Cette thèse porte sur l’analyse des apports des approches participatives épidémiologiques (PE) dans l’amélioration de la surveillance de la fièvre aphteuse (FA), en particulier dans l’implication des éleveurs à l’échelle locale. Le premier objectif était d’évaluer l’efficacité de la surveillance et de la vaccination contre la FA à l’échelle locale en utilisant PE. Le deuxième objectif était d’évaluer la faisabilité d’application des outils de PE pour améliorer l’implication des éleveurs dans la surveillance de la FA au Vietnam. Les méthodes de PE ont compris des entretiens informelles (en groupes ou individuels), des outils de notation (classement par paires, empilement proportionnel, matrice de notation), des outils de visualisation (cartographie, lignes de temps, diagramme d’écoulement) et d’outil sociologique appelée méthode Q. 122 entretiens en groupe, 467 entretiens individuels, 339 questionnaires ont été effectuées en 2014 et 2015. 409 sérums et 152 fluides d’oesophagiens ont été prélevées. Les enquêtes par questionnaire, les tests d’ELISA et de rtRT-PCR et la modélisation de Bayésienne ont été utilisées pour valider la performance de PE dans la surveillance de la FA. La maladie a été considérée comme la problème la plus importante dans la production animale. La FA était la maladie la plus importante pour la production laitière, suivie par la septicémie hémorragique. Pour la production de bovin de viande, elle a été enregistrée dans l'ordre inverse. La maladie la plus importante pour la production porcine était le syndrome reproducteur et respiratoire porcin tandis que la FA était classé en quatrième. Les agriculteurs ont des capacités de diagnostic différentiel des maladies en fonction des symptômes cliniques. La prévalence sérique de la FA a été estimée à 23% pour la population 1 (proche la frontière du Cambodge) et 31% pour la population 2 (loin de la frontière du Cambodge), respectivement. La sensibilité et la spécificité de PE a été estimée à 59% et 81%, respectivement. La valeur prédictive positive et négative a été estimée à 48% et 86% pour la population 1 et 58% et 81% pour la population 2, respectivement. La présence du sérotype A, de la lignée A/Asia/Sea-97 et du sérotype O, lignées O/ME-SA/PanAsia et O/SEA/Mya-98 a soutenu la circulation du virus par des mouvements transfrontalières des animaux. Les fermes laitières ont appliquées la quarantaine, la désinfection et la vaccination comme méthodes de prévention. Les fermes de bovin de viande ont préférées la propreté et les bonnes pratiques de gestion de l'élevage. Les fermes porcines ont considérées que toutes les méthodes de prévention avaient la même importance. Trois discours «Croire», «Confiance», «Défi», représentés les perceptions communes des éleveurs et représentés 57,3% de la variance, ont été identifiés en utilisant méthode Q. Les éleveurs ont pris eux-mêmes les décisions de vaccination et se sont sentis plus en sécurité après la vaccination contre la FA. Cependant, une partie de la population étudiée n'a pas considérée la vaccination comme le premier choix de prévention. L'analyse de sensibilité de rapport de bénéfice-coût de la vaccination de la FA a montré que la vaccination était rentable pour tous les types de production, même si l'augmentation du coût de la vaccination et la diminution du prix de lait et de viande. 18 nouveaux villages sentinelles ont été identifiés comme potentiellement infectés par la FA. 77 animaux soupçonnés ont été confirmés positives avec la FA. La sensibilité et la spécificité de PE a été estimée à 0,75 et 0,65 respectivement. L'efficacité de PE pour détecter une épidémie de FA au Vietnam ont été démontrée. La vaccination a était montré la méthode la plus économique et la plus efficace pour prévenir la FA. Grâce à l'application des outils simples et adaptables qui facilitent la participation directe et active des éleveurs, PE permet d'obtenir une meilleure acceptabilité de la surveillance et des informations