Mem Inst Oswaldo Cruz, Rio de Janeiro, VOLUME 121 | 2026
Research Articles

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

Sérvio Pontes Ribeiro1,2,+, Camila de Paula Dias1,2, Rafael Vieira Duarte2,4, Maria Fernanda Brito de Almeida2, Luccas Gabriel Ferreira Malta1, José Dilermando Andrade Filho3, Alexandre Barbosa Reis4, Marcos Horácio Pereira1, Carlos EV Grelle5, Jesus G Valenzuela6, Tiago Donatelli Serafim6, Nelder Figueredo Gontijo1

1Universidade Federal de Minas Gerais, Instituto de Ciências Biológicas, Departamento de Parasitologia, Laboratório de Fisiologia de Insetos Hematófagos, Belo Horizonte, MG, Brasil
2Universidade Federal de Ouro Preto, Instituto de Ciências Exatas e Biológicas, Núcleo de Pesquisa em Ciências Biológicas, Laboratório de Ecologia do Adoecimento e Florestas, Ouro Preto, MG, Brasil
3Fundação Oswaldo Cruz-Fiocruz, Instituto René Rachou, Grupo de Estudos em Leishmanioses, Belo Horizonte, MG, Brasil
4Universidade Federal de Ouro Preto, Escola de Farmácia, Departamento de Análises Clínicas, Núcleo de Pesquisa em Ciências Biológicas, Laboratório de Imunopatologia, Ouro Preto, MG, Brasil
5Universidade Federal do Rio de Janeiro, Departamento de Ecologia, Rio de Janeiro, RJ, Brasil
6National Institutes of Health, National Institute of Allergy and Infectious Diseases, Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, Rockville, MD, USA

DOI: 10.1590/0074-02760250190
4490 views 616 downloads
Print Email PDF
ABSTRACT

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.

