Assessment of Three Commercially Available Serologic Assays for Detection of Antibodies to Mycobacterium tuberculosis and Identification of Active Tuberculosis

Abstract

Tuberculosis (TB) caused byApproximately nine million new cases of disease and over two million deaths result from tuberculosis (TB) each year (29,56). It is estimated that over one-third of the world's population is infected, with ϳ95% of all cases occurring in developing countries. Global measures attempting to reduce the transmission of TB are currently in place.An essential component of TB control efforts is to identify and treat individuals with active TB disease. The ability to correctly identify individuals with latent TB infection who will progress to active TB disease is vital to this goal (9, 49). Current test procedures are inadequate to accurately detect and identify active TB disease (14,27,30,31,41,44). These shortcomings result in the unnecessary treatment of many individuals who may not need it (3,17,32,45). While the tuberculin skin test (TST) and the QuantiFERON-TB Gold (QFT-G), the traditional methods for latent TB infection screening, rely on the cell-mediated response, the humoral response appears to correlate with the progression of the infection to active TB disease (5,6,11,15,20,21).Many studies have been conducted to evaluate the utility of individual specific Mycobacterium tuberculosis antigens for detecting antibodies in patients with active TB disease (1,7,10,11,20,21,25,26,29,38,39,45,46). Several of these antigens have been developed into commercial assays capable of detecting M. tuberculosis antibodies (4,28,35,53). This study evaluates three commercially available enzyme-linked immunosorbent assays (ELISAs) for their ability to detect immunoglobulin G (IgG) antibodies to M. tuberculosis in patients with active TB disease. MATERIALS AND METHODSHuman sera. The procedures followed were in accordance with the ethical standards established by the University of Utah and are in accordance with the Helsinki Declaration of 1975. This study was approved by the Institutional Review Board of the University of Utah, IRB 17152. All patient samples included in this study were deidentified to meet the Health Information Portability and Accountability Act (HIPAA) patient confidentiality guidelines.Serum samples were stored at Ϫ70°C until testing commenced and were then stored at 2 to 8°C while testing was performed. The whole-blood samples were processed immediately after collection. Samples with discrepant results were tested again by each respective assay to ensure reproducibility. A total of 209 samples were used and divided into four groups.Risk factors that were evaluated for exposure to TB included work in the health care field, laboratory work (especially in mycobacteriology laboratories and specimen processing), immigration from or travel to an country where TB is endemic, and exposure to persons with known active disease. Work in a mycobacteriology laboratory, exposure to a known active case, or immigration from a country where TV is endemic were considered high risk for exposure. Work in a health care field was considered moderate risk.Group I serum samples consisted of 88 samples from h...

A Critical Appraisal of the Ban on Serological Tests for Tuberculosis Usefulness of Serological Monitoring of Tuberculosis Antibodies during the Treatment of TB Patients

“…All reported poor sensitivity. Yet, the study [32] referenced as #5 in the indicting meta-analysis, announces 50% sensitivity for the Anda-TB test in HIV-patients. Production of humoral antibodies in HIV-infected subjects is rare because the immuno-depression inflicted by HIV also affects TB: the negative results observed are not "false negatives" but "true negatives" traced to immuno-depression.…”

“…Production of humoral antibodies in HIV-infected subjects is rare because the immuno-depression inflicted by HIV also affects TB: the negative results observed are not "false negatives" but "true negatives" traced to immuno-depression. The study [32] mentioned in reference #5 of the meta analysis presents a particular interest because it also focused on the identification of latent infections. Basing its judgment on references #3 and #24, it reported for the Anda Biologicals TB ELISA a positivity rate of 30.8%, which was said to be about 10 times higher than the expected conversion rate of 3% to 5% from latent TB infection to active TB infection rates.…”

“…This evaluation of 20% or more of reactivation risk reflects more accurately the true level of the conversion rate in a general population in regions with a high TB incidence. If the authors of the different studies [12,32] had drawn correct conclusions from their own data and references, the Anda-TB test would have appeared as an excellent test to detect latent infections and the WHO would not have banned it.…”

Assessment of Five Antigens from Mycobacterium tuberculosis for Serodiagnosis of Tuberculosis

“…Serodiagnosis is characterized by convenient sampling, low costs, easy operation, and rapid determination. Several antigens from M. tuberculosis have been developed into commercial kits, like MycoDot kit (which uses lipoarabinomannan [LAM]), InBios Active TbDetect IgG enzyme-linked immunosorbent assay (ELISA), IBL M. tuberculosis IgG ELISA, Anda Biologicals TB ELISA, and Linonex TB kits (2,16). However, commercially available serological tests for pulmonary TB and EPTB have variable accuracies and a limited clinical role (20,21,22).…”

Excretory Secretory Proteins Released during Growth of Mycobacterium tuberculosis (H37Ra), With Diagnostic Potential in Pulmonary and Extra Pulmonary Tuberculosis

“…Although the development of the Xpert MTB/RIF assay is undoubtedly a landmark event, clinical and control programmatic effects and costeffectiveness remain problems in resource limited developing countries [5]. Three commercially available serologic assays were evaluated for detection of antibodies in active TB infection namely, InBios Active TB detect IgG ELISA, IBL M. tb IgG ELISA and Anda Biologics TB ELISA [6]. InBios Active TB detect IgG ELISA, which is quite superior to other kits utilizes several antigens like Mtb81, Mtb8, Mtb48 and MPT 32, 38 KDa antigen and two additional proprietary antigens.…”