Coinfecção Schistosoma-Leishmania: análise espacial de regiões coendêmicas e impacto da esquistossomose mansoni na leishmaniose tegumentar experimental

Abstract

Schistosomiasis and leishmaniasis are two highly important diseases with overlapping transmission areas. However, there are only a few studies approaching the occurrence and possible impacts of Schistosoma-Leishmania co-infections. There is evidence that this co-infection leads to worse clinical outcomes, affects the immune response, and reduces treatment effectiveness. Therefore, the present study aims to identify regions co-endemic for schistosomiasis and tegumentary leishmaniasis and evaluate the effects of the previous S. mansoni infection on the immunopathogenesis and parasitism of L. amazonensis. To determine countries where Schistosoma-Leishmania co-infections are more likely to occur, an endemicity map was constructed based on data from The Global Health Observatory in 2022. Forty countries were considered co-endemic, 23 of which presented high level of schistosomiasis transmission. For a regional analysis, an ecological study using analyses of indicators of spatial association was conducted on confirmed cases of tegumentary leishmaniasis and schistosomiasis in Minas Gerais, between 2013 and 2017, obtained from SINAN and SISPCE databases. Spatial correlation analyses between the two diseases identified 61 municipalities as having concomitantly high incidences, particularly in the Caratinga microregion. This study allowed the identification of areas with a higher potential for co-endemicity, towards which health authorities should direct their efforts. To evaluate the impacts of the experimental co-infection, BALB/c mice were co-infected with L. amazonensis 8 weeks after S. mansoni infection. Weight, footpad thickness and mortality were evaluated weekly for 10 weeks post-co-infection, and organs were harvested for analysis. The co-infection induced a more pronounced hepatomegaly, as well as less footpad swelling with higher L. amazonensis parasite load. In footpad homogenate and popliteal-lymph node cell culture of co-infected mice, Th1 cytokine levels were maintained, and IL-5 and IL-10 concentrations were increased in relation to mice with only leishmaniasis. Histopathological analysis of footpads revealed larger and more numerous areas of necrosis in co-infected mice, along with more abundant amastigotes. To better describe macrophage function, peritoneal cells from non-infected mice and mice 8 weeks post-S. mansoni infection were transferred to mice infected with L. amazonensis, both reducing lesion thickness compared with the control. Therefore, the previous infection with S. mansoni can alter the immune microenvironment in the L. amazonensis infection site, leading to increased tissue loss and amastigote proliferation, as well as worsening liver disease.