Occurrence of influenza antivirals and resistance development in influenza A viruses in aquatic environments: A risk assessment
4 affiliations
- 1Department of Epidemiology and Global health, Umeå University, Umeå, Sweden
- 2Department of Natural Science, Design and Sustainable Development, Mid Sweden University, Östersund, Sweden
- 3Department of Chemistry, Umeå University, Umeå, Sweden
- 4Department of Medical Sciences, Uppsala University, Uppsala, Sweden
Abstract
Influenza antivirals (IAs) have been detected in aquatic environments inhabited by dabbling ducks, the natural reservoir of influenza A virus (IAV), raising concerns about the development of antiviral resistance. Because novel human IAV strains often contain genetic material of avian origin, this may contribute to resistance in viruses with pandemic potential. This study aimed to assess the environmental risk posed by four IAs—oseltamivir carboxylate (OC), zanamivir (ZA), peramivir (PE), and amantadine (AM)—based on their potential for environmental release, environmental stability, and induction of antiviral resistance. The assessment combined data from new experiments on (1) environmental release and (2) environmental stability of PE, AM, OC, and ZA, with results from previously published in vivo experiments in a mallard model examining (3) resistance development to OC, PE, and ZA in IAV. The risk of environmental release was assessed as high for OC, AM, and PE, and very high for ZA. Environmental stability ranged from very high to low, in the order PE > AM > OC > ZA. The potential to induce resistance in IAV was similar for PE and OC, and lower for ZA. Overall, the environmental risk ranking was PE > OC > ZA, with PE and OC posing the highest risks. Prudent use of IAs requires balancing the risk of resistance development against clinical benefit. In cases of complicated influenza or in high-risk patient groups, the clinical benefits are substantial and justify IA use. However, in uncomplicated influenza among otherwise healthy individuals, the clinical benefit is limited, and the risk of resistance development should be carefully considered. Among the evaluated antivirals, ZA showed the lowest environmental risk and should be preferred when feasible.
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BibTeX
@article{lindstrom2026occurrence,
title = {{Occurrence of influenza antivirals and resistance development in influenza A viruses in aquatic environments: A risk assessment}},
author = {Hanna Söderström Lindström and Sara H. Norström and Chaojun Tang and Richard H. Lindberg and Josef D. Järhult},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0358447},
url = {https://doi.org/10.1371/journal.pone.0358447},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Occurrence of influenza antivirals and resistance development in influenza A viruses in aquatic environments: A risk assessment
AU - Hanna Söderström Lindström
AU - Sara H. Norström
AU - Chaojun Tang
AU - Richard H. Lindberg
AU - Josef D. Järhult
PY - 2026
DA - 2026/09/21
JO - PLOS One
DO - 10.1371/journal.pone.0358447
UR - https://doi.org/10.1371/journal.pone.0358447
AB - Influenza antivirals (IAs) have been detected in aquatic environments inhabited by dabbling ducks, the natural reservoir of influenza A virus (IAV), raising concerns about the development of antiviral resistance. Because novel human IAV strains often contain genetic material of avian origin, this may contribute to resistance in viruses with pandemic potential. This study aimed to assess the environmental risk posed by four IAs—oseltamivir carboxylate (OC), zanamivir (ZA), peramivir (PE), and amantadine (AM)—based on their potential for environmental release, environmental stability, and induction of antiviral resistance. The assessment combined data from new experiments on (1) environmental release and (2) environmental stability of PE, AM, OC, and ZA, with results from previously published in vivo experiments in a mallard model examining (3) resistance development to OC, PE, and ZA in IAV. The risk of environmental release was assessed as high for OC, AM, and PE, and very high for ZA. Environmental stability ranged from very high to low, in the order PE > AM > OC > ZA. The potential to induce resistance in IAV was similar for PE and OC, and lower for ZA. Overall, the environmental risk ranking was PE > OC > ZA, with PE and OC posing the highest risks. Prudent use of IAs requires balancing the risk of resistance development against clinical benefit. In cases of complicated influenza or in high-risk patient groups, the clinical benefits are substantial and justify IA use. However, in uncomplicated influenza among otherwise healthy individuals, the clinical benefit is limited, and the risk of resistance development should be carefully considered. Among the evaluated antivirals, ZA showed the lowest environmental risk and should be preferred when feasible.
SN - 1932-6203
ER -