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Purpose: The aim of this study is to model the impact of needle exchange interventions on human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Methods: In order to model the impact of needle exchange interventions, behavioural effects (sexual and drug use) were translated into estimates of the number of HIV and HCV cases averted by the programs through a mathematical model. Behavioural effects data on 63 clients had been collected previously by two Health Units in Ontario. The secondary data were analyzed to estimate the number of HIV and HCV cases averted while accounting for co-infection. A Bernoulli process model was used to estimate the number of averted cases for the condom distribution and counselling aspects of the needle exchange intervention. A modification of the Bernoulli process model was used for needle exchange interventions to account for drug use behaviours. Furthermore, this model estimated the number of cases averted while also accounting for the clients’ partner’s co-infection status. Once the number of HIV and HCV cases averted was determined, a cost analysis was conducted to estimate the net medical savings of the interventions. Costs were converted to 2011 Canadian dollars. Results: Of the 63 clients, 21.40 HIV and 5.18 HCV cases were directly averted by the needle exchange intervention when HIV/HCV co-infection status of the partner was not taken into account. When the clients’ partners’ co-infection status was taken into account, lesser numbers were directly averted by the needle exchange intervention. The discounted medical savings averted were $6,950,028 and $6,741,331 when co-infection was and was not accounted for, respectively, for the 63 individuals. Conclusion: The study demonstrated a different modeling method to account for HIV and HCV cases averted in the context of needle exchange. This study provides a foundation for future large scale cost-effectiveness studies. / Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2014-04-29 13:45:07.698

RATIONALE: A low cost point of care test (POCT) to diagnose hepatitis C virus (HCV) viremia could be a critical step toward HCV elimination. The aim of this study is to inform the limit of detection (LOD) for an affordable POC test. METHODS: This study analyzed a convenience sample of cross-sectional HCV testing data from reference laboratories and clinical research studies in 9 countries. Participants of all ages with quantified HCV viremia were included. We analyzed the distribution of HCV viral load for the first detectable HCV RNA available, and derived the clinical sensitivity for a POCT with an LOD of 3 log IU/mL. Bivariate and multivariate analyses were then performed to identify demographic and clinical characteristics associated with low-level viremia (< 3 log IU/mL). RESULTS: The dataset included 53,295 participants from Cambodia, Canada, Cameroon, Georgia, Indonesia, Malaysia, Pakistan, Thailand, and Vietnam. Log HCV RNA was normally distributed, and ≥ 3 log IU/mL corresponded with clinical sensitivity of 98%. Neither HIV co-infection nor cirrhosis were significantly associated with low-level viremia, whereas bivariate analyses showed increased odds of 2.47 (95% CI 2.04, 2.99) for low-level HCV RNA among those ≤ 30 years old compared to those > 30, and an OR of 1.17 (1.02, 1.34) among females compared to males. Stepwise multivariate regression found no significant confounding. CONCLUSION: In this global dataset, a POCT with a LOD of 3 log IU/mL would identify 98% of chronic HCV infections. The increase OR among those ≤ 30 years old year olds is likely explained by a greater frequency among younger persons of recent infection, where fluctuating viremia is well described. A POCT for HCV that could identify persons with 3 log IU/mL or greater would likely facilitate affordable product development and expand the reach of HCV testing in resource-limited settings. / 2019-03-17T00:00:00Z

