Abstract
BackgroundThe use of early morning sputum samples (EMS) to diagnose tuberculosis (TB) can result in treatment delay given the need for the patient to return to the clinic with the EMS, increasing the chance of patients being lost during their diagnostic workup. However, there is little evidence to support the superiority of EMS over spot sputum samples. In this new analysis of the REMoxTB study, we compare the diagnostic accuracy of EMS with spot samples for identifying Mycobacterium tuberculosis pre- and post-treatment.MethodsPatients who were smear positive at screening were enrolled into the study. Paired sputum samples (one EMS and one spot) were collected at each trial visit pre- and post-treatment. Microscopy and culture on solid LJ and liquid MGIT media were performed on all samples; those missing corresponding paired results were excluded from the analyses.ResultsData from 1115 pre- and 2995 post-treatment paired samples from 1931 patients enrolled in the REMoxTB study were analysed. Patients were recruited from South Africa (47%), East Africa (21%), India (20%), Asia (11%), and North America (1%); 70% were male, median age 31 years (IQR 24–41), 139 (7%) co-infected with HIV with a median CD4 cell count of 399 cells/μL (IQR 318–535). Pre-treatment spot samples had a higher yield of positive Ziehl–Neelsen smears (98% vs. 97%, P = 0.02) and LJ cultures (87% vs. 82%, P = 0.006) than EMS, but there was no difference for positivity by MGIT (93% vs. 95%, P = 0.18). Contaminated and false-positive MGIT were found more often with EMS rather than spot samples. Surprisingly, pre-treatment EMS had a higher smear grading and shorter time-to-positivity, by 1 day, than spot samples in MGIT culture (4.5 vs. 5.5 days, P < 0.001). There were no differences in time to positivity in pre-treatment LJ culture, or in post-treatment MGIT or LJ cultures. Comparing EMS and spot samples in those with unfavourable outcomes, there were no differences in smear or culture results, and positive results were not detected earlier in Kaplan–Meier analyses in either EMS or spot samples.ConclusionsOur data do not support the hypothesis that EMS samples are superior to spot sputum samples in a clinical trial of patients with smear positive pulmonary TB. Observed small differences in mycobacterial burden are of uncertain significance and EMS samples do not detect post-treatment positives any sooner than spot samples.
Highlights
The use of early morning sputum samples (EMS) to diagnose tuberculosis (TB) can result in treatment delay given the need for the patient to return to the clinic with the EMS, increasing the chance of patients being lost during their diagnostic workup
The diagnosis of TB is largely based on smear microscopy of expectorated sputum samples, and will likely continue to be so in those resource-limited settings unable to afford the roll-out of Xpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) and for whom the World Health Organization (WHO) highlights the critical need for ensuring quality of microscopy networks [11]
We aim to compare the value of EMS and spot sputum samples and hypothesize that early morning and spot sputum are clinically equivalent in terms of positive yield, their sensitivity for culture in solid and liquid media, and measures of mycobacterial load in a large, well-characterised group of patients being treated for TB as part of the REMoxTB study
Summary
The use of early morning sputum samples (EMS) to diagnose tuberculosis (TB) can result in treatment delay given the need for the patient to return to the clinic with the EMS, increasing the chance of patients being lost during their diagnostic workup. There is little evidence to support the superiority of EMS over spot sputum samples In this new analysis of the REMoxTB study, we compare the diagnostic accuracy of EMS with spot samples for identifying Mycobacterium tuberculosis pre- and post-treatment. The financial burden can equal several months’ salary and may exacerbate or push people into poverty [4, 5] These costs apply to patients found to have TB, and to the vast majority who have an alternative cause for their symptoms. Factors that may influence the results of TB smear microscopy include the volume and quality of the sputum sample collected, the time to processing and transport conditions, and the proficiency of the microscopist
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