Implications of Tuberculosis Sputum Culture Test Sensitivity on Accuracy of Other Diagnostic Modalities.
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ABSTRACT:
SUBMITTER: Parker RA
PROVIDER: S-EPMC6396855 | biostudies-literature | 2019 Mar
REPOSITORIES: biostudies-literature
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Implications of Tuberculosis Sputum Culture Test Sensitivity on Accuracy of Other Diagnostic Modalities.
American journal of respiratory and critical care medicine 20190301 5
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| S-EPMC6396856 | biostudies-literature
Project description:In Sub-Saharan Africa, African giant pouched rats (Cricetomys gambianus) are trained to identify TB patients by smelling sputum. We conducted a systematic review and meta-analysis of the data to see if this novel method is comparable to traditional laboratory screening and detection methods like Ziehl-Neelsen stain-based assays (ZN) and bacterial culture. The search and data processing strategy is registered at PROSPERO (CRD42019123629). Medline via PubMed, EMBASE, Web of Science, and Cochrane Library databases were systematically searched for the keywords "pouched rat" and "tuberculosis". Data from 53,181 samples obtained from 24,600 patients were extracted from seven studies. Using sample-wise detection, the sensitivity of the studies was 86.7% [95% CI 80.4-91.2%], while the specificity was 88.4% [95% CI 79.7-93.7%]. For patient-wise detection, the sensitivity was 81.3% [95% CI 64.0-91.4%], while the specificity was 73.4% [95% CI 62.8-81.9%]. Good and excellent classification was assessed by hierarchical summary receiver-operating characteristic analysis for patient-wise and sample-wise detections, respectively. Our study is the first systematic review and meta-analysis of the above relatively inexpensive and rapid screening method. The results indicate that African giant pouched rats can discriminate healthy controls from TB individuals by sniffing sputum with even a higher accuracy than a single ZN screening.
| S-EPMC7820466 | biostudies-literature
Project description:BackgroundIn application studies of latent class analysis (LCA) evaluating imperfect diagnostic tests, residual dependence among the diagnostic tests still remain even after conditioning on the true disease status due to measured variables known to affect prevalence and/or alter diagnostic test accuracy. Presence of severe comorbidities such as HIV in pulmonary tuberculosis (PTB) diagnosis alter the prevalence of PTB and affect the diagnostic performance of the available imperfect tests in use. This violates two key assumptions of LCA: (1) that the diagnostic tests are independent conditional on the true disease status (2) that the sensitivity and specificity remain constant across subpopulations. This leads to incorrect inferences.MethodsThrough simulation we examined implications of likely model violations on estimation of prevalence, sensitivity and specificity among passive case-finding presumptive PTB patients with or without HIV. Jointly conditioning on PTB and HIV, we generated independent results for five diagnostic tests and analyzed using Bayesian LCA with Probit regression, separately for sets of five and three diagnostic tests using four working models allowing: (1) constant PTB prevalence and diagnostic accuracy (2) varying PTB prevalence but constant diagnostic accuracy (3) constant PTB prevalence but varying diagnostic accuracy (4) varying PTB prevalence and diagnostic accuracy across HIV subpopulations. Vague Gaussian priors with mean 1 and unknown variance were assigned to the model parameters with unknown variance assigned Inverse Gamma prior.ResultsModels accounting for heterogeneity in diagnostic accuracy produced consistent estimates while the model ignoring it produces biased estimates. The model ignoring heterogeneity in PTB prevalence only is less problematic. With five diagnostic tests, the model assuming homogenous population is robust to violation of the assumptions.ConclusionWell-chosen covariate-specific adaptations of the model can avoid bias implied by recognized heterogeneity in PTB patient populations generating otherwise dependent test results in LCA.
| S-EPMC9468460 | biostudies-literature
Project description:BackgroundDevelopment of a non-sputum test using readily-obtainable biospecimens remains a global priority for tuberculosis (TB) control. We quantified lipoarabinomannan (LAM) concentrations, a pathogen biomarker for Mycobacterium tuberculosis, in urine, plasma and serum for real-world diagnostic accuracy of pulmonary TB among people living with and without HIV.MethodsWe conducted a prospective diagnostic study among adults with TB symptoms in South Africa. We measured LAM concentrations in time-matched urine, plasma and serum with an electrochemiluminescence immunoassay using two capture antibodies (FIND 28 and S4-20). From the completed cohort, we randomly selected 210 participants (2 cases: 1 control) based on sensitivity estimates, and we compared diagnostic accuracy of LAM measurements against the microbiological reference standard.FindingsUrine and blood specimens from 210 of 684 adults enrolled were tested for LAM. Among 138 TB-positive adults (41% female), median urine LAM was 137 pg/mL and 52 pg/mL by FIND 28 and S4-20, respectively. Average LAM concentrations were highest in HIV-positive participants with CD4+ T cells <200 cells/mm3. Urine LAM by S4-20 achieved diagnostic sensitivity of 62% (95% CI: 53%-70%) and specificity of 99% (95% CI: 96%-100%). Plasma and serum LAM by FIND 28 showed similar sensitivity (70%, 95% CI: 62%-78%) and comparable specificities (90%, 95% CI: 82%-97%; 94%, 95% CI: 88%-99%). Diagnostic sensitivity of urine LAM by S4-20 was higher among participants without HIV (41%, 95% CI: 24%-61%) compared to HIV-positive participants with CD4 ≥200 cells/mm3 (20%, 95% CI: 8%-39%).InterpretationDetection of LAM was achievable in non-sputum specimens for pulmonary TB, but additional analyte concentration or signal amplification may be required to achieve diagnostic accuracy targets.FundingBill and Melinda Gates Foundation.