Submitted by Alessandra Portugal (alessandradf@ioc.fiocruz.br) on 2013-10-01T01:06:28Z No. of bitstreams: 1 Tese Mestrado MT 2010 Viviane F Meneses.pdf: 1266674 bytes, checksum: 3a1ab36412880125693e28ed53b23715 (MD5) / Made available in DSpace on 2013-10-01T01:06:28Z (GMT). No. of bitstreams: 1 Tese Mestrado MT 2010 Viviane F Meneses.pdf: 1266674 bytes, checksum: 3a1ab36412880125693e28ed53b23715 (MD5) Previous issue date: 2010 / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil / A infecção pelo vírus da hepatite C (HCV) é um problema de saúde pública, não somente no Brasil, mas em todo o mundo. A disponibilidade de testes diagnósticos data de 1989, quando foi caracterizado o genoma do HCV. A partir desses estudos foi possível o desenvolvimento de testes que permitem a detecção de anticorpos contra o HCV, como os testes imunoenzimáticos (ELISA ou enzyme-linked immunosorbent assay) e RIBA (recombinant immunoblot assay), bem como técnicas para detecção qualitativa e quantitativa do RNA do HCV por meio da reação em cadeia de polimerase (PCR) e técnicas para determinação dos genótipos do HCV. Recentemente, foi lançado um teste comercial de detecção simultânea de anticorpos anti-HCV e antígeno core do HCV, cujos estudos têm demonstrado uma redução significativa no período de janela imunológica quando comparado à detecção de anticorpos anti-HCV, tornando-o de grande eficácia para o diagnóstico precoce. Dessa forma, o presente estudo teve como objetivo avaliar o desempenho do teste imunoenzimático baseado na detecção simultânea de anticorpos anti-HCV e antígenos core do HCV (Murex HCV Combinação Ag/Ac) no diagnóstico de pacientes com infecção aguda e crônica pelo HCV. A partir da análise do banco de dados do Programa de Diagnóstico Molecular da Hepatite C, foram selecionadas amostras de soro de pacientes com infecção crônica e com resultados inconclusivos de anti-HCV, além de amostras negativas para controle negativo e de um painel de casos agudos de hepatite C. Estas amostras foram submetidas ao teste Murex HCV Combinação Ag/Ac, ao teste de detecção de anticorpos anti-HCV (HCV Ab; RADIM) e testes de detecção qualitativa e quantitativa do HCV-RNA (COBAS AMPLICOR HCV Detection v2.0 e COBASTM AMPLICOR HCV MONITOR v2.0). Os resultados foram registrados em banco de dados criado no programa Access e analisados com auxílio do programa estatístico EpiInfo versão 3.3.2. O teste Murex HCV Combinação Ag/Ac, além de ser de fácil e rápida execução, demonstrou ótimo desempenho em comparação com os outros testes sorológicos e moleculares analisados, sendo 100% eficiente na detecção de amostras reativas independente do genótipo e do subtipo infectante. O teste Murex HCV Combinação Ag/Ac forneceu resultados 100% concordantes com os resultados obtidos pelos outros testes realizados nos diferentes grupos, excetuando-se apenas o grupo de amostras de pacientes com resultados inconclusivos de anti-HCV, onde o teste Murex HCV Combinação Ag/Ac teve uma concordância de 96,4% em relação à detecção de anticorpos anti-HCV. Contudo, o teste Murex HCV Combinação Ag/Ac pode ser uma alternativa para o diagnóstico molecular da infecção pelo HCV em países em desenvolvimento, onde a utilização dos testes baseados em NAT ainda é pouco exequível. / A infecção pelo vírus da hepatite C (HCV) é um problema de saúde pública, não somente no Brasil, mas em todo o mundo. A disponibilidade de testes diagnósticos data de 1989, quando foi caracterizado o genoma do HCV. A partir desses estudos foi possível o desenvolvimento de testes que permitem a detecção de anticorpos contra o HCV, como os testes imunoenzimáticos (ELISA ou enzyme-linked immunosorbent assay) e RIBA (recombinant immunoblot assay), bem como técnicas para detecção qualitativa e quantitativa do RNA do HCV por meio da reação em cadeia de polimerase (PCR) e técnicas para determinação dos genótipos do HCV. Recentemente, foi lançado um teste comercial de detecção simultânea de anticorpos anti-HCV e antígeno core do HCV, cujos estudos têm demonstrado uma redução significativa no período de janela imunológica quando comparado à detecção de anticorpos anti-HCV, tornando-o de grande eficácia para o diagnóstico precoce. Dessa forma, o presente estudo teve como objetivo avaliar o desempenho do teste imunoenzimático baseado na detecção simultânea de anticorpos anti-HCV e antígenos core do HCV (Murex HCV Combinação Ag/Ac) no diagnóstico de pacientes com infecção aguda e crônica pelo HCV. A partir da análise do banco de dados do Programa de Diagnóstico Molecular da Hepatite C, foram selecionadas amostras de soro de pacientes com infecção crônica e com resultados inconclusivos de anti-HCV, além de amostras negativas para controle negativo e de um painel de casos agudos de hepatite C. Estas amostras foram submetidas ao teste Murex HCV Combinação Ag/Ac, ao teste de detecção de anticorpos anti-HCV (HCV Ab; RADIM) e testes de detecção qualitativa e quantitativa do HCV-RNA (COBAS AMPLICOR HCV Detection v2.0 e COBASTM AMPLICOR HCV MONITOR v2.0). Os resultados foram registrados em banco de dados criado no programa Access e analisados com auxílio do programa estatístico EpiInfo versão 3.3.2. O teste Murex HCV Combinação Ag/Ac, além de ser de fácil e rápida execução, demonstrou ótimo desempenho em comparação com os outros testes sorológicos e moleculares analisados, sendo 100% eficiente na detecção de amostras reativas independente do genótipo e do subtipo infectante. O teste Murex HCV Combinação Ag/Ac forneceu resultados 100% concordantes com os resultados obtidos pelos outros testes realizados nos diferentes grupos, excetuando-se apenas o grupo de amostras de pacientes com resultados inconclusivos de anti-HCV, onde o teste Murex HCV Combinação Ag/Ac teve uma concordância de 96,4% em relação à detecção de anticorpos anti-HCV. Contudo, o teste Murex HCV Combinação Ag/Ac pode ser uma alternativa para o diagnóstico molecular da infecção pelo HCV em países em desenvolvimento, onde a utilização dos testes baseados em NAT ainda é pouco exequível.

