Orientador: Fernando Yamamoto Chiba / Banca: Tânia Adas Saliba / Banca: Symone Cristina Teixeira / Resumo: A hepatite B representa um sério problema de saúde pública, devido ao número elevado de indivíduos portadores da doença e às complicações decorrentes de sua evolução. A vacinação é a principal forma de prevenção e torna-se primordial, especialmente, entre os cirurgiões-dentistas e as auxiliares em saúde bucal, devido à exposição frequente à materiais biológicos, instrumentais e ambientes contaminados. O teste anti-HBs, para verificação da imunidade, ainda é um método pouco utilizado pelos profissionais da saúde, pois é pouco relatado na literatura. Considerando a importância da prevenção da hepatite B e a escassez de pesquisas sobre a verificação da imunidade dos profissionais de saúde, no presente estudo objetivou-se avaliar a cobertura vacinal da hepatite B, o resultado do teste anti-HBs, a realização prévia do teste, a interpretação do resultado do mesmo e o recebimento de orientações sobre a doença em cirurgiões-dentistas e auxiliares em saúde bucal do Sistema Único de Saúde de 9 cidades do Noroeste Paulista. Para este propósito, foi aplicado um questionário semiestruturado e auto administrado com questões referentes ao perfil sóciodemográfico, cobertura vacinal, verificação da imunidade e recebimento de orientações sobre a patologia. Para verificar a imunidade à doença, foi utilizado o método imunocromatográfico, por meio do teste anti-HBs. A análise estatística descritiva e os testes Qui-quadrado e Exato de Fisher, ao nível de significância de 5% foram realizados. Do to... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Hepatitis B is a serious public health problem due to the high number of individuals with the disease and complications due to its evolution. Vaccination is the main form of prevention and is especially important among dentists and dental auxiliaries due to frequent exposure to contaminated biological materials, instrumental and environments. The anti-HBs test, for the verification of immunity, is still a method little used by the health professionals, because this approach is few reported in the literature. Considering the importance of the prevention of hepatitis B and the scarcity of researches about the verification of the immunity of health professionals, the present study aimed to evaluate vaccine coverage, anti-HBs test result, previous test performance, interpretation of the result of the test and the receipt of guidelines about hepatitis B in dentists and dental auxiliaries of the Brazil's national health system of 9 cities of the Northwest of the São Paulo state. For this purpose, a semi-structured and self-administered questionnaire was applied with questions regarding socio- demographic profile, vaccination coverage, verification of immunity and receipt of guidelines about the pathology. Then, to verify the presence of antibodies against the disease, the immunochromatographic method was used by the anti-HBs test. Descriptive statistical analysis and Fisher's exact test and Chi-square test at a significance level of 5% were performed. Of the 74 dentists, 64... (Complete abstract click electronic access below) / Mestre

Um estudo de caso-controle para investigar a associação entre a hanseníase e infecção pelo vírus da hepatite B (VHB) foi conduzido no período de 1992/93, na cidade de Goiânia e municípios contíguos - Estado de Goiás. Avaliou-se, também, a distribuição espacial da hanseníase neste aglomerado urbano. Inicialmente, os indivíduos com suspeita clínica de hanseníase foram submetidos a exames baciloscópicos e histopatológicos, independentemente da rotina do Programa de Controle de Hanseníase. Do total de 855 pacientes recémdiagnosticados de hanseníase, 600 eram residentes em área urbana, e foram categorizados em casos multibacilares (31,3 por cento ), paucibacilares (51,8 por cento ) e prováveis (16,8 por cento ). Foi realizada análise descritiva desta casuística, havendo nítida predominância do sexo masculino na forma multibacilar de hanseníase. A distribuição espacial dos