Impairment of theSchistosoma mansoni–Specific Immune Responses Elicited by Treatment with Praziquantel in Ugandans with HIV‐1 Coinfection

Abstract

We show that Ugandan adults coinfected with Schistosoma mansoni and human immunodeficiency virus type 1 (HIV-1) are able to mount S. mansoni-specific immune responses but that few such responses increase after treatment with praziquantel (PZQ). Levels of soluble worm antigen (SWA)-specific immunoglobulin (Ig) G1, IgG2, IgG3, IgG4, interleukin (IL)-4, and IL-5 increased significantly in HIV-negative participants after treatment with PZQ, whereas most soluble egg antigen-specific antibody responses and levels of interferon- gamma were unaltered. Only levels of SWA-specific IL-5 increased in HIV-1-coinfected participants after treatment. These deficiencies in immune responses may account for the previously reported increased susceptibility to infection and reinfection with S. mansoni in individuals coinfected with HIV-1.

Effect of praziquantel treatment of Schistosoma mansoni during pregnancy on intensity of infection and antibody responses to schistosome antigens: results of a randomised, placebo-controlled trial

“…These boosts in antibodies at six weeks post-treatment were consistent with those observed at five weeks post-treatment [36], three months post-treatment [37] and at six months post-treatment [27] among S. mansoni infected non-pregnant individuals in endemic areas. Similar increases in antibodies were recently reported following treatment among non-pregnant adults from a new focus of S. mansoni infection [38].…”

Treatment ofSchistosoma mansoniInfection Increases Helminth‐Specific Type 2 Cytokine Responses and HIV‐1 Loads in Coinfected Ugandan Adults

“…It is believed that such treatment-induced responses may be useful in generating protective antischistosomal immunity [9,25]. Studies have demonstrated that HIV-1 infection suppresses posttreatment cytokine responses, which may partly explain increased reinfection rates among HIV-1-infected adults [14,26,27]. In this study, concentrations of SWA-specific IL-5 and IL-13 and SEA-specific IL-5 increased significantly after treatment, as did the proportion of subjects with detectable SWA-specific IL-4, IL-5, and IL-13 and SEA-specific IL-5 responses; the absence of significant increases in posttreatment SEA-specific IL-4 and IL-13 responses may partly reflect smaller numbers of subjects but does accord with findings in HIV-1-negative subjects [9].…”

“…Alternatively, it may be a real effect of HIV-1 immunosuppression. Data showing failure to augment antibody responses in HIV-1-infected subjects suggest that some posttreatment type 2 responses are impaired [14]; presumably, mechanisms of eosinophil proliferation independent of-or requiring higher levels of-type 2 cytokines explain this impaired eosinophil production.…”

“…Damage to the worm tegument exposes antigens that induce strong type 2 immune responses, characterized by increased production of schistosome-specific interleukin (IL)-4, IL-5, and IgG; total IgE concentration; peripheral blood eosinophil counts; and histamine concentrations [8][9][10][11][12][13][14]. Such an increase in type 2 responses might be expected to affect the wider immune response, with suppressed type 1 cytokine responses and increased type 2 cytokine responses to unrelated antigens [8][9][10][11][12][13][14]. Thus, rather than improving immune function in coinfected adults, praziquantel treatment might be associated, at least transiently, with a loss of useful HIV-1-specific immune responses and acceleration of viral replication, leading to increased HIV-1 disease progression.…”

Gastrointestinal parasites in the immunocompromised

“…The authors suggest that this may lead to more rapid progression of HIV infection should a previously HIV-negative individual with schistosomiasis become infected with HIV. After treatment with praziquantel, HIV-positive Ugandans were unable to mount S. mansoni specific immunological responses, which may partly explain their increased susceptibility to reinfection [58].…”