Dissertations / Theses on the topic 'Hyperendemic'

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Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
A hanseníase ou mal de Hansen (MH), causada pelo patógeno Mycobacterium leprae, ainda constitui um problema de saúde pública no Brasil, e em especial no Maranhão. A doença é hiperendêmica em 77 municípios do Estado. A resposta imune ao patógeno de indivíduos dessas regiões permanece obscuro podendo contribuir na manutenção da hiperendemia. Por isso, este estudo teve por objetivo caracterizar o perfil clínico-epidemiológico e imunológico de pacientes infectados por M. leprae, e de seus contatos, procedentes de área hiperendêmica. Para o desenvolvimento deste trabalho foi realizado um estudo transversal foi realizado nos municípios de Açailândia, Imperatriz e São Luís, no período 2009 a 2012. Pacientes e contatos foram clinicamente avaliados e tiveram os dados epidemiológicos coletados. Uma amostra de sangue foi obtida para realização das sorologias para detecção de anticorpos IgM anti-PGL1 pelos testes de ELISA e ML-Flow, e dosagem de citocinas e quimiocinas. A análise descritiva demonstrou que a maioria dos pacientes eram adultos, do gênero masculino, diagnosticados principalmente com as formas intermediárias da doença (60%). Incapacidades físicas foram detectadas em 35% dos casos, a maioria da forma multibacilar (MB). Os contatos de pacientes MB, em idade adulta, do sexo feminino, de convívio intradomiciliar e com parentesco de primeiro grau com os pacientes foram maioria. Anticorpos anti-PGL1 foram encontrados em 42,6% dos casos e 12% dos contatos pelo ML-Flow. E ainda em 36,8% dos casos e 12,5 % dos contatos pela técnica do ELISA. A concordância dos testes foi moderada, porém significativa (K=0,423). A soropositividade ao PGL1 está associada às variáveis epidemiológicas de casos, principalmente. Observou-se que casos e contatos apresentam alta produção de IL-17A. Pacientes MB e contatos possuem altas concentrações séricas de IL-6. Os da forma virchowiana tem reduzida produção de TGF-β1. CXCL9 e CXCL10 foram evidentes nos MB, enquanto CXCL8 estava presente em contatos. Os aspectos avaliados confirmam o caráter hiperendêmico e a manutenção de fatores de riscos para o adoecimento de contatos. O perfil imunológico observado abre perspectivas para o conhecimento e elucidação da patogenia em regiões de grande circulação do M. leprae.
Leprosy, caused by the pathogen Mycobacterium leprae, it is a public health problem in Brazil yet, especially in Maranhão. The disease is hyperendemic in 77 counties of the State. Immune response to the pathogen of individuals in these regions remains unclear and may be contributing to maintenance of high endemicity. Therefore, this study aimed to characterize epidemiological and immunological profile of patients infected with M. leprae, and their contacts, from hyperendemic regions. Cross-sectional study was accomplished in Açailândia, Imperatriz and São Luís counties, 2009-2012. Patients and contacts were clinically evaluated and had their epidemiological data collected. A blood sample was obtained for performing serological tests IgM anti-PGL1 detection by ELISA and ML-Flow and measurement of cytokines and chemokines. Descriptive analysis showed that most patients were adults, male, diagnosed with intermediate forms mainly (60%). Physical disabilities were detected in 35% of cases, most of multibacillary form (MB). The contacts were MB patients in adult age, female, household and first-degree kinship. PGL1 antibodies were found in 42.6% of cases and 12% of contacts by ML-Flow, 36.8% of cases and 12.5% of contacts by the ELISA procedure. Concordance tests was moderate but significant (K = 0.423). PGL1 seropositivity is associated with epidemiologic features of cases, mostly. It was observed that patients and contacts present high IL-17A production. MB patients and contacts have high IL-6 serum concentration. Patients with lepromatous form had reduced TGF-β1 production. CXCL9 and CXCL10 were apparent in MB, while CXCL8 was present in contacts. The evaluated aspects confirm high endemicity and maintenance of risk factors for contact illness. Immune profile observed opens perspectives to understanding and elucidation of pathogenesis in regions where M. leprae has large circulation.

Chlamydia trachomatis is the leading infectious cause of preventable blindness and the most common sexually transmitted bacterium worldwide. Trachoma presents an environment in which to investigate chlamydial pathogenicity, the conjunctivae serving as an accessible model with an objectively observable phenotype. The Bijagós Archipelago is a unique setting where trachoma is hyperendemic. The primary aims of this study were to use novel molecular, bioinformatic and geostatistical approaches in conjunction with population-based clinical and epidemiological metadata to investigate the micro-epidemiology of ocular C. trachomatis and active trachoma in this population. The prevalence of trachoma and ocular C. trachomatis infection have been documented, and socio-environmental risk factors have been identified that may be important in the implementation of trachoma elimination activities in these communities. A strong association was found between C. trachomatis ocular load (estimated using droplet digital PCR) and the level of conjunctival inflammation. Geostatistical analyses suggest that ocular C. trachomatis load may be important in transmission, as spatial clusters of high load infections were identified, whilst spatial clusters of low load infections were absent. This study includes the first population-based pathogen genome-wide association scan (GWAS) for C. trachomatis, using high quality next generation whole genome sequence data obtained directly from clinical samples. The genomewide associations with conjunctival inflammation (incE) and C. trachomatis load (mutY and CTA_0271) present genes involved in specific biological characteristics of C. trachomatis, the functions of which suggest that early interactions with host cells are important in C. trachomatis pathogenesis. Pathogen GWAS, applied in this context, is a powerful approach in the identification of multiple targets for further study in pathogenesis and directed study of potential vaccine candidates, allowing a greater understanding of association and interaction of genes on a genome-wide scale. Following a single round of mass drug treatment with oral azithromycin (MDA) in these communities the prevalence of active trachoma and ocular C. trachomatis were significantly reduced. Individual and median loads of C. trachomatis were reduced and the highest burden of disease and infection were concentrated in young children. Spatial clustering of infection identified using geostatistical tools was intensified following MDA, but the number of clusters of high load infections was reduced. The severity of conjunctival inflammation was reduced following MDA. This study suggests that chlamydial load is important in disease pathogenesis and may be important in transmission of infection. Geospatial tools may be useful in the context of MDA to identify clusters of infection and thresholds of C. trachomatis bacterial load that may be important foci of transmission. The association between conjunctival inflammation and C. trachomatis load may reflect pathogen virulence. This is supported by the presence of genome-wide associations with C. trachomatis load and conjunctival inflammation identified by pathogen GWAS. Further epidemiological, in vitro and in silico studies are required to provide a more complete picture of the relationship between disease severity, bacterial load and chlamydial diversity in the context of transmission and elimination dynamics.