pacientes possibilitou, através da análise exploratória das taxas de detecção, discriminar estratos de risco intra-urbano. Para o estudo de caso-controle, 552 pacientes de hanseníase de 1 O a 70 anos foram incluídos. Os controles (N =552) foram selecionados de indivíduos com ausência de sinais e sintomas sugestivos de hanseníase oriundos da demanda espontânea de ambulatórios de 7 unidades de saúde, localizadas na região de procedência dos casos. Os participantes - casos e controles - foram entrevistados para avaliar fatores de risco para hanseníase e infecção pelo vírus da hepatite B. Foram coletadas amostras de sangue para detecção de marcadores ao vírus da hepatite B pela técnica de ELISA. Comparou-se a prevalência de marcadores de exposição (anti-HBc), de imunidade (anti-HBs) e de portador (AgHBs) entre casos e controles. Foram avaliados como potenciais fatores de confusão: sexo, idade, condições sócio-econômicas, estado nutricional, cicatriz vacinal de BCG e utilização dos serviços de saúde. Casos e controles foram similares quanto às características sócio-econômicas e nutricionais indicando que o princípio de selecionar controles da mesma base populacional que os casos parece ter sido adequado. Cicatriz vacinal de BCG esteve estatisticamente associada aos diferentes tipos de hanseníase. Houve maior proporção de indivíduos hospitalizados nos útimos 5 anos entre casos que em controles indicando que o emparelhamento por local de residência não eliminou completamente as diferenças entre os grupos em relação ao uso dos serviços de saúde. Entre os participantes do estudo, 18,1 por cento dos casos e 19,6 por cento dos controles foram soropositivos ao anti-HBc. Em análise multivariada, utilizando-se o modelo de regressão logística politômica, a associação da hanseníase e anti-HBc entre casos e controles apresentou odds ratio de 0,9 (IC95 por cento O, 7-1 ,3) para a categoria de multibacilar; 1,0 (IC 95 por cento 0,7-1,3) para a de paucibacilar e 1,1 (IC95 por cento 0,8-1,5) para a de provável. Estes resultados mostraram que subgrupos de casos e os controles estiveram igualmente expostos ao vírus da hepatite B. As proporções de indivíduos imunes foram semelhantes nos grupos de casos (9,2 por cento ) e controles (10,2 por cento ). Casos multibacilares responderam à exposição viral com formação de anticorpos protetores, qualitativa e quantitativamente de maneira semelhante aos pacientes paucibacilares e grupo controle. Os resultados dos índices de persistência de infecção (PPI) indicaram não haver diferença quanto ao clearance do antígeno viral nos subgrupos de casos e controles. Os resultados obtidos nesta investigação mostraram nos subgrupos de casos e controles: (i) prevalências semelhantes dos marcadores de exposição, de imunidade e de estado de portador; (ii) capacidade similar para produção de anticorpos protetores, avaliada através dos percentuais do marcador anti-HBs e, quantitativamente, através do Índice de Elisa e (iii) baixa probabilidade de persistência da antigenemia mensurada pelo PPI. Em conclusão, não houve evidências epidemiológicas de uma associação entre hanseníase e infecção pelo vírus da hepatite B, avaliada através de estudo de caso-controle, conduzido em área de baixa endemicidade ao VHB e alta endemicidade de hanseníase. / A case-control study was conducted in Goiânia, Central Brazil, a highly endemic area for leprosy and Iow endemic region for hepatitis B virus (HBV) infection. The purpose was to investigate the association between leprosy types and hepatitis B infection. The spatial distribution of leprosy in urban area was assessed. Between 1992 and 1993, newly detected leprosy cases (N=855) were investigated and 600 cases lived in the urban area. They were classified in multibacillary (31.3 per cent ), paucibacillary (51.8 per cent ) and probable cases (16.8 per cent ) according to histopathological and baciloscopic exams, independently of the leprosy control routine. The majority of multibacillary cases was males. Detection rates of leprosy were calculated by mapping cases and several risk strata were identified by using exploratory data analysis. This methodology seems to be particularly useful for targeting control activities in urban areas. Cases were 552 leprosy patients from the urban area and adjacent counties, between the ages of 1O and 70 years who self-referred or were referred to the main outpatient clinic for treatment in the region. 