key words: parasite-responsive landscapes American visceral leishmaniasis disease ecology insect vectors Lutzomyia longipalpis canids
REFERENCES
01. Karesh WB, Dobson A, Lloyd-Smith JO, Lubroth J, Dixon MA, Bennett M, et al. Ecology of zoonoses: natural and unnatural histories. Lancet. 2012; 380(9857): 1936-45. doi:10.1016/S0140- 6736(12)61678-X.
02. Murray KA, Preston N, Allen T, Zambrano-Torrellio C, Hosseini PR, Daszak P. Global biogeography of human infectious diseases. Proc Natl Acad Sci USA. 2015; 112(41): 12746-51. doi:10.1073/ pnas.1507442112.
03. Dutra DA, Poulin R, Ferreira FC. Evolutionary consequences of vector-borne transmission: how using vectors shapes host, vector and pathogen evolution. Parasitology. 2022; 149(13): 1667-78. doi:10.1017/S0031182022001378.
04. Antonovics J, Thrall P, Jarosz A, Stratton D. Ecological genetics of metapopulations: the Silene-Ustilago plant-pathogen system. In: Real L, editor. Ecological genetics. Princeton: Princeton University Press; 1994. p. 146-70.
05. Höckerstedt L, Numminen E, Ashby B, Boots M, Norberg A, Laine AL. Spatially structured eco-evolutionary dynamics in a host-pathogen interaction render isolated populations vulnerable to disease. Nat Commun. 2022; 13: 6018. doi:10.1038/s41467-022-33665-3.
06. Leggett HC, Buckling A, Long GH, Boots M. Generalism and the evolution of parasite virulence. Trends Ecol Evol. 2013; 28(10): 592-6. doi:10.1016/j.tree.2013.07.002.
07. Powell JR, Gloria-Soria A, Kotsakiozi P. Recent history of Aedes aegypti: vector genomics and epidemiology records. BioScience. 2018; 68(11): 854-60. doi:10.1093/biosci/biy119.
08. Rose NH, Sylla M, Badolo A, Lutomiah J, Ayala D, Aribodor OB, et al. Climate and urbanization drive mosquito preference for humans. Curr Biol. 2020; 30(18): 3570-3579.e6. doi:10.1016/j. cub.2020.06.092.9.
09. Price PW. General concepts on the evolutionary biology of parasites. Evolution. 1977; 31(2): 405-20. doi:10.1111/j.1558-5646.1977. tb01021.x.
10. Powell JR, Tabachnick WJ. History of domestication and spread of Aedes aegypti - A Review. Mem Inst Oswaldo Cruz. 2013; 108(Suppl. 1): 11-7. doi:10.1590/0074-0276130395.
11. Al-Ghafli H, Barribeau SM. Double trouble: trypanosomatids with two hosts have lower infection prevalence than single-host trypanosomatids. Evol Med Public Health. 2023; 11(1): 202-18. doi:10.1093/emph/eoad014.
12. Lainson R, Rangel EF. Lutzomyia longipalpis and the eco-epidemiology of American visceral leishmaniasis, with particular reference to Brazil - A Review. Mem Inst Oswaldo Cruz. 2005; 100(8): 811-27. doi:10.1590/S0074-02762005000800001.
13. Steverding D. The history of leishmaniasis. Parasit Vectors. 2017; 10: 82. doi:10.1186/s13071-017-2028-5.
14. Keesing F, Ostfeld RS. Impacts of biodiversity and biodiversity loss on zoonotic diseases. Proc Natl Acad Sci USA. 2021; 118(17): e2023540118. doi:10.1073/pnas.2023540118.
15. Perri AR, Feuerborn TR, Frantz LAF, Larson G, Malhi RS, Meltzer DJ, et al. Dog domestication and the dual dispersal of people and dogs into the Americas. Proc Natl Acad Sci USA. 2021; 118(6): e2010083118. doi:10.1073/pnas.2010083118.
16. Serpell JA. Commensalism or cross-species adoption? A critical review of theories of wolf domestication. Front Vet Sci. 2021; 8: 662370. doi:10.3389/fvets.2021.662370.
17. Petter F. L’origine des mammifères domestiques. In: La Vie des Mammifères. Paris: Bordas; 1972.
18. Nozais J-P. The origin and dispersion of human parasitic diseases in the Old World (Africa, Europe and Madagascar). Mem Inst Oswaldo Cruz. 2003; 98(Suppl. 1): 13-9.
19. Vilà C, Savolainen P, Maldonado JE, Amorim IR, Rice JE, Honeycutt RL, et al. Multiple and ancient origins of the domestic dog. Science. 1997; 276(5319): 1687-9. doi:10.1126/science.276.5319.1687.
20. Abbona CC, Lebrasseur O, Prevosti FJ, Peralta E, Venanzi LG, Frantz L, et al. Patagonian partnerships: the extinct Dusicyon avus and its interaction with prehistoric human communities. R Soc Open Sci. 2024; 11: 231835. doi:10.1098/rsos.231835.
21. Chavez DE, Gronau I, Hains T, Dikow RB, Frandsen PB, Figueiró HV, et al. Comparative genomics uncovers the evolutionary history, demography, and molecular adaptations of South American canids. Proc Natl Acad Sci USA. 2022; 119(34): e2205986119. doi:10.1073/pnas.2205986119.
22. Deane LM. Leishmaniose visceral no Brasil. Estudos sobre reservatórios e transmissores realizados no Estado do Ceará. Rio de Janeiro: Serviço Nacional de Educação Sanitária; 1956. 162 pp.
