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Abnormalities suggestive of latent tuberculosis infection on chest radiography; how specific are they?

ABSTRACT: Background:Several radiological features have been reported in association with latent tuberculosis infection (LTBI) but it has not been studied which are specific. The aim of this study was to evaluate allegedly characteristic abnormalities on chest radiography (CXR) in patients with LTBI compared to uninfected controls. Methods:From 236 patients tested with QuantiFERON-TB Gold In-Tube (QFT), the CXR was re-evaluated in a blinded fashion for fibrotic scarring, (non-)calcified nodules and pleural thickening. LTBI was defined as presence of a positive QFT result and/or positive tuberculin skin test result stratified by Bacille Calmette-Guérin-vaccination status. Results:Any predefined abnormality of LTBI was observed in 116/236 (49.2%) patients, the frequency not being different between groups. However, the specificity for LTBI of a fibrotic scar ? 2 cm2 was 100% [95% CI: 92.0%-100%] and of a calcified nodule ?1.5?mm was 95.7% [95% CI: 85.2%-99.5%]. The frequency of non-calcified nodules and pleural thickening did not differ between groups. Conclusion:Only a fibrotic scar ? 2 cm2 and/or a calcified nodule ?1.5?mm were significantly associated with LTBI. This finding is clinically relevant mainly in patients who are at significant risk of TB reactivation and in whom indirect diagnostic tests may be unreliable.

SUBMITTER: Uzorka JW

PROVIDER: S-EPMC6830153 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Abnormalities suggestive of latent tuberculosis infection on chest radiography; how specific are they?

Uzorka Jonathan W JW Kroft Lucia J M LJM Bakker Jaap A JA van Zwet Erik W EW Huisman Erik E Prins Corine C van der Zwan Cornelis J CJ Ottenhoff Tom H M THM Arend Sandra M SM

Journal of clinical tuberculosis and other mycobacterial diseases 20190125

<h4>Background</h4>Several radiological features have been reported in association with latent tuberculosis infection (LTBI) but it has not been studied which are specific. The aim of this study was to evaluate allegedly characteristic abnormalities on chest radiography (CXR) in patients with LTBI compared to uninfected controls.<h4>Methods</h4>From 236 patients tested with QuantiFERON-TB Gold In-Tube (QFT), the CXR was re-evaluated in a blinded fashion for fibrotic scarring, (non-)calcified nod ...[more]

PMID: 31720416

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Project description:To assess the frequency and spectrum of abnormalities on routine screening chest radiographs in the pre-employment evaluation of health care workers with positive tuberculin skin test (TST) results.The institutional review board approved this HIPAA-compliant retrospective study and waived the need for written informed patient consent. Chest radiographic reports of all 2586 asymptomatic individuals with positive TST results who underwent pre-employment evaluation between January 1, 2003, and December 31, 2007, were evaluated to determine the frequency of detection of evidence of active tuberculosis (TB) or latent TB infection (LTBI) and the spectrum of imaging findings. All chest radiographs interpreted as positive were reviewed by an experienced board-certified radiologist. If there was a discrepancy between the two readings, a second experienced radiologist served as an independent and final arbiter. Any follow-up chest radiographs or computed tomographic images that had been acquired by employee health services or by the employee's private physician as a result of a suspected abnormality detected at initial screening were also evaluated.Of the 159 (6.1%) chest radiographic examinations that yielded abnormal results, there were no findings that were consistent with active TB. There were 92 cases of calcified granulomas, calcified lymph nodes, or both; 25 cases of apical pleural thickening; 16 cases of fibrous scarring; and 31 cases of noncalcified nodules. All cases of fibrous scarring involved an area smaller than 2 cm(2). All noncalcified nodules were 4 mm in diameter or smaller, with the exception of one primary lung malignancy and one necrotizing granuloma (negative for acid-fast bacilli) that grew Mycobacterium kansasii on culture.Universal chest radiography in a large pre-employment TB screening program was of low yield in the detection of active TB or increased LTBI reactivation risk, and it provided no assistance in deciding which individuals to prioritize for LTBI treatment.