qualifiées. / This PhD thesis aimed at evaluating the contribution of participatory epidemiology (PE) to improve the foot-and-mouth disease (FMD) surveillance and control activities, especially the involvement of farmers at local level. The first objective aimed at assessing the effectiveness of the FMD surveillance and vaccination strategy at local level by using PE approach. The second objective aimed at assessing the feasibility of applying PE tools to improve the involvement of farmers in the FMD surveillance in Vietnam. PE methods performed in our study included informal interviews (focus group and individual), scoring tools (pairwise ranking, proportional pilling, disease impact matrix scoring and disease signs matrix scoring), visualization tools (mapping, timeline, flow chart) and sociological tools called Q methodology. 122 focus groups, 467 individual interviews, 339 questionnaire surveys were performed during two field studies in 2014 and 2015. 409 sera and 152 probang samples were taken. Conventional questionnaire surveys, Bayesian modelling and laboratory test (ELISA and rtRT-PCR) was used to validate the performance of PE in FMD surveillance. Disease was considered as the most important issues in animal production. FMD was the most important disease for dairy cattle production, followed by haemorrhagic septicaemia. For beef cattle production, it was recorded in reverse order. The most important disease for pig production was porcine reproductive and respiratory syndrome while FMD was ranked fourth. Farmers showed their abilities in differential diagnostic of important diseases based on its clinical symptoms. Sero-prevalence of FMD were estimated at 23% for population 1 (bordering with Cambodia) and 31% for population 2 (locating far from the border), respectively. Sensitivity and Specificity of PE were found to be 59% and 81%, respectively. The positive and negative predictive value were found to be 48% and 86% for population 1 and 58% and 81% for population 2, respectively. The presence of serotype A, lineage A/Asia/Sea-97 and serotype O with two separate lineages, O/ME-SA/PanAsia and O/SEA/Mya-98 supported virus circulation through trans-boundary animal movement activities. Dairy farms frequently applied quarantine, disinfection and vaccination as prevention methods. Beef farms preferred cleanliness and good husbandry management practices. Pig farms considered that all prevention methods had the same importance. Three distinct discourses “Believe”, “Confidence”, “Challenge”, representing common perceptions among farmers and accounting for 57.3 % of the variance, were identified based on Q methodology. Farmers take vaccination decisions themselves without being influenced by other stakeholders and feel more secure after FMD vaccination campaigns. However, part of the studied population did not consider vaccination to be the first choice of prevention strategy. The benefitcost ratio of FMD vaccination for dairy cow production in large-scale and in small-scale and meat cattle production were 37.2, 30.0 and 7.3, respectively. The sensibility analysis showed that FMD vaccination was profitable for all of production types even through the increase of vaccine cost and decrease of market price of milk and slaughter cattle. From the focus groups organized at sentinel villages, 18 new villages were identified as potentially infected by FMD. 77 suspected animals were confirmed positive for FMD, with viral serotypes O and A. Sensitivity and specificity of participatory surveillance were recorded at 0.75 and 0.65, respectively. The effectiveness of PE in FMD surveillance system to detect outbreak in Vietnam was demonstrated. It was demonstrated that vaccination was the most effective and economic method to prevent FMD. Through the application of simple, adaptive tools which facilitate direct and active participation of farmers, PE allowed to reach a better acceptability of surveillance and to obtain qualified information.

