The effect of new Mycobacterium tuberculosis infection on the sensitivity of prognostic TB signatures

BACKGROUND: Tests that identify individuals at greatest risk of TB will allow more efficient targeting of preventive therapy. The WHO target product profile for such tests defines optimal sensitivity of 90% and minimum sensitivity of 75% for predicting incident TB. The CORTIS (Correlate of Risk Targeted Intervention Study) evaluated a blood transcriptomic signature (RISK11) for predicting incident TB in a high transmission setting. RISK11 is able to predict TB disease progression but optimal prognostic performance was limited to a 6-month horizon.METHODS: Using a mathematical model, we estimated how subsequent Mycobacterium tuberculosis (MTB) infection may have contributed to the decline in sensitivity of RISK11. We calculated the effect at different RISK11 thresholds (60% and 26%) and for different assumptions about the risk of MTB infection.RESULTS: Modelled sensitivity over 15 months, excluding new infection, was 28.7% (95% CI 12.3–74.1) compared to 25.0% (95% CI 12.7–45.9) observed in the trial. Modelled sensitivity exceeded the minimum criteria (>75%) over a 9-month horizon at the 60% threshold and over 12 months at the 26% threshold.CONCLUSIONS: The effect of new infection on prognostic signature performance is likely to be small. Signatures such as RISK11 may be most useful in individuals, such as household contacts, where probable time of infection is known.

Comparative sensitivity evaluation for 122 CE-marked rapid diagnostic tests for SARS-CoV-2 antigen, Germany, September 2020 to April 2021

Introduction Numerous CE-marked SARS-CoV-2 antigen rapid diagnostic tests (Ag RDT) are offered in Europe, several of them with unconfirmed quality claims. Aim We performed an independent head-to-head evaluation of the sensitivity of SARS-CoV-2 Ag RDT offered in Germany. Methods We addressed the sensitivity of 122 Ag RDT in direct comparison using a common evaluation panel comprised of 50 specimens. Minimum sensitivity of 75% for panel specimens with a PCR quantification cycle (Cq) ≤ 25 was used to identify Ag RDT eligible for reimbursement in the German healthcare system. Results The sensitivity of different SARS-CoV-2 Ag RDT varied over a wide range. The sensitivity limit of 75% for panel members with Cq ≤ 25 was met by 96 of the 122 tests evaluated; 26 tests exhibited lower sensitivity, few of which failed completely. Some RDT exhibited high sensitivity, e.g. 97.5 % for Cq < 30. Conclusions This comparative evaluation succeeded in distinguishing less sensitive from better performing Ag RDT. Most of the evaluated Ag RDT appeared to be suitable for fast identification of acute infections associated with high viral loads. Market access of SARS-CoV-2 Ag RDT should be based on minimal requirements for sensitivity and specificity.

Comparative sensitivity evaluation for 122 CE-marked SARS-CoV-2 antigen rapid tests

Objective Independent evaluation of the sensitivity of CE-marked SARS-CoV-2 antigen rapid diagnostic tests (Ag RDT) offered in Germany. Method The sensitivity of 122 Ag RDT was adressed using a common evaluation panel. Minimum sensitivity of 75% for panel members with CT<25 was used for differentiation of devices eligible for reimbursement in in the German healthcare system. Results The sensitivity of different SARS-CoV-2 Ag RDT varied over a wide range. The sensitivity limit of 75% for panel members with CT <25 was met by 96 of the 122 tests evaluated; 26 tests exhibited lower sensitivity, few of which were completely failing. Some devices exhibited high sensitivity, e.g. 100% for CT<30. Conclusion This comparative evaluation succeeded to distinguish less sensitive from better performing Ag RDT. Most of the Ag RDT evaluated appear to be suitable for fast identification of acute infections associated with high viral loads. Market access of SARS-CoV-2 Ag RDT should be based on minimal requirements for sensitivity and specificity.

