Diagnosis Of Pulmonary Tuberculosis Research Articles

RTP4, a Biomarker Associated with Diagnosing Pulmonary Tuberculosis and Pan-Cancer Analysis.

Pulmonary tuberculosis (PTB) is a global epidemic of infectious disease; the purpose of our study was to explore new potential biomarkers for the diagnosis of pulmonary tuberculosis and to use the biomarkers for further pan-cancer analysis. Four microarray gene expression sets were downloaded from the GEO public databases and conducted for further analysis. Healthy control (HC) samples and samples of pulmonary tuberculosis (PTB) were calculated with enrichment scores in folate biosynthesis pathways. The scores acted as a new phenotype combined with clinical information (control or PTB) for subsequent analysis. Weight gene coexpression network analysis (WGCNA) was used to seek the modules mostly related to PTB and folate biosynthesis in training sets. Twenty-nine coexistence genes were screened by intersecting the genes in the green-yellow module of GSE28623 and the brown module of GSE83456. We used the protein-protein interaction network analysis to narrow the gene range to search for hub genes. Then, we downloaded the unified and standardized pan-cancer data set from the UCSC database for correlations between biomarkers and prognosis and tumor stage differences. Eventually, RTP4 was selected as a biomarker. To verify the reliability of this biomarker, an area under the ROC (AUC) was calculated in gene sets (GSE28623, GSE83456, and GSE34608). Lastly, to explore the difference in RTP4 expression before and after antituberculosis treatment, the GSE31348 gene set was enrolled to compare the expressions in weeks 0 and 26. The results showed significant differences between these two time points (p < 0.001). RTP4 was significantly upregulated in the pulmonary tuberculosis group compared to the healthy control group in three gene sets and downregulated after antituberculosis therapy in one gene set. These results suggest that RTP4 can be used as a potential biomarker in diagnosing tuberculosis. The results of pan-cancer analysis showed that high expression of RTP4 in 4 tumor types was positively correlated with poor prognosis and high expression of RTP4 in 6 tumor types was negatively correlated with poor prognosis. We found significant differences in the expression of the RTP4 gene at different stages in 5 types of tumors. RTP4 might be a new potential biomarker for diagnosing pulmonary tuberculosis.

Rapid Diagnosis of Recurrent Paucibacillary Tuberculosis.

The rapid diagnosis of tuberculosis recurrence can be challenging due to persistently positive detection of Mycobacterium tuberculosis-specific DNA from sputum and bronchopulmonary samples in the absence of active disease. We compared the diagnostic accuracy of the detection of M. tuberculosis-specific DNA by either Xpert (January 2010-June 2018) or Xpert Ultra (July 2018-June 2020) and M. tuberculosis-specific ELISPOT in bronchoalveolar lavage (BAL) samples with M. tuberculosis culture results from sputum or bronchopulmonary samples in patients with suspected recurrence of pulmonary tuberculosis. Among 44 individuals with previous tuberculosis and a presumptive diagnosis of recurrent pulmonary tuberculosis, 4/44 (9.1%) were diagnosed with recurrent tuberculosis by culture. DNA of M. tuberculosis was detected by Xpert in BAL fluid in 1/4 (25%) individuals with recurrent tuberculosis and in 2/40 (5%) cases with past tuberculosis without recurrence, while BAL-ELISPOT with a cut-off of >4,000 early secretory antigenic target-6-specific or culture filtrate protein-10-specific interferon-γ-producing lymphocytes per 1 million BAL-lymphocytes was positive in 4/4 (100%) individuals with recurrent tuberculosis and in 2/40 (5%) cases of past tuberculosis without recurrence. M. tuberculosis-specific BAL-ELISPOT is more accurate than BAL-Xpert for the diagnosis of paucibacillary tuberculosis recurrence.

