PET-CT-guided characterisation of progressive, preclinical tuberculosis infection and its association with low-level circulating Mycobacterium tuberculosis DNA in household contacts in Leicester, UK: a prospective cohort study.
PET-CT-guided characterisation of progressive, preclinical tuberculosis infection and its association with low-level circulating Mycobacterium tuberculosis DNA in household contacts in Leicester, UK: a prospective cohort study.
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PET-CT 引导下的进展性临床前结核感染特征及其与英国莱斯特家庭接触者中低水平循环结核分枝杆菌 DNA 的关联：一项前瞻性队列研究。
DOI：
10.1016/s2666-5247(23)00289-6
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Kim JW
中科院分区：
文献类型：
--
作者：
Kim JW
研究背景初发结核病是结核分枝杆菌感染的一种进展状态，其发展为结核病的风险增加，其特征尚不清楚。动物模型提示进行性感染与菌血症相关。循环结核分枝杆菌DNA先前已通过使用Actiphage（一种基于噬菌体的实时PCR检测方法）在肺结核中检测到。我们的目的是研究是否连续[18F]氟脱氧葡萄糖（[18 F]FDG）-PET-CT可用于确定早期结核病的状态和进展轨迹，并检查这些PET-CT结果是否与基于Actiphage的循环结核分枝杆菌DNA检测相关。在英国莱斯特，与肺结核患者有家庭接触且具有潜伏性结核感染临床表型的无症状成人（年龄≥16岁）。在基线时对参与者的血液样本进行Actiphage测试，并在基线和3个月后进行[18 F]FDG PET-CT。根据[18 F]FDG摄取的定量（最大标准化摄取值[SUVmax]）和分布，将基线PET-CT特征分类为阳性、不确定或阴性。在[18F]FDG摄取的合适部位进行微生物采样。3个月后[18F]FDG摄取的变化定量分类为进行性、稳定或消退。参与者接受治疗，如果确定了早期结核病的特征，定义为结核分枝杆菌的微生物检测或进行性PET-CT变化。结果在2020年8月5日至11月5日期间招募了20名接触者;其中16名参与者的IFNγ释放试验（QuantiFERON-TB Gold Plus [QFT]）结果呈阳性，表明结核病感染。基线PET-CT扫描在10次接触中为阳性（均为QFT阳性），6次接触中为不确定（3次QFT阳性），4次接触中为阴性（3次QFT阳性）。8例PET-CT阳性接触者中有4例（3例通过培养，1例通过Xpert MTB/RIF Ultra检测）从胸内淋巴结或支气管冲洗液中鉴定出结核分枝杆菌，并接受了全面的抗结核治疗。另外两名未采样的PET-CT阳性接触者也接受了治疗：一名肺[18 F]FDG摄取（SUVmax 9·4）的患者接受了经验性抗结核治疗，另一名显示进行性[18 F]FDG摄取的患者接受了预防性治疗。10名基线时摄取[18F]FDG的未治疗接触者（7名QFT阳性）在随访时有稳定或正在消退的变化，12个月后仍无结核病。阳性的基线Actiphage检测与需要治疗的早期结核病特征的存在相关（p=0·018）。解释早期结核病的微生物和炎症特征可以在PET-CT上可视化，并且与血液中结核分枝杆菌的检测相关，支持结核病风险的病原体导向血液生物标志物的开发。
BackgroundIncipient tuberculosis, a progressive state ofMycobacterium tuberculosisinfection with an increased risk of developing into tuberculosis disease, remains poorly characterised. Animal models suggest an association of progressive infection with bacteraemia. CirculatingM tuberculosisDNA has previously been detected in pulmonary tuberculosis by use of Actiphage, a bacteriophage-based real-time PCR assay. We aimed to investigate whether serial [18F]fluorodeoxyglucose ([18F]FDG)-PET-CT could be used to characterise the state and progressive trajectory of incipient tuberculosis, and examine whether these PET-CT findings are associated with Actiphage-based detection of circulatingM tuberculosisDNA.MethodsWe did a prospective 12-month cohort study in healthy, asymptomatic adults (aged ≥16 years) who were household contacts of patients with pulmonary tuberculosis, and who had a clinical phenotype of latent tuberculosis infection, in Leicester, UK. Actiphage testing of participants' blood samples was done at baseline, and [18F]FDG PET-CT at baseline and after 3 months. Baseline PET-CT features were classified as