The global spread of drug-resistant influenza
- 24 August 2011
- journal article
- Published by The Royal Society in Journal of The Royal Society Interface
- Vol. 9 (69), 648-656
- https://doi.org/10.1098/rsif.2011.0427
Abstract
Resistance to oseltamivir, the most widely used influenza antiviral drug, spread to fixation in seasonal influenza A(H1N1) between 2006 and 2009. This sudden rise in resistance seemed puzzling given the low overall level of the oseltamivir usage and the lack of a correlation between local rates of resistance and oseltamivir usage. We used a stochastic simulation model and deterministic approximations to examine how such events can occur, and in particular to determine how the rate of fixation of the resistant strain depends both on its fitness in untreated hosts as well as the frequency of antiviral treatment. We found that, for the levels of antiviral usage in the population, the resistant strain will eventually spread to fixation, if it is not attenuated in transmissibility relative to the drug-sensitive strain, but not at the speed observed in seasonal H1N1. The extreme speed with which the resistance spread in seasonal H1N1 suggests that the resistant strain had a transmission advantage in untreated hosts, and this could have arisen from genetic hitchhiking, or from the mutations responsible for resistance and compensation. Importantly, our model also shows that resistant virus will fail to spread if it is even slightly less transmissible than its sensitive counterpart—a finding of relevance given that resistant pandemic influenza (H1N1) 2009 may currently suffer from a small, but nonetheless experimentally perceptible reduction in transmissibility.Keywords
This publication has 38 references indexed in Scilit:
- Population biological principles of drug-resistance evolution in infectious diseasesThe Lancet Infectious Diseases, 2011
- Generation and Characterization of Recombinant Pandemic Influenza A(H1N1) Viruses Resistant to Neuraminidase InhibitorsThe Journal of Infectious Diseases, 2011
- Pandemic H1N1 2009 influenza virus with the H275Y oseltamivir resistance neuraminidase mutation shows a small compromise in enzyme activity and viral fitnessJournal of Antimicrobial Chemotherapy, 2010
- Oseltamivir-Resistant Variants of the 2009 Pandemic H1N1 Influenza A Virus Are Not Attenuated in the Guinea Pig and Ferret Transmission ModelsJournal of Virology, 2010
- Permissive Secondary Mutations Enable the Evolution of Influenza Oseltamivir ResistanceScience, 2010
- Genetic Makeup of Amantadine-Resistant and Oseltamivir-Resistant Human Influenza A/H1N1 VirusesJournal of Clinical Microbiology, 2010
- Oseltamivir-Resistant Influenza A Viruses Are Transmitted Efficiently among Guinea Pigs by Direct Contact but Not by AerosolJournal of Virology, 2008
- Homologous Recombination Is Very Rare or Absent in Human Influenza A VirusJournal of Virology, 2008
- The genomic and epidemiological dynamics of human influenza A virusNature, 2008
- Mapping the Antigenic and Genetic Evolution of Influenza VirusScience, 2004