Investigation of OMNIgene·SPUTUM performance in delayed tuberculosis testing by smear, culture, and Xpert MTB/RIF assays in Uganda.

PubMed

Kelly-Cirino, C D; Musisi, E; Byanyima, P; Kaswabuli, S; Andama, A; Sessolo, A; Sanyu, I; Zawedde, J; Curry, P S; Huang, L

2017-06-01

OMNIgene·SPUTUM (OM-S) is a sample transport reagent designed to work with all tuberculosis diagnostics while eliminating the need for cold chain. OM-S-treated sputum samples were assayed in several tests after multiday holds. Raw sputa from 100 patients underwent direct smear microscopy, were manually split and assigned to the OM-S group [OM-S added at collection (no other processing required) and tested after 0- to 5-day holds at room temperature] or standard-of-care (SOC) group (NaOH/N-acetyl l-cysteine decontamination, all tested on day of collection). Concentrated smear microscopy, Lowenstein Jensen (LJ) culture, and mycobacteria growth indicator tube (MGIT) culture were performed. For patients with negative direct smear, a second sample was split, with SOC (raw sputum) and OM-S portions (sediment) tested in the Xpert MTB/RIF (Xpert) assay. OM-S group and SOC group results were strongly concordant on all four tests [range, 89% (MGIT)-97% (Xpert)]. OM-S MGIT, LJ, and Xpert tests were in statistical agreement with SOC MGIT as reference. OM-S specimens had lower culture contamination rates (3% vs. 10% LJ; 2% vs. 5% MGIT) but required, on average, 5.6 additional days to become MGIT-positive. The findings suggest that samples held/transported in OM-S are compatible with smear microscopy, LJ or MGIT culture, and Xpert, and perform comparably to fresh sputum samples. Larger feasibility studies are warranted. Copyright © 2017. Published by Elsevier Ltd.

Automated chest-radiography as a triage for Xpert testing in resource-constrained settings: a prospective study of diagnostic accuracy and costs

NASA Astrophysics Data System (ADS)

Philipsen, R. H. H. M.; Sánchez, C. I.; Maduskar, P.; Melendez, J.; Peters-Bax, L.; Peter, J. G.; Dawson, R.; Theron, G.; Dheda, K.; van Ginneken, B.

2015-07-01

Molecular tests hold great potential for tuberculosis (TB) diagnosis, but are costly, time consuming, and HIV-infected patients are often sputum scarce. Therefore, alternative approaches are needed. We evaluated automated digital chest radiography (ACR) as a rapid and cheap pre-screen test prior to Xpert MTB/RIF (Xpert). 388 suspected TB subjects underwent chest radiography, Xpert and sputum culture testing. Radiographs were analysed by computer software (CAD4TB) and specialist readers, and abnormality scores were allocated. A triage algorithm was simulated in which subjects with a score above a threshold underwent Xpert. We computed sensitivity, specificity, cost per screened subject (CSS), cost per notified TB case (CNTBC) and throughput for different diagnostic thresholds. 18.3% of subjects had culture positive TB. For Xpert alone, sensitivity was 78.9%, specificity 98.1%, CSS $13.09 and CNTBC $90.70. In a pre-screening setting where 40% of subjects would undergo Xpert, CSS decreased to $6.72 and CNTBC to $54.34, with eight TB cases missed and throughput increased from 45 to 113 patients/day. Specialists, on average, read 57% of radiographs as abnormal, reducing CSS ($8.95) and CNTBC ($64.84). ACR pre-screening could substantially reduce costs, and increase daily throughput with few TB cases missed. These data inform public health policy in resource-constrained settings.

Evaluation of Cepheid's Xpert MTB/Rif test on pleural fluid in the diagnosis of pleural tuberculosis in a high prevalence HIV/TB setting.

PubMed

Lusiba, John K; Nakiyingi, Lydia; Kirenga, Bruce J; Kiragga, Agnes; Lukande, Robert; Nsereko, Maria; Ssengooba, Willy; Katamba, Achilles; Worodria, William; Joloba, Moses L; Mayanja-Kizza, Harriet

2014-01-01

Diagnosis of pleural tuberculosis (TB) using routinely available diagnostic methods is challenging due to the paucibacillary nature of the disease. Histopathology and pleural tissue TB culture involves an invasive procedure which requires expertise and appropriate equipment, both often unavailable in many health units. Xpert MTB/Rif test has been widely evaluated in sputum specimens but data on its performance in pleural TB is scarce. We evaluated the accuracy of Cepheid's Xpert MTB/Rif test on pleural fluid in the diagnosis of pleural TB in Uganda. Consenting adult patients with exudative pleural effusions underwent pleural biopsy and the tissue obtained subjected to Lowenstein-Jensen and mycobacterial growth indicator tube MTB cultures and histopathology. Pleural fluid for Xpert MTB/Rif testing was also collected. Data on socio-demographic characteristics, clinical symptoms, HIV status and CD4 count were also collected. Sensitivity, specificity, positive and negative predictive values of Xpert MTB/Rif test on pleural fluid in pleural TB diagnosis were calculated using pleural tissue MTB culture and/or histopathology as the reference standard. Of the 116 participants [female 50%, mean age 34 (SD ±13], 87/116 (75%) had pleural TB confirmed on pleural tissue culture and/or histopathology. The Xpert MTB/Rif test identified 25 (28.7%) of the 87 confirmed pleural TB cases. The sensitivity and specificity of Xpert MTB/Rif test were 28.7% and 96.6% respectively while the positive and negative predictive values were 96.1% and 31.1% respectively. Xpert MTB/Rif test on pleural fluid does not accurately diagnose pleural TB and therefore cannot be used as an initial evaluation test in patients with suspected pleural TB. New, rapid and accurate tests for the diagnosis of pleural TB are still warranted.

Evaluation of Cepheid's Xpert MTB/RIF Test on Pleural Fluid in the Diagnosis of Pleural Tuberculosis in a High Prevalence HIV/TB Setting

PubMed Central

Kirenga, Bruce J.; Kiragga, Agnes; Lukande, Robert; Nsereko, Maria; Ssengooba, Willy; Katamba, Achilles; Worodria, William; Joloba, Moses L.; Mayanja-Kizza, Harriet

2014-01-01

Background Diagnosis of pleural tuberculosis (TB) using routinely available diagnostic methods is challenging due to the paucibacillary nature of the disease. Histopathology and pleural tissue TB culture involves an invasive procedure which requires expertise and appropriate equipment, both often unavailable in many health units. Xpert MTB/Rif test has been widely evaluated in sputum specimens but data on its performance in pleural TB is scarce. We evaluated the accuracy of Cepheid's Xpert MTB/Rif test on pleural fluid in the diagnosis of pleural TB in Uganda. Methods Consenting adult patients with exudative pleural effusions underwent pleural biopsy and the tissue obtained subjected to Lowenstein-Jensen and mycobacterial growth indicator tube MTB cultures and histopathology. Pleural fluid for Xpert MTB/Rif testing was also collected. Data on socio-demographic characteristics, clinical symptoms, HIV status and CD4 count were also collected. Sensitivity, specificity, positive and negative predictive values of Xpert MTB/Rif test on pleural fluid in pleural TB diagnosis were calculated using pleural tissue MTB culture and/or histopathology as the reference standard. Results Of the 116 participants [female 50%, mean age 34 (SD ±13], 87/116 (75%) had pleural TB confirmed on pleural tissue culture and/or histopathology. The Xpert MTB/Rif test identified 25 (28.7%) of the 87 confirmed pleural TB cases. The sensitivity and specificity of Xpert MTB/Rif test were 28.7% and 96.6% respectively while the positive and negative predictive values were 96.1% and 31.1% respectively. Conclusion Xpert MTB/Rif test on pleural fluid does not accurately diagnose pleural TB and therefore cannot be used as an initial evaluation test in patients with suspected pleural TB. New, rapid and accurate tests for the diagnosis of pleural TB are still warranted. PMID:25051491

The New Xpert MTB/RIF Ultra: Improving Detection of Mycobacterium tuberculosis and Resistance to Rifampin in an Assay Suitable for Point-of-Care Testing

PubMed Central

Simmons, Ann Marie; Rowneki, Mazhgan; Parmar, Heta; Cao, Yuan; Ryan, Jamie; Banada, Padmapriya P.; Deshpande, Srinidhi; Shenai, Shubhada; Gall, Alexander; Glass, Jennifer; Krieswirth, Barry; Schumacher, Samuel G.; Nabeta, Pamela; Tukvadze, Nestani; Rodrigues, Camilla; Skrahina, Alena; Tagliani, Elisa; Cirillo, Daniela M.; Davidow, Amy; Denkinger, Claudia M.; Persing, David; Kwiatkowski, Robert; Jones, Martin

2017-01-01

ABSTRACT The Xpert MTB/RIF assay (Xpert) is a rapid test for tuberculosis (TB) and rifampin resistance (RIF-R) suitable for point-of-care testing. However, it has decreased sensitivity in smear-negative sputum, and false identification of RIF-R occasionally occurs. We developed the Xpert MTB/RIF Ultra assay (Ultra) to improve performance. Ultra and Xpert limits of detection (LOD), dynamic ranges, and RIF-R rpoB mutation detection were tested on Mycobacterium tuberculosis DNA or sputum samples spiked with known numbers of M. tuberculosis H37Rv or Mycobacterium bovis BCG CFU. Frozen and prospectively collected clinical samples from patients suspected of having TB, with and without culture-confirmed TB, were also tested. For M. tuberculosis H37Rv, the LOD was 15.6 CFU/ml of sputum for Ultra versus 112.6 CFU/ml of sputum for Xpert, and for M. bovis BCG, it was 143.4 CFU/ml of sputum for Ultra versus 344 CFU/ml of sputum for Xpert. Ultra resulted in no false-positive RIF-R specimens, while Xpert resulted in two false-positive RIF-R specimens. All RIF-R-associated M. tuberculosis rpoB mutations tested were identified by Ultra. Testing on clinical sputum samples, Ultra versus Xpert, resulted in an overall sensitivity of 87.5% (95% confidence interval [CI], 82.1, 91.7) versus 81.0% (95% CI, 74.9, 86.2) and a sensitivity on sputum smear-negative samples of 78.9% (95% CI, 70.0, 86.1) versus 66.1% (95% CI, 56.4, 74.9). Both tests had a specificity of 98.7% (95% CI, 93.0, 100), and both had comparable accuracies for detection of RIF-R in these samples. Ultra should significantly improve TB detection, especially in patients with paucibacillary disease, and may provide more-reliable RIF-R detection. PMID:28851844

[Use of the Xpert® MTB/RIF test in routine screening of new cases of pulmonary tuberculosis in an endemic area].

PubMed

Horo, K; N'Guessan, R; Koffi, M-O; Kouamé-N'Takpé, N; Koné, A; Samaké, K; Koffi, L; Ahui, B J M; Brou-Gode, C V; N'Gom, A; Kouassi, B A; Koffi, N; Aka-Danguy, E

2017-09-01

Developed initially for the diagnosis of multidrug-resistant tuberculosis, the Xpert ® MTB/RIF test has shown to be useful for the diagnosis of tuberculosis, especially among HIV-infected subjects. The objective of the study was to determine the contribution of the Xpert ® MTB/RIF test for routine pulmonary tuberculosis diagnosis in an endemic area. We undertook a prospective study among patients presenting with cough and sputum. The sputum was submitted to microscopic examination, to the Xpert ® MTB/RIF test and cultured by the Mycobacteria growth indicator tube (MGIT) technique. The study compared cases of pulmonary tuberculosis confirmed by a positive sputum culture and cases with cough but negative sputum culture. In multivariate analysis, the factors associated with positive cultures were the following: male gender, cough for more than 2 weeks, loss of weight and fever. The estimated clinical suspicion score consisted of 4 signs each having a coefficient of 1. The sensitivity of each clinical sign varied between 79 and 94%. In 348 cases of negative microscopic examination (composed of 295 cases with score<4 and 53 cases with score=4), the predictive positive value of the Xpert ® MTB/RIF was 80% for a score equal to 4 and 40.9% for a score<4. In cases of negative microscopic examination of the sputum, the Xpert ® MRT/RIF test should be undertaken if the score=4. The diagnosis of tuberculosis in endemic zones could be improved by using the Xpert ® MTB/RIF. Copyright © 2017 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Effect of Introducing Xpert MTB/RIF to Test and Treat Individuals at Risk of Multidrug-Resistant Tuberculosis in Kazakhstan: A Prospective Cohort Study.

PubMed

van Kampen, Sanne Christine; Tursynbayeva, Aigul; Koptleuova, Aliya; Murzakhmetova, Zauresh; Murzabekova, Zauresh; Bigalieva, Lyazzat; Aubakirova, Moldir; Pak, Svetlana; van den Hof, Susan

2015-01-01

Xpert MTB/RIF (Xpert) was piloted in Kazakhstan to detect tuberculosis (TB) and rifampicin resistance (RR-)TB among individuals at risk of multidrug-resistant (MDR-) TB. This study assessed the performance of Xpert compared to conventional diagnostic methods, RR-TB case detection among various risk groups, treatment initiation and time to diagnosis and treatment. Eligible individuals were tested with Xpert, smear microscopy, culture and drug-susceptibility testing (DST) at the national TB reference laboratory and three provincial laboratories. Data was collected prospectively from August 2012 to May 2013 from routine laboratory and treatment registers. A total of 5,611 Xpert tests were performed mostly targeting contacts of MDR-TB patients, 'other' presumptive MDR-TB patients, and retreatment cases (26%, 24% and 22%, respectively). Compared to phenotypic DST, the positive predictive value of Xpert to detect RR-TB was 93.1% and 96.4% and the negative predictive value was 94.6% and 92.7% using solid and liquid culture media, respectively. RR-TB detection was highest among (former) prisoners, retreatment cases, people living with HIV/AIDS (PLWHA), and TB patients with positive smears after intensive phase of treatment (59%, 58%, 54% and 53% among TB positives, respectively). 88.9% of RR-TB patients were registered to have started second-line TB treatment. Median time to diagnosis with Xpert was 0.0 days (IQR 0.0-1.0), time from diagnosis to start of first-line treatment 3.0 days (IQR 1.0-7.0), and to start of second-line treatment 7.0 days (IQR 4.0-16). Compared to conventional culture and DST, Xpert had a shorter result turn-around-time and excellent concordance to detect RR-TB. Time from sputum collection to start of second-line treatment was reduced to one week. The yield of Xpert could be maximized by increasing referrals from penitentiary and HIV centers to TB centers.

Impact of Xpert MTB/RIF rollout on management of tuberculosis in a South African community.

PubMed

Schmidt, B-M; Geldenhuys, H; Tameris, M; Luabeya, A; Mulenga, H; Bunyasi, E; Scriba, T; Hatherill, M

2017-11-27

The Xpert MTB/RIF test shortens the time to microbiological confirmation of pulmonary tuberculosis (TB) under research conditions. To evaluate the field impact of Xpert MTB/RIF rollout on TB diagnostic yield and time to treatment in a South African (SA) community. We compared TB investigation outcomes for 6-month calendar periods before and after Xpert MTB/RIF rollout in a semi-rural area of SA. The proportion of adult patients who tested positive by sputum smear microscopy, liquid culture or Xpert MTB/RIF and the proportion of positive sputum smear, liquid culture or Xpert MTB/RIF tests were compared. Secondary outcomes included time to laboratory diagnosis and treatment initiation. Data were collected from the National Health Laboratory Service database and from the Western Cape Provincial Department of Health TB register. Regional rollout of Xpert MTB/RIF testing occurred in 2013. Of the 15 629 patients investigated in the post-rollout period, 7.9% tested positive on GeneXpert, compared with 6.4% of the 10 741 investigated in the pre-rollout period who tested positive by sputum smear microscopy (p<0.001). Median laboratory processing time was <1 day for Xpert MTB/RIF (interquartile range (IQR) 0 - 1) compared with 1 day (IQR 0 - 16) for sputum smear microscopy (p=0.001). The median time to TB treatment initiation was 4 days (IQR 2 - 8) after rollout compared with 5 days (IQR 2 - 14) before (p=0.001). Patients investigated for suspected pulmonary TB were more likely to be diagnosed after rollout of Xpert MTB/RIF testing, although the benefit to diagnostic yield was modest, and Xpert MTB/RIF testing was associated with a marginal improvement in time to treatment initiation.

Point -of -care testing (POCT) in molecular diagnostics: Performance evaluation of GeneXpert HCV RNA test in diagnosing and monitoring of HCV infection.

PubMed

Gupta, Ekta; Agarwala, Pragya; Kumar, Guresh; Maiwall, Rakhi; Sarin, Shiv Kumar

2017-03-01

Molecular testing at the point-of-care may turn out to be game changer for HCV diagnosis and treatment monitoring, through increased sensitivity, reduced turnaround time, and ease of performance. One such assay GeneXpert ® has recently been released. Comparative analysis between performances of GeneXpert ® and Abbott HCV-RNA was done. 174 HCV infected patients were recruited and, one time plasma samples from 154 patients and repeated samples from 20 patients, obtained at specific treatment time-points (0, 4, 12 and 24) weeks were serially re-tested on Xpert ® . Genotype 3 was the commonest, seen in 80 (66%) of the cases, genotype 1 in 34 (28.3%), genotype 4 in 4 (3.3%) and genotypes 2 and 5 in 1 (0.8%) each. Median HCV RNA load was 4.69 log 10 (range: 0-6.98log 10 ) IU/ml. Overall a very good correlation was seen between the two assays (R 2 =0.985), concordance of the results between the assays was seen in 138 samples (89.6%). High and low positive standards were tested ten times on Xpert ® to evaluate the precision and the coefficient of variation was 0.01 for HPC and 0.07 for the LPC. Monitoring of patients on two different regimes of treatment, pegylated interferon plus ribavirin and sofosbuvir plus ribavirin was done by both the systems at baseline, 4, 12 and 24 weeks. Perfect correlation between the assays in the course of therapy at different treatment time- point in genotypes 3 and 1 was seen. The study demonstrates excellent performance of the Xpert ® HCV assay in viral load assessment and in treatment course monitoring consistency. Copyright © 2017 Elsevier B.V. All rights reserved.

Cost-effectiveness of supplementing a broth-enriched culture test with the Xpert meticillin-resistant Staphylococcus aureus (MRSA) assay for screening inpatients at high risk of MRSA.

PubMed

Li, J; Ulvin, K; Biboh, H; Kristiansen, I S

2012-12-01

Meticillin-resistant Staphylococcus aureus (MRSA) represents a considerable challenge for health care in terms of complications and costs. Whilst bacteriological culture remains the most common method for detecting MRSA, the polymerase-chain-reaction-based Xpert MRSA assay was introduced to Ullevål Oslo University Hospital, Norway in 2009. To estimate the cost-effectiveness of supplementing a broth-enriched culture test with the Xpert MRSA assay in comparison with using the culture test alone as part of an active surveillance strategy. A decision-tree model was developed to compare the current strategy (broth-enriched culture test) with two new strategies using the Xpert MRSA assay (daytime and 24 h). Costs and outcomes (length of pre-emptive isolation, number of unavailable room-hours, quality of life) were measured. The current strategy was more expensive (NOK16,984 per patient) than the daytime Xpert strategy and 24 h Xpert strategy (NOK7360 and NOK3690 per patient, respectively). The new strategies reduced the length of pre-emptive isolation per patient (by 43.9 h and 57.5 h for the daytime Xpert strategy and 24 h Xpert strategy, respectively), and also the number of unavailable room-hours per case (by 57.1 h and 77.7 h, respectively). The improvement in patients' quality-adjusted life years (QALYs) was nominal (2.4*10(-4) and 3.0*10(-4) QALYs per patient for the daytime Xpert strategy and 24 h Xpert strategy, respectively). The sensitivity analyses indicated that these results were robust to reasonable changes in the model parameters. The 24 h Xpert strategy appears to be the best strategy for active surveillance as it reduces costs and unfavourable outcomes compared with the other strategies, while improving favourable outcomes under reasonable assumptions. Copyright © 2012 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Multicenter Evaluation of the Cepheid Xpert Methicillin-Resistant Staphylococcus aureus (MRSA) Test as a Rapid Screening Method for Detection of MRSA in Nares▿

PubMed Central

Wolk, D. M.; Picton, E.; Johnson, D.; Davis, T.; Pancholi, P.; Ginocchio, C. C.; Finegold, S.; Welch, D. F.; de Boer, M.; Fuller, D.; Solomon, M. C.; Rogers, B.; Mehta, M. S.; Peterson, L. R.

2009-01-01

The first U.S. multicenter clinical trial to assess the performance of the Cepheid Xpert MRSA assay (Xpert MRSA) was conducted. The assay is a qualitative test designed for the rapid detection of methicillin-resistant Staphylococcus aureus (MRSA) directly from nares swabs. This novel test combines integrated nucleic acid extraction and automated real-time PCR for the detection of a MRSA-specific signature sequence. A total of 1,077 nares specimens were collected from seven geographically distinct health care sites across the United States with prevalence rates ranging from 5.2% to 44%. Nares specimens were tested by (i) the Xpert MRSA assay, (ii) direct culture on CHROMagar MRSA medium (direct CM culture), and (iii) broth-enriched culture (Trypticase soy broth with 6.5% sodium chloride) followed by plating onto CHROMagar MRSA medium (broth-enriched CM culture). When direct CM culture was designated the reference method, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the Xpert MRSA assay were 94.3%, 93.2%, 73.0%, and 98.8%, respectively. When broth-enriched CM culture was used as the reference method, the clinical sensitivity, specificity, PPV, and NPV of the Xpert MRSA assay were 86.3%, 94.9%, 80.5%, and 96.6%, respectively. The BD GeneOhm MRSA (BDGO) assay was performed as a comparative molecular method. No statistical performance differences were observed between the Xpert MRSA and BDGO assays when they were compared to culture methods. From this large-scale, multicenter clinical comparison, we conclude that the Xpert MRSA assay is a simple, rapid, and accurate method for performing active surveillance for MRSA in a variety of health care populations. PMID:19129414

Rifampicin Resistance and Multidrug-Resistant Tuberculosis Detection Using Xpert MTB/RIF in Wuhan, China: A Retrospective Study.

PubMed

Huang, Hai; Zhang, Yanlin; Li, Sheng; Wang, Jun; Chen, Jun; Pan, Zhiyun; Gan, Hui

2018-06-01

The Xpert MTB/RIF test (Cepheid, Sunnyvale, CA) can simultaneously detect the Mycobacterium tuberculosis (MTB) complex DNA and rifampicin (RFP) resistance and can rapidly determine RFP resistance and predict multidrug-resistant tuberculosis (MDR-TB). In this study, we analyzed clinical examination results of a hospital specializing in TB treatment in Wuhan, Hubei, China, and examined the use of traditional culture and drug-sensitive test (DST) results as a gold standard to assess the diagnosis value of the Xpert MTB/RIF test in RFP resistance and MDR-TB. A total of 2,910 specimens were received in the Mycobacteriology Laboratory, Wuhan Pulmonary Hospital, for Xpert MTB/RIF testing between December 2013 and December 2014. After the results were reviewed by exclusion criteria, 1,066 Xpert test results were eligible for our study. We then compared the Xpert test results with sputum acid-fast bacilli staining, cultures, and DST results. In total, Xpert correctly identified 96.71% (147/152) RFP-resistant TB and 98.25% (898/914) RFP-sensitive TB specimens. Of the 147 RFP-resistant TB specimens detected by Xpert, 122 MDR-TB (82.99%) were identified by traditional culture and DST techniques. Xpert can simultaneously detect MTB and RFP resistance with high sensitivity and specificity. Thus, Xpert testing aids in saving a considerable amount of time in the diagnosis and treatment of MDR-TB.

GeneXpert MTB/RIF Testing in the Management of Patients with Active Tuberculosis; A Real Life Experience from Saudi Arabia.

PubMed

Omrani, Ali S; Al-Otaibi, Mohammed F; Al-Ateah, Souad M; Al-Onazi, Fahad M; Baig, Kamran; El-Khizzi, Noura A; Albarrak, Ali M

2014-03-01

GeneXpert MTB/RIF is a real-time PCR assay with established diagnostic performance in pulmonary and extra-pulmonary forms of tuberculosis. The aim of this study was to assess the contribution of GeneXpert MTB/RIF assay to the management of patients with any form of active tuberculosis in a single large tertiary center in Saudi Arabia, with a special focus on the impact on time to start of antituberculous therapy compared with Ziehl-Neelsen (ZN) smears and mycobacterial cultures. Clinical, radiological and laboratory records for all patients who were commenced on antituberculous therapy between March 2011 and February 2013 were retrospectively reviewed. A total of 140 patients were included, 38.6% of which had pulmonary tuberculosis. GeneXpert MTB/RIF was requested for only 39.2% of patients and was the only reason for starting antituberculous therapy for only 12.1%. The median time to a positive GeneXpert MTB/RIF result was 0 days (IQR 3) compared with 0 day (IQR 1) for smear microscopy (P > 0.999) and 22 days (IQR 21) for mycobacterial cultures (P < 0.001). No patients discontinued antituberculous therapy because of a negative GeneXpert MTB/RIF result. In a setting wherein physicians are highly experienced in the diagnosis and treatment of tuberculosis, GeneXpert MTB/RIF was remarkably under-utilized and had only a limited impact on decisions related to starting or stopping antituberculous therapy. Cost-effectiveness and clinical utility of routine testing of all smear-negative clinical samples submitted for tuberculosis investigations by GeneXpert MTB/RIF warrant further study.

Xpert® MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults.

PubMed

Steingart, Karen R; Schiller, Ian; Horne, David J; Pai, Madhukar; Boehme, Catharina C; Dendukuri, Nandini

2014-01-21

Accurate, rapid detection of tuberculosis (TB) and TB drug resistance is critical for improving patient care and decreasing TB transmission. Xpert® MTB/RIF assay is an automated test that can detect both TB and rifampicin resistance, generally within two hours after starting the test, with minimal hands-on technical time. The World Health Organization (WHO) issued initial recommendations on Xpert® MTB/RIF in early 2011. A Cochrane Review on the diagnostic accuracy of Xpert® MTB/RIF for pulmonary TB and rifampicin resistance was published January 2013. We performed this updated Cochrane Review as part of a WHO process to develop updated guidelines on the use of the test. To assess the diagnostic accuracy of Xpert® MTB/RIF for pulmonary TB (TB detection), where Xpert® MTB/RIF was used as both an initial test replacing microscopy and an add-on test following a negative smear microscopy result.To assess the diagnostic accuracy of Xpert® MTB/RIF for rifampicin resistance detection, where Xpert® MTB/RIF was used as the initial test replacing culture-based drug susceptibility testing (DST).The populations of interest were adults presumed to have pulmonary, rifampicin-resistant or multidrug-resistant TB (MDR-TB), with or without HIV infection. The settings of interest were intermediate- and peripheral-level laboratories. The latter may be associated with primary health care facilities. We searched for publications in any language up to 7 February 2013 in the following databases: Cochrane Infectious Diseases Group Specialized Register; MEDLINE; EMBASE; ISI Web of Knowledge; MEDION; LILACS; BIOSIS; and SCOPUS. We also searched the metaRegister of Controlled Trials (mRCT) and the search portal of the WHO International Clinical Trials Registry Platform to identify ongoing trials. We included randomized controlled trials, cross-sectional studies, and cohort studies using respiratory specimens that allowed for extraction of data evaluating Xpert® MTB/RIF against the

Xpert® Mtb/Rif assay for pulmonary tuberculosis and rifampicin resistance in adults

PubMed Central

Steingart, Karen R; Sohn, Hojoon; Schiller, Ian; Kloda, Lorie A; Boehme, Catharina C; Pai, Madhukar; Dendukuri, Nandini

2013-01-01

Background Accurate and rapid detection of tuberculosis (TB) and drug resistance are critical for improving patient care and decreasing the spread of TB. Xpert® MTB/RIF assay (Xpert) is a rapid, automated test that can detect both TB and rifampicin resistance, within two hours after starting the test, with minimal hands-on technical time, but is more expensive than conventional sputum microscopy. Objectives To assess the diagnostic accuracy of Xpert for pulmonary TB (TB detection), both where Xpert was used as an initial test replacing microscopy, and where Xpert was used as an add-on test following a negative smear microscopy result. To assess the diagnostic accuracy of Xpert for rifampicin resistance detection where Xpert was used as the initial test, replacing conventional culture-based drug susceptibility testing. The population of interest was adults suspected of having pulmonary TB or multidrug-resistant TB (MDR-TB), with or without HIV infection. Search methods We performed a comprehensive search of the following databases: Cochrane Infectious Diseases Group Specialized Register; MEDLINE; EMBASE; ISI Web of Knowledge; MEDION; LILACS; BIOSIS; and SCOPUS. We also searched the metaRegister of Controlled Trials (mRCT) and the search portal of the WHO International Clinical Trials Registry Platform to identify ongoing trials. We performed searches on 25 September 2011 and we repeated them on 15 December 2011, without language restriction. Selection criteria We included randomized controlled trials, cross-sectional, and cohort studies that used respiratory specimens to compare Xpert with culture for detecting TB and Xpert with conventional phenotypic drug susceptibility testing for detecting rifampicin resistance. Data collection and analysis For each study, two review authors independently extracted a set of data using a standardized data extraction form. When possible, we extracted data for subgroups by smear and HIV status. We assessed the quality of studies

An evaluation of false-positive rifampicin resistance on the Xpert MTB/RIF.

PubMed

Cayci, Yeliz Tanriverdi; Bilgin, Kemal; Coban, Ahmet Yilmaz; Birinci, Asuman; Durupınar, Belma

2017-11-01

Mycobacterium tuberculosis (MTB) is one of the most significant causes of mortality and morbidity. Early diagnose is important especially in multiple drug resistant tuberculosis to avoid transmission. Traditional techniques requires at least one to three weeks for diagnosis of tuberculosis. Diagnostic delays with multiple drug resistant tuberculosis are associated with worse clinical outcomes and increased transmission The Xpert MTB/RIF assay is one of the new diagnostic device for the diagnosis of tuberculosis and rapid detection of rifampicin resistance. We assessed the performance of Xpert MTB/RIF assay for detecting rifampicin resistance using phenotypic drug susceptibility tests as automated BD MGIT 960. Total of 2136 specimens were included in the study. Xpert MTB/RIF testing was performed on samples, using version 4 cartridges, according to the manufacturer's recommendations. The MTBC culture and first-line phenotypic DST were performed in automated BD MGIT 960 (Becton & Dickinson, USA) according to the recommendations of the manufacturer. Agar proportion was used in the case of inconsistency for rifampicin resistance. Thirty-four samples (19 respiratory and 15 nonrespiratory samples) were determined as positive for M. tuberculosis complex by Xpert MTB/RIF (Cepheid GeneXpert® System, USA). Xpert MTB/RIF assay detected 4/34 (11.7%) specimens as rifampicin resistant. One of the rifampicin resistant isolates was determined susceptible in MGIT 960 automated system. This isolate was also tested with agar proportion method and found susceptible to rifampicin. The Xpert MTB/RIF assay can be used as first-line assay for the detection of M. tuberculosis. However, microbiologists must be aware of the limitations of the assay.

Evaluation of OMNIgene®•SPUTUM-stabilised sputum for long-term transport and Xpert® MTB/RIF testing in Nepal.

PubMed

Maharjan, B; Kelly-Cirino, C D; Weirich, A; Curry, P S; Hoffman, H; Avsar, K; Shrestha, B

2016-12-01

German Nepal TB Project, National Tuberculosis Reference Laboratory, Kathmandu, Nepal. To evaluate whether transporting samples in OMNIgene®•SPUTUM (OM-S) reagent from a peripheral collection site to a central laboratory in Nepal can improve tuberculosis (TB) detection and increase the sensitivity of Xpert® MTB/RIF testing. One hundred sputum samples were split manually. Each portion was assigned to the OM-S group (OM-S added at collection, airline-couriered without cold chain, no other processing required) or the standard-of-care (SOC) group (samples airline-couriered on ice, sodium hydroxide + N-acetyl-L-cysteine processing required at the laboratory). Smear microscopy and Xpert testing were performed. Transport time was 2-13 days. Overall smear results were comparable (respectively 58% and 56% smear-negative results in the OM-S and SOC groups). The rate of smear-positive, Mycobacterium tuberculosis-positive (MTB+) sample detection was identical for both treatment groups, at 95%. More smear-negative MTB+ samples were detected in the OM-S group (17% vs. 13%, P = 0.0655). Sputum samples treated with OM-S can undergo multiday ambient-temperature transport and yield comparable smear and Xpert results to those of SOC samples. Further investigation with larger sample sizes is required to assess whether treating sputum samples with OM-S could increase the sensitivity of Xpert testing in smear-negative samples.

Xpert® Mtb/Rif assay for pulmonary tuberculosis and rifampicin resistance in adults

PubMed Central

Steingart, Karen R; Schiller, Ian; Horne, David J; Pai, Madhukar; Boehme, Catharina C; Dendukuri, Nandini

2014-01-01

Background Accurate, rapid detection of tuberculosis (TB) and TB drug resistance is critical for improving patient care and decreasing TB transmission. Xpert® MTB/RIF assay is an automated test that can detect both TB and rifampicin resistance, generally within two hours after starting the test, with minimal hands-on technical time. The World Health Organization (WHO) issued initial recommendations on Xpert® MTB/RIF in early 2011. A Cochrane Review on the diagnostic accuracy of Xpert® MTB/RIF for pulmonary TB and rifampicin resistance was published January 2013. We performed this updated Cochrane Review as part of a WHO process to develop updated guidelines on the use of the test. Objectives To assess the diagnostic accuracy of Xpert® MTB/RIF for pulmonary TB (TB detection), where Xpert® MTB/RIF was used as both an initial test replacing microscopy and an add-on test following a negative smear microscopy result. To assess the diagnostic accuracy of Xpert® MTB/RIF for rifampicin resistance detection, where Xpert® MTB/RIF was used as the initial test replacing culture-based drug susceptibility testing (DST). The populations of interest were adults presumed to have pulmonary, rifampicin-resistant or multidrug-resistant TB (MDR-TB), with or without HIV infection. The settings of interest were intermediate- and peripheral-level laboratories. The latter may be associated with primary health care facilities. Search methods We searched for publications in any language up to 7 February 2013 in the following databases: Cochrane Infectious Diseases Group Specialized Register; MEDLINE; EMBASE; ISI Web of Knowledge; MEDION; LILACS; BIOSIS; and SCOPUS. We also searched the metaRegister of Controlled Trials (mRCT) and the search portal of the WHO International Clinical Trials Registry Platform to identify ongoing trials. Selection criteria We included randomized controlled trials, cross-sectional studies, and cohort studies using respiratory specimens that allowed for

Reliability of the Xpert HPV assay to detect high-risk human papillomavirus DNA in a colposcopy referral population.

PubMed

Castle, Philip E; Smith, Katherine M; Davis, Thomas E; Schmeler, Kathleen M; Ferris, Daron G; Savage, Ashlyn H; Gray, Jermaine E; Stoler, Mark H; Wright, Thomas C; Ferenczy, Alex; Einstein, Mark H

2015-01-01

The Xpert HPV Assay (Xpert; Cepheid, Sunnyvale, CA) was developed for the multianalytic GeneXpert platform. In a colposcopy referral population of 708 women living in the United States, two cervical specimens, A and B, were collected, and both were tested by the Xpert assay for high-risk human papillomavirus (hrHPV) DNA, permitting an evaluation of its test reliability. Specimen B was also tested by Hybrid Capture 2 (hc2; Qiagen, Germantown, MD) and the cobas HPV Test (cobas; Roche Molecular Systems, Pleasanton, CA). The κ and percent agreement for any hrHPV for the two Xpert results were 0.88 and 94.5%, respectively. There was no statistical difference in testing positive on both specimens by Xpert (P = .62). The sensitivity for detection of cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) was 89.0% using specimen A and 90.4% using specimen B for Xpert, 90.4% for cobas, and 81.6% for hc2. The Xpert assay was sensitive and reliable for the detection of hrHPV and the identification of women with CIN2+. Copyright© by the American Society for Clinical Pathology.

Cost-benefit analysis of Xpert MTB/RIF for tuberculosis suspects in German hospitals.

PubMed

Diel, Roland; Nienhaus, Albert; Hillemann, Doris; Richter, Elvira

2016-02-01

Our objective was to assess the cost-benefit of enhancing or replacing the conventional sputum smear with the real-time PCR Xpert MTB/RIF method in the inpatient diagnostic schema for tuberculosis (TB).Recent data from published per-case cost studies for TB/multidrug-resistant (MDR)-TB and from comparative analyses of sputum microscopy, mycobacterial culture, Xpert MTB/RIF and drug susceptibility testing, performed at the German National Reference Center for Mycobacteria, were used. Potential cost savings of Xpert MTB/RIF, based on test accuracy and multiple cost drivers, were calculated for diagnosing TB/MDR-TB suspects from the hospital perspective.Implementing Xpert MTB/RIF as an add-on in smear-positive and smear-negative TB suspects saves on average €48.72 and €503, respectively, per admitted patient as compared with the conventional approach. In smear-positive and smear-negative MDR-TB suspects, cost savings amount to €189.56 and €515.25 per person, respectively. Full replacement of microscopy by Xpert MTB/RIF saves €449.98. In probabilistic Monte-Carlo simulation, adding Xpert MTB/RIF is less costly in 46.4% and 76.2% of smear-positive TB and MDR-TB suspects, respectively, but 100% less expensive in all smear-negative suspects. Full replacement by Xpert MTB/RIF is also consistently cost-saving.Using Xpert MTB/RIF as an add-on to and even as a replacement for sputum smear examination may significantly reduce expenditures in TB suspects. Copyright ©ERS 2016.

A Comprehensive Evaluation of Xpert MTB/RIF Assay With Bronchoalveolar Lavage Fluid as a Single Test or Combined With Conventional Assays for Diagnosis of Pulmonary Tuberculosis in China: A Two-Center Prospective Study

PubMed Central

Pan, Xiaofu; Yang, Shoufeng; Deighton, Margaret A.; Qu, Yue; Hong, Liang; Su, Feifei

2018-01-01

Introduction: The Xpert MTB/RIF is recommended by the World Health Organization as a first line rapid test for the diagnosis of pulmonary tuberculosis (TB); however, China does not routinely use this test, partially due to the lack of a sufficient number of systematic evaluations of this assay in local patients. The aims of this study were to comprehensively assess the diagnostic performance of Xpert MTB/RIF, either alone or in combination with conventional assays for the diagnosis of pulmonary TB in adult Chinese patients. Methods: Xpert MTB/RIF tests were performed in 190 adult patients with suspected pulmonary TB, using bronchoalveolar lavage fluid (BALF) as test specimens. In parallel, conventional tests were carried out using the same BALF samples. Using two different reference standards, the performance of Xpert MTB/RIF, conventional assays and their combinations were evaluated. Results: Using mycobacterial culture as the reference comparator, Xpert MTB/RIF was found to be superior to smear-microscopy in detecting Mycobacterium tuberculosis. When final diagnosis, based on clinical criteria, was employed as the reference standard, Xpert MTB/RIF showed an even higher accuracy of 72.1%, supported by a sensitivity of 61.1% and specificity of 96.6%. Xpert MTB/RIF also demonstrated a powerful capability to identify pulmonary TB cases undetected by culture or smear-microscopy. Combining smear-microscopy and Xpert MTB/RIF was found to be the most accurate early predictor for pulmonary TB. Rifampicin resistance reported by Xpert MTB/RIF slightly deviated from that by phenotypic antibiotic susceptibility testing and requires further study with a larger sample size. Conclusion: This two-center prospective study highlights the value of Xpert MTB/RIF with BALF in diagnosing pulmonary TB in adult Chinese patients. These findings might contribute to the optimization of current diagnostic algorithms for pulmonary TB in China. PMID:29593688

A Comprehensive Evaluation of Xpert MTB/RIF Assay With Bronchoalveolar Lavage Fluid as a Single Test or Combined With Conventional Assays for Diagnosis of Pulmonary Tuberculosis in China: A Two-Center Prospective Study.

PubMed

Pan, Xiaofu; Yang, Shoufeng; Deighton, Margaret A; Qu, Yue; Hong, Liang; Su, Feifei

2018-01-01

Introduction: The Xpert MTB/RIF is recommended by the World Health Organization as a first line rapid test for the diagnosis of pulmonary tuberculosis (TB); however, China does not routinely use this test, partially due to the lack of a sufficient number of systematic evaluations of this assay in local patients. The aims of this study were to comprehensively assess the diagnostic performance of Xpert MTB/RIF, either alone or in combination with conventional assays for the diagnosis of pulmonary TB in adult Chinese patients. Methods: Xpert MTB/RIF tests were performed in 190 adult patients with suspected pulmonary TB, using bronchoalveolar lavage fluid (BALF) as test specimens. In parallel, conventional tests were carried out using the same BALF samples. Using two different reference standards, the performance of Xpert MTB/RIF, conventional assays and their combinations were evaluated. Results: Using mycobacterial culture as the reference comparator, Xpert MTB/RIF was found to be superior to smear-microscopy in detecting Mycobacterium tuberculosis . When final diagnosis, based on clinical criteria, was employed as the reference standard, Xpert MTB/RIF showed an even higher accuracy of 72.1%, supported by a sensitivity of 61.1% and specificity of 96.6%. Xpert MTB/RIF also demonstrated a powerful capability to identify pulmonary TB cases undetected by culture or smear-microscopy. Combining smear-microscopy and Xpert MTB/RIF was found to be the most accurate early predictor for pulmonary TB. Rifampicin resistance reported by Xpert MTB/RIF slightly deviated from that by phenotypic antibiotic susceptibility testing and requires further study with a larger sample size. Conclusion: This two-center prospective study highlights the value of Xpert MTB/RIF with BALF in diagnosing pulmonary TB in adult Chinese patients. These findings might contribute to the optimization of current diagnostic algorithms for pulmonary TB in China.

Performance of Xpert® MTB/RIF among tuberculosis outpatients in Lilongwe, Malawi.

PubMed

Chikaonda, Tarsizio; Nguluwe, Nelson; Barnett, Brian; Gokhale, Runa H; Krysiak, Robert; Thengolose, Isaac; Rosenberg, Nora E; Stanley, Christopher; Mpunga, James; Hoffman, Irving F; Hosseinipour, Mina; Scott, Lesley; Stevens, Wendy

2017-01-01

Xpert ® MTB/RIF is a molecular test for the detection of Mycobacterium tuberculosis and rifampicin resistance. It is considered to be a great advance over smear microscopy and culture. However, there is very little information regarding the performance characteristics of Xpert MTB/RIF in Malawi. We aimed to evaluate the performance of Xpert MTB/RIF in a Malawian setting. Stored sputum pellets were processed on Xpert MTB/RIF between June 2012 and May 2014. Results were compared to mycobacteria growth indicator tube and Löwenstein-Jensen cultures, LED fluorescent microscopy and GenoType ® MTBDR plus assay. Rifampicin resistance was confirmed by DNA sequencing. Of the 348 specimens with valid Xpert MTB/RIF results, 129/348 (37%) were smear-positive and 198/348 (57%) were culture-positive. Xpert MTB/RIF demonstrated a sensitivity of 93.8% (95% CI 89.4% - 96.8%) and specificity of 97.4% (95% CI 93.5% - 99.3%), with a positive predictive value of 97.8% (95% CI 94.6% - 99.4%) and a negative predictive value of 92.6% (95% CI 87.4% - 96.1%). Xpert MTB/RIF correctly identified 185/186 (99.5%) rifampicin-sensitive and 2/2 (100%) rifampicin-resistant M. tuberculosis strains. Mutations were not detected by sequencing in one isolate which was rifampicin resistant on Xpert MTB/RIF but sensitive on MTBDR plus . Four non-tuberculous mycobacteria grew from four smear-negative specimens, namely, M. avium ( n = 1) and M. intracellulare ( n = 3). No cross-reactivity was observed with any of the non-tuberculous mycobacteria when using Xpert MTB/RIF. When fully implemented, Xpert MTB/RIF may have an impact on patient care in Malawi. The increased diagnostic yield of Xpert MTB/RIF over smear microscopy can increase laboratory-confirmed tuberculosis detection and ensure that treatment is given to appropriate individuals or groups.

Catching the missing million: experiences in enhancing TB & DR-TB detection by providing upfront Xpert MTB/RIF testing for people living with HIV in India.

PubMed

Raizada, Neeraj; Sachdeva, Kuldeep Singh; Sreenivas, Achuthan; Kulsange, Shubhangi; Gupta, Radhey Shyam; Thakur, Rahul; Dewan, Puneet; Boehme, Catharina; Paramsivan, Chinnambedu Nainarappan

2015-01-01

A critical challenge in providing TB care to People Living with HIV (PLHIV) is establishing an accurate bacteriological diagnosis. Xpert MTB/RIF, a highly sensitive and specific rapid tool, offers a promising solution in addressing these challenges. This study presents results from PLHIV taking part in a large demonstration study across India wherein upfront Xpert MTB/RIF testing was offered to all presumptive PTB cases in public health facilities. The study covered a population of 8.8 million across 18 sub-district level tuberculosis units (TU), with one Xpert MTB/RIF platform established at each TU. All HIV-infected patients suspected of TB (both TB and Drug Resistant TB (DR-TB)) accessing public health facilities in study area were prospectively enrolled and provided upfront Xpert MTB/RIF testing. 2,787 HIV-infected presumptive pulmonary TB cases were enrolled and 867 (31.1%, 95% Confidence Interval (CI) 29.4‒32.8) HIV-infected TB cases were diagnosed under the study. Overall 27.6% (CI 25.9-29.3) of HIV-infected presumptive PTB cases were positive by Xpert MTB/RIF, compared with 12.9% (CI 11.6-14.1) who had positive sputum smears. Upfront Xpert MTB/RIF testing of presumptive PTB and DR-TB cases resulted in diagnosis of 73 (9.5%, CI 7.6‒11.8) and 16 (11.2%, CI 6.7‒17.1) rifampicin resistance cases, respectively. Positive predictive value (PPV) for rifampicin resistance detection was high 97.7% (CI 89.3‒99.8), with no significant difference with or without prior history of TB treatment. The study results strongly demonstrate limitations of using smear microscopy for TB diagnosis in PLHIV, leading to low TB and DR-TB detection which can potentially lead to either delayed or sub-optimal TB treatment. Our findings demonstrate the usefulness and feasibility of addressing this diagnostic gap with upfront of Xpert MTB/RIF testing, leading to overall strengthening of care and support package for PLHIV.

Catching the Missing Million: Experiences in Enhancing TB & DR-TB Detection by Providing Upfront Xpert MTB/RIF Testing for People Living with HIV in India

PubMed Central

Raizada, Neeraj; Sachdeva, Kuldeep Singh; Sreenivas, Achuthan; Kulsange, Shubhangi; Gupta, Radhey Shyam; Thakur, Rahul; Dewan, Puneet; Boehme, Catharina; Paramsivan, Chinnambedu Nainarappan

2015-01-01

Background A critical challenge in providing TB care to People Living with HIV (PLHIV) is establishing an accurate bacteriological diagnosis. Xpert MTB/RIF, a highly sensitive and specific rapid tool, offers a promising solution in addressing these challenges. This study presents results from PLHIV taking part in a large demonstration study across India wherein upfront Xpert MTB/RIF testing was offered to all presumptive PTB cases in public health facilities. Method The study covered a population of 8.8 million across 18 sub-district level tuberculosis units (TU), with one Xpert MTB/RIF platform established at each TU. All HIV-infected patients suspected of TB (both TB and Drug Resistant TB (DR-TB)) accessing public health facilities in study area were prospectively enrolled and provided upfront Xpert MTB/RIF testing. Result 2,787 HIV-infected presumptive pulmonary TB cases were enrolled and 867 (31.1%, 95% Confidence Interval (CI) 29.4‒32.8) HIV-infected TB cases were diagnosed under the study. Overall 27.6% (CI 25.9–29.3) of HIV-infected presumptive PTB cases were positive by Xpert MTB/RIF, compared with 12.9% (CI 11.6–14.1) who had positive sputum smears. Upfront Xpert MTB/RIF testing of presumptive PTB and DR-TB cases resulted in diagnosis of 73 (9.5%, CI 7.6‒11.8) and 16 (11.2%, CI 6.7‒17.1) rifampicin resistance cases, respectively. Positive predictive value (PPV) for rifampicin resistance detection was high 97.7% (CI 89.3‒99.8), with no significant difference with or without prior history of TB treatment. Conclusion The study results strongly demonstrate limitations of using smear microscopy for TB diagnosis in PLHIV, leading to low TB and DR-TB detection which can potentially lead to either delayed or sub-optimal TB treatment. Our findings demonstrate the usefulness and feasibility of addressing this diagnostic gap with upfront of Xpert MTB/RIF testing, leading to overall strengthening of care and support package for PLHIV. PMID:25658091

Increased detection of smear-negative pulmonary tuberculosis by GeneXpert MTB/RIF® assay after bleach concentration.

PubMed

Tadesse, Mulualem; Aragaw, Dossegnaw; Rigouts, Leen; Abebe, Gemeda

2016-06-01

The GeneXpert MTB/RIF assay (Xpert) was endorsed as the initial diagnostic tool in people suspected of human immunodeficiency virus-associated or drug-resistant tuberculosis (TB). However, information regarding the performance of Xpert for diagnosing smear-negative TB in high burden settings remains limited. We evaluated the diagnostic accuracy of Xpert and the impact of bleach concentration on the performance of Xpert using smear-negative sputum samples from human immunodeficiency virus-negative patients. One spot and one morning smear-negative sputum samples per patient were examined using Xpert and culture at the Mycobacteriology Research Center of Jimma University, Ethiopia. The sputum culture on both Löwenstein-Jensen and/or Mycobacteria Growth Indicator Tube was the gold-standard. Of 185 smear-negative presumptive pulmonary TB cases, 19 (10.3%) had culture-proven TB. The sensitivity of Xpert on spot and morning sputum was similar (63.2%). Testing two specimens per patient insignificantly increased the sensitivity of Xpert. Bleach concentration and pelleting improved the sensitivity of Xpert over unprocessed sputum in paired samples (73.8% vs. 63.2%) without affecting the specificity (95%). Bleach concentration and pelleting allowed an additional seven cases of TB (missed on the first and second direct Xperts) to be detected, five of which were from culture-negative cases. Testing of a single sputum sample by Xpert can reach reasonable sensitivity and results would be available on the same day, avoiding loss of patients and treatment delay. The sensitivity of Xpert was improved after bleach concentration and pelleting, although its added value needs further study on a larger scale. Copyright © 2016 Asian-African Society for Mycobacteriology. Published by Elsevier Ltd. All rights reserved.

Impact of point-of-care implementation of Xpert® MTB/RIF: product vs. process innovation.

PubMed

Schumacher, S G; Thangakunam, B; Denkinger, C M; Oliver, A A; Shakti, K B; Qin, Z Z; Michael, J S; Luo, R; Pai, M; Christopher, D J

2015-09-01

Both product innovation (e.g., more sensitive tests) and process innovation (e.g., a point-of-care [POC] testing programme) could improve patient outcomes. To study the respective contributions of product and process innovation in improving patient outcomes. We implemented a POC programme using Xpert(®) MTB/RIF in an out-patient clinic of a tertiary care hospital in India. We measured the impact of process innovation by comparing time to diagnosis with routine testing vs. POC testing. We measured the impact of product innovation by comparing accuracy and time to diagnosis using smear microscopy vs. POC Xpert. We enrolled 1012 patients over a 15-month period. Xpert had high accuracy, but the incremental value of one Xpert over two smears was only 6% (95%CI 3-12). Implementing Xpert as a routine laboratory test did not reduce the time to diagnosis compared to smear-based diagnosis. In contrast, the POC programme reduced the time to diagnosis by 5.5 days (95%CI 4.3-6.7), but required dedicated staff and substantial adaptation of clinic workflow. Process innovation by way of a POC Xpert programme had a greater impact on time to diagnosis than the product per se, and can yield important improvements in patient care that are complementary to those achieved by introducing innovative technologies.

Performance of the Xpert HIV-1 Viral Load Assay: a Systematic Review and Meta-analysis

PubMed Central

Nash, Madlen; Huddart, Sophie; Badar, Sayema; Baliga, Shrikala; Saravu, Kavitha

2018-01-01

ABSTRACT Viral load (VL) is the preferred treatment-monitoring approach for HIV-positive patients. However, more rapid, near-patient, and low-complexity assays are needed to scale up VL testing. The Xpert HIV-1 VL assay (Cepheid, Sunnyvale, CA) is a new, automated molecular test, and it can leverage the GeneXpert systems that are being used widely for tuberculosis diagnosis. We systematically reviewed the evidence on the performance of this new tool in comparison to established reference standards. A total of 12 articles (13 studies) in which HIV patient VLs were compared between Xpert HIV VL assay and a reference standard VL assay were identified. Study quality was generally high, but substantial variability was observed in the number and type of agreement measures reported. Correlation coefficients between Xpert and reference assays were high, with a pooled Pearson correlation (n = 8) of 0.94 (95% confidence interval [CI], 0.89, 0.97) and Spearman correlation (n = 3) of 0.96 (95% CI, 0.86, 0.99). Bland-Altman metrics (n = 11) all were within 0.35 log copies/ml of perfect agreement. Overall, Xpert HIV-1 VL performed well compared to current reference tests. The minimal training and infrastructure requirements for the Xpert HIV-1 VL assay make it attractive for use in resource-constrained settings, where point-of-care VL testing is most needed. PMID:29386266

Performance of the Xpert HIV-1 Viral Load Assay: a Systematic Review and Meta-analysis.

PubMed

Nash, Madlen; Huddart, Sophie; Badar, Sayema; Baliga, Shrikala; Saravu, Kavitha; Pai, Madhukar

2018-04-01

Viral load (VL) is the preferred treatment-monitoring approach for HIV-positive patients. However, more rapid, near-patient, and low-complexity assays are needed to scale up VL testing. The Xpert HIV-1 VL assay (Cepheid, Sunnyvale, CA) is a new, automated molecular test, and it can leverage the GeneXpert systems that are being used widely for tuberculosis diagnosis. We systematically reviewed the evidence on the performance of this new tool in comparison to established reference standards. A total of 12 articles (13 studies) in which HIV patient VLs were compared between Xpert HIV VL assay and a reference standard VL assay were identified. Study quality was generally high, but substantial variability was observed in the number and type of agreement measures reported. Correlation coefficients between Xpert and reference assays were high, with a pooled Pearson correlation ( n = 8) of 0.94 (95% confidence interval [CI], 0.89, 0.97) and Spearman correlation ( n = 3) of 0.96 (95% CI, 0.86, 0.99). Bland-Altman metrics ( n = 11) all were within 0.35 log copies/ml of perfect agreement. Overall, Xpert HIV-1 VL performed well compared to current reference tests. The minimal training and infrastructure requirements for the Xpert HIV-1 VL assay make it attractive for use in resource-constrained settings, where point-of-care VL testing is most needed. Copyright © 2018 Nash et al.

Advances in tuberculosis diagnostics: the Xpert MTB/RIF assay and future prospects for a point-of-care test

PubMed Central

Lawn, Stephen D; Mwaba, Peter; Bates, Matthew; Piatek, Amy; Alexander, Heather; Marais, Ben J; Cuevas, Luis E; McHugh, Timothy D; Zijenah, Lynn; Kapata, Nathan; Abubakar, Ibrahim; McNerney, Ruth; Hoelscher, Michael; Memish, Ziad A; Migliori, Giovanni Battista; Kim, Peter; Maeurer, Markus; Schito, Marco; Zumla, Alimuddin

2015-01-01

Rapid progress has been made in the development of new diagnostic assays for tuberculosis in recent years. New technologies have been developed and assessed, and are now being implemented. The Xpert MTB/RIF assay, which enables simultaneous detection of Mycobacterium tuberculosis (MTB) and rifampicin (RIF) resistance, was endorsed by WHO in December, 2010. This assay was specifically recommended for use as the initial diagnostic test for suspected drug-resistant or HIV-associated pulmonary tuberculosis. By June, 2012, two-thirds of countries with a high tuberculosis burden and half of countries with a high multidrug-resistant tuberculosis burden had incorporated the assay into their national tuberculosis programme guidelines. Although the development of the Xpert MTB/RIF assay is undoubtedly a landmark event, clinical and programmatic effects and cost-effectiveness remain to be defined. We review the rapidly growing body of scientific literature and discuss the advantages and challenges of using the Xpert MTB/RIF assay in areas where tuberculosis is endemic. We also review other prospects within the developmental pipeline. A rapid, accurate point-of-care diagnostic test that is affordable and can be readily implemented is urgently needed. Investment in the tuberculosis diagnostics pipeline should remain a major priority for funders and researchers. PMID:23531388

Performance of Xpert® MTB/RIF among tuberculosis outpatients in Lilongwe, Malawi

PubMed Central

Nguluwe, Nelson; Gokhale, Runa H.; Krysiak, Robert; Thengolose, Isaac; Rosenberg, Nora E.; Stanley, Christopher; Mpunga, James; Hoffman, Irving F.; Hosseinipour, Mina; Scott, Lesley; Stevens, Wendy

2017-01-01

Background Xpert® MTB/RIF is a molecular test for the detection of Mycobacterium tuberculosis and rifampicin resistance. It is considered to be a great advance over smear microscopy and culture. However, there is very little information regarding the performance characteristics of Xpert MTB/RIF in Malawi. Objective We aimed to evaluate the performance of Xpert MTB/RIF in a Malawian setting. Methods Stored sputum pellets were processed on Xpert MTB/RIF between June 2012 and May 2014. Results were compared to mycobacteria growth indicator tube and Löwenstein-Jensen cultures, LED fluorescent microscopy and GenoType® MTBDRplus assay. Rifampicin resistance was confirmed by DNA sequencing. Results Of the 348 specimens with valid Xpert MTB/RIF results, 129/348 (37%) were smear-positive and 198/348 (57%) were culture-positive. Xpert MTB/RIF demonstrated a sensitivity of 93.8% (95% CI 89.4% – 96.8%) and specificity of 97.4% (95% CI 93.5% – 99.3%), with a positive predictive value of 97.8% (95% CI 94.6% – 99.4%) and a negative predictive value of 92.6% (95% CI 87.4% – 96.1%). Xpert MTB/RIF correctly identified 185/186 (99.5%) rifampicin-sensitive and 2/2 (100%) rifampicin-resistant M. tuberculosis strains. Mutations were not detected by sequencing in one isolate which was rifampicin resistant on Xpert MTB/RIF but sensitive on MTBDRplus. Four non-tuberculous mycobacteria grew from four smear-negative specimens, namely, M. avium (n = 1) and M. intracellulare (n = 3). No cross-reactivity was observed with any of the non-tuberculous mycobacteria when using Xpert MTB/RIF. Conclusion When fully implemented, Xpert MTB/RIF may have an impact on patient care in Malawi. The increased diagnostic yield of Xpert MTB/RIF over smear microscopy can increase laboratory-confirmed tuberculosis detection and ensure that treatment is given to appropriate individuals or groups. PMID:28879160

Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis and rifampicin resistance: a prospective multicentre diagnostic accuracy study.

PubMed

Dorman, Susan E; Schumacher, Samuel G; Alland, David; Nabeta, Pamela; Armstrong, Derek T; King, Bonnie; Hall, Sandra L; Chakravorty, Soumitesh; Cirillo, Daniela M; Tukvadze, Nestani; Bablishvili, Nino; Stevens, Wendy; Scott, Lesley; Rodrigues, Camilla; Kazi, Mubin I; Joloba, Moses; Nakiyingi, Lydia; Nicol, Mark P; Ghebrekristos, Yonas; Anyango, Irene; Murithi, Wilfred; Dietze, Reynaldo; Lyrio Peres, Renata; Skrahina, Alena; Auchynka, Vera; Chopra, Kamal Kishore; Hanif, Mahmud; Liu, Xin; Yuan, Xing; Boehme, Catharina C; Ellner, Jerrold J; Denkinger, Claudia M

2018-01-01

The Xpert MTB/RIF assay is an automated molecular test that has improved the detection of tuberculosis and rifampicin resistance, but its sensitivity is inadequate in patients with paucibacillary disease or HIV. Xpert MTB/RIF Ultra (Xpert Ultra) was developed to overcome this limitation. We compared the diagnostic performance of Xpert Ultra with that of Xpert for detection of tuberculosis and rifampicin resistance. In this prospective, multicentre, diagnostic accuracy study, we recruited adults with pulmonary tuberculosis symptoms presenting at primary health-care centres and hospitals in eight countries (South Africa, Uganda, Kenya, India, China, Georgia, Belarus, and Brazil). Participants were allocated to the case detection group if no drugs had been taken for tuberculosis in the past 6 months or to the multidrug-resistance risk group if drugs for tuberculosis had been taken in the past 6 months, but drug resistance was suspected. Demographic information, medical history, chest imaging results, and HIV test results were recorded at enrolment, and each participant gave at least three sputum specimen on 2 separate days. Xpert and Xpert Ultra diagnostic performance in the same sputum specimen was compared with culture tests and drug susceptibility testing as reference standards. The primary objectives were to estimate and compare the sensitivity of Xpert Ultra test with that of Xpert for detection of smear-negative tuberculosis and rifampicin resistance and to estimate and compare Xpert Ultra and Xpert specificities for detection of rifampicin resistance. Study participants in the case detection group were included in all analyses, whereas participants in the multidrug-resistance risk group were only included in analyses of rifampicin-resistance detection. Between Feb 18, and Dec 24, 2016, we enrolled 2368 participants for sputum sampling. 248 participants were excluded from the analysis, and 1753 participants were distributed to the case detection group (n=1439

A multisite assessment of the quantitative capabilities of the Xpert MTB/RIF assay.

PubMed

Blakemore, Robert; Nabeta, Pamela; Davidow, Amy L; Vadwai, Viral; Tahirli, Rasim; Munsamy, Vanisha; Nicol, Mark; Jones, Martin; Persing, David H; Hillemann, Doris; Ruesch-Gerdes, Sabine; Leisegang, Felicity; Zamudio, Carlos; Rodrigues, Camilla; Boehme, Catharina C; Perkins, Mark D; Alland, David

2011-11-01

The Xpert MTB/RIF is an automated molecular test for Mycobacterium tuberculosis that estimates bacterial burden by measuring the threshold-cycle (Ct) of its M. tuberculosis-specific real-time polymerase chain reaction. Bacterial burden is an important biomarker for disease severity, infection control risk, and response to therapy. Evaluate bacterial load quantitation by Xpert MTB/RIF compared with conventional quantitative methods. Xpert MTB/RIF results were compared with smear-microscopy, semiquantiative solid culture, and time-to-detection in liquid culture for 741 patients and 2,008 samples tested in a multisite clinical trial. An internal control real-time polymerase chain reaction was evaluated for its ability to identify inaccurate quantitative Xpert MTB/RIF results. Assays with an internal control Ct greater than 34 were likely to be inaccurately quantitated; this represented 15% of M. tuberculosis-positive tests. Excluding these, decreasing M. tuberculosis Ct was associated with increasing smear microscopy grade for smears of concentrated sputum pellets (r(s) = -0.77) and directly from sputum (r(s) =-0.71). A Ct cutoff of approximately 27.7 best predicted smear-positive status. The association between M. tuberculosis Ct and time-to-detection in liquid culture (r(s) = 0.68) and semiquantitative colony counts (r(s) = -0.56) was weaker than smear. Tests of paired same-patient sputum showed that high viscosity sputum samples contained ×32 more M. tuberculosis than nonviscous samples. Comparisons between the grade of the acid-fast bacilli smear and Xpert MTB/RIF quantitative data across study sites enabled us to identify a site outlier in microscopy. Xpert MTB/RIF quantitation offers a new, standardized approach to measuring bacterial burden in the sputum of patients with tuberculosis.

Diagnostic accuracy of Xpert MTB/RIF assay for musculoskeletal tuberculosis: a meta-analysis.

PubMed

Wen, Hai; Li, Pengzhi; Ma, Hong; Lv, Guohua

2017-01-01

Xpert MTB/RIF assay, a rapid and automated real-time nucleic acid amplification test, has been reported for the diagnosis of musculoskeletal tuberculosis (TB) in current years. This meta-analysis aims to determine the diagnostic accuracy of Xpert for the detection of musculoskeletal TB and rifampicin (RIF) resistance. We searched PubMed, Embase, China National Knowledge Infrastructure, and Wanfang for original articles published up to 1st June 2017 to identify studies in which the Xpert assay was applied to diagnose musculoskeletal TB. Pooled estimates were calculated using a random-effects model or a fixed-effects model according to heterogeneity. Summary receiver operating characteristic curves and the area under the curve (AUC) were used to summarize overall diagnostic performance. Deeks' test was performed to evaluate potential publication bias. Twelve studies were identified with a pooled sensitivity and specificity of respectively 0.81 (95% confidence interval [CI] 0.78-0.83) and 0.83 (95% CI 0.80-0.86) of Xpert for the diagnosis of musculoskeletal TB. Xpert was highly sensitive (0.89, 95% CI 0.79-0.95) and highly specific (0.96, 95% CI 0.92-0.98) in detecting RIF resistance. AUC (over 0.9) suggested a relatively high level of overall diagnostic accuracy of Xpert for detecting musculoskeletal TB and RIF resistance. Prevalence and reference standard were indicated to be sources of heterogeneity between studies. No publication bias was found. This study provides available evidence of the rapid and effective role of Xpert in diagnosing musculoskeletal TB and detecting RIF resistance.

[Application value of Xpert MTB/RIF in diagnosis of spinal tuberculosis and detection of rifampin resistance].

PubMed

Jin, Yang-Hui; Shi, Shi-Yuan; Zheng, Qi; Shen, Jian; Ying, Xiao-Zhang; Wang, Yi-Fan

2017-09-25

To investigate the application value of Xpert MTB/RIF in diagnosis of spinal tuberculosis and detection of rifampin resistance. The 109 pus specimens were obtained from patients who were primaryly diagnosed as spinal tuberculosis. All of the pus specimens were detected by acid-fast stain, liquid fast culturing by BACTEC MGIT 960 and Xpert MTB/RIF assay to definite the differences in sensitivity and specificity of mycobacterium tuberculosis among detecting methods. Pus specimens obtained by different methods were deteceded by MTB/RIF test to analyze the self-influence on Xpert MTB/RIF test. The result of liquid fast culturing by BACTEC MGIT 960 was used as the gold standard; and the value of Xpert MTB/RIF assay in detecting rifampin resistance was analyzed. The sensitivity of acid-fast stain, liquid fast culturing by BACTEC MGIT 960 and Xpert MTB/RIF assay were 25.92%, 48.15%, 77.78%, respectively. The sensitivity of pus specimens obtained from open surgery, ultrasound positioning puncture and biopsy the sensitivity were 83.78%, 76.47%, 44.68% respectively deteceded by MTB/RIF test. According to the gold standard of the results of liquid fast culturing by BACTEC MGIT 960 assay, the sensitivity and specificity of Xpert MTB/RIF assay in detecting rifampin resistance were 80%(4/5) and 90.70%(39/43), respectively. Xpert MTB/RIF assay has higher value in diagnosis of spinal tuberculosi, and also can detect rifampin resistance. The number of mycobacterium tuberculosis in pus specimens has a great influence in the sensitivity of Xpert MTB/RIF assay.

Comparison of Xpert MTB/RIF with line probe assay for detection of rifampin-monoresistant Mycobacterium tuberculosis.

PubMed

Rufai, Syed Beenish; Kumar, Parveen; Singh, Amit; Prajapati, Suneel; Balooni, Veena; Singh, Sarman

2014-06-01

The MTBDRplus line probe assay (LPA) and Xpert MTB/RIF have been endorsed by the World Health Organization for the rapid diagnosis of drug-resistant tuberculosis. However, there is no clarity regarding the superiority of one over the other. In a double-blinded prospective study, we evaluated the efficacy of the Xpert MTB/RIF on samples that were first tested by LPA under the revised national tuberculosis control program of India. A total of 405 sputum samples from suspected drug-resistant tuberculosis patients were included. Of these, 285 smear-positive samples were subjected to LPA. Seventy-two (25.8%) samples showed multidrug resistance, 62 (22.2%) showed rifampin monoresistance, 29 (10.3%) showed isoniazid monoresistance, and 116 (41.5%) were pan-susceptible. Six (2.1%) of the samples gave invalid results. Of the 62 rifampin-monoresistant samples by LPA, 38 (61.4%) showed rifampin resistance, while 21 (33.8%) were found susceptible to rifampin by Xpert MTB/RIF using cartridge version G4. Three (4.8%) samples gave an error. Of the 116 pan-susceptible samples, only 83 were available for Xpert MTB/RIF testing; 4 (5.1%) were rifampin resistant, 74 (94.8%) were susceptible, and 5 (6.0%) showed an error. The 25 discrepant samples were further subjected to MGIT960 drug susceptibility testing. The MGIT960 results showed 100% agreement with LPA results but only 64.4% agreement with Xpert MTB/RIF results. Sequencing analysis of discrepant samples showed 91.3% concordance with LPA but only 8.7% concordance with the Xpert MTB/RIF assay. These findings indicate that by using Xpert MTB/RIF testing we might be underestimating the burden of drug-resistant tuberculosis and indicate that country-specific probes need to be designed to increase the sensitivity of the Xpert MTB/RIF. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Comparison of Xpert MTB/RIF with Line Probe Assay for Detection of Rifampin-Monoresistant Mycobacterium tuberculosis

PubMed Central

Rufai, Syed Beenish; Kumar, Parveen; Singh, Amit; Prajapati, Suneel; Balooni, Veena

2014-01-01

The MTBDRplus line probe assay (LPA) and Xpert MTB/RIF have been endorsed by the World Health Organization for the rapid diagnosis of drug-resistant tuberculosis. However, there is no clarity regarding the superiority of one over the other. In a double-blinded prospective study, we evaluated the efficacy of the Xpert MTB/RIF on samples that were first tested by LPA under the revised national tuberculosis control program of India. A total of 405 sputum samples from suspected drug-resistant tuberculosis patients were included. Of these, 285 smear-positive samples were subjected to LPA. Seventy-two (25.8%) samples showed multidrug resistance, 62 (22.2%) showed rifampin monoresistance, 29 (10.3%) showed isoniazid monoresistance, and 116 (41.5%) were pan-susceptible. Six (2.1%) of the samples gave invalid results. Of the 62 rifampin-monoresistant samples by LPA, 38 (61.4%) showed rifampin resistance, while 21 (33.8%) were found susceptible to rifampin by Xpert MTB/RIF using cartridge version G4. Three (4.8%) samples gave an error. Of the 116 pan-susceptible samples, only 83 were available for Xpert MTB/RIF testing; 4 (5.1%) were rifampin resistant, 74 (94.8%) were susceptible, and 5 (6.0%) showed an error. The 25 discrepant samples were further subjected to MGIT960 drug susceptibility testing. The MGIT960 results showed 100% agreement with LPA results but only 64.4% agreement with Xpert MTB/RIF results. Sequencing analysis of discrepant samples showed 91.3% concordance with LPA but only 8.7% concordance with the Xpert MTB/RIF assay. These findings indicate that by using Xpert MTB/RIF testing we might be underestimating the burden of drug-resistant tuberculosis and indicate that country-specific probes need to be designed to increase the sensitivity of the Xpert MTB/RIF. PMID:24648554

Diagnostic performance of smear microscopy and incremental yield of Xpert in detection of pulmonary tuberculosis in Rwanda.

