Schistosoma haematobium , S. intercalatum , S. japonicum , S. mansoni , and S. rodhaini in mice: relationship between patterns of lung migration by schistosomula and perfusion recovery of adult worms

Rheinberg, Christian E.; Moné, Hélène; Caffrey, Conor R.; Imbert-Establet, D.; Jourdane, J.; Ruppel, Andreas

doi:10.1007/s004360050407

Cited by 44 publications

(31 citation statements)

References 23 publications

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“…The length of time required for this migration depends on the species of schistosome, but for S. mansoni it is nominally 14 d [28,29]. By day 49 p.i., at the time of worm recovery, male and female worms have matured and paired, and eggs are found in the liver, intestine, and feces [30].…”

Section: Resultsmentioning

confidence: 99%

Schistosomiasis Mansoni: Novel Chemotherapy Using a Cysteine Protease Inhibitor

et al. 2007

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BackgroundSchistosomiasis is a chronic, debilitating parasitic disease infecting more than 200 million people and is second only to malaria in terms of public health importance. Due to the lack of a vaccine, patient therapy is heavily reliant on chemotherapy with praziquantel as the World Health Organization–recommended drug, but concerns over drug resistance encourage the search for new drug leads.Methods and FindingsThe efficacy of the vinyl sulfone cysteine protease inhibitor K11777 was tested in the murine model of schistosomiasis mansoni. Disease parameters measured were worm and egg burdens, and organ pathology including hepato- and splenomegaly, presence of parasite egg–induced granulomas in the liver, and levels of circulating alanine aminotransferase activity as a marker of hepatocellular function. K11777 (25 mg/kg twice daily [BID]), administered intraperitoneally at the time of parasite migration through the skin and lungs (days 1–14 postinfection [p.i.]), resulted in parasitologic cure (elimination of parasite eggs) in five of seven cases and a resolution of other disease parameters. K11777 (50 mg/kg BID), administered at the commencement of egg-laying by mature parasites (days 30–37 p.i.), reduced worm and egg burdens, and ameliorated organ pathology. Using protease class-specific substrates and active-site labeling, one molecular target of K11777 was identified as the gut-associated cathepsin B1 cysteine protease, although other cysteine protease targets are not excluded. In rodents, dogs, and primates, K11777 is nonmutagenic with satisfactory safety and pharmacokinetic profiles.ConclusionsThe significant reduction in parasite burden and pathology by this vinyl sulfone cysteine protease inhibitor validates schistosome cysteine proteases as drug targets and offers the potential of a new direction for chemotherapy of human schistosomiasis.

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Section: Resultsmentioning

confidence: 99%

Schistosomiasis Mansoni: Novel Chemotherapy Using a Cysteine Protease Inhibitor

et al. 2007

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“…It has been suggested that the rapid migration and extended host range of S. japonicum are due to distinct cercarial enzymes which facilitate rapid passage through the mammalian host (Ruppel et al, 2004;Chlichlia et al, 2005). Conversely, studies of lung migration in the mouse model show that S. haematobium is slower in its migration to, and egress from, the lung than other species (Rheinberg et al, 1998). Finally, the pre-patent period of infection and the associated host immune response to worm antigens alone is of shortest duration in S. japonicum infection and most prolonged in S. haematobium infection (Loker, 1983).…”

Section: Introductionmentioning

confidence: 92%

“…In addition to the different disease manifestations associated with each Schistosoma species, these pathogens also differ significantly with respect to host range, speed and success of schistosomulum migration and duration of the pre-patent period (Loker, 1983;Gui et al, 1995;Rheinberg et al, 1998;He et al, 2002). Schistosoma japonicum parasitizes the broadest range of natural definitive hosts among the Schistosomatidae (Loker, 1983).…”

Section: Introductionmentioning

confidence: 99%

Conservation of CD4+ T cell-dependent developmental mechanisms in the blood fluke pathogens of humans

Lamb

Crow

Lim

et al. 2007

International Journal for Parasitology

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Schistosoma blood flukes are trematode parasites with a cosmopolitan distribution that infect over 200 million people globally. We previously showed that Schistosoma mansoni growth and development in the mammalian host is dependent on signals from host CD4 + T cells. To gain insight into the mechanisms that underlie this dependence, we sought to determine the evolutionary origins and limits of this aspect of the host-pathogen relationship. By infecting RAG-1 −/− mice with a range of different schistosome species and strains, we tested several hypotheses concerning the time during Schistosoma evolution at which this dependence arose, and whether this dependence is specific to Schistosoma or is also found in other blood flukes. Our data indicate that the developmental dependence on CD4 + T cells previously described for S. mansoni is conserved in the evolutionarily basal species Schistosoma japonicum, suggesting this developmental adaptation arose early in Schistosoma evolution. We also demonstrate that the development of the more evolutionarily-derived species Schistosoma haematobium and Schistosoma intercalatum are dependent on adaptive immune signals. Together, these data suggest that the blood fluke parasites of humans utilize common mechanisms to infect their hosts and to co-opt immune signals in the coordination of parasite development. Thus, exploitation of host-schistosome interactions to impair or prevent parasite development may represent a novel approach to combating of all the schistosome pathogens of humans.

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“…Unfortunately, transdermal infection of mice with S. haematobium cercariae, the route of natural infection of humans, results in very low rates of worm maturation and egg deposition in the pelvic organs, the key site of human pathology [31]. Infection of hamsters and non-human primates with S. haematobium cercariae leads to worm maturation and oviposition [32].…”

Section: The Inflammatory Environment During Acute and Chronic S Haementioning

confidence: 99%

Controversies and challenges in research on urogenital schistosomiasis-associated bladder cancer

Honeycutt

Hammam

et al. 2014

Trends in Parasitology

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Urogenital schistosomiasis, infection with Schistosoma haematobium, is linked to increased risk for the development of bladder cancer, but the importance of various mechanisms responsible for this association remains unclear, in part due to lack of sufficient and appropriate animal models. New advances in the study of this parasite, bladder regenerative processes, and human schistosomal bladder cancers may shed new light on the complex biological processes that connect S. haematobium infection to bladder carcinogenesis.

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Schistosoma haematobium , S. intercalatum , S. japonicum , S. mansoni , and S. rodhaini in mice: relationship between patterns of lung migration by schistosomula and perfusion recovery of adult worms

Cited by 44 publications

References 23 publications

Schistosomiasis Mansoni: Novel Chemotherapy Using a Cysteine Protease Inhibitor

Schistosomiasis Mansoni: Novel Chemotherapy Using a Cysteine Protease Inhibitor

Conservation of CD4+ T cell-dependent developmental mechanisms in the blood fluke pathogens of humans

Controversies and challenges in research on urogenital schistosomiasis-associated bladder cancer

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