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Etudes descriptive, épidémiologique, moléculaire et spatiale des souches Mycobacterium tuberculosis circulant à Antananarivo, Madagascar

Abstract : For improving the fight against tuberculosis in Madagascar, we decided to conduct studies on the analysis of the diversity and spatio-temporally distribution of BK genotypes circulating in Madagascar for analyzing the TB transmission mode and the potential origins of Malagasy TB. More specifically, It is to study the genetic diversity and distribution of genotypes of M. tuberculosis strains in the country to assess the transmission level of the disease and to identify the potential sources of Malagasy TB; secondly, to study the diversity of the endemic strain of Madagascar, SIT109, in order to assess the transmission level of the strain inside the island and its level of evolution; and third, to identify TB transmission areas by combining spatial analysis and genotyping, starting with a pilot study in the capital.To achieve this, 1014 BK representative of Madagascar isolated in 2005 to 2007 were typed by the spoligotyping. Defined genotypes were used to estimate the TB transmission level and the identification of potential sources of malagasy TB; after, 156 endemic BK from Madagascar bearing the identity SIT109 were typed by the MIRU-VNTR (Mycobacterial Interspersed Repetitive Units – Variable Interspersed Repeatitive Units) method to study their diversity, their evolution level and the level of TB transmission at a single strain; and finally, 523 patients were recruited in Antananarivo in 2013 in order to type by spoligotyping their BK, to identify from their genotype those that are potentially associated with recent transmission cases and to analyze their spatial clustering by the Kulldorff method.The results showed a high genetic diversity of BK circulating in the country with a predominance of two strains, “East African Indian and “Tuscan”; a particular distribution of BK genotypes in the capital compared to the other provinces and particular similarities of the BK circulating with countries such as the USA, France, Italy, Denmark, Saudi Arabia or the Netherlands; a high variety of SIT109 strains and their distribution throughout the country; as well as four TB cases associated with recent transmission spatial clusters in the capital.This study allowed us to determine that the TB transmission in Madagascar is still very active and it is done on a very large scale, a small part of TB in Madagascar could be imported by the origin populations but the majority of cases is due to relatively recent importations of BK from several regions of the world. Twelve Fokontany in the capital corresponds to TB high risk transmission areas and need special attention to those responsible for the control of TB in Madagascar and finally the method combining genotyping and spatial analysis allows the detection of these high risk areas and could be used for the “Programme National de Lutte contre la TB” as a decision tool for orientation of the TB fight strategies throughout Madagascar
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Noël Harijaona Ratovonirina. Etudes descriptive, épidémiologique, moléculaire et spatiale des souches Mycobacterium tuberculosis circulant à Antananarivo, Madagascar. Médecine humaine et pathologie. Université Paris-Saclay; Université d'Antananarivo; Institut Pasteur (Tananarive), 2017. Français. ⟨NNT : 2017SACLS527⟩. ⟨tel-01784738⟩

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