Skip to main content
SearchLoginLogin or Signup

Review 2: "Blood RNA Signatures Outperform CRP Triage of Tuberculosis Lymphadenitis and Pericarditis"

The reviewers agree that the study has high validity and stong evidence. However, they note a significant limitation is the researchers only evaluated 2 types of EPTB: pericarditis and lymphadenitis, limiting the generalizability to TB as a whole.

Published onJul 22, 2024
Review 2: "Blood RNA Signatures Outperform CRP Triage of Tuberculosis Lymphadenitis and Pericarditis"
1 of 2
key-enterThis Pub is a Review of
Blood RNA signatures outperform CRP triage of tuberculosis lymphadenitis and pericarditis
Blood RNA signatures outperform CRP triage of tuberculosis lymphadenitis and pericarditis
Description

Background Limited data are available on the diagnostic accuracy of blood RNA biomarker signatures for extrapulmonary TB (EPTB). We addressed this question among people investigated for TB lymphadenitis and TB pericarditis, in Cape Town, South Africa. Methods We enrolled 440 consecutive adults referred to a hospital for invasive sampling for presumptive TB lymphadenitis (n=300) or presumptive TB pericarditis (n=140). Samples from the site of disease underwent culture and/or molecular testing for Mycobacterium tuberculosis complex (Mtb). Discrimination of patients with and without TB defined by microbiology or cytology reference standards was evaluated using seven previously reported blood RNA signatures by area under the receiver-operating characteristic curve (AUROC) and sensitivity/specificity at predefined thresholds, benchmarked against blood C-reactive protein (CRP) and the World Health Organization (WHO) target product profile (TPP) for a TB triage test. Decision curve analysis (DCA) was used to evaluate the clinical utility of the best performing blood RNA signature and CRP. Results Data from 374 patients for whom results were available from at least one microbiological test from the site of disease, and blood CRP and RNA measurements, were included. Using microbiological results as the reference standard in the primary analysis (N=204 with TB), performance was similar across lymphadenitis and pericarditis patients. In the pooled analysis of both cohorts, all RNA signatures had comparable discrimination with AUROC point estimates ranging 0.77-0.82, superior to that of CRP (0.61, 95% confidence interval 0.56-0.67). The best performing signature (Roe3) achieved an AUROC of 0.82 (0.77-0.86). At a predefined threshold of 2 standard deviations (Z2) above the mean of a healthy reference control group, this signature achieved 78% (72-83%) sensitivity and 69% (62-75%) specificity. In this setting, DCA revealed that Roe3 offered greater net benefit than other approaches for services aiming to reduce the number needed to investigate with confirmatory testing to <4 to identify each case of TB. Interpretation RNA biomarkers show better accuracy and clinical utility than CRP to trigger confirmatory TB testing in patients with TB lymphadenitis and TB pericarditis, but still fall short of the WHO TPP for TB triage tests. Funding South African MRC, EDCTP2, NIH/NIAID, Wellcome Trust, NIHR, Royal College of Physicians London.

RR:C19 Evidence Scale rating by reviewer:

  • Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.

***************************************

Review: The manuscript investigates the diagnostic accuracy of blood RNA biomarkers for tuberculosis (TB) lymphadenitis and pericarditis, as opposed to C-reactive protein (CRP). The work is important because it addresses the difficulties in diagnosing extrapulmonary tuberculosis (EPTB), a disease that occasionally necessitates intrusive therapies. The study aims to mitigate this by evaluating non-invasive blood markers.

Strengths:

The paper addresses an important problem in tuberculosis especially for patients with EPTB. The study offers a potentially less invasive and more effective diagnosis approach by concentrating on blood RNA signatures. The research is ensured to be firmly based on the body of current literature by the review of studies on diagnostic accuracy, which includes a thorough search approach. The method used in the study to compare several biomarkers strengthens the validity of the results. The validity of the conclusions is strengthened by the application of thorough statistical studies, such as ROC curves and comparative diagnostics. The paper unequivocally demonstrates that blood RNA biomarkers have better diagnostic accuracy than CRP. 

Weaknesses:

The research is restricted to two extrapulmonary TB types pericarditis and lymphadenitis, which may limit the applicability of the findings to other types of tuberculosis. To further corroborate the findings, a wider spectrum of EPTB symptoms should be included in future investigations. Since the research was done in an area where HIV and TB were highly prevalent, it's possible that the conclusions won't apply to areas where these diseases are less common. Biomarkers' ability to diagnose may varies depending on the population.

Conclusions:

The study shows that blood RNA signatures are more accurate than CRP for EPTB, which makes a substantial contribution to TB diagnostics. The strengths in study design, statistical analysis, and clinical relevance outweigh the limitations, making a strong case for the adoption of these biomarkers in clinical settings. To extend the results to other TB types and geographic regions, further validation studies are required. 

Comments
1
?
bam owax:

Thank you! You start as a small cell and navigate a large map filled with other players and randomly generated pellets called agar io online.