La réponse humorale à immunoglobulines A (IgA) constitue un des principaux mécanismes immunologiques permettant de maintenir l'homéostasie intestinale. L'initiation de la réponse IgA se déroule dans les tissus lymphoides associés à l'intestin, où la reconnaissance des antigènes intestinaux entraine l'activation des lymphocytes B naïfs, la commutation isotypique vers IgA et leur différenciation en plasmocytes. Mon travail de thèse a consisté à étudier la contribution du foie et des cellules dendritiques plasmacytoides (pDC) dans la réponse IgA intestinale. L'utilisation de deux modèles murins permettant la déplétion sélective des pDC nous a permis de démontrer que, en dépit de données publiées montrant leur capacité à engager la réponse IgA in vitro, les pDC ne sont pas nécessaires in vivo pour l'induction ou le maintien de la réponse IgA homéostatique. Nous montrons ensuite que le foie abrite une population importante de plasmocytes à IgA. Chez la souris, nous montrons que ces cellules possèdent des caractéristiques phénotypiques distinctes des plasmocytes de l'intestin et proviennent de lymphocytes B récemment activés dans les plaques de Peyer. A l'homéostasie, ces plasmocytes hépatiques secrètent des IgA dirigées contre les bactéries de la flore intestinale. Enfin, dans un modèle murin de consommation chronique d'alcool, nous montrons une corrélation entre une augmentation de cette population cellulaire, une élévation sérique des IgA et des dépôts d'IgA hépatiques, deux désordres fréquemment observés chez les patients atteints d hépatopathies alcooliques. Nos données indiquent donc que le foie constitue un site effecteur alternatif de la réponse / IgA humoral response is one of the main mechanisms by which immune homeostasis is maintained in the intestine. The IgA response is initiated in gut-associated lymphoid tissues, where recognition of intestinal antigens drives naïve B cell activation, IgA class-switch recombination and plasma cell differentiation. My thesis work addressed the contribution of the liver and plasmacytoid dendritic cells (pDCs) in intestinal IgA response. By using two complementary mouse models allowing for selective depletion of pDCs, we have demonstrated that, in contrast to published work showing their ability to drive IgA response in vitro, pDCs are dispensable in vivo for the induction and the maintenance of homeostatic intestinal IgA responses.Then, we showed that the liver contains an important population of IgA plasma cells. In mice, we demonstrated that these cells harbor distinct phenotypic characteristics in comparison to intestinal IgA plasma cells, and are derived from B cells recently activated in Peyer’s patches. At homeostasis, hepatic IgA plasma cells secrete IgA directed against bacteria from intestinal flora. Finally, in a mouse model of chronic ethanol consumption, we found a correlation between an increase in hepatic igA plasma cell population, elevation of serum iGA and IgA deposits in liver sinusoids, two disorders frequently observed in alcoholic liver disease patients. Thus, our results indicate that the liver constitutes an alternative effector site for IgA response initiated in the intestine

Introduction and Background: Measles, mumps and rubella (MMR) are infectious diseases, primarily of childhood, which cause significant mortality and morbidity globally. These infections are, however, vaccine preventable and there is potential for them to be eradicated worldwide through the strategic use of organised population immunisation programmes. Following the introduction of the MMR vaccination in the UK in 1988, uptake was initially good and a high level of population vaccination coverage was achieved. This was sustained until 1998 when a study by Dr Wakefield and colleagues was published in the Lancet suggesting the theoretical possibility of an association between MMR and Autism/bowel disease. Intense media coverage followed, uptake of MMR vaccine fell to less than 80% in Somerset, and community outbreaks of measles, which had almost been eliminated in the UK, began to reappear. The Wakefield study was subsequently discredited and was eventually retracted by the Lancet in 2010. In August 2008 the Chief Medical Officer announced a national MMR catch-up campaign, targeting all children between the age of 13 months and 18 years who had either not been vaccinated against measles, mumps and rubella, or had only partial immunisation. These children were invited again for vaccination and the campaign was completed in January 2009. This study was undertaken to explore, in depth, the quantitative data available in respect of the uptake of MMR at the time of the 2009 campaign, and also to provide new qualitative data in relation to the attitudes, beliefs and experience of MMR and immunisation services of parents who continued to decline MMR for their children after the 2009 campaign, in order to identify factors which affected parental decision-making, add to the wider knowledge base, and to use this knowledge to improve the future development of immunisation services in Somerset. Methods: The overall objective of the study was to investigate a number of