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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 金傳春(Chwan-Chuen King) | |
dc.contributor.author | Yi-Shiuan Li | en |
dc.contributor.author | 李宜軒 | zh_TW |
dc.date.accessioned | 2021-06-13T00:02:43Z | - |
dc.date.available | 2011-08-13 | |
dc.date.copyright | 2007-08-13 | |
dc.date.issued | 2007 | |
dc.date.submitted | 2007-07-30 | |
dc.identifier.citation | Azeredo, E.L., Zagne, S.M., Santiago, M.A., Gouvea, A.S., Santana, A.A., Neves-Souza, P.C., Nogueira, R.M., Miagostovich, M.P. and Kubelka, C.F. (2001) Characterisation of lymphocyte response and cytokine patterns in patients with dengue fever. Immunobiology 204, 494-507.
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Immunology/ Richard A Goldsby, Thomas J. Kindt, Barbara A. Osborne and Janis Kuby.—5th edition 2003 p.276-298; A13-A15 趙黛瑜 (2003) 1998-99年台南第三型登革病毒導致登革出血熱爆發流行之流行病學探究暨病毒分子變異群與疾病嚴重程度之相關性 國立台灣大學公共衛生學院流行病學研究所博士論文 宋紫玲 (2001) 登革病毒之基因分析及定量國立台灣大學醫學院微生物學硏究所碩士論文 吳民惠 (2004) 台灣地區第二型登革病毒的分子流行病學 國立台灣大學公共衛生學院流行病學研究所碩士論文 王慧婷 (2003) 台灣地區2002-2003年登革熱與登革出血熱病人T淋巴球上CD38活化與病毒量、可溶性TNF-受體、IL-15及其臨床病癥之關係 國立台灣大學公共衛生學院流行病學研究所碩士論文 沈倬光 (2003) 人類化學激素及其受體在登革熱與登革出血熱病人所扮演的角色國立台灣大學公共衛生學院流行病學研究所碩士論文 林鶯熹, 吳淑靜, 徐爾烈, 鄧華真, 何兆美, 白秀華 2002年台灣登革熱流行區埃及斑蚊的抗藥性. 台灣昆蟲. 2003;23:11. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/28206 | - |
dc.description.abstract | 登革出血熱(Dengue hemorrhagic fever, DHF)與登革熱(Dengue fever, DF)是由登革病毒(Dengue virus, DENV)所引起的急性蟲媒傳染病,其流行中滋生嚴重病例之致病機制至今仍無法完全解釋。本研究包含兩大部分:(一) 2006年通報至台灣疾管局之全國登革確定病例進行流行病學分析,及(二)登革病毒免疫流行病學深入探究,由定點醫師收集2006年高屏地區登革流行中發病而願參與者之血液,利用同一人不同發病時點的樣本進行病例對照研究,以第三型登革病毒即時定量反轉錄聚合酶連鎖反應[One-step TaqMan-based real-time reverse transcriptase polymerase chain reaction (RT-PCR)]及液相多重蛋白定量技術(BD™ Cytometric Bead Array, CBA),分別偵測血清中病毒量及各種細胞激素/化學激素(Cytokines/Chemokines)之濃度,是第一次整合流行病學、免疫學、病毒學及臨床表徵四角度之貫穿數據分析,欲探討同一病人不同發病時程(急性期、退燒期、恢復期)之病毒量、Th1/Th2免疫/發炎反應的細胞激素/化學激素及其交互作用是否與健康對照組不同;又同一流行區隨時間之拉長與傳播密度之增高是否其臨床症狀呈現更趨嚴重度之關聯性 | zh_TW |
dc.description.abstract | Mechanisms of dengue hemorrhagic fever (DHF) caused by dengue virus (DENV) have attracted many interests. To our knowledge, this is the first study that integrated epidemiology, clinical manifestations, immunology and virology to investigate the changing patterns of viral and host immune responses along the epidemic of dengue /DHF that might be associated with the increasing severity of DHF cases. This study involved two parts: (1) epidemiological analysis of the 2006 epidemic of dengue /DHF in southern Taiwan, and (2) immuno-epidemiological case-control study on the interplays between viral and human host factors at three different stages of disease process of patients (acute, defervescence, and convalescent) and in various epidemic time periods (early, middle and late) and areas (high or low transmission intensity). Blood samples of DF/DHF patients in southern Taiwan from June to December in 2006 collected by our sentinel physicians through active surveillance plus age-/gender-matched healthy controls were used to measure the viral load and the concentrations of cytokines and chemokines by one-step dengue virus serotype 3 (DENV-3) specific TaqMan-based real-time reverse transcriptase polymerase chain reaction (RT-PCR) and BD™ Cytometric Bead Array (CBA) respectively. Through comparison in quantitative measurements of Th1/Th2 and inflammatory cytokines and chemokines and their association with viral load and clinical manifestations/severity plus subsequent stratification and multivariate epidemiological data analysis, we can elucidate immuno-pathogenesis mechanism(s) of DHF at both individual and population levels under the unique epidemiological characteristics of dengue in Taiwan.
