In the United States, the South has a disproportionate burden of cervical cancer, yet research reporting regional prevalence of human papillomavirus (HPV) infection is scarce. Since 2008, Virginia has passed a HPV vaccine mandate and Louisiana a HPV education bill. This dissertation estimated the prevalence of HPV infection among females and assessed the impact of Virginia’s and Louisiana’s HPV vaccination policy on vaccination among adolescent females. The first manuscript estimated the prevalence of HPV infection using data from 4,250 females collected during the 2007–2010 National Health and Nutrition Examination Survey. Among 14–26 year-olds, the prevalence of high-risk oncogenic HPV was 25.6% (95% CI: 22.4 ̶ 33.3) in the South and 29.1% (95% CI: 24.8 ̶ 33.8) in the rest of the country (p= 0.15). Among 27–59 year-olds, infection rates were 20.9% (95% CI: 17.4 ̶ 24.9) for the South and 14.5% (95% CI: 12.9 ̶ 16.3) for the rest of the country (p=0.0001). The second manuscript assessed the impact of Virginia’s HPV vaccine mandate on vaccination using National Immunization Survey-Teen 2008-2012 data (n=3,203). A difference-in-differences estimation and logistic regression analysis were performed with South Carolina and Tennessee serving as comparison states. Virginia’s mandate was not associated with an increase in vaccination rates. Physician recommendation was strongly associated with vaccination in the Virginia-South Carolina (aOR=10.3; p=0.0001) and Virginia-Tennessee analyses (aOR=9.33; 95%CI: 6.11 ̶ 14.3). The third manuscript assessed the impact of Louisiana’s HPV education policy on vaccination using difference-in-differences estimation and logistic regression analysis, with Alabama and Mississippi as comparison states (n=2,327). There was no evidence that the policy increased vaccination rates. Physician recommendation was associated with vaccination in the Louisiana-Alabama (aOR=7.74; 95% CI: 5.22 ̶ 11.5) and Louisiana-Mississippi comparison (aOR=7.05; 95% CI: 4.6 ̶ 10.5). This study found a higher prevalence of HPV infection among females aged 27 ̶ 59 years in the South compared to the rest of the country. Additionally, physician recommendation was strongly associated with vaccination despite HPV policy implementation. These findings highlight the importance of physician recommendation for HPV vaccination and the need for recommended cervical cancer screening, particularly in the South.

Staphylococcus aureus est un pathogène opportuniste au potentiel de virulence élevé et particulièrement diversifié. Responsable d'intoxications alimentaires, d'infections localisées suppurées et, dans certains cas extrêmes, d’infections systémiques graves, celui-ci est pleinement capable de causer la mortalité chez des patients immunodéprimés. Pourtant, S. aureus est également la cause de divers types d’infections à fort caractère chronique et de persistance chez l’homme et les animaux, infections qui sont difficiles à traiter par antibiothérapie, et qui le plus souvent échappent au contrôle du système immunitaire. Les mammites à S. aureus sont considérées comme l’une des maladies majeures chez les bovins d’élevage, causant de lourdes pertes économiques pour l’industrie laitière. Elles se caractérisent fréquemment par des formes sous-cliniques et chroniques, rendant leur diagnostic et contrôle difficiles. La vaccination contre les infections intramammaires à S. aureus pourrait permettre de protéger les animaux contre les nouvelles infections, diminuant la propagation contagieuse du pathogène lors de la traite, et permettre ainsi de réduire la prévalence de celui-ci dans les troupeaux. Pourtant, aucune formulation n’a pu montrer de réelle efficacité de protection à ce jour. Puisque le déploiement d’une immunité adaptative strictement basée sur la réponse en anticorps n’est pas adéquat pour protéger contre un pathogène chronique tel que S. aureus, le besoin criant de développer de nouvelles méthodes et formulations de vaccin se penche maintenant sur l’amélioration de la réponse à médiation cellulaire, considérée indispensable pour une meilleure protection. Les vaccins vivants atténués, basés sur leur capacité à imiter une infection naturelle, ont su prouver leur efficacité dans le développement d’immunités spécifiques et fortes contre de nombreux microorganismes, en particulier les pathogènes intracellulaires et chroniques. On a démontré que ces souches atténuées pouvait être utilisées comme vecteurs antigéniques et aider à balancer la réponse vers des fonctions effectrices de l’immunité qui permettent de combattre plus adéquatement ce type d’infections. Cette étude a eu pour objectif principal la construction d’une souche atténuée de S. aureus pour l’utilisation à titre de vaccin vivant contre les infections intramammaires. Cette souche vaccinale atténuée est fondée sur la stabilisation génétique du phénotype small-colony variant, à la fois comme base d’atténuation de la virulence et comme facteur permettant l’internalisation temporaire et non destructive dans les cellules de l’hôte. Cette souche a été caractérisée et évaluée dans un modèle d’infection de cellules en culture et dans un modèle in vivo de mammite chez la souris, qui ont tous deux pu confirmer sa robuste atténuation et établir un première preuve de son innocuité comme vaccin.