social, demographic and geographic characteristics of parents and children associated with MMR uptake, to compare these characteristics within and between defined sub-sets of the Somerset population, and to explore the basis on which parents in Somerset make decisions in relation to MMR immunisation. The study design adopted was a ‘mixed methods’ approach comprising of a cross-sectional design with three sequential phases - an exploration of baseline epidemiological data; a survey conducted with parents of children who remained unimmunised after 2009; and finally, semi-structured interviews with a sub-set of these parents. Results: The key findings from the study are: Parents who decline MMR for their children are not a homogenous group, but consist of a number of sub-groups each of which have different motives, decision pathways and predicted outcomes in relation to potential to change their mind and accept MMR There are differences in geographic distribution between the two age groups investigated Whilst the ‘Wakefield’ study did, and still does have, an impact, it is not the only or most important factor in their continuing decision-making. There is evidence that health professionals have a key role in addressing parental concerns in respect of immunisation. GP practice was the most significant factor associated with uptake in the Phase 1 study, and this was further confirmed in interviews with parents. Parents make decisions through engagement, through communicating and relating to others and this offers a potential mechanism for health professionals to influence decisions through open engagement with parents. Discussion and Conclusions: Three parent sub-groups were identified (Single Vaccines; Medical Comorbidities and Natural Health). These sub-groups were further investigated and factors associated with the decision-making pathways of each group were identified. This resulted in the development of the ‘MMR Parent Engagement Framework’ as a tool for use by professionals in planning their interactions with parents to improve and encourage more open dialogue in order to positively influence parental decision-making in relation to accepting MMR or other vaccinations. From a commissioning perspective, embedding frameworks such as this in service specifications offers a more cost-effective approach to improving immunisation uptake than funding large, poorly targeted catch-up campaigns. It is therefore recommended that further research is undertaken to provide evidence of the effectiveness of the approach in practice, and to inform future commissioning decisions. Additional recommendations to improve the effectiveness and delivery of immunisation services are also made in respect of GP Practice specific factors, independent schools, ethnic minority communities, vaccine overload, media, and data validation. The study has already directly influenced changes in current practice at both a local and a national level.

Les anticorps monoclonaux anti-cytokine ont constitué une révolution dans le traitement des maladies inflammatoires chroniques, mais leur utilisation présente des inconvénients (non réponse, résistance, effets secondaires, coûts élevés).Notre équipe développe une stratégie alternative originale, l’immunisation active à base de peptides de cytokines. Elle a pour but de faire synthétiser, par l’organisme même du patient, des anticorps neutralisant les effets pathogènes dus à l’excès de cytokines.Durant ma thèse, j’ai montré que l’immunisation active contre un peptide dérivé de l’IL-6 murine est protectrice dans un modèle murin de sclérodermie systémique. L’immunisation de singes avec l’équivalent humain entraîne une réduction significative des réactions inflammatoires locales suite à l’induction d’une réaction d’HSR. De plus, l’immunisation active contre deux peptides dérivés de l’IL-1β et de l’IL-23 conduit à la réduction de la sévérité de l’EAE.Ces résultats confortent l’intérêt de cibler les cytokines par l’approche d’immunisation active à base de peptides, qui pourra permettre de diversifier l’offre thérapeutique actuellement disponible. / Monoclonal antibodies have been a revolution for the treatment of chronic inflammatory diseases, but their use shows major drawbacks (non-response, resistance, side effects and prohibitive costs).Our team develops an original alternative strategy: anti-cytokine peptide-based active immunization.The aim of the approach is to make the patient’s own organism produce antibodies capable of neutralizing the pathogenic effects of cytokine overproduction.During my PhD, I have demonstrated that active immunization against an IL-6 murine peptide confers clinical protection in a murine model of systemic sclerosis. Monkeys immunized against the human peptide also showed a significant decrease of local inflammatory reactions following a delayed-type hypersensitivity reaction. Moreover, active immunization against an IL-1β and an IL-23 murinepeptide led to a reduction of the severity of the EAE in mice.These results comfort the interest of anti-cytokine peptide-based active immunization, which should eventually widen the choice of therapeutics available for the patients.

