DIAgnostics for Multidrug Resistant Tuberculosis in Africa
DIAgnostics for Multidrug Resistant Tuberculosis in Africa
Recent advances in molecular diagnostics of tuberculosis, especially the GeneXpert
 Mycobacterium tuberculosis/Rifampicin test have reduced the time to diagnose Rifampicin
 Resistant Tuberculosis (RR-TB) but only rifampicin resistance is diagnosed, leading to
 presumptive diagnosis of resistance to isoniazid and maybe other drugs. Thus in low and
 middle income countries, most drug sensitivity testing relies on phenotypic drug resistance
 testing, which takes up to 4 months. In addition, currently, culture on monthly sputum
 samples is recommended by the World Health Organization for follow-up of Rifampicin Resistant
 Tuberculosis patients under treatment. Unfortunately, culture is often not locally available
 and samples need to be transported from field to culture laboratories. The associated
 transport delays lead to high rates of contamination and false negative culture, particularly
 in laboratories in low resource settings. Many gaps for the diagnosis and management of RR-TB
 patients still need to be addressed and the DIAMA project (DIAgnostics for Multidrug
 resistant tuberculosis in Africa) study aims to address some of them.
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. Building on existing networks and research collaborations previously
 funded by the European & Developing Countries Clinical Trials Partnership (EDCTP), this
 project involved partners in West, Central, and East Africa. It aims to evaluate and
 implement rapid and accurate molecular tests for several anti Tuberculosis drugs, to replace
 the current dependency on phenotypic drug resistance testing, which takes up to 4 months and
 is technically so demanding that few laboratories can perform it correctly.

 The project builds on the continuous surveillance of Tuberculosis 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 several key anti
 tuberculosis drugs. Partners are recruiting all patients with rifampicin resistant
 Tuberculosis, and a subset of those with rifampicin sensitive Tuberculosis. In a first phase,
 sputum will be shipped for the Deeplex assay, for comparison against phenotypic DST, the
 reference method for detecting resistance to 1st and 2nd line drugs. In addition, since Whole
 Genome Sequencing is the "reference" of molecular tests, Deeplex assay will also be validated
 again this test. In a second phase, Cepheid 2nd line Xpert and Molbio Truenat test, two
 'lower tech' tests at the last stages of laboratory validations, will also be validated. The
 Cepheid Xpert 2nd line cartridge can be implemented in existing Xpert machines used for the
 Xpert MTB/Rif assays. These tests will be compared versus the Deeplex assay and versus WGS

 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 Tuberculosis Programmes,
 so that Multi Drug Resistant Tuberculosis patients can swiftly start appropriate treatment.
 The added-value of this system will be evaluated as a pilot study in some 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 (FDA) vital stain microscopy, measurement of
 the bacterial load using the Xpert MTB/Rif as well as precursor of ribosomal RNA measurement
 (pre-rRNA).

 Together, these advances are expected to dramatically improve the currently dismal prognosis
 of MDR-TB in health systems in resource-poor settings.
Inclusion criteria:

 -  Being ≥ 15 year old

 -  Having a positive test on GeneXpert (M. tuberculosis) with or without resistance
 detected to rifampicin

 -  Willing and able to provide written informed consent, or for minors: assent from and
 consent from a legal representative

 Exclusion Criteria: None