The Role of Mycobacterium Tuberculosis Detection on Oral Mucosa in Diagnosis of Pulmonary Tuberculosis

Background. Tuberculosis is one of the world's health problems, with larger mortality rate than HIV/AIDS. In order to control this disease, a new and inexpensive diagnostic method is needed. Oral samples, such as buccal mucosa epithelium, can be an alternative specimen, other than sputum, in the diagnosis of tuberculosis. Purpose. This study aimed to analyze the presence of Mycobacterium tuberculosis on buccal swabbing of tuberculosis patients. Method. Study was conducted on 18 new pulmonary tuberculosis patients in TB DOTS unit of Dr. Soetomo General Hospital. Each subject was swabbed on the buccal mucosa of the oral cavity for subsequent examination of PCR, AFB, and culture to detect Mycobacterium tuberculosis in the oral cavity. Result. The results showed that Mycobacterium tuberculosis was detected from 2 study subjects (11%) using PCR, whereas in AFB and culture examination methods no Mycobacterium tuberculosis was detected on buccal mucosa of the oral cavity. Conclusion. This study showed that Mycobacterium tuberculosis was detected on buccal mucosa swab of tuberculosis patients based on PCR technique, but this method is less suitable in diagnosis of pulmonary tuberculosis.

Evolving role of chest radiographs for diagnosis of pediatric pulmonary tuberculosis.

Chest radiographs (CXR) have played an important and evolving role in diagnosis, classification and management of pediatric pulmonary tuberculosis (TB). During the pre-chemotherapy era, CXR aided in determining infectiousness, mainly to guide isolation practices, by detecting calcified and non-calcified lymphadenopathy. The availability of TB chemotherapy from the mid-1900s increased the urgency to find accurate diagnostic tools for what had become a treatable disease. Chestradiographs provided the mainstay of diagnosis in children, despite high inter-reader variability limiting its accuracy. The development of cross-sectional imaging modalities, such as computed tomography, provided more accurate intra-thoracic lymph node assessment, but these modalitieshave major availability, cost and radiation exposure disadvantages. As a consequence, CXR remains the most widely used modality for childhood pulmonary TB diagnosis, given its relatively low cost and accessibility. Publication of the revised 2022 World Health Organization Consolidated TB guidelines added practical value to CXR interpretation in children, by allowing the selection of children for shorter TB treatment using radiological signs of severity of disease, that have high reliability. This article provides a review of the historical journey and evolving role of CXR in pediatric pulmonaryTB.

DIAGNOSTIC ROLE OF GASTRIC ASPIRATION IN SMEAR NEGATIVE PULMONARY TUBERCULOSIS IN ADULT

To study the diagnostic utility of gastric aspiration in sputum negative pulmonary tuberculosis by identifying gastric smear for AFB and culture.To compare the outcome among HIV positive and negative individuals. To study how many were false negative due to improper techniques in sputum sample submission. To compare the radiological patterns with yield in gastric aspiration.To investigate the role of bronchoscopy in smears negative pulmonary tuberculosis.From this study, gastric aspirate for smear positivity among sputum smear negative pulmonary tuberculosis was 24% and gastric culture positivity was 22%. Gastric aspirate for AFB smear and culture can be used as a tool in diagnosis of pulmonary tuberculosis in patients who cannot submit sputum and patients who are smear negative as suggested by the study.Gastric aspirate performed on 2 consecutive days may improve the diagnostic yield.Gastric aspirate performed among HIV positive patients was only 10%.Gastric aspirate positivity in culture had a high yield among chest xray with suspected pulmonary tuberculosis with consolidation pattern(38%).There is practice of prescribing fluoroquinolone for community acquired pneumonia in private. The patients seeking treatment in a tertiary care centre are not naïve population .Many of them would have had treatment and exposed to fluoroqunilones before presenting to us and hence these patients are at the risk of developing fluroquinolone resistant pulmonary tuberculosis. DOTS program in India is functioning at the level of primary health centre where sophisticated techniques like bronchoscopy are not available, patient presenting with no sputum under suspicion of tuberculosis, gastric aspirate can be performed as a diagnostic technique which is a simple outpatient procedure.

GeneXpert and Acid-Fast Bacilli Smear for Diagnosis of Pulmonary Tuberculosis in a Tertiary Care Center of Rural Nepal