A epidemiologia da hanseníase tem demonstrado a utilização de ferramentas clínicas, moleculares e imunológicas, para o mapeamento dos principais focos de ocorrência da doenças e de áreas de alto risco de adoecimento. Programas de controle da hanseníase, doença de longo período de incubação, em que os contatos são os principais grupos de risco, devem estabelecer todos os procedimentos disponíveis para o controle desse agravo. Objetiva-se estudar aspectos epidemiológicos clínicos e imunológicos da hanseníase em município hiperendêmico do Maranhão. Estudo de epidemiológico descritivo, realizado com 599 contatos, entre outubro de 2009 a outubro de 2011, no Serviço de Dermatologia no ambulatório do Hospital Universitário da Universidade Federal do Maranhão unidade Presidente Dutra São Luís - MA. Foi observado que a maioria dos contatos foi do gênero feminino com 57,17%, a faixa etária predominante acima de 15 anos, ou seja, (64,59%) com maior frequência na faixa de 20 a 59 anos, idade adulta e produtiva e o tipo de convívio predominante é o intradomiciliar com 74,95%, a forma clínica foi HT (30,00%), a classificação operacional mais frequente foi a MB com 61,90% do gênero feminino; a maioria apresentou somente uma cicatriz vacinal pela BCG, destacou-se o gênero masculino com 63,00%. O teste Elisa apresentou percentual de 63,50% e o ML-Flow 64,00%. Considerando o resultado dos testes Elisa e ML-FLOW sugere-se a utilização das técnicas imunológicas como ferramentas necessárias para o diagnóstico precoce, controle e vigilância dos contatos como forma de interromper a cadeia de transmissão da hanseníase na cidade pesquisada.
Leprosy epidemiology has demonstrated the usefulness of clinical, molecular and immunological tools for geographical identification of the main disease occurrence foci and also of high risk disease acquiring areas. Leprosy control programs must consider its long incubation period, during which nearby contacts are the main disease risk group, and should make use of all available procedures for disease control. This paper aims to study clinical, epidemiological end immunological aspects of leprosy in a hyper endemic county of Maranhão state. Its a descriptive epidemiological study made with 599 leprosy contacts from October 2009 to October 2011 in the clinic of the Dermatology service at the Presidente Dutra unit of Maranhão Federal University Hospital. Most contacts observed were female (57,17%), more than 15 years old (64,59%), mostly between ages 20-59, an adult and productive life span. Household contact was the most frequent (74,95%) as was tuberculoid leprosy (30,00%). MB operational classification was most frequent (61,90% of females), most presenting one BCG vaccine scar, with males amounting to 63,00%. ELISA test was positive in 63,5% and ML-flow in 64,00%. These two test results suggests the use of immunological techniques as necessary tools for precocious diagnosis, surveillance and control of leprosy contacts as a means of interrupting leprosy transmission chain in the analyzed county.

Fascioliasis is a worldwide emerging snail-borne zoonotic trematodiasis with a great spreading capacity linked to animal and human movements, climate change, and anthropogenic modifications of freshwater environments. South America is the continent with more human endemic areas caused by Fasciola hepatica, mainly in high altitude areas of Andean regions. The Peruvian Cajamarca area presents the highest human prevalences reported, only lower than those in the Bolivian Altiplano. Sequencing of the complete rDNA ITS-2 allowed for the specific and haplotype classification of lymnaeid snails collected in seasonal field surveys along a transect including 2007–3473 m altitudes. The species Galba truncatula (one haplotype preferentially in higher altitudes) and Pseudosuccinea columella (one haplotype in an isolated population), and the non-transmitting species Lymnaea schirazensis (two haplotypes mainly in lower altitudes) were found. Climatic seasonality proved to influence G. truncatula populations in temporarily dried habitats, whereas L. schirazensis appeared to be more climatologically independent due to its extreme amphibious ecology. Along the southeastern transect from Cajamarca city, G. truncatula and L. schirazensis shared the same site in 7 localities (46.7% of the water collections studied). The detection of G. truncatula in 11 new foci (73.3%), predominantly in northern localities closer to the city, demonstrate that the Cajamarca transmission risk area is markedly wider than previously considered. Lymnaea schirazensis progressively increases its presence when moving away from the city. Results highlight the usefulness of lymnaeid surveys to assess borders of the endemic area and inner distribution of transmission foci. Similar lymnaeid surveys are still in need to be performed in the wide northern and western zones of the Cajamarca city. The coexistence of more than one lymnaeid transmitting species, together with a morphologically indistinguishable non-transmitting species and livestock movements inside the area, conform a complex scenario which poses difficulties for the needed One Health control intervention.
Ministerio de Economía y Competitividad
Revisión por pares

