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Randomized Controlled Trial
. 2011 Jul;8(7):e1000443.
doi: 10.1371/journal.pmed.1000443. Epub 2011 Jul 12.

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

Luis Eduardo Cuevas  1 , Mohammed Ahmed Yassin, Najla Al-Sonboli, Lovett Lawson, Isabel Arbide, Nasher Al-Aghbari, Jeevan Bahadur Sherchand, Amin Al-Absi, Emmanuel Nnamdi Emenyonu, Yared Merid, Mosis Ifenyi Okobi, Juliana Olubunmi Onuoha, Melkamsew Aschalew, Abraham Aseffa, Greg Harper, Rachel Mary Anderson de Cuevas, Kristin Kremer, Dick van Soolingen, Carl-Michael Nathanson, Jean Joly, Brian Faragher, Stephen Bertel Squire, Andrew Ramsay
Affiliations
Randomized Controlled Trial

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

Luis Eduardo Cuevas et al. PLoS Med. 2011 Jul.

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.

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Conflict of interest statement

AR is employed by WHO/TDR the organization which administered the USAID and BMGF grants that funded the study. AR is Secretary of the New Diagnostics Working Group, Stop TB Partnership.

Figures

Figure 1
Figure 1. CONSORT flow diagram of the study.
Figure 2
Figure 2. Number of patients submitting the first, the first two, and all three specimens, by scheme.
Error bars represent the upper limit of the 95% confidence limits.
See this image and copyright information in PMC

Comment in

References

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