Les nouveaux immunosuppresseurs utilisés en transplantation rénale depuis le début des années 2000 :mycophenolate mofetil (MMF), tacrolimus, Neoral (nouvelle formulation de la cyclosporine-Sandimmun) et les inhibiteurs du mTOR ont amélioré le contrôle du risque de rejet, ainsi que la survie du greffon. Ces progrès sont contrebalancés par un risque accru d’infections. Nous avons évalué l'impact des nouveaux immunosuppresseurs sur les défenses humorales anti-infectieuses en 2 parties. Pour la première partie, nous avons étudié les réponses humorales primaires contre des antigènes protéiques. La 1ère étude montre que les réponses après l’administration d’un anticorps monoclonal anti-CD3 (OKT3) en induction sont profondément et additionnellement inhibées par le MMF comparé à l'AZA, et par le Neoral comparé au Sandimmun, ce qui empêche la neutralisation de ce puissant immunosuppresseur. La 2ème étude analyse les réponses au vaccin adjuvanté contre l’influenza H1N1 pandémique de 2009. Seuls 44% des transplantés rénaux ont développé une séroconversion, contre 57% de patients hémodialysés et 90% de contrôles sains. Nous observons aussi que le MMF limite l’augmentation des titres d’anticorps après vaccination par rapport à l’AZA. <p>Pour la seconde partie, nous observons l’évolution de composants de l’immunité humorale et innée au cours de la 1ère année de greffe. La 3ème étude montre que l’incidence de l’hypogammaglobulinémie atteint 45% à 3 mois de greffe, et est encore de 30% à 1 an. Les taux de MBP diminuent progressivement ce qui augmente le risque de sepsis et d’infection virale (CMV), tandis que l’hypogammaglobulinémie combinée :IgG + [IgA ou IgM] est corrélée avec une incidence élevée d’infections précoces (86%, RR :2, P=0.048), surtout d’origine respiratoire. La 4ème étude, indique que les immunosuppresseurs diminuent intensément les titres en Ac spécifiques induits avant la greffe :les Ac anti-pneumococciques, de nature polysaccharidique (Ac T-indépendants) et surtout les Ac anti-Anatoxine tétanique, de nature protéique (Ac T-dépendants). L’ensemble de notre observation conclut que les immunosuppresseurs actuels, et plus particulièrement le Mycophenolate diminuent fortement la production et le maintien des immunoglobulines, et ont un impact infectieux important. Il en découle que les stratégies de vaccination recommandées méritent d'être appliquées et que la vigilance à l'égard des pathogènes doit être implémentée. <p> / Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished

This study investigated caregivers' perceptions with regard to vaccine-preventable diseases in terms of six constructs of the Health Belief Model. A qualitative research design that is explorative, descriptive and contextual in nature was employed in order to understand and describe the perceptions influencing access and utilisation of services that lead to missed immunisation opportunities and consequently outbreaks of vaccine-preventable diseases. The data-collection techniques were individual unstructured in-depth interviews, field notes and clinical records. The sample consisted of twenty two (N=22) caregivers who volunteered to be interviewed. The study has highlighted that caregivers' perceptions or cognitive factors play an important role for having children in completing immunisation schedule to protect the public from vaccine-preventable diseases. It is recommended that mass media programmes are needed to address the role of vaccines in reducing high morbidity and mortality rates caused by vaccine preventable diseases and improvement in access to immunisation services. / Health Studies / MPH (Health Studies)

This study investigated caregivers' perceptions with regard to vaccine-preventable diseases in terms of six constructs of the Health Belief Model. A qualitative research design that is explorative, descriptive and contextual in nature was employed in order to understand and describe the perceptions influencing access and utilisation of services that lead to missed immunisation opportunities and consequently outbreaks of vaccine-preventable diseases. The data-collection techniques were individual unstructured in-depth interviews, field notes and clinical records. The sample consisted of twenty two (N=22) caregivers who volunteered to be interviewed. The study has highlighted that caregivers' perceptions or cognitive factors play an important role for having children in completing immunisation schedule to protect the public from vaccine-preventable diseases. It is recommended that mass media programmes are needed to address the role of vaccines in reducing high morbidity and mortality rates caused by vaccine preventable diseases and improvement in access to immunisation services. / Health Studies / MPH (Health Studies)

