A Multi-Country Non-Inferiority Cluster Randomized Trial of Frontloaded Smear Microscopy for the Diagnosis of Pulmonary Tuberculosis

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

来源：PLOS MEDICINE, 2011, 8(7): e1000443.

DOI：10.1371/journal.pmed.1000443

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.

• 出版日期2011-7
• 单位河北医科大学