Epidemiological analysis of the 1076 official confirmed dengue cases [1057 dengue fever (DF) cases and 19 DHF cases] reported to Taiwan-CDC showed that the overall incidence rate was 0.822 per million and case fatality rate of DHF was 21.05% (4/19). DENV-3 was the dominant serotype (81.7%, 389/476). Most indigenous dengue cases occurred in Kaohsiung and Pingtung (98.14%, 949/967) and its incidence rate was 2.670 per million. The age older than 40 was one of the risk factors contributing to DF (56.5%, 597/1057) and DHF (63.2%, 12/19) (p=0.014) but the percentage of DHF cases in children ≦17 year-old in 2006 was higher than that in 2002 (31.6%, 6/19 vs. 7.9%, 16/230). Areas near the boundary of Kaohsiung City and Fungshan City were the most severe epidemic regions, similar to the 2002 severe epidemic sites in Taiwan. The dynamic diffusion of dengue cases over the 2006 epidemic periods showed relocation besides the neighborhood spreading. In the immuno-epidemiological investigation, we collected serum samples of 47 DF, 14 DHF and 14 healthy controls after the re-confirmation of their clinical category as DF and DHF cases by two experienced physicians of infections [mean±sd (range) of age: 47.6±17.4(5~74)、45.2±23.1(1~79) and 40.4±26.8 (12-79) years]. Symptoms/signs of classical dengue were found in more than 50% of dengue cases but DHF cases manifested more petechiae, loss of appetite and easily getting tired. Both DF and DHF patients had atypical lymphocytes and abnormal liver function (GOT: 71.53±47.75 vs. 38.67±17.43 units) only at defervescence stage, thrombocytopenia (112.20±89.36 vs. 126.69±86.34 K/ml). DHF compared to DF patients had prolonged activated partial thromboplastin time (APTT: 37.91±9.50 vs. 54.32±17.90 sec), more lymphocytes at acute and defervescence stage but lower numbers of monocytes at acute stage (9.00±4.46 vs. 5.23±2.53, p=0.022). About half (29/61, 47.5%) of dengue patients had chronic illness, particularly hypertension (14.8%, 9/61) and diabetes (11.5%, 7/61). Virological and immunological analysis found that secondary dengue virus infection was more common than primary infection (77.0%, 47/61) in all dengue patients. Higher viral load was found in acute phase (n=18) than defervescence (n=25) of those dengue patients with secondary infection patients [RNA mean±SD: 3.16±2.57 log copies/ml vs.0.76±1.55 log copies/ml, p=0.001), and the similar results were found in the all DF patients (p=0.001). Additionally, the levels of the 5 cytokines (IL-1β, IL-2, IL-4, IL-10, TNF-α, IFN-γ) and 4 chemokines (RANTES, IP-10, MCP-1, MIG) of DF patients were higher than those of DHF patients whereas the levels of the IL-6 and IL-8 were much higher in DHF patients (IL-6: 6.5±5.1 vs. 20.7±16.2 pg/ml; IL-8: 85.8±306.1 vs. 498.2±1179.0 pg/ml). Additionally, the levels of IL-2 and IFN-γ in defervescence stage of DF patients were higher than those of DHF patients (IL-2: 8.6±6.2 pg/ml vs. 4.1±4.9 pg/ml, p=0.078; 52.6±141.8 vs. 8.8±8.1pg/ml, p=0.038). It indicates that immune activation of T cells decreased once the clinical severity increased. Particularly, IL-2 levels at 1-3 days after onset of illness interacted with viral load and RANTES in acute phase were negatively related to the duration of illness [β slope=0.09 (p=0.02) and β=-0.04 (p=0.03) in multiple linear regression after controlling of age, co-morbidity and days of rash. Furthermore, viral load was positively associated with the duration of illness after controlling of age, co-morbidity and days of rash. In other words, any of the three conditions including: (1) decreasing of IL-2 and RNATES without changes of viral load, or (2) decreasing IL-2 concomitant with increasing of viral load without changes of RANTES, or (3) increasing viral load that would lead to long duration of illness, serving for prognosis of clinical severity. Interestingly, Moreover, the level of IL-2 