Une dynamique saisonnière régulière (hyperendémie) et épidémique est observée pour les méningites à méningocoques et pneumocoques dans la ceinture africaine des méningites. Comprendre cette dynamique est essentiel pour une meilleure prévention et modélisation. Les hyperendémies serait liées à un risque accru de méningite chez les porteurs sains du méningocoque et du pneumocoque ; ou une transmission accrue de ces bactéries par les porteurs sains et les personnes malades en saison sèche. Nous avons développé trois modèles mathématiques des méningites, incluant l’une ou la combinaison des deux hypothèses. Les modèles étaient paramétrés sur base des connaissances actuelles de la biologie et la physiopathologie des méningocoques et des pneumocoques. Nous avons comparé les performances des modèles à prédire les cas de méningites bactérienne aiguë notifiés par des formations sanitaires au Burkina Faso entre 2004-2010, dans le cadre de la surveillance des méningites. Les prédictions des modèles étaient satisfaisantes (R2, 0.72, 0.86, 0.87). Forcer la saisonnalité de la transmission seule ou et du risque de méningite permettent de mieux prédire l'amplitude des hyperendémies saisonnières. Cependant, le modèle incluant la saisonnalité de la transmission seule nécessitait un taux d'invasion constant plus élevé. Ces résultats suggèrent que des variations saisonnières du risque de méningite et de transmission des bactéries contribuent aux hyperendémies saisonnières. En conséquence, des interventions réduisant le risque de transmission et d’invasion bactériennes, pendant la saison sèche, seraient nécessaires pour limiter la saisonnalité de la méningite bactérienne en Afrique
Pathophysiological mechanisms underlying the seasonal dynamic and epidemic occurrence of bacterial meningitis in the African meningitis belt remain unknown. Regular seasonality (hyperendemicity) is observed for meningococcal and pneumococcal meningitis. Understanding this is critical for better prevention and modelling. The two main hypotheses for hyperendemicity during the dry season imply an increased risk of invasive disease given asymptomatic carriage of meningococci and pneumococci; or an increased transmission of these bacteria from carriers and ill individuals. We developed three mathematical models of seasonal hyperendemicity, featuring one or a combination of the two hypotheses. Models were parameterized based on current knowledge on meningococcal and pneumococcal biology and pathophysiology. We compared the models’ performance in reproducing weekly incidences cases of acute bacterial meningitis reported by health centres in Burkina Faso during 2004–2010, through meningitis surveillance. All models performed well (R2, 0.72, 0.86, 0.87). Seasonal forcing transmission only or and risk of meningitis better captured amplitude of seasonal incidence. However, seasonal forcing transmission alone required a higher constant invasion rate. These results suggest a combination of seasonal changes of the risk of invasive disease and carriage transmission is involved in hyperendemic bacterial meningitis in the African meningitis belt. Consequently, interventions reducing the risk of nasopharyngeal invasion and the bacteria transmission, especially during the dry season are believed to be needed to limit the recurrent seasonality of bacterial meningitis in the meningitis belt

碩士
高雄醫學大學
醫學社會學與社會工作學研究所
100
Background/Aim: The maritime part of Tzukuan Township is a documented HCV hyperendemic countryside in Taiwan with an extremely high prevalence rate of 41.6% among adults. The study aimed to assess the secular trend of HCV epidemics in this area. Methods: A consecutive 5-year of screening program has been launched in this hyperendemic area. The prevalence of anti-HCV seropositivity was evaluated in an annual manner. The potential risks of transmission were also assessed. The statistical tests were two-tailed and p < 0.05 was considered statistically significant. All procedures were performed using JMP version 9. Results: There were 312, 626, 282, 766, and 933 residents participated this screening program in 2008 to 2010 respectively. There was a significant decreasing trend of prevalence, ranging from 34.94% (109/312) in 2006, 31.79% (199/626) in 2007, 38.3% (108/282) in 2008, 24.67% (189/766) in 2009, and 22.16% (207/933) in 2010. Conclusion: In conclusion, our study shows the current status of epidemiological data about HCV infection among adults in southern Taiwan. There are different demographic features in HCV infection.

