A research project
The 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).
This project is part of the EDCTP2 programme supported by the European Union
Summary of the Project
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 severals 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 is built on the continuous surveillance of TB retreatment patients for rifampicin resistance. Nine africans partners are involved in this project such are Benin, Cameroon, Democratic Republic of Congo, Ethiopia, Guinea, Mali, Nigeria, Rwanda and Senegal.
Some 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 severals 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, sputa are shipped for the Deeplex® Myc-TB assay, for comparison against phenotypic Drug Susceptibility Testing (pDST) and Whole Genome Sequencing (WGS), the reference methods for detecting resistance to 1st and 2nd line anti-TB drugs.
In a second phase, MolBio Truenat™ and Cepheid 2nd line Xpert, two ‘lower tech’ tests are being implemented in some countries that have established recruitment of retreatment patients. The TrueNat Molbio test is a micro chip based real-time PCR assay that is able to detect mutations in three 2nd line antituberculosis drugs and can work on rechargeable battery. The Cepheid Xpert 2nd line cartridge can be implemented in existing Xpert machines used for the Xpert MTB/Rif assays and detect resistance to 6 anti tuberculosis drugs. These two tests will be compared versus the Deeplex assay, pDST and WGS.
The Cepheid Xpert 2nd line cartridges testing is ongoing in DIAMA sites while MolBio TrueNat testing is planned to start in the following weeks.
Using the latest advances in DataTocare software developed by one of the project partners, molecular results are communicated in real time to the National TB Programmes, so that MDR patients can swiftly start appropriate treatment. The added-value of this system is evaluated as a pilot study in Benin.
Lastly, once patients have initiated MDR treatment, they are monitored for treatment success by faster alternative approaches to the WHO recommended monthly cultures: serial sputum samples 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.