23. Lainson R, Dye C, Shaw JJ, MacDonald DW, Courtenay O, Souza AAA, et al. Amazonian visceral leishmaniasis - distribution of the vector Lutzomyia longipalpis (Lutz & Neiva) in relation to the fox Cerdocyon thous (Linn.) and the efficiency of this reservoir host as a source of infection. Mem Inst Oswaldo Cruz. 1990; 85(1): 135-7.
24. Leblois R, Kuhls K, François O, Schönian G, Wirth T. Guns, germs and dogs: on the origin of Leishmania chagasi. Infect Genet Evol. 2011; 11(6): 1091-5. doi:10.1016/j.meegid.2011.04.004.
25. Carreira JCA, Brazil RP, dos Santos CB, Silva AVM. Lutzomyia longipalpis breeding - a probable breeding substrate for Lutzomyia longipalpis in nature. Open J Anim Sci. 2018; 8: 370-80. doi:10.4236/ojas.2018.84028.
26. Obidziński A, Głogowski R. Changes of forest flora composition in vicinity of dens of red fox and sets of Eurasian badger. Pol J Ecol. 2005; 53: 197-213.
27. Forattini OP. Entomologia médica. Vol. 4. Psychodidae - Phlebotominae. Leishmanioses. Bartonelose. São Paulo: Edgard Blücher; 1973. 658 pp.
28. Bueno L, Isnardis A. Peopling central Brazilian plateau at the onset of the holocene: building territorial histories. Quat Int. 2018; 473: 144-60. doi:10.1016/j.quaint.2018.01.006.
29. Moreno-Mayar JV, Vinner L, Damgaard PB, de la Fuente C, Chan J, Spence JP, et al. Early human dispersals within the Americas. Science. 2018; 362(6419): eaav2621. doi:10.1126/science.aav2621.
30. Goldberg A, Mychajliw AM, Hadly EA. Post-invasion demography of prehistoric humans in South America. Nature. 2016; 532(7598): 232-5. doi:10.1038/nature17176.
31. Ferraz T, Villagran XS, Nägele K, Radzevičiūtė R, Lemes RB, Salazar-Garcíaet DC, et al. Genomic history of coastal societies from eastern South America. Nat Ecol Evol. 2023; 7(8): 1315-30. doi:10.1038/s41559-023-02114-9.
32. Souza JG, Mateos JA, Madella M. Archaeological expansions in tropical South America during the late Holocene: assessing the role of demic diffusion. PLoS One. 2020; 15(5): e0232367. doi:10.1371/journal.pone.0232367.
33. Silva MAC, Ferraz T, Couto-Silva CM, Lemes RB, Nunes K, Comas D, et al. Population histories and genomic diversity of South American natives. Mol Biol Evol. 2022; 39(1): msab339. doi:10.1093/molbev/msab339.
34. Prates L. Crossing the boundary between humans and animals: the extinct fox Dusicyon avus from a hunter-gatherer mortuary context in Patagonia (Argentina). Antiquity. 2014; 88: 1201-12.
35. Jansen DC, Cavalcanti LF, Lamblém HS. Mapa de potencialidade de ocorrência de cavernas no Brasil, na escala 1:2.500.000. RBEsp. 2012; 2(1).
36. Rocha MC, Costa LAF, James MJ. A GIS-based spatial analysis of the distribution of caves in Brazil. Braz Geogr J. 2019; 9: 149-62.
37. Pasquali AKS, Baggio RA, Boeger WA, Gonzalez-Britez N, Guedes DC, Chaves EC, et al. Dispersion of Leishmania (Leishmania) infantum in central-southern Brazil: evidence from an integrative approach. PLoS Negl Trop Dis. 2019; 13(8): e0007639. doi:10.1371/journal.pntd.0007639.
38. Somerfield PJ, Clarke KR, Gorley RN. Analysis of similarities (ANOSIM) for 2-way layouts using a generalised ANOSIM statistic, with comparative notes on PERMANOVA. Austral Ecol. 2021; 46(6): 911-26. doi:10.1111/aec.13059.
39. Hammer Ø. PAST: paleontological statistics reference manual. Version 4.13. Oslo: Natural History Museum, University of Oslo; 2023
40. Ready P. Epidemiology of visceral leishmaniasis. Clin Epidemiol. 2014; 6: 147-54. doi:10.2147/CLEP.S44267.
41. Baneth G, Nasereddin A, Abdeen Z, Jaffe CL. Leishmania tropica infection in wild and domestic canines. Parasit Vectors. 2014; 7(Suppl. 1): O27. doi:10.1186/1756-3305-7-S1-O27.
42. de Souza CSF, Calabrese KS, Abreu-Silva AL, Carvalho LOP, Cardoso FO, Dorval MEMC, et al. Leishmania amazonensis isolated from human visceral leishmaniasis: histopathological analysis and parasitological burden in different inbred mice. Histol Histopathol. 2018; 33(7): 705-16. doi:10.14670/HH-11-965.
43. Lainson R, Shaw JJ. Evolution, classification and geographical distribution. In: Peters W, Killick-Kendrick R, editors. The leishmaniases in biology and medicine. Vol. 1. Biology and Epidemiology. London: Academic Press; 1987. p. 1-120.
