Is there immunity to Schistosoma japonicum?

The Oriental schistosome, Schistosoma japonicum, unlike the other two major schistosomes that infect humans (S. mansoni and S. haematobium), is a zoonotic species. The transmission dynamics and the potential effects of host-related regulatory factors, including immunity, are likely to be distinct for this parasite. Here, Allen Ross and collaborators from Australia, China and the Philippines discuss recently published and established epidemiological and laboratory data bearing on anti-infection immunity to Asian schistosomiasis, and contrast these findings with the emerging picture of development of anti-infection immunity against the African schistosomes. Implications for vaccines and other control strategies for schistosomiasis japonica are also discussed.     

Are Biomphalaria snails resistant to Schistosoma mansoni?

Among Biomphalaria glabrata/Schistosoma mansoni snail-trematode combinations, it appears that some parasites succeed whilst others fail to infect snails. Snails that become infected are termed susceptible hosts. Those which are not infected are traditionally determined as 'resistant'. Here the concept of B. glabrata resistance to S. mansoni is re-examined in the light of additional observations. It is suggested that, in B. glabrata/S. mansoni, compatibility is tested independently for each individual miracidium and host, and that the success or failure of an infection does not depend on the snail susceptibility/resistance status, but on the 'matched' or 'mismatched' status of the host and parasite phenotypes.     

Schistosoma intercalatum: an endangered species in Cameroon?

Despite the extremely wide distribution of both intermediate (snail) and definitive hosts, the species Schistosoma intercalatum has a highly restricted distribution in parts of West Africa (Cameroon, Equatorial Guinea, Gabon, Nigeria, Democratic Republic of Congo and S?o Tomé). Recent studies showed that the epidemiology of this species is very dynamic, including invasions and extinctions. This article reviews the epidemiology of S. intercalatum in Cameroon, where the species is endangered, and analyses its overall status in Africa. The possible reasons for the limited distribution of S. intercalatum are discussed.     

A Mathematical Model of Schistosoma mansoni in Biomphalaria glabrata with Control Strategies

We describe and analyze a mathematical model for schistosomiasis in which infected snails are distinguished from susceptible through increased mortality and no reproduction. We based the model on the same derivation as Anderson and May (J. Anim. Ecol. 47:219–247, 1978), Feng and Milner (A New Mathematical Model of Schistosomiasis, Mathematical Models in Medical and Health Science, Nashville, TN, 1997. Innov. Appl. Math., Vanderbilt Univ. Press, Nashville, pp. 117–128, 1998), and May and Anderson (J. Anim. Ecol. 47:249–267, 1978), but used logistic growth both in human and snail hosts. We introduce a parameter r, the effective coverage of medical treatment/prevention to control the infection. We determine a reproductive number for the disease directly related to its persistence and extinction. Finally, we obtain a critical value for r that indicates the minimum treatment effort needed in order to clear out the disease from the population.     

Atypical properties of a conventional calcium channel β subunit from the platyhelminth Schistosoma mansoni

Background

Serotonin induces fluid secretion from Calliphora salivary glands by the parallel activation of the InsP₃/Ca²⁺ and cAMP signaling pathways. We investigated whether cAMP affects 5-HT-induced Ca²⁺ signaling and InsP₃-induced Ca²⁺ release from the endoplasmic reticulum (ER).

Results

Increasing intracellular cAMP level by bath application of forskolin, IBMX or cAMP in the continuous presence of threshold 5-HT concentrations converted oscillatory [Ca²⁺]_i changes into a sustained increase. Intraluminal Ca²⁺ measurements in the ER of β-escin-permeabilized glands with mag-fura-2 revealed that cAMP augmented InsP₃-induced Ca²⁺ release in a concentration-dependent manner. This indicated that cAMP sensitized the InsP₃ receptor Ca²⁺ channel for InsP₃. By using cAMP analogs that activated either protein kinase A (PKA) or Epac and the application of PKA-inhibitors, we found that cAMP-induced augmentation of InsP₃-induced Ca²⁺ release was mediated by PKA not by Epac. Recordings of the transepithelial potential of the glands suggested that cAMP sensitized the InsP₃/Ca²⁺ signaling pathway for 5-HT, because IBMX potentiated Ca²⁺-dependent Cl^- transport activated by a threshold 5-HT concentration.

Conclusion

This report shows, for the first time for an insect system, that cAMP can potentiate InsP₃-induced Ca²⁺ release from the ER in a PKA-dependent manner, and that this crosstalk between cAMP and InsP₃/Ca²⁺ signaling pathways enhances transepithelial electrolyte transport.     

