tetano
Editor, Senior Moderator
Antimicrob Agents Chemother. 2015 Jun 15. pii: AAC.00886-15. [Epub ahead of print]
[h=1]Influenza A(H7N9) Acquires Resistance Related NA-I222T Substitution when Infected Mallards are Exposed to Low Levels of Oseltamivir in Water.[/h] Gillman A[SUP]1[/SUP], Nykvist M[SUP]2[/SUP], Muradrasoli S[SUP]3[/SUP], S?derstr?m H[SUP]4[/SUP], Wille M[SUP]5[/SUP], Daggfeldt A[SUP]6[/SUP], Br?jer C[SUP]7[/SUP], Waldenstr?m J[SUP]5[/SUP], Olsen B[SUP]2[/SUP], J?rhult JD[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza A virus (IAV) has its natural reservoir in wild waterfowl and new human IAVs often contain gene segments originating from avian IAVs. Treatment options for severe human influenza are principally restricted to neuraminidase inhibitors (NAIs), among which oseltamivir is stockpiled in preparedness for influenza pandemics. There is evolutionary pressure in the environment for resistance development to oseltamivir in avian IAVs, as the active metabolite oseltamivir carboxylate (OC) passes largely un-degraded through sewage treatment to river water where waterfowl reside.In an in vivo Mallard (Anas platyrhynchos) model, we tested if low-pathogenic avian influenza A(H7N9) virus could become resistant if the host was exposed to low levels of OC. Ducks were experimentally infected and OC was added to their water, where after infection and transmission was maintained by successive introductions of uninfected birds. Daily fecal samples were tested for IAV excretion, genotype and phenotype.Following Mallard exposure of 2.5 μg/L OC, the resistance related NA-I222T substitution, was detected within 2 days during the first passage and was found in all viruses sequenced from subsequently introduced ducks. The substitution generated 8-fold and 2.4-fold increase in IC[SUB]50[/SUB] for OC (p< 0.001) and zanamivir (p = 0.016), respectively. We conclude that OC exposure of IAV hosts, in the same concentration magnitude as found in the environment, may result in amino acid substitutions leading to changed antiviral sensitivity in an IAV subtype that can be highly pathogenic to humans. A prudent use of oseltamivir and resistance surveillance of IAVs in wild birds is warranted.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 26077257 [PubMed - as supplied by publisher] Free full text
[h=1]Influenza A(H7N9) Acquires Resistance Related NA-I222T Substitution when Infected Mallards are Exposed to Low Levels of Oseltamivir in Water.[/h] Gillman A[SUP]1[/SUP], Nykvist M[SUP]2[/SUP], Muradrasoli S[SUP]3[/SUP], S?derstr?m H[SUP]4[/SUP], Wille M[SUP]5[/SUP], Daggfeldt A[SUP]6[/SUP], Br?jer C[SUP]7[/SUP], Waldenstr?m J[SUP]5[/SUP], Olsen B[SUP]2[/SUP], J?rhult JD[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza A virus (IAV) has its natural reservoir in wild waterfowl and new human IAVs often contain gene segments originating from avian IAVs. Treatment options for severe human influenza are principally restricted to neuraminidase inhibitors (NAIs), among which oseltamivir is stockpiled in preparedness for influenza pandemics. There is evolutionary pressure in the environment for resistance development to oseltamivir in avian IAVs, as the active metabolite oseltamivir carboxylate (OC) passes largely un-degraded through sewage treatment to river water where waterfowl reside.In an in vivo Mallard (Anas platyrhynchos) model, we tested if low-pathogenic avian influenza A(H7N9) virus could become resistant if the host was exposed to low levels of OC. Ducks were experimentally infected and OC was added to their water, where after infection and transmission was maintained by successive introductions of uninfected birds. Daily fecal samples were tested for IAV excretion, genotype and phenotype.Following Mallard exposure of 2.5 μg/L OC, the resistance related NA-I222T substitution, was detected within 2 days during the first passage and was found in all viruses sequenced from subsequently introduced ducks. The substitution generated 8-fold and 2.4-fold increase in IC[SUB]50[/SUB] for OC (p< 0.001) and zanamivir (p = 0.016), respectively. We conclude that OC exposure of IAV hosts, in the same concentration magnitude as found in the environment, may result in amino acid substitutions leading to changed antiviral sensitivity in an IAV subtype that can be highly pathogenic to humans. A prudent use of oseltamivir and resistance surveillance of IAVs in wild birds is warranted.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 26077257 [PubMed - as supplied by publisher] Free full text