碩士
台北醫學院
公共衛生學研究所
90
A study was carried out to develop the extraction method and determine arsenic species in the main varieties of aquaculture seafood in blackfoot disease hyperendemic areas. Besides, the relationship between arsenic species of aquaculture ponds and marine arsenic species was explored. Biota samples were extracted with methanol/water (1/1) by Soxhlet extraction apparatus. The extracts were evaporated to dryness by cold evaporator, dissolved again in water, and filtered through C18 column. The concentrations of Arsenite, arsenate, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) of extracts were measured by high performance liquid chromatography linked to hydride generator and atomic absorption spectrometry (HPLC-HG-AAS). Moreover, arsenobetaine was analyzed by HPLC-ultra violet (UV)-HG-AAS. The concentrations of arsenic species were determined in 71 mouthbreeder (oreochromis mossambicus) and 26 hard clam (meretrix lusoria) samples that were aquacultured in Putai, Ichu, Peimen, and Hsuehchia areas. Oyster (Crassotrea gigas) samples were collected from Putai, Anping, Hsiangshan, Tungshih, Tungkang, and Wangkung areas. The concentrations of arsenic species in biota samples and aquaculture pond water were analyzed. There were twenty-four percentage of aquaculture ponds arsenic concentrations higher than the standard of Drinking Water Act. The arsenic concentrations of Putai and Peimen pond water were higher than those of Ichu and Hsuehchia. Total arsenic and inorganic arsenic levels of aquaculture fish were lower than oyster and hard clam. Arsenite concentration in fish was significantly correlated with inorganic arsenic concentration in pond water. Arsenate level in fish was significantly correlated with the body length, width and weight of fish. Comparing the arsenic species with oyster, fish and hard clam, the inorganic percentage of total arsenic in oyster was lowest, and arsenobetaine percentage of total arsenic in fish was highest. Arsenite concentration of oyster collected from Putai was higher than that from Anping. Although fish and hard clam were collected from aquaculture ponds, the percentage of MMA and DMA relative to the sum of arsenic and its metabolites in fish was higher than in hard clam. The percentage of arsenite relative to the sum of arsenic and its metabolites in fish was lower than in hard clam. These results suggested that arsenic metabolic capability of fish was better than that of hard clam. The percentage of arsenite in bivalve, such as hard clam and oyster, relative to the sum of arsenic and its metabolites in hard clam was higher than that in oyster. It suggested that arsenic concentration of hard clam cultured in aquaculture ponds was higher than oyster bred in ocean. The inferior marine animals accumulate inorganic arsenic easily because their metabolism capabilities are fairly low.

碩士
台北醫學院
公共衛生學研究所
89
This study was conducted to explore the relationship among nitric oxide synthase gene polymorphism, arsenic methylation capability, and the prevalence of hypertension in blackfoot disease hyperendemic area in Taiwan. Three villages, Homei, Fuhsin and Hsinming of Putai Township on the southwestern coast of Taiwan Island were selected as the study area. The residents aged 30 or more years old, who lived at least 5 days a week in the villages were recruited into this study from January to February 1989. Each study subject was personally interviewed by well-trained interviewers with standardized interview techniques and with a structured questionnaire. The history of living in the arseniasis endemic area and duration of drinking artesian well water, together with life style variables including alcohol drinking, cigarette smoking and dietary habit, as well as personal and family history of disease were obtained in the interview. In addition, the study subjects received physical examination and the fasting bloods were collected. Serum and buffy coat were separated and stored in -70℃ for the analysis of clinical biochemistry indies and nitric oxide synthase gene polymorphism. The serum samples of 327 study subjects were collected from 1993 who had urinary arsenic species data were randomly recruited as study subjects in this study. DNA was extracted from buffy coat to analyze nitric oxide synthase（eNOS） gene polymorphism utilizing polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) We found no difference in the eNOS gene polymorphism between hypertension patients and normal tension controls. On the other hand, we found that age, sex, body mass index (BMI), cumulative arsenic exposure were significantly positively related with the risk of hypertension after adjustment with eNOS gene polymorphism and arsenic metabolism capability. The higher the cumulative arsenic exposure and the lower arsenic metabolism capability increase the risk of hypertension after adjustment with age, sex, BMI, eNOS gene polymorphism. In the eNOS codon 298 (wt/wt), the odds ratio of hypertension was related with age, sex, BMI, and arsenic metabolism capability. But, the eNOS codon 298 (wt/vt) and eNOS codon 298 (vt/vt) did not related. On the other hand, in the eNOS codon 298 (wt/wt), the higher the cumulative arsenic exposure and the lower arsenic metabolism capability increase the risk of hypertension after age, sex, BMI, eNOS gene polymorphism adjustment. The same result was shown in the eNOS codon 298 (wt/vt) and eNOS codon 298 (vt/vt).

碩士
台北醫學院
公共衛生學研究所
90
The relationship between hypertension and manganese superoxide dismutase (MnSOD) gene polymorphism has been studied in the blackfoot disease endemic area. The study subjects who were over 30 years old and lived at least 5 days a week in the three villages were recruited. The data of study subjects were collected in 1989 and biological samples were obtained from 1989 to 1997. Two well-trained public health nurses performed a standardized personal interview based on a structured questionnaire. Information obtained from the interview included demographic characteristics, alcohol drinking and cigarette smoking, working and residential history, history of well water consumption as well as family history of hypertension. Moreover, DNA was extracted from buffy coat to analyze the Val/Ala variant in the mitochondrial targeting sequence in MnSOD gene utilizing polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Serum was measured for all trans-retinol, a-tocopherol, lycopene,B-carotene by high performance liquid chromatography (HPLC).The relative risk of MnSOD Val/Ala and Ala/Ala genotype was twice increment than the MnSOD Val/Val genotype after adjusting the traditional risk factors of hypertension and cumulative arsenic exposure. After adjustment for age, sex, body mass index (BMI) and cumulative arsenic exposure, MnSOD Val/Ala and Ala/Ala genotype people had higher relative risk than MnSOD Val/Val genotype people in any concentration of triglyceride and vitamin E. The relative risk of hypertension for MnSOD Val/Val genotype people in lower cumulative arsenic exposure, normal BMI and lower triglyceride level was decreased after age and sex were adjusted. The odds ratios of MnSOD Val/Val genotype and cumulative arsenic exposure over 10.2 ppm*year was 7.9, and significantly higher than MnSOD Val/Val genotype and cumulative arsenic exposure lower than 10.2 ppm*year after adjusting the important risk factors. Besides, whether lower triglyceride, LDL-cholesterol and vitamin E concentration, the relative risk of hypertension was increasing in the case of people with cumulative arsenic exposure over 10.2 ppm*year. The results of this study suggested that MnSOD gene polymorphism may be a genetic susceptible factor of hypertension and MnSOD genotype may modify individual hypertension risk. Acquired environment exposure, life style and dietary habit were also very important risk factors for hypertension.

