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Background It is difficult to diagnose tuberculosis (TB), particularly sputum-scarce pulmonary TB and extrapulmonary TB, using conventional diagnostic tests. Since these cases require additional invasive procedures to obtain appropriate specimens, new non-invasive diagnostic tests are needed. Plasma cell-free DNA (cfDNA) detection has gained interest as a novel diagnostic test for TB as it is convenient and less invasive. Therefore, we investigated the performance of enriched cfDNA for diagnosing pulmonary TB and extrapulmonary TB. Methods All patients suspected to have TB, who consented to the use of blood for detecting cfDNA, were prospectively enrolled from January 2019 to June 2020. We categorised the patients as confirmed, probable, possible TB, and not-TB. We compared the performance of cfDNA with those of conventional diagnostic tests. Results Among the 96 patients enrolled, 40 (41.7%) had TB, including 34 with confirmed TB and six probable TB, and 41 (42.7%) did not have TB. Acid-fast bacilli microscopy, Xpert MTB/RIF, and mycobacterial culture results were positive in 12 (31.6%), 22 (61.1%), and 25 (65.8%) patients, respectively. The sensitivity and specificity of cfDNA were 80.0% and 78.1%, respectively. While the sensitivity and specificity of cfDNA were similar to those of interferon-gamma releasing assay (IGRA) (sensitivity 80.6% and specificity 71.4%), the combined sensitivity and specificity of the two assays were 94.4% and 64.3%, respectively, which can be used to rule out TB. Conclusions Plasma cfDNA assay seems to be a useful adjunct to the current tests for diagnosing TB, especially when used in combination with IGRA for ruling out TB.AbbreviationsTBtuberculosiscfDNAcell-free DNAPCRpolymerase chain reactionAFBacid-fast bacilliIGRAinterferon-gamma releasing assayCTcomputed tomographyHIVhuman immunodeficiency virus.

BACKGROUND Q fever endocarditis is a major cause of culture-negative endocarditis. The role of Coxellia burnetii is underestimated because it is difficult to diagnose. We investigated the significance of C. burnetii as the cause of culture-negative endocarditis and vascular infection by examining blood and tissue specimens using serological testing and polymerase chain reaction (PCR). METHODS All patients with infective endocarditis or large vessel vasculitis were prospectively enrolled at a tertiary-care hospital from May 2016 through September 2020. Q fever endocarditis and vascular infection were diagnosed based on: (1) positive PCR for a cardiac valve or vascular tissue, (2) positive PCR for blood or phase I immunoglobulin G (IgG) ≥ 6400, or (3) phase I IgG ≥ 800 and < 6400 with morphologic abnormality. PCR targeted C. burnetii transposase gene insertion element IS1111a. RESULTS Of the 163 patients, 40 (25%) had culture-negative endocarditis (n = 35) or vascular infection (n = 5). Of the 40 patients, 24 (60%) were enrolled. Eight (33%) were diagnosed with Q fever endocarditis or vascular infection. Of these 8 patients, 6 had suspected acute Q fever endocarditis or vascular infection with negative phase I IgG. Six patients were not treated for C. burnetii, 4 were stable after surgery. One patient died due to surgical site infection after 5 months post-operatively and one died due to worsening underlying disease. CONCLUSIONS Approximately one-third of patients with culture-negative endocarditis and vascular infection was diagnosed as Q fever. Q fever endocarditis and vascular infection may be underestimated in routine clinical practice in South Korea.KEY MESSAGEQ fever endocarditis and vascular infection may be underestimated in routine clinical practice, thus, try to find evidence of C. burnetti infection in suspected patients by all available diagnostic tests including PCR.