elevated at later period of the epidemic (>37 wk) (β=4.52, p=0.03) but declined at areas with increasing of transmission intensity (β=-4.94, p=0.02) (R2adj=0.22). The levels of inflammatory cytokine TNF-α in acute phase also negatively correlated with the interaction between duration of an epidemic wave and intensity of transmission (β=-2.31, p=0.03) (R2adj =0.15). Therefore, we suggested that population-based dynamic changes of immune responses rather than viral load occurred at different periods and various geographical areas during the epidemic of dengue/DHF. In conclusion, defects in the levels of IL-2 and IFN-γ found at defervescence of DHF patients and the activation of IL-6 and IL-8 in Taiwan were different from the “cytokine cascade only” reported in the sera of severe DHF/DSS patients in South East Asian countries where dengue was endemic or hyper-endemic. This implies that different environments of epidemic areas might involve different mechanisms of immuno-pathogenesis of DHF. Future efforts are needed to measure the levels of innate immunity and type I interferon at different time points of infectious process to fully understand the causal inference of series interactions between viral and host factors under different environmental conditions that enhance the immunopathogenesis of DHF. | en |
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dc.description.tableofcontents | Chinese Acknowledgements………………………………………………………… i
English Acknowledgements…………………………………………………………. ii Chinese Abstract…………………………………………………………………….. iii English Abstract……………………………………………………………………... vii Chapter 1 Introduction……………………………………………………………… 1 Chapter 2 Literature Review………………………….............................................. 3 2.1 Introduction of Dengue Virus………………………………………………….. 3 2.2 Epidemiology of dengue/DHF in Taiwan…………………………………….... 3 2.3 Clinical Symptoms and Hematological Measurements of DF vs. DHF……….. 5 2.4 Primary Infection vs. Secondary Infection of Dengue Virus…………………... 6 2.5 Viral Load and Disease Severity……………………………………………….. 8 2.6 Important Cytokines/ Chemokines Related to Dengue………………………… 9 2.6.1 Innate Immunity and Acute Phase Responses…………………………….. 10 2.6.2. Inflammatory Cytokines/Chemokines……………………………………. 11 2.6.3. Immunologically Regulatory and Deactivator Cytokines/Chemokines…...12 Chapter 3 Objectives, Specific Aims and Hypotheses……………………………...14 3.1 Objectives…………………………………………………………………...…. 14 3.2 Specific Aims…………………………………………………………………... 14 3.3 Hypotheses……………………………………………………………………... 15 Chapter 4 Materials and Methods………………………………………………….. 18 4.1 Study Design and Study Populations…………………………………………... 18 4.1.1 Epidemiological Analysis of the 2006 Epidemic of Dengue/DHF in Taiwan………………………………………………………………….. 18 4.1.2 Overall Study Design, Study Area and Period…………………………… 18 4.2 Data Collections………………………………………………………………... 20 4.2.1 Clinical Information and Case Definition…………………………………. 20 4.2.2 Questionnaire……………………………………………………………… 21 4.3 Spatial and Temporal Mapping………………………………………………….. 21 4.4 Laboratory Methods……………………………………………………………... 22 4.4.1 Laboratory Diagnosis of Dengue………………………………………….. 22 4.4.2 Measurements of Viral Load Using Real time RT-PCR………………..… 23 4.4.3 Measurements of Human Cytokines and Chemokines by BD™ Cytometric Bead Array (CBA)………………………………………………………… 24 4.5 Statistical Tests………………………………………………………………… 24 Chapter 5 Results……………………………………………………………………. 26 5.1 Epidemiological Characteristics of the Confirmed Dengue Cases Reported to Taiwan-CDC in 2006…………………………………………………………… 26 5.1.1 Incidence Rate of the 2006 Nationwide Confirmed Dengue Cases……… 26 5.1.2 Demographical Information and Age-Specific Incidence Rates of the 2006 Nationwide Confirmed Dengue Cases Compared with the 2002 Dengue Cases……………………………………………………………………... 27 5.1.3 Temporal and Spatial Epidemiological Characteristics of the Confirmed Dengue Cases…………………………………………………………….. 