碩士
高雄醫學院
醫學研究所
87
HCV is the second cause of chronic hepatitis and hepatocellular carcinoma in Taiwan . To shed light on the status and clinical characteristics of the HGV infection in the HCV hyperendemic area, we studied the presence of HGV viremia and anti-E2 antibodies, the relation of HGV infection to the clinical characteristics, the factors influencing the seroconversion of anti-E2 antibodies and possible association of hepatitis B, C and G viruses among residents of Mashagou where is a highly endemic area for HCV located in the southwestern coastal area of Taiwan.as an HCV hyperendemic area model. Materials and Methods: Serum of two hundred residents of Mashagou were tested for alanine aminotransferase (ALT), HBsAg, second-generation HCV antibody (anti-HCV), HCV RNA and HGV RNA by nested RT-PCR using 5'untranslated region (5'UTR)-specific primers, and anti-E2 antibody by an enzyme linked immunosorbent assay. The prevalence of serum HGV RNA and anti-E2 antibodies were also investigated in 400 consecutive volunteer blood donors. Statistical analyses: Frequency was compared between groups using the chi-square test or Fisher's exact test, and group means were compared using the t test. Stepwise logistic regression method was used to analyze the study data. Results: The prevalence of HGV viremia, anti-E2 and HGV exposure among residents of Mashagou were significantly higher than those among volunteer blood donors (17.0% vs. 3.3%, 25.5% vs. 7.5% and 39.5% vs. 10.3%, respectively; all p<0.001). The prevalence of HGV exposure was significantly higher in individuals exposed to HCV than in those without HCV exposure (45.8% vs. 24.1%, respectively; p=0.005). None of sex, age, ALT levels, marker of chronic HBV infection and HCV genotype distribution was related to the exposure of HGV. The rate of anti-E2 seroconversion in Mashagou patients exposed to HGV (57.0%) was similar to that of blood donor (68.3%). Male had significant higher rate of anti-E2 seroconversion than female did (71.0% vs. 47.9%; p=0.04) in Mashagou rather than blood donors (male: 71.0%; female: 60.0%). None of age, ALT levels, markers of chronic HBV infection and HCV exposure was related to anti-E2 seroconversion. There was no difference of serum ALT levels between HGV viremic and non-viremic individuals in each group by the status of HBsAg and HCV RNA.The mean ALT level was significantly higher in those positive for HCV RNA with or without other viral markers (HBsAg and HGV RNA) than in those negative for HCV RNA. Based on multiple logistic regression analyses, significant factors associated ALT elevation was HCV RNA with odds ratio and 95% confidence interval of 6.96 and 2.60-18.7. Conclusions: In HCV hyperendemic area of Taiwan, HGV infection is closed associated with HCV infection. With minimal pathogenic-effect of HGV infection after exposure of HGV, HCV rather than HGV played the most important clinical hepatopathic role. HGV had lower persistent infection rate than HCV and there was no influence on the recovery from HGV infection by HCV infection. The reasons for the higher seroconversion rate in male than female in HCV endemic area can not be provided and need further evaluation.

碩士
台北醫學院
公共衛生學研究所
87
To examine the association between serum micronutrient level and prevalence of hypertension/diabetes residents living in Homei, Fuhsin and Hsinming villages, the blackfoot disease hyperendemic area, in Pautai Township of Chiayi County in Taiwan. Study subjects were 1571 residents, >30 years old, who lived in the study area ≧5 days a week. During the year of 1988-1989, study subjects were interviewed by trained public health nurses using structured questionnaires. Information obtained included sociodemographic characteristics, residential history, history of drinking high-arsenic artesian well water, and lifestyle. In addition, hypertension and diabetes health examinations were conducted. And blood samples were collected after fasting. Sera from the blood samples were kept at -70℃, till regulatory blood test and micronutrient measurement. 941 study subjects participated the health examination, and 403 study subjects were determined for micronutrient levels. high-pressure liquid chromatography was used to measure serum retinol,α-tocopherol, lycopene and β-carotene levels. Serum retinol and α-tocopherol levels of women were significantly lower than those of men. The levels of β-carotene in women were significantly higher than those in men. Diabetes patients showed significantly higher levels of serum α-tocopherol than those of controls. Other micronutrients exhibited no statistical difference between diabetes patients and controls. Serum α-tocopherol levels were positive associated with cumulative arsenic exposure. For hypertension, after adjustment for age, sex, other risk factors (cigarette smoking, alcohol drinking, high-density lipoprotein/cholesterol ratio), significant association was acquired between body mass index or cumulative arsenic exposure and the odds ratio of hypertension. A significantly lower odds ratio of hypertension was observed with the high levels of serum α-tocopherol and low cumulative arsenic exposure. For diabetes, after adjustment for age, sex, other risk factors (cigarette smoking, alcohol drinking, high-density lipoprotein/cholesterol ratio), there were significant higher the odds ratios of diabetes in women and in older subjects. An increased odds ratio of diabetes, though not statistically significant, was found in the group with high cumulative arsenic exposure. High levels of serum retinol and low cumulative arsenic exposure showed lower the odds ratio of diabetes, though it was not statistically significantly.