Introduction: Mycobacterium tuberculosis is the second most infectious cause of death in adults globally and is major health trouble in Nepal. The diagnosis of pulmonary tuberculosis is mainly carried by acid-fast bacilli smear microscopy, culture on Lowenstein–Jensen media, and GeneXpert MTB/RIF assay. This study aimed to evaluate the GeneXpert MTB/RIF and Acid-Fast Bacilli stain smear used for the diagnosis of pulmonary tuberculosis.&#x0D; Methods: A cross-sectional study was performed at Karnali Academy of Health Sciences, Jumla, from July 2021 to June 2022. Our study population comprised 390 probable cases of pulmonary tuberculosis from the ages of 2 to 92 years. A total of 390 sputum specimens from suspected presumptive tuberculosis sufferers were tested using the direct smear staining technique of Acid-Fast Bacilli stain smear and GeneXpert for the detection of MTB/RIF. The GeneXpert MTB/RIF technique was compared with the Acid-Fast Bacilli stain smear. Patient’s demographic details, sputum AFB smear, and GeneXpert test results were collected and entered in working Performa. Data were analyzed using SPSS 16.0.&#x0D; Results: Out of 390 samples 13.84% were positive for Mycobacterium tuberculosis via GeneXpert MTB/RIF assay while 5.12% were positive through AFB microscopy which was statistically significant (p&lt;.0001). When compared with GeneXpert, taking GeneXpert as the gold standard in the rural setup of Nepal the sensitivity of AFB staining was 37.03%, while its specificity was 90.81%.&#x0D; Conclusions: GeneXpert MTB/RIF is a rapid test that can aid in the timely diagnosis of Mycobacterium tuberculosis, facilitating the timely treatment in the rural area.

Comparison of gastric lavage/sputum and stool specimens in the diagnosis of pediatric pulmonary tuberculosis- A pilot study

Background and ObjectiveGlobal TB report 2021 mentions 11 % prevalence of pediatric TB, whereas 5.65% of the cases were reported from India in 2020. India features in the list of TB high burden countries, HIV-TB high burden and MDR-TB high burden countries. The diagnosis of pulmonary tuberculosis in children is difficult as they tend to swallow the sputum, invasive techniques of gastric aspirates needs to be followed and the disease itself is paucibacillary. The disease progresses rapidly in young children and hence rapid diagnosis is needed. Obtaining appropriate respiratory samples for diagnosis is difficult especially in primary care settings. Stool sample is easy to obtain and since children swallow sputum, it can be used to diagnose pulmonary tuberculosis. With this background, a pilot study was planned to evaluate the accuracy of the Xpert MTB/RIF assay for the detection of MTB in stool specimens obtained from pediatric pulmonary TB patients confirmed either by gastric lavage(GL) or sputum(SP) Xpert MTB/RIF assay. In addition, the results of microscopy of stool specimen were compared with that of gastric lavage/ sputum (GL/SP) specimen by Ziehl-Neelsen (ZN) and fluorescent light-emitting diode (LED) staining. Material and methodsA prospective study was carried out on 50 GL/SP Xpert MTB/RIF assay positive children (0-14 years). Stool specimens from these children were processed for Xpert MTB/RIF assay. The GL/SP and stool specimens were processed for ZN and Auramine O fluorescent microscopy as well. ResultsFluorescent staining detected acid fast bacilli (AFB) in 24 GL/SP and 16 stool specimens as compared to 20 GL/SP and 10 stool specimens by ZN staining. Stool Xpert MTB/ RIF assay was positive in 29 out of 50 children. Rifampicin resistance was detected in 13 of the 50 (26%) GL/SP specimens. Of these 13 children, rifampicin resistance was detected in 7 stool specimens, rifampicin indeterminate resistance was detected in one specimen and in the remaining 5 children, M.tuberculosis was not detected in stool. ConclusionStool is a good non-invasive specimen for the detection of pulmonary TB in children, especially in remote areas, where invasive techniques cannot be performed for sample collection.

Finger printing-RFLP analysis of chromosomal IS6110 insertion sequence and PCR diagnosis of pulmonary tuberculosis, isolated from patients in El Hajeb region of Morocco

Tuberculosis (TB) is one of the contagious diseases caused by M. tuberculosis (MTB) bacteria. Prompt diagnosis is one of the active solutions to control the spread of this infection. Besides, a targeted, specific and non-complex diagnosis can prove promising in this type of epidemic. This study was designed to compare the efficiencies of a diagnosis by Ziehl-Neelsen staining (ZN) and by the polymerase chain reaction (PCR) technique. Samples presented smear-positive pulmonary TB were subjected to Chromosomal restriction fragment length polymorphism of IS6110 (IS6110-RFLP) for fingerprinting profile determination.The results showed that out of 100 sputum samples of suspected case, 53 were positive. Numbers of positive individuals for tuberculosis obtained by the different diagnostic techniques, to know, (ZN staining; culture and PCR) were respectively: 6, 25 and 22. Chromosomal RFLP fingerprinting profile revealed the presence of five different genotypes obtained from seven tested isolates.These results suggest that molecular techniques are alternative tool for fast and specific diagnosis of pulmonary MTB from sputum.

