院內結核菌暴露事件與傳播風險：根本原因分析與病例對照研究

Nosocomial Exposure to Tuberculosis and Risk of Transmission: Root Causes Analysis and Case-Control Study

楊雅仁(Ya-Jen Yang)

指導教授 ： 方啓泰

共同指導教授 ： 王振源(Jann-Yuan Wang)

國立臺灣大學/公共衛生學院/公共衛生碩士學位學程/碩士(2022年)

https://doi.org/10.6342/NTU202201692

摘要

背景
如何透過醫療機構感染管制在預防結核病傳播方面發揮關鍵角色與作用，保障醫療同仁與醫院其他病友健康與安全，是結核病的管理上面臨的責任與挑戰，回溯性的分析顯示，在現今的感染管制措施下，臺大醫院院內結核菌意外暴露事件仍有逐年增加的趨勢（chi-square趨勢檢定p=0.003），值得進一步去探究、分析不同暴露時間與不同情境所造成接觸者不同的感染風險狀況，與引發暴露感染的根本原因。
研究目的
本研究目的為了解結核病指標個案延遲診斷、結核菌傳播的危險因子與根本原因，作為早期診斷與治療之參考，以期能夠及早介入、避免院內感染及後續聚集事件發生。藉由了解影響結核病接觸傳染危險的相關因素，提供未來制定結核病感染管制措施之參考，並探討疫調進行時人力與時間如何有最高成本效益的分配。這樣的研究，可作為未來院內感染管制措施、國家結核病政策制定之參考。
方法
本研究設計為回溯性世代研究，主要利用2016年01月01日至2019年12月31日臺大醫院發生之結核病院內暴露事件，納入215名指標個案，953名非醫療人員接觸者，將有IGRA陽性接觸者之56名指標個案定義為傳染性個案，其中有47名曾於急診造成暴露。接觸者皆為陰性之159名指標個案為非傳染性個案，找出院內傳染的危險因子，並以根本原因分析歸因出造成暴露事件指標個案3類情境：情境1為住院一開始未懷疑結核病；情境2為住院一開始懷疑結核病但檢驗陰性或尚未有結果；情境3為住院後結核病再活化個案，就管理、醫療團隊及病人等因素，深入探討造成暴露事件之根本原因。本研究於109年5月7日研究計畫申請通過臺大醫院研究倫理委員會審查(案號：202004038RINC)，研究執行過程中謹守病人隱私及資料保密。
結果
比較傳染性與非傳染性指標個案2組人口統計學基本特徵，顯示具有傳染力的個案，年紀較輕，有菸、酒、檳榔習慣，達統計顯著意義(p<0.05)。痰液抹片耐酸性染色結果顯示，痰抹片陽性者較易造成傳染(p<0.001)，弱陽性與強陽性2組人口統計學基本屬性、傳染期、診斷時間皆無顯著差異，但在共病上，強陽性個案有較高比例的人有免疫系統性疾病(12.9% vs. 2.2%，p=0.017)。
傳播風險因子多變項分析結果顯示，現在或曾有抽菸習慣、執行抽痰之飛沫微粒處置醫療行為以及痰液抹片耐酸性染色結果陽性，是造成傳播之危險因子，勝算比(Odds ratio, OR)為7.04(95%信賴區間：3.08 – 16.09)、2.71（95%信賴區間：1.15 – 6.38）、4.49（95%信賴區間：1.98 – 10.19）；進一步使用多變項分層分析探討痰塗片強陽性、弱陽性、與陰性的傳染風險差別顯示，以強陽性為參考組別分析，強陽性和弱陽性的風險並無統計上的差異，而以陰性為參考組別統計結果顯示，痰塗片陰性的風險，約是其他兩組的20%，痰塗片強陽性比弱陽性比陰性指標個案傳染風險比為4:5:1。
針對3組指標個案情境，進行暴露時間、延遲診斷時間以及接觸者人數、陽性率分析結果顯示情境1、2、3各有20、27、9名指標個案，各造成30名、35名、15名接觸者IGRA陽性，感染率為34%、51%、41%。其中以情境2的傳染力最高，被傳染的人數也最多，分析發現當中雖有11名個案在一開始住院時因為痰液抹片耐酸性染色陽性而即時隔離，但從開立醫囑、取得檢體送驗、到最後得知報告結果過程有所耽擱，致使隔離時間延遲3至5天；情境1與情境3，顯示個案有較多癌症或免疫疾病，為疾病分期或治療入院。
結論
215例指標個案中，56例（26.0%）造成結核菌傳播，接觸者IGRA陽性率為15.9%。為減少結核病的醫院傳播，感染控制政策和措施應考量針對吸煙、院內執行會產生飛沫微粒的醫療處置行為進行管理，同時也必須盡可能提早診斷痰塗片耐酸性染色陽性的結核病人。
情境根本原因分析結果顯示取痰與檢驗的速度是需要著力的地方，建議宣導醫療人員當臨床上個案疑似結核病，應盡快進行咳痰技巧衛教之後取得痰檢體並宣導當臨床上高度疑似結核病時，除了開立痰液抹片耐酸性染色檢驗外，可同時開立TB-NAA以利快速獲得檢驗結果；依標準檢驗流程，內部應有查核機制。
進行員工在職教育宣導，當個案有免疫系統性共病或接受免疫抑制劑(包含類固醇)治療、癌症共病者時，應持續監測(注意)是否有結核病之疑慮；當高度疑似結核病時，應盡快進行痰結核菌核酸增幅檢測（TB-NAA）及抹片耐酸性染色、分枝桿菌培養，醫療上在評估此類個案影像學時，應該永遠都要考慮是否有結核病的可能，也提醒臨床若病人入住非胸腔或感染專科別，針對胸部影像學有疑慮時，可照會胸腔或感染科專科以及早診斷結核病，減少結核菌傳播風險。