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.

La vaccination est souvent mal perçue par la population générale. Pour rassurer cette dernière, il serait intéressant de créer une plateforme vaccinale pouvant prédire, in vitro, les risques associés à la prise d’un vaccin. L’objectif de cette thèse est de mettre au point les prémices de cette plateforme. Le principe est simple: obtenir la signature inflammatoire d’un vaccin candidat pour évaluer son innocuité. Pour cela, cette signature sera comparée à celles obtenues par des vaccins actuellement sur le marché ou induites par des pathogènes.Durant cette thèse, nous avons sélectionné une liste de biomarqueurs pouvant être utilisés pour déterminer la signature inflammatoire d’un vaccin. Pour mettre au point cette liste, nous avons utilisé différents modèles inflammatoires (VIH et ligands TLR) et la cytométrie de masse. Par la suite, nous avons mis au point des tests in vitro pour obtenir les signatures inflammatoires induites par le Vaccinia Virus ou le Modified Vaccinia virus Ankara, tous deux utilisés pour éradiquer la variole. Nous avons identifié des signatures inflammatoires spécifiques pour chacun de ces virus, à la fois chez des individus sains et chez des patients infectés par le VIH.La poursuite de ces études, par l’obtention d’un grand nombre de signatures provenant de vaccins sur le marché ou induites par des pathogènes, pourrait permettre de finaliser la mise en place de cette plateforme. En effet, l’obtention de ces dernières permettrait d’obtenir des signatures de référence qui pourraient prédire la dangerosité d’un vaccin. / Vaccination is often not well regarded by the general population. To reassure this latest, it will be interesting to set up an in vitro platform predicting the vaccine safety. The aim of this thesis is to develop the beginnings of this platform. The principle is simple, to get inflammatory signature of a candidate vaccine to evaluate it safety. For that, this signature will be compared with those obtained by vaccine currently on the market or by pathogens.During this thesis, we selected a list of biomarkers that can be used to determinate the inflammatory signature of a vaccine. To obtain this list, we used different inflammatory models (HIV and TLR ligands) and the mass cytometry. Then, we had developed in vitro test to obtain inflammatory signatures induced by Vaccinia Virus or Modified Vaccinia virus Ankara, each used to eradicate the smallpox. We identified specific inflammatory signatures for each virus, both in healthy individuals and HIV-infected humans.The continuation of these studies, by obtaining a large number of signatures coming from vaccines on the market or induced by pathogens, could make it possible to finalize the setting up of this platform. Indeed, the obtaining of the latter would make it possible to obtain reference signatures which could predict the dangerousness of a vaccine.