44. Bejarano EE, Uribe S, Rojas W, Vélez ID. Presence of Lutzomyia evansi, a vector of American visceral leishmaniasis, in an urban area of the Colombian Caribbean coast. Trans R Soc Trop Med Hyg. 2001; 95(1): 27-8. doi:10.1016/S0035-9203(01)90320-7.
45. Saraiva L, Silva RA, Rugani JMN, Pereira AAP, Rêgo FD, Lima ACVMR, et al. Survey of sand flies (Diptera: Psychodidae) in an environmentally protected area in Brazil. PLoS One. 2015; 10(8): e0134845. doi:10.1371/journal.pone.0134845.
46. Oliveira FE, Galati EAB, Oliveira AGD, Rangel EF, Carvalho BMD. Ecological niche modelling and predicted geographic distribution of Lutzomyia cruzi, vector of Leishmania infantum in South America. PLoS Negl Trop Dis. 2018; 12(7): e0006684. doi:10.1371/journal.pntd.0006684.
47. Carvalho MR, Valença HF, Silva FJ, Pita-Pereira D, Pereira TA, Britto C, et al. Natural Leishmania infantum infection in Migonemyia migonei (França, 1920) (Diptera: Psychodidae: Phlebotominae), the putative vector of visceral leishmaniasis in Pernambuco State, Brazil. Acta Trop. 2010; 116(1): 108-10. doi:10.1016/j.actatropica. 2010.03.009.
48. Lysenko AJ. Distribution of leishmaniasis in the Old World. Bull World Health Organ. 1971; 44(4): 515-20.
49. Feliciangeli MD. Natural breeding places of phlebotomine sandflies. Med Vet Entomol. 2004; 18(1): 71-80. doi:10.1111/j.0269- 283X.2004.0487.x.
50. Majumder SS, Paul M, Sal S, Bhadra A. Denning habits of freeranging dogs reveal preference for human proximity. Sci Rep. 2016; 6: 32014. doi:10.1038/srep32014.
51. Webb SD. The great American biotic interchange: patterns and processes. Ann Mo Bot Gard. 2006; 93(2): 245-57.
52. Costa PL, Dantas-Torres F, Silva FJ, Guimarães VCFV, Gaudêncio K, Brandão-Filho SP. Ecology of Lutzomyia longipalpis in an area of visceral leishmaniasis transmission in north-eastern Brazil. Acta Trop. 2013; 126(2): 99-102. doi:10.1016/j.actatropica. 2013.01.011.
53. Feathers JK, Kipnis R, Piló L, Arroyo-Kalin M, Coblentz D. How old is Luzia? Luminescence dating and stratigraphic integrity at Lapa Vermelha, Lagoa Santa, Brazil. Geoarchaeology. 2010; 25(3): 395-436. doi:10.1002/gea.20316.
54. Ribeiro SP. Evolutionary ecology of host-parasite interactions applied to human-evolved diseases [PhD thesis]. Belo Horizonte: Universidade Federal de Minas Gerais; 2023. 153 pp.
55. Gaspar M, Klokler D, DeBlasis P. Were Sambaqui people buried in the trash? Archaeology, physical anthropology, and the evolution of the interpretation of Brazilian shell mounds. In: Roksandic M, Souza SMM, Eggers S, Burchell M, Klokler D, editors. The cultural dynamics of Shell-Matrix sites. Albuquerque: University of New Mexico Press; 2014. p. 91-100.
56. Klokler D. A ritually constructed shell mound: feasting at the Jabuticabeira II site. In: Roksandic M, Souza SMM, Eggers S, Burchell M, Klokler D, editors. The cultural dynamics of Shell-Matrix sites. Albuquerque: University of New Mexico Press; 2014. p. 91-100.
57. Meggers BJ. Environmental limitation on the development of culture. Am Anthropol. 1954; 56(5): 801-24.
58. Utida G, Cruz FW, Santos RV, Sawakuchi AO, Wang H, Pessenda LCR, et al. Climate changes in Northeastern Brazil from deglacial to Meghalayan periods and related environmental impacts. Quat Sci Rev. 2020; 250: 106655. doi:10.1016/j.quascirev.2020.106655.
59. Schaan DP. The nonagricultural chiefdoms of Marajó Island. In: Silverman H, Isbell WH, editors. Handbook of South American archaeology. New York: Springer; 2008. p. 339-57.
60. Meggers BJ. The mystery of the Marajoara: an ecological solution. Amazoniana. 2001; 16: 421-40.
61. Silveira FT, Sousa Jr EC, Silvestre RVD, Vasconcelos dos Santos T, Sosa-Ochoa W, Valeriano CZ, et al. Comparative genomic analyses of New and Old World viscerotropic leishmanine parasites: further insights into the origins of visceral leishmaniasis agents. Microorganisms. 2022; 11(1): 25. doi:10.3390/microorganisms11010025.
62. Pacheco AS. A conquista do ocidente Marajoara: índios, portugueses e religiosos em reinvenções históricas. In: Schaan DP, Martins CP, editors. Muito além dos campos: arqueologia e história na Amazônia Marajoara. Belém: Gknoronha; 2010. p. 11-30.
63. Bettendorff JF. Crônica dos padres da Companhia de Jesus no Estado do Maranhão. Belém: FCPTN-SECULT; 1990.
64. Carson JF, Whitney BS, Mayle FE, Iriarte J, Prumers H, Soto JD, et al. Environmental impact of geometric earthwork construction in pre-Columbian Amazonia. Proc Natl Acad Sci USA. 2013; 110(29): 10497-502. doi:10.1073/pnas.1321770111.

