Dataset Information

A multi-country non-inferiority cluster randomized trial of frontloaded smear microscopy for the diagnosis of pulmonary tuberculosis.

ABSTRACT:

Background

More than 50 million people around the world are investigated for tuberculosis using sputum smear microscopy annually. This process requires repeated visits and patients often drop out.

Methods and findings

This clinical trial of adults with cough ?2 wk duration (in Ethiopia, Nepal, Nigeria, and Yemen) compared the sensitivity/specificity of two sputum samples collected "on the spot" during the first visit plus one sputum sample collected the following morning (spot-spot-morning [SSM]) versus the standard spot-morning-spot (SMS) scheme. Analyses were per protocol analysis (PPA) and intention to treat (ITT). A sub-analysis compared just the first two smears of each scheme, spot-spot and spot-morning. In total, 6,627 patients (3,052 SSM/3,575 SMS) were enrolled; 6,466 had culture and 1,526 were culture-positive. The sensitivity of SSM (ITT, 70.2%, 95% CI 66.5%-73.9%) was non-inferior to the sensitivity of SMS (PPA, 65.9%, 95% CI 62.3%-69.5%). Similarly, the specificity of SSM (ITT, 96.9%, 95% CI 93.2%-99.9%) was non-inferior to the specificity of SMS (ITT, 97.6%, 95% CI 94.0%-99.9%). The sensitivity of spot-spot (ITT, 63.6%, 95% CI 59.7%-67.5%) was also non-inferior to spot-morning (ITT, 64.8%, 95% CI 61.3%-68.3%), as the difference was within the selected -5% non-inferiority limit (difference ITT?=?1.4%, 95% CI -3.7% to 6.6%). Patients screened using the SSM scheme were more likely to provide the first two specimens than patients screened with the SMS scheme (98% versus 94.2%, p<0.01). The PPA and ITT analysis resulted in similar results.

Conclusions

The sensitivity and specificity of SSM are non-inferior to those of SMS, with a higher proportion of patients submitting specimens. The scheme identifies most smear-positive patients on the first day of consultation.

Trial registration

Current Controlled Trials ISRCTN53339491. Please see later in the article for the Editors' Summary.

SUBMITTER: Cuevas LE

PROVIDER: S-EPMC3134460 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A multi-country non-inferiority cluster randomized trial of frontloaded smear microscopy for the diagnosis of pulmonary tuberculosis.

Cuevas Luis Eduardo LE Yassin Mohammed Ahmed MA Al-Sonboli Najla N Lawson Lovett L Arbide Isabel I Al-Aghbari Nasher N Sherchand Jeevan Bahadur JB Al-Absi Amin A Emenyonu Emmanuel Nnamdi EN Merid Yared Y Okobi Mosis Ifenyi MI Onuoha Juliana Olubunmi JO Aschalew Melkamsew M Aseffa Abraham A Harper Greg G de Cuevas Rachel Mary Anderson RM Kremer Kristin K van Soolingen Dick D Nathanson Carl-Michael CM Joly Jean J Faragher Brian B Squire Stephen Bertel SB Ramsay Andrew A

PLoS medicine 20110712 7

<h4>Background</h4>More than 50 million people around the world are investigated for tuberculosis using sputum smear microscopy annually. This process requires repeated visits and patients often drop out.<h4>Methods and findings</h4>This clinical trial of adults with cough ≥2 wk duration (in Ethiopia, Nepal, Nigeria, and Yemen) compared the sensitivity/specificity of two sputum samples collected "on the spot" during the first visit plus one sputum sample collected the following morning (spot-spo ...[more]

