Background The Hepatitis B Virus (HBV) is a blood-borne infection affecting around 2 billion people at any given time and is commonly transmitted through Mother to Child Transmission (MTCT). Preventative measures include vaccinations, particularly the timely Birth Dose (TBD) given within 24 hours of birth. Timing is crucial for the efficacy of the TBD, and is influenced by various factors. São Tomé and Príncipe is one of seven sub-Saharan African countries with a TBD policy. This study aims to observe the different proportions of children receiving adequate or inadequate vaccinations against HBV, as well as to analyse the risk factors that may lead to inadequate vaccination. Methods Secondary data from the São Tomé and Príncipe Demographic Health Survey from 2008-2009 was analysed in this study. Dose delays for all children and those at risk were described. An associative analysis looked at the potential risk factors for inadequate TBD vaccination. Results A high coverage rate for vaccinations was found (>85%), however, the majority were delayed, with only 1% and 4% on time, and mean a TBD administration of 2(SD±2) months after birth, in all children, versus children at risk. Children born to mothers with positive HBV status and low wealth were significantly more likely to receive the TBD on time. Conclusion The majority of vaccinations, including the TBD were inadequately administered, denoting a concern of transmission to children born at risk. Additionally, socioeconomic factors were found to be factors influencing the provision of the TBD

Introdução: A adesão ao tratamento da hepatite B crônica na vida real tem sido pouco estudada em todo o mundo. Neste estudo, foram avaliados os desfechos virológicos e de adesão ao tratamento antiviral de longo prazo em pacientes monoinfectados com hepatite B crônica. Métodos: Trata-se de um estudo prospectivo de coorte com pacientes portadores de hepatite B crônica (n = 183), tratados com adefovir, entecavir, lamivudina e / ou tenofovir, realizado em um centro de referência terciário brasileiro. A adesão ao tratamento foi avaliada por um questionário validado, denominado CEAT-HBV, em três momentos (2010/2011, 2013/2014 e 2014/2015). As variantes de resistência às drogas para hepatite B e a farmacocinética de um único ponto foram determinadas por sequenciamento e cromatografia líquida com espectrômetro de massa em tandem, respectivamente. Resultados: CEAT-HBV identificou 79/183 (43%) pacientes em não-adesão ao tratamento antiviral e entre esses, 53/79 (67%) tinham maior frequência de HBV DNA positiva. Porém, 38% (70/183) tiveram carga viral positiva sugerindo não resposta ao tratamento. As mais frequentes variantes de resistência aos antivirais foram M204I/V (78%), L180M (59%), L80I (15%), V173L (7%) e Q215H (6%). As principais causas associadas com a ausência de resposta ao tratamento antiviral foram variantes de resistência às drogas (39%), variantes de resistência às drogas e não adesão (23%), não adesão (13%), duração de tratamento insuficiente (10%), e indeterminada (16%). A farmacocinética de dose única indicou 48% (31/65) de não adesão ao antiviral. Dois anos depois da primeira avaliação, o CEAT-HBV indicou que 101/143 (71%) pacientes estavam em adesão ao tratamento, baseado na análise da população per-protocol. Entretanto, 21% (40/183) dos pacientes não puderam ser avaliados e foram excluídos. As principais razões para exclusão foram óbito (20/183), 11 dos 20 óbitos causados pelo carcinoma hepatocelular, perda de seguimento (16/183) e outras (4/183). Todos os participantes receberam nesse momento uma cartilha para orientação do tratamento. A terceira avaliação do CEAT-HBV (2014/2015) mostrou que 112/135 (83%) pacientes estavam em adesão ao tratamento (população per-protocol) e 8/143 (6%) foram excluídos. Desfechos de longo prazo mostraram que a taxa de adesão baseado no CEAT-HBV continua a aumentar após 4 anos (p < 0,001). Conclusões: Nossos dados realçam a importância do monitoramento da avaliação de adesão à terapia para hepatite B crônica. Desfechos de adesão de longo prazo podem ser dinâmicos e é possível aumentar a taxa de migração para o grupo com adesão/HBV DNA negativa / Background: Chronic hepatitis B (CHB) real-life treatment adherence has been poorly studied worldwide. In this study, it was evaluated long term virological and adherence outcomes regarding antiviral treatment in monoinfected CHB patients. Methods: A prospective cohort study with CHB patients (n=183) treated with adefovir, entecavir, lamivudine and / or tenofovir was performed in a Brazilian reference tertiary center. Treatment adherence was evaluated by a validate questionnaire named CEAT-HBV within three year-periods (2010/2011, 2013/2014 and 2014/2015). HBV drug resistance variants and single-dose pharmacokinetics were determined by sequencing and LC-MS/MS, respectively. Results: CEAT-HBV identified 79/183 (43%) patients with non-adherence to antiviral treatment and among them, 53/79 (67%) were more frequently viral load positive. However, 38% (70/183) had positive viral loads suggesting treatment non-response. Most frequent antiviral resistance variants were M204I/V (78%), L180M (59%), L80I (15%), V173L (7%) and Q215H (6%). The main causes associated with nonresponse to antiviral treatment were drug resistance variants (39%), drug resistance variants and nonadherence together (23%), non-adherence (13%), insufficient treatment duration (10%), and undetermined (16%). Single-dose pharmacokinetics indicated 48% (31/65) antiviral non-adherence. Two years after the first assessment, the CEATHBV indicated that 101/143 (71%) patients were adhered treatment, on basis of an analysis of the per-protocol population. However, 21% (40/183) of the patients could not be evaluated and were excluded. The main reasons for exclusion were death (20/183), 11 out 20 deaths due to hepatocellular carcinoma, loss to follow up (16/183) and others (4/183). HBV booklet was used for medical education. The third CEAT-HBV assessment (2014/2015) showed that 112/135 (83%) patients were on treatment adherence (per-protocol population) and 8/143 (6%) were excluded. Longterm evaluation showed that adherence rate based on CEAT-HBV continue to increase after 4-years (p < 0.001). Conclusions: Our data highlights the importance of CHB therapy adherence assessment monitoring. Long-term adherence outcomes may be dynamic and it is possible to increase the migration rate to adherence/HBV DNA negative group

Atualmente várias substâncias estão sendo avaliadas quanto à sua possível atividade adjuvante, apresentando alta potência, mas também alta toxicidade, que os impede de serem introduzidos numa rotina clínica, como o lipopolissacarídio (LPS), componente da parede celular das bactérias Gram negativas. Estudos têm estimulado o desenvolvimento de derivados de LPS com propriedades potencialmente úteis, um dos exemplos mais conhecidos é o monofosforil lipídio A (MPL), desenvolvido como adjuvante para a aplicação em vacinas de uso humano. O objetivo deste estudo foi caracterizar um sub-produto do LPS de Bordetella pertussis (BpLipídioA), através do desenvolvimento e padronização de testes de controle de qualidade, visando a posterior utilização deste sub-produto como adjuvante vacinal. O conhecimento adquirido sobre o produto durante as fases de pesquisa e desenvolvimento conduziu à seleção de testes físico-químicos, biológicos e microbiológicos, bem como sua faixa de aceitação e limites de detecção. A atividade adjuvante deste produto foi realizada com a Vacina de Hepatite B Recombinante e apresentou resultados promissores. O BpLipídioA foi formulado em emulsão óleo em água, onde foi verificada a estabilidade deste composto. A utilização deste produto em emulsão ou suspensão apresentou-se possível e permite a redução da quantidade de antígeno na dose vacinal, o que aumenta a capacidade de produção das vacinas. / Currently a number of substances are being evaluated for possible adjuvant activity, with high power but also high toxicity, which prevents them from being introduced into clinical routine, such as lipopolysaccharide (LPS), cell wall component of Gram negative bacteria. The aim of this study was to characterize a byproduct of Bordetella pertussis LPS (BpLipídioA), through the development and standardization of quality control tests in order to later use this sub-product as an adjuvant vaccine. The knowledge about the product during all phases of research and development led to the selection of optimal physico-chemical, biological and microbiological tests as well as its acceptable range and detection limits. The adjuvant activity of this product was performed with the recombinant hepatitis B vaccine, which showed promissory results. Using this product in emulsion or suspension forms had to be possible to reduce the amount of antigen in the vaccine dose, which increases the installed production capacity of vaccines.

