Single- or mixed-sex Schistosoma japonicum infections of intermediate host snails in hilly areas of Anhui, China.

Schistosomiasis japonicum is one of the most serious communicable diseases, and the transmission of the parasite is dependent of its complex life cycle on which many factors can have an impact. Multiple infections comprising both male and female schistosome within snail intermediate hosts, for example, would facilitate parasite transmission. However, no research on Schistosoma japonicum communities in field-collected Oncomelania hupensis hupensis in relation to schistosome sex has been reported. Therefore, snail survey was performed in a hilly region of Anhui, China, and single- or mixed-sex schistosome infections of snails were detected with final host mouse infection. A total of 8,563 snails were sampled in the field, and 67 were identified with schistosome infections. Of these infected snails, 46 were selected for final host infection. From this, 21 snails were infected with female schistosome, 23 with males and 2 with both males and females. More worms were recovered for snails with mixed-sex infections than with single-sex infection and for snails with male schistosome infection than with female infection (P<0.001). The observed frequency of mixed-sex infections of snails was significantly higher than would be expected if randomly distributed (P<0.01). The ratio male/female of schistosome infections in snails was nearly equal and up to 95.65 % (44/46) of infected snails were single-sex infection. Schistosome infections in snails collected from the hilly area of Anhui Province were not randomly distributed but over-dispersed.

RNAi silencing of type V collagen in Schistosoma japonicum affects parasite morphology, spawning, and hatching.

Type V collagen is a component of non-cartilaginous tissues and is important in the determination of fibril structure and matrix organization, although its functions are still poorly understood. In this report, RNA interference (RNAi) approaches were used to investigate the effects of knockdown of the schistosome type V collagen (SjColV) gene. In this study, three different short interfering (si) RNAs targeting different regions of the gene were designed to suppress the expression of SjColV in Schistosoma japonicum using a soaking method. By establishing controls for measuring off-target RNAi effects, we found that different siRNA sequences had different levels of effectiveness. Although all the siRNAs tested reduced SjColV transcript levels, the S1 siRNA consistently reduced SjColV expression to >99 % of the control. In the following experiments, S1 siRNA was adapted to inhibit SjColV expression, and the silencing effects were detected by real-time PCR and Western blot. The spawning and egg hatching of parasites were calculated, while the worms' morphology was taken by scanning electron microscopy. The results show that silencing the expression of SjColV significantly affects the spawning and egg hatching of S. japonicum, and it also affects the worms' morphology.

Histopathological changes of juvenile Schistosoma japonicum harbored in mice treated orally with mefloquine at a smaller single dose.

The histopathological changes of 14-day-old Schistosoma japonicum induced by a smaller single dose of mefloquine have been studied. Twenty-three mice infected with 60-80 S. japonicum cercariae for 14 days were treated orally with mefloquine at a single dose of 200 mg/kg (free base), and groups of three mice were killed at various intervals posttreatment. The liver of each mouse was removed, fixed and processed routinely, and examined by light microscopy. Eight hours posttreatment, 38.2% and 39.8% of schistosomulum sections were classified as degenerated and dead, respectively. The degenerated schistosomula revealed in high dilatation of gut with disruption of gut mucosa, swelling of the worm body accompanied by looseness or extensive lysis of parenchymal tissues, and focal swelling or peeling of tegument, while dead worms showed that their damaged tegument adhered to the vessel and inflammatory cell attached on and penetrated into the worm body. Twenty-four hours to 3 days posttreatment, the degenerated schistosomulum sections decreased from 28.1% to 8.2%, while the sections of dead schistosomula increased from 60.0% to 74.8%. At these time periods, the damage intensity of degenerated schistosomula aggravated, while dead schistosomula showed disintegration of internal structures infiltrated by eosinophil-predominant inflammatory cells to form the dead worm abscess. Seven days to 14 days posttreatment, no normal schistosomulum section was observed, and the percentages of degenerated and dead worms further decreased from 3.4% to 3.0% and 34.4% to 12.6%, respectively. Meanwhile, 62.2% to 84.4% of dead worms developed to dead worm granulomas and part of them situated in early stage. Twenty-eight days posttreatment, only dead worm granulomas were observed in the liver sections and part of them developed to late stage. The results indicate that a smaller single mefloquine dose 200 mg/kg exhibits a potential and fast killing effect against S. japonicum juvenile and induces severe histopathological lesions.

