A rubéola é uma doença infecciosa aguda, normalmente com um curso clínico suave. Porém quando adquirida nas primeiras 12 semanas de gestação, pode causar severos defeitos de nascimento, conhecida como Síndrome da Rubéola Congênita (SRC). A caracterização genética do vírus da rubéola é feita analisando a seqüência da região hipervariável do gene da glicoproteína E1. Este estudo, apresenta a primeira caracterização molecular de do vírus da rubéola isolados no estado de São Paulo, Brasil. As amostras (sangue, urina, swab de orofaringe, explante de fígado, produto de aborto e fluido cerebrospinal) foram coletados entre 1997 e 2004 de pacientes com sintomas clínicos de rubéola. O gene E1 vírus da rubéola foi amplificado pela reação em cadeia da polimerase em cadeia diretamente de espécimes clínicos e isolados, e os fragmentos de DNA obtidos foram seqüenciados. As seqüências foram alinhadas para a analise filogenética, com seqüências representativas dos diferentes genótipos do vírus da rubéola. Vinte e nove isolados foram obtidos, incluindo isolados relacionados com insuficiência hepática aguda, encefalite e infecções congênitas. A análise filogenética mostrou que 19 dos 29 virus da rubéola isolados pertencem ao genótipo 1a, e 10 pertencem ao genótipo 1G. Este trabalho demonstrou dois genótipos do vírus da rubéola circularam simultaneamente entre os anos de 1997-2004. / Rubella is an acute infectious disease with normally a mild clinical course. However, infections during pregnancy, especially before week 12 of gestation (WG), can cause severe birth defects known as congenital rubella syndrome (CRS). Genetic characterization of wild-type rubella virus is based on sequence analysis of a hypervariable region of the glycoprotein E1 gene. This study presents the first molecular characterization of isolates from São Paulo, Brazil. Samples (blood, urine, oropharyngeal swab, explanted liver, product of conception and cerebrospinal fluid) were collected between 1997 and 2004 from patients with clinical symptoms of rubella. The rubella virus E1 gene coding region was amplified by reverse transcriptase polymerase chain reaction directly from clinical specimens and isolates, and the resulting DNA fragments were sequenced. Sequences were assigned to genotypes by phylogenetic analysis with rubella virus reference sequences. Twenty-nine isolates were obtained, including isolates from acute liver failure, encephalitis and congenital infections. Phylogenetic analysis showed that 19 out of 29 isolated in the São Paulo strains of rubella virus belonged to genotype 1a, and 10 strains to genotype 1G. This work demonstrated two genotypes of RV circulated simultaneously between years 1997 and 2004 in the state of São Paulo. The information reported in this paper may be useful for contributes to understand better the molecular epidemiology of RV in São Paulo, Brazil.

This thesis is devoted to designing and applying advanced algorithmical and statistical tools for analysis of NGS data related to cancer and infection diseases. NGS data under investigation are obtained either from host samples or viral variants. Recently, random peptide phage display libraries (RPPDL) were applied to studies of host's antibody response to different diseases. We study human antibody response to breast cancer and mouse antibody response to Lyme disease by sequencing of the whole antibody repertoire profiles which are represented by RPPDL. Alternatively, instead of sequencing immune response NGS can be applied directly to a viral population within an infected host. Specifically, we analyze the following RNA viruses: the human immunodeficiency virus (HIV) and the infectious bronchitis virus (IBV). Sequencing of RNA viruses is challenging because there are many variants inside population due to high mutation rate. Our results show that NGS helps to understand RNA viruses and explore their interaction with infected hosts. NGS also helps to analyze immune response to different diseases, trace changing of immune response at different disease stages.

