Rapid diagnosis of pulmonary tuberculosis by combined molecular and immunological methods

Jafari, Claudia; Olaru, Ioana D.; Daduna, Franziska; Ernst, Martin; Heyckendorf, Jan; Lange, Christoph; Kalsdorf, Barbara

doi:10.1183/13993003.02189-2017

Cited by 13 publications

(14 citation statements)

References 31 publications

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“…Similarly, IGRAs showed a moderate performance in ruling out ATB in Xpertindividuals in a high-TB/HIV burden setting (Theron et al, 2012). Intriguingly, a recent study showed that T-SPOT with BALF with a cut-off of >4000 early secretory antigenic target-6-or culture filtrate protein-10-specific interferon-g-producing lymphocytes per 10 7 lymphocytes was able to identify 88.9% of AFB -/Xpert -patients with culture-proven MTB (Jafari et al, 2018), although the sample size of this study is small. It will be interesting to determine if BALF-based T-SPOT MDC and TBAg/PHA ratios can better predict TB disease within a large AFB -/Xpertpopulation.…”

Section: No Ntmmentioning

confidence: 99%

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

Peng

Song

Wang

et al. 2021

Front. Cell. Infect. Microbiol.

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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.

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Section: No Ntmmentioning

confidence: 99%

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

Peng

Song

Wang

et al. 2021

Front. Cell. Infect. Microbiol.

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“…Currently, the Xpert© MTB/RIF assay (Cepheid Inc, Sunnyvale, Calif., USA) is what comes close to a rapid molecular diagnostic tuberculosis test although it is dependent on good quality sputum sample ( 19 ). Tuberculosis diagnosis can also be through the detection of host biomarkers or pathogen biomarkers such as Mycobacterium tuberculosis (Mtb) products ( 20 ).…”

Section: Resultsmentioning

confidence: 99%

Past and Present Approaches to Diagnosis of Active Pulmonary Tuberculosis

2021

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Tuberculosis disease continues to contribute to the mortality burden globally. Due to the several shortcomings of the available diagnostic methods, tuberculosis disease continues to spread. The difficulty to obtain sputum among the very ill patients and the children also affects the quick diagnosis of tuberculosis disease. These challenges warrant investigating different sample types that can provide results in a short time. Highlighted in this review are the approved pulmonary tuberculosis diagnostic methods and ongoing research to improve its diagnosis. We used the PRISMA guidelines for systematic reviews to search for studies that met the selection criteria for this review. In this review we found out that enormous biosignature research is ongoing to identify host biomarkers that can be used as predictors of active PTB disease. On top of this, more research was also being done to improve already existing diagnostic tests. Host markers required more optimization for use in different settings given their varying sensitivity and specificity in PTB endemic and non-endemic settings.

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“…Individually, IgG and IgA antibodies against MIF could not achieve good sensitivity and specificity, respectively, in order to replace conventional diagnostics. In previous studies, higher predictive power could be achieved when tests of multiple markers were combined [25][26][27]. Because statistically significant differences in anti-MIF antibody levels existed between study groups, it may be possible to increase the predictive power of the existing method by combining it with other known markers.…”

Section: Discussionmentioning

confidence: 99%

Usefulness of the IgA and IgG Responses to Macrophage Migration Inhibitory Factor for the Diagnosis of Tuberculosis

Lee

Kim

et al. 2020

Diagnostics

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Serological tests offer the potential in order to improve the diagnosis of tuberculosis (TB). Macrophage migration inhibitory factor (MIF) plays a protective role in infection control in TB; however, to date, no studies on antibody responses to MIF have been reported. We measured immunoglobulin (Ig)A and IgG responses to MIF in individuals with either active tuberculosis (ATB; n = 65), latent tuberculosis (LTBI; n = 53), or in non-infected individuals (NI; n = 62). The QuantiFERON-TB Gold In-Tube (QFT-GIT) assay was used in order to screen for LTBI. The level of IgA against MIF was significantly lower in LTBI and ATB patients than in NI individuals, was significantly related to LTBI and ATB diagnosis, and it could discriminate between LTBI and ATB. In contrast, the level of IgG against MIF was significantly lower in LTBI patients than in NI individuals and was significantly related to LTBI diagnosis. Anti-MIF IgG levels were significantly lower in AFB-negative TB, minimal TB, and new ATB patients, than in the NI group. IgA and IgG levels against MIF both showed significant negative correlations with IFN-γ levels, as assessed using the QFT-GIT test. Although none of the antibodies could achieve high diagnostic predictive power individually, our results suggest the possibility of using IgA antibody responses to MIF in the diagnosis of LTBI and ATB.

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Rapid diagnosis of pulmonary tuberculosis by combined molecular and immunological methods

Cited by 13 publications

References 31 publications

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

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

Past and Present Approaches to Diagnosis of Active Pulmonary Tuberculosis

Usefulness of the IgA and IgG Responses to Macrophage Migration Inhibitory Factor for the Diagnosis of Tuberculosis

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