Thesis (MPH)--University of Limpopo, 2010. / Introduction: Hepatitis B is a serious liver disease caused by the hepatitis B virus (HBV), with an estimated 360 million chronic infections worldwide, about a million of which die each year from chronic liver diseases. In South Africa (SA) over 50% of the population has been infected by HBV, and at least 3 million people are chronic HBV carriers. Chronic HBV carriers have the potential of transmitting HBV parenterally in the hospital setting, thus health care workers (HCWs) are at risk of contracting HBV, with the most likely exposure being via a needle stick injury (NSI). There is an effective vaccine against HBV which is recommended by the SA Department of Health, yet previous studies have shown that most HCWs are not vaccinated. Aim and objectives: The study aimed to investigate the knowledge, attitudes and practices regarding hepatitis B vaccination amongst HCWs in the Ekurhuleni Metro. Objectives were to determine: (1) the level of knowledge of HCWs about vaccination against HBV; (2) the attitudes of HCWs towards vaccination against HBV; (3) the practices of HCWs regarding HBV prevention and (4) the barriers to / predictors for effective HBV vaccination among HCWs at Ekurhuleni Metro Materials and Methods: This was a cross-sectional descriptive study which made use of a self-administered questionnaire that was sent to Ekurhuleni nurses and doctors who were working in 3 public hospitals, 7 district clinics, and 110 general practices. Results: Two hundred and fifteen questionnaires were distributed and 161 were returned giving an overall response rate of 74.9%. HCWs do not report their NSI; over a third [37.6% (41/81)] always reported the NSI; while 72% (116/161) of HCWs had been vaccinated, only 61.2% (71/116) of those vaccinated had received all 3 doses of the vaccine. For knowledge of HBV vaccination, 66.5% (107/161) scored poor; 31.7% (51/161) scored moderate; and 1.8% (3/161) scored high. For attitudes towards HBV vaccination, 0.6% (1/160) scored negative; 24.4% (39/160) scored neutral; and 74.5% (120/160) scored positive. A positive attitude score was a significant predictor for being vaccinated (OR=1.13, p=0.007) Conclusion: Guidelines should be put in place to increase vaccination uptake and reduce the risk of exposure to HBV infection by HCWs

Although Australian epidemiology of HBV and HCV has been well described for populations groups at higher risk, but the information available for groups generally considered to be lower risk is much more limited. An understanding of the prevalence of these infections and their risk factors in antenatal women is important to guide testing policy and practice. A study was therefore conducted of the epidemiology of hepatitis B and hepatitis C infection in women. In addition, women were asked about their experience with antenatal testing. A total of 516 women participated in the survey, of these 479 (95%) women had been tested for HCV antibodies .The prevalence of HCV antibodies was 4% overall, and 2% among women who were unaware of their HCV status prior to their antenatal test. A history of injecting drug use and residing with a HCV positive person were significantly associated with HCV infection in multivariate analyses. HBV testing was conducted in 468 (99.6%) of women, and the overall prevalence was 2%. Risk factors identified were birthplace in countries of South East Asia. Women were asked about their perception of antenatal testing and pre-test information. Nearly a third (143, 30.5%) of women who had been tested for HCV infection either said that they did not know whether they had been tested, or said that they had declined testing. The corresponding proportion for HBV infection was 28.8% (135). Over 65% and 66% of women said that had not received any information about testing for HCV and HBV respectively. The finding that virtually all antenatal women were being tested for HCV was in contrast to government and non-government organisation policies of ???selective??? screening in place during the study period. Of concern was the substantial proportion of women who were tested despite reporting that they had declined their clinician???s offer to test for HCV and HBV, and the large number of women who reported an absence of pre-test information. Women who said they had received information reported the delivery and quality of information varied according to the antenatal clinician group, but perceived the overall quality as poor.

Hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma and liver cirrhosis worldwide. HBV vaccination can prevent new infections, but effective antiviral drugs are not available for a large number of HBV infected patients. To develop novel antiviral drugs, a better understanding of the regulation of HBV gene expression is vital. One important aspect is to understand how HBV hijacks the cellular machinery to export unspliced RNAs from the nucleus of a cell to the site of incorporation into new HBV particles. The HBV post-transcriptional regulatory element (HBV PRE) is a cis acting RNA element found in all HBV transcripts. It has been reported to play an important role in the nuclear export of HBV mRNAs. Moreover, it has the ability to enhance expression of intronless as well as unspliced transcripts. Despite concerted investigations, the functional core element of HBV PRE remains unknown and the exact mechanism of how HBV PRE mediates nuclear export is unclear. This project first produced a complete HBV genome with comprehensive annotation of both coding regions and regulatory signals, which was then used for comparative genomic analysis. The functional elements of the HBV PRE were first subjected to analysis in silico. The HBV PRE is highly conserved among HBVs. Based on this sequence conservation and prediction of conserved RNA secondary structure, potentially functional HBV PRE elements including the previously reported elements (HBV SLα and HBV SLβ) were identified. Experimental deletion analysis of the HBV PRE sequence showed that the effect of each of these elements on the intronless reporter gene�s expression was similar to that of the entire full length HBV PRE. Thus, the results suggested that overall HBV PRE function was not due to additive effects from the individual elements. Surprisingly, a specific sub-section of HBV PRE decreased the level of reporter gene expression. This sub-section has not been identified previously, thus it is a novel HBV PRE inhibitory element. Further analyses using specific reporter assays revealed that the HBV PRE enhanced expression of an unspliced reporter gene whereas the RNA nuclear export elements of retroviruses, CTE (in MPMV) and RRE (in HIV-1) were not able to. Therefore, these results indicate that HBV PRE is involved in inhibition of splicing and it utilizes a different mechanism from CTE and RRE. Interestingly, HBV PRE was observed to be unable to enhance the expression of an intronless luciferase gene. Therefore, HBV PRE is not able to enhance cytoplasmic expression of all intronless transcripts. This project also addressed the idea that the RNA-binding protein, polypyrimidine tract binding protein (PTB) is a positive trans-acting factor for HBV PRE function. Transient expression of exogenous PTB in cultured cells showed no specific effect on constructs containing HBV PRE. Moreover, reduction of endogenous PTB by RNAi did not affect HBV PRE function. Therefore, the results presented in this project do not support the hypothesis that PTB plays a role in HBV PRE function. Given that HBV PRE is highly conserved and present in all HBV transcripts, it makes a good target site for novel molecular therapeutic treatments such as siRNA. To identify potential siRNA target sites within HBV PRE, an RNAi study using a plasmid expressing shRNA against HBV PRE was done. The results from the RNAi study revealed that the expression of a reporter gene could be significantly reduced by siRNA targeted to the HBV PRE. Overall, this project produced a highly annotated HBV genome that can be used as the reference sequence for comparative genomic analysis. Moreover, this work identified novel regulatory elements within HBV PRE that are likely to play an important role in HBV gene expression. Furthermore, the study also identified an excellent siRNA target site within HBV PRE that may inhibit HBV gene expression.

Hepatitis B is a serious global health problem with over 2 billion people infected worldwide and 350 million suffering from chronic hepatitis B (CHB) infection. Infection can lead to chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) accounting for 320,000 deaths per year. Numerous treatments are available, but with a growing number of therapies each with considerable trade-offs, the optimal treatment strategy is not transparent. This dissertation investigates the relative efficacy of treatments for CHB and estimates the health related quality of life (HRQOL) and health utilities of mild to advanced CHB patients. A systematic review of published randomized controlled trials comparing surrogate outcomes for the first year of treatment was performed. Bayesian mixed treatment comparison meta-analysis was used to synthesize odds ratios, including 95% credible intervals and predicted probabilities of each outcome comparing all currently available treatments in HBeAg-positive and/or HBeAg-negative CHB patients. Among HBeAg-positive patients, tenofovir and entecavir were most effective, while in HBeAg-negative patients, tenofovir was the treatment of choice. Health state utilities and HRQOL for patients with CHB stratified by disease stage were elicited from patients attending tertiary care clinics at the University Health Network in Toronto. Respondents completed the standard gamble, EQ5D, Health Utilities Index Mark 3 (HUI3), Short-Form 36 version-2 and a demographics survey in their preferred language of English, Cantonese or Mandarin. Patient charts were accessed to determine disease stage and co-morbidities. The study included 433 patients of which: 294 had no cirrhosis, 79 had compensated cirrhosis, 7 had decompensated cirrhosis, 23 had HCC and 30 had received liver transplants. Mean standard gamble utilities were 0.89, 0.87, 0.82, 0.84 and 0.86 for the respective disease stages. HRQOL in CHB patients was only impaired at later stages of disease. Neither chronic infection nor antiviral treatment lowered HRQOL. Patients with CHB do not experience lower HRQOL as seen in patients with hepatitis C. The next step in this area of research is to incorporate the estimates synthesized by the current studies into a decision model evaluating the cost-effectiveness of treatment to provide guidance on the optimal therapy for patients with HBeAg-positive and HBeAg-negative CHB.