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Bc. Eva Davidovová Supervisor: prof. PharmDr. Petr Pávek, Ph.D. Title of diploma thesis: Viral hepatitis: novel insights and novel therapeutic interventions. Viral hepatitis is a well-known worldwide problem. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are characterized by the development of serious complications, especially with regard to the transition to the chronic stage of the disease, associated with the development of fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Interactions between viruses and host cells are quite complicated and not always fully understood. In general, the infection cycle of viruses is a multi-step process. A closer understanding of the entire life cycle of the virus is a major prerequisite for the invention of effective drugs. Viral hepatitis B and C have long been treated mainly with interferon alfa. Ribavirin was later added to HCV treatment and nucleoside / nucleotide analogs (NA) were introduced for HBV. Interferon was later pegylated to improve its properties. However, these drugs did not provide sufficient efficacy and were additionally associated with a number of side effects. It is precisely because of these disadvantages of the current...

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Inter- and intra-host Hey variation was investigated. First. a polymerase chain reactionrestriction fragment length polymorphism procedure was used to assign genotypes and subtypes to Hey infecting 567 individuals (comprising haemophilia patients, blood donors, intravenous drug users, attenders of antenatal and genito-urinary medicine clinics and chronic liver disease patients) from England and Wales. The majority of infections were associated with types 3a, 1 a and 1 b, and genotype distributions were generally similar in different sub-populations. Only 1 % of individuals were identified as being infected with more than one subtype. The intra-host variability of Hey in a selection of haemophilia patients, blood donors and intravenous drug users was then studied. For each individual, peR clones derived from the NS5b and 5' non-coding regions of the Hey genome were screened for sequence differences by denaturing gradient gel electrophoresis (DGGE) and nucleotide sequencing. The complexity and diversity of Hey quasi species, though differing between individuals, could not be correlated with the risk group to which the study patients belonged. Furthermore, no mixed genotype or subtype infections were identified. Thus the hypothesis that multiply exposed individuals are infected with a greater variety of HCY variants could not be substantiated. The DGGE procedure was further used to investigate the hypothesis that HCY genetic evolution occurs uniformly in patients during the acute phase of infection. Changes in diversity in the HCY hypervariable region 1 in individuals undergoing seroconversion were observed to differ between patients, thereby negating that hypothesis. Moreover, in a given individual, Hey could be subjected to either positive or negative selective pressure. Thus, factors other than the acute-phase host response determine the course of Hey genetic evolution.

1 / Fatma Aboulnasr