Stool specimen for diagnosis of pulmonary tuberculosis in adults: a systematic review

ObjectiveTo assess the diagnostic accuracy of stool specimens to diagnose pulmonary tuberculosis (PTB) in adults.DesignSystematic review.Data sourcesMEDLINE (Ovid), Embase (Ovid), Web of Science and the Cochrane database were searched from...

The role of differentially expressed miR-660 in peripheral blood lymphocytes of patients with pulmonary tuberculosis

Objective: This study aimed to investigate the significance of miRNA expression levels in peripheral blood lymphocytes of patients clinically diagnosed with pulmonary tuberculosis. Method: Pulmonary tuberculosis-related datasets in the Gene Expression Omnibus (GEO) database were analyzed, and DE-miRNAs were screened for Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment to construct a DE-miRNA-DE-mRNA network. The peripheral blood lymphocytes of 10 patients with pulmonary tuberculosis, 10 patients with rifampicin-resistant tuberculosis, and 10 healthy volunteers were selected for validation of RNA expression levels. qRT-PCR was done to verify the expression of DE-miRNA, and Western blotting was done to check the expression levels of genes of associated pathways. Results: Differential expression of miR-660 was found in pulmonary tuberculosis through data analysis and literature mining. The differential expression was also confirmed by qRT-PCR in samples from patients and healthy controls. The expression of miR-660 was significantly upregulated (p < 0.01) in pulmonary tuberculosis and rifampicin-resistant pulmonary tuberculosis patients compared to the healthy controls. According to western blotting results, the expression levels of P-NF-κB and AKT in pulmonary tuberculosis patients and NF-κB, P-NF-κB, AKT, and p-AKT in rifampicin-resistant tuberculosis patients were significantly upregulated (p < 0.01). Conclusion: The high expression levels of miR-660 may activate the AKT/NF-κB signaling pathway and has the potential to serve as a potential biomarker for the diagnosis of pulmonary tuberculosis.

Evaluation of prognostic inflammatory and systemic inflammatory response indices in auxiliary diagnosis of bacteria-negative pulmonary tuberculosis: A diagnostic accuracy study.

Although molecular biology has made great progress in recent years, the detection rate of mycobacterium tuberculosis (MTB) is still not ideal. This study aimed to evaluate the role of prognostic inflammatory index (PII) and systemic inflammatory response index (SIRI) in the auxiliary diagnosis of bacteria-negative pulmonary tuberculosis (TB). Sixty patients diagnosed with bacteria-negative pulmonary TB at the Affiliated Hospital of Qinghai University between October 2019 and September 2022 were randomly selected as the case group, and seventy patients with nontuberculous pulmonary infection in the same department of the same hospital during the same period were randomly selected as the control group. Baseline data and values of erythrocyte sedimentation rate (ESR), lymphocyte count (LY), neutrophil count (NE), monocyte count (MO), albumin (ALB), prealbumin (PA), C-reactive protein (CRP), fibrinogen (FIB), neutrophil-to-lymphocyte ratio (NLR), PII, and SIRI were compared between the 2 groups. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficacy of PII and SIRI in the diagnosis of bacteria-negative pulmonary TB. No significant differences were found between the 2 groups in terms of sex and age (P > .05); however significant differences were observed in relation to body mass index (BMI), ESR, LY, NE, MO, ALB, PA, CRP, FIB, NLR, PII, and SIRI (P < .05). ROC curve analysis showed that area under curve (AUC) value {0.84 [95% CI (0.77, 0.90)]} and specificity {82.86% [95% CI (72.0, 90.8)]} of PII were the highest, while the sensitivity {86.67 [95% CI (75.4, 94.1)]} of NLR + PII was the highest. Pairwise comparison of the 7 indicators of ROC curve was performed, and only the diagnostic efficiency of NLR and NLR + PII was statistically significant (Z = 2.36, P = .02 < .05). NLR, PII, SIRI, pairwise combinations, and NLR + PII + SIRI showed auxiliary diagnostic values for bacteria-negative pulmonary TB, among which PII had the highest diagnostic value and specificity, while NLR + PII had the highest sensitivity.