Neste estudo, hipotetizou-se que existia alta incidência de cirurgiões dentistas com baixa cobertura vacinal para hepatite B e positividade para contato prévio ou corrente para a hepatite viral do tipo B. O presente estudo transversal avaliou a condição vacinal e perfil sorológico dos cirurgiões dentistas para hepatite viral do tipo B no município de Porto Velho/RO - Brasil. Foram analisadas pela técnica de ELISA oitenta amostras de sangue (soro) dos cirurgiões dentistas residentes no município de Porto Velho/RO, visando a detecção dos marcadores sorológicos do Vírus da hepatite B: HBsAg, anti HBc total, anti-HBc IgM e anti-HBs. As amostras anti HBc Total positivas foram testadas para o marcador anti HBc IgM. Foram analisados os achados laboratoriais com dados de formação profissional, uso de equipamento de proteção individual (EPI) e índice vacinal entre os profissionais. Os dados foram comparados utilizando-se o teste Kruskal-Wallis (p< 0,05). Dos cirurgiões dentistas avaliados, 45% faziam clínica geral e 38% relataram atualizar-se profissionalmente uma vez ao ano. A maioria (p< 0,05) dos participantes (59%) recebeu as três doses da vacina contra hepatite B e 11% apenas duas doses. Dentre os que receberam três doses a maior (p< 0,05) frequência (47%) apresentou soroconversão decorrente da vacinação. Embora abaixo do número esperado de 100%, a maioria dos cirurgiões dentistas de Porto Velho recebeu as três doses da vacina o que em geral acarretou imunidade. Entretanto, o perfil sorológico nem sempre foi compatível com a cobertura vacinal. Nossos achados sugerem a necessidade de execução de provas laboratoriais para confirmação e/ou monitoramento do perfil sorológico decorrente da vacinação contra hepatite B. / This search supposed that it had a high incidence of dentists with low vaccine covering for hepatitis B and a positive for previous or current contact for the virus hepatitis of type B. The transversal study evaluated the vaccines condition and serum profile of the dentists for viral hepatitis of type B in Porto Velhos city in Rondonias state Brazil. eighty samples of blood (serum) of the resident surgeons had been analyzed by the ELISAs technique of the dentists in Porto Velhos city, to only find out about the serums detention markers of the Virus of hepatitis B: HBsAg, anti total HBc, anti-HBc IgM and anti-HBs. The positive samples anti Total HBc had been tested for the marker anti HBc IgM. And also it had been analyzed at the lab findings with data of professional formation, equipment used as an individual protection (EPI) and vaccine index between the professionals. The data had been compared using the test Kruskal-Wallis ( p< 0,05) from the people that had been participated. As a result we can say that from dentists analyzed, 45% were in a general clinical and 38% told that to bring up to date once a year. Most of them (59%) received three quantities against Hepatitis B and 11% only with two quantities. Between the people that received three quantities, showed another serum due to the vaccine. Although the number was not expected, most of the dentists from Porto Velho received three doses of the vaccine which it caused immunity. However, the serum profile nor always it was compatible the vaccine covering. Our findings suggest the necessity of execution of labs tests for confirmation and/or a coordination of the serum profile of the vaccination against hepatitis B.

Les travaux exposés dans cette thèse sont le reflet d'années d'efforts consacrées à la mise en place de diagnostics de qualités des hépatites virales au Laos au sein du Centre d'infectiologie Lao Christophe Mérieux (CILM), dont je suis aujourd'hui la directrice scientifique. En introduction, nous avons tenu à présenter les caractéristiques socio-économiques du Laos et ses défis sanitaires pour atteindre les Millennium Development Goals, qui guident les politiques publiques de pays en situation de développement. Nous avons jugé important de souligner ces points tout comme la présentation du CILM pour faire comprendre au lecteur le contexte de réalisation de ce travail. C'est grâce à une bio-banque riche de plus de 7,000 échantillons biologiques de patients infectés par les virus des hépatites virales B et C, que nous avons pu poser la question de recherche clé de cette thèse : Comment évoluent les hépatites virales chez les patients reçus depuis une dizaine d'années au CILM ? Cette question en a fait émerger une deuxième concernant la qualité du diagnostic dans les centres de soins à Vientiane. Ainsi, nous nous sommes intéressés aux kits de diagnostic rapide de l'hépatite B utilisés dans les structures de soins de Vientiane, comparés au standard utilisé dans notre laboratoire. Ces travaux, qui ont donné lieu à la publication de 2 articles (un troisième article a été soumis), jouent un rôle capital pour le pays, car ils donnent des axes d'intervention aux autorités de santé publique laotiennes pour combattre ce fléau. Nous avons choisi une présentation dichotomique des hépatites virales avec une partie dédiée aux hépatites