Confocal laser scanning microscopic observation on adult Schistosoma japonicum harbored in mice following treatment with single-dose mefloquine.

The aim of the present study is to assess the mefloquine-induced alteration of adult Schistosoma japonicum using confocal laser scanning microscopy (CLSM). Eight out of ten mice infected with 60-80 S. japonicum cercariae for 35 days were treated orally with mefloquine at a single dose of 400 mg/kg. Four groups of two mice were killed at 24 h and 3, 7, and 14 days post-treatment, and schistosomes were collected by perfusion from the liver and mesenteric veins, fixed in 70% alcohol, stained with acid carmine, and examined by CLSM. Worms obtained from untreated mice served as controls. Twenty-four hours post-treatment, focal tegument of adult male and female worms, which composed of fine and short villus-like materials, became thicker and longer, or disorder arrangement, while the musculatures beneath the tegument revealed in focal and irregular swelling with various degrees. In the gut of male and female schistosomes, severe dilatation accompanied by swelling, collapse, and peeling of gut mucosa was universal. In the reproductive organs, no apparent alteration in the testis structure of male worms was seen, while in female worms, slight damage to the ovary included loose arrangement of mature ovary cells accompanied by some of them degenerated and collapsed. As to vitelline glands, severe damage, such as swelling, indistinction, fusion or collapse of vitelline cells, and apparent swelling of parenchymal tissues in vitelline gland lobules, was seen. Meanwhile, abnormal ova emerged in the uterus at this time point. Three to 7 days post-treatment, the damage to the worms aggravated either in extent or in severity along with time. In some focally swollen worm body, the parenchymal tissues revealed in severe swelling. In addition, a large piece of degenerated and necrotic parenchymal tissues emerged closed to the severe destructed oral or ventral sucker. In the gut of male and female worms, the major alterations manifested by focal collapse or peeling of mucosa, and desquamation of gut epithelial cells. As to the reproductive organs, the testes of male worms revealed in reduction of size, decrease in number of germinative cells, and some of them showed degeneration and collapse, or destruction of the capsule around the testis. In female worms, some ovaries only showed degenerated and collapsed cells accompanied with many cell fragments. Meanwhile, almost all of the vitelline cells lost their definition, which revealed in indistinct cell structure, fusion of some cells, and formation of many cell fragments due to their collapse. Fourteen days post-treatment, only some male worms survived the treatment were collected. Their tegument and musculature showed prominent recovery, but severe damage to the gut and testes was still observed. Our results confirm that under the observation by CLSM, mefloquine exhibits destructive effect on adult S. japonicum, particularly the morphological structure of digestive system and reproductive system of the worms.

Worm morphology of Schistosoma japonicum using confocal laser scanning microscopy.

Male and female Schistosoma japonicum worms have dissimilar appearances in their final host. In this study, a morphometric and morphological assessment of whole worms derived from unisexual and mixed infections in mice was conducted using confocal laser scanning microscopy. Worms from mixed infections showed significant morphological changes between 15 and 25 days post-infection (PI). On the fifteenth day PI, 33% of males had formed the conspicuous gynecophoric canal, but only 8% of them had testicular lobes containing a few germinative cells; 13% of females had incipient ovaries with a few immature ovarian cells inside. On the twentieth day PI, the testicular lobes contained more germinative cells in all male worms, while female worms presented vitelline glands. On the twenty-fifth day PI, more germinative cells were observed in the male testicular lobes, and differentiated cells were present in the female ovaries. All worms had fully developed reproductive organs from 30 days PI onwards. Morphometric analysis showed significant differences between mixed and unisexual infections at 35 days PI. Ovaries of worms from unisexual infections contained cells in one stage of maturation and vitelline glands had undifferentiated cells. Our study of S. japonicum provides a detailed comparison of different morphological traits from worms of mixed and unisexual infections throughout development.