PubMed

Ngabonziza, Jean Claude Semuto; Ssengooba, Willy; Mutua, Florence; Torrea, Gabriela; Dushime, Augustin; Gasana, Michel; Andre, Emmanuel; Uwamungu, Schifra; Nyaruhirira, Alaine Umubyeyi; Mwaengo, Dufton; Muvunyi, Claude Mambo

2016-11-08

Tuberculosis control program of Rwanda is currently phasing in light emitting diode-fluorescent microscopy (LED-FM) as an alternative to Ziehl-Neelsen (ZN) smear microscopy. This, alongside the newly introduced Xpert (Cepheid, Sunnyvale, CA, USA) is expected to improve diagnosis of tuberculosis and detection of rifampicin resistance in patients at health facilities. We assessed the accuracy of smear microscopy and the incremental sensitivity of Xpert at tuberculosis laboratories in Rwanda. This was a cross-sectional study involving four laboratories performing ZN and four laboratories performing LED-FM microscopy. The laboratories include four intermediate (ILs) and four peripheral (PLs) laboratories. After smear microscopy, the left-over of samples, of a single early-morning sputum from 648 participants, were tested using Xpert and mycobacterial culture as a reference standard. Sensitivity of each test was compared and the incremental sensitivity of Xpert after a negative smear was assessed. A total of 96 presumptive pulmonary tuberculosis participants were culture positive for M. tuberculosis. The overall sensitivity in PL of ZN was 55.1 % (40.2-69.3 %), LED-FM was 37 % (19.4-57.6 %) and Xpert was 77.6 % (66.6-86.4 %) whereas in ILs the same value for ZN was 58.3 % (27.7-84.8 %), LED-FM was 62.5 % (24.5-91.5 %) and Xpert was 90 (68.3-98.8 %). The sensitivity for all tests was significantly higher among HIV-negative individuals (all test p <0.05). The overall incremental sensitivity of Xpert over smear microscopy was 32.3 %; p < 0.0001. The incremental sensitivity of Xpert was statistically significant for both smear methods at PL (32.9 %; p = 0.001) but not at the ILs (30 %; p = 0.125) for both smear methods. Our study findings of the early implementation of the LED-FM did not reveal significant increment in sensitivity compared to the method being phased out (ZN). This study showed a significant incremental sensitivity for Xpert from

Clinical evaluation of the cartridge-based GeneXpert human papillomavirus assay in women referred for colposcopy.

PubMed

Einstein, Mark H; Smith, Katherine M; Davis, Thomas E; Schmeler, Kathleen M; Ferris, Daron G; Savage, Ashlyn H; Gray, Jermaine E; Stoler, Mark H; Wright, Thomas C; Ferenczy, Alex; Castle, Philip E

2014-06-01

High-risk human papillomavirus (hrHPV) testing is now being introduced as a potential primary screening test for improved detection of cervical precancer and cancer. Current U.S. Food and Drug Administration-approved tests are batch tests that take several hours to complete. A rapid, non-batch test might permit point-of-care (POC) testing, which can facilitate same-day screen and management strategies. For a non-batch, random-access platform (GeneXpert; Cepheid, Sunnyvale, CA), a prototype hrHPV assay (Xpert) has been developed where testing for 14 hrHPV types can be completed in 1 h. In the first clinical evaluation, Xpert was compared to two validated hrHPV tests, the cobas HPV test (cobas, Roche Molecular Systems) and Hybrid Capture 2 (hc2, Qiagen), and to histologic outcomes using specimens from colposcopy referral populations at 7 clinical sites in the United States (n = 697). The sensitivity of Xpert for cervical intraepithelial neoplasia grade 2 or more severe diagnoses (CIN2+) (n = 141) was equal to that of cobas (90.8% versus 90.8%, P = 1) and greater than that of hc2 (90.8% versus 81.6%, P = 0.004). Xpert was more specific than cobas (42.6% versus 39.6%, P = 0.02) and less specific than hc2 (42.6% versus 47.7%, P < 0.001). Similar results were observed for cervical intraepithelial neoplasia grade 3 or higher (CIN3+) (n = 91). HPV16 detection by Xpert identified 41.8% of the CIN2+ specimens with a positive predictive value (PPV) of 54.6%. By comparison, HPV16 detection by cobas identified 42.6% of the CIN2+ specimens with a PPV of 55.0%. hrHPV detection by the Xpert demonstrated excellent clinical performance for identifying women with CIN2+ and CIN3+ that was comparable to that of currently available clinically validated tests. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

False-Positive Xpert MTB/RIF Results in Retested Patients with Previous Tuberculosis: Frequency, Profile, and Prospective Clinical Outcomes.

PubMed

Theron, Grant; Venter, Rouxjeane; Smith, Liezel; Esmail, Aliasgar; Randall, Philippa; Sood, Vishesh; Oelfese, Suzette; Calligaro, Greg; Warren, Robin; Dheda, Keertan

2018-03-01

Globally, Xpert MTB/RIF (Xpert) is the most widely used PCR test for the diagnosis of tuberculosis (TB). Positive results in previously treated patients, which are due to old DNA or active disease, are a diagnostic dilemma. We prospectively retested sputum from 238 patients, irrespective of current symptoms, who were previously diagnosed to be Xpert positive and treated successfully. Patients who retested as Xpert positive and culture negative were exhaustively investigated (repeat culture, chest radiography, bronchoscopy with bronchoalveolar lavage, long-term clinical follow-up). We evaluated whether the duration since previous treatment completion, mycobacterial burden (the Xpert cycle threshold [ C T ] value), and reclassification of Xpert-positive results with a very low semiquantitation level to Xpert-negative results reduced the rate of false positivity. A total of 229/238 (96%) of patients were culture negative. Sixteen of 229 (7%) were Xpert positive a median of 11 months (interquartile range, 5 to 19 months) after treatment completion. The specificity was 93% (95% confidence interval [CI], 89 to 96%). Nine of 15 (40%) Xpert-positive, culture-negative patients reverted to Xpert negative after 2 to 3 months (1 patient declined further participation). Patients with false-positive Xpert results had a lower mycobacterial burden than patients with true-positive Xpert results ( C T , 28.7 [95% CI, 27.2 to 30.4] versus 17.6 [95% CI, 16.9 to 18.2]; P < 0.001), an increased likelihood of a chest radiograph not compatible with active TB (5/15 patients versus 0/5 patients; P = 0.026), and less-viscous sputum (15/16 patients versus 2/5 patients whose sputum was graded as mucoid or less; P = 0.038). All patients who initially retested as Xpert positive and culture negative ("Xpert false positive") were clinically well without treatment after follow-up. The duration since the previous treatment poorly predicted false-positive results (a duration of ≤2 years identified

Enhancing TB case detection: experience in offering upfront Xpert MTB/RIF testing to pediatric presumptive TB and DR TB cases for early rapid diagnosis of drug sensitive and drug resistant TB.

PubMed

Raizada, Neeraj; Sachdeva, Kuldeep Singh; Nair, Sreenivas Achuthan; Kulsange, Shubhangi; Gupta, Radhey Shayam; Thakur, Rahul; Parmar, Malik; Gray, Christen; Ramachandran, Ranjani; Vadera, Bhavin; Ekka, Shobha; Dhawan, Shikha; Babre, Ameet; Ghedia, Mayank; Alavadi, Umesh; Dewan, Puneet; Khetrapal, Mini; Khanna, Ashwini; Boehme, Catharina; Paramsivan, Chinnambedu Nainarappan

2014-01-01

Diagnosis of pulmonary tuberculosis (PTB) in children is challenging due to difficulties in obtaining good quality sputum specimens as well as the paucibacillary nature of disease. Globally a large proportion of pediatric tuberculosis (TB) cases are diagnosed based only on clinical findings. Xpert MTB/RIF, a highly sensitive and specific rapid tool, offers a promising solution in addressing these challenges. This study presents the results from pediatric groups taking part in a large demonstration study wherein Xpert MTB/RIF testing replaced smear microscopy for all presumptive PTB cases in public health facilities across India. The study covered a population of 8.8 million across 18 programmatic sub-district level tuberculosis units (TU), with one Xpert MTB/RIF platform established at each study TU. Pediatric presumptive PTB cases (both TB and Drug Resistant TB (DR-TB)) accessing any public health facilities in study area were prospectively enrolled and tested on Xpert MTB/RIF following a standardized diagnostic algorithm. 4,600 pediatric presumptive pulmonary TB cases were enrolled. 590 (12.8%, CI 11.8-13.8) pediatric PTB were diagnosed. Overall 10.4% (CI 9.5-11.2) of presumptive PTB cases had positive results by Xpert MTB/RIF, compared with 4.8% (CI 4.2-5.4) who had smear-positive results. Upfront Xpert MTB/RIF testing of presumptive PTB and presumptive DR-TB cases resulted in diagnosis of 79 and 12 rifampicin resistance cases, respectively. Positive predictive value (PPV) for rifampicin resistance detection was high (98%, CI 90.1-99.9), with no statistically significant variation with respect to past history of treatment. Upfront access to Xpert MTB/RIF testing in pediatric presumptive PTB cases was associated with a two-fold increase in bacteriologically-confirmed PTB, and increased detection of rifampicin-resistant TB cases under routine operational conditions across India. These results suggest that routine Xpert MTB/RIF testing is a promising solution to

Evaluation of Xpert MTB/RIF assay in children with presumed pulmonary tuberculosis in Papua New Guinea.

PubMed

Kasa Tom, Sharon; Welch, Henry; Kilalang, Cornelia; Tefuarani, Nakapi; Vince, John; Lavu, Evelyn; Johnson, Karen; Magaye, Ruth; Duke, Trevor

2018-05-01

The Gene Xpert MTB/ RIF assay (Xpert) is used for rapid, simultaneous detection of Mycobacterium tuberculosis (MTB) and rifampicin resistance. This study examined the accuracy of Xpert in children with suspected pulmonary tuberculosis (PTB). Children admitted to Port Moresby General Hospital with suspected PTB were prospectively enrolled between September 2014 and March 2015. They were classified into probable, possible and TB-unlikely groups. Sputum or gastric aspirates were tested by Xpert and smear microscopy; mycobacterial culture was undertaken on a subset. Children were diagnosed with TB on the basis of standard criteria which were used as the primary reference standard. Xpert, smear for acid-fast bacilli (AFB) and the Edwards TB score were compared with the primary reference standard. A total of 93 children ≤14 years with suspected PTB were enrolled; 67 (72%) were classified as probable, 21 (22%) possible and 5 (5.4%) TB-unlikely. Eighty were treated for TB based on the primary reference standard. Xpert was positive in 26/93 (28%) MTB cases overall, including 22/67 (33%) with probable TB and 4/21 (19%) with possible TB. Three (13%) samples identified rifampicin resistance. Xpert confirmed more cases of TB than AFB smear (26 vs 13, p = 0.019). The sensitivity of Xpert, AFB smear and an Edwards TB score of ≥7 was 31% (25/80), 16% (13/80) and 90% (72/80), respectively, and the specificity was 92% (12/13), 100% (13/13) and 31% (4/13), respectively, when compared with the primary reference standard. Xpert sensitivity is sub-optimal and cannot be relied upon for diagnosing TB, although a positive result is confirmatory. A detailed history and examination, standardised clinical criteria, radiographs and available tests remain the most appropriate way of diagnosing TB in children in resource-limited countries. Xpert helps confirm PTB better than AFB smear, and identifies rifampicin resistance. Practical guidelines should be used to identify children who

Is Xpert MTB/RIF appropriate for diagnosing tuberculous pleurisy with pleural fluid samples? A systematic review.

PubMed

Huo, Zhen-Yu; Peng, Li

2018-06-25

Tuberculous pleurisy (TP) presents a diagnostic problem due to the limitations of traditional diagnostic methods. Different studies with the Xpert MTB/RIF assay have drawn variable conclusions about its values in TP diagnosis. We conducted a meta-analysis to assess whether the Xpert MTB/RIF assay is appropriate for the diagnosis of TP using pleural fluid samples. A systematic search of four literature databases in English and Chinese language was performed to identify studies involving the use of Xpert MTB/RIF in patients with TP confirmed by plural biopsy and/or mycobacterial culture. Pooled sensitivity, specificity and accordance proportion were calculated, and the forest plots were generated to assess the accuracy of Xpert MTB/RIF for TP diagnosis. We identified 23 studies meeting our inclusion criteria. The pooled sensitivity and specificity of Xpert MTB/RIF were 30% (95% CI: 21-42%, I 2  = 87.93%) and 99% (95% CI: 97-100%, I 2  = 96.20%), respectively, and the area under the SROC curve (AUC) of Xpert MTB/RIF was 0.86 (95% CI: 0.83-0.89). Compared with drug susceptibility testing (DST), the pooled accordance rate of Xpert MTB/RIF in detecting rifampicin-susceptible cases and rifampicin-resistant cases was 99% (95% CI: 95-104%, I 2  = 8.7%) and 94% (95% CI: 86-102%), respectively. Our analysis suggests that the Xpert MTB/RIF assay is of limited value as a screening test for TP but has a high potential for confirming TP diagnosis and differentiating TP from non-TB diseases using pleural fluid samples.

Implementation Research to Inform the Use of Xpert MTB/RIF in Primary Health Care Facilities in High TB and HIV Settings in Resource Constrained Settings.

PubMed

Muyoyeta, Monde; Moyo, Maureen; Kasese, Nkatya; Ndhlovu, Mapopa; Milimo, Deborah; Mwanza, Winfridah; Kapata, Nathan; Schaap, Albertus; Godfrey Faussett, Peter; Ayles, Helen

2015-01-01

The current cost of Xpert MTB RIF (Xpert) consumables is such that algorithms are needed to select which patients to prioritise for testing with Xpert. To evaluate two algorithms for prioritisation of Xpert in primary health care settings in a high TB and HIV burden setting. Consecutive, presumptive TB patients with a cough of any duration were offered either Xpert or Fluorescence microscopy (FM) test depending on their CXR score or HIV status. In one facility, sputa from patients with an abnormal CXR were tested with Xpert and those with a normal CXR were tested with FM ("CXR algorithm"). CXR was scored automatically using a Computer Aided Diagnosis (CAD) program. In the other facility, patients who were HIV positive were tested using Xpert and those who were HIV negative were tested with FM ("HIV algorithm"). Of 9482 individuals pre-screened with CXR, Xpert detected TB in 2090/6568 (31.8%) with an abnormal CXR, and FM was AFB positive in 8/2455 (0.3%) with a normal CXR. Of 4444 pre-screened with HIV, Xpert detected TB in 508/2265 (22.4%) HIV positive and FM was AFB positive in 212/1920 (11.0%) in HIV negative individuals. The notification rate of new bacteriologically confirmed TB increased; from 366 to 620/ 100,000/yr and from 145 to 261/100,000/yr at the CXR and HIV algorithm sites respectively. The median time to starting TB treatment at the CXR site compared to the HIV algorithm site was; 1(IQR 1-3 days) and 3 (2-5 days) (p<0.0001) respectively. Use of Xpert in a resource-limited setting at primary care level in conjunction with pre-screening tests reduced the number of Xpert tests performed. The routine use of Xpert resulted in additional cases of confirmed TB patients starting treatment. However, there was no increase in absolute numbers of patients starting TB treatment. Same day diagnosis and treatment commencement was achieved for both bacteriologically confirmed and empirically diagnosed patients where Xpert was used in conjunction with CXR.

Comparison between Roche and Xpert in HIV-1 RNA quantitation: A high concordance between the two techniques except for a CRF02_AG subtype variant with high viral load titters detected by Roche but undetected by Xpert.

PubMed

Avidor, Boaz; Matus, Natalia; Girshengorn, Shirley; Achsanov, Svetlana; Gielman, Simona; Zeldis, Irene; Schweitzer, Inbal; Adler, Amos; Turner, Dan

2017-08-01

HIV-1 viral load (VL) testing is important to predict viral progression and to monitor the response to antiretroviral therapy. New HIV-1 VL tests are continuously introduced to the market. Their performance is usually compared to Abbott and/or Roche HIV-1 VL assays, as reference. The Xpert HIV-1 VL test was recently introduced, but its performance compared to Roche has not been sufficiently studied. To compare the Xpert assay with Roche and to assess its use in the HIV clinical laboratory. A total of 383 plasma samples of HIV-1 infected patients previously tested by Roche, were retrospectively tested by Xpert to determine concordance between the two assays. Samples included a diversity of HIV-1 subtypes and a wide range of VLs. There was a high concordance between the two assays, except for a CRF02_AG subtype variant with high VL titters, that was detected by Roche but undetected by Xpert. The 5' long terminal repeat gene region of this virus, targeted by the Xpert assay, was amplified and sequenced. A 25 nucleotide insert was identified, but was unmatched to any known sequences of HIV-1. This particular insert, however could not explain the false-negativity by the Xpert assay. This study underlines the challenge to routine VL testing due to the high genetic diversity of HIV-1. Clinicians should, therefore be advised that a negative VL in cases where the clinical picture does not match the laboratory report, might in fact be, a false-negative result of the VL assay. Copyright © 2017 Elsevier B.V. All rights reserved.

GeneXpert MTB/RIF Assay for the Diagnosis of Tuberculous Lymphadenitis on Concentrated Fine Needle Aspirates in High Tuberculosis Burden Settings.

PubMed

Tadesse, Mulualem; Abebe, Gemeda; Abdissa, Ketema; Aragaw, Dossegnaw; Abdella, Kedir; Bekele, Alemayehu; Bezabih, Mesele; Apers, Ludwig; de Jong, Bouke C; Rigouts, Leen

2015-01-01

The diagnosis of tuberculous lymphadenitis (TBL) remains challenging. The routinely used methods (cytology and smear microscopy) have sub-optimal sensitivity. Recently, WHO recommends GeneXpert to be used as the initial diagnostic test in patients suspected of having extra-pulmonary tuberculosis (EPTB). However, this was a conditional recommendation due to very low-quality evidence available and more studies are needed. In this study we evaluated the performance of Xpert for the diagnosis of TBL on concentrated fine needle aspirates (FNA) in Southwest Ethiopia. FNA was collected from presumptive TBL cases. Two smears were prepared from each aspirate and processed for cytology and conventional microscopy. The remaining aspirate was treated with N-acetyl-L-cysteine-NaOH and centrifuged for 15minutes at 3000g. The concentrated sediment was used for culture and Xpert test. Capilia TB-Neo test was used to differentiate M. tuberculosis complex (MTBC) from non-tuberculous mycobacteria (NTM). Composite bacteriological methods (culture and/or smear microscopy) were considered as a reference standard. Out of 143 enrolled suspects, 64.3% (92/143) were confirmed TBL cases by the composite reference standard (CRS). Xpert detected M. tuberculosis complex (MTBC) in 60.1% (86/143) of the presumptive TBL cases. The sensitivity of Xpert compared to CRS was 87.8% [95% CI: 81.0-94.5] and specificity 91.1% [95% CI: 82.8-99.4]. The sensitivity was 27.8% for smear microscopy and 80% for cytology compared to CRS. Cytology showed the lowest specificity (57.8%). Xpert was positive in 4 out of 45 culture- and smear-negative cases. Among 47 cytomorphologically non-TBL cases, 15 were positive on Xpert. More than half of Xpert-positive cases were in the range of very low cut-off threshold values (28Xpert-positive cases. Xpert test showed a high sensitivity and specificity for the diagnosis of TBL on concentrated FNA samples. In

Implementation Research to Inform the Use of Xpert MTB/RIF in Primary Health Care Facilities in High TB and HIV Settings in Resource Constrained Settings

PubMed Central

Muyoyeta, Monde; Moyo, Maureen; Kasese, Nkatya; Ndhlovu, Mapopa; Milimo, Deborah; Mwanza, Winfridah; Kapata, Nathan; Schaap, Albertus; Godfrey Faussett, Peter; Ayles, Helen

2015-01-01

Background The current cost of Xpert MTB RIF (Xpert) consumables is such that algorithms are needed to select which patients to prioritise for testing with Xpert. Objective To evaluate two algorithms for prioritisation of Xpert in primary health care settings in a high TB and HIV burden setting. Method Consecutive, presumptive TB patients with a cough of any duration were offered either Xpert or Fluorescence microscopy (FM) test depending on their CXR score or HIV status. In one facility, sputa from patients with an abnormal CXR were tested with Xpert and those with a normal CXR were tested with FM (“CXR algorithm”). CXR was scored automatically using a Computer Aided Diagnosis (CAD) program. In the other facility, patients who were HIV positive were tested using Xpert and those who were HIV negative were tested with FM (“HIV algorithm”). Results Of 9482 individuals pre-screened with CXR, Xpert detected TB in 2090/6568 (31.8%) with an abnormal CXR, and FM was AFB positive in 8/2455 (0.3%) with a normal CXR. Of 4444 pre-screened with HIV, Xpert detected TB in 508/2265 (22.4%) HIV positive and FM was AFB positive in 212/1920 (11.0%) in HIV negative individuals. The notification rate of new bacteriologically confirmed TB increased; from 366 to 620/ 100,000/yr and from 145 to 261/100,000/yr at the CXR and HIV algorithm sites respectively. The median time to starting TB treatment at the CXR site compared to the HIV algorithm site was; 1(IQR 1-3 days) and 3 (2-5 days) (p<0.0001) respectively. Conclusion Use of Xpert in a resource-limited setting at primary care level in conjunction with pre-screening tests reduced the number of Xpert tests performed. The routine use of Xpert resulted in additional cases of confirmed TB patients starting treatment. However, there was no increase in absolute numbers of patients starting TB treatment. Same day diagnosis and treatment commencement was achieved for both bacteriologically confirmed and empirically diagnosed patients

Diagnostic accuracy and turnaround time of the Xpert MTB/RIF assay in routine clinical practice.

PubMed

Kwak, Nakwon; Choi, Sun Mi; Lee, Jinwoo; Park, Young Sik; Lee, Chang-Hoon; Lee, Sang-Min; Yoo, Chul-Gyu; Kim, Young Whan; Han, Sung Koo; Yim, Jae-Joon

2013-01-01

The Xpert MTB/RIF assay was introduced for timely and accurate detection of tuberculosis (TB). The aim of this study was to determine the diagnostic accuracy and turnaround time (TAT) of Xpert MTB/RIF assay in clinical practice in South Korea. We retrospectively reviewed the medical records of patients in whom Xpert MTB/RIF assay using sputum were requested. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the diagnosis of pulmonary tuberculosis (PTB) and detection of rifampicin resistance were calculated. In addition, TAT of Xpert MTB/RIF assay was compared with those of other tests. Total 681 patients in whom Xpert MTB/RIF assay was requested were included in the analysis. The sensitivity, specificity, PPV and NPV of Xpert MTB/RIF assay for diagnosis of PTB were 79.5% (124/156), 100.0% (505/505), 100.0% (124/124) and 94.0% (505/537), respectively. Those for the detection of rifampicin resistance were 57.1% (8/14), 100.0% (113/113), 100.0% (8/8) and 94.9% (113/119), respectively. The median TAT of Xpert MTB/RIF assay to the report of results and results confirmed by physicians in outpatient settings were 0 (0-1) and 6 (3-7) days, respectively. Median time to treatment after initial evaluation was 7 (4-9) days in patients with Xpert MTB/RIF assay, but was 21 (7-33.5) days in patients without Xpert MTB/RIF assay. Xpert MTB/RIF assay showed acceptable sensitivity and excellent specificity for the diagnosis of PTB and detection of rifampicin resistance in areas with intermediate TB burden. Additionally, the assay decreased time to the initiation of anti-TB drugs through shorter TAT.

Diagnostic Accuracy and Turnaround Time of the Xpert MTB/RIF Assay in Routine Clinical Practice

PubMed Central

Kwak, Nakwon; Choi, Sun Mi; Lee, Jinwoo; Park, Young Sik; Lee, Chang-Hoon; Lee, Sang-Min; Yoo, Chul-Gyu; Kim, Young Whan; Han, Sung Koo; Yim, Jae-Joon

2013-01-01

The Xpert MTB/RIF assay was introduced for timely and accurate detection of tuberculosis (TB). The aim of this study was to determine the diagnostic accuracy and turnaround time (TAT) of Xpert MTB/RIF assay in clinical practice in South Korea. We retrospectively reviewed the medical records of patients in whom Xpert MTB/RIF assay using sputum were requested. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the diagnosis of pulmonary tuberculosis (PTB) and detection of rifampicin resistance were calculated. In addition, TAT of Xpert MTB/RIF assay was compared with those of other tests. Total 681 patients in whom Xpert MTB/RIF assay was requested were included in the analysis. The sensitivity, specificity, PPV and NPV of Xpert MTB/RIF assay for diagnosis of PTB were 79.5% (124/156), 100.0% (505/505), 100.0% (124/124) and 94.0% (505/537), respectively. Those for the detection of rifampicin resistance were 57.1% (8/14), 100.0% (113/113), 100.0% (8/8) and 94.9% (113/119), respectively. The median TAT of Xpert MTB/RIF assay to the report of results and results confirmed by physicians in outpatient settings were 0 (0–1) and 6 (3–7) days, respectively. Median time to treatment after initial evaluation was 7 (4–9) days in patients with Xpert MTB/RIF assay, but was 21 (7–33.5) days in patients without Xpert MTB/RIF assay. Xpert MTB/RIF assay showed acceptable sensitivity and excellent specificity for the diagnosis of PTB and detection of rifampicin resistance in areas with intermediate TB burden. Additionally, the assay decreased time to the initiation of anti-TB drugs through shorter TAT. PMID:24204834

Evaluation of Xpert MTB/RIF assay performance in the diagnosis of abdominal tuberculosis.

PubMed

Kumar, Suraj; Bopanna, Sawan; Kedia, Saurabh; Mouli, Pratap; Dhingra, Rajan; Padhan, Rajesh; Kohli, Mikashmi; Chaubey, Jigyasa; Sharma, Rohini; Das, Prasenjit; Dattagupta, S; Makharia, Govind; Sharma, S K; Ahuja, Vineet

2017-04-01

The use of genetic probes for the diagnosis of pulmonary tuberculosis (TB) has been well described. However, the role of these assays in the diagnosis of intestinal tuberculosis is unclear. We therefore assessed the diagnostic utility of the Xpert Mycobacterium tuberculosis /rifampicin (MTB/RIF) assay, and estimated the prevalence of multidrug-resistant (MDR) TB in the Indian population. Of 99 patients recruited, 37 had intestinal TB; two control groups comprised 43 with Crohn's disease (CD) and 19 with irritable bowel syndrome. Colonoscopy was performed before starting any therapy; mucosal biopsies were subjected to histopathology, acid-fast bacilli staining, Lowenstein-Jensen culture, and nucleic acid amplification testing using the Xpert MTB/RIF assay. Patients were followed up for 6 months to confirm the diagnosis and response to therapy. A composite reference standard was used for diagnosis of TB and assessment of the diagnostic utility of the Xpert MTB/RIF assay. Of 37 intestinal TB patients, the Xpert MTB/RIF assay was positive in three of 37 (8.1%), but none had MDR-TB. The sensitivity, specificity, positive predictive value, and negative predictive value of the Xpert MTB/RIF assay was 8.1%, 100%, 100%, and, 64.2%, respectively. The Xpert MTB/RIF assay has low sensitivity but high specificity for intestinal TB, and may be helpful in endemic tuberculosis areas, when clinicians are faced with difficulty differentiating TB and CD. Based on the Xpert MTB/RIF assay, the prevalence of intestinal MDR-TB is low in the Indian population.

Three year evaluation of Xpert MTB/RIF in a low prevalence tuberculosis setting: A Scottish perspective.

PubMed

Parcell, Benjamin J; Jarchow-MacDonald, Anna A; Seagar, Amie-Louise; Laurenson, Ian F; Prescott, Gordon J; Lockhart, Michael

2017-05-01

Xpert MTB/RIF (Cepheid) is a rapid molecular assay shown to be sensitive and specific for pulmonary tuberculosis (TB) diagnosis in highly endemic countries. We evaluated its diagnostic performance in a low TB prevalence setting, examined rifampicin resistance detection and quantitative capabilities predicting graded auramine microscopy and time to positivity (TTP) of culture. Xpert MTB/RIF was used to test respiratory samples over a 3 year period. Samples underwent graded auramine microscopy, solid/liquid culture, in-house IS6110 real-time PCR, and GenoType MTBDRplus (HAIN Lifescience) to determine rifampicin and/or isoniazid resistance. A total of 2103 Xpert MTB/RIF tests were performed. Compared to culture sensitivity was 95.8%, specificity 99.5%, positive predictive value (PPV) 82.1%, and negative predictive value (NPV) 99.9%. A positive correlation was found between auramine microscopy grade and Xpert MTB/RIF assay load. We found a clear reduction in the median TTP as Xpert MTB/RIF assay load increased. Rifampicin resistance was detected. Xpert MTB/RIF was rapid and accurate in diagnosing pulmonary TB in a low prevalence area. Rapid results will influence infection prevention and control and treatment measures. The excellent NPV obtained suggests further work should be carried out to assess its role in replacing microscopy. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

[Evaluation of Xpert® MTB/RIF technique for Mycobacterium tuberculosis complex detection in extra-respiratory specimens].

PubMed

García, Patricia; Balcells, M Elvira; Castillo, Claudia; Miranda, Carolina; Geoffroy, Enrique; Román, Juan C; Wozniak, Aniela

2017-08-01

Extra-pulmonary tuberculosis (TB) represents the 26.2% of total TB cases in Chile. Culture is the gold standard method, but the process is extremely slow. Xpert®MTB/RIF technique detects Mycobacterium tuberculosis complex (MTBc) through real time PCR in less than 3 h. However, it has been validated only for respiratory specimens. We aimed to determine the performance of Xpert®MTB/RIF test in detecting MTBc in extra-respiratory specimens compared with a combined gold standard consisting in a positive (liquid and solid) mycobacterial culture and/or a positive validated molecular method (q-RPC, Cobas®TaqMan®-MTB). Fifty extra-respiratory specimens were analyzed, from which 25 were positive and 25 negative for MTBc based on the combined gold standard. The 25 positive specimens had a positive result by Xpert®MTB/RIF; from the 25 negative specimens, 24 had a negative result and one had a positive result. We obtained an overall concordance of 98% between Xpert®MTB/RIF and the combined gold standard. Xpert®MTB/RIF test was able to detect 12 smear-negative specimens and 3 culture-negative specimens, all of them corresponding to extra-pulmonary TB cases. Xpert®MTB/RIF showed similar sensitivity to q-RPC in detecting MTBc in extra-respiratory specimens. This procedure allowed a substantial reduction in the time of diagnosis.

Cost-effectiveness analysis of the Xpert MTB/RIF assay for rapid diagnosis of suspected tuberculosis in an intermediate burden area.

PubMed

You, Joyce H S; Lui, Grace; Kam, Kai Man; Lee, Nelson L S

2015-04-01

We examined, from a Hong Kong healthcare providers' perspective, the cost-effectiveness of rapid diagnosis with Xpert in patients hospitalized for suspected active pulmonary tuberculosis (PTB). A decision tree was designed to simulate outcomes of three diagnostic assessment strategies in adult patients hospitalized for suspected active PTB: conventional approach, sputum smear plus Xpert for acid-fast bacilli (AFB) smear-negative, and a single sputum Xpert test. Model inputs were derived from the literature. Outcome measures were direct medical cost, one-year mortality rate, quality-adjusted life-years (QALYs) and incremental cost per QALY (ICER). In the base-case analysis, Xpert was more effective with higher QALYs gained and a lower mortality rate when compared with smear plus Xpert by an ICER of USD99. A conventional diagnostic approach was the least preferred option with the highest cost, lowest QALYs gained and highest mortality rate. Sensitivity analysis showed that Xpert would be the most cost-effective option if the sensitivity of sputum AFB smear microscopy was ≤74%. The probabilities of Xpert, smear plus Xpert and a conventional approach to be cost-effective were 94.5%, 5.5% and 0%, respectively, in 10,000 Monte Carlo simulations. The Xpert sputum test appears to be a highly cost-effective diagnostic strategy for patients with suspected active PTB in an intermediate burden area like Hong Kong. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Implementation of the Xpert MTB/RIF assay for tuberculosis in Mongolia: a qualitative exploration of barriers and enablers.

PubMed

Rendell, Nicole L; Bekhbat, Solongo; Ganbaatar, Gantungalag; Dorjravdan, Munkhjargal; Pai, Madhukar; Dobler, Claudia C

2017-01-01

The aim of our study was to identify barriers and enablers to implementation of the Xpert MTB/RIF test within Mongolia's National Tuberculosis Program. Twenty-foursemi-structured interviews were conducted between June and September 2015 with laboratory staff and tuberculosis physicians in Mongolia's capital Ulaanbaatar and regional towns where Xpert MTB/RIF testing had been implemented. Interviews were recorded, transcribed, translated and analysed thematically using NVIVO qualitative analysis software. Eight laboratory staff (five from the National Tuberculosis Reference Laboratory in Ulaanbaatar and three from provincial laboratories) and sixteen tuberculosis physicians (five from the Mongolian National Center for Communicable Diseases in Ulaanbaatar, four from district tuberculosis clinics in Ulaanbaatar and seven from provincial tuberculosis clinics) were interviewed. Major barriers to Xpert MTB/RIF implementation identified were: lack of awareness of program guidelines; inadequate staffing arrangements; problems with cartridge supply management; lack of local repair options for the Xpert machines; lack of regular formal training; paper based system; delayed treatment initiation due to consensus meeting and poor sample quality. Enablers to Xpert MTB/RIF implementation included availability of guidelines in the local language; provision of extra laboratory staff, shift working arrangements and additional modules; capacity for troubleshooting internally; access to experts; opportunities for peer learning; common understanding of diagnostic algorithms and decentralised testing. Our study identified a number of barriers and enablers to implementation of Xpert MTB/RIF in the Mongolian National Tuberculosis Program. Lessons learned from this study can help to facilitate implementation of Xpert MTB/RIF in other Mongolian locations as well as other low-and middle-income countries.

[Role of GeneXpert MTB/RIF test in the screening for pulmonary tuberculosis at the General Referral Provincial Hospital of Bukavu, in the East of the Democratic Republic of the Congo: balance after 10 months of use].

PubMed

Lupande, David; Kaishusha, David; Mihigo, Carine; Itongwa, Moise; Yenga, Gustave; Katchunga, Philippe

2017-01-01

In sub-Saharan Africa, diagnostic methods for tuberculosis are inadequate and are essentially based on microscopy. They constitute a real obstacle to the control of tuberculosis. This study aimed to evaluate the performance of GeneXpert MTB/RIF test compared to classical Ziehl-Neelsen staining at the the general referral provincial hospital of Bukavu, in the east of the Democratic Republic of the Congo after 10 months of use. The results of Ziehl-Neelsen staining and GeneXpert MTB/RIF molecular biology test performed in 452 patients with suspected tuberculosis were collected. This study compares the validity of these different diagnostic tests in the detection of tuberculosis. In the entire group, the frequency of the pulmonary tuberculosis was 16.3%. The positivity rate was significantly higher in GeneXpert MTB/RIF test than in Ziehl-Neelsen staining in the entire group (15.9% vs 9.3%, p = 0.03) and in HIV seropositive patients (52.0% vs 24.0%; p = 0.007). However, the sensitivity of GeneXpert MTB/RIF test compared to that in Ziehl-Neelsen staining wasn't maximum (95.2%). Finally, GeneXpert MTB/RIF test detected rifampicin resistance in 20.8%. This study confirms the superiority of GeneXpert MTB/RIF test compared to Ziehl-Neelsen staining in the detection of tuberculosis and in the prediction of multi-resistance. Its systematic use coupled with Ziehl-Neelsen staining would better control tuberculosis in sub-Saharan Africa.

Diagnostic accuracy of quantitative PCR (Xpert MTB/RIF) for tuberculous meningitis in a high burden setting: a prospective study.

PubMed

Patel, Vinod B; Theron, Grant; Lenders, Laura; Matinyena, Brian; Connolly, Cathy; Singh, Ravesh; Coovadia, Yacoob; Ndung'u, Thumbi; Dheda, Keertan

2013-10-01

Tuberculous meningitis (TBM) is difficult to diagnose promptly. The utility of the Xpert MTB/RIF test for the diagnosis of TBM remains unclear, and the effect of host- and sample-related factors on test performance is unknown. This study sought to evaluate the sensitivity and specificity of Xpert MTB/RIF for the diagnosis of TBM. 235 South-African patients with a meningeal-like illness were categorised as having definite (culture or Amplicor PCR positive), probable (anti-TBM treatment initiated but microbiological confirmation lacking), or non-TBM. Xpert MTB/RIF accuracy was evaluated using 1 ml of uncentrifuged and, when available, 3 ml of centrifuged cerebrospinal fluid (CSF). To evaluate the incremental value of MTB/RIF over a clinically based diagnosis, test accuracy was compared to a clinical score (CS) derived using basic clinical and laboratory information. Of 204 evaluable patients (of whom 87% were HIV-infected), 59 had definite TBM, 64 probable TBM, and 81 non-TBM. Overall sensitivity and specificity (95% CI) were 62% (48%-75%) and 95% (87%-99%), respectively. The sensitivity of Xpert MTB/RIF was significantly better than that of smear microscopy (62% versus 12%; p = 0.001) and significantly better than that of the CS (62% versus 30%; p = 0.001; C statistic 85% [79%-92%]). Xpert MTB/RIF sensitivity was higher when centrifuged versus uncentrifuged samples were used (82% [62%-94%] versus 47% [31%-61%]; p = 0.004). The combination of CS and Xpert MTB/RIF (Xpert MTB/RIF performed if CS<8) performed as well as Xpert MTB/RIF alone but with a ∼10% reduction in test usage. This overall pattern of results remained unchanged when the definite and probable TBM groups were combined. Xpert MTB/RIF was not useful in identifying TBM among HIV-uninfected individuals, although the sample was small. There was no evidence of PCR inhibition, and the limit of detection was ∼80 colony forming units per millilitre. Study limitations included a predominantly HIV

Diagnostic Accuracy of Quantitative PCR (Xpert MTB/RIF) for Tuberculous Meningitis in a High Burden Setting: A Prospective Study

PubMed Central

Patel, Vinod B.; Theron, Grant; Lenders, Laura; Matinyena, Brian; Connolly, Cathy; Singh, Ravesh; Coovadia, Yacoob; Ndung'u, Thumbi; Dheda, Keertan

2013-01-01

Background Tuberculous meningitis (TBM) is difficult to diagnose promptly. The utility of the Xpert MTB/RIF test for the diagnosis of TBM remains unclear, and the effect of host- and sample-related factors on test performance is unknown. This study sought to evaluate the sensitivity and specificity of Xpert MTB/RIF for the diagnosis of TBM. Methods and Findings 235 South-African patients with a meningeal-like illness were categorised as having definite (culture or Amplicor PCR positive), probable (anti-TBM treatment initiated but microbiological confirmation lacking), or non-TBM. Xpert MTB/RIF accuracy was evaluated using 1 ml of uncentrifuged and, when available, 3 ml of centrifuged cerebrospinal fluid (CSF). To evaluate the incremental value of MTB/RIF over a clinically based diagnosis, test accuracy was compared to a clinical score (CS) derived using basic clinical and laboratory information. Of 204 evaluable patients (of whom 87% were HIV-infected), 59 had definite TBM, 64 probable TBM, and 81 non-TBM. Overall sensitivity and specificity (95% CI) were 62% (48%–75%) and 95% (87%–99%), respectively. The sensitivity of Xpert MTB/RIF was significantly better than that of smear microscopy (62% versus 12%; p = 0.001) and significantly better than that of the CS (62% versus 30%; p = 0.001; C statistic 85% [79%–92%]). Xpert MTB/RIF sensitivity was higher when centrifuged versus uncentrifuged samples were used (82% [62%–94%] versus 47% [31%–61%]; p = 0.004). The combination of CS and Xpert MTB/RIF (Xpert MTB/RIF performed if CS<8) performed as well as Xpert MTB/RIF alone but with a ∼10% reduction in test usage. This overall pattern of results remained unchanged when the definite and probable TBM groups were combined. Xpert MTB/RIF was not useful in identifying TBM among HIV-uninfected individuals, although the sample was small. There was no evidence of PCR inhibition, and the limit of detection was ∼80 colony forming units per millilitre. Study

Results from early programmatic implementation of Xpert MTB/RIF testing in nine countries

PubMed Central

2014-01-01

Background The Xpert MTB/RIF assay has garnered significant interest as a sensitive and rapid diagnostic tool to improve detection of sensitive and drug resistant tuberculosis. However, most existing literature has described the performance of MTB/RIF testing only in study conditions; little information is available on its use in routine case finding. TB REACH is a multi-country initiative focusing on innovative ways to improve case notification. Methods We selected a convenience sample of nine TB REACH projects for inclusion to cover a range of implementers, regions and approaches. Standard quarterly reports and machine data from the first 12 months of MTB/RIF implementation in each project were utilized to analyze patient yields, rifampicin resistance, and failed tests. Data was collected from September 2011 to March 2013. A questionnaire was implemented and semi-structured interviews with project staff were conducted to gather information on user experiences and challenges. Results All projects used MTB/RIF testing for people with suspected TB, as opposed to testing for drug resistance among already diagnosed patients. The projects placed 65 machines (196 modules) in a variety of facilities and employed numerous case-finding strategies and testing algorithms. The projects consumed 47,973 MTB/RIF tests. Of valid tests, 7,195 (16.8%) were positive for MTB. A total of 982 rifampicin resistant results were found (13.6% of positive tests). Of all tests conducted, 10.6% failed. The need for continuous power supply was noted by all projects and most used locally procured solutions. There was considerable heterogeneity in how results were reported and recorded, reflecting the lack of standardized guidance in some countries. Conclusions The findings of this study begin to fill the gaps among guidelines, research findings, and real-world implementation of MTB/RIF testing. Testing with Xpert MTB/RIF detected a large number of people with TB that routine services failed to

Results from early programmatic implementation of Xpert MTB/RIF testing in nine countries.

PubMed

Creswell, Jacob; Codlin, Andrew J; Andre, Emmanuel; Micek, Mark A; Bedru, Ahmed; Carter, E Jane; Yadav, Rajendra-Prasad; Mosneaga, Andrei; Rai, Bishwa; Banu, Sayera; Brouwer, Miranda; Blok, Lucie; Sahu, Suvanand; Ditiu, Lucica

2014-01-02

The Xpert MTB/RIF assay has garnered significant interest as a sensitive and rapid diagnostic tool to improve detection of sensitive and drug resistant tuberculosis. However, most existing literature has described the performance of MTB/RIF testing only in study conditions; little information is available on its use in routine case finding. TB REACH is a multi-country initiative focusing on innovative ways to improve case notification. We selected a convenience sample of nine TB REACH projects for inclusion to cover a range of implementers, regions and approaches. Standard quarterly reports and machine data from the first 12 months of MTB/RIF implementation in each project were utilized to analyze patient yields, rifampicin resistance, and failed tests. Data was collected from September 2011 to March 2013. A questionnaire was implemented and semi-structured interviews with project staff were conducted to gather information on user experiences and challenges. All projects used MTB/RIF testing for people with suspected TB, as opposed to testing for drug resistance among already diagnosed patients. The projects placed 65 machines (196 modules) in a variety of facilities and employed numerous case-finding strategies and testing algorithms. The projects consumed 47,973 MTB/RIF tests. Of valid tests, 7,195 (16.8%) were positive for MTB. A total of 982 rifampicin resistant results were found (13.6% of positive tests). Of all tests conducted, 10.6% failed. The need for continuous power supply was noted by all projects and most used locally procured solutions. There was considerable heterogeneity in how results were reported and recorded, reflecting the lack of standardized guidance in some countries. The findings of this study begin to fill the gaps among guidelines, research findings, and real-world implementation of MTB/RIF testing. Testing with Xpert MTB/RIF detected a large number of people with TB that routine services failed to detect. The study demonstrates the

Structured patient education: the X-PERT Programme.

PubMed

Deakin, Trudi; Whitham, Claire

2009-09-01

The X-PERT Programme seeks to develop the knowledge, skills and confidence in diabetes treatment for health-care professionals and diabetes self-management. The programme trains health-care professionals to deliver the six-week structured patient education programme to people with diabetes. Over 850 health-care professionals have attended the X-PERT 'Train the Trainer' course and audit results document improved job satisfaction and competence in diabetes treatment and management. National audit statistics for X-PERT implementation to people with diabetes illustrate excellent attendance rates, improved diabetes control, reduced weight, blood pressure, cholesterol and waist circumference and more confidence in self-managing diabetes that has impacted positively on quality of life.

Implementation of the Xpert MTB/RIF assay for tuberculosis in Mongolia: a qualitative exploration of barriers and enablers

PubMed Central

Bekhbat, Solongo; Ganbaatar, Gantungalag; Dorjravdan, Munkhjargal; Pai, Madhukar; Dobler, Claudia C.

2017-01-01

Objective The aim of our study was to identify barriers and enablers to implementation of the Xpert MTB/RIF test within Mongolia’s National Tuberculosis Program. Methods Twenty-foursemi-structured interviews were conducted between June and September 2015 with laboratory staff and tuberculosis physicians in Mongolia’s capital Ulaanbaatar and regional towns where Xpert MTB/RIF testing had been implemented. Interviews were recorded, transcribed, translated and analysed thematically using NVIVO qualitative analysis software. Results Eight laboratory staff (five from the National Tuberculosis Reference Laboratory in Ulaanbaatar and three from provincial laboratories) and sixteen tuberculosis physicians (five from the Mongolian National Center for Communicable Diseases in Ulaanbaatar, four from district tuberculosis clinics in Ulaanbaatar and seven from provincial tuberculosis clinics) were interviewed. Major barriers to Xpert MTB/RIF implementation identified were: lack of awareness of program guidelines; inadequate staffing arrangements; problems with cartridge supply management; lack of local repair options for the Xpert machines; lack of regular formal training; paper based system; delayed treatment initiation due to consensus meeting and poor sample quality. Enablers to Xpert MTB/RIF implementation included availability of guidelines in the local language; provision of extra laboratory staff, shift working arrangements and additional modules; capacity for troubleshooting internally; access to experts; opportunities for peer learning; common understanding of diagnostic algorithms and decentralised testing. Conclusion Our study identified a number of barriers and enablers to implementation of Xpert MTB/RIF in the Mongolian National Tuberculosis Program. Lessons learned from this study can help to facilitate implementation of Xpert MTB/RIF in other Mongolian locations as well as other low-and middle-income countries. PMID:28717600

Evaluation of GeneXpert MTB/RIF for detecting Mycobacterium tuberculosis in a hospital in China.

PubMed

Tang, Tingyu; Liu, Fang; Lu, Xiaoling; Huang, Qingdong

2017-04-01

Objective To evaluate the performance of GeneXpert MTB/RIF in diagnosing pulmonary tuberculosis (TB) in China. Methods This cross-sectional study included sputum specimens of 240 suspected TB cases. Specimens were examined by light microscopy for the presence of acid-fast bacilli, which were cultured by the BACTEC MGIT 960 (M960) system and detected by the GeneXpert MTB/RIF assay. The positive rate, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and average turnaround time of methods were evaluated. Results The positive rate was 36.6% (87/238) for the GeneXpert MTB/RIF assay and 34.0% (81/238) by M960 culture, with no significant difference between methods (χ 2  = 0.33, p > 0.05). According to culture results, sensitivity of the GeneXpert MTB/RIF assay was 84.0% (68/81), specificity was 87.8% (129/147), the PPV was 78.2% (68/87), and the NPV was 87.2% (129/148). The agreement for results between Gene Xpert MTB/RIF and the M960 system was 82.8% and the Kappa value was 0.73. Conclusion The GeneXpert MTB/RIF assay is a simple, rapid, and accurate test for detecting Mycobacterium tuberculosis in sputum specimens.

Case report of a false positive result of the Xpert® MTB/RIF assay for rifampicin resistance in Mycobacterium tuberculosis complex.

PubMed

Claessens, Jolien; Mathys, Vanessa; Derdelinckx, Inge; Saegeman, Veroniek

2017-06-01

In the present case, we report a false positive result for the detection of rifampicin (RIF) resistance by the Xpert ® MTB/RIF assay, version G4.Miliary Mycobacterium tuberculosis infection (miliary TB) was suspected in a 50-year old Angolan woman. Imaging of the thorax and abdomen displayed diffuse lesions. The Xpert ® MTB/RIF assay conducted on the broncho-alveolar lavage (BAL) fluid was positive for TB and positive for RIF resistance. Confirmatory molecular tests and the phenotypic drug susceptibility determination supported the diagnosis of TB but not RIF resistance. The patient was treated successfully with a conventional therapeutic scheme. Because, the Xpert ® MTB/RIF assay allows the simultaneous detection of TB and RIF resistance, the World Health Organisation (WHO) recommends its use as initial diagnostic test, over microscopy, culture and phenotypic drug susceptibility testing. Even though specificity of the Xpert ® MTB/RIF assay version G4 is high, false positive test results remain possible and have to be considered for the interpretation of the RIF resistance detection by Xpert ® MTB/RIF assay.

LPA or GeneXpert in the diagnosis of multidrug-resistant tuberculosis.

PubMed

Mindru, Roxana; Spinu, Victor; Popescu, Oana

2016-01-01

Facing a constant increase of multidrug-resistant tuberculosis (MDR-TB), there is large need for routine use of new diagnostic tests, based on molecular techniques that allow both a rapid diagnosis for TB complex and rapid identification of resistance mutations. The resistances are due to genetic factors: accumulation of changes within the genome structure, acquisition or loss of genes, spontaneous mutations in chromosomal genes, and changes that induce selection of resistant strains during a suboptimal treatment. The bacteriology laboratory plays a crucial role in the making of the diagnosis, monitoring and preventing TB transmission. World Health Organization offers consistent recommendations in favour of use of Xpert MTB/RIF, GeneXpert platform, as initial diagnostic test in adults and children suspected of TB, because it can simultaneously determine the presence of Mycobacterium tuberculosis and the Rifampicin resistance, which is a surrogate marker of MDR strains. The very high sensibility and specificity, also in the smear negative samples, as well as the short time needed for the results, make Xpert MTB/RIF a valuable tool in the fight against TB. Other recommended tests are: LPA, which identifies M. Tuberculosis complex, the Rifancim and Isoniazid resistance; MTBDR plus or, for second line anti-TB drugs, the MTBDRsl.

The additional role of Xpert MTB/RIF in the diagnosis of intrathoracic tuberculous lymphadenitis.

PubMed

Lee, Jinwoo; Choi, Sun Mi; Lee, Chang-Hoon; Lee, Sang-Min; Yim, Jae-Joon; Yoo, Chul-Gyu; Kim, Young Whan; Han, Sung Koo; Park, Young Sik

2017-06-01

Diagnosis of intrathoracic tuberculosis (TB) lymphadenitis remains a challenge because of difficulties in obtaining adequate tissue and the lack of a sensitive test. Recently, Xpert MTB/RIF assay is being used for rapid diagnosis of pulmonary TB, but it has not yet been widely validated in intrathoracic TB lymphadenitis. The aim of this study was to assess the additional role of Xpert MTB/RIF in diagnosing intrathoracic TB lymphadenitis using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) specimen. Consecutive patients who underwent Xpert MTB/RIF assay using EBUS-TBNA specimen from January 2012 and November 2013 at a tertiary referral hospital were recruited. Among them, the cases with malignant lymph nodes were excluded. Among 73 patients, 13 (17.8%) cases were diagnosed with intrathoracic TB lymphadenitis. In detail, 10 patients were diagnosed using conventional methods only (histology or AFB culture) and 3 patients were additionally diagnosed when adding Xpert MTB/RIF assay. The median time to diagnosis using Xpert MTB/RIF (1 day) was shorter than conventional methods (3 days for histology, 14 days for AFB culture). Rifampin resistance was not detected in any patients. In patients with enlarged intrathoracic lymph nodes and low suspicion of malignancy, combination of conventional diagnostic methods with Xpert MTB/RIF could lead to additional and rapid diagnosis of intrathoracic TB lymphadenitis. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Detection of Norovirus by BD MAX™, Xpert® Norovirus, and xTAG® Gastrointestinal Pathogen Panel in stool and vomit samples.

PubMed

McHugh, Martin P; Guerendiain, Daniel; Hardie, Alison; Kenicer, Juliet; MacKenzie, Laura; Templeton, Kate E

2018-06-08

Norovirus is a leading cause of infectious gastroenteritis, characterized by outbreaks of diarrhoea and vomiting in closed settings. Nucleic acid amplification tests allow rapid and sensitive laboratory diagnosis of norovirus, with a number of commercial platforms now available. Evaluate the performance of the Becton Dickinson BD-MAX™System, Cepheid Xpert® Norovirus Assay, and Luminex xTAG® Gastrointestinal Pathogen Panel (GPP) for norovirus detection in stool. Assess the performance of the Xpert® Norovirus Assay and BD-MAX™ in vomit samples. 163 diarrhoeal stool samples were tested on four diagnostic systems (laboratory-defined real time RT-PCR (assigned as gold standard), BD MAX™, Xpert® Norovirus Assay, and xTAG® GPP). A further 70 vomit samples were tested on the Xpert and BD MAX platforms. In stool, sensitivity and specificity of the BD-MAX™ was 96.8% and 100%, for Xpert® Norovirus Assay was 91.9% and 100%, and for xTAG® GPP was 79.0% and 87.1%. In vomit samples positive and negative percent agreement was 95.6% and 92.0%, between the BD-MAX™ and Xpert® Norovirus. The BD-MAX™ System with user defined settings and the Xpert® Norovirus Assay showed acceptable sensitivity and specificity for detection of norovirus from stool and vomit. The xTAG GPP assay was less reliable for norovirus detection but can detect a number of other clinically useful enteropathogens. Clinical laboratories must consider skill mix, budget, and sample throughput to determine the best fit for their service. Copyright © 2018 Elsevier B.V. All rights reserved.

Scaling-up the Xpert MTB/RIF assay for the detection of tuberculosis and rifampicin resistance in India: An economic analysis

PubMed Central

Khaparde, Sunil; Nair, Sreenivas Achuthan; Denkinger, Claudia; Sachdeva, Kuldeep Singh; Paramasivan, Chinnambedu Nainarappan; Salhotra, Virender Singh; Vassall, Anna; Hoog, Anja van't

2017-01-01

Background India is considering the scale-up of the Xpert MTB/RIF assay for detection of tuberculosis (TB) and rifampicin resistance. We conducted an economic analysis to estimate the costs of different strategies of Xpert implementation in India. Methods Using a decision analytical model, we compared four diagnostic strategies for TB patients: (i) sputum smear microscopy (SSM) only; (ii) Xpert as a replacement for the rapid diagnostic test currently used for SSM-positive patients at risk of drug resistance (i.e. line probe assay (LPA)); (iii) Upfront Xpert testing for patients at risk of drug resistance; and (iv) Xpert as a replacement for SSM for all patients. Results The total costs associated with diagnosis for 100,000 presumptive TB cases were: (i) US$ 619,042 for SSM-only; (ii) US$ 575,377 in the LPA replacement scenario; (iii) US$ 720,523 in the SSM replacement scenario; and (iv) US$ 1,639,643 in the Xpert-for-all scenario. Total cohort costs, including treatment costs, increased by 46% from the SSM-only to the Xpert-for-all strategy, largely due to the costs associated with second-line treatment of a higher number of rifampicin-resistant patients due to increased drug-resistant TB (DR-TB) case detection. The diagnostic costs for an estimated 7.64 million presumptive TB patients would comprise (i) 19%, (ii) 17%, (iii) 22% and (iv) 50% of the annual TB control budget. Mean total costs, expressed per DR-TB case initiated on treatment, were lowest in the Xpert-for-all scenario (US$ 11,099). Conclusions The Xpert-for-all strategy would result in the greatest increase of TB and DR-TB case detection, but would also have the highest associated costs. The strategy of using Xpert only for patients at risk for DR-TB would be more affordable, but would miss DR-TB cases and the cost per true DR-TB case detected would be higher compared to the Xpert-for-all strategy. As such expanded Xpert strategy would require significant increased TB control budget to ensure that

Systematic review: Comparison of Xpert MTB/RIF, LAMP and SAT methods for the diagnosis of pulmonary tuberculosis.

PubMed

Yan, Liping; Xiao, Heping; Zhang, Qing

2016-01-01

Technological advances in nucleic acid amplification have led to breakthroughs in the early detection of PTB compared to traditional sputum smear tests. The sensitivity and specificity of loop-mediated isothermal amplification (LAMP), simultaneous amplification testing (SAT), and Xpert MTB/RIF for the diagnosis of pulmonary tuberculosis were evaluated. A critical review of previous studies of LAMP, SAT, and Xpert MTB/RIF for the diagnosis of pulmonary tuberculosis that used laboratory culturing as the reference method was carried out together with a meta-analysis. In 25 previous studies, the pooled sensitivity and specificity of the diagnosis of tuberculosis were 93% and 94% for LAMP, 96% and 88% for SAT, and 89% and 98% for Xpert MTB/RIF. The I(2) values for the pooled data were >80%, indicating significant heterogeneity. In the smear-positive subgroup analysis of LAMP, the sensitivity increased from 93% to 98% (I(2) = 2.6%), and specificity was 68% (I(2) = 38.4%). In the HIV-infected subgroup analysis of Xpert MTB/RIF, the pooled sensitivity and specificity were 79% (I(2) = 72.9%) and 99% (I(2) = 64.4%). In the HIV-negative subgroup analysis for Xpert MTB/RIF, the pooled sensitivity and specificity were 72% (I(2) = 49.6%) and 99% (I(2) = 64.5%). LAMP, SAT and Xpert MTB/RIF had comparably high levels of sensitivity and specificity for the diagnosis of tuberculosis. The diagnostic sensitivity and specificity of three methods were similar, with LAMP being highly sensitive for the diagnosis of smear-positive PTB. The cost effectiveness of LAMP and SAT make them particularly suitable tests for diagnosing PTB in developing countries. Copyright © 2015 Elsevier Ltd. All rights reserved.

Rapid Diagnosis of Tuberculosis with the Xpert MTB/RIF Assay in High Burden Countries: A Cost-Effectiveness Analysis

PubMed Central

Vassall, Anna; van Kampen, Sanne; Sohn, Hojoon; Michael, Joy S.; John, K. R.; den Boon, Saskia; Davis, J. Lucian; Whitelaw, Andrew; Nicol, Mark P.; Gler, Maria Tarcela; Khaliqov, Anar; Zamudio, Carlos; Perkins, Mark D.; Boehme, Catharina C.; Cobelens, Frank

2011-01-01

Background Xpert MTB/RIF (Xpert) is a promising new rapid diagnostic technology for tuberculosis (TB) that has characteristics that suggest large-scale roll-out. However, because the test is expensive, there are concerns among TB program managers and policy makers regarding its affordability for low- and middle-income settings. Methods and Findings We estimate the impact of the introduction of Xpert on the costs and cost-effectiveness of TB care using decision analytic modelling, comparing the introduction of Xpert to a base case of smear microscopy and clinical diagnosis in India, South Africa, and Uganda. The introduction of Xpert increases TB case finding in all three settings; from 72%–85% to 95%–99% of the cohort of individuals with suspected TB, compared to the base case. Diagnostic costs (including the costs of testing all individuals with suspected TB) also increase: from US$28–US$49 to US$133–US$146 and US$137–US$151 per TB case detected when Xpert is used “in addition to” and “as a replacement of” smear microscopy, respectively. The incremental cost effectiveness ratios (ICERs) for using Xpert “in addition to” smear microscopy, compared to the base case, range from US$41–$110 per disability adjusted life year (DALY) averted. Likewise the ICERS for using Xpert “as a replacement of” smear microscopy range from US$52–$138 per DALY averted. These ICERs are below the World Health Organization (WHO) willingness to pay threshold. Conclusions Our results suggest that Xpert is a cost-effective method of TB diagnosis, compared to a base case of smear microscopy and clinical diagnosis of smear-negative TB in low- and middle-income settings where, with its ability to substantially increase case finding, it has important potential for improving TB diagnosis and control. The extent of cost-effectiveness gain to TB programmes from deploying Xpert is primarily dependent on current TB diagnostic practices. Further work is required during

Cost analysis of different diagnostic algorithms for pulmonary tuberculosis varying in placement of Xpert MTB/RIF.

PubMed

Chadha, V K; Sebastian, George; Kumar, P

2016-01-01

We undertook cost analysis for diagnosis of pulmonary tuberculosis (PTB) using present algorithm under Revised National Tuberculosis Control programme and using Xpert MTB/RIF (Xpert) as frontline test or in conjunction with smear microscopy and/or chest radiography. Costs were estimated for different strategies: (A) present algorithm involving sputum smear examination followed by antibiotic trial in smear negative patients, repeat smear examination (RE) if symptoms continue and chest radiography if RE negative; (B) direct Xpert; (C) smear microscopy followed by Xpert in smear negative patients; (D) radiography followed by Xpert in those having abnormal pulmonary shadows; and (E) smear examination followed by radiography among smear negative patients and Xpert in presence of abnormal pulmonary shadow. Cost to program was estimated lowest with Strategy A and highest with Strategy B. Compared to the latter, program cost reduces by 7%, 4.5%, and 17.4% by strategies C, D, and E, respectively. Cost to the group of individuals with presumptive PTB and their attendants is significantly higher for Strategy A compared to other four strategies. Among the latter, the patients' cost was minimum with Strategy B and maximum with Strategy C. Program cost per case diagnosed was lowest by Strategy A and highest by Strategy B. Patient cost per case diagnosed was highest by Strategy A and lowest by Strategy B. Using Xpert, Strategy E had the lowest program as well as overall cost per case diagnosed. Strategy E may be chosen for diagnosis of PTB. When resources would no longer be a constraint, direct Xpert would reduce costs incurred by the patients. Copyright © 2016 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

The Impact and Cost of Scaling up GeneXpert MTB/RIF in South Africa

PubMed Central

Meyer-Rath, Gesine; Schnippel, Kathryn; Long, Lawrence; MacLeod, William; Sanne, Ian; Stevens, Wendy; Pillay, Sagie; Pillay, Yogan; Rosen, Sydney

2012-01-01

Objective We estimated the incremental cost and impact on diagnosis and treatment uptake of national rollout of Xpert MTB/RIF technology (Xpert) for the diagnosis of pulmonary TB above the cost of current guidelines for the years 2011 to 2016 in South Africa. Methods We parameterised a population-level decision model with data from national-level TB databases (n = 199,511) and implementation studies. The model follows cohorts of TB suspects from diagnosis to treatment under current diagnostic guidelines or an algorithm that includes Xpert. Assumptions include the number of TB suspects, symptom prevalence of 5.5%, annual suspect growth rate of 10%, and 2010 public-sector salaries and drug and service delivery costs. Xpert test costs are based on data from an in-country pilot evaluation and assumptions about when global volumes allowing cartridge discounts will be reached. Results At full scale, Xpert will increase the number of TB cases diagnosed per year by 30%–37% and the number of MDR-TB cases diagnosed by 69%–71%. It will diagnose 81% of patients after the first visit, compared to 46% currently. The cost of TB diagnosis per suspect will increase by 55% to USD 60–61 and the cost of diagnosis and treatment per TB case treated by 8% to USD 797–873. The incremental capital cost of the Xpert scale-up will be USD 22 million and the incremental recurrent cost USD 287–316 million over six years. Conclusion Xpert will increase both the number of TB cases diagnosed and treated and the cost of TB diagnosis. These results do not include savings due to reduced transmission of TB as a result of earlier diagnosis and treatment initiation. PMID:22693561

Diagnostic usefulness of Xpert MTB/RIF assay for detection of tuberculous meningitis using cerebrospinal fluid.

PubMed

Rufai, Syed Beenish; Singh, Amit; Singh, Jitendra; Kumar, Parveen; Sankar, Manimuthu Mani; Singh, Sarman

2017-08-01

Tuberculous meningitis (TBM) is the most severe form of extra-pulmonary tuberculosis (TB) due to association of diseases with high rates of mortality and morbidity. Diagnosis continues to be a clinical challenge as microbiological confirmation is rare and time consuming resulting in delayed treatment. Xpert MTB/RIF assay is a rapid and simple test, which has been endorsed by World Health Organization as an initial diagnostic test for the diagnosis of TBM. However, evidence still lacks for its performance on cerebrospinal fluid (CSF) for the diagnosis of TBM especially from India. A total of 267 CSF samples from patients with high clinico-radiological suspicion of TBM were included in this study. Ziehl-Neelsen (ZN) staining, BACTEC Mycobacterial Growth Indicator Tube (MGIT-960) culture system, and Xpert MTB/RIF assay (using cartridge version G4) were tested on all samples. Of total 267 samples, all were negative for smear AFB and 52 (19.5%) were culture positive by MGIT-960 culture system. However, out of 52 (19.5%) cultures detected positive by MGIT-960, 5 (9.6%) were detected as resistant to rifampicin. Xpert MTB/RIF assay was positive in 38 (14.2%) samples and negative in 223 (83.5%) samples. Cartridge error was detected in 6 (2.2%) samples, which could not be repeated due to insufficient sample volume. The sensitivity and specificity of Xpert MTB/RIF assay in comparison to MGIT-960 was 55.1% (95%, CI: 40.2-69.3) and 94.8% (95%, CI: 90.9-97.4) respectively. Overall, Xpert MTB/RIF assay detected 38 (14.2%) as positive for MTB of which 4 (10.5%), 31 (81.6%) and 3 (7.9%) were found to be rifampicin resistant, sensitive and indeterminate respectively. Xpert MTB/RIF assay showed lower sensitivity as compared to MGIT 960 culture for the diagnosis of TBM from CSF samples. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

High prevalence of multidrug-resistant tuberculosis among patients with rifampicin resistance using GeneXpert Mycobacterium tuberculosis/rifampicin in Ghana.

PubMed

Boakye-Appiah, Justice K; Steinmetz, Alexis R; Pupulampu, Peter; Ofori-Yirenkyi, Stephen; Tetteh, Ishmael; Frimpong, Michael; Oppong, Patrick; Opare-Sem, Ohene; Norman, Betty R; Stienstra, Ymkje; van der Werf, Tjip S; Wansbrough-Jones, Mark; Bonsu, Frank; Obeng-Baah, Joseph; Phillips, Richard O

2016-06-01

Drug-resistant strains of tuberculosis (TB) represent a major threat to global TB control. In low- and middle-income countries, resource constraints make it difficult to identify and monitor cases of resistance using drug susceptibility testing and culture. Molecular assays such as the GeneXpert Mycobacterium tuberculosis/rifampicin may prove to be a cost-effective solution to this problem in these settings. The objective of this study is to evaluate the use of GeneXpert in the diagnosis of pulmonary TB since it was introduced into two tertiary hospitals in Ghana in 2013. A 2-year retrospective audit of clinical cases involving patients who presented with clinically suspected TB or documented TB not improving on standard therapy and had samples sent for GeneXpert testing. GeneXpert identified 169 cases of TB, including 17 cases of rifampicin-resistant TB. Of the seven cases with final culture and drug susceptibility testing results, six demonstrated further drug resistance and five of these were multidrug-resistant TB. These findings call for a scale-up of TB control in Ghana and provide evidence that the expansion of GeneXpert may be an optimal means to improve case finding and guide treatment of drug-resistant TB in this setting. Copyright © 2016. Published by Elsevier Ltd.

Cost Analysis of Tuberculosis Diagnosis in Cambodia with and without Xpert® MTB/RIF for People Living with HIV/AIDS and People with Presumptive Multidrug-resistant Tuberculosis.

PubMed

Pallas, Sarah Wood; Courey, Marissa; Hy, Chhaily; Killam, Wm Perry; Warren, Dora; Moore, Brittany

2018-06-04

The Xpert ® MTB/RIF (Xpert) test has been shown to be effective and cost-effective for diagnosing tuberculosis (TB) under conditions with high HIV prevalence and HIV-TB co-infection but less is known about Xpert's cost in low HIV prevalence settings. Cambodia, a country with low HIV prevalence (0.7%), high TB burden, and low multidrug-resistant (MDR) TB burden (1.4% of new TB cases, 11% of retreatment cases) introduced Xpert into its TB diagnostic algorithms for people living with HIV (PLHIV) and people with presumptive MDR TB in 2012. The study objective was to estimate these algorithms' costs pre- and post-Xpert introduction in four provinces of Cambodia. Using a retrospective, ingredients-based microcosting approach, primary cost data on personnel, equipment, maintenance, supplies, and specimen transport were collected at four sites through observation, records review, and key informant consultations. Across the sample facilities, the cost per Xpert test was US$33.88-US$37.11, clinical exam cost US$1.22-US$1.84, chest X-ray cost US$2.02-US$2.14, fluorescent microscopy (FM) smear cost US$1.56-US$1.93, Ziehl-Neelsen (ZN) smear cost US$1.26, liquid culture test cost US$11.63-US$22.83, follow-on work-up for positive culture results and Mycobacterium tuberculosis complex (MTB) identification cost US$11.50-US$14.72, and drug susceptibility testing (DST) cost US$44.26. Specimen transport added US$1.39-US$5.21 per sample. Assuming clinician adherence to the algorithms and perfect test accuracy, the normative cost per patient correctly diagnosed under the post-Xpert algorithms would be US$25-US$29 more per PLHIV and US$34-US$37 more per person with presumptive MDR TB (US$41 more per PLHIV when accounting for variable test sensitivity and specificity). Xpert test unit costs could be reduced through lower cartridge prices, longer usable life of GeneXpert ® (Cepheid, USA) instruments, and increased test volumes; however, epidemiological and test eligibility conditions in

Accuracy of giant African pouched rats for diagnosing tuberculosis: comparison with culture and Xpert® MTB/RIF.

PubMed

Mulder, C; Mgode, G F; Ellis, H; Valverde, E; Beyene, N; Cox, C; Reid, S E; Van't Hoog, A H; Edwards, T L

2017-11-01

Enhanced tuberculosis (TB) case finding using detection rats in Tanzania. To assess the diagnostic accuracy of detection rats compared with culture and Xpert® MTB/RIF, and to compare enhanced case-finding algorithms using rats in smear-negative presumptive TB patients. A fully paired diagnostic accuracy study in which sputum of new adult presumptive TB patients in Tanzania was tested using smear microscopy, 11 detection rats, culture and Xpert. Of 771 eligible participants, 345 (45%) were culture-positive for Mycobacterium tuberculosis, and 264 (34%) were human immunodeficiency virus (HIV) positive. The sensitivity of the detection rats was up to 75.1% (95%CI 70.1-79.5) when compared with culture, and up to 81.8% (95%CI 76.0-86.5) when compared with Xpert, which was statistically significantly higher than the sensitivity of smear microscopy. Corresponding specificity was 40.6% (95%CI 35.9-45.5) compared with culture. The accuracy of rat detection was independent of HIV status. Using rats for triage, followed by Xpert, would result in a statistically higher yield than rats followed by light-emitting diode fluorescence microscopy, whereas the number of false-positives would be significantly lower than when using Xpert alone. Although detection rats did not meet the accuracy criteria as standalone diagnostic or triage testing for presumptive TB, they have additive value as a triage test for enhanced case finding among smear-negative TB patients if more advanced diagnostics are not available.

Performance of Xpert MTB/RIF on Ascitic Fluid Samples for Detection of Abdominal Tuberculosis.

