scholarly journals SeeTB: A novel alternative to sputum smear microscopy to diagnose tuberculosis in high burden countries

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Vikas Pandey ◽  
Pooja Singh ◽  
Saumya Singh ◽  
Naresh Arora ◽  
Neha Quadir ◽  
...  

Abstract Microscopy-based tuberculosis (TB) diagnosis i.e. Ziehl-Neelsen screening still remains the primary diagnostic method in resource poor and high TB burden countries, however this method has poor sensitivity (~60%). Bringing three million TB patients who are left undiagnosed under the treatment has been a major focus as part of END-TB strategy across the world. We have developed a portable set-up called ‘SeeTB’ that converts a bright-field microscope into fluorescence microscope (FM) with minimal interventions. SeeTB, a total internal reflection-based fluorescence excitation system allows visualization of auramine-O stained bacilli efficiently with high signal-to-noise ratio. Along with the device, we have developed a sputum-processing reagent called ‘CLR’ that homogenizes and digests the viscous polymer matrix of sputum. We have compared the performance of SeeTB system in 237 clinical sputum samples along with FM, GeneXpert and liquid culture. In comparison with culture as gold standard, FM has sensitivity of 63.77% and SeeTB has improved sensitivity to 76.06%. In comparison with GeneXpert, FM has sensitivity of 73.91% while SeeTB has improved sensitivity to 85.51%. However, there is no significant change in the specificity between FM and SeeTB system. In short, SeeTB system offers the most realistic option for improved TB case identification in resource-limited settings.

2020 ◽  
Author(s):  
Brett M. Babin ◽  
Gabriela Fernandez-Cuervo ◽  
Jessica Sheng ◽  
Ori Green ◽  
Alvaro A. Ordonez ◽  
...  

AbstractTuberculosis (TB) is a top-ten cause of death worldwide. Successful treatment is often limited by insufficient diagnostic capabilities, especially at the point of care in low-resource settings. The ideal diagnostic must be fast, cheap, and require minimal clinical resources while providing high sensitivity, selectivity, and the ability to differentiate live from dead bacteria. We describe here the development of a Fast, Luminescent, and Affordable Sensor of Hip1 (FLASH) for the diagnosis and monitoring of drug sensitivity of Mycobacterium tuberculosis (Mtb). FLASH is a selective chemiluminescent substrate for the Mtb protease Hip1 that when processed, produces visible light that can be measured with a high signal to noise ratio using inexpensive sensors. FLASH is sensitive to fmol of recombinant Hip1 enzyme in vitro and can detect as few as thousands of Mtb cells in culture or in human sputum samples within minutes. The probe is highly selective for Mtb compared to other non-tuberculous mycobacteria and can distinguish live from dead cells. Importantly, FLASH can be used to measure antibiotic killing of Mtb in culture with greatly accelerated timelines compared to traditional protocols. Overall, FLASH has the potential to enhance both TB diagnostics and drug resistance monitoring in resource-limited settings.One Sentence SummaryA luminescent probe enables sensitive detection of Mycobacterium tuberculosis for diagnostics, treatment monitoring, and drug susceptibility testing.


2019 ◽  
Vol 205 ◽  
pp. 09009 ◽  
Author(s):  
Li Liu ◽  
Damianos Agathangelou ◽  
Thomas Roland ◽  
Olivier Crégut ◽  
Thibaud Duchanois ◽  
...  

We demonstrate the implementation of a broadband fluorescence up-conversion set-up with high signal-to-noise ratio and dynamic range allowing for the detection of weak luminescence from triplet states in Fe(II) NHC complexes. Based on the experimentally determined radiative rates and the emission spectra, these states have dominant MLCT character.


Author(s):  
Abraham ◽  
Nwobodo ◽  
Ngwu ◽  
Onwuatuegwu ◽  
Nwaogwugwu ◽  
...  

Tuberculosis and human Immuno-deficiency virus co-epidemics remain a major public health challenge particularly in resource limited settings. This study determined the prevalence of HIV co-infection among TB patients and the risk factors among patients attending Holly memorial Hospital Ochadamu, Ofu L.G.A., Kogi State, Nigeria. Two hundred (200) patients participated in the research, out of which one hundred and seventy three (173) were already confirmed to be HIV positive. Sputum samples were collected by experts into sample bottles aseptically for Acid fast Bacilli test for Mycobacterium tuberculosis; while blood samples were collected by trained nurses from the same candidates by venepuncture into anticoagulated bottles for HIV screening to re- confirm their status. Questionnaires were also administered to obtain some important demographic data. Sputum smear microscopy was carried out to test for Acid Fast Bacilli. Rapid haemagglutination assay was carried out to re-confirm the HIV status of the patients. Results showed that Twenty seven (27) patients signifying 13.5 % were TB/HIV co-infected. There was significant (p<0.05) relationship between TB and HIV status of the patients and clinical symptoms (dry cough, cough with sputum, weight loss and fever). There is need to study Immuno-haematological indices (CD4 count, Full Blood Count and ESR) routinely to monitor TB and HIV patients on regular basis in order to reduce morbidity and mortality associated with the diseases.