The recombinant Hepatitis B surface antigen vaccine inadequately protects those living with HIV from Hepatitis B virus infection. This study utilized saved serum samples from a retrospective cohort of persons with HIV and documented vaccine-induced HBsAb seroconversion to determine factors associated with persistence of protective levels of HBsAb (≥10mIU/ml). HBsAb levels fell below 10mIU/ml in 27% of the cohort after a median follow-up of 43 months. HIV viral load suppression (<50copies/ml) at the time of vaccination was the major factor associated with persistence of protective levels of HBsAb (OR 3.83, p <0.01). Among individuals who lost protective levels of HBsAb, booster doses of vaccine re-instated the development of protective levels of HBsAb. Delaying or repeating HBV vaccination until after suppression of HIV viral load is achieved should be considered HBV antibody levels should be followed over time and boosters given with loss of protective levels of HBsAb.

The recombinant Hepatitis B surface antigen vaccine inadequately protects those living with HIV from Hepatitis B virus infection. This study utilized saved serum samples from a retrospective cohort of persons with HIV and documented vaccine-induced HBsAb seroconversion to determine factors associated with persistence of protective levels of HBsAb (≥10mIU/ml). HBsAb levels fell below 10mIU/ml in 27% of the cohort after a median follow-up of 43 months. HIV viral load suppression (<50copies/ml) at the time of vaccination was the major factor associated with persistence of protective levels of HBsAb (OR 3.83, p <0.01). Among individuals who lost protective levels of HBsAb, booster doses of vaccine re-instated the development of protective levels of HBsAb. Delaying or repeating HBV vaccination until after suppression of HIV viral load is achieved should be considered HBV antibody levels should be followed over time and boosters given with loss of protective levels of HBsAb.

Hepatitis B is a serious global health problem with over 2 billion people infected worldwide and 350 million suffering from chronic hepatitis B (CHB) infection. Infection can lead to chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) accounting for 320,000 deaths per year. Numerous treatments are available, but with a growing number of therapies each with considerable trade-offs, the optimal treatment strategy is not transparent. This dissertation investigates the relative efficacy of treatments for CHB and estimates the health related quality of life (HRQOL) and health utilities of mild to advanced CHB patients. A systematic review of published randomized controlled trials comparing surrogate outcomes for the first year of treatment was performed. Bayesian mixed treatment comparison meta-analysis was used to synthesize odds ratios, including 95% credible intervals and predicted probabilities of each outcome comparing all currently available treatments in HBeAg-positive and/or HBeAg-negative CHB patients. Among HBeAg-positive patients, tenofovir and entecavir were most effective, while in HBeAg-negative patients, tenofovir was the treatment of choice. Health state utilities and HRQOL for patients with CHB stratified by disease stage were elicited from patients attending tertiary care clinics at the University Health Network in Toronto. Respondents completed the standard gamble, EQ5D, Health Utilities Index Mark 3 (HUI3), Short-Form 36 version-2 and a demographics survey in their preferred language of English, Cantonese or Mandarin. Patient charts were accessed to determine disease stage and co-morbidities. The study included 433 patients of which: 294 had no cirrhosis, 79 had compensated cirrhosis, 7 had decompensated cirrhosis, 23 had HCC and 30 had received liver transplants. Mean standard gamble utilities were 0.89, 0.87, 0.82, 0.84 and 0.86 for the respective disease stages. HRQOL in CHB patients was only impaired at later stages of disease. Neither chronic infection nor antiviral treatment lowered HRQOL. Patients with CHB do not experience lower HRQOL as seen in patients with hepatitis C. The next step in this area of research is to incorporate the estimates synthesized by the current studies into a decision model evaluating the cost-effectiveness of treatment to provide guidance on the optimal therapy for patients with HBeAg-positive and HBeAg-negative CHB.

