Reduced efficacy of treatment of strongyloidiasis in HTLV-I carriers related to enhanced expression of IFN-gamma and TGF-beta1

Abstract

Strongyloidiasis, a human intestinal infection caused by Strongyloides stercoralis (S. stercoralis), is difficult to cure with drugs. In particular, a decrease of the efficacy of treatment has been reported in patients dually infected with S. stercoralis and human T-cell leukaemia virus type I (HTLV-I), both of which are endemic in Okinawa, Japan. However, the factors influencing this resistance remain unclear. In the present study, patients infected with S. stercoralis, with or without HTLV-I infection, were treated with albendazole, followed up for one year and separated into two groups, cured and non-cured. The cure rate of S. stercoralis was lower in HTLV-I carriers (P < 0.05). Serum levels of S. stercoralis-specific IgA, IgE, IgG, IgG1 and IgG4 antibodies were estimated, and a decrease of IgE (P < 0.05) and an increase of IgG4 (P < 0.05) were observed in the non-cured group, especially in HTLV-I carriers. RT-PCR of cytokines using peripheral blood mononuclear cells revealed that S. stercoralis patients with HTLV-I showed a high frequency of expression of IFN-gamma and TGF-beta1, whereas those without HTLV-I showed no expression of these cytokines. IFN-gamma- and TGF-beta1-positive HTLV-I carriers showed a decrease of IgE (P < 0.05), an increase of IgG4 (P < 0.01) and a lower cure rate (P < 0.01) compared with those who were negative for both cytokines. These results suggest that persistent infection with HTLV-I affected S. stercoralis-specific immunity and reduced therapeutic efficacy.

Fig. 1

Comparison of the expression of IFN-γ, TGF-β1, IL-4 and IL-13 among the patients with or without S. stercoralis or HTLV-I. Sixteen IFN-γ-positive and 17 TGF-β1-positive patients were observed among 27 patients co-infected with S. stercoralis and HTLV-I. There were no IFN-γ-positive and one TGF-β1-positive patient observed among 24 patients with S. stercoralis but not HTLV-I. Both IFN-γ and TGF-β1 were positive in all HTLV-I carriers without S. stercoralis (nine of nine), while very few expressions were found in normal controls (0 of 12 for IFN-γ and one of 12 for TGF-β1). Very few expressions and no significant differences were observed for IL-4 and IL-13 in all groups. Representative results are displayed. M, marker; –, negative control; +, positive control.