Erratum for the Research Article: “A rapid triage test for active pulmonary tuberculosis in adult patients with persistent cough” by R. Ahmad, L. Xie, M. Pyle, M. F. Suarez, T. Broger, D. Steinberg, S. M. Ame, M. G. Lucero, M. J. Szucs, M. MacMullan, F. S. Berven, A. Dutta, D. M. Sanvictores, V. L. Tallo, R. Bencher, D. P. Eisinger, U. Dhingra, S. Deb, S. M. Ali, S. Mehta, W. W. Fawzi, I. D. Riley, S. Sazawal, Z. Premji, R. Black, C. J . L. Murray, B. Rodriguez, S. A. Carr, D. R. Walt, M. A. Gillette

Improved tuberculosis (TB) prevention and control depend critically on the development of a simple, readily accessible rapid triage test to stratify TB risk. We hypothesized that a blood protein-based host response signature for active TB (ATB) could distinguish it from other TB-like disease (OTD) in adult patients with persistent cough, thereby providing a foundation for a point-of-care (POC) triage test for ATB. Three adult cohorts consisting of ATB suspects were recruited. A bead-based immunoassay and machine learning algorithms identified a panel of four host blood proteins, interleukin-6 (IL-6), IL-8, IL-18, and vascular endothelial growth factor (VEGF), that distinguished ATB from OTD. An ultrasensitive POC-amenable single-molecule array (Simoa) panel was configured, and the ATB diagnostic algorithm underwent blind validation in an independent, multinational cohort in which ATB was distinguished from OTD with receiver operator characteristic–area under the curve (ROC-AUC) of 0.80 [95% confidence interval (CI), 0.75 to 0.85], 80% sensitivity (95% CI, 73 to 85%), and 65% specificity (95% CI, 57 to 71%). When host antibodies against TB antigen Ag85B were added to the panel, performance improved to 86% sensitivity and 69% specificity. A blood-based host response panel consisting of four proteins and antibodies to one TB antigen can help to differentiate ATB from other causes of persistent cough in patients with and without HIV infection from Africa, Asia, and South America. Performance characteristics approach World Health Organization (WHO) target product profile accuracy requirements and may provide the foundation for an urgently needed blood-based POC TB triage test.

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Evaluation of the diagnostic performance of laboratory-based c-reactive protein as a triage test for active pulmonary tuberculosis

PLoS ONE ◽

10.1371/journal.pone.0254002 ◽

2021 ◽

Vol 16 (7) ◽

pp. e0254002

Author(s):

Thomas H. A. Samuels ◽

Romain Wyss ◽

Stefano Ongarello ◽

David A. J. Moore ◽

Samuel G. Schumacher ◽

...

Keyword(s):

Pulmonary Tuberculosis ◽

C Reactive Protein ◽

Characteristic Analysis ◽

Serum Samples ◽

Retrospective Case ◽

Active Pulmonary Tuberculosis ◽

Reactive Protein ◽

District Hospitals ◽

Cutoff Points ◽

Triage Test

Introduction A highly sensitive triage test that captures most symptomatic patients at increased likelihood of having pulmonary tuberculosis (PTB) would ‘rule-out’ lower-risk patients from expensive confirmatory testing. Although studies have assessed the diagnostic accuracy of a C-reactive protein (CRP) triage test for PTB in HIV+ patients, limited data are available from HIV- cohorts. Materials and methods In this retrospective case-control study, 765 serum samples were selected from FIND’s biobank. Each sample had been collected from an adult presenting with respiratory symptomatology to district hospitals in South Africa and referral hospitals in Cambodia, Peru, Georgia and Vietnam between 2007–2017. Serum CRP measurements were obtained using a laboratory-based assay. CRP cutoff-points of ≥8mg/L and ≥10mg/L were predefined as a positive triage test result. The PTB reference standard was two contemporaneously collected sputum liquid culture results. Results CRP demonstrated an overall sensitivity for PTB of 79.8% (95%CI 75.5–83.5) and 77.7% (95%CI 73.4–81.6) for cutoff-points of 8mg/L and 10mg/L respectively. Specificity was 62.8% (95%CI 57.8–67.6%) and 66.6% (95%CI 61.1–70.7) respectively. Area-under-the-curve using Receiver Operating Characteristic analysis was 0.77 (95%CI 0.74–0.81). Threshold analysis showed optimal CRP cutoff-points were higher in HIV+ than HIV- participants. An algorithm in which CRP triage was followed by confirmatory Xpert MTB/Rif testing achieved a sensitivity of 75.1% (95%CI 69.0–80.4%) whilst decreasing Xpert usage by 40.6%. Discussion CRP may not meet the challenge of a catch-all TB triage test. However, it shows promise in HIV+ individuals. Further research is required in a prospective study using point-of-care platforms to further evaluate its capabilities.