552 controls were selected from among self-referred outpatients from 7 health centers geographically located in areas where the cases came from. The main criteria for eligibility for control subjects was that they must not have any signs or symptoms indicative of leprosy. Blood samples were collected for all participants to determine serological markers of HBV infection and tested by enzyme immunoabsorbent assay technique (ELISA). Cases and controls were interviewed in order to evaluate risk factors for leprosy and hepatitis B vírus (HBV) infection. Prevalence of HBV exposure (anti-HBc), immunity (anti-HBs) and carrier status (AgHBs) were compared among cases and controls. Cases and controls were also compared for age, sex, socio-economic conditions, nutritional status, BCG scars and previous hospitalization. The participants had similar socio-economic pattern and also nutrition status, suggesting that the source of control selection was adequate for controlling for the most common confounding variables. BCG vaccine appeared to provide protection against multibacillary and paucibacillary types of leprosy and percentage of hospitalization was higher among cases. Prevalence of anti-HBc was similar among leprosy cases (18.1 per cent ) compared to controls (19.6 per cent ). An analysis of association between anti-HBc infection and leprosy types in terms of odds ratio, calculated by polytomous logistic regression, showed no positive association: multibacillary (OR=0.9 CI95 per cent 0.7-1.3); paucibacillary (OR= 1.0 CI95 per cent 0.7-1.3) and probable (OR= 1.1 CI95 per cent 0.8-1.5). The main findings of the case-control study were: (i) cases and controls had similar leveis of viral exposure, immune and carrier status (íi) the persistence of antigen response (PPI) was low among cases and controls respectively; (iii) ELISA índices were similar among multibacillary, paucibacillary and control group indicating that all participants mount antibody response to viral infection. In conclusion, there was no association between multibacillary leprosy and HBV infection in this setting.

Orientadores: Fernando Lopes Gonçales Junior, Neiva Sellan Lopes Gonçales / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-07T22:44:35Z (GMT). No. of bitstreams: 1 Tonetto_PriscilaAparecida_M.pdf: 2027435 bytes, checksum: ec4453a66ae541917395dc0f14142ed8 (MD5) Previous issue date: 2006 / Resumo: O vírus da hepatite B (VHB) pode ser classificado em oito principais genótipos (A-H), e essa classificação tem uma distribuição geográfica determinada. Os genótipos do VHB podem influenciar na progressão de doença. O objetivo foi determinar os genótipos e os subtipos do VHB e correlacioná-los com as variáveis clínicas epidemiológicas, laboratoriais e histológicas. Foram determinados os genótipos de 139 amostras de soro de pacientes infectados pelo VHB, coletadas em Campinas, no estado de São Paulo, Brasil. O método para genotipagem utilizado foi o seqüenciamento parcial do gene S do VHB. Os primers utilizados foram desenhados a partir de seqüências do gene S, com genótipo determinado, depositadas no GenBank. Todas as seqüências obtidas foram comparadas com as seqüências depositadas no GenBank para determinação dos genótipos. O genótipo A (55%) do VHB foi o mais predominante na população, seguido pelos genótipos C (3%), D (38%) e F (4%). Entre os pacientes infectados pelos genótipos A e D, observou-se uma provável descendência africana de 18% (14/76) e 11% (6/53), respectivamente. Entre os quatro pacientes infectados pelo genótipo C, dois possuíam descendência asiática e dois eram caucasianos. Todos os pacientes infectados pelo genótipo F eram caucasianos sem ascendência indígena relatada. Aproximadamente 30% dos pacientes