Project description:Tuberculosis (TB) remains one of the most severe infectious diseases. It is still of paramount importance to establish more accurate, rapid, and efficient diagnostic methods. Since infection with Mycobacterium tuberculosis (M. tb) is largely mediated through the respiratory tract, IgA responses against mycobacterial proteins are worthy of investigation for their potential clinical utility. In this study, the IgA response targeting lipoprotein Z (LppZ) was determined by using a homemade ELISA with plasma of TB patients (N = 125), LTBI individuals (N = 92), healthy controls (HCs) (N = 165), as well as TB patients undergoing anti-TB treatment (N = 9). In parallel the antigen-specific IFN-? release from PBMCs triggered by LppZ and M. tb-specific ESAT-6 or CFP-10 was detected by using an ELISPOT assay. It was found that the LppZ-specific IgA level was dramatically higher in TB patients than in HCs (p < 0.0001). Compared to that before anti-TB treatment, the LppZ-specific IgA level decreased substantially after 2 months of anti-TB treatment (p = 0.0297) and remained at low levels until the end of the treatment. What is more, pulmonary TB patients exhibited significantly higher LppZ-specific IgA-values than extra-pulmonary TB patients (p = 0.0296). Interestingly, the LppZ-specific IgA-values were negatively correlated to the amounts of IFN-? released in response to LppZ with statistical significance (r = -0.5806, p = 0.0002). LppZ-specific IgA level was also higher in LTBI individuals than in HCs (p < 0.0001). Additionally there were some PPD+ HC individuals with high LppZ-specific IgA levels but the potential of this assay for identifying leaky LTBI in PPD+ HCs needs to be further investigated through follow-up studies. The sensitivity of detecting TB solely with ESAT-6 or CFP-10-specific IFN-? release was increased by including the LppZ-specific IgA results, respectively, from 86.11 to 100% and 88.89 to 100%; the sensitivity of screening for LTBI was increased from 80.36 to 83.93% and 57.14 to 69.64%, respectively. The higher LppZ-specific IgA responses in TB and LTBI populations than in controls indicated high immunoreactivity to LppZ upon M. tb infection. Although the assay was not efficient enough for independent application in sero-diagnosis, LppZ-specific IgA might become a complementary biomarker for the improvement of TB and LTBI screening.

Project description:We conducted a tuberculosis (TB) prevalence survey and evaluated the screening methods used in our survey, to assess if screening in TB prevalence surveys could be simplified, and to assess the accuracy of screening algorithms that may be applicable for active case finding.All participants with a positive screen on either a symptom questionnaire, chest radiography (CXR) and/or sputum smear microscopy submitted sputum for culture. HIV status was obtained from prevalent cases. We estimated the accuracy of modified screening strategies with bacteriologically confirmed TB as the gold standard, and compared these with other survey reports. We also assessed whether sequential rather than parallel application of symptom, CXR and HIV screening would substantially reduce the number of participants requiring CXR and/or sputum culture.Presence of any abnormality on CXR had 94% (95%CI 88-98) sensitivity (92% in HIV-infected and 100% in HIV-uninfected) and 73% (95%CI 68-77) specificity. Symptom screening combinations had significantly lower sensitivity than CXR except for 'any TB symptom' which had 90% (95%CI 84-95) sensitivity (96% in HIV-infected and 82% in HIV-uninfected) and 32% (95%CI 30-34) specificity. Smear microscopy did not yield additional suspects, thus the combined symptom/CXR screen applied in the survey had 100% (95%CI 97-100) sensitivity. Specificity was 65% (95%CI 61-68). Sequential application of first a symptom screen for 'any symptom', followed by CXR-evaluation and different suspect criteria depending on HIV status would result in the largest reduction of the need for CXR and sputum culture, approximately 36%, but would underestimate prevalence by 11%.CXR screening alone had higher accuracy compared to symptom screening alone. Combined CXR and symptom screening had the highest sensitivity and remains important for suspect identification in TB prevalence surveys in settings where bacteriological sputum examination of all participants is not feasible.