| S-EPMC11481603 | biostudies-literature
Project description:IntroductionNecrotising enterocolitis (NEC) is one of the most serious conditions in newborn infants, affecting up to 10% of very low birth weight (VLBW) infants. Mortality rates can rise as high as 60%.The suspected diagnosis is confirmed with typical findings on abdominal radiography (AR) such as pneumatosis intestinalis (PI), portal vein gas (PVG) and in extreme cases pneumoperitoneum. Abdominal ultrasound (AUS) can depict PI, PVG and pnuemoperitoneum (in some cases ahead of AR), but it also provides other crucial information such as bowel wall viability (thickness or thinning) and free abdominal fluid. These additional findings are helpful in diagnosing and managing NEC.Methods and analysisThe hypothesis being tested is that preforming an AR in patients with clinical symptoms of NEC, but inconclusive/normal AR will enhance detection rates, and expedite treatment in infants born at <32 weeks. Additionally, the time needed to initiate treatment, according to decision made based on AR or AR and AUS will also be compared. The use of AUS together with AR as an add-on test may increase the accuracy of diagnosing NEC and expedite life-saving treatment. We plan to recruit 200 VLBW infants, who are most prone to NEC. It will also be the first multicentre study evaluating the use of AUS as an add-on test, enabling us to recruit a significantly higher number of patients compared with published studies.Ethics and disseminationThe Bioethical Committee of the Medical University of Warsaw has approved the study (KB 130/2017). We plan to submit our findings to international peer-reviewed journals. Abstract will be submitted to local and international conferences.Trial registration numberNCT03188380; Protocol version: V.2.08.2019; Pre-results.
| S-EPMC7375631 | biostudies-literature
Project description:BackgroundPulmonary tuberculosis (PTB) diagnosis relies on sputum examination, a challenge in sputum-scarce patients. Alternative non-invasive sampling methods such as face mask sampling (FMS) have been proposed.ObjectiveTo evaluate the value of FMS for PTB diagnosis by assessing its agreement with sputum samples processed by GeneXpert MTB/RIF (Ultra)(Xpert) testing, and describe FMS sensitivity and specificity.MethodsThis was a prospective study conducted at the Carrière TB clinic in Guinea. Presumptive TB patients willing to participate were asked to wear a surgical mask containing a polyvinyl alcohol (PVA) strip for thirty minutes. Subsequently, two spot sputum samples were collected, of which one was processed by microscopy on site and the other by Xpert in Guinea's National Reference Laboratory of Mycobacteriology (LNRM). The first 30 FMS were processed at the Supranational Reference Laboratory in Antwerp, Belgium, and the following 118 FMS in the LNRM.ResultsOne hundred fifty patients participated, of whom 148 had valid results for both mask and sputum. Sputum smear microscopy was positive for 47 (31.8%) patients while sputum-Xpert detected MTB in 54 (36.5%) patients. Among the 54 patients testing sputum-Xpert positive, 26 (48.1%) yielded a positive FMS-Xpert result, while four sputum-Xpert negative patients tested positive for FMS and 90 patients were Xpert-negative for both sputum and mask samples, suggesting a moderate level of agreement (k-value of 0.47). The overall mask sensitivity was 48.1%, with 95.7% specificity.ConclusionIn our setting, Xpert testing on FMS did not yield a high level of agreement to sputum sample.
| S-EPMC10486030 | biostudies-literature
Project description:Nucleic acid amplification tests are increasingly used to diagnose tuberculosis (TB) due to their speed and sensitivity compared to sputum smear microscopy. However, these tests fail to equal culture's sensitivity with sputum smear microscopy negative specimens and therefore cannot be used to rule out TB disease. For molecular tests to match culture's sensitivity, they must detect ≤10 genomic copies of Mycobacterium tuberculosis (MTB) DNA, the limit of detection of culture, process ≥1 ml of sputum ensuring sufficient number of MTB are in the reaction, and efficiently remove sputum associated inhibitors from this large sample. Here we report the preliminary characterization of XtracTB Assay, a MTB testing protocol designed for inclusion in either an integrated point-of-care platform or a high throughput automated central laboratory system. The test combines DNA sequence specific sample prep to reduce the co-extraction of qPCR inhibitors with the amplification of two MTB specific loci (IS6110 and senX3-regX3) to increase test sensitivity and minimize the likelihood of false negatives. The analytical sensitivity of the XtracTB Assay was 5 genomic copies/ml of sputum rivaling that of culture. Furthermore, 142 valid test results yield clinical sensitivity of 94.9% (95% CI: 90.1-99.9) and specificity of 100% (95% CI: 90.0-100.0).
