Despite being widely available for sale in low-and-middle income countries, commercial serological tests used to detect active tuberculosis (by identifying antibodies to the tuberculosis-causing bacterium in a blood sample) do not accurately diagnose TB and, furthermore, often test positive when the patient does not have TB (false positive) and test negative when the patient actually has TB (false negative). In addition, as shown in India, the use of such tests is not cost effective as compared to other tests available for TB.
These findings from two studies led by Madhukar Pai from McGill University and Montreal Chest Institute in Montreal, Canada, and published in this week's PLoS Medicine, formed the basis of a policy issued by the World Health Organization (WHO) on 20 July 2011 (available at: www.who.int/tb/features_archive/20july11_end_to_inaccurate_tb_blood_tests/en/index.html) advising against the use of currently available serological tests for the diagnosis of tuberculosis. WHO recommended: "These tests should not be used in individuals suspected of active pulmonary or extra-pulmonary TB, irrespective of their HIV status." The WHO policy strongly encourages further targeted research to identify new tests for TB diagnosis and alternative serological tests which would need to have much improved accuracy.
In the first article with Karen Steingart of the University of Washington, Seattle, USA as first author, the authors report searching the literature for relevant studies evaluating the accuracy of commercial serological tests. In their systematic review, they report that the sensitivity of serological tests (the proportion of patients with confirmed TB with a positive serological test), ranged from 0% to 100% and their specificities (the proportion of patients who did not have confirmed TB with a negative serological test) ranged from 31% to 100%. For extrapulmonary tuberculosis (TB infection affecting parts of the body other than the lungs), sensitivities and specificities for each test also varied greatly, ranging from 0% to 100% and 59% to 100%, respectively. The authors found that, overall, the quality of evidence regarding diagnostic accuracy of serological tests was very low for both pulmonary and extrapulmonary tuberculosis.
The authors conclude: "Despite expansion of the literature since 2006, commercial serological tests continue to produce inconsistent and imprecise estimates of sensitivity and specificity."
In an associated study with David Dowdy of Johns Hopkins University, Baltimore, USA as first author, the authors analyzed the cost-effectiveness of TB serological tests from the perspective of tuberculosis control in India, compared to other diagnostic tests. They found that if used as an initial test for tuberculosis in India, serology would result in more DALYs (years of healthy life lost because of premature death or disability), more secondary infections, and more false-positive diagnoses than sputum smear microscopy while increasing costs per patient to the Indian tuberculosis control sector.
The authors conclude: "In India, sputum smear microscopy remains the most cost-effective diagnostic test available for active TB; efforts to increase access to quality-assured microscopy should take priority." Where quality microscopy is available, WHO-endorsed tests such as liquid cultures should be introduced to improve TB diagnosis.
Article by Steingart et al.
Funding: This systematic review was commissioned by the WHO with funding provided by USAID through a grant administered by the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR). No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. KRS serves as Coordinator of the Evidence Synthesis and Policy subgroup of Stop TB Partnership's New Diagnostics Working Group (NDWG). AR served as the secretary of the NDWG (2006-10) and is employed by WHO/TDR, the agency that administered the grant used to fund this systematic review. AR contributed to the conception and design of the systematic review and critical revision of and decision to publish the manuscript. MP is a recipient of a New Investigator Award from the Canadian Institutes of Health Research (CIHR). This funding source had no role in the preparation of this manuscript, nor the decision to submit the manuscript for publication. MP serves as an external consultant for the Bill & Melinda Gates Foundation. MP also serves as a co-chair of the NDWG. KRS, AR, MP, and SL were involved in the WHO Expert Group process that reviewed the evidence on serological tests. KRS was involved as a systematic reviewer in the World Health Organization Expert Group process that reviewed the evidence on serological tests in July 2010. MP serves on the editorial boards of PLoS Medicine and PLoS One.
Citation: Steingart KR, Flores LL, Dendukuri N, Schiller I, Laal S, et al. (2011) Commercial Serological Tests for the Diagnosis of Active Pulmonary and Extrapulmonary Tuberculosis: An Updated Systematic Review and Meta-Analysis. PLoS Med 8(8): e1001062. doi:10.1371/journal.pmed.1001062
CONTACT:
Dr. Madhukar Pai
Associate Professor
McGill University
Dept. of Epidemiology, Biostatistics & Occupational Health
1020 Pine Avenue West
Montreal, Quebec H3A 1A2
Canada
+1 514-398-5422
madhukar.pai@mcgill.ca
Article by Dowdy et al.
Funding: This work was funded by the Stop TB Partnership's New Diagnostics Working Group, via the subgroup on Evidence Synthesis. MP is a recipient of support from the Canadian Institutes of Health Research (CIHR). No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: None of the authors have any financial/industry conflicts to declare. All authors participated in the WHO Expert Group meeting on TB serological tests held in July 2010. KRS and MP have contributed to published and updated meta-analyses on TB serological tests. The updated meta-analysis on TB serological tests was commissioned by WHO with funding provided by USAID through a grant administered by the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR). KRS and MP are affiliated with the Stop TB Partnership's New Diagnostics Working Group. KRS serves as co-chair of the Evidence Synthesis subgroup of Stop TB Partnership's New Diagnostics Working Group, while MP serves as Co-chair of the Working Group. MP also serves as a consultant to the Bill & Melinda Gates Foundation (BMGF). BMGF had no involvement in this manuscript. MP serves on the editorial boards of PLoS Medicine and PLoS One.
Citation: Dowdy DW, Steingart KR, Pai M (2011) Serological Testing Versus Other Strategies for Diagnosis of Active Tuberculosis in India: A Cost-Effectiveness Analysis. PLoS Med 8(8): e1001074. doi:10.1371/journal.pmed.1001074
CONTACT:
Dr. Madhukar Pai
Associate Professor
McGill University
Dept. of Epidemiology, Biostatistics & Occupational Health
1020 Pine Avenue West
Montreal, Quebec H3A 1A2
Canada
+1 514-398-5422
madhukar.pai@mcgill.ca
Journal
PLoS Medicine