An “In-Depth” Description of the Small Non-coding RNA Population of Schistosoma japonicum Schistosomulum

Parasitic flatworms of the genus Schistosoma are the causative agents of schistosomiasis, which afflicts more than 200 million people yearly in tropical regions of South America, Asia and Africa. A promising approach to the control of this and many other diseases involves the application of our understanding of small non-coding RNA function to the design of safe and effective means of treatment. In a previous study, we identified five conserved miRNAs from the adult stage of Schistosoma japonicum. Here, we applied Illumina Solexa high-throughput sequencing methods (deep sequencing) to investigate the small RNAs expressed in S. japonicum schistosomulum (3 weeks post-infection). This has allowed us to examine over four million sequence reads including both frequently and infrequently represented members of the RNA population. Thus we have identified 20 conserved miRNA families that have orthologs in well-studied model organisms and 16 miRNA that appear to be specific to Schistosoma. We have also observed minor amounts of heterogeneity in both 3′ and 5′ terminal positions of some miRNA as well as RNA fragments resulting from the processing of miRNA precursor. An investigation of the genomic arrangement of the 36 identified miRNA revealed that seven were tightly linked in two clusters. We also identified members of the small RNA population whose structure indicates that they are part of an endogenously derived RNA silencing pathway, as evidenced by their extensive complementarities with retrotransposon and retrovirus-related Pol polyprotein from transposon.     

Efficiency of ginger (Zingbar officinale) against Schistosoma mansoni infection during host–parasite association

The possible protective effect of ethanolic extract of ginger against infection with Schistosome mansonii was evaluated in mice. The extract was given daily for 45 days beginning at either 2nd day or 45 days post infection. Oral supplementation of ginger extract to infected animals was effective in reducing worm burden and the egg load in the liver and intestine which coincided with the reduction in granuloma diameters. Ginger extract had also the effect to offset liver fibrosis in response to S. mansoni infection indicated by reduced liver hydroxyproline level and serum alpha–fetoprotein (AFP). The extract reduces some inflammatory mediators that play a crucial role in schistosomal liver fibrosis and its complications. These include liver xanthine oxidase (XO); nitric oxide (NO); tumour necrosis factor–alpha (TNF-α); immunoglobins E, G, and M (Ig-E, Ig-G and Ig-M, respectively), and interleukin 4, 10 and 12 (IL-4, IL-10 and IL-12, respectively). Administration of ginger extract ameliorated the infection-induced alterations in serum gamma-glutamyl transferase (GGT), alanine amintransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). It was concluded that oral administration of ginger extract to S. mansoni infected mice could minimize the deleterious effects of this parasite on the vital functions of infected animals.     

Hybridization between different strains of Schistosoma intercalatum Fisher, 1934 from Cameroun and Za?re

The offspring from hybridization experiments between Schistosoma intercalatum, Cameroun (intermediate host Bulinus forskalii) and S. intercalatum, Za?re (intermediate host B. globosus) was investigated. Reciprocal crosses between the two forms were performed. F1- and F2-miracidia developed in both parental intermediate hosts. The minimum prepatent period was 24 days at 26 degrees C, an average of the prepatent periods for the two parental strains. The total cercariae production per 100 exposed snails decreased sharply from 121 000 for the parental strain from Cameroun in B. forskalii to 21 000 and 5000 from the F1- and F2-generations, respectively. The figures for S. intercalatum, Za?re in B. globosus were 270 000, 134 000 and 3000, respectively. F1- and F2-generations were from the cross between males from Cameroun and females from Za?re. The viablility of the four cross-breeding experiments carried out (two with each combinations of the parental strains) were low. It was only possible to obtain F2-cercariae. No miracidia were hatched from eggs produced by the F2-gerneation.     

Polyparasitism with Schistosoma mansoni,geohelminths, and intestinal protozoa in rural Côte d'Ivoire

Single species infections with schistosomes, geohelminths, and intestinal protozoans are common over large parts of sub-Saharan Africa, and it is expected that polyparasitism affects a considerable proportion of the population, hence posing a great toll on public health. However, few investigations have been carried out to quantify the extent of polyparasitism. Here, a detailed assessment is reported for the epidemiology of Schistosoma mansoni, geohelminths, and intestinal protozoan infections, with particular emphasis on polyparasitism among 260 community members in rural C?te d'Ivoire. Schistosoma mansoni, Entamoeba coli, and hookworm were the predominant species with prevalences of 71.5, 64.6, and 51.9%, respectively. Only 8 individuals displayed no infection, whereas two-thirds of the population harbored 3 or more parasites concurrently. There were a series of significant pairwise parasite co-occurrences, e.g., between S. mansoni and hookworms and between S. mansoni and E. coli. It is concluded that polyparasitism in the population studied here was very common, which is probably the case also in other areas of rural C?te d'Ivoire and elsewhere in sub-Saharan Africa. These findings call for integrated approaches to effectively control multiple parasitic and protozoan infections.     