碩士
國立臺灣大學
預防醫學研究所
93
Background Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease. However, little is known about prevalence and incidence rate and its determinants in hyperendemic hepatitis B/C area. Objectives We aimed to (1) estimate prevalence and incidence of NAFLD; (2) to develop early indicators other than abdominal sonography to identify suspected NAFLD; (3) and to elucidate the effect of determinants, particularly metabolic syndrome (MS), on NAFLD and fatty liver taking viral hepatitis and other life style factors into account. Methods A total of 67804 study subjects were enrolled for analysis derived from a community-based screening program in Keelung, Taiwan. One of the diseases for screening in this program was liver cancer with two stage method where participants were assessed by positive results of five markers, HBsAg (+), Anti-HCV (+), abnormal aspartate aminotranferase(AST) and abnormal alanine aminotranferase(ALT), and high level of α-fetoprotein of whom were subsequently referred to undergo sonography to identify liver diseases including fatty liver, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. To estimate prevalence and incidence of fatty liver, we classified the memberships of screened population into two groups, case cohort who had already fatty liver disease and normal cohort who were free of NAFLD while participants attended first screen. To estimate the prevalence of NAFLD, we used data from the results of first screen to estimate prevalence of NAFLD. To estimate the incidence of FLD, the normal cohort was followed up at regular interval of one year to ascertain newly diagnosed NAFLD. Likelihood ratio test or Receiver operating characteristics (ROC) was applied to determine the optimal cutoff point based on ALT, serum uric acid and BMI. Prevalence/Incidence Ratio method was used to estimate average duration staying in NAFLD. Cox regression time-dependent model was used to assess the influence of relevant determinants on NAFLD. Results By using abdominal sonography as the method for detecting NAFLD, the overall prevalence rate for the high risk group with positive results participants aged 20 years or older was 35.38%, with being 38.22% for male and 33.25% for female. The overall incidence rate of NAFLD in this high-risk group was 14.92% with 15.11% for male and 14.82% for female. By the application of cut-off score, -0.59, with the combination of three variables (log(ALT), BMI, and log(serum)), overall prevalence and incidence of NAFLD for the underlying general population were 28% and 7.5%. The application of the concept of the ratio of prevalence to incidence yielded 2.37 years of average duration of NAFLD among this high-risk group. For the general population of NAFLD with the application of three variables, the application of the concept of the ratio of prevalence to incidence rate yielded 3.76 years of average duration of NAFLD. After controlling for these factors in the univariate analysis in each other, the effect of MS on elevated ALT still remained statistically significant (aOR=2.57 (2.41-2.75)). The most remarkable effect was seen in subject without HBV and HCV infection (aOR=3.28 (3.03-3.54)), followed by HBV (+) and HCV (+) (aOR=2.61 (1.14-5.95)) , and HBV (+) and HCV (-) (aOR=1.53 (1.29-1.83)). In addition to MS, other significant risk factors included hypercholesterolemia (aOR=1.15 (1.08-1.22)), hyperurecemia (aOR=1.70 (1.61-1.81)), and betel quids chewing (aOR=1.19 (1.08-1.31)). After controlling for these factors in the univariate analysis in each other, the effect of MS on the risk for NAFLD was dependent on the presence of viral hepatitis B/C. The most remarkable effect was seen in subject with HBV and HCV infection (aOR=7.76 (1.31-45.90)), followed by HBV (+) and HCV (-) (aOR=1.89 (1.31-2.72)). The effect of MS on the risk for NAFLD was statistically significant in subjects in the absence of HCV and absence of HBV (1.71 (1.36-2.15)).The effect of MS on the risk for NAFLD was marginally statistically significant in subjects in the presence of HCV but absence of HBV (1.82 (0.99-3.33)). , and HBV (+) and HCV (-) (aOR=1.53 (1.29-1.83)). In addition to MS, only Hyperuricemia (aOR=1.30 (1.03-1.63)), and exercise (aOR=0.76 (0.67-0.87)). The equivalent association in subjects with ALT < 45 mg/dL found that the effect of MS on NAFLD was statistically significant after controlling other significant factors. Hyperuricemia was another independent risk factor for NAFLD after controlling for other significant risk factors. Conclusions The present study used a population-based prospective study to estimate incidence and prevalence of NAFLD for high-risk group as well as general population. The effect of relevant correlates, particularly MS (direct and indirect effect through elevated ALT), on NAFLD was heterogeneous with the presence of hepatitis B/C infection. Hyperuricemia and high BMI may be considered as another two independent factors for NAFLD.