Validity of Examination of Complex Specific Antigen Mycobacterium Tuberculosis Rapid Immunochromatography Method in Patients with Pulmonary Tuberculosis

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis which can be transmitted from one person to another by inhaling droplets coughed or sneezed by an infected person. One of the most recent technologies today is the rapid immunochromatography (ICT) method for testing TB antigens. This test detects antigens secreted by Mycobacterium tuberculosis, namely the early secretory antigenic target 6 kDa protein (ESAT6), culture filtrate protein (CFP 10), and Mycobacterium tuberculosis protein (MPT64) encoded by region of difference genes (RDI, RD2, and RD3). The purpose of this study was to determine the validity of TB ICT antigens in diagnosing pulmonary tuberculosis. The research method used is a diagnostic test with a cross-sectional study design. The population of this study was all pulmonary TB patients who were examined at the Prof. Hospital Laboratory. W.Z. John. The samples used in this study amounted to 81 samples which were preceded by smear examination and then 47 samples of M. tuberculosis culture on Lowenstein Jensen media which was used as the gold standard, the results of the examination were 41 samples growing and 6 samples not growing. The sensitivity and specificity of the Rapid ICT TB antigen test were 75.61% and 100%, respectively. The conclusion of the rapid ICT TB antigen test has high validity, so it can be used as an alternative laboratory test for the diagnosis of pulmonary TB.

Utility of the BACTEC MGIT 960 TB system for recovery of mycobacteria

Background and Objectives: Pulmonary tuberculosis (PTB) remains a public health issue in Nigeria. The rapid diagnosis of PTB is essential for the early initiation of treatment and management of patients. The utility of the BACTEC MGIT 960 TB system was evaluated and compared with the Lowenstein Jensen (LJ) culture method for the recovery of Mycobacteria from sputum samples. Methods: A total of 2400 sputum samples submitted to the South East TB Zonal Reference Laboratory, Amachara Umuahia, Nigeria were tested. Samples were decontaminated using the standard N-Acetyl-L-Cysteine Sodium Hydroxide method and concentrated before processing. The processed samples were inoculated into both MGIT 960 tubes and LJ medium and incubated accordingly. Results: From all sputum samples, Mycobacteria were recovered from 201 (8.4%) sputum samples by the MGIT 960 system and 175 (7.3%) by LJ culture (p=0.014). The sensitivity for MGIT and LJ culture for mycobacteria were 95.0% and 80.1%, respectively. Among the 201 MGIT-positive cultures, 127 (63.2%) were identified as Mycobacterium tuberculosis complex and 74 (36.8%) as Mycobacteria other than tuberculosis (MOTT). The recovery rate of MTBC from LJ-positive samples was 84.0% and MOTT 16.0%. MGIT 960 identified more MOTT than LJ culture (p=0.045). The contamination rate associated with MGIT and LJ culture was 4.1% and 2.5%, respectively (p=0.037). The time to detection of mycobacteria in MGIT 960 and LJ was 14.8 days and 33.2 days, respectively. Conclusion: MGIT 960 has good diagnostic accuracy. It provided a more rapid and higher recovery of all mycobacteria than the LJ culture.

Clinical assistant decision-making model of tuberculosis based on electronic health records