28 5.2 Comparison in Demographical, Clinical and Epidemiological Characteristics of the Recruited Dengue Cases for Immuno epidemiological Studies in Taiwan in 2006………………………………………………………………….………….. 31 5.2.1 Demographical Characteristics of the Recruited Subjects in Immuno epidemiological Study…………………………………………………… 31 5.2.2 Epidemic Curve of the Subjects in Immuno-epidemiological Study…….. 31 5.2.3 Past History of Dengue, Japanese Encephalitis, and Medical History of Other Illness……………………………………………………………… 31 5.2.4 The Comparisons of Clinical Symptoms/Signs, Results of Liver Function, and Hematological Measurements between DF versus DHF in the 2006 Study’s Case Cohort……………………………………………………... 33 5.3 Kinetic Distributions of Viral Load in Acute and Defervescence Phases……….. 35 5.3.1 Comparison of the Kinetic Patterns of Viral Load in Acute Phase and Defervescence in DF versus DHF Cases and their Relationships with Fever Days……………………………………………………………………… 35 5.3.2 Comparison of the Viral Load in Acute and Defervescence Phases in DF versus DHF Cases Stratified by History of DENV infection……………. 36 5.4 Kinetic Distributions of Cytokines/Chemokines in Three Sampling Time Periods………………………………………………………………………….. 36 5.4.1 Comparison of the Cytokines/Chemokines in Acute, Defervescence and Convalescence Phases in DF versus DHF cases in 2006………………... 37 5.4.2 Individual Analysis of the 10 DF and 7 DHF Samples Grouping by the Level of IL-2 Secretion…………………………………………………... 39 5.5 Multivariate Analysis……………………………………………………………. 42 5.5.1 Logistic Regression Model for Analysis of Factors Associated with DHF versus DF…………………………………………………………... 42 5.5.2 Linear Regression Model for Analysis of Duration of Illness…………… 44 Chapter 6 Discussion………………………………………………………………... 47 6.1 Unique Characteristics of the 2006 Epidemic of Dengue/DHF in Taiwan…………………………………………………………………………. 47 6.1.1 The 2006 Epidemic of Dengue/DHF in Taiwan…………………............. 47 6.1.2 Similarities and Differences in the Temporal and Spatial Characteristics of the Epidemic of Dengue/DHF in 2006 vs. 2002 in Kaohsiung City and Fungshan City……………………………………………………….. 49 6.2 Levels and Kinetic Changes of Viral Load among Several Studies……………. 51 6.2.1 Similarities and Differences in Kinetic Patterns of DENV-3 Viral Load in DF vs. DHF Compared to Other Studies………………………………… 51 6.2.2 Similarities and Differences in Levels of Viral Load, Disease Severity and the Scales of Outbreaks in Various DENV Serotypes.………………......... 52 6.3 The Comparison of Kinetic Changes in Levels of Cytokines/ Chemokines among Several Studies…………………………………………………………………. 52 6.3.1 Similar and Different Kinetic Patterns of Cytokines/ Chemokines in DF vs. DHF Compared to Other South East Asian Countries.…………………… 53 6.3.2 Difference in Our Study Population Compared to the Studies in South East Asian Countries………………………………………………………. 54 6.4 Factors Related to the Emergence of DHF Cases and Severity of Dengue Epidemic– Valuable Experiences in Taiwan………………………………………………… 56 6.5 Study Limitations…………………………………………………………………. 57 6.5.1 Study Populations………………………………………………………… 57 6.5.2 Specimens’ Collections…………………………………………………….. 59 6.5.3 Recall Bias and Missing Data in Questionnaires…………………………... 60 6.6 Future Directions…………………………………………………………………. 60 6.6.1 Study Design: Community-based Cohort Study……………………………60 6.6.2 Other Immunological Measurements………………………………………. 61 6.6.3 Other Viral Measurements…………………………………………………. 63 6.6.4 Data Analysis………………………………………………………………. 64 References……………………………………………………………………………. 65 Tables…………………………………………………………………………………. 69 Figures………………………………………………………………………………... 