Der Einzeller Eimeria tenella zählt zu den hochpathogenen Parasiten des Haushuhns und ist Verursacher der Blinddarm-Kokzidiose, eine Erkrankung, die zu hohen ökonomischen Belastungen in der Geflügelindustrie führt. Zur Zeit existiert noch kein Impfstoff, der auf Basis von einzelnen Antigenen wirksam ist. Insbesondere die Identifizierung und Charakterisierung von sekretorischen Proteinen, welche an der Parasit-Wirtszell-Interaktion beteiligt sind, könnte einen Beitrag zur Entwicklung einer Immunprophylaxe darstellen. Ziel dieser Arbeit war es, sekretorische E. tenella-Proteine zu identifizieren und ausgewählte cDNA-Sequenzen in DNA-Immunisierungsstudien zu überprüfen. Um ein DNA-Immunisierungsprotokoll für Hühner zu erarbeiten, wurden die cDNAs von drei schon bekannten E. tenella-Antigenen alleine oder in Fusion zur cDNA des stabilisierenden enhanced green fluorescence protein (EGFP) in zwei unterschiedliche DNA-Immunisierungsvektoren (pCDNA3, pVR1012) kloniert. Die Überprüfung der Serokonversion zeigte, dass nach DNA-Immunisierung von Hühnern mit beiden Vektoren bzw. mit und ohne EGFP-Fusion vergleichbare Immunantworten induziert wurden. D.h. mit dem etablierten DNA-Immunisierungsprotokoll konnte eine Expression heterologer (Eimerien) Gene im Huhn erzielt werden. Um neue sekretorische E. tenella-Proteine zu identifizieren wurden bioinformatische und experimentelle Methoden eingesetzt. Über die bioinformatischen Analysen wurden aus E. tenella-expressed sequence tag (EST)-Datenbanken 54 putativ sekretierte E. tenella-Sequenzen extrahiert für die aufgrund ihrer beschriebenen Funktion und Lokalisierung eine Beteiligung an der Wirts-Parasit-Interaktion abgeleitet wurde. Mittels funktioneller Komplementierung in Hefen konnten aus einer E. tenella-Sporozoiten-cDNA-Bank 25 sekretorische Sequenzen identifiziert werden. Die cDNA-Sequenzen von 13 neu identifizierten sekretorischen Proteinen wurden in DNA-Immunisierungsstudien überprüft. Die Ergebnisse zeigten, dass beide Methoden geeignet sind, um sekretorische Proteine von E. tenella zu identifizieren. Aufgrund der Erkenntnisse dieser Arbeit, sollten jedoch weitere verbesserte Immunisierungsprotokolle erarbeitet werden, um die immunprotektive Wirkung der isolierten Kandidaten-Antigene von E. tenella in Hühnern zu überprüfen. Wie die vorliegende Arbeit bestätigt, eignet sich die Methode der DNA-Immunisierung vermutlich als Grundlage solcher Verfahren, wobei zukünftig die Induktion der essentiellen intestinalen Immunantwort im Vordergrund stehen sollte. / The protozoan parasite Eimeria tenella is highly pathogenic in chickens and causes caecal coccidosis that contribute to high economic losses in poultry farming. At the moment no vaccine based on a single antigen is available. The identification and characterization of proteins that are involved in host parasite interaction could particularly contribute to the development of immunoprophylactic control strategies. In order to establish a DNA immunisation protocol, cDNA of three already known E. tenella antigens were subcloned alone or in fusion to the stabilising fusion partner enhanced green flurescence protein (EGFP) into two different DNA immunisation vectors (pCDNA3, pVR1012). Following DNA immunisation of chickens using both vectors with or without EGFP fusion, respectively, the induction of comparable immune responses were shown by serum conversion. This implies it was possible to achieve heterologous (Eimeria) gene expression in chickens with the established immunisation protocol. In order to identify new E. tenella secretory proteins bioinformatic and experimental approaches were used. Following bioinformatic analysis 54 putatively secretory E. tenella sequences were identified for which roles in host parasite interaction were surmised, due to their localisation and function. The identification of secreted proteins from a E. tenella sporozoite cDNA library using a functional complementation assay in yeast resulted in 25 unique sequences. The cDNA of 13 newly identified secretory proteins were tested in DNA immunisation studies. The results showed that both methods are capable of identifying secretory proteins of E. tenella. Owing to the results presented here, new immunisation protocols should be established to test the immune protective capacity of candidate antigens of E. tenella in chickens. The present study confirmed the method of DNA immunisation as a basic tool for such new protocols. In future, however, DNA immunisation protocols should focus on the induction of essential intestinal immune responses.