BackgroundTuberculosis is a dangerous infectious disease with the largest number of reported cases in China every year. Preventing missed diagnosis has an important impact on the prevention, treatment, and recovery of tuberculosis. The earliest pulmonary tuberculosis prediction models mainly used traditional image data combined with neural network models. However, a single data source tends to miss important information, such as primary symptoms and laboratory test results, that is available in multi-source data like medical records and tests. In this study, we propose a multi-stream integrated pulmonary tuberculosis diagnosis model based on structured and unstructured multi-source data from electronic health records. With the limited number of lung specialists and the high prevalence of tuberculosis, the application of this auxiliary diagnosis model can make substantial contributions to clinical settings.MethodsThe subjects were patients at the respiratory department and infectious cases department of a large comprehensive hospital in China between 2015 to 2020. A total of 95,294 medical records were selected through a quality control process. Each record contains structured and unstructured data. First, numerical expressions of features for structured data were created. Then, feature engineering was performed through decision tree model, random forest, and GBDT. Features were included in the feature exclusion set as per their weights in descending order. When the importance of the set was higher than 0.7, this process was concluded. Finally, the contained features were used for model training. In addition, the unstructured free-text data was segmented at the character level and input into the model after indexing. Tuberculosis prediction was conducted through a multi-stream integration tuberculosis diagnosis model (MSI-PTDM), and the evaluation indices of accuracy, AUC, sensitivity, and specificity were compared against the prediction results of XGBoost, Text-CNN, Random Forest, SVM, and so on.ResultsThrough a variety of characteristic engineering methods, 20 characteristic factors, such as main complaint hemoptysis, cough, and test erythrocyte sedimentation rate, were selected, and the influencing factors were analyzed using the Chinese diagnostic standard of pulmonary tuberculosis. The area under the curve values for MSI-PTDM, XGBoost, Text-CNN, RF, and SVM were 0.9858, 0.9571, 0.9486, 0.9428, and 0.9429, respectively. The sensitivity, specificity, and accuracy of MSI-PTDM were 93.18%, 96.96%, and 96.96%, respectively. The MSI-PTDM prediction model was installed at a doctor workstation and operated in a real clinic environment for 4 months. A total of 692,949 patients were monitored, including 484 patients with confirmed pulmonary tuberculosis. The model predicted 440 cases of pulmonary tuberculosis. The positive sample recognition rate was 90.91%, the false-positive rate was 9.09%, the negative sample recognition rate was 96.17%, and the false-negative rate was 3.83%.ConclusionsMSI-PTDM can process sparse data, dense data, and unstructured text data concurrently. The model adds a feature domain vector embedding the medical sparse features, and the single-valued sparse vectors are represented by multi-dimensional dense hidden vectors, which not only enhances the feature expression but also alleviates the side effects of sparsity on the model training. However, there may be information loss when features are extracted from text, and adding the processing of original unstructured text makes up for the error within the above process to a certain extent, so that the model can learn data more comprehensively and effectively. In addition, MSI-PTDM also allows interaction between features, considers the combination effect between patient features, adds more complex nonlinear calculation considerations, and improves the learning ability of the model. It has been verified using a test set and via deployment within an actual outpatient environment.

Utility of GeneXpert MTB/RIF in the Rapid Diagnosis of Extra Pulmonary Tuberculosis

Introduction: The diagnosis of extrapulmonary tuberculosis (EPTB) is a challenge. World Health Organization (WHO) recommends the use of GeneXpert MTB/RIF assay [Cepheid, United States of America (USA)], using a heminested real-time polymerase chain reaction (PCR) to amplify a Mycobacterium tuberculosis-specific sequence of the rpoB gene for the rapid and simultaneous detection of M. tb complex (MTBC) and resistance to rifampicin from a clinical specimen. The purpose of this study is to evaluate the performance of the GeneXpert MTB/RIF test with conventional mycobacterial culture in EPTB specimens. Materials and methods: This prospective study (February–October 2017, 11 months) includes data on 287 EPTB specimens that were processed by conventional culture on Lowenstein–Jensen (LJ) medium and the rapid molecular-based GeneXpert MTB/RIF assay system. Results: Among the 287 EPTB samples tested, GeneXpert detected the deoxyribonucleic acid of MTBC in 51 samples (17.8%). Standard bacteriological assays, including acid-fast bacilli microscopy and culture, were positive in 26 (9.1%) and 35 (12.1%) specimens respectively. The performance of GeneXpert results was evaluated against culture as a gold standard. The overall sensitivity and specificity of the Xpert assay were calculated to be 94.6 and 94.4%, respectively. The sensitivity of the Xpert assay with tissue specimens was 84.6 and 80.7% specificity, while there was 86.6% sensitivity and 98.1% specificity with the body fluids. Conclusion: GeneXpert had high performance than culture for the EPTB specimen. It can be a useful tool for the early diagnosis of patients with high clinical suspicion of EPTB. The other major advantage of GeneXpert is that it simultaneously detects rifampicin resistance within 2 hours.

