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We compared age-related seroprevalence of Trypanosoma cruzi infection with history of vector control interventions and social and ecological changes in three historically endemic departments of Cordoba province, Argentina, covering an area of 42,600 km(2) of the Gran Chaco region. Using a cross sectional design, blood samples of 5240 people between 6 months and 40 years of age, living in 192 rural communities were analyzed to detect T. cruzi infection using ELISA tests, and confirmed with indirect immunofluorescent antibody test and indirect haemoagglutination. Overall seroprevalence was 5.4%, 7.9% and 7.5% in the north, northwest and west studied areas (average for all areas 6.95%). Seroprevalence for T cruzi increased with population age, especially in age classes older than 15 years of age. Communities of the north and west areas showed 0.59% seroprevalence for T. cruzi in children below 15 years of age, whereas children of the same age in the northwest region showed a seroprevalence of 3.08%. Comparative analyses indicate that vector control activities and land use changes during the last decades are the most likely causes of the overall reduction of T. cruzi prevalence. Results suggest that the vectorial transmission of T. cruzi has been strongly reduced and probably interrupted in the north and west areas, but it is still active in the northwestern rural settlements of Córdoba province., (Copyright 2009 Elsevier B.V. All rights reserved.)