positive, indeterminate, or negative, on the basis of the quantitation (maximum standardised uptake value [SUVmax]) and distribution of [18F]FDG uptake. Microbiological sampling was done at amenable sites of [18F]FDG uptake. Changes in [18F]FDG uptake after 3 months were quantitatively categorised as progressive, stable, or resolving. Participants received treatment if features of incipient tuberculosis, defined as microbiological detection ofM tuberculosisor progressive PET-CT change, were identified.Findings20 contacts were recruited between Aug 5 and Nov 5, 2020; 16 of these participants had a positive result on IFNγ release assay (QuantiFERON-TB Gold Plus [QFT]) indicating tuberculosis infection. Baseline PET-CT scans were positive in ten contacts (all QFT positive), indeterminate in six contacts (three QFT positive), and negative in four contacts (three QFT positive). Four of eight PET-CT-positive contacts sampled hadM tuberculosisidentified (three through culture, one through Xpert MTB/RIF Ultra test) from intrathoracic lymph nodes or bronchial wash and received full antituberculosis treatment. Two further unsampled PET-CT-positive contacts were also treated: one with [18F]FDG uptake in the lung (SUVmax9·4) received empirical antituberculosis treatment and one who showed progressive [18F]FDG uptake received preventive treatment. The ten untreated contacts with [18F]FDG uptake at baseline (seven QFT positive) had stable or resolving changes at follow-up and remained free of tuberculosis disease after 12 months. A positive baseline Actiphage test was associated with the presence of features of incipient tuberculosis requiring treatment (p=0·018).InterpretationMicrobiological and inflammatory features of incipient tuberculosis can be visualised on PET-CT and are associated withM tuberculosisdetection in the blood, supporting the development of pathogen-directed blood biomarkers of tuberculosis risk.FundingMRC Confidence in Concept.
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影响因子：
82.9
作者：
Esmail, Hanif;Lai, Rachel P.;Lesosky, Maia;Wilkinson, Katalin A.;Graham, Christine M.;Coussens, Anna K.;Oni, Tolu;Warwick, James M.;Said-Hartley, Qonita;Koegelenberg, Coenraad F.;Walzl, Gerhard;Flynn, JoAnne L.;Young, Douglas B.;Barry, Clifton E., III;O'Garra, Anne;Wilkinson, Robert J.
通讯作者：
Wilkinson, Robert J.
18F-FDG 正电子发射断层扫描/计算机断层扫描的放射学病变结果提示旧愈肺结核和预测复发的高风险迹象：一项回顾性研究
影响因子：
4.6
作者：
Yuanyuan Ji;C. Shao;Yong;Guangrui Shao;Jingsong Zheng
通讯作者：
Jingsong Zheng
DOI：
10.1016/s1473-3099(17)30488-7
发表时间：
2017-12
期刊：
The Lancet. Infectious diseases
影响因子：
--
作者：
Yoon C;Semitala FC;Atuhumuza E;Katende J;Mwebe S;Asege L;Armstrong DT;Andama AO;Dowdy DW;Davis JL;Huang L;Kamya M;Cattamanchi A
通讯作者：
Cattamanchi A
影响因子：
3.7
作者：
Tornack J;Reece ST;Bauer WM;Vogelzang A;Bandermann S;Zedler U;Stingl G;Kaufmann SH;Melchers F
通讯作者：
Melchers F