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研究生:傅涵
研究生(外文):Han Fu
論文名稱:以數理模式評估介入措施對臺灣結核病傳播之影響
論文名稱(外文):Evaluating The Impact of Potential Interventions on The Tuberculosis Epidemic in Taiwan
指導教授:林先和林先和引用關係
口試委員:方啟泰江振源陳昶勳
口試日期:2014-07-02
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:流行病學與預防醫學研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文種類:學術論文
論文出版年:2014
畢業學年度:102
語文別:英文
論文頁數:63
中文關鍵詞:結核病傳染病數理模型介入措施臺灣
外文關鍵詞:tuberculosisepidemic modellinginterventionsTaiwan
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若要制訂有效的結核病防治政策,首先要了解結核病的傳播方式以及相關介入措施的評估方法。然而,目前對於結核病新發個案中新感染與舊感染分別的比重仍不清楚,亦缺乏介入措施對於整體疫情的影響評估。本研究以傳染病數理模式探討臺灣的結核病流行動態,同時加入年齡結構以呈現人口變化與疾病傳播間的關係,並以1957年至1993年的八次全國結核病盛行率以及2010年的年齡別發生率為校正基準。在假設最年長與最年輕族群的結核病發病率相差五倍下,模擬結果呈現與實際通報資料相近的年齡別發生率趨勢,因此以此校正後的模型分析新舊感染與介入措施的貢獻。隨著結核病個案治療延遲時間的縮短,新感染在結核病傳播的角色逐漸式微,而舊感染再活化成為主要的發病途徑,成為臺灣在2010年58.2%新發個案之來源。另外,接觸者追蹤在過去結核病發生率的下降趨勢中具有一定的貢獻;而綜合出生率提升、接觸者潛伏感染治療與糖尿病患血糖控制等介入下,在最佳情況下可以使以2025年的發生率較2015年下降18.6%。從老年人具有高發病率的模型假設下可以看出共病現象與結核病發生危險性的關聯,此模型的分析結果也顯示舊感染目前雖為結核病新發個案之主要來源,但連帶造成之新感染亦不可忽視。最後,介入措施之評估指出潛伏感染治療與血糖控制在未來控制結核病疫情上具有潛力,但將來擴大潛伏感染治療至年齡較高的接觸者時,需要將可能引發的肝毒性一併考量。

Background:
The relative contribution of recent infection and remote reactivation to the current tuberculosis (TB) epidemiology remains unclear and has important implications for the design of TB control policy. As one of the main active case finding strategies for TB control, contact tracing can improve case detection of active TB and prevent disease progression of latent TB. However, the impact of contact tracing on TB epidemic has not been well evaluated.
Methods:
We built an age-structured compartmental model of TB transmission to capture the transmission dynamic of TB in Taiwan over the past decades. We calibrated the model to reflect the declining trend of TB prevalence observed in the eight national prevalence surveys (1957-1993) and the age-specific notification rate (2010). Based on the calibrated model, we further estimated the relative contributions of recent and remote transmission and evaluated the impact of contact tracing on the annual declining rate in notified rate.
Results:
In order to fit the age pattern of TB incidence in Taiwan, we assigned an age-dependent gradient for the parameters of primary progression rate and reactivation rate in the model. Using the calibrated model, we found that the proportion of remote reactivation among incident cases increased gradually with the declining TB prevalence, and reached 58.2% in 2010. The implementation of contact tracing for finding active TB cases had contributed to the decline in TB incidence in the past decade. With the combined scenarios for ageing trend, DM control and LTBI prophylaxis under the best-case scenario, the proportion of TB incidence reduction by 2025 was 18.6%.
Discussion:
The model-based analysis revealed a strong age-dependent pattern in the risk of disease infection and progression, indicating the potential high TB risk caused by comorbidities among elders. Although reactivation has contributed to the majority of TB incident cases, recent transmission still accounts for a substantial proportion of TB epidemic. To intensify the interventions for TB control, DM control among the elders and expanding the latent TB treatment to older adults were the potential approaches. However, the hepatotoxicity of preventive treatment in older adults should be carefully evaluated and monitored before scaling up the program.

Acknowledgement ... i
摘要 ... ii
Abstract ... iii
Content ... v
Chapter 1 Introduction ... 1
1.1 Tuberculosis epidemiology ... 1
1.2 Transmission dynamics of TB ... 2
1.3 TB Interventions in Taiwan ... 3
1.4 Study designs for evaluating TB interventions ... 5
1.5 Study aims ... 6
Chapter 2 Methods ... 8
2.1 Basic model structure ... 8
2.1.1 Natural history of TB transmission ... 8
2.1.2 Population and age structure ... 9
2.2 Modeling the impacts of TB interventions ... 10
2.2.1 Contact tracing for active TB cases ... 10
2.2.2 LTBI preventive therapy for young contacts ... 11
2.2.3 Ageing effect ... 11
2.2.4 Scaling-up the LTBI preventive therapy among contacts ... 12
2.2.5 DM control ... 12
2.3 Model Parameters ... 13
2.4 Model fitting ... 14
2.4.1 Age pattern of total population from 1950 to 2000 ... 14
2.4.2 Population-based prevalence from 1957 to 1993 ... 14
2.4.3 Age-specific notification rate in 2010 ... 15
2.4.4 Latent TB prevalence in 2000 ... 15
2.5 Outcome measurements ... 16
2.5.1 Relative contributions of recent transmission and reactivation ... 16
2.5.2 Impact of potential interventions ... 17
2.6 Uncertainty analysis ... 17
Chapter 3 Results ... 18
3.1 Relative contributions of recent transmission and reactivation ... 18
3.2 Impacts of existing interventions ... 18
3.3 Scenarios for TB control in the future ... 19
3.3.1 Ageing effect ... 19
3.3.2 Scaling-up LTBI prophylaxis among contacts ... 19
3.3.3 DM control among total population ... 20
3.3.4 Combined effect of potential interventions ... 20
3.4 Uncertainty analysis ... 21
Chapter 4 Discussions ... 22
4.1 Main findings ... 22
4.2 Relative contribution of recent transmission and reactivation ... 22
4.3 Age-specific pattern in TB transmission ... 23
4.4 Comparison of interventions ... 23
4.5 Strengths and limitations ... 24
4.6 Study implications and further research ... 25
References... 27
Figures ... 34
Tables ... 49
Appendix ... 56

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