Reduction in tissue egg load and maintenance of resistance to challenge in mice infected with Schistosoma mansoni, following combined treatment with praziquantel and an antifibrotic agent.
Antifibrotic therapy with beta-aminoproprionitrile (BAPN), when combined with praziquantel (PZQ) treatment of mice infected with Schistosoma mansoni, led to a marked change in the temporal pattern of parasite egg excretion. The rate of egg excretion was higher and terminated sooner and the tissue egg load was smaller in mice treated with BAPN and PZQ than in mice treated with PZQ alone. Some of the mice that received the combined treatment were challenged 2 or 5 weeks after PZQ treatment; they retained a high level of resistance to challenge, similar to that observed in untreated, infected mice. In contrast, mice given only PZQ were as susceptible to challenge as the uninfected control mice. The activity of peritoneal macrophages, as measured by their production of hydrogen peroxide, nitric oxide and tumour necrosis factor alpha in vitro, was only elevated in cells obtained from untreated, infected mice. These results demonstrate that modulation of granuloma formation by combined antifibrotic/PZQ therapy significantly changes the dynamics of egg granuloma formation and attenuates the host's resistance to challenge infection.
Giboda
M
M
San Juan Bautista School of Medicine, Puerto Rico.
Smith
J M
JM
Prichard
R K
RK
D000629:Aminopropionitrile / Q000627:therapeutic use*; D000818:Animals; D004359:Drug Therapy, Combination; D005243:Feces / Q000469:parasitology; D005260:Female; D006099:Granuloma / Q000517:prevention & control; D007422:Intestines / Q000469:parasitology; D008099:Liver / Q000469:parasitology; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010270:Parasite Egg Count; D011223:Praziquantel / Q000627:therapeutic use*; D012555:Schistosomiasis mansoni / Q000188:drug therapy* / Q000469:parasitology*; D013997:Time Factors
D000629:Aminopropionitrile; D011223:Praziquantel