| 1. |
- Gillman, Anna, et al.
(författare)
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Oseltamivir-Resistant Influenza A (H1N1) Virus Strain with an H274Y Mutation in Neuraminidase Persists without Drug Pressure in Infected Mallards
- 2015
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Ingår i: Applied and Environmental Microbiology. - : American Society for Microbiology. - 0099-2240 .- 1098-5336. ; 81:7, s. 2378-2383
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Tidskriftsartikel (refereegranskat)abstract
- Influenza A virus (IAV) has its natural reservoir in wild waterfowl and emerging human IAVs often contain gene segments from avian viruses. The active drug metabolite of oseltamivir (oseltamivir carboxylate (OC)), stockpiled as Tamiflu® for influenza pandemic preparedness, is not removed by conventional sewage treatment and has been detected in river water. There, it may there exert evolutionary pressure on avian IAV in waterfowl, resulting in development of resistant viral variants. A resistant avian IAV can circulate among wild birds only if resistance does not restrict viral fitness and if the resistant virus can persist without continuous drug pressure. In this in vivo Mallard (Anas platyrhynchos) study we tested if an OC-resistant avian IAV strain (A(H1N1)/NA-H274Y) could retain resistance while drug pressure was gradually removed. Successively infected Mallards were exposed to decreasing levels of OC, and fecal samples were analyzed for neuraminidase sequence and phenotypic resistance. No reversion to wild-type virus was observed during the experiment, which included 17 days of viral transmission in 10 ducks exposed to OC concentrations below resistance induction levels. We conclude that resistance in avian IAV, induced by OC exposure of the natural host, can persist in absence of the drug. Thus, there is a risk that human pathogenic IAVs that evolve from IAVs circulating among wild birds may contain resistance mutations. An oseltamivir resistant pandemic IAV would be a substantial public health threat. Therefore, our observations underscore the need for prudent oseltamivir use, upgraded sewage treatment and resistance surveillance of IAV in wild birds.
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| 2. |
- Wallensten, Anders, et al.
(författare)
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Surveillance of influenza A virus in migratory waterfowl in northern Europe
- 2007
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Ingår i: Emerging Infectious Diseases. - 1080-6040 .- 1080-6059. - 1080-6040 ; 13:3, s. 404-411
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Tidskriftsartikel (refereegranskat)abstract
- We conducted large-scale, systematic sampling of influenza type A virus in migratory waterfowl (mostly mallards [Anas platyrhynchos]) at Ottenby Bird Observatory, southeast Sweden. As with previous studies, we found a higher prevalence in fall than spring, and among juveniles compared with adults. However, in contrast to other studies, we found that prevalence in spring was sometimes high (mean 4.0%, highest 9.5%). This finding raises the possibility that ducks are capable of perpetuating influenza A virus of different subtypes and subtype combinations throughout the year and from 1 year to the next. Isolation of the H5 and H7 subtypes was common, which suggests risk for transmission to sensitive domestic animals such as poultry. We argue that wild bird screening can function as a sentinel system, and we give an example of how it could have been used to forecast a remote and deadly outbreak of influenza A in poultry.
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| 3. |
- Avril, Alexis, et al.
(författare)
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Capturing individual-level parameters of influenza A virus dynamics in wild ducks using multistate models
- 2016
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Ingår i: Journal of Applied Ecology. - : Wiley. - 0021-8901 .- 1365-2664. ; 53:4, s. 1289-1297
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Tidskriftsartikel (refereegranskat)abstract
- Disease prevalence in wildlife is governed by epidemiological parameters (infection and recovery rates) and response to infection, both of which vary within and among individual hosts. Studies quantifying these individual-scale parameters and documenting their source of variation in wild hosts are fundamental for predicting disease dynamics. Such studies do not exist for the influenza A virus (IAV), despite its strong impact on the global economy and public health. Using capture-recaptures of 3500 individual mallards Anas platyrhynchos during seven migration seasons at a stopover site in southern Sweden, we provide the first empirical description of the individual-based mechanisms of IAV dynamics in a wild reservoir host. For most years, prevalence and risk of IAV infection peaked at a single time during the autumn migration season, but the timing, shape and intensity of the infection curve showed strong annual heterogeneity. In contrast, the seasonal pattern of recovery rate only varied in intensity across years. Adults and juveniles displayed similar seasonal patterns of infection and recovery each year. However, compared to adults, juveniles experienced twice the risk of becoming infected, whereas recovery rates were similar across age categories. Finally, we did not find evidence that infection influenced the timing of emigration.Synthesis and applications. Our study provides robust empirical estimates of epidemiological parameters for predicting influenza A virus (IAV) dynamics. However, the strong annual variation in infection curves makes forecasting difficult. Prevalence data can provide reliable surveillance indicators as long as they catch the variation in infection risk. However, individual-based monitoring of infection is required to verify this assumption in areas where surveillance occurs. In this context, monitoring of captive sentinel birds kept in close contact with wild birds is useful. The fact that infection does not impact the timing of migration underpins the potential for mallards to spread viruses rapidly over large geographical scales. Hence, we strongly encourage IAV surveillance with a multistate capture-recapture approach along the entire migratory flyway of mallards.