A cross-sectional study: a breathomics based pulmonary tuberculosis detection method

BackgroundDiagnostics for pulmonary tuberculosis (PTB) are usually inaccurate, expensive, or complicated. The breathomics-based method may be an attractive option for fast and noninvasive PTB detection.MethodExhaled breath samples were collected from 518 PTB patients and 887 controls and tested on the real-time high-pressure photon ionization time-of-flight mass spectrometer. Machine learning algorithms were employed for breathomics analysis and PTB detection mode, whose performance was evaluated in 430 blinded clinical patients.ResultsThe breathomics-based PTB detection model achieved an accuracy of 92.6%, a sensitivity of 91.7%, a specificity of 93.0%, and an AUC of 0.975 in the blinded test set (n = 430). Age, sex, and anti-tuberculosis treatment does not significantly impact PTB detection performance. In distinguishing PTB from other pulmonary diseases (n = 182), the VOC modes also achieve good performance with an accuracy of 91.2%, a sensitivity of 91.7%, a specificity of 88.0%, and an AUC of 0.961.ConclusionsThe simple and noninvasive breathomics-based PTB detection method was demonstrated with high sensitivity and specificity, potentially valuable for clinical PTB screening and diagnosis.

A united model for diagnosing pulmonary tuberculosis with random forest and artificial neural network.

Background: Pulmonary tuberculosis (PTB) is a chronic infectious disease and is the most common type of TB. Although the sputum smear test is a gold standard for diagnosing PTB, the method has numerous limitations, including low sensitivity, low specificity, and insufficient samples. Methods: The present study aimed to identify specific biomarkers of PTB and construct a model for diagnosing PTB by combining random forest (RF) and artificial neural network (ANN) algorithms. Two publicly available cohorts of TB, namely, the GSE83456 (training) and GSE42834 (validation) cohorts, were retrieved from the Gene Expression Omnibus (GEO) database. A total of 45 and 61 differentially expressed genes (DEGs) were identified between the PTB and control samples, respectively, by screening the GSE83456 cohort. An RF classifier was used for identifying specific biomarkers, following which an ANN-based classification model was constructed for identifying PTB samples. The accuracy of the ANN model was validated using the receiver operating characteristic (ROC) curve. The proportion of 22 types of immunocytes in the PTB samples was measured using the CIBERSORT algorithm, and the correlations between the immunocytes were determined. Results: Differential analysis revealed that 11 and 22 DEGs were upregulated and downregulated, respectively, and 11 biomarkers specific to PTB were identified by the RF classifier. The weights of these biomarkers were determined and an ANN-based classification model was subsequently constructed. The model exhibited outstanding performance, as revealed by the area under the curve (AUC), which was 1.000 for the training cohort. The AUC of the validation cohort was 0.946, which further confirmed the accuracy of the model. Conclusion: Altogether, the present study successfully identified specific genetic biomarkers of PTB and constructed a highly accurate model for the diagnosis of PTB based on blood samples. The model developed herein can serve as a reliable reference for the early detection of PTB and provide novel perspectives into the pathogenesis of PTB.

Time to diagnosis and treatment of pulmonary tuberculosis in indigenous peoples: a systematic review

BackgroundTime to diagnosis and treatment is a major factor in determining the likelihood of tuberculosis (TB) transmission and is an important area of intervention to reduce the reservoir of TB infection and prevent disease and mortality. Although Indigenous peoples experience an elevated incidence of TB, prior systematic reviews have not focused on this group. We summarize and report findings related to time to diagnosis and treatment of pulmonary TB (PTB) among Indigenous peoples, globally.MethodsA Systematic review was performed using Ovid and PubMed databases. Articles or abstracts estimating time to diagnosis, or treatment of PTB among Indigenous peoples were included with no restriction on sample size with publication dates restricted up to 2019. Studies that focused on outbreaks, solely extrapulmonary TB alone in non-Indigenous populations were excluded. Literature was assessed using the Hawker checklist. Registration Protocol (PROSPERO): CRD42018102463.ResultsTwenty-four studies were selected after initial assessment of 2021 records. These included Indigenous groups from five of six geographical regions outlined by the World Health Organization (all except the European Region). The range of time to treatment (24–240 days), and patient delay (20 days–2.5 years) were highly variable across studies and, in at least 60% of the studies, longer in Indigenous compared to non-Indigenous peoples. Risk factors associated with longer patient delays included poor awareness of TB, type of health provider first seen, and self-treatment.ConclusionTime to diagnosis and treatment estimates for Indigenous peoples are generally within previously reported ranges from other systematic reviews focusing on the general population. However among literature examined in this systematic review that stratified by Indigenous and non-Indigenous peoples, patient delay and time to treatment were longer compared to non-Indigenous populations in over half of the studies. Studies included were sparse and highlight an overall gap in literature important to interrupting transmission and preventing new TB cases among Indigenous peoples. Although, risk factors unique to Indigenous populations were not identified, further investigation is needed as social determinants of health among studies conducted in medium and high incidence countries may be shared across both population groups.Trial registration N/a.