Background During the coronavirus disease 2019 (COVID-19) pandemic, the incidence of rhinovirus (RV) is inversely related to the intensity of non-pharmacological interventions (NPIs), such as universal mask wearing and physical distancing. Methods Using RV surveillance data, changes in the effect of NPIs were investigated in South Korea during the pandemic. The time to the first visible effect of NPIs after the onset of NPIs (T1), time to the maximum effect (T2), and duration of the maximum effect (T3) were measured for each surge. For each week, the RVdiff [(RV incidence during the pandemic) − (RV incidence within 5 years before the pandemic)] was calculated, and number of weeks for RVdiff to be below zero after NPIs (time to RVdiff ≤ 0) and number of weeks RVdiff remains below zero after NPIs (duration of RVdiff ≤ 0) were measured for each surge. Results During the study period, four surges of COVID-19 were reported. As the pandemic progressed, T1 and T2 increased, but T3 decreased. Additionally, the “time to RVdiff of ≤ 0” increased and “duration of RVdiff of ≤ 0” decreased. These changes became more pronounced during the third surge (mid-November 2020), before the introduction of the COVID-19 vaccine, and from the emergence of the delta variant. Conclusion The effect of NPIs appears slower, the duration of the effect becomes shorter, and the intensity also decreases less than a year after the onset of the pandemic owing to people’s exhaustion in implementing NPIs. These findings suggest that the COVID-19 response strategy must be completely overhauled., Graphical Abstract

Despite the accuracy of nucleic acid amplification tests (NAATs), rapid antigen tests (RATs) for severe acute respiratory syndrome coronavirus-2 are widely used as point-of-care tests. A total of 282 pairs of reverse transcription-polymerase chain reaction and Standard Q COVID-19 Ag tests were serially conducted for 68 patients every 3-4 days until their discharge. Through a field evaluation of RATs using direct nasopharyngeal swabs, the sensitivities were 84.6% and 87.3% for

Background: Active surveillance tests for carbapenemase-producing Enterobacteriaceae (CPE) are recommended in patients showing risk factors for colonization by these bacteria. There are limited data however on whether surveillance tests for anatomic sites other than the stool would be useful to detect CPE colonization, and we investigated this in our present study.Methods: Retrospective analysis was performed on cases at our tertiary care hospital during a 5-year period. Patients with CPE colonization had been admitted to our surgical intensive care unit (SICU) or sub-ICU for liver transplantation in this period and undergone surveillance tests for both the stool and other sites. Patients were grouped as stool CPE negative (but which included CPE positive cases from initial sputum and other site tests) or positive. Results: Among the total study cohort of 158 patients, 138 (87.3%) were included in the stool CPE positive group and the remaining 20 (12.7%) in the stool CPE negative group. While the sensitivity of CPE surveillance testing of the stool was 87.3% (95% CI 81.1-92.1), the sensitivity when combining stool and sputum samples was 93.7% (88.7-96.9). The transmission rates were similar for patients showing CPE positivity in the stool, sputum and other sites, at 4.8% (27/557), 4.7% (3/64), and 6.7% (1/15), respectively (p = 0.95).Conclusions: The sensitivity of CPE detection in a stool sample is suboptimal for ruling out CPE colonization and the transmission rates are similar between stool-positive or -negative cases. Thus, combining surveillance of the stool with other sites may be needed for detecting CPE.

In hematopoietic stem cell transplant recipients, the incidence of tuberculosis in positive interferon-γ release assay (IGRA) without isoniazid prophylaxis (3.58/100 person-years) was higher than in negative or indeterminate IGRA (1.15/100 person-years; P = .01) and in positive IGRA with isoniazid prophylaxis (0/100 person-years; P = .09). The number needed to treat was 22 (95% confidence interval, 12–99) with positive IGRA results.

