Meta-analysis to compare the accuracy of GeneXpert, MODS and the WHO 2007 algorithm for diagnosis of smear-negative pulmonary tuberculosis

Abstract

BackgroundSmear-negative pulmonary tuberculosis (SN-PTB), which is common in HIV-infected patients, is difficult to diagnose using smear microscopy alone. In 2007, the WHO developed an algorithm to improve the diagnosis and management of smear-negative tuberculosis in HIV prevalent and resource constrained settings. Implementation of the algorithm required individuals with presumptive TB to be initially evaluated using two sputum microscopy examinations followed by clinical diagnosis that may include chest X-ray and antibiotic treatment in smear-negative individuals. Since that time, the WHO has endorsed several new tests for diagnosis of tuberculosis. However, it is unclear how the new tests perform when compared to the WHO 2007 algorithm in diagnosis of SN-PTB. Using meta-analysis study design, we summarized and compared the accuracy of Xpert® MTB/Rif assay (GeneXpert) and Microscopic Observation Drug Susceptibility assay (MODS), with the WHO 2007 algorithm in the diagnosis of SN-PTB.MethodsA systematic review and meta-analysis of publications on GeneXpert, or MODS, or the WHO 2007 algorithm for diagnosis of SN-PTB, using culture as reference test was performed. Meta-Disc software was used to obtain pooled sensitivity and specificity of the diagnostic methods. Heterogeneity in the accuracy estimates was tested by reviewing the generated forest plots, sROC curves and the Spearman correlation coefficient of the logit of true positive rate versus the logit of false positive rate.ResultsTwenty-four publications on all three diagnostic methods were meta-analyzed. The pooled sensitivity and specificity for detection of smear-negative pulmonary tuberculosis were 67% and 98% for GeneXpert, 73% and 91% for MODS, and 61% and 69% for WHO 2007 algorithm, respectively. The sensitivity of GeneXpert reduced from 67% to 54% when sub-group analysis of studies with patient HIV prevalence ≥30% was performed.ConclusionThe GeneXpert, MODS, and the WHO algorithm have moderate to high accuracy for the diagnosis of SN-PTB. However, the accuracy of the tests is extremely variable. The setting and context under which the tests are conducted in addition to several other factors could explain this variability. There is therefore need to investigate these factors further. The information from these studies would inform the adoption and placement of these new tests.

Accuracy of LAMP-TB Method for Diagnosing Tuberculosis in Haiti

“…Recently Walusimbi et al (14) reviewed its diagnostic performance and reported that its pooled sensitivity for smear-negative, culture-positive cases, based on 15 different reports, was 67z, and that the specificity was 98z, which are again comparable to the LAMP-TB test results of this study.…”

Rapid Detection of Mycobacterium tuberculosis in Sputum Samples by Cepheid Xpert Assay: A Clinical Study

“…Latest generation liquid culture diagnostics and molecular line probe assays are costly and cannot be performed in resource-limited settings, due to need for biosafety measures and specialised staff [4]. Besides technical expertise and biosafety concerns, LowensteinJensen (LJ) method, "the gold standard test", takes several weeks to produce result causing delayed onset of treatment [6]. In December 2010, WHO recommended use of a new Cartridge Based Nucleic Acid Amplification test (CB-NAAT), named GeneXpert system [1].…”

“…Prompt and accurate TB diagnosis are prerequisite for early and effective treatment thereby reducing tuberculosis burden, but there are number of difficulties in achieving the goal. Sputum smear microscopy is inefficient due to its variable sensitivity particularly in patients with sputum smearnegative and/or extrapulmonary disease, and drug-resistant TB [4][5][6]. Latest generation liquid culture diagnostics and molecular line probe assays are costly and cannot be performed in resource-limited settings, due to need for biosafety measures and specialised staff [4].…”

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

“…Overall, further guidelines are needed to address these gaps in diagnosis for GeneXpert negative and sputum scarce patients. 25 …”

“…25 In high HIV-TB burden environments, empiric treatment is often used to offset the diagnostic limitations and provide, possibly, same day treatment to decompensating patients. [21][22][23][24][25] The few studies presenting diagnostic information on GeneXpert negative individuals suggest that smear microscopy and chest x-ray have limited utility in detecting culture positive, Xpert negative, extrapulmonary or disseminated TB. 6,11 For sputum scarce patients, rapid diagnostics using other samples such as urine (urine LAM or urine GeneXpert) or blood may prove more feasible for testing.…”