[Preparation of agar-paraffin double-embedded longitudinal sections of Schistosoma japonicum].

Schistosoma japonicum adults are pre-embedded in a double-layer agar and made the block, then dehydrated with alcohol, isobutyl alcohol and n-butyl alcohol. Various staining procedures can be conducted after conventional sectioning and dewaxing. Complete longitudinal serial sections of the pre-embedded worms can be obtained, and the desired sections can be easily located accurately.

RNAi silencing of calcium-regulated heat-stable protein of 24 kDa in Schistosoma japonicum affects parasite growth.

The calcium-regulated heat-stable protein of 24 kDa (CRHSP-24) is a major calcineurin phosphoprotein that functions in multiple signal transduction pathways in cell metabolism. Schistosomes are multicellular parasites that infect 200 million people worldwide, even though treatment has been available for two decades. To determine the function of schistosome CRHSP-24 (SjCRHSP-24), we successfully knocked down SjCRHSP-24 in Schistosoma japonicum by RNA interference (RNAi). By establishing controls for measuring off-target RNAi effects, we found that different double-stranded (dsRNA) sequences had different levels of effectiveness. While all tested dsRNAs reduced CRHSP-24 transcript levels, the S2 dsRNA consistently reduced CRHSP-24 expression to >95% of the control. Knockdown of the SjCRHSP-24 gene significantly affected the morphology and vitality of S. japonicum.

Further observation on histopathological alterations of adult Schistosoma japonicum harbored in mice following treatment with mefloquine at a smaller single dose.

The purpose of the present study is to assess the histopathological alterations of adult schistosomes caused by a smaller dose of mefloquine. Mice were infected with Schistosoma japonicum cercariae for 35 days and then treated with a single 200 mg/kg oral dose of mefloquine. Groups of mice were killed between 12 h and 28 days posttreatment, and the livers were removed, fixed, and processed routinely and examined by light microscopy. Twelve hours to 48 h or 3 days posttreatment, 10.3% to 53.3% of male worms and 10% to 25% of female worms shifted to the liver revealed normal appearance. However, 46.7% to 69.2% of male worms and 45.5% to 75% of female worms showed signs of degeneration, including moderate or high swelling of tegument and/or muscles with roughing surface or formation of small vesicles beneath the tegument or collapse of damaged tegument, light swelling of parenchymal tissues, and light dilatation of gut. These histopathological changes aggravated either in extent or in severity along with time, especially the speed of emergence of dead worm granuloma that was faster in female worms than in male ones. In female worms, severe damage to the vitelline glands was universal, which was characterized by necrosis and karyopyknosis of vitelline cells and emergence of small vacuoles among the vitelline gland lobules. Seven days to 28 days posttreatment, almost all of the female worms shifted to the liver were classified as dead or dead worm granuloma, while the percentage of dead male worm and its granuloma examined in the liver was 52.1% to 53.3%. The results indicate that smaller dose of mefloquine (200 mg/kg) still shows strong histopathological response to kill female schistosomes, but its lethal effect against male worms is weakened.

[Identification and functional study of the Schistosoma japonicum epidermal growth factor receptor gene].

OBJECTIVE: To characterize the epidermal growth factor receptor (EGFR) gene in Schistosoma japonicum (SjEGFR gene) and investigate the role of the EGFR gene in regulating the growth, reproductive system, maturation and fecundity of S. japonicum. METHODS: Rapid amplification of cDNA ends (RACE) was performed to obtain the full length of the SjEGFR gene, and the SjEGFR gene expression was quantified in different developmental stages of S. japonicum using a quantitative real-time PCR (qPCR) assay. The tissue localization of the SjEGFR gene was detected in 22-day parasite using whole-mount in situ hybridization (WISH). Following RNA interference (RNAi)-induced knockdown of the SjEGFR gene, the worm length, pairing rate and worm burden of S. japonicum were measured, and the worm morphology was observed using optical microscopy and confocal microscopy. RESULTS: The SjEGFR gene was identified with a conserved tyrosine-kinase active site, and the SjEGFR gene expression was detected at various developmental stages in male and female parasites. WISH showed that the transcript of the SjEGFR gene was localized on the tegument and in the digestive organs of S. japonicum. RNAi-induced SjEGFR knockdown resulted in marked suppression of the worm growth, smaller size of male testicles that contained more immature spermatocytes, and apparent impairment of ovary and vitelline gland development. In addition, no eggs were found in the uterus of SjEGFR knocked-down female parasites, indicating the interruption of egg production. CONCLUSIONS: Inhibition of SjEGFR expression may remarkably suppress the growth and maturation of S. japonicum, and interrupt the egg production.

