Open AccessProlonged Influenza Virus Shedding and Emergence of Antiviral Resistance in Immunocompromised Patients and Ferrets
Author(s) -
Erhard van der Vries,
Koert J. Stittelaar,
Geert van Amerongen,
Edwin J. B. Veldhuis Kroeze,
Leon de Waal,
Pieter L. A. Fraaij,
Roland J.W. Meesters,
Theo M. Luider,
Bart C.H. van der Nagel,
Birgit C. P. Koch,
Arnold G. Vulto,
Martin Schutten,
Albert D. M. E. Osterhaus
Publication year - 2013
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1003343
Subject(s) - oseltamivir , virology , virus , viral shedding , pandemic , biology , viral replication , influenza a virus , medicine , immunology , covid-19 , disease , infectious disease (medical specialty)
Immunocompromised individuals tend to suffer from influenza longer with more serious complications than otherwise healthy patients. Little is known about the impact of prolonged infection and the efficacy of antiviral therapy in these patients. Among all 189 influenza A virus infected immunocompromised patients admitted to ErasmusMC, 71 were hospitalized, since the start of the 2009 H1N1 pandemic. We identified 11 (15%) cases with prolonged 2009 pandemic virus replication (longer than 14 days), despite antiviral therapy. In 5 out of these 11 (45%) cases oseltamivir resistant H275Y viruses emerged. Given the inherent difficulties in studying antiviral efficacy in immunocompromised patients, we have infected immunocompromised ferrets with either wild-type, or oseltamivir-resistant (H275Y) 2009 pandemic virus. All ferrets showed prolonged virus shedding. In wild-type virus infected animals treated with oseltamivir, H275Y resistant variants emerged within a week after infection. Unexpectedly, oseltamivir therapy still proved to be partially protective in animals infected with resistant virus. Immunocompromised ferrets offer an attractive alternative to study efficacy of novel antiviral therapies.