Elimination of Schistosoma mansoni Adult Worms by Rhesus Macaques: Basis for a Therapeutic Vaccine?

Background

Among animal models of schistosomiasis, the rhesus macaque is unique in that an infection establishes but egg excretion rapidly diminishes, potentially due to loss of adult worms from the portal system via shunts or death by immune attack.

Principal Findings

To investigate this, six rhesus macaques were exposed to Schistosoma mansoni cercariae and the infection monitored until portal perfusion at 18 weeks. Despite a wide variation in worm numbers recovered, fecal egg output and circulating antigen levels indicated that a substantial population had established in all animals. Half the macaques had portal hypertension but only one had portacaval shunts, ruling out translocation to the lungs as the reason for loss of adult burden. Many worms had a shrunken and pallid appearance, with degenerative changes in intestines and reproductive organs. Tegument, gut epithelia and muscles appeared cytologically intact but the parenchyma was virtually devoid of content. An early and intense IgG production correlated with low worm burden at perfusion, and blood-feeding worms cultured in the presence of serum from these animals had stunted growth. Using immunoproteomics, gut digestive enzymes, tegument surface hydrolases and antioxidant enzymes were identified as targets of IgG in the high responder animals.

Significance

It appears that worms starve to death after cessation of blood feeding, as a result of antibody-mediated processes. We suggest that proteins in the three categories above, formulated to trigger the appropriate mechanisms operating in rhesus macaques, would have both prophylactic and therapeutic potential as a human vaccine.     

Does multiple hosts mean multiple parasites? Population genetic structure of Schistosoma japonicum between definitive host species

Multi-host parasites, those capable of infecting more than one species of host, are responsible for the majority of all zoonotic, emerging or persistent human and animal diseases and are considered one of the major challenges for the biomedical sciences in the 21st century. We characterized the population structure of the multi-host parasite Schistosoma japonicum in relation to its definitive host species by genotyping miracidia collected from humans and domestic animals across five villages around the Yangtze River in Anhui Province, mainland China, using microsatellite markers. High levels of polymorphisms were observed and two main genetic clusters were identified which separated water buffalo, cattle and humans from goats, pigs, dogs and cats. We thereby believe that we present the first evidence of definitive host-based genetic variation in Schistosoma japonicum which has important epidemiological, evolutionary, medical and veterinary implications.     

Inbreeding within human Schistosoma mansoni: do host-specific factors shape the genetic composition of parasite populations?

The size, structure and distribution of host populations are key determinants of the genetic composition of parasite populations. Despite the evolutionary and epidemiological merits, there has been little consideration of how host heterogeneities affect the evolutionary trajectories of parasite populations. We assessed the genetic composition of natural populations of the parasite Schistosoma mansoni in northern Senegal. A total of 1346 parasites were collected from 14 snail and 57 human hosts within three villages and individually genotyped using nine microsatellite markers. Human host demographic parameters (age, gender and village of residence) and co-infection with Schistosoma haematobium were documented, and S. mansoni infection intensities were quantified. F-statistics and clustering analyses revealed a random distribution (panmixia) of parasite genetic variation among villages and hosts, confirming the concept of human hosts as ‘genetic mixing bowls'' for schistosomes. Host gender and village of residence did not show any association with parasite genetics. Host age, however, was significantly correlated with parasite inbreeding and heterozygosity, with children being more infected by related parasites than adults. The patterns may be explained by (1) genotype-dependent ‘concomitant immunity'' that leads to selective recruitment of genetically unrelated worms with host age, and/or (2) the ‘genetic mixing bowl'' hypothesis, where older hosts have been exposed to a wider variety of parasite strains than children. The present study suggests that host-specific factors may shape the genetic composition of schistosome populations, revealing important insights into host–parasite interactions within a natural system.     

Repeated Schistosoma japonicum Infection Following Treatment in Two Cohorts: Evidence for Host Susceptibility to Helminthiasis?

Background

In light of multinational efforts to reduce helminthiasis, we evaluated whether there exist high-risk subpopulations for helminth infection. Such individuals are not only at risk of morbidity, but may be important parasite reservoirs and appropriate targets for disease control interventions.

Methods/Principal Findings

We followed two longitudinal cohorts in Sichuan, China to determine whether there exist persistent human reservoirs for the water-borne helminth, Schistosoma japonicum, in areas where treatment is ongoing. Participants were tested for S. japonicum infection at enrollment and two follow-up points. All infections were promptly treated with praziquantel. We estimated the ratio of the observed to expected proportion of the population with two consecutive infections at follow-up. The expected proportion was estimated using a prevalence-based model and, as highly exposed individuals may be most likely to be repeatedly infected, a second model that accounted for exposure using a data adaptive, machine learning algorithm. Using the prevalence-based model, there were 1.5 and 5.8 times more individuals with two consecutive infections than expected in cohorts 1 and 2, respectively (p<0.001 in both cohorts). When we accounted for exposure, the ratio was 1.3 (p = 0.013) and 2.1 (p<0.001) in cohorts 1 and 2, respectively.

Conclusions/Significance

We found clustering of infections within a limited number of hosts that was not fully explained by host exposure. This suggests some hosts may be particularly susceptible to S. japonicum infection, or that uncured infections persist despite treatment. We propose an explanatory model that suggests that as cercarial exposure declines, so too does the size of the vulnerable subpopulation. In low-prevalence settings, interventions targeting individuals with a history of S. japonicum infection may efficiently advance disease control efforts.     

Biomphalaria tenagophila potencial vector of Schistosoma mansoni in the Paraná River basin (Argentina and Paraguay)

Susceptibility and compatibility experiments were carried out with 700 Biomphalaria tenagophila from the Paraná River basin exposed to infection with Schistosoma mansoni. Individual infection was performed with 10 miracidia of SJ2 strain from the Paraiba valley (Brazil) originally infective to B. tenagophila. These snails were laboratory-breed progeny of B. tenagophila collected from six localities of Argentina and one from Paraguay. From Argentina: Rincón de Vences (7%) and Posadas (11%) became infected with S. mansoni and the calculation of Frandsen's index (TCP/100) shows that they were Class II poorly compatible. Those snails from Goya (22%), Maloyas (5%), and Berón de Astrada (3%) were Class III compatible to the S. mansoni. None of the 100 snails exposed from Caá-Catí became infected (Class 0 incompatible). Tested samples from Paraguay (Encarnación) were infected (20%) and compatible (Class III). It was also studied the persistence of the infection in 244 snails of the first generation (F1) of those that were susceptible from three places. It was demonstrated an increment of the susceptibility in the F1 from Maloyas (chi2 = 27.22; p = 0.0001) and Posadas (chi2 = 4.24; p = 0.04). The results point out the possibility that schistosomiasis might be able to spread into the Paraná River basin where B. tenagophila exists.     

Do mice genetically selected for resistance to oral tolerance provide selective advantage for Schistosoma mansoni infection?

A highly evolved relationship exists between the parasitic flatworm Schistosoma mansoni and its vertebrate hosts that include the use of host immune signals by parasites. The S. mansoni infection was studied in two strains of mice genetically selected, over 18 generations of assortative mating, for extreme phenotypes of susceptibility (TS) and resistance (TR) to immunological tolerance. The objective was to observe whether the different host genetic backgrounds affected the outcome of experimental schistosomiasis. Fecal egg excretion, tissue egg count, worm recovery, and adult worm morphology and morphometry were monitored throughout the period of infection. TR mice presented total fecal egg excretion and thickness of tegument in adult male worms significantly higher than TS mice. Therefore, the comparative analysis of mice with extreme phenotypes of immunological response turns out to be useful in host-parasite relationship studies. Our results suggest that the TR mouse immunological profile provides a more favorable environment for the development of S. mansoni.     

Interplay of cysteinyl leukotrienes and TGF-β in the activation of hepatic stellate cells from Schistosoma mansoni granulomas

Hepatic stellate cells (HSCs) have a critical role in liver physiology, and in the pathogenesis of liver inflammation and fibrosis. Here, we investigated the interplay between leukotrienes (LT) and TGF-β in the activation mechanisms of HSCs from schistosomal granulomas (GR-HSCs). First, we demonstrated that GR-HSCs express 5-lipoxygenase (5-LO), as detected by immunolocalization in whole cells and confirmed in cell lysates through western blotting and by mRNA expression through RT-PCR. Moreover, mRNA expression of 5-LO activating protein (FLAP) and LTC₄-synthase was also documented, indicating that GR-HSCs have the molecular machinery required for LT synthesis. Morphological analysis of osmium and Oil-Red O-stained HSC revealed large numbers of small lipid droplets (also known as lipid bodies). We observed co-localization of lipid droplet protein marker (ADRP) and 5-LO by immunofluorescence microscopy. We demonstrated that GR-HSCs were able to spontaneously release cysteinyl-LTs (CysLTs), but not LTB_4, into culture supernatants. CysLT production was highly enhanced after TGF-β-stimulation. Moreover, the 5-LO inhibitor zileuton and 5-LO gene deletion were able to inhibit the TGF-β-stimulated proliferation of GR-HSCs, suggesting a role for LTs in HSC activation. Here, we extend the immunoregulatory function of HSC by demonstrating that HSC from liver granulomas of schistosome-infected mouse are able to release Cys-LTs in a TGF-β-regulated manner, potentially impacting pathogenesis and liver fibrosis in schistosomiasis.