Es gibt wenige Erkenntnisse über den Zusammenhang zwischen Lamivudin induzierten Resistenzmutationen und Hepatitis B Genotypen. Die vorliegende Studie untersucht das Verhältnis zwischen diesen Mutationen und den Hepatitis B Genotypen A-D. Die Datenbank der US-amerikanischen Kongressbibliothek (Pubmed) wurde nach den Begriffen „HBV OR hepatitis B”, „YMDD”, „genotype”, und „lamivudine” durchsucht. Alle in dieser Suche gefundenen Arbeiten, die bis Juni 2009 veröffentlicht worden waren, wurden in die Studie eingeschlossen. Die Ergebnisse der Literaturanalyse wurden mit den Hepatitis B-Genomdaten zweier Referenzlabore in Tübingen und Melbourne verglichen. Insgesamt konnten 29 Arbeiten aus der Datenbankrecherche in die Literaturanalyse eingeschlossen werden. Diese Studien enthielten Daten zu insgesamt 827 Patienten, deren Hepatitis B Genotyp bekannt war und die eine Lamivudinresistenzmutation aufwiesen. In statistischen Untersuchungen konnte nachgewiesen werden, dass die rtM204V-Mutation die dominierende Mutation bei Infektionen mit Genotyp A ist. Dieses Ergebnis konnte durch die Analyse der Genomdaten der Referenzlabore bestätigt werden. Ferner konnte gezeigt werden, dass bei den Genotypen A, B, und D die rtL180M-Mutation hochsignifikant mit der rtM204V-Mutation verknüpft ist. Die Dissertationsschrift enthält neben dem Artikel „Mutation pattern of lamivudine resistance in relation to hepatitis B genotypes: hepatitis B genotypes differ in their lamivudine resistance associated mutation pattern“ (Damerow, H, Yuen L et al.; J Med Virol. 2010 Nov; 82(11):1850-8) eine Einführung in die Rationale der Studie, eine Zusammenfassung der Ergebnisse sowie ein Fazit.

Se estudiaron 236 historias clínicas de pacientes atendidos en el Hospital Edgardo Rebagliati Martins, desde el año 2000 hasta julio del 2004.con fibrosis o cirrosis hepática por hepatitis viral B y C con el objetivo de evaluar el valor de diagnóstico de la ultrasonografía en comparación con el diagnóstico histopatológico. Se aplicó un sistema de puntaje ultrasonográfico a cada paciente de acuerdo a los signos US clasificándolos en una escala de 4-11. Se transcribieron los puntajes histopatológicos según el sistema METAVIR y se evaluó la sensibilidad, especificidad, valor predictivo positivo y valor predictivo negativo para la puntuación US, compuesta de superficie, parénquima, borde hepático y pared porta. A partir del punto óptimo se hallaron gráficos de curvas ROC lo que permitió tener una mejor visión de las pruebas de diagnostico. Se halló que una puntuación US 6 fue el mejor punto de corte para la predicción de Cirrosis y fibrosis grado III relacionados a HBV y HCV, con sensibilidad, la especificidad, el valor predictivo positivo y el valor predictivo negativo de 97.2%, 71.4%, 89.9%, 90.95 respectivamente. Las puntuaciones US están altamente y significativamente correlacionado 0.73(P<0.01) con la histopatología. La ultrasonografía en el diagnostico de la fibrosis y cirrosis por hepatitis B y C, muestra un mayor valor en la sensibilidad (85.39), la especificidad (85.71) y exactitud (85.59) en relación a la superficie del hígado. Los resultados demuestran que la ultrasonografía es un examen confiable para el diagnostico de la cirrosis y la fibrosis hepática tanto para la hepatitis viral B y C, aunque con mayor predicción para la hepatitis viral B. Los datos permiten concluir que la fibrosis y la cirrosis por hepatitis B y C, pueden ser correctamente diagnosticadas con un 85.59% de exactitud empleando un solo signo ultrasonográfico (superficie del hígado).

published_or_final_version / abstract / Medicine / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / toc / Medicine / Master / Master of Philosophy