De nombreuses études suggèrent que linhibition de la voie alterne du complément de lhôte est nécessaire aux parasites hématophages pour leur permettre daccomplir leur repas sanguin. Une revue décrivant ces études a été publiée dans Developmental and Comparative Immunology (Schroeder et al., (2009) Dev. Comp. Immunol. 33, 5-13). Plusieurs études suggèrent que linhibition de la voie alterne de lhôte par les protéines salivaires de tiques est importante pour lacquisition du repas sanguin et la transmission subséquente de pathogènes à lhôte infesté. Confortant cette hypothèse, une protéine salivaire capable dinhiber la voie alterne du complément a été clonée chez la tique américaine Ixodes scapularis (Valenzuela et al., (2000) J. Biol. Chem. 275, 18717-18723). Cette protéine, appelée Isac, ne présente aucune homologie avec les autres molécules anti-complément connues à ce jour, suggérant que cette protéine a été acquise au cours de lévolution par un mécanisme dévolution convergente. En plus de cet aspect fondamental, Isac représente un candidat antigénique prometteur pour le développement dun vaccin anti-tique potentiellement capable dinduire le rejet de la tique et/ou de prévenir la transmission des pathogènes. Le but initial de cette thèse était didentifier le ou les homologue(s) de la protéine Isac de la tique américaine Ixodes scapularis chez la tique européenne Ixodes ricinus. De façon intéressante, deux séquences différentes ont été isolées du transcriptome des glandes salivaires de la tique I. ricinus (Daix et al., (2007) Insect Mol. Biol. 16 (2), 155-166). Lexpression de ces séquences a révélé quelles codent pour des protéines secrétées capables dinhiber la voie alterne du complément. Ces protéines ont été appelées IRAC I et II pour « Ixodes ricinus anti-complement protein I and II ». La caractérisation des IRACs à laide danticorps monoclonaux a permis de révéler que ces deux protéines sont exprimées de façon constitutive au sein des glandes salivaires de la tique Ixodes ricinus et sont sur-exprimées au cours du repas sanguin. Létude de lexpression des protéines IRAC I et IRAC II au sein de la population dIxodes ricinus a révélé que ces deux protéines sont des paralogues codés par des gènes différents et non par des allèles dun même locus. Enfin, des analyses phylogéniques portant sur les différentes séquences codant pour les protéines homologues à Isac isolées chez les tiques Ixodes scapularis, Ixodes ricinus et Ixodes pacificus ont révélé que les tiques appartenant au complexe Ixodes ricinus codent pour une famille encore non décrite de molécules anti complément qui se sont diversifiées au cours de lévolution par un processus de sélection darwinienne positive. Les analyses phylogéniques des IRACs suggèrent que ces séquences ont subi une diversification par un processus de pression de sélection darwinienne positive, menant probablement à des molécules possédant des propriétés biologiques différentes. Dans la seconde étude, nous avons testé lhypothèse de travail selon laquelle chaque paralogue pourrait posséder des activités inhibitrices différentes à lencontre du complément de différentes espèces dhôtes naturels, contribuant ainsi à élargir le spectre dhôte des tiques I. ricinus. Les résultats obtenus démontrent que cette hypothèse est correcte (Schroeder et al., (2007) Microbes Infect. 9 (2), 247-250). Dans la troisième et dernière étude de ce manuscrit, nous avons testé le potentiel des protéines IRACs comme candidat antigénique pour le développement dun vaccin anti tique. Des recombinants de lherpèsvirus bovin 4 (BoHV-4) exprimant IRAC I ou IRAC II ont été produits. De façon intéressante, nous avons observé que bien que les recombinants BoHV-4 expriment de hauts taux de protéines IRACs fonctionnelles in vitro, les lapins immunisés à laide des recombinants BoHV-4 exprimant les IRACs ne développent pas de réponse humorale détectable à lencontre des transgènes. Dans le but daugmenter limmunogénicité des IRACs exprimés comme transgène, une seconde génération de recombinants