"March 2004" / Includes bibliographical references (leaves 213-272) / xxiii, 272 leaves ; ill. (some col.), plates ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Paediatrics, 2004

<p>Most pathogens enter the body via mucosal surfaces. In contrast to parenterally administered vaccination, mucosal vaccination has the advantage of eliciting both a systemic and a local mucosal immune response. An oral biodegradable adjuvant with these features would have great potential. </p><p>This thesis has focused on the development of a new oral vaccine against diphtheria. Biodegradable polyacryl starch microparticles were used as a mucosal adjuvant. Diphtheria toxin or cross-reacting material of diphtheria toxin (CRM197) was covalently conjugated to the microparticles and fed to mice by oral gavage. Formaldehyde treatment was also studied as a means of either detoxifying (diphtheria toxin) or stabilising (CRM197) these formulations. All formulations given to mice orally or parenterally, but not intranasally, induced a strong systemic immune response and diphtheria toxin neutralising antibodies. Only formulations administered orally induced a mucosal IgA response as well. </p><p>The non-toxic recombinant protein CRM197 proved to be a promising antigen candidate in an oral diphtheria vaccine when conjugated to the microparticles. Mild treatment of CRM197 with formaldehyde before conjugation to the starch microparticles potentiated the immunogenicity of the formulation. However, no immune response was detected in healthy volunteers after administration of this vaccine in a phase I trial. The possible reasons for the difference in response between mouse and man are discussed.</p><p>The use of cDNA expression macro array technology was also evaluated as a tool in vaccine-related research. Tetanus toxoid and aluminium phosphate were used as model parenteral antigen and adjuvant. It was concluded that the antigen modulates the molecular mechanisms of the aluminium phosphate adjuvant to a greater extent than previously recognised.</p>

Most pathogens enter the body via mucosal surfaces. In contrast to parenterally administered vaccination, mucosal vaccination has the advantage of eliciting both a systemic and a local mucosal immune response. An oral biodegradable adjuvant with these features would have great potential. This thesis has focused on the development of a new oral vaccine against diphtheria. Biodegradable polyacryl starch microparticles were used as a mucosal adjuvant. Diphtheria toxin or cross-reacting material of diphtheria toxin (CRM197) was covalently conjugated to the microparticles and fed to mice by oral gavage. Formaldehyde treatment was also studied as a means of either detoxifying (diphtheria toxin) or stabilising (CRM197) these formulations. All formulations given to mice orally or parenterally, but not intranasally, induced a strong systemic immune response and diphtheria toxin neutralising antibodies. Only formulations administered orally induced a mucosal IgA response as well. The non-toxic recombinant protein CRM197 proved to be a promising antigen candidate in an oral diphtheria vaccine when conjugated to the microparticles. Mild treatment of CRM197 with formaldehyde before conjugation to the starch microparticles potentiated the immunogenicity of the formulation. However, no immune response was detected in healthy volunteers after administration of this vaccine in a phase I trial. The possible reasons for the difference in response between mouse and man are discussed. The use of cDNA expression macro array technology was also evaluated as a tool in vaccine-related research. Tetanus toxoid and aluminium phosphate were used as model parenteral antigen and adjuvant. It was concluded that the antigen modulates the molecular mechanisms of the aluminium phosphate adjuvant to a greater extent than previously recognised.

Bakgrund    HPV, humant papillomvirus, är den vanligast sexuellt överförbara sjukdomen i världen. HPV kan orsaka kondylom, vilket innebär könsvårtor, men det kan även ge gynekologiska cellförändringar som kan leda till livmoderhalscancer. Syfte            Syftet var att undersöka vilken kunskap och inställning gymnasieelever, som inte ingår i vaccinationsåldern, hade till HPV och HPV-vaccination samt om det fanns några könsskillnader. Metod   En kvantitativ enkätstudie genomfördes på en gymnasieskola i Uppsala, Sverige. Enkätdistribueringen skedde vid två tillfällen och 58 (98,3 %) ifyllda enkäter kunde inhämtas, varav 38 var flickor och 20 var pojkar. Resultat    Flickorna på skolan hade en generellt högre andel rätt svar på enkäten, och totalt var det 21 (55,2 %) av flickorna som var vaccinerade medan endast 1 (5 %) av pojkarna. Av samtliga elever var det 22 (37,9 %) som kunde besvara frågan rätt angående hur många typer av HPV-virus det finns, dock kunde 51 (87,9 %) besvara frågan rätt om hur man skyddar sig mot HPV-viruset. Signifikant könsskillnad hittades i kunskapsfrågan gällande om HPV kan orsaka livmoderhalscancer (p&lt;0,045) där flickorna hade flest rätt svar på frågan. Det var fler vaccinerade flickor jämfört med pojkar (p&lt;0,001) och signifikant fler pojkar som kunde tänka sig att vaccineras (p&lt;0,019). Majoriteten, 68 %, av eleverna var positiva till den befintliga HPV-vaccinationen. Slutsats     