潛伏性結核感染的研究: HIV陰性病人

Abstract

1. 卡介苗接種者潛伏結核感染率較低: 一監獄收容人之橫斷面研究 目的: 探討卡介苗接種對結核感染的保護效用是否持續到成年。 方法: 於一所位於北臺灣收容超過3000人的監獄，在愛滋病毒檢測陰性的收容人進行潛伏結核感染的橫斷面研究。本研究使用剋肺勞結核菌感染檢驗 (QuantiFERON gold in tube，QFT-IT) 檢查，潛伏結核感染的定義為QFT-IT ≥0.35 IU/ml。近期潛伏結核感染 (Recent LTBI) 定義則為QFT-IT ≥0.7 IU/ml。分析時以年齡分層來分析卡介苗疤痕數與潛伏結核感染與近期潛伏結核感染風險之間是否有顯著負相關。本研究經過倫理委員會事前審查通過，所有參與者瞭解研究內容且簽署同意書。 結果: 在2385位參加者中，25% QFT-IT ≥0.35 IU/ml。隨著年齡越大，潛伏結核感染 (14%, 32% and 50%) 的盛行率就越高 (18-34歲、35-54歲和≥55歲) (Cochran–Mantel–Haenszel method, p<0.001)。而在上述三個年齡層中，卡介苗疤痕數與潛伏結核感染與近期潛伏結核感染風險均呈現顯著負相關 (Cochran–Mantel–Haenszel method, p<0.001)。 結論: 近期潛伏結核感染風險與卡介苗疤痕數間的顯著負相關意味：在卡介苗接種後的數十年，接種仍然對結核感染有保護作用。這發現可供各國新生兒卡介苗政策的參考。並且值得進一步進行前瞻性世代研究，以證實卡介苗對成人的保護力。

2. 監獄收容人潛伏結核感染治療: 一隨機對照試驗 場所: 台灣北部一監獄 研究目的: 比較每日服用rifampin四個月 (4R) 或每日服用isoniazid六個月 (6H) 兩種治療潛伏結核感染的處方在監獄收容人的安全性與完成率。 設計: 這是一個在HIV陰性監獄收容人之非盲隨機對照試驗。收案對象為沒有活動性結核病，且皮膚結核菌素測試及剋肺勞結核菌感染檢驗 (QuantiFERON gold in tube，QFT-IT)結果均陽性之受檢收容人。排除條件則為肝功能基礎值 (麩丙酮酸轉脢, glutamic pyruvic transaminase,GPT) ≥ 120 U/L，黃膽指數≥ 2.4 U/L，或血小板 <150 k/mm3。研究的主要終點為因為任何不良事件造成潛伏結核感染治療之中斷。 結果: 參加者 (373位，14%為B型肝炎表面抗原陽性，21%為C型肝炎表面抗原陽性) 在都治關懷之下，依照分層(B型肝炎、C型肝炎及兩年刑期) 隨機分派接受4R 或6H的處方治療。接受4R治療者 (190人) 與6H治療者(183人)比較，碰到因為任何不良事件造成潛伏結核感染治療之中斷的機會較低 (所有的不良反應2% vs. 12%, p< 0.001; 及肝毒性 0% vs. 8%, p<0.001)，且完成潛伏結核感染治療的機會較高 (86% vs. 78%, p=0.041)。 結論: 對於監獄收容人來說，相較於每日isoniazid六個月 (6H)，每日rifampin四個月 (4R) 的安全性及完成率皆較高。

3. 兒童接觸者的結核病發病風險: 預測評分表之發展及驗證 背景: 結核病接觸者檢查及追蹤耗時費力，迄今仍無接觸者發病風險預測指標可作為追蹤優先次序的參考。 目標: 以例行接觸者檢查登錄資料發展及驗證一簡單實用的結核病發病風險預測評分表。 方法: 發展世代是由2008-2009年間，全國十二歲及以下9411位接觸者兒童組成；我們使用多變項考克斯迴歸模式來預測活動性結核病發病的風險。驗證世代則是由2005年全國的2405位兒童接觸者組成。我們計算模式的接受者操作曲線下面積 (area under the receiver operating characteristic curves，AUROC)，以及不同評分所預測的接觸者發病風險。 測量及主要結果: 我們發展了一個八分評分系統，包括接觸者皮膚結核菌素測試、指標個案的痰塗片陽性、居住在高發生地區及性別。由發展世代計算出來的AUROC為0.872 (95% CI: 0.810–0.935)而驗證世代則為0.900 (95% CI: 0.830–0.969)。預估評分為7, 6, 5, 4, 3 及2分者，其三年內活動性結核病發病風險分別為100%, 7.8%, 4.3%, 1.0%, 0.7% 及0.2%。 結論: 我們成功地發展及驗證一個結核病接觸者發病風險預估評分系統，能夠從十二歲及以下接觸者兒童中辨認出高發病風險個案，優先予以安排主動胸部X光追蹤或潛伏結核感染治療。