PubMed

Rufai, Syed Beenish; Singh, Sarman; Singh, Amit; Kumar, Parveen; Singh, Jitendra; Vishal, Anand

2017-01-01

Diagnosis of abdominal tuberculosis (TB) from ascitic fluid samples using routinely available diagnostic methods is challenging due to its paucibacillary nature. Although performance of Xpert MTB/RIF assay has been evaluated extensively on pulmonary samples, its performance on extrapulmonary samples is still under evaluation. The objective of this study was to find out the performance of Xpert MTB/RIF on ascitic fluid samples obtained from suspected cases of abdominal TB. Performance was compared with Mycobacterium growth indicator tube-960 (MGIT-960) culture and in-house multiplex polymerase chain reaction (PCR). The latter detects and differentiates Mycobacterium tuberculosis and nontuberculous mycobacteria simultaneously. Sixty-seven patients suspected of probable/possible abdominal TB were included in this observational, prospective study. All samples were tested by Ziehl-Neelsen staining, MGIT-960 culture, in-house multiplex PCR, and Xpert MTB/RIF assay. All 67 samples were smear negative. Seventeen (25.4%) were MGIT-960 culture positive while 12 (17.9%) were detected positive by the Xpert MTB/RIF assay and 9 (13.4%) by in-house multiplex PCR. Sensitivity and specificity of the Xpert MTB/RIF assay compared with the MGIT-960 culture were 70.6% (95%, confidence interval [CI]: 44.1-89.7) and 100% (95%, CI: 92.8-100) and that of in-house multiplex PCR were 52.9% (95%, CI: 30.9-73.8) and 100% (95%, CI: 92.8-100), respectively. Diagnostic yield of Xpert MTB/RIF assay on ascitic fluid samples was lower than MGIT-960 culture. We thus emphasize on the need for urgent discovery of new biomarkers for paucibacillary TB.

Rapid microbiological screening for tuberculosis in HIV-positive patients on the first day of acute hospital admission by systematic testing of urine samples using Xpert MTB/RIF: a prospective cohort in South Africa.

PubMed

Lawn, Stephen D; Kerkhoff, Andrew D; Burton, Rosie; Schutz, Charlotte; van Wyk, Gavin; Vogt, Monica; Pahlana, Pearl; Nicol, Mark P; Meintjes, Graeme

2015-08-14

Autopsy studies of HIV/AIDS-related hospital deaths in sub-Saharan Africa reveal frequent failure of pre-mortem diagnosis of tuberculosis (TB), which is found in 34-64 % of adult cadavers. We determined the overall prevalence and predictors of TB among consecutive unselected HIV-positive adults requiring acute hospital admission and the comparative diagnostic yield obtained by screening urine and sputum samples obtained on day 1 of admission with Xpert MTB/RIF (Xpert). To determine overall TB prevalence accurately, comprehensive clinical sampling (sputum, urine, blood plus other relevant samples) was done and TB was defined by detection of Mycobacterium tuberculosis in any sample using Xpert and/or mycobacterial liquid culture. To evaluate a rapid screening strategy, we compared the diagnostic yield of Xpert testing sputum samples and urine samples obtained with assistance from a respiratory study nurse in the first 24 h of admission. Unselected HIV-positive acute adult new medical admissions (n = 427) who were not receiving TB treatment were enrolled irrespective of clinical presentation or symptom profile. From 2,391 cultures and Xpert tests done (mean, 5.6 tests/patient) on 1,745 samples (mean, 4.1 samples/patient), TB was diagnosed in 139 patients (median CD4 cell count, 80 cells/μL). TB prevalence was very high (32.6 %; 95 % CI, 28.1-37.2 %; 139/427). However, patient symptoms and risk factors were poorly predictive for TB. Overall, ≥1 non-respiratory sample(s) tested positive in 115/139 (83 %) of all TB cases, including positive blood cultures in 41/139 (29.5 %) of TB cases. In the first 24 h of admission, sputum (spot and/or induced samples) and urine were obtainable from 37.0 % and 99.5 % of patients, respectively (P <0.001). From these, the proportions of total TB cases (n = 139) that were diagnosed by Xpert testing sputum, urine or both sputum and urine combined within the first 24 h were 39/139 (28.1 %), 89/139 (64.0 %) and 108/139 (77.7 %) cases

Identification of Mycobacterium tuberculosis and rifampin resistance in clinical specimens using the Xpert MTB/RIF assay.

PubMed

Kim, Cheol-Hong; Hyun, In Gyu; Hwang, Yong Il; Kim, Dong-Gyu; Lee, Chang Youl; Lee, Myung Goo; Jung, Ki-Suck; Woo, Heungjeong; Hyun, Jeongwon; Kim, Hyun Soo; Park, Myung Jae

2015-01-01

The Xpert MTB/RIF assay is a novel real-time polymerase chain reaction technique for the detection of the Mycobacterium tuberculosis (MTB) complex and rifampin (RIF) resistance. We evaluated the performance of this assay in identifying MTB and resistance to RIF in clinical specimens. We analyzed clinical specimens from 383 patients with suspected TB who were hospitalized at a secondary hospital in Korea. Specimens were processed using the Xpert MTB/RIF assay, acid-fast bacilli smear and culture, and drug susceptibility test (DST). Among the 444 clinical samples analyzed, the Xpert MTB/RIF assay identified MTB in 56 (13.8%) of 405 respiratory specimens, but did not detect MTB in the remaining 39 non-respiratory specimens. Of the 65 pulmonary TB patients, 52 (80.0%) were confirmed by using mycobacterial culture as a reference standard. The sensitivity, specificity, PPV, and NPV of the Xpert MTB/RIF assay were 73.85%, 99.03%, 94.12%, and 94.72%, respectively. Among five patients with RIF resistance determined by the Xpert MTB/RIF assay, four (80%) were confirmed as suffering from multidrug-resistant (MDR) TB by DST. The Xpert MTB/RIF assay appears to be an accurate, simple, and useful technique for detecting MTB, especially in respiratory specimens. However, RIF resistance, if detected, should be verified with DST. © 2015 by the Association of Clinical Scientists, Inc.

Impact of GeneXpert MTB/RIF assay on triage of respiratory isolation rooms for inpatients with presumed tuberculosis: a hypothetical trial.

PubMed

Chaisson, Lelia H; Roemer, Marguerite; Cantu, David; Haller, Barbara; Millman, Alexander J; Cattamanchi, Adithya; Davis, J Lucian

2014-11-15

Placing inpatients with presumed active pulmonary tuberculosis in respiratory isolation pending results of serial sputum acid-fast bacilli (AFB) smear microscopy is standard practice in high-income countries. However, this diagnostic strategy is slow and yields few tuberculosis diagnoses. We sought to determine if replacing microscopy with the GeneXpert MTB/RIF (Xpert) nucleic acid amplification assay could reduce testing time and usage of isolation rooms. We prospectively followed inpatients at San Francisco General Hospital undergoing tuberculosis evaluation. We performed smear microscopy and Xpert testing on concentrated sputum, and calculated diagnostic accuracy for both strategies in reference to serial sputum mycobacterial culture. We measured turnaround time for microscopy and estimated hypothetical turnaround times for Xpert on concentrated and unconcentrated sputum. We compared median and total isolation times for microscopy to those estimated for the 2 Xpert strategies. Among 139 patients with 142 admissions, median age was 54 years (interquartile range [IQR], 43-60 years); 32 (23%) patients were female, and 42 (30%) were HIV seropositive. Serial sputum smear microscopy and a single concentrated sputum Xpert had identical sensitivity (89%; 95% confidence interval [CI], 52%-100%) and similar specificity (99% [95% CI, 96%-100%] vs 100% [95% CI, 97%-100%]). A single concentrated sputum Xpert could have saved a median of 35 hours (IQR, 24-36 hours) in unnecessary isolation compared with microscopy, and a single unconcentrated sputum Xpert, 45 hours (IQR, 35-46 hours). Replacing serial sputum smear microscopy with a single sputum Xpert could eliminate most unnecessary isolation for inpatients with presumed tuberculosis, greatly benefiting patients and hospitals. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Xpert MTB/RIF for rapid detection of rifampicin-resistant Mycobacterium tuberculosis from pulmonary tuberculosis patients in Southwest Ethiopia.

PubMed

Tadesse, Mulualem; Aragaw, Dossegnaw; Dimah, Belayneh; Efa, Feyisa; Abebe, Gemeda

2016-12-01

Accurate and rapid detection of drug-resistant strains of tuberculosis (TB) is critical for early initiation of treatment and for limiting the transmission of drug-resistant TB. Here, we investigated the accuracy of Xpert MTB/RIF for detection of rifampicin (RIF) resistance, and whether this detection predicts the presence of multidrug resistant (MDR) TB in Southwest Ethiopia. Smear- or culture-positive sputa obtained from TB patients with increased suspicion of drug resistance were included in this study. GenoType MTBDRplus line-probe assays (LPAs) and Xpert MTB/RIF tests were performed on smear-positive sputum specimens and on cultured isolates for smear-negative specimens. We performed routine drug-susceptibility testing using LPA as the reference standard for confirmation of RIF and isoniazid (INH) resistance. First-line drug-susceptibility results were available for 67 Mycobacterium tuberculosis complex-positive sputum specimens using the LPA test, with our preliminary results indicating that 30% (20/67) were MDR-TB, 3% (2/67) were RIF monoresistant, 6% (4/67) were INH monoresistant, and 61% (41/67) were susceptible to both RIF and INH. Relative to routine RIF-susceptibility testing (LPA), Xpert MTB/RIF detected all RIF resistance correctly, with 100% sensitivity and 97.8% specificity and a positive-predictive value of 95.7%. Of the 23 RIF-resistant strains according to Xpert MTB/RIF, 87% (20/23) were resistant to both RIF and INH (MDR), 8.7% (2/23) were RIF monoresistant, and 4.3% (1/23) were sensitive to RIF according to the LPA test. A high proportion of RIF resistance was documented among patients previously categorized as failure cases (50%, 10/20), followed by relapse cases (31.6%, 6/19) and defaulters (28.6%, 2/7). Xpert MTB/RIF was highly effective at identifying RIF-resistant strains in smear- or culture-positive samples. RIF resistance based on Xpert MTB/RIF results could be used to estimate MDR and allow rapid initiation of MDR-TB treatment in

Performance evaluation of Xpert MTB/RIF in a moderate tuberculosis incidence compared with TaqMan MTB and TRCRapid M.TB.

PubMed

Tsuyuguchi, Kazunari; Nagai, Hideaki; Ogawa, Kenji; Matsumoto, Tomoshige; Morimoto, Kozo; Takaki, Akiko; Mitarai, Satoshi

2017-02-01

Xpert MTB/RIF is an automated nucleic acid amplification test (NAT) that can detect the presence of Mycobacterium tuberculosis complex (MTC) in clinical specimens as well as rifampicin (RIF) resistance resulting from rpoB mutation. Despite its high sensitivity and specificity for diagnosing tuberculosis (TB) with or without RIF resistance, the clinical performance of the test is variable. In this study, we evaluated the performance of Xpert MTB/RIF in a setting of moderate TB burden and high medical resources. A total of 427 sputum specimens were obtained from 237 suspected TB cases. Of these, 159 were identified as active TB, while the other 78 were non-TB diseases. The overall sensitivity and specificity of MTC detection by Xpert MTB/RIF using culture results as a reference were 86.8% [95% confidence interval (CI): 81.8%-90.6%] and 96.8% (95% CI: 93.1%-98.5%), respectively. Among MTC-positive culture specimens, Xpert MTB/RIF positivity was 95.2% (95% CI: 91.2%-97.5%) in smear-positive and 44.7% (95% CI 30.1-60.3) in smear-negative specimens. Xpert MTB/RIF was similar to other NATs (TaqMan MTB and TRCRapid M.TB) in terms of performance. Xpert MTB/RIF detected 25 RIF-resistant isolates as compared to 22 with the mycobacterial growth indicator tube antimicrobial susceptibility testing system, yielding a sensitivity of 100% (95% CI: 85.1%-100%) and specificity of 98.3% (95% CI: 95.1%-99.4%). These results indicate that although sensitivity in smear-negative/culture-positive specimens was relatively low, Xpert MTB/RIF is a useful diagnostic tool for detecting TB and RIF resistance even in settings of moderate TB burden. Copyright © 2016. Published by Elsevier Ltd.

Laboratory diagnosis of Clostridium difficile infection: Comparison of Techlab C. diff Quik Chek Complete, Xpert C. difficile, and multistep algorithmic approach.

PubMed

Seo, Ja Young; Jeong, Ji Hun; Kim, Kyung Hee; Ahn, Jeong-Yeal; Park, Pil-Whan; Seo, Yiel-Hea

2017-11-01

Clostridium difficile is a major pathogen responsible for nosocomial infectious diarrhea. We explored optimal laboratory strategies for diagnosis of C. difficile infection (CDI) in our clinical settings, a 1400-bed tertiary care hospital. Using 191 fresh stool samples from adult patients, we evaluated the performance of Xpert C. difficile (Xpert CD), C. diff Quik Chek Complete (which simultaneously detects glutamate dehydrogenase [GDH] and C. difficile toxins [CDT]), toxigenic culture, and a two-step algorithm composed of GDH/CDT as a screening test and Xpert CD as a confirmatory test. Clostridium difficile was detected in 35 samples (18.3%), and all isolates were toxigenic strains. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value of each assay for detecting CDI were as follows: Quik Chek Complete CDT (45.7%, 100%, 100%, 89.1%), Quik Chek Complete GDH (97.1%, 99.4%, 97.1%, 99.4%), Xpert CD (94.3%, 100%, 100%, 98.7%), and toxigenic culture (91.4%, 100%, 100%, 98.1%). A two-step algorithm performed identically with Xpert CD assay. Our data showed that most C. difficile isolates from adult patients were toxigenic. We demonstrated that a two-step algorithm based on GDH/CDT assay followed by Xpert CD assay as a confirmatory test was rapid, reliable, and cost effective for diagnosis of CDI in an adult patient setting with high prevalence of toxigenic C. difficile. © 2017 Wiley Periodicals, Inc.

Evaluation of GeneXpert MTB/RIF for detection of pulmonary tuberculosis at peripheral tuberculosis clinics.

PubMed

Shao, Yan; Peng, Hong; Chen, Cheng; Zhu, Tao; Ji, Ming; Jiang, Wei; Zhu, Wei; Zhai, Xiang Jun; Lu, Wei

2017-04-01

Tuberculosis is one of the most common infectious diseases in China, while delayed patient finding obstructed disease control, especially for smear-negative patients. The current study was undertaken to evaluate the diagnostic accuracy of GeneXpert MTB/RIF compared with conventional methods in the detection of pulmonary tuberculosis patients. A total of 295 spot sputum samples from confirmed pulmonary tuberculosis patients were evaluated from September 2014 to June 2015. Each sample was examined by acid-fast bacillus smear microscopy, culture and GeneXpert MTB/RIF. The sputum culture on Löwenstein-Jensen (L-J) was considered as the gold-standard. After testing by smear, 68.81% (203/295) was negative and 31.19% (92/295) was positive. As the gold-standard, L-J culture detected 37.97% (112/295) positive of all specimens, while the positivity for GeneXpert MTB/RIF was 46.44% (137/295). Compared with L-J culture, the combined sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for GeneXpert MTB/RIF were 94.64%, 82.97%, 77.37% and 96.18% respectively. For smear-negative specimens, the sensitivity, specificity, PPV and NPV for GeneXpert MTB/RIF were 96.00%, 83.05%, 44.44% and 99.32%; while for smear-positive specimens, the corresponding accuracy values were 94.25%, 80.00%, 98.80% and 44.44%. The findings of study indicated that GeneXpert MTB/RIF assay demonstrated a high sensitivity in detecting Mycobacterium tuberculosis compared to smear method and a high NPV among smear negative patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Novel multi-day sputum transport reagent works with routine tuberculosis tests and eliminates need for cold chain: Preliminary study of compatibility with the Xpert® MTB/RIF assay.

PubMed

Kelly-Cirino, Cassandra D; Curry, Patricia S; Marola, Jamie L; Helstrom, Niels K; Salfinger, Max

2016-11-01

OMNIgene®•SPUTUM (OM-S) is a sputum transport reagent designed to work with all tuberculosis diagnostics and eliminate the need for cold chain. The aim of this preliminary study was to assess the compatibility of OM-S-treated sputum with the Xpert® MTB/RIF assay. Fifty-five characterized sputa from the FIND TB Specimen Bank were used. Compatibility of OM-S was assessed for both Xpert sample preparation methods: H.1 protocol (sediment, n=25) and H.2 protocol (direct expectorate, n=30). All controls were prepared using the H.2 protocol. Results revealed 100% concordance of MTB/RIF results for all except the low-positive group in the H.1 study arm (n=10; 88% concordance). OM-S-treated sputa were successful in both protocols; if the Xpert buffer is not added during the H.2 procedure, sample viscosity may require repeat testing. Using OM-S could offer users flexibility in clinical testing algorithms. Larger compatibility studies are warranted, particularly with respect to MTB/RIF results for low-positive samples. Copyright © 2016 Elsevier Inc. All rights reserved.

Diagnostic accuracy of GeneXpert MTB/RIF in musculoskeletal tuberculosis: High sensitivity in tissue samples of HIV-infected and HIV-uninfected patients.

PubMed

Held, M; Laubscher, M; Workman, L; Zar, H J; Dunn, R

2017-09-22

GeneXpert MTB/RIF is useful for the diagnosis of pulmonary TB in adults, but there is limited evidence on its usefulness in extrapulmonary TB. To investigate the diagnostic accuracy of GeneXpert MTB/RIF in HIV-infected and HIV-uninfected patients with suspected musculoskeletal TB. A prospective study of patients with suspected musculoskeletal (bone and joint) TB was undertaken. The diagnostic accuracy of GeneXpert MTB/RIF was compared with the reference standards of culture and histopathology. A total of 206 biopsies from 201 patients (23% HIV-infected) were evaluated. The sensitivity and specificity of GeneXpert MTB/RIF was 92.3% (84/91) and 99.1% (114/115), respectively. GeneXpert MTB/RIF detected 8.8% more cases than culture (84/91 (92.3%) v. 76/91 (83.5%), respectively; p=0.069). GeneXpert MTB/RIF also detected all 4 multidrug-resistant TB cases and an additional 2 rifampicin-resistant cases in culture-negative samples. The sensitivity of GeneXpert MTB/RIF in HIV-infected patients was 96.9% (31/32) v. 89.6% (43/48) in HIV-uninfected patients (p=0.225). GeneXpert MTB/RIF is an accurate test for the detection of TB in tissue samples of HIV-infected and HIV-uninfected patients with suspected musculoskeletal TB. A positive GeneXpert MTB/RIF result should be regarded as microbiological confirmation of TB.

Use of GeneXpert Remnants for Drug Resistance Profiling and Molecular Epidemiology of Tuberculosis in Libreville, Gabon.

PubMed

Alame-Emane, Amel Kévin; Pierre-Audigier, Catherine; Aboumegone-Biyogo, Oriane Cordelia; Nzoghe-Mveang, Amandine; Cadet-Daniel, Véronique; Sola, Christophe; Djoba-Siawaya, Joël Fleury; Gicquel, Brigitte; Takiff, Howard E

2017-07-01

Multidrug-resistant (MDR) and extensively drug resistant (XDR) strains of Mycobacterium tuberculosis pose major problems for global health. The GeneXpert MTB/RIF (Xpert) assay rapidly detects resistance to rifampin (RIF r ), but for detection of the additional resistance that defines MDR-TB (MDR tuberculosis) and XDR-TB, and for molecular epidemiology, specimen cultures and a biosafe infrastructure are generally required. We sought to determine whether the remnants of sputa prepared for the Xpert assay could be used directly to find mutations associated with drug resistance and to study molecular epidemiology, thus providing precise characterization of MDR-TB cases in countries lacking biosafety level 3 (BSL3) facilities for M. tuberculosis cultures. After sputa were processed and run on the Xpert instrument, the leftovers of the samples prepared for the Xpert assay were used for PCR amplification and sequencing or for a line probe assay to detect mutations associated with resistance to additional drugs, as well as for molecular epidemiology with spoligotyping and selective mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing. Of 130 sputum samples from Gabon tested with the Xpert assay, 124 yielded interpretable results; 21 (17%) of these were determined to be RIF r Amplification and sequencing or a line probe assay of the Xpert remnants confirmed 18/21 samples as MDR, corresponding to 12/116 (9.5%) new and 6/8 (75%) previously treated TB patients. Spoligotyping and MIRU typing with hypervariable loci identified an MDR Beijing strain present in five samples. We conclude that the remnants of samples processed for the Xpert assay can be used in PCRs to find mutations associated with the resistance to the additional drugs that defines MDR and XDR-TB and to study molecular epidemiology without the need for culturing or a biosafe infrastructure. Copyright © 2017 Alame-Emane et al.

Evaluation of Xpert MTB/RIF Versus AFB Smear and Culture to Identify Pulmonary Tuberculosis in Patients With Suspected Tuberculosis From Low and Higher Prevalence Settings

PubMed Central

Luetkemeyer, Anne F.; Firnhaber, Cynthia; Kendall, Michelle A.; Wu, Xingye; Mazurek, Gerald H.; Benator, Debra A.; Arduino, Roberto; Fernandez, Michel; Guy, Elizabeth; Johnson, Pamela; Metchock, Beverly; Sattler, Fred; Telzak, Edward; Wang, Yun F.; Weiner, Marc; Swindells, Susan; Sanne, Ian M.; Havlir, Diane V.; Grinsztejn, Beatriz; Alland, David

2016-01-01

Background. The Xpert MTB/RIF (Xpert) assay is a rapid nucleic acid amplification test widely used in settings of high tuberculosis prevalence to detect tuberculosis as well as rpoB mutations associated with rifampin resistance. Data are needed on the diagnostic performance of Xpert in lower-prevalence settings to inform appropriate use for both tuberculosis detection and the need for respiratory isolation. Methods. Xpert was compared to 2 sputum samples, each evaluated with acid-fast bacilli (AFB) smear and mycobacterial culture using liquid and solid culture media, from participants with suspected pulmonary tuberculosis from the United States, Brazil, and South Africa. Results. Of 992 participants enrolled with evaluable results, 22% had culture-confirmed tuberculosis. In 638 (64%) US participants, 1 Xpert result demonstrated sensitivity of 85.2% (96.7% in participants with AFB smear-positive [AFB+] sputum, 59.3% with AFB smear-negative [AFB–] sputum), specificity of 99.2%, negative predictive value (NPV) of 97.6%, and positive predictive value of 94.9%. Results did not differ between higher- and low-prevalence settings. A second Xpert assay increased overall sensitivity to 91.1% (100% if AFB+, 71.4% if AFB–), with specificity of 98.9%. In US participants, a single negative Xpert result predicted the absence of AFB+/culture-positive tuberculosis with an NPV of 99.7%; NPV of 2 Xpert assays was 100%, suggesting a role in removing patients from airborne infection isolation. Xpert detected tuberculosis DNA and mutations associated with rifampin resistance in 5 of 7 participants with rifampin-resistant, culture-positive tuberculosis. Specificity for rifampin resistance was 99.5% and NPV was 98.9%. Conclusions. In the United States, Xpert testing performed comparably to 2 higher-tuberculosis-prevalence settings. These data support the use of Xpert in the initial evaluation of tuberculosis suspects and in algorithms assessing need for respiratory isolation

Xpert MTB/RIF assay for diagnosis of pulmonary tuberculosis in sputum specimens in remote health care facility.

PubMed

Geleta, Dereje Assefa; Megerssa, Yoseph Cherinet; Gudeta, Adugna Negussie; Akalu, Gizachew Taddesse; Debele, Melaku Tesfaye; Tulu, Kassu Desta

2015-10-19

Xpert MTB/RIF assay is considered as a great advance over conventional smear and culture in the diagnosis of TB and MDR-TB by simultaneously detecting M.tuberculosis and rifampicin resistance bacilli. However, very little information regarding the performance characteristics of Xpert MTB/RIF assay is available in Ethiopia. Therefore, the purpose of this study was to evaluate the performance of Xpert MTB/RIF assay compared to conventional sputum smear and culture methods for the diagnosis of pulmonary tuberculosis in remote health care facility. A paired expectorated sputum samples were obtained from 227 consecutively recruited patients with signs and symptoms suggestive of tuberculosis at Karamara hospital during December 2013 to May 2014. One of the sputum specimen was tested directly by Ziehl-Neelsen staining and Xpert MTB/RIF assay without NALC-NaOH decontamination. The other of pair of sputa specimen was cultured for isolation of TB bacilli by conventional methods. Diagnostic performance of Xpert MTB/RIF assay and AFB smear microscopy were calculated against culture as the gold standard. Overall 25.5% (58/227) samples were positive for Mycobacterium tuberculosis complex (MTBC) by MGIT and/or LJ media of which 36.2% (21/58) and 65.5% (35/58) were positive by AFB smear microscopy and Xpert MTB/RIF respectively. The sensitivity, specificity, as well as the positive and negative predictive value of Xpert MTB/RIF assay were 65.5% (95% CI: 53.3-77.7%), 96.3% (95% CI: 93.4-99.2%), 86.4% (95% CI: 76.2-96.5%), and 88.6% (95% CI: 83.9-93.3%) respectively. Eighteen of 58 (31%) cases that were smear microscopy negative, were positive by Xpert MTB/RIF assay. Although Xpert MTB/RIF assay demonstrated high sensitivity in detecting MTBC in sputum specimens compared with conventional AFB smear microscopy, it demonstrated suboptimal sensitivity in smear negative patients compared to conventional culture.

Evaluating the Diagnostic Accuracy of Xpert MTB/RIF Assay in Pulmonary Tuberculosis

PubMed Central

Sharma, Surendra K; Kohli, Mikashmi; Yadav, Raj Narayan; Chaubey, Jigyasa; Bhasin, Dinkar; Sreenivas, Vishnubhatla; Sharma, Rohini; Singh, Binit K

2015-01-01

Pulmonary tuberculosis still remains a major communicable disease worldwide. In 2013, 9 million people developed TB and 1.5 million people died from the disease. India constitutes 24% of the total TB burden. Early detection of TB cases is the key to successful treatment and reduction of disease transmission. Xpert MTB/RIF, an automated cartridge-based molecular technique detects Mycobacterium tuberculosis and rifampicin resistance within two hours has been endorsed by WHO for rapid diagnosis of TB. Our study is the first study from India with a large sample size to evaluate the performance of Xpert MTB/RIF assay in PTB samples. The test showed an overall sensitivity and specificity of 95.7% (430/449) and 99.3% (984/990) respectively. In smear negative-culture positive cases, the test had a sensitivity of 77.7%. The sensitivity and specificity for detecting rifampicin resistance was 94.5% and 97.7% respectively with respect to culture as reference standard. However, after resolving the discrepant samples with gene sequencing, the sensitivity and specificity rose to 99.0% and 99.3% respectively. Hence, while solid culture still forms the foundation of TB diagnosis, Xpert MTB/RIF proposes to be a strong first line diagnostic tool for pulmonary TB cases. PMID:26496123

Improvement of the Xpert Carba-R Kit for the Detection of Carbapenemase-Producing Enterobacteriaceae

PubMed Central

Fusaro, Mathieu

2016-01-01

The Xpert Carba-R kit, version 2 (v2), which has been improved for the efficient detection of blaOXA-181 and blaOXA-232 genes, was tested on a collection of 150 well-characterized enterobacterial isolates that had a reduced susceptibility to carbapenems. The performance of the Xpert Carba-R v2 was high, as it was able to detect the five major carbapenemases (NDM, VIM, IMP, KPC, and OXA-48). Thus, it is now well adapted to the carbapenemase-producing Enterobacteriaceae epidemiology of many countries worldwide. PMID:27021332

Real-Life Clinical Practice of Using the Xpert MTB/RIF Assay in Thailand.

PubMed

Kawkitinarong, Kamon; Suwanpimolkul, Gompol; Kateruttanakul, Pairaj; Manosuthi, Weerawat; Ubolyam, Sasiwimol; Sophonphan, Jiratchaya; Avihingsanon, Anchalee; Ruxrungtham, Kiat

2017-05-15

Delayed diagnosis of tuberculosis (TB) and drug-resistant TB are major challenges of TB control in Thailand. This study assessed the practicality of the Xpert MTB/RIF assay in a real-life setting with high prevalence of human immunodeficiency virus (HIV) infection and pulmonary tuberculosis (PTB). This prospective study was conducted at 3 large tertiary care hospitals. Patients who had suspected PTB were enrolled into the study. Expectorated sputum samples were sent for staining, mycobacterial culture, and Xpert MTB/RIF. Four hundred ninety-four patients were enrolled. From 355 cases with final diagnosis of PTB, 263 (71.8%) had definite diagnosis and 92 cases had probable diagnosis. Among TB culture-positive cases, Xpert MTB/RIF had 100% and 81% sensitivity in sputum smear-positive and smear-negative groups, respectively. The specificity was 95.7%. The sensitivity and positive predictive value of Xpert MTB/RIF in culture-negative but clinically diagnosed PTB was 37.8% and 83.8%, respectively. Centrifugation was required in 59% cases with scanty sputum. Five cases were false-positive by Xpert MTB/RIF in patients with nontuberculous mycobacteria, old PTB scar, and immune reconstitution syndrome. Discordant rifampicin susceptibility results of Xpert MTB/RIF and mycobacteria growth indicator tube (MGIT) were confirmed by using rpoB gene sequencing, which raised the sensitivity of Xpert MTB/RIF in detecting rifampicin resistance to 93.8%. Xpert MTB/RIF is an effective tool in diagnosing PTB but will be more cost-effective for sputum-negative patients and in settings with high prevalence of rifampicin resistance. Early diagnosis of TB results in early treatment and implementation of strategies to limit spreading of TB. Sputum centrifugation may increase the yield of Xpert MTB/RIF. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Performance du GeneXpert MTB/RIF® dans le diagnostic de la tuberculose extra-pulmonaire à Dakar: 2010-2015

PubMed Central

Diallo, Awa Ba; Kollo, Abdoulkader Issifi; Camara, Makhtar; Lo, Seynabou; Ossoga, Gedeon Walbang; Mbow, Moustapha; Karam, Farba; Niang, Mame Yacine Fall; Thiam, Aliou; Diawara, Awa Ndiaye; Mboup, Souleymane; Diallo, Aissatou Gaye

2016-01-01

Introduction Le défi des pays en voie de développement est la disponibilité de méthodes de diagnostic rapide et précis pour le management de la tuberculose. Des techniques moléculaires offrent cet avantage et nous avons utilisé le test GeneXpert MTB/RIF dans le diagnostic de la tuberculose extra-pulmonaire pour évaluer sa performance par rapport aux méthodes conventionnelles. Méthodes Entre 2010 et 2015, 544 échantillons cliniques extra-pulmonaires ont été recueillis et traitées par la microscopie, la culture et le GeneXpert. L'étude de la sensibilité aux antituberculeux a été effectué avec le MGIT 960. Le Génotype MTBDRplus a été utilisé pour confirmer les cas de résistance à la rifampicine détectés par le système GX. Résultats La population d'étude de 544 patients incluait 55,15% d'hommes et 44,85% de femmes. L'âge des patients variait entre 1 à 92 avec la majorité dans le groupe d'âge 18-45 ans. La sensibilité et la spécificité globale de la microscopie étaient de 43,86% et 98,36%, et pour le GeneXpert® 94,74% et 97,95% respectivement avec 95% IC. Deux résultats de résistance à la rifampicine discordants ont été trouvées entre le test GeneXpert et la méthode phénotypique. Les résultats du test MTBDRplus ont montré une concordance de 100% avec ceux du MGIT 960 pour les cas discordants de résistance à la rifampicine. Conclusion Cette étude a montré que le test GeneXpert a une plus grande sensibilité pour le diagnostic de routine de la tuberculose extra-pulmonaire et devrait être utilisé à la place de la microscopie. Les cas de résistance à la rifampicine détectés par le GeneXpert doivent être confirmés par d'autres tests moléculaires avant d'initier un traitement. PMID:28292091

Xpert®MTB/RIF for the Diagnosis of Tuberculosis in a Remote Arctic Setting: Impact on Cost and Time to Treatment Initiation.

PubMed

Oxlade, Olivia; Sugarman, Jordan; Alvarez, Gonzalo G; Pai, Madhukar; Schwartzman, Kevin

2016-01-01

Tuberculosis (TB) remains a significant health problem in the Canadian Arctic. Substantial health system delays in TB diagnosis can occur, in part due to the lack of capacity for onsite microbiologic testing. A study recently evaluated the yield and impact of a rapid automated PCR test (Xpert®MTB/RIF) for the diagnosis of TB in Iqaluit (Nunavut). We conducted an economic analysis to evaluate the expected cost relative to the expected reduction in time to treatment initiation, with the addition of Xpert®MTB/RIF to the current diagnostic and treatment algorithms used in this setting. A decision analysis model compared current microbiologic testing to a scenario where Xpert®MTB/RIF was added to the current diagnostic algorithm for active TB, and incorporated costs and clinical endpoints from the Iqaluit study. Several sensitivity analyses that considered alternative use were also considered. We estimated days to TB diagnosis and treatment initiation, health system costs, and the incremental cost per treatment day gained for each individual evaluated for possible TB. With the addition of Xpert®MTB/RIF, costs increased while days to TB treatment initiation were reduced. The incremental cost per treatment day gained (per individual investigated for TB) was $164 (95% uncertainty range $85, $452). In a sensitivity analysis that considered hospital discharge after a single negative Xpert®MTB/RIF, the Xpert®MTB/RIF scenario was cost saving. Adding Xpert®MTB/RIF to the current diagnostic algorithm for TB in Nunavut appears to reduce time to diagnosis and treatment at reasonable cost. It may be especially well suited to overcome some of the other logistical barriers that are unique to this and other remote communities.

Xpert Flu for point-of-care diagnosis of human influenza in industrialized countries.

PubMed

Salez, Nicolas; Nougairede, Antoine; Ninove, Laetitia; Zandotti, Christine; de Lamballerie, Xavier; Charrel, Rémi N

2014-05-01

Respiratory infections, particularly those caused by influenza viruses, represent the third-most important cause of death in the world due to infectious diseases. Nevertheless, despite the enormous publicity attracted by epidemics due to these viruses, laboratory diagnosis, documentation and recording of respiratory diseases is still unsatisfactory. Available diagnostic tests capable of providing results rapidly are either limited and insufficiently sensitive or highly sensitive and specific but insufficiently rapid. Considerable investment and research efforts have been made towards the development of new diagnostics for influenza A and B viruses and the Xpert(®) Flu assay (Cepheid(®), CA, USA) has emerged as one of the most promising. In this article, we review current knowledge of the Xpert Flu test, discuss its potential value as a point-of-care test and outline the potential leads for future development.

The effect of the Xpert MTB/RIF test on the time to MDR-TB treatment initiation in a rural setting: a cohort study in South Africa's Eastern Cape Province.

PubMed

Iruedo, Joshua; O'Mahony, Don; Mabunda, Sikhumbuzo; Wright, Graham; Cawe, Busisiwe

2017-01-21

There are significant delays in initiation of multidrug-resistant tuberculosis (MDR -TB) treatment. The Xpert MTB/RIF test has been shown to reduce the time to diagnosis and treatment of MDR-TB predominantly in urban centres. This study describes the time to treatment of MDR-TB and the effect of Xpert MTB/RIF on time to treatment in a deprived rural area in South Africa. This was a retrospective cohort study analysing the medical records of patients diagnosed with MDR-TB in King Sabata Dalindyebo Sub-District between 2009 and 2014. Numerical data were reported using the Kruskal-Wallis and Wilcoxon sum rank tests and categorical data compared using the two-sample test of proportions. Of the 342 patients with MDR-TB identified, 285 were eligible for analysis, of whom 145 (61.4%) were HIV positive. The median time from sputum collection to MDR-TB diagnosis was 27 days (IQR: 2-45) and differed significantly between diagnostic modalities: Xpert MTB/RIF, 1 day (IQR: 1-4; n = 114: p < 0.0001); Line Probe Assay 12 days (IQR: 8-21; n = 28; p < 0.0001); and culture/phenotypic drug sensitivity testing 45 days (IQR: 39-59; n = 143: p < 0.0001). The time from diagnosis to treatment initiation was 14 days (IQR: 8-27) and did not differ significantly between diagnostic modality. The median time from sputum collection to treatment initiation was 49 days (IQR: 20-69) but differed significantly between diagnostic modalities: Xpert MTB/RIF, 18 days (IQR: 11-27; n = 114; p < 0.0001); Line Probe Assay 29 days (IQR: 14.5-53; n = 28; p < 0.0001); and culture/phenotypic drug sensitivity, 64 days (IQR: 50-103; n = 143: P < 0.0001). Age, sex and HIV status did not influence the time intervals. Xpert MTB/RIF significantly reduced the time to MDR-TB treatment in a deprived rural setting as a result of a reduced time to diagnosis. However, the national target of five days was not achieved. Further research is needed to explore and

Use of Xpert MTB/RIF in Decentralized Public Health Settings and Its Effect on Pulmonary TB and DR-TB Case Finding in India.

PubMed

Sachdeva, Kuldeep Singh; Raizada, Neeraj; Sreenivas, Achuthan; Van't Hoog, Anna H; van den Hof, Susan; Dewan, Puneet K; Thakur, Rahul; Gupta, R S; Kulsange, Shubhangi; Vadera, Bhavin; Babre, Ameet; Gray, Christen; Parmar, Malik; Ghedia, Mayank; Ramachandran, Ranjani; Alavadi, Umesh; Arinaminpathy, Nimalan; Denkinger, Claudia; Boehme, Catharina; Paramasivan, C N

2015-01-01

Xpert MTB/RIF, the first automated molecular test for tuberculosis, is transforming the diagnostic landscape in high-burden settings. This study assessed the impact of up-front Xpert MTB/RIF testing on detection of pulmonary tuberculosis (PTB) and rifampicin-resistant PTB (DR-TB) cases in India. This demonstration study was implemented in 18 sub-district level TB programme units (TUs) in India in diverse geographic and demographic settings covering a population of 8.8 million. A baseline phase in 14 TUs captured programmatic baseline data, and an intervention phase in 18 TUs had Xpert MTB/RIF offered to all presumptive TB patients. We estimated changes in detection of TB and DR-TB, the former using binomial regression models to adjust for clustering and covariates. In the 14 study TUs, which participated in both phases, 10,675 and 70,556 presumptive TB patients were enrolled in the baseline and intervention phase, respectively, and 1,532 (14.4%) and 14,299 (20.3%) bacteriologically confirmed PTB cases were detected. The implementation of Xpert MTB/RIF was associated with increases in both notification rates of bacteriologically confirmed TB cases (adjusted incidence rate ratio [aIRR] 1.39; CI 1.18-1.64), and proportion of bacteriological confirmed TB cases among presumptive TB cases (adjusted risk ratio (aRR) 1.33; CI 1.6-1.52). Compared with the baseline strategy of selective drug-susceptibility testing only for PTB cases at high risk of drug-resistant TB, Xpert MTB/RIF implementation increased rifampicin resistant TB case detection by over fivefold. Among, 2765 rifampicin resistance cases detected, 1055 were retested with conventional drug susceptibility testing (DST). Positive predictive value (PPV) of rifampicin resistance detected by Xpert MTB/RIF was 94.7% (CI 91.3-98.1), in comparison to conventional DST. Introduction of Xpert MTB/RIF as initial diagnostic test for TB in public health facilities significantly increased case-notification rates of all

Use of Xpert MTB/RIF in Decentralized Public Health Settings and Its Effect on Pulmonary TB and DR-TB Case Finding in India

PubMed Central

Sachdeva, Kuldeep Singh; Raizada, Neeraj; Sreenivas, Achuthan; van't Hoog, Anna H.; van den Hof, Susan; Dewan, Puneet K.; Thakur, Rahul; Gupta, R. S.; Kulsange, Shubhangi; Vadera, Bhavin; Babre, Ameet; Gray, Christen; Parmar, Malik; Ghedia, Mayank; Ramachandran, Ranjani; Alavadi, Umesh; Arinaminpathy, Nimalan; Denkinger, Claudia; Boehme, Catharina; Paramasivan, C. N.

2015-01-01

Background Xpert MTB/RIF, the first automated molecular test for tuberculosis, is transforming the diagnostic landscape in high-burden settings. This study assessed the impact of up-front Xpert MTB/RIF testing on detection of pulmonary tuberculosis (PTB) and rifampicin-resistant PTB (DR-TB) cases in India. Methods This demonstration study was implemented in 18 sub-district level TB programme units (TUs) in India in diverse geographic and demographic settings covering a population of 8.8 million. A baseline phase in 14 TUs captured programmatic baseline data, and an intervention phase in 18 TUs had Xpert MTB/RIF offered to all presumptive TB patients. We estimated changes in detection of TB and DR-TB, the former using binomial regression models to adjust for clustering and covariates. Results In the 14 study TUs, which participated in both phases, 10,675 and 70,556 presumptive TB patients were enrolled in the baseline and intervention phase, respectively, and 1,532 (14.4%) and 14,299 (20.3%) bacteriologically confirmed PTB cases were detected. The implementation of Xpert MTB/RIF was associated with increases in both notification rates of bacteriologically confirmed TB cases (adjusted incidence rate ratio [aIRR] 1.39; CI 1.18-1.64), and proportion of bacteriological confirmed TB cases among presumptive TB cases (adjusted risk ratio (aRR) 1.33; CI 1.6-1.52). Compared with the baseline strategy of selective drug-susceptibility testing only for PTB cases at high risk of drug-resistant TB, Xpert MTB/RIF implementation increased rifampicin resistant TB case detection by over fivefold. Among, 2765 rifampicin resistance cases detected, 1055 were retested with conventional drug susceptibility testing (DST). Positive predictive value (PPV) of rifampicin resistance detected by Xpert MTB/RIF was 94.7% (CI 91.3-98.1), in comparison to conventional DST. Conclusion Introduction of Xpert MTB/RIF as initial diagnostic test for TB in public health facilities significantly increased

Evaluation of the Xpert MTB/RIF assay for diagnosis of tuberculosis and rifampin resistance in county-level laboratories in Hunan province, China.

PubMed

Hu, Peilei; Bai, Liqiong; Liu, Fengping; Ou, Xichao; Zhang, Zhiying; Yi, Songlin; Chen, Zhongnan; Gong, Daofang; Liu, Binbin; Guo, Jingwei; Tan, Yunhong

2014-01-01

The Xpert MTB/RIF showed high sensitivity and specificity in previous studies carried out in different epidemiological and geographical settings and patient populations in high-burden tuberculosis (TB) countries. However, there were little data obtained by validation or demonstration study of the assay in China. In this study, the performance of Xpert MTB/RIF was investigated in two county-level laboratories in Hunan Province, China. Consecutive patients with suspected pulmonary tuberculosis (PTB) and suspicion for multidrug-resistant tuberculosis (MDR-TB) were enrolled. For each patient suspected to have PTB, three sputum specimens (one spot sputum, one night sputum, and one morning sputum) were collected and each sputum was tested with smear microscopy, Löwenstein-Jensen (LJ) culture, and Xpert MTB/RIF test. For comparison across subgroups and testing methods, 95% confidence intervals were calculated. All analyses were done with SPSS 16.0, and P < 0.05 was regarded as significant. For case detection, the sensitivity of Xpert MTB/RIF was 100% for smear- and culture-positive TB and 88.6% for smear-negative and culture-positive TB; the overall sensitivity was 94.5% for all culture-positive patients. The specificity was 99.8%. The sensitivity of Xpert MTB/RIF assay was 22.0% in clinical TB patients and the specificity reached 100.0% in the group of patients who are infected with nontuberculous mycobacteria. For the detection of rifampin resistance, the sensitivity of MTB/RIF RIF-resistance detection was 92.9%, and the specificity was 98.7%. Of the 26 Xpert MTB/RIF-positive and RIF-resistant patients confirmed by LJ proportion tests, 20 (76.9%) patients were infected by MDR-TB. The Xpert MTB/RIF assay is a highly sensitive and specific method for diagnosis of TB and RIF resistance, which will enable it to have the potential to be used in county-level laboratories and lead to the reduction of the infectious pool and improvements in TB control in China. Further

Comparative Study of GeneXpert with ZN Stain and Culture in Samples of Suspected Pulmonary Tuberculosis

PubMed Central

Bajaj, Ashish; Bhatia, Vinay; Dutt, Sarjana

2016-01-01

Introduction Tuberculosis remains one of the deadliest communicable diseases. There are number of tests available for the diagnosis of tuberculosis but conventional microscopy has low sensitivity and culture although gold standard, but takes longer time for positivity. On the other side, Nucleic acid amplification techniques due to its rapidity and sensitivity not only help in early diagnosis and management of tuberculosis especially in patients with high clinical suspicion like immunocompromised patients, history of contact with active tuberculosis patient etc., but also curtail the transmission of the disease. Aim To evaluate the sensitivity, specificity, positive predictive value and negative predictive value of Nucleic acid amplification assay (GeneXpert) using respiratory samples in patients with suspected pulmonary tuberculosis and compare with AFB smear microscopy (Ziehl Neelsen stain) and Acid Fast Bacilli (AFB) culture. Materials and Methods We retrospectively reviewed the respiratory samples of suspected pulmonary tuberculosis (including Bronchoalveolar lavage and sputum) of 170 patients from Jan 2015 to Nov 2015 for ZN stain, culture and GeneXpert (Xpert® MTB/Rif assay). The sensitivity, specificity, PPV and NPV of GeneXpert and ZN microscopy were calculated using Liquid culture of Mycobacterium tuberculosis as gold standard. Results A total of 170 patient samples were evaluated in final analysis. Of these, 14 samples were positive by all three methods used in our study. The overall sensitivity, specificity, PPV and NPV of GeneXpert were 86.8%, 93.1%, 78.5% and 96% respectively and for BAL sample, 81.4%, 93.4%, 73.3% and 95.7% respectively. The overall sensitivity and specificity of AFB smear microscopy were 22.2%, % and 78.5% respectively and for BAL sample 22.2% and 100% respectively. For AFB negative samples sensitivity and specificity were 79.1% and 93.1% respectively. Conclusion GeneXpert has a higher sensitivity than AFB smear microscopy in

Xpert(®) MTB/RIF for improved case detection of extra-pulmonary TB in a tertiary care setting in urban India.

PubMed

Nataraj, G; Kanade, S; Mehta, P

2016-07-01

Department of microbiology at a tertiary care hospital, Mumbai, India. To determine 1) the sensitivity and specificity of the Xpert(®) MTB/RIF assay in comparison with microscopy and culture in extra-pulmonary tuberculosis (EPTB), and 2) the number of additional cases of EPTB and rifampicin (RMP) resistance detected using this assay. The study was conducted from July 2013 to April 2015. All consecutive patients with clinically suspected EPTB referred for microscopic examination to the Department of Microbiology that were sufficient in specimen volume were included in the study. Of the 728 specimens included in the study, respectively 5.5%, 23.5% and 20.9% were positive on smear, culture and Xpert. Compared to culture, Xpert had a sensitivity of 84.2% (95%CI 81.4-86.6) and specificity of 98.2% (95%CI 90-104). All specimens with high and medium load on assay were positive on culture; 28 (18.4%) specimens were RMP-resistant and 124 (81.6%) were Xpert-susceptible. No additional RMP-resistant cases were detected using Xpert as compared to phenotypic drug susceptibility testing. The ability of the Xpert assay to rapidly detect a significantly greater number of bacteriologically confirmed EPTB cases, including RMP-resistant cases, makes it an important diagnostic tool in a TB-endemic country.

Rapid diagnosis of pulmonary tuberculosis in African children in a primary care setting by use of Xpert MTB/RIF on respiratory specimens: a prospective study.

PubMed

Zar, Heather J; Workman, Lesley; Isaacs, Washiefa; Dheda, Keertan; Zemanay, Widaad; Nicol, Mark P

2013-08-01

In children admitted to hospital, rapid, accurate diagnosis of pulmonary tuberculosis with the Xpert MTB/RIF assay is possible, but no paediatric studies have been done in the primary care setting, where most children are given care, and where microbiological diagnosis is rarely available. We assessed the diagnostic accuracy of Xpert MTB/RIF in children in primary care. For this prospective study, we obtained repeat induced sputum and nasopharyngeal aspirate specimens from children (<15 years) with suspected pulmonary tuberculosis at a clinic in Khayeliwtsha, Cape Town, South Africa. We compared the diagnostic accuracy of Xpert MTB/RIF with a reference standard of culture and smear microscopy on induced sputum specimens. For the main analysis, specificity of Xpert MTB/RIF versus liquid culture, we included only children with two interpretable Xpert MTB/RIF and induced sputum culture results. Between Aug 1, 2010, and July 30, 2012, we enrolled 384 children (median age 38·3 months, IQR 21·2-56·5) who had one paired induced sputum and nasopharyngeal specimen, 309 (81%) of whom had two paired specimens. Five children (1%) tested positive for tuberculosis by smear microscopy, 26 (7%) tested positive by Xpert MTB/RIF, and 30 (8%) tested positive by culture. Xpert MTB/RIF on two induced sputum specimens detected 16 of 28 culture-confirmed cases (sensitivity of 57·1%, 95% CI 39·1-73·5) and on two nasopharyngeal aspirates detected 11 of 28 culture-confirmed cases (sensitivity of 39·3, 23·6-57·6; p=0·18). The specificity of Xpert MTB/RIF on induced sputum was 98·9% (95% CI 96·9-99·6) and on nasopharyngeal aspirates was 99·3% (97·4-99·8). Our findings suggest that Xpert MTB/RIF on respiratory secretions is a useful test for rapid diagnosis of paediatric pulmonary tuberculosis in primary care. National Institutes of Health, National Health Laboratory Services Research Trust, the Medical Research Council of South Africa, the National Research Foundation South

Improvement of the Xpert Carba-R Kit for the Detection of Carbapenemase-Producing Enterobacteriaceae.

PubMed

Dortet, Laurent; Fusaro, Mathieu; Naas, Thierry

2016-06-01

The Xpert Carba-R kit, version 2 (v2), which has been improved for the efficient detection of blaOXA-181 and blaOXA-232 genes, was tested on a collection of 150 well-characterized enterobacterial isolates that had a reduced susceptibility to carbapenems. The performance of the Xpert Carba-R v2 was high, as it was able to detect the five major carbapenemases (NDM, VIM, IMP, KPC, and OXA-48). Thus, it is now well adapted to the carbapenemase-producing Enterobacteriaceae epidemiology of many countries worldwide. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Reassessment of the positive predictive value and specificity of Xpert MTB/RIF: a diagnostic accuracy study in the context of community-wide screening for tuberculosis.

PubMed

Ho, Jennifer; Nguyen, Phuong Thi Bich; Nguyen, Thu Anh; Tran, Khoa Hien; Van Nguyen, Son; Nguyen, Nhung Viet; Nguyen, Hoa Binh; Luu, Khanh Boi; Fox, Greg J; Marks, Guy B

2016-09-01

Community-wide screening for tuberculosis with Xpert MTB/RIF as a primary screening tool overcomes some of the limitations of conventional screening. However, concerns exist about the low positive predictive value of this test in screening settings. We did a cross-sectional assessment of this diagnostic test to directly estimate the actual positive predictive value of Xpert MTB/RIF when used in the setting of community-wide screening for tuberculosis, and to draw an inference about the specificity of the test for tuberculosis detection. Field staff visited households in 60 randomly selected villages in Ca Mau province, Vietnam. We included people aged 15 years or older who provided written informed consent and were able to produce 0·5 mL or more of sputum, irrespective of reported symptoms. Participants were tested with Xpert MTB/RIF, then those with positive results had two further sputum samples tested for smear microscopy and culture, and underwent chest radiography at the provincial TB Health Center. The positive predictive value of Xpert MTB/RIF was compared against two reference standards for tuberculosis diagnosis-a positive sputum culture for Mycobacterium tuberculosis, and a positive sputum culture or a chest radiograph consistent with active pulmonary tuberculosis. We then calculated the specificity of Xpert MTB/RIF for tuberculosis detection on the basis of these positive predictive values and disease prevalence in this setting. 43 435 adults consented to screening with Xpert MTB/RIF. Sputum samples of 0·5 mL or greater were collected from 23 202 participants, producing 22 673 valid results. 169 participants had positive Xpert MTB/RIF results (0·39% of those screened and 0·75% of those with valid sputum results). The positive predictive value of Xpert MTB/RIF was 61·0% (95% CI 52·8-68·7) when compared against a positive sputum culture and 83·9% (76·8-89·2) when compared against a positive sputum culture or chest radiograph consistent with

Role of Xpert MTB/RIF in differentiating tuberculosis from sarcoidosis in patients with mediastinal lymphadenopathy undergoing EBUS-TBNA: a study of 147 patients.

PubMed

Dhooria, Sahajal; Gupta, Nalini; Bal, Amanjit; Sehgal, Inderpaul Singh; Aggarwal, Ashutosh Nath; Sethi, Sunil; Behera, Digambar; Agarwal, Ritesh

2016-10-07

In patients with intrathoracic lymphadenopathy, differentiating tuberculosis from sarcoidosis is often difficult. We hypothesized that Xpert MTB/RIF assay, a semi-automated hemi-nested PCR would help in this regard. To evaluate the performance of Xpert MTB/RIF in the differential diagnosis of tuberculosis and sarcoidosis. This was a retrospective analysis of patients with intrathoracic lymphadenopathy who underwent endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA), and were diagnosed as either tuberculosis or sarcoidosis. The results of Xpert MTB/RIF assay, tuberculin skin test and endosonographic characteristics (heterogeneous echotexture and coagulation necrosis sign) of the lymph nodes were compared between the two groups. During the study period, 465 EBUS procedures were performed and a diagnosis of sarcoidosis (n=94) or tuberculosis (n=53) was made in 147 patients. Xpert MTB/RIF was positive in 26 (49.1%) and two (2.1%) patients with tuberculosis and sarcoidosis, respectively. The sensitivity, specificity, positive and negative predictive values of Xpert MTB/RIF in the diagnosis of tuberculosis were 49.1 %, 97.9%, 92.9% and 77.3%, respectively. The presence of any of the four features namely positive Xpert MTB/RIF, positive tuberculin skin test, heterogeneous echotexture of the lymph nodes, or the presence of endosonographic coagulation necrosis sign yielded a sensitivity and negative predictive value of 83.0% and 88.0%, respectively in the diagnosis of tuberculosis versus sarcoidosis. Xpert MTB/RIF has good specificity and positive predictive value in the diagnosis of tuberculosis, and is a useful investigation in separating tuberculosis from sarcoidosis.

Tuberculosis Case Finding With Combined Rapid Point-of-Care Assays (Xpert MTB/RIF and Determine TB LAM) in HIV-Positive Individuals Starting Antiretroviral Therapy in Mozambique.

PubMed

Floridia, Marco; Ciccacci, Fausto; Andreotti, Mauro; Hassane, Archa; Sidumo, Zita; Magid, Nurja A; Sotomane, Horacio; David, Muhlavasse; Mutemba, Elsa; Cebola, Junia; Mugunhe, Remigio Josè; Riccardi, Fabio; Marazzi, Maria Cristina; Giuliano, Marina; Palombi, Leonardo; Mancinelli, Sandro

2017-11-13

Tuberculosis is a major health concern in several countries, and effective diagnostic algorithms for use in human immunodeficiency virus (HIV)-positive patients are urgently needed. At prescription of antiretroviral therapy, all patients in 3 Mozambican health centers were screened for tuberculosis, with a combined approach: World Health Organization (WHO) 4-symptom screening (fever, cough, night sweats, and weight loss), a rapid test detecting mycobacterial lipoarabinomannan in urine (Determine TB LAM), and a molecular assay performed on a sputum sample (Xpert MTB/RIF; repeated if first result was negative). Patients with positive LAM or Xpert MTB/RIF results were referred for tuberculosis treatment. Among 972 patients with a complete diagnostic algorithm (58.5% female; median CD4 cell count, 278/μL; WHO HIV stage I, 66.8%), 98 (10.1%) tested positive with Xpert (90, 9.3%) or LAM (34, 3.5%) assays. Compared with a single-test Xpert strategy, dual Xpert tests improved case finding by 21.6%, LAM testing alone improved it by 13.5%, and dual Xpert tests plus LAM testing improved it by 32.4%. Rifampicin resistance in Xpert-positive patients was infrequent (2.5%). Among patients with positive results, 22 of 98 (22.4%) had no symptoms at WHO 4-symptom screening. Patients with tuberculosis diagnosed had significantly lower CD4 cell counts and hemoglobin levels, more advanced WHO stage, and higher HIV RNA levels. Fifteen (15.3%) did not start tuberculosis treatment, mostly owing to rapidly deteriorating clinical conditions or logistical constraints. The median interval between start of the diagnostic algorithm and start of tuberculosis treatment was 7 days. The prevalence of tuberculosis among Mozambican HIV-positive patients starting antiretroviral therapy was 10%, with limited rifampicin resistance. Use of combined point-of-care tests increased case finding, with a short time to treatment. Interventions are needed to remove logistical barriers and prevent presentation

Population Health Impact and Cost-Effectiveness of Tuberculosis Diagnosis with Xpert MTB/RIF: A Dynamic Simulation and Economic Evaluation

PubMed Central

Menzies, Nicolas A.; Cohen, Ted; Lin, Hsien-Ho; Murray, Megan; Salomon, Joshua A.

2012-01-01

Background The Xpert MTB/RIF test enables rapid detection of tuberculosis (TB) and rifampicin resistance. The World Health Organization recommends Xpert for initial diagnosis in individuals suspected of having multidrug-resistant TB (MDR-TB) or HIV-associated TB, and many countries are moving quickly toward adopting Xpert. As roll-out proceeds, it is essential to understand the potential health impact and cost-effectiveness of diagnostic strategies based on Xpert. Methods and Findings We evaluated potential health and economic consequences of implementing Xpert in five southern African countries—Botswana, Lesotho, Namibia, South Africa, and Swaziland—where drug resistance and TB-HIV coinfection are prevalent. Using a calibrated, dynamic mathematical model, we compared the status quo diagnostic algorithm, emphasizing sputum smear, against an algorithm incorporating Xpert for initial diagnosis. Results were projected over 10- and 20-y time periods starting from 2012. Compared to status quo, implementation of Xpert would avert 132,000 (95% CI: 55,000–284,000) TB cases and 182,000 (97,000–302,000) TB deaths in southern Africa over the 10 y following introduction, and would reduce prevalence by 28% (14%–40%) by 2022, with more modest reductions in incidence. Health system costs are projected to increase substantially with Xpert, by US$460 million (294–699 million) over 10 y. Antiretroviral therapy for HIV represents a substantial fraction of these additional costs, because of improved survival in TB/HIV-infected populations through better TB case-finding and treatment. Costs for treating MDR-TB are also expected to rise significantly with Xpert scale-up. Relative to status quo, Xpert has an estimated cost-effectiveness of US$959 (633–1,485) per disability-adjusted life-year averted over 10 y. Across countries, cost-effectiveness ratios ranged from US$792 (482–1,785) in Swaziland to US$1,257 (767–2,276) in Botswana. Assessing outcomes over a 10-y period

Cost-effectiveness of the Xpert® MTB/RIF assay for tuberculosis diagnosis in Brazil.

PubMed

Pinto, M; Steffen, R E; Cobelens, F; van den Hof, S; Entringer, A; Trajman, A

2016-05-01

The Xpert® MTB/RIF assay is being implemented as a substitute for sputum smear microscopy (SSM) in many low and high tuberculosis (TB) burden countries, including Brazil, a country with low multidrug resistance and moderate human immunodeficiency virus co-infection rates. Brazilian National TB Programme (NTP). We estimated the incremental cost-effectiveness ratio (ICER) of Xpert as a substitute for two SSM tests in the diagnosis of drug-susceptible TB. The costs for confirming each additional case and for avoiding treatment due to false-positive empirical diagnoses were estimated. The ICER was US$943 for each additional TB diagnosis and US$356 for each additional TB diagnosis with bacteriological confirmation, assuming 80% specificity of clinical diagnosis using both strategies. For every 100 000 patients with suspected TB, the NTP would spend an additional US$1.2 million per year to confirm 3344 more TB patients. The model was highly sensitive to specificity of clinical diagnosis after a negative test. Although the NTP has no threshold for cost-effectiveness, our model can provide support for decision makers in Brazil and other countries with a low prevalence of drug resistance among TB patients. Financial benefit can potentially be expected if physicians rely more on a negative Xpert result and empirical treatment is reduced.

Revised device labeling for the Cepheid Xpert MTB/RIF assay for detecting Mycobacterium tuberculosis.

PubMed

2015-02-27

The Food and Drug Administration (FDA) has cleared the Xpert MTB/RIF Assay (Cepheid; Sunnyvale, California) with an expanded intended use that includes testing of either one or two sputum specimens as an alternative to examination of serial acid-fast stained sputum smears to aid in the decision of whether continued airborne infection isolation (AII) is warranted for patients with suspected pulmonary tuberculosis. This change reflects the outcome of a recent multicenter international study demonstrating that negative Xpert MTB/RIF Assay results from either one or two sputum specimens are highly predictive of the results of two or three negative acid-fast sputum smears.

Analytical Performance Characteristics of the Cepheid GeneXpert Ebola Assay for the Detection of Ebola Virus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pinsky, Benjamin A.; Sahoo, Malaya K.; Sandlund, Johanna

The recently developed Xpert® Ebola Assay is a novel nucleic acid amplification test for simplified detection of Ebola virus (EBOV) in whole blood and buccal swab samples. The assay targets sequences in two EBOV genes, lowering the risk for new variants to escape detection in the test. The objective of this report is to present analytical characteristics of the Xpert® Ebola Assay on whole blood samples. Our study evaluated the assay’s analytical sensitivity, analytical specificity, inclusivity and exclusivity performance in whole blood specimens. EBOV RNA, inactivated EBOV, and infectious EBOV were used as targets. The dynamic range of the assay,more » the inactivation of virus, and specimen stability were also evaluated. The lower limit of detection (LoD) for the assay using inactivated virus was estimated to be 73 copies/mL (95% CI: 51–97 copies/mL). The LoD for infectious virus was estimated to be 1 plaque-forming unit/mL, and for RNA to be 232 copies/mL (95% CI 163–302 copies/mL). The assay correctly identified five different Ebola viruses, Yambuku-Mayinga, Makona-C07, Yambuku-Ecran, Gabon-Ilembe, and Kikwit-956210, and correctly excluded all non-EBOV isolates tested. The conditions used by Xpert® Ebola for inactivation of infectious virus reduced EBOV titer by ≥6 logs. In conclusion, we found the Xpert® Ebola Assay to have high analytical sensitivity and specificity for the detection of EBOV in whole blood. It offers ease of use, fast turnaround time, and remote monitoring. The test has an efficient viral inactivation protocol, fulfills inclusivity and exclusivity criteria, and has specimen stability characteristics consistent with the need for decentralized testing. The simplicity of the assay should enable testing in a wide variety of laboratory settings, including remote laboratories that are not capable of performing highly complex nucleic acid amplification tests, and during outbreaks where time to detection is critical.« less

Analytical Performance Characteristics of the Cepheid GeneXpert Ebola Assay for the Detection of Ebola Virus

PubMed Central

Pinsky, Benjamin A.; Sahoo, Malaya K.; Sandlund, Johanna; Kleman, Marika; Kulkarni, Medha; Grufman, Per; Nygren, Malin; Kwiatkowski, Robert; Baron, Ellen Jo; Tenover, Fred; Denison, Blake; Higuchi, Russell; Van Atta, Reuel; Beer, Neil Reginald; Carrillo, Alda Celena; Naraghi-Arani, Pejman; Mire, Chad E.; Ranadheera, Charlene; Grolla, Allen; Lagerqvist, Nina; Persing, David H.

2015-01-01

Background The recently developed Xpert® Ebola Assay is a novel nucleic acid amplification test for simplified detection of Ebola virus (EBOV) in whole blood and buccal swab samples. The assay targets sequences in two EBOV genes, lowering the risk for new variants to escape detection in the test. The objective of this report is to present analytical characteristics of the Xpert® Ebola Assay on whole blood samples. Methods and Findings This study evaluated the assay’s analytical sensitivity, analytical specificity, inclusivity and exclusivity performance in whole blood specimens. EBOV RNA, inactivated EBOV, and infectious EBOV were used as targets. The dynamic range of the assay, the inactivation of virus, and specimen stability were also evaluated. The lower limit of detection (LoD) for the assay using inactivated virus was estimated to be 73 copies/mL (95% CI: 51–97 copies/mL). The LoD for infectious virus was estimated to be 1 plaque-forming unit/mL, and for RNA to be 232 copies/mL (95% CI 163–302 copies/mL). The assay correctly identified five different Ebola viruses, Yambuku-Mayinga, Makona-C07, Yambuku-Ecran, Gabon-Ilembe, and Kikwit-956210, and correctly excluded all non-EBOV isolates tested. The conditions used by Xpert® Ebola for inactivation of infectious virus reduced EBOV titer by ≥6 logs. Conclusion In summary, we found the Xpert® Ebola Assay to have high analytical sensitivity and specificity for the detection of EBOV in whole blood. It offers ease of use, fast turnaround time, and remote monitoring. The test has an efficient viral inactivation protocol, fulfills inclusivity and exclusivity criteria, and has specimen stability characteristics consistent with the need for decentralized testing. The simplicity of the assay should enable testing in a wide variety of laboratory settings, including remote laboratories that are not capable of performing highly complex nucleic acid amplification tests, and during outbreaks where time to detection

Analytical Performance Characteristics of the Cepheid GeneXpert Ebola Assay for the Detection of Ebola Virus

DOE PAGES

Pinsky, Benjamin A.; Sahoo, Malaya K.; Sandlund, Johanna; ...

2015-11-12

The recently developed Xpert® Ebola Assay is a novel nucleic acid amplification test for simplified detection of Ebola virus (EBOV) in whole blood and buccal swab samples. The assay targets sequences in two EBOV genes, lowering the risk for new variants to escape detection in the test. The objective of this report is to present analytical characteristics of the Xpert® Ebola Assay on whole blood samples. Our study evaluated the assay’s analytical sensitivity, analytical specificity, inclusivity and exclusivity performance in whole blood specimens. EBOV RNA, inactivated EBOV, and infectious EBOV were used as targets. The dynamic range of the assay,more » the inactivation of virus, and specimen stability were also evaluated. The lower limit of detection (LoD) for the assay using inactivated virus was estimated to be 73 copies/mL (95% CI: 51–97 copies/mL). The LoD for infectious virus was estimated to be 1 plaque-forming unit/mL, and for RNA to be 232 copies/mL (95% CI 163–302 copies/mL). The assay correctly identified five different Ebola viruses, Yambuku-Mayinga, Makona-C07, Yambuku-Ecran, Gabon-Ilembe, and Kikwit-956210, and correctly excluded all non-EBOV isolates tested. The conditions used by Xpert® Ebola for inactivation of infectious virus reduced EBOV titer by ≥6 logs. In conclusion, we found the Xpert® Ebola Assay to have high analytical sensitivity and specificity for the detection of EBOV in whole blood. It offers ease of use, fast turnaround time, and remote monitoring. The test has an efficient viral inactivation protocol, fulfills inclusivity and exclusivity criteria, and has specimen stability characteristics consistent with the need for decentralized testing. The simplicity of the assay should enable testing in a wide variety of laboratory settings, including remote laboratories that are not capable of performing highly complex nucleic acid amplification tests, and during outbreaks where time to detection is critical.« less

Xpert MTB/RIF diagnosis of childhood tuberculosis from sputum and stool samples in a high TB-HIV-prevalent setting.

PubMed

Orikiriza, Patrick; Nansumba, Margaret; Nyehangane, Dan; Bastard, Mathieu; Mugisha, Ivan Taremwa; Nansera, Denis; Mwanga-Amumpaire, Juliet; Boum, Yap; Kumbakumba, Elias; Bonnet, Maryline

2018-05-08

The Xpert MTB/RIF assay is a major advance for diagnosis of tuberculosis (TB) in high-burden countries but is limited in children by their difficulty to produce sputum. We investigated TB in sputum and stool from children with the aim of improving paediatric TB diagnosis. A prospective cohort of children with presumptive TB, provided two sputum or induced sputum at enrolment in a regional referral hospital in Uganda. Stool was collected from those started on TB treatment. All specimen were tested for Xpert MTB/RIF, mycobacteria growth indicator tube (MGIT), Lowenstein Jensen cultures and microscopy (except stool). We compared TB detection between age categories and assessed the performance of Xpert MTB/RIF in sputum and stool. Of the 392 children enrolled, 357 (91.1%) produced at least one sputum sample. Sputum culture yield was 13/357 (3.6%): 3/109 (2.6%), 3/89 (3.2%), 3/101 (2.6%) and 4/44 (8.2%) among children of < 2, 2-5, ≥ 5-10 and > 10 years, respectively (p = 0.599). Xpert MTB/RIF yield was 14/350 (4.0%): 3/104 (2.9%), 4/92 (4.3%), 3/88 (2.9%) and 4/50 (.0%), respectively (p = 0.283). Sensitivity and specificity of Xpert MTB/RIF in sputum against sputum culture were 90.9% (95% CI 58.7-99.8) and 99.1% (99.1-99.8). In stool, it was 55.6% (21.2-86.3) and 98.2% (98.2-100) against Xpert MTB/RIF and culture in sputum. Only a minority of children had microbiologically confirmed TB with a higher proportion in children above 10 years. Although sensitivity of Xpert MTB/RIF in stool was low, with good optimization, it might be a good alternative to sputum in children.

COMPARISON OF GeneXpert MTB/RIF ASSAY WITH CONVENTIONAL AFB SMEAR FOR DIAGNOSIS OF PULMONARY TUBERCULOSIS IN NORTHEASTERN THAILAND.

PubMed

Reechaipichitkul, Wipa; Suleesathira, Tanapong; Chaimanee, Prajaub

2017-03-01

Among infectious agents, Mycobacterium tuberculosis remains one of the most significant causes of death worldwide. Rapid and accurate diagnosis of pulmonary tuberculosis (TB) remains a great challenge. GeneXpert MTB/RIF assay is a novel integrated diagnostic system for rapid diagnosis of TB and particularly of rifampicin-resistant strains. A study was conducted between January 2010 and December 2014 to compare the performance of the sputum GeneXpert MTB/RIF assay with the conventional sputum AFB smear for diagnosis of active pulmonary TB in Thailand, a country with a high burden of this disease. Of the 125 patients who had cough and/or prolonged fever together with abnormal chest radiograph, 63 were diagnosed as having pulmonary TB by mycobacterium culture assay, while the remaining subjects were considered of having TB-like conditions, viz non-tuberculous mycobacterium infection (NTM), bacterial pneumonia or bronchogenic carcinoma. Two-thirds of the patients had underlying diseases, eg, diabetes mellitus (19 patients), autoimmune diseases (14), and HIV (6). Among patients with positive diagnosis of M. tuberculosis infection, 30 were AFB smear positive and 53 by sputum GeneXpert MTB/RIF method; among patients negative for M. tuberculosis infection, 4 were AFB smear positive and 5 by GeneXpert MTB/ RIF assay. Sensitivity and specificity of the sputum AFB smear and GeneXpertMTB/ RIF assay test were 48% (95% CI: 35-61) and 84% (95% CI: 73-92), and 94% (95% CI: 84-98) and 92% (95% CI: 82-97), respectively. Diagnostic performance of the GeneXpert MTB/RIF assay among AFB smear positive patients was higher than among AFB smear negative patients (adjusted OR 6.7; 95% CI: 2.3-19.9). Earlier diagnosis of pulmonary TB using GeneXpert MTB/RIF assay will lead to earlier appropriate treatment and provide opportunities to interrupt TB transmission.