2010 ◽  
Vol 17 (10) ◽  
pp. 1539-1547 ◽  
Author(s):  
Gregory C. Ireton ◽  
Rena Greenwald ◽  
Hong Liang ◽  
Javan Esfandiari ◽  
Konstantin P. Lyashchenko ◽  
...  

ABSTRACT Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis, with several million new cases detected each year. Current methods of diagnosis are time-consuming and/or expensive or have a low level of accuracy. Therefore, new diagnostics are urgently needed to address the global tuberculosis burden and to improve control programs. Serological assays remain attractive for use in resource-limited settings because they are simple, rapid, and inexpensive and offer the possibility of detecting cases often missed by routine sputum smear microscopy. The aim of this study was to identify M. tuberculosis seroreactive antigens from a panel of 103 recombinant proteins selected as diagnostic candidates. Initial library screening by protein array analysis and enzyme-linked immunosorbent assay (ELISA) identified 42 antigens with serodiagnostic potential. Among these, 25 were novel proteins. The reactive antigens demonstrated various individual sensitivities, ranging from 12% to 78% (specificities, 76 to 100%). When the antigens were analyzed in combinations, up to 93% of antibody responders could be identified among the TB patients. Selected seroreactive proteins were used to design 3 new polyepitope fusion proteins. Characterization of these antigens by multiantigen print immunoassay (MAPIA) revealed that the vast majority of the TB patients (90%) produced antibody responses. The results confirmed that due to the remarkable variation in immune recognition patterns, an optimal multiantigen cocktail should be designed to cover the heterogeneity of antibody responses and thus achieve the highest possible test sensitivity.


2020 ◽  
Vol 64 (1-4) ◽  
pp. 951-958
Author(s):  
Tianhao Liu ◽  
Yu Jin ◽  
Cuixiang Pei ◽  
Jie Han ◽  
Zhenmao Chen

Small-diameter tubes that are widely used in petroleum industries and power plants experience corrosion during long-term services. In this paper, a compact inserted guided-wave EMAT with a pulsed electromagnet is proposed for small-diameter tube inspection. The proposed transducer is noncontact, compact with high signal-to-noise ratio and unattractive to ferromagnetic tubes. The proposed EMAT is designed with coils-only configuration, which consists of a pulsed electromagnet and a meander pulser/receiver coil. Both the numerical simulation and experimental results validate its feasibility on generating and receiving L(0,2) mode guided wave. The parameters for driving the proposed EMAT are optimized by performance testing. Finally, feasibility on quantification evaluation for corrosion defects was verified by experiments.


2018 ◽  
Author(s):  
Satish Kodali ◽  
Liangshan Chen ◽  
Yuting Wei ◽  
Tanya Schaeffer ◽  
Chong Khiam Oh

Abstract Optical beam induced resistance change (OBIRCH) is a very well-adapted technique for static fault isolation in the semiconductor industry. Novel low current OBIRCH amplifier is used to facilitate safe test condition requirements for advanced nodes. This paper shows the differences between the earlier and novel generation OBIRCH amplifiers. Ring oscillator high standby leakage samples are analyzed using the novel generation amplifier. High signal to noise ratio at applied low bias and current levels on device under test are shown on various samples. Further, a metric to demonstrate the SNR to device performance is also discussed. OBIRCH analysis is performed on all the three samples for nanoprobing of, and physical characterization on, the leakage. The resulting spots were calibrated and classified. It is noted that the calibration metric can be successfully used for the first time to estimate the relative threshold voltage of individual transistors in advanced process nodes.


Nanophotonics ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 2569-2576 ◽  
Author(s):  
Lu Li ◽  
Lihui Pang ◽  
Qiyi Zhao ◽  
Yao Wang ◽  
Wenjun Liu

AbstractTransition metal dichalcogenides have been widely utilized as nonlinear optical materials for laser pulse generation applications. Herein, we study the nonlinear optical properties of a VS2-based optical device and its application as a new saturable absorber (SA) for high-power pulse generation. Few-layer VS2 nanosheets are deposited on the tapered region of a microfiber to form an SA device, which shows a modulation depth of 40.52%. After incorporating the microfiber-VS2 SA into an Er-doped fiber laser cavity, passively Q-switched pulse trains could be obtained with repetition rates varying from 95 to 233 kHz. Under the pump power of 890 mW, the largest output power and shortest pulse duration are measured to be 43 mW and 854 ns, respectively. The high signal-to-noise ratio of 60 dB confirms the excellent stability of the Q-switching state. To the best of our knolowdge, this is the first illustration of using VS2 as an SA. Our experimental results demonstrate that VS2 nanomaterials have a large potential for nonlinear optics applications.


