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Tamiflu® - Use It a...
Tamiflu® - Use It and Lose It?
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- Järhult, Josef D., 1975- (författare)
- Uppsala universitet,Infektionssjukdomar
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- Olsen, Björn, Professor (preses)
- Uppsala universitet,Institutionen för medicinska vetenskaper
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- Söderström, Hanna, Dr. (preses)
- Umeå universitet, Kemiska institutionen
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- Waldenström, Jonas, Docent (preses)
- Linnéuniversitetet Kalmar, Institutionen för naturvetenskap
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- Webster, Robert G., Professor (opponent)
- St. Jude Children's Research Hospital, Department of Infectious Diseases
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(creator_code:org_t)
- ISBN 9789155482251
- Uppsala : Acta Universitatis Upsaliensis, 2011
- Engelska 60 s.
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Serie: Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 1651-6206 ; 725
- Relaterad länk:
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Influenza A viruses cause seasonal and pandemic outbreaks that range from mild infections to the disastrous Spanish Flu. Resistance to neuraminidase inhibitors (NAIs) is a growing problem as these drugs constitute a vital part of treatment strategies and pandemic preparedness plans worldwide. Oseltamivir (Tamiflu®) is the mostly used NAI. Its active metabolite, oseltamivir carboxylate (OC), is excreted from treated patients and degrades poorly in sewage treatment plants and surface water. Thus, OC can enter aquatic environments where the natural influenza reservoir, dabbling ducks, can be exposed to the substance and resistance could develop. If NAI resistance is established in influenza viruses circulating among wild birds, the resistance can form part of a virus re-entering the human population either by reassortment or by direct transmission. In this thesis, evidence is presented that OC is present in the waterways during a seasonal influenza outbreak in Japan, a country in which oseltamivir is liberally used. Furthermore, when mallards were infected with an influenza A/H1N1 virus and subjected to low, environmental-like concentrations of OC, resistance developed through acquisition of the well-known resistance mutation H274Y. The influenza infection in the mallards was mainly intestinal, had a rapid onset and was progressing in a longitudinal fashion in the intestine. Finally, influenza A viruses isolated from wild mallards in Sweden and containing resistance-related mutations were examined by a neuraminidase inhibition assay. The viruses did not have a decreased sensitivity to NAIs, but had mutations with a resistance-enhancing potential. Thus, OC is present in the environment and environmental-like concentrations of OC induce resistance in influenza viruses of dabbling ducks. The present resistance situation among wild birds is not well understood but the existence of H274Y among wild birds, though rare, and the spread of the former seasonal A/H1N1 virus containing H274Y among humans indicate that resistance mutations could establish themselves also among wild birds. An oseltamivir-resistant pandemic or a human-adapted highly-pathogenic avian influenza virus are frightening scenarios as oseltamivir is a cornerstone in the defense in those situations. There is a need for further studies, surveillance in wild birds and for a prudent use of antivirals.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
Nyckelord
- influenza
- oseltamivir
- Tamiflu
- resistance development
- H274Y
- environment
- pharmaceuticals
- mallard
- dabbling duck
- avian influenza
- influensa
- resistensutveckling
- miljö
- läkemedel
- gräsand
- Infektionssjukdomar
- Infectious Diseases
Publikations- och innehållstyp
- vet (ämneskategori)
- dok (ämneskategori)
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