PMID: 21765808

Similar Datasets

Project description:BackgroundThe diagnosis of tuberculosis (TB) in resource-limited settings relies on Ziehl-Neelsen (ZN) smear microscopy. LED fluorescence microscopy (LED-FM) has many potential advantages over ZN smear microscopy, but requires evaluation in the field. The aim of this study was to assess the sensitivity/specificity of LED-FM for the diagnosis of pulmonary TB and whether its performance varies with the timing of specimen collection.Methods and findingsAdults with cough ?2 wk were enrolled consecutively in Ethiopia, Nepal, Nigeria, and Yemen. Sputum specimens were examined by ZN smear microscopy and LED-FM and compared with culture as the reference standard. Specimens were collected using a spot-morning-spot (SMS) or spot-spot-morning (SSM) scheme to explore whether the collection of the first two smears at the health care facility (i.e., "on the spot") the first day of consultation followed by a morning sample the next day (SSM) would identify similar numbers of smear-positive patients as smears collected via the SMS scheme (i.e., one on-the-spot-smear the first day, followed by a morning specimen collected at home and a second on-the-spot sample the second day). In total, 529 (21.6%) culture-positive and 1,826 (74.6%) culture-negative patients were enrolled, of which 1,156 (49%) submitted SSM specimens and 1,199 (51%) submitted SMS specimens. Single LED-FM smears had higher sensitivity but lower specificity than single ZN smears. Using two LED-FM or two ZN smears per patient was 72.8% (385/529, 95% CI 68.8%-76.5%) and 65.8% (348/529, 95% CI 61.6%-69.8%) sensitive (p<0.001) and 90.9% (1,660/1,826, 95% CI 89.5%-92.2%) and 98% (1,790/1,826, 95% CI 97.3%-98.6%) specific (p<0.001). Using three LED-FM or three ZN smears per patient was 77% (408/529, 95% CI 73.3%-80.6%) and 70.5% (373/529, 95% CI 66.4%-74.4%, p<0.001) sensitive and 88.1% (95% CI 86.5%-89.6%) and 96.5% (95% CI 96.8%-98.2%, p<0.001) specific. The sensitivity/specificity of ZN smear microscopy and LED-FM did not vary between SMS and SSM.ConclusionsLED-FM had higher sensitivity but, in this study, lower specificity than ZN smear microscopy for diagnosis of pulmonary TB. Performance was independent of the scheme used for collecting specimens. The introduction of LED-FM needs to be accompanied by appropriate training, quality management, and monitoring of performance in the field.Trial registrationCurrent Controlled Trials ISRCTN53339491. Please see later in the article for the Editors' Summary.

Project description:BackgroundAbundant evidence on Xpert MTB/RIF accuracy for diagnosing tuberculosis (TB) and rifampicin resistance has been produced, yet there are few data on the population benefit of its programmatic use. We assessed whether the implementation of Xpert MTB/RIF in routine conditions would (1) increase the notification rate of laboratory-confirmed pulmonary TB to the national notification system and (2) reduce the time to TB treatment initiation (primary endpoints).Methods and findingsWe conducted a stepped-wedge cluster-randomized trial from 4 February to 4 October 2012 in 14 primary care laboratories in two Brazilian cities. Diagnostic specimens were included for 11,705 baseline (smear microscopy) and 12,522 intervention (Xpert MTB/RIF) patients presumed to have TB. Single-sputum-sample Xpert MTB/RIF replaced two-sputum-sample smear microscopy for routine diagnosis of pulmonary TB. In total, 1,137 (9.7%) tests in the baseline arm and 1,777 (14.2%) in the intervention arm were positive (p<0.001), resulting in an increased bacteriologically confirmed notification rate of 59% (95% CI = 31%, 88%). However, the overall notification rate did not increase (15%, 95% CI = -6%, 37%), and we observed no change in the notification rate for those without a test result (-3%, 95% CI = -37%, 30%). Median time to treatment decreased from 11.4 d (interquartile range [IQR] = 8.5-14.5) to 8.1 d (IQR = 5.4-9.3) (p = 0.04), although not among confirmed cases (median 7.5 [IQR = 4.9-10.0] versus 7.3 [IQR = 3.4-9.0], p = 0.51). Prevalence of rifampicin resistance detected by Xpert was 3.3% (95% CI = 2.4%, 4.3%) among new patients and 7.4% (95% CI = 4.3%, 11.7%) among retreatment patients, with a 98% (95% CI = 87%, 99%) positive predictive value compared to phenotypic drug susceptibility testing. Missing data in the information systems may have biased our primary endpoints. However, sensitivity analyses assessing the effects of missing data did not affect our results.ConclusionsReplacing smear microscopy with Xpert MTB/RIF in Brazil increased confirmation of pulmonary TB. An additional benefit was the accurate detection of rifampicin resistance. However, no increase on overall notification rates was observed, possibly because of high rates of empirical TB treatment.Trial registrationClinicalTrials.gov NCT01363765. Please see later in the article for the Editors' Summary.

