Harnessing Big Data to Optimize an Algorithm for Rapid Diagnosis of Pulmonary Tuberculosis in a Real-World Setting

Abstract

BackgroundThe prompt diagnosis of pulmonary tuberculosis (PTB) remains a challenge in clinical practice. The present study aimed to optimize an algorithm for rapid diagnosis of PTB in a real-world setting.Methods28,171 adult inpatients suspected of having PTB in China were retrospectively analyzed. Bronchoalveolar lavage fluid (BALF) and/or sputum were used for acid-fast bacilli (AFB) smear, Xpert MTB/RIF (Xpert), and culture. A positive mycobacterial culture was used as the reference standard. Peripheral blood mononuclear cells (PBMC) were used for T-SPOT.TB. We analyzed specimen types’ effect on these assays’ performance, determined the number of smears for diagnosing PTB, and evaluated the ability of these assays performed alone, or in combination, to diagnose PTB and nontuberculous mycobacteria (NTM) infections.ResultsSputum and BALF showed moderate to substantial consistency when they were used for AFB smear or Xpert, with a higher positive detection rate by BALF. 3-4 smears had a higher sensitivity than 1-2 smears. Moreover, simultaneous combination of AFB and Xpert correctly identified 44/51 of AFB+/Xpert+ and 6/7 of AFB+/Xpert- cases as PTB and NTM, respectively. Lastly, when combined with AFB/Xpert sequentially, T-SPOT showed limited roles in patients that were either AFB+ or Xpert+. However, T-SPOTMDC (manufacturer-defined cut-off) showed a high negative predicative value (99.1%) and suboptimal sensitivity (74.4%), and TBAg/PHA (ratio of Mycobacterium tuberculosis-specific antigens to phytohaemagglutinin spot-forming cells, which is a modified method calculating T-SPOT.TB assay results) ≥0.3 demonstrated a high specificity (95.7%) and a relatively low sensitivity (16.3%) in AFB-/Xpert- patients.ConclusionsConcurrently performing AFB smear (at least 3 smears) and Xpert on sputum and/or BALF could aid in rapid diagnosis of PTB and NTM infections in a real-world high-burden setting. If available, BALF is preferred for both AFB smear and Xpert. Expanding this algorithm, PBMC T-SPOTMDC and TBAg/PHA ratios have a supplementary role for PTB diagnosis in AFB-/Xpert- patients (moderately ruling out PTB and ruling in PTB, respectively). Our findings may also inform policy makers’ decisions regarding prevention and control of TB in a high burden setting.

Combination of HLA-DR on Mycobacterium tuberculosis-Specific Cells and Tuberculosis Antigen/Phytohemagglutinin Ratio for Discriminating Active Tuberculosis From Latent Tuberculosis Infection

“…Therefore, the combination of these two indicators could mainly contribute to improving the specificity, not the sensitivity. Second, we found that the sensitivity of TBAg/PHA ratio on distinguishing ATB from LTBI in this study was obviously lower than those reported in several previous studies ( 22 ), while similar with the utility obtained in a recent real-world data analysis from China ( 38 ) and another study from Japan ( 39 ). It was observed that the studies with good performance were often performed with patient exclusion such as immunosuppression.…”

Cerebrospinal fluid protein levels are elevated 100 times in a Leptomeningeal metastasis patient: a case report and literature review

“…Non-tuberculous mycobacteria (NTM) refer generally to mycobacteria other than Mycobacterium tuberculosis complex (MTB) and Mycobacterium leprae. Moreover, MTB and NTM infections often cause indistinguishable clinical symptoms, but their treatment can be vastly different (Peng et al, 2021 ). Clinically, the low prevalence of NTM infections puts them rarely in the differential diagnosis of CNS infections, which occurs more frequently in patients with immunosuppression.…”

Sensitivity of PCR analysis (melting curve method) in diagnosis of Pulmonary Tuberculosis (PTB) based on Bronchoalveolar Lavage (BAL) by bronchoscope

“…To some extent, these screening tests may hinder the early diagnosis and treatment of PTB. 19 PCR is a technique that amplifies DNA and RNA in vitro through DNA replication. 20 PCR assays for M. tb detection have the following advantages: 1) bacteria at a concentration lower than the detectable levels of regular screening tests can be identified after DNA or RNA amplification, which is beneficial to the early diagnosis of PTB 21 ; 2) PCR assays are more sensitive to PTB without cavitation compared with traditional approaches; 3) in addition to viable bacteria, dead bacteria without DNA degradation can also be amplified to identify lesions in the lungs and prevent missed or erroneous diagnosis; 22 4) PCR reagents work in parallel with anti-TB drugs to examine whether M. tb DNA has been completely degraded through quantitative determination.…”