Reduced efficacy of treatment of strongyloidiasis in HTLV-I carriers related to enhanced expression of IFN-γ and TGF-β1

Abstract

SUMMARYStrongyloidiasis, 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-g and TGF-b1, whereas those without HTLV-I showed no expression of these cytokines. IFN-g-and TGF-b1-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.

Strongyloides stercoralis infection in the immunocompromised host

“…Relapsing Strongyloides infection despite treatment should prompt consideration of HTLV-1 infection [27]. HTLV-1 enhances susceptibility to Strongyloides infection as a result of diminished immunoglobulin E levels and a bias toward a T helper 1 rather than T helper 2 immune response [28]. In turn, Strongyloides may facilitate HTLV-1 virus replication, as suggested by a measurable decline in HTLV-1 messenger RNA levels in one patient after treatment with ivermectin [29].…”

“…Ivermectin has superior efficacy when compared with albendazole, the cure rates of which range from 45% to 77% [42,44]. Decreased cure rates have been observed in patients with HTLV-1 coinfection regardless of treatment regimen [28]. The US Centers for Disease Control and Prevention has recommended presumptive predeparture treatment of refugees at risk for Strongyloides [3•].…”

Five Cases of Recurrent Meningitis Associated with Chronic Strongyloidiasis

“…2,3 Previous reports suggested patients with coinfection with strongyloidiasis and HTLV-1 may be associated with decreased IgE levels and a higher rate of refractoriness to albendazole treatment. 13,14 We found that all of our patients were seropositive for HTLV-1 infection, however, no other concomitant risk factors were observed.…”

Clinical conditions associated withintestinal strongyloidiasis in Rio de Janeiro, Brazil

“…This association has been reported in Brazil by Furtado et al (17) . The synergistic effects of co-infection with HTLV and S. stercoralis, which have been demonstrated, suggest that co-infected patients exhibit elevated parasite burdens and HTLV-1 proviral loads (18) (19) (20) . With respect to the interaction between strongyloidiasis and acquired immunodefi ciency syndrome (AIDS), our study indicated that the frequency of HIV infection tended to be higher among S. stercoralis-positive patients than among S. stercoralisnegative patients but that this difference was not statistically signifi cant.…”