Next generation blood tests for detecting tuberculosis at the point-of-care: Overcoming challenges in product development

AbstractTo control tuberculosis (TB), it is necessary to detect the disease and provide effective treatment to avert its progression and to interrupt any onward transmission from infectious pulmonary cases. Traditional diagnostic methods rely on the detection of the Mycobacterium tuberculosis (MTB) bacilli in clinical samples such as sputum. Testing is usually done on patients that have been coughing for some time, when transmission is likely to have already occurred. The impact of the GeneXpert MTB/RIF assay has so far had a limited impact on TB control because of its high cost and limited accessibility. A number of follow-up nucleic acid amplification technologies are being evaluated, but they also rely on testing for the presence of the bacteria in sputum. Diagnosing extra-pulmonary disease and TB in children remains very difficult and tests are needed that detect all forms of the disease. For developing countries with a high burden of TB, technology is needed that is robust, affordable and will avoid diagnostic delay; the tests must be readily accessible to the community without waiting for patients to self-refer to a TB testing clinic. Compromises may be needed between accuracy and access where a rapid imperfect test that can be used to test people in their community will have more benefit than a more perfect test that is not accessible. Traditional serological tests have failed for TB because of the complexity of the disease, but by testing for multiple markers, sensitivity and specificity can be improved and it is possible to differentiate latent infection and active disease. Examples of new assays that have the potential to change TB control shall be provided. The challenge now is to develop, manufacture, and distribute detection platforms that are safe, robust and affordable. Recent studies have revealed the market for TB diagnostics to be fragmented and small. Consultation with manufacturers has revealed that access to finance, management of intellectual property, regulatory acceptance and in some countries the lack of distribution networks are significant barriers to innovation. The lack of financial incentives and expectation of poor returns on investment discourages commercial companies, and there is a need for the not-for-profit and academic sectors to expand their role in product development and delivery. Biologists and technologists must work with manufacturers and healthcare providers to overcome the economic and political barriers to product development, manufacture and distribution. To this end, guidelines and a ‘road map’ for taking new in vitro diagnostic medical devices to market have been developed to raise awareness and sensitize the TB research community for the need for innovation in product delivery