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| 4. |
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| 5. |
- Elmberg, Johan, 1960-, et al.
(författare)
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Vart tog fågelinfluensan vägen?
- 2010
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Ingår i: Vår fågelvärld. ; 69:3, s. 8-12
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 6. |
- Elmberg, Johan, et al.
(författare)
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Vart tog fågelinfluensan vägen?
- 2010
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Ingår i: Vår Fågelvärld. ; 69:3, s. 8-12
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 7. |
- Gillman, Anna, et al.
(författare)
-
Oseltamivir-Resistant Influenza A (H1N1) Virus Strain with an H274Y Mutation in Neuraminidase Persists without Drug Pressure in Infected Mallards
- 2015
-
Ingår i: Applied and Environmental Microbiology. - : American Society for Microbiology. - 0099-2240 .- 1098-5336. ; 81:7, s. 2378-2383
-
Tidskriftsartikel (refereegranskat)abstract
- Influenza A virus (IAV) has its natural reservoir in wild waterfowl, and emerging human IAVs often contain gene segments from avian viruses. The active drug metabolite of oseltamivir (oseltamivir carboxylate [OC]), stockpiled as Tamiflu for influenza pandemic preparedness, is not removed by conventional sewage treatment and has been detected in river water. There, it may exert evolutionary pressure on avian IAV in waterfowl, resulting in the development of resistant viral variants. A resistant avian IAV can circulate among wild birds only if resistance does not restrict viral fitness and if the resistant virus can persist without continuous drug pressure. In this in vivo mallard (Anas platyrhynchos) study, we tested whether an OC-resistant avian IAV (H1N1) strain with an H274Y mutation in the neuraminidase (NA-H274Y) could retain resistance while drug pressure was gradually removed. Successively infected mallards were exposed to decreasing levels of OC, and fecal samples were analyzed for the neuraminidase sequence and phenotypic resistance. No reversion to wild-type virus was observed during the experiment, which included 17 days of viral transmission among 10 ducks exposed to OC concentrations below resistance induction levels. We conclude that resistance in avian IAV that is induced by exposure of the natural host to OC can persist in the absence of the drug. Thus, there is a risk that human-pathogenic IAVs that evolve from IAVs circulating among wild birds may contain resistance mutations. An oseltamivir-resistant pandemic IAV would pose a substantial public health threat. Therefore, our observations underscore the need for prudent oseltamivir use, upgraded sewage treatment, and surveillance for resistant IAVs in wild birds.
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| 8. |
- Gillman, Anna, et al.
(författare)
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Resistance Mutation R292K Is Induced in Influenza A(H6N2) Virus by Exposure of Infected Mallards to Low Levels of Oseltamivir
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:8
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Tidskriftsartikel (refereegranskat)abstract
- Resistance to neuraminidase inhibitors (NAIs) is problematic as these drugs constitute the major treatment option for severe influenza. Extensive use of the NAI oseltamivir (Tamiflu(R)) results in up to 865 ng/L of its active metabolite oseltamivir carboxylate (OC) in river water. There one of the natural reservoirs of influenza A, dabbling ducks, can be exposed. We previously demonstrated that an influenza A(H1N1) virus in mallards (Anas platyrhynchos) exposed to 1 mu g/L of OC developed oseltamivir resistance through the mutation H274Y (N2-numbering). In this study, we assessed the resistance development in an A(H6N2) virus, which belongs to the phylogenetic N2 group of neuraminidases with distinct functional and resistance characteristics. Mallards were infected with A(H6N2) while exposed to 120 ng/L, 1.2 mu g/L or 12 mu g/L of OC in their sole water source. After 4 days with 12 mu g/L of OC exposure, the resistance mutation R292K emerged and then persisted. Drug sensitivity was decreased approximate to 13,000-fold for OC and approximate to 7.8-fold for zanamivir. Viral shedding was similar when comparing R292K and wild-type virus indicating sustained replication and transmission. Reduced neuraminidase activity and decrease in recovered virus after propagation in embryonated hen eggs was observed in R292K viruses. The initial, but not the later R292K isolates reverted to wild-type during egg-propagation, suggesting a stabilization of the mutation, possibly through additional mutations in the neuraminidase (D113N or D141N) or hemagglutinin (E216K). Our results indicate a risk for OC resistance development also in a N2 group influenza virus and that exposure to one NAI can result in a decreased sensitivity to other NAIs as well. If established in influenza viruses circulating among wild birds, the resistance could spread to humans via re-assortment or direct transmission. This could potentially cause an oseltamivir-resistant pandemic; a serious health concern as preparedness plans rely heavily on oseltamivir before vaccines can be mass-produced.
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