Modulation of blood fluke development in the liver by hepatic CD4+ lymphocytes.

We have identified an alternate developmental pathway in the life cycle of the trematode pathogen Schistosoma mansoni. This pathway is used in immunodeficient hosts in which the parasite fails to receive appropriate signals from the host immune system. Helminth development is altered at an early stage during infection, resulting in the appearance of attenuated forms that prolong survival of host and parasite. Hepatic CD4+ T lymphocyte populations are an integral component of the immune signal recognized by the parasite.

Histopathological alteration of juvenile Schistosoma japonicum in mice following treatment with single-dose mefloquine.

This study aims to observe the histopathological alterations in schistosomula of Schistosoma japonicum induced by mefloquine. Mice were infected with S. japonicum cercariae, and after 14 days, a single dose of mefloquine (400 mg/kg) was administered orally. After 8 h, 24 h, 3 days, 7 days, and 14 days, groups of two to three mice were sacrificed, and livers were removed, fixed and processed routinely, and examined by light microscopy. After 8 h, 51.5% of the schistosomula examined showed degeneration, which included high dilatation of gut, desquamation of gut epithelial cells, swelling of tegument, muscles, and parenchymal tissues, and adherence of inflammatory cells to the damaged tegument of the juveniles. After 24 h, the percentage of dead worm and degenerated worm were 43.2% and 48.4%, respectively, and the intensity of damage increased, including severe swelling and vesiculation of tegument, collapse of damaged gut, and loss of definition in the internal structure. In addition, dead worms were infiltrated by eosinophil-predominated inflammatory cells. After 3 days, more than 96% of schistosomula were severely degenerated and dead, and some of them were focally or extensively infiltrated by inflammatory cells accompanied by necrosis of internal structure. Seven to 14 days after treatment, most dead schistosomula developed to dead worm granulomas with the percentages of 60.1-86.3%, while those of dead schistosomula were 26.7-8.4%. The results indicate that mefloquine exhibits an extensive and severe damage to juvenile S. japonicum harbored in mice.

The in vitro effect of mefloquine and praziquantel against juvenile and adult Schistosoma japonicum.