94 Autobiography............................................................................................................104 Appendixes…………………………………………………………………………..105 Table Contents Table 1: The Total Numbers of Confirmed Indigenous and Imported Dengue Cases and Affected Areas in Taiwan, 1981-2006……………………………………… 69 Table 2: Summary of Literature Review of the Seven Studies on Published Years, Study Areas and Periods, Sample Sizes, Age Groups and the Clinical Symptoms between Dengue Fever (DF) and Dengue Hemorrhagic Fever (DHF)/ Dengue Shock Syndrome (DSS) Patients……………………………………………. 70 Table 3: Summary of Literature Review of the Seven Studies on Published Year, Study Area and Period, Sample Size, Age and the Clinical Chemistry Measurements between Dengue Fever (DF) and Dengue Hemorrhagic Fever (DHF)/Dengue Shock Syndrome (DSS) Patients……………………………………………. 72 Table 4: Summary of the Two Immune Theories Proposed to Explain the Immuno Pathogenesis Associated to Primary and Secondary Infections of Dengue... 74 Table 5: Summary of Literature Review of Studies on Published Year, Study Area and Period, Sample Size, Age and the Secreted Levels of Cytokines/Chemokines Related to Dengue Fever (DF) and Dengue Hemorrhagic Fever (DHF)/ Dengue Shock Syndrome (DSS) Patients………………………………….. 75 Table 6: Demographic Characteristics of All Confirmed Dengue Patients Reported to the Centers for Disease Control in Taiwan (Taiwan-CDC), 2006………….. 77 Table 7: Age-specific Incidence Rates of Total Confirmed Dengue and Dengue Hemorrhagic Fever Cases in (a) Taiwan and (b) Major Affected Areas in Kaohsiung City, Kaohsiung County, and Pingtung County in 2006………. 78 Table 8: Comparisons among Different Temporal Risk Types of Dengue Cases in Kaohsiung City and Fungshan City in Taiwan in (a) 2002 and (b) 2006….. 79 Table 9: Demographic Characteristics of 61 Patients with Dengue Fever versus Dengue Hemorrhagic Fever in Southern Taiwan in 2006…………………………… 80 Table 10: Past Dengue History of the 47 DF and 14 DHF Patients Recruited in our Immuno-epidemiological study who had Dengue Illness in Southern Taiwan in 2006…………………………………………………………………….. 81 Table 11: The Year Acquiring Past Dengue in the 47 DF and 14 DHF Patients Recruited in our Immuno-epidemiological study in Southern Taiwan in 2006……… 81 Table 12: Past History of Japanese Encephalitis (JE) and JE Vaccination the 47 DF and 14 DHF Recruited in our Immuno-epidemiological study in Southern Taiwan in 2006…………………………………………………………………….. 82 Table 13: Clinical Histories of Past Other Illness or Co-morbidity in 47 DF and 14 DHF Patients Recruited in our Immuno-epidemiological study in Southern Taiwan in 2006……………………………………………………………. 82 Table 14: The Three Major Underlying Diseases in 25 DF and 4 DHF Patients Recruited in our Immuno-epidemiological study in Southern Taiwan in 2006……………………………………………………………………….. 82 Table 15: The Duration, Median and Range of Clinical Symptoms between 47 DF and 14 DHF Patients Recruited in our Immuno-epidemiological study in Southern Taiwan in 2006………………………………………………….. 83 Table 16: The Results of Hematological Measurements and Liver Function Tests at 3 Sampling Time Points between 47 DF and 14 DHF Patients Recruited in our Immuno-epidemiological study in Southern Taiwan in 2006…………….. 84 Table 17: Comparison of the Viral Load of DENV-3 at Acute and Defervescence Phases between the 47 DF and 14 DHF Cases Recruited in our Immuno-epidemiological study in Southern Taiwan……………………... 86 Table 18: Correlations between Age and Levels of 7 Cytokines and 5 Chemokines at Acute Phase, Defervescence and Convalescence in the 61 Dengue Patients Recruited in our Immuno-epidemiological study in Southern Taiwan in 2006……………………………………………………………………….. 87 Table 19: The Means and Media of the Secreted Levels of the 7 Cytokines and 5 Chemokines among 47 DF, 14 DHF and 14 Healthy Controls Recruited in our Immuno-epidemiological study in Southern Taiwan in 2006………… 88 Table 20: Detailed Information on Age, Duration of Viremia, Viral Clearance Rate, the 4 Cytokines (IL-2, IL-10, IFN-γand IL-10) and 2 Chemokines (RANTES and IL-8) in Paired Serum Samples Collected from the 10 DF Patients in Two Groups with Different Patterns of Levels of IL-2 and the 5 DHF Patients……………………………………………………………………. 