Commercial Serological Antibody Detection Tests for the Diagnosis of Pulmonary Tuberculosis: A Systematic Review

Abstract

BackgroundThe global tuberculosis epidemic results in nearly 2 million deaths and 9 million new cases of the disease a year. The vast majority of tuberculosis patients live in developing countries, where the diagnosis of tuberculosis relies on the identification of acid-fast bacilli on unprocessed sputum smears using conventional light microscopy. Microscopy has high specificity in tuberculosis-endemic countries, but modest sensitivity which varies among laboratories (range 20% to 80%). Moreover, the sensitivity is poor for paucibacillary disease (e.g., pediatric and HIV-associated tuberculosis). Thus, the development of rapid and accurate new diagnostic tools is imperative. Immune-based tests are potentially suitable for use in low-income countries as some test formats can be performed at the point of care without laboratory equipment. Currently, dozens of distinct commercial antibody detection tests are sold in developing countries. The question is “do they work?”Methods and FindingsWe conducted a systematic review to assess the accuracy of commercial antibody detection tests for the diagnosis of pulmonary tuberculosis. Studies from all countries using culture and/or microscopy smear for confirmation of pulmonary tuberculosis were eligible. Studies with fewer than 50 participants (25 patients and 25 control participants) were excluded. In a comprehensive search, we identified 68 studies. The results demonstrate that (1) overall, commercial tests vary widely in performance; (2) sensitivity is higher in smear-positive than smear-negative samples; (3) in studies of smear-positive patients, Anda-TB IgG by enzyme-linked immunosorbent assay shows limited sensitivity (range 63% to 85%) and inconsistent specificity (range 73% to 100%); (4) specificity is higher in healthy volunteers than in patients in whom tuberculosis disease is initially suspected and subsequently ruled out; and (5) there are insufficient data to determine the accuracy of most commercial tests in smear microscopy–negative patients, as well as their performance in children or persons with HIV infection.ConclusionsNone of the commercial tests evaluated perform well enough to replace sputum smear microscopy. Thus, these tests have little or no role in the diagnosis of pulmonary tuberculosis. Lack of methodological rigor in these studies was identified as a concern. It will be important to review the basic science literature evaluating serological tests for the diagnosis of pulmonary tuberculosis to determine whether useful antigens have been described but their potential has not been fully exploited. Activities leading to the discovery of new antigens with immunodiagnostic potential need to be intensified.

Smear-Negative Pulmonary Tuberculosis

“…Positivity of the Gene Xpert test has been found to be related to the basil load in the sample (26). Sensitivity of Anda-TB IgG, which is a serological diagnostic test developed in recent years, in smear-positive patients is 63-85% and its specificity is 73-100% and no sufficient information about the use of this test in smear-negative patients is available (27). WHO suggests not using serological tests in pulmonary and extrapulmonary tuberculosis diagnosis because of the inconsistency and impreciseness of their sensitivity and specificity values (28).…”

Strategies for immunohistochemical protein localization using antibodies: What did we learn from neurotransmitter transporters in glial cells and neurons

“…Morrow and Friedrich, 2003;Roth, 2006;Rhodes and Trimmer, 2006;Steingart et al, 2007;Smith, 2006;Fritschy, 2008;Couchman, 2009;Kalyuzhny, 2009;Holmseth et al, 2012a;Herrera et al, 2013;Griffiths and Lucocq, 2014). After all, the biomedical research community relies directly or indirectly on precise protein localization data because interpretation of the other methods (e.g.…”

Serodiagnosis of tuberculous lymphadenitis using a combination of antigens

“…Thus there is a great need to develop simple, rapid, affordable and user-friendly methods to diagnose EPTB. Serological tests would be of great value in resource-poor settings and there are commercial serological tests available that may be used in the diagnosis of EPTB but they are highly variable with respect to sensitivity (0 to 100%) and specificity (59 to 100%) [6].…”