Mefloquine, an antimalarial drug, has been found to be effective against various stages of schistosomes in vivo. The purpose of the study is to explore the in vitro effect of mefloquine against adult and juvenile Schistosoma japonicum and to compare its efficacy with praziquantel. Three-hour-old schistosomula were prepared by penetrating the mouse skin with schistosome cercariae, while schistosomes 7-, 14-, and 35-day-old were collected from mice infected with S. japonicum cercariae for 7, 14, and 35 days by perfusion. Schistosomes were placed to each of 24 wells of a Falcon plate and maintained in Hanks' balanced salt solution-20% calf serum. Besides observation on the direct in vitro effect of mefloquine and praziquantel, adult worms exposed to mefloquine and praziquantel for 1 and 4 h were transferred to the medium without the drugs and incubated continuously for another 72 h. The reversible effect of mefloquine and praziquantel was assessed by the recovery of the worm motor activity and parasite survival. The minimal effective concentration of mefloquine against adult schistosomes in vitro was 10 microg/mL, which revealed that the worm motor activity was first stimulated, then decreased significantly, followed by bleb formation, focal swelling and elongation of the worm body, cessation of gut peristalsis, and death of 56.3% (18/32) worms within 24-72 h. Similar appearance was seen in the adult worms exposed to higher mefloquine concentration of 20 and 30 microg/mL, but all worms died within 4-24 h. The adult schistosomes exposed to praziquantel 1-30 microg/mL showed fast spasmodic contraction of the worm body, followed by bleb formation along the tegument, feeble movement of oral sucker, and death of a part of males and females 72 h after incubation. When male and female schistosomes exposed to mefloquine 10 and 20 microg/mL for 1 and 4 h were transferred to the medium without the drug, no apparent recovery of worm motor activity and survival was seen. In case of worms exposed to praziquantel at the same concentration for 1 and 4 h before replacement of drug-free medium, a well recovery of worm motor activity, looseness of worm body, and reduction or disappearance of blebs along the tegument were observed. Mefloquine also exhibited in vitro effect against 3-h-old and 7- and 14-day-old schistosomula which was similar to that seen in adult worms, but all or parts of worms showed decrease in motor activity or even death (3-h-old and 7-day-old schistosomula) at a lower mefloquine concentration of 5 microg/mL. In 14 day-old schistosomula exposed to praziquantel 1-30 microg/mL, spasmodic contraction and significant decrease in motor activity of the worm body with movement of oral and ventral suckers were observed, but no death of worm was seen during a 3-day incubation period. The results indicate that in vitro mefloquine exhibits a direct killing effect against adult and juvenile S. japonicum which is different from that of praziquantel. Meanwhile, the juvenile schistosomes are more susceptible to mefloquine than the adult ones. Furthermore, the in vitro effect of mefloquine against adult schistosomes is irreversible, while that of praziquantel is reversible.

Effect of single-dose oral mefloquine on the morphology of adult Schistosoma japonicum in mice.

It has been recently documented that the antimalarial drug mefloquine shows in vivo activity against schistosomes. In the present study, we assessed the effect of mefloquine on the morphology of adult Schistosoma japonicum worms. Mice were infected with S. japonicum cercariae for 35 days and then treated with a single 400-mg/kg oral dose of mefloquine. Groups of mice were killed between 24 h and 14 days post-treatment and worms were recovered from the liver and mesenteric veins, fixed in 70% alcohol, stained with acid carmine, and examined under a light microscope. Worms obtained from nontreated mice served as controls. S. japonicum recovered from mice 24 h post-treatment had severely dilated guts and the entire worm body was swollen. Meanwhile, reproductive glands, including the testis, ovary, and vitelline gland, showed signs of degeneration. Damage further progressed, particularly among vitelline glands, which resulted in disturbance of ova formation and cessation of oviposition 3 days post-treatment. Three to 7 days after mefloquine administration, adherence of host leukocytes on the damaged tegument was observed. Our results confirm that mefloquine possesses antischistosomal properties, exhibiting a rapid onset of action and causing extensive morphologic damage to adult S. japonicum.

Comparative analysis of transcriptional profiles of Schistosoma japonicum adult worms derived from primary-infected and re-infected water buffaloes.

BACKGROUND: Schistosoma japonicum (S. japonicum) is an important zoonotic parasite that is prevalent in China and parts of Southeast Asia. Water buffaloes are an important reservoir and the main transmission sources of S. japonicum. However, self-curing and resistance to re-infection have been observed in water buffaloes. RESULTS: In this study, we compared the morphometry and differences in transcriptional expression of adult S. japonicum worms recovered from primary-infected and re-infected water buffaloes using Illumina RNA-sequencing (RNA-Seq) technology. Results of morphometry analysis revealed that adult S. japonicum worms recovered from re-infected water buffaloes were runtish with smaller organs. The ventral length of male worms was shorter in re-infected buffaloes (328 ± 13 vs 273 ± 8 µm, P < 0.05), and in female worms the oral sucker length (44 ± 3 vs 33 ± 5 µm, P < 0.05), ovary length (578 ± 23 vs 297 ± 27 µm, P < 0.05) and width (150 ± 8 vs 104 ± 9 µm, P < 0.05) were shorter, with fewer eggs in the uteri (41 ± 2 vs 12 ± 1, P < 0.05). Of 13,605 identified genes, 112 were differentially expressed, including 51 upregulated and 61 downregulated genes, in worms from re-infected compared with primary-infected water buffaloes. Gene ontology (GO) enrichment analysis revealed that GO terms such as "oxidation-reduction process", "calcium-dependent phospholipid binding", "lipid binding" and "calcium ion binding" were significantly enriched in downregulated genes, whereas GO terms related to metabolism and biosynthesis were significantly enriched in upregulated genes. The results revealed that the downregulation of some important genes might contribute to a reduction in worm numbers and maldevelopment of surviving worms in re-infected water buffaloes. Furthermore, upregulation of genes related to metabolic processes and biosynthesis might be a compensatory mechanism of worms in disadvantageous environments. CONCLUSIONS: To our knowledge, our results present the first large-scale transcriptional expression study identifying the differences between adult S. japonicum worms from primary-infected and re-infected water buffaloes, and particularly emphasize differential expression that may affect the survival and growth of worms in re-infected water buffalo. This will provide new insight into screening for anti-schistosome targets and vaccine candidates.