Eleverna hade generellt sett en låg kunskapsnivå gällande HPV men trots det var det ändå mer än hälften av flickorna som var vaccinerade. Behov av ytterligare kunskap om HPV och HPV-vaccination till befolkningen behövs. / Background HPV, human papilloma virus, is the most common sexually transmitted disease in the world. HPV can cause genital warts and gynaecological dysplasia, which can lead to cervical cancer. Objective The objective was to describe the amount of knowledge the students had regarding HPV and the HPV-vaccination. Another objective was to describe how many of the students who were vaccinated and to study the existing attitudes towards HPV and the HPV-vaccination. The last objective was to compare whether there was any gender differences. Methods  A quantitative survey study was conduced at an upper secondary school in Uppsala, Sweden. The distribution of the surveys occurred on two occasions and 58 (98,3 %) completed surveys were collected. Results The girls had a generally higher percentage of correct answers on the survey. About 55 % (n=21) of the girls were vaccinated but only 5 %(n=1) of the boys. Regarding how many types of HPV there are 22(37,9 %) of the students answered correctly, although 51 (87,9 %) knew how to protect themselves against a possible infection. Significant differences in gender were found in the question whether HPV can cause cervical cancer or not (p=0,045) and whether the students would be willing to take the vaccine or not (p=0,019). The majority of the students, 68 %, were in favour of the existing HPV vaccination. Conclusion Although the students generally had poor knowledge regarding HPV the majority of the girls had taken the vaccine. The need of further knowledge is vast.

Japanese encephalitis virus (JEV), a member of the family flaviviridae, is one of the most important pathogens of the developing countries, causing high mortality and morbidity amongst children. The present study is aimed at the development of a DNA vaccine for Japanese Encephalitis (JE). As a first step towards developing a DNA vaccine for JE, an eukaryotic expression plasmid encoding the envelope (E) glycoprotein of Japanese Encephalitis Virus (pCMXENV) was constructed. This plasmid expresses the E protein intracellularly, when transfected into Vero cells in culture. Several independent immunization and intracerebral (i.e.) JEV challenge experiments were carried out and the results indicate that 51% and 59% of the mice are protected from lethal i.e. JEV challenge, when immunized with pCMXENV via intramuscular (i.m.) and intranasal (i.n.) routes respectively. JEV-specific antibodies were not detected in pCMXENV-immunized mice either before or after challenge. JEV-specific T cells were observed in mice immunized with pCMXENV, which increased significantly after JEV challenge indicating the presence of vaccination-induced memory T cells. Enhanced production of interferon-y (EFN-y) and complete absence of interleukin-4 (IL-4) in splenocytes of pCMXENV-immunized mice on restimulation with JEV antigens in vitro indicated that the protection is likely to be mediated by T helper (Th) lymphocytes of the Thl sub type. These results demonstrated that immunization with a plasmid DNA expressing intracellular form of JEV E protein confers significant protection against i.e. JEV challenge even in the absence of detectable antiviral antibodies. We then examined the potency of JEV DNA vaccines as well as that of the inactivated mouse brain derived BIKEN vaccine in the i.e. challenge model. The results indicate that all the mice immunized with BIKEN JE vaccine were protected against i.e. JEV challenge while 50% protection was observed in case of mice immunized with pJME or pJNSl and 38% protection was observed in pCMXENV-immunized mice. Immunization with both pJME and pJNSl resulted in 66% protection. These results indicate that the BIKEN JE vaccine confers better protection against i.e. JEV challenge than DNA vaccines. The fact that the BIKEN vaccine conferred better protection against i.e. JEV challenge than DNA vaccines indicated that the i.e. JEV challenge model can be exploited further to examine the potency of different DNA vaccine constructs. Towards this goal, we constructed plasmids that encode secretory or nonsecretory forms of JEV E protein and examined their potency in the i.e. JEV challenge model. Our results indicate that i.m. immunization of mice with plasmid encoding secretory form of JEV E protein confers higher level (75%-80%) protection than those encoding nonsecretory forms. Cytokine analysis of splenocytes isolated from DNA immunized mice after stimulation in vitro with JEV revealed that immunization with plasmid encoding secretory form of JEV E protein induces both Thl and Th2 responses while those encoding nonsecretory forms induce only Thl type of response. Thus, synthesis of secretory form of JEV E protein results in an altered immune response leading better protection against i.e. JEV challenge. Based on our studies, we propose that both cellular and humoral immune responses play a key role in protective immunity against i.e. JEV challenge and DNA vaccines that can induce higher levels of neutralizing antibodies will be as efficient as the BIKEN vaccine in conferring protection against i.e. JEV challenge.

