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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.

A rapid and sensitive diagnosis is crucial for the management of tuberculosis (TB). A simple and label-free approach via homobifunctional imidoesters with a microfluidic platform (SLIM) assay 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 from cases of suspected PTB. Patients with clinically suspected PTB were prospectively enrolled and 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 their clinical features and conventional laboratory results, including the Xpert assay. A total of 272 patients (with TB

Background A few studies have mentioned that post-bronchoscopy sputum (PBS) could improve the diagnostic yield in pauci-bacillary pulmonary tuberculosis (PTB). Therefore, we evaluated the diagnostic yield of PBS for diagnosing pauci-bacillaryPTB. Methods Clinical data of immunocompromised adult patients with pauci-bacillary PTB were retrospectively retrieved at a tertiary hospital in Seoul, South Korea over a 5-year period. We analyzed patients who underwent bronchoscopy examinations for diagnosing pauci-bacillary PTB. Results Ninety patients were finally analyzed. Of these patients, 76 patients were tested with PBS. Six (8%) of these patients had positive results on AFB smear of PBS alone. Additionally, 52 patients (68%) had positive results on mycobacterial culture and 12 (16%) had positive results on mycobacterial culture of PBS exclusively. Therefore, in this study population, a total of 18 patients (20%) were finally diagnosed as having PTB with PBS results only, even though AFB smear microscopy and culture of other specimens had negative results. Conclusions PBS could improve the diagnostic yield by 20% when diagnosing pauci-bacillary PTB. In addition, about 8% of the patients could be diagnosed rapidly because of AFB smear microscopy positivity for PBS. Therefore, PBS use should be considered as a complementary diagnostic approach in patients with suspected pauci-bacillary PTB.

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

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

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

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

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.

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.