eram HBeAg positivo e 70% eram HBeAg negativo. A carga viral do DNA-VHB foi aproximadamente cinco vezes mais alta entre os HBeAg positivo quando comparada aos HBeAg negativo. Os genótipos A e D são os mais prevalentes entre os pacientes, aparentemente em virtude da imigração européia em nossa região / Abstract: Hepatitis B virus (HBV) can be classified into eight major genotypes (A-H) that have mainly a geographic distribution. The HBV genotype may influence disease progression. Our objective was to determine the genotypes and the subtypes of HBV and to correlate them with the with variables clinical epidemiologies, laboratories and histological. Hepatitis B virus genotypes were determined in 139 plasma samples collected in Campinas, in the state of São Paulo, Brazil from HBV-infected patients. A method for genotyping hepatitis B virus by partial HBsAg gene sequencing with primers common to all known genotypes was developed. The results of sequencing corresponded to those found in HBV isolates obtained from GenBank, including all of the known HBV genotypes. HBV genotype A was predominant in our sample, appearing in 76 patients (55%), while genotypes C, D and F was found in 4 (3%), 53 (38%) and 6 (4%) of the patients, respectively. Among the patients infected by genotypes A and D, were observed a probably African descendents of the 18.3% (14/76) and 11.3% (6/53), respectively. Among the genotype C infected patients, 2 (50%) were of Asian descendents and 2 were Caucasians. The genotype F infected patients were all Caucasians without told indigenous origin. About 30% of the patients were HBeAg positive and 70% were HBeAg negative. The viral load of HBV-DNA was about 5 times higher among HBeAg positive than in HBeAg-negative patients. Genotypes A and D were the most prevalent among our HBV-infected patients, apparently a consequence of the types of immigration to our region / Mestrado / Ciencias Basicas / Mestre em Ciências Médicas

Orientador: Helaine Maria Besteti Pires Mayer Milanez / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-24T05:11:32Z (GMT). No. of bitstreams: 1 Candido_ElaineCristina_M.pdf: 1043425 bytes, checksum: 4797b5103af38ecbe53b5dd29b496856 (MD5) Previous issue date: 2013 / Resumo: Objetivos: avaliar a transmissão vertical (TV) em gestantes portadoras de hepatite B crônica, em um serviço universitário. Sujeitos e Método: foram analisadas as sorologias para hepatite B de todas as gestantes atendidas no serviço entre 2000 e 2005, identificando-se as HbsAg +; nessas foi realizado levantamento de prontuários, avaliando a presença do marcador de replicação viral (HbeAg positivo), imunoprofilaxia neonatal e taxa de TV. Análise de dados: foi avaliada a proporção de casos com HbsAg+ e nessas a presença do HbeAg. Para as portadoras de hepatite B, analisaram-se características clínicas e epidemiológicas através de frequências simples e a presença de TV. Resultados: entre 2000 e 2005 foram rastreadas para hepatite B no CAISM 5638 mulheres; dessas 28 (0,5%) apresentavam HbsAg+, definindo-se como portadoras crônicas. Não se encontrou nenhuma com replicação viral (HbeAg+). A idade média foi de 25 anos, com escolaridade média de sete anos, sendo 57% de brancas. O número de gestações médio foi de dois, sendo 52% de nulíparas. A categoria de exposição foi ignorada em 20; em quatro a via foi a sexual, em duas por TV e em duas por uso de drogas. A média de Idade gestacional ao parto foi de 38 semanas, com uma taxa de cesárea de 42%. O peso médio ao nascimento foi de 3094g e todos os recém-nascidos apresentaram boas condições de vitalidade e receberam imunoprofilaxia neonatal (vacina e imunoglobulina específica) nas primeiras horas de vida. Não houve TV. Conclusões: Nas gestantes atendidas no período, a prevalência de hepatite B crônica foi de 0,5%. Todas as crianças receberam imunoprofilaxia neonatal nas primeiras horas de vida e não ocorreu nenhum caso de TV, reforçando que para as gestantes sem replicação viral, as medidas de imunoprofilaxia neonatal protegeram a totalidade de seus recém-nascidos / Abstract: The purpose