PLoS Medicine (Jul 2011)

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

  • Luis Eduardo Cuevas,
  • 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

DOI
https://doi.org/10.1371/journal.pmed.1000443
Journal volume & issue
Vol. 8, no. 7
p. e1000443

Abstract

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BackgroundMore 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 findingsThis 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%, pConclusionsThe 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 registrationCurrent Controlled Trials ISRCTN53339491. Please see later in the article for the Editors' Summary.