Project description:BackgroundGiven that there is no rapid and effective method for distinguishing active tuberculosis (ATB) from latent tuberculosis infection (LTBI), the discrimination between these two statuses remains challenging. This study sought to investigate the value of nutritional indexes and tuberculosis-specific antigen/phytohemagglutinin ratio (TBAg/PHA ratio) for distinguishing ATB from LTBI.MethodsParticipants were consecutively recruited based on positive T-SPOT.TB results between January 2018 and January 2020. ATB was diagnosed by positive mycobacterial culture and/or positive GeneXpert MTB/RIF, with clinical symptoms and radiological characteristics suggestive of ATB. Individuals with positive T-SPOT.TB but without the evidence of ATB were defined as LTBI. Patients younger than 17 years and undergoing anti-TB treatment were excluded.ResultsA total of 709 (312 ATB and 397 LTBI) and another 309 (120 ATB and 189 LTBI) subjects were respectively recruited from Tongji Hospital (Qiaokou cohort) and Sino-French New City Hospital (Caidian cohort). The level of prealbumin was significantly lower in ATB than in LTBI. With a cut-off value of 139 mg/L, the sensitivity and specificity of prealbumin in distinguishing ATB from LTBI were 50.96% (45.41%-56.51%) and 91.69% (88.97%-94.40%). Meanwhile, TBAg/PHA ratio was found statistically higher in ATB compared with LTBI. If using the threshold of 0.29, the sensitivity and specificity of TBAg/PHA ratio were 65.71% (60.44%-70.97%) and 90.93% (88.11%-93.76%), respectively. Moreover, the combination of prealbumin and TBAg/PHA ratio (obtaining by diagnostic model) yielded better specificity (90.18%, [87.25%-93.10%]) and sensitivity (87.18%, [83.47%-90.89%]), while the clinical utility index (CUI) positive and CUI negative were respectively 0.76 and 0.81. After anti-TB treatment, TBAg/PHA ratio was declined while the level of prealbumin was restored (Wilcoxon test, P < 0.001). Furthermore, the performance of diagnostic model obtained in Qiaokou cohort was confirmed in Caidian cohort.ConclusionsThe diagnostic model based on combination of prealbumin and TBAg/PHA ratio is a rapid and accurate tool for discriminating ATB from LTBI.

Project description:BackgroundIn Australia, demand for specialist infectious diseases services exceeds capacity to provide timely management of latent tuberculosis infection (LTBI) in areas of high refugee and asylum seeker settlement. A model for treating LTBI patients in primary care has been developed and piloted in a refugee-focused primary health service (Monash Health Refugee Health and Wellbeing [MHRHW]) and a universal primary care clinic. This study reports on the development and evaluation of the model, focusing on the model feasibility, and barriers and enablers to its success.MethodsA convergent mix-methods design was used to evaluate the model for treating LTBI patients in primary care, where a prospective cohort study of patients commencing treatment either at MHRHW or the universal primary care clinic determined the model feasibility, while focus groups with clinicians directly involved in treating these patients explored barriers and enablers to sustainability and success of the model.ResultsFrom January 2017 to April 2018, 65 patients with confirmed LTBI presented at participating clinics. Treatment was accepted by 31 (48%) patients, of whom 15(48%) were treated at MHRHW and 16 (52%) at the universal primary care clinic. The 6-months' treatment completion rate was higher at MHRHW compared to the universal primary care clinic (14 (93%) compared to 9 (56%) respectively, p = 0.0373). Reasons for non-completion included adverse reaction, opting out and relocation. At the completion of the pilot, 15 clinicians participated in two focus groups. Clinicians identified barriers and enablers for successful LTBI management at patient, provider, organisational and clinical levels. While barriers for treatment completion and adherence were consistent across the two pilot sites, enablers, such as resources to facilitate patient education and follow-up, were available only at MHRHW.ConclusionScreening and management of LTBI patients can be achieved within the primary care setting, considerate of barriers and enablers at patient, provider, organisational and clinical levels. Upscaling of a primary care response to the management of LTBI will require supporting primary care clinics with resources to employ dedicated clinical staff for patient education, follow-up communication and monitoring medication adherence.

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Abnormalities suggestive of latent tuberculosis infection on chest radiography; how specific are they?

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Abnormalities suggestive of latent tuberculosis infection on chest radiography; how specific are they?

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