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.

Based on surface area, South Africa is currently ranked 8th in planting genetically modified (GM) crops in the world. The stem borer, Busseola fusca (Fuller) (Lepidoptera: Noctuidae) is of economic importance throughout sub–Saharan Africa. Bt maize (MON810) has been grown to control lepidopterous stem borers in South Africa since its first release in 1998. The first report of resistance to Bt maize was made in the Christiana area of South Africa in 2007. The objectives of this study were to evaluate the status of resistance of populations of B. fusca to Bt maize; to evaluate farmers' perceptions of the regulatory aspects guiding the planting of Bt maize and refugia and how the field situation developed between 1998 and 2010; to compare the fitness of the fertility, fecundity and longevity of Bt–resistant and susceptible B. fusca populations and to determine if there are fitness costs associated with resistance of B. fusca to Bt maize. Questionnaire surveys were conducted amongst 185 farmers in seven districts throughout the maize production region. The questionnaire addressed signing of contracts upon purchasing GM seed, refuge compliance, pest management practices, perceived benefits and risks relating to Bt maize. In order to study fitness and fitness costs that may be associated with resistance development, the life history parameters of known Bt–resistant and susceptible populations were compared in the laboratory using a diapauses–as well as second–generation populations collected in maize fields. The following parameters were compared between different stem borers populations and treatments: pupal mass, moth longevity, fecundity, fertility, larval mass and survival, and sex ratio. This study confirmed resistance of B. fusca to the Cry1Ab toxin (MON810) and that larvae collected from refugia at Vaalharts were resistant and survived on Bt maize. Compliance to refugia requirements was low especially during the initial 5 – 7 years after release. An alarmingly high number of farmers applied insecticides as preventative sprays on Bt maize and refugia. Except for moth longevity and LT50– values, no other fitness costs were observed to be associated with the resistance trait in the highly resistant B. fusca population used in this study. The LT50 may indicate some degree of fitness cost but does not translate into observable costs in terms of fecundity, larval mass and survival. The absence of fitness costs may promote the use of alternative Bt–resistance management strategies, such as the introduction of a multigene strategy. The introduction of a stacked event such as MON89034 which produces more than one protein with activity active against the resistant target pest, together with compliance to the refuge strategy, is most likely the only solution to managing Btresistant stem borer populations in South Africa. / Thesis (Ph.D. (Environmental Science))--North-West University, Potchefstroom Campus, 2011.

Based on surface area, South Africa is currently ranked 8th in planting genetically modified (GM) crops in the world. The stem borer, Busseola fusca (Fuller) (Lepidoptera: Noctuidae) is of economic importance throughout sub–Saharan Africa. Bt maize (MON810) has been grown to control lepidopterous stem borers in South Africa since its first release in 1998. The first report of resistance to Bt maize was made in the Christiana area of South Africa in 2007. The objectives of this study were to evaluate the status of resistance of populations of B. fusca to Bt maize; to evaluate farmers' perceptions of the regulatory aspects guiding the planting of Bt maize and refugia and how the field situation developed between 1998 and 2010; to compare the fitness of the fertility, fecundity and longevity of Bt–resistant and susceptible B. fusca populations and to determine if there are fitness costs associated with resistance of B. fusca to Bt maize. Questionnaire surveys were conducted amongst 185 farmers in seven districts throughout the maize production region. The questionnaire addressed signing of contracts upon purchasing GM seed, refuge compliance, pest management practices, perceived benefits and risks relating to Bt maize. In order to study fitness and fitness costs that may be associated with resistance development, the life history parameters of known Bt–resistant and susceptible populations were compared in the laboratory using a diapauses–as well as second–generation populations collected in maize fields. The following parameters were compared between different stem borers populations and treatments: pupal mass, moth longevity, fecundity, fertility, larval mass and survival, and sex ratio. This study confirmed resistance of B. fusca to the Cry1Ab toxin (MON810) and that larvae collected from refugia at Vaalharts were resistant and survived on Bt maize. Compliance to refugia requirements was low especially during the initial 5 – 7 years after release. An alarmingly high number of farmers applied insecticides as preventative sprays on Bt maize and refugia. Except for moth longevity and LT50– values, no other fitness costs were observed to be associated with the resistance trait in the highly resistant B. fusca population used in this study. The LT50 may indicate some degree of fitness cost but does not translate into observable costs in terms of fecundity, larval mass and survival. The absence of fitness costs may promote the use of alternative Bt–resistance management strategies, such as the introduction of a multigene strategy. The introduction of a stacked event such as MON89034 which produces more than one protein with activity active against the resistant target pest, together with compliance to the refuge strategy, is most likely the only solution to managing Btresistant stem borer populations in South Africa. / Thesis (Ph.D. (Environmental Science))--North-West University, Potchefstroom Campus, 2011.