BACKGROUND: Recently there has been a shift in the global health arena towards maternal immunization as the missing link to protect mother, fetus, and infant. However, as research is being conducted across the maternal immunization portfolio to address underlying immunological mechanisms, effectiveness, stability, and safety, there is minimal data regarding acceptance from the perspective of women and providers, specifically in low-resource settings. Serving as a factor that informs a global and national recommendation for vaccine use, closing this knowledge gap will be necessary to reach policy decisions, develop strategies to introduce maternal vaccines into National Immunization Programs, and secure uptake of such policies on the part of intended beneficiaries. METHODS: Qualitative data was collected across three health facilities (urban, peri-urban, rural) via focus group discussions (women), key informant interviews (family/community members), and clinical vignettes (women). Thematic analysis was guided by the World Health Organization’s Model of Determinants of Vaccine Hesitancy using the seven stages of the Framework Method. RESULTS: Results demonstrated that while women showed confidence in the safety and efficacy of vaccines, hesitancy towards maternal vaccination was fostered by misinformation, religious beliefs, use of traditional medicine, social norms, family involvement, and concerns about risk benefit profiles. In contrast, providers expressed service delivery barriers such as long wait times, husband involvement in decision-making, and religion as main reasons why women were hesitant to be vaccinated during pregnancy. Providers believed that these barriers could easily be overcome with proper outreach, education, and modifications to service delivery. Additionally, providers displayed confidence in their own understanding of the vaccine ecosystem and the level of knowledge women possessed about vaccines. CONCLUSION: To ensure the full potential of maternal vaccines, policies, national strategies, and implementation approaches will need to consider knowledge, attitudes, and beliefs expressed by women and providers, as well as the cultural dynamics of the setting in which vaccines are being administered. Furthermore, research is required to understand the relative strength of explanatory factors in deciding to be vaccinated during pregnancy, as well as exploration of how these factors change over time and contribute to policy and program implementation approaches. / 2022-09-30T00:00:00Z

The objectives of this study are: (1) To compare the effectiveness of two dosing schedules of hepatitis B vaccine in achieving compliance within the vaccines; (2) To determine the immunization requirements in U.S. pharmacy schools both at admission and before the students begin clinical clerkships; and, (3) To design an immunization program for pharmacy students at the University of the Pacific in an attempt to enhance compliance.

Une augmentation au moins transitoire de la ploïdie est un événement fréquent de l'oncogenèse. L'hyperploïdisation déclenche un stress du réticulum endoplasmique (RE) caractérisé par l'hyperphosphorylation du facteur d'initiation eucaryote 2α (eIF2α) qui induit l'exposition consécutive de la calréticuline à la surface cellulaire. La calréticuline exerce un effet « adjuvant » en tant que un signal "mange-moi", pour les cellules dendritiques, entrainant un contrôle immunitaire de la tumeur par les lymphocytes T CD8+. Nous avons étudié la possibilité que l'hyperploïdisation puisse également affecter l'antigénicité des cellules cancéreuses en modifiant l'immunopeptidome. Cependant, la vaccination avec des peptides candidats n’a pas réussi à induire des réponses inhibitrices de la croissance tumorale de cellules hyperploïdes in vivo. Nous concluons donc que l'hyperploïdie augmente principalement l'immunogénicité des cellules cancéreuses en affectant leur adjuvanticité (via l’expression de calréticuline) plutôt que leur antigénicité. Nous montrons de plus que des fibrosarcomes induits par méthylcholanthrène (MCA), développés dans des souris Rag2-/-γc-/- immunodéficientes (mais pas dans des souris sauvages), sont particulièrement hyperploïdes, en corrélation avec une teneur en ADN plus élevée, une augmentation de la surface nucléaire, ainsi que l'hyperphosphorylation de eIF2α,. De telles cellules forment des tumeurs dans les souris Rag2-/-γc-/- (dépourvues de cellules T, B et NK) ainsi que dans les souris Rag2-/- (dépourvues de lymphocytes T et B) sans différence entre les deux souches de souris, suggérant que l'absence de cellules B et T est suffisante pour que ces cellules prolifèrent. Pour mesurer ces paramètres, nous avons développé un outil d'analyse morphométrique applicable à l'immunohistochimie. Cet algorithme identifie et quantifie automatiquement la surface des noyaux et l'intensité de la phosphorylation de eIF2α dans une région d'intérêt périnucléaire. Des analyses comparatives ont validé la précision de cette méthode, qui peut être utilisée pour étudier la ploïdie et le stress du RE dans les cancers in situ. / An at least transient increase of ploidy, usually by whole genome duplication, is a frequent event in oncogenesis. Hyperploidization triggers an endoplasmic reticulum (ER) stress characterized by the hyperphosphorylation of the eukaryotic initiation factor 2α (eIF2α), with leads to the exposure of calreticulin to the cell surface. Calreticulin is acting like an "adjuvant" effect as a "eat me" signal, for dendritic cells, ultimately eliciting immune control by CD8 + T lymphocytes. We investigated the possibility that hyperploidization might also affect the antigenicity of cancer cells by altering the immunopeptidome. However, vaccination with candidate peptides was unable to elicit tumor growth-inhibitory responses against hyperploid cells in vivo. We conclude that hyperploidy increases the immunogenicity of cancer cells mostly through their adjuvanticity (through calreticulin exposure) rather than their antigenicity. We also show that when developed in Rag2 - / - γc - / - immunodeficient mice (but not in WT mice) fibrosarcomas induced by methylcholanthrene (MCA) are particularly hyperploid, correlating with higher DNA content, increased nuclear surface, as well as the hyperphosphorylation of eIF2α. These cells are able to form tumors in Rag2 - / - γc - / - recipients (which lack T, B and NK cells) as well as in Rag2 - / - recipients (which only lack T and B lymphocytes) without any difference between the two strains, suggesting that the absence of B and T cells is enough to allow these cells to grow. To measure these parameters, we developed a morphometric analysis tool that is applicable to immunohistochemistry. This software automatically identifies and quantifies the surface of nuclei and the intensity of eIF2α phosphorylation within a perinuclear region of interest. Comparative analyzes validated the accuracy of this method, which can be used to investigate ploidy and ER stress in cancers in situ.

