Plasma indoleamine 2,3-dioxygenase, a highly sensitive blood-based screening tool for active tuberculosis disease in HIV-infected pregnant women

AbstractOutside of the ongoing COVID-19 pandemic, tuberculosis is the leading cause of infectious disease mortality globally. Currently, there is no commercially available point-of-care diagnostic that is rapid, inexpensive, and highly sensitive for the diagnosis of active tuberculosis disease. Here we describe the development and optimization of a novel, highly sensitive prototype bioelectronic tuberculosis antigen (BETA) assay to detect tuberculosis-specific antigen, CFP10, in small-volume serum and urine samples. In this proof-of-concept study we evaluated the performance of the BETA assay using clinical specimens collected from presumptive tuberculosis patients from three independent cohorts. Circulating CFP10 antigen was detected in ALL serum (n = 19) and urine (n = 3) samples from bacteriologically confirmed tuberculosis patients who were untreated or had less than one week of treatment at time of serum collection, successfully identifying all culture positive tuberculosis patients. No CFP10 antigen was detected in serum (n = 7) or urine (n = 6) samples from individuals who were determined to be negative for tuberculosis disease. Additionally, antigen quantification using the BETA assay of paired serum samples collected from tuberculosis patients (n = 8) both before and after treatment initiation, indicate consistently declining within-person levels of CFP10 antigen during treatment. This novel, low-cost assay demonstrates potential as a rapid, non-sputum-based, point-of-care tool for the diagnosis of tuberculosis disease.

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Faculty Opinions recommendation of Predictive value of a whole blood IFN-gamma assay for the development of active tuberculosis disease after recent infection with Mycobacterium tuberculosis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1120649.576874 ◽

2008 ◽

Author(s):

Ric Price ◽

Krispin Hajkowicz

Keyword(s):

Mycobacterium Tuberculosis ◽

Whole Blood ◽

Predictive Value ◽

Active Tuberculosis ◽

Recent Infection ◽

Ifn Gamma ◽

Tuberculosis Disease ◽

Gamma Assay

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NESTROFT—A Cost-Effective Mass Screening Tool for the Detection of β-Thalassemia Carrier Status in Anemic Pregnant Women: A Step Toward Reducing the National Disease Burden

Journal of Laboratory Physicians ◽

10.1055/s-0041-1732493 ◽

2021 ◽

Author(s):

Manasi Gosavi ◽

Ramesh Chavan ◽

M. B. Bellad

Keyword(s):

Pregnant Women ◽

Effective Mass ◽

Mass Screening ◽

Predictive Value ◽

Screening Tool ◽

Hematological Parameters ◽

False Negative ◽

Cost Effective ◽

Mean Corpuscular Hemoglobin ◽

Carrier Status

Abstract Introduction β-Thalassemias are inherited hemoglobinopathies commonly encountered in practice. With chances of a promising cure being rare, the prevention of births with this disorder should assume priority, especially in low-resource countries. This can be achieved by the implementation of a mass screening program that is reliable and, at the same time, cost-effective. Objectives This study focuses on the utility of Naked Eye Single Tube Red Cell Osmotic Fragility Test (NESTROFT) as a mass screening tool to detect thalassemia carriers. Hematological parameters that may predict carrier status were also evaluated. Materials and Methods Hemoglobin estimation was performed on all consented pregnant women. If the patient was found to have hemoglobin < 11 g/dL, the blood sample was subjected to other routine hematological tests along with peripheral smear examination. NESTROFT was performed using 0.36% saline solution. Confirmation was done using high-performance liquid chromatography (HPLC). Statistical Analysis Data obtained were tabulated using version 21 of the Statistical Package for Social Sciences. Means, standard deviations, and percentages were used to describe the sample. Chi-square test and Students’ “t” test were used to identify differences between the groups. Results Of 441 pregnant women enrolled, 206 were found to be anemic. Nineteen (9.2%) of the anemic pregnant women were detected to be carriers of hemoglobinopathies. Among the hematological parameters, mean red blood cell count and reticulocyte count were higher, while mean corpuscular hemoglobin concentration was lower in carriers. Also, carriers were more likely to present with microcytic hypochromic anemia. NESTROFT showed a sensitivity of 84.21%, specificity of 96.25%, a positive predictive value of 69.56%, and a negative predictive value of 98.36%. A false-positive result was seen in 3.74% of the tests, while a false negative result was seen in 15.78% of the tests. Conclusions NESTROFT (0.36%) can be used as a simple and cost-effective mass screening tool for the detection of carrier status. This should be followed by confirmation using HPLC or hemoglobin electrophoresis.

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Use of Calcium Channel Blockers and Risk of Active Tuberculosis Disease

Hypertension ◽

10.1161/hypertensionaha.120.15534 ◽

2021 ◽

Vol 77 (2) ◽

pp. 328-337

Author(s):

Chien-Chang Lee ◽

Meng-tse Gabriel Lee ◽

Wan-Ting Hsu ◽

James Yeongjun Park ◽

Lorenzo Porta ◽

...

Keyword(s):

Calcium Channel ◽

Risk Score ◽

Calcium Channel Blockers ◽

Lower Risk ◽

Disease Risk ◽

Active Tuberculosis ◽

Channel Blockers ◽

Disease Risk Score ◽

Subgroup Analyses ◽

Tuberculosis Disease

Calcium channel blockers (CCBs) are known to reduce the availability of iron—an important mineral for intracellular pathogens. Nonetheless, whether the use of CCBs modifies the risk of active tuberculosis in the clinical setting remains unclear. To determine whether CCBs may modify the risk of active tuberculosis disease, we conducted a nested case-control study using the National Health Insurance Research Database of Taiwan between January 1999 and December 2011. Conditional logistic regression and disease risk score adjustment were used to calculate the risk of active tuberculosis disease associated with CCB use. Subgroup analyses investigated the effect of different types of CCBs and potential effect modification in different subpopulations. A total of 8164 new active tuberculosis cases and 816 400 controls were examined. Use of CCBs was associated with a 32% decrease in the risk of active tuberculosis (relative risk [RR], 0.68 [95% CI, 0.58–0.78]) after adjustment with disease risk score. Compared with nonuse of CCBs, the use of dihydropyridine CCBs was associated with a lower risk of tuberculosis (RR, 0.63 [95% CI, 0.53–0.79]) than nondihydropyridine CCBs (RR, 0.73 [95% CI, 0.57–0.94]). In contrast, use of β-blockers (RR, 0.99 [95% CI, 0.83–1.12]) or loop diuretics (RR, 0.88 [95% CI, 0.62–1.26]) was not associated with lower risk of tuberculosis. In subgroup analyses, the risk of tuberculosis associated with the use of CCBs was similar among patients with heart failure or cerebrovascular diseases. Our study confirms that use of dihydropyridine CCBs decreases the risk of active tuberculosis.

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