碩士
台北醫學院
醫學研究所
85
The objective of this study is to elucidate the association among ischemic heart disease,chronic arsenic exposure indices, serum micronutrients(vitaminA, vitamin E, lycopene, α-carotene, β-carotene), urinary arsenic species(AsIII,DMA, MMA and AsV) and other risk factors. 74 prevalence cases of ischemic heart disease and 193 age-sex-matched healthy controls were selected from a study cohort of residents lived in three villages where blackfoot disease was hyperendemic. Urinary arsenic species were isolated by high performance liquid chromatography.(HPLC) and determined by automic absorption spectrometry(AAS). Serum micronutrients were determined by Htomic absorption spectrometry. There was no significant difference between urinary arsenic species and ischemic heart disease except total arsenic level. A significant dose-response relationship was observed between ischemic heart disease and drinking high- arsenic artesian well water.The relation was boarderline significant after adjustment for age,sex,α-caroteneor β- carotene, total cholesterol level, body mass index(BMI) and hypertension. There was a negtive dose-response relationship between α-carotene or β-caroteneand ischemic heart diseas. The relation on β-carotene was also significant and α-carotene was boraderline significant after adjustment for age, sex, drinkinghigh-arsenic artesian well water, total cholesterol, BNI and hypertension. Otherrisk factors, except hypertention, such as serum triglyceride, cholesterol, high density lipoprotein, low density lipoprotein, apolipoprotein A1, apolipoprotein B concentration, smoking, alcohol drinking, and liver function indices, had no significant association with ischemic heart diseas.

博士
國立臺灣大學
生物環境系統工程學研究所
97
Arsenic (As) in seafood receives public attention because it is potential hazardous to human health and frequently presents at high concentration levels. Humans are exposed to various sources of As (food, water, soil and air), but exposure via ingesting seafood is by far the most important one. This study estimates the potential carcinogenic risk of ingesting inorganic As in aquacultural fish and shellfish in the blackfoot disease (BFD) hyperendemic areas of Taiwan, using geostatistical methods and geographic information systems. Five aquacultural species, tilapia (Oreochromis mossambicus), milkfish (Chanos chanos), mullet (Mugil cephalus), clams (Meretrix lusoria) and oysters (Crassostrea gigas), are taken into account. We herein construct a rational ingestion risk diagram with considering the concentration of inorganic As and risk-based daily ingestion rate of aquaculture species. Moreover, the rational consumption rates of fish and shellfish farmed in As-affected groundwater areas are evaluated. Target cancer risks (TRs) of ingesting As contents in aquaculture fish and shellfish are spatially mapped to assess potential risks to human health and to elucidate the safety of As-polluted groundwater use in fish ponds. Owing to sparse measured data, Monte Carlo simulation and sequential indicator simulation are used to propagate the uncertainty and assessed parameters. For the first assessment (Chapter 2), the human health risk associated with ingesting inorganic As through consumption of farmed oysters in Taiwan is estimated. The results reveal that the ratio of mean concentration among the four townships of inorganic As to total concentration of As in oysters is approximately 1.64%. The estimated target cancer risks (TR), based on a 95% occurrence probability from ingesting inorganic As by consuming oysters at a rate of 18.6–56 g/day, range from 1.26×10-5 to 3.82×10-5. Moreover, a target hazard quotient (THQ) associated with ingesting inorganic As through oyster consumption at a rate of 18.6–56 g/day range from 0.071 to 0.214. Based on the estimation of the TR model, an ingestion rate of 1.6 g/day is recommended to meet the 95th percentile of carcinogenic risk, 10-6, for exposure to inorganic As through the consumption of oysters in Taiwan. Furthermore, this study investigated the relationship between As content in clams and their environment, including sediment and pond water (Chapter 3). The bioaccumulation of As in clams in their exposure environment and the potential carcinogenic risks associated with the ingestion of As in aquaculture clams are probabilistically evaluated. The average ratios of inorganic As contents to total As contents in clams ranged from 12.3% to 14.0% which are much higher than that found in the farmed oysters, indicating that humans may expose to larger quantities of inorganic As by ingesting the same amount of clams as oysters. The results of the risk assessment indicate that potential carcinogenic risks associated with consumption of clams from the BFD area rangs from slightly (4.52×10-6) to largely (80.7×10-6) exceeding the acceptable target risk. Based on the estimation of the TR model, a 0.18 g/day-person of the safe ingestion rate of clams in the BFD region is recommended. For integration of spatial information, an integrated GIS-based approach for assessing potential carcinogenic risks via food-chain exposure of ingesting inorganic As in aquaculture species in the As-affected groundwater areas is presented (Chpater 4). The analyzed results reveal that clams farmed in the western coastal ponds and milkfish farmed in the southwestern coastal ponds have the high risks to human health and tilapia cultivated mainly in the inland ponds only has high risks at the 95th percentile of TR. As-contaminated groundwater used for clams and milkfish ponds should be significantly reduced. The fact that mullet has low risks to human health revealed that As-affected groundwater can be used successively in mullet ponds. Finally, with the goal to propose the suitable consumption rates of seafood, five aquacultural species, tilapia, milkfish, mullet, clams and oysters farmed in As-affected groundwater areas are taken into account to estimate the risk-based rational consumption rates (Chapter 5). Based on the provisional tolerable weekly intake (PTWI) of 15 μg inorganic As/kg body weight suggested by the Food and Agriculture Organization/World Health Organization (FAO/WHO), the daily basis of inorganic As intake of 6.37 μg/day for provisional tolerable daily intake for fish and shellfish (PTDI ) for an adult Taiwanese is transformed. The total dietary intakes estimate for inorganic As in fish and shellfish are 0.52, 1.20, 2.17, 3.95 and 9.22 μg/day, respectively, for 5th, 25th, 50th, 75th and 95th percentiles.The 95th percentile of 9.22 μg/day is higher than PTDI. The rational consumption rate of fish and shellfish is evaluated based on the maximum acceptable lifetime risk. According to the relationship between concentrations of inorganic As (Cinorg) and risk based daily ingestion rate (RBIRf), a tolerance zone with risk range from 1×10-5 to 6.07×10-5 is graphically constructed to define the rational consumption rate of fish and shellfish for general public in Taiwan The study concludes that the integration of spatial information in assessing and managing potential carcinogenic health risk via ingestion of farmed fish and shellfish in blackfoot disease hyperendemic areas has been proposed. It suggests an effective framework for public health officials in Taiwan in assessing potential carcinogenic risks and informs consumers to wisely choose aquacultural products from As-affected groundwater areas.