B et une partie dédiée à l'hépatite C en raison de l'émergence d'une troisième question de recherche plus fondamentale. Il s'agit du risque de développement du cancer du foie chez les patients infectés, risque différent suivant que l'on est porteur d'une hépatite B ou d'une C. En effet, les outils diagnostiques pour déterminer la magnitude de ce risque sont peu ou pas accessibles pour les patients au Laos. [...] / The work presented in this thesis reflects many years of effort to devoted the implementation of quality diagnostics of viral hepatitis in Laos at the Centre d'infectiologie Lao Christophe Mérieux (CILM), of which I am now the scientific director. In the introduction, we wanted to present the socio-economic characteristics of Laos and its health challenges in order to achieve the Millennium Development Goals (MDG), which guide public policies in developing countries. We felt it was important to highlight these points as well as the presentation of the CILM to help the readers to understand the context in which this work was carried out. It is thanks to a bio-bank with more than 7,000 biological samples from patients infected with viral hepatitis B and C viruses, that we were able to ask the key research question of this thesis: What is the evolution of patients infected by viral hepatitis B/C who have been follow the viral load at CILM for the past ten years or so? This question raised a second one concerning the quality of diagnosis in health centres in Vientiane. For example, we were interested in the rapid diagnostic kits for hepatitis B used in Vientiane's health facilities, compared to the standard used in our laboratory. This work, which has resulted in the publication of 2 articles (a third article has been submitted), plays a crucial role for the country, as it provides Laotian public health authorities with a focus for action to combat this scourge.

Madagascar fait partie de la zone de haute endémicité pour l‟hépatite B dont le profil de circulation varie selon la ruralité de la zone d‟habitation. De par son insularité et les origines de ses peuplements, nous avons supposé que ce profil de circulation du VHB était dû à la variabilité du VHB et à l‟hétérogénéité du profil de transmission. Ce projet de thèse a pour objectif principal de déterminer les facteurs épidémiologiques et moléculaires influençant la dynamique de transmission et l‟évolution vers les complications de l‟infection par le virus de l‟hépatite B à Madagascar. Résultats : la séroprévalence globale pondérée en Ag HBs est de 6,9% avec des variations allant de 0% à 26% selon les zones géographiques considérées. La prévalence augmente en s‟éloignant des grandes villes et des principales routes nationales les reliant et chez les individus à faible statutsocio-économique. L‟étude du flux génétique des souches virales de l‟hépatite B montre que les zones les plus reculées représentent un réservoir pour la dissémination du virus. L‟infection par le virus de l‟hépatite B est responsable de 31% des maladies hépatiques chroniques rencontrées dans les services hospitaliers investigués à Antananarivo. L‟introduction du VHB s‟est probablement faite au cours du XIXème siècle. Sa propagation à l‟intérieur du pays a pris une allure exponentielle durant les années 80s probablement durant les épidémies de paludisme et suite à des réutilisations des matériels d‟injections. Conclusion : Les résultats de ces différents travaux nous ont permis de plaider pour une politique de lutte visant en particulier les zones très reculées de l‟île où la prévalence en AgHBs est la plus importante. / Madagascar is part of endemic region of HBV. Distribution is different in rural and urban area. The historic of human settlement and its insularity might impact distribution and molecular characteristic of HBV in Madagascar, we then supposed that difference observed in distribution and prevalence of HBV were due to viral variability and different pattern of viral transmission. Therefore, the main objective of this thesis was to determine molecular and epidemiological pattern that may influence dynamic transmission and complications of infection. Results: weighted prevalence of HBsAg was 6.9%. It varied from 3% to 26% according to area of sampling. Populations with a low socio-economic status and those living in rural areashad a significantly higher seroprevalence of HBsAg. Gene flow study showed rural area remain important in virus diffusion.HBV infection was found to be responsible of 31% of chronic liver disease encountered in the main public hospital in the capital of the country. Because of its recent emergence, its introduction dated from XIX century during colonization period. Its expansion during 1980s might be due to use of unsafe injection material mainly during malaria epidemic. Conclusion: The result of these work allowed us to advocate for a policy of struggle, in particular in the very remote areas of the island where the HBsAg prevalence is the most important and where care and preventive measures such as vaccinations are scarce.