| S-EPMC5473816 | biostudies-literature
Project description:Evaluation of tests for the diagnosis of childhood pulmonary tuberculosis (CPTB) is complicated by the absence of an accurate reference test. We present a Bayesian latent class analysis in which we evaluated the accuracy of 5 diagnostic tests for CPTB. We used data from a study of 749 hospitalized South African children suspected to have CPTB from 2009 to 2014. The following tests were used: mycobacterial culture, smear microscopy, Xpert MTB/RIF (Cepheid Inc.), tuberculin skin test (TST), and chest radiography. We estimated the prevalence of CPTB to be 27% (95% credible interval (CrI): 21, 35). The sensitivities of culture, Xpert, and smear microscopy were estimated to be 60% (95% CrI: 46, 76), 49% (95% CrI: 38, 62), and 22% (95% CrI: 16, 30), respectively; specificities of these tests were estimated in accordance with prior information and were close to 100%. Chest radiography was estimated to have a sensitivity of 64% (95% CrI: 55, 73) and a specificity of 78% (95% CrI: 73, 83). Sensitivity of the TST was estimated to be 75% (95% CrI: 61, 84), and it decreased substantially among children who were malnourished and infected with human immunodeficiency virus (56%). The specificity of the TST was 69% (95% CrI: 63%, 76%). Furthermore, it was estimated that 46% (95% CrI: 42, 49) of CPTB-negative cases and 93% (95% CrI: 82; 98) of CPTB-positive cases received antituberculosis treatment, which indicates substantial overtreatment and limited undertreatment.
| S-EPMC5100832 | biostudies-literature
Project description:BackgroundStool is a potential sample for diagnosing Mycobacterium tuberculosis (Mtb) in patients with difficulty in expectorating. However, high mycobacterial culture contamination rates and Xpert MTB/RIF Ultra test error rates on stool samples have limited its use. OMNIgene SPUTUM (OM-S) is a sample transport reagent with characteristics of sputum decontamination while maintaining viable Mtb. We evaluated the impact of OM-S on Mtb diagnostic yield from stool using smear microscopy, Xpert MTB/RIF Ultra, and culture among presumptive TB patients.MethodsPaired stool and expectorated sputum samples were collected from consecutive Ugandan adults undergoing diagnostic evaluation for pulmonary TB between June 2018 and June 2019. Stool was divided into 2 portions: one was homogenized in OM-S (OM-S stool) and the other in PBS (PBS stool) as control. Both sputum and processed stool were tested for Mtb using concentrated smear fluorescence microscopy (CFM), Xpert MTB/RIF Ultra (Xpert) and Mycobacteria Growth Indicator Tube (MGIT) culture. Sensitivity, specificity, and predictive values for each test were calculated against sputum MGIT culture as the reference standard.ResultsOf the 200 participants, 120 (60%) were male, 73 (37%) were HIV positive (median CD4 120 cells/uL (IQR 43-297)) and 128 (64%) had confirmed pulmonary TB by sputum MGIT culture. Seven (4%) OM-S stool Xpert samples reported errors while 47 (25%) and 103 (61%) were contaminated on OM-S stool MGIT and PBS stool MGIT, respectively. OM-S stool MGIT was able to accurately diagnose 56 of the contaminated PBS stool MGIT samples compared to only 5 of the contaminated OM-S stool MGIT samples diagnosed by PBS stool MGIT. Sensitivity (95% Confidence Interval, CI) 89% (83-94) for OM-S stool Xpert was higher compared to that of OM-S stool MGIT 60% (51-69) and PBS stool MGIT 42% (32-52). Specificity (95%CI) 91% (82-97) was also higher for OM-S stool Xpert compared to OM-S stool MGIT 64% (51-75) and PBS stool MGIT 26% (16-38).ConclusionStool processed with OM-S showed potential to improve Mtb diagnostic yield and reduce rates of indeterminate results when tested on Xpert and MGIT culture. The method may thus be of value in Mtb detection among patients with difficulty to expectorate.
| S-EPMC10121033 | biostudies-literature
Project description:Culturing and genomic sequencing of Mycobacterium tuberculosis (MTB) from tuberculosis (TB) cases is the basis for many research and clinical applications. The alternative, culture-free sequencing from diagnostic samples, is promising but poses challenges to obtain and analyse the MTB genome. Paradoxically, culture is assumed to impose a diversity bottleneck, which, if true, would entail unexplored consequences. To unravel this paradox we generate high-quality genomes of sputum-culture pairs from two different settings after developing a workflow for sequencing from sputum and a tailored bioinformatics analysis. Careful downstream comparisons reveal sources of sputum-culture incongruences due to false positive/negative variation associated with factors like low input MTB DNA or variable genomic depths. After accounting for these factors, contrary to the bottleneck dogma, we identify a 97% variant agreement within sputum-culture pairs, with a high correlation also in the variants' frequency (0.98). The combined analysis from five different settings and more than 100 available samples shows that our results can be extrapolated to different TB epidemic scenarios, demonstrating that for the cases tested culture accurately mirrors clinical samples.
| S-EPMC11377819 | biostudies-literature