Trabajo presentado en Applied Bioinformatics and Public Health Microbiology Cambridge, UK, 5-7 June 201

Alex Rosenthal

Andrei Gabrielian

Comas, Iñaki

Iza Khurtsilava

Moreno-Molina, Miguel

Natalia Shubladze

Nestan Tukvadze

Rusudan Aspindzelashvili

Sergo Vashakidze

Vilaplana, Cristina

Zaza Avaliani

Digital.CSIC

P56  High percentage of mixed infections in a high MDR-TB country identified from lung surgery samples Miguel Moreno-Molina (1), Natalia Shubladze (2), Andrei Gabrielian (3), Sergo Vashakidze (2), Iza Khurtsilava (2), Nestan Tukvadze (2), Rusudan Aspindzelashvili (2), Zaza Avaliani (2), Cristina Vilaplana (4), Alex Rosenthal (3), Iñaki Comas (1,5) 1) Biomedicine Institute of Valencia - CSIC (Spain), 2) National Center for TB and Lung Diseases of Georgia, 3) NIH/NIAID (USA), 4) UTE - Germans Trias i Pujol Institute (Spain), 5) CIBER in Epidemiology and Public Health (Spain) Mixed infections happen when at least two unrelated strains of the same pathogen can be detected in an individual. This heterogeneity does not occur due to within-host clonal evolution but from multiple transmission events to the recipient. Such phenomenon has been linked to worse clinical outcomes in Mycobacterium tuberculosis infections, as undetected strains presenting different antibiotic resistance profiles can lead to treatment failure. Also, TB vaccine development strongly depends on the capacity of a vaccine to mount a proper immune response to avoid infection with a virulent strain, a context in which estimating the frequency of mixed infections is invaluable. Here, we present a study of the extent of mixed infections in Georgia, a high burden setting in which up to 11% of new TB cases are MDR/RR-TB. We obtained NGS data from cultures derived from surgery and sputum samples from 15 patients. Combined with a customized bioinformatics pipeline we enhanced the detection of multiple strains as opposed to just using a clinical sputum sample, enabling us to identify an unprecedented number of mixed infection cases of up to ~45% of the patients analyzed. We also characterized transmission using 358 clinical samples and detected 26 transmission clusters, 9 of which contained a sample from our surgery patients' dataset, allowing us to trace the history of several mixed infections. Our results suggest that the magnitude of mixed infections in high-burden settings is likely to be underestimated when only using sputum samples. Our results have implications on clinical outcomes and to understand the impact of candidate vaccines. 

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High percentage of mixed infections in a high MDR-TB country identified from lung surgery samples

High percentage of mixed infections in a high MDR-TB country identified from lung surgery samples

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