Epidemic models help researchers understand and predict the nature of a potential epidemic. This study analyzes and improves network evolution technology that evolves contact networks so that simulated epidemics on the network mimic a specified epidemic pattern. The evolutionary algorithm incorporates the novel recentering-restarting algorithm, which is adopted into the optimizer to allow for efficient search of the space of networks. It also implements the toggle-delete representation which allows for broader search of solution space. Then, a diffusion character based method is used for analyzing the contact networks. A comparison of simulated epidemics that result from changing patient zero for a single contact network is performed. It is found that the location of patient zero is important for the behaviour of an epidemic. The social fabric representation is invented and then tested for parameter choices. The response to vaccination strategies (including ring vaccination) is then tested by incorporating them into the epidemic simulations. / Ontario Graduate Scholarship (OGS), Natural Sciences and Engineering Research Council of Canada (NSERC)

Vaccination är en av de mest kostnadseffektiva åtgärderna inom sjukvården. Sveriges vaccinationsprogram innefattar tio sjukdomar och barnets femte dos ges vid fem års ålder. Barn i förskoleåldern befinner sig i ett utvecklingsstadium vilket kan försvåra vaccination. Tidigare studier beskriver svårigheter och den stress sjuksköterskor upplever i samband med vaccination av barn, kunskapsbrist finns däremot kring hur barnen bör hanteras. Syftet med studien var att utifrån betydelsefulla händelser beskriva barnhälsovårdssköterskans (BHVsköterskans) erfarenheter och agerande vid vaccination av förskolebarn som inte vill medverka. Studien utgick från kritisk incident teknik (CIT). Datainsamlingen utfördes i ett landsting i södra Sverige där elva BHV-sköterskor intervjuades. Intervjuerna transkriberades och analyserades. Etiska överväganden gjordes utifrån gällande riktlinjer. I resultatet framkom ett huvudområde avseende BHV-sköterskans erfarenheter, BHV-sköterskans observationer vid vaccination. Två huvudområden framkom angående BHV-sköterskans agerande: BHVsköterskan främjar vaccination och BHV-sköterskan beslutar kring genomförande av vaccination. Slutsatser och implikationer visar att interaktion mellan förskolebarn, föräldrar och BHV-sköterskan är viktigt och leder till en delaktighet och positiva erfarenheter av vaccination. Förslag på praktiskt agerande framkommer vilket kan främja och underlätta vaccination av förskolebarn. / Vaccination is one of the most cost-effective actions in health care. The program for vaccination in Sweden includes ten diseases and the fifth dose is given when children are five years old. Preschoolers are in a development stage that makes vaccination more difficult. Studies describe the difficulties nurses experience in relation to vaccination of children; lack of knowledge is experienced about procedures to handle the situations. The aim of the study was to describe critical incidents by the Primary Child Health Care (PCHC) nurse’s descriptions and actions during vaccination of preschoolers who resist vaccination. Critical Incident Technique was used during the study. Data collection was made in a county council in the south of Sweden. Eleven PCHC nurses were interviewed. The interviews were transcribed and analysed. Ethical considerations based on current guidelines were made. Results revealed one main area about PCHC nurse’s descriptions: The PCHC nurses observations at vaccination. Two main areas were revealed about PCHC nurse’s actions: The PCHC nurse promotes vaccinations and the PCHC nurse makes a decision about implementation of the vaccinations. Conclusions clarify the importance of interaction between preschoolers, parents and the PCHC nurses leading to participation and positive experiences of vaccination. Suggestions for practical action reveal to promote and facilitate vaccination of preschooler.