Financial support: This work was supported by the CNPq (Grant/Award Numbers: 303680/2020-2, 442499/2023-0 and 402949/2022-6), FAPEMIG (Grant/Award Number: PPM-00792-18. Project “Applications of genomics in the context of OneHealth” - identifier RED-00181-23). This research was supported in part by the Intramural Research Program of the National Institutes of Health (NIH).
+ Corresponding author: serviopr@gmail.com | ORCID https://orcid.org/0000-0002-0191-8759
Received 24 July 2025
Accepted 08 October 2025

HOW TO CITE
Ribeiro SP, Dias CP, Duarte RV, de Almeida MFB, Malta LGF, Andrade Filho JD, et al. Holocene man-occupied caves and transformed wetlands as facilitating factors for Leishmania infantum in South America. Mem Inst Oswaldo Cruz. 2025; 120: e250190.

HANDLING EDITOR
Elisa Cupolillo | ORCID https://orcid.org/0000-0002-0620-3250

Our Location

Memórias do Instituto Oswaldo Cruz

Av. Brasil 4365, Castelo Mourisco 
sala 201, Manguinhos, 21040-900 
Rio de Janeiro, RJ, Brazil

Tel.: +55-21-2562-1222

This email address is being protected from spambots. You need JavaScript enabled to view it.

Support Program

logo iocb

01 news 18 01

faperj   cnpq capes

Site Map

Member Login