Age stratified seroepidemiological studies play a crucial role in the design and assessment of vaccination strategies. An existing multiplex bead immunoassay for measles, mumps, rubella and varicella zoster virus antibodies together with a newly developed multiplex bead immunoassay for herpes simplex virus type 1 and type 2 antibodies were used to investigate the age-related seroepidemiology of these viruses in England during 2012.To develop the HSV-1 and HSV-2 antibody assay, attempts were made to produce full length of HSV-1 and HSV-2 glycoprotein G using a baculovirus vector expression system. While HSV-1 gG protein was produced, the proteins were extensively aggregated. Native glycoprotein G molecules undergo partial removal of HSV-1 signal sequence and HSV-1 short membrane anchor sequence during post translational modification. It is possible that such post translational modification is not performed when protein is processed in insect cell culture. Attempts to produce an HSV-2 glycoprotein G were not successful. It is possible that the high GC-content of HSV-2 glycoprotein G led to poor fidelity of copying the PCR amplification sequence. Commercially available truncated HSV-1 gG and HSV-2 gG were therefore used to develop a duplex microbead immunoassay for the simultaneous detection of specific HSV antibodies in human sera. The resultant assays performed with low sensitivity and specificity (HSV-1 of 89% and 66%, respectively and for HSV-2 of 79% and 85%, respectively) compared to the reference HerpeSelect ELISA.The MMRV multiplex bead immunoassay proved rapid, and required minimal sample volume to semi-quantify MMRV specific antibodies. The seroepidemiology of MMR results was compared with previous seroepidemiological studies performed in 1996 in England. The comparison showed an increase in the proportion of individuals who were positive for mumps and measles antibodies in the 2012 survey. The proportion of individuals positive for rubella was essentially unchanged. The increase in the proportion of individuals positive for mumps and measles antibodies in 2012 show the effectiveness of the change in MMR vaccination policy for England from 1996 onward. For VZV, the proportion of individuals who were positive for varicella antibodies between the 1996 and 2012 serological surveys were essentially unchanged. The comparison showed that most young children are susceptible to VZV. At this level of immunity, it can be expected that varicella will continue to produce epidemics of infection in the population, unless varicella vaccination is implemented as a part of routine childhood vaccination.

The rubella virus (RV) was the first virus shown to be teratogenic in humans. The wealth of data on the clinical symptoms associated with congenital rubella syndrome is in stark contrast to an incomplete understanding of the forces leading to the teratogenic alterations in humans. This applies not only to RV, but also to congenital viral infections in general and includes (1) the mode of vertical transmission, even at early gestation, (2) the possible involvement of inflammation as a consequence of an activated innate immune response, and (3) the underlying molecular and cellular alterations. With the progress made in the development of pluripotent stem cell-based models including organoids and embryoids, it is now possible to assess congenital virus infections on a mechanistic level. Moreover, antiviral treatment options can be validated, and newly emerging viruses with a potential impact on human embryonal development, such as that recently reflected by the Zika virus (ZIKV), can be characterized. Here, we discuss human cytomegalovirus (HCMV) and ZIKV in comparison to RV as viruses with well-known congenital pathologies and highlight their analysis on current models for the early phase of human development. This includes the implications of their genetic variability and, as such, virus strain-specific properties for their use as archetype models for congenital virus infections. In this review, we will discuss the use of induced pluripotent stem cells (iPSC) and derived organoid systems for the study of congenital virus infections with a focus on their prominent aetiologies, HCMV, ZIKV, and RV. Their assessment on these models will provide valuable information on how human development is impaired by virus infections; it will also add new insights into the normal progression of human development through the analysis of developmental pathways in the context of virus-induced alterations. These are exciting perspectives for both developmental biology and congenital virology.