Introduktion: Antibiotikaresistens är idag ett av de största globala hoten mot folkhälsan. Antibiotikaresistens innebär att bakterier blir resistenta mot läkemedlet antibiotika, vilket leder till att sjukdomar som tidigare varit behandlingsbara med antibiotika blir svårbehandlade eller icke behandlingsbara. Detta leder i sin tur till högre dödlighet, längre sjukhusvistelser samt en högre kostnad för vården. Resistensen sker även naturligt men det är tydligt att överanvändning och missbrukning av antibiotikan skyndar på resistensutvecklingen avsevärt. Syfte: Syftet med den här studien är att undersöka människors beteende gällande antibiotikaanvändning utifrån ett antibiotikaresistent perspektiv. Metod: Det här är en empirisk studie som genomförts i form av en enkätundersökning.Studiedesign är en tvärsnittsdesign. Denna design innebär att data samlas in från mer än ettenda fall vid en viss tidpunkt. Studiepopulationen består av män och kvinnor i åldersgruppen18 år och uppåt utan en övre gräns.Resultat: Resultatet visar att respondenterna är medvetna om antibiotikaresistens och 88,7 %svarar att de är medvetna om att det finns antibiotikaresistens, 87,3 % följer läkarens behandlingsrekommendation. Resultatet visar att 18,3 % skulle kunna tänka sig att köpa antibiotika receptfritt på apotek utomlands utan en läkares ordination om de blir sjuka och 25 % av dem har en högskoleutbildning/universitetsutbildning. Slutsats: Generellt sett visar studien på att det finns en medvetenhet om antibiotikaresistens,vilket också visar sig i respondenternas beteende. Respondenternas beteende följer med vadsom bidrar till att resistensutvecklingen minskar i samhället som handlar om att följa läkarensbehandlingsrekommendation samt att inte köpa receptfria antibiotika. Restriktivt användandeav antibiotika bidrar till minskad resistens. / Introduction: Antibiotic resistance is today one of the biggest global threats to public health. Antibiotic resistance means that bacteria become resistant to the drug antibiotics, which leads to diseases that have previously been treatable with antibiotics becoming difficult to treat or not treatable, which in turn leads to a higher mortality, longer hospital stays and a higher cost of care. The resistance also occurs naturally, but it is clear that overuse and misuse of the antibiotic accelerates the development of resistance considerably. Aim: The aim of this study is to investigate human behavior regarding antibiotic use from an antibiotic-resistant perspective. Method: This is an empirical study conducted in the form of a survey. Study design is a cross-sectional design. This design means that data is collected from more than a single case at a given time. Study populations consists of men and women in the age group 18 years and older without an upper limit. Results: The results show that the respondents are aware of antibiotic resistance and 88.7 % answer that they are aware that there is antibiotic resistance. 87.3% follow the doctor's treatment recommendation. The results show that 18.3% could buy antibiotics without a prescription at pharmacies abroad without a doctor's prescription if they become ill and 25 % of them have a university education. Conclusion: In general, the study shows that there is an awareness of antibiotic resistance, which is also reflected in the respondents' behavior. The respondents' behavior follows what contributes to reducing the development of resistance in society, which is about following the doctor's treatment recommendation and not to buy over-the-counter antibiotics. Restrictive use of antibiotics contributes to reduced resistance.

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