JESSICA MASTRODOMENICO An Examination of the Socio-Demographic Characteristics Associated with Adult Vaccination Prevalence for Preventable Diseases in the United States Background: An estimated 50,000 adults in the United States (U.S.) die each year from one of 10 vaccine preventable diseases. For those who survive vaccine preventable infections, health care costs and loss of income become more significant. While children in the U.S. aged 0-2 exhibit vaccine prevalence rates of almost 90%, some adult vaccine prevalence rates in the U.S. population are reported to be nearly 30-40% less than the goals set forth by Healthy People 2010. The purpose of this study was to examine the associations between socio-demographic characteristics of U.S. adults and adult vaccination prevalence for pneumococcal, hepatitis A, hepatitis B, tetanus, and pertussis. Methods: Data from the 2008 National Health Interview Survey were assessed examining various health indicators and characteristics of non-institutionalized adults and children. The sample was restricted to adults ≥18 years of age. Odds ratios were calculated and multivariate logistic regression was also conducted. P-values of <0.05 and 95% confidence intervals were used to determine statistical significance. Results: There were 21781 total observations; 19.3% received the pneumococcal vaccine, 9.4% received the hepatitis A vaccine, 27.2% received the hepatitis B vaccine, 55.1% received the tetanus vaccine, and 15.2% received the pertussis vaccine. Of the socio-demographic characteristics examined, age, health insurance, marital status, and education were significant for either all five or at least four of the vaccines included in this study. As one might expect those who reported health insurance and those who had a higher level of education usually had a higher likelihood of vaccine receipt as compared to those without health insurance and those with less than a high school education. Age associations varied due to age-related recommendations for certain vaccines such as pneumococcal (recommended for adults ≥65). Compared to the married population (referent), marital status results varied, but for reasons unclear. Whites, the referent group, were the most likely to be vaccinated as compared to Blacks, Hispanics/Latinos, and Asians. Hispanics/Latinos typically had the lowest likelihood of vaccination in this examination. Conclusions: This study further explores the impact of socio-demographic disparities on vaccination status and adds new information to the literature regarding adult vaccination rates for preventable diseases. While research exists related to strengthening interventions such as patient reminder systems, those who do not see the same health care providers on a regular basis remain at risk for lower vaccination prevalence. It is important to better understand the role of social determinants of health, specifically in terms of vaccinations. Future research is needed to further characterize the association of socio-demographic factors with receipt of optional vaccines in adults.

Hepatitis C virus (HCV) is a small single stranded RNA virus, that belongs to the Flaviviridae family. HCV can be classified into six major genotypes and more than 50 subtypes.

Recently a new Flavivirus, GB Virus C also referred to as Hepatitis G virus (GBV-C/HGV) was identified in humans with indeterminate hepatitis . Whilst in non-African countries this discovery led to an enormous enthusiasm to elucidate an association with liver disease, very little was known about the prevalence and pathogenicity of GBV-C/HGV infection in KwaZulu Natal, South Africa, where Hepatitis B Virus (HBV) infection is endemic and infection with the Human immunodeficiency virus (HIV) is a catastropic health problem. Sera from patients with liver disease (chronic liver disease [n = 98]; alcoholic liver disease [n = 50]); high risk groups (haemodialysis patients [n = 70]; HIV positive mothers and their babies [n = 75]) and control groups (alcoholics without liver disease [n = 35] and blood donors from the four racial groups [n = 232]) were screened for GBV-C/HGV RNA and Anti-E2 antibodies by reverse transcription polymerase chain reaction (RT-PCR) and an enzyme linked immunosorbent assay (ELISA), respectively. Overall 43.9% (43/98) of patients with chronic liver disease; 60 % (30/50) of patients with alcoholic liver disease; 47.1% (33/70) of haemodialysis patients; 60% (21/35) of alcoholics without liver disease and 31.9% (74/232) of blood donors (Africans] 44/76; 5.9%); Asians (5/52; 9.6%); Whites (15/49; 30.6%) and "Coloureds" [mixed origin] (9/54; 16.6%)]) were exposed to GBV-C/HGV infection as determined by the detection of Anti-E2 &/or RNA in serum. There was a significant difference in the prevalence of GBV-C/HGV infection (RNA &/or anti E2) between African blood donors and the other racial groups (p < 0.001), between blood donors and haemodialysis patients (p = 0.02) and or patients with chronic liver disease (p =0.04). There was no significant difference in the prevalence of GBV-C/HGV between African blood donors (45/76, 59.2%) and alcoholics with and without liver disease (30/50, 60% and 21/35, 60%, respectively). Anti-E2 antibodies and GBV-C/HGV RNA were almost mutually exclusive. GBV-C/HGV infected dialysis patients tended to have had more transfusions (p = 0.03) and had a longer duration of dialysis than non infected patients, indicating that the majority of patients on maintenance haemodialysis acquire their GBV-C/HGV infection through the transfusions they receive. There was no evidence for in utero and/or intrapartum transmission of GBV-C/HGY. However, there is some mother-to-infant transmission of GBV-C/HGV, though it is very probable that in KZN GBV-C/HGV is transmitted by as yet undefined non-parenteral routes. Sequence and phylogenetic analysis of the 5' non-coding region (5' NCR) and E2 gene segments of the GBV-C/HGV genome identified an additional "genotype" (Group 5) of GBV-C/HGV that is distinct from all other known GBV-C/HGV sequences (Groups 1-4). Although there is a high prevalence of Group 5 GBV-C/HGV isolates in KZN, there was no significant difference in liver biochemistry between GBV-C/HGV infected and noninfected patients with liver disease or between blood donors in each of the four racial groups. There was no significant differences in CD4 (461.12 ± 163.28 vs 478.42 ± 181.22) and CD8 (680.83 ± 320.36 vs 862.52 ± 354.48) absolute cell counts between HIV positive patients co-infected with GBV-C/HGV and those not infected with GBV-C/HGV, respectively. However, significantly higher relative CD3 [80.0 ± 4.17% vs 70.99 ± 19.79%] (p = 0.015), gamma delta T cells (yLT) [3.22± 1.30% vs 2.15 ± 29.12%] (p = 0.052) and lower CD 30 [35.45 ± 17.86% vs 50.59 ± 9.20%] (p = 0.041) status were observed in GBV-C/HGV positive compared to GBV-C/HGV negative HIV infected patients, respectively. Although there is a high prevalence of novel Group isolates of GBV-C/HGV in KZN, the lack of elevated liver enzymes and clinical hepatitis in blood donors and haemodialysis patients suggests that GBV-C/HGV is not associated with liver disease. HBV and not GBV-C/HGV modifies the course of alcoholic liver disease. The relatively higher number of CD3 cells and increased yLT expression, together with a decrease in CD 30 cells tends to suggest an association with protection and or delayed progression of HIV disease in GBV-C/HGV infected patients. Whilst GBV-C/HGV is not associated with liver disease, it may be an important commensal in HIV infected patients. / Thesis (Ph.D.)-University of Natal, 2003.