of this paper is to evaluate mother-to-child transmission of chronic hepatitis B in a university hospital. Subjects and methods: Hepatitis B serologic studies were pooled from all pregnant women referred to this prenatal service from 2000 to 2005. HBsAg positive patients were selected and, for those, clinical, laboratory and epidemiologic data were analyzed, including presence of HBeAg marker, immunoprophylactic procedures for the newborn and mother-to-child transmission rates. Data analysis: HBsAg carriers were characterized for clinical and epidemiologic factors associated with mother-to-child transmission. Results: Between 2000 and 2005, 5638 pregnant women were referred to high-risk prenatal care at our facility; of these, 28 women (0,5%) were HbsAg+ ¿ defined as chronic Hepatitis B virus (HBV) carriers. None of these were seropositive for HBeAg. Mean age was 25 years with a mean of 7 years of formal education and 57% were white; 52% were nulliparous. Exposure to hepatitis B virus was ignored in 20 women, sexual in 4, from mother-to-child transmission in 2 and associated with drug use in 2. Mean gestational age at delivery was 38 weeks with cesarean delivery in 42% of women. Mean weight at birth was 3094g and all newborns presented with good vitality and received immunoprophylactic procedures. There were no cases of mother-to-child transmission. Conclusion: Among all pregnant women seen at this tertiary high risk prenatal care facility between 2000 and 2005, chronic HBV infection was detected in 0,5% of patients. All newborns received immunoprophylaxis during the first hours after delivery and no case of mother-to-child transmission was detected. Our findings support that, among pregnant chronic HBV carriers without serologic evidence of active viral replication, immunoprophylactic measures are effective in preventing mother-to-child transmission in all instances / Mestrado / Saúde Materna e Perinatal / Mestra em Ciências da Saúde

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

Indiana University-Purdue University Indianapolis (IUPUI) / Despite the lifecycle of the hepatitis B virus (HBV) being extensively investigated and described, there remains a significant gap in our knowledge of arguably one of the most crucial steps in the HBV lifecycle, the formation and maintenance of a covalently closed circular DNA (cccDNA) reservoir. Advancements in our understanding of host factors and pathways involved in cccDNA formation have been made through hypothesis driven studies and shRNA/siRNA screenings. We sought to create a targeted-unbiased assay to directly observe host factor-rcDNA interactions. This was achieved through an rcDNA Co-Immunoprecipitation paired Mass Spectrometry (rcDNA-CoIP/MS) assay. We created a DNA oligo complimentary to the open portion of the HBV rcDNA, labeled with biotin, to facilitate easy precipitation of nuclear rcDNA and complexed proteins. Proteins precipitated were analyzed through liquid chromatography paired mass spectrometry (LC/MS). Along with previously reported host factors, several factors of DNA damage repair pathways/complexes were also identified. A component of the UV-DDB complex, DDB1, surfaced as a hit. UV-DDB/rcDNA binding was confirmed through ChIP-qPCR. DDB2, the DNA damage binding component of the UV-DDB complex was knocked out in HepG2-NTCP and HepAD38 cells. This resulted in a significant decrease in the formation of cccDNA in DDB2 knockout cell lines following infection or induction. The subsequent reduction of downstream indicators of cccDNA formation such as viral RNA and proteins, HBcAg and HBeAg, showed a consistent decrease with cccDNA levels. Ectopic expression of DDB2 in the knockout cell lines rescued HBV phenotypes of cccDNA levels and its downstream indicators. Inactive mutant DDB2 plasmids were also transfected into the DDB2 K/O cell lines and failed to rescue cccDNA indicators. We therefore showed through a novel assay that we can discover novel viral rcDNA-host interactions, such as the UV-DDB complex recruiting DNA repair pathways to “repair” rcDNA to cccDNA.