Rabies has been reported in Tanzania, mainly in the southern highland regions, since 1954. To date, rabies is endemic in all districts in Tanzania and efforts are being made to contain the disease. It was determined that mass vaccination of at least 70% of an animal population is most effective, in terms of profitability and cost, in reducing transmission of rabies. The current approach for vaccination in Tanzanian villages takes some features from the EPI method but is rather basic and unreliable. This mini-dissertation proposes using a sampling technique which incorporates the spatial component of the village data and minimises the walking distance between the sampled houses while ensuring the 70% coverage of the animal population. / Mini Dissertation(MSc)--University of Pretoria, 2017. / STATOMET The Centre for Artificial Intelligence Research (CAIR) National Research Foundation of South Africa (NRF CSUR grant number 90315) / Statistics / MSc / Unrestricted

Feline hyperthyroidism is an important disorder in middle-aged and older cats. The cause and pathogenesis of the disease is still unknown and there are few published incidence rates or prevalence estimates. A descriptive cross-sectional study was conducted to determine the prevalence of and potential risk factors for feline hyperthyroidism in Hong Kong. Serum thyroxine (T4) was measured in 305 cats 10 years and older that presented at various veterinary clinics in Hong Kong between June 2006 and August 2007. The veterinarians taking the samples completed a questionnaire regarding the health of each cat. Each owner completed a questionnaire regarding vaccination history, internal and external parasite control, diet and the environment of their cat. Serum total T4 concentration was determined by use of a commercially available radioimmunoassay kit (Coat-a-count®, DPC®). For total T4 the feline reference interval was 12.8-50.0 nmol/L (1.0-3.9 ug/dL). All cats with a serum total T4 concentration of greater than 50.0 nmol/L were classified as hyperthyroid. Alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities were measured in all the samples. The prevalence of feline hyperthyroidism in Hong Kong was estimated at 3.93% (95% CI : 2.05-6.77) and there was no significant difference in prevalence between healthy (3.16%) and sick (4.37%) cats. This demonstrates that although this disease is present in Hong Kong, the prevalence is lower than the reported prevalence in other parts of the world. Risk factors that were examined included age, sex, breed, number of cats in household, vaccinations, parasite control, indoor environment, type of diet and type of water. Risk factors for hyperthyroidism identified by multivariate analysis were age and breed. Affected cats were more likely to be older (>15 years) and domestic shorthair cats were less likely to be diagnosed with hyperthyroidism than the other breeds combined. There was no statistically significant relationship between sex, vaccinations, parasite control or indoor environment and the development of hyperthyroidism. There was also no statistically significant relationship between the consumption of a canned food diet by the cats and hyperthyroidism. There were no characteristic clinical features amongst the cats that were hyperthyroid and only one cat exhibited the typical clinical syndrome of ravenous appetite with severe weight loss. The lack of distinctive clinical signs could be due to the presence of a mild or early form of the disease, but can also be due to an atypical form of the disease. This study showed that the disease needs to be considered if any of the following factors are present in an older cat : polyphagia, diarrhoea, and a significant raise in ALT and ALP activities. This study concluded that the prevalence of hyperthyroidism in cats in Hong Kong is less than in most other parts of the world, despite the presence of previously identified risk factors. Comparative epidemiological studies will be necessary to compare the presence of possible risk factors between feline populations in Hong Kong and elsewhere. / Dissertation (MSc)--University of Pretoria, 2008. / Companion Animal Clinical Studies / unrestricted