碩士
臺灣大學
預防醫學研究所
95
Among causal models, a sufficient cause-component model differs from the other models in that it provides more information on causal mechanisms and defines biologic effects of several risk factors, particularly including strengths of association and their joint interaction effects. The advantage of looking at sufficient causes for the disease of interest is to give a clue to the mechanism of disease in question. We conducted a hospital-based case-control study with the inclusion of DM as a risk factor to elucidate the causal relationship leading to HCC after controlling for other major risk factors of HCC. In this hospital-based case control study, we corroborated the association between DM and HCC in Taiwan, where viral hepatitis B and C are hyperendemic. The estimated population attributable proportion indicated that diabetes accounted for 18.7% of HCC cases given 7% prevalence of diabetes. The independent contribution to the development of HCC cases in the absence of HBV and HCV infection was around 7.5%. In addition, we applied the method from the literature to calculate the adjusted population attributable proportion. We also developed a Bayesian acyclic graphic model to calculate the adjusted PAF and 95% confidence intervals.

The present study, carried out in heavily infected communities in northern Cameroon, was designed to determine the prevalence of urinary tract lesions and their association with Schistosoma haematobium (S.h.) infection and to assess the validity functional, parasitologic and bacteriologic parameters in the identification of persons at high risk for these lesions Schistosoma haematobium infection status, morphologic changes in the urinary tract (as detected by ultrasonography), functional and bacteriologic changes in the urine were determined on 980 persons selected randomly after stratification by age, sex and intensity of infection. Inclusion of egg-free controls from a hypoendemic area further facilitated measurement of association of lesions with bilharzial infection Lesions of the lower urinary tract were very frequent in the study population living in hyperendemic communities. Bladder wall hypertrophies (78%), bladder wall irregularities (67%) and bladder wall tumor/s (34%) were observed. History of persistent hematuria, level of current S.h. egg output, and massive proteinuria ($<$99 mg/dl) were the best predictors of these lesions. Large bladder tumors were, however, also strongly associated with excretion of nitrites (bacterial metabolites) in the urine and/or presence of significant bacteriuria. On the other hand, S.h. infection was associated with increased prevalence of positive excretion of urinary nitrites (14% in infected versus 2% in controls) and with increased risk for bacteriuria among children 5-14 year old (8% in infected versus 3% in the controls) Congestion of the upper urinary tract (UUT) was less frequent (4% for Hydroureter and 14% for hydronephrosis) and more confined to bilharzian patients (Less than 1 percent of controls were affected). The group at the highest risk included persons with combined LUT hyperplasia and evidence of bacterial superinfection, for whom prevalence of UUT congestion was more than 10 times higher than in controls Pathologic changes in LUT or UUT were very rare in persons with neither past history of chronic hematuria nor with current S.h. infection, most of whom were found in the control group from the hypoendemic area Observation of circadian variation in both S.h. urinary egg output and related functional changes (hematuria, proteinuria) have lead field investigators to focus their attention on midday voided urine. The present study has shown that testing first morning urine specimens could provide additional information (nitrite and bacteriuria) shown to be of high predictive value for severe uropathies. (Abstract shortened by UMI.)
acase@tulane.edu

Three studies were done in children from the Eastern Cape Province of South Africa, an area highly endemic for hepatitis B virus (HBV) infection. The objective of the first study was to investigate the epidemiology and age of acquisition of HBV infection in a community based, age stratified sample of children from 0-6 years of age (n=2299), to provide a pre-immunisation baseline measure of this infection in the population targeted for HBV immunisation in South Africa. The results suggest that there is a significant burden of HBV infection in the population targeted for immunisation (overall, 10.4% HBsAg positivity and 15.7% positive 61-72 month age group) with a high rate of chronic carriers in the early age groups of 0-6 (8.1%) and 7-12 (8.9%) months. In the second study the HBV genotypes in a randomly selected group of chronically infected individuals from the same population (n=57) was determined. The aim was to supply information regarding the naturally circulating HBV genotypes in children from this area similarly, to provide baseline information to enable the future detection of escape mutants after low dose HBV immunisation had been introduced. The predominant HBV genotype identified was A' (85.7%), genotype D was found in 11.4% and A in 2.9% of the amplified specimens. These findings suggest a unique circulation of HBV genotypes in the Eastern Cape compared to the other genotypes currently identified in South Africa. In the final study, the effectiveness under field conditions of a low-dose plasma derived (LDPD) HBV vaccine chosen for the EPI programme in South Africa was assessed. Children presenting for routine immunisations at 6 weeks of age were randomly assigned to receive either LDPD HBV vaccine through the normal clinic route (n=119) or a recombinant paediatric HBV vaccine (n=108) given under controlled conditions. Both vaccines were administered at 6 ,1 0 and 14 weeks of age. At one month after the last vaccination, LDPD vaccine induced levels of anti-HBs s 10 mlU/ml in 42.2% (95% Cl 27.99-57.77) of immunised infants whereas recombinant vaccine induced protective antibody levels in 88.6% (95% Cl 74.66-95.74) of immunised infants. These results suggest a poor performance of the LDPD vaccine under field conditions in Eastern Cape infants.