BoHV-4 a été produite. Ceux-ci induisent lexpression des IRACs sous la forme de protéines de fusion transmembranaires à la surface des cellules infectées. Linoculation de ces recombinants à des lapins a engendré le développement dune forte réponse humorale à lencontre des IRACs. Néanmoins, cette réponse immune na pas engendré deffet majeur sur le repas sanguin de femelles Ixodes ricinus placées sur les lapins immunisés. / An increasing number of studies demonstrate that inhibition of host complement activation is crucial for completion of the blood feeding process of hematophagous parasites. A review of these studies has been published in Developmental and Comparative Immunology (Schroeder et al., (2009) Dev. Comp. Immunol. 33, 5-13). Several observations suggest that inhibition of the host complement alternative pathway by tick salivary proteins is crucial for the achievement of blood feeding and efficient transmission of the pathogens transmitted by the parasite. Strongly supporting this conclusion, a salivary protein able to inhibit the alternative pathway was cloned from the American tick Ixodes scapularis (Valenzuela et al., (2000) J. Biol. Chem. 275, 18717-18723). Interestingly, this molecule, termed Isac, has no similarity to any previously reported anti-complement molecules suggesting that it has been acquired through a mechanism of convergent evolution. In addition to this fundamental aspect, Isac is also a promising candidate antigen for the development of an anti-tick vaccine potentially able to induce the reject of the tick and/or to prevent the transmission of the pathogens. The initial goal of the present work was to clone the orthologue of Isac from the European tick Ixodes ricinus. Interestingly, two different sequences were isolated from the transcriptome of I. ricinus salivary glands (Daix et al., (2007) Insect Mol. Biol. 16 (2), 155-166). Expression of these sequences revealed that they both encode secreted proteins able to inhibit the complement alternative pathway. These proteins were called I. ricinus anticomplement (IRAC) protein I and II. Further characterization of IRACs using monoclonal antibodies revealed that both proteins are expressed constitutively in I. ricinus salivary glands and are up-regulated during blood feeding. Analysis of a series of individual ticks revealed that all ticks tested express both IRAC I and IRAC II, demonstrating that they are the products of different genes and not of alleles of the same locus. Finally, phylogenetic analyses of the I. ricinus IRAC I and II sequences together with homologues from I. scapularis and I. pacificus demonstrates that ticks belonging to the Ixodes ricinus complex encode a new family of relatively small anti-complement molecules undergoing diversification by positive Darwinian selection. Phylogenetic analyses of IRACs suggested that these sequences were diversifying by a process of positive Darwinian selection, possibly leading to molecules with different biological properties. In the second study, we tested the hypothesis that each paralogue may have different inhibitory activities against the complement of different natural host species, thereby contributing to broaden the host range of I. ricinus ticks. The data obtained demonstrated that this working hypothesis is correct (Schroeder et al., (2007) Microbes Infect. 9 (2), 247-250). In the third and last chapter of the present manuscript, we addressed the potential of IRAC I and II as candidate antigens for the development of an anti-tick vaccine. Bovine herpesvirus 4 (BoHV-4) recombinants expressing IRAC I or II were produced. Interestingly, we observed that although both recombinants expressed high levels of functional IRAC proteins in vitro, our attempts to immunize rabbits against IRACs via infection with these viruses invariably failed. In order to improve the immunogenicity of IRACs expressed as transgene, a second generation of BoHV-4 recombinants was produced. The latter expressed IRACs as transmembrane fusion proteins on cell surface. Comparison of the vaccine potential of BoHV-4 recombinant viruses expressing either secreted or transmembrane IRAC proteins revealed that while the former did not induce a detectable immune response against IRACs, the latter led to high titers of anti-IRAC antibodies. However, the immune response induced against IRACs did not lead to the reject of the tick but only slightly increased the duration of the blood feeding process.