The hepatitis B virus (HBV) is a common virus, with two billion people infected worldwide. It causes approximately 600,000 deaths each year, despite the availability of an effective vaccine since 1982. Maize as a platform for oral vaccination can supply a heat stable vaccine, which does not require syringes or trained personnel to administer. The Hepatitis B Surface antigen was transformed into maize and this seed was used to evaluate expression levels through the breeding process. The transgene was transferred into two elite maize inbreds by backcrossing. Highest expressing ears were selected each generation until approximately 99% commercial parent was obtained with a single gene coding for the vaccine present. Selected individuals were crossed to create hybrid plants. This work was done to create high expressing high yielding lines that could be used as a plant-based oral vaccine for Hepatitis B.

Malgré l’existence d’un vaccin préventif efficace, l’infection chronique par le virus de l’hépatite B (HBV) demeure un problème majeur de santé publique. La persistance de l’infection par HBV étant clairement associée à des réponses immunitaires insuffisantes, l’immunothérapie par le vaccin à base d’ADN nu, visant à stimuler les réponses humorales et cellulaires, apparaît comme particulièrement pertinente pour la thérapie des hépatites B chroniques. Toutefois, l’efficacité thérapeutique d’une telle stratégie reste limitée chez l’homme, d’où la nécessité d’optimiser cette approche vaccinale pour une utilisation ultérieure en clinique. Ainsi, l’objectif général de ce travail de thèse était d’explorer, avec le modèle du DHBV (« Duck Hepatitis B Virus »), étroitement apparenté au HBV humain, si l’administration du vaccin à ADN par électroporation (EP) pouvait davantage améliorer son efficacité prophylactique et thérapeutique. Nous avons montré, dans un 1er temps chez des canards naïfs, que l’administration du vaccin à ADN par EP permet de potentialiser le pouvoir neutralisant et d’élargir le répertoire épitopique de la réponse humorale dirigée contre la protéine d’enveloppe du DHBV, même avec des doses d’ADN relativement faibles. Dans un 2ème temps, nous avons montré chez des animaux chroniquement infectés par le DHBV, que l’administration par EP du vaccin à ADN ciblant les protéines structurales du DHBV et le DuIFN-γ améliore considérablement l’efficacité thérapeutique du vaccin, notamment au regard de la séroconversion et de la clairance virale. Les résultats ainsi obtenus confirment l’intérêt majeur de cette approche vaccinale pour la thérapie des hépatites B chroniques / Despite the existence of an effective prophylactic vaccine, chronic hepatitis B virus (HBV) infection remains a major public health problem. Since persistence of HBV infection is mostly associated with insufficient immune responses, therefore DNA vaccination capable of activating both humoral and cellular immune responses appears as a pertinent strategy for chronic hepatitis B therapy. However, the efficacy of such therapeutic approach remains limited in humans. Improvement of DNA vaccine efficacy is therefore needed for future therapeutic applications in clinic. The main objective of this thesis was to investigate in the duck hepatitis B virus (DHBV) model, whether the protective and therapeutic efficacy of DNA vaccine can be enhanced using EP-based delivery system. Firstly, we showed in naïve ducks that EP-based delivery was able to improve the dose efficiency of DNA vaccine and to maintain a highly neutralizing, multi-specific B-cell response even with relatively low DNA doses, suggesting that it may be an effective approach for chronic hepatitis B therapy at clinically feasible DNA dose. Secondly, we showed in chronic DHBV-carriers that in vivo EP is able to dramatically enhance the therapeutic potency of DNA vaccine targeting hepadnaviral proteins. Indeed, this approach was able to consistently restore humoral immune response and to sustainably decrease and even clear viral infection. Thus, these data strongly support the use of this approach for chronic hepatitis B therapy in humans

