A novel aptamer-based test for the rapid and accurate diagnosis of pleural tuberculosis

Kumari, Pooja; Lavania, Surabhi; Tyagi, Shaifali; Dhiman, Abhijeet; Rath, Deepak; Anthwal, Divya; Gupta, Rakesh Kumar; Sharma, Neera; Gadpayle, Adesh Kumar; Taneja, Rajesh; Sharma, Lokesh Kumar; Ahmad, Yusra; Sharma, Tarun; Haldar, Sagarika; Tyagi, Jaya Sivaswami

doi:10.1016/j.ab.2018.10.019

Cited by 37 publications

(27 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In spite of the availability of several diagnostic platforms; no test has proved to be solely adequate for diagnosing ATB [4,19,42]. The detection of circulating cellfree M. tuberculosis DNA (cfMTB-DNA) has recently emerged as a tool for diagnosing paucibacillary forms of TB such as tuberculous meningitis and pleural TB [30][31][32][34][35][36][37]. In the present study, to the best of our knowledge, we for the first time assessed the utility of cfMTB-DNA for ATB diagnosis.…”

Section: Discussionmentioning

confidence: 99%

“…Circulating cell-free M. tuberculosis DNA (referred as cfMTB-DNA from here onwards) refers to the fragments of cell-free M. tuberculosis DNA that may have been released from dying human cells and mycobacteria in biological fluids [33]. cfMTB-DNA detection has shown a sensitivity ranging from 50%-79.5% by PCR for pleural TB and 56.5-100% for tuberculous meningitis diagnosis with � 92% specificity in various studies [30][31][32][34][35][36][37]. To the best of our belief, this is the first study to evaluate the utility of cfMTB-DNA detection in ascitic fluid samples for ATB diagnosis.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Utility of circulating cell-free Mycobacterium tuberculosis DNA for the improved diagnosis of abdominal tuberculosis

et al. 2020

Self Cite

View full text Add to dashboard Cite

Abdominal tuberculosis (ATB) continues to pose a major diagnostic challenge for clinicians due to its nonspecific clinical presentation, variable anatomical location and lack of sensitive diagnostic tools. In spite of the development of several assays till date; no single test has proved to be adequate for ATB diagnosis. In this study, we for the first time report the detection of circulating cell-free Mycobacterium tuberculosis (M. tuberculosis) DNA (cfMTB-DNA) in ascitic fluid (AF) samples and its utility in ATB diagnosis. Sixty-five AF samples were included in the study and processed for liquid culture, cytological, biochemical and molecular assays. A composite reference standard (CRS) was formulated to categorize the patients into 'Definite ATB' (M. tuberculosis culture positive, n = 2), 'Probable ATB' (n = 16), 'Possible ATB' (n = 13) and 'Non-TB' category (n = 34). Two molecular assays were performed, namely, the novel cfMTB-DNA qPCR assay targeting M. tuberculosis devR gene and Xpert MTB/RIF assay (Xpert), and their diagnostic accuracy was assessed using CRS as reference standard. Clinical features such as fever, loss of weight, abdominal distension and positive Mantoux were found to be strongly associated with ATB disease (p<0.05). cfMTB-DNA qPCR had a sensitivity of 66.7% (95% CI:40.9,86.7) with 97.1% specificity (95% CI:84.7,99.9) in 'Definite ATB' and 'Probable ATB' group collectively. The sensitivity increased to 70.9% (95% CI:51.9,85.8) in the combined 'Definite', 'Probable' and 'Possible' ATB group with similar specificity. The cfMTB-DNA qPCR assay performed significantly better than the Xpert assay which demonstrated a poor sensitivity of �16.7% with 100% (95% CI:89.7,100) specificity (p<0.001). We conclude that cfMTB-DNA qPCR assay is an accurate molecular test that can provide direct evidence of M. tuberculosis etiology and has promise to pave the way for improving ATB diagnosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Utility of circulating cell-free Mycobacterium tuberculosis DNA for the improved diagnosis of abdominal tuberculosis

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Although the lungs are most commonly involved, extrapulmonary tuberculosis accounted for 15% of all tuberculosis cases according to the WHO in 2016. 1,2 As a common type of extrapulmonary tuberculosis, intraspinal tuberculosis occurs increasingly, although its accurate incidence is unknown, which is in the same situation as intraspinal metastasis. 3 Both intraspinal tuberculosis and metastatic cancer may be rare, but they are difficult to differentiate because of their similar presentations and the high negative incidence of microbiological test for tuberculosis in cerebrospinal fluid (CSF) and their prognoses are completely different.…”

Section: Introductionmentioning

confidence: 99%

“…3 Both intraspinal tuberculosis and metastatic cancer may be rare, but they are difficult to differentiate because of their similar presentations and the high negative incidence of microbiological test for tuberculosis in cerebrospinal fluid (CSF) and their prognoses are completely different. 1,4 Most patients with intraspinal tuberculosis can achieve remarkable recovery after early diagnosis and treatment, whereas intraspinal metastatic cancers have a poor treatment response and poor prognosis. [5][6][7] To the best of our knowledge, although the optimal treatment of both diseases remains controversial, early accurate diagnosis can be helpful to improve neurological deficits and quality of life.…”