OBJETIVOS: Avaliar os efeitos da rubéola durante a gestação, sobre o feto, o recém-nascido e a criança. CASUÍSTICA E MÉTODO: Analisamos 35 gestantes com suspeita de rubéola que foram divididas em dois grupos. Grupo 1: 15 pacientes que apresentaram quadro clínico com comprovação sorológica. Grupo2: 20 pacientes com IgM positiva na rotina pré-natal, na ausência de quadro clínico. O seguimento ultrasonográfico mensal foi realizado em todas as pacientes e as do grupo 1 foram encaminhadas também para propedêutica invasiva. Foram também realizadas a ecocardiografia fetal e a Dopplervelocimetria. As placentas foram submetidas a exame anátomo-patológico. Os recém-nascidos vivos foram avaliados através de exame clínico e sorológico, além do potencial evocado auditivo, ultra-sonografia de crânio, fundo de olho e ecocardiografia pós-natal. RESULTADOS: No grupo 1: a infecção fetal ocorreu em 9 casos, sendo que o risco de transmissão vertical entre 2 a 14 semanas foi de 64,9%. A malformação ocorreu em 37,5% dos infectados. A ultrasonografia revelou crescimento intra-uterino retardado simétrico em todos os fetos infectados que atingiram o terceiro trimestre, tendo se iniciado, em média com 25,1 semanas. A cordocentese foi realizada em 9 pacientes e, todos os casos infectados, apresentavam IgM positiva e eritroblastose no sangue de cordão. A PCR no líquido amniótico foi positiva em todos os 3 casos em que ela foi realizada. 50% das placentas dos fetos infectados apresentava sinais sugestivos de infecção viral. A idade gestacional média do parto entre os infectados foi de 33,8 semanas e o peso médio ao nascimento foi 1365,6g.Todos os 6 nascidos-vivos infectados foram classificados como pequenos para a idade gestacional e apresentaram disacusia. A sobrevida entre os infectados, num seguimento pós-natal médio de 35,2 meses, foi de 62,5%. No grupo 2: a infecção não foi comprovada em nenhum dos recém-nascidos vivos, porém em um caso pudemos demonstrar a infecção congênita pelo vírus de Epstein-Barr. CONCLUSÕES: A transmissão vertical da rubéola no primeiro trimestre parece poder variar entre as populações, bem como a presença dos defeitos associados à infecção. Tanto o diagnóstico invasivo, como o ultrasonográfico apresentaram boa sensibilidade e especificidade. Pudemos estabelecer o padrão de crescimento fetal associado à infecção. A presença isolada de IgM positiva para rubéola na gestação não teve boa correlação com a presença de infecção neonatal, porém pode se associar à presença de outras infecções congênitas. / OBJECTIVES: Our aim was to analyse rubella effects on the fetus, new-born and child. MATERIAL AND METHODS: We analysed 35 patients with suspicious rubella during pregnancy. According to presence or absence of symptoms they were divided in two groups. Group 1: 15 patients presenting rash in which serology was positive. Grupo2: 20 symptomless patients found to have positive IgM during routine prenatal care. Monthly ultrasonographic evaluation was accomplished in all patients and in group 1 they were also offered prenatal invasive testing. Fetal echocardiography and Dopplers were performed. After birth, the placentas were submitted to pathological examination. The liveborn babies had clinical and serological examination. Auditory tests, brain scan, fundoscopy and postnatal echocardiography were also performed. RESULTS: In group 1: fetal infection occurred in 9 cases and vertical transmission between 2 to 14 weeks was 64,9%. Malformation was present in 37,5% of infected cases. Ultrasound revealed symmetrical intra-uterine growth retardation in all infected fetuses that reached the third trimester, and started around 25,1 weeks. Cordocentesis was accomplished in 9 cases and all the infected ones, presented positive IgM and erythroblastosis in cord blood. PCR in the amniotic fluid was positive in all 3 cases it was performed. 50% of the infected fetuses placentas presented signs of viral infection. The average gestacional age of delivery among infected cases was 33,8 weeks and medium birth weight was 1365,6g. All 6 liveborn infected babies were small for gestacional age and presented deafness. Survival among infected cases was 62,5%, medium follow-up was 35,2 months. In group 2: the infection was not demonstrated in any of neonates, although we could demonstrate a congenital infection caused by the Epstein-Barr virus. CONCLUSIONS: Vertical transmission of the rubella in the first trimester seems to vary among different populations, as well as the presence of the associated defects in the new-born. Invasive diagnosis and ultrasonographic follow-up presented good sensitivity and specificity. We could establish the pattern of fetal grown associated to the infection. The isolated presence of a positive rubella IgM in pregnancy did not correlated with congenital rubella, but it can be related to other congenital infections.

