Integrated strategies to optimize sputum smear microscopy: a prospective observational study

Abstract

Rationale: Smear-positive tuberculosis (TB) case detection rates are far below targets in most low-income countries. The standard approach to smear microscopy involves sputum collection over multiple days and examination of sputum smears by light microscopy (LM), an insensitive and time-consuming technique.

Objective: To determine whether two alternative approaches can increase smear-positive case detection by increasing the efficiency (single-specimen microscopy) or sensitivity (light-emitting diode [LED] fluorescence microscopy [FM]) of TB suspect evaluation.

Methods: We enrolled patients with cough of 2 weeks or more admitted to Mulago Hospital in Kampala, Uganda and collected spot and early morning sputum specimens. We compared the diagnostic accuracy of four prespecified strategies based on the number of sputum specimens collected (one specimen versus two specimens) and the type of microscopy (LM versus LED FM) using mycobacterial culture as a reference standard.

Measurements and main results: Two hundred thirty-three of 464 (50%) patients had culture-positive TB. There was no difference in sensitivity between single-specimen and two-specimen strategies when smears were examined with LM (55 vs. 56%; difference, -1%; 95% confidence interval [CI], -5 to +2%) or LED FM (61 vs. 64%; difference, -3%; 95% CI, -7 to +1%). LED FM was more sensitive than LM with both the single-specimen (61 vs. 55%; difference, 6%; 95% CI, 2-10%) and two-specimen strategies (64 vs. 56%; difference, 8%; 95% CI, 3-12%). Findings were similar among the HIV-infected patient subset (n = 321 patients).

Conclusions: In low-income, high TB burden settings, single-specimen microscopy and LED FM, either alone or in combination, could considerably increase identification of smear-positive TB cases.

Figure 1.

Smear microscopy strategies. The standard approach to smear microscopy involves collection of sputum specimens over 2 days and examination of one direct smear prepared from each specimen (top panel). Single-specimen microscopy refers to a same-day microscopy strategy that involves collection of only one sputum specimen and examination of two smears prepared from this single specimen (bottom panel). With both strategies, smears can be examined either using conventional light microscopy or light-emitting diode (LED) fluorescence microscopy.

Figure 2.

Study population. Of 492 tuberculosis (TB) suspects enrolled, 464 (94%) were included in the analysis. The prevalence of culture-positive TB was 50% among included patients.