Section: Introductionmentioning

confidence: 99%

<p>Differentiation of Intraspinal Tuberculosis and Metastatic Cancer Using Magnetic Resonance Imaging</p>

Song

et al. 2020

IDR

View full text Add to dashboard Cite

This study aimed to explore the differences in the magnetic resonance imaging (MRI) findings between intraspinal tuberculosis and metastatic cancer, which may aid in making the correct diagnosis. Patients and Methods: The clinical features and MRI findings of 15 patients with intraspinal tuberculosis and 11 patients with intraspinal metastatic cancers were retrospectively analyzed. Results: The mean ages of the patients with intraspinal tuberculosis and metastatic cancer were 26.3 (15-42) and 52.1 (38-67) years, respectively. All intraspinal tuberculosis cases were secondary to primary extraspinal tuberculosis, including tuberculous meningitis (11/15), as well as pulmonary (9/15), vertebral (5/15), urinary tract (1/15), abdominal (1/15), cervical lymph node (1/15), and multisystem tuberculosis (9/15). The intraspinal metastases originated from the breast (5/11), lung (3/11), kidney (1/11), ovarian (1/11), and nasopharyngeal cancers (1/11). Both intraspinal tuberculosis and metastatic cancers presented with multiple intra-and extramedullary lesions throughout all regional segments of the spinal canal, accompanied by irregularly thickened meninges. Intraspinal tuberculous lesions had indistinct edges that integrated with each other, most of them exhibiting obvious enhancement on MRI. Conversely, intraspinal metastatic lesions were distinctly separated with clear edges and exhibited lesser enhanced MRI than intraspinal tuberculosis. Conclusion: A combined analysis of clinical features and MRI findings may be helpful in differentiating intraspinal tuberculosis from metastatic cancer.

show abstract

“…In recent years, functional nucleic acids known as aptamers (DNA or RNA) have demonstrated the ability to potentially overcome the limitations associated with antibodies. [21][22][23][24][25][26] Owing to these attributes, aptamers are regarded as a strong chemical rival of antibodies, with an ability to replace antibodies in all possible diagnostic formats. 22,27 Furthermore, in the last few years, aptamers have demonstrated their utility in the detection of diverse analytes ranging from small molecules to antigens to enzymes to hormones and even whole bacterial or cancer cells.…”

Section: Introductionmentioning

confidence: 99%

<p>Structural switching electrochemical DNA aptasensor for the rapid diagnosis of tuberculous meningitis</p>

Das¹,

Dhiman²,

Mishra³

et al. 2019

IJN

Self Cite

View full text Add to dashboard Cite

Background: Tuberculous meningitis (TBM) is the most devastating manifestation of extrapulmonary tuberculosis. About 33% of TBM patients die due to very late diagnosis of the disease. Conventional diagnostic methods based on signs and symptoms, cerebrospinal fluid (CSF) smear microscopy or liquid culture suffer from either poor sensitivity or long turnaround time (up to 8 weeks). Therefore, in order to manage the disease efficiently, there is an urgent and unmet need for a rapid and reliable diagnostic test. Methods: In the current study, to address the diagnostic challenge of TBM, a highly rapid and sensitive structural switching electrochemical aptasensor was developed by combining the electrochemical property of methylene blue (MB) with the molecular recognition ability of a ssDNA aptamer. To demonstrate the clinical diagnostic utility of the developed aptasensor, a blinded study was performed on 81 archived CSF specimens using differential pulse voltammetry. Results: The electrochemical aptasensor developed in the current study can detect as low as 10 pg HspX in CSF background and yields a highly discriminatory response (P,0.0001) for TBM and not-TBM categories with ~95% sensitivity and ~97.5% specificity and has the ability to deliver sample-to-answer in #30 minutes. Conclusion: In summary, we demonstrate a new aptamer-based electrochemical biosensing strategy by exploiting the target-induced structural switching of H63 SL-2 M6 aptamer and electroactivity of aptamer-tagged MB for the detection of HspX in CSF samples for the diagnosis of TBM. Further, the clinical utility of this sensor could be extended for the diagnosis of other forms of tuberculosis in the near future.

show abstract

A novel aptamer-based test for the rapid and accurate diagnosis of pleural tuberculosis

Cited by 37 publications

References 36 publications

Utility of circulating cell-free Mycobacterium tuberculosis DNA for the improved diagnosis of abdominal tuberculosis

Utility of circulating cell-free Mycobacterium tuberculosis DNA for the improved diagnosis of abdominal tuberculosis

<p>Differentiation of Intraspinal Tuberculosis and Metastatic Cancer Using Magnetic Resonance Imaging</p>

<p>Structural switching electrochemical DNA aptasensor for the rapid diagnosis of tuberculous meningitis</p>

Contact Info

Product

Resources

About