OBJETIVOS: Avaliar os efeitos da rubéola durante a gestação, sobre o feto, o recém-nascido e a criança. CASUÍSTICA E MÉTODO: Analisamos 35 gestantes com suspeita de rubéola que foram divididas em dois grupos. Grupo 1: 15 pacientes que apresentaram quadro clínico com comprovação sorológica. Grupo2: 20 pacientes com IgM positiva na rotina pré-natal, na ausência de quadro clínico. O seguimento ultrasonográfico mensal foi realizado em todas as pacientes e as do grupo 1 foram encaminhadas também para propedêutica invasiva. Foram também realizadas a ecocardiografia fetal e a Dopplervelocimetria. As placentas foram submetidas a exame anátomo-patológico. Os recém-nascidos vivos foram avaliados através de exame clínico e sorológico, além do potencial evocado auditivo, ultra-sonografia de crânio, fundo de olho e ecocardiografia pós-natal. RESULTADOS: No grupo 1: a infecção fetal ocorreu em 9 casos, sendo que o risco de transmissão vertical entre 2 a 14 semanas foi de 64,9%. A malformação ocorreu em 37,5% dos infectados. A ultrasonografia revelou crescimento intra-uterino retardado simétrico em todos os fetos infectados que atingiram o terceiro trimestre, tendo se iniciado, em média com 25,1 semanas. A cordocentese foi realizada em 9 pacientes e, todos os casos infectados, apresentavam IgM positiva e eritroblastose no sangue de cordão. A PCR no líquido amniótico foi positiva em todos os 3 casos em que ela foi realizada. 50% das placentas dos fetos infectados apresentava sinais sugestivos de infecção viral. A idade gestacional média do parto entre os infectados foi de 33,8 semanas e o peso médio ao nascimento foi 1365,6g.Todos os 6 nascidos-vivos infectados foram classificados como pequenos para a idade gestacional e apresentaram disacusia. A sobrevida entre os infectados, num seguimento pós-natal médio de 35,2 meses, foi de 62,5%. No grupo 2: a infecção não foi comprovada em nenhum dos recém-nascidos vivos, porém em um caso pudemos demonstrar a infecção congênita pelo vírus de Epstein-Barr. CONCLUSÕES: A transmissão vertical da rubéola no primeiro trimestre parece poder variar entre as populações, bem como a presença dos defeitos associados à infecção. Tanto o diagnóstico invasivo, como o ultrasonográfico apresentaram boa sensibilidade e especificidade. Pudemos estabelecer o padrão de crescimento fetal associado à infecção. A presença isolada de IgM positiva para rubéola na gestação não teve boa correlação com a presença de infecção neonatal, porém pode se associar à presença de outras infecções congênitas. / OBJECTIVES: Our aim was to analyse rubella effects on the fetus, new-born and child. MATERIAL AND METHODS: We analysed 35 patients with suspicious rubella during pregnancy. According to presence or absence of symptoms they were divided in two groups. Group 1: 15 patients presenting rash in which serology was positive. Grupo2: 20 symptomless patients found to have positive IgM during routine prenatal care. Monthly ultrasonographic evaluation was accomplished in all patients and in group 1 they were also offered prenatal invasive testing. Fetal echocardiography and Dopplers were performed. After birth, the placentas were submitted to pathological examination. The liveborn babies had clinical and serological examination. Auditory tests, brain scan, fundoscopy and postnatal echocardiography were also performed. RESULTS: In group 1: fetal infection occurred in 9 cases and vertical transmission between 2 to 14 weeks was 64,9%. Malformation was present in 37,5% of infected cases. Ultrasound revealed symmetrical intra-uterine growth retardation in all infected fetuses that reached the third trimester, and started around 25,1 weeks. Cordocentesis was accomplished in 9 cases and all the infected ones, presented positive IgM and erythroblastosis in cord blood. PCR in the amniotic fluid was positive in all 3 cases it was performed. 50% of the infected fetuses placentas presented signs of viral infection. The average gestacional age of delivery among infected cases was 33,8 weeks and medium birth weight was 1365,6g. All 6 liveborn infected babies were small for gestacional age and presented deafness. Survival among infected cases was 62,5%, medium follow-up was 35,2 months. In group 2: the infection was not demonstrated in any of neonates, although we could demonstrate a congenital infection caused by the Epstein-Barr virus. CONCLUSIONS: Vertical transmission of the rubella in the first trimester seems to vary among different populations, as well as the presence of the associated defects in the new-born. Invasive diagnosis and ultrasonographic follow-up presented good sensitivity and specificity. We could establish the pattern of fetal grown associated to the infection. The isolated presence of a positive rubella IgM in pregnancy did not correlated with congenital rubella, but it can be related to other congenital infections.