GeneXpert MTB/RIF for rapid diagnosis and rifampin resistance detection of endobronchial tuberculosis.

PubMed

Zhang, Qin; Zhang, Qing; Sun, Bing-Qi; Liu, Chang; Su, An-Na; Wang, Xiao-Han; Liu, Na; Zhang, Juan; Kang, Jian; Hou, Gang

2018-04-24

Delayed diagnosis and treatment of tuberculosis (TB) contribute to poor outcomes, especially for endobronchial TB (EBTB), which typically leads to tracheobronchial stenosis. Finding rapid and accurate diagnostic tools for EBTB is crucial. GeneXpert Mycobacterium tuberculosis (MTB)/rifampin (RIF) was recommended by the World Health Organization (WHO) as a standard molecular biological diagnostic technique for MTB. The aim of this study was to evaluate the efficacy of GeneXpert MTB/RIF for diagnosing EBTB and for evaluating RIF resistance. Biopsy tissue and bronchial brushings from EBTB patients were prospectively assessed with GeneXpert MTB/RIF. The diagnostic yields of auramine O-stained sputum smears and bronchial brush smears were obtained, and the results were compared with the cultures of sputum and biopsy tissues for MTB. In 61 confirmed cases of EBTB, the sensitivities of sputum smear, bronchial brush smear, sputum culture and tissue culture to diagnose EBTB were 13.1%, 32.8%, 36.1% and 68.9%, respectively. For bronchial brushings and biopsies, our data showed sensitivities of 57.4% and 63.9%, respectively, and a specificity of 100% for GeneXpert MTB/RIF, and these results were superior to those of sputum smears, bronchial brush smears and sputum culture. GeneXpert MTB/RIF for bronchial brushings and biopsies showed complementarity in its diagnostic performance. Resistance to RIF was identified in 17.4% (8/46) of GeneXpert MTB-positive cases. GeneXpert MTB/RIF may enable more rapid EBTB diagnosis and determination of RIF resistance, which are crucial for timely treatment. © 2018 Asian Pacific Society of Respirology.

Evaluation of GeneXpert MTB/RIF for detection of Mycobacterium tuberculosis complex and rpo B gene in respiratory and non-respiratory clinical specimens at a tertiary care teaching hospital in Saudi Arabia.

PubMed

Somily, Ali M; Barry, Mazin A; Habib, Hanan A; Alotaibi, Fawzia E; Al-Zamil, Fahad A; Khan, Mohammed A; Sarwar, Mohammed S; Bakhash, Nawab D; Alrabiaah, Abdulkarim A; Shakoor, Zahid A; Senok, Abiola C

2016-12-01

To assess the performance of Xpert MTB/RIF, an automated molecular test for Mycobacterium tuberculosis (MTB) and resistance to rifampin (RIF), against smear microscopy and culture method for diagnosis of MTB infection. Methods: This is a retrospective analysis of 103 respiratory and 137 non-respiratory patient specimens suspected of tuberculosis at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia performed between April 2014 and March 2015. Each sample underwent smear microscopy, mycobacterial culture, and GeneXpert MTB/RIF test. Results: Fifteen out of 103 respiratory samples were smear and culture positive, whereas 9 out of 137 non-respiratory samples were smear positive. Out of 9 smear positive specimens, 8 were also culture positive. All 15 culture positive respiratory samples were detected by Xpert MTB/RIF (sensitivity  and positive predictive value [PPV]=100%). Similarly, all 8 culture positive non-respiratory specimens were identified by Xpert MTB/RIF (sensitivity 100%; PPV 88.8%). The Xpert MTB/RIF detected only one false positive result in 88 smear negative respiratory specimens (specificity 98.9%; negative predictive value [NPV]= 100%). All 125 smear negative non-respiratory specimens tested negative by culture and Xpert MTB/RIF (sensitivity, specificity, PPV, NPV= 100%). Conclusion: The performance of Xpert MTB/RIF was comparable to the gold standard culture method for identification of MTB in both respiratory and non-respiratory clinical specimens.

Evaluation of GeneXpert MTB/RIF for detection of Mycobacterium tuberculosis complex and rpo B gene in respiratory and non-respiratory clinical specimens at a tertiary care teaching hospital in Saudi Arabia

PubMed Central

Somily, Ali M.; Barry, Mazin A.; Habib, Hanan A.; Alotaibi, Fawzia E.; Al-Zamil, Fahad A.; Khan, Mohammed A.; Sarwar, Mohammed S.; Bakhash, Nawab D.; Alrabiaah, Abdulkarim A.; Shakoor, Zahid A.; Senok, Abiola C.

2016-01-01

Objectives To assess the performance of Xpert MTB/RIF, an automated molecular test for Mycobacterium tuberculosis (MTB) and resistance to rifampin (RIF), against smear microscopy and culture method for diagnosis of MTB infection. Methods This is a retrospective analysis of 103 respiratory and 137 non-respiratory patient specimens suspected of tuberculosis at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia performed between April 2014 and March 2015. Each sample underwent smear microscopy, mycobacterial culture, and GeneXpert MTB/RIF test. Results Fifteen out of 103 respiratory samples were smear and culture positive, whereas 9 out of 137 non-respiratory samples were smear positive. Out of 9 smear positive specimens, 8 were also culture positive. All 15 culture positive respiratory samples were detected by Xpert MTB/RIF (sensitivity and positive predictive value [PPV]=100%). Similarly, all 8 culture positive non-respiratory specimens were identified by Xpert MTB/RIF (sensitivity 100%; PPV 88.8%). The Xpert MTB/RIF detected only one false positive result in 88 smear negative respiratory specimens (specificity 98.9%; negative predictive value [NPV]= 100%). All 125 smear negative non-respiratory specimens tested negative by culture and Xpert MTB/RIF (sensitivity, specificity, PPV, NPV= 100%). Conclusion The performance of Xpert MTB/RIF was comparable to the gold standard culture method for identification of MTB in both respiratory and non-respiratory clinical specimens. PMID:27874159

Rolling Out Xpert® MTB/RIF for TB Detection in HIV-Infected Populations:An Opportunity for Systems Strengthening.

PubMed

Pathmanathan, Ishani; Date, Anand; Coggin, William L; Nkengasong, John; Piatek, Amy S; Alexander, Heather

2017-03-31

To eliminate preventable deaths, disease and suffering due to tuberculosis (TB), improved diagnostic capacity is critical. The Cepheid Xpert ® MTB/RIF assay is recommended by the World Health Organization as the initial diagnostic test for people with suspected HIV-associated TB. However, despite high expectations, its scale-up in real-world settings has faced challenges, often due to the systems that support it. In this commentary we discuss needs and opportunities for systems strengthening to support widespread scale-up of Xpert ® MTB/RIF as they relate to each step within the TB diagnostic cascade, from finding presumptive patients, to collecting, transporting and testing sputum specimens, to reporting and receiving results, to initiating and monitoring treatment and, ultimately, to ensuring successful and timely treatment and cure. Investments in evidence-based interventions at each step along the cascade and within the system as a whole will augment not only the utility of Xpert ® MTB/RIF, but also the successful implementation of future diagnostic tests. Xpert ® MTB/RIF will only improve patient outcomes if optimally implemented within the context of strong TB programs and systems. Roll-out of this technology to people living with HIV and others in resource-limited settings offers the opportunity to leverage current TB and HIV laboratory, diagnostic and programmatic investments, while also addressing challenges and strengthening coordination between laboratory systems, laboratory-program interfaces, and TB-HIV program interfaces. If successful, the benefits of this tool could extend beyond progress towards global End TB Strategy goals, to improve system-wide capacity for global disease detection and control.

Xpert MTB/Rif for the diagnosis of extrapulmonary tuberculosis--an experience from a tertiary care centre in South India.

PubMed

Suzana, Shirly; Ninan, Marilyn M; Gowri, Mahasampath; Venkatesh, Krishnan; Rupali, Priscilla; Michael, Joy S

2016-03-01

The Xpert MTB/Rif, with a detection limit of 131 CFU/ml, plays a valuable role in the diagnosis of extrapulmonary tuberculosis, both susceptible and resistant. This study aims at evaluating the Xpert MTB/Rif for the same, at a tertiary care centre in south India, assessing it against both culture and a composite gold standard (CGS). We tested consecutive samples from patients suspected of extrapulmonary tuberculosis with Xpert MTB/Rif, evaluated its sensitivity and specificity against solid and/or liquid culture and CGS. An individual analysis of different sample types (tissue biopsies, fluids, pus, lymph node biopsies and CSF) given an adequate sample size, against both culture and CGS, was also performed. In total, 494 samples were analysed against culture. Compared to culture, the sensitivity of Xpert MTB/Rif was 89% (95% CI 0.81-0.94) and its specificity was 74% (95% CI 0.70-0.78). When Xpert MTB/Rif was compared to the CGS, pooled sensitivity was 62% (95% CI 0.56-0.67) and specificity was 100% (95% CI 0.91-1.00). This assay performs better than the currently available conventional laboratory methods. The rapidity with which results are obtained is an added advantage, and its integration into a routine diagnostic protocol must be considered. © 2015 John Wiley & Sons Ltd.

Xpert MTB/RIF Assay for Pulmonary Tuberculosis and Rifampicin Resistance in Children: a Meta-Analysis.

PubMed

Wang, X W; Pappoe, F; Huang, Y; Cheng, X W; Xu, D F; Wang, H; Xu, Y H

2015-01-01

The Xpert MTB/RIF assay has been recommended by WHO to replace conventional microscopy, culture, and drug resistance tests. It simultaneously detects both Mycobacterium tuberculosis infection (TB) and resistance to rifampicin (RIF) within two hours. The objective was to review the available research studies on the accuracy of the Xpert MTB/RIF assay for diagnosing pulmonary TB and RIF-resistance in children. A comprehensive search of Pubmed and Embase was performed up to October 28, 2014. We identified published articles estimating the diagnostic accuracy of the Xpert MTB/RIF assay in children with or without HIV using culture or culture plus clinical TB as standard reference. QUADAS-2 tool was used to evaluate the quality of the studies. A summary estimation for sensitivity, specificity, diagnostic odds ratios (DOR), and the area under the summary ROC curve (AUC) was performed. Meta-analysis was used to establish the overall accuracy. 11 diagnostic studies with 3801 patients were included in the systematic review. The overall analysis revealed a moderate sensitivity and high specificity of 65% (95% CI: 61 - 69%) and 99% (95% CI: 98 - 99%), respectively, and a pooled diagnostic odds ratio of 164.09 (95% CI: 111.89 - 240.64). The AUC value was found to be 0.94. The pooled sensitivity and specificity for paediatric rifampicin resistance were 94.0% (95% CI: 80.0 - 93.0%) and 99.0% (95% CI: 95.0 - 98.0%), respectively. Hence, the Xpert MTB/RIF assay has good diagnostic and rifampicin performance for paediatric pulmonary tuberculosis. The Xpert MTB/RIF is sensitive and specific for diagnosing paediatric pulmonary TB. It is also effective in detecting rifamnicin resistance. It can, therefore, be used as an initial diagnostic tool.

Evaluation of Xpert® MTB/RIF Assay in Induced Sputum and Gastric Lavage Samples from Young Children with Suspected Tuberculosis from the MVA85A TB Vaccine Trial.

PubMed

Bunyasi, Erick Wekesa; Tameris, Michele; Geldenhuys, Hennie; Schmidt, Bey-Marrie; Luabeya, Angelique Kany Kany; Mulenga, Humphrey; Scriba, Thomas J; Hanekom, Willem A; Mahomed, Hassan; McShane, Helen; Hatherill, Mark

2015-01-01

Diagnosis of childhood tuberculosis is limited by the paucibacillary respiratory samples obtained from young children with pulmonary disease. We aimed to compare accuracy of the Xpert® MTB/RIF assay, an automated nucleic acid amplification test, between induced sputum and gastric lavage samples from young children in a tuberculosis endemic setting. We analyzed standardized diagnostic data from HIV negative children younger than four years of age who were investigated for tuberculosis disease near Cape Town, South Africa [2009-2012]. Two paired, consecutive induced sputa and early morning gastric lavage samples were obtained from children with suspected tuberculosis. Samples underwent Mycobacterial Growth Indicator Tube [MGIT] culture and Xpert MTB/RIF assay. We compared diagnostic yield across samples using the two-sample test of proportions and McNemar's χ2 test; and Wilson's score method to calculate sensitivity and specificity. 1,020 children were evaluated for tuberculosis during 1,214 admission episodes. Not all children had 4 samples collected. 57 of 4,463[1.3%] and 26 of 4,606[0.6%] samples tested positive for Mycobacterium tuberculosis on MGIT culture and Xpert MTB/RIF assay respectively. 27 of 2,198[1.2%] and 40 of 2,183[1.8%] samples tested positive [on either Xpert MTB/RIF assay or MGIT culture] on induced sputum and gastric lavage samples, respectively. 19/1,028[1.8%] and 33/1,017[3.2%] admission episodes yielded a positive MGIT culture or Xpert MTB/RIF assay from induced sputum and gastric lavage, respectively. Sensitivity of Xpert MTB/RIF assay was 8/30[26.7%; 95% CI: 14.2-44.4] for two induced sputum samples and 7/31[22.6%; 11.4-39.8] [p = 0.711] for two gastric lavage samples. Corresponding specificity was 893/893[100%;99.6-100] and 885/890[99.4%;98.7-99.8] respectively [p = 0.025]. Sensitivity of Xpert MTB/RIF assay was low, compared to MGIT culture, but diagnostic performance of Xpert MTB/RIF did not differ sufficiently between induced sputum

Evaluation of the GeneXpert MTB/RIF assay on extrapulmonary and respiratory samples other than sputum: a low burden country experience.

PubMed

Pandey, Sushil; Congdon, Jacob; McInnes, Bradley; Pop, Alina; Coulter, Christopher

2017-01-01

The aim of this study was to assess the performance of the GeneXpert MTB/RIF assay on extrapulmonary (EP) and respiratory (non-sputum) clinical samples of patients suspected of having tuberculosis (TB) from Queensland, Australia. A total of 269 EP and respiratory (non-sputum) clinical samples collected from Qld patients who were suspected of having TB were subjected to the GeneXpert MTB/RIF analysis, Ziehl-Neelsen (ZN) staining, Mycobacterium tuberculosis (MTB) culture and drug susceptibility testing. Phenotypic and genotypic data were compared. The overall performance analysis of the GeneXpert MTB/RIF assay for detection of MTB complex demonstrated sensitivity of 89%, specificity of 95%, PPV of 89% and NPV of 95% using culture as a reference standard. The GeneXpert MTB/RIF analysis of acid-fast bacilli (AFB) smear positive samples and AFB smear negative samples showed sensitivities of 100% and 77%, respectively. Looking at individual EP and respiratory (non-sputum) sample types, the sensitivity ranged from 60% to 100% although the specificity ranged from 33% to 100% with the specificity of lymph node tissue biopsy being the lowest. The GeneXpert MTB/RIF assay detected 11% more TB cases than culture and 27% more cases than ZN microscopy. Due to insufficient numbers of presenting rifampicin resistance cases, performance analysis of the GeneXpert MTB/RIF assay on rifampicin resistance could not be carried out. The GeneXpert MTB/RIF assay is potentially valuable for TB diagnosis in the majority of the EP and respiratory (other than sputum) samples in our setting. Although the GeneXpert MTB/RIF assay provides rapid diagnostic results, the overall sensitivity to rule out the disease is suboptimal for some specimen types. Performance varied according to specimen type and AFB smear status. The sensitivity and specificity of lymph node tissue was 63% and 33%. Care must be taken when using the GeneXpert MTB/RIF assay for detection of MTB in lymph node tissue samples. All

The role of Xpert MTB/RIF assay in the diagnosis of tubercular spondylodiscitis.

PubMed

Arockiaraj, Justin; Michael, Joy S; Amritanand, Rohit; David, Kenny Samuel; Krishnan, Venkatesh

2017-12-01

This study aims to assess the accuracy of the Xpert MTB/RIF assay in the diagnosis of tubercular spondylodiscitis and to identify its role in detecting Rifampicin resistance in patients with infective spondylodiscitis. A retrospective study including 348 patients suspected to have infective spondylodiscitis was done. Tissue/pus samples obtained were sent for culture, histopathology and Xpert MTB/RIF assay. All patients who were confirmed to have tubercular spondylodiscitis and those patients who were suspected on clinico-radiological basis were also treated with anti-tuberculous chemotherapy for a period of 9 months. The efficacy of the Xpert MTB/RIF assay was assessed in terms of sensitivity and specificity when compared to culture, histopathology, and Composite reference standard (CRS). During this study period of 24 months, a total of 348 patients were treated for infective spondylodiscitis. 254 patients were treated for tuberculosis following a smear positivity, culture positivity, and histopathology report or empirically based on clinico-radiological findings. The sensitivity and specificity of the Xpert MTB/RIF assay when compared to culture were 88.4 and 63.7%, respectively. When compared to both culture and histopathology reports it was 80.9 and 80.6%. The sensitivity and specificity of the Xpert MTB/RIF assay when compared to composite reference standard were 71.2 and 100%, respectively. The sensitivity of the assay to detect Rifampicin resistance was 100%. The prevalence of Rifampicin resistance was 5.1%. This study recommends Xpert MTB/RIF assay for early detection of Mycobacterium tubercular spondylodiscitis and Rifampicin resistance.

Implementation and Operational Research: Clinical Impact of the Xpert MTB/RIF Assay in Patients With Multidrug-Resistant Tuberculosis.

PubMed

Padayatchi, Nesri; Naidu, Naressa; Yende-Zuma, Nonhlanhla; OʼDonnell, Max Roe; Naidoo, Kogieleum; Augustine, Stanton; Zumla, Alimuddin; Loveday, Marian

2016-09-01

The Xpert MTB/RIF assay has been widely implemented in South Africa for rapid tuberculosis (TB) screening. However, its usefulness in management and improving treatment outcomes in patients with multidrug-resistant TB (MDR-TB) remains undefined. The aim of this study was to evaluate the clinical impact of introduction of the Xpert MTB/RIF assay in patients with MDR-TB. We enrolled 921 patients with MDR-TB, who presented to a specialist drug-resistant TB facility in KwaZulu-Natal, South Africa, pre- and post-rollout and implementation of the Xpert MTB/RIF assay. Clinical, laboratory, chest radiograph, and follow-up data from 108 patients with MDR-TB, post-introduction of the Xpert MTB/RIF assay (Xpert group) in November 2010, were analyzed and compared with data from 813 MDR-TB patients from the pre-MTB/RIF assay period (Conventional group), July 2008-2010. Primary impact measure was "treatment success" (World Health Organization definition) at 24 months. Secondary outcomes were time to treatment initiation and disease morbidity. There were no significant differences in treatment success rates between the pre-Xpert MTB/RIF and post-Xpert MTB/RIF groups (54% versus 56.5%, P = 0.681). Median time to treatment initiation was 20 days (interquartile range, 13-31) in the Xpert group versus 92 days (interquartile range, 69-120) in the Conventional group (P < 0.001). Although use of Xpert MTB/RIF assay significantly reduces the time to initiation of MDR-TB treatment, it had no significant impact on treatment outcomes of patients with MDR-TB. Studies on the impact of the Xpert MTB/RIF assay usage on transmission of MDR-TB are required.

Rapid Identification of Five Classes of Carbapenem Resistance Genes Directly from Rectal Swabs by Use of the Xpert Carba-R Assay

PubMed Central

Cantón, Rafael; Carretto, Edoardo; Peterson, Lance R.; Sautter, Robert L.; Traczewski, Maria M.

2017-01-01

ABSTRACT Carbapenemase-producing organisms (CPO) have been identified by global health leaders as an urgent threat. Detection of patients with gastrointestinal carriage of CPO is necessary to interrupt their spread within health care facilities. In this multisite study, we assessed the performance of the Xpert Carba-R test, a rapid real-time quantitative PCR (qPCR) assay that detects five families of carbapenemase genes (blaIMP, blaKPC, blaNDM, blaOXA-48, and blaVIM) directly from rectal swab specimens. Using dual swabs, specimens from 755 patients were collected and tested prospectively. An additional 432 contrived specimens were prepared by seeding well-characterized carbapenem-susceptible and -nonsusceptible strains into a rectal swab matrix and inoculating them onto swabs prior to testing. Antimicrobial susceptibility testing, broth enriched culture, and DNA sequencing were performed by a central laboratory blind to the Xpert Carba-R results. The Xpert Carba-R assay demonstrated a positive percentage of agreement (PPA) between 60 and 100% for four targets (blaKPC, blaNDM, blaVIM, and blaOXA-48) and a negative percentage of agreement (NPA) ranging between 98.9 and 99.9% relative to the reference method (culture and sequencing of any carbapenem-nonsusceptible isolate). There were no prospective blaIMP-positive samples. Contrived specimens demonstrated a PPA between 95 and 100% and an NPA of 100% for all targets. Testing of rectal swabs directly using the Xpert Carba-R assay is effective for rapid detection and identification of CPO from hospitalized patients. PMID:28515213

Accuracy of different Xpert MTB/Rif implementation strategies in programmatic settings at the regional referral hospitals in Uganda: Evidence for country wide roll out

PubMed Central

Sekibira, Rogers; Kirenga, Bruce; Katamba, Achilles; Joloba, Moses

2018-01-01

Background Xpert MTB/RIF assay is a highly sensitive test for TB diagnosis, but still costly to most low-income countries. Several implementation strategies instead of frontline have been suggested; however with scarce data. We assessed accuracy of different Xpert MTB/RIF implementation strategies to inform national roll-out. Methods This was a cross-sectional study of 1,924 adult presumptive TB patients in five regional referral hospitals of Uganda. Two sputum samples were collected, one for fluorescent microscopy (FM) and Xpert MTB/RIF examined at the study site laboratories. The second sample was sent to the Uganda Supra National TB reference laboratory for culture using both Lowenstein Jensen (LJ) and liquid culture (MGIT). We compared the sensitivities of FM, Xpert MTB/RIF and the incremental sensitivity of Xpert MTB/RIF among patients negative on FM using LJ and/or MGIT as a reference standard. Results A total 1924 patients were enrolled of which 1596 (83%) patients had at least one laboratory result and 1083 respondents had a complete set of all the laboratory results. A total of 328 (30%) were TB positive on LJ and /or MGIT culture. The sensitivity of FM was n (%; 95% confidence interval) 246 (63.5%; 57.9–68.7) overall compared to 52 (55.4%; 44.1–66.3) among HIV positive individuals, while the sensitivity of Xpert MTB/RIF was 300 (76.2%; 71.7–80.7) and 69 (71.6%; 60.5–81.1) overall and among HIV positive individuals respectively. Overall incremental sensitivity of Xpert MTB/RIF was 60 (36.5%; 27.7–46.0) and 20 (41.7%; 25.5–59.2) among HIV positive individuals. Conclusion Xpert MTB/RIF has a higher sensitivity than FM both in general population and HIV positive population. Xpert MTB/RIF offers a significant increase in terms of diagnostic sensitivity even when it is deployed selectively i.e. among smear negative presumptive TB patients. Our results support frontline use of Xpert MTB/RIF assay in high HIV/TB prevalent countries. In settings with

Accuracy of different Xpert MTB/Rif implementation strategies in programmatic settings at the regional referral hospitals in Uganda: Evidence for country wide roll out.

PubMed

Muttamba, Winters; Ssengooba, Willy; Sekibira, Rogers; Kirenga, Bruce; Katamba, Achilles; Joloba, Moses

2018-01-01

Xpert MTB/RIF assay is a highly sensitive test for TB diagnosis, but still costly to most low-income countries. Several implementation strategies instead of frontline have been suggested; however with scarce data. We assessed accuracy of different Xpert MTB/RIF implementation strategies to inform national roll-out. This was a cross-sectional study of 1,924 adult presumptive TB patients in five regional referral hospitals of Uganda. Two sputum samples were collected, one for fluorescent microscopy (FM) and Xpert MTB/RIF examined at the study site laboratories. The second sample was sent to the Uganda Supra National TB reference laboratory for culture using both Lowenstein Jensen (LJ) and liquid culture (MGIT). We compared the sensitivities of FM, Xpert MTB/RIF and the incremental sensitivity of Xpert MTB/RIF among patients negative on FM using LJ and/or MGIT as a reference standard. A total 1924 patients were enrolled of which 1596 (83%) patients had at least one laboratory result and 1083 respondents had a complete set of all the laboratory results. A total of 328 (30%) were TB positive on LJ and /or MGIT culture. The sensitivity of FM was n (%; 95% confidence interval) 246 (63.5%; 57.9-68.7) overall compared to 52 (55.4%; 44.1-66.3) among HIV positive individuals, while the sensitivity of Xpert MTB/RIF was 300 (76.2%; 71.7-80.7) and 69 (71.6%; 60.5-81.1) overall and among HIV positive individuals respectively. Overall incremental sensitivity of Xpert MTB/RIF was 60 (36.5%; 27.7-46.0) and 20 (41.7%; 25.5-59.2) among HIV positive individuals. Xpert MTB/RIF has a higher sensitivity than FM both in general population and HIV positive population. Xpert MTB/RIF offers a significant increase in terms of diagnostic sensitivity even when it is deployed selectively i.e. among smear negative presumptive TB patients. Our results support frontline use of Xpert MTB/RIF assay in high HIV/TB prevalent countries. In settings with limited access, mechanisms to refer smear negative

Has universal screening with Xpert® MTB/RIF increased the proportion of multidrug-resistant tuberculosis cases diagnosed in a routine operational setting?

PubMed Central

Dunbar, Rory; Caldwell, Judy; Lombard, Carl; Beyers, Nulda

2017-01-01

Setting Primary health services in Cape Town, South Africa where the introduction of Xpert® MTB/RIF (Xpert) enabled simultaneous screening for tuberculosis (TB) and drug susceptibility in all presumptive cases. Study aim To compare the proportion of TB cases with drug susceptibility tests undertaken and multidrug-resistant tuberculosis (MDR-TB) diagnosed pre-treatment and during the course of 1st line treatment in the previous smear/culture and the newly introduced Xpert-based algorithms. Methods TB cases identified in a previous stepped-wedge study of TB yield in five sub-districts over seven one-month time-points prior to, during and after the introduction of the Xpert-based algorithm were analysed. We used a combination of patient identifiers to identify all drug susceptibility tests undertaken from electronic laboratory records. Differences in the proportions of DST undertaken and MDR-TB cases diagnosed between algorithms were estimated using a binomial regression model. Results Pre-treatment, the probability of having a DST undertaken (RR = 1.82)(p<0.001) and being diagnosed with MDR-TB (RR = 1.42)(p<0.001) was higher in the Xpert-based algorithm than in the smear/culture-based algorithm. For cases evaluated during the course of 1st-line TB treatment, there was no significant difference in the proportion with DST undertaken (RR = 1.02)(p = 0.848) or MDR-TB diagnosed (RR = 1.12)(p = 0.678) between algorithms. Conclusion Universal screening for drug susceptibility in all presumptive TB cases in the Xpert-based algorithm resulted in a higher overall proportion of MDR-TB cases being diagnosed and is an important strategy in reducing transmission. The previous strategy of only screening new TB cases when 1st line treatment failed did not compensate for cases missed pre-treatment. PMID:28199375

Evaluation of the Xpert MTB/RIF Performance on Tissues: Potential Impact on Airborne Infection Isolation at a Tertiary Cancer Care Center.

PubMed

McMillen, Tracy; Usiak, Shauna C; Chen, Liang Hua; Gomez, Luz; Ntiamoah, Peter; Hameed, Meera R; Budvytiene, Indre; Banaei, Niaz; Kamboj, Mini; Babady, N Esther

2018-04-01

OBJECTIVES In this study, we sought to evaluate the performance of the Xpert MTB/RIF (Cepheid) assay for the detection of Mycobacterium tuberculosis (MTB) complex DNA on fresh and formalin-fixed, paraffin-embedded (FFPE) tissue specimens from oncology patients in an area with a low prevalence of tuberculosis. We also aimed to retrospectively assess the potential impact of Xpert MTB/RIF on the duration of airborne infection isolation (AII). SETTING A 473-bed, tertiary-care cancer center in New York City. DESIGN A total of 203 tissue samples (101 FFPE and 102 fresh) were tested using Xpert MTB/RIF, including 133 pulmonary tissue samples (65.5%) and 70 extrapulmonary tissue samples (34.5%). Acid-fast bacilli (AFB) culture was used as the diagnostic gold standard. The limit of detection (LOD) and reproducibility were also evaluated for both samples types using contrived specimens. The potential impact of the Xpert MTB PCR assay on tissue samples from AII patients on AII duration was retrospectively assessed. RESULTS Using the Xpert MTB/RIF for fresh tissue specimens, the sensitivity was 50% (95% CI, 1.3%-98.7%) and the specificity was 99% (95% CI, 94.5%-99.9%). For FFPE tissue specimens, the sensitivity was 100% (95% CI, 63.1%-100%) and the specificity was 98.3% (95% CI, 95.5%-100%. The LOD was 103 colony-forming units (CFU)/mL for both fresh and FFPE tissue specimens, and the Xpert MTB/RIF was 100% reproducible at concentrations 10 times that of the LOD. With an expected turnaround time of 24 hours, the Xpert MTB PCR could decrease the duration of AII from a median of 8 days to a median of 1 day. CONCLUSIONS The Xpert MTB/RIF assay offers a valid option for ruling out Mycobacterium tuberculosis complex (MTBC) on tissue samples from oncology patients and for minimizing AII resource utilization. Infect Control Hosp Epidemiol 2018;39:462-466.

Added value of molecular assay Xpert MTB/RIF compared to sputum smear microscopy to assess the risk of tuberculosis transmission in a low-prevalence country.

PubMed

Opota, O; Senn, L; Prod'hom, G; Mazza-Stalder, J; Tissot, F; Greub, G; Jaton, K

2016-07-01

Airborne precautions are required at hospital admission for patients with suspected pulmonary tuberculosis. The isolation is maintained until 3 serially collected sputum smears are acid-fast bacilli negative, a time- and labor-intensive method with limited sensitivity and specificity, which has a great impact on patient flow management. We evaluated the possibility of replacing the result of microscopy by the semiquantitative result of the molecular point-of-care test Xpert MTB/RIF to assess patients' transmission risk to quickly guide airborne isolation decisions in low-endemic countries. The performance of the Xpert MTB/RIF, used as a first-line test, was compared to the results of microscopy for specimens (n=242) collected from May 2010 to December 2014 in Lausanne, Switzerland. The sensitivity and specificity of Xpert MTB/RIF were 91.5% (65/71) and 99.6% (170/171), respectively, vs. 64.8% (46/71) and 94.2% (161/171) for microscopy. Samples with negative Xpert MTB/RIF were all smear negative for Mycobacterium tuberculosis (negative predictive value, 100%). The semiquantitative results of Xpert MTB/RIF-high, medium, low or very low-were found to correlate with acid-fast bacilli detection: positive predictive value of 100% (6/6), 96.5% (27/28), 52.2% (12/23) and 11.1% (1/9) respectively. Finally, when including clinical criteria, we identified 11 smear-negative but Xpert MTB/RIF-positive patients with a significant transmission potential. In conclusion, our data support the introduction of an Xpert MTB/RIF-based strategy as a replacement of smear microscopy for a faster and more accurate management of tuberculosis patients' transmission risk in a low-prevalence country. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Comparison of Xpert MTB/RIF Assay and GenoType MTBDRplus DNA Probes for Detection of Mutations Associated with Rifampicin Resistance in Mycobacterium tuberculosis.

PubMed

Rahman, Arfatur; Sahrin, Mahfuza; Afrin, Sadia; Earley, Keith; Ahmed, Shahriar; Rahman, S M Mazidur; Banu, Sayera

2016-01-01

GeneXpert MTB/RIF (Xpert) and Genotype MTBDRplus (DRplus) are two World Health Organization (WHO) endorsed probe based molecular drug susceptibility testing (DST) methods for rapid diagnosis of drug resistant tuberculosis. Both methods target the same 81 bp Rifampicin Resistance Determining Region (RRDR) of bacterial RNA polymerase β subunit (rpoB) for detection of Rifampicin (RIF) resistance associated mutations using DNA probes. So there is a correspondence of the probes of each other and expected similarity of probe binding. We analyzed 92 sputum specimens by Xpert, DRplus and LJ proportion method (LJ-DST). We compared molecular DSTs with gold standard LJ-DST. We wanted to see the agreement level of two molecular methods for detection of RIF resistance associated mutations. The 81bp RRDR region of rpoB gene of discrepant cases between the two molecular methods was sequenced by Sanger sequencing. The agreement of Xpert and DRplus with LJ-DST for detection of RIF susceptibility was found to be 93.5% and 92.4%, respectively. We also found 92.4% overall agreement of two molecular methods for the detection of RIF susceptibility. A total of 84 out of 92 samples (91.3%) had agreement on the molecular locus of RRDR mutation by DRplus and Xpert. Sanger sequencing of 81bp RRDR revealed that Xpert probes detected seven of eight discrepant cases correctly and DRplus was erroneous in all the eight cases. Although the overall concordance with LJ-DST was similar for both Xpert and DRplus assay, Xpert demonstrated more accuracy in the detection of RIF susceptibility for discrepant isolates compared with DRplus. This observation would be helpful for the improvement of probe based detection of drug resistance associated mutations especially rpoB mutation in M. tuberculosis.

Performance of the Xpert MTB/RIF assay for the diagnosis of pulmonary tuberculosis and rifampin resistance in a low-incidence, high-resource setting.

PubMed

Rice, Jason P; Seifert, Marva; Moser, Kathleen S; Rodwell, Timothy C

2017-01-01

Performance of the Xpert MTB/RIF assay, designed to simultaneously detect Mycobacterium tuberculosis complex (MTBC) and rifampin (RIF) resistance, has been well documented in low-resource settings with high TB-incidence. However, few studies have assessed its accuracy in low TB incidence settings. We evaluated the performance of Xpert MTB/RIF using clinical sputum specimens routinely collected from suspect pulmonary TB patients over a 4-year time period in San Diego County, California. Xpert MTB/RIF results were compared to acid-fast bacilli (AFB) smear microscopy, mycobacterial culture, and phenotypic drug susceptibility testing (DST). Of 751 sputum specimens, 134 (17.8%) were MTBC culture-positive and 2 (1.5%) were multidrug-resistant (MDR). For the detection of MTBC, Xpert MTB/RIF sensitivity was 89.6% (97.7% and 74.5% in smear-positive and -negative sputa, respectively) and specificity was 97.2%; while AFB smear sensitivity and specificity were 64.9% and 77.8%, respectively. Xpert MTB/RIF detected 35 of 47 smear-negative culture-positive specimens, and excluded 124 of 137 smear-positive culture-negative specimens. Xpert MTB/RIF also correctly excluded 99.2% (121/122) of nontuberculous mycobacteria (NTM) specimens, including all 33 NTM false-positives by smear microscopy. For the detection of RIF resistance, Xpert MTB/RIF sensitivity and specificity were 100% and 98.3%, respectively. Our findings demonstrate that Xpert MTB/RIF is able to accurately detect MTBC and RIF resistance in routinely collected respiratory specimens in a low TB-incidence setting, with comparable performance to that achieved in high-incidence settings; and suggest that under these conditions the assay has particular utility in detecting smear-negative TB cases, excluding smear-positive patients without MTBC disease, and differentiating MTBC from NTM.

Performance of the Xpert MTB/RIF assay for the diagnosis of pulmonary tuberculosis and rifampin resistance in a low-incidence, high-resource setting

PubMed Central

Rice, Jason P.; Moser, Kathleen S.; Rodwell, Timothy C.

2017-01-01

Performance of the Xpert MTB/RIF assay, designed to simultaneously detect Mycobacterium tuberculosis complex (MTBC) and rifampin (RIF) resistance, has been well documented in low-resource settings with high TB-incidence. However, few studies have assessed its accuracy in low TB incidence settings. We evaluated the performance of Xpert MTB/RIF using clinical sputum specimens routinely collected from suspect pulmonary TB patients over a 4-year time period in San Diego County, California. Xpert MTB/RIF results were compared to acid-fast bacilli (AFB) smear microscopy, mycobacterial culture, and phenotypic drug susceptibility testing (DST). Of 751 sputum specimens, 134 (17.8%) were MTBC culture-positive and 2 (1.5%) were multidrug-resistant (MDR). For the detection of MTBC, Xpert MTB/RIF sensitivity was 89.6% (97.7% and 74.5% in smear-positive and -negative sputa, respectively) and specificity was 97.2%; while AFB smear sensitivity and specificity were 64.9% and 77.8%, respectively. Xpert MTB/RIF detected 35 of 47 smear-negative culture-positive specimens, and excluded 124 of 137 smear-positive culture-negative specimens. Xpert MTB/RIF also correctly excluded 99.2% (121/122) of nontuberculous mycobacteria (NTM) specimens, including all 33 NTM false-positives by smear microscopy. For the detection of RIF resistance, Xpert MTB/RIF sensitivity and specificity were 100% and 98.3%, respectively. Our findings demonstrate that Xpert MTB/RIF is able to accurately detect MTBC and RIF resistance in routinely collected respiratory specimens in a low TB-incidence setting, with comparable performance to that achieved in high-incidence settings; and suggest that under these conditions the assay has particular utility in detecting smear-negative TB cases, excluding smear-positive patients without MTBC disease, and differentiating MTBC from NTM. PMID:29016684

Comparison of Cepheid Xpert Flu/RSV XC and BioFire FilmArray for Detection of Influenza A, Influenza B, and Respiratory Syncytial Virus.

PubMed

Wahrenbrock, Mark G; Matushek, Scott; Boonlayangoor, Sue; Tesic, Vera; Beavis, Kathleen G; Charnot-Katsikas, Angella

2016-07-01

The Xpert Flu/RSV XC was compared to the FilmArray respiratory panel for detection of influenza (Flu) A, Flu B, and respiratory syncytial virus (RSV), using 128 nasopharyngeal swabs. Positive agreements were 100% for Flu A and RSV and 92.3% for Flu B. The Xpert may be useful in clinical situations when extensive testing is not required and may serve an important role in laboratories already performing broader respiratory panel testing. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Tuberculous spondylitis diagnosed through Xpert MTB/RIF assay in urine: a case report.

PubMed

Sikalengo, George; Ramirez, Adria; Faini, Diana; Mwamelo, Kim; Battegay, Manuel; Jugheli, Levan; Hatz, Christoph; Reither, Klaus; Letang, Emilio

2016-09-26

centrifuged urine, with no resistance to rifampicin. We report two cases of suspected tuberculous spondylitis diagnosed through Xpert MTB/RIF in urine samples from a rural Tanzanian hospital. Urine testing using Xpert MTB/RIF reflects disseminated disease and renal involvement, and may offer a feasible additional diagnostic approach for Pott's disease in rural Africa.

Burden of tuberculosis in intensive care units in Cape Town, South Africa, and assessment of the accuracy and effect on patient outcomes of the Xpert MTB/RIF test on tracheal aspirate samples for diagnosis of pulmonary tuberculosis: a prospective burden of disease study with a nested randomised controlled trial.

PubMed

Calligaro, Gregory L; Theron, Grant; Khalfey, Hoosain; Peter, Jonathan; Meldau, Richard; Matinyenya, Brian; Davids, Malika; Smith, Liezel; Pooran, Anil; Lesosky, Maia; Esmail, Aliasgar; Miller, Malcolm G; Piercy, Jenna; Michell, Lancelot; Dawson, Rodney; Raine, Richard I; Joubert, Ivan; Dheda, Keertan

2015-08-01

There are few prospective data about the incidence and mortality associated with pulmonary tuberculosis in intensive care units (ICUs), and none on the accuracy and clinical effect of the Xpert-MTB/RIF assay in this setting. We aimed to measure the frequency of culture-positive tuberculosis in ICUs in Cape Town, South Africa and to assess the performance and effect on patient outcomes of Xpert MTB/RIF versus smear microscopy for diagnosis of tuberculosis. We did a prospective burden of disease study with a randomised controlled substudy at the ICUs of four hospitals in Cape Town. Mechanically ventilated adults (≥18 years) with suspected pulmonary tuberculosis admitted between Aug 1, 2010, and July 31, 2013 (irrespective of the reason for admission), were prospectively investigated by culture, and by Xpert-MTB/RIF testing or smear microscopy, of tracheal aspirate samples. In the substudy, patients were randomly assigned (1:1), via a computer-generated allocation list, to smear microscopy or Xpert MTB/RIF. Participants, caregivers, and outcome assessors were not masked to group assignment. Only the laboratory staff were blinded to the clinical details of the participants. In November, 2012, Xpert MTB/RIF was adopted as the initial diagnostic test for respiratory samples in Western Cape province. Thereafter, patients received Xpert MTB/MIF and culture as standard of care. For the whole study cohort, the primary outcome was the frequency of bacteriologically confirmed tuberculosis. The primary endpoint of the randomised substudy was the proportion of culture-positive patients on treatment at 48 h after enrolment. The randomised substudy is registered with ClinicalTrials.gov, number NCT01530568. We investigated 341 patients for suspected pulmonary tuberculosis out of a total of 2309 ICU admissions. 46 (15%) of 317 patients included in the final analysis had a positive test for tuberculosis (Xpert MTB/RIF or culture). Culture-positive patients who failed to initiate

Evaluation of the Xpert Flu test and comparison with in-house real-time RT-PCR assays for detection of influenza virus from 2008 to 2011 in Marseille, France.

PubMed

Salez, N; Ninove, L; Thirion, L; Gazin, C; Zandotti, C; de Lamballerie, X; Charrel, R N

2012-04-01

Rapid documentation of respiratory specimens can have an impact on the management of patients and their relatives in terms of preventive and curative measures. We compared the results of the Xpert(®) Flu assay (Cepheid) with three real-time RT-PCR assays using 127 nasopharyngeal samples, of which 75 were positive for influenza A (with 52 identified as A/H1N1-2009) and 52 were positive for influenza B. The Xpert(®) Flu assay presented a quasi-absence of non-interpretable tests, and showed sensitivity and specificity of 100% and 100% for Flu A, 98.4% and 100% for A/H1N1-2009, and 80.7% and 100% for Flu B. © 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.

Evaluation of pulmonary tuberculosis case detection improvement with the deployment of XpertMTB/Rif in the tuberculosis control program of cross River State, Nigeria.

PubMed

Ochang, Ernest Afu; Emanghe, Ubleni E; Ewa, Atana; Otu, Akaninyene; Offor, Jonah B; Odo, Micheal; Etokidem, Aniekan; Afirima, Barinadaa; Owuna, Oju Eni; Obeten, Sunday M; Meremikwu, Martin M

2017-01-01

Global indices show that Nigeria has the highest tuberculosis (TB)-related mortality rate. Overdependence on Ziehl-Neelsen (ZN) smear microscopy for diagnosis and human immunodeficiency virus (HIV)/AIDS has limited control efforts. The new polymerase chain reaction-based XpertMTB/Rif (Cepheid Inc., CA, USA), which detects Mycobacterium tuberculosis and rifampicin resistance, was introduced in Cross River State in 2014. We evaluated the increment in pulmonary TB case detection following introduction of XpertMTB/Rif into the Cross River State TB control program. Data from three XpertMTB/Rif centers in Cross River were prospectively collected from June 2014 to December 2015. One spot specimen and one early morning sputum specimen were collected from each patient and tested using microscopy while one specimen was used for XpertMTB/Rif. A total of 2326 patients comprising 47.4.0% (1103) males and 52.6% (1223) females were evaluated. Their mean age was 38.8 years (range 4-89 years); 42.6% (991) were HIV positive and 50.9% (1183) HIV negative, and for 6.5% (158) HIV status was unknown. XpertMTB/Rif detected M. tuberculosis in 22.9% (534) of patients, while 16.8% (391) were ZN smear positive. Smear microscopy missed 24.5% (131/534) of cases (P < 0.0001). When patients where categorized according to HIV status, XpertMTB/Rif detected 23.7% (280/1183) and ZN smear microscopy detected 18.5% (219/1183) of HIV-negative patients. XpertMTB/Rif detected 21.5% (213/991) and ZN smear 14.1% (140/991) of HIV-positive patients. TB case detection was significantly higher in HIV-negative patients than in HIV-positive patients when either XpertMTB/Rif and/or ZN was used (P = 0.018 and 0.012, respectively). The use of XpertMTB/Rif has significantly increased TB case detection and data in Cross River State. Scale-up of additional strategies such as culture is still required to improve TB detection in HIV patients.

Xpert MTB/RIF assay can be used on archived gastric aspirate and induced sputum samples for sensitive diagnosis of paediatric tuberculosis.

PubMed

Singh, Sarman; Singh, Amit; Prajapati, Suneel; Kabra, Sushil K; Lodha, Rakesh; Mukherjee, Aparna; Singh, Varinder; Hesseling, Anneke C; Grewal, Harleen M S

2015-09-29

Tuberculosis (TB) in children is neglected, mainly due to lack of sensitive diagnostic tools. Recently Xpert MTB/RIF assay has revolutionized the diagnostic field, but its usefulness in pediatric TB has not been reported from India and no report is available on its use on long term archived samples. We recruited 130 pediatric patients with probable intrathoracic tuberculosis and their gastric aspirate (GA) and induced sputum (IS) samples on 2 consecutive days were collected between January 2009 and December 2012. All samples (n = 520) were subjected to smear examination, BACTEC-MGIT culture and in-house multiplex PCR. An aliquot of each sample was stored at -80 °C and tested in Xpert MTB/RIF assay in 2013. Sample wise and patient wise detection rate of smear microscopy was 4.4 % and 10 %, while for BACTEC-MGIT culture this rate was 24.4 % and 46.9 %, respectively. Of the 130 day 1 GA samples, 31.5 % and 27.7 % day 2 GA samples were culture positive. Only 17.7 % GA samples were positive on both days. Of the 130 IS samples collected on day 1 and day 2, 15.4 % and 23.1 % samples were culture positive. A combination of GA and IS yielded best results. Combining both GA and IS, the overall sensitivity of Xpert MTB/RIF on smear and culture positive samples was 95.6 %. In smear negative and culture positive samples its sensitivity was 62.5 %. The duration of sample storage impacted the Xpert MTB/RIF test performance (p = 0.0001). In smear positive samples stored for 650-849 days, its sensitivity was 85.7 % and 77.1 % for IS and GA samples which dropped to 33.3 % and 50 %, respectively, if stored for more than 1050 days. Confirmatory diagnosis of tuberculosis particularly in children is a medical challenge. No laboratory or radiological test can reach to a satisfactory level of diagnostic sensitivity. However, in this study we found that combination of multiple samples and multiple diagnostic tests can give much better yield, though not optimum. In present study

Rapid molecular TB diagnosis: evidence, policy making and global implementation of Xpert MTB/RIF.

PubMed

Weyer, Karin; Mirzayev, Fuad; Migliori, Giovanni Battista; Van Gemert, Wayne; D'Ambrosio, Lia; Zignol, Matteo; Floyd, Katherine; Centis, Rosella; Cirillo, Daniela M; Tortoli, Enrico; Gilpin, Chris; de Dieu Iragena, Jean; Falzon, Dennis; Raviglione, Mario

2013-07-01

If tuberculosis (TB) is to be eliminated as a global health problem in the foreseeable future, improved detection of patients, earlier diagnosis and timely identification of rifampicin resistance will be critical. New diagnostics released in recent years have improved this perspective but they require investments in laboratory infrastructure, biosafety and staff specialisation beyond the means of many resource-constrained settings where most patients live. Xpert MTB/RIF, a new assay employing automated nucleic acid amplification to detect Mycobacterium tuberculosis, as well as mutations that confer rifampicin resistance, holds the promise to largely overcome these operational challenges. In this article we position Xpert MTB/RIF in today's TB diagnostic landscape and describe its additional potential as an adjunct to surveillance and surveys, taking into account considerations of pricing and ethics. In what could serve as a model for the future formulation of new policy on diagnostics, we trace the unique process by which the World Health Organization consulted international expertise and systematically assessed published evidence and freshly emerging experience from the field ahead of its endorsement of the Xpert MTB/RIF technology in 2010, summarise subsequent research findings and guidance on who to test and how, and provide perspectives on scaling up the new technology.

A comparison between the efficiency of the Xpert MTB/RIF assay and nested PCR in identifying Mycobacterium tuberculosis during routine clinical practice.

PubMed

Kim, Cheol-Hong; Woo, Heungjeong; Hyun, In Gyu; Kim, Changhwan; Choi, Jeong-Hee; Jang, Seung-Hun; Park, Sang Myeon; Kim, Dong-Gyu; Lee, Myung Goo; Jung, Ki-Suck; Hyun, Jeongwon; Kim, Hyun Soo

2014-06-01

Polymerase chain reaction (PCR) for the detection of Mycobacterium tuberculosis (MTB) is more sensitive, specific, and rapid than the conventional methods of acid-fast bacilli (AFB) smear and culture. The aim of this study was to determine if the Xpert MTB/rifampicin (RIF) assay had additional advantages over nested PCR for the detection of MTB in a geographical area with intermediate tuberculosis (TB) incidence. Between February and December 2013, the Xpert MTB/RIF assay and MTB nested PCR, as well as AFB smear and culture, were simultaneously performed on 198 clinical samples (160 pulmonary and 38 non-pulmonary specimens) collected from 171 patients hospitalized at Hallym University Medical Center for possible TB. The accuracy of the diagnosis of MTB culture-positive TB and the turnaround time of reporting laboratory results were calculated and compared. Rifampin resistance by the Xpert MTB/RIF assay was reviewed with that of conventional drug susceptibility testing (DST). The sensitivity, specificity, and positive and negative predictive values of the Xpert MTB/RIF assay and MTB nested PCR for diagnosis of MTB culture-positive pulmonary TB were 86.1% vs. 69.4% (P=0.1563), 97.8% vs. 94.1% (P=0.2173), 91.2% vs. 75.8% (P=0.1695), and 96.4% vs. 92.0% (P=0.2032), respectively. The median turnaround times of the Xpert MTB/RIF assay and MTB nested PCR were 0 [0-4] days and 4 [1-11] days, respectively (P<0.001). Two cases of rifampin resistance, as determined by the Xpert MTB/RIF assay, were found to be multi-drug resistant (MDR) pulmonary TB by DST. The Xpert MTB/RIF assay seemed to be sensitive, specific, and comparable to nested PCR for identifying MTB among clinically suspected TB patients, and the assay can be valuable in giving a timely identification of resistance to rifampin.

Rapid detection of Mycobacterium tuberculosis and rifampicin resistance in extrapulmonary tuberculosis and sputum smear-negative pulmonary suspects using Xpert MTB/RIF.

PubMed

Ullah, Irfan; Javaid, Arshad; Masud, Haleema; Ali, Mazhar; Basit, Anila; Ahmad, Waqas; Younis, Faisal; Yasmin, Rehana; Khan, Afsar; Jabbar, Abdul; Husain, Masroor; Butt, Zahid Ahmad

2017-04-01

Tuberculosis (TB) is a serious public health problem in developing countries such as Pakistan. Rapid diagnosis of TB and detection of drug resistance are very important for timely and appropriate management of multidrug-resistant TB (MDR-TB). The purpose of this study was to determine the diagnostic efficacy of the Xpert MTB/RIF assay for rapid diagnosis of TB and detection of rifampicin (RIF) resistance in extrapulmonary and smear-negative pulmonary TB suspects. A total of 98 bronchoalveolar lavage fluid (BALF) and 168 extrapulmonary specimens were processed by Xpert MTB/RIF. Culture results are considered as the gold standard for diagnosis of TB, and drug susceptibility testing for detection of RIF resistance. Diagnostic efficacy was measured in terms of sensitivity, specificity and positive and negative predictive values. The Xpert MTB/RIF assay detected 40 (40.8 %) of 98 BALF of presumptive pulmonary TB and 60 (35.7 %) of 168 extrapulmonary specimens. Sensitivity and specificity of the Xpert MTB/RIF assay for detection of TB was 86 and 88.4 %, respectively. The positive predictive value was 71.5 % while negative predictive value was 95.1 %. The Xpert MTB/RIF assay is a rapid and simple technique with high sensitivity and specificity for diagnosing TB and detecting drug resistance in extrapulmonary and smear-negative TB cases.

Comparison of TB-LAMP, GeneXpert MTB/RIF and culture for diagnosis of pulmonary tuberculosis in The Gambia.

PubMed

Bojang, Adama L; Mendy, Francis S; Tientcheu, Leopold D; Otu, Jacob; Antonio, Martin; Kampmann, Beate; Agbla, Schadrac; Sutherland, Jayne S

2016-03-01

Diagnosis of tuberculosis (TB) remains difficult, particularly in resource-limited settings. The development of nucleic acid-based tests for detection of Mycobacterium tuberculosis complex (MTBC) has significantly increased sensitivity compared to conventional smear microscopy and provides results within a matter of hours compared to weeks for the current gold-standard, liquid culture. In this study we performed side-by-side comparison of mycobacterial detection assays on sputum samples from 285 subjects presenting with symptoms suggestive of TB in The Gambia and a cross-sectional cohort of 156 confirmed TB patients with a median of 2 months of treatment. A novel assay, Loop-Mediated Amplification test for TB (TB-LAMP), was compared to smear microscopy, MGIT culture and GeneXpert MTB/RIF for all samples. When culture was used as the reference standard, we found an overall sensitivity for TB-LAMP of 99% (95% CI: 94.5-99.8) and specificity of 94% (95% CI: 89.3-96.7). When latent class analysis was performed, TB-LAMP had 98.6% (95% CI: 95.9-100) sensitivity and 99% (95% CI: 98.2-100) specificity compared to 91.1% (95% CI: 86.1-96) sensitivity and 100% (95% CI: 98.2-100) specificity for MGIT culture. GeneXpert had the highest sensitivity 99.1% (95% CI: 97.1-100) but the lowest specificity 96% (95% CI: 92.6-98.3). Both TB-LAMP and GeneXpert showed high sensitivity and specificity regardless of age or strain of infection. Our findings show the diagnostic utility of both GeneXpert and TB-LAMP in The Gambia. Whilst TB-LAMP requires less infrastructure, it is unable to detect drug-resistant patterns and therefore would be most suitable as a screening test for new TB cases in peripheral health clinics. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Diagnosis of Concurrent Pulmonary Tuberculosis and Tuberculous Otitis Media Confirmed by Xpert MTB/RIF in the United States.

PubMed

Tompkins, Kathleen M; Reimers, Melissa A; White, Becky L; Herce, Michael E

2016-05-01

Tuberculosis (TB) remains an important cause of infectious morbidity in the United States (US), necessitating timely and accurate diagnosis. We report a case of concurrent pulmonary and extrapulmonary TB presenting as tuberculous otitis media in a hospitalized US patient admitted with cough, night sweats, and unilateral purulent otorrhea. Diagnosis was made by smear microscopy and rapidly confirmed by Xpert MTB/RIF-a novel, automated nucleic acid amplification test for the rapid detection of drug-susceptible and drug-resistant TB. This case adds to the growing body of evidence validating Xpert MTB/RIF as an effective tool for the rapid diagnosis of extrapulmonary TB, even in low TB-prevalence settings such as the US, when testing is performed on non-respiratory specimens.

Diagnosis of Concurrent Pulmonary Tuberculosis and Tuberculous Otitis Media Confirmed by Xpert MTB/RIF in the United States

PubMed Central

Tompkins, Kathleen M.; Reimers, Melissa A.; White, Becky L.; Herce, Michael E.

2015-01-01

Tuberculosis (TB) remains an important cause of infectious morbidity in the United States (US), necessitating timely and accurate diagnosis. We report a case of concurrent pulmonary and extrapulmonary TB presenting as tuberculous otitis media in a hospitalized US patient admitted with cough, night sweats, and unilateral purulent otorrhea. Diagnosis was made by smear microscopy and rapidly confirmed by Xpert MTB/RIF—a novel, automated nucleic acid amplification test for the rapid detection of drug-susceptible and drug-resistant TB. This case adds to the growing body of evidence validating Xpert MTB/RIF as an effective tool for the rapid diagnosis of extrapulmonary TB, even in low TB-prevalence settings such as the US, when testing is performed on non-respiratory specimens. PMID:27346926

Performance of the G4 Xpert® MTB/RIF assay for the detection of Mycobacterium tuberculosis and rifampin resistance: a retrospective case-control study of analytical and clinical samples from high- and low-tuberculosis prevalence settings.

PubMed

Dharan, Nila J; Blakemore, Robert; Sloutsky, Alex; Kaur, Devinder; Alexander, Richard C; Ghajar, Minoo; Musser, Kimberlee A; Escuyer, Vincent E; Rowlinson, Marie-Claire; Crowe, Susanne; Laniado-Laborin, Rafael; Valli, Eloise; Nabeta, Pamela; Johnson, Pamela; Alland, David

2016-12-20

The Xpert ® MTB/RIF (Xpert) assay is a rapid PCR-based assay for the detection of Mycobacterium tuberculosis complex DNA (MTBc) and mutations associated with rifampin resistance (RIF). An updated version introduced in 2011, the G4 Xpert, included modifications to probe B and updated analytic software. An analytical study was performed to assess Xpert detection of mutations associated with rifampin resistance in rifampin-susceptible and -resistant isolates. A clinical study was performed in which specimens from US and non-US persons suspected of tuberculosis (TB) were tested to determine Xpert performance characteristics. All specimens underwent smear microscopy, mycobacterial culture, conventional drug-susceptibility testing and Xpert testing; DNA from isolates with discordant rifampin resistance results was sequenced. Among 191 laboratory-prepared isolates in the analytical study, Xpert sensitivity for detection of rifampin resistance associated mutations was 97.7% and specificity was 90.8%, which increased to 99.0% after DNA sequencing analysis of the discordant samples. Of the 1,096 subjects in the four clinical studies, 49% were from the US. Overall, Xpert detected MTBc in 439 of 468 culture-positive specimens for a sensitivity of 93.8% (95% confidence interval [CI]: 91.2%-95.7%) and did not detect MTBc in 620 of 628 culture-negative specimens for a specificity of 98.7% (95% CI: 97.5%-99.4%). Sensitivity was 99.7% among smear-positive cases, and 76.1% among smear-negative cases. Non-determinate MTBc detection and false-positive RIF resistance results were low (1.2 and 0.9%, respectively). The updated Xpert assay retained the high sensitivity and specificity of the previous assay versions and demonstrated low rates of non-determinate and RIF resistance false positive results.

Initial experience with GeneXpert MTB/RIF assay in the Arkansas Tuberculosis Control Program.

PubMed

Patil, Naveen; Saba, Hamida; Marco, Asween; Samant, Rohan; Mukasa, Leonard

2014-01-01

Mycobacterium tuberculosis remains one of the most significant causes of death from an infectious agent. Rapid and accurate diagnosis of pulmonary and extra-pulmonary tuberculosis (TB) is still a great challenge. The GeneXpert MTB/RIF assay is a novel integrated diagnostic system for the diagnosis of tuberculosis and rapid detection of Rifampin (RIF) resistance in clinical specimens. In 2012, the Arkansas Tuberculosis Control Program introduced GeneXpert MTB/RIF assay to replace the labour-intensive Mycobacterium Tuberculosis Direct (MTD) assay. To rapidly diagnose TB within two hours and to simultaneously detect RIF resistance. Describe the procedure used to introduce GeneXpert MTB/RIF assay in the Arkansas Tuberculosis Control Program.Characterise the current gap in rapid M. tuberculosis diagnosis in Arkansas.Assess factors that predict acid fast bacilli (AFB) smearnegative but culture-positive cases in Arkansas.Illustrate, with two case reports, the role of GeneXpert MTB/RIF assay in reduction of time to confirmation of M. tuberculosis diagnosis in the first year of implementation. Between June 2012 and June 2013, all AFB sputum smearpositive cases and any others, on request by the physician, had GeneXpert MTB/RIF assay performed as well as traditional M. tuberculosis culture and susceptibilities using Mycobacteria Growth Indicator Tube (MGIT) 960 and Löwenstein-Jensen (LJ) slants. Surveillance data for January 2009-June 2013 was analysed to characterise sputum smear-negative but culture-positive cases. Seventy-one TB cases were reported from June 2012- June 2013. GeneXpert MTB/RIF assay identified all culture-positive cases as well as three cases that were negative on culture. Also, this rapid assay identified all six smear-negative but M. tuberculosis culture-positive cases; two of these cases are described as case reports. GeneXpert MTB/RIF assay has made rapid TB diagnosis possible, with tremendous potential in determining isolation of TB suspects on one

Clostridium difficile Testing in the Clinical Laboratory by Use of Multiple Testing Algorithms ▿

PubMed Central

Novak-Weekley, Susan M.; Marlowe, Elizabeth M.; Miller, John M.; Cumpio, Joven; Nomura, Jim H.; Vance, Paula H.; Weissfeld, Alice

2010-01-01

The incidence of Clostridium difficile infection (CDI) has risen almost 3-fold in the United States over the past decade, emphasizing the need for rapid and accurate tests for CDI. The Cepheid Xpert C. difficile assay is an integrated, closed, nucleic acid amplification system that automates sample preparation and real-time PCR detection of the toxin B gene (tcdB). A total of 432 stool specimens from symptomatic patients were tested by a glutamate dehydrogenase (GDH) assay, a toxin A and B enzyme immunoassay (EIA), the Xpert C. difficile assay, and a cell culture cytotoxicity neutralization assay (CCCN). The results of these methods, used individually and in combination, were compared to those of toxigenic culture. Results for the Xpert C. difficile assay alone showed a sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of 94.4, 96.3, 84.0, and 98.8%, while the EIA alone gave corresponding values of 58.3, 94.7, 68.9, and 91.9%, respectively. An algorithm using the GDH assay and the EIA (plus the CCCN if the EIA was negative) showed corresponding values of 83.1, 96.7, 83.1, and 96.1%. The Xpert C. difficile assay was statistically superior to the EIA (P, <0.001 by Fisher's exact test) and to the GDH-EIA-CCCN algorithm (P, 0.0363). Combining the GDH and Xpert C. difficile assays lowered both the sensitivity and the NPV of the Xpert assay. The GDH-EIA-CCCN procedure required, on average, 2 days to complete testing on GDH-positive results, while testing by the Xpert C. difficile assay was completed, on average, in less than 1 h. Xpert C. difficile testing yielded the highest sensitivity and NPV, in the least amount of time, of the individual- and multiple-test algorithms evaluated in this study. PMID:20071552

Xpert MTB/RIF assay for diagnosis of pulmonary tuberculosis in children: a prospective, multi-centre evaluation.

PubMed

Reither, Klaus; Manyama, Christina; Clowes, Petra; Rachow, Andrea; Mapamba, Daniel; Steiner, Andreas; Ross, Amanda; Mfinanga, Elirehema; Sasamalo, Mohamed; Nsubuga, Martin; Aloi, Francesco; Cirillo, Daniela; Jugheli, Levan; Lwilla, Fred

2015-04-01

Following endorsement by the World Health Organisation, the Xpert MTB/RIF assay has been widely incorporated into algorithms for the diagnosis of adult tuberculosis (TB). However, data on its performance in children remain scarce. This prospective, multi-centre study evaluated the performance of Xpert MTB/RIF to diagnose pulmonary tuberculosis in children. Children older than eight weeks and younger than 16 years with suspected pulmonary tuberculosis were enrolled at three TB endemic settings in Tanzania and Uganda, and assigned to five well-defined case definition categories: culture-confirmed TB, highly probable TB, probable TB, not TB, or indeterminate. The diagnostic accuracy of Xpert MTB/RIF was assessed using culture-confirmed TB cases as reference standard. In total, 451 children were enrolled. 37 (8%) had culture-confirmed TB, 48 (11%) highly probably TB and 62 probable TB (13%). The Xpert MTB/RIF assay had a sensitivity of 68% (95% CI, 50%-82%) and specificity of 100% (95% CI, 97%-100%); detecting 1.7 times more culture-confirmed cases than smear microscopy with a similar time to detection. Xpert MTB/RIF was positive in 2% (1/48) of highly probable and in 3% (2/62) of probable TB cases. Xpert MTB/RIF provided timely results with moderate sensitivity and excellent specificity compared to culture. Low yields in children with highly probable and probable TB remain problematic. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Limited value of whole blood Xpert(®) MTB/RIF for diagnosing tuberculosis in children.

PubMed

Pohl, Christian; Rutaihwa, Liliana K; Haraka, Frederick; Nsubuga, Martin; Aloi, Francesco; Ntinginya, Nyanda E; Mapamba, Daniel; Heinrich, Norbert; Hoelscher, Michael; Marais, Ben J; Jugheli, Levan; Reither, Klaus

2016-10-01

We evaluated the ability of the Xpert(®) MTB/RIF assay to detect Mycobacterium tuberculosis in whole blood of children with tuberculosis in tuberculosis endemic settings with high rates of HIV infection. From June 2011 to September 2012 we prospectively enrolled children with symptoms or signs suggestive of tuberculosis at three research centres in Tanzania and Uganda. After clinical assessment, respiratory specimens were collected for microscopy and culture, as well as whole blood for Xpert(®) MTB/RIF. Children were classified according to standardised case definitions. A total of 232 children were evaluated; 14 (6.0%) had culture-confirmed tuberculosis. The Xpert(®) MTB/RIF assay detected M. tuberculosis in 5/232 (2.2%) blood samples with 1 (0.4%) error reading and presumably 1 (0.4%) false-positive result. The sensitivity of the assay in children with culture-confirmed (1/14) versus no tuberculosis (1/117) was 7.1% (95% CI, 1.3-31.5). Three of the five Xpert(®) MTB/RIF positive patients had negative cultures, but were classified as probable tuberculosis cases. Assay sensitivity against a composite reference standard (culture-confirmed, highly probable or probable tuberculosis) was 5.4% (95% CI, 2.1-13.1). Whole blood Xpert(®) MTB/RIF demonstrated very poor sensitivity, although it may enhance the diagnostic yield in select cases, with culture-negative tuberculosis. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Performance Characteristics of the Cepheid Xpert vanA Assay for Rapid Identification of Patients at High Risk for Carriage of Vancomycin-Resistant Enterococci

PubMed Central

Gilhuley, Kathleen; Cianciminio-Bordelon, Diane; Tang, Yi-Wei

2012-01-01

We compared the performance characteristics of culture and the Cepheid Xpert vanA assay for routine surveillance of vancomycin-resistant enterococci (VRE) from rectal swabs in patients at high risk for VRE carriage. The Cepheid Xpert vanA assay had a limit of detection of 100 CFU/ml and correctly detected 101 well-characterized clinical VRE isolates with no cross-reactivity in 27 non-VRE and related culture isolates. The clinical sensitivity, specificity, positive predictive value, and negative predictive value of the Xpert vanA PCR assay were 100%, 96.9%, 91.3%, and 100%, respectively, when tested on 300 consecutively collected rectal swabs. This assay provides excellent predictive values for prompt identification of VRE-colonized patients in hospitals with relatively high rates of VRE carriage. PMID:22972822

Evaluation of the Cepheid Xpert MTB/RIF assay

PubMed Central

Shinnick, Thomas M; Starks, Angela M; Alexander, Heather L; Castro, Kenneth G

2018-01-01

The lack of capacity to provide laboratory confirmation of a diagnosis of tuberculosis disease (TB) is contributing to enormous gaps in the ability to find, treat and follow TB patients. WHO estimates that globally only about 57% of the notified new cases of pulmonary TB in 2012 and about 19% of rifampicin-resistant TB cases were laboratory confirmed. The Cepheid Xpert® MTB/RIF assay has been credited with revolutionizing laboratory testing to aid in the diagnosis of TB and rifampicin-resistant TB. This semi-automated test can detect both the causative agent of TB and mutations that confer rifampicin resistance from clinical specimens within 2 h after starting the test. In this article, we review the performance of the test, its pathway to regulatory approval and endorsement, guidelines for its use and lessons learned from the implementation of the test in low-burden, high-resource countries and in high-burden, low-resource countries. PMID:25373876

[Contribution of the Xpert MTB/RIF to the etiological diagnosis of tuberculous pleurisy].

PubMed

Touré, N O; Wayzani, M; Thiam, K; Cissé, M F; Mbaye, F B

2017-09-01

Performance of the Xpert MTB/RIF for the detection of Mycobacterium tuberculosis in pleural liquid is poorly described. The aim of this study was to determine its usefulness for the etiological diagnosis of a tuberculous pleurisy. We performed a descriptive cross-sectional study, with analytical design, including all the patients having a unilateral serofibrinous pleurisy, exudative, lymphocytic, and sterile. The diagnosis of pleural tuberculosis was considered based on epidemiological, clinical, paraclinical and therapeutic arguments. The Xpert MTB/RIF of the pleural fluid was carried out among all patients. Pleural tuberculosis was confirmed in 301 patients. The median age was 32years. Our study has included 217 men (72.1%) with a final sex ratio of 2.6. The cost of the pleural biopsy coupled with histology made it practicable in only 90 patients (29.9%) with a yield of 80%. The Xpert MTB/RIF of the pleural liquid was positive in only 10 patients (3.3% of the cases). Gene amplification by Xpert MTB/RIF of the pleural liquid is much less effective in establishing the diagnosis of tuberculous pleurisy than pleural biopsy, which remains the gold standard. Copyright © 2017 SPLF. Published by Elsevier Masson SAS. All rights reserved.

The Xpert® MTB/RIF assay in routine diagnosis of pulmonary tuberculosis: A multicentre study in Lithuania.

PubMed

Pimkina, Edita; Zablockis, Rolandas; Nikolayevskyy, Vladyslav; Danila, Edvardas; Davidaviciene, Edita

2015-11-01

Drug-resistant tuberculosis (TB) is an important public health problem in Lithuania with MDR rates in new cases reaching 11% in 2012. Currently available diagnostic tools are not fully adequate for an accurate and rapid result for diagnosis of TB and MDR-TB. To evaluate the performance of Xpert(®) MTB/RIF assay for an early diagnosis of TB and detection of rifampicin (RIF) resistance in routine settings in Lithuania. A total of 833 individual respiratory samples obtained from patients previously treated for TB and MDR-TB contacts were tested using the Xpert MTB/RIF assay. Performance characteristics of the assay for TB and RIF resistance detection were calculated using culture and phenotypical DST results as a gold standard. The overall sensitivity and specificity of the Xpert MTB/RIF assay for TB detection were 93.7% and 91.7%, respectively with the sensitivity for smear-negative specimens reaching 82.5%. Resistance to RIF was detected in 81 (20.7%) primary specimens with no false negative results; there were 4/225 (1.8%) false-positives among strains sensitive to rifampicin. Overall sensitivity and specificity of the molecular assay for detection of RIF resistance calculated against phenotypic DST results were 100% and 98.2%, respectively. Our results demonstrate very good performance of the Xpert MTB/RIF assay for the detection of TB and RIF resistance on primary respiratory specimens. It provides strong evidence that implementation of the assay for routine laboratory diagnosis in high drug-resistance settings may improve and facilitate TB diagnosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prospective and retrospective evaluation of the Cepheid Xpert® Flu/RSV XC assay for rapid detection of influenza A, influenza B, and respiratory syncytial virus.

PubMed

Salez, Nicolas; Nougairede, Antoine; Ninove, Laetitia; Zandotti, Christine; de Lamballerie, Xavier; Charrel, Remi N

2015-04-01

A total of 281 clinical specimens (nasal swabs and nasopharyngeal aspirates) were tested with the Xpert® Flu/RSV XC. The results were compared to those obtained with the real-time retro transcriptase-polymerase chain reaction assays routinely used in our laboratory. The Xpert® Flu/RSV XC showed sensitivity/specificity of 97.8%/100% and 97.9%/100% for flu and respiratory syncytial virus, respectively. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluation of the Cepheid® Xpert®C. difficile binary toxin (BT) diagnostic assay.

