Tuberculosis (TB) serological tests almost exclusively rely on antibody recognition of antigens of Mycobacterium tuberculosis by the humoral immune response, as opposed to antigen recognition by the cellular immune response (e.g. interferon-gamma release assays). An accurate serological test that could provide rapid diagnosis of TB and in a suitable format (e.g. point-of-care) would be particularly useful both as a replacement for laboratory-based tests and for extending TB diagnosis to lower levels of health services, especially those without on-site laboratories. Although no serological TB test is recommended by international guidelines for clinical use nor approved by the US Food and Drug Administration, dozens of distinct commercial serological tests (also referred to as ‘commercial serodiagnostics’ in this document) are marketed in many parts of the world, especially in developing countries with weak regulatory systems.
Several systematic reviews and one laboratory-based evaluation on this topic have been published. Two reviews evaluating commercial tests for pulmonary TB (68 studies) and extrapulmonary TB (21 studies) found sensitivity and specificity of these tests to be highly variable.1-3 A meta-analysis of non-commercial tests for pulmonary TB (254 datasets including 51 distinct single antigens and 30 distinct multiple-antigen combinations) identified potential candidate antigens for inclusion in an antibody detection based TB test in HIV-uninfected and -infected individuals; however, no antigen or antigen combination achieved sufficient sensitivity to replace smear microscopy.2 Previous systematic reviews of rapid TB serodiagnostic tests (literature search through 2003, seven datasets) reported pooled sensitivity and specificity values of 34% and 91% respectively, in studies meeting at least two design-related criteria.4
In 2005, the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) performed an evaluation of 19 commercially available rapid diagnostic TB tests (‘rapid’ defined as having a test result available in less than 15 minutes).5 The evaluation reported that, in comparison with culture plus clinical follow-up, commercial tests provided sensitivity and specificity values of 1% to 60% and 53% to 99%, respectively.
Since the publication of previous reviews, the evidence base has grown and approaches to meta-analyses of diagnostic tests have evolved. WHO-STB and TDR therefore commissioned an updated systematic review to synthesize new evidence since 2006 on the diagnostic accuracy of commercial tests for pulmonary and extrapulmonary TB. In addition, the findings from the previous TDR evaluation are summarised below.
The systematic review and this document are limited to commercial serological tests only. In-house tests are likely to be less standardised, have less quality assurance during manufacture, and are prone to be more operator dependent. As a result, the quality issues of limitations, precision, consistency, directness and probable publication bias are expected to be more severe.