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Abstract #542 An Unusual Initial Presentation of Active Pulmonary Tuberculosis: Severe Hypercalcemia with Altered Mental Status and Renal Failure

Endocrine Practice ◽

10.1016/s1530-891x(20)47219-2 ◽

2018 ◽

Vol 24 ◽

pp. 130

Author(s):

Matthew Mandell ◽

Jennifer Velasco ◽

Armand Krikorian ◽

Anupama Ananth ◽

Joumana Chaiban ◽

...

Keyword(s):

Renal Failure ◽

Pulmonary Tuberculosis ◽

Mental Status ◽

Altered Mental Status ◽

Initial Presentation ◽

Active Pulmonary Tuberculosis ◽

Severe Hypercalcemia

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Electroconvulsive and insulin coma therapy in the presence of active pulmonary tuberculosis

PsycEXTRA Dataset ◽

10.1037/e534382008-003 ◽

1955 ◽

Author(s):

Louis Weinstein

Keyword(s):

Pulmonary Tuberculosis ◽

Active Pulmonary Tuberculosis ◽

Insulin Coma ◽

Insulin Coma Therapy

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Deep-Learning Based Automated Detection Algorithm for Active Pulmonary Tuberculosis on Chest Radiographs: Diagnostic Performance in Systematic Screening of Asymptomatic Individuals

SSRN Electronic Journal ◽

10.2139/ssrn.3369785 ◽

2019 ◽

Author(s):

Jong Hyuk Lee ◽

Sunggyun Park ◽

Eui Jin Hwang ◽

Jin Mo Goo ◽

Woo Young Lee ◽

...

Keyword(s):

Deep Learning ◽

Pulmonary Tuberculosis ◽

Diagnostic Performance ◽

Detection Algorithm ◽

Automated Detection ◽

Chest Radiographs ◽

Systematic Screening ◽

Active Pulmonary Tuberculosis ◽

Asymptomatic Individuals

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Metabolism of Heterogenic Hemoglobins

Blood ◽

10.1182/blood.v22.3.334.334 ◽

1963 ◽

Vol 22 (3) ◽

pp. 334-341 ◽

Cited By ~ 10

Author(s):

RICHARD D. LEVERE ◽

HERBERT C. LICHTMAN ◽

Joan Levine

Keyword(s):

Pulmonary Tuberculosis ◽

Sickle Cell ◽

Sickle Cell Trait ◽

Hemoglobin S ◽

Active Pulmonary Tuberculosis ◽

Hemoglobin A ◽

Abnormal Hemoglobin

Abstract The relative rates of incorporation of Fe59 into heterogenic hemoglobins was studied in four patients with sickle cell trait. Three of the patients were free of superimposed disease, while one had active pulmonary tuberculosis. In all subjects there was a significantly greater incorporation of radioiron, per milligram of hemoglobin, into hemoglobin S than into hemoglobin A. The data indicate that in sickle cell trait the rates of synthesis of the heterogenic hemoglobins are not proportional to their circulating concentrations. Two interpretations appear possible. Since the size of the intra-marrow pool of hemoglobin S was not known, it is possible that there exists a smaller preformed pool of the abnormal hemoglobin, with the isotope making its appearance first in hemoglobin S. However, it is also possible that hemoglobin S is synthesized at a rate which is greater than that reflected by its circulating concentration. This implies that the relative concentrations of hemoglobin S and hemoglobin A vary from erythrocyte to erythrocyte, and that those cells with the greatest proportion of hemoglobin S are selectively destroyed.

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