A comparison of ancient parasites as seen from archeological contexts and early medical texts in China.

This paper integrates our knowledge from traditional Chinese medical texts and archeological findings to discuss parasitic loads in early China. Many studies have documented that several different species of eukaryotic endoparasites were present in early human populations throughout China. Nevertheless, comprehensive paleoparasitological records from China are patchy, largely due to taphonomic and environmental factors. An examination of early Chinese medical texts allows us to fill in some of the gaps and counteract apparent biases in the current archeoparasitological records. By integrating the findings of paleoparasitology with historic textual sources, we show that parasites have been affecting the lives of humans in China since ancient times. We discuss the presence and prevalence of three groups of parasites in ancient China: roundworm (Ascaris lumbricoides), Asian schistosoma (Schistosoma japonicum), and tapeworm (Taenia sp.). We also examine possible factors that favored the spread of these endoparasites among early humans. Therefore, this paper not only aims to reveal how humans have been affected by endoparasites, but also addresses how early medical knowledge developed to cope with the parasitic diseases.

[Morphological observation on the reproductive system of adult Schistosoma japonicum under confocal laser scanning microscopy].

BALB/c mice were infected with Schistosoma japonicum cercariae (40+/-2 per mouse) through abdominal skin. Mice were sacrificed after 35 days to acquire the adult worms which were then fixed, stained, clarified, dehydrated and mounted. The specimens were observed under the confocal laser scanning microscope. The overall morphology of the adult worms was displayed distinctly, especially the testicular lobes, seminal vesicle and genital pore of the male, reproductive system, and the ovary, vitelline glands, oviduct, vitelline duct, seminal receptacle, ootype, mehlis gland, uterus, genital pore and eggs of female reproductive system. The confocal laser scanning microscopy is an alternative method to research organs, tissues and cell structure of schistosome worm.

[In vitro effect of 5-hydroxytryptamine on motility and length of Schistosoma japonicum primary sporocysts].

OBJECTIVE: To study in vitro the effect of 5-hydroxytryptamine (5-HT) on the motility and length of primary sporocysts of Schistosoma japonicum and select the optimal concentration and time of 5-HT. METHODS: Eggs of S. japonicum were harvested from livers of the infected mice 6-8 weeks after infection, which were then incubated with water. The miracidia were axenically cultured in 1/2 RPMI 1640 containing 10% calf serum and a moderate amount of antibiotics (100 U/ml penicillin G and 100 microg/ml streptomycin) for 48 hours. They became mother sporocysts and were divided into two groups. Parasites in the first group were treated by 5-HT under concentrations of 0, 0.1, 1, 10, 100 and 1000 micromol/L for 48 hours, respectively. Those parasites in the second group were treated by 5-HT of 10 micromol/L for 0.16, 6, 24 and 48 hours, respectively. The motility, length and succinic dehydrogenase (SDH) activity of the parasites were measured under Olympus microscope. RESULTS: Along with the increase of 5-HT concentration, the motility and length of the mother sporocysts all increased gradually. With the 5-HT concentration of 10 micromol/L, both of them reached a maximum value, being (65.6 +/- 1.5)% and (131.4 +/- 9.2) microm respectively. Meanwhile, along with the prolongation of treatment time, the motility and length also increased gradually. The motility reached a maximal value at 24 hours post-treatment. So did the length and SDH activity of the parasites at 48 hours post-treatment. CONCLUSION: 5-HT shows a significant effect on the motility and length of mother sporocysts of S. japonicum and its optimal concentration is 10 micromol/L under in vitro conditions.

