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Host and Pathogen Determinants of TB Disease and Transmission in TanzaniaHost and Pathogen Determinants of TB Disease and Transmission in Tanzania

M Zwyer(3,4) J Hella(1) E Windels(5) M Sasamalo(1) S Borrell(3,4) D Portevin(3,4) K Reiter(3,4) T Stadler(5) L Quintana-Murci(2) J Fellay(6) S Gagneux(3,4) D Brites(3,4)

1:Ifakara Health Institute; 2:Institute Pasteur; 3:Swiss Tropical and Public Health Institute; 4:University of Basel; 5:ETH Zurich; 6:EPFL

The outcome of TB infection and disease is highly variable and known to be influenced by host, pathogen and environmental factors. How genomic variation in the Mycobacterium tuberculosis complex (MTBC) interacts with human genetic diversity in shaping these variable outcomes, however, has rarely been studied. Here, we analyzed the human and MTBC genomes from N=1,472 TB patients from Dar es Salaam, Tanzania. Our findings show that the TB epidemic in Dar es Salaam is driven by several genotypes of MTBC Lineages (L) 1, L2, L3 and L4. Phylodynamic modelling suggests that the most prevalent L1 strains have a reduced transmission rate compared to other strains. Yet, we also see that the overall fitness of L1 strains is similar to most other strains. These data suggest longer infectious period in patients infected with L1, raising the possibility of L1 being more likely to cause sub-clinical TB. When adding the human genomic data to our analyses, we find that a high proportion of “Western Bantu” ancestry in patients infected with the most common MTBC genotype in Dar es Salaam is protective against severe lung damage, suggesting a possible mechanism underlying the geographical distribution of some of the most prevalent MTBC genotypes in Africa. In conclusion, we show that i) the MTBC genotypes differ in their life-history traits, possibly reflecting differences in transmission strategies, and ii) the interaction between MTBC and human genomic diversity modulates disease TB outcome. Taken together, our findings might explain some of the phylogeographical characteristics of the human-adapted MTBC.

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