In this study, we investigated the diagnostic utility of the cytokine profile of the cerebrospinal fluid (CSF) and enzyme-linked immunospot (ELISPOT) assays of patients with suspected tuberculous meningitis (TBM). We prospectively enrolled adult patients with suspected TBM, and CSF specimens were analyzed for 18 cytokines/chemokines and soluble programmed death protein 1 (PD-1) and programmed death ligand 1 (PD-L1). Enzyme-linked immunospot assays were performed on mononuclear cells from the CSF (CSF-MCs) and peripheral blood (PBMCs). A total of 87 patients with meningitis, including 42 TBM-suspected patients and 45 non-TBM patients, were enrolled. Excluding the 32 patients with possible TBM, 10 patients with TBM and 45 patients with non-TBM were finally analyzed. Levels of adenosine deaminase (ADA), interleukin 12 subunit β (IL-12p40), IL-13, macrophage inflammatory protein α (MIP-1α), and soluble PD-1 and PD-L1 in the CSF were significantly higher in the TBM group than in the non-TBM group (P < 0.05). The optimal cutoff values for the sensitivities and specificities of the test methods for diagnosing TBM with small samples of 10 cases of definite or probable TBM were as follows: ADA > 6.95 U/L, 70% and 81%; IL-12p40 > 52.04 pg/mL, 80% and 73%; IL-13 > 0.44 pg/mL, 90% and 47%; MIP-1α > 8.83 pg/mL, 80% and 62%; soluble PD-1 > 35.87 pg/mL, 80% and 63%; soluble PD-L1 > 24.19 pg/mL, 80% and 61%; CSF-MC ELISPOT > 13.5 spots/250,000 CSF-MC, 30% and 91%; and PBMC ELISPOT > 14 spots/250,000 PBMCs, 50% and 78%, respectively. Therefore, CSF IL-12p40, IL-13, MIP-1α, and soluble PD-1 and PD-L1 concentrations appear to be useful adjuncts for diagnosing TBM.

The clinical characteristics and outcomes of Streptococcus dysgalactiae subspecies equisimilis (SDSE) bacteremia cases have not been adequately evaluated. We retrospectively enrolled consecutive adult patients with SDSE or S. agalactiae (group B streptococci, GBS) bacteremia at a tertiary care hospital (Republic of Korea) from August 2012 to December 2016. We compared the incidence, seasonality, clinical characteristics, and outcomes of 52 SDSE bacteremia cases with 151 GBS bacteremia cases. The incidence of SDSE and GBS bacteremia in these patients was 1.28/100,000 and 4.22/100,000 person-days, respectively. Most SDSE bacteremia cases were of community-onset infection (SDSE 94.2% vs GBS 83.4%; p = 0.052). Lancefield group G was the most common bacteria type among SDSE isolates (43/47; 91.5%). Patients with SDSE bacteremia were older (median, 68.0 years vs 61.0 years; p = 0.03). In both groups, solid tumor was the most common underlying disease, and more than half of the patients were immunocompromised (51.9% vs 54.3%; p = 0.77). Chronic kidney disease was more common in the SDSE group (19.2% vs 5.3%; p

제1형 자가면역성 췌장염은 그 보고 빈도가 국내에서 점차 증가하는 추세이며 췌장에 국한된 질환이라기보다는 IgG4 연관 질환의 일환으로 이해되고 있다. IgG4 연관 질환은 췌장 외에도 담관, 침샘, 콩팥, 후복막 등의 다양한 장기를 침범할 수 있다. 저자들은 자가면역성 췌장염 환자에서 동반된 악성 위궤양 모양의 위 병변을 IgG4 연관 질환의 임상상으로 진단하고 스테로이드 치료 후 췌장과 위 병변 모두 호전된 증례를 경험하였기에 문헌고찰과 함께 보고하는 바이다.

췌장 신경내분비종양 중 일부는 발견 초기부터 전이가 동반되어 발견될 수 있으며, 그중 간 전이가 가장 흔하다고 알려져 있다. 하지만 다른 질환이 췌장 신경내분비종양과 동반될 수 있으므로, 신중한 접근이 필요하다. 특히 검사 중 원발병변과 상이한 영상 소견이 관찰되는 경우 조직 검사를 포함한 적극적인 검사를 고려하여야 하겠다. 본 증례에서는 췌장신경내분비종양에 동반된 원발성 간 림프종의 증례로, 원위부 췌장절제술 및 비장절제술 시행 후 원발성 간 림프종에 대하여 외래에서 추적 관찰하며 향후 치료 방침을 결정할 예정이다.

