Remembering the basics: interventions to improve sputum collection for tuberculosis diagnosis
Authors: Chad M Centner, Mark Patrick Nicol
Journal: The Lancet Global Health (2017)

WHO estimates that 30–50% of people with tuberculosis are untreated, in part because of underdiagnosis.1WHOGlobal tuberculosis report 2016. World Health Organization, Geneva2016Google Scholar Patients with undiagnosed (or diagnosed and untreated) tuberculosis are most likely to transmit infection, so strategies to reduce disease burden should focus on improving the pathway to care for patients. The past decade has seen welcome innovations in diagnostic technology, notably the Xpert MTB/RIF assay, which is significantly more sensitive than smear microscopy and provides rapid identification of rifampicin resistance.2Boehme CC Nabeta P Hillemann D et al.Rapid molecular detection of tuberculosis and rifampin resistance.N Engl J Med. 2010; 363: 1005-1015Crossref PubMed Scopus (1726) Google Scholar WHO has recently made recommendations on the use of the next-generation Xpert assay, the Xpert MTB/RIF Ultra, which has improved sensitivity.3WHOWHO meeting report of a technical expert consultation: non-inferiority analysis of Xpert MTF/RIF Ultra compared to Xpert MTB/RIF. World Health Organization, Geneva2017Google Scholar However, the pathway to care has many steps, and the systematic review and meta-analysis of sputum collection methods by Sumona Datta and colleagues,4Datta S Shah L Gilman RH Evans CA Comparison of sputum collection methods for tuberculosis diagnosis: a systematic review and pairwise and network meta-analysis.Lancet Glob Health. 2017; (published online June 15)http://dx.doi.org/10.1016/S2214-109X(17)30201-2Summary Full Text Full Text PDF PubMed Scopus (46) Google Scholar in this issue of The Lancet Global Health, is a timely reminder that the diagnostic test is just one step. By examining the available evidence, Datta and colleagues show that two simple interventions increased the diagnostic performance of microbiological testing. Pooling of sputum samples collected over a period of several hours increased the diagnostic performance of smear microscopy 1·6 times and of culture 1·7 times, compared with collection of a single timepoint or spot sample (the reference standard), while the delivery of standardised instruction before the provision of sputum samples increased the performance of smear microscopy 1·4 times compared with the standard of care. The implications of implementing these interventions require careful consideration. In 2010, WHO recommended the spot-spot algorithm, whereby patients with presumptive tuberculosis provide two, on demand, spot sputum samples on the day of presentation.5WHOSame-day-diagnosis of tuberculosis by microscopy. 2010http://www.who.int/entity/tb/publications/2011/tb_microscopy_9789241501606/en/index.htmlGoogle Scholar The algorithm, based on a systematic review and meta-analysis of the literature,6Davis JL Cattamanchi A Cuevas LE Hopewell PC Steingart KR Diagnostic accuracy of same-day microscopy versus standard microscopy for pulmonary tuberculosis: a systematic review and meta-analysis.Lancet Infect Dis. 2013; 13: 147-154Summary Full Text Full Text PDF PubMed Scopus (86) Google Scholar is intended to reduce loss to follow-up without compromising diagnosis. Although Datta and colleagues' study did not address the incremental performance of collecting more than one sputum sample, pooling of sputum over a lengthy period requires additional clinic visits and is unlikely to be compatible with a spot-spot algorithm. Increased patient and health-care costs, and loss to follow up associated with these additional visits, would need to be balanced against increased diagnostic performance. Whether a pooled sample collected during the patient's visit to the health-care facility would show similar benefit remains to be shown. Similarly, important questions on sputum instruction remain. What are the current practices regarding instruction and what specific instructions would have the greatest effect? How should these instructions be presented? Written instructions in the form of a brochure probably have limited utility,7Lee YJ Shin S Roh EY et al.The effectiveness of a brochure describing an acceptable method of sputum collection for tuberculosis testing.Int J Tuberc Lung Dis. 2013; 17: 1587-1589Crossref PubMed Scopus (6) Google Scholar particularly in areas where literacy is low. One study found a substantial increase in diagnostic performance for participants who viewed an instructional video.8Mhalu G Hella J Doulla B et al.Do instructional videos on sputum submission result in increased tuberculosis case detection? A randomized controlled trial.PLOS One. 2015; 10: e0138413Crossref PubMed Scopus (18) Google Scholar Implementation of a videographic intervention would allow presentation of other educational material as well.9Shelke SC Adhav PS Moonan PK et al.Photovoice: a novel approach to improving antituberculosis treatment adherence in Pune, India.Tuberc Res Treat. 