PubMed

McGovern, Alan M; Androga, Grace O; Moono, Peter; Collins, Deirdre A; Foster, Niki F; Chang, Barbara J; Riley, Thomas V

2018-06-01

Strains of Clostridium difficile producing only binary toxin (CDT) are found commonly in animals but not humans. However, human diagnostic tests rarely look for CDT. The Cepheid Xpert C. difficile BT assay detects CDT with equal sensitivity (≥92%) in human and animal faecal samples. Copyright © 2018 Elsevier Ltd. All rights reserved.

Clinical Evaluation of the Cepheid Xpert TV Assay for Detection of Trichomonas vaginalis with Prospectively Collected Specimens from Men and Women

PubMed Central

Gaydos, C. A.; Davis, T.; Marrazzo, J.; Furgerson, D.; Taylor, S. N.; Smith, B.; Bachmann, L. H.; Ackerman, R.; Spurrell, T.; Ferris, D.; Burnham, C.-A. D.; Reno, H.; Lebed, J.; Eisenberg, D.; Kerndt, P.; Philip, S.; Jordan, J.; Quigley, N.

2017-01-01

ABSTRACT Trichomoniasis is the most prevalent curable sexually transmitted disease (STD). It has been associated with preterm birth and the acquisition and transmission of HIV. Recently, nucleic acid amplification tests (NAAT) have been FDA cleared in the United States for detection of Trichomonas vaginalis in specimens from both women and men. This study reports the results of a multicenter study recently conducted using the Xpert TV (T. vaginalis) assay to test specimens from both men and women. On-demand results were available in as little as 40 min for positive specimens. A total of 1,867 women and 4,791 men were eligible for inclusion in the analysis. In women, the performance of the Xpert TV assay was compared to the patient infected status (PIS) derived from the results of InPouch TV broth culture and Aptima NAAT for T. vaginalis. The diagnostic sensitivities and specificities of the Xpert TV assay for the combined female specimens (urine samples, self-collected vaginal swabs, and endocervical swabs) ranged from 99.5 to 100% and 99.4 to 99.9%, respectively. For male urine samples, the diagnostic sensitivity and specificity were 97.2% and 99.9%, respectively, compared to PIS results derived from the results of broth culture for T. vaginalis and bidirectional gene sequencing of amplicons. Excellent performance characteristics were seen using both female and male specimens. The ease of using the Xpert TV assay should result in opportunities for enhanced screening for T. vaginalis in both men and women and, hopefully, improved control of this infection. PMID:29167292

Clinical Evaluation of the Cepheid Xpert TV Assay for Detection of Trichomonas vaginalis with Prospectively Collected Specimens from Men and Women.

PubMed

Schwebke, Jane R; Gaydos, C A; Davis, T; Marrazzo, J; Furgerson, D; Taylor, S N; Smith, B; Bachmann, L H; Ackerman, R; Spurrell, T; Ferris, D; Burnham, C A; Reno, H; Lebed, J; Eisenberg, D; Kerndt, P; Philip, S; Jordan, J; Quigley, N

2018-02-01

Trichomoniasis is the most prevalent curable sexually transmitted disease (STD). It has been associated with preterm birth and the acquisition and transmission of HIV. Recently, nucleic acid amplification tests (NAAT) have been FDA cleared in the United States for detection of Trichomonas vaginalis in specimens from both women and men. This study reports the results of a multicenter study recently conducted using the Xpert TV ( T. vaginalis ) assay to test specimens from both men and women. On-demand results were available in as little as 40 min for positive specimens. A total of 1,867 women and 4,791 men were eligible for inclusion in the analysis. In women, the performance of the Xpert TV assay was compared to the patient infected status (PIS) derived from the results of InPouch TV broth culture and Aptima NAAT for T. vaginalis The diagnostic sensitivities and specificities of the Xpert TV assay for the combined female specimens (urine samples, self-collected vaginal swabs, and endocervical swabs) ranged from 99.5 to 100% and 99.4 to 99.9%, respectively. For male urine samples, the diagnostic sensitivity and specificity were 97.2% and 99.9%, respectively, compared to PIS results derived from the results of broth culture for T. vaginalis and bidirectional gene sequencing of amplicons. Excellent performance characteristics were seen using both female and male specimens. The ease of using the Xpert TV assay should result in opportunities for enhanced screening for T. vaginalis in both men and women and, hopefully, improved control of this infection. Copyright © 2018 Schwebke et al.

Evaluation of Xpert® MTB/RIF and Ustar EasyNAT™ TB IAD for diagnosis of tuberculous lymphadenitis of children in Tanzania: a prospective descriptive study.

PubMed

Bholla, Maira; Kapalata, Neema; Masika, Edward; Chande, Hassan; Jugheli, Levan; Sasamalo, Mohamed; Glass, Tracy R; Beck, Hans-Peter; Reither, Klaus

2016-06-06

Fine needle aspiration biopsy has become a standard approach for diagnosis of peripheral tuberculous lymphadenitis. The aim of this study was to compare the performance of Xpert MTB/RIF and Ustar EasyNAT TB IAD nucleic acid amplification assays, against acid-fast bacilli microscopy, cytology and mycobacterial culture for the diagnosis of TB lymphadenitis in children from a TB-endemic setting in Tanzania. Children of 8 weeks to 16 years of age, suspected of having TB lymphadenitis, were recruited at a district hospital in Tanzania. Fine needle aspirates of lymph nodes were analysed using acid-fast bacilli microscopy, liquid TB culture, cytology, Xpert MTB/RIF and EasyNAT. Latent class analysis and comparison against a composite reference standard comprising "culture and/or cytology" was done, to assess the performance of Xpert MTB/RIF and EasyNAT for the diagnosis of TB lymphadenitis. Seventy-nine children were recruited; 4 were excluded from analysis. Against a composite reference standard of culture and/or cytology, Xpert MTB/RIF and EasyNAT had a sensitivity and specificity of 58 % and 93 %; and 19 % and 100 % respectively. Relative to latent class definitions, cytology had a sensitivity of 100 % and specificity of 94.7 %. Combining clinical assessment, cytology and Xpert MTB/RIF may allow for a rapid and accurate diagnosis of childhood TB lymphadenitis. Larger diagnostic evaluation studies are recommended to validate these findings and on Xpert MTB/RIF to assess its use as a solitary initial test for TB lymphadenitis in children.

The sensitivity and specificity of using a computer aided diagnosis program for automatically scoring chest X-rays of presumptive TB patients compared with Xpert MTB/RIF in Lusaka Zambia.

PubMed

Muyoyeta, Monde; Maduskar, Pragnya; Moyo, Maureen; Kasese, Nkatya; Milimo, Deborah; Spooner, Rosanna; Kapata, Nathan; Hogeweg, Laurens; van Ginneken, Bram; Ayles, Helen

2014-01-01

To determine the sensitivity and specificity of a Computer Aided Diagnosis (CAD) program for scoring chest x-rays (CXRs) of presumptive tuberculosis (TB) patients compared to Xpert MTB/RIF (Xpert). Consecutive presumptive TB patients with a cough of any duration were offered digital CXR, and opt out HIV testing. CXRs were electronically scored as normal (CAD score ≤ 60) or abnormal (CAD score > 60) using a CAD program. All patients regardless of CAD score were requested to submit a spot sputum sample for testing with Xpert and a spot and morning sample for testing with LED Fluorescence Microscopy-(FM). Of 350 patients with evaluable data, 291 (83.1%) had an abnormal CXR score by CAD. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CXR compared to Xpert were 100% (95%CI 96.2-100), 23.2% (95%CI 18.2-28.9), 33.0% (95%CI 27.6-38.7) and 100% (95% 93.9-100), respectively. The area under the receiver operator curve (AUC) for CAD was 0.71 (95%CI 0.66-0.77). CXR abnormality correlated with smear grade (r = 0.30, p<0.0001) and with Xpert CT(r = 0.37, p<0.0001). To our knowledge this is the first time that a CAD program for TB has been successfully tested in a real world setting. The study shows that the CAD program had high sensitivity but low specificity and PPV. The use of CAD with digital CXR has the potential to increase the use and availability of chest radiography in screening for TB where trained human resources are scarce.

Performance of point-of-care Xpert HIV-1 plasma viral load assay at a tertiary HIV care centre in Southern India.

PubMed

Swathirajan, Chinnambedu Ravichandran; Vignesh, Ramachandran; Boobalan, Jayaseelan; Solomon, Sunil Suhas; Saravanan, Shanmugam; Balakrishnan, Pachamuthu

2017-10-01

Sustainable suppression of HIV replication forms the basis of anti-retroviral therapy (ART) medication. Thus, reliable quantification of HIV viral load has become an essential factor to monitor the effectiveness of the ART. Longer turnaround-time (TAT), batch testing and technical skills are major drawbacks of standard real-time PCR assays. The performance of the point-of-care Xpert HIV-1 viral load assay was evaluated against the Abbott RealTime PCR m2000rt system. A total of 96 plasma specimens ranging from 2.5 log10 copies ml -1 to 4.99 log10 copies ml -1 and proficiency testing panel specimens were used. Precision and accuracy were checked using the Pearson correlation co-efficient test and Bland-Altman analysis. Compared to the Abbott RealTime PCR, the Xpert HIV-1 viral load assay showed a good correlation (Pearson r=0.81; P<0.0001) with a mean difference of 0.27 log10 copies ml -1 (95 % CI, -0.41 to 0.96 log10 copies ml -1 ; sd, 0.35 log10 copies ml -1 ). Reliable and ease of testing individual specimens could make the Xpert HIV-1 viral load assay an efficient alternative method for ART monitoring in clinical management of HIV disease in resource-limited settings. The rapid test results (less than 2 h) could help in making an immediate clinical decision, which further strengthens patient care.

Evaluation of the Cepheid Xpert Flu Assay for rapid identification and differentiation of influenza A, influenza A 2009 H1N1, and influenza B viruses.

PubMed

Novak-Weekley, S M; Marlowe, E M; Poulter, M; Dwyer, D; Speers, D; Rawlinson, W; Baleriola, C; Robinson, C C

2012-05-01

The Xpert Flu Assay cartridge is a next-generation nucleic acid amplification system that provides multiplexed PCR detection of the influenza A, influenza A 2009 H1N1, and influenza B viruses in approximately 70 min with minimal hands-on time. Six laboratories participated in a clinical trial comparing the results of the new Cepheid Xpert Flu Assay to those of culture or real-time PCR with archived and prospectively collected nasal aspirate-wash (NA-W) specimens and nasopharyngeal (NP) swabs from children and adults. Discrepant results were resolved by DNA sequence analysis. After discrepant-result analysis, the sensitivities of the Xpert Flu Assay for prospective NA-W specimens containing the influenza A, influenza A 2009 H1N1, and influenza B viruses compared to those of culture were 90.0%, 100%, and 100%, respectively, while the sensitivities of the assay for prospective NP swabs compared to those of culture were 100%, 100%, and 100%, respectively. The sensitivities of the Xpert Flu Assay for archived NA-W specimens compared to those of Gen-Probe ProFlu+ PCR for the influenza A, influenza A 2009 H1N1, and influenza B viruses were 99.4%, 98.4%, and 100%, respectively, while the sensitivities of the Xpert Flu Assay for archived NP swabs compared to those of ProFlu+ were 98.1%, 100%, and 93.8%, respectively. The sensitivities of the Xpert Flu Assay with archived NP specimens compared to those of culture for the three targets were 97.5%, 100%, and 93.8%, respectively. We conclude that the Cepheid Xpert Flu Assay is an accurate and rapid method that is suitable for on-demand testing for influenza viral infection.

Prospective evaluation of the Alere i Influenza A&B nucleic acid amplification versus Xpert Flu/RSV.

PubMed

Nguyen Van, J C; Caméléna, F; Dahoun, M; Pilmis, B; Mizrahi, A; Lourtet, J; Behillil, S; Enouf, V; Le Monnier, A

2016-05-01

The rapid and accurate detection of influenza virus in respiratory specimens is required for optimal management of patients with acute respiratory infections. Because of the variability of the symptoms and the numerous other causes of influenza-like illness, the diagnosis of influenza cannot be made on the basis of clinical criteria alone. Thus, rapid influenza diagnostic tests have been developed such as the Alere i Influenza A&B isothermal nucleic acid assay. We prospectively evaluated the performance of the Alere i Influenza A&B assay in comparison with our routine Xpert Flu/RSV assay. Positive samples were subtyped according to the protocol from the National Influenza Center (Paris, France). A total of 96 respiratory nasal swab samples were analyzed: with both methods, 38 were positive and 56 were negative. Samples were prospectively collected from January 20 to April 8, 2015, from patient (86 adult and 10 pediatric patients) presenting with an influenza-like illness through the French influenza season. In comparison with the Xpert Flu/RSV assay, the overall sensitivity and specificity of the Alere i Influenza A&B assay were 95% and 100%, respectively. Our results indicate that the Alere i Influenza A&B assay has a good overall analytical performance and a high degree of concordance with the PCR-based Xpert Flu/RSV assay. The Alere i Influenza A&B isothermal nucleic acid amplification test is a powerful tool for influenza detection due to its high sensitivity and specificity as well as its ability to generate results within 15min. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of the BD MAX MRSA XT to the Cepheid™ Xpert® MRSA assay for the molecular detection of methicillin-resistant Staphylococcus aureus from nasal swabs.

PubMed

Mehta, Sanjay R; Estrada, Jasmine; Ybarra, Juan; Fierer, Joshua

2017-04-01

Variation in MRSA genotypes may affect the sensitivity of molecular assays to detect this organism. We compared 2 commonly used screening assays, the Cepheid™ Xpert® MRSA and the BD MAX™ MRSA XT on consecutively obtained nasal swabs from 479 subjects. Specimens giving discordant results were subjected to additional microbiologic and molecular testing. Six hundred forty-two (97.6%) of the 658 test results were concordant. Of the 16 discordant results from 12 subjects, additional results suggested that 9 (60%) of the 15 MRSA XT assays were likely correct, and 6 (40%) of the 15 Xpert® assays were likely correct. One discordant result could not be resolved. A mecA dropout and novel mec right-extremity junction (MREJ) sites led to false-positive and negative results by Xpert®. While both assays performed well, continued vigilance is needed to monitor for Staphylococcus aureus with novel MREJ sites, mecA dropouts, and mecC, leading to inaccurate results in screening assays. Published by Elsevier Inc.

[Comparison of the efficacies of cross priming amplification and RealAmp with XpertMTB/RIF for the diagnosis of pulmonary tuberculosis at peripheral microscopic center].

PubMed

Wang, S H; Zheng, D W; Zhu, Y K; Ma, X G; Shi, J; Ou, X C; Li, H; Xing, J; Zhao, Y L

2018-02-12

Objective: To compare the efficacies of cross priming amplification (CPA) and RealAmp with XpertMTB/RIF for the diagnosis of pulmonary tuberculosis(TB) at peripheral microscopic centers. Methods: From December of 2014 to December of 2015, 3 193 patients suspected with TB were enrolled consecutively at 3 county level TB clinical clinics in Zhongmu, Xinmi and Dengzhou of Henan province. Totally 3 193 collected sputum samples were detected by smear microscopy, L-J media culture, CPA, RealAmp and Xpert MTB/RIF. The culture positive samples were tested by MPB64 for strain identification. The sensitivity and specificity of CPA, RealAmp and Xpert MTB/RIF were calculated according to L-J solid culture results and clinical diagnosis results. Results: The sensitivity of CPA, RealAmp and Xpert MTB/RIF were 85.5%(413/483), 85.5%(413/483) and 87.9%(422/480), respectively, compared with L-J solid culture, the difference among the 3 methods being not significant(χ(2)=1.6, P >0.05). The specificity of CPA, RealAmp and Xpert MTB/RIF were 96.8%(2 624/2 170), 93.2%(2 527/2 170) and 95.3%(2 567/2 170) compared with culture; and there was a significantly statistic difference among the 3 methods(χ(2)=37.8, P <0.001). The sensitivity of smear microscopy, culture, CPA, RealAmp and Xpert MTB/RIF was 21.7%(300/1 383), 34.9%(483/1 383), 34.6%(478/1 383), 39.2%(542/1 383) and 38.1%(526/1 381) compared with clinical diagnosis. The sensitivity of CPA, RealAmp and Xpert MTB/RIF was higher than that of smear (χ(2) =31.9, P <0.01), but there was no significantly statistic difference between the 3 molecular methods(χ(2)=2.9, P >0.05). The specificity of smear microscopy, L-J solid culture, CPA, RealAmp and Xpert MTB/RIF was 100%(1 810/1 810), 100%(1 810/1 810), 98.8%(1 789/1 810), 98.8%(1 756/1 810) and 97.0%(1 788/1 810), and there was no significantly statistic difference among the 3 molecular methods(χ(2)=0.16, P >0.05). Conclusion: The capability of CPA and RealAmp for diagnosing pulmonary

Evaluation of the Xpert® MTB/RIF assay and microscopy for the diagnosis of Mycobacterium tuberculosis in Namibia.

PubMed

Mavenyengwa, Rooyen T; Shaduka, Emma; Maposa, Innocent

2017-01-11

Tuberculosis (TB) kills approximately two million people and infects around nine million worldwide annually. Its proper management, especially in resource-limited settings, has been hindered by the lack of rapid and easy-to-use diagnostic tests. Sputum smear microscopy remains the cheapest, readily available diagnostic method but it only identifies less than half of the patients with a HIV/TB co-infection because the bacilli would have disseminated from the lungs to other areas of the body. The fully automated Xpert® MTB/RIF assay is a promising innovation for diagnosing TB and detecting resistance to rifampicin. This study aimed to evaluate the use of Xpert® MTB/RIF assay and microscopy in the diagnosis of Mycobacterium tuberculosis in Namibia, by determining the disease's epidemiology and calculating the proportion of cases infected just with TB and those with a resistance to rifampicin among the total suspected cases of TB in the country. This retrospective study analysed TB cases that were diagnosed using both the Xpert® MTB/RIF assay and microscopy. Data were collected from patient records from the Meditech laboratory information system of the Namibia Institute of Pathology for the time period of July 2012-April 2013. Data from 13 regions were collected. The total number of specimens collected from patients with symptoms of pulmonary TB was 1 842. Of these, 594 (32.20%) were found to be positive for MTB by Xpert® MTB/RIF assay, out of which 443 (24.05%) were also found to be positive by microscopy. The remainder was negative. The male patients were more resistant to rifampicin when compared to the female patients. Tuberculosis is widely distributed throughout Namibia, with slightly more males infected than females. Most TB patients are also co-infected with HIV. Both microscopy and Xpert® MTB/RIF assay are crucial for the diagnosis of TB in the country. Screening diagnostic efforts should focus on the sexually active HIV positive male population who could

Validation of the Cepheid GeneXpert for Detecting Ebola Virus in Semen.

PubMed

Loftis, Amy James; Quellie, Saturday; Chason, Kelly; Sumo, Emmanuel; Toukolon, Mason; Otieno, Yonnie; Ellerbrok, Heinzfried; Hobbs, Marcia M; Hoover, David; Dube, Karine; Wohl, David A; Fischer, William A

2017-02-01

Ebola virus (EBOV) RNA persistence in semen, reported sexual transmission, and sporadic clusters at the end of the 2013-2016 epidemic have prompted recommendations that male survivors refrain from unprotected sex unless their semen is confirmed to be EBOV free. However, there is no fully validated assay for EBOV detection in fluids other than blood. The Cepheid Xpert Ebola assay for EBOV RNA detection was validated for whole semen and blood using samples obtained from uninfected donors and spiked with inactivated EBOV. The validation procedure incorporated standards from Clinical and Laboratory Standards Institute and Good Clinical Laboratory Practices guidelines for evaluating molecular devices for use in infectious disease testing. The assay produced limits of detection of 1000 copies/mL in semen and 275 copies/mL in blood. Limits of detection for both semen and blood increased with longer intervals between collection and testing, with acceptable results obtained up to 72 hours after specimen collection. The Cepheid Xpert Ebola assay is accurate and precise for detecting EBOV in whole semen. A validated assay for EBOV RNA detection in semen informs the care of male survivors of Ebola, as well as recommendations for public health. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

The utility of Xpert MTB/RIF performed on bronchial washings obtained in patients with suspected pulmonary tuberculosis in a high prevalence setting.

PubMed

Barnard, Dewald A; Irusen, Elvis M; Bruwer, Johannes W; Plekker, Danté; Whitelaw, Andrew C; Deetlefs, Jacobus D; Koegelenberg, Coenraad F N

2015-09-16

Xpert MTB/RIF has been shown to have a superior sensitivity to microscopy for acid fast bacilli (AFB) in sputum and has been recommended as a standard first line investigation for pulmonary tuberculosis (PTB). Bronchoscopy is a valuable tool in diagnosing PTB in sputum negative patients. There is limited data on the utility of Xpert MTB/RIF performed on bronchial lavage specimens. Our aim was to evaluate the diagnostic efficiency of Xpert MTB/RIF performed on bronchial washings in sputum scarce/negative patients with suspected PTB. All patients with a clinical and radiological suspicion of PTB who underwent bronchoscopy between January 2013 and April 2014 were included. The diagnostic efficiencies of Xpert MTB/RIF and microscopy for AFB were compared to culture for Mycobacterium tuberculosis. Thirty nine of 112 patients were diagnosed with culture-positive PTB. Xpert MTB/RIF was positive in 36/39 with a sensitivity of 92.3% (95% CI 78-98%) for PTB, which was superior to that of smear microscopy (41%; 95% CI 26.0-57.8%, p = 0.005). The specificities of Xpert MTB/RIF and smear microscopy were 87.7% (95% CI 77.4-93.9%) and 98.6% (95% CI 91.6%-99.9%) respectively. Xpert MTB/RIF had a positive predictive value of 80% (95% CI; 65-89.9%) and negative predictive value of 95.5% (95% CI 86.6-98.8%). 3/9 patients with Xpert MTB/RIF positive culture negative results were treated for PTB based on clinical and radiological findings. Xpert MTB/RIF has a higher sensitivity than smear microscopy and similar specificity for the immediate confirmation of PTB in specimens obtained by bronchial washing, and should be utilised in patients with a high suspicion of pulmonary tuberculosis.

Performance of the Xpert MTB/RIF assay in the diagnosis of tuberculosis in formalin-fixed, paraffin-embedded tissues.

PubMed

Polepole, Pascal; Kabwe, Mwila; Kasonde, Mpanga; Tembo, John; Shibemba, Aaron; O'Grady, Justin; Kapata, Nathan; Zumla, Alimuddin; Bates, Matthew

2017-01-01

Extrapulmonary tuberculosis (EPTB), which accounts for 10%-40% of the global burden of TB, with the highest incidence in Sub-Saharan Africa, is strongly associated with human immunodeficiency virus infection. Diagnosing EPTB is challenging, and recently, there has been a concerted effort to evaluate the latest molecular diagnostics for diagnosing TB in a range of specimen types. The Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA, USA) is one such technology, which simultaneously detects Mycobacterium tuberculosis and rifampicin resistance. Our objective was to evaluate the accuracy of the Xpert MTB/RIF assay for the diagnosis of EPTB and detection of rifampicin resistance in routinely processed formalin-fixed, paraffin-embedded (FFPE) tissues, compared with histological detection of TB as the gold standard. A convenience set of 100 biobanked FFPE tissues, including lymph nodes (n = 64), male genital tract tissue (n = 10), abdominal tissue (n = 8), female genital tissue (n = 5), breast tissue (n = 5), synovial tissue (n = 4), skin (n = 2), tongue tissue (n = 1), and thyroid (n = 1), from routine cases of clinically suspected EPTB admitted to the University Teaching Hospital, Lusaka, Zambia, were analyzed using the Xpert MTB/RIF assay and in-house polymerase chain reaction (PCR) assay targeting IS6110, in parallel with Ziehl-Neelsen (ZN) staining, against histology as the gold standard. Some 66% of specimens had histological evidence of TB infection. ZN staining was positive for TB in 8% of cases, and Xpert MTB/RIF was positive for TB in 25% of cases. Taking histology as the gold standard, the sensitivity and specificity were as follows: In lymph tissue the accuracy of the Xpert MTB/RIF assay was 41% (95%CI 27-57), not significantly better than ZN or the in-house PCR assay. In non-lymph tissue the sensitivity of the in-house PCR assay was 82% (95%CI: 56%-95%), significantly higher than the Xpert MTB/RIF assay (P = 0.004). The Xpert MTB/RIF assay indicated rifampicin

Feasibility, accuracy, and clinical effect of point-of-care Xpert MTB/RIF testing for tuberculosis in primary-care settings in Africa: a multicentre, randomised, controlled trial.

PubMed

Theron, Grant; Zijenah, Lynn; Chanda, Duncan; Clowes, Petra; Rachow, Andrea; Lesosky, Maia; Bara, Wilbert; Mungofa, Stanley; Pai, Madhukar; Hoelscher, Michael; Dowdy, David; Pym, Alex; Mwaba, Peter; Mason, Peter; Peter, Jonny; Dheda, Keertan

2014-02-01

The Xpert MTB/RIF test for tuberculosis is being rolled out in many countries, but evidence is lacking regarding its implementation outside laboratories, ability to inform same-day treatment decisions at the point of care, and clinical effect on tuberculosis-related morbidity. We aimed to assess the feasibility, accuracy, and clinical effect of point-of-care Xpert MTB/RIF testing at primary-care health-care facilities in southern Africa. In this pragmatic, randomised, parallel-group, multicentre trial, we recruited adults with symptoms suggestive of active tuberculosis from five primary-care health-care facilities in South Africa, Zimbabwe, Zambia, and Tanzania. Eligible patients were randomly assigned using pregenerated tables to nurse-performed Xpert MTB/RIF at the clinic or sputum smear microscopy. Participants with a negative test result were empirically managed according to local WHO-compliant guidelines. Our primary outcome was tuberculosis-related morbidity (measured with the TBscore and Karnofsky performance score [KPS]) in culture-positive patients who had begun anti-tuberculosis treatment, measured at 2 months and 6 months after randomisation, analysed by intention to treat. This trial is registered with Clinicaltrials.gov, number NCT01554384. Between April 12, 2011, and March 30, 2012, we randomly assigned 758 patients to smear microscopy (182 culture positive) and 744 to Xpert MTB/RIF (185 culture positive). Median TBscore in culture-positive patients did not differ between groups at 2 months (2 [IQR 0-3] in the smear microscopy group vs 2 [0·25-3] in the MTB/RIF group; p=0·85) or 6 months (1 [0-3] vs 1 [0-3]; p=0·35), nor did median KPS at 2 months (80 [70-90] vs 90 [80-90]; p=0·23) or 6 months (100 [90-100] vs 100 [90-100]; p=0·85). Point-of-care MTB/RIF had higher sensitivity than microscopy (154 [83%] of 185 vs 91 [50%] of 182; p=0·0001) but similar specificity (517 [95%] 544 vs 540 [96%] of 560; p=0·25), and had similar sensitivity to

Prospective and Retrospective Evaluation of the Performance of the FDA-Approved Cepheid Xpert Flu/RSV XC Assay.

PubMed

Arbefeville, Sophie; Thonen-Kerr, Elizabeth; Ferrieri, Patricia

2017-11-08

Rapid and accurate detection of respiratory viruses is important in patient care and in guiding therapy and infection prevention policy. Rapid viral antigen assays are simple to perform and provide results within 15 to 30 minutes but are limited by their modest-to-moderate sensitivity. Molecular assays are more sensitive and specific but require more technical time and expertise and are more expensive. We verified the performance of the Xpert Flu/RSV XC assay prospectively, using patient respiratory samples from the 2014-2015 respiratory season, and, retrospectively, with frozen patient samples from the previous respiratory season. A total of 60 specimens were assayed on the Xpert Flu/RSV XC assay and by the GenMark Diagnostics eSensor Respiratory Viral Panel. The sensitivity of the Xpert Flu/RSV XC for Flu A was 100% (23/23), for Flu B, 80% (8/10), and for respiratory syncytial virus (RSV), 94.1% (16/17), compared to the reference assay (GenMark). The specificity was 100%. Eight specimens were positive for viruses other than Flu A/B or RSV, and this did not interfere with detection of targets in the Xpert assay. We demonstrated that the performance of the Xpert Flu/RSV XC was comparable to the more comprehensive molecular respiratory assay. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Successful off-label use of the Cepheid Xpert GBS in a late-onset neonatal meningitis by Streptococcus agalactiae.

PubMed

Savini, Vincenzo; Marrollo, Roberta; Coclite, Eleonora; Fusilli, Paola; D'Incecco, Carmine; Fazii, Paolo

2014-01-01

We report the case of a late-onset neonatal meningitis by Streptococcus agalactiae (group B Streptococcus - GBS) that was diagnosed with a latex agglutination assay (on cerebrospinal fluid, CSF), as well as by using, for the first time, Xpert GBS (Cepheid, US) on CSF. Due to empirical antibiotics given before sampling, both CSF and blood culture were negative, so the abovementioned diagnostics was crucial. Moreover, the Xpert GBS assay, performed according to an off-label, modified protocol (the system is designed for GBS-carriage intrapartum screening, based on a completely automated real time-Polymerase Chain Reaction) quickly detected the organism's genome target. Although further investigation on this test's performace on CSF is required, then, we trust it may be a promising, quick and precise diagnostic method for infections in newborns.

Rifampicin resistance mutations in the 81 bp RRDR of rpoB gene in Mycobacterium tuberculosis clinical isolates using Xpert® MTB/RIF in Kampala, Uganda: a retrospective study.

PubMed

Mboowa, Gerald; Namaganda, Carolyn; Ssengooba, Willy

2014-09-04

Introduction of Xpert® MTB/RIF assay has revolutionalised the diagnosis of tuberculosis (TB) by simultaneously detecting the bacteria and resistance to rifampicin (rif), a surrogate marker for multi-drug resistant TB (MDR-TB) as well as one of the principal first-line anti-tuberculosis drugs. In general, rpoB mutations can be found in 96.1% of rif-resistant Mycobacterium tuberculosis (MTB) strains worldwide and these mutations usually are located in a region at the 507-533rd amino acid residuals (81 bp) in the MTB rpoB gene, which is referred to as Rifampicin-resistance-determining region (RRDR). In this study, we determined the frequency of MDR-TB in Kampala using Xpert® MTB/RIF in comparison with the agar proportion method using Middlebrook 7H11and further determined the frequency of probes for different rpoB gene mutations using Xpert® MTB/RIF assay in the 81 bp RRDR. A total of 1501 specimens received at Mycobacteriology laboratory, Makerere University for Xpert testing between May 2011 and May 2014 were analysed by Xpert® MTB/RIF assay. Specimens that were positive for both MTB and rifampicin resistance were further subjected to a complete first line anti-mycobacterial drug susceptibility testing using Middlebrook 7H11 agar proportion method (APM). Xpert® MTB/RIF assay detected 313 MTB positive specimens and out of which 12 specimens had both MTB and rifampicin- resistance conferred by four different rpoB gene mutations in the 81 bp-RRDR of MTB, further one (1/12), specimen was found to be rifampicin mono-resistant on APM while the 11 were found to be MDR-TB. Probes associated with the observed rif- resistance were as follows: E (7/12), B (3/12), A (1/12), D (1/12) and no rif-resistance was associated with probe C. No specimen yielded rif-resistance associated with more than one probe failure (mutation combinations). Probe D was associated with rifampicin mono-resistant. MDR-TB was at 3.5% in the studied population. Mutations associated with Probe E

Comparison of GeneXpert MTB/RIF assay and LED-FM microscopy for the diagnosis of extra pulmonary tuberculosis in Khyber Pakhtunkhwa, Pakistan.

PubMed

Khan, Anwar Sheed; Ali, Sajid; Khan, Muhammad Tahir; Ahmed, Sajjad; Khattak, Yasir; Abduljabbar; Irfan, Muhammad; Sajjad, Wasim

2018-04-27

GeneXpert is one of the recent technological instruments used to diagnose tuberculosis in a short span of time. In this study, the performance of GeneXpert MTB/RIF assay for the diagnosis of extrapulmonary tuberculosis (EPTB) was compared with light-emitting diode Fluorescent Microscopy (LED-FM) in Khyber Pakhtunkhwa, Pakistan. A total of 737 EPTB samples were collected from tuberculosis (TB) suspected patients. Out of these samples, male to female ratio was 53% (n=390) to 47% (n=347) respectively. The sensitivity and specificity was 73% and 100% for GeneXpert, while 40% and 100% for LED-FM microscopy. This shows that the sensitivity of GeneXpert is 40-50%, higher than LED-FM microscopy. GeneXpert also detected low number of bacilli as compared to LED-FM microscopy. Copyright © 2018 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

Genotypic, Phenotypic and Clinical Validation of GeneXpert in Extra-Pulmonary and Pulmonary Tuberculosis in India

PubMed Central

Singh, Urvashi B.; Pandey, Pooja; Mehta, Girija; Bhatnagar, Anuj K.; Mohan, Anant; Goyal, Vinay; Ahuja, Vineet; Ramachandran, Ranjani; Sachdeva, Kuldeep S.; Samantaray, Jyotish C.

2016-01-01

Background Newer molecular diagnostics have brought paradigm shift in early diagnosis of tuberculosis [TB]. WHO recommended use of GeneXpert MTB/RIF [Xpert] for Extra-pulmonary [EP] TB; critics have since questioned its efficiency. Methods The present study was designed to assess the performance of GeneXpert in 761 extra-pulmonary and 384 pulmonary specimens from patients clinically suspected of TB and compare with Phenotypic, Genotypic and Composite reference standards [CRS]. Results Comparison of GeneXpert results to CRS, demonstrated sensitivity of 100% and 90.68%, specificity of 100% and 99.62% for pulmonary and extra-pulmonary samples. On comparison with culture, sensitivity for Rifampicin [Rif] resistance detection was 87.5% and 81.82% respectively, while specificity was 100% for both pulmonary and extra-pulmonary TB. On comparison to sequencing of rpoB gene [Rif resistance determining region, RRDR], sensitivity was respectively 93.33% and 90% while specificity was 100% in both pulmonary and extra-pulmonary TB. GeneXpert assay missed 533CCG mutation in one sputum and dual mutation [517 & 519] in one pus sample, detected by sequencing. Sequencing picked dual mutation [529, 530] in a sputum sample sensitive to Rif, demonstrating, not all RRDR mutations lead to resistance. Conclusions Current study reports observations in a patient care setting in a high burden region, from a large collection of pulmonary and extra-pulmonary samples and puts to rest questions regarding sensitivity, specificity, detection of infrequent mutations and mutations responsible for low-level Rif resistance by GeneXpert. Improvements in the assay could offer further improvement in sensitivity of detection in different patient samples; nevertheless it may be difficult to improve sensitivity of Rif resistance detection if only one gene is targeted. Assay specificity was high both for TB detection and Rif resistance detection. Despite a few misses, the assay offers major boost to early

Impact of Laboratory Practice Changes on the Diagnosis of Tuberculosis with the Introduction of Xpert MTB/RIF in Kiribati.

PubMed

Tonganibeia, Alfred; Harries, Anthony D; Merilles, Onofre Edwin A; Tarataake, Tekaibeti; Tiira, Teatao; Kienene, Takeieta

2018-02-01

The Republic of Kiribati, Central Pacific, has the largest tuberculosis epidemic in the region. There is a national tuberculosis control program, which has used smear microscopy for acid-fast bacilli as the main diagnostic tool for many years. In 2015, an Xpert MTB/RIF machine was procured and became functional within the tuberculosis hospital. The aim of this cross-sectional study, using routinely collected data, was to determine the effects of introducing Xpert MTB/RIF on laboratory smear microscopy practices and the pattern of registered tuberculosis cases. Between February 2015 and January 2016, there were 220 Xpert MTB/RIF assays performed with 6.4% errors and 15% detection of Mycobacterium tuberculosis: one patient showed rifampicin-resistance. One year before and after introducing Xpert MTB/RIF, the number of presumptive tuberculosis patients increased by 9% from 2,138 to 2,322. There were no changes in demographic characteristics, smear-positive results, or acid-fast bacilli grade between the two periods. The number of specimens cultured for Mycobacterium tuberculosis significantly declined from 638 to zero, with 76 positive MTB cultures before and none after introducing Xpert MTB/RIF. There was a significant change in the profile of registered tuberculosis cases with more children (34% versus 21%) and fewer bacteriologically-confirmed cases (29% versus 43%) - P < .001. Since the deployment of Xpert MTB/RIF in Kiribati, there have been a small number of assays performed and this has been associated with no adverse effects on smear microscopy, a stoppage in mycobacterial cultures, and a change in the types and categories of diagnosed tuberculosis.

Assessment of the patient, health system, and population effects of Xpert MTB/RIF and alternative diagnostics for tuberculosis in Tanzania: an integrated modelling approach.

PubMed

Langley, Ivor; Lin, Hsien-Ho; Egwaga, Saidi; Doulla, Basra; Ku, Chu-Chang; Murray, Megan; Cohen, Ted; Squire, S Bertel

2014-10-01

Several promising new diagnostic methods and algorithms for tuberculosis have been endorsed by WHO. National tuberculosis programmes now face the decision on which methods to implement and where to place them in the diagnostic algorithm. We used an integrated model to assess the effects of different algorithms of Xpert MTB/RIF and light-emitting diode (LED) fluorescence microscopy in Tanzania. To understand the effects of new diagnostics from the patient, health system, and population perspective, the model incorporated and linked a detailed operational component and a transmission component. The model was designed to represent the operational and epidemiological context of Tanzania and was used to compare the effects and cost-effectiveness of different diagnostic options. Among the diagnostic options considered, we identified three strategies as cost effective in Tanzania. Full scale-up of Xpert would have the greatest population-level effect with the highest incremental cost: 346 000 disability-adjusted life-years (DALYs) averted with an additional cost of US$36·9 million over 10 years. The incremental cost-effectiveness ratio (ICER) of Xpert scale-up ($169 per DALY averted, 95% credible interval [CrI] 104-265) is below the willingness-to-pay threshold ($599) for Tanzania. Same-day LED fluorescence microscopy is the next most effective strategy with an ICER of $45 (95% CrI 25-74), followed by LED fluorescence microscopy with an ICER of $29 (6-59). Compared with same-day LED fluorescence microscopy and Xpert full rollout, targeted use of Xpert in presumptive tuberculosis cases with HIV infection, either as an initial diagnostic test or as a follow-on test to microscopy, would produce DALY gains at a higher incremental cost and therefore is dominated in the context of Tanzania. For Tanzania, this integrated modelling approach predicts that full rollout of Xpert is a cost-effective option for tuberculosis diagnosis and has the potential to substantially reduce

Operational modelling: the mechanisms influencing TB diagnostic yield in an Xpert® MTB/RIF-based algorithm.

PubMed

Dunbar, R; Naidoo, P; Beyers, N; Langley, I

2017-04-01

Cape Town, South Africa. To compare the diagnostic yield for smear/culture and Xpert® MTB/RIF algorithms and to investigate the mechanisms influencing tuberculosis (TB) yield. We developed and validated an operational model of the TB diagnostic process, first with the smear/culture algorithm and then with the Xpert algorithm. We modelled scenarios by varying TB prevalence, adherence to diagnostic algorithms and human immunodeficiency virus (HIV) status. This enabled direct comparisons of diagnostic yield in the two algorithms to be made. Routine data showed that diagnostic yield had decreased over the period of the Xpert algorithm roll-out compared to the yield when the smear/culture algorithm was in place. However, modelling yield under identical conditions indicated a 13.3% increase in diagnostic yield from the Xpert algorithm compared to smear/culture. The model demonstrated that the extensive use of culture in the smear/culture algorithm and the decline in TB prevalence are the main factors contributing to not finding an increase in diagnostic yield in the routine data. We demonstrate the benefits of an operational model to determine the effect of scale-up of a new diagnostic algorithm, and recommend that policy makers use operational modelling to make appropriate decisions before new diagnostic algorithms are scaled up.

Feasibility of Xpert Ebola Assay in Médecins Sans Frontières Ebola Program, Guinea

PubMed Central

Chaillet, Pascale; Sow, Mamadou Saliou; Amand, Mathieu; van Vyve, Charlotte; Jonckheere, Sylvie; Crestani, Rosa; Sprecher, Armand; Van Herp, Michel; Chua, Arlene; Piriou, Erwan; Koivogui, Lamine; Antierens, Annick

2016-01-01

Rapid diagnostic methods are essential in control of Ebola outbreaks and lead to timely isolation of cases and improved epidemiologic surveillance. Diagnosis during Ebola outbreaks in West Africa has relied on PCR performed in laboratories outside this region. Because time between sampling and PCR results can be considerable, we assessed the feasibility and added value of using the Xpert Ebola Assay in an Ebola control program in Guinea. A total of 218 samples were collected during diagnosis, treatment, and convalescence of patients. Median time for obtaining results was reduced from 334 min to 165 min. Twenty-six samples were positive for Ebola virus. Xpert cycle thresholds were consistently lower, and 8 (31%) samples were negative by routine PCR. Several logistic and safety issues were identified. We suggest that implementation of the Xpert Ebola Assay under programmatic conditions is feasible and represents a major advance in diagnosis of Ebola virus disease without apparent loss of assay sensitivity. PMID:26812466

Feasibility of Xpert Ebola Assay in Médecins Sans Frontières Ebola Program, Guinea.

PubMed

Van den Bergh, Rafael; Chaillet, Pascale; Sow, Mamadou Saliou; Amand, Mathieu; van Vyve, Charlotte; Jonckheere, Sylvie; Crestani, Rosa; Sprecher, Armand; Van Herp, Michel; Chua, Arlene; Piriou, Erwan; Koivogui, Lamine; Antierens, Annick

2016-02-01

Rapid diagnostic methods are essential in control of Ebola outbreaks and lead to timely isolation of cases and improved epidemiologic surveillance. Diagnosis during Ebola outbreaks in West Africa has relied on PCR performed in laboratories outside this region. Because time between sampling and PCR results can be considerable, we assessed the feasibility and added value of using the Xpert Ebola Assay in an Ebola control program in Guinea. A total of 218 samples were collected during diagnosis, treatment, and convalescence of patients. Median time for obtaining results was reduced from 334 min to 165 min. Twenty-six samples were positive for Ebola virus. Xpert cycle thresholds were consistently lower, and 8 (31%) samples were negative by routine PCR. Several logistic and safety issues were identified. We suggest that implementation of the Xpert Ebola Assay under programmatic conditions is feasible and represents a major advance in diagnosis of Ebola virus disease without apparent loss of assay sensitivity.

[Budget impact of the incorporation of GeneXpert MTB/RIF for diagnosis of pulmonary tuberculosis from the perspective of the Brazilian Unified National Health System, Brazil, 2013-2017].

PubMed

Pinto, Márcia Ferreira Teixeira; Steffen, Ricardo; Entringer, Aline; Costa, Ana Carolina Carioca da; Trajman, Anete

2017-10-09

The study aimed to estimate the budget impact of GeneXpert MTB/RIF for diagnosis of tuberculosis from the perspective of the Brazilian National Program for Tuberculosis Control, drawing on a static model using the epidemiological method, from 2013 to 2017. GeneXpert MTB/RIF was compared with two diagnostic sputum smear tests. The study used epidemiological, population, and cost data, exchange rates, and databases from the Brazilian Unified National Health System. Sensitivity analysis of scenarios was performed. Incorporation of GeneXpert MTB/RIF would cost BRL 147 million (roughly USD 45 million) in five years and would have an impact of 23 to 26% in the first two years and some 11% between 2015 and 2017. The results can support Brazilian and other Latin American health administrators in planning and managing the decision on incorporating the technology.

Impact of Xpert MTB/RIF for TB diagnosis in a primary care clinic with high TB and HIV prevalence in South Africa: a pragmatic randomised trial.

PubMed

Cox, Helen S; Mbhele, Slindile; Mohess, Neisha; Whitelaw, Andrew; Muller, Odelia; Zemanay, Widaad; Little, Francesca; Azevedo, Virginia; Simpson, John; Boehme, Catharina C; Nicol, Mark P

2014-11-01

Xpert MTB/RIF is approved for use in tuberculosis (TB) and rifampicin-resistance diagnosis. However, data are limited on the impact of Xpert under routine conditions in settings with high TB burden. A pragmatic prospective cluster-randomised trial of Xpert for all individuals with presumptive (symptomatic) TB compared to the routine diagnostic algorithm of sputum microscopy and limited use of culture was conducted in a large TB/HIV primary care clinic. The primary outcome was the proportion of bacteriologically confirmed TB cases not initiating TB treatment by 3 mo after presentation. Secondary outcomes included time to TB treatment and mortality. Unblinded randomisation occurred on a weekly basis. Xpert and smear microscopy were performed on site. Analysis was both by intention to treat (ITT) and per protocol. Between 7 September 2010 and 28 October 2011, 1,985 participants were assigned to the Xpert (n = 982) and routine (n = 1,003) diagnostic algorithms (ITT analysis); 882 received Xpert and 1,063 routine (per protocol analysis). 13% (32/257) of individuals with bacteriologically confirmed TB (smear, culture, or Xpert) did not initiate treatment by 3 mo after presentation in the Xpert arm, compared to 25% (41/167) in the routine arm (ITT analysis, risk ratio 0.51, 95% CI 0.33-0.77, p = 0.0052). The yield of bacteriologically confirmed TB cases among patients with presumptive TB was 17% (167/1,003) with routine diagnosis and 26% (257/982) with Xpert diagnosis (ITT analysis, risk ratio 1.57, 95% CI 1.32-1.87, p<0.001). This difference in diagnosis rates resulted in a higher rate of treatment initiation in the Xpert arm: 23% (229/1,003) and 28% (277/982) in the routine and Xpert arms, respectively (ITT analysis, risk ratio 1.24, 95% CI 1.06-1.44, p = 0.013). Time to treatment initiation was improved overall (ITT analysis, hazard ratio 0.76, 95% CI 0.63-0.92, p = 0.005) and among HIV-infected participants (ITT analysis, hazard ratio 0.67, 95% CI 0.53-0.85, p = 0

Assessment and Optimization of the GeneXpert Diagnostic Platform for Detection of Ebola Virus RNA in Seminal Fluid.

PubMed

Pettitt, James; Higgs, Elizabeth; Fallah, Mosoka; Nason, Martha; Stavale, Eric; Marchand, Jonathan; Reilly, Cavan; Jensen, Kenneth; Dighero-Kemp, Bonnie; Tuznik, Kaylie; Logue, James; Bolay, Fatorma; Hensley, Lisa

2017-02-15

Recent studies have suggested that Ebola virus (EBOV) ribonucleic acid (RNA) potentially present in the semen of a large number of survivors of Ebola virus disease (EVD) in Western Africa may contribute to sexual transmission of EVD and generate new clusters of cases in regions previously declared EVD-free. These findings drive the immediate need for a reliable, rapid, user-friendly assay for detection of EBOV RNA in semen that is deployable to multiple sites across Western Africa. In this study, we optimized the Xpert EBOV assay for semen samples by adding dithiothreitol. Compared to the assays currently in use in Liberia (including Ebola Zaire Target 1, major groove binder real-time-polymerase chain reaction assays, and original Xpert EBOV assay), the modified Xpert EBOV assay demonstrated greater sensitivity than the comparator assays. Thus, the modified Xpert EBOV assay is optimal for large-scale monitoring of EBOV RNA persistence in male survivors. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Impact of Xpert MTB/RIF for TB Diagnosis in a Primary Care Clinic with High TB and HIV Prevalence in South Africa: A Pragmatic Randomised Trial

PubMed Central

Cox, Helen S.; Mbhele, Slindile; Mohess, Neisha; Whitelaw, Andrew; Muller, Odelia; Zemanay, Widaad; Little, Francesca; Azevedo, Virginia; Simpson, John; Boehme, Catharina C.; Nicol, Mark P.

2014-01-01

Background Xpert MTB/RIF is approved for use in tuberculosis (TB) and rifampicin-resistance diagnosis. However, data are limited on the impact of Xpert under routine conditions in settings with high TB burden. Methods and Findings A pragmatic prospective cluster-randomised trial of Xpert for all individuals with presumptive (symptomatic) TB compared to the routine diagnostic algorithm of sputum microscopy and limited use of culture was conducted in a large TB/HIV primary care clinic. The primary outcome was the proportion of bacteriologically confirmed TB cases not initiating TB treatment by 3 mo after presentation. Secondary outcomes included time to TB treatment and mortality. Unblinded randomisation occurred on a weekly basis. Xpert and smear microscopy were performed on site. Analysis was both by intention to treat (ITT) and per protocol. Between 7 September 2010 and 28 October 2011, 1,985 participants were assigned to the Xpert (n = 982) and routine (n = 1,003) diagnostic algorithms (ITT analysis); 882 received Xpert and 1,063 routine (per protocol analysis). 13% (32/257) of individuals with bacteriologically confirmed TB (smear, culture, or Xpert) did not initiate treatment by 3 mo after presentation in the Xpert arm, compared to 25% (41/167) in the routine arm (ITT analysis, risk ratio 0.51, 95% CI 0.33–0.77, p = 0.0052). The yield of bacteriologically confirmed TB cases among patients with presumptive TB was 17% (167/1,003) with routine diagnosis and 26% (257/982) with Xpert diagnosis (ITT analysis, risk ratio 1.57, 95% CI 1.32–1.87, p<0.001). This difference in diagnosis rates resulted in a higher rate of treatment initiation in the Xpert arm: 23% (229/1,003) and 28% (277/982) in the routine and Xpert arms, respectively (ITT analysis, risk ratio 1.24, 95% CI 1.06–1.44, p = 0.013). Time to treatment initiation was improved overall (ITT analysis, hazard ratio 0.76, 95% CI 0.63–0.92, p = 0.005) and among HIV-infected participants

Comparison between the diagnostic validities of Xpert MTB/RIF and interferon-γ release assays for tuberculous pericarditis using pericardial tissue.

PubMed

Yu, Guocan; Ye, Bo; Chen, Da; Zhong, Fangming; Chen, Gang; Yang, Jun; Xu, Liliang; Xu, Xudong

2017-01-01

This study aimed to assess the diagnostic performance of Xpert MTB/RIF for tuberculous pericarditis (TBP) using pericardial tissues. The study involved 30 patients admitted with suspected TBP from January-December 2016; three patients were later excluded. The interferon-γ release assay (T-SPOT.TB) and the Xpert MTB/RIF test were performed using peripheral blood and pericardial tissues, respectively. TBP was confirmed using pericardial histopathology and a composite reference standard (CRS). We analyzed the sensitivity, specificity, predictive value (PV), likelihood ratio (LR), and area under curve (AUC) of both assays. Fourteen patients were confirmed as TBP, 10 as non-TBP, and 3 as probable TBP. The sensitivity, specificity, positive PV (PPV), negative PV (NPV), PLR, NLR, and AUC (95% confidence interval [CI]) of the Xpert MTB/RIF assay were 78.6% (49.2-95.3%) and 70.6% (44.0-89.7%); 92.3% (64.0-99.8%) and 100% (69.2-100%); 91.7% (61.5-99.8%) and 100% (73.5-100%); 80.0% (51.9-95.7%) and 66.7% (38.4-88.2%); 10.21 (1.52-68.49) and the PLR value was undefined with CRS as the reference; 0.23 (0.08-0.64) and 0.29(0.14-0.61); and 0.854 (0.666-0.959) and 0.853 (0.664-0.959), against histopathology and CRS, respectively. The sensitivity, specificity, PPV, NPV, PLR, NLR, and AUC values (95% CI) of T-SPOT.TB were 92.9% (66.1-99.8%) and 94.1% (71.3-99.9%); 15.4% (1.9-45.5%) and 20.0% (2.5-55.6%); 54.2% (32.8-74.5%) and 66.7% (44.7-84.4%); 66.7% (9.4-99.2%) and 66.7% (9.4-99.2%); 1.10 (0.83-1.44) and 1.18 (0.84-1.6); 0.46 (0.05-4.53) and 0.29 (0.03-2.85); and 0.541(0.340-0.733) and 0.571(0.367-0.758), against histopathology and CRS, respectively. The differences in sensitivity, PPV, and AUC of Xpert MTB/RIF and T-SPOT.TB were not statistically significant (P > 0.05), compared to those of histopathology and CRS. However, the differences in specificity and NPV of the two assays were significant (P < 0.05), compared to those of histopathology and CRS. Xpert MTB/RIF test is a

A prospective study of the prevalence of tuberculosis and bacteraemia in Bangladeshi children with severe malnutrition and pneumonia including an evaluation of Xpert MTB/RIF assay.

PubMed

Chisti, Mohammod Jobayer; Graham, Stephen M; Duke, Trevor; Ahmed, Tahmeed; Ashraf, Hasan; Faruque, Abu Syed Golam; La Vincente, Sophie; Banu, Sayera; Raqib, Rubhana; Salam, Mohammed Abdus

2014-01-01

Severe malnutrition is a risk factor for pneumonia due to a wide range of pathogens but aetiological data are limited and the role of Mycobacterium tuberculosis is uncertain. We prospectively investigated severely malnourished young children (<5 years) with radiological pneumonia admitted over a 15-month period. Investigations included blood culture, sputa for microscopy and mycobacterial culture. Xpert MTB/RIF assay was introduced during the study. Study children were followed for 12 weeks following their discharge from the hospital. 405 eligible children were enrolled, with a median age of 10 months. Bacterial pathogens were isolated from blood culture in 18 (4.4%) children, of which 72% were Gram negatives. Tuberculosis was confirmed microbiologically in 7% (27/396) of children that provided sputum - 10 by culture, 21 by Xpert MTB/RIF assay, and 4 by both tests. The diagnostic yield from induced sputum was 6% compared to 3.5% from gastric aspirate. Sixty (16%) additional children had tuberculosis diagnosed clinically that was not microbiologically confirmed. Most confirmed tuberculosis cases did not have a positive contact history or positive tuberculin test. The sensitivity and specificity of Xpert MTB/RIF assay compared to culture was 67% (95% CI: 24-94) and 92% (95% CI: 87-95) respectively. Overall case-fatality rate was 17% and half of the deaths occurred in home following discharge from the hospital. TB was common in severely malnourished Bangladeshi children with pneumonia. X-pert MTB/RIF assay provided higher case detection rate compared to sputum microscopy and culture. The high mortality among the study children underscores the need for further research aimed at improved case detection and management for better outcomes.

Evaluating the diagnostic accuracy of the Xpert MTB/RIF assay on bronchoalveolar lavage fluid: A retrospective study.

PubMed

Lu, Yanjun; Zhu, Yaowu; Shen, Na; Tian, Lei; Sun, Ziyong

2018-02-08

Limited data on the diagnostic accuracy of the Xpert MTB/RIF assay using bronchoalveolar lavage fluid from patients with suspected pulmonary tuberculosis (PTB) have been reported in China. Therefore, a retrospective study was designed to evaluate the diagnostic accuracy of this assay. Clinical, radiological, and microbiological characteristics of 238 patients with suspected PTB were reviewed retrospectively. The sensitivity, specificity, positive predictive value, and negative predictive value for the diagnosis of active PTB were calculated for the Xpert MTB/RIF assay using TB culture or final diagnosis based on clinical and radiological evaluation as the reference standard. The sensitivity and specificity of the Xpert MTB/RIF assay were 84.5% and 98.9%, respectively, and those for smear microscopy were 36.2% and 100%, respectively, when compared to the culture method. However, compared with the sensitivity and specificity of final diagnosis based on clinical and radiological evaluation, the sensitivity and specificity of the assay were 72.9% and 98.7%, respectively, which were significantly higher than those for smear microscopy. The Xpert MTB/RIF assay on bronchoalveolar lavage fluid could serve as an additional rapid diagnostic tool for PTB in a high TB-burden country and improve the time to TB treatment initiation in patients with PTB. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Establishing Ebola Virus Disease (EVD) diagnostics using GeneXpert technology at a mobile laboratory in Liberia: Impact on outbreak response, case management and laboratory systems strengthening

PubMed Central

Condell, Orla; Wasunna, Christine; Kpaka, Jonathan; Zwizwai, Ruth; Nuha, Mahmood; Fallah, Mosoka; Freeman, Maxwell; Harris, Victoria; Miller, Mark; Baller, April; Massaquoi, Moses; Katawera, Victoria; Saindon, John; Bemah, Philip; Hamblion, Esther; Castle, Evelyn; Williams, Desmond; Gasasira, Alex; Nyenswah, Tolbert

2018-01-01

The 2014–16 Ebola Virus Disease (EVD) outbreak in West Africa highlighted the necessity for readily available, accurate and rapid diagnostics. The magnitude of the outbreak and the re-emergence of clusters of EVD cases following the declaration of interrupted transmission in Liberia, reinforced the need for sustained diagnostics to support surveillance and emergency preparedness. We describe implementation of the Xpert Ebola Assay, a rapid molecular diagnostic test run on the GeneXpert platform, at a mobile laboratory in Liberia and the subsequent impact on EVD outbreak response, case management and laboratory system strengthening. During the period of operation, site coordination, management and operational capacity was supported through a successful collaboration between Ministry of Health (MoH), World Health Organization (WHO) and international partners. A team of Liberian laboratory technicians were trained to conduct EVD diagnostics and the laboratory had capacity to test 64–100 blood specimens per day. Establishment of the laboratory significantly increased the daily testing capacity for EVD in Liberia, from 180 to 250 specimens at a time when the effectiveness of the surveillance system was threatened by insufficient diagnostic capacity. During the 18 months of operation, the laboratory tested a total of 9,063 blood specimens, including 21 EVD positives from six confirmed cases during two outbreaks. Following clearance of the significant backlog of untested EVD specimens in November 2015, a new cluster of EVD cases was detected at the laboratory. Collaboration between surveillance and laboratory coordination teams during this and a later outbreak in March 2016, facilitated timely and targeted response interventions. Specimens taken from cases during both outbreaks were analysed at the laboratory with results informing clinical management of patients and discharge decisions. The GeneXpert platform is easy to use, has relatively low running costs and can

Establishing Ebola Virus Disease (EVD) diagnostics using GeneXpert technology at a mobile laboratory in Liberia: Impact on outbreak response, case management and laboratory systems strengthening.

PubMed

Raftery, Philomena; Condell, Orla; Wasunna, Christine; Kpaka, Jonathan; Zwizwai, Ruth; Nuha, Mahmood; Fallah, Mosoka; Freeman, Maxwell; Harris, Victoria; Miller, Mark; Baller, April; Massaquoi, Moses; Katawera, Victoria; Saindon, John; Bemah, Philip; Hamblion, Esther; Castle, Evelyn; Williams, Desmond; Gasasira, Alex; Nyenswah, Tolbert

2018-01-01

The 2014-16 Ebola Virus Disease (EVD) outbreak in West Africa highlighted the necessity for readily available, accurate and rapid diagnostics. The magnitude of the outbreak and the re-emergence of clusters of EVD cases following the declaration of interrupted transmission in Liberia, reinforced the need for sustained diagnostics to support surveillance and emergency preparedness. We describe implementation of the Xpert Ebola Assay, a rapid molecular diagnostic test run on the GeneXpert platform, at a mobile laboratory in Liberia and the subsequent impact on EVD outbreak response, case management and laboratory system strengthening. During the period of operation, site coordination, management and operational capacity was supported through a successful collaboration between Ministry of Health (MoH), World Health Organization (WHO) and international partners. A team of Liberian laboratory technicians were trained to conduct EVD diagnostics and the laboratory had capacity to test 64-100 blood specimens per day. Establishment of the laboratory significantly increased the daily testing capacity for EVD in Liberia, from 180 to 250 specimens at a time when the effectiveness of the surveillance system was threatened by insufficient diagnostic capacity. During the 18 months of operation, the laboratory tested a total of 9,063 blood specimens, including 21 EVD positives from six confirmed cases during two outbreaks. Following clearance of the significant backlog of untested EVD specimens in November 2015, a new cluster of EVD cases was detected at the laboratory. Collaboration between surveillance and laboratory coordination teams during this and a later outbreak in March 2016, facilitated timely and targeted response interventions. Specimens taken from cases during both outbreaks were analysed at the laboratory with results informing clinical management of patients and discharge decisions. The GeneXpert platform is easy to use, has relatively low running costs and can be

Comparative Evaluation of the Diagnostic Performance of the Prototype Cepheid GeneXpert Ebola Assay

PubMed Central

Jansen van Vuren, Petrus; Grobbelaar, Antoinette; Storm, Nadia; Conteh, Ousman; Konneh, Kelfala; Kamara, Abdul; Sanne, Ian

2015-01-01

The Ebola virus disease (EVD) outbreak in West Africa has highlighted an urgent need for point-of-care (POC) assays for the diagnosis of this devastating disease in resource-limited African countries. The diagnostic performance characteristics of a prototype Cepheid GeneXpert Ebola POC used to detect Ebola virus (EBOV) in stored serum and plasma samples collected from suspected EVD cases in Sierra Leone in 2014 and 2015 was evaluated. The GeneXpert Ebola POC is a self-contained single-cartridge automated system that targets the glycoprotein (GP) and nucleoprotein (NP) genes of EBOV and yields results within 90 min. Results from 281 patient samples were compared to the results of a TaqMan real-time reverse transcription-PCR (RT-PCR) targeting the polymerase gene and performed on two real-time PCR machines. Agreement between the three platforms was 100% at cycle threshold (CT) values of ≤34.99, but discordant results were noted between CT values of 35 and 45.The diagnostic sensitivity of the three platforms was 100% in 91 patient samples that were confirmed to be infectious by virus isolation. All three molecular platforms detected viral EBOV RNA in additional samples that did not contain viable EBOV. The analytical sensitivity of the GeneXpert Ebola POC for the detection of NP was higher, and comparable to that of polymerase gene detection, than that for the detection of GP when using a titrated laboratory stock of EBOV. There was no detectable cross-reactivity with other hemorrhagic fever viruses or arboviruses. The GeneXpert Ebola POC offers an easy to operate and sensitive diagnostic tool that can be used for the rapid screening of suspected EVD cases in treatment or in holding centers during EVD outbreaks. PMID:26637383

Accurate PCR Detection of Influenza A/B and Respiratory Syncytial Viruses by Use of Cepheid Xpert Flu+RSV Xpress Assay in Point-of-Care Settings: Comparison to Prodesse ProFlu.

PubMed

Cohen, Daniel M; Kline, Jennifer; May, Larissa S; Harnett, Glenn Eric; Gibson, Jane; Liang, Stephen Y; Rafique, Zubaid; Rodriguez, Carina A; McGann, Kevin M; Gaydos, Charlotte A; Mayne, Donna; Phillips, David; Cohen, Jason

2018-02-01

The Xpert Flu+RSV Xpress Assay is a fast, automated in vitro diagnostic test for qualitative detection and differentiation of influenza A and B viruses and respiratory syncytial virus (RSV) performed on the Cepheid GeneXpert Xpress System. The objective of this study was to establish performance characteristics of the Xpert Flu+RSV Xpress Assay compared to those of the Prodesse ProFlu+ real-time reverse transcription-PCR (RT-PCR) assay (ProFlu+) for the detection of influenza A and B viruses as well as RSV in a Clinical Laboratory Improvement Amendments (CLIA)-waived (CW) setting. Overall, the assay, using fresh and frozen nasopharyngeal (NP) swabs, demonstrated high concordance with results of the ProFlu+ assay in the combined CW and non-CW settings with positive percent agreements (PPA) (100%, 100%, and 97.1%) and negative percent agreements (NPA) (95.2%, 99.5%, and 99.6%) for influenza A and B viruses and RSV, respectively. In conclusion, this multicenter study using the Cepheid Xpert Flu+RSV Xpress Assay demonstrated high sensitivities and specificities for influenza A and B viruses and RSV in ∼60 min for use at the point-of-care in the CW setting. Copyright © 2018 American Society for Microbiology.

Use of the Xpert(®) MTB/RIF assay for diagnosing pulmonary tuberculosis comorbidity and multidrug-resistant TB in obstetrics and gynaecology inpatient wards at the University Teaching Hospital, Lusaka, Zambia.

PubMed

Bates, Matthew; Ahmed, Yusuf; Chilukutu, Lophina; Tembo, John; Cheelo, Busiku; Sinyangwe, Sylvester; Kapata, Nathan; Maeurer, Markus; O'Grady, Justin; Mwaba, Peter; Zumla, Alimuddin

2013-09-01

In high-tuberculosis (TB)-endemic countries, comorbidity of pulmonary TB in hospitalised patients with non-communicable diseases is well documented. In this study, we evaluated the use of the Xpert(®) MTB/RIF assay for the detection of concomitant pulmonary TB in patients admitted to the University Teaching Hospital, Lusaka, Zambia, with a primary obstetric or gynaecological condition. The Study population were inpatients admitted with a primary obstetric or gynaecological problem who had a concomitant cough and were able to expectorate a sputum sample. Sputum samples from 94 patients were analysed for the presence of Mycobacterium tuberculosis (M.tb) by standard smear microscopy, MGIT culture, MGIT drug-susceptibility testing (DST) and the Xpert(®) MTB/RIF assay. The sensitivity and specificity of the Xpert(®) MTB/RIF assay were evaluated against the culture gold standard. Twenty-six of 94 (27.7%) patients had culture-confirmed pulmonary TB. The Xpert(®) MTB/RIF assay had a sensitivity of 80.8% [95% CI: 60.0-92.7%]) compared against MGIT culture. The Xpert(®) MTB/RIF assay was more sensitive than sputum smear microscopy (21/26 (80.8%) vs. 13/26 (50.0%), P = 0.02) and detected an additional eight culture-confirmed cases. Culture DST analysis identified two monoresistant M.tb strains: one resistant to rifampicin (rifampicin sensitive by the Xpert(®) MTB/RIF assay) and one to ethambutol. HIV infection was linked with a 3-fold increase in risk of TB, accounting for 87.5% (21/24) of TB cases. 50% of cases presented as comorbidities with other communicable diseases (CDs) and non-communicable diseases (NCDs). As an alternative to sputum microscopy, the Xpert(®) MTB/RIF assay provides a sensitive, specific and rapid method for the diagnosis of pulmonary TB in obstetric or gynaecological inpatients. Pulmonary TB is an important cause of concomitant comorbidity to the obstetric or gynaecological condition necessitating admission. TB and HIV comorbidities with other

Comparison between the diagnostic validities of Xpert MTB/RIF and interferon-γ release assays for tuberculous pericarditis using pericardial tissue

PubMed Central

Yu, Guocan; Zhong, Fangming; Chen, Gang; Yang, Jun; Xu, Liliang

2017-01-01

Background This study aimed to assess the diagnostic performance of Xpert MTB/RIF for tuberculous pericarditis (TBP) using pericardial tissues. Methods The study involved 30 patients admitted with suspected TBP from January–December 2016; three patients were later excluded. The interferon-γ release assay (T-SPOT.TB) and the Xpert MTB/RIF test were performed using peripheral blood and pericardial tissues, respectively. TBP was confirmed using pericardial histopathology and a composite reference standard (CRS). We analyzed the sensitivity, specificity, predictive value (PV), likelihood ratio (LR), and area under curve (AUC) of both assays. Results Fourteen patients were confirmed as TBP, 10 as non-TBP, and 3 as probable TBP. The sensitivity, specificity, positive PV (PPV), negative PV (NPV), PLR, NLR, and AUC (95% confidence interval [CI]) of the Xpert MTB/RIF assay were 78.6% (49.2–95.3%) and 70.6% (44.0–89.7%); 92.3% (64.0–99.8%) and 100% (69.2–100%); 91.7% (61.5–99.8%) and 100% (73.5–100%); 80.0% (51.9–95.7%) and 66.7% (38.4–88.2%); 10.21 (1.52–68.49) and the PLR value was undefined with CRS as the reference; 0.23 (0.08–0.64) and 0.29(0.14–0.61); and 0.854 (0.666–0.959) and 0.853 (0.664–0.959), against histopathology and CRS, respectively. The sensitivity, specificity, PPV, NPV, PLR, NLR, and AUC values (95% CI) of T-SPOT.TB were 92.9% (66.1–99.8%) and 94.1% (71.3–99.9%); 15.4% (1.9–45.5%) and 20.0% (2.5–55.6%); 54.2% (32.8–74.5%) and 66.7% (44.7–84.4%); 66.7% (9.4–99.2%) and 66.7% (9.4–99.2%); 1.10 (0.83–1.44) and 1.18 (0.84–1.6); 0.46 (0.05–4.53) and 0.29 (0.03–2.85); and 0.541(0.340–0.733) and 0.571(0.367–0.758), against histopathology and CRS, respectively. The differences in sensitivity, PPV, and AUC of Xpert MTB/RIF and T-SPOT.TB were not statistically significant (P > 0.05), compared to those of histopathology and CRS. However, the differences in specificity and NPV of the two assays were significant

Modeling the patient and health system impacts of alternative xpert® MTB/RIF algorithms for the diagnosis of pulmonary tuberculosis in Addis Ababa, Ethiopia.

PubMed

Tesfaye, Abraham; Fiseha, Daniel; Assefa, Dawit; Klinkenberg, Eveline; Balanco, Silvia; Langley, Ivor

2017-05-02

To reduce global tuberculosis (TB) burden, the active disease must be diagnosed quickly and accurately and patients should be treated and cured. In Ethiopia, TB diagnosis mainly relies on spot-morning-spot (SMS) sputum sample smear analysis using Ziehl-Neelsen staining techniques (ZN). Since 2014 targeted use of xpert has been implemented. New diagnostic techniques have higher sensitivity and are likely to detect more cases if routinely implemented. The objective of our study was to project the effects of alternative diagnostic algorithms on the patient, health system, and costs, and identify cost-effective algorithms that increase TB case detection in Addis Ababa, Ethiopia. An observational quantitative modeling framework was applied using the Virtual Implementation approach. The model was designed to represent the operational and epidemiological context of Addis Ababa, the capital city of Ethiopia. We compared eight diagnostic algorithm with ZN microscopy, light emitting diode (LED) fluorescence microscopy and Xpert MTB/RIF. Interventions with an annualized cost per averted disability adjusted life year (DALY) of less than the Gross Domestic Product (GDP) per capita are considered cost-effective interventions. With a cost lower than the average per-capita GDP (US$690 for Ethiopia) for each averted disability adjusted life year (DALY), three of the modeled algorithms are cost-effective. Implementing them would have important patient, health system, and population-level effects in the context of Addis Ababa ❖ The full roll-out of Xpert MTB/RIF as the primary test for all presumptive TB cases would avert 91170 DALYs (95% credible interval [CrI] 54888 - 127448) with an additional health system cost of US$ 11.6 million over the next 10 years. The incremental cost-effectiveness ratio (ICER) is $370 per DALY averted. ❖ Same day LED fluorescence microscopy for all presumptive TB cases combined with Xpert MTB/RIF targeted to HIV-positive and High multidrug resistant

Opinions and Use of Psychological Tests: A Survey of Clinical Psychologists

ERIC Educational Resources Information Center

Wade, Terry C.; Baker, Timothy B.

1977-01-01

Five hundred clinical psychologists were surveyed about their use and opinions of psychological tests. Results showed that both objective and projective tests are used by clinical psychologists of all major therapeutic orientations. (Author)

Assessment of the sensitivity and specificity of Xpert MTB/RIF assay as an early sputum biomarker of response to tuberculosis treatment.

