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Paragonimus
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
Pham Ngoc Doanh, Haruhiko Maruyama, David Blair, Yukifumi Nawa
Many variants of ELISA have been described, such as indirect ELISA, two-site capture ELISA, and cystatin capture ELISA.40 Indirect ELISA is one of the most widely used methods. Various antigens have been used to detect specific antibodies in patient serum. These include crude antigen extracts of adult or juvenile worms, excretory-secretory products, recombinant peptides, and various purified or partially purified antigens including cysteine proteases or egg extracts of Paragonimus worms. Excretory-secretory antigens provided higher sensitivity than did somatic antigens (100% as opposed to 91.3%).74 Several cysteine proteases of P. westermani purified from crude somatic extracts of adult worms have been used for immunological tests, such as the cruzipain-like cysteine protease (Pw28CCP).75 Subsequently, Pw28CCP was cloned, and the recombinant protein was expressed. The protease is useful for differential diagnosis of active paragonimiasis from chronic calcified infection.75 Recently, a synthetic peptide has been applied for detection of IgG4 antibody.76
Animal models for the study of innate immunity: protozoan infections in fish
Published in G. F. Wiegertjes, G. Flik, Host-Parasite Interactions, 2004
Maaike Joerink, Jeroen P.J. Saeij, James L. Stafford, Miodrag Belosevic, Geert F. Wiegertjes
Recently, more information on the trypanosome molecules responsible for a preferential stimulation of alternatively activated-type macrophages has become available. Cruzipain (syn. cruzain), a highly immunogenic glycoprotein of about 52–58 kDa with a highly mannose glycosylated C-terminal domain is a major T. cruzi antigen found in every developmental form of the parasite. Giordanengo and co-authors (2002) found an increase of urea associated with a decrease in nitrate levels after injection of cruzipain, suggesting this cysteine protease preferentially up-regulates the arginase pathway. Macrophages from immune mice cultured with cruzipain showed high urea levels but no increased nitrite levels. Cruzipain was found to directly activate macrophages to increase arginase activity, possibly interacting through the mannose receptor. For Cryptobia salmositica, a close relative of T. borreli, a cysteine protease with an important role in protein metabolism for the parasite has recently been identified. The chemical properties (e.g. molecular weight, substrate and inhibitor specificity, pH optimum) were found similar to cysteine proteases found in, for example, T. cruzi (Zuo and Woo, 1998). This suggests that the presence of cysteine proteases could be a general feature of kinetoplastid parasites and opens possibilities for isolating and testing the supposedly superior ability of ‘danilewskyipain’ versus ‘borrelipain’ to induce arginase activity in carp macrophages. We aim to use our in vitro culture system for macrophages (IVDHKM, 27°C) to test the ability of T. borreli and T. danilewskyi to induce either nitric oxide or arginase activity in carp macrophages.
Are patents important indicators of innovation for Chagas disease treatment?
Published in Expert Opinion on Therapeutic Patents, 2023
Andrea Pestana Caroli, Felipe R. P. Mansoldo, Veronica S. Cardoso, Celso Luiz Salgueiro Lage, Flavia L. Carmo, Claudiu T Supuran, Alane Beatriz Vermelho
The patent EP2225196A1 [55] corresponds to nitrile-containing inhibitors derivatives with action against cysteine peptidases from Trypanosoma cruzi, African trypanosomiasis, and Leishmaniasis. Some patents were lapsed or discontinued concerning the peptidases target, such as the US20090247471A1 [56]. A recent systematic review of the literature [57] about the efficacy of thiazolidine and its imidazolidine derivatives against amastigotes of Trypanosoma cruzi was published. It was demonstrated that the compound 2-Iminothiazolidin-4-one 18 was effective with better results than benznidazole against amastigotes which are prevalent in the chronic phase of CD. This compound’s action mechanism is probably the inhibition of cruzipain (cysteine peptidase) and structural modification in the parasite not yet identified. In this context, the patent WO2012119212A1 [58] proposes using imidazolidine and thiazolidine compounds to treat Chagas disease.
Oxidative stress implications for therapeutic vaccine development against Chagas disease
Published in Expert Review of Vaccines, 2021
Subhadip Choudhuri, Lizette Rios, Juan Carlos Vázquez-Chagoyán, Nisha Jain Garg
T. cruzi expresses cruzipain in all of its developmental stages, and cruzipain is shown to be essential for amastigote replication and parasite virulence [127,128]. T. cruzi also expresses a papain-like cysteine protease inhibitor, Chagasin, to fine-tune the proteolytic functions of cruzipain during parasite differentiation and invasion [129]. Cerny et al [130] showed the therapeutic potential of cruzipain encoding DNA, delivered with granulocyte macrophage colony stimulating factor (GM-CSF) intramuscularly or with Salmonella delivery system orally in mice infected with T. cruzi. Authors noted that cruzipain DNA vaccine adjuvanted with GM-CSF encoding plasmid or Salmonella reduced the acute parasite burden, mortality, and cardiac injury markers and enhanced the antigen-specific IgG response [130]. In another study, therapeutic potential of DNA combining cruzipain and Chagasin was tested. The DNAs of both antigens and GM-CSF adjuvant were orally administrated using an attenuated Salmonella strain in acutely infected mice. The bi-component therapy was found to be better than either of the mono-component therapy in eliciting antigen- and parasite-specific antibodies and IFN-γ secretion by lymphocytes and provided rapid control of acute parasitemia and decreased the tissue damage in chronic stage of the infection [129,131,132] (Table 1).
The use of qPCR in human Chagas disease: a systematic review
Published in Expert Review of Molecular Diagnostics, 2019
Luciana Hagström, Ana Luisa Pereira Marques, Nadjar Nitz, Mariana Machado Hecht
The standard protocols used to detect antibodies anti-T. cruzi are Enzyme-linked immunosorbent assays (ELISA), indirect hemagglutination and indirect immunofluorescence [9]. These tests have different principles of antibody recognition, improving the diagnosis of T. cruzi infection. Although their routine application, some problems are quite frequent in serological diagnosis, notably cross-reaction [10,11], which is more frequent using polyclonal antisera. A common cause of cross-reactivity is molecular mimicry between parasite- and self-epitopes. In this regard, several T. cruzi antigens (e.g. cruzipain and shed acute phase antigen – SAPA) are similar to host proteins, producing false diagnosis in Chagas disease screening serological assays [12]. Moreover, the previous infection with other parasites, such as the trypanosomatid T. rangeli, Leishmania spp or the apicomplexa Plasmodium spp, can also result in misdiagnosis. According to T. cruzi antigens source (crude extracts or recombinant proteins), the possibility of cross-reaction may increase or decrease [12].