The introduction of dedicated phlebotomy teams certified for blood collection has been reported to be highly cost-effective by reducing contamination rates. However, data on their effects on blood volume and true positive rate are limited. Therefore, we investigated the effect of replacing interns with a phlebotomy team on blood culture results. We performed a 24-month retrospective, quasi-experimental study before and after the introduction of a phlebotomy team dedicated to collecting blood cultures in a 2700-bed tertiary-care hospital. The microbiology laboratory database was used to identify adult patients with positive blood culture results. During the study period, there were no changes in blood collection method, blood culture tubes, and the application of antiseptic measures. Blood volume was measured by the BACTEC™ FX system based on red blood cell metabolism. A total of 162,207 blood cultures from 23,563 patients were analyzed, comprising 78,673 blood cultures during the intern period and 83,534 during the phlebotomy team period. Blood volume increased from a mean of 2.1 ml in the intern period to a mean of 5.6 ml in the phlebotomy team period (p

Background Active surveillance tests for carbapenemase-producing Enterobacteriaceae (CPE) are recommended in patients showing risk factors for colonization by these bacteria. There are limited data however on whether surveillance tests for anatomic sites other than the stool would be useful to detect CPE colonization, and we investigated this in our present study. Methods Retrospective analysis was performed on cases at our tertiary care hospital during a 5-year period. The study patients with CPE colonization had been admitted to our surgical intensive care unit (SICU) or sub-ICU for liver transplantation in this period and undergone surveillance tests for both the stool and other sites. Patients were grouped as stool CPE negative (but which included CPE positive cases from initial sputum and other site tests) or positive. Results Among the total study cohort of 158 patients, 138 (87.3%) were included in the stool CPE positive group and the remaining 20 (12.7%) in the stool CPE negative group. While the sensitivity of CPE surveillance testing of the stool was 87.3% (95% CI 81.1-92.1), the sensitivity when combining stool and sputum samples was 93.7% (88.7-96.9). The transmission rates were similar for patients showing CPE positivity in the stool, sputum and other sites, at 4.8% (27/557), 4.7% (3/64), and 6.7% (1/15), respectively (p = 0.95). Conclusion The sensitivity of CPE detection in a stool sample is suboptimal for ruling out CPE colonization and the transmission rates are similar between stool-positive or -negative cases. Combining surveillance of the stool with other sites may be needed for detecting CPE. Disclosures All Authors: No reported disclosures

While chest CT provides important clue for diagnosis of miliary tuberculosis (TB), patients are occasionally missed on initial CT, which might delay the diagnosis. This study was to evaluate the clinical and radiological characteristics of radiologically missed miliary TB. Total 117 adult patients with microbiologically confirmed miliary TB in an intermediate TB-burden country were included. ‘Missed miliary TB’ were defined as the case in which miliary TB was not mentioned as a differential diagnosis in the initial CT reading. Clinical characteristics and radiologic findings including the predominant nodule size, demarcation of miliary nodules and disease extent on CT were retrospectively evaluated. Findings were compared between the missed and non-missed miliary TB groups. Multivariable analyses were performed to determine independent risk factors of missed miliary TB. Of 117 patients with miliary TB, 13 (11.1%) were classified as missed miliary TB; these patients were significantly older than those with non-missed miliary TB (median age, 71 vs 57 years, P = .024). There was a significant diagnostic delay in the missed miliary TB group (P