PubMed

Friedrich, Sven O; Rachow, Andrea; Saathoff, Elmar; Singh, Kasha; Mangu, Chacha D; Dawson, Rodney; Phillips, Patrick Pj; Venter, Amour; Bateson, Anna; Boehme, Catharina C; Heinrich, Norbert; Hunt, Robert D; Boeree, Martin J; Zumla, Alimuddin; McHugh, Timothy D; Gillespie, Stephen H; Diacon, Andreas H; Hoelscher, Michael

2013-08-01

An accurate biomarker is urgently needed to monitor the response to treatment in patients with pulmonary tuberculosis. The Xpert MTB/RIF assay is a commercially available real-time PCR that can be used to detect Mycobacterium-tuberculosis-specific DNA sequences in sputum samples. We therefore evaluated this assay with serial sputum samples obtained over 26 weeks from patients undergoing treatment for tuberculosis. We analysed sputum samples from 221 patients with smear-positive tuberculosis enrolled at two sites (Cape Town, South Africa, and Mbeya, Tanzania) of a multicentre randomised clinical trial REMoxTB of antituberculosis treatment on a weekly basis (weeks 0 to 8), then at weeks 12, 17, 22, and 26 after treatment initiation. The Xpert MTB/RIF results over time were compared with the results of standard smear microscopy and culture methods. We obtained and analysed 2741 sputum samples from 221 patients. The reduction in positivity rates with Xpert MTB/RIF were slower than those with the standard methods. At week 8, positive results were obtained for 62 (29%) of 212 sputum samples with smear microscopy, 46 (26%) of 175 with solid culture (Löwenstein-Jensen medium), 77 (42%) of 183 with liquid culture (Bactec MGIT960 system), and 174 (84%) of 207 with Xpert MTB/RIF; at 26 weeks, positive results were obtained for ten (5%) of 199, four (3%) of 157, seven (4%) of 169, and 22 (27%) of 83 sputum samples, respectively. The reduction in detection of quantitative M tuberculosis DNA with Xpert MTB/RIF correlated with smear grades (ρ=-0·74; p<0·0001), solid culture grades (ρ=-0·73; p<0·0001), and time to liquid culture positivity (ρ=0·73; p<0·0001). Compared with the combined binary smear and culture results as a reference standard, the Xpert MTB/RIF assay had high sensitivity (97·0%, 95% CI 95·8-97·9), but poor specificity (48·6%, 45·0-52·2). The poor specificity precludes the use of the Xpert MTB/RIF assay as a biomarker for monitoring tuberculosis

The performance of Luminex ARIES® Flu A/B & RSV and Cepheid Xpert® Flu/RSV XC for the detection of influenza A, influenza B, and respiratory syncytial virus in prospective patient samples.

PubMed

McMullen, Phillip; Boonlayangoor, Sue; Charnot-Katsikas, Angella; Beavis, Kathleen G; Tesic, Vera

2017-10-01

The demand for rapid, accurate viral testing has increased the number of assays available for the detection of viral pathogens. One of the newest FDA cleared platforms is the Luminex ARIES ® Flu A/B & RSV, which is a fully automated, real-time PCR-based assay used for detection of influenza A, influenza B, and respiratory syncytial virus (RSV). We sought to compare the performance of Luminex ARIES ® Flu A/B & RSV assay to the Cepheid Xpert ® Flu/RSV XC assay for rapid Flu and RSV testing. A series of consecutive nasopharyngeal specimens received in the clinical microbiology laboratory during peak influenza season at a major academic center in Chicago, IL, were prospectively tested, using both the ARIES ® Flu A/B & RSV and Xpert ® Flu/RSV XC assays, side by side. Discrepant results were tested on the BioFire FilmArray ® Respiratory Panel for resolution. A total of 143 consecutive nasopharyngeal specimens, obtained from patients ranging from six months to ninety-three years in age were received between January 1st, 2017 and March 21st, 2017. There was 96.6% agreement between the two assays for detection influenza A, 100% agreement for detection influenza B and RSV, and 98.9% agreement for negative results. The Xpert ® Flu/RSV XC performed with an average turn-around time of approximately 60min, compared to the ARIES ® Flu A/B & RSV of approximately 120min. Both assays were equally easy to perform, with a similar amount of hands-on technologist time for each platform. Overall, these results indicate that both tests are comparable in terms of result agreement and technical ease-of-use. The Xpert ® Flu/RSV XC assay did produce results with less turn-around-time, approximately 60min quicker than the ARIES ® Flu A/B & RSV. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of the yield of tuberculosis among contacts of multidrug-resistant and drug-sensitive tuberculosis patients in Ethiopia using GeneXpert as a primary diagnostic test.

PubMed

Hiruy, Nebiyu; Melese, Muluken; Habte, Dereje; Jerene, Degu; Gashu, Zewdu; Alem, Genetu; Jemal, Ilili; Tessema, Belay; Belayneh, Beza; Suarez, Pedro G

2018-06-01

This study compared the yield of tuberculosis (TB) among contacts of multidrug-resistant tuberculosis (MDR-TB) index cases with that in drug-sensitive TB (DS-TB) index cases in a program setting. A comparative cross-sectional study was conducted among contacts of sputum smear-positive new DS-TB index cases and MDR-TB index cases. After contacts were screened, GeneXpert was used for the diagnosis of TB. The study included 111 MDR-TB and 119 DS-TB index cases. A total of 340 and 393 contacts of MDR-TB and DS-TB index cases, respectively, were traced, of whom 331 among MDR-TB contacts and 353 among DS-TB contacts were screened. There were 20 (6%) presumptive TB cases for MDR-TB contacts and 41 (11%) for DS-TB contacts. The prevalence of TB among MDR-TB contacts was 2.7% and among DS-TB contacts was 4.0%. The majority of the MDR-TB contacts diagnosed with TB had MDR-TB; the reverse was true for DS-TB. The yield of TB among contacts of MDR-TB and DS-TB patients using GeneXpert was high as compared to the population-level prevalence. The likelihood of diagnosing rifampicin-resistant TB among contacts of MDR-TB index cases was higher in comparison with contacts of DS-TB index cases. The use of GeneXpert in DS-TB contact investigation has the added advantage of diagnosing rifampicin-resistant TB cases when compared to the use of the nationally recommended acid-fast bacillus (AFB) microscopy for DS-TB contact investigation. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Diagnostic accuracy of Xpert MTB/RIF for tuberculosis detection in different regions with different endemic burden: A systematic review and meta-analysis.

PubMed

Li, Shiying; Liu, Bin; Peng, Mingli; Chen, Min; Yin, Wenwei; Tang, Hui; Luo, Yuxuan; Hu, Peng; Ren, Hong

2017-01-01

To estimate the diagnostic accuracy of Xpert MTB/RIF, a systematic review and meta-analysis were carried out. Up to June 20, 2015, multiple databases were screened for relevant studies. Accordingly, 106 studies included 52,410 samples were selected. Diagnostic accuracy of Xpert MTB/RIF for TB detection was validated against either culture or a composite reference standard (CRS). Additionally, selected studies were further subgrouped in four groups based on sample's type, subject's age, status of HIV co-infection and smear-positivity. The overall pooled sensitivity and specificity of Xpert MTB/RIF was 0.85 (95% confidence interval [CI] 0.82-0.88) and 0.98 (95% CI 0.96-0.98), respectively, compared to culture; while it was 0.59 (95% CI 0.44-0.72) and 0.99 (95% CI 0.97-1.00) compared to CRS. The overall sensitivity was lower in countries with high TB prevalence than countries with middle/low prevalence (0.84, 95% CI: 0.80-0.88 versus 0.89, 95% CI: 0.84-0.93). Furthermore, Xpert MTB/RIF has higher sensitivity in patients with positive smears (0.99, 95% CI 0.97-0.99), in patients with pulmonary TB samples (0.87, 95% CI 0.83-0.90), in adults (0.82, 95% CI 0.76-0.86) and in HIV-positive patients (0.81, 95% CI 0.73-0.87). Taken together, Xpert MTB/RIF is a quick and accurate diagnostic assay for TB which will significantly help the physicians to make their clinical decisions.

Xpert® MTB/RIF: Usefulness for the diagnosis of tuberculosis and resistance to rifampicin.

PubMed

Vergara Gómez, Andrea; González-Martín, Julià; García-Basteiro, Alberto L

2017-11-09

The advent of the Xpert® MTB/RIF technique was a revolution in the diagnosis of tuberculosis, especially in areas with high incidence and low resources. It allows the detection of Mycobacterium tuberculosis complex and simultaneously the most common resistance mutations to rifampicin in less than 2h. For respiratory samples the sensitivity is very high, but it decreases for extrapulmonary samples and children. Although it is faster and simpler than conventional methods, it presents some limitations and new and better techniques are needed to reduce the number of cases and deaths caused by tuberculosis. This review aims to assess the scientific evidence around the diagnostic performance of Xpert® MTB/RIF in different types of samples and populations, as well as analyse its strengths and limitations for TB diagnosis. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Evaluation of the Xpert MTB/RIF assay for the diagnosis of smear-negative pulmonary and extrapulmonary tuberculosis in Madagascar.

PubMed

Rakotoarivelo, R; Ambrosioni, J; Rasolofo, V; Raberahona, M; Rakotosamimanana, N; Andrianasolo, R; Ramanampamonjy, R; Tiaray, M; Razafimahefa, J; Rakotoson, J; Randria, M; Bonnet, F; Calmy, A

2018-04-01

To evaluate the feasibility of the implementation of a commercial rapid molecular diagnostic test (Xpert MTB/RIF) for the routine diagnosis of smear-negative or extrapulmonary tuberculosis (TB) and its diagnostic accuracy, and to assess HIV prevalence in a real-life setting in Madagascar. This study was set in a tertiary care hospital in Madagascar. A prospective cohort study was conducted of all consecutive cases with suspected smear-negative and/or extrapulmonary TB over a 2-year period. Cases were classified as proven, probable, or possible TB cases, or as having an alternative diagnosis. Of the 363 patients included, 183 (50.4%) had suspected smear-negative pulmonary TB and 180 (49.6%) had suspected extrapulmonary TB. For proven cases, the sensitivity, specificity, positive and negative predictive values of Xpert MTB/RIF were 82.4%, 98.8%, 98.3%, and 86.6%, respectively; for proven and probable cases grouped together, these values were 65%, 98.8%, 98.5%, and 64%, respectively. The diagnostic accuracy was slightly lower for extrapulmonary TB compared to smear-negative pulmonary TB. The prevalence of HIV infection was 12.1%, but almost half of these cases did not have TB (alternative diagnosis group). The implementation of a rapid diagnosis programme for TB in a resource-poor setting is feasible. The performance of the Xpert-MTB/RIF was remarkable in this difficult-to-diagnose population. HIV prevalence in this study was much higher than the prevalence reported in the general population in Madagascar, in patients with TB and patients with conditions other than TB. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Counseling Psychologists' Uses of and Opinions about Psychological Tests: A Contemporary Perspective.

ERIC Educational Resources Information Center

Watkins, C. Edward Jr.; And Others

1988-01-01

Assessed counseling psychologists' (N=630) uses of and opinions about psychological tests. Found psychologists used both objective and projective tests, using objective tests more. Psychologists recommended counseling students learn about tests because they answer assessment needs and provide personality structure information. Found the…

Direct Detection by the Xpert MTB/RIF Assay and Characterization of Multi and Poly Drug-Resistant Tuberculosis in Guinea-Bissau, West Africa

PubMed Central

Ponce, Gema; Sanca, Lilica; Mané, Morto; Armada, Ana; Machado, Diana; Vieira, Fina; Gomes, Victor F.; Martins, Elisabete; Colombatti, Raffaella; Riccardi, Fabio; Perdigão, João; Sotero, Joana; Portugal, Isabel; Couto, Isabel; Atouguia, Jorge; Rodrigues, Amabélia; Viveiros, Miguel

2015-01-01

Background This study aimed to evaluate the usefulness of the Xpert MTB/RIF assay for the rapid direct detection of M. tuberculosis complex (MTBC) strains and rifampicin resistance associated mutations in a resource-limited setting such as Guinea-Bissau and its implications in the management of tuberculosis (TB) and drug resistant tuberculosis, complementing the scarce information on resistance and genotypic diversity of MTBC strains in this West African country. Methods and Results This cross-sectional prospective study included 100 consecutive TB patients with positive acid-fast smears at two months of anti-tuberculosis treatment or in a re-treatment situation, between May and December 2012. Resistance to rifampicin was detected using the GeneXpert system and the Xpert MTB/RIF assay. MTBC isolates obtained with the BACTEC MGIT 960 system were tested for susceptibility to first- and second-line anti-tuberculosis drugs. Overall, the prevalence of multidrug-resistant tuberculosis (MDR-TB) was found to be 9 cases. Of these, 67% (6 patients) of confirmed MDR-TB cases had no past history of TB treatment and 33% (3 patients) were previously treated cases. Extensively drug-resistant TB was not found. Molecular typing of the MDR-TB strains revealed recent transmission patterns of imported MDR strains. Conclusions The Xpert MTB/RIF assay was reliable for the detection of rifampicin resistant MTBC strains directly from sputum samples of patients undergoing first-line treatment for two months, being more trustworthy than the simple presence of acid-fast bacilli in the smear. Its implementation is technically simple, does not require specialized laboratory infrastructures and is suitable for resource-limited settings when a regular source of electricity and maintenance is available as well as financial and operation sustainability is guaranteed by the health authorities. A high prevalence of MDR-TB among patients at risk of MDR-TB after two months of first-line treatment was

GeneXpert HIV-1 quant assay, a new tool for scale up of viral load monitoring in the success of ART programme in India.

PubMed

Kulkarni, Smita; Jadhav, Sushama; Khopkar, Priyanka; Sane, Suvarna; Londhe, Rajkumar; Chimanpure, Vaishali; Dhilpe, Veronica; Ghate, Manisha; Yelagate, Rajendra; Panchal, Narayan; Rahane, Girish; Kadam, Dilip; Gaikwad, Nitin; Rewari, Bharat; Gangakhedkar, Raman

2017-07-21

Recent WHO guidelines identify virologic monitoring for diagnosing and confirming ART failure. In view of this, validation and scale up of point of care viral load technologies is essential in resource limited settings. A systematic validation of the GeneXpert® HIV-1 Quant assay (a point-of-care technology) in view of scaling up HIV-1 viral load in India to monitor the success of national ART programme was carried out. Two hundred nineteen plasma specimens falling in nine viral load ranges (<40 to >5 L copies/ml) were tested by the Abbott m2000rt Real Time and GeneXpert HIV-1 Quant assays. Additionally, 20 seronegative; 16 stored specimens and 10 spiked controls were also tested. Statistical analysis was done using Stata/IC and sensitivity, specificity, PPV, NPV and %misclassification rates were calculated as per DHSs/AISs, WHO, NACO cut-offs for virological failure. The GeneXpert assay compared well with the Abbott assay with a higher sensitivity (97%), specificity (97-100%) and concordance (91.32%). The correlation between two assays (r = 0.886) was statistically significant (p < 0.01), the linear regression showed a moderate fit (R 2  = 0.784) and differences were within limits of agreement. Reproducibility showed an average variation of 4.15 and 3.52% while Lower limit of detection (LLD) and Upper limit of detection (ULD) were 42 and 1,740,000 copies/ml respectively. The misclassification rates for three viral load cut offs were not statistically different (p = 0.736). All seronegative samples were negative and viral loads of the stored samples showed a good fit (R 2  = 0.896 to 0.982). The viral load results of GeneXpert HIV-1 Quant assay compared well with Abbott HIV-1 m2000 Real Time PCR; suggesting its use as a Point of care assay for viral load estimation in resource limited settings. Its ease of performance and rapidity will aid in timely diagnosis of ART failures, integrated HIV-TB management and will facilitate the UNAIDS 90-90-90 target.

Diagnostic accuracy of Xpert MTB/RIF for tuberculosis detection in different regions with different endemic burden: A systematic review and meta-analysis

PubMed Central

Li, Shiying; Liu, Bin; Peng, Mingli; Chen, Min; Yin, Wenwei; Tang, Hui; Luo, Yuxuan; Ren, Hong

2017-01-01

Purpose To estimate the diagnostic accuracy of Xpert MTB/RIF, a systematic review and meta-analysis were carried out. Methods Up to June 20, 2015, multiple databases were screened for relevant studies. Results Accordingly, 106 studies included 52,410 samples were selected. Diagnostic accuracy of Xpert MTB/RIF for TB detection was validated against either culture or a composite reference standard (CRS). Additionally, selected studies were further subgrouped in four groups based on sample’s type, subject’s age, status of HIV co-infection and smear-positivity. The overall pooled sensitivity and specificity of Xpert MTB/RIF was 0.85 (95% confidence interval [CI] 0.82–0.88) and 0.98 (95% CI 0.96–0.98), respectively, compared to culture; while it was 0.59 (95% CI 0.44–0.72) and 0.99 (95% CI 0.97–1.00) compared to CRS. The overall sensitivity was lower in countries with high TB prevalence than countries with middle/low prevalence (0.84, 95% CI: 0.80–0.88 versus 0.89, 95% CI: 0.84–0.93). Furthermore, Xpert MTB/RIF has higher sensitivity in patients with positive smears (0.99, 95% CI 0.97–0.99), in patients with pulmonary TB samples (0.87, 95% CI 0.83–0.90), in adults (0.82, 95% CI 0.76–0.86) and in HIV-positive patients (0.81, 95% CI 0.73–0.87). Conclusions Taken together, Xpert MTB/RIF is a quick and accurate diagnostic assay for TB which will significantly help the physicians to make their clinical decisions. PMID:28708844

XPERT DESIGN AND DIAGNOSTICS' (XDD) IN-SITU CHEMICAL OXIDATION PROCESS USING POTASSIUM PERMANGANATE (KMNO4)

EPA Science Inventory

Xpert Design and Diagnostic's (XDD)potassium permanganate in situ chemical oxidation (ISCO) process was evaluated under the EPA Superfund Innovative Technology Evaluation (SITE) Program at the former MEC Building site located in Hudson, New Hampshire. At this site, both soil and ...

[Evaluation of an Xpert EV (Cepheid®) molecular diagnostic technique for enteroviral meningitis].

PubMed

Alonso Pérez, Natalia; Sagastizabal Cardelus, Belén; Prieto Tato, Luis Manuel; Guillén Martín, Sara; González Torralba, Ana; García Bermejo, Isabel; Ramos Amador, José Tomás

2017-10-01

Polymerase chain reaction (PCR) assays have shown to be useful and quick for the diagnosis of enterovirus in aseptic meningitis. The aim of our study was to analyse the changes in clinical practice after the introduction of a real-time polymerase chain reaction (RT-PCR) technique using the Xpert EV (Cepheid ® ) assay for the qualitative detection of enterovirus RNA in cerebrospinal fluid specimens from children with suspected viral meningitis. A retrospective study was performed in children older than 1year, diagnosed with enterovirus meningitis in a third level hospital from November 2006 to February 2013. The first period, before the availability of Xpert EV (Cepheid ® ) (Group1, November 2006-August 2010) was compared with the later period (Group2, September 2010-February 2013). Clinical characteristics, the mean length of stay, and the cost per inpatient cases, were compared between the 2periods. Forty-one patients (60.9% male) were included, with a median age of 64 months (interquartile range 28-96). Twenty-six patients (63.4%) were included in Group2. There were non-statistically significant differences in the epidemiological, disease severity, and laboratory characteristics between both periods of study. A significant difference was observed in the mean length of stay, with it being shorter in Group2 (48hours vs 40.5hours, P=.039), and a significant lower inpatient cost per case (€779.77 vs €656.05, P<.05). Xpert EV (Cepheid ® ) assay was useful for decreasing the length of hospital stay and the costs associated with hospitalisation in children with enterovirus meningitis. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

The Importance of Implementation Strategy in Scaling Up Xpert MTB/RIF for Diagnosis of Tuberculosis in the Indian Health-Care System: A Transmission Model

PubMed Central

Salje, Henrik; Andrews, Jason R.; Deo, Sarang; Satyanarayana, Srinath; Sun, Amanda Y.; Pai, Madhukar; Dowdy, David W.

2014-01-01

Background India has announced a goal of universal access to quality tuberculosis (TB) diagnosis and treatment. A number of novel diagnostics could help meet this important goal. The rollout of one such diagnostic, Xpert MTB/RIF (Xpert) is being considered, but if Xpert is used mainly for people with HIV or high risk of multidrug-resistant TB (MDR-TB) in the public sector, population-level impact may be limited. Methods and Findings We developed a model of TB transmission, care-seeking behavior, and diagnostic/treatment practices in India and explored the impact of six different rollout strategies. Providing Xpert to 40% of public-sector patients with HIV or prior TB treatment (similar to current national strategy) reduced TB incidence by 0.2% (95% uncertainty range [UR]: −1.4%, 1.7%) and MDR-TB incidence by 2.4% (95% UR: −5.2%, 9.1%) relative to existing practice but required 2,500 additional MDR-TB treatments and 60 four-module GeneXpert systems at maximum capacity. Further including 20% of unselected symptomatic individuals in the public sector required 700 systems and reduced incidence by 2.1% (95% UR: 0.5%, 3.9%); a similar approach involving qualified private providers (providers who have received at least some training in allopathic or non-allopathic medicine) reduced incidence by 6.0% (95% UR: 3.9%, 7.9%) with similar resource outlay, but only if high treatment success was assured. Engaging 20% of all private-sector providers (qualified and informal [providers with no formal medical training]) had the greatest impact (14.1% reduction, 95% UR: 10.6%, 16.9%), but required >2,200 systems and reliable treatment referral. Improving referrals from informal providers for smear-based diagnosis in the public sector (without Xpert rollout) had substantially greater impact (6.3% reduction) than Xpert scale-up within the public sector. These findings are subject to substantial uncertainty regarding private-sector treatment patterns, patient care-seeking behavior

Rifampicin resistance mutations in the 81 bp RRDR of rpoB gene in Mycobacterium tuberculosis clinical isolates using Xpert MTB/RIF in Khyber Pakhtunkhwa, Pakistan: a retrospective study.

PubMed

Ullah, Irfan; Shah, Aamer Ali; Basit, Anila; Ali, Mazhar; Khan, Afsar; Ullah, Ubaid; Ihtesham, Muhammad; Mehreen, Sumaira; Mughal, Anita; Javaid, Arshad

2016-08-12

Multi-drug resistant tuberculosis (MDR-TB) is a major public health problem especially in developing countries. World Health Organization (WHO) recommends use of Xpert MTB/RIF assay to simultaneously detecting Mycobacterium tuberculosis (MTB) and rifampicin (RIF) resistance. The primary objective of this study was to determine the frequency of MDR-TB in patients suspected to have drug resistance in Khyber Pakhtunkhwa. The frequency of probes for various rpoB gene mutations using Xpert MTB/RIF assay within 81 bp RRDR (Rifampicin Resistance Determining Region) was the secondary objective. A total of 2391 specimens, received at Programmatic Management of Drug Resistant TB (PMDT) Unit, Lady Reading Hospital (LRH) Peshawar, Pakistan, between October 2011 and December 2014, were analyzed by Xpert MTB/RIF test. MTB positive with rifampicin resistance were further analyzed to first line anti-mycobacterial drug susceptibility testing (DST) using middle brook 7H10 medium. The data was analyzed using statistical software; SPSS version 18. Out of 2391 specimens, 1408 (59 %) were found positive for MTB and among them, 408 (29 %) showed rifampicin-resistance with four different rpoB gene mutations within 81 bp RRDR. The frequency of various probes among RIF-resistant isolates was observed as: probe E, in 314 out of 408 isolates; B, 44 out of 408; A, 5 out of 408; D, 34 out of 408; and probe C was observed among 6 out of 408 RIF-resistant isolates. The probe A&B and E&D mutation combination was found in only 1 isolate in each case, while B&D mutation combination was detected among 3 out of 408 RIF-resistant isolates. Hence, it is concluded from our study on a selected population, 29 % of patients had MDR-TB. Probe E related mutations (also known as codon 531and 533) were the most common rpoB genetic mutation [314 (77 %)], acknowledged by Xpert MTB/RIF assay. Least mutation was detected within the sequence 511 (1.2 %).

A feasibility study of the Xpert MTB/RIF test at the peripheral level laboratory in China.

PubMed

Ou, Xichao; Xia, Hui; Li, Qiang; Pang, Yu; Wang, Shengfen; Zhao, Bing; Song, Yuanyuan; Zhou, Yang; Zheng, Yang; Zhang, Zhijian; Zhang, Zhiying; Li, Junchen; Dong, Haiyan; Chi, Junying; Zhang, Jack; Kam, Kai Man; Huan, Shitong; Jun, Yue; Chin, Daniel P; Zhao, Yanlin

2015-02-01

To evaluate the performance of Xpert MTB/RIF (MTB/RIF) in the county-level tuberculosis (TB) laboratory in China. From April 2011 to January 2012, patients with suspected multidrug-resistant tuberculosis (MDR-TB) and non-MDR-TB were enrolled consecutively from four county-level TB laboratories. The detection of Mycobacterium tuberculosis (MTB) by MTB/RIF was compared to detection by Löwenstein-Jensen culture. The detection of rifampin resistance was compared to detection by conventional drug-susceptibility testing. The impact of multiple specimens on the performance of MTB/RIF was also evaluated. A total of 2142 suspected non-MDR-TB cases and 312 suspected MDR-TB cases were enrolled. For MTB detection in suspected non-MDR-TB cases, the sensitivity and specificity of MTB/RIF were 94.4% and 90.2%, respectively. The sensitivity in smear-negative patients was 88.8%. For the detection of rifampin resistance in suspected non-MDR-TB cases, the sensitivity and specificity of MTB/RIF were 87.1% and 97.9%, respectively. For the detection of rifampin resistance in suspected MDR-TB cases, the sensitivity and specificity of MTB/RIF were 87.1% and 91.0%, respectively. Using multiple sputum specimens had no significant influence on the performance of MTB/RIF for MTB detection. The introduction of MTB/RIF could increase the accuracy of detection of MTB and rifampin resistance in peripheral-level TB laboratories in China. One single specimen is adequate for TB diagnosis by MTB/RIF. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Survey of Expert Opinion on Intelligence: Causes of International Differences in Cognitive Ability Tests

PubMed Central

Rindermann, Heiner; Becker, David; Coyle, Thomas R.

2016-01-01

Following Snyderman and Rothman (1987, 1988), we surveyed expert opinions on the current state of intelligence research. This report examines expert opinions on causes of international differences in student assessment and psychometric IQ test results. Experts were surveyed about the importance of culture, genes, education (quantity and quality), wealth, health, geography, climate, politics, modernization, sampling error, test knowledge, discrimination, test bias, and migration. The importance of these factors was evaluated for diverse countries, regions, and groups including Finland, East Asia, sub-Saharan Africa, Southern Europe, the Arabian-Muslim world, Latin America, Israel, Jews in the West, Roma (gypsies), and Muslim immigrants. Education was rated by N = 71 experts as the most important cause of international ability differences. Genes were rated as the second most relevant factor but also had the highest variability in ratings. Culture, health, wealth, modernization, and politics were the next most important factors, whereas other factors such as geography, climate, test bias, and sampling error were less important. The paper concludes with a discussion of limitations of the survey (e.g., response rates and validity of expert opinions). PMID:27047425

Brief Report: High Sensitivity and Specificity of the Cepheid Xpert HIV-1 Qualitative Point-of-Care Test Among Newborns in Botswana.

PubMed

Ibrahim, Maryanne; Moyo, Sikhulile; Mohammed, Terence; Mupfumi, Lucy; Gaseitsiwe, Simani; Maswabi, Kenneth; Ajibola, Gbolahan; Gelman, Rebecca; Batlang, Oganne; Sakoi, Maureen; Auletta-Young, Chloe; Makhema, Joseph; Lockman, Shahin; Shapiro, Roger L

2017-08-15

HIV point-of-care (POC) testing allows for early infant HIV diagnosis and treatment, but POC accuracy at birth and in the setting of antiretroviral prophylaxis for the prevention of mother-to-child HIV transmission is unknown. We evaluated the Cepheid Xpert HIV-1 Qual POC test against the Roche Taqman HIV-1 DNA polymerase chain reaction (PCR) platform using dried blood spots from 15 HIV-infected and 75 HIV-exposed uninfected newborns. These infants were screened for HIV at <96 hours of life at 5 hospital maternity wards in Botswana; all infants received postexposure antiretroviral prophylaxis with single-dose nevirapine and zidovudine, and most mothers received 3-drug antiretroviral therapy in pregnancy and at delivery. Fourteen of the 15 PCR positive samples tested positive by Cepheid POC, yielding a sensitivity of 93.3% (95% confidence interval: 68.1 to 99.8). Baseline viral load among positive infants ranged from <40 to >10,000,000 copies/mL, with a median of 2403 copies/mL. The HIV RNA for the infant with false-negative POC testing was 1661 copies/mL. Of note, 2 infants with low HIV RNA (<40 and 272 copies/mL) were correctly identified as HIV positive by Cepheid POC. All the 75 PCR-negative samples tested negative by Cepheid POC, yielding a specificity of 100% (95% confidence interval: 96.1 to 100). Our study demonstrates high sensitivity and specificity for the Cepheid POC assay in the first week of life despite early infection and antiretroviral prophylaxis. This platform may be a useful approach for adding early infant HIV diagnosis to current testing programs.

Testing Some Notions of the Fact/Opinion Distinction in Libel.

ERIC Educational Resources Information Center

Cohen, Jeremy; And Others

A study of reader response to newspaper articles in a defamatory context tested: (1) the judicial assumption that the macro-environment in which statements appear is important to a reader's distinguishing between fact and opinion; (2) the possibility that a byline may influence a reader's characterization of statements; and (3) the idea that…

Performance of a Cartridge-Based Assay for Detection of Clinically Significant Human Papillomavirus (HPV) Infection: Lessons from VALGENT (Validation of HPV Genotyping Tests)

PubMed Central

Geraets, Daan; Cuzick, Jack; Cadman, Louise; Moore, Catherine; Vanden Broeck, Davy; Padalko, Elisaveta; Quint, Wim; Arbyn, Marc

2016-01-01

The Validation of Human Papillomavirus (HPV) Genotyping Tests (VALGENT) studies offer an opportunity to clinically validate HPV assays for use in primary screening for cervical cancer and also provide a framework for the comparison of analytical and type-specific performance. Through VALGENT, we assessed the performance of the cartridge-based Xpert HPV assay (Xpert HPV), which detects 14 high-risk (HR) types and resolves HPV16 and HPV18/45. Samples from women attending the United Kingdom cervical screening program enriched with cytologically abnormal samples were collated. All had been previously tested by a clinically validated standard comparator test (SCT), the GP5+/6+ enzyme immunoassay (EIA). The clinical sensitivity and specificity of the Xpert HPV for the detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) and CIN3+ relative to those of the SCT were assessed as were the inter- and intralaboratory reproducibilities according to international criteria for test validation. Type concordance for HPV16 and HPV18/45 between the Xpert HPV and the SCT was also analyzed. The Xpert HPV detected 94% of CIN2+ and 98% of CIN3+ lesions among all screened women and 90% of CIN2+ and 96% of CIN3+ lesions in women 30 years and older. The specificity for CIN1 or less (≤CIN1) was 83% (95% confidence interval [CI], 80 to 85%) in all women and 88% (95% CI, 86 to 91%) in women 30 years and older. Inter- and intralaboratory agreements for the Xpert HPV were 98% and 97%, respectively. The kappa agreements for HPV16 and HPV18/45 between the clinically validated reference test (GP5+/6+ LMNX) and the Xpert HPV were 0.92 and 0.91, respectively. The clinical performance and reproducibility of the Xpert HPV are comparable to those of well-established HPV assays and fulfill the criteria for use in primary cervical cancer screening. PMID:27385707

Comparative evaluation of three chromogenic media combined with broth enrichment and the real-time PCR-based Xpert MRSA assay for screening of methicillin-resistant Staphylococcus aureus in nasal swabs.

PubMed

Lee, Seungok; Park, Yeon-Joon; Park, Kang-Gyun; Jekarl, Dong Wook; Chae, Hyojin; Yoo, Jin-Kyung; Seo, Sin Won; Choi, Jung Eun; Lim, Jung Hye; Heo, Seon Mi; Seo, Ju Hee

2013-07-01

We evaluated the performance of three chromogenic media (Brilliance agar I [Oxoid, UK], Brilliance agar II [Oxoid], and ChromID MRSA [Biomérieux, France]) combined with broth enrichment and the Xpert MRSA assay for screening of methicillin-resistant Staphylococcus aureus (MRSA). We obtained 401 pairs of duplicate nasal swabs from 321 patients. One swab was suspended overnight in tryptic soy broth; 50-µL aliquots of suspension were inoculated on the three chromogenic media. Brilliance agar I and II were examined after 24 hr, and ChromID MRSA, after 24 and 48 hr. The paired swab was processed directly using real-time PCR-based Xpert MRSA assay. True positives, designated as MRSA growth in any of the culture media, were detected with the prevalence of 17% in our institution. We report the sensitivity, specificity, positive predictive value, and negative predictive value of MRSA growth as follows: 92.3%, 94.0%, 75.9%, and 98.4% in Brilliance agar I (24 hr); 92.7%, 97.9%, 90.0%, and 98.5% in Brilliance agar II (24 hr); 95.6%, 95.8%, 82.3%, and 99.1% in ChromID MRSA (24 hr); 100%, 92.5%, 73.1%, and 100% in ChromID MRSA (48 hr); 92.6%, 96.7%, 85.1%, and 98.5% in Xpert MRSA assay. The agreement between the enriched culture and Xpert MRSA assay was 96.0%. Three chromogenic culture media combined with enrichment and Xpert MRSA assay demonstrated similar capabilities in MRSA detection. The Xpert MRSA assay yielded results comparable to those of culture methods, saving 48-72 hr, thus facilitating earlier detection of MRSA in healthcare settings.

Women's opinions of legal requirements for drug testing in prenatal care.

PubMed

Tucker Edmonds, Brownsyne; Mckenzie, Fatima; Austgen, MacKenzie B; Carroll, Aaron E; Meslin, Eric M

2017-07-01

To explore women's attitudes and perceptions regarding legal requirements for prenatal drug testing. Web-based survey of 500 US women (age 18-45) recruited from a market research survey panel. A 24-item questionnaire assessed their opinion of laws requiring doctors to routinely verbal screen and urine drug test patients during pregnancy; recommendations for consequences for positive drug tests during pregnancy; and opinion of laws requiring routine drug testing of newborns. Additional questions asked participants about the influence of such laws on their own care-seeking behaviors. Data were analyzed for associations between participant characteristics and survey responses using Pearson's chi-squared test. The majority of respondents (86%) stated they would support a law requiring verbal screening of all pregnant patients and 73% would support a law requiring universal urine drug testing in pregnancy. Fewer respondents were willing to support laws that required verbal screening or urine drug testing (68% and 61%, respectively) targeting only Medicaid recipients. Twenty-one percent of respondents indicated they would be offended if their doctors asked them about drug use and 14% indicated that mandatory drug testing would discourage prenatal care attendance. Women would be more supportive of policies requiring universal rather than targeted screening and testing for prenatal drug use. However, a noteworthy proportion of women would be discouraged from attending prenatal care - a reminder that drug testing policies may have detrimental effects on maternal child health.

Use of Cepheid Xpert Carba-R® for Rapid Detection of Carbapenemase-Producing Bacteria in Abdominal Septic Patients Admitted to Intensive Care Unit

PubMed Central

Russotto, Vincenzo; Graziano, Giorgio; Geraci, Daniela; Saporito, Laura; Cocorullo, Gianfranco; Raineri, Santi Maurizio; Mammina, Caterina; Giarratano, Antonino

2016-01-01

Early institution of effective antibiotic therapy and source control are pivotal to improve survival of abdominal septic patients. Xpert® Carba-R is a real time polymerase chain reaction assay for rapid detection and differentiation of five genes (blaKPC, blaVIM, blaOXA-48, blaIMP-1, blaNDM) responsible for carbapenem resistance. We performed an observational study investigating the clinical usefulness and applicability of Xpert® Carba-R to detect carbapenem resistance in abdominal septic patients admitted to intensive care unit. We compared the results of Xpert® Carba-R with standard microbiological culture. We collected a set of two rectal/stomia swabs and two swabs from abdominal drainage fluid for each patient. We included 20 patients for a total of 45 comparisons between the two methods. In our clinical setting, the overall performance of Xpert® Carba-R for detection of carbapenem resistance in the presence of genes detectable and non-detectable by the method was: sensitivity 50% (95% CI 24.6–75.3); specificity 93.1% (95% CI 77.2–99.1); positive predictive value (PPV) 80% (95% CI 44.4–97.5); negative predictive value (NPV) 77.1% (95% CI 56.9–89.6). The inter-rater agreement was 0.47 (SE 0.14; 95% CI 0.20–0.74). When considering the only 5 mechanisms of resistance detected by both methods, the overall diagnostic performance was: sensitivity 100% (95% CI 69.1–100), specificity 94.2 (95% CI 80.8–99.3), PPV 83.3 (95% CI 59.6–97.9) and NPV 100% (95% CI 89.4–100). The inter-rater agreement was 0.88 (SE 0.08; 95% CI 0.71–1). Xpert® Carba-R may be considered an additional diagnostic tool for early diagnosis of carbapenem resistance in abdominal septic patients. Clinicians should be aware of their epidemiology before its introduction in the diagnostic protocol of their intensive care units. PMID:27490684

Use of Cepheid Xpert Carba-R® for Rapid Detection of Carbapenemase-Producing Bacteria in Abdominal Septic Patients Admitted to Intensive Care Unit.

PubMed

Cortegiani, Andrea; Russotto, Vincenzo; Graziano, Giorgio; Geraci, Daniela; Saporito, Laura; Cocorullo, Gianfranco; Raineri, Santi Maurizio; Mammina, Caterina; Giarratano, Antonino

2016-01-01

Early institution of effective antibiotic therapy and source control are pivotal to improve survival of abdominal septic patients. Xpert® Carba-R is a real time polymerase chain reaction assay for rapid detection and differentiation of five genes (blaKPC, blaVIM, blaOXA-48, blaIMP-1, blaNDM) responsible for carbapenem resistance. We performed an observational study investigating the clinical usefulness and applicability of Xpert® Carba-R to detect carbapenem resistance in abdominal septic patients admitted to intensive care unit. We compared the results of Xpert® Carba-R with standard microbiological culture. We collected a set of two rectal/stomia swabs and two swabs from abdominal drainage fluid for each patient. We included 20 patients for a total of 45 comparisons between the two methods. In our clinical setting, the overall performance of Xpert® Carba-R for detection of carbapenem resistance in the presence of genes detectable and non-detectable by the method was: sensitivity 50% (95% CI 24.6-75.3); specificity 93.1% (95% CI 77.2-99.1); positive predictive value (PPV) 80% (95% CI 44.4-97.5); negative predictive value (NPV) 77.1% (95% CI 56.9-89.6). The inter-rater agreement was 0.47 (SE 0.14; 95% CI 0.20-0.74). When considering the only 5 mechanisms of resistance detected by both methods, the overall diagnostic performance was: sensitivity 100% (95% CI 69.1-100), specificity 94.2 (95% CI 80.8-99.3), PPV 83.3 (95% CI 59.6-97.9) and NPV 100% (95% CI 89.4-100). The inter-rater agreement was 0.88 (SE 0.08; 95% CI 0.71-1). Xpert® Carba-R may be considered an additional diagnostic tool for early diagnosis of carbapenem resistance in abdominal septic patients. Clinicians should be aware of their epidemiology before its introduction in the diagnostic protocol of their intensive care units.

[Detection of Staphylococcus aureus resistant to methicillin (MRSA) by molecular biology (Cepheid GeneXpert IL, GeneOhm BD, Roche LightCycler, Hyplex Evigene I2A) versus screening by culture: Economic and practical strategy for the laboratory].

PubMed

Laudat, P; Demondion, E; Jouannet, C; Charron, J; Chillou, C; Salaun, V; Mankikian, B

2012-06-01

is: (1) get results at day 0 for batch of samples (n<10): all molecular biology techniques; (2) beyond 10 samples: LightCycler (Roche) automated or Hyplex (I2A) manual; (3) when the result at day 1 is sufficient, the use of chromogenic agar with a reading of less than 18h as BBL CHROMagar MRSA II (BD) remains the most economical; (4) to be sure that a patient admitted at Day 0, even at night's emergency, is not carrier of MRSA: only Cepheid GeneXpert technology (IL). Furthermore, Cepheid GeneXpert (IL) allows performing several tests in parallel. The rapidity of this system can help control the transmission and make better use of antibiotics. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Evaluation of Xpert C. difficile, BD MAX Cdiff, IMDx C. difficile for Abbott m2000, and Illumigene C. difficile Assays for Direct Detection of Toxigenic Clostridium difficile in Stool Specimens.

PubMed

Shin, Bo-Moon; Yoo, Sun Mee; Shin, Won Chang

2016-03-01

We evaluated the performance of four commercial nucleic acid amplification tests (NAATs: Xpert C. difficile, BD MAX Cdiff, IMDx C. difficile for Abbott m2000, and Illumigene C. difficile) for direct and rapid detection of Clostridium difficile toxin genes. We compared four NAATs on the same set of 339 stool specimens (303 prospective and 36 retrospective specimens) with toxigenic culture (TC). Concordance rate among four NAATs was 90.3% (306/339). Based on TC results, the sensitivity and specificity were 90.0% and 92.9% for Xpert; 86.3% and 89.3% for Max; 84.3% and 94.4% for IMDx; and 82.4% and 93.7% for Illumigene, respectively. For 306 concordant cases, there were 11 TC-negative/NAATs co-positive cases and 6 TC-positive/NAATs co-negative cases. Among 33 discordant cases, 18 were only single positive in each NAAT (Xpert, 1; Max, 12; IMDx, 1; Illumigene, 4). Positivity rates of the four NAATs were associated with those of semi-quantitative cultures, which were maximized in grade 3 (>100 colony-forming unit [CFU]) compared with grade 1 (<10 CFU). Commercial NAATs may be rapid and reliable methods for direct detection of tcdA and/or tcdB in stool specimens compared with TC. Some differences in the sensitivity of the NAATs may partly depend on the number of toxigenic C. difficile in stool specimens.

Epidemiology of Rifampicin Resistant Tuberculosis and Common Mutations in rpoB Gene of Mycobacterium tuberculosis: A Retrospective Study from Six Districts of Punjab (India) Using Xpert MTB/RIF Assay.

PubMed

Kaur, Ramandeep; Jindal, Neerja; Arora, Shilpa; Kataria, Shajla

2016-01-01

Xpert MTB/RIF assay has revolutionized the diagnosis of tuberculosis (TB) by simultaneously detecting the bacteria and resistance to rifampicin (RIF), a surrogate marker for multidrug-resistant TB (MDR-TB) in <2 h. The RIF resistance pattern in Malwa region of Punjab, India, is not documented. Here, we report the epidemiology of RIF-resistant TB and mutations in rpoB gene of Mycobacterium tuberculosis (MTB). A total of 1612 specimens received between October 2013 and February 2015 were tested by Xpert MTB/RIF assay following manufacturer's instructions. The results thus obtained were analyzed using SPSS version 20.0.0 (SPSS Inc., Chicago, IL, USA) statistical software. RIF resistance was statistically higher in previously treated patients in comparison to the new patients (P = 0.006) and in patients with acid fast-Bacilli (AFB) positive smears to AFB-negative smears (P = 0.048). RIF resistance mutations in 130 specimens revealed frequency of E 73/130 (56%), B 28/130 (21.5%), D 18/130 (13.8%), A 11/130 (8.4%), and C 1/130 (0.7%) while in one specimen, mutation combination, i.e., mutations associated with more than one probe (A and B both) was present. Xpert MTB/RIF assay is a user-friendly screening tool for detection of MTB and RIF resistance from suspected TB/MDR cases in a shorter period of time. It could also serve as a useful technique to have simultaneous preliminary information regarding the mutation pattern of RIF resistance in MTB isolates.

[Test evaluation and strategy proposal to detect and to characterize carbapenemase-producing gram negative bacilli].

PubMed

Muñoz, Constanza; Zumarán, Cecilia; González, Tamara; Wozniak, Aniela; Castillo, Claudia; García, Patricia

2017-08-01

The detection of carbapenemase-producing gram negative bacilli is complicated, because there are available multiple options of test. The confirmation of the enzyme by molecular characterization is not available in all laboratories in our country. To propose a fast, efficient and simple strategy to detect and confirm CPB. 39 CPB isolates and 8 non-producing were used to evaluate the phenotypic test Carba NP, CarbAcineto NP and Blue-Carba, validating the test Xpert® Carba-R, to be used directly with bacterial colonies with conventional PCR. The sensitivity of Carba NP, CarbAcineto NP and Blue-Carba was 79,5; 87,2 y 84,6%, respectively; and specificity was 79.5; 87.2 and 84.6%, respectively. The limit of detection of Xpert® Carba-R was different for each carbapenemasa: 40.8 ufc/reaction to KPC and NDM and 30.6 ufc/reaction to VIM. On isolates with decreased susceptibility to carbapenems we propose to use as screening the test CarbAcineto NP, follow by Xpert®Carba-R to characterize the carbapenemase and adopt specific infection control measures.

Do adjunct tuberculosis tests, when combined with Xpert MTB/RIF, improve accuracy and the cost of diagnosis in a resource-poor setting?

PubMed Central

Theron, Grant; Pooran, Anil; Peter, Jonny; van Zyl-Smit, Richard; Mishra, Hridesh Kumar; Meldau, Richard; Calligaro, Greg; Allwood, Brian; Sharma, Surendra Kumar; Dawson, Rod; Dheda, Keertan

2017-01-01

Information regarding the utility of adjunct diagnostic tests in combination with Xpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) is limited. We hypothesised adjunct tests could enhance accuracy and/or reduce the cost of tuberculosis (TB) diagnosis prior to MTB/RIF testing, and rule-in or rule-out TB in MTB/RIF-negative individuals. We assessed the accuracy and/or laboratory-associated cost of diagnosis of smear microscopy, chest radiography (CXR) and interferon-γ release assays (IGRAs; T-SPOT-TB (Oxford Immunotec, Oxford, UK) and QuantiFERON-TB Gold In-Tube (Cellestis, Chadstone, Australia)) combined with MTB/RIF for TB in 480 patients in South Africa. When conducted prior to MTB/RIF: 1) smear microscopy followed by MTB/RIF (if smear negative) had the lowest cost of diagnosis of any strategy investigated; 2) a combination of smear microscopy, CXR (if smear negative) and MTB/RIF (if imaging compatible with active TB) did not further reduce the cost per TB case diagnosed; and 3) a normal CXR ruled out TB in 18% of patients (57 out of 324; negative predictive value (NPV) 100%). When downstream adjunct tests were applied to MTB/RIF-negative individuals, radiology ruled out TB in 24% (56 out of 234; NPV 100%), smear microscopy ruled in TB in 21% (seven out of 24) of culture-positive individuals and IGRAs were not useful in either context. In resource-poor settings, smear microscopy combined with MTB/RIF had the highest accuracy and lowest cost of diagnosis compared to either technique alone. In MTB/RIF-negative individuals, CXR has poor rule-in value but can reliably rule out TB in approximately one in four cases. These data inform upon the programmatic utility of MTB/RIF in high-burden settings. PMID:22075479

Opinion Expression as a Rational Behavior.

ERIC Educational Resources Information Center

Kim, Sei-Hill

This study looks at individuals' opinion expressions as a rational behavior based on a conscious calculus of expected benefits and costs (economic analysis). The influences of "issue benefit,""opinion congruence," and "issue knowledge," as sources of benefits and costs on opinion expression were hypothesized and tested. The study also examined the…

Evaluation of the Cepheid Xpert MTB/RIF assay for direct detection of Mycobacterium tuberculosis complex in respiratory specimens.

PubMed

Marlowe, Elizabeth M; Novak-Weekley, Susan M; Cumpio, Joven; Sharp, Susan E; Momeny, Michelle A; Babst, Anna; Carlson, Jonathan S; Kawamura, Masae; Pandori, Mark

2011-04-01

A total of 217 specimens submitted for routine smear and culture from three different sites within the western United States were used to evaluate the GeneXpert MTB/RIF assay (for research use only) (Cepheid, Sunnyvale, CA). Overall agreement compared to culture was 89% (98% for smear positives and 72% for smear negatives) for detection of Mycobacterium tuberculosis.

"I Do Feel Like a Scientist at Times": A Qualitative Study of the Acceptability of Molecular Point-Of-Care Testing for Chlamydia and Gonorrhoea to Primary Care Professionals in a Remote High STI Burden Setting.

PubMed

Natoli, Lisa; Guy, Rebecca J; Shephard, Mark; Causer, Louise; Badman, Steven G; Hengel, Belinda; Tangey, Annie; Ward, James; Coburn, Tony; Anderson, David; Kaldor, John; Maher, Lisa

2015-01-01

Point-of-care tests for chlamydia (CT) and gonorrhoea (NG) could increase the uptake and timeliness of testing and treatment, contribute to improved disease control and reduce reproductive morbidity. The GeneXpert (Xpert CT/NG assay), suited to use at the point-of-care, is being used in the TTANGO randomised controlled trial (RCT) in 12 remote Australian health services with a high burden of sexually transmissible infections (STIs). This represents the first ever routine use of a molecular point-of-care diagnostic for STIs in primary care. The purpose of this study was to explore the acceptability of the GeneXpert to primary care staff in remote Australia. In-depth qualitative interviews were conducted with 16 staff (registered or enrolled nurses and Aboriginal Health Workers/Practitioners) trained and experienced with GeneXpert testing. Interviews were digitally-recorded and transcribed verbatim prior to content analysis. Most participants displayed positive attitudes, indicating the test was both easy to use and useful in their clinical context. Participants indicated that point-of-care testing had improved management of STIs, resulting in more timely and targeted treatment, earlier commencement of partner notification, and reduced follow up efforts associated with client recall. Staff expressed confidence in point-of-care test results and treating patients on this basis, and reported greater job satisfaction. While point-of-care testing did not negatively impact on client flow, several found the manual documentation processes time consuming, suggesting that improved electronic connectivity and test result transfer between the GeneXpert and patient management systems could overcome this. Managing positive test results in a shorter time frame was challenging for some but most found it satisfying to complete episodes of care more quickly. In the context of a RCT, health professionals working in remote primary care in Australia found the GeneXpert highly acceptable

“I Do Feel Like a Scientist at Times”: A Qualitative Study of the Acceptability of Molecular Point-Of-Care Testing for Chlamydia and Gonorrhoea to Primary Care Professionals in a Remote High STI Burden Setting

PubMed Central

Natoli, Lisa; Guy, Rebecca J.; Shephard, Mark; Causer, Louise; Badman, Steven G.; Hengel, Belinda; Tangey, Annie; Ward, James; Coburn, Tony; Anderson, David; Kaldor, John; Maher, Lisa

2015-01-01

Background Point-of-care tests for chlamydia (CT) and gonorrhoea (NG) could increase the uptake and timeliness of testing and treatment, contribute to improved disease control and reduce reproductive morbidity. The GeneXpert (Xpert CT/NG assay), suited to use at the point-of-care, is being used in the TTANGO randomised controlled trial (RCT) in 12 remote Australian health services with a high burden of sexually transmissible infections (STIs). This represents the first ever routine use of a molecular point-of-care diagnostic for STIs in primary care. The purpose of this study was to explore the acceptability of the GeneXpert to primary care staff in remote Australia. Methods In-depth qualitative interviews were conducted with 16 staff (registered or enrolled nurses and Aboriginal Health Workers/Practitioners) trained and experienced with GeneXpert testing. Interviews were digitally-recorded and transcribed verbatim prior to content analysis. Results Most participants displayed positive attitudes, indicating the test was both easy to use and useful in their clinical context. Participants indicated that point-of-care testing had improved management of STIs, resulting in more timely and targeted treatment, earlier commencement of partner notification, and reduced follow up efforts associated with client recall. Staff expressed confidence in point-of-care test results and treating patients on this basis, and reported greater job satisfaction. While point-of-care testing did not negatively impact on client flow, several found the manual documentation processes time consuming, suggesting that improved electronic connectivity and test result transfer between the GeneXpert and patient management systems could overcome this. Managing positive test results in a shorter time frame was challenging for some but most found it satisfying to complete episodes of care more quickly. Conclusions In the context of a RCT, health professionals working in remote primary care in Australia

GeneXpert MTB/RIF dans le dépistage de la tuberculose pulmonaire à l’Hôpital Provincial Général de Référence de Bukavu, à l’Est de la République Démocratique du Congo: quelles leçons tirées après 10 mois d’utilisation?

PubMed Central

Lupande, David; Kaishusha, David; Mihigo, Carine; Itongwa, Moise; Yenga, Gustave; Katchunga, Philippe

2017-01-01

Introduction En Afrique subsaharienne, les méthodes de diagnostic de la tuberculose sont insuffisantes et reposent essentiellement sur la microscopie. Elles constituent un réel frein pour le contrôle de la tuberculose. La présente étude voudrait évaluer les performances du GeneXpert MTB/RIF vis à vis de la microscopie classique de Ziehl-Neelsen à l’Hôpital Provincial Général de Référence de Bukavu, à l’Est de la République Démocratique du Congo après 10 mois d’utilisation. Méthodes Les résultats de la coloration au Ziehl-Neelsen et de la biologie moléculaire sur GeneXpert MTB/RIF de 452 patients suspects de tuberculose ont été colligés. La validité d’un test par rapport à l’autre dans la détection de la tuberculose a été étudiée. Résultats Dans le groupe entier, la fréquence de la tuberculose pulmonaire était de 16.3%. La positivité était significativement plus élevée pour le GeneXpert MTB/RIF que pour le Ziehl-Neelsen dans le groupe entier (15.9% vs 9.3%, p= 0.03) et chez les séropositifs pour le VIH (52.0% vs 24.0%; p = 0.007). Cependant, la sensibilité de GeneXpert MTB/RIF comparé au Ziehl-Neelsen n’était pas maximale (95.2%). Enfin, GeneXpert MTB/RIF a détecté 20.8% de résistance à la rifampicine. Conclusion La présente étude confirme la supériorité de GeneXpert MTB/RIF sur la coloration de Ziehl-Neelsen dans la détection de la tuberculose et dans la prédiction de la multi résistance. Son utilisation systématique couplée au Ziehl-Neelsen permettrait de mieux contrôler la tuberculose en Afrique subSaharienne. PMID:29187929

Performance of the Abbott RealTime MTB RIF/INH resistance assay when used to test Mycobacterium tuberculosis specimens from Bangladesh.

PubMed

Kostera, Joshua; Leckie, Gregor; Abravaya, Klara; Wang, Hong

2018-01-01

The Abbott RealTime MTB RIF/INH Resistance Assay (RT MTB RIF/INH) is an assay for the detection of rifampicin (RIF)- and/or isoniazid (INH)-resistant Mycobacterium tuberculosis (MTB). The assay can be used to test sputum, bronchial alveolar lavage, and N-Acetyl-L-Cysteine (NALC)/NaOH pellets prepared from these samples. The assay can be used in direct testing mode, or in reflex mode following a MTB positive result produced by its companion assay, Abbott RT MTB. In this study, the direct testing mode was used to test paired sputum and NALC/NaOH pellets prepared from sputum collected from Bangladesh TB patients. One hundred and thirty two paired samples were tested. The RT MTB RIF/INH inhibition rate was 0%. One hundred and twenty-two paired samples had results above the assay limit of detection and were analyzed by comparing with results from phenotypic drug sensitivity testing, GeneXpert MTB/RIF (Xpert), and MTBDR plus (Hain). RT MTB RIF/INH results were in good agreement with those of GeneXpert and Hain. The ability of this assay to detect RIF and INH resistance may contribute to the global control of multidrug resistant tuberculosis.

Evaluation of the Cepheid Xpert MTB/RIF Assay for Direct Detection of Mycobacterium tuberculosis Complex in Respiratory Specimens▿

PubMed Central

Marlowe, Elizabeth M.; Novak-Weekley, Susan M.; Cumpio, Joven; Sharp, Susan E.; Momeny, Michelle A.; Babst, Anna; Carlson, Jonathan S.; Kawamura, Masae; Pandori, Mark

2011-01-01

A total of 217 specimens submitted for routine smear and culture from three different sites within the western United States were used to evaluate the GeneXpert MTB/RIF assay (for research use only) (Cepheid, Sunnyvale, CA). Overall agreement compared to culture was 89% (98% for smear positives and 72% for smear negatives) for detection of Mycobacterium tuberculosis. PMID:21289151

Committee Opinion No. 693: Counseling About Genetic Testing and Communication of Genetic Test Results.

PubMed

2017-04-01

Given the increasing availability and complexity of genetic testing, it is imperative that the practicing obstetrician-gynecologist or other health care provider has a firm comprehension of the benefits, limitations, and risks of offering a specific genetic test, as well as the importance of appropriate pretest and posttest counseling. The purpose of this Committee Opinion is to provide an outline of how obstetrician-gynecologists and other health care providers can best incorporate these tests into their current practices and provide appropriate pretest and posttest counseling to patients. Obstetrician-gynecologists and other health care providers should determine which tests will be offered as the standard in their practices so that similar testing strategies are made available to all patients. Practices should have procedures in place that ensure timely disclosure of test results to patients. As with any medical test, expectations regarding the performance of a genetic test should be discussed with the patient before the test is ordered. After counseling, patients should have the option to decline any or all testing. Pretest and posttest counseling should be done in a clear, objective, and nondirective fashion, which allows patients sufficient time to understand information and make informed decisions regarding testing and further evaluation or treatment. In addition to counseling each patient about her own personal risk, obstetrician-gynecologists and other health care providers should counsel patients regarding the risk for family members, including their potential to have affected offspring.

Prospective comparison of RT-PCR/ESI-MS to Prodesse ProFlu Plus and Cepheid GenXpert for the detection of Influenza A and B viruses.

PubMed

Hardick, Justin; Dugas, Andrea; Goheen, Joshua; Rothman, Richard; Gaydos, Charlotte

2015-03-01

RT-PCR/ESI-MS has previously demonstrated the capability to detect and identify respiratory viral pathogens in nasopharyngeal swabs. This study expands on previous research by performing a prospective evaluation of RT-PCR/ESI-MS to detect and identify Influenza A and B viruses compared to Prodesse ProFlu Plus and combined ProFlu Plus and Cepheid Xpert Flu. ProFlu Plus was also used as a gold standard for comparison for respiratory syncytial virus detection. Using ProFlu Plus as a gold standard, RT-PCR/ESI-MS had sensitivity and specificity of 82.1% (23/28) and 100% (258/258), respectively, for Influenza A, 100% (16/16) and 99.6% (269/270), respectively for Influenza B, and 88.6% (39/44) and 99.6% (241/242) for any Influenza virus. Using matching results from ProFlu Plus and Xpert Flu as a gold standard, RT-PCR/ESI-MS had 85.2% (23/27) and 100% (259/259) sensitivity and specificity respectively for Influenza A, 100% (14/14) and 99.6% (270/272), respectively for Influenza B virus. Overall, RT-PCR/ESI-MS was not as sensitive as the combined gold standard of ProFlu Plus and Xpert Flu, although it has the capability of detecting other respiratory viruses. Copyright © 2015 Elsevier B.V. All rights reserved.

Evaluation of RayXpert® for shielding design of medical facilities

NASA Astrophysics Data System (ADS)

Derreumaux, Sylvie; Vecchiola, Sophie; Geoffray, Thomas; Etard, Cécile

2017-09-01

In a context of growing demands for expert evaluation concerning medical, industrial and research facilities, the French Institute for radiation protection and nuclear safety (IRSN) considered necessary to acquire new software for efficient dimensioning calculations. The selected software is RayXpert®. Before using this software in routine, exposure and transmission calculations for some basic configurations were validated. The validation was performed by the calculation of gamma dose constants and tenth value layers (TVL) for usual shielding materials and for radioisotopes most used in therapy (Ir-192, Co-60 and I-131). Calculated values were compared with results obtained using MCNPX as a reference code and with published values. The impact of different calculation parameters, such as the source emission rays considered for calculation and the use of biasing techniques, was evaluated.

Bottom-up or top-down: unit cost estimation of tuberculosis diagnostic tests in India.

PubMed

Rupert, S; Vassall, A; Raizada, N; Khaparde, S D; Boehme, C; Salhotra, V S; Sachdeva, K S; Nair, S A; Hoog, A H Van't

2017-04-01

Of 18 sites that participated in an implementation study of the Xpert® MTB/RIF assay in India, we selected five microscopy centres and two reference laboratories. To obtain unit costs of diagnostic tests for tuberculosis (TB) and drug-resistant TB. Laboratories were purposely selected to capture regional variations and different laboratory types. Both bottom-up and the top-down methods were used to estimate unit costs. At the microscopy centres, mean bottom-up unit costs were respectively US$0.83 (range US$0.60-US$1.10) and US$12.29 (US$11.61-US$12.89) for sputum smear microscopy and Xpert. At the reference laboratories, mean unit costs were US$1.69 for the decontamination procedure, US$9.83 for a solid culture, US$11.06 for a liquid culture, US$29.88 for a drug susceptibility test, and US$18.18 for a line-probe assay. Top-down mean unit cost estimates were higher for all tests, and for sputum smear microscopy and Xpert these increased to respectively US$1.51 and US$13.58. The difference between bottom-up and top-down estimates was greatest for tests performed at the reference laboratories. These unit costs for TB diagnostics can be used to estimate resource requirements and cost-effectiveness in India, taking into account geographical location, laboratory type and capacity utilisation.

Explaining opinion polarisation with opinion copulas.

PubMed

Askitas, Nikolaos

2017-01-01

An empirically founded and widely established driving force in opinion dynamics is homophily i.e. the tendency of "birds of a feather" to "flock together". The closer our opinions are the more likely it is that we will interact and converge. Models using these assumptions are called bounded confidence models (BCM) as they assume a tolerance threshold after which interaction is unlikely. They are known to produce one or more clusters, depending on the size of the bound, with more than one cluster being possible only in the deterministic case. Introducing noise, as is likely to happen in a stochastic world, causes BCM to produce consensus which leaves us with the open problem of explaining the emergence and sustainance of opinion clusters and polarisation. We investigate the role of heterogeneous priors in opinion formation, introduce the concept of opinion copulas, argue that it is well supported by findings in Social Psychology and use it to show that the stochastic BCM does indeed produce opinion clustering without the need for extra assumptions.

Explaining opinion polarisation with opinion copulas

PubMed Central

2017-01-01

An empirically founded and widely established driving force in opinion dynamics is homophily i.e. the tendency of “birds of a feather” to “flock together”. The closer our opinions are the more likely it is that we will interact and converge. Models using these assumptions are called bounded confidence models (BCM) as they assume a tolerance threshold after which interaction is unlikely. They are known to produce one or more clusters, depending on the size of the bound, with more than one cluster being possible only in the deterministic case. Introducing noise, as is likely to happen in a stochastic world, causes BCM to produce consensus which leaves us with the open problem of explaining the emergence and sustainance of opinion clusters and polarisation. We investigate the role of heterogeneous priors in opinion formation, introduce the concept of opinion copulas, argue that it is well supported by findings in Social Psychology and use it to show that the stochastic BCM does indeed produce opinion clustering without the need for extra assumptions. PMID:28829802

Committee Opinion No. 693 Summary: Counseling About Genetic Testing and Communication of Genetic Test Results.

PubMed

2017-04-01

Given the increasing availability and complexity of genetic testing, it is imperative that the practicing obstetrician-gynecologist or other health care provider has a firm comprehension of the benefits, limitations, and risks of offering a specific genetic test, as well as the importance of appropriate pretest and posttest counseling. The purpose of this Committee Opinion is to provide an outline of how obstetrician-gynecologists and other health care providers can best incorporate these tests into their current practices and provide appropriate pretest and posttest counseling to patients. Obstetrician-gynecologists and other health care providers should determine which tests will be offered as the standard in their practices so that similar testing strategies are made available to all patients. Practices should have procedures in place that ensure timely disclosure of test results to patients. As with any medical test, expectations regarding the performance of a genetic test should be discussed with the patient before the test is ordered. After counseling, patients should have the option to decline any or all testing. Pretest and posttest counseling should be done in a clear, objective, and nondirective fashion, which allows patients sufficient time to understand information and make informed decisions regarding testing and further evaluation or treatment. In addition to counseling each patient about her own personal risk, obstetrician-gynecologists and other health care providers should counsel patients regarding the risk for family members, including their potential to have affected offspring.

Opinion Leadership, Poverty, and Information Sharing.

ERIC Educational Resources Information Center

Chatman, Elfreda A.

1987-01-01

This test of theory of opinion leadership in a low-income environment addressed three questions: (1) whether opinion leaders exist, their characteristics, and their role in information dissemination; (2) what the information world of this population is; and (3) whether this population views the library as a source of useful information. (EM)

XpertTrack: Precision Autonomous Measuring Device Developed for Real Time Shipments Tracker.

PubMed

Viman, Liviu; Daraban, Mihai; Fizesan, Raul; Iuonas, Mircea

2016-03-10

This paper proposes a software and hardware solution for real time condition monitoring applications. The proposed device, called XpertTrack, exchanges data through the GPRS protocol over a GSM network and monitories temperature and vibrations of critical merchandise during commercial shipments anywhere on the globe. Another feature of this real time tracker is to provide GPS and GSM positioning with a precision of 10 m or less. In order to interpret the condition of the merchandise, the data acquisition, analysis and visualization are done with 0.1 °C accuracy for the temperature sensor, and 10 levels of shock sensitivity for the acceleration sensor. In addition to this, the architecture allows increasing the number and the types of sensors, so that companies can use this flexible solution to monitor a large percentage of their fleet.

Opinion strength influences the spatial dynamics of opinion formation

PubMed Central

Baumgaertner, Bert O.; Tyson, Rebecca T.; Krone, Stephen M.

2016-01-01

Opinions are rarely binary; they can be held with different degrees of conviction, and this expanded attitude spectrum can affect the influence one opinion has on others. Our goal is to understand how different aspects of influence lead to recognizable spatio-temporal patterns of opinions and their strengths. To do this, we introduce a stochastic spatial agent-based model of opinion dynamics that includes a spectrum of opinion strengths and various possible rules for how the opinion strength of one individual affects the influence that this individual has on others. Through simulations, we find that even a small amount of amplification of opinion strength through interaction with like-minded neighbors can tip the scales in favor of polarization and deadlock. PMID:28529381

OpinionFlow: Visual Analysis of Opinion Diffusion on Social Media.

PubMed

Wu, Yingcai; Liu, Shixia; Yan, Kai; Liu, Mengchen; Wu, Fangzhao

2014-12-01

It is important for many different applications such as government and business intelligence to analyze and explore the diffusion of public opinions on social media. However, the rapid propagation and great diversity of public opinions on social media pose great challenges to effective analysis of opinion diffusion. In this paper, we introduce a visual analysis system called OpinionFlow to empower analysts to detect opinion propagation patterns and glean insights. Inspired by the information diffusion model and the theory of selective exposure, we develop an opinion diffusion model to approximate opinion propagation among Twitter users. Accordingly, we design an opinion flow visualization that combines a Sankey graph with a tailored density map in one view to visually convey diffusion of opinions among many users. A stacked tree is used to allow analysts to select topics of interest at different levels. The stacked tree is synchronized with the opinion flow visualization to help users examine and compare diffusion patterns across topics. Experiments and case studies on Twitter data demonstrate the effectiveness and usability of OpinionFlow.

Impact of a rapid molecular test for positive blood cultures from neonatal intensive care patients on clinical management: a retrospective audit.

PubMed

Koh, L L; O'Rourke, S; Brennan, M; Clooney, L; Cafferkey, M; McCallion, N; Drew, R J

2018-05-01

Both Staphylococcus aureus and coagulase negative Staphylococci are common causes of late-onset neonatal sepsis in the neonatal intensive care unit (NICU), usually relating to intravascular access device infections. This project aimed to review the impact on antimicrobial treatment and clinical outcome in the NICU setting, of the introduction of the Xpert MRSA/SA BC test (Cepheid, USA) for the identification of staphylococci in blood cultures. A retrospective audit was carried out of the pre- and post-intervention periods; the intervention was the introduction of the Xpert MRSA/SA BC test. In total, 88 neonates had positive blood cultures with Staphylococcus spp., comprising 42 neonates in the pre-intervention and 46 in the post-intervention groups. The pre-intervention group had a higher birth weight (1.541 kg vs. 1.219 kg, p = 0.05) and higher platelet count (288 vs. 224 × 10 9 /L, p = 0.05). There was a trend towards a shorter duration of antimicrobial therapy in term infants and in the length of admission; however, this was not statistically significant (p = 0.2). All of the nine infants post-intervention with significant bacteraemia (S. aureus =3, CoNS =6) were changed to the optimal antimicrobial at the time the result was available. This study shows that the introduction of the Xpert MRSA/SA BC test can lead to a reduction in the length of admission and duration of antimicrobials in term infants; however, the difference was not statistically significant. All nine infants with clinically significant bacteraemia were treated with the appropriate antimicrobial when the Xpert MRSA/SA BC test result was available.

Knowledge and Opinion on the Nuclear Freeze: A Test of Three Models.

ERIC Educational Resources Information Center

Tankard, James W., Jr.

To explore how knowledge influences opinion in foreign policy, results of a survey on voter familiarity with and attitude toward nuclear policy issues were compared with three theoretical models of the knowledge/opinion relationship: (1) the enlightenment model--as knowledge increases, support for belligerent foreign policy stands decreases; (2)…

Modelling the public opinion transmission on social networks under opinion leaders

NASA Astrophysics Data System (ADS)

Li, Zuozhi; Li, Meng; Ji, Wanwan

2017-06-01

In this paper, based on Social Network Analysis (SNA), the social network model of opinion leaders influencing the public opinion transmission is explored. The hot event, A Female Driver Was Beaten Due To Lane Change, has characteristics of individual short-term and non-government intervention, which is used to data extraction, and formed of the network structure on opinion leaders influencing the public opinion transmission. And the evolution mechanism are analyzed in the three evolutionary situations. Opinion leaders influence micro-blogging public opinion on social network evolution model shows that this type of network public opinion transmission is largely constrained by opinion leaders, so the opinion leaders behavior supervising on the spread of this public opinion is pivotal, and which has a guiding significance.

Experience, knowledge, and opinions about childhood genetic testing in Batten disease.

PubMed

Adams, Heather R; Rose, Katherine; Augustine, Erika F; Kwon, Jennifer M; deBlieck, Elisabeth A; Marshall, Frederick J; Vierhile, Amy; Mink, Jonathan W; Nance, Martha A

2014-02-01

Policies for genetic testing in children (GTIC) focus on medical or psychosocial benefit to the child, discouraging or prohibiting carrier testing, and advising caution regarding pre-symptomatic diagnosis if no treatment exists. This study sought to understand parents' perspectives on these issues and determine their experiences and knowledge related to genetic testing for Batten disease - a set of inherited neurodegenerative diseases of childhood onset for which no disease modifying therapies yet exist. Parents of children with Batten disease completed a survey of their knowledge of genetics, experience with genetic testing, and opinions regarding GTIC. 54% had sought genetic testing for non-affected family members, including predictive diagnosis of healthy, at-risk children. Participation in any genetic counseling was associated with greater knowledge on questions about genetics. The majority of parents felt it was better to know ahead of time that a child would develop Batten disease, believed that this knowledge would not alter how they related to their child, and that parents should have the final say in deciding whether to obtain GTIC. Parents of children with an inherited disease are knowledgeable about genetics and wish to establish predictive or carrier status of at-risk children. Copyright © 2013 Elsevier Inc. All rights reserved.

