Elucidation of Cellular Responses in Non-human Primates With Chronic Schistosomiasis Followed by Praziquantel Treatment

Abstract

For decades, mass drug treatment with praziquantel (PZQ) has been utilized to treat schistosomiasis, yet reinfection and the risk of drug resistance are among the various factors precluding successful elimination of schistosomiasis. Tractable models that replicate "real world" field conditions are crucial to effectively evaluate putative schistosomiasis vaccines. Herein, we describe the cellular immune responses and cytokine expression profiles under field conditions that include prior infection with schistosomes followed by treatment with PZQ. Baboons were exposed to Schistosoma mansoni cercariae through trickle infection over 5 weeks, allowed for chronic disease to develop, and then treated with PZQ. Peripheral blood mononuclear cells (PBMCs) were monitored for cellular immune response(s) at each disease stage and PZQ therapy. After initial infection and during chronic disease, there was an increase in non-classical monocytes, NK and NKT cells while the CD4:CD8 T cell ratio inverted from a 2:1 to 1:2.5. The cytokine expressions of PBMCs after trickle infections were polarized more toward a Th2 response with a gradual increase in Th1 cytokine expression at chronic disease stage. Following PZQ treatment, with the exception of an increase in B cells, immune cell populations reverted back toward naïve levels; however, expression of almost all Th1, Th2, and Th17 cytokines was significantly increased. This preliminary study is the first to follow the cellular immune response and cytokine expression profiles in a non-human primate model simulating field conditions of schistosomiasis and PZQ therapy, providing a promising reference in predicting the immune response to future vaccines for schistosomiasis.

In vivo assessment of the antischistosomal activity of curcumin loaded nanoparticles versus praziquantel in the treatment of Schistosoma mansoni

“…On the other www.nature.com/scientificreports/ hand, we could confirm that the PZQ treatment didn't show a complete eradication of worms, while most of the male and female worms were remain alive. A previous investigation revealed that at four weeks pi in mice groups treated with PZQ, there were some male worms still alive which agree with our findings 42,43 . Remarkably, the mono-treatment of Schistosomiasis with curcumin alone was less effective in reducing the worm burden (45.45%) compared to PZQ (72.72%).…”

“…On the other hand, we could confirm that the PZQ treatment didn’t show a complete eradication of worms, while most of the male and female worms were remain alive. A previous investigation revealed that at four weeks pi in mice groups treated with PZQ, there were some male worms still alive which agree with our findings 42 , 43 .…”

Schistosomiasis Pulmonary Arterial Hypertension

“…Non-human primates have been used to study schistosomiasis pathogenesis (100), and other groups have studied HIV-related PH in non-human primates (101), but to our knowledge there have been no studies of PH in non-human primates using A B FIGURE 5 | Mouse models (A). Cercariae infection model (B).…”

“…Non-human primates have been used to study schistosomiasis pathogenesis ( 100 ), and other groups have studied HIV-related PH in non-human primates ( 101 ), but to our knowledge there have been no studies of PH in non-human primates using schistosomiasis. Other animal models are also possible, and there is a report that PH can occur in schistosomiasis-infected hamsters ( 102 ).…”

Recent Advances and Methodological Considerations on Vaccine Candidates for Human Schistosomiasis

“…Following PZQ treatment, immune cell populations reverted back towards naïve pre-treatment levels with the exception of an increase in B cells; however, expression of Th1, Th2, and Th17 cytokines was significantly increased. The implications of such findings for vaccine studies in baboons and humans remain unclear (177).…”