Comparison of two methods for acquisition of sputum samples for diagnosis of suspected tuberculosis in smear-negative or sputum-scarce people: a randomised controlled trial

Abstract

Summary Background Sputum obtained either under instruction from a health-care worker or through induction can improve case detection of active tuberculosis. However, the best initial sputum sampling strategy for adults with suspected smear-negative or sputum-scarce tuberculosis in primary care is unclear. We compared these two methods of sample acquisition in such patients. Methods In this randomised controlled trial, we enrolled adults (age ≥18 years) with sputum-scarce or smear-negative suspected tuberculosis from three primary care clinics in Cape Town, South Africa. Patients were randomly assigned (1:1) to receive either health-care worker instruction or induction to obtain sputum samples. Neither patients nor investigators were masked to allocation. The primary outcome was the proportion of patients who had started treatment after 8 weeks in a modified intention-to-treat population. Secondary outcomes were proportions starting treatment within different time periods, proportion of patients producing sputum for diagnosis, adverse effects, sputum samples’ quality, and case detection by diagnostic method. This study is registered with ClinicalTrials.gov, number NCT01545661. Findings We enrolled 481 patients, of whom 213 were assigned to health-care worker instruction versus 268 assigned to induction. The proportion of patients who started treatment in the 8 weeks after enrolment did not differ significantly between groups (53/213 [25%] vs 73/268 [27%]; OR 0.88, 95% CI 0.57–1.36; p=0.56). A higher proportion of instructed versus induced patients initiated empiric treatment based on clinical and radiography findings (32/53 [60%] vs 28/73 [38%]; p=0.015). An adequate sputum sample ≥1 mL was acquired in a lower proportion of instructed versus induced patients (164/213 [77%] vs 238/268 [89%]; p<0.0001), and culture-based diagnostic yield was lower in instructed versus induced patients (24/213 [11%] vs 51/268 [19%]; p=0.020). However, same-day tuberculosis case detection was similar in both groups using either smear microscopy (13/213 [6%] vs 22/268 [8%]; p=0.38) or Xpert-MTB/RIF assay (13/89 [15%] vs 20/138 [14%]; p=0.98). No serious adverse events occurred in either group; side-effects related to sample acquisition were reported in 32 of 268 (12%) patients who had sputum induction and none who had instruction. Cost per procedure was lower for instructed than for induced patients (US$2.14 vs US$7.88). Interpretation Although induction provides an adequate sample and a bacteriological diagnosis more frequently than instruction by a health-care worker, it is more costly, does not result in a higher proportion of same-day diagnoses, and—because of widespread empiric treatment—may not result in more patients starting treatment. Thus, healthcare worker instruction might be the preferred strategy for initial collection of sputum samples in adults with suspected sputum-scarce or smear-negative tuberculosis in a high burden primary care setting. Funding South African National Research Foundation, European Commiss...

Intra-gastric string test: an effective tool for diagnosing tuberculosis in adults unable to produce sputum

“…10,25 This is what the string test device could potentially offer. However, the potential for greatly increased access of the string test, especially given the good prospects for producing the test locally, and the possibility of shortening the duration of the intragastric downtime even further (from 2 h to 1 h) would facilitate routine implementation of the test.…”

“…6 While sputum induction and gastric aspiration both show good detection yields, the need for stringent infection control measures for sputum induction and clinicians' reluctance to use gastric aspiration impede their broad implementation, especially at low-level health facilities. [6][7][8][9][10][11] A simpler, inexpensive method of specimen retrieval suitable for remote areas in lowresource settings is therefore needed.…”

Policy to practice: impact of GeneXpert MTB/RIF implementation on the TB spectrum of care in Lilongwe, Malawi

“…No sputum induction process was available as per standard hospital protocol. 16 Clinic aides transported samples from the wards to the lab facility and testing at the lab facility took place Monday through Friday, 08:00 to 17:00 h. Results were communicated with the patient's medical care team as soon as they were available, between 08:00 and 17:00 h during weekdays.…”

“…12,16 The sample was processed adhering to the standardized protocol and quality control procedures of the UNC Project laboratory. GeneXpert testing was performed on the sputum sample according to the manufacturer's operation instructions.…”

“…17 Our findings are similar to other studies in South Africa and Uganda that also reported this paradoxical phenomenon of high utilization of empiric treatment in the GeneXpert era. 16,18,19 Notably, even in settings with extensive diagnostics, TB can be missed. Autopsy studies in both the pre and post ART eras have demonstrated high rates of undiagnosed TB infection.…”