Background: A rapid and sensitive diagnosis is crucial for the successful management of tuberculosis (TB). The SLIM assay, a novel label-free pathogen enrichment using a microfluidic system, showed a higher sensitivity than the Xpert MTB/RIF assay in the diagnosis of pulmonary TB (PTB). Here, we evaluated the efficacy of the SLIM assay for oral swab samples in the diagnosis of PTB. Methods: Patients with clinically suspected PTB were prospectively enrolled from May 2019 to October 2020. Oral swab samples were processed using the SLIM assay and the attending physicians were blinded to the results of the SLIM assay. TB cases were defined as those treated with anti-TB chemotherapy for at least 6 months at the discretion of the specialists based on clinical features and conventional laboratory results including the Xpert assay. Findings: A total of 272 patients (TB, n=128 [47·1%]; not TB, n=144 [52·9%]; mean age, 59·8 years) were enrolled. Overall, the sensitivity of the oral swab-based SLIM assay (65·6%) was higher than that of the sputum-based Xpert assay (43·4%; p=0·001). Specifically, the SLIM oral swab assay showed a notably higher sensitivity in culture-negative TB cases compared with the Xpert assay (64·7% vs 9·4%; p=0·001). The specificities of the SLIM and the Xpert were 86·1% and 100%, respectively. Interpretation: The oral swab-based SLIM assay showed a superior sensitivity for TB diagnosis over the sputum-based Xpert assay, especially for culture-negative cases. The novel non-sputum-based diagnostic method may confer a better performance in paucibacillary TB compared with the currently available sputum-based methods. Funding: This work was supported by the Korea Medical Device Development Fund grant funded by the Korean government (Project Number: 202011C07-00), the grants from Asan Institute for Life Sciences (2019-7043) and the Ministry of Science, ICT and Future Planning (MSIP) through the National Research Foundation of Korea (NRF) (2020R1A2C2007148). Declaration of Interest: None to declare. Ethical Approval: The institutional review boards of Asan Medical Center (2018-0020) and Severance hospital (4-2018-0029) approved this study, and the protocols of this study were registered in clinicaltrials.gov (NCT03423550).

Diagnosis of Q fever is difficult due to the lack of distinct clinical features that distinguish it from other febrile diseases. Serologic testing is the gold standard method for diagnosing Q fever, but antibody formation may not be detectable for 2 to 3 weeks from symptom onset, limiting early diagnosis. We thus evaluated the diagnostic utility of polymerase chain reaction (PCR) to detect Coxellia burnetii DNA in serum from patients with suspected acute Q fever. All adult patients with suspected acute Q fever were prospectively enrolled at a tertiary-care hospital from January 2016 through July 2018. Acute Q fever was diagnosed using clinical and laboratory criteria: fever with at least one other symptoms (myalgia, headache, pneumonia, or hepatitis) and single phase II immunoglobulin G (IgG) antibody titers ≥1:200 or immunoglobulin M (IgM) antibody titer ≥1:50 (probable), or a fourfold increase or seroconversion in phase II IgG antibody titers as measured by indirect immunofluorescence assays between paired samples (confirmed). We performed PCR targeting the transposase gene insertion element IS1111a of C. burnetii. Of the 35 patients with suspected acute Q fever, 16 (46%) were diagnosed with acute Q fever including 8 probable and 8 confirmed cases; the remaining 19 (54%) were diagnosed with other febrile diseases. The proportion of males diagnosed with Q fever was higher than those diagnosed with other febrile diseases (88% vs 44%, P = .03), but there were no other significant differences in clinical characteristics between the 2 groups. The Q fever PCR sensitivity was 81% (95% confidence interval [CI], 54–96), specificity was 90% (95% CI, 67–99), positive predictive value was 87% (95% CI, 63–96), and negative predictive value was 85% (95% CI, 67–94). Q fever PCR testing using blood from patients with suspected acute Q fever seems to be a rapid and useful test for early diagnosis of Q fever.

