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Développement de méthodes pour le diagnostic, le contrôle, la surveillance de la tuberculose à bacilles ultra-résistants et des souches épidémiques Beijing

Abstract : MDR / XDR (multidrug and extensively resistant to tuberculosis) TB caused by Mycobacterium tuberculosis is still a global public health problem. The study and identification of mutations responsible for resistance are important factors for the control and surveillance of MDR / XDR TB. The expansion of the L2 / Beijing lineage, a family of strains originating from South-East of China (Guangxi) and potentially more virulent, complicates the control of this disease. In this context, we have developed TB-EFI and TB IS-NTF / RINT, two high-speed, multiplexed and high-throughput molecular methods ready to use (developed on the Luminex xMap system). We initiated the development of a molecular method by the selection of relevant molecular markers for the discrimination of Beijing strains by the MLPA technique. TB-EFI is a test that identifies frequent mutations (single nucleotide polymorphisms) in the genes associated with the resistance of Mycobacterium tuberculosis strains to second-line anti-TB drugs including Fluoroquinolone, Injectable, and first-line antituberculosis drug, Ethambutol. TB-EFI may be used in retrospective studies to monitor resistance in a population. The IS-NTF / RINT test is a test specific to Beijing strains that types the IS6110 insertion sequence within the NTF locus (Ancient / Modern) and detects the mutations responsible for the resistance of these strains to Rifampicin and Isoniazid (the two leading primary antibiotics). This test is of paramount importance for the identification and control of epidemic strains, but also for a vision on the evolution of the phenomenon of resistance in time and space. It is not very discriminating among Beijing strains. In view of complete and precise discrimination of the Beijing strains, we have proposed a set of SNPs that will be used for a technique that will be called MLPA-Beijing. In addition, these methods as well as spoligotyping on microbeads allowed us to carry out molecular epidemiological studies of tuberculosis in Kazakhstan, Papua New Guinea, Italy, Mozambique and Peru. The techniques developed in this thesis could contribute significantly to the control of XDR tuberculosis in hot-spot areas, and to the global monitoring of the evolution of Beijing strains especially epidemic MDR strains.
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Submitted on : Friday, November 30, 2018 - 12:06:08 PM
Last modification on : Saturday, September 12, 2020 - 3:14:57 AM
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  • HAL Id : tel-01940509, version 1


Jésutondin Bernice Mélaine Klotoe. Développement de méthodes pour le diagnostic, le contrôle, la surveillance de la tuberculose à bacilles ultra-résistants et des souches épidémiques Beijing. Santé publique et épidémiologie. Université Paris-Saclay, 2018. Français. ⟨NNT : 2018SACLS379⟩. ⟨tel-01940509⟩



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