Newborn hearing screening has become an increasingly important element of neonatal care in developed countries whilst only a few fragmented screening programmes are evident in developing countries. The numerous socio-economic, cultural and healthcare barriers in developing contexts do not, however, negate or diminish the need to ensure optimal outcomes for infants with hearing loss through early identification and intervention programmes. South Africa has taken a first step toward addressing this need by publishing a Year 2002 Hearing Screening Position Statement that was produced by the Professional Board for Speech, Language and Hearing Professions of the Health Professions Council of South Africa. Interim recommendations are made toward universal newborn hearing screening programmes in three contexts: well-baby nurseries,; neonatal intensive care units (NICU) and Maternal and Child Health (MCH) clinics through their 6-week immunisation programmes. Although these clinics constitute an unfamiliar hearing screening context, they are essential platforms toward widespread screening of the majority of infants in South Africa. An urgent need therefore exists to ascertain the feasibility of hearing screening programmes at MCH 6-week immunisation clinics in order to guide the future implementation of widespread hearing screening services in South Africa. To attend to this need, an exploratory descriptive design that jointly implements quantitative and qualitative methods in a dominant-less-dominant model of triangulation was utilised to critically describe a screening programme conducted at two MCH clinics in Hammanskraal (a developing, peri-urban South African community). The quantitative methods included a structured interview to compile biographical and risk information; high frequency immittance measurements; hearing screening with OAE and AABR according to specified protocols, and diagnostic assessment of referred infants. The qualitative methods included field notes and critical reflections describing clinics as screening contexts and elucidating interactional processes involved in sustaining programmes. A total number of 510 infant-caregiver pairs were enrolled as subjects during the five-month research period. Results indicate that clinics not only provide a suitable context, but also the possibility of effective collaborations toward facilitating effective initial infant hearing screening programmes. The caregivers and infants who attended the clinics demonstrated significant degrees of socio-economic deprivation. They also reported an increased incidence of risk indicators exacerbating the population’s risk for congenital hearing loss, poor participation in the hearing screening/follow-up process, and subsequent poor involvement in a family-centred early intervention process for infants identified with hearing loss. The screening protocol effectively classified infants into risk categories for hearing loss and established useful norms for high frequency immittance in infants. The efficiency of the programme was acceptable considering the short period of implementation, but inefficient coverage with the AABR and poor follow-up return rates were obtained at the clinics. Despite prevailing barriers, the MCH 6-week immunisation clinics showed promise as platforms for widespread hearing screening programmes for infants in South Africa. The clinical implications and recommendations that emerged from the research conducted in this study were compiled and presented in the form of a preliminary service delivery model for infant hearing screening at MCH clinics. / Thesis (DPhil (Communication Pathology))--University of Pretoria, 2004. / Speech-Language Pathology and Audiology / unrestricted

La vaccination qui est le sujet sur lequel porte cette recherche est une des questions de santé publique les plus importantes; elle fait néanmoins l’objet de nombreuses controverses. Dans le contexte de cette thèse, c’est plutôt l’accès à la vaccination qui est mis en question. La présente recherche vise à analyser une stratégie d’amélioration de la couverture vaccinale à l’aide d’une évaluation de processus extensive en trois étapes faisant suite à une documentation approfondie du contexte. En effet, la recherche analyse les perceptions et les facteurs d’influence de la couverture vaccinale avant l’intervention, les assises conceptuelles et théoriques de cette intervention, l’implantation et la réception de l’intervention et enfin les résultats et les mécanismes mis en œuvre pour les atteindre. Les résultats indiquent que la vaccination s’insère dans l’ensemble des stratégies locales de protection fondées sur des notions endogènes du risque. Ces éléments culturels associés à des facteurs