The purpose of this study was to investigate whether mandatory universal precautions changed nurses' body fluid exposure and reporting rates, hepatitis B vaccination rates, and human immunodeficiency virus (HIV) testing rates. Random cross-sectional surveys of nurses in Tennessee were conducted in 1991 and 1993 (n = 145 in 1991; n = 143 in 1993). The questionnaire in both surveys included frequency of body fluid exposures and reporting in the past year, and whether or not the respondent had received the hepatitis B vaccine or had been HIV tested. Findings indicated that self reported needlestick injuries decreased by 69%, and other sharps injuries decreased by 81%. Only 4.1% of all exposure incidents reported on this anonymous survey were reported to employee health officials, as required. Body fluid exposure incidents were the most common form of exposure (81%) and the most underreported. Hepatitis B vaccinations significantly increased (61.4% to 82.5%), with a nonsignificant increase in HIV testing (47.2% to 55.6%) from 1991 to 1993. Findings of this study suggest that the universal precautions regulatory mandate has been effective in increasing nurses' compliance to universal precautions. Body fluid contacts were significantly underreported and showed no decrease between 1991 and 1993.

Mathematical models have long been used to describe complex biological interactions with the aim of predicting mechanistic interactions hard to distinguish from data. This dissertation uses modeling, mathematical analyses, and data fitting techniques to provide hypotheses on the mechanisms of immune response formation and function. The immune system, comprised of the innate and adaptive immune responses, is responsible for protecting the body against invading pathogens, with disease or vaccine induced immune memory leading to fast responses to subsequent infections. While there is some agreement about the underlying mechanisms of adaptive immune memory, innate immune memory is poorly understood. Stimulation with lipopolysaccharide induces differential phenotypes in innate immune cells depending on the strength of the stimulus, such that a secondary lipopolysaccharide encounter of a constant dose results in either strong or weak inflammatory cytokine expression. We model the biochemical kinetics of three molecules involved in macrophages responses to lipopolysaccharide and find that once a macrophage is programed to show a weak inflammatory response this cannot be reverted. Contrarily, a secondary lipopolysaccharide stimulus of a very high dose or applied prior to waning of the effects of the primary stimulus can induce a phenotype switch in macrophages initially programed to show strong inflammatory responses. Some pathogens, such as the hepatitis B virus, have developed strategies that hinder an efficient innate immune response. Hepatitis B virus infection is a worldwide pandemic with approximately 257 million chronically infected people. One beneficial event in disease progression is the seroclearance of hepatitis B e antigen often in combination with hepatitis B antibody formation. We propose mathematical models of within-host interactions and use them to predict that hepatitis B e antibody formation causes hepatitis B e antigen seroclearance and the subsequent reactivation of cytotoxic T cell immune responses. We use the model to quantify the time between antibody formation and antigen clearance and the average monthly hepatocyte turnover during that time. We further expand the study of hepatitis B infection, by investigating the kinetics of the virus under an experimental drug administered during a clinical trial. Available drugs usually fail to induce hepatitis B s antigen clearance, defined as the functional cure point of chronic hepatitis B infections. Drug therapy clinical trials that combined RNA interference drug ARC-520 with entecavir have shown promising results in reducing hepatitis B s antigen titers. We develop pharmacokinetic-pharmacodynamic models describing the mechanistic interactions of the drugs, hepatitis B virus DNA, and virus proteins. We fit the model to clinical trial data and predict that ARC-520 alone is responsible for the reduction of hepatitis B s and e antigens, while entecavir is the driving force behind viral reduction. This work was supported by Simons Foundation, Grant No. 427115, and National Science Foundation, Grant No. 1813011. / Doctor of Philosophy / Mathematical models have long been used to describe complex biological interactions with the aim of predicting interactions that explain observed data and informing new experiments. This dissertation uses modeling, mathematical analyses, and data fitting techniques to provide hypotheses on the mechanisms of immune response formation and function. The immune system, comprised of the innate and adaptive immune responses, is responsible for protecting the body against invading pathogens, such as viruses, bacteria, or fungi. If an immune response to a secondary pathogen encounter differs from the response when the body first encounters the specific pathogen, this is called immune memory. The mechanisms underlying the memory of immune responses are well understood in the context of adaptive immune responses, but less so for