We evaluated the diagnostic performance of a simple and label-free pathogen enrichment method using homobifunctional imidoesters (HI) and a microfluidic system, called the SLIM assay, followed by real-time PCR from cerebrospinal fluid (CSF) in human immunodeficiency virus (HIV)-uninfected patients with suspected tuberculous meningitis (TBM). Patients with suspected TBM were prospectively enrolled in a tertiary hospital in an intermediate tuberculosis (TB)-burden country during a 30-month period. TBM was classified according to the uniform case definition. Definite and probable TBM were regarded as the reference standards for TBM, and possible TBM and not-TBM as the reference standards for not-TBM. Of 72 HIV-uninfected patients with suspected TBM, 10 were diagnosed with definite ( n = 2) and probable ( n = 8) TBM by the uniform case definition. The sensitivity of the SLIM assay was 100% (95% confidence interval [CI], 69 to 100%) compared with definite or probable TBM, and it was superior to those of mycobacterial culture (20% [95% CI, 3 to 56%]) and the Xpert MTB/RIF assay (0% [95% CI, 0 to 31%]). Of 21 possible TBM and 41 not-TBM patients by the uniform case definition, 5 possible TBM and no not-TBM patients gave positive results in the SLIM assay. The specificity of the SLIM assay was 92% (95% CI, 82 to 97%; 5/62). We demonstrated that the SLIM assay had a very high sensitivity and specificity with small samples of 10 cases of definite or probable TBM. Further studies are needed to confirm this finding and to compare the SLIM assay with mycobacterial culture, Xpert MTB/RIF, and Xpert MTB/RIF Ultra assays in a larger prospective cohort of patients with suspected TBM, including both HIV-infected and HIV-uninfected cases.

Background Invasive aspergillosis (IA) is an opportunistic fungal infection that mostly occurs in immunocompromised patients, such as those having hematologic malignancy or receiving hematopoietic stem cell transplantation. Inhalation of Aspergillus spores is the main transmission route of IA in immunocompromised patients. Construction work in hospitals is a risk factor for environmental fungal contamination. We measured airborne fungal contamination and the incidence of IA among immunocompromised patients, and evaluated their correlation with different types of construction works. Methods Our tertiary hospital in Seoul, Korea underwent facility construction from September 2017 to February 2018. We divided the entire construction period into period 1 (heavier works: demolition and excavation) and period 2 (lighter works: framing, interior designing, plumbing, and finishing). We conducted monthly air sampling for environmental spore surveillance in three hematologic wards. We evaluated the incidence of IA among all immunocompromised patients hospitalized in the three hematologic wards (2 adult wards and 1 pediatric ward) during this period. IA was categorized into proven, probable, and possible aspergillosis based on the revised European Organization for Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSG) criteria. Results A total of 15 patients was diagnosed with proven (1 case), probable (8 cases), or possible (6 cases) hospital-acquired IA during period 1. In period 2, 14 patients were diagnosed with either proven (1 case), probable (10 cases), or possible (3 cases) hospital-acquired IA. Total mold and Aspergillus spp. spore levels in the air tended to be higher in period 1 (p = 0.06 and 0.48, respectively). The incidence rate of all IA by the EORTC/MSG criteria was significantly higher in period 1 than in period 2 (1.891 vs. 0.930 per 1000 person-days, p = 0.05). Conclusions Airborne fungal spore levels tended to be higher during the period with heavier construction works involving demolition and excavation, during which the incidence of IA was significantly higher as well. We recommend monitoring airborne fungal spore levels during construction periods in hospitals with immunocompromised patients. Subsequently, the effect of airborne fungal spore level monitoring in reducing hospital-acquired IA should be evaluated. Electronic supplementary material The online version of this article (10.1186/s13756-019-0543-1) contains supplementary material, which is available to authorized users.

Background Pauci-bacillary pulmonary tuberculosis (TB) can be delayed to diagnose and start anti-TB therapy, especially in immunocompromised patients. We therefore evaluated the clinical and radiologic features of these delayed cases. Methods Immunocompromised adult patients with pauci-bacillary pulmonary TB were retrospectively enrolled in a tertiary hospital in an intermediate–TB burden country over a 5-year period. We defined “missed TB” or “not-missed TB” patients as those who started anti-TB therapy after or before positive mycobacterial culture results, respectively. Results Of 258 patients, 134 (52%) were classified in the missed TB group, and 124 (48%) in the not-missed TB group. Positive results of molecular tests including MTB polymerase chain reaction and/or Xpert TB/RIF were only obtained in the not-missed TB group (54/106, 54%). The median diagnostic delay in the missed TB group was longer than in the other group (30 vs 6 days; P < .001). In the missed TB group, the most common working diagnoses were pneumonia (46, 34%) and lung metastasis of malignancy (40, 30%). Typical radiologic findings for TB, such as upper lobe predominance and centrilobular nodules with tree-in-bud appearance, were less common in the missed TB group than in the other group. Old age (odds ratio [OR], 1.03), solid organ transplant (OR, 3.46), solid tumor (OR, 3.83), and hematologic malignancy (OR, 4.04) were independently associated with missed TB. Conclusions Care is needed to differentiate pauci-bacillary TB, especially in immunocompromised patients with the mentioned risk factors, even without the usual radiologic features of TB. Additional rapid diagnostic tests to rule out pauci-bacillary TB are urgently needed.