關鍵字

結核病 ； 院內傳播 ； 暴露事件 ； 根本原因分析 ； 感染控制

並列摘要

Rationale
How to prevent the transmission of Mycobacterium tuberculosis complex and to protect the health and safety of health care workers and patients in the hospital is the responsibility and challenge of infection control unit. Using chi-square test for trend, the incidents of nosocomial TB exposure continued to increase year by year under current infection control measures (p=0.003). This implied it is worth exploring and analyzing the infection risk of contacts caused by different index, exposure times and environment, and the root cause of the tuberculosis exposure events.
Objectives
The aim is to understand the delayed diagnosis of tuberculosis, the risk factors and root causes of tuberculosis transmission, for early diagnosis and treatment, so as to enable early intervention and avoid nosocomial infections and subsequent clustering events. By understanding the relevant factors affecting the risk of TB contact infection, this study can provide the evidences for resources allocation during contact investigation and policy making for nosocomial TB control.
Methods
This retrospective cohort study analyzed the tuberculosis exposure events occurred in National Taiwan University Hospital from 01 January 2016 to 31 December 2019 to explore the risk factors for the event. 215 index cases d and 953 non-medical personnel contacts were included. The 56 index cases of IGRA-positive contacts were defined as infectious cases, of which 47 had been exposed in the emergency department. The 159 index cases whose contacts were all negative were non-infectious cases, the risk factors for nosocomial infection were identified, and the exposure events were attributed by using the root cause analysis.
The index cases were identified to 3 categories : Category 1 was that tuberculosis was not suspected at the beginning of hospitalization ; Category 2: tuberculosis was suspected at the beginning of hospitalization but the test was negative or no results were obtained; Category 3 was a case of reactivation of tuberculosis after hospitalization. To explore the risk factors for the event, and investigated factors associated with delayed diagnosis of tuberculosis (TB) by using the method of Root Cause Analysis. The study process was approved by Research Ethics Committee of National Taiwan University Hospital ( NTUH-REC No.：202004038RINC).
Results
Comparing the basic demographic characteristics of the two groups of infectious and non-infectious index cases showed that the infectious cases were younger, and had the habit of smoking, drinking, and betel nut, which was statistically significant (p<0.05). The results of acid-fast stain of sputum smears showed that those with positive sputum smears were more likely to cause infection (p<0.001). In terms of disease, a higher proportion of strong positive cases had immune system diseases (12.9% vs. 2.2%, p = 0.017).
Multivariate analysis of transmission risk factors showed that the current or former smoking habit, the medical behavior of sputum droplet disposal, and the positive acid-fast stain result of the sputum smear were the risk factors for transmission. The odds ratio (OR) was 7.04 (95% confidence interval: 3.08 – 16.09), 2.71 (95% confidence interval: 1.15 – 6.38), 4.49 (95% confidence interval: 1.98 – 10.19); The difference in infection risk between strong positive, weakly positive, and negative smears shows that, with the strong positive as the reference group, there is no statistical difference in the risk of strong positive and weak positive, while the statistical results of the negative as the reference group show that, The risk of negative sputum smear was about 20% of that of the other two groups. The ratio of infection risk between strong positive vs. weak positive vs. negative index cases was 4:5:1.
For the three categories, the exposure time, delayed diagnosis time, the number of contacts, and the positive rate analysis showed that category 1, 2, and 3 had 20, 27, and 9 index cases, respectively, resulting in 30, 35, and 15 cases. Contacts were positive for IGRA, and the infection rates were 34%, 51%, and 41%.
Category 2 has the highest infectivity and has the largest number of infected people. The analysis found that although 11 cases were immediately isolated due to positive acid-fast sputum smears at the beginning of hospitalization, but the test result from time to report resulting in a delay of 3 to 5 days for the isolation time; category 1 and category 3 showed that the case had more cancer or immune diseases, and was admitted to the hospital for disease staging or treatment.
Conclusions
In 215 index cases, 56 (26.0%) caused tuberculosis transmission, and the IGRA positive rate of contacts was 15.9%. Infection control policies and measures should pay attention to current or ex-smoking patients, aerosol-generating procedures, and early diagnosis of tuberculosis patients with positive acid-fast stains on sputum smears as early as possible to reduce nosocomial transmission of tuberculosis.
The results of the root cause analysis show that the sputum collection and testing process needs to be focused. It is recommended to publicize medical staff that when a case is suspected of tuberculosis, they should conduct health education on expectoration skills as soon as possible, when tuberculosis is high suspected, in addition to the sputum smear for acid-fast staining test, TB-NAA can be issued at the same time to facilitate rapid acquisition of test results; according to the standard inspection process, there should be an internal inspection mechanism.
Carry out on-the-job education and publicity for employees. When a case has an immune system comorbidity, or is receiving immunosuppressant (including steroid), or has a cancer comorbidity, continuous monitoring (attention) should be given to whether there is any suspicion of tuberculosis; when there is a high suspicion of tuberculosis, the nucleic acid amplification test (TB-NAA), smear acid-fast stain, and mycobacterial culture should be performed as soon as possible. When evaluating the imaging of such cases, the possibility of tuberculosis should always be considered. If a patient is admitted to a non-chest or infection specialty, if he or she has doubts about chest imaging, he or she can consult a chest or infectious disease specialist for early diagnosis of tuberculosis to reduce the risk of tuberculosis transmission.

並列關鍵字

tuberculosis ； nosocomial transmission ； texposure events ； root causes analysis ； infection control

參考文獻

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