Evaluation of kit-based loop-mediated isothermal amplification (TB-LAMP) assay in the diagnosis of tubercular lymphadenitis
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Background. The rapid and accurate diagnosis of tubercular lymphadenitis remains a challenging task today. The World Health Organization (WHO) endorsed the LoopAMP MTBC kit (TB-LAMP) as a replacement for sputum smear microscopy in the diagnosis of pulmonary tuberculosis (PTB). However, no prospective diagnostic accuracy study of TB-LAMP for tubercular lymphadenitis in adults has been performed yet. The current study evaluated the diagnostic performance of TB-LAMP in tubercular lymphadenitis (LNTB).
Methods. In a prospective observational study conducted at a tertiary care hospital in India, 90 subjects (age >18 years) suspected of LNTB were recruited consecutively and followed up for 6 months between January 2019 and December 2020. Samples were processed for microscopy, culture, GeneXpert, histopathology and TB-LAMP. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of TB-LAMP against the composite reference standard (CRS) and culture were determined.
Results. TB-LAMP showed a sensitivity of 83.78 % (95 % CI, 73.76–90.47) and a specificity of 81.25 % (95 % CI, 56.99–93.41), respectively, against the CRS. The PPV and NPV were 95.38 % (95 % CI, 87.29–98.42) and 52.00 % (95 % CI, 33.50–69.97), respectively. TB-LAMP showed a sensitivity of 88.89 % (95 % CI, 71.94–96.15) and a specificity of 36.17 % (95 % CI, 23.97–50.46), respectively, against culture. The PPV and NPV were 44.44 % (95 % CI, 32–57.62) and 85 % (95 % CI, 63.96–94.76), respectively.
Conclusion. TB-LAMP can be used instead of conventional microscopy for the diagnosis of TB in lymph node specimens at primary healthcare centres. It provides rapid and cost-effective diagnosis of LNTB in resource-limited settings due to good sensitivity and NPV.
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I am pleased to tell you that your article has now been accepted for publication in Access Microbiology. The work presented is clear and the arguments well formed. The manuscript is well written and contributes to the literature. Thank you for addressing all reviewers comments satisfactorily and in a timely manner.
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Thank you for submitting your manuscript for publication in Access Microbiology. It has been examined by expert reviewers who have concluded that the work is of potential interest to the readership of Access Microbiology. However, based on the comments received, a minor amendment of this manuscript will be required before a decision can be made on its publication. I will be pleased to consider a revised manuscript along with a document including a point by point response to each of the reviewers comments. Your revised manuscript may be returned to one or more of the original reviewers, along with your itemised response to the reviewers’ comments.
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Comments to Author
Methodology , analysis are satisfactory. It is observed that biopsy was done for 19 subjects and hence histopathology reports should have been available. Correlation of LAMP with histopathology /FNAC pathology findings have not bee included in the paper. What was the correlation? Were positive results detected for biopsies with other diagnosis esp malignancy? What could have been the impact on such positives on original disease? This is important since LMP is being recommended at periphaeral facilities without adequate infrastructure.
Please rate the manuscript for methodological rigour
Very good
Please rate the quality of the presentation and structure of the manuscript
Good
To what extent are the conclusions supported by the data?
Strongly …
Comments to Author
Methodology , analysis are satisfactory. It is observed that biopsy was done for 19 subjects and hence histopathology reports should have been available. Correlation of LAMP with histopathology /FNAC pathology findings have not bee included in the paper. What was the correlation? Were positive results detected for biopsies with other diagnosis esp malignancy? What could have been the impact on such positives on original disease? This is important since LMP is being recommended at periphaeral facilities without adequate infrastructure.
Please rate the manuscript for methodological rigour
Very good
Please rate the quality of the presentation and structure of the manuscript
Good
To what extent are the conclusions supported by the data?
Strongly support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
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Comments to Author
Reviewer's response for manuscript "ACMI-D-23-00131- Evaluation of kit-based loop-mediated isothermal amplification (TB-LAMP) assay in the diagnosis of tubercular lymphadenitis" Tubercular lymphadenitis (LNTB) which is an important health concern today. Diagnostic methods that are appropriate for use in low-resource settings are important for rapid diagnosis and its treatment. In the present manuscript use of loop-mediated isothermal amplification (LAMP) techniques for the diagnosis of pulmonary tuberculosis has been extensively investigated and compared to smear microscopy and Xpert MTB/RIF, with the WHO subsequently recommending that TB-LAMP may replace sputum smear microscopy. This recommendation does not, however, apply to non-pulmonary TB and to my knowledge this technique is not widely used. …
Comments to Author
Reviewer's response for manuscript "ACMI-D-23-00131- Evaluation of kit-based loop-mediated isothermal amplification (TB-LAMP) assay in the diagnosis of tubercular lymphadenitis" Tubercular lymphadenitis (LNTB) which is an important health concern today. Diagnostic methods that are appropriate for use in low-resource settings are important for rapid diagnosis and its treatment. In the present manuscript use of loop-mediated isothermal amplification (LAMP) techniques for the diagnosis of pulmonary tuberculosis has been extensively investigated and compared to smear microscopy and Xpert MTB/RIF, with the WHO subsequently recommending that TB-LAMP may replace sputum smear microscopy. This recommendation does not, however, apply to non-pulmonary TB and to my knowledge this technique is not widely used. Diagnostic methods for LNTB have greatly improved in recent years, and recent Cochrane reviews have investigated the applicability of Xpert MTB/RIF for extrapulmonary tuberculosis, showing it is helpful diagnostic tool, and looks at drug resistance. TB-LAMP may be a potential alternative, but probably will need to have demonstrable advantages over Xpert to replace it and the authors do not really articulate this in the background. The study adopts a prospective observational approach which is a robust study type for investigating diagnostic test accuracy. The study attempts to compare TB-LAMP for diagnosis of LNTB with other diagnostic methods which is useful for quantifying the value of diagnostic tools. Through this study, it has been shown that TB-LAMP has comparable diagnostic accuracy to GeneXpert and can be considered an alternative to AFB and microscopy in resource-poor settings as a point-of-care test. Below are the specific comments: 1. How was the lymph node specimens processed, this needs to be explained as the workflow is for sputum only. Were the specimens decontaminated? Please provide appropriate steps. When the authors say culture/smear being positive along with response to treatment. Were these always considered in conjugation or were any cases considered positive even if they were only smear positive? 2. One important analysis to do is with sputum smear microscopy only. Potentially that will have a higher impact as the WHO guidance is to potentially replace sputum smear microscopy in countries or places that solely rely on smear microscopy. This has not been analyzed and discussed in the paper. The intended use of this technology needs to be indicated. 3. The authors should also mention the generalizability aspect in their results. The patients were taken from a tertiary care Centre. The deployment of this technology is at POC level, where the bacillary load might be even less and difficult to diagnose the disease. This should be mentioned in their discussion section as one of the potential concerns. 4. Reasons for why few cases were GX+ Lamp- and vice versa should be discussed. In-depth knowledge of molecular markers, technical performance of different techniques and rationales for comparison between the two tests are lacking. After these changes manuscript can be accepted for publication.
Please rate the manuscript for methodological rigour
Good
Please rate the quality of the presentation and structure of the manuscript
Good
To what extent are the conclusions supported by the data?
Strongly support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
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