Thesis (MScMedSc)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: Despite the decreased rate of HBV horizontal transmission in South Africa (SA) due to the HB vaccine, the risk of perinatal transmission remains of concern, especially in HIV/HBV co-infected women. Loss of HBV immune control, resulting in higher HBV replication and thus increasing the risk of transmission is described in HIV/HBV co-infected women. Chronic hepatitis is a well-recognized risk factor for hepatocellular carcinoma (HCC). The presence of specific HBV mutations has been reported in chronic and HCC patients and is used in algorithms for the prediction of HCC in CHB patients in Asia. While these mutations are extensively described in male patients, little is known regarding the antenatal and paediatric populations. This study aimed to determine the prevalence of HBV infection in HIV-exposed infants and to investigate the presence of HCC-related mutations in pregnant women and HIV-exposed children in SA. Residual samples of infants born to HIV-infected mothers were collected from the P1041 study previously conducted in SA. HBV markers (HBsAg, anti-HBs and anti-HBc) were tested on the Architect (Abbott). HBsAg positive samples were tested for HBV DNA to determine HBV viral loads. HBV strains were characterised by sequencing of the HBsAg gene and genotypes were determined by phylogenetic analysis using HepSEQ (www.hepseq.org.uk). For the HCC-related mutations investigation, samples and data were collected from three HBV-related studies: the NHLS Paediatric Study, an Antenatal Study and the current study. Pre-S, basal core promoter (BCP) and pre-core data was collected from all samples. Multiple alignments were formed and the nucleotide sequences of these extracts were translated into protein sequences. These protein sequences were compared manually to the HBV reference genes to identify HCC-related mutations. Of 850 HIV-exposed infants tested, three infants were positive for both HBsAg and HBV DNA. Two samples show evidence of past, but cleared HBV infection. Sequence analysis showed that the infants were infected with a subgenotype A1. At follow up, only one infant and mother were able to be traced and contacted. The infant was HIV-infected and had been on an ART regimen, including lamivudine for two years. HBV testing showed that the infant was HBsAg positive and had an undetectable viral load. Core sequence analysis showed clustering between mother and infant sequences. Transmission of mutant HBV previously associated with HCC prompted the question of what the prevalence of mutations in the antenatal and paediatric population is. In this investigation of HCC-related mutations study, a higher prevalence of combined pre-S, BCP and pre-core mutations was found in HIV-infected as compared to HIV-uninfected women. This study shows that vertical transmission is occurring in HIV-exposed infants in SA despite HB vaccination. Data described in this study suggests the importance of HB vaccination closer to the time of birth in SA. Moreover, data on the higher prevalence of HCC-related mutations in HIV-infected pregnant women provide a background for further longitudinal studies to confirm these findings and their implications in SA. / AFRIKAANSE OPSOMMING: As gevolg van die beskikbaarheid van die Hepatitis B virus (HBV) entstof , het horisontale transmissie van die virus drasties in Suid-Afrika (SA) verminder. Ten spyte hiervan, is daar steeds ‘n hoë risiko van perinatale transmissie van swanger vroue na hulle babas, dit word veral gesien met MIV/HBV positiewe vroue. Dit is wyd beskryf dat vroue wat mede-besmet is met MIV/HBV gewoonlik beheer verloor oor hulle immuunstelsel, wat lei tot ‘n hoër mate van HBV replikasie en dus ‘n hoër risiko van virus oordrag. Kroniese hepatitis is wel bekend as ‘n hoë risiko faktor vir HCC. Die teenwoordigheid van spesifieke HBV mutasies in kroniese en HCC pasiënte word alreeds in Asië gebruik in sekere algoritmes en formules om infeksie aan te dui en te voorspel. Hierdie mutasies is omvattend beskryf in manlike pasiënte, maar baie min is bekend in voorgeboorte en pediatriese gevalle. In hierdie studie het ons die teenwoordigheid van HCC-verwante mutasies in swanger vroue en MIV-blootgestelde kinders in Suid-Afrika ondersoek. Monsters is verkry van babas gebore van MIV-positiewe moeders van die P1041 studie wat voorheen in SA gedoen is. Die HBV merkers (HbsAg, teen-HBs en teen-HBc) was op die Architect (Abbott) getoets. HBsAg positiewe monsters was getoets vir HBV DNA om die virale lading te bepaal. Die verskeidenheid HBV stamme was gekarakteriseer deur die virus se nukleïensuur volgordes te bepaal. Die verskillende genotipes is bepaal deur filogenetiese analises te doen met behulp van die HepSEQ (www.hepseq.org.uk) program. Vir die HCC-verwante mutasie studie is monsters en data vergelyk met 3 HBV-verwante studies: die NHLS pediatriese studie, ‘n voorgeboorte studie en hierdie