2014; 2014: 4Google Scholar Cultural factors might require consideration: Khan and colleagues10Khan MS Dar O Sismanidis C Shah K Godfrey-Faussett P Improvement of tuberculosis case detection and reduction of discrepancies between men and women by simple sputum-submission instructions: a pragmatic randomised controlled trial.Lancet. 2007; 369: 1955-1960Summary Full Text Full Text PDF PubMed Scopus (106) Google Scholar showed differences in the effectiveness of an instructional intervention depending on the sex of the participant with presumptive tuberculosis. Regardless of these considerations, an instructional intervention is an attractive strategy that would probably incur few additional costs8Mhalu G Hella J Doulla B et al.Do instructional videos on sputum submission result in increased tuberculosis case detection? A randomized controlled trial.PLOS One. 2015; 10: e0138413Crossref PubMed Scopus (18) Google Scholar, 10Khan MS Dar O Sismanidis C Shah K Godfrey-Faussett P Improvement of tuberculosis case detection and reduction of discrepancies between men and women by simple sputum-submission instructions: a pragmatic randomised controlled trial.Lancet. 2007; 369: 1955-1960Summary Full Text Full Text PDF PubMed Scopus (106) Google Scholar and have minimal effect on health-care workers' time.8Mhalu G Hella J Doulla B et al.Do instructional videos on sputum submission result in increased tuberculosis case detection? A randomized controlled trial.PLOS One. 2015; 10: e0138413Crossref PubMed Scopus (18) Google Scholar, 10Khan MS Dar O Sismanidis C Shah K Godfrey-Faussett P Improvement of tuberculosis case detection and reduction of discrepancies between men and women by simple sputum-submission instructions: a pragmatic randomised controlled trial.Lancet. 2007; 369: 1955-1960Summary Full Text Full Text PDF PubMed Scopus (106) Google Scholar, 11Interactive Research & Development (IRD), Pakistan“Good sputum, better diagnosis”—(English) instructional video for sputum submission. May 10, 2013https://youtu.be/92dT_1kbbekGoogle Scholar Good quality evidence is required to influence policy, and this should be borne in mind when considering the studies included in the meta-analysis by Datta and colleagues, which were of variable quality. Some studies included a comparator or uninstructed group that was not well defined and was probably difficult to control; the absence of blinding is inherent to the nature of the intervention. Further limitations of the meta-analysis included the low number of available studies, the absence of a consistent between-study reference standard, methodological heterogeneity, and incomplete data (eg, analysis at the level of the individual sputum sample was not possible for all studies). Finally, how would the interventions identified in this meta-analysis affect the performance of molecular diagnostic assays? The Xpert MTB/RIF assay (and the newer Xpert MTB/RIF Ultra) have intermediate sensitivity, between that of smear microscopy and culture.2Boehme CC Nabeta P Hillemann D et al.Rapid molecular detection of tuberculosis and rifampin resistance.N Engl J Med. 2010; 363: 1005-1015Crossref PubMed Scopus (1726) Google Scholar, 3WHOWHO meeting report of a technical expert consultation: non-inferiority analysis of Xpert MTF/RIF Ultra compared to Xpert MTB/RIF. World Health Organization, Geneva2017Google Scholar It seems likely that the incremental improvement in performance associated with these interventions would have a similar effect on the performance of molecular assays. This study reminds us not to neglect potentially simple and cost-effective interventions, which have been shown to improve diagnostic performance. New, highly sensitive diagnostics, particularly those suitable for true point-of-care use in low-resource settings, are urgently needed. However, even in the absence of such tools, substantial gains can be made by improving attention towards the basics, such as sample collection, in our efforts to close the gaps in the pathway to care for patients with tuberculosis. MPN reports grants from the Foundation for Innovative New Diagnostics and the US National Institutes of Health, outside the submitted work. CMC declares no competing interests. Comparison of sputum collection methods for tuberculosis diagnosis: a systematic review and pairwise and network meta-analysisTuberculosis diagnoses were substantially increased by either pooled collection or by providing instruction on how to produce a sputum sample taken at any time of the day. Both interventions had a similar effect to that reported for the introduction of new, expensive laboratory tests, and therefore warrant further exploration in the drive to end the global tuberculosis epidemic. Full-Text PDF Open Access