Evaluation of Purified Protein Derivative Changes Based on Mediastinal Lymph Node Density

Background: The present study evaluated purified protein derivative (PPD) changes based on mediastinal lymph node density. Methods: This cross-sectional observational study was performed on 130 patients who were referred to Valiasr and Amir Al-Momenin Hospitals in Arak, Iran for a CT scan for non-infectious and non-tumor reasons. The gender of the patients was recorded, and they then underwent non-contrast CT, and their mediastinal lymph node density was measured and recorded based on the Hounsfield units. Patients were evaluated for changes in the tuberculin test. The induration diameter obtained from the tuberculin test was recorded for each individual. Data analysis was then carried out using SPSS software ver. 20. Results: There was a positive correlation between mediastinal lymph node density and tuberculin test induration diameter, so larger induration diameter in the tuberculin test results in increasing lymph node density result (r = 0.416, P &lt; 0.001). There was a negative correlation between mediastinal lymph node density and age, i.e., mediastinal lymph node density decreased with increasing age (P &lt; 0.001, r = -0.616). Lymph node density was higher in men than in women (P = 0.022). Conclusions: There is a positive correlation between the mediastinal lymph node density and the tuberculin test induration diameter, and the tuberculin test induration diameter increases with increasing lymph node density. There is a negative correlation between the mediastinal lymph node density and age, i.e., the mediastinal lymph node density decreases with increasing age. Lymph node density was also higher in men than in women. Therefore, the results can help ensure an earlier diagnosis of pulmonary tuberculosis, and measuring the mediastinal lymph node density is recommended.

Performance of microbiological tests for tuberculosis diagnostic according to the type of respiratory specimen: A 10-year retrospective study.

The microbial diagnosis of tuberculosis (TB) remains challenging and relies on multiple microbiological tests performed on different clinical specimens. Polymerase chain reactions (PCRs), introduced in the last decades has had a significant impact on the diagnosis of TB. However, questions remain about the use of PCRs in combination with conventional tests for TB, namely microscopy and culture. We aimed to determine the performance of microscopy, culture and PCR for the diagnosis of pulmonary tuberculosis according to the type of clinical specimen in order to improve the diagnostic yield and to avoid unnecessary, time and labor-intensive tests. We conducted a retrospective study (2008-2018) on analysis (34'429 specimens, 14'358 patients) performed in our diagnostic laboratory located in the Lausanne University Hospital to compare the performance of microbiological tests on sputum, induced sputum, bronchial aspirate and bronchoalveolar lavage (BAL). We analysed the performance using a classical "per specimen" approach and a "per patient" approach for paired specimens collected from the same patient. The overall sensitivities of microscopy, PCR and culture were 0.523 (0.489, 0.557), 0.798 (0.755, 0.836) and 0.988 (0.978, 0.994) and the specificity were 0.994 (0.993, 0.995), 1 (0.999, 1) and 1 (1, 1). Microscopy displayed no significant differences in sensitivity according to the type of sample. The sensitivities of PCR for sputum, induced sputum, bronchial aspirate and BAL were, 0.821 (0.762, 0.871), 0.643 (0.480, 0.784), 0.837 (0.748, 0.904) and 0.759 (0.624, 0.865) respectively and the sensitivity of culture were, 0.993 (0.981, 0.998), 0.980 (0.931, 0.998), 0.965 (0.919, 0.988), and 1 (0.961, 1) respectively. Pairwise comparison of specimens collected from the same patient reported a significantly higher sensitivity of PCR on bronchial aspirate over BAL (p < 0.001) and sputum (p < 0.05) and a significantly higher sensitivity of culture on bronchial aspirate over BAL (p < 0.0001). PCR displayed a higher sensitivity and specificity than microscopy for all respiratory specimens, a rational for a smear-independent PCR-based approach to initiate tuberculosis microbial diagnostic. The diagnosis yield of bronchial aspirate was higher than BAL. Therefore, PCR should be systematically performed also on bronchial aspirates when available.