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研究生:詹珮君
研究生(外文):Pei-Chun Chan
論文名稱:嬰兒時期接種過卡介苗的兒童其皮膚結核菌素測試反應的分布
論文名稱(外文):Distribution of Tuberculin Skin Test with Purified Protein Derivatives in Children under High Coverage of Bacillus Calmette-Guérin
指導教授:陳建仁陳建仁引用關係
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:流行病學研究所
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:2007
畢業學年度:95
語文別:英文
論文頁數:36
中文關鍵詞:皮膚結核菌素測試幼童及兒童結核病
外文關鍵詞:tuberculin skin testinfant and childrentuberculosis
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目標:欲得知在中度結核病盛行國家, 施打過卡介苗之三個月到十四歲兒童, 其皮膚結核菌素測試反應的分布,並進一步獲得正常反應的上限臨界值
方法:對按規定接種卡介苗且無免疫不全的孩童以結核菌素 PPD RT 23進行橫斷面研究。利用學童補接種前所建立的標準曲線推算出的年感染率,來對照不同年齡的受試者的反應分布。兩者之間利用goodness of fit找出最佳的臨界值,且利用曝露於痰抹片陽性結核病患之家庭內接觸者孩童的皮膚結核菌素測試反應,算出此臨界值的敏感度。
結果:由八百五十位兒童的皮膚結核菌素測試反應分析顯示,卡介苗對皮膚結核菌素測試反應的影響,在接種後逐年降低且陽性率在七歲之後不降反升。對於零到七歲的兒童,21, 20, 19, 18, 17, 16, 15, 14公釐與標準曲線推算出的年感染率差異最小,而對於八到十四歲的兒童12公釐則是最佳臨界值。 曝露於痰抹片陽性結核病患之家庭內接觸者孩童,其皮膚結核菌素測試分布不似一般兒童有與年齡相關的變化。相反的,陽性率不論年齡維持一定,故我們建議在曝露於痰抹片陽性結核病患之家庭內接觸者孩童,不論年齡一律使用10公釐當作臨界值。這組臨界值,若用於沒有已知得結核之危險因子, 臨床沒有結核病表現,沒有免疫不全的孩子,其特異性為89.8%,而且27.5%的家庭內接觸者孩童會被判定為陽性。
結論:在沒有更新的潛在性結核病感染的診斷工具能被廣泛使用前,皮膚結核菌素測試仍是診斷潛在性結核病感染最重要的診斷工具。本研究提供在一個中度結核病盛行國家, 施打過卡介苗之兒童, 皮膚結核菌素測試反應的分布。由於這個反應的分布是雙峰型的,有必要在不同年齡,不同危險性的兒童,使用不同的臨界值。文中建議的臨界值提供相當高的特異度及敏感度。依照年齡及危險性而有不同的臨界值,找出應該提供追蹤或治療的潛在性結核病感染兒童,對於結核病控制的策略是有幫助的。
Objective: 1) To examine the distribution of reaction to the tuberculin skin test (TST) in Bacillus Calmette-Guérin (BCG) vaccinated children aged from 3 months to 14 years in a country with moderate risk of tuberculosis; and 2) to approximate the proper cutoff point for upper limit of normal size.
Methods: A cross-sectional study of TST with purified protein derivative (PPD RT 23 2TU) was conducted among those children who had received BCG as schedule, and no known immuno-compromised status. The distribution of reaction of TST grouping by different age groups were compared with the standard curve composed by annual risk of infection from pre-vaccination TST evaluation. Goodness of fit was used to check the best cutoff points and were further accessed the sensitivity by a dataset of TST from children with household contact of sputum positive confirmed tuberculosis (TB) case.
Results: 850 eligible data was analyzed. According to distribution of positivity of TST, the effect of BCG on TST decreased after vaccination and the positivity reversed after 7 year-old. The cutoff points for age from 0~7 year-old would be 21, 20,19, 18, 17, 16, 15, 14 mm accordingly to minimize the effect of BCG on TST during this age period and 12 mm for 8 to 14 year-old. From children with household sputum positive contact, the distribution of their TST reaction before age of seven was not age-dependent as general population. On the contrary, it was fairly stable, 10 mm was thus recommended for children with household contact of sputum positive confirmed TB case. These cutoff points provided a specificity of 89.8% in children without known risk of TB infection, clinical TB manifestation and immuno-compromised status, and 27.5% of children with household contact of sputum positive case would be positive.
Conclusions: Before new diagnostic tool for LTBI could be used world-widely, TST is still the most important tool for evaluation of LTBI. The study provided a normal distribution of TST size for BCG vaccinated children in a country with moderate risk of TB. Since it was a bi-modal distribution of TST reaction, using age specific, risk based cut-off value for children was mandatory. Our cutoff points provided high specificity and sensitivity. Risk based, age specific cutoffs can be helpful to select children who need closely follow up or LTBI treatment as a strategy for TB control.
口試委員會審定書………………………………………………… II
誌謝………………………………………………………………… III
中文摘要………………………………………………………………IV
英文摘要………………………………………………………………VI
目錄…………………………………………………………………VIII
圖目錄 …………………………………………………………………X
Introduction…………………………………………………………1
Materials and methods……………………………………………3
Study site and group I children………………………………3
Data collection……………………………………………………3
Procedure of TST……………………………………………………4
Exclusion criteria and follow-up procedures……………… 5
Sample size estimation and procedure of sampling…………5
Group II children (2nd grade schoolchildren without BCG scar)……………………………6
Group III children (contacts with sputum smear-positive confirmed TB cases)…………7
Statistical analysis……………………………………………7
Determination of the duration of BCG effect on TST………7
Annual risk of tuberculosis infection (ARTI) ………………7
Goodness of fit………………………………………………………8
Comparison of cutoff points for positive TST in different countries ………………………9
Sensitivity and Specificity………………………………………10
Ethical Approval……………………………………………………10
Results…………………………………………………………………11
Discussion……………………………………………………………16
Acknowledgement……………………………………………………22
References……………………………………………………………23
Appendix A …………………………………………………………34
Appendix B …………………………………………………………35

圖目錄
Figure 1. Frequency distribution of TST size of 850 BCG-vaccinated children without household contact of tuberculosis patients (Group I children)………………………………………………30
Figure 2. Positivity curve from Group I children using four different TST cutoff point sets (12 mm, 15 mm, 21mm, and changing cutoff points derived from regression analysis) and stander curve of infection estimated from Group II children without BCG scar……………………………………………………… 31
Figure 3. Frequency distribution of TST size of 3,523 children with household contact of sputum-positive tuberculosis cases (Group III children)………………………………32
Figure 4. Median size of TST between BCG vaccinated children with/without household contact of TB cases……………………………………………33
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