People with hepatitis C (HCV) face stigma and discrimination because of the association of this disease with injecting drug use (IDU). Research has found that many instances of HCV-related discrimination occur in the health care sector. Health care workers' beliefs about their HCV positive clients are likely to influence how they relate to clients and their treatment delivery. This research assessed the implicit and explicit attitudes of both health care workers and their HCV positive injecting drug using (HCV+) clients toward each other and then established whether these affect the treatment experiences of health care workers and clients. The sample consisted of 60 health care workers (doctors and nurses), 120 HCV+ and 120 HCV- clients, recruited from the same treatment facility. Participants were given a series of attitude and treatment experiences measures to complete. Data illustrate that while health care workers' and HCV+ clients' explicit attitudes towards each other were positive, clients with HCV still rated their health care workers less highly and reported less satisfaction with their treatment than HCV- clients. Analyses also indicated that more conservative health care workers displayed greater prejudice toward their HCV+ clients because they believe that injecting drug use is controllable. This prejudice toward IDUs on the part of health care workers was associated with worry about the behaviour of IDU clients and this worry in turn predicted differences in treatment experiences reported by HCV+ and HCV- clients. These data support the contention that health care worker concerns, particularly those related to injecting drug use, underlie discriminatory treatment of people with HCV. Finally the research also addressed the impact of health care worker contact with HCV+ clients on their attitudes towards this group. Analysis revealed that while health care workers who have had more contact with people with HCV show more positive explicit attitudes, they also show less favourable implicit attitudes toward IDUs. This may reflect the difficulties and stresses associated in caring for IDUs and may provide insight into the hidden costs involved for health care workers working with a population that may be challenging and at times difficult to manage.

The use of mathematical models in studying disease epidemics can be diverse, from the focused study of the role of a single determinant of the epidemic, or to the overall estimation of morbidity and mortality. In using simple deterministic models, a balance is struck between biological and social complexities, and the high data input demands of mathematical models. This thesis aims to apply the use of deterministic mathematical models to the studies of HIV and hepatitis C epidemiology in the Asia-Pacific region. In Australia, about 85% of reported HIV cases are among homosexual men. Casual homosexual partnerships made up 40% of incident HIV cases in 1995 increasing to 65% in 2004. In the state of New South Wales, it was estimated that over 7,500 people were living with HIV/AIDS in 2005, increasing to over 10,000 by 2016 with existing levels of intervention. Intervention measures were estimated to have prevented some 44,500 cases, the majority being among injecting drug users through the Needle and Syringe Programmes. Models for the HIV epidemics in developing countries were also developed incorporating multiple routes of HIV transmission. For Papua New Guinea, it was estimated 64,000 people were living with HIV/AIDS in 2005, rising to over 500,000 by 2025 with current levels of intervention. High levels of interventions, in particular increased condom use, will be required to achieve a stabilisation or reduction in HIV prevalence. In East Timor, the HIV epidemic is still in the early stages with 138 people estimated to be living with HIV/AIDS, rising to 5,000 by 2025 with minimal intervention. For HCV, models of the epidemic in Australia showed HCV incidence peaking in 1999, followed by a decline reaching 9,700 incident cases in 2005. Of 197,000 estimated chronic HCV cases in 2005, 58% had stage F 0/1 liver disease, 15% F 2/3 liver disease, and 2% HCV-related cirrhosis. Models estimated 210 and 105 people developed HCV-related liver failure and hepatocellular carcinoma, respectively. Comparisons of modelled HCV long-term sequelae projections with linkage data showed relatively good agreement, despite discrepancies in liver-related deaths. To decrease the number of chronic HCV, at least a tripling of treatment coverage would be required. These models provide estimates of the current levels of epidemics as well as projections of future scenarios under different intervention strategies, which have an important role in the planning of strategies, as well as assessment of previous epidemic conditions.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 5 uppsatser.