Project description:BackgroundEarly diagnosis and treatment are one of the key strategies of tuberculosis control globally, and there are strong efforts in detecting and treating tuberculosis cases in Ethiopia. Smear microscopy examination has been a routine diagnostic test for pulmonary tuberculosis diagnosis in resource-constrained settings for decades. Recently, many countries, including Ethiopia, are scaling up the use of Gene Xpert without the evaluation of the cost and cost-effectiveness implications of this strategy. Therefore, this study evaluated the cost and cost-effectiveness of Gene Xpert (MTB/RIF) and smear microscopy tests to diagnosis tuberculosis patients in Ethiopia.MethodsWe compared the costs and cost-effectiveness of tuberculosis diagnosis using smear microscopy and Gene Xpert among 1332 patients per intervention in the Arsi zone. We applied combinations of top-down and bottom-up costing approaches. The costs were estimated from the health providers' perspective within one year (2017-2018). We employed "cases detected" as an effectiveness measure, and the incremental cost-effectiveness ratio was calculated by dividing the changes in cost and change in effectiveness. All costs and incremental cost-effectiveness ratio were reported in 2018 US$.ResultsThe unit cost per test for Gene Xpert was $12.9 whereas it is $3.1 for AFB smear microscopy testing. The cost per TB case detected was $77.9 for Gene Xpert while it was $55.8 for the smear microscopy method. The cartridge kit cost accounted for 42% of the overall Gene Xpert's costs and the cost of the reagents and consumables accounted for 41.3% ($1.3) of the unit cost for the smear microscopy method. The ICER for the Gene Xpert strategy was $20.0 per tuberculosis case detected.ConclusionUsing Gene Xpert as a routine test instead of standard care (smear microscopy) can be potentially cost-effective. In the cost scenario analysis, the price of the cartridge, the number of tests performed per day, and the life span of the capital equipment were the drivers of the unit cost of the Gene Xpert method. Therefore, Gene Xpert can be a part of the routine TB diagnostic testing strategy in Ethiopia.

Project description:IntroductionTajikistan has a laboratory network with three levels of tuberculosis (TB) laboratories. The external quality assessment (EQA) of sputum smear microscopy was implemented in 2007. The objective of this study was to evaluate the EQA system and identify potential performance improvement strategies in TB microscopic laboratories in Sughd, Tajikistan.MethodsThis is a cross-sectional study based on retrospective record review and secondary data analyses on Acid-Fast Bacilli (AFB) microscopy data and EQA reading results collected between the first quarter of 2011 and the fourth quarter of 2013. Descriptive analyses were conducted to examine the overview of microscopy laboratories activities, EQA results, and laboratory performance.ResultOf the 123,874 smears examined between 2011 and 2013, 11,522 (9.30%) were re-checked by the EQA system. The population TB screening rate rose from 0.46% in 2011 to 0.57% in 2013, and the case positivity rate decreased from 6.98% to 4.80%. The regional EQA results showed a reduction in high false-positive, high false-negative, and low false-negative errors. False-positive errors had decreased from 0.13% in 2011 to 0.07% in 2013, and false-negative errors from 0.91% in 2011 to 0.15% in 2013. Regional sensitivity of smear microscopy, when compared to re-checking controller, increased from 88.2% in 2011 to 97.2% in 2013. The regional specificity level remained relatively stable at above 99%.ConclusionOur study found that a decreasing trend of case positivity rate from 2011 to 2013 in Sughd, though the overall laboratory workload was on the rise. In addition, EQA results showed an overall error reduction and an improved sensitivity of smear microscopy in the region. The overview of microscopic laboratory activities and the actual evaluation of the EQA system on sputum smear microscopy complement each other in providing a better picture on the progress of TB laboratory strengthening. We recommend similar approaches to be adapted by future evaluations on TB microscopic laboratories, particularly among countries of high burden. Interactive training and feedback loops are crucial to improving TB surveillance in Tajikistan.

Dataset Information

A multi-country non-inferiority cluster randomized trial of frontloaded smear microscopy for the diagnosis of pulmonary tuberculosis.

Background

Methods and findings

Conclusions

Trial registration

Publications

A multi-country non-inferiority cluster randomized trial of frontloaded smear microscopy for the diagnosis of pulmonary tuberculosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets