Conservation of CD4+ T cell-dependent developmental mechanisms in the blood fluke pathogens of humans.
(73/234)
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 utilise 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 all of the schistosome pathogens of humans. (+info)
Schistosome vaccines: a critical appraisal.
(74/234)
An effective schistosome vaccine is a desirable control tool but progress towards that goal has been slow. Protective immunity has been difficult to demonstrate in humans, particularly children, so no routes to a vaccine have emerged from that source. The concept of concomitant immunity appeared to offer a paradigm for a vaccine operating against incoming larvae in the skin but did not yield the expected dividends. The mining of crude parasite extracts, the use of monoclonal antibodies and protein selection based on immunogenicity produced a panel of vaccine candidates, mostly of cytoplasmic origin. However, none of these performed well in independent rodent trials, but glutathione-S-transferase from Schistosoma haematobium is currently undergoing clinical trials as an anti-fecundity vaccine. The sequencing of the S. mansoni transcriptome and genome and the development of proteomic and microarray technologies has dramatically improved the possibilities for identifying novel vaccine candidates, particularly proteins secreted from or exposed at the surface of schistosomula and adult worms. These discoveries are leading to a new round of protein expression and protection experiments that will enable us to evaluate systematically all the major targets available for immune intervention. Only then will we know if schistosomes have an Achilles' heel. (+info)
Activity of praziquantel on in vitro transformed Schistosoma mansoni sporocysts.
(75/234)
Praziquantel (PZQ) is effective against all the evolutive phases of Schistosoma mansoni. Infected Biomphalaria glabrata snails have their cercarial shedding interrupted when exposed to PZQ. Using primary in vitro transformed sporocysts, labeled with the probe Hoechst 33258 (indicator of membrane integrity), and lectin of Glycine max (specific for carbohydrate of N-acetylgalactosamine membrane), we evaluated the presence of lysosomes at this evolutive phase of S. mansoni, as well as the influence of PZQ on these acidic organelles and on the tegument of the sporocyst. Although the sporocyst remained alive, it was observed that there was a marked contraction of its musculature, and there occurred a change in the parasite's structure. Also, the acidic vesicles found in the sporocysts showed a larger delimited area after contact of the parasites with PZQ. Damages to the tegument was also observed, as show a well-marked labeling either with Hoechst 33258 or with lectin of Glycine max after contact of sporocysts with the drug. These results could partially explain the interruption/reduction mechanism of cercarial shedding in snails exposed to PZQ. (+info)
The schistosome enzyme that activates oxamniquine has the characteristics of a sulfotransferase.
(76/234)
Available evidence suggests that the antischistosomal drug oxamniquine is converted to a reactive ester by a schistosome enzyme that is missing in drug-resistant parasites. This study presents data supporting the idea that the active ester is a sulfate and the activating enzyme is a sulfotransferase. Evidence comes from the fact that the parasite extract loses its activating capability upon dialysis, implying the requirement of some dialyzable cofactor. The addition of the sulfate donor 3'-phosphoadenosine 5'-phosphosulfate (PAPS) restored activity of the dialyzate, a strong indication that a sulfotransferase is probably involved. Classical sulfotransferase substrates like beta-estradiol and quercetin competitively inhibited the activation of oxamniquine. Furthermore, these substrates could be sulfonated in vitro using an extract of sensitive (but not resistant) schistosomes. Gel filtration analysis showed that the activating factor eluted in a fraction corresponding to a molecular mass of about 32 kDa, which is the average size of typical sulfotransferase subunits. Ion exchange and affinity chromatography confirmed the sulfotransferase nature of the enzyme. Putative sulfotransferases present in schistosome databases are being examined for their possible role as oxamniquine activators. (+info)
Asymptomatic schistosomiasis in a young Sudanese refugee.
(77/234)
In 2004-2005, approximately 13,000 refugees settled in Australia, 70% of them from Africa. Schistosomiasis is one of the many illnesses endemic in Africa and approximately 40% of refugees have been found to be infected by this parasite. It has the potential to cause serious morbidity and mortality in those who are infected and after malaria is the second most prevalent tropical disease worldwide. Australia is not known to have an appropriate snail vector and so schistosomiasis is unlikely to be a public health problem. This article presents a case that demonstrates one of the sequelae of schistosomiasis - pipe stem cirrhosis - with associated splenomegaly and oesophageal varices. (+info)
Differentiation of Schistosoma haematobium from related schistosomes by PCR amplifying an inter-repeat sequence.
(78/234)
Schistosoma haematobium infects nearly 150 million people, primarily in Africa, and is transmitted by select species of local bulinid snails. These snails can host other related trematode species as well, so that effective detection and monitoring of snails infected with S. haematobium requires a successful differentiation between S. haematobium and any closely related schistosome species. To enable differential detection of S. haematobium DNA by simple polymerase chain reaction (PCR), we designed and tested primer pairs from numerous newly identified Schistosoma DNA repeat sequences. However, all pairs tested were found unsuitable for this purpose. Differentiation of S. haematobium from S. bovis, S. mattheei, S. curassoni, and S. intercalatum (but not from S. margrebowiei) was ultimately accomplished by PCR using one primer from a newly identified repeat, Sh110, and a second primer from a known schistosomal splice-leader sequence. For evaluation of residual S. haematobium transmission after control interventions, this differentiation tool will enable accurate monitoring of infected snails in areas where S. haematobium is sympatric with the most prevalent other schistosome species. (+info)
Cercarial dermatitis and lake eutrophication in south-central Chile.
(79/234)
Cercarial dermatitis is caused by exposure to the cercariae of schistosome species which have birds or mammals as their definitive hosts. A public alarm was raised in the summer of 2004 when this parasitic disease was observed for the first time in south-central Chile at Laguna Chica de San Pedro (36 degrees 51'' S, 73 degrees 05'' W). Swimmers at this eutrophic lake were surveyed in order to estimate the amount of cercarial dermatitis in the area; participants were observed during the summers of 2004 and 2005 for clinical signs of cercarial dermatitis and 25 Chilina dombeyana snails were collected monthly from Laguna Chica de San Pedro during one year and then examined for animal schistosome cercariae. We found that 3% of the swimmers had pruritic maculopapular rashes on their legs, arms, necks, or other body parts and that between 9.1% (May 2006) and 52.4% (November 2004) of the snails examined were infected with the bird schistosome cercariae Trichobilharzia sp. (+info)
An improved and secreted luciferase reporter for schistosomes.
(80/234)
Schistosomes are multicellular parasites of humans exhibiting interesting biological adaptations to their parasitic lifestyle. Concerted and in depth analyses of these adaptations and their cell and molecular biology requires further development of molecular genetic tools in schistosomes. In the current study, we demonstrate that a Gaussia luciferase reporter leads to significantly higher levels of luciferase activity in schistosomes compared to other tested luciferases. In addition, Gaussia luciferase can be secreted into culture media enabling non-invasive analysis of reporter activity. The secretion of Gaussia luciferase should allow a variety of new experimental paradigms for schistosome studies. Comparison of biolistic and electroporation transfection methods using luciferase RNA reporters and the luciferase acitivty produced indicates that electroporation of sporocysts and schistosomula is the most efficient transfection method for the four stages analyzed. These data should facilitate additional studies in schistosomes and provide a framework for further development of DNA transfection and gene expression analysis. (+info)