spesifieke studie. Voor-S, basale kern promoter en voor-kern data was van alle monsters bekom. ‘n Veelvoudige belyning was gedoen met die nukleïensuur volgordes van die verskeie DNA ekstrakte, wat daarna vertaal is in proteïen volgordes. Hierdie proteïenvolgordes translasie was by hand vergelyk met verwysings gene om die relatiewe HCC mutasies te probeer identifiseer. Van die 850 blootgestelde MIV babas wat getoets is, het 3 positief getoets vir beide HbsAg en HBV DNA. Twee monsters het bewys van verlede , maar vrygestelde HBV infeksie. Data analise bewys dat die babas met subtipe A1 besmet was. Ons kon slegs een moeder en baba paar opvolg en kontak vir verdere toetse. Die baba was MIV-positief en was op antiretrovirale behandeling , insluitend lamivudine, vir ten minste 2 jaar. HBV toetse het gewys dat die baba HbsAg positief is en ‘n onopspoorbare virale lading gehad het. Kern nukleïensuur volgorde analise het groepering getoon tussen die ma en baba se virus monsters . Die transmissie van die mutante HBV wat geassosieer is met HCC het gelei tot die vraag wat die voorkomssyfer is van hierdie spesifieke mutasies in die voorgeboorte en pediatriese populasies in SA. In hierdie studie het ons ‘n hoër gekombineerde voorkomssyfer gevind van die voor-S, basale kern promoter en voor-kern mutasies in MIV-positiewe vroue, in vergelyking met MIV-negatiewe vroue. Hierdie studie bewys dus dat vertikale transmissie van HBV in blootgestelde MIV babas steeds plaasvind, ten spyte van HBV inenting. Die data wat in hierdie studie beskryf was dui daarop dat die belangrikheid van HBV inenting nader aan die tyd van die geboorte in SA gegee moet word.As gevolg van die hoë voorkomssyfer van HCC-verwante mutasies in swanger vroue, is daar verdere longitudinale studies nodig om hierdie bevindinge en hul implikasies in SA te bevestig.

La lutte pour les ressources est un phénomène qui a débuté dès l'apparition d'organismes reproductifs et dont la description a été initiée par Malthus puis remarquablement synthétisée et étendue à la biologie sous le terme d'évolution par Darwin en 1859 dans « De l'origine des espèces ». Si le concept est ancien à l'échelle des sciences biologiques, il continue à caractériser des domaines à l'époque insoupçonnés par son auteur tels que la virologie. En effet, les virus hautement variables tels que le virus de l'immunodéficience humaine (VIH), de l'hépatite B (VHB) et de l'hépatite C (VHC) sont présents sous forme de quasi espèce au sein de leur environnement réplicatif, c'est à dire qu'une multitude de virus génétiquement proche mais distincts coexistent au sein de cet espace qu'ils doivent partager selon les mêmes règles générales que les êtres vivants. Ainsi, lorsque des pressions de sélection s'exercent (immunitaires, antivirales…), une redistribution des variants majoritaires est observé au bénéfice de variants minoritaires mieux adaptés à cet environnement changeant. La modélisation mathématique et informatique de la capacité mutationnelle et la dynamique d'adaptation des variants minoritaires au travers de 6 études de cohortes de patients infectés, par la technique ultra-sensible de pyroséquençage haut débit associée à des logiciels originaux ont permis de mettre en évidence, caractériser et évaluer l'impact de marqueurs diagnostics permettant de prédire la résistance aux antiviraux mais aussi de caractériser de nouvelles cibles antivirales. / Struggle for resources is a worldwide rule which has been first described by Malthus and extended to whole world of living organisms by Darwin in 1859 in “Origin of species”. Today, this concept has been enlarged to virological field, and is particularly adapted to describe highly variable viruses like Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) which have a quasispecies distribution in infected patients characterized by the co-existence of a number of distinct but related viral populations. Selection pressure on viral replicative environment (immune, antiviral drug treatment…), generally lead to a redistribution of the viral quasispecies with an increasing of the best adapted minor viral variants at the expense of major viral populations. Mathematical and bioinformatic modelization of this phenomenon through 6 infected patients cohorts by means of ultra-deep sequencing and an original bioinformatic package allowed discovery, characterization and evaluation of new diagnostic markers that could be used to prevent resistance emergence to antiviral drugs and to characterized new therapeutics antiviral targets.