Introduction: Hepatitis B is a highly contagious infection. Basic knowledge about hepatitis B is necessary; with more knowledge people take preventive actions against hepatitis B, such as using stick proof cannulas. In Thailand an expected number of 8-20% of the population are currently carriers of the HBV infection.   Aim: The aim of the study was to investigate the knowledge about hepatitis B and the attitudes towards the vaccination among Thai university students.   Method: A cross-sectional study with a quantitative method was used. 280 students participated in the study, and the response rate was 93.9 %. The data was analysed using SPSS Statistics 20.   Result: Both genders had poor knowledge about hepatitis B, however 91.1 % of the students had heard about hepatitis B. About half of the students (55.4 %) knew correctly that hepatitis B is sexually transmitted and 40.0 % of the students knew that hepatitis B could cause liver cancer. There was no significant difference in knowledge between the genders. The attitudes towards the vaccine were satisfactory between both genders, 89.3 % of the students knew that healthy people need the vaccination and 81.1 % believed that they would receive the vaccination. However, only 43.6 % knew that the vaccination could be free or low cost through certain programs. There was a significant difference (p-value = 0.042) between the genders; the male students had a more positive attitude towards the vaccine than the female students.   Conclusion: The results from the Thai students showed that more information about the Hepatitis infection is needed to raise awareness among this certain group of people. Information about how it is transmitted is essential to improve the public health. It is also important to improve the individual's self-care, to encourage them to receive the vaccination. From a nursing point of view improving the knowledge about HBV and a positive attitude towards the vaccine in the prolonging contribute to improve the public health by getting a lower rate of cases with HBV.

Le phénomène dit de domestication moléculaire qui a été rapporté pour certains transposons à ADN a abouti à la formation de néogènes qui codent des protéines potentiellement impliquées dans la stabilité du génome de part une activité recombinase. L’objectif de ce travail est d’étudier l’expression de 23 recombinases néogéniques d’intérêt dérivées de transpsons à ADN dans une série de cancers colorectaux. Nous avons fabriqué de nouveaux anticorps performants pour l’étude en western blot et en immunofluorescence de l’expression du gène SETMAR qui code pour la protéine Metnase dans des lignées cancéreuse différentes et dans des tissus du côlon tumoraux et normaux. Nos résultats démontrent que la vaccination d’ADN avec la formulation utilisée est une méthode qui donne de meilleurs résultats que l'injection de peptide ou protéines purifiées. Nous avons observé une expression de la protéine metnase dans des lignées cancéreuses de cancer du côlon, de leucémie et de cancer du sein. Le niveau d’expression de cette protéine Metnase dans le cancer du côlon semble être associé au statut MSI ce qui suggère un rôle de cette protéine dans les mécanismes de carcinogenèse et de progression tumorale. / During a phenomena known as molecular domestication has been reported for some DNA transposons leading to the formation of Neogenes which encode proteins potentially involved in the genome stability. The objective of this work is to study the expression of 23 neogenic recombinases of interest derived from DNA transpsons in a series of frozen colorectal cancers. We have manufactured new effective antibodies for the study of the expression of SETMAR gene which encode Metnase protein in different cancer cell lines and tissues of colon tumoral and normal by the method of Western blot and immunofluorescence. Our results demonstrate that DNA vaccination with the formulation used here is a method that gives better results than the injection of peptide or purified proteins. We observed an expression of Metnase protein in cell lines of colorectal cancer, leukemia and breast cancer. The level of expression of the Metnase protein in colon cancer appears to be associated to the MSI status which suggests a role for this protein in the mechanisms of carcinogenesis and tumor progression.