Impact of combination chemotherapy with praziquantel and gentamicin or doxycycline on acute hepatic and intestinal schistosomiasis in BALB/c mice

Background and aims

Marked divergences in the immunological mechanisms that regulate the pathophysiology of acute and chronic schistosomiasis have a direct influence on pathological outcomes and antiparasitic chemotherapy responses at different stages of Schistosoma mansoni infection. In that way, this study evaluated the impact of combination antiparasitic chemotherapy, involving gentamicin (GEN) and doxycycline (DOX) in combination with praziquantel (PZQ) on the development of acute hepatic and intestinal schistosomiasis in mice.

Methods

BALB/cmice were randomized into five experimental groups, and the formation of hepatic and intestinal granulomas was evaluated by histopathological and histomorphometric analyses, quantification of hepatic parasite load, and biochemical parameters (ALT, AST, ALP, and albumin).

Main findings

PZQ + DOX combination potentiated hepatic granulomatous inflammation, diffuse fibrosis and ALT circulating levels, indicating greater morphofunctional liver damage. AST levels were increased in PZQ + GEN-treated animals. This response corroborated the histopathological findings, indicating an accelerated modulation towards the chronic phase as manifested by reduced granuloma size compared to infected untreated animals.

Conclusion

PZQ combination with DOX and GEN induced differential modulation of the granulomatous inflammation, with DOX aggravating this process and GEN exerting protective effects by accelerating schistosomiasis resolution in S. mansoni-infected mice.