1. Lower prevalence of tuberculosis infection in BCG vaccinees: a cross-sectional study in adult prison inmates Objectives To address whether the effect of the Bacillus Calmette-Guerin (BCG) vaccination against tuberculosis (TB) infection lasts to adulthood. Methods A cross-sectional study on the prevalence of LTBI among HIV-negative men, using QuantiFERONR-TB Gold In-tube (QFT-IT), was conducted at a prison with >3,000 inmates in northern Taiwan. A QFT-IT ≥ 0.35 IU/ml was defined as LTBI. A QFT-IT ≥ 0.7 IU/ml was defined as recent LTBI. The association between the number of BCG scars and LTBI stratified by age was analysed. The study procedure was approved by institutional review board and all participants gave written informed consent before receiving screening tests. Results Among the 2385 participants, 25% had a QFT-IT ≥ 0.35 IU/ml. Increasing LTBI (14%, 32% and 50%) was observed with increased age (18-35 years, 35-54 years and ≥ 55 years) (p<0.001 by the Cochran-Armitage Trend Test). The number of BCG scars were found to be inversely correlated with QFT-IT results for both LTBI and recent LTBI in all three age groups (p<0.001 by Cochran-Mantel-Haenszel statistics). Conclusions Our results suggest that the BCG vaccine seems to have a protective effect in adults decades after vaccination according to the number of recent infections (QFT-IT ≥ 0.7 IU/ml). This finding has important implications for national policy of BCG vaccination. Further prospective cohort studies on the protective effect of the BCG vaccination against TB infection in adults are warranted. 2. Latent tuberculosis infection treatment for prison inmates: a randomised controlled trial Setting A prison in northern Taiwan Objective To compare safety and completion rate of the 4-month daily rifampin regimen (4R) versus standard 6-month daily isoniazid regimen (6H) for latent tuberculosis infection (LTBI) in prison inmates Design This was an open-label randomised trial among HIV-negative male inmates. Inmates without active tuberculosis but tested positive for both tuberculin skin test and QuantiFERONR-TB Gold In-tube were eligible, but those with baseline glutamic pyruvic transaminase (GPT) levels ≥ 120 U/L, bilirubin levels ≥ 2.4 U/L, or a platelet count <150 k/mm3 were excluded. The primary endpoint was any adverse event that resulted in discontinuation of LTBI therapy. Results Participants (n=373, 14% HBsAg-positive; 21% anti-HCV-positive) were randomised (stratified by HBV, HCV status, and 2-year prison term) to receive either 4R or 6H by directly observed therapy. 4R group (n=190) were less likely to experience an adverse event leading to discontinued therapy (2% vs. 12%, p< 0.001, for all adverse event; and 0% vs. 8%, p<0.001, for hepatotoxicity), and more likely to complete the LTBI treatment (86% vs. 78%, p=0.041), compared with 6H group (n=183). Conclusions 4R is safer and has a higher completion rate than 6H as LTBI treatment for male prison inmates. 3. Risk for Tuberculosis in Child Contacts: Development and Validation of a Predictive Score Rationale: Contact investigation of persons exposed to tuberculosis (TB) is resource intensive. To date, no clinical prediction rule for tuberculosis risk exists for use as a guide during contact investigation. Objectives: We sought to develop and validate a simple and easy-to-use predictive score for TB risk, using data routinely available during contact investigation. Methods: The development cohort consisted of 9411 children aged 0-12 years from 2008-2009 national contacts cohort. We used a multivariate Cox proportional hazards model to predict the risk of developing active TB. The validation cohort consisted of 2405 children from 2005 national contacts cohort. We calculated area under the receiver operating characteristic curves (AUROC) of the model, as well as the predicted risk of TB for contacts with different score. Measurements and Main Results: An 8-point scoring system was developed, including reaction to tuberculin skin test of the contacts, as well as smear-positivity, residence in high incidence areas and gender of the index cases. AUROC was 0.872 (95% CI: 0.810–0.935) for the development cohort and 0.900 (95% CI: 0.830–0.969) for the validation cohort. The risk of developing active TB within 3 years is 100%, 7.8%, 4.3%, 1.0%, 0.7% and 0.2% for contacts with risk scores of 7, 6, 5, 4, 3 and 2, respectively. Conclusions: A risk predictive score was developed and validated to identify child contacts aged 0-12 years at increased risk for active TB. This predictive score can help to prioritize active case-finding or latent TB infection treatments among children exposed to TB.