Abstract

BackgroundSputum concentration increases the sensitivity of smear microscopy for the diagnosis of tuberculosis (TB), but few studies have investigated this method in human immunodeficiency virus (HIV)-infected individuals.MethodsWe performed a prospective, blinded evaluation of direct and concentrated Ziehl-Neelsen smear microscopy on a single early-morning sputum sample in HIV-infected patients with > 2 weeks of cough hospitalized in Kampala, Uganda. Direct and concentrated smear results were compared with results of Lowenstein-Jensen culture.ResultsOf 279 participants, 170 (61%) had culture-confirmed TB. The sensitivity of direct and concentrated smear microscopy was not significantly different (51% vs. 52%, difference 1%, 95% confidence interval (CI): [-7%, 10%], p = 0.88). However, when results of both direct and concentrated smears were considered together, sensitivity was significantly increased compared with either method alone (64%, 95% CI: [56%, 72%], p < 0.01 for both comparisons) and was similar to that of direct smear results from consecutive (spot and early-morning) specimens (64% vs. 63%, difference 1%, 95% CI: [-6%, 8%], p = 0.85). Among 109 patients with negative cultures, one had a positive direct smear and 12 had positive concentrated smears (specificity 99% vs. 89%, difference 10%, 95% CI: [2%, 18%], p = 0.003). Of these 13 patients, 5 (38%) had improved on TB therapy after two months.ConclusionSputum concentration did not increase the sensitivity of light microscopy for TB diagnosis in this HIV-infected population. Given the resource requirements for sputum concentration, additional studies using maximal blinding, high-quality direct microscopy, and a rigorous gold standard should be conducted before universally recommending this technique.

Highlights

  • Sputum concentration increases the sensitivity of smear microscopy for the diagnosis of tuberculosis (TB), but few studies have investigated this method in human immunodeficiency virus (HIV)-infected individuals

  • Of the 279 patients included in the study, 143 (51%) were positive for TB on culture of the early-morning sputum specimen used for comparison of direct and concentrated smear results

  • Sputum concentration did not increase the sensitivity of light microscopy for TB diagnosis in this prospective, blinded evaluation of 279 hospitalized, HIV-infected adults in Kampala, Uganda

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Summary

Introduction

Sputum concentration increases the sensitivity of smear microscopy for the diagnosis of tuberculosis (TB), but few studies have investigated this method in human immunodeficiency virus (HIV)-infected individuals. Direct smear microscopy is rapid, inexpensive [2,3,4], highly specific [57], and capable of identifying the most infectious cases of TB [7,8,9], but its sensitivity is limited, in those with human immunodeficiency virus (HIV) co-infection [10,11,12,13]. The difficulty in blinding readers as to whether a specimen is concentrated presents an inherent risk of bias in studies of sputum concentration. Few studies have employed the clear design and reporting requirements required to minimize this inherent risk [21] or evaluated sputum concentration in populations with high HIV prevalence [22,23,24,25,26]

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