Holocene man-occupied caves and transformed wetlands as facilitating factors for Leishmania infantum in South America

BACKGROUND: In the Holocene, South American humans transformed large extensions of the continent, especially in cave ecosystems. Such transformations produced predictable eutrophic habitats that could have attracted foxes and further favored the adaptation of Lutzomyia longipalpis, insect vector of American Visceral Leishmaniosis (AVL), to human-contaminated habitats. OBJECTIVES: Here we present spatial analyses on the distribution of caves, Holocene human populations, the present-days main wild reservoirs of Leishmania infantum, Cerdocyon thous and Lycalopex vetulus, and the vector Lu. longipalpis in Brazil. METHODS: The presence or absence of Lu. longipalpis in function of cave abundance, based on coordinates of all recorded samples (Fiocruz and GBIF database and literature), and cave locations taken from ICMBio/CECAV database, were tested by contingency table. The overlap in the distribution of Lu. longipalpis, C. thous and L. vetulus with humans from Holocene was tested by permutational multivariate analysis of variance (PERMANOVA) from a nonmetric multidimensional scaling (NMDS), using published archaeological data on human demography and ICMBio's data on caves and foxes. FINDINGS: Caves are present in 18% of Brazilian municipalities, and Lu. longipalpis were significantly more frequent in these places than in municipalities without caves. Native humans and foxes have broader distributions than caves but co-occurred with Lu. longipalpis in cave-ecosystems. MAIN CONCLUSION: The most relevant implication of our findings is that visceral leishmaniasis should be considered a long-term human related disease, associated with few sandfly species well adapted to our modified, and heavily contaminated, environments.