Experience, Knowledge, and Opinions about Childhood Genetic Testing in Batten Disease

PubMed Central

Rose, Katherine; Augustine, Erika F.; Kwon, Jennifer M.; deBlieck, Elisabeth A.; Marshall, Frederick J.; Vierhile, Amy; Mink, Jonathan W.; Nance, Martha A.

2013-01-01

Background and Objectives Policies for genetic testing in children (GTIC) focus on medical or psychosocial benefit to the child, discouraging or prohibiting carrier testing, and advising caution regarding pre-symptomatic diagnosis if no treatment exists. This study sought to understand parents’ perspectives on these issues and determine their experiences and knowledge related to genetic testing for Batten disease – a set of inherited neurodegenerative diseases of childhood onset for which no disease modifying therapies yet exist. Methods Parents of children with Batten disease completed a survey of their knowledge of genetics, experience with genetic testing, and opinions regarding GTIC. Results 54% had sought genetic testing for non-affected family members, including predictive diagnosis of healthy, at-risk children. Participation in any genetic counseling was associated with greater knowledge on questions about genetics. The majority of parents felt it was better to know ahead of time that a child would develop Batten disease, believed that this knowledge would not alter how they related to their child, and that parents should have the final say in deciding whether to obtain GTIC. Conclusions Parents of children with an inherited disease are knowledgeable about genetics and wish to establish predictive or carrier status of at-risk children. PMID:24246680

XpertTrack: Precision Autonomous Measuring Device Developed for Real Time Shipments Tracker

PubMed Central

Viman, Liviu; Daraban, Mihai; Fizesan, Raul; Iuonas, Mircea

2016-01-01

This paper proposes a software and hardware solution for real time condition monitoring applications. The proposed device, called XpertTrack, exchanges data through the GPRS protocol over a GSM network and monitories temperature and vibrations of critical merchandise during commercial shipments anywhere on the globe. Another feature of this real time tracker is to provide GPS and GSM positioning with a precision of 10 m or less. In order to interpret the condition of the merchandise, the data acquisition, analysis and visualization are done with 0.1 °C accuracy for the temperature sensor, and 10 levels of shock sensitivity for the acceleration sensor. In addition to this, the architecture allows increasing the number and the types of sensors, so that companies can use this flexible solution to monitor a large percentage of their fleet. PMID:26978360

Comparison of Diagnostic Algorithms for Detecting Toxigenic Clostridium difficile in Routine Practice at a Tertiary Referral Hospital in Korea.

PubMed

Moon, Hee-Won; Kim, Hyeong Nyeon; Hur, Mina; Shim, Hee Sook; Kim, Heejung; Yun, Yeo-Min

2016-01-01

Since every single test has some limitations for detecting toxigenic Clostridium difficile, multistep algorithms are recommended. This study aimed to compare the current, representative diagnostic algorithms for detecting toxigenic C. difficile, using VIDAS C. difficile toxin A&B (toxin ELFA), VIDAS C. difficile GDH (GDH ELFA, bioMérieux, Marcy-l'Etoile, France), and Xpert C. difficile (Cepheid, Sunnyvale, California, USA). In 271 consecutive stool samples, toxigenic culture, toxin ELFA, GDH ELFA, and Xpert C. difficile were performed. We simulated two algorithms: screening by GDH ELFA and confirmation by Xpert C. difficile (GDH + Xpert) and combined algorithm of GDH ELFA, toxin ELFA, and Xpert C. difficile (GDH + Toxin + Xpert). The performance of each assay and algorithm was assessed. The agreement of Xpert C. difficile and two algorithms (GDH + Xpert and GDH+ Toxin + Xpert) with toxigenic culture were strong (Kappa, 0.848, 0.857, and 0.868, respectively). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of algorithms (GDH + Xpert and GDH + Toxin + Xpert) were 96.7%, 95.8%, 85.0%, 98.1%, and 94.5%, 95.8%, 82.3%, 98.5%, respectively. There were no significant differences between Xpert C. difficile and two algorithms in sensitivity, specificity, PPV and NPV. The performances of both algorithms for detecting toxigenic C. difficile were comparable to that of Xpert C. difficile. Either algorithm would be useful in clinical laboratories and can be optimized in the diagnostic workflow of C. difficile depending on costs, test volume, and clinical needs.

Kinetic model for multidimensional opinion formation

NASA Astrophysics Data System (ADS)

Boudin, Laurent; Monaco, Roberto; Salvarani, Francesco

2010-03-01

In this paper, we deal with a kinetic model to describe the evolution of the opinion in a closed group with respect to a choice between multiple options (e.g., political parties), which takes into account two main mechanisms of opinion formation, namely, the interaction between individuals and the effect of the mass media. We numerically test the model in some relevant cases and eventually provide an existence and a uniqueness result for it.

Development and verification of an agent-based model of opinion leadership.

PubMed

Anderson, Christine A; Titler, Marita G

2014-09-27

The use of opinion leaders is a strategy used to speed the process of translating research into practice. Much is still unknown about opinion leader attributes and activities and the context in which they are most effective. Agent-based modeling is a methodological tool that enables demonstration of the interactive and dynamic effects of individuals and their behaviors on other individuals in the environment. The purpose of this study was to develop and test an agent-based model of opinion leadership. The details of the design and verification of the model are presented. The agent-based model was developed by using a software development platform to translate an underlying conceptual model of opinion leadership into a computer model. Individual agent attributes (for example, motives and credibility) and behaviors (seeking or providing an opinion) were specified as variables in the model in the context of a fictitious patient care unit. The verification process was designed to test whether or not the agent-based model was capable of reproducing the conditions of the preliminary conceptual model. The verification methods included iterative programmatic testing ('debugging') and exploratory analysis of simulated data obtained from execution of the model. The simulation tests included a parameter sweep, in which the model input variables were adjusted systematically followed by an individual time series experiment. Statistical analysis of model output for the 288 possible simulation scenarios in the parameter sweep revealed that the agent-based model was performing, consistent with the posited relationships in the underlying model. Nurse opinion leaders act on the strength of their beliefs and as a result, become an opinion resource for their uncertain colleagues, depending on their perceived credibility. Over time, some nurses consistently act as this type of resource and have the potential to emerge as opinion leaders in a context where uncertainty exists. The

Pathways to multidrug-resistant tuberculosis diagnosis and treatment initiation: a qualitative comparison of patients' experiences in the era of rapid molecular diagnostic tests.

PubMed

Naidoo, Pren; van Niekerk, Margaret; du Toit, Elizabeth; Beyers, Nulda; Leon, Natalie

2015-10-28

Although new molecular diagnostic tests such as GenoType MTBDRplus and Xpert® MTB/RIF have reduced multidrug-resistant tuberculosis (MDR-TB) treatment initiation times, patients' experiences of diagnosis and treatment initiation are not known. This study aimed to explore and compare MDR-TB patients' experiences of their diagnostic and treatment initiation pathway in GenoType MTBDRplus and Xpert® MTB/RIF-based diagnostic algorithms. The study was undertaken in Cape Town, South Africa where primary health-care services provided free TB diagnosis and treatment. A smear, culture and GenoType MTBDRplus diagnostic algorithm was used in 2010, with Xpert® MTB/RIF phased in from 2011-2013. Participants diagnosed in each algorithm at four facilities were purposively sampled, stratifying by age, gender and MDR-TB risk profiles. We conducted in-depth qualitative interviews using a semi-structured interview guide. Through constant comparative analysis we induced common and divergent themes related to symptom recognition, health-care access, testing for MDR-TB and treatment initiation within and between groups. Data were triangulated with clinical information and health visit data from a structured questionnaire. We identified both enablers and barriers to early MDR-TB diagnosis and treatment. Half the patients had previously been treated for TB; most recognised recurring symptoms and reported early health-seeking. Those who attributed symptoms to other causes delayed health-seeking. Perceptions of poor public sector services were prevalent and may have contributed both to deferred health-seeking and to patient's use of the private sector, contributing to delays. However, once on treatment, most patients expressed satisfaction with public sector care. Two patients in the Xpert® MTB/RIF-based algorithm exemplified its potential to reduce delays, commencing MDR-TB treatment within a week of their first health contact. However, most patients in both algorithms experienced

Sensitive Detection of Francisella tularensis Directly from Whole Blood by Use of the GeneXpert System.

PubMed

Banada, Padmapriya P; Deshpande, Srinidhi; Chakravorty, Soumitesh; Russo, Riccardo; Occi, James; Meister, Gabriel; Jones, Kelly J; Gelhaus, Carl H; Valderas, Michelle W; Jones, Martin; Connell, Nancy; Alland, David

2017-01-01

Francisella tularensis is a potential bioterrorism agent that is highly infectious at very low doses. Diagnosis of tularemia by blood culture and nucleic acid-based diagnostic tests is insufficiently sensitive. Here, we demonstrate a highly sensitive F. tularensis assay that incorporates sample processing and detection into a single cartridge suitable for point-of-care detection. The assay limit of detection (LOD) and dynamic range were determined in a filter-based cartridge run on the GeneXpert system. F. tularensis DNA in buffer or CFU of F. tularensis was spiked into human or macaque blood. To simulate detection in human disease, the assay was tested on blood drawn from macaques infected with F. tularensis Schu S4 at daily intervals. Assay detection was compared to that with a conventional quantitative PCR (qPCR) assay and blood culture. The assay LOD was 0.1 genome equivalents (GE) per reaction and 10 CFU/ml F. tularensis in both human and macaque blood. In infected macaques, the assay detected F. tularensis on days 1 to 4 postinfection in 21%, 17%, 60%, and 83% of macaques, respectively, compared to conventional qPCR positivity rates of 0%, 0%, 30%, and 100% and CFU detection of blood culture at 0%, 0%, 0%, and 10% positive, respectively. Assay specificity was 100%. The new cartridge-based assay can rapidly detect F. tularensis in bloodstream infections directly in whole blood at the early stages of infection with a sensitivity that is superior to that of other methods. The simplicity of the automated testing procedures may make this test suitable for rapid point-of-care detection. Copyright © 2016 American Society for Microbiology.

Cost-effectiveness of novel algorithms for rapid diagnosis of tuberculosis in HIV-infected individuals in Uganda.

PubMed

Shah, Maunank; Dowdy, David; Joloba, Moses; Ssengooba, Willy; Manabe, Yukari C; Ellner, Jerrold; Dorman, Susan E

2013-11-28

Xpert MTB/RIF ('Xpert') and urinary lateral-flow lipoarabinomannan (LF-LAM) assays offer rapid tuberculosis (TB) diagnosis. This study evaluated the cost-effectiveness of novel diagnostic algorithms utilizing combinations of Xpert and LF-LAM for the detection of active TB among people living with HIV. Cost-effectiveness analysis using data from a comparative study of LF-LAM and Xpert, with a target population of HIV-infected individuals with signs/symptoms of TB in Uganda. A decision-analysis model compared multiple strategies for rapid TB diagnosis:sputum smear-microscopy; sputum Xpert; smear-microscopy combined with LF-LAM; and Xpert combined with LF-LAM. Primary outcomes were the costs and DALY's averted for each algorithm. Cost-effectiveness was represented using incremental cost-effectiveness ratios (ICER). Compared with an algorithm of Xpert testing alone, the combination of Xpert with LF-LAM was considered highly cost-effective (ICER $57/DALY-averted) at a willingness to pay threshold of Ugandan GDP per capita. Addition of urine LF-LAM testing to smear-microscopy was a less effective strategy than Xpert replacement of smear-microscopy, but was less costly and also considered highly cost-effective (ICER $33 per DALY-averted) compared with continued usage of smear-microscopy alone. Cost-effectiveness of the Xpert plus LF-LAM algorithm was most influenced by HIV/ART costs and life-expectancy of patients after TB treatment. The addition of urinary LF-LAM to TB diagnostic algorithms for HIV-infected individuals is highly cost-effective compared with usage of either sputum smear-microscopy or Xpert alone.

Eliciting expert opinion for economic models: an applied example.

PubMed

Leal, José; Wordsworth, Sarah; Legood, Rosa; Blair, Edward

2007-01-01

Expert opinion is considered as a legitimate source of information for decision-analytic modeling where required data are unavailable. Our objective was to develop a practical computer-based tool for eliciting expert opinion about the shape of the uncertainty distribution around individual model parameters. We first developed a prepilot survey with departmental colleagues to test a number of alternative approaches to eliciting opinions on the shape of the uncertainty distribution around individual parameters. This information was used to develop a survey instrument for an applied clinical example. This involved eliciting opinions from experts to inform a number of parameters involving Bernoulli processes in an economic model evaluating DNA testing for families with a genetic disease, hypertrophic cardiomyopathy. The experts were cardiologists, clinical geneticists, and laboratory scientists working with cardiomyopathy patient populations and DNA testing. Our initial prepilot work suggested that the more complex elicitation techniques advocated in the literature were difficult to use in practice. In contrast, our approach achieved a reasonable response rate (50%), provided logical answers, and was generally rated as easy to use by respondents. The computer software user interface permitted graphical feedback throughout the elicitation process. The distributions obtained were incorporated into the model, enabling the use of probabilistic sensitivity analysis. There is clearly a gap in the literature between theoretical elicitation techniques and tools that can be used in applied decision-analytic models. The results of this methodological study are potentially valuable for other decision analysts deriving expert opinion.

Political opinion formation: Initial opinion distribution and individual heterogeneity of tolerance

NASA Astrophysics Data System (ADS)

Jin, Cheng; Li, Yifu; Jin, Xiaogang

2017-02-01

Opinion dynamics on networks have received serious attention for its profound prospects in social behaviours and self-organized systems. However, political opinion formation, as one typical and significant case, remains lacking in discussion. Previous agent-based simulations propose various models that are based on different mechanisms like the coevolution between network topology and status transition. Nonetheless, even under the same network topology and with the same simple mechanism, forming opinions can still be uncertain. In this work, we propose two features, the initial distribution of opinions and the individual heterogeneity of tolerances on opinion changing, in political opinion formation. These two features are imbedded in the network construction phase of a classical model. By comparing multi simple-party systems, along with a detailed analysis on the two-party system, we capture the critical phenomenon of fragmentation, polarization and consensus both in the persistent stable stage and in-process. We further introduce the average ratio of nearest neighbours to characterize the stage of opinion formation. The results show that the initial distribution of opinions leads to different evolution results on similar random networks. In addition, the existence of stubborn nodes plays a special role: only nodes that are extremely stubborn can cause the change of final opinion distribution while in other cases they only delay the time to reach stability. If stubborn nodes are small in number, their effects are confined within a small range. This theoretical work goes deeper on an existing model, it is an early exploration on qualitative and quantitative simulation of party competition.

An evaluation of automated chest radiography reading software for tuberculosis screening among public- and private-sector patients

PubMed Central

Rahman, Md Toufiq; Codlin, Andrew J.; Rahman, Md Mahfuzur; Nahar, Ayenun; Reja, Mehdi; Islam, Tariqul; Qin, Zhi Zhen; Khan, Md Abdus Shakur; Banu, Sayera

2017-01-01

Computer-aided reading (CAR) of medical images is becoming increasingly common, but few studies exist for CAR in tuberculosis (TB). We designed a prospective study evaluating CAR for chest radiography (CXR) as a triage tool before Xpert MTB/RIF (Xpert). Consecutively enrolled adults in Dhaka, Bangladesh, with TB symptoms received CXR and Xpert. Each image was scored by CAR and graded by a radiologist. We compared CAR with the radiologist for sensitivity and specificity, area under the receiver operating characteristic curve (AUC), and calculated the potential Xpert tests saved. A total of 18 036 individuals were enrolled. TB prevalence by Xpert was 15%. The radiologist graded 49% of CXRs as abnormal, resulting in 91% sensitivity and 58% specificity. At a similar sensitivity, CAR had a lower specificity (41%), saving fewer (36%) Xpert tests. The AUC for CAR was 0.74 (95% CI 0.73–0.75). CAR performance declined with increasing age. The radiologist grading was superior across all sub-analyses. Using CAR can save Xpert tests, but the radiologist's specificity was superior. Differentiated CAR thresholds may be required for different populations. Access to, and costs of, human readers must be considered when deciding to use CAR software. More studies are needed to evaluate CAR using different screening approaches. PMID:28529202

An evaluation of automated chest radiography reading software for tuberculosis screening among public- and private-sector patients.

PubMed

Rahman, Md Toufiq; Codlin, Andrew J; Rahman, Md Mahfuzur; Nahar, Ayenun; Reja, Mehdi; Islam, Tariqul; Qin, Zhi Zhen; Khan, Md Abdus Shakur; Banu, Sayera; Creswell, Jacob

2017-05-01

Computer-aided reading (CAR) of medical images is becoming increasingly common, but few studies exist for CAR in tuberculosis (TB). We designed a prospective study evaluating CAR for chest radiography (CXR) as a triage tool before Xpert MTB/RIF (Xpert).Consecutively enrolled adults in Dhaka, Bangladesh, with TB symptoms received CXR and Xpert. Each image was scored by CAR and graded by a radiologist. We compared CAR with the radiologist for sensitivity and specificity, area under the receiver operating characteristic curve (AUC), and calculated the potential Xpert tests saved.A total of 18 036 individuals were enrolled. TB prevalence by Xpert was 15%. The radiologist graded 49% of CXRs as abnormal, resulting in 91% sensitivity and 58% specificity. At a similar sensitivity, CAR had a lower specificity (41%), saving fewer (36%) Xpert tests. The AUC for CAR was 0.74 (95% CI 0.73-0.75). CAR performance declined with increasing age. The radiologist grading was superior across all sub-analyses.Using CAR can save Xpert tests, but the radiologist's specificity was superior. Differentiated CAR thresholds may be required for different populations. Access to, and costs of, human readers must be considered when deciding to use CAR software. More studies are needed to evaluate CAR using different screening approaches. Copyright ©ERS 2017.

Leader's opinion priority bounded confidence model for network opinion evolution

NASA Astrophysics Data System (ADS)

Zhu, Meixia; Xie, Guangqiang

2017-08-01

Aiming at the weight of trust someone given to participate in the interaction in Hegselmann-Krause's type consensus model is the same and virtual social networks among individuals with different level of education, personal influence, etc. For differences between agents, a novelty bounded confidence model was proposed with leader's opinion considered priority. Interaction neighbors can be divided into two kinds. The first kind is made up of "opinion leaders" group, another kind is made up of ordinary people. For different groups to give different weights of trust. We also analyzed the related characteristics of the new model under the symmetrical bounded confidence parameters and combined with the classical HK model were analyzed. Simulation experiment results show that no matter the network size and initial view is subject to uniform distribution or discrete distribution. We can control the "opinion-leader" good change the number of views and values, and even improve the convergence speed. Experiment also found that the choice of "opinion leaders" is not the more the better, the model well explain how the "opinion leader" in the process of the evolution of the public opinion play the role of the leader.

Survival of extreme opinions

NASA Astrophysics Data System (ADS)

Hsu, Jiann-wien; Huang, Ding-wei

2009-12-01

We study the survival of extreme opinions in various processes of consensus formation. All the opinions are treated equally and subjected to the same rules of changing. We investigate three typical models to reach a consensus in each case: (A) personal influence, (B) influence from surroundings, and (C) influence to surroundings. Starting with uniformly distributed random opinions, our calculated results show that the extreme opinions can survive in both models (A) and (B), but not in model (C). We obtain a conclusion that both personal influence and passive adaptation to the environment are not sufficient enough to eradicate all the extreme opinions. Only the active persuasion to change the surroundings eliminates the extreme opinions completely.

Cost-Effectiveness of Automated Digital Microscopy for Diagnosis of Active Tuberculosis.

PubMed

Jha, Swati; Ismail, Nazir; Clark, David; Lewis, James J; Omar, Shaheed; Dreyer, Andries; Chihota, Violet; Churchyard, Gavin; Dowdy, David W

2016-01-01

Automated digital microscopy has the potential to improve the diagnosis of tuberculosis (TB), particularly in settings where molecular testing is too expensive to perform routinely. The cost-effectiveness of TB diagnostic algorithms using automated digital microscopy remains uncertain. Using data from a demonstration study of an automated digital microscopy system (TBDx, Applied Visual Systems, Inc.), we performed an economic evaluation of TB diagnosis in South Africa from the health system perspective. The primary outcome was the incremental cost per new TB diagnosis made. We considered costs and effectiveness of different algorithms for automated digital microscopy, including as a stand-alone test and with confirmation of positive results with Xpert MTB/RIF ('Xpert', Cepheid, Inc.). Results were compared against both manual microscopy and universal Xpert testing. In settings willing to pay $2000 per incremental TB diagnosis, universal Xpert was the preferred strategy. However, where resources were not sufficient to support universal Xpert, and a testing volume of at least 30 specimens per day could be ensured, automated digital microscopy with Xpert confirmation of low-positive results could facilitate the diagnosis of 79-84% of all Xpert-positive TB cases, at 50-60% of the total cost. The cost-effectiveness of this strategy was $1280 per incremental TB diagnosis (95% uncertainty range, UR: $340-$3440) in the base case, but improved under conditions likely reflective of many settings in sub-Saharan Africa: $677 per diagnosis (95% UR: $450-$935) when sensitivity of manual smear microscopy was lowered to 0.5, and $956 per diagnosis (95% UR: $40-$2910) when the prevalence of multidrug-resistant TB was lowered to 1%. Although universal Xpert testing is the preferred algorithm for TB diagnosis when resources are sufficient, automated digital microscopy can identify the majority of cases and halve the cost of diagnosis and treatment when resources are more scarce and

Opinion dynamics in activity-driven networks

NASA Astrophysics Data System (ADS)

Li, Dandan; Han, Dun; Ma, Jing; Sun, Mei; Tian, Lixin; Khouw, Timothy; Stanley, H. Eugene

2017-10-01

Social interaction between individuals constantly affects the development of their personal opinions. Previous models such as the Deffuant model and the Hegselmann-Krause (HK) model have assumed that individuals only update their opinions after interacting with neighbors whose opinions are similar to their own. However, people are capable of communicating widely with all of their neighbors to gather their ideas and opinions, even if they encounter a number of opposing attitudes. We propose a model in which agents listen to the opinions of all their neighbors. Continuous opinion dynamics are investigated in activity-driven networks with a tolerance threshold. We study how the initial opinion distribution, tolerance threshold, opinion-updating speed, and activity rate affect the evolution of opinion. We find that when the initial fraction of positive opinion is small, all opinions become negative by the end of the simulation. As the initial fraction of positive opinions rises above a certain value —about 0.45— the final fraction of positive opinions sharply increases and eventually equals 1. Increased tolerance threshold δ is found to lead to a more varied final opinion distribution. We also find that if the negative opinion has an initial advantage, the final fraction of negative opinion increases and reaches its peak as the updating speed λ approaches 0.5. Finally we show that the lower the activity rate of individuals, the greater the fluctuation range of their opinions.

Public Opinion as Collective Coorientation.

ERIC Educational Resources Information Center

Tipton, Leonard; And Others

To conceptualize public opinion as something other than "mere aggregation" of individual opinions requires systemic models that identify component parts of public opinion and their structural/functional relationships. Operationalization requires asking respondents not only their individual opinion, but also their perception of public…

Opinion evolution influenced by informed agents

NASA Astrophysics Data System (ADS)

Fan, Kangqi; Pedrycz, Witold

2016-11-01

Guiding public opinions toward a pre-set target by informed agents can be a strategy adopted in some practical applications. The informed agents are common agents who are employed or chosen to spread the pre-set opinion. In this work, we propose a social judgment based opinion (SJBO) dynamics model to explore the opinion evolution under the influence of informed agents. The SJBO model distinguishes between inner opinions and observable choices, and incorporates both the compromise between similar opinions and the repulsion between dissimilar opinions. Three choices (support, opposition, and remaining undecided) are considered in the SJBO model. Using the SJBO model, both the inner opinions and the observable choices can be tracked during the opinion evolution process. The simulation results indicate that if the exchanges of inner opinions among agents are not available, the effect of informed agents is mainly dependent on the characteristics of regular agents, including the assimilation threshold, decay threshold, and initial opinions. Increasing the assimilation threshold and decay threshold can improve the guiding effectiveness of informed agents. Moreover, if the initial opinions of regular agents are close to null, the full and unanimous consensus at the pre-set opinion can be realized, indicating that, to maximize the influence of informed agents, the guidance should be started when regular agents have little knowledge about a subject under consideration. If the regular agents have had clear opinions, the full and unanimous consensus at the pre-set opinion cannot be achieved. However, the introduction of informed agents can make the majority of agents choose the pre-set opinion.

Diagnostic accuracy of nucleic acid amplification tests (NAATs) in urine for genitourinary tuberculosis: a systematic review and meta-analysis.

PubMed

Altez-Fernandez, Carlos; Ortiz, Victor; Mirzazadeh, Majid; Zegarra, Luis; Seas, Carlos; Ugarte-Gil, Cesar

2017-06-05

Genitourinary tuberculosis is the third most common form of extrapulmonary tuberculosis. Diagnosis is difficult because of unspecific clinical manifestations and low accuracy of conventional tests. Unfortunately, the delayed diagnosis impacts the urinary tract severely. Nucleic acid amplification tests yield fast results, and among these, new technologies can also detect drug resistance. There is lack of consensus regarding the use of these tests in genitourinary tuberculosis; we therefore aimed to assess the accuracy of nucleic acid amplification tests in the diagnosis of genitourinary tuberculosis and to evaluate the heterogeneity between studies. We did a systematic review and meta-analysis of research articles comparing the accuracy of a reference standard and a nucleic acid amplification test for diagnosis of urinary tract tuberculosis. We searched Medline, EMBASE, Web of Science, LILACS, Cochrane Library, and Scopus for articles published between Jan 1, 1990, and Apr 14, 2016. Two investigators identified eligible articles and extracted data for individual study sites. We analyzed data in groups with the same index test. Then, we generated pooled summary estimates (95% CIs) for sensitivity and specificity by use of random-effects meta-analysis when studies were not heterogeneous. We identified eleven relevant studies from ten articles, giving information on PCR, LCR and Xpert MTB/RIF tests. All PCR studies were "in-house" tests, with different gene targets and had several quality concerns therefore we did not proceed with a pooled analysis. Only one study used LCR. Xpert studies were of good quality and not heterogeneous, pooled sensitivity was 0·87 (0·66-0·96) and specificity was 0·91 (0·84-0·95). PCR studies were highly heterogeneous. Among Xpert MTB/RIF studies, specificity was favorable with an acceptable confidence interval, however new studies can update meta-analysis and get more precise estimates. Further high-quality studies are urgently needed

Transferring embryos with genetic anomalies detected in preimplantation testing: an Ethics Committee Opinion.

PubMed

2017-05-01

Patient requests for transfer of embryos with genetic anomalies linked to serious health-affecting disorders detected in preimplantation testing are rare but do exist. This Opinion sets out the possible rationales for a provider's decision to assist or decline to assist in such transfers. The Committee concludes in most clinical cases it is ethically permissible to assist or decline to assist in transferring such embryos. In circumstances in which a child is highly likely to be born with a life-threatening condition that causes severe and early debility with no possibility of reasonable function, provider transfer of such embryos is ethically problematic and highly discouraged. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Opinion Integration and Summarization

ERIC Educational Resources Information Center

Lu, Yue

2011-01-01

As Web 2.0 applications become increasingly popular, more and more people express their opinions on the Web in various ways in real time. Such wide coverage of topics and abundance of users make the Web an extremely valuable source for mining people's opinions about all kinds of topics. However, since the opinions are usually expressed as…

A novel automatic molecular test for detection of multidrug resistance tuberculosis in sputum specimen: A case control study.

PubMed

Li, Qiang; Ou, Xi C; Pang, Yu; Xia, Hui; Huang, Hai R; Zhao, Bing; Wang, Sheng F; Zhao, Yan L

2017-07-01

MiniLab tuberculosis (ML TB) assay is a new automatic diagnostic tool for diagnosis of multidrug resistance tuberculosis (MDR-TB). This study was conducted with aims to know the performance of this assay. Sputum sample from 224 TB suspects was collected from tuberculosis suspects seeking medical care at Beijing Chest hospital. The sputum samples were directly used for smear and ML TB test. The left sputum sample was used to conduct Xpert MTB/RIF, Bactec MGIT culture and drug susceptibility test (DST). All discrepancies between the results from DST, molecular and phenotypic methods were confirmed by DNA Sequencing. The sensitivity and specificity of ML TB test for detecting MTBC from TB suspects were 95.1% and 88.9%, respectively. The sensitivity for smear negative TB suspects was 64.3%. For detection of RIF resistance, the sensitivity and specificity of ML TB test were 89.2% and 95.7%, respectively. For detection of INH resistance, the sensitivity and specificity of ML TB test were 78.3% and 98.1%, respectively. ML TB test showed similar performance to Xpert MTB/RIF for detection of MTBC and RIF resistance. In addition, ML TB also had good performance for INH resistance detection. Copyright © 2017. Published by Elsevier Ltd.

Nonconformity defines the self: the role of minority opinion status in self-concept clarity.

PubMed

Morrison, Kimberly Rios; Wheeler, S Christian

2010-03-01

Drawing on distinctiveness and social identity theories, the present studies tested whether minority opinion holders would have a more clearly defined sense of self than majority opinion holders. In Study 1, participants who were induced to believe that they held a minority opinion on a controversial issue had higher subsequent self-concept clarity scores than did those who were induced to believe that they held a majority opinion, controlling for self-esteem. Furthermore, the relationship between minority opinion status and self-concept clarity was strongest among participants whose opinions were highly expressive of their values (Studies 2 and 3), as well as among participants who identified strongly with the group in which they were a minority (Study 3). Theoretical and practical implications of these results are discussed.

Expert opinion vs. empirical evidence

PubMed Central

Herman, Rod A; Raybould, Alan

2014-01-01

Expert opinion is often sought by government regulatory agencies when there is insufficient empirical evidence to judge the safety implications of a course of action. However, it can be reckless to continue following expert opinion when a preponderance of evidence is amassed that conflicts with this opinion. Factual evidence should always trump opinion in prioritizing the information that is used to guide regulatory policy. Evidence-based medicine has seen a dramatic upturn in recent years spurred by examples where evidence indicated that certain treatments recommended by expert opinions increased death rates. We suggest that scientific evidence should also take priority over expert opinion in the regulation of genetically modified crops (GM). Examples of regulatory data requirements that are not justified based on the mass of evidence are described, and it is suggested that expertise in risk assessment should guide evidence-based regulation of GM crops. PMID:24637724

Comprehensive embryo testing. Experts' opinions regarding future directions: an expert panel study on comprehensive embryo testing.

PubMed

Hens, Kristien; Dondorp, Wybo J; Geraedts, Joep P M; de Wert, Guido M

2013-05-01

four Western Europe countries. As willingness to participate in this study may be connected with expectations regarding the pace and direction of future developments, selection bias cannot be excluded. The introduction of comprehensive screening techniques in embryo testing calls for further ethical reflection that is grounded in empirical work. Specifically, there is a need for studies querying the opinions of infertile couples undergoing IVF/PGS regarding the desirability of embryo screening beyond aneuploidy. This research was supported by the CSG, Centre for Society and Life Sciences (project number: 70.1.074). The authors declare no conflict of interest. N/A.

The Role of Social Context in Shaping Student-Athlete Opinions

PubMed Central

2014-01-01

How do student-athletes form opinions? This is a particularly important question given ongoing debates about whether student-athletes should be paid and/or allowed to unionize. These debates concern the rights and benefits accrued directly to student-athletes, and thus, understanding their attitudes is of obvious import. Yet, virtually no recent work has delved into how student-athletes form opinions on these issues. We fill this gap with a theoretical framework that predicts changes in social context alter opinions. This leads to the hypothesis that opinions will change once a student-athlete completes his/her career and finds him/herself in a distinct social network. We test the prediction with a survey, implemented in 2012, of one of the most notable athletic conferences in the National Collegiate Athletic Association (NCAA): the Big Ten. We find that post-career student-athletes demonstrate higher levels of support for pay for play and unionization. Our results suggest that student-athletes' opinions seem to depend on their extant social contexts. While our data, from 2012, neither speak to current opinions – given the quickly evolving landscape of college athletics – nor demonstrate what reforms may be “best,” they do accentuate the power of social context in shaping student-athletes' attitudes. PMID:25522052

The role of social context in shaping student-athlete opinions.

PubMed

Druckman, James N; Gilli, Mauro; Klar, Samara; Robison, Joshua

2014-01-01

How do student-athletes form opinions? This is a particularly important question given ongoing debates about whether student-athletes should be paid and/or allowed to unionize. These debates concern the rights and benefits accrued directly to student-athletes, and thus, understanding their attitudes is of obvious import. Yet, virtually no recent work has delved into how student-athletes form opinions on these issues. We fill this gap with a theoretical framework that predicts changes in social context alter opinions. This leads to the hypothesis that opinions will change once a student-athlete completes his/her career and finds him/herself in a distinct social network. We test the prediction with a survey, implemented in 2012, of one of the most notable athletic conferences in the National Collegiate Athletic Association (NCAA): the Big Ten. We find that post-career student-athletes demonstrate higher levels of support for pay for play and unionization. Our results suggest that student-athletes' opinions seem to depend on their extant social contexts. While our data, from 2012, neither speak to current opinions - given the quickly evolving landscape of college athletics - nor demonstrate what reforms may be "best," they do accentuate the power of social context in shaping student-athletes' attitudes.

Public Opinion and the NCAA Proposal 42.

ERIC Educational Resources Information Center

Cross, Lawrence H.; Koball, Elizabeth G.

1991-01-01

Surveyed opinions on the National Collegiate Athletic Association's Proposal 42 using a convenience sample of 872 persons. Most respondents felt that college admission tests are biased. Concludes that the controversy will be resolved when American society comes to grips with inequalities in educational and socioeconomic opportunity. (DM)

Characteristics associated with requests by pathologists for second opinions on breast biopsies

PubMed Central

Geller, Berta M; Nelson, Heidi D; Weaver, Donald L; Frederick, Paul D; Allison, Kimberly H; Onega, Tracy; Carney, Patricia A; Tosteson, Anna N A; Elmore, Joann G

2018-01-01

Aims Second opinions in pathology improve patient safety by reducing diagnostic errors, leading to more appropriate clinical treatment decisions. Little objective data are available regarding the factors triggering a request for second opinion despite second opinion consultations being part of the diagnostic system of pathology. Therefore we sought to assess breast biopsy cases and interpreting pathologists characteristics associated with second opinion requests. Methods Collected pathologist surveys and their interpretations of 60 test set cases were used to explore the relationships between case characteristics, pathologist characteristics and case perceptions, and requests for second opinions. Data were evaluated by logistic regression and generalised estimating equations. Results 115 pathologists provided 6900 assessments; pathologists requested second opinions on 70% (4827/6900) of their assessments 36% (1731/4827) of these would not have been required by policy. All associations between case characteristics and requesting second opinions were statistically significant, including diagnostic category, breast density, biopsy type, and number of diagnoses noted per case. Exclusive of institutional policies, pathologists wanted second opinions most frequently for atypia (66%) and least frequently for invasive cancer (20%). Second opinion rates were higher when the pathologist had lower assessment confidence, in cases with higher perceived difficulty, and cases with borderline diagnoses. Conclusions Pathologists request second opinions for challenging cases, particularly those with atypia, high breast density, core needle biopsies, or many co-existing diagnoses. Further studies should evaluate whether the case characteristics identified in this study could be used as clinical criteria to prompt system-level strategies for mandating second opinions. PMID:28465449

Rifampicin resistance in mycobacterium tuberculosis patients using GeneXpert at Livingstone Central Hospital for the year 2015: a cross sectional explorative study.

PubMed

Masenga, Sepiso K; Mubila, Harrison; Hamooya, Benson M

2017-09-22

Since the recent introduction of GeneXepert for the detection of Tuberculosis (TB) drug resistance mutations in both primary resistance and acquired resistance in Zambia, little has been documented in literature on the issue of rifampicin resistance especially in the face of a high National TB burden. The study aimed to determine the prevalence of rifampicin resistance in tuberculosis patients at Livingstone Central Hospital for the year 2015. This was a cross sectional study conducted at Livingstone Central Hospital where we reviewed 152 records (from January 1, 2015 to 31st December, 2015) involving patients who presented with clinically suspected TB or documented TB, whose samples were sent to the laboratory for GeneXpert Mycobacterium tuberculosis/rifampicin testing. Statistical evaluations used a one-sample test of proportion and Fisher's exact test. The age of participants ranged from 8 months to 73 years old (median = 34). Of the participants with complete data on gender, 99 (66%) and 52 (34%) were males and females respectively. The TB co-infection with HIV prevalence was 98.3% (p < 0.001). Prevalence of rifampicin resistance was 5.9% and there was no statistical significant difference between being male or female (p = 0.721). We were able to show from our study, evidence of rifampicin resistance at Livingstone Central Hospital. Hence, there was need for further in-depth research and appropriate interventions (i.e close follow-up and patient care for drug resistance positive patients).

Stochastic opinion formation in scale-free networks

DOE Office of Scientific and Technical Information (OSTI.GOV)

M. Bartolozzi; D. B. Leinweber; A. W. Thomas

2005-10-01

The dynamics of opinion formation in large groups of people is a complex nonlinear phenomenon whose investigation is just beginning. Both collective behavior and personal views play an important role in this mechanism. In the present work we mimic the dynamics of opinion formation of a group of agents, represented by two states 1, as a stochastic response of each agent to the opinion of his/her neighbors in the social network and to feedback from the average opinion of the whole. In the light of recent studies, a scale-free Barabsi-Albert network has been selected to simulate the topology of themore » interactions. A turbulent-like dynamics, characterized by an intermittent behavior, is observed for a certain range of the model parameters. The problem of uncertainty in decision taking is also addressed both from a topological point of view, using random and targeted removal of agents from the network, and by implementing a three-state model, where the third state, zero, is related to the information available to each agent. Finally, the results of the model are tested against the best known network of social interactions: the stock market. A time series of daily closures of the Dow-Jones index has been used as an indicator of the possible applicability of our model in the financial context. Good qualitative agreement is found.« less

Evaluation of the RealTime HIV-1, Xpert HIV-1, and Aptima HIV-1 Quant Dx Assays in Comparison to the NucliSens EasyQ HIV-1 v2.0 Assay for Quantification of HIV-1 Viral Load.

PubMed

Mor, Orna; Gozlan, Yael; Wax, Marina; Mileguir, Fernando; Rakovsky, Avia; Noy, Bina; Mendelson, Ella; Levy, Itzchak

2015-11-01

HIV-1 RNA monitoring, both before and during antiretroviral therapy, is an integral part of HIV management worldwide. Measurements of HIV-1 viral loads are expected to assess the copy numbers of all common HIV-1 subtypes accurately and to be equally sensitive at different viral loads. In this study, we compared for the first time the performance of the NucliSens v2.0, RealTime HIV-1, Aptima HIV-1 Quant Dx, and Xpert HIV-1 viral load assays. Plasma samples (n = 404) were selected on the basis of their NucliSens v2.0 viral load results and HIV-1 subtypes. Concordance, linear regression, and Bland-Altman plots were assessed, and mixed-model analysis was utilized to compare the analytical performance of the assays for different HIV-1 subtypes and for low and high HIV-1 copy numbers. Overall, high concordance (>83.89%), high correlation values (Pearson r values of >0.89), and good agreement were observed among all assays, although the Xpert and Aptima assays, which provided the most similar outputs (estimated mean viral loads of 2.67 log copies/ml [95% confidence interval [CI], 2.50 to 2.84 log copies/ml] and 2.68 log copies/ml [95% CI, 2.49 to 2.86 log copies/ml], respectively), correlated best with the RealTime assay (89.8% concordance, with Pearson r values of 0.97 to 0.98). These three assays exhibited greater precision than the NucliSens v2.0 assay. All assays were equally sensitive for subtype B and AG/G samples and for samples with viral loads of 1.60 to 3.00 log copies/ml. The NucliSens v2.0 assay underestimated A1 samples and those with viral loads of >3.00 log copies/ml. The RealTime assay tended to underquantify subtype C (compared to the Xpert and Aptima assays) and subtype A1 samples. The Xpert and Aptima assays were equally efficient for detection of all subtypes and viral loads, which renders these new assays most suitable for clinical HIV laboratories. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Competing opinion diffusion on social networks.

PubMed

Hu, Haibo

2017-11-01

Opinion competition is a common phenomenon in real life, such as with opinions on controversial issues or political candidates; however, modelling this competition remains largely unexplored. To bridge this gap, we propose a model of competing opinion diffusion on social networks taking into account degree-dependent fitness or persuasiveness. We study the combined influence of social networks, individual fitnesses and attributes, as well as mass media on people's opinions, and find that both social networks and mass media act as amplifiers in opinion diffusion, the amplifying effect of which can be quantitatively characterized. We analytically obtain the probability that each opinion will ultimately pervade the whole society when there are no committed people in networks, and the final proportion of each opinion at the steady state when there are committed people in networks. The results of numerical simulations show good agreement with those obtained through an analytical approach. This study provides insight into the collective influence of individual attributes, local social networks and global media on opinion diffusion, and contributes to a comprehensive understanding of competing diffusion behaviours in the real world.

Opinion competition dynamics on multiplex networks

NASA Astrophysics Data System (ADS)

Amato, R.; Kouvaris, N. E.; San Miguel, M.; Díaz-Guilera, A.

2017-12-01

Multilayer and multiplex networks represent a good proxy for the description of social phenomena where social structure is important and can have different origins. Here, we propose a model of opinion competition where individuals are organized according to two different structures in two layers. Agents exchange opinions according to the Abrams-Strogatz model in each layer separately and opinions can be copied across layers by the same individual. In each layer a different opinion is dominant, so each layer has a different absorbing state. Consensus in one opinion is not the only possible stable solution because of the interaction between the two layers. A new mean field solution has been found where both opinions coexist. In a finite system there is a long transient time for the dynamical coexistence of both opinions. However, the system ends in a consensus state due to finite size effects. We analyze sparse topologies in the two layers and the existence of positive correlations between them, which enables the coexistence of inter-layer groups of agents sharing the same opinion.

Non-consensus Opinion Models on Complex Networks

NASA Astrophysics Data System (ADS)

Li, Qian; Braunstein, Lidia A.; Wang, Huijuan; Shao, Jia; Stanley, H. Eugene; Havlin, Shlomo

2013-04-01

Social dynamic opinion models have been widely studied to understand how interactions among individuals cause opinions to evolve. Most opinion models that utilize spin interaction models usually produce a consensus steady state in which only one opinion exists. Because in reality different opinions usually coexist, we focus on non-consensus opinion models in which above a certain threshold two opinions coexist in a stable relationship. We revisit and extend the non-consensus opinion (NCO) model introduced by Shao et al. (Phys. Rev. Lett. 103:01870, 2009). The NCO model in random networks displays a second order phase transition that belongs to regular mean field percolation and is characterized by the appearance (above a certain threshold) of a large spanning cluster of the minority opinion. We generalize the NCO model by adding a weight factor W to each individual's original opinion when determining their future opinion (NCO W model). We find that as W increases the minority opinion holders tend to form stable clusters with a smaller initial minority fraction than in the NCO model. We also revisit another non-consensus opinion model based on the NCO model, the inflexible contrarian opinion (ICO) model (Li et al. in Phys. Rev. E 84:066101, 2011), which introduces inflexible contrarians to model the competition between two opinions in a steady state. Inflexible contrarians are individuals that never change their original opinion but may influence the opinions of others. To place the inflexible contrarians in the ICO model we use two different strategies, random placement and one in which high-degree nodes are targeted. The inflexible contrarians effectively decrease the size of the largest rival-opinion cluster in both strategies, but the effect is more pronounced under the targeted method. All of the above models have previously been explored in terms of a single network, but human communities are usually interconnected, not isolated. Because opinions propagate not

Opinion mining feature-level using Naive Bayes and feature extraction based analysis dependencies

NASA Astrophysics Data System (ADS)

Sanda, Regi; Baizal, Z. K. Abdurahman; Nhita, Fhira

2015-12-01

Development of internet and technology, has major impact and providing new business called e-commerce. Many e-commerce sites that provide convenience in transaction, and consumers can also provide reviews or opinions on products that purchased. These opinions can be used by consumers and producers. Consumers to know the advantages and disadvantages of particular feature of the product. Procuders can analyse own strengths and weaknesses as well as it's competitors products. Many opinions need a method that the reader can know the point of whole opinion. The idea emerged from review summarization that summarizes the overall opinion based on sentiment and features contain. In this study, the domain that become the main focus is about the digital camera. This research consisted of four steps 1) giving the knowledge to the system to recognize the semantic orientation of an opinion 2) indentify the features of product 3) indentify whether the opinion gives a positive or negative 4) summarizing the result. In this research discussed the methods such as Naï;ve Bayes for sentiment classification, and feature extraction algorithm based on Dependencies Analysis, which is one of the tools in Natural Language Processing (NLP) and knowledge based dictionary which is useful for handling implicit features. The end result of research is a summary that contains a bunch of reviews from consumers on the features and sentiment. With proposed method, accuration for sentiment classification giving 81.2 % for positive test data, 80.2 % for negative test data, and accuration for feature extraction reach 90.3 %.

Characteristics associated with requests by pathologists for second opinions on breast biopsies.

PubMed

Geller, Berta M; Nelson, Heidi D; Weaver, Donald L; Frederick, Paul D; Allison, Kimberly H; Onega, Tracy; Carney, Patricia A; Tosteson, Anna N A; Elmore, Joann G

2017-11-01

Second opinions in pathology improve patient safety by reducing diagnostic errors, leading to more appropriate clinical treatment decisions. Little objective data are available regarding the factors triggering a request for second opinion despite second opinion consultations being part of the diagnostic system of pathology. Therefore we sought to assess breast biopsy cases and interpreting pathologists characteristics associated with second opinion requests. Collected pathologist surveys and their interpretations of 60 test set cases were used to explore the relationships between case characteristics, pathologist characteristics and case perceptions, and requests for second opinions. Data were evaluated by logistic regression and generalised estimating equations. 115 pathologists provided 6900 assessments; pathologists requested second opinions on 70% (4827/6900) of their assessments 36% (1731/4827) of these would not have been required by policy. All associations between case characteristics and requesting second opinions were statistically significant, including diagnostic category, breast density, biopsy type, and number of diagnoses noted per case. Exclusive of institutional policies, pathologists wanted second opinions most frequently for atypia (66%) and least frequently for invasive cancer (20%). Second opinion rates were higher when the pathologist had lower assessment confidence, in cases with higher perceived difficulty, and cases with borderline diagnoses. Pathologists request second opinions for challenging cases, particularly those with atypia, high breast density, core needle biopsies, or many co-existing diagnoses. Further studies should evaluate whether the case characteristics identified in this study could be used as clinical criteria to prompt system-level strategies for mandating second opinions. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Competing opinion diffusion on social networks

PubMed Central

2017-01-01

Opinion competition is a common phenomenon in real life, such as with opinions on controversial issues or political candidates; however, modelling this competition remains largely unexplored. To bridge this gap, we propose a model of competing opinion diffusion on social networks taking into account degree-dependent fitness or persuasiveness. We study the combined influence of social networks, individual fitnesses and attributes, as well as mass media on people’s opinions, and find that both social networks and mass media act as amplifiers in opinion diffusion, the amplifying effect of which can be quantitatively characterized. We analytically obtain the probability that each opinion will ultimately pervade the whole society when there are no committed people in networks, and the final proportion of each opinion at the steady state when there are committed people in networks. The results of numerical simulations show good agreement with those obtained through an analytical approach. This study provides insight into the collective influence of individual attributes, local social networks and global media on opinion diffusion, and contributes to a comprehensive understanding of competing diffusion behaviours in the real world. PMID:29291101

Method for Expressing Public Opinions Concerning the Introduction of an Emerging Technology to Society

NASA Astrophysics Data System (ADS)

Yamamoto, Satoshi; Ito, Kyoko; Ohnishi, Satoshi; Nishida, Shogo

Emerging technology may have considerable social impact. Because emerging technology has not yet been introduced in society, it is needed general public express its opinions on emerging technology. It is important that expressing opinion must have social spirit. A method to limit facility of the Internet and activate social spirit is proposed. Evaluation experiment were conducted to test the effectiveness of the proposed method, and the participant could express opinion with social spirit.

Rapid Detection of Staphylococcus aureus and Methicillin-Resistant S. aureus (MRSA) in Wound Specimens and Blood Cultures: Multicenter Preclinical Evaluation of the Cepheid Xpert MRSA/SA Skin and Soft Tissue and Blood Culture Assays▿

PubMed Central

Wolk, D. M.; Struelens, M. J.; Pancholi, P.; Davis, T.; Della-Latta, P.; Fuller, D.; Picton, E.; Dickenson, R.; Denis, O.; Johnson, D.; Chapin, K.

2009-01-01

A multicenter preclinical evaluation was conducted to evaluate the performance of two Cepheid Xpert assays for detection of methicillin-resistant Staphylococcus aureus (MRSA) and S. aureus. Sensitivity was 97.1% and 98.3% for MRSA in wound and blood culture specimens, respectively. Sensitivity was 100% for S. aureus from both specimen types. PMID:19144803

Education through Fiction: Acquiring Opinion-Forming Skills in the Context of Genomics

ERIC Educational Resources Information Center

Knippels, Marie-Christine P. J.; Severiens, Sabine E.; Klop, Tanja

2009-01-01

The present study examined the outcomes of a newly designed four-lesson science module on opinion-forming in the context of genomics in upper secondary education. The lesson plan aims to foster 16-year-old students' opinion-forming skills in the context of genomics and to test the effect of the use of fiction in the module. The basic hypothesis…

Accelerating access to quality TB care for pediatric TB cases through better diagnostic strategy in four major cities of India.

PubMed

Raizada, Neeraj; Khaparde, Sunil D; Salhotra, Virender Singh; Rao, Raghuram; Kalra, Aakshi; Swaminathan, Soumya; Khanna, Ashwani; Chopra, Kamal Kishore; Hanif, M; Singh, Varinder; Umadevi, K R; Nair, Sreenivas Achuthan; Huddart, Sophie; Prakash, C H Surya; Mall, Shalini; Singh, Pooja; Saha, B K; Denkinger, Claudia M; Boehme, Catharina; Sarin, Sanjay

2018-01-01

Diagnosis of TB in children is challenging, and is largely based on positive history of contact with a TB case, clinical and radiological findings, often without microbiological confirmation. Diagnostic efforts are also undermined by challenges in specimen collection and the limited availability of high sensitivity, rapid diagnostic tests that can be applied with a quick turnaround time. The current project was undertaken in four major cities of India to address TB diagnostic challenges in pediatric population, by offering free of cost Xpert testing to pediatric presumptive TB cases, thereby paving the way for better TB care. A high throughput lab was established in each of the four project cities, and linked to various health care providers across the city through rapid specimen transportation and electronic reporting linkages. Free Xpert testing was offered to all pediatric (0-14 years) presumptive TB cases (both pulmonary and extra-pulmonary) seeking care at public and private health facilities. The current project enrolled 42,238 pediatric presumptive TB cases from April, 2014 to June, 2016. A total of 3,340 (7.91%, CI 7.65-8.17) bacteriologically confirmed TB cases were detected, of which 295 (8.83%, CI 7.9-9.86) were rifampicin-resistant. The level of rifampicin resistance in the project cohort was high. Overall Xpert yielded a high proportion of valid results and TB detection rates were more than three-fold higher than smear microscopy. The project provided same-day testing and early availability of results led to rapid treatment initiation and success rates and very low rates of treatment failure and loss to follow-up. The current project demonstrated the feasibility of rolling out rapid and upfront Xpert testing for pediatric presumptive TB cases through a single Xpert lab per city in an efficient manner. Rapid turnaround testing time facilitated prompt and appropriate treatment initiation. These results suggest that the upfront Xpert assay is a promising

Accelerating access to quality TB care for pediatric TB cases through better diagnostic strategy in four major cities of India

PubMed Central

Raizada, Neeraj; Khaparde, Sunil D.; Salhotra, Virender Singh; Rao, Raghuram; Kalra, Aakshi; Swaminathan, Soumya; Khanna, Ashwani; Chopra, Kamal Kishore; Hanif, M.; Singh, Varinder; Umadevi, K. R.; Nair, Sreenivas Achuthan; Huddart, Sophie; Prakash, C. H. Surya; Mall, Shalini; Singh, Pooja; Saha, B. K.; Denkinger, Claudia M.; Boehme, Catharina

2018-01-01

Background Diagnosis of TB in children is challenging, and is largely based on positive history of contact with a TB case, clinical and radiological findings, often without microbiological confirmation. Diagnostic efforts are also undermined by challenges in specimen collection and the limited availability of high sensitivity, rapid diagnostic tests that can be applied with a quick turnaround time. The current project was undertaken in four major cities of India to address TB diagnostic challenges in pediatric population, by offering free of cost Xpert testing to pediatric presumptive TB cases, thereby paving the way for better TB care. Methods A high throughput lab was established in each of the four project cities, and linked to various health care providers across the city through rapid specimen transportation and electronic reporting linkages. Free Xpert testing was offered to all pediatric (0–14 years) presumptive TB cases (both pulmonary and extra-pulmonary) seeking care at public and private health facilities. Results The current project enrolled 42,238 pediatric presumptive TB cases from April, 2014 to June, 2016. A total of 3,340 (7.91%, CI 7.65–8.17) bacteriologically confirmed TB cases were detected, of which 295 (8.83%, CI 7.9–9.86) were rifampicin-resistant. The level of rifampicin resistance in the project cohort was high. Overall Xpert yielded a high proportion of valid results and TB detection rates were more than three-fold higher than smear microscopy. The project provided same-day testing and early availability of results led to rapid treatment initiation and success rates and very low rates of treatment failure and loss to follow-up. Conclusion The current project demonstrated the feasibility of rolling out rapid and upfront Xpert testing for pediatric presumptive TB cases through a single Xpert lab per city in an efficient manner. Rapid turnaround testing time facilitated prompt and appropriate treatment initiation. These results suggest

5 CFR 2638.313 - Agency opinions.

Code of Federal Regulations, 2010 CFR

2010-01-01

....313 Administrative Personnel OFFICE OF GOVERNMENT ETHICS GOVERNMENT ETHICS OFFICE OF GOVERNMENT ETHICS AND EXECUTIVE AGENCY ETHICS PROGRAM RESPONSIBILITIES Formal Advisory Opinion Service § 2638.313 Agency opinions. If the designated agency ethics official issues a written opinion concerning the application of...

Cost analysis of nucleic acid amplification for diagnosing pulmonary tuberculosis, within the context of the Brazilian Unified Health Care System.

PubMed

Pinto, Márcia; Entringer, Aline Piovezan; Steffen, Ricardo; Trajman, Anete

2015-01-01

We estimated the costs of a molecular test for Mycobacterium tuberculosis and resistance to rifampin (Xpert MTB/RIF) and of smear microscopy, within the Brazilian Sistema Único de Saúde (SUS, Unified Health Care System). In SUS laboratories in the cities of Rio de Janeiro and Manaus, we performed activity-based costing and micro-costing. The mean unit costs for Xpert MTB/RIF and smear microscopy were R$35.57 and R$14.16, respectively. The major cost drivers for Xpert MTB/RIF and smear microscopy were consumables/reagents and staff, respectively. These results might facilitate future cost-effectiveness studies and inform the decision-making process regarding the expansion of Xpert MTB/RIF use in Brazil.

Choice Shift in Opinion Network Dynamics

NASA Astrophysics Data System (ADS)

Gabbay, Michael

Choice shift is a phenomenon associated with small group dynamics whereby group discussion causes group members to shift their opinions in a more extreme direction so that the mean post-discussion opinion exceeds the mean pre-discussion opinion. Also known as group polarization, choice shift is a robust experimental phenomenon and has been well-studied within social psychology. In opinion network models, shifts toward extremism are typically produced by the presence of stubborn agents at the extremes of the opinion axis, whose opinions are much more resistant to change than moderate agents. However, we present a model in which choice shift can arise without the assumption of stubborn agents; the model evolves member opinions and uncertainties using coupled nonlinear differential equations. In addition, we briefly describe the results of a recent experiment conducted involving online group discussion concerning the outcome of National Football League games are described. The model predictions concerning the effects of network structure, disagreement level, and team choice (favorite or underdog) are in accord with the experimental results. This research was funded by the Office of Naval Research and the Defense Threat Reduction Agency.

Opinion Dynamics with Confirmation Bias

PubMed Central

Allahverdyan, Armen E.; Galstyan, Aram

2014-01-01

Background Confirmation bias is the tendency to acquire or evaluate new information in a way that is consistent with one's preexisting beliefs. It is omnipresent in psychology, economics, and even scientific practices. Prior theoretical research of this phenomenon has mainly focused on its economic implications possibly missing its potential connections with broader notions of cognitive science. Methodology/Principal Findings We formulate a (non-Bayesian) model for revising subjective probabilistic opinion of a confirmationally-biased agent in the light of a persuasive opinion. The revision rule ensures that the agent does not react to persuasion that is either far from his current opinion or coincides with it. We demonstrate that the model accounts for the basic phenomenology of the social judgment theory, and allows to study various phenomena such as cognitive dissonance and boomerang effect. The model also displays the order of presentation effect–when consecutively exposed to two opinions, the preference is given to the last opinion (recency) or the first opinion (primacy) –and relates recency to confirmation bias. Finally, we study the model in the case of repeated persuasion and analyze its convergence properties. Conclusions The standard Bayesian approach to probabilistic opinion revision is inadequate for describing the observed phenomenology of persuasion process. The simple non-Bayesian model proposed here does agree with this phenomenology and is capable of reproducing a spectrum of effects observed in psychology: primacy-recency phenomenon, boomerang effect and cognitive dissonance. We point out several limitations of the model that should motivate its future development. PMID:25007078

Impacts of opinion leaders on social contagions

NASA Astrophysics Data System (ADS)

Liu, Quan-Hui; Lü, Feng-Mao; Zhang, Qian; Tang, Ming; Zhou, Tao

2018-05-01

Opinion leaders are ubiquitous in both online and offline social networks, but the impacts of opinion leaders on social behavior contagions are still not fully understood, especially by using a mathematical model. Here, we generalize the classical Watts threshold model and address the influences of the opinion leaders, where an individual adopts a new behavior if one of his/her opinion leaders adopts the behavior. First, we choose the opinion leaders randomly from all individuals in the network and find that the impacts of opinion leaders make other individuals adopt the behavior more easily. Specifically, the existence of opinion leaders reduces the lowest mean degree of the network required for the global behavior adoption and increases the highest mean degree of the network that the global behavior adoption can occur. Besides, the introduction of opinion leaders accelerates the behavior adoption but does not change the adoption order of individuals. The developed theoretical predictions agree with the simulation results. Second, we randomly choose the opinion leaders from the top h % of the highest degree individuals and find an optimal h % for the network with the lowest mean degree that the global behavior adoption can occur. Meanwhile, the influences of opinion leaders on accelerating the adoption of behaviors become less significant and can even be ignored when reducing the value of h % .

OpinionSeer: interactive visualization of hotel customer feedback.

PubMed

Wu, Yingcai; Wei, Furu; Liu, Shixia; Au, Norman; Cui, Weiwei; Zhou, Hong; Qu, Huamin

2010-01-01

The rapid development of Web technology has resulted in an increasing number of hotel customers sharing their opinions on the hotel services. Effective visual analysis of online customer opinions is needed, as it has a significant impact on building a successful business. In this paper, we present OpinionSeer, an interactive visualization system that could visually analyze a large collection of online hotel customer reviews. The system is built on a new visualization-centric opinion mining technique that considers uncertainty for faithfully modeling and analyzing customer opinions. A new visual representation is developed to convey customer opinions by augmenting well-established scatterplots and radial visualization. To provide multiple-level exploration, we introduce subjective logic to handle and organize subjective opinions with degrees of uncertainty. Several case studies illustrate the effectiveness and usefulness of OpinionSeer on analyzing relationships among multiple data dimensions and comparing opinions of different groups. Aside from data on hotel customer feedback, OpinionSeer could also be applied to visually analyze customer opinions on other products or services.

Opinion formation on social media: An empirical approach

NASA Astrophysics Data System (ADS)

Xiong, Fei; Liu, Yun

2014-03-01

Opinion exchange models aim to describe the process of public opinion formation, seeking to uncover the intrinsic mechanism in social systems; however, the model results are seldom empirically justified using large-scale actual data. Online social media provide an abundance of data on opinion interaction, but the question of whether opinion models are suitable for characterizing opinion formation on social media still requires exploration. We collect a large amount of user interaction information from an actual social network, i.e., Twitter, and analyze the dynamic sentiments of users about different topics to investigate realistic opinion evolution. We find two nontrivial results from these data. First, public opinion often evolves to an ordered state in which one opinion predominates, but not to complete consensus. Second, agents are reluctant to change their opinions, and the distribution of the number of individual opinion changes follows a power law. Then, we suggest a model in which agents take external actions to express their internal opinions according to their activity. Conversely, individual actions can influence the activity and opinions of neighbors. The probability that an agent changes its opinion depends nonlinearly on the fraction of opponents who have taken an action. Simulation results show user action patterns and the evolution of public opinion in the model coincide with the empirical data. For different nonlinear parameters, the system may approach different regimes. A large decay in individual activity slows down the dynamics, but causes more ordering in the system.

Opinion Formation Models on a Gradient

PubMed Central

Gastner, Michael T.; Markou, Nikolitsa; Pruessner, Gunnar; Draief, Moez

2014-01-01

Statistical physicists have become interested in models of collective social behavior such as opinion formation, where individuals change their inherently preferred opinion if their friends disagree. Real preferences often depend on regional cultural differences, which we model here as a spatial gradient g in the initial opinion. The gradient does not only add reality to the model. It can also reveal that opinion clusters in two dimensions are typically in the standard (i.e., independent) percolation universality class, thus settling a recent controversy about a non-consensus model. However, using analytical and numerical tools, we also present a model where the width of the transition between opinions scales , not as in independent percolation, and the cluster size distribution is consistent with first-order percolation. PMID:25474528

[Medical data security in medico-legal opinioning].

PubMed

Susło, Robert; Swiatek, Barbara

2005-01-01

Medical data security can be approached in medico-legal opinioning in three main situations: security of medical data, on which the opinion should be based, opinioning itself and whether the medical data security was properly ensured and ensuring medical data security during medico-legal opinion giving. The importance of medical data security, during collecting, processing and storing, as well in medical as in legal institutions, is of major importance for the possibility of providing a proper medico-legal opinion. Theoretically speeking, it is possible to give a proper medico-legal opinion using incorrect data, but the possibility is low. When the expert is given improper, unreadable, incomplete or even bogus in part or in the whole medical data it is extremely possible, that he fails in giving his opinion. The term "medical data" was defined and subsequently there was a brief review of medical data storing methods made and specific threats bound with them, based on modern literature. The authors also pointed out possible methods of preventing the threats. They listed Polish as well as international regulations and laws concerning the problem, accenting the importance of preserving medical data for the purposes of medico-legal opinioning.

Cost analysis of nucleic acid amplification for diagnosing pulmonary tuberculosis, within the context of the Brazilian Unified Health Care System

PubMed Central

Pinto, Márcia; Entringer, Aline Piovezan; Steffen, Ricardo; Trajman, Anete

2015-01-01

ABSTRACT We estimated the costs of a molecular test for Mycobacterium tuberculosis and resistance to rifampin (Xpert MTB/RIF) and of smear microscopy, within the Brazilian Sistema Único de Saúde (SUS, Unified Health Care System). In SUS laboratories in the cities of Rio de Janeiro and Manaus, we performed activity-based costing and micro-costing. The mean unit costs for Xpert MTB/RIF and smear microscopy were R$35.57 and R$14.16, respectively. The major cost drivers for Xpert MTB/RIF and smear microscopy were consumables/reagents and staff, respectively. These results might facilitate future cost-effectiveness studies and inform the decision-making process regarding the expansion of Xpert MTB/RIF use in Brazil. PMID:26785963

A user-friendly, open-source tool to project impact and cost of diagnostic tests for tuberculosis

PubMed Central

Dowdy, David W; Andrews, Jason R; Dodd, Peter J; Gilman, Robert H

2014-01-01

Most models of infectious diseases, including tuberculosis (TB), do not provide results customized to local conditions. We created a dynamic transmission model to project TB incidence, TB mortality, multidrug-resistant (MDR) TB prevalence, and incremental costs over 5 years after scale-up of nine alternative diagnostic strategies. A corresponding web-based interface allows users to specify local costs and epidemiology. In settings with little capacity for up-front investment, same-day microscopy had the greatest impact on TB incidence and became cost-saving within 5 years if delivered at $10/test. With greater initial investment, population-level scale-up of Xpert MTB/RIF or microcolony-based culture often averted 10 times more TB cases than narrowly-targeted strategies, at minimal incremental long-term cost. Xpert for smear-positive TB had reasonable impact on MDR-TB incidence, but at substantial price and little impact on overall TB incidence and mortality. This user-friendly modeling framework improves decision-makers' ability to evaluate the local impact of TB diagnostic strategies. DOI: http://dx.doi.org/10.7554/eLife.02565.001 PMID:24898755

Opinion evolution in different social acquaintance networks

NASA Astrophysics Data System (ADS)

Chen, Xi; Zhang, Xiao; Wu, Zhan; Wang, Hongwei; Wang, Guohua; Li, Wei

2017-11-01

Social acquaintance networks influenced by social culture and social policy have a great impact on public opinion evolution in daily life. Based on the differences between socio-culture and social policy, three different social acquaintance networks (kinship-priority acquaintance network, independence-priority acquaintance network, and hybrid acquaintance network) incorporating heredity proportion ph and variation proportion pv are proposed in this paper. Numerical experiments are conducted to investigate network topology and different phenomena during opinion evolution, using the Deffuant model. We found that in kinship-priority acquaintance networks, similar to the Chinese traditional acquaintance networks, opinions always achieve fragmentation, resulting in the formation of multiple large clusters and many small clusters due to the fact that individuals believe more in their relatives and live in a relatively closed environment. In independence-priority acquaintance networks, similar to Western acquaintance networks, the results are similar to those in the kinship-priority acquaintance network. In hybrid acquaintance networks, similar to the Chinese modern acquaintance networks, only a few clusters are formed indicating that in modern China, opinions are more likely to reach consensus on a large scale. These results are similar to the opinion evolution phenomena in modern society, proving the rationality and applicability of network models combined with social culture and policy. We also found a threshold curve pv+2 ph=2.05 in the results for the final opinion clusters and evolution time. Above the threshold curve, opinions could easily reach consensus. Based on the above experimental results, a culture-policy-driven mechanism for the opinion dynamic is worth promoting in this paper, that is, opinion dynamics can be driven by different social cultures and policies through the influence of heredity and variation in interpersonal relationship networks. This

The Identification of Teacher Opinion Leaders: An Element in a Change Strategy for Agricultural Education.

ERIC Educational Resources Information Center

Johnson, Cecil Heyward

To gain some insight and understanding of the opinion leadership phenomenon as an element of a change strategy for agricultural education, a means of identifying and investigating the personal and social characteristics of teachers identified as opinion leaders was developed. Chi square, "t" test, and Spearman's rank order correlation…

Brazilian doctors' perspective on the second opinion strategy before a C-section.

PubMed

Osis, Maria José Duarte; Cecatti, José Guilherme; de Pádua, Karla Simônia; Faúndes, Anibal

2006-04-01

To describe the opinion of doctors who participated in the Latin American Study on Cesarean section in Brazil regarding the second opinion strategy when faced with the decision of performing a C-section. Seventy-two doctors from the hospitals where the study took place (where the second opinion was routinely sought) and 70 from the control group answered a pre-tested self-administered structured questionnaire. Descriptive tables were prepared based on the frequency of relevant variables on opinion of physicians regarding: effectiveness of the application of the second opinion strategy; on whether they would recommend implementation of this strategy and reasons for not recommending it in private institutions; feasibility of the strategy implementation and reasons for not considering this implementation feasible in private institutions. Half of the doctors from the intervention hospitals (50%) and about two thirds of those in the control group (65%) evaluated the second opinion as being or having the potential of being effective/very effective in their institutions. The great majority of those interviewed from both intervention and control hospitals considered this strategy feasible in public (87% and 95% respectively) but not in private hospitals (64% and 70% respectively), mainly because in the latter the doctors would not accept interference from a colleague in their decision-making process. Although the second opinion strategy was perceived as effective in reducing C-section rates, doctors did not regard it feasible outside the public health system in Brazil.

A survey of student opinions on ethical design standards in Taiwan.

PubMed

Lee, Yingying; You, Manlai; Yang, Ming-Ying

2015-04-01

Design ethics has been offered as a course in undergraduate design programs in Taiwan for over a decade, but research on teaching design ethics and the results of teaching these courses is scant. We conducted two tests to examine (1) the effect of an ethics course, and (2) the differences among the effects of design department, gender, and study year on student opinions regarding ethical design standards (EDSs) at the National Yunlin University of Science and Technology (YunTech) in Taiwan. The participants comprised 934 undergraduates (660 women and 274 men) from the five design departments at YunTech's College of Design from Years 1-4. The results confirmed the effect of an ethics course on student EDS opinions. In addition, we observed significant variations among students according to design departments, suggesting that the characteristics of the design departments also affected students' EDS opinions. The results indicated that gender did not significantly affect design students' EDS opinions; however, students in their early years of study produced higher scores than those in their advanced years of study did, based on the six EDS opinions. The implications of these results for teaching design ethics and future research are discussed in this paper.

Opinion Summarizationof CustomerComments

NASA Astrophysics Data System (ADS)

Fan, Miao; Wu, Guoshi

Web 2.0 technologies have enabled more and more customers to freely comment on different kinds of entities, such as sellers, products and services. The large scale of information poses the need and challenge of automatic summarization. In many cases, each of the user-generated short comments implies the opinions which rate the target entity. In this paper, we aim to mine and to summarize all the customer comments of a product. The algorithm proposed in this researchis more reliable on opinion identification because it is unsupervised and the accuracy of the result improves as the number of comments increases. Our research is performed in four steps: (1) mining the frequent aspects of a product that have been commented on by customers; (2) mining the infrequent aspects of a product which have been commented by customers (3) identifying opinion words in each comment and deciding whether each opinion word is positive, negative or neutral; (4) summarizing the comments. This paper proposes several novel techniques to perform these tasks. Our experimental results using comments of a number of products sold online demonstrate the effectiveness of the techniques.

The impact of competing zealots on opinion dynamics

NASA Astrophysics Data System (ADS)

Verma, Gunjan; Swami, Ananthram; Chan, Kevin

2014-02-01

An individual’s opinion on an issue is greatly impacted by others in his or her social network. Most people are open-minded and ready to change their opinion when presented evidence; however, some are zealots or inflexibles, that is, individuals who refuse to change their opinion while staunchly advocating an opinion in hopes of convincing others. Zealotry is present in opinions of significant personal investment, such as political, religious or corporate affiliation; it tends to be less commonplace in opinions involving rumors or fashion trends. In this paper, we examine the effect that zealots have in a population whose opinion dynamics obey the naming game model. We present numerical and analytical results about the number and nature of steady state solutions, demonstrating the existence of a bifurcation in the space of zealot fractions. Our analysis indicates conditions under which a minority zealot opinion ultimately prevails, and conditions under which neither opinion attains a majority. We also present numerical and simulation analysis of finite populations and on networks with partial connectivity.