socioéconomiques et aux rapports entre parents et services de santé concourent à expliquer un niveau relativement bas de couverture vaccinale complète de 50% avant l’intervention. L’analyse exploratoire de l’intervention indique que celle-ci intègre une théorie initiale implicite et une philosophie. L’intervention finale était évaluable; cependant, la validation de sa théorie a été compromise par des écarts dans l’implantation. L’approche descriptive montre des taux de réalisation d’activités assez élevés, une atteinte de plus de 95% des cibles et un niveau de réception acceptable, ce qui indique que l’intervention est une stratégie réalisable mais à améliorer. La couverture vaccinale après l’intervention est de 87%; elle est influencée positivement par les niveaux de connaissance élevés des parents et le fait pour les enfants d’être nés dans un centre de santé, et négativement par l’éloignement par rapport au site de vaccination. L’atteinte des résultats suit la procédure principale d’amélioration du niveau de connaissance des parents. Celle-ci est basée sur un mécanisme latent qui est la perception des « opportunités » que fournit la vaccination pour prévenir divers risques sanitaires, sociaux et économiques. Cependant, des approches complémentaires tentent de maximiser les effets de l’intervention en utilisant les pouvoirs conférés aux relais communautaires féminins et la coercition sociale. Cette recherche contribue à éclairer la relation entre l’évaluation du processus et l’analyse de l’évaluabilité, à conceptualiser et opérationnaliser autrement les notions de doses d’intervention administrées et de doses reçues. Sur le plan de la pratique, la recherche contribue à proposer l’amélioration des profils de personnel pour les activités de vaccination et la vulgarisation de la stratégie. Des propositions sont faites pour l’amélioration de l’intervention et l’information des institutions de financement des interventions. / Immunization is one of the most important subjects in public health despite constant on-going controversies. In the context of this research it is more its accessibility that is at issue. This particular research is situated in the perspective of the comprehensive approaches to evaluation and analyses an immunization improvement strategy using a three steps process evaluation after documenting its context. The perceptions and factors influencing immunization coverage before the intervention are assessed, as well as the conceptual and theoretical foundations of the intervention, the implementation and reception of the intervention and mechanisms used to attain the results. The results indicate that immunization is integrated into the local strategies used for protection and grounded in the local concept of risk. Results show also that the context associated with socioeconomic factors and the relations between parents and health services contribute to explain the relatively low complete immunization coverage rate (50.3%) before the intervention. The exploratory analysis indicates that the intervention had an implicit theory and a philosophy. Although the intervention was adequate for an evaluation, discrepancies in the implantation compromised the possibilities of validating its initial theory and philosophy. The descriptive analysis showed that more than 95% of the recipients were reached by the intervention and the received dose of intervention was acceptable indicating that the intervention is a workable strategy that needs to be improved. The complete immunization coverage after the intervention was 87.3%; it was influenced positively by factors including parents’ level of knowledge and the fact that the child was born in a health center, and negatively by the long distances from household to immunization place. The strategies involved in the attainment of the results used parents’ knowledge improvement as a principal procedure. This contains an underlying mechanism mainly related to the perception of the opportunities that immunization permits for preventing various health, social and economic risks. However, complementary approaches tend to maximize intervention outcome by using the power given to female community immunization facilitators and social coercion. The research contributes to highlight the relationship between evaluability assessment and process evaluation, to propose a new conceptual and operational understanding of dose of intervention administered and dose of intervention received. On practical grounds, this research recommended the improvement of the immunization activities staff profile and the widespread adoption of the strategy after it improvement. Indications are provided to improve the intervention and to inform founding agencies.