Effect of combined praziquantel and recombinant glutathione S-transferase on resistance to reinfection in murine Schistosomiasis mansoni.
This study was undertaken to evaluate the effect of recombinant Schistosoma mansoni-26 Glutathione S-transferase (rSm 26 GST) or soluble egg antigen (SEA) alone and in addition to praziquantel (PZQ) on the state of resistance to S. mansoni reinfection. The associated changes in the immune responses were evaluated. The experimental group of mice were injected intravenously before S. mansoni infection (80 cercariae/mouse) either with rSm26 GST (1 microgx4) or SEA (10 microgx4) in addition to PZQ (2x500 mg/kg) administered 6 weeks post-infection. Seven control groups were used, three of them were the infected (80 cercariae/mouse), the challenged (240 cercariae/mouse) and the infected challenged controls (80+240 cercariae/mouse). The rest of the four groups were the treated controls receiving: the GST-Lyzate, rSmGST, SEA and PZQ in the same doses and at the same timings. Challenge infection was conducted for all the groups 8 weeks post-infection. Animals were sacrificed 3 weeks post-challenge. After sacrifice animals were perfused and percentage resistance to reinfection was calculated. Immune responses were assessed by the measurement of hepatic granuloma diameter, intralesional T-cell phenotypes and serum immunoglobulin isotypes. The highest percentage of resistance to reinfection was observed in rGST-treated group while the lowest percentage of resistance was detected in PZQ-treated group. Whereas in mice receiving combined rGST or SEA and PZQ, percentage resistance to reinfection was significantly higher than that in PZQ treated mice. The remarkable reduction in granuloma diameter in rGST-treated group with or without PZQ was associated with decrease in the intralesional L(3)T(4)(+) and increase in Lyt(2)(+) T-cell phenotypes. However, no special relationship was observed between the percentage of resistance and the changes in granuloma diameter or intralesional T-cell phenotypes. The increase in percentage resistance to reinfection was found accompanied by increased anti SWAP IgE. Combined rGST and PZQ provided the complementary goals of improved state of resistance to reinfection 'which was compromized after cure with PZQ' and the maximal reduction in granuloma diameter.
Botros
S S
SS
Pharmacology, Parasitology and Immunology Departments, Theodor Bilharz Institute, P.O. Box 30, Imbaba, 12411, Guiza, Egypt.
Makary
E A
EA
Ahmed
K M
KM
Ibrahim
A M
AM
Nashed
N N
NN
El-Nahal
H M
HM
Doughty
B L
BL
Hassanein
H I
HI
D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage*; D000909:Antibodies, Helminth / Q000097:blood; D004359:Drug Therapy, Combination; D005982:Glutathione Transferase / Q000008:administration & dosage*; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000145:classification; D016130:Immunophenotyping; D051379:Mice; D008810:Mice, Inbred C57BL; D011223:Praziquantel / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage; D012008:Recurrence; D012555:Schistosomiasis mansoni / Q000188:drug therapy* / Q000276:immunology
D000871:Anthelmintics; D000909:Antibodies, Helminth; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D007073:Immunoglobulin E; D011223:Praziquantel; D005982:Glutathione Transferase