innate immune responses. Stimulation with lipopolysaccharide, a cell wall component of many bacteria, programs innate immune cells, such as macrophages, to be in one of two states, called phenotypes, depending on the strength of the stimulus. Based on their phenotype the macrophages show either a weak or strong inflammatory response upon a secondary lipopolysaccharide encounter of a constant dose. We model the biochemical kinetics of three molecules involved in macrophages responses to lipopolysaccharide. We find that once a macrophage is programed to show a weak inflammatory response this cannot be reverted. Contrarily, a secondary lipopolysaccharide stimulus that is either of a very high dose or applied before the effects of the primary stimulus have waned, can induce a phenotype switch in macrophages initially programed to show strong inflammatory responses. Some pathogens, such as the hepatitis B virus, have developed strategies that hinder an efficient innate immune response. Hepatitis B virus infection is a worldwide pandemic with approximately 257 million chronically infected people. Hepatitis B e antigen is a protein that infected liver cells release into blood and that impairs adaptive immune responses. It is considered a beneficial event in disease progression, and called hepatitis B e antigen clearance, when hepatitis B e antigen becomes indetectable in a patient's blood. We propose mathematical models of interactions between liver cells, the virus, hepatitis B e antigens and hepatitis B e antibodies, which neutralize the antigens. We predict that antibody formation causes antigen clearance and a reactivation of immune responses. We furthermore use the model to quantify the time between antibody formation and antigen clearance and the average number of liver cells killed during that time. We further expand the study of hepatitis B infection, by investigating the kinetics of the virus under an experimental drug administered during a clinical trial. Available drugs rarely induce hepatitis B s antigen clearance, but clinical trials that combined a novel drug, called ARC-520, with the commonly used drug entecavir have shown promising results in reducing hepatitis B s antigen titers in the blood of infected patients. Following the clearance of hepatitis B s antigen, a protein that is released by infected cells and impairs adaptive immunity, the body usually has the capability to control the infection without medication. We develop mathematical models describing the interactions of the drugs, hepatitis B virus, and virus proteins. We fit the model to clinical trial data and predict that ARC-520 alone is responsible for the reduction of hepatitis B s and e antigens, while entecavir is the driving force behind viral reduction.

Antiviral therapy for patients infected with hepatitis B virus is only partially efficient. The field is in high demand for understanding the connections between the virus, immune responses, short-term and long-term drug efficacy and the overall health of the liver. A mathematical model was introduced in 2009 to help elucidate the host-virus dynamics after the start of therapy. The model allows the study of complicated viral patterns observed in HBV patients. In our research, we will analyze this model to determine the biological markers (e.g. liver proliferation, immune responses, and drug efficacy) that determine the different decay patterns. We will also investigate how such markers affect the length of therapy and the amount of liver damage. / Master of Science

Yes / A study was conducted to determine the seroprevalence of chronic hepatitis B virus (HBV) infection among children and their mothers on Kwajalein Atoll in the Marshall Islands two decades after routine vaccination was introduced in the 1990s. Mothers’ knowledge and attitudes towards HBV disease and vaccination were also assessed. Methods: Results of a national seroprevalence survey conducted in 2016–2017 and antenatal records were used to determine the prevalence of HBV seropositivity in children aged 6–8 years and their biological mothers. The associations between demographic, social and vaccination-related factors and seropositivity were explored using Fisher’s exact tests. Results: HBV seroprevalence was 0.3% in children and 6.8% in their mothers (during pregnancy). Coverage of timely HBV vaccination was 90.3% for the birth dose and was significantly associated with factors related to place of residence (P < 0.001), place of birth (P < 0.001) and number of antenatal visits (P < 0.001). Maternal attitudes towards infant vaccination and antenatal screening were largely positive (95.8% and 96.7%, respectively) despite low vaccination rates (20.9%) among mothers. Knowledge levels were low for disease complications, treatment and transmission. Discussion: Prevalence of HBV in children and mothers residing on Kwajalein Atoll in 2016–2017 was lower than the national average for the Marshall Islands. Timely birth dose administration appears to have been effective in preventing mother-to-child transmission of HBV in this setting and should be promoted in remote settings where antiviral therapy is not available. Provision of out-of-cold-chain HBV vaccines should be considered to improve access in remote settings.