Prolonged Excretion of Amantadine-Resistant Influenza A Virus Quasi Species after Cessation of Antiviral Therapy in an Immunocompromised Patient

Abstract

Phenotypic and molecular studies were conducted to characterize multiple influenza A isolates recovered from an immunocompromised patient who died of viral and fungal pneumonitis. The recovery of amantadine-resistant isolates was correlated with the detection of 2 drug-resistant M2 variants (codons 27 and 31) in combination with a wild-type virus. The mutant viruses persisted within the viral population in variable proportions >1 month after cessation of antiviral therapy. These results confirm animal studies reported elsewhere regarding the genetic stability of influenza M2 mutants and their potential for transmission in humans.

2012/13 influenza vaccine effectiveness against hospitalised influenza A(H1N1)pdm09, A(H3N2) and B: estimates from a European network of hospitals

“…[240][241][242][243] Cancer patients and transplant recipients are also at high risk of infection with influenza virus, including nosocomial acquisition of influenza. [244][245][246] In addition, immunosuppressed individuals are at elevated risk of developing an antiviral resistant influenza infection in response to an antiviral treatment regimen; high rates of resistant infection have been documented in this group for seasonal [247][248][249] and influenza A(H1N1)pdm virus. [250,251] Vaccine performance Individuals with respiratory/cardiovascular conditions Influenza vaccine effectiveness has been demonstrated in some populations with asthma, COPD, and chronic lung diseases.…”

Generation and Characterization of Recombinant Influenza A (H1N1) Viruses Harboring Amantadine Resistance Mutations

“…However, the emergence of drugresistant viruses has been shown to occur rapidly during treatment as a result of single-amino-acid substitutions at position 26, 27, 30, 31, or 34 within the transmembrane domain of the M2 protein (9,12). It has been also reported that two or more M2 mutant virus variants could be recovered from amantadine-treated children and immunocompromised patients (2,9,12). A recent report showed that H3N2-infected individuals shed more amantadine-resistant variants than their H1N1 counterparts (11).…”

Characterization of a Neuraminidase-Deficient Influenza A Virus as a Potential Gene Delivery Vector and a Live Vaccine

“…Treatment with neuraminidase (NA) inhibitors clearly improves the course of influenza in patients (14), but these antiviral compounds must be administered early in the infection to be effective. Moreover, the emergence of drug-resistant variants remains a concern (1,35), although resistance to NA inhibitors is less common than resistance to amantadine or rimantadine (12,25,37). Thus, vaccination of large human populations affords the best protection against influenza outbreaks.…”