91 Table 21: Hematological and Liver Function Measurements of the Paired/Triple Serum Samples Collected from the 10 DF Patients in the Two Groups with Different Patterns of IL-2 and 5 DHF Patients Recruited in our Immuno-epidemiological study in Southern Taiwan in 2006…………….. 92 Table 22: Multivariate Analysis of Factors Influencing the Disease Severity of DHF after Controlling of Age, Co-morbidities, and Past History of Dengue by Linear or Logistic Regression Analyses in 61 Patients Recruited in our Immuno-epidemiological study in Southern Taiwan, 2006………………. 93 Figure Contents Figure 1: A Map of the Study Area of the 2006 Epidemic of Dengue/DHF in Kaohsiung and Pingtung in Southern Taiwan…………………………… 94 Figure 2: A Flow Chart of Overall Study Design, Data Collection, Laboratory Measurements, and Data Analysis……………………………………….. 95 Figure 3: An Epidemic Curve of the 2006 Confirmed DF and DHF Cases plus Percentages of DHF/Total Dengue Cases in Taiwan by the Week of the Onset of Dengue Illness …………………………………………………. 96 Figure 4: The Geographical Distributions of (a) Dengue Fever, (b) Dengue Hemorrhagic Fever and (c) Total Dengue Cases in Kaohsiung City and Fungshan City of Southern Taiwan in 2006…………………………….. 96 Figure 5: Comparisons of the Dynamic Spreading Patterns of Confirmed Dengue Cases over the five Periods during the Epidemic of Dengue/DHF in Kaohsiung City and Fungshan City in (a) 2002 and (b) 2006……………. 97 Figure 6: The Spatial Distributions of the 3 Epidemiological Indices (Frequency, Duration, Intensity) of the 2006 Confirmed Dengue Cases in Kaohsiung City and Fungshan City in (a) 2002 and (b) 2006, Normalized by Standard Deviation……………………………………………………….. 98 Figure 7: Three Maps of the Eight Spatial Risk Areas with Three Temporal Characteristics in (a) 2002 (b) 2006 and (c) the Overlap Areas in Both 2002 and 2006…………………………………………………………………. 99 Figure 8: Onset Weeks of the Confirmed DF and DHF Cases plus Percentages of DHF/total Cases Recruited in our Immuno-epidemiological Study in southern Taiwan in 2006………………………………………………….. 99 Figure 9: The Kinetic Patterns in the Levels of DENV-3 Viral Load on Two Different Days after the Onset of Fever and Their Relationships with Fever Days...100 Figure 10: The Levels of (a) IP-10 (b) IL-10 at Convalescence and (c) RANTES at defervescence by Age and Their Correlation Plots……………………… 101 Figure 11: Kinetic Patterns of the Viral Load of DENV-3 and the Levels of IL-2, IL-8, RANTES and IL-10 in the Two Representative DF Cases with (a) high and (2) low levels of IL-2 at Defervescence and (c) one DHF sample…………………………………………………………………….102 | |
dc.language.iso | en | |
dc.title | 免疫流行病學:2006年台灣地區登革熱/登革出血熱病人病毒量、免疫反應、臨床嚴重度及流行病學特徵之關係 | zh_TW |
dc.title | Immunoepidemiology: The Relationship among Epidemiological Characteristics, Clinical Severity, Viral Load and Immune Responses in Patients of Dengue Fever versus Dengue Hemorrhagic Fever in Taiwan, 2006 | en |
dc.type | Thesis | |
dc.date.schoolyear | 95-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 何美鄉(Mei-Shang Ho),李文宗(Wen-Chung Lee),吳漢忠(Han-Chung Wu),伍安怡(Betty A. Wu-Hsieh),江伯倫(Bor-Luen Chiang),顧家綺(Chia-Chi Ku),高全良(Chuan-Liang Kao) | |
dc.subject.keyword | 登革熱/登革出血熱,病毒量與致病,免疫致病機轉,細胞激素/化學激素,流行嚴重機轉,蟲媒傳染病,台灣, | zh_TW |
dc.subject.keyword | dengue fever/dengue hemorrhagic fever,viral load and disease progression,mechanism of immuno-pathogenesis,cytokine/chemokine,mechanism of epidemiological severity,vector-born infectious disease,Taiwan, | en |
dc.relation.page | 116 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2007-07-31 | |
dc.contributor.author-college | 公共衛生學院 | zh_TW |
dc.contributor.author-dept | 流行病學研究所 | zh_TW |
顯示於系所單位: | 流行病學與預防醫學研究所 |
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