Whole Virus Detection using Paper Potentiometry

Paper-based sensors, microfluidic platforms and electronic devices have attracted attention in the past couple of decades because they are flexible, can be recycled easily, environmentally friendly, and inexpensive. Here we report a paper aptamer-based potentiometric sensor to detect the whole Zika virus for the first time with a minimum sensitivity of 2.6 nV/Zika and the minimum detectable signal (MDS) of 0.8x1e6 Zika. Our paper sensor works very similar to a P-N junction where a junction is formed between two different wet regions with different electrochemical potentials near each other on the paper. These two regions with slightly different ionic contents, ionic species and concentrations, produce a potential difference given by the Nernst equation. Our paper sensor consisted of a 2-3 mm x 10 mm segments of a paper with a conducting silver paint contact patches on its two ends. The paper is soaked in a buffer solution containing aptamers designed to bind to the capsid proteins on Zika. Atomic force microscopy studies were carried out to show both the aptamer and Zika become immobilized in the paper. We then added the Zika (in its own buffer or simulant Urine) to the region close to one of the silver-paint contacts. The Zika virus (40 nm diameter with 43 kDa or 7.1x10-20 gm weight), became immobilized in the paper&rsquo;s pores and bonded with the resident aptamers creating a concentration gradient. The potential measured between the two silver paint contacts reproducibly became more negative as upon adding the Zika. We also showed that an LCD powered by the sensor, can be used to detect the sensor output.

Whole Virus Detection Using Paper Potentiometry and Aptamers

Paper-based sensors, microfluidic platforms and electronic devices have attracted attention in the past couple of decades because they are flexible, can be recycled easily, environmentally friendly, and inexpensive. Here we report a paper aptamer-based potentiometric sensor to detect the whole Zika virus for the first time with a minimum sensitivity of 2.6 nV/Zika and the minimum detectable signal (MDS) of 1.2x106 Zika. Our paper sensor works very similar to a P-N junction where a junction is formed between two different wet regions with different electrochemical potentials near each other on the paper. These two regions with slightly different ionic contents, ionic species and concentrations, produce a potential difference given by the Nernst equation. Our paper sensor consisted of a 2-3 mm x 10 mm segments of a paper with a conducting silver paint contact patches on its two ends. The paper is soaked in a buffer solution containing aptamers designed to bind to the capsid proteins on Zika. Atomic force microscopy studies were carried out to show both the aptamer and Zika become immobilized in the paper. We then added the Zika (in its own buffer) to the region close to one of the silver-paint contacts. The Zika virus (40 nm diameter with 43 kDa or 7.1x10-20 gm weight), became immobilized in the paper&rsquo;s pores and bonded with the resident aptamers creating a concentration gradient. The potential measured between the two silver paint contacts reproducibly became more negative as upon adding the Zika. We also showed that an LCD powered by the sensor, can be used to detect the sensor output.

Influence of Charge Carriers Concentration and Mobility on the Gas Sensing Behavior of Tin Dioxide Thin Films

In order to investigate function of carrier behavior on gas-sensing properties, tin oxide-based films with different carrier concentration and mobility were obtained, by magnetron sputtering from the powder target, which was followed by further oxygen-management though the annealing treatment. The microstructure, surface morphology, electrical properties and gas sensitivity were characterized by XRD, Raman spectrum, photoluminescence spectrum, atomic force microscope, the hall effect system and electrochemical workstation, respectively. The results showed that all SnO2-based films had a tetragonal rutile phase with (101) preferred orientation. The introduction of fluorine and regulation of oxygen vacancies tuned carrier concentration from 1015/cm3 to 1021/cm3 and mobility from 102 cm2/V·s to 10−1 cm2/V·s. The decreasing carrier concentration as well as increasing mobility had a positively important function to improve the sensitivity of SnO2-based films. The air-annealed SnO2 film with lowest carrier concentration had a maximum sensitivity of R = 5.0, while vacuum-annealed SnO2:F film with the highest carrier concentration being the minimum sensitivity. This puts forward a novel reference for the design and application of SnO2-based gas sensing films.