Symmetry breaking in the opinion dynamics of a multi-group project organization

NASA Astrophysics Data System (ADS)

Zhu, Zhen-Tao; Zhou, Jing; Li, Ping; Chen, Xing-Guang

2012-10-01

A bounded confidence model of opinion dynamics in multi-group projects is presented in which each group's opinion evolution is driven by two types of forces: (i) the group's cohesive force which tends to restore the opinion back towards the initial status because of its company culture; and (ii) nonlinear coupling forces with other groups which attempt to bring opinions closer due to collaboration willingness. Bifurcation analysis for the case of a two-group project shows a cusp catastrophe phenomenon and three distinctive evolutionary regimes, i.e., a deadlock regime, a convergence regime, and a bifurcation regime in opinion dynamics. The critical value of initial discord between the two groups is derived to discriminate which regime the opinion evolution belongs to. In the case of a three-group project with a symmetric social network, both bifurcation analysis and simulation results demonstrate that if each pair has a high initial discord, instead of symmetrically converging to consensus with the increase of coupling scale as expected by Gabbay's result (Physica A 378 (2007) p. 125 Fig. 5), project organization (PO) may be split into two distinct clusters because of the symmetry breaking phenomenon caused by pitchfork bifurcations, which urges that apart from divergence in participants' interests, nonlinear interaction can also make conflict inevitable in the PO. The effects of two asymmetric level parameters are tested in order to explore the ways of inducing dominant opinion in the whole PO. It is found that the strong influence imposed by a leader group with firm faith on the flexible and open minded follower groups can promote the formation of a positive dominant opinion in the PO.

Phase transitions in Nowak Sznajd opinion dynamics

NASA Astrophysics Data System (ADS)

Wołoszyn, Maciej; Stauffer, Dietrich; Kułakowski, Krzysztof

2007-05-01

The Nowak modification of the Sznajd opinion dynamics model on the square lattice assumes that with probability β the opinions flip due to mass-media advertising from down to up, and vice versa. Besides, with probability α the Sznajd rule applies that a neighbour pair agreeing in its two opinions convinces all its six neighbours of that opinion. Our Monte Carlo simulations and mean-field theory find sharp phase transitions in the parameter space.

A Self-Categorization Explanation for Opinion Consensus Perceptions

ERIC Educational Resources Information Center

Zhang, Jinguang; Reid, Scott A.

2013-01-01

The public expression of opinions (and related communicative activities) hinges upon the perception of opinion consensus. Current explanations for opinion consensus perceptions typically focus on egocentric and other biases, rather than functional cognitions. Using self-categorization theory we showed that opinion consensus perceptions flow from…

Nonconsensus opinion model on directed networks

NASA Astrophysics Data System (ADS)

Qu, Bo; Li, Qian; Havlin, Shlomo; Stanley, H. Eugene; Wang, Huijuan

2014-11-01

Dynamic social opinion models have been widely studied on undirected networks, and most of them are based on spin interaction models that produce a consensus. In reality, however, many networks such as Twitter and the World Wide Web are directed and are composed of both unidirectional and bidirectional links. Moreover, from choosing a coffee brand to deciding who to vote for in an election, two or more competing opinions often coexist. In response to this ubiquity of directed networks and the coexistence of two or more opinions in decision-making situations, we study a nonconsensus opinion model introduced by Shao et al. [Phys. Rev. Lett. 103, 018701 (2009), 10.1103/PhysRevLett.103.018701] on directed networks. We define directionality ξ as the percentage of unidirectional links in a network, and we use the linear correlation coefficient ρ between the in-degree and out-degree of a node to quantify the relation between the in-degree and out-degree. We introduce two degree-preserving rewiring approaches which allow us to construct directed networks that can have a broad range of possible combinations of directionality ξ and linear correlation coefficient ρ and to study how ξ and ρ impact opinion competitions. We find that, as the directionality ξ or the in-degree and out-degree correlation ρ increases, the majority opinion becomes more dominant and the minority opinion's ability to survive is lowered.

Evaluation of 12 strategies for obtaining second opinions to improve interpretation of breast histopathology: simulation study

PubMed Central

Tosteson, Anna NA; Pepe, Margaret S; Longton, Gary M; Nelson, Heidi D; Geller, Berta; Carney, Patricia A; Onega, Tracy; Allison, Kimberly H; Jackson, Sara L; Weaver, Donald L

2016-01-01

Objective To evaluate the potential effect of second opinions on improving the accuracy of diagnostic interpretation of breast histopathology. Design Simulation study. Setting 12 different strategies for acquiring independent second opinions. Participants Interpretations of 240 breast biopsy specimens by 115 pathologists, one slide for each case, compared with reference diagnoses derived by expert consensus. Main outcome measures Misclassification rates for individual pathologists and for 12 simulated strategies for second opinions. Simulations compared accuracy of diagnoses from single pathologists with that of diagnoses based on pairing interpretations from first and second independent pathologists, where resolution of disagreements was by an independent third pathologist. 12 strategies were evaluated in which acquisition of second opinions depended on initial diagnoses, assessment of case difficulty or borderline characteristics, pathologists’ clinical volumes, or whether a second opinion was required by policy or desired by the pathologists. The 240 cases included benign without atypia (10% non-proliferative, 20% proliferative without atypia), atypia (30%), ductal carcinoma in situ (DCIS, 30%), and invasive cancer (10%). Overall misclassification rates and agreement statistics depended on the composition of the test set, which included a higher prevalence of difficult cases than in typical practice. Results Misclassification rates significantly decreased (P<0.001) with all second opinion strategies except for the strategy limiting second opinions only to cases of invasive cancer. The overall misclassification rate decreased from 24.7% to 18.1% when all cases received second opinions (P<0.001). Obtaining both first and second opinions from pathologists with a high volume (≥10 breast biopsy specimens weekly) resulted in the lowest misclassification rate in this test set (14.3%, 95% confidence interval 10.9% to 18.0%). Obtaining second opinions only for

38 CFR 14.507 - Opinions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... involving veterans' benefits under laws administered by the Department of Veterans Affairs shall be... been a material change in controlling statute or regulation, a superseding written legal opinion by the... in the Office of the General Counsel. Written legal opinions involving veterans' benefits under laws...

Anisotropic opinion dynamics

NASA Astrophysics Data System (ADS)

Neirotti, Juan

2016-07-01

We consider the process of opinion formation in a society of interacting agents, where there is a set B of socially accepted rules. In this scenario, we observed that agents, represented by simple feed-forward, adaptive neural networks, may have a conservative attitude (mostly in agreement with B ) or liberal attitude (mostly in agreement with neighboring agents) depending on how much their opinions are influenced by their peers. The topology of the network representing the interaction of the society's members is determined by a graph, where the agents' properties are defined over the vertexes and the interagent interactions are defined over the bonds. The adaptability of the agents allows us to model the formation of opinions as an online learning process, where agents learn continuously as new information becomes available to the whole society (online learning). Through the application of statistical mechanics techniques we deduced a set of differential equations describing the dynamics of the system. We observed that by slowly varying the average peer influence in such a way that the agents attitude changes from conservative to liberal and back, the average social opinion develops a hysteresis cycle. Such hysteretic behavior disappears when the variance of the social influence distribution is large enough. In all the cases studied, the change from conservative to liberal behavior is characterized by the emergence of conservative clusters, i.e., a closed knitted set of society members that follow a leader who agrees with the social status quo when the rule B is challenged.

Opinion evolution in different social acquaintance networks.

PubMed

Chen, Xi; Zhang, Xiao; Wu, Zhan; Wang, Hongwei; Wang, Guohua; Li, Wei

2017-11-01

Social acquaintance networks influenced by social culture and social policy have a great impact on public opinion evolution in daily life. Based on the differences between socio-culture and social policy, three different social acquaintance networks (kinship-priority acquaintance network, independence-priority acquaintance network, and hybrid acquaintance network) incorporating heredity proportion p h and variation proportion p v are proposed in this paper. Numerical experiments are conducted to investigate network topology and different phenomena during opinion evolution, using the Deffuant model. We found that in kinship-priority acquaintance networks, similar to the Chinese traditional acquaintance networks, opinions always achieve fragmentation, resulting in the formation of multiple large clusters and many small clusters due to the fact that individuals believe more in their relatives and live in a relatively closed environment. In independence-priority acquaintance networks, similar to Western acquaintance networks, the results are similar to those in the kinship-priority acquaintance network. In hybrid acquaintance networks, similar to the Chinese modern acquaintance networks, only a few clusters are formed indicating that in modern China, opinions are more likely to reach consensus on a large scale. These results are similar to the opinion evolution phenomena in modern society, proving the rationality and applicability of network models combined with social culture and policy. We also found a threshold curve p v +2p h =2.05 in the results for the final opinion clusters and evolution time. Above the threshold curve, opinions could easily reach consensus. Based on the above experimental results, a culture-policy-driven mechanism for the opinion dynamic is worth promoting in this paper, that is, opinion dynamics can be driven by different social cultures and policies through the influence of heredity and variation in interpersonal relationship networks. This

Opinion Dynamics with Disagreement and Modulated Information

NASA Astrophysics Data System (ADS)

Sîrbu, Alina; Loreto, Vittorio; Servedio, Vito D. P.; Tria, Francesca

2013-04-01

Opinion dynamics concerns social processes through which populations or groups of individuals agree or disagree on specific issues. As such, modelling opinion dynamics represents an important research area that has been progressively acquiring relevance in many different domains. Existing approaches have mostly represented opinions through discrete binary or continuous variables by exploring a whole panoply of cases: e.g. independence, noise, external effects, multiple issues. In most of these cases the crucial ingredient is an attractive dynamics through which similar or similar enough agents get closer. Only rarely the possibility of explicit disagreement has been taken into account (i.e., the possibility for a repulsive interaction among individuals' opinions), and mostly for discrete or 1-dimensional opinions, through the introduction of additional model parameters. Here we introduce a new model of opinion formation, which focuses on the interplay between the possibility of explicit disagreement, modulated in a self-consistent way by the existing opinions' overlaps between the interacting individuals, and the effect of external information on the system. Opinions are modelled as a vector of continuous variables related to multiple possible choices for an issue. Information can be modulated to account for promoting multiple possible choices. Numerical results show that extreme information results in segregation and has a limited effect on the population, while milder messages have better success and a cohesion effect. Additionally, the initial condition plays an important role, with the population forming one or multiple clusters based on the initial average similarity between individuals, with a transition point depending on the number of opinion choices.

Identifying opinion leaders to promote behavior change.

PubMed

Valente, Thomas W; Pumpuang, Patchareeya

2007-12-01

This article reviews 10 techniques used to identify opinion leaders to promote behavior change. Opinion leaders can act as gatekeepers for interventions, help change social norms, and accelerate behavior change. Few studies document the manner in which opinion leaders are identified, recruited, and trained to promote health. The authors categorize close to 200 studies that have studied or used opinion leaders to promote behavior change into 10 different methods. They present the advantages and disadvantages of the 10 opinion leader identification methods and provide sample instruments for each. Factors that might influence programs to select one or another method are then discussed, and the article closes with a discussion of combining and comparing methods.

How Public Opinion is Formed

ERIC Educational Resources Information Center

Block, Edward M.

1977-01-01

Investigates the evolution of the definition of public relations by examining cultural and personal determinants of public opinion. Outlines functions of communicators and opinionmakers in forming and influencing public opinion. Available from: Public Relations Review, Ray Hiebert, Dean, College of Journalism, University of Maryland, College Park,…

The Sensitivity and Specificity of Loop-Mediated Isothermal Amplification (LAMP) Assay for Tuberculosis Diagnosis in Adults with Chronic Cough in Malawi.

PubMed

Nliwasa, Marriott; MacPherson, Peter; Chisala, Palesa; Kamdolozi, Mercy; Khundi, McEwen; Kaswaswa, Kruger; Mwapasa, Mphatso; Msefula, Chisomo; Sohn, Hojoon; Flach, Clare; Corbett, Elizabeth L

2016-01-01

Current tuberculosis diagnostics lack sensitivity, and are expensive. Highly accurate, rapid and cheaper diagnostic tests are required for point of care use in low resource settings with high HIV prevalence. To investigate the sensitivity and specificity, and cost of loop-mediated isothermal amplification (LAMP) assay for tuberculosis diagnosis in adults with chronic cough compared to Xpert® MTB/RIF, fluorescence smear microscopy. Between October 2013 and March 2014, consecutive adults at a primary care clinic were screened for cough, offered HIV testing and assessed for tuberculosis using LAMP, Xpert® MTB/RIF and fluorescence smear microscopy. Sensitivity and specificity (with culture as reference standard), and costs were estimated. Of 273 adults recruited, 44.3% (121/273) were HIV-positive and 19.4% (53/273) had bacteriogically confirmed tuberculosis. The sensitivity of LAMP compared to culture was 65.0% (95% CI: 48.3% to 79.4%) with 100% (95% CI: 98.0% to 100%) specificity. The sensitivity of Xpert® MTB/RIF (77.5%, 95% CI: 61.5% to 89.2%) was similar to that of LAMP, p = 0.132. The sensitivity of concentrated fluorescence smear microscopy with routine double reading (87.5%, 95% CI: 73.2% to 95.8%) was higher than that of LAMP, p = 0.020. All three tests had high specificity. The lowest cost per test of LAMP was at batch size of 14 samples (US$ 9.98); this was lower than Xpert® MTB/RIF (US$ 13.38) but higher than fluorescence smear microscopy (US$ 0.65). The sensitivity of LAMP was similar to Xpert® MTB/RIF but lower than fluorescence smear microscopy; all three tests had high specificity. These findings support the Malawi policy that recommends a combination of fluorescence smear microscopy and Xpert® MTB/RIF prioritised for people living with HIV, already found to be smear-negative, or being considered for retreatment of tuberculosis.

The Sensitivity and Specificity of Loop-Mediated Isothermal Amplification (LAMP) Assay for Tuberculosis Diagnosis in Adults with Chronic Cough in Malawi

PubMed Central

Nliwasa, Marriott; MacPherson, Peter; Chisala, Palesa; Kamdolozi, Mercy; Khundi, McEwen; Kaswaswa, Kruger; Mwapasa, Mphatso; Msefula, Chisomo; Sohn, Hojoon; Flach, Clare; Corbett, Elizabeth L.

2016-01-01

Background Current tuberculosis diagnostics lack sensitivity, and are expensive. Highly accurate, rapid and cheaper diagnostic tests are required for point of care use in low resource settings with high HIV prevalence. Objective To investigate the sensitivity and specificity, and cost of loop-mediated isothermal amplification (LAMP) assay for tuberculosis diagnosis in adults with chronic cough compared to Xpert® MTB/RIF, fluorescence smear microscopy. Methods Between October 2013 and March 2014, consecutive adults at a primary care clinic were screened for cough, offered HIV testing and assessed for tuberculosis using LAMP, Xpert® MTB/RIF and fluorescence smear microscopy. Sensitivity and specificity (with culture as reference standard), and costs were estimated. Results Of 273 adults recruited, 44.3% (121/273) were HIV-positive and 19.4% (53/273) had bacteriogically confirmed tuberculosis. The sensitivity of LAMP compared to culture was 65.0% (95% CI: 48.3% to 79.4%) with 100% (95% CI: 98.0% to 100%) specificity. The sensitivity of Xpert® MTB/RIF (77.5%, 95% CI: 61.5% to 89.2%) was similar to that of LAMP, p = 0.132. The sensitivity of concentrated fluorescence smear microscopy with routine double reading (87.5%, 95% CI: 73.2% to 95.8%) was higher than that of LAMP, p = 0.020. All three tests had high specificity. The lowest cost per test of LAMP was at batch size of 14 samples (US$ 9.98); this was lower than Xpert® MTB/RIF (US$ 13.38) but higher than fluorescence smear microscopy (US$ 0.65). Conclusion The sensitivity of LAMP was similar to Xpert® MTB/RIF but lower than fluorescence smear microscopy; all three tests had high specificity. These findings support the Malawi policy that recommends a combination of fluorescence smear microscopy and Xpert® MTB/RIF prioritised for people living with HIV, already found to be smear-negative, or being considered for retreatment of tuberculosis. PMID:27171380

Students' Opinions about Ubiquitous Delivery of Standardized English Exams

ERIC Educational Resources Information Center

Litzler Jerman, Mary Frances; Garcia Laborda, Jesus

2016-01-01

This paper discusses the results of a study conducted with 218 students in the final year of high school to determine their opinions about the feasibility of using a tablet PC for delivery of a standardized English language test. One such test could be the English paper of the exam given to students upon completion of the Baccalaureate program in…

28 CFR 80.11 - Effect of FCPA Opinion.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Effect of FCPA Opinion. 80.11 Section 80.11 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) FOREIGN CORRUPT PRACTICES ACT OPINION PROCEDURE § 80.11 Effect of FCPA Opinion. Except as specified in § 80.10, an FCPA Opinion will not bind or...

28 CFR 80.8 - Attorney General opinion.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Attorney General opinion. 80.8 Section 80.8 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) FOREIGN CORRUPT PRACTICES ACT OPINION PROCEDURE § 80.8 Attorney General opinion. The Attorney General or his designee shall, within 30 days after...

Physical examination and laboratory tests in the management of patients with rheumatoid arthritis: development of recommendations for clinical practice based on published evidence and expert opinion.

PubMed

Pham, Thao; Gossec, Laure; Fautrel, Bruno; Combe, Bernard; Flipo, René-Marc; Goupille, Philippe; Le Loët, Xavier; Mariette, Xavier; Puéchal, Xavier; Wendling, Daniel; Schaeverbeke, Thierry; Sibilia, Jean; Sany, Jacques; Dougados, Maxime

2005-05-01

To develop recommendations for the physical and laboratory-test follow-up of patients with rheumatoid arthritis (RA) seen in everyday practice, using evidence from the literature, supplemented with expert opinion when needed. A scientific committee selected 7-10 questions using the Delphi consensus procedure. Evidence-based responses to each question were sought in the literature and were then used by a panel to develop recommendations. To fill in gaps in knowledge from the literature, the panelists relied on their personal opinion. The seven questions dealt with the physical and laboratory-test follow-up of RA and the factors predicting disease severity. The literature review identified 799 articles whose title and abstract suggested relevance to the study. Elimination of articles that provided no data on the study topic left 128 original articles. The panel developed seven recommendations, one for each question, which were accepted by consensus. Recommendations about the physical and laboratory-test follow-up of patients with RA seen in everyday practice were developed. Because they constitute an objective foundation built by consensus among experts, should improve the uniformity and quality of care provided to RA patients in everyday practice.

Identifying Opinion Leaders to Promote Behavior Change

ERIC Educational Resources Information Center

Valente, Thomas W.; Pumpuang, Patchareeya

2007-01-01

This article reviews 10 techniques used to identify opinion leaders to promote behavior change. Opinion leaders can act as gatekeepers for interventions, help change social norms, and accelerate behavior change. Few studies document the manner in which opinion leaders are identified, recruited, and trained to promote health. The authors categorize…

[First results of a German second opinion program show high patient satisfaction and large discrepancies between initial therapy recommendations and second opinion].

PubMed

Weyerstraß, Jan; Prediger, Barbara; Neugebauer, Edmund; Pieper, Dawid

2018-02-23

Although legally anchored, there are no empirical results from German second opinion programs. In this study, various aspects within a population of a second opinion program are examined. In this study patients were analyzed who sought a second opinion in the period from August 2011 to December 2016. Differences in patient characteristics, differentiated by agreement of first and second opinion, were analyzed using multivariate logistic regression. Patients' satisfaction and quality of life were examined one, three and six months after obtaining the second opinion. In total, 1,414 patients sought a second opinion. Most frequent medical indications were the knee (38.7 %), the back (26.8 %), the hip (11.7 %), and the shoulder (10.2 %). Except for the indication (p=0.035), no patient characteristic had influence on the conformation of the second opinion. Approximately two out of three initial recommendations were not confirmed by the specialists. 89 % of the patients were satisfied or very satisfied with the second opinion and the service offered. The second opinion offers patients the opportunity to seek an additional independent medical opinion and thus provide support for decision making. Further research is needed to examine the reasons for the high discrepancies between the first and second opinions. Copyright © 2018. Published by Elsevier GmbH.

Opinion dynamics in a group-based society

NASA Astrophysics Data System (ADS)

Gargiulo, F.; Huet, S.

2010-09-01

Many models have been proposed to analyze the evolution of opinion structure due to the interaction of individuals in their social environment. Such models analyze the spreading of ideas both in completely interacting backgrounds and on social networks, where each person has a finite set of interlocutors. In this paper we analyze the reciprocal feedback between the opinions of the individuals and the structure of the interpersonal relationships at the level of community structures. For this purpose we define a group-based random network and we study how this structure co-evolves with opinion dynamics processes. We observe that the adaptive network structure affects the opinion dynamics process helping the consensus formation. The results also show interesting behaviors in regards to the size distribution of the groups and their correlation with opinion structure.

Applications of flow-networks to opinion-dynamics

NASA Astrophysics Data System (ADS)

Tupikina, Liubov; Kurths, Jürgen

2015-04-01

Networks were successfully applied to describe complex systems, such as brain, climate, processes in society. Recently a socio-physical problem of opinion-dynamics was studied using network techniques. We present the toy-model of opinion-formation based on the physical model of advection-diffusion. We consider spreading of the opinion on the fixed subject, assuming that opinion on society is binary: if person has opinion then the state of the node in the society-network equals 1, if the person doesn't have opinion state of the node equals 0. Opinion can be spread from one person to another if they know each other, or in the network-terminology, if the nodes are connected. We include into the system governed by advection-diffusion equation the external field to model such effects as for instance influence from media. The assumptions for our model can be formulated as the following: 1.the node-states are influenced by the network structure in such a way, that opinion can be spread only between adjacent nodes (the advective term of the opinion-dynamics), 2.the network evolution can have two scenarios: -network topology is not changing with time; -additional links can appear or disappear each time-step with fixed probability which requires adaptive networks properties. Considering these assumptions for our system we obtain the system of equations describing our model-dynamics which corresponds well to other socio-physics models, for instance, the model of the social cohesion and the famous voter-model. We investigate the behavior of the suggested model studying "waiting time" of the system, time to get to the stable state, stability of the model regimes for different values of model parameters and network topology.

Evaluation of 12 strategies for obtaining second opinions to improve interpretation of breast histopathology: simulation study.

PubMed

Elmore, Joann G; Tosteson, Anna Na; Pepe, Margaret S; Longton, Gary M; Nelson, Heidi D; Geller, Berta; Carney, Patricia A; Onega, Tracy; Allison, Kimberly H; Jackson, Sara L; Weaver, Donald L

2016-06-22

 To evaluate the potential effect of second opinions on improving the accuracy of diagnostic interpretation of breast histopathology.  Simulation study.  12 different strategies for acquiring independent second opinions.  Interpretations of 240 breast biopsy specimens by 115 pathologists, one slide for each case, compared with reference diagnoses derived by expert consensus.  Misclassification rates for individual pathologists and for 12 simulated strategies for second opinions. Simulations compared accuracy of diagnoses from single pathologists with that of diagnoses based on pairing interpretations from first and second independent pathologists, where resolution of disagreements was by an independent third pathologist. 12 strategies were evaluated in which acquisition of second opinions depended on initial diagnoses, assessment of case difficulty or borderline characteristics, pathologists' clinical volumes, or whether a second opinion was required by policy or desired by the pathologists. The 240 cases included benign without atypia (10% non-proliferative, 20% proliferative without atypia), atypia (30%), ductal carcinoma in situ (DCIS, 30%), and invasive cancer (10%). Overall misclassification rates and agreement statistics depended on the composition of the test set, which included a higher prevalence of difficult cases than in typical practice.  Misclassification rates significantly decreased (P<0.001) with all second opinion strategies except for the strategy limiting second opinions only to cases of invasive cancer. The overall misclassification rate decreased from 24.7% to 18.1% when all cases received second opinions (P<0.001). Obtaining both first and second opinions from pathologists with a high volume (≥10 breast biopsy specimens weekly) resulted in the lowest misclassification rate in this test set (14.3%, 95% confidence interval 10.9% to 18.0%). Obtaining second opinions only for cases with initial interpretations of atypia, DCIS, or invasive

Use of Ancillary Carbapenemase Tests To Improve Specificity of Phenotypic Definitions for Carbapenemase-Producing Enterobacteriaceae.

PubMed

Miller, Shelley A; Hindler, Janet A; Chengcuenca, Angelo; Humphries, Romney M

2017-06-01

Carbapenemase-producing Enterobacteriaceae (CPE) are a significant threat to public health. In 2015, CDC revised the surveillance definition for CPE to include all Enterobacteriaceae resistant to any carbapenem tested. However, this definition is associated with poor specificity. We evaluated the performance of this definition, compared to carbapenemase PCR, for a collection of 125 Enterobacteriaceae We also investigated the impact of ancillary testing for carbapenemase of isolates that met the CDC CPE surveillance definition. The two ancillary tests evaluated were the Xpert Carba-R assay, a molecular test, and the carbapenem inactivation method (CIM). Two variables were evaluated for the CIM: suspension of organisms in double-distilled water (ddH 2 O) versus tryptic soy broth (TSB) to incubate disks, and incubation of plates for 6 h versus 18 to 20 h. The sensitivity and specificity of the Carba-R assay were 100% compared to the results of in-house PCR. The sensitivities of the CIM performed with TSB were 94.6% when read at 6 h and 97.7% when read at 18 to 20 h; the sensitivities with ddH 2 O were 88.0% when read at 6 h and 93.0% when incubated for 18 to 20 h. The specificity was 100% for all variables tested. Without ancillary testing, the sensitivity of the CDC definition was 98.9% for CPE, and the specificity was 6.1%. Testing isolates that screened positive by the CDC definition with the Xpert Carba-R did not change the sensitivity, and it improved the specificity to 100%. Similarly, the use of the CIM (TSB and 18 to 20 h of incubation) to confirm screen-positive isolates resulted in a sensitivity of 95.6% and specificity of 100%. Copyright © 2017 American Society for Microbiology.

Discrepancy and Disliking Do Not Induce Negative Opinion Shifts

PubMed Central

Flache, Andreas; Mäs, Michael

2016-01-01

Both classical social psychological theories and recent formal models of opinion differentiation and bi-polarization assign a prominent role to negative social influence. Negative influence is defined as shifts away from the opinion of others and hypothesized to be induced by discrepancy with or disliking of the source of influence. There is strong empirical support for the presence of positive social influence (a shift towards the opinion of others), but evidence that large opinion differences or disliking could trigger negative shifts is mixed. We examine positive and negative influence with controlled exposure to opinions of other individuals in one experiment and with opinion exchange in another study. Results confirm that similarities induce attraction, but results do not support that discrepancy or disliking entails negative influence. Instead, our findings suggest a robust positive linear relationship between opinion distance and opinion shifts. PMID:27333160

17 CFR 200.63 - Commission opinions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... AND ETHICS; AND INFORMATION AND REQUESTS Canons of Ethics § 200.63 Commission opinions. The opinions... guided in his decisions by a deep regard for the integrity of the system of law which he administers. He...

Practical problems in aggregating expert opinions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Booker, J.M.; Picard, R.R.; Meyer, M.A.

1993-11-01

Expert opinion is data given by a qualified person in response to a technical question. In these analyses, expert opinion provides information where other data are either sparse or non-existent. Improvements in forecasting result from the advantageous addition of expert opinion to observed data in many areas, such as meteorology and econometrics. More generally, analyses of large, complex systems often involve experts on various components of the system supplying input to a decision process; applications include such wide-ranging areas as nuclear reactor safety, management science, and seismology. For large or complex applications, no single expert may be knowledgeable enough aboutmore » the entire application. In other problems, decision makers may find it comforting that a consensus or aggregation of opinions is usually better than a single opinion. Many risk and reliability studies require a single estimate for modeling, analysis, reporting, and decision making purposes. For problems with large uncertainties, the strategy of combining as diverse a set of experts as possible hedges against underestimation of that uncertainty. Decision makers are frequently faced with the task of selecting the experts and combining their opinions. However, the aggregation is often the responsibility of an analyst. Whether the decision maker or the analyst does the aggregation, the input for it, such as providing weights for experts or estimating other parameters, is imperfect owing to a lack of omniscience. Aggregation methods for expert opinions have existed for over thirty years; yet many of the difficulties with their use remain unresolved. The bulk of these problem areas are summarized in the sections that follow: sensitivities of results to assumptions, weights for experts, correlation of experts, and handling uncertainties. The purpose of this paper is to discuss the sources of these problems and describe their effects on aggregation.« less

32 CFR 1698.2 - Requests for advisory opinions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... ADVISORY OPINIONS § 1698.2 Requests for advisory opinions. (a) Any male born after December 31, 1959 who... advisory opinion as to the liability of any male person born after December 31, 1959 who has attained 18...

32 CFR 1698.2 - Requests for advisory opinions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... ADVISORY OPINIONS § 1698.2 Requests for advisory opinions. (a) Any male born after December 31, 1959 who... advisory opinion as to the liability of any male person born after December 31, 1959 who has attained 18...

Opinion data mining based on DNA method and ORA software

NASA Astrophysics Data System (ADS)

Tian, Ru-Ya; Wu, Lei; Liang, Xiao-He; Zhang, Xue-Fu

2018-01-01

Public opinion, especially the online public opinion is a critical issue when it comes to mining its characteristics. Because it can be formed directly and intensely in a short time, and may lead to the outbreak of online group events, and the formation of online public opinion crisis. This may become the pushing hand of a public crisis event, or even have negative social impacts, which brings great challenges to the government management. Data from the mass media which reveal implicit, previously unknown, and potentially valuable information, can effectively help us to understand the evolution law of public opinion, and provide a useful reference for rumor intervention. Based on the Dynamic Network Analysis method, this paper uses ORA software to mine characteristics of public opinion information, opinion topics, and public opinion agents through a series of indicators, and quantitatively analyzed the relationships between them. The results show that through the analysis of the 8 indexes associating with opinion data mining, we can have a basic understanding of the public opinion characteristics of an opinion event, such as who is important in the opinion spreading process, the information grasping condition, and the opinion topics release situation.

Community Size, Perceptions of Majority Opinion and Opinion Expression.

ERIC Educational Resources Information Center

Salmon, Charles T.; Oshagan, Hayg

A study examined structural determinants of opinion expression by merging two theoretical perspectives: the "spiral of silence" model advanced by Elisabeth Noelle-Neumann, and the structural approach to communication research offered by Phillip Tichenor, George Donohue, and Clarice Olien. The study also distinguished between different…

2001 traffic safety issues opinion survey.

DOT National Transportation Integrated Search

2002-02-01

As a means of determining public opinion on specific traffic safety issues, a public opinion survey was conducted. A total of 4,500 mail surveys were sent to a stratified sample of drivers selected from the drivers license file. The state was divided...

German second-opinion network for testicular cancer: sealing the leaky pipe between evidence and clinical practice.

PubMed

Zengerling, Friedemann; Hartmann, Michael; Heidenreich, Axel; Krege, Susanne; Albers, Peter; Karl, Alexander; Weissbach, Lothar; Wagner, Walter; Bedke, Jens; Retz, Margitta; Schmelz, Hans U; Kliesch, Sabine; Kuczyk, Markus; Winter, Eva; Pottek, Tobias; Dieckmann, Klaus-Peter; Schrader, Andres Jan; Schrader, Mark

2014-06-01

In 2006, the German Testicular Cancer Study Group initiated an extensive evidence-based national second-opinion network to improve the care of testicular cancer patients. The primary aims were to reflect the current state of testicular cancer treatment in Germany and to analyze the project's effect on the quality of care delivered to testicular cancer patients. A freely available internet-based platform was developed for the exchange of data between the urologists seeking advice and the 31 second-opinion givers. After providing all data relevant to the primary treatment decision, urologists received a second opinion on their therapy plan within <48 h. Endpoints were congruence between the first and second opinion, conformity of applied therapy with the corresponding recommendation and progression-free survival rate of the introduced patients. Significance was determined by two-sided Pearson's χ2 test. A total of 1,284 second-opinion requests were submitted from November 2006 to October 2011, and 926 of these cases were eligible for further analysis. A discrepancy was found between first and second opinion in 39.5% of the cases. Discrepant second opinions led to less extensive treatment in 28.1% and to more extensive treatment in 15.6%. Patients treated within the framework of the second-opinion project had an overall 2-year progression-free survival rate of 90.4%. Approximately every 6th second opinion led to a relevant change in therapy. Despite the lack of financial incentives, data from every 8th testicular cancer patient in Germany were submitted to second-opinion centers. Second-opinion centers can help to improve the implementation of evidence into clinical practice.

Social opinion dynamics is not chaotic

NASA Astrophysics Data System (ADS)

Lim, Chjan; Zhang, Weituo

2016-08-01

Motivated by the research on social opinion dynamics over large and dense networks, a general framework for verifying the monotonicity property of multi-agent dynamics is introduced. This allows a derivation of sociologically meaningful sufficient conditions for monotonicity that are tailor-made for social opinion dynamics, which typically have high nonlinearity. A direct consequence of monotonicity is that social opinion dynamics is nonchaotic. A key part of this framework is the definition of a partial order relation that is suitable for a large class of social opinion dynamics such as the generalized naming games. Comparisons are made to previous techniques to verify monotonicity. Using the results obtained, we extend many of the consequences of monotonicity to this class of social dynamics, including several corollaries on their asymptotic behavior, such as global convergence to consensus and tipping points of a minority fraction of zealots or leaders.

A hybrid model for opinion formation

NASA Astrophysics Data System (ADS)

Borra, Domenica; Lorenzi, Tommaso

2013-06-01

This paper presents a hybrid model for opinion formation in a large group of agents exposed to the persuasive action of a small number of strong opinion leaders. The model is defined by coupling a finite difference equation for the dynamics of leaders opinion with a continuous integro-differential equation for the dynamics of the others. Such a definition stems from the idea that the leaders are few and tend to retain original opinions, so that their dynamics occur on a longer time scale with respect to the one of the other agents. A general well-posedness result is established for the initial value problem linked to the model. The asymptotic behavior in time of the related solution is characterized for some general parameter settings, which mimic distinct social scenarios, where different emerging behaviors can be observed. Analytical results are illustrated and extended through numerical simulations.

U.S. aerospace industry opinion of the effect of computer-aided prediction-design technology on future wind-tunnel test requirements for aircraft development programs

NASA Technical Reports Server (NTRS)

Treon, S. L.

1979-01-01

A survey of the U.S. aerospace industry in late 1977 suggests that there will be an increasing use of computer-aided prediction-design technology (CPD Tech) in the aircraft development process but that, overall, only a modest reduction in wind-tunnel test requirements from the current level is expected in the period through 1995. Opinions were received from key spokesmen in 23 of the 26 solicited major companies or corporate divisions involved in the design and manufacture of nonrotary wing aircraft. Development programs for nine types of aircraft related to test phases and wind-tunnel size and speed range were considered.

Phase Transition in Opinion Diffusion in Social Networks

DTIC Science & Technology

2012-05-01

the opinions of social agents diffuse in a network under a so-called hard-interaction model, in which the agents inter- act more strongly with...gent behavior. Index Terms— opinion diffusion , opinion dynamics, social net- works, phase transition, herding. 1. INTRODUCTION The study of the

Quantitative Agent Based Model of Opinion Dynamics: Polish Elections of 2015

PubMed Central

Sobkowicz, Pawel

2016-01-01

We present results of an abstract, agent based model of opinion dynamics simulations based on the emotion/information/opinion (E/I/O) approach, applied to a strongly polarized society, corresponding to the Polish political scene between 2005 and 2015. Under certain conditions the model leads to metastable coexistence of two subcommunities of comparable size (supporting the corresponding opinions)—which corresponds to the bipartisan split found in Poland. Spurred by the recent breakdown of this political duopoly, which occurred in 2015, we present a model extension that describes both the long term coexistence of the two opposing opinions and a rapid, transitory change due to the appearance of a third party alternative. We provide quantitative comparison of the model with the results of polls and elections in Poland, testing the assumptions related to the modeled processes and the parameters used in the simulations. It is shown, that when the propaganda messages of the two incumbent parties differ in emotional tone, the political status quo may be unstable. The asymmetry of the emotions within the support bases of the two parties allows one of them to be ‘invaded’ by a newcomer third party very quickly, while the second remains immune to such invasion. PMID:27171226

Naive Bayes as opinion classifier to evaluate students satisfaction based on student sentiment in Twitter Social Media

NASA Astrophysics Data System (ADS)

Candra Permana, Fahmi; Rosmansyah, Yusep; Setiawan Abdullah, Atje

2017-10-01

Students activity on social media can provide implicit knowledge and new perspectives for an educational system. Sentiment analysis is a part of text mining that can help to analyze and classify the opinion data. This research uses text mining and naive Bayes method as opinion classifier, to be used as an alternative methods in the process of evaluating studentss satisfaction for educational institution. Based on test results, this system can determine the opinion classification in Bahasa Indonesia using naive Bayes as opinion classifier with accuracy level of 84% correct, and the comparison between the existing system and the proposed system to evaluate students satisfaction in learning process, there is only a difference of 16.49%.

A lexicon based method to search for extreme opinions.

PubMed

Almatarneh, Sattam; Gamallo, Pablo

2018-01-01

Studies in sentiment analysis and opinion mining have been focused on many aspects related to opinions, namely polarity classification by making use of positive, negative or neutral values. However, most studies have overlooked the identification of extreme opinions (most negative and most positive opinions) in spite of their vast significance in many applications. We use an unsupervised approach to search for extreme opinions, which is based on the automatic construction of a new lexicon containing the most negative and most positive words.

Reducing STD/HIV stigmatizing attitudes through community popular opinion leaders in Chinese markets

PubMed Central

Rice, Ronald E.; Wu, Zunyou; Li, Li; Detels, Roger; Rotheram-Borus, Mary Jane

2013-01-01

Reducing STDs and HIV/AIDS incidence requires campaigns designed to change knowledge, attitudes and practices of risky sexual behavior and its consequences. In China, a significant obstacle to such changes is the stigma associated with these diseases. Thus one campaign intervention strategy is to train credible community popular opinion leaders to discuss these issues in everyday social venues. This study tested the effectiveness of such an approach on reducing HIV/AIDS stigma, across two years, from a sample of over 4500 market vendors, in three conditions. Results showed an increasing growth in market communication about intervention messages, and concomitant declines in stigmatizing attitudes, across time, with the greatest changes in community popular opinion leaders, significant changes in intervention non-opinion leaders, and little change in the control markets. PMID:24944433

Reducing STD/HIV stigmatizing attitudes through community popular opinion leaders in Chinese markets.

PubMed

Rice, Ronald E; Wu, Zunyou; Li, Li; Detels, Roger; Rotheram-Borus, Mary Jane

2012-12-01

Reducing STDs and HIV/AIDS incidence requires campaigns designed to change knowledge, attitudes and practices of risky sexual behavior and its consequences. In China, a significant obstacle to such changes is the stigma associated with these diseases. Thus one campaign intervention strategy is to train credible community popular opinion leaders to discuss these issues in everyday social venues. This study tested the effectiveness of such an approach on reducing HIV/AIDS stigma, across two years, from a sample of over 4500 market vendors, in three conditions. Results showed an increasing growth in market communication about intervention messages, and concomitant declines in stigmatizing attitudes, across time, with the greatest changes in community popular opinion leaders, significant changes in intervention non-opinion leaders, and little change in the control markets.

Diagnostic accuracy, incremental yield and prognostic value of Determine TB-LAM for routine diagnostic testing for tuberculosis in HIV-infected patients requiring acute hospital admission in South Africa: a prospective cohort.

PubMed

Lawn, Stephen D; Kerkhoff, Andrew D; Burton, Rosie; Schutz, Charlotte; Boulle, Andrew; Vogt, Monica; Gupta-Wright, Ankur; Nicol, Mark P; Meintjes, Graeme

2017-03-21

We previously reported that one-third of HIV-positive adults requiring medical admission to a South African district hospital had laboratory-confirmed tuberculosis (TB) and that almost two-thirds of cases could be rapidly diagnosed using Xpert MTB/RIF-testing of concentrated urine samples obtained on the first day of admission. Implementation of urine-based, routine, point-of-care TB screening is an attractive intervention that might be facilitated by use of a simple, low-cost diagnostic tool, such as the Determine TB-LAM lateral-flow rapid test for HIV-associated TB. Sputum, urine and blood samples were systematically obtained from unselected HIV-positive adults within 24 hours of admission to a South African township hospital. Additional clinical samples were obtained during hospitalization as clinically indicated. TB was defined by the detection of Mycobacterium tuberculosis in any sample using Xpert MTB/RIF or liquid culture. The diagnostic yield, accuracy and prognostic value of urine-lipoarabinomannan (LAM) testing were determined, but urine-LAM results did not inform treatment decisions. Consecutive HIV-positive adult acute medical admissions not already receiving TB treatment (n = 427) were enrolled regardless of clinical presentation or symptoms. TB was diagnosed in 139 patients (TB prevalence 32.6%; median CD4 count 80 cells/μL). In the first 24 hours of admission, sputum (spot and/or induced) samples were obtained from 37.0% of patients and urine samples from 99.5% of patients (P < 0.001). The diagnostic yields from these specimens were 19.4% (n = 27/139) for sputum-microscopy, 26.6% (n = 37/139) for sputum-Xpert, 38.1% (n = 53/139) for urine-LAM and 52.5% (n = 73/139) for sputum-Xpert/urine-LAM combined (P < 0.01). Corresponding yields among patients with CD4 counts <100 cells/μL were 18.9%, 24.3%, 55.4% and 63.5%, respectively (P < 0.01). The diagnostic yield of urine-LAM was unrelated to respiratory symptoms, and

A lexicon based method to search for extreme opinions

PubMed Central

Gamallo, Pablo

2018-01-01

Studies in sentiment analysis and opinion mining have been focused on many aspects related to opinions, namely polarity classification by making use of positive, negative or neutral values. However, most studies have overlooked the identification of extreme opinions (most negative and most positive opinions) in spite of their vast significance in many applications. We use an unsupervised approach to search for extreme opinions, which is based on the automatic construction of a new lexicon containing the most negative and most positive words. PMID:29799867

Determinants of PCR performance (Xpert MTB/RIF), including bacterial load and inhibition, for TB diagnosis using specimens from different body compartments

PubMed Central

Theron, Grant; Peter, Jonny; Calligaro, Greg; Meldau, Richard; Hanrahan, Colleen; Khalfey, Hoosain; Matinyenya, Brian; Muchinga, Tapuwa; Smith, Liezel; Pandie, Shaheen; Lenders, Laura; Patel, Vinod; Mayosi, Bongani M.; Dheda, Keertan

2014-01-01

The determinants of Xpert MTB/RIF sensitivity, a widely used PCR test for the diagnosis of tuberculosis (TB) are poorly understood. We compared culture time-to-positivity (TTP; a surrogate of bacterial load), MTB/RIF TB-specific and internal positive control (IPC)-specific CT values, and clinical characteristics in patients with suspected TB who provided expectorated (n = 438) or induced sputum (n = 128), tracheal aspirates (n = 71), bronchoalveolar lavage fluid (n = 152), pleural fluid (n = 76), cerebral spinal fluid (CSF; n = 152), pericardial fluid (n = 131), or urine (n = 173) specimens. Median bacterial load (TTP in days) was the strongest associate of MTB/RIF positivity in each fluid. TTP correlated with CT values in pulmonary specimens but not extrapulmonary specimens (Spearman's coefficient 0.5043 versus 0.1437; p = 0.030). Inhibition affected a greater proportion of pulmonary specimens than extrapulmonary specimens (IPC CT > 34: 6% (47/731) versus 1% (4/381; p < 0.0001). Pulmonary specimens had greater load than extrapulmonary specimens [TTPs (interquartile range) of 11 (7–16) versus 22 (18–33.5) days; p < 0.0001]. HIV-infection was associated with a decreased likelihood of MTB/RIF-positivity in pulmonary specimens but an increased likelihood in extrapulmonary specimens. Mycobacterial load, which displays significant variation across different body compartments, is the main determinant of MTB/RIF-positivity rather than PCR inhibition. MTB/RIF CT is a poor surrogate of load in extrapulmonary specimens. PMID:25014250

10 CFR 590.404 - Final opinions and orders.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Final opinions and orders. 590.404 Section 590.404 Energy DEPARTMENT OF ENERGY (CONTINUED) NATURAL GAS (ECONOMIC REGULATORY ADMINISTRATION) ADMINISTRATIVE PROCEDURES WITH RESPECT TO THE IMPORT AND EXPORT OF NATURAL GAS Opinions and Orders § 590.404 Final opinions and...

Environment and Public Opinion in Minnesota.

ERIC Educational Resources Information Center

Tichenor, P. J.; And Others

Surveys conducted in Minnesota in 1969 and 1970 to obtain public opinion regarding environmental issues are discussed. Several generalizations are made about the state of public opinion about the environmental issue, as follows: (1) The environmental issue has reached public prominence through a sequence from professional and interest-group…

Opinion versus evidence for the need to move away from animal testing.

PubMed

Hartung, Thomas

2017-01-01

Science is based on facts and their discourse. Willingly or unwillingly, facts are mixed with opinion, i.e., views or judgments formed, not necessarily based on fact or knowledge. This is often necessary, where we have controversial facts or no definitive evidence yet, because we need to take decisions or have to prioritize. Evidence-based approaches aim at identifying the facts and their quality objectively and transparently; they are now increasingly embraced in toxicology, especially by employing systematic reviews, meta-analyses, quality scoring, risk-of-bias tools, etc. These are core to Evidence-based Toxicology. Such approaches aim at minimizing opinion, the "eminence-based" part of science. Animal experiments are the basis of a lot of our textbook knowledge in the life sciences, have helped to develop desperately needed therapies, and have made this world a safer place. However, they represent only one of the many possible approaches to accomplish all these things. Like all approaches, they come with shortcomings, and their true contribution is often overrated. This article aims to summarize their limitations and challenges beside the ethical and economical concerns (i.e., costs and duration as well as costs following wrong decisions in product development): they include reproducibility, inadequate reporting, statistical under-powering, lack of inter-species predictivity, lack of reflection of human diversity and of real-life exposure. Each and every one of these increasingly discussed aspects of animal experiments can be amended, but this would require enormous additional resources. Together, they prompt a need to engineer a new paradigm to ensure the safety of patients and consumers, new products and therapies.

Continuous Opinion Dynamics Under Bounded Confidence:. a Survey

NASA Astrophysics Data System (ADS)

Lorenz, Jan

Models of continuous opinion dynamics under bounded confidence have been presented independently by Krause and Hegselmann and by Deffuant et al. in 2000. They have raised a fair amount of attention in the communities of social simulation, sociophysics and complexity science. The researchers working on it come from disciplines such as physics, mathematics, computer science, social psychology and philosophy. In these models agents hold continuous opinions which they can gradually adjust if they hear the opinions of others. The idea of bounded confidence is that agents only interact if they are close in opinion to each other. Usually, the models are analyzed with agent-based simulations in a Monte Carlo style, but they can also be reformulated on the agent's density in the opinion space in a master equation style. The contribution of this survey is fourfold. First, it will present the agent-based and density-based modeling frameworks including the cases of multidimensional opinions and heterogeneous bounds of confidence. Second, it will give the bifurcation diagrams of cluster configuration in the homogeneous model with uniformly distributed initial opinions. Third, it will review the several extensions and the evolving phenomena which have been studied so far, and fourth it will state some open questions.

Opinion Dynamics with Heterogeneous Interactions and Information Assimilation

ERIC Educational Resources Information Center

Mir Tabatabaei, Seydeh Anahita

2013-01-01

In any modern society, individuals interact to form opinions on various topics, including economic, political, and social aspects. Opinions evolve as the result of the continuous exchange of information among individuals and of the assimilation of information distributed by media. The impact of individuals' opinions on each other forms a network,…

History, Philosophy, and Public Opinion Research.

ERIC Educational Resources Information Center

Herbst, Susan

1993-01-01

Argues for the importance of the classical tradition (broad, speculative, and historically informed writing and research) in public opinion research. Argues that asking large, normative questions about public opinion processes, trying to build grand theory, and taking history seriously will enrich the field and command the attention of scholars in…

Modelling Influence and Opinion Evolution in Online Collective Behaviour

PubMed Central

Gend, Pascal; Rentfrow, Peter J.; Hendrickx, Julien M.; Blondel, Vincent D.

2016-01-01

Opinion evolution and judgment revision are mediated through social influence. Based on a large crowdsourced in vitro experiment (n = 861), it is shown how a consensus model can be used to predict opinion evolution in online collective behaviour. It is the first time the predictive power of a quantitative model of opinion dynamics is tested against a real dataset. Unlike previous research on the topic, the model was validated on data which did not serve to calibrate it. This avoids to favor more complex models over more simple ones and prevents overfitting. The model is parametrized by the influenceability of each individual, a factor representing to what extent individuals incorporate external judgments. The prediction accuracy depends on prior knowledge on the participants’ past behaviour. Several situations reflecting data availability are compared. When the data is scarce, the data from previous participants is used to predict how a new participant will behave. Judgment revision includes unpredictable variations which limit the potential for prediction. A first measure of unpredictability is proposed. The measure is based on a specific control experiment. More than two thirds of the prediction errors are found to occur due to unpredictability of the human judgment revision process rather than to model imperfection. PMID:27336834

Analysis and application of opinion model with multiple topic interactions.

PubMed

Xiong, Fei; Liu, Yun; Wang, Liang; Wang, Ximeng

2017-08-01

To reveal heterogeneous behaviors of opinion evolution in different scenarios, we propose an opinion model with topic interactions. Individual opinions and topic features are represented by a multidimensional vector. We measure an agent's action towards a specific topic by the product of opinion and topic feature. When pairs of agents interact for a topic, their actions are introduced to opinion updates with bounded confidence. Simulation results show that a transition from a disordered state to a consensus state occurs at a critical point of the tolerance threshold, which depends on the opinion dimension. The critical point increases as the dimension of opinions increases. Multiple topics promote opinion interactions and lead to the formation of macroscopic opinion clusters. In addition, more topics accelerate the evolutionary process and weaken the effect of network topology. We use two sets of large-scale real data to evaluate the model, and the results prove its effectiveness in characterizing a real evolutionary process. Our model achieves high performance in individual action prediction and even outperforms state-of-the-art methods. Meanwhile, our model has much smaller computational complexity. This paper provides a demonstration for possible practical applications of theoretical opinion dynamics.

Opinion formation of free speech on the directed social network

NASA Astrophysics Data System (ADS)

Su, Jiongming; Ma, Hongxu; Liu, Baohong; Li, Qi

2014-12-01

A dynamical model with continuous opinion is proposed to study how the speech order and the topology of directed social network affect the opinion formation of free speech. In the model, agents express their opinions one by one with random order (RO) or probability order (PO), other agents paying attentions to the speaking agent, receive provider's opinion, update their opinions and then express their new opinions in their turns. It is proved that with the same agent j repeats its opinion more, other agents who pay their attentions to j and include j's opinion in their confidence level at initial time, will continue approaching j's opinion. Simulation results reveal that on directed scale-free network: (1) the model for PO forms fewer opinion clusters, larger maximum cluster (MC), smaller standard deviation (SD), and needs less waiting time to reach a middle level of consensus than RO; (2) as the parameter of scale-free degree distribution decreases or the confidence level increases, the results often get better for both speech orders; (3) the differences between PO and RO get smaller as the size of network decreases.

29 CFR 18.610 - Religious beliefs or opinions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 1 2014-07-01 2013-07-01 true Religious beliefs or opinions. 18.610 Section 18.610 Labor... OFFICE OF ADMINISTRATIVE LAW JUDGES Rules of Evidence Witnesses § 18.610 Religious beliefs or opinions. Evidence of the beliefs or opinions of a witness on matters of religion is not admissible for the purpose...

29 CFR 18.610 - Religious beliefs or opinions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true Religious beliefs or opinions. 18.610 Section 18.610 Labor... OFFICE OF ADMINISTRATIVE LAW JUDGES Rules of Evidence Witnesses § 18.610 Religious beliefs or opinions. Evidence of the beliefs or opinions of a witness on matters of religion is not admissible for the purpose...

42 CFR 57.1511 - Opinion of legal counsel.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Opinion of legal counsel. 57.1511 Section 57.1511... Personnel § 57.1511 Opinion of legal counsel. At appropriate stages in the application and approval... memorandum or opinion of legal counsel with respect to the legality of any proposed note issue, the legal...

42 CFR 57.1511 - Opinion of legal counsel.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Opinion of legal counsel. 57.1511 Section 57.1511... Personnel § 57.1511 Opinion of legal counsel. At appropriate stages in the application and approval... memorandum or opinion of legal counsel with respect to the legality of any proposed note issue, the legal...

29 CFR 18.610 - Religious beliefs or opinions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 1 2011-07-01 2011-07-01 false Religious beliefs or opinions. 18.610 Section 18.610 Labor... OFFICE OF ADMINISTRATIVE LAW JUDGES Rules of Evidence Witnesses § 18.610 Religious beliefs or opinions. Evidence of the beliefs or opinions of a witness on matters of religion is not admissible for the purpose...

29 CFR 18.610 - Religious beliefs or opinions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 1 2013-07-01 2013-07-01 false Religious beliefs or opinions. 18.610 Section 18.610 Labor... OFFICE OF ADMINISTRATIVE LAW JUDGES Rules of Evidence Witnesses § 18.610 Religious beliefs or opinions. Evidence of the beliefs or opinions of a witness on matters of religion is not admissible for the purpose...

29 CFR 18.610 - Religious beliefs or opinions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 1 2012-07-01 2012-07-01 false Religious beliefs or opinions. 18.610 Section 18.610 Labor... OFFICE OF ADMINISTRATIVE LAW JUDGES Rules of Evidence Witnesses § 18.610 Religious beliefs or opinions. Evidence of the beliefs or opinions of a witness on matters of religion is not admissible for the purpose...

Rise of an alternative majority against opinion leaders

NASA Astrophysics Data System (ADS)

Tucci, K.; González-Avella, J. C.; Cosenza, M. G.

2016-03-01

We investigate the role of opinion leaders or influentials in the collective behavior of a social system. Opinion leaders are characterized by their unidirectional influence on other agents. We employ a model based on Axelrod's dynamics for cultural interaction among social agents that allows for non-interacting states. We find three collective phases in the space of parameters of the system, given by the fraction of opinion leaders and a quantity representing the number of available states: one ordered phase having the state imposed by the leaders; another nontrivial ordered phase consisting of a majority group in a state orthogonal or alternative to that of the opinion leaders, and a disordered phase, where many small groups coexist. We show that the spontaneous rise of an alternative group in the presence of opinion leaders depends on the existence of a minimum number of long-range connections in the underlying network. This phenomenon challenges the common idea that influentials are fundamental to propagation processes in society, such as the formation of public opinion.

Opinion diversity and community formation in adaptive networks

NASA Astrophysics Data System (ADS)

Yu, Y.; Xiao, G.; Li, G.; Tay, W. P.; Teoh, H. F.

2017-10-01

It is interesting and of significant importance to investigate how network structures co-evolve with opinions. In this article, we show that, a simple model integrating consensus formation, link rewiring, and opinion change allows complex system dynamics to emerge, driving the system into a dynamic equilibrium with the co-existence of diversified opinions. Specifically, similar opinion holders may form into communities yet with no strict community consensus; and rather than being separated into disconnected communities, different communities are connected by a non-trivial proportion of inter-community links. More importantly, we show that the complex dynamics may lead to different numbers of communities at the steady state with a given tolerance between different opinion holders. We construct a framework for theoretically analyzing the co-evolution process. Theoretical analysis and extensive simulation results reveal some useful insights into the complex co-evolution process, including the formation of dynamic equilibrium, the transition between different steady states with different numbers of communities, and the dynamics between opinion distribution and network modularity.

49 CFR 1503.645 - Expert or opinion witnesses.

Code of Federal Regulations, 2010 CFR

2010-10-01

... PROCEDURES Rules of Practice in TSA Civil Penalty Actions § 1503.645 Expert or opinion witnesses. An employee of the agency may not be called as an expert or opinion witness, for any party other than TSA, in any... an expert or opinion witness for TSA in any proceeding governed by this subpart to which the...

[A study of the value of three molecular diagnostic techniques in the diagnosis of tuberculosis].

PubMed

Huang, Fang; Dang, Liyun; Sun, Huiping; Yang, Han; Wu, Xia

2015-09-01

To evaluate the diagnostic value of real-time fluorescent RNA isothermal amplification detection technology (simultaneous amplification and testing, SAT), Mycobacterium nucleic acid detection (PCR-fluorescence probe)method (TB-NTM-PCR) and Xpert MTB/RIF detection in the diagnosis of tuberculosis. A total of 378 sputum specimens from pulmonary tuberculosis patients were collected between April to July 2014 in Xi'an Thoracic Tumor and Tuberculosis Hospital. The specimens were detected by 5 methods at the same time including acid-fast stain, SAT method, TB-NTM-PCR method, TB 960 rapid liquid culture and Xpert MTB/RIF. The sensitivity and specificity of SAT method, TB-NTM-PCR method and Xpert MTB/RIF were calculated according to the results of TB 960 rapid liquid culture and staining. The difference among all the 3 methods was analyzed by Chi-squared test. The positive rate of SAT-TB,TB-NTM-PCR and Xpert MTB/RIF were 37.6% (142/378), 37.8% (143/378) and 53.4% (202/378), respectively. In specimens both positive for acid-fast stain and culture, the positive rate of SAT method was 84.6% (77/91), that of TB-NTM-PCR was 91.2% (83/91), and that of Xpert MTB/RIF was 96.7% (88/91), the difference being significant (P=0.018 2). In specimens negative for acid-fast stain but positive for culture, the positive rate of SAT method was 61.9% (60 /97), that of TB-NTM-PCR was 44.3% (43/97), and that of Xpert MTB/RIF was 80.4% (78/97), the difference being significant (P<0.000 1). In specimens both negative for acid-fast stain and culture, the positive rate of SAT method was 1.6% (3/185), that of TB-NTM-PCR was 6.5% (12/185), and that of Xpert MTB/RIF was 16.8% (31/185), the difference being significant (P=0.018). In specimens positive for acid-fast stain but negative for culture, the number of positive samples of SAT,TB-NTM-PCR and Xpert MTB/RIF were 3 (3/5), 5 (5/5),and 5 (5/5), respectively. With the result of TB 960 rapid liquid culture and staining as the reference, Xpert MTB

Accuracy and impact of Xpert MTB/RIF for the diagnosis of smear-negative or sputum-scarce tuberculosis using bronchoalveolar lavage fluid.

PubMed

Theron, Grant; Peter, Jonny; Meldau, Richard; Khalfey, Hoosain; Gina, Phindile; Matinyena, Brian; Lenders, Laura; Calligaro, Gregory; Allwood, Brian; Symons, Gregory; Govender, Ureshnie; Setshedi, Mashiko; Dheda, Keertan

2013-11-01

The accuracy and impact of new tuberculosis (TB) tests, such as Xpert MTB/RIF, when performed on bronchoalveolar lavage fluid (BALF) obtained from patients with sputum-scarce or smear-negative TB is unclear. South African patients with suspected pulmonary TB (n=160) who were sputum-scarce or smear-negative underwent bronchoscopy. MTB/RIF was performed on uncentrifuged BALF (1 ml) and/or a resuspended pellet of centrifuged BALF (∼10 ml). Time to TB detection and anti-TB treatment initiation were compared between phase one, when MTB/RIF was performed as a research tool, and phase two, when it was used for patient management. 27 of 154 patients with complete data had culture-confirmed TB. Of these, a significantly lower proportion were detected by smear microscopy compared with MTB/RIF (58%, 95% CI 39% to 75% versus 93%, 77% to 98%; p<0.001). Of the 127 patients who were culture negative, 96% (91% to 98%) were MTB/RIF negative. When phase two was compared with phase one, MTB/RIF reduced the median days to TB detection (29 (18-41) to 0 (0-0); p<0.001). However, more patients initiated empirical therapy (absence of a positive test in those commencing treatment) in phase one versus phase two (79% (11/14) versus 28% (10/25); p=0.026). Consequently, there was no detectable difference in the overall proportion of patients initiating treatment (26% (17/67; 17% to 37%) versus 36% (26/73; 26% to 47%); p=0.196) or the days to treatment initiation (10 (1-49) versus 7 (0-21); p=0.330). BALF centrifugation, HIV coinfection and a second MTB/RIF did not result in detectable changes in accuracy. MTB/RIF detected TB cases more accurately and more rapidly than smear microscopy and significantly reduced the rate of empirical treatment.

Accuracy and impact of Xpert MTB/RIF for the diagnosis of smear-negative or sputum-scarce tuberculosis using bronchoalveolar lavage fluid

PubMed Central

Theron, Grant; Peter, Jonny; Meldau, Richard; Khalfey, Hoosain; Gina, Phindile; Matinyena, Brian; Lenders, Laura; Calligaro, Gregory; Allwood, Brian; Symons, Gregory; Govender, Ureshnie; Setshedi, Mashiko; Dheda, Keertan

2017-01-01

Rationale The accuracy and impact of new tuberculosis (TB) tests, such as Xpert MTB/RIF, when performed on bronchoalveolar lavage fluid (BALF) obtained from patients with sputum-scarce or smear-negative TB is unclear. Methods South African patients with suspected pulmonary TB (n=160) who were sputum-scarce or smear-negative underwent bronchoscopy. MTB/RIF was performed on uncentrifuged BALF (1 ml) and/or a resuspended pellet of centrifuged BALF (~10 ml). Time to TB detection and anti-TB treatment initiation were compared between phase one, when MTB/RIF was performed as a research tool, and phase two, when it was used for patient management. Results 27 of 154 patients with complete data had culture-confirmed TB. Of these, a significantly lower proportion were detected by smear microscopy compared with MTB/RIF (58%, 95% CI 39% to 75% versus 93%, 77% to 98%; p<0.001). Of the 127 patients who were culture negative, 96% (91% to 98%) were MTB/RIF negative. When phase two was compared with phase one, MTB/RIF reduced the median days to TB detection (29 (18–41) to 0 (0–0); p<0.001). However, more patients initiated empirical therapy (absence of a positive test in those commencing treatment) in phase one versus phase two (79% (11/14) versus 28% (10/25); p=0.026). Consequently, there was no detectable difference in the overall proportion of patients initiating treatment (26% (17/67; 17% to 37%) versus 36% (26/73; 26% to 47%); p=0.196) or the days to treatment initiation (10 (1–49) versus 7 (0–21); p=0.330). BALF centrifugation, HIV coinfection and a second MTB/RIF did not result in detectable changes in accuracy. Conclusions MTB/RIF detected TB cases more accurately and more rapidly than smear microscopy and significantly reduced the rate of empirical treatment. PMID:23811536

Evaluation of the 'Fitting to Outcomes eXpert' (FOX®) with established cochlear implant users.

PubMed

Buechner, Andreas; Vaerenberg, Bart; Gazibegovic, Dzemal; Brendel, Martina; De Ceulaer, Geert; Govaerts, Paul; Lenarz, Thomas

2015-01-01

To evaluate the possible impact of 'Fitting to Outcomes eXpert (FOX(®))' on cochlear implant (CI) fitting in a clinic with extensive experience of fitting a range of CI systems, as a way to assess whether a software tool such as FOX is able to complement standard clinical procedures. Ten adult post-lingually deafened and unilateral long-term users of the Advanced Bionics(TM) CI system (Clarion CII or HiRes 90K(TM)) underwent speech perception assessment with their current clinical program. One cycle 'iteration' of FOX optimization was performed and the program adjusted accordingly. After a month of using both clinical and FOX programs, a second iteration of FOX optimization was performed. Following this, the assessments were repeated without further acclimatization. FOX prescribed programming modifications in all subjects. Soundfield-aided thresholds were significantly lower for FOX than the clinical program. Group speech scores in noise were not significantly different between the two programs but three individual subjects had improved speech scores with the FOX MAP, two had worse speech scores, and five were the same. FOX provided a standardized approach to fitting based on outcome measures rather than comfort alone. The results indicated that for this group of well-fitted patients, FOX improved outcomes in some individuals. There were significant changes, both better and worse, in individual speech perception scores but median scores remained unchanged. Soundfield-aided thresholds were significantly improved for the FOX group.

"We Don't Want Your Opinion": Knowledge Construction and the Discourse of Opinion in the Equity Classroom

ERIC Educational Resources Information Center

Diangelo, Robin; Sensoy, Ozlem

2009-01-01

As educators who teach courses that examine social power, we often struggle with a specific form of resistance in the equity-oriented classroom: "That's just [the author]'s opinion." This "opinion discourse" emerges when students study scholarship that unsettles dominant knowledge claims and methods or when students are themselves asked to situate…

Public Opinion toward Sexuality Education: Findings among One South Florida County

ERIC Educational Resources Information Center

Howard-Barr, Elissa; Moore, Michele Johnson; Weiss, Josie A.; Jobli, Edessa

2011-01-01

As part of a community plan to implement abstinence-based sexuality education, this study assessed opinions toward sexuality education among residents. Respondents (N = 1,090) were selected by random digit dialing. The survey, adopted from previous national studies, assessed attitudes towards sexuality education. Chi-square tests of significance…

Feasibility of a new model for early detection of patients with multidrug-resistant tuberculosis in a developed setting of eastern China.

PubMed

Liu, Zhengwei; Pan, Aizhen; Wu, BeiBei; Zhou, Lin; He, Haibo; Meng, Qiong; Chen, Songhua; Pang, Yu; Wang, Xiaomeng

2017-10-01

The poor detection rate of multidrug-resistant tuberculosis (MDR-TB) highlights the urgent need to explore new case finding model to improve the detection of MDR-TB in China. The aim of this study was to evaluate the feasibility of a new model that combines molecular diagnostics and sputum transportation for early detection of patients with MDR-TB in Zhejiang. From May 2014 to January 2015, TB suspects were continuously enrolled at six county-level designated TB hospitals in Zhejiang. Each patient gave three sputum samples, which were submitted to laboratory for smear microscopy, solid culture and GeneXpert. The specimens from rifampin (RIF)-resistant cases detected by GeneXpert, and positive cultures were transported from county-level to prefecture-level laboratories for line probe analysis (LPA) and drug susceptibility testing (DST). The performance and interval of MDR-TB detection of the new model were compared with those of conventional model. A total of 3151 sputum specimens were collected from TB suspects. The sensitivity of GeneXpert for detecting culture-positive cases was 92.7% (405/437), and its specificity was 91.3% (2428/2659). Of 16 RIF-resistant cases detected by DST, GeneXpert could correctly identify 15 cases, yielding a sensitivity of 93.8% (15/16). The specificity of GeneXpert for detecting RIF susceptibility was 100.0% (383/383). The average interval to diagnosis of the conventional DST model was 56.5 days, ranging from 43 to 71 days, which was significantly longer than that of GeneXpert plus LPA (22.2 days, P < 0.01). Our data demonstrate that the combination of improved molecular TB tests and sputum transportation could significantly shorten the time required for detection of MDR-TB, which will bring benefits for preventing an epidemic of MDR-TB in this high-prevalence setting. © 2017 John Wiley & Sons Ltd.

Discordance between MTB/RIF and Real-Time Tuberculosis-Specific Polymerase Chain Reaction Assay in Bronchial Washing Specimen and Its Clinical Implications.

PubMed

Jo, Yong Suk; Park, Ju-Hee; Lee, Jung Kyu; Heo, Eun Young; Chung, Hee Soon; Kim, Deog Kyeom

2016-01-01

The prevalence and clinical implications of discordance between Xpert MTB/RIF assays and the AdvanSure TB/NTM real-time polymerase chain reaction (PCR) for bronchial washing specimens have not been studied in pulmonary TB (PTB) patients. The discordant proportion and its clinical impact were evaluated in 320 patients from the bronchoscopy registry whose bronchial washing specimens were tested simultaneously with Xpert MTB/RIF and the TB/NTM PCR assay for three years, and the accuracy of the assays, including the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were studied. The clinical risk factors for discordance and false positivity of assays were also studied. Among 130 patients who were clinically diagnosed with PTB, 64 patients showed positive acid-fast bacilli culture results, 56 patients showed positive results in molecular methods and clinician diagnosed PTB without results of microbiology in 10 patients. The sensitivity, specificity, PPV, and NPV were 80.0%, 98.95%, 98.1%, and 87.9%, respectively, for Xpert MTB/RIF and 81.5%, 92.6%, 88.3%, and 88.0%, respectively, for TB/NTM PCR. The discordant proportion was 16.9% and was higher in culture-negative PTB compared to culture-confirmed PTB (24.3% vs. 9.4%, p = 0.024). However, there were no significant differences in the clinical characteristics, regardless of the discordance. The diagnostic yield increased with an additional assay (7.7% for Xpert MTB/RIF and 9.2% for TB/NTM PCR). False positivity was less common in patients tested with Xpert MTB/RIF (1.05% vs. 7.37%, p = 0.0035). No host-related risk factor for false positivity was identified. The Xpert MTB/RIF and TB/NTM PCR assay in bronchial washing specimens can improve the diagnostic yields for PTB, although there were considerable discordant results without any patient-related risk factors.

The association between money and opinion in academic emergency medicine.

PubMed

Birkhahn, Robert H; Blomkalns, Andra; Klausner, Howard; Nowak, Richard; Raja, Ali S; Summers, Richard; Weber, Jim E; Briggs, William M; Arkun, Alp; Diercks, Deborah

2010-05-01

Financial conflicts of interest have come under increasing scrutiny in medicine, but their impact has not been quantified. Our objective was to use the results of a national survey of academic emergency medicine (EM) faculty to determine if an association between money and personal opinion exists. We conducted a web-based survey of EM faculty. Opinion questions were analyzed with regard to whether the respondent had either 1) received research grant money or 2) received money from industry as a speaker, consultant, or advisor. Responses were unweighted, and tests of differences in proportions were made using Chi-squared tests, with p<0.05 set for significance. We received responses from 430 members; 98 (23%) received research grants from industry, while 145 (34%) reported fee-for-service money. Respondents with research money were more likely to be comfortable accepting gifts (40% vs. 29%) and acting as paid consultants (50% vs. 37%). They had a more favorable attitude with regard to societal interactions with industry and felt that industry-sponsored lectures could be fair and unbiased (52% vs. 29%). Faculty with fee-for-service money mirrored those with research money. They were also more likely to believe that industry-sponsored research produces fair and unbiased results (61% vs. 45%) and less likely to believe that honoraria biased speakers (49% vs. 69%). Accepting money for either service or research identified a distinct population defined by their opinions. Faculty engaged in industry-sponsored research benefitted socially (collaborations), academically (publications), and financially from the relationship.

A mobile phone application for the collection of opinion data for forest planning purposes.

PubMed

Kangas, Annika; Rasinmäki, Jussi; Eyvindson, Kyle; Chambers, Philip

2015-04-01

The last 30 years has seen an increase in environmental, socio-economic, and recreational objectives being considered throughout the forest planning process. In the Finnish context these are considered mainly at the regional level potentially missing out on more local issues and problems. Such local information would be most efficiently collected with a participatory GIS approach. A mobile participatory GIS application called Tienoo was developed as a tool for collecting location-specific opinions of recreational and aesthetical characteristics of forests and forest management. The application also contains information the user can access regarding the practical details of the area, for instance about the recreational infrastructure. The application was tested in Ruunaa National Hiking Area, North Karelia, Eastern Finland. Through this application it is possible to continuously collect geolocated preference information. As a result, the collected opinions have details which can be located in both time and space. This allows for the possibility to monitor the changes in opinions when the stands are treated, and it also allows for easily analyzing the effect of time of year on the opinions. It is also possible to analyze the effect of the spatial location and the forest characteristics on the opinions using GIS analysis.