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Chagas disease is a neglected tropical disease strongly associated with low socioeconomic status, affecting nearly 8 million people–mainly Latin Americans. The current infection risk is based on acute case reports, most of which are typically associated with oral transmissions. In the semi-arid region of Northeastern Brazil, serious outbreaks of this transmission type have surged in the last years. One of those occurred in the city of Marcelino Vieira (2016), in the state of Rio Grande do Norte. Rural residents of four municipalities surrounding Marcelino Vieira ingested sugar cane juice–which was probably ground with Trypanosoma cruzi infected insects. The structure of domiciliary unities (DUs) in the rural area of Marcelino Vieira was investigated to better understand the factors related to the outbreaks in this region–which was combined with entomological indicators. We found triatomines (mainly Triatoma brasiliensis) in 54%(36/67) of DUs and all rocky outcrops inspected (n= 7). Overall, 26%(119/458) of examined T. brasiliensis were infected by T. cruzi in artificial ecotopes, with almost the same prevalence in the sylvatic environment (23%; 35/154). The local variation in T. cruzi prevalence (variating from 0%-100%) was highly correlated with the presence of some ecotopes where the insects were found; and we identified those linked to high natural triatomine infection prevalence by T. cruzi (mainly wood/tile/brick piles). Ninety-five percent of people interviewed recognized the triatomines and knew the classic route (vector-borne) of transmission of disease. However, only 7.5% admitted knowledge that Chagas disease can also be acquired orally …