Background Tuberculous meningitis (TBM) is the most severe form of tuberculosis, but differentiating between the diagnosis of TBM and viral meningitis (VM) is difficult. Thus, we have developed machine-learning modules for differentiating TBM from VM. Material and Methods For the training data, confirmed or probable TBM and confirmed VM cases were retrospectively collected from five teaching hospitals in Korea between January 2000 - July 2018. Various machine-learning algorithms were used for training. The machine-learning algorithms were tested by the leave-one-out cross-validation. Four residents and two infectious disease specialists were tested using the summarized medical information. Results The training study comprised data from 60 patients with confirmed or probable TBM and 143 patients with confirmed VM. Older age, longer symptom duration before the visit, lower serum sodium, lower cerebrospinal fluid (CSF) glucose, higher CSF protein, and CSF adenosine deaminase were found in the TBM patients. Among the various machine-learning algorithms, the area under the curve (AUC) of the receiver operating characteristics of artificial neural network (ANN) with ImperativeImputer for matrix completion (0.85; 95% confidence interval 0.79 - 0.89) was found to be the highest. The AUC of the ANN model was statistically higher than those of all the residents (range 0.67 - 0.72, P

While the Xpert MTB/RIF assay (Cepheid Sunnyvale, CA, USA) has greater than 95% sensitivity for identifying acid-fast bacilli (AFB) smear-positive tuberculosis (TB) cases, for smear-negative pulmonary tuberculosis (PTB) the sensitivity was as low as 60% [1, 2]. To address the low sensitivity of current TB diagnostics for AFB smear-negative cases, we developed a simple and label-free pathogen enrichment using homobifunctional imidoesters (HIs) using a microfluidic (SLIM) platform followed by conventional MTB PCR to extract low amounts of pathogens from clinical samples [3]. In this study, we compared the diagnostic performance of the SLIM assay with the Xpert MTB/RIF for PTB diagnosis in a country with an intermediate TB burden and a low human immunodeficiency virus burden. The SLIM assay were performed by using 1 mL and 2 mL aliquots of sputum, respectively. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: None Conflict of interest: None Conflict of interest: None Conflict of interest: None Conflict of interest: None Conflict of interest: None Conflict of interest: None Conflict of interest: None Conflict of interest: None Conflict of interest: None

Summary Objectives The IFN-γ-release assay (IGRA) cannot differentiate active tuberculosis (TB) from latent TB infection (LTBI). We hypothesized that the TNF-α-release assay (TARA) combined with IGRA might discriminate active TB from not active TB without LTBI. Methods Adult patients with suspected TB, and with unrelated diseases such as herpes zoster as controls, were enrolled in an intermediate TB-burden country. Patients with confirmed or probable TB were regarded as active TB, and patients with not active TB were further classified as those having not active TB with and without LTBI based on IGRA results. The IGRA and TARA by using ELISPOT assays were performed on peripheral mononuclear cells. Results Thirty six patients with active TB and 53 patients including 18 not active TB with LTBI and 35 not active TB without LTBI were finally included. The sensitivity and specificity of the IGRA for those patients found to have active TB were 94% (CI, 80-99) and 66% (CI 52-78), respectively. Combining the IGRA and the TARA substantially increased the specificity for active TB (93%, CI, 82-98; P = 0.001) compared with the IGRA only, without compromising sensitivity (89%, CI, 73-96; P = 0.67). Conclusions Combining the IGRA and TARA appears to be useful for diagnosing active TB.