Suppression of VAMP2 Alters Morphology of the Tegument and Affects Glucose uptake, Development and Reproduction of Schistosoma japonicum.

Schistosomiasis caused by schsitosomes is a serious global public health concern. The tegument that surrounds the worm is critical to the schistosomes survival. The tegument apical membrane undergoes a continuous process of rupture and repair owing to membranous vacuoles fusing with the plasma membrane. Vesicle-associated membrane protein 2 (VAMP2), a member of soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNAREs) is required for membrane fusion. Here, we used RNA interference (RNAi) to knock down the expression of VAMP2 of Schistosoma japonicum (SjVAMP2), and both real-time PCR and western blot analysis confirmed the suppression of this molecule, as well as the suppression of the transcript levels of schistosome glucose transporters (SGTP1 and SGTP4), and insulin receptors (SjIR1 and SjIR2). SjVAMP2-suppressed worms exhibited a lower viability, and phenotypic alterations were also observed in the tegument. Moreover, the glucose consumption of SjVAMP2-suppressed worms decreased significantly in 4 and 6 days, respectively, as well as a significant reduction in egg production. We also observed a significant reduction in worm burden and hepatic eggs burden in two independent RNAi experiment in vivo, and minor pathological changes in mice treated with SjVAMP2 specific small interfering (si)RNA. These findings reveal that SjVAMP2 may play important roles in the maintenance of tegument, glucose uptake, worm development and egg production in schistosomes.

The history of schistosomiasis japonica in Taiwan.

Studies of schistosomiasis japonica in Taiwan indicate that the Formosan strain of Schistosoma japonicum is zoophilic in nature. After the discovery of the adult worm of S. japonicum in 1914, a considerable number of epidemiologic studies and experimental infection studies were conducted. This paper is a review of the history of schistosomiasis japonica in Taiwan from before World War II to 2003.

Evidence That Rhesus Macaques Self-Cure from a Schistosoma japonicum Infection by Disrupting Worm Esophageal Function: A New Route to an Effective Vaccine?

BACKGROUND: Rhesus macaques are unusual among schistosome hosts, self-curing from an established infection and thereafter manifesting solid immunity against a challenge, an ideal model for vaccine development. Previously, the immunological basis of self-cure was confirmed; surviving worms had ceased feeding but how immunological pressure achieved this was unclear. The schistosome esophagus is not simply a conduit for blood but plays a central role in its processing. Secretions from the anterior and posterior esophageal glands mix with incoming blood causing erythrocyte lysis and tethering and killing of leucocytes. METHODOLOGY/PRINCIPAL FINDINGS: We have analysed the self-cure process in rhesus macaques infected with Schistosoma japonicum. Faecal egg output and circulating antigen levels were used to chart the establishment of a mature worm population and its subsequent demise. The physiological stress of surviving females at perfusion was especially evident from their pale, shrunken appearance, while changes in the structure and function of the esophagus were observed in both sexes. In the anterior region electron microscopy revealed that the vesicle secretory process was disrupted, the tips of lining corrugations being swollen by greatly enlarged vesicles and the putative sites of vesicle release obscured by intense deposits of IgG. The lumen of the posterior esophagus in starving worms was occluded by cellular debris and the lining cytoplasmic plates were closely adherent, also potentially preventing secretion. Seven proteins secreted by the posterior gland were identified and IgG responses were detected to some or all of them. Intrinsic rhesus IgG colocalized with secreted SjMEGs 4.1, 8.2, 9, 11 and VAL-7 on cryosections, suggesting they are potential targets for disruption of function. CONCLUSIONS/SIGNIFICANCE: Our data suggest that rhesus macaques self-cure by blocking esophagus function with antibody; the protein products of the glands provide a new class of potential vaccine targets.