Tuberculosis infection is a major cause of death and morbidity worldwide. Sputum microscopy remains the most commonly used primary diagnostic test, even though it is recognized as having only modest sensitivity. Bacteriological culture remains the reference test but requires high levels of containment and takes weeks to give results, while molecular tests such as the Cepheid GeneXpert MTB/RIF have the potential to largely match bacteriological culture as the “gold standard” for diagnosis of active pulmonary TB, but have high cost and moderate logistical challenges. Either culture or molecular methods are needed to identify drug resistance in order to guide appropriate therapy, but given the cost and logistical challenges in these tests, there is a need for integrated strategies to detect the maximum number of infections through screening, in order to triage patients for confirmatory tests including drug sensitivity.
Serological testing is ideal for large-scale screening including at the point-of-care, but antibody-based tests for TB have a very poor track record, with the WHO recommending against the use of such tests on the basis of their inadequate performance in both sensitivity and specificity. We will discuss new findings on the diversity of the antibody response that provide promise for development of improved serological tests for active MTb infection, providing part of an integrated solution for improved case-finding and disease control along with confirmatory and drug sensitivity tests such as GeneXpert.