Made available in DSpace on 2011-05-04T12:36:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2009 / Considerando a carga e gravidade da Síndrome da Rubéola Congênita (SRC), uma campanha nacional de vacinação de mulheres com idade entre 12 e 39 anos foi realizada no Brasil em 2001-2002 com a meta de imunizar mais de 30 milhões de mulheres. A possibilidade de vacinar mulheres grávidas motivou a iniciativa de acompanhar gestantes vacinadas inadvertidamente (GVI) contra rubéola. Os objetivos do estudo foram descrever o estado imunológico das mulheres, detectar infecção congênita pelo vírus vacinal (ICR) e estimar o risco de SRC e ICR associado ao vírus vacinal. Realizou-se um estudo prospectivo não controlado no qual as taxas de SRC e ICR vacinais foram comparadas a dados históricos. O estudo foi conduzido em 7 Estados:Rio de Janeiro, São Paulo, Pernambuco, Minas Gerais, Bahia, Rio Grande do Sul e Goiás. Métodos laboratoriais incluíram teste sorológico rubéola-específico para IgM e IgG, PCR para detecção viral e seqüenciamento genômico para diferenciação viral. Uma GVI suscetível foi definida como aquela testada para rubéola até 30 dias após a vacinação e apresentou IgM positivo e IgG negativo. SRC associada à vacinação foi definida pela presença dos critérios da Organização Mundial da Saúde para a SRC em recém-nascidos de GVI suscetível, apresentando IgG+ e com vírus vacinal identificado. De um total de 16.435.776 mulheres vacinadas, 20.395 estavam grávidas no momento da vacinação. Destas, 2.330 (11,4 por cento) foram consideradas suscetíveis à rubéola. No acompanhamento de 1.797 recém-nascidos foram identificados 63 (3,5 por cento) IgM positivos configurando ICR. Os resultados das 2230 gestações em 5 Estados incluíram 80 (3,4 por cento) abortos e 11 (0,5 por cento) natimortos. Dados clínicos de 47 dos 63 casos de IRC mostraram 5 recém-nascidos com baixo peso, 4 prematuros, 1 comunicação inter-atrial e 1 sopro cardíaco aos 35 dias de vida, os quais não são compatíveis com SRC. A taxa de ICR foi de 3,5 por cento e nenhum caso de SRC foi detectado. Nossos dados reforçam as recomendações de (1) manter a contra-indicação de vacinação na gravidez e (2) não interromper a gravidez em caso de vacinação inadvertida. / Considering the burden and severity of Congenital Rubella Syndrome (CRS), a countrywide vaccination campaign was conducted in Brazil in 2001 and 2002 with the goal of immunizing over 30 million women aged 12 to 39 years. The possibility of vaccinating women unaware of their pregnancy prompted an initiative to identify and follow-up pregnant women inadvertently vaccinated (PWIV) against rubella. The objectives of this study were: to describe the immunological status of these women and ascertain vaccine virus infection in neonates born to women susceptible to rubella infection at the time of vaccination, and to estimate the risk of Congenital Rubella Infection (CRI) and CRS in neonates associated with the vaccine virus. This was a prospective uncontrolled study, in which rates of CRI and CRS due to the vaccine were compared with data from historic control group. The study was conducted in seven states of the country: Rio de Janeiro, São Paulo, Pernambuco, Minas Gerais, Bahia, Rio Grande do Sul, and Goiás. Laboratory methods included serum enzyme immune assay (EIA) for rubella IgM and IgG detection, PCR for viral detection and genomic sequencing for viral differentiation. A susceptible PWIV was defined as one tested for rubella within 30 days after vaccination and presented positive IgM and negative IgG. CRI associated with vaccination was defined as a newborn to a susceptible PWIV presenting with positive rubella IgM and having the vaccine virus identified but without CRS syndrome. CRS associated with vaccination was defined as a newborn to a susceptible PWIV who fulfilled the WHO criteria for CRS syndrome, presenting with positive rubella IgM and having the vaccine virus identified. From a total of 16,435,776 women, 20,395 were pregnant at the time of vaccination. Among these, 2,330 (11.4%) were considered susceptible at vaccination. The follow-up of 1,797 (77.1%) newborns disclosed 63 (3.5%) IgM positive, which was considered vaccine-associated CRI. Outcomes of 2,230 pregnancies in 5 states include 80 abortions (3.4%), and 11 stillborns (0.5%). Clinical data from 47 of the 63 CRI cases (75%) disclosed: 5 low birth weight, 4 preterm, 1 inter-atrium communication, and 1 cardiac murmur at 35 days of life, which are not compatible with CRS definitions. The rate of CRI was 3.5% and no CRS cases were detected. Our data support the recommendation (1) that pregnancy should remain a contraindication to vaccination and precautions should be taken to avoid vaccination within 28 days of vaccination; and (2) that in case vaccination occurs within 28 days of pregnancy, interruption of pregnancy should not be conducted.