Author(s):  
Tade Bagbi ◽  
Ningthoukhongjam Reema ◽  
S. Bhagyabati Devi ◽  
Thangjam Gautam Singh ◽  
Mohammad Jaleel ◽  
...  

Abstract Introduction Tuberculosis (TB) in people living with human immunodeficiency virus (PLHIV) is difficult to diagnose due to fewer organisms in sputum and extrapulmonary samples. Sputum culture takes 4 to 8 weeks for growth of the mycobacteria. Delayed treatment for TB in PLHIV leads to increased mortality. This study evaluated cartridge-based nucleic acid amplification test (CBNAAT) as a diagnostic tool for diagnosis of pulmonary TB (PTB) and extrapulmonary TB (EPTB) in PLHIV in the second most HIV prevalent state in India and for comparing its efficacy between Ziehl–Neelsen (ZN) staining sputum smear–positive and sputum smear–negative TB. Methods This cross-sectional study was conducted in RIMS, Imphal, with 167 PLHIV patients, age 15 years or older, having signs and symptoms of TB. Appropriate samples for sputum microscopy and CBNAAT were sent. Conclusion The overall sensitivity of sputum smear for acid-fast bacillus (AFB) was found to be 30.71% and that of CBNAAT was 38.57%. Sensitivity of CBNAAT for sputum smear–positive and sputum smear–negative TB was 100 and 11.3%, respectively. Sensitivity of ZN smear for AFB of EPTB sample was 48.1% and that of CBNAAT was 59.25%. In both PTB and EPTB, CBNAAT showed an increase in diagnosis of microbiologically confirmed PTB cases by 7.8 and 11.1%, respectively, over and above the cases diagnosed by ZN smear microscopy. Rifampicin resistance was detected in five patients. We conclude that CBNAAT is a rapid test with better sensitivity in diagnosis of PTB and EPTB in PLHIV, compared with ZN smear microscopy. It detects rifampicin resistance for multidrug-resistant TB and helps in early treatment intervention.


2021 ◽  
Vol 13 (1) ◽  
pp. 168781402098732
Author(s):  
Ayisha Nayyar ◽  
Ummul Baneen ◽  
Syed Abbas Zilqurnain Naqvi ◽  
Muhammad Ahsan

Localizing small damages often requires sensors be mounted in the proximity of damage to obtain high Signal-to-Noise Ratio in system frequency response to input excitation. The proximity requirement limits the applicability of existing schemes for low-severity damage detection as an estimate of damage location may not be known  a priori. In this work it is shown that spatial locality is not a fundamental impediment; multiple small damages can still be detected with high accuracy provided that the frequency range beyond the first five natural frequencies is utilized in the Frequency response functions (FRF) curvature method. The proposed method presented in this paper applies sensitivity analysis to systematically unearth frequency ranges capable of elevating damage index peak at correct damage locations. It is a baseline-free method that employs a smoothing polynomial to emulate reference curvatures for the undamaged structure. Numerical simulation of steel-beam shows that small multiple damages of severity as low as 5% can be reliably detected by including frequency range covering 5–10th natural frequencies. The efficacy of the scheme is also experimentally validated for the same beam. It is also found that a simple noise filtration scheme such as a Gaussian moving average filter can adequately remove false peaks from the damage index profile.


2021 ◽  
Vol 10 (15) ◽  
pp. 3249
Author(s):  
Annelies W. Mesman ◽  
Seung-Hun Baek ◽  
Chuan-Chin Huang ◽  
Young-Mi Kim ◽  
Sang-Nae Cho ◽  
...  

An estimated 15–20% of patients who are treated for pulmonary tuberculosis (TB) are culture-negative at the time of diagnosis. Recent work has focused on the existence of differentially detectable Mycobacterium tuberculosis (Mtb) bacilli that do not grow under routine solid culture conditions without the addition of supplementary stimuli. We identified a cohort of TB patients in Lima, Peru, in whom acid-fast bacilli could be detected by sputum smear microscopy, but from whom Mtb could not be grown in standard solid culture media. When we attempted to re-grow Mtb from the frozen sputum samples of these patients, we found that 10 out of 15 could be grown in a glycerol-poor/lipid-rich medium. These fell into the following two groups: a subset that could be regrown in glycerol after “lipid-resuscitation”, and a group that displayed a heritable glycerol-sensitive phenotype that were unable to grow in the presence of this carbon source. Notably, all of the glycerol-sensitive strains were found to be multidrug resistant. Although whole-genome sequencing of the lipid-resuscitated strains identified 20 unique mutations compared to closely related strains, no single genetic lesion could be associated with this phenotype. In summary, we found that lipid-based media effectively fostered the growth of Mtb from a series of sputum smear-positive samples that were not culturable in glycerol-based Lowenstein–Jensen or 7H9 media, which is consistent with Mtb’s known preference for non-glycolytic sources during infection. Analysis of the recovered strains demonstrated that both genetic and non-genetic mechanisms contribute to the observed differential capturability, and suggested that this phenotype may be associated with drug resistance.


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