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Project Topic
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The proposed DIAMA (DIAgnostics for Multidrug resistant tuberculosis in Africa) study aims to address current gaps in the diagnosis and management of patients with Multi-Drug-Resistant (MDR) tuberculosis (TB). Building on existing networks and research collaborations previously funded by EDCTP, this project involved partners in West-, Central, and East Africa. It aims to evaluate and implement rapid and accurate molecular tests for 14 anti-TB drugs, to replace the current dependency on phenotypic drug resistance testing (DST), which takes up to 4 months and is technically so demanding that few laboratories can perform these tests correctly. The project builds on the continuous surveillance of TB retreatment patients for rifampicin resistance. Two African partners (Benin and Rwanda) with advanced molecular laboratories are establishing reference laboratories for the ‘Deeplex’ assay, a novel multiplex deep sequencing-based drug resistance diagnostic platform that simultaneously provides sequence information of genes that confer resistance to 14 key anti-TB drugs. Partners are recruiting all retreatment patients with rifampicin resistant TB, and a subset of those with rifampicin sensitive TB. In a first phase, sputum will be shipped for the Deeplex assay, for comparison against phenotypic Drug Susceptibility Testing (DST), the reference method for detecting resistance to 1st and 2nd line anti-TB drugs.In a second phase, InSilixa and Cepheid 2nd line Xpert, two ‘lower tech’ tests at the last stages of laboratory validations, will be implemented in all countries that have established recruitment of retreatment patients. The InSilixa lab-on-chip assay, powered by a smartphone, is able to query 117 drug resistance conferring mutations at around $20 per test. The Cepheid Xpert 2nd line cartridge can be implemented in existing Xpert machines used for theXpert MTB/Rif assays. These two tests will be compared versus the Deeplex assay. Using the latest advances in DataTocare software developed by one of the project partners, molecular results will be communicated in real time to the National TB Programmes, so that MDR patients can swiftly start appropriate treatment. The added-value of this system will be evaluated as a pilot study in two sites. Lastly, once patients have initiated MDR treatment, they will be monitored for treatment success by faster alternative approaches to the WHO recommended monthly cultures: serial sputum samples will have Fluorescein DiAcetate vital stain microscopy and measurement of the bacterial load using the Xpert MTB/Rif. Together, these advances are expected to dramatically improve the currently dismal prognosis of MDR-TB in health systems in resource-poor settings. For the first year of the project, the study protocol was finalized and all study documents elaborated. The protocol has been submitted to ethical committees in all nine sites and ethical approval was obtained in all but two sites. Patient recruitment has started in one site (Rwanda). Project Website: DIAMA website.
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