La protéine tyrosine kinase c-Src est surexprimée et activée dans de nombreux cancers. De manière remarquable, Src est activé dans plus de 80% des adénocarcinomes coliques où il joue un rôle dans la carcinogenèse et la progression vers un phénotype métastatique. c-Src et son homologue viral v-Src activent un grand nombre de voies cellulaires permettant à la tumeur de proliférer, de résister à la mort cellulaire et d’acquérir des capacités accrues de migration et d’angiogenèse. Au cours de ma thèse nous avons mis en évidence un mécanisme inattendu d’échappement à l’apoptose de fibroblastes murins surexprimant de manière stable v-Src et de plusieurs lignées tumorales humaines (coliques en particulier) présentant une activité c-Src dérégulée. Nous avons montré que Src stimule la dégradation protéasomedépendantede la protéine Bik, un membre pro-apoptotique de la famille Bcl-2, connu pour être un suppresseur de tumeurs. Cette régulation post-traductionnelle du niveau d’expression de Bik est à l’origine d’une forte résistance de la voie mitochondriale de l’apoptose. L’inhibition de l’activité kinase de Src ou le blocage de la dégradation de Bik par le protéasome permettent de restaurer des concentrations normales de la protéine Bik dans les cellules transformées et de les restaurer efficacement l’apoptose. En revanche, l’inhibition des protéines anti-apoptotiques de la famille Bcl-2 par l’ABT-737 semble moins efficace. Par ailleurs, nous avons également contribué à mettre en évidence le rôle anti-migratoire et anti-invasif du lithium sur des cellules transformées par Src. Le mécanisme moléculaire mis en jeu implique l’activation redox des protéines tyrosine phosphatases cellulaires. Enfin, nous avons participé à l’étude de peptides mimant les hélices centrales d’insertion de Bax, Bcl-xL et Bid, représentant les trois sous-groupes de protéines de la famille Bcl-2. Nous avons comparé leur comportement vis-à-vis d’une monocouche lipidique mimant la membrane mitochondriale externe ainsi que leur capacité à perméabiliser des mitochondries isolées. Nos résultats nous ont permis de proposer que les fragments centraux d’insertion membranaire des protéines Bcl-2 seraient directement impliqués dans la divergence fonctionnelle des différents sous groupes qui composent la famille / C-Src tyrosine kinase is overexpressed and activated in a number of cancers. Remarkably, Src is deregulated in more than 80% of colorectal adenocarcinoma, playing a role in carcinogenesis and progression toward a metastatic phenotype. c-Src and v-Src activate a large number of intracellular pathways which allow the tumor to proliferate, to evade the cell death machinery and to acquired enhanced migratory and angiogenic abilities. During my PhD, we discovered an unknown mechanism to evade apoptosis developed by murine fibroblasts stably overexpressing v-Src and by some human tumor cell lines with c-Srcb deregulation. We have shown that Src stimulate the proteasomal degradation of the Bik protein, a proapoptotic member of the Bcl-2 family proteins known to act as a tumor suppressor. This post-translationnal regulation of the Bik protein expression level leads to a strong resistance of the mitochondrial pathway of apoptosis. Inhibition of the Src kinase activity or of the Bik proteasome-dependent degradation restore normal levels of the Bik protein and efficiently resensitize these cells to apoptosis. Inhibition of the antiapoptotic Bcl-2 proteins by ABT737 seems to be less efficient in these cells. We also contribute to show that lithium suppresses motility and invasivity of v-Src transformed cells. The molecular mechanism involve a redox activation of the protein tyrosine phosphatases. Finally, we compared the membrane behavior and the ability to permeabilize mitochondria of synthetic peptides derived from the central helical hairpin of Bax,Bcl-xL and Bid. We showed that these structurally analogous domains have distinct membrane behavior which could account for the functional divergence between the Bcl-2 family members

This is an historical investigation into the provision of education services for deaf children in the State of New South Wales in Australia since 1860. The main focus is those deaf children without additional disabilities who have been placed in mainstream classes, special classes for the deaf and special schools for the deaf. The study places this group at centre stage in order to better understand their educational situation in the late 1990s. The thesis has taken a chronological and thematic approach. The chapters are defined by significant events that impacted on the education of the deaf, such as the establishment of special schools in New South Wales, the rise of the oral movement, and aftermath of the rubella epidemic in Australia during the 1940s. Within each chapter, there is a core of key elements around which the analysis is based. These key elements tend to be based on institutions, players, and specific educational features, such as the mode of instruction or the curriculum. The study found general agreement that language acquisition was a fundamental prerequisite to academic achievement. Yet the available evidence suggests that educational programs for most deaf children in New South Wales have seldom focused on ensuring adequate language acquisition in conjunction with the introduction of academic subjects. As a result, language and literacy competencies of deaf students in general have frequently been acknowledged as being below those of five their hearing counterparts, to the point of presenting a barrier to successful post-secondary study. It is proposed that the reasons for the academic failings of the deaf are inherent in five themes. / PhD Doctorate