Les paramyxovirus possèdent deux glycoprotéines d’enveloppe (gps): la protéine F, permettant la fusion avec la cellule hôte, et la protéine d’attachement appelée G, H ou HN. Les gps H et F d’une souche vaccinale du virus de la rougeole peuvent être incorporées sur des vecteurs lentiviraux (H/F-LV) permettant une transduction efficace des lymphocytes T et B humains non stimulés, habituellement réfractaires. Nous avons montré que les vecteurs H/F-LV sont capables de transduire des cellules B cancéreuses, activées et quiescentes, contrairement aux VSV-G-LV classiques. Leur utilisation in vivo est cependant confrontée à la présence d’anticorps neutralisants induits par la vaccination, dirigés majoritairement contre H. Après la mutation des 2 épitopes immunodominants de H, les vecteurs conservent leur tropisme et échappent à la neutralisation par les anticorps monoclonaux, mais sont toujours neutralisés par le sérum humain. Les souches émergentes de rougeole de génotype D, qui paraissent résister à la vaccination, présentent une glycosylation supplémentaire de la H. Introduite dans notre mutant, elle permet aux H/F-LV de transduire efficacement les cellules T et B en présence de sérum ou de sang total. Les pneumovirinae (le Virus Respiratoire Syncytial et le Métapneumovirus Humain (HMPV)) sont la première cause d’infections respiratoires chez le nourrisson, il n’existe pas de vaccin contre ces virus. Nous avons mis au point un système de Virus-Like Particle rétrovirales incorporant les gps F et G de HMPV (HMPV-VLPs). Injectées à des souris, les HMPV-VLP induisent une forte réponse d’anticorps neutralisants. De plus, suite à une épreuve virale, les souris sont protégées de l’infection par hMPV. / Paramyxoviruses contain two envelope glycoproteins : the F protein allowing fusion with the host cell and an attachment protein, called G, H or HN. Lentiviral vectors pseudotyped with the Edmonston measles virus hemagglutinin and fusion glycoproteins (H/F-LVs) allowed for the first time efficient transduction of quiescent human T and B cells. We showed that H/F-LVs were also able to efficiently transduce quiescent and activated cancer B cells, in contrast to the classical VSV-G-LVs. However, a major obstacle in the use of H/F-LVs in vivo is that most of the human population is vaccinated against measles inducing a humoral immune response exclusively directed against H. LVs pseudotyped with H-glycoproteins mutated in the 2 major epitopes escaped inactivation by monoclonal antibodies but were still neutralized by human serum. Consequently, we took advantage of newly emerged MV-D genotypes that were less sensitive to MV vaccination due to a different glycosylation pattern. The mutation responsible was introduced into the mutated H/F-LVs allowing efficient transduction of quiescent lymphocytes in the presence of high concentration of MV antibody-positive human serum or total blood. Pneumovirinae (Respiratory Syncitial Virus and human metapnemovirus (HMPV)) are the leading cause of respiratory infections in infants and no vaccine is available against these viruses. We designed retroviral Virus-Like Particle incorporating HMPV F and G gps (HMPV-VLPs). HMPV-VLPs injected to mice induce a strong neutralizing antibody immune response in vivo. Furthermore, upon a viral challenge, HMPV-VLP vaccinated mice are protected against hMPV infection.