persons with suspected influenza virus infections who were at high risk for severe disease (3).

Before the 2007–08 influenza season, the development of oseltamivir-resistant influenza was rare (4), mainly occurring among persons who were more likely to have prolonged virus shedding, such as children (5) and immunocompromised patients (6). Patients with subtype H1N1 oseltamivir-resistant strains had the same point mutation in the viral neuraminidase gene (H275Y) that is known to confer high-level resistance to oseltamivir (7), but the mutation was associated with reduced infectivity and replicative ability (8). During the 2007–08 season, transmissible influenza A (H1N1) viruses resistant to oseltamivir (with the H275Y mutation) emerged and became predominant over susceptible subtype H1N1 viruses (4,9). The influenza A pandemic (H1N1) 2009 virus was initially reported as fully susceptible to the neuraminidase inhibitors (oseltamivir and zanamivir) but resistant to adamantanes, having the S31N (serine to asparagine) mutation in the M2 ion channel (10).

On July 8, 2009, the World Health Organization reported the first sporadic cases of oseltamivir-resistant pandemic (H1N1) 2009 infection in Denmark; Japan; and Hong Kong Special Administrative Region, People’s Republic of China (11). By April 28, 2010, a total of 285 oseltamivir-resistant cases had been reported worldwide (12), including 45 in the United Kingdom. Three clusters each were reported from Wales (13); the United Kingdom; North Carolina, USA (14); and Vietnam (15). All of the pandemic (H1N1) 2009 oseltamivir-resistant viruses had the previously described H275Y mutation. No reassortment between the pandemic (H1N1) 2009 virus and the seasonal oseltamivir-resistant subtype H1N1 influenza strain has been detected (16–18), and all of the oseltamivir-resistant viruses have retained sensitivity to zanamivir.

This report describes the epidemiologic, clinical, and demographic characteristics of patients with oseltamivir-resistant pandemic (H1N1) 2009 virus infections in England and Scotland. It also identifies risk factors for severe infection and for the emergence of oseltamivir-resistant virus to inform modifications to current recommendations for the use of antiviral drugs for treatment and prophylaxis of influenza A pandemic (H1N1) 2009 virus infection.

Methods

full-text:
Oseltamivir-Resistant Pandemic (H1N1) 2009 Virus Infection in England and Scotland, 2009–2010 - Vol. 17 No. 10 - October 2011 - Emerging Infectious Disease journal - CDC

Suggested citation for this article: Calatayud L, Lackenby A, Reynolds A, McMenamin J, Phin NF, Zambon MC, et al. Oseltamivir-resistant pandemic (H1N1) 2009 virus infection in England and Scotland, 2009–2010. [serial on the Internet]. 2011 Oct [date cited]. http://dx.doi.org/10.3201/eid1710.110117