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Title: Immunomodulation by isometamidium (Samorin®) enhances prophylaxis against Trypanosoma congolense infection
Author: Choongo, Kennedy
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1997
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Pre-infection results showed a significant increase in IFN-γ production by sheep PBMC 14 to 21 days post ISMM administration when cultured with live trypanosomes, while cultures from the control group were negative. No significant amounts of IFN-γ were detected in all groups during the infection period. Significant differences between the control and prophylactic groups in PBMC proliferative responses to trypanosomes were observed from 21 days after ISMM treatment until about 21 days post infection when cell viability in both groups significant dropped below the normal level. Increases in B-cells in the control and treated groups 14 to 21 days after infection were significantly higher than in the prophylactic groups. A significant decrease in CD4+ T-cells was recorded in the control and treated groups 14 to 21 days post infection, while in the prophylactic group no changes were observed. The ratio of CD4+:CD8+ T-cells significantly dropped 21 days post infection in the control and treated groups, while it increased in the prophylactic group. There were no differences in CD8+, CD5+ and γδ+ T-cell responses. Trypanosome specific IgG antibodies in serum of the prophylactic group were significantly higher than those in the control, while they were absent in the treated group. Following BCG vaccination, in vivo proliferation in the ISMM treated group was significantly less than the BCG control while the ratio of CD4+:CD8+ T-cells was higher in the ISMM group. Also, ISMM prevented a decrease in the percentage of CD4+ T cells and minimised a decrease in CD5+ and γδ+ cells. However, it had no effect on CD8+ T cells, B cells, and PPD skin test. ISMM was trypanostatic in vitro and T cell suppression decreased the prepatent period in prophylactically treated mice. In conclusion, ISMM prophylaxis modified cellular and antibody responses to T. congolense infection probably via the IFN-γ and IL-12 feedback mechanisms. This immunomodulation enhanced prophylaxis and appears not be specific to trypanosome antigens since similar changes were observed following BCG vaccination, although the end result of an infection may depend on the type of host animal and nature of antigen.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available