No description available.

El objetivo del presente trabajo fue determinar la seroprevalencia del virus de la hepatitis C (VHC) y de la B (VHB) en donadores militares y civiles que acudieron al Banco de Sangre del Hospital Naval así como los factores de riesgo asociados. Se trata de un estudio transversal, descriptivo y retrospectivo, cuyos datos epidemiológicos y resultados del tamizaje general se obtuvieron de los Libros de registros del Banco de Sangre e Historias Clínicas en el caso de los donantes militares, en el período comprendido de Enero de 1999 hasta Abril de 2004. El Test de MUREX HBsAg Versión 3 y Hepanostika Anti-HBc UniForm fueron empleados para Hepatis B, mientras que para el virus de la Hepatitis C se utilizó el Test de Elisa de tercera generación. Un total de 7009 donantes fueron registrados entre 1999 y 2004. Se incluyeron en el presente estudio 320, aquellos que presentaban anticuerpos contra el virus C (anti-VHC) y, para el virus de la hepatitis B: Antígeno de superficie (AgSupHBV) y/o Antígeno Core-IgG. Los datos recolectados fueron procesados y analizados en el paquete estadístico SPSS versión 10 para Windows: Prueba de Ji cuadrado o Prueba de Fisher. RESULTADOS: La prevalencia de portadores de VHC y VHB fue de 0.74% y 0.34%, respectivamente. La mayor población de infectados se encuentra entre los 18 y 30 años y corresponde al personal de la sanidad naval para la Hepatitis B y de Infantería de Marina para la Hepatitis C. No se pudo encontrar factores de riesgo relacionados en ninguna de las dos etiologias debido a una tasa de negación del 96,4% del total de donantes. CONCLUSIONES: Los resultados demuestran una baja prevalencia de infección por virus de hepatitis B, pero elevada para la hepatitis C de acuerdo a los reportes nacionales e internacionales. La pobre o nula asociación entre los factores de riesgo y la enfermedad por hepatitis B y C, que estaría en relación a la limitada efectividad y poca utilidad de la AEC. Se hace necesario que el escrutinio, a través de la encuesta de predonación, sea mas completo, diseñando un cuestionario capaz de detectar más factores de riesgo, probablemente determinanates en la transmisión de los virus de la hepatitis B y C. / The aim of the present work was to determine the seroprevalence of the virus of the hepatitis C (VHC) and of the hepatitis B (VHB) in military and civil donors who came to the Bank of Blood of the Navy Hospital as well as the associate factors of risk. It is a question of a transverse, descriptive and retrospective study realized in the Bank of Blood, which information epidemiological and proved from the general tamizaje was obtained of the Books of records of the Bank of Blood and Clinical Histories in case of the military donors, in the included period of January, 1999 until April, 2004. Murex’s Test HBsAg Version 3 and Hepanostika Anti-HBc UniForm were used for Hepatitis B, whereas for the virus of the Hepatitis C there was in use Elisa's Test of third generation. A whole of 7009 donors was registered between 1999 and 2004.Were included in the present study 320, those who were presenting antibodies against the virus C (anti-VHC) and for the virus of hepatitis B: Surface antigen (HBsAg) and/or Antigen Core-IgG. The information was gathered, percentages were obtained and the results were analyzed by means of SPSS 10 Windows version Statistics Program: chi-square or Fisher’s Tests. RESULTS: The prevalence of carriers of VHC and VHB was 0.74% and 0.34%, respectively. The principal infection people are between 18 to 30 years old, and belong to health navy personal for HBV infection and Marine Infantry for HCV infection. It couldn’t find risks factors in relation to the two etiologists, due a negative rate of 96,4%. CONCLUSIONS: The results suggest a low prevalence of infection for VHB but high for VHC infection in the studied population as it are indicate in the national and international reports. The poor or useless association between de risks factors and the illness it could be in relation to a limited effective and a poor utility of de Confidential Autoexclusion Exam. It’s necessary that this exam must be complete and have the property to identify more risks factors on the transmission of HBV and HCV.

published_or_final_version / Nursing Studies / Master / Master of Nursing