Schistosomiasis is a chronic disease caused by trematode flatworms of the genus Schistosoma. The disease remains a serious public health problem in endemic countries and affects at least 207 million people worldwide. A definite diagnosis of the disease plays a key role in the control of schistosomiasis. The detection of schistosome circulating antigens (CAs) is an effective approach to discriminate between previous exposure and current infection. Different methods have been investigated for detecting the CAs. However, the components of the schistosome CAs remain unclear. In this study, we analyzed the CAs in sera of patients infected with Schistosoma japonicum.
Poyang Lake, the largest fresh water lake in China, is the major transmission site of Schistosoma japonicum in China. Epidemics of schistosomiasis japonica have threatened the health of residents and stunted social-economic development there.
Baracktrema obamai n. gen., n. sp. infects the lung of geoemydid turtles (black marsh turtle, Siebenrockiella crassicollis [type host] and southeast Asian box turtle, Cuora amboinensis) in the Malaysian states of Perak, Perlis, and Selangor. Baracktrema and Unicaecum Stunkard, 1925 are the only accepted turtle blood fluke genera having the combination of a single cecum, single testis, oviducal seminal receptacle, and uterine pouch. Baracktrema differs from Unicaecum by having a thread-like body approximately 30â50Ã longer than wide and post-cecal terminal genitalia. Unicaecum has a body approximately 8â12Ã longer than wide and terminal genitalia that are anterior to the distal end of the cecum. The new genus further differs from all other accepted turtle blood fluke genera by having a cecum that is highly convoluted for its entire length, a spindle-shaped ovary between the cirrus sac and testis, a uterine pouch that loops around the primary vitelline collecting duct, a Laurer’s canal, and a dorsal common genital pore. Phylogenetic analysis of the D1-D3 domains of the nuclear large subunit ribosomal DNA (28S) revealed, with high nodal support and as predicted by morphology, that Baracktrema and Unicaecum share a recent common ancestor and form a clade sister to the freshwater turtle blood flukes of Spirorchis, paraphyletic Spirhapalum, and Vasotrema and that, collectively, these flukes were sister to all other tetrapod blood flukes (Hapalorhynchus + Griphobilharzia plus the marine turtle blood flukes and schistosomes). Pending a forthcoming emended morphological diagnosis of the family, the clade including Spirorchis spp., paraphyletic Spirhapalum, Vasotrema, Baracktrema, and Unicaecum is a likely placeholder for “Spirorchiidae Stunkard, 1921” (type genus Spirorchis MacCallum, 1918; type species Spirorchis innominatus Ward, 1921). The present study comprises the 17th blood fluke known to infect geoemydid turtles and the first proposal of a new genus of turtle blood fluke in 21 yr.
While the dispersal of hosts and vectors-through active or passive movement-is known to facilitate the spread and re-emergence of certain infectious diseases, little is known about the movement ecology of Oncomelania spp., intermediate snail host of the parasite Schistosoma japonicum, and its consequences for the spread of schistosomiasis in East and Southeast Asia. In China, despite intense control programs aimed at preventing schistosomiasis transmission, there is evidence in recent years of re-emergence and persistence of infection in some areas, as well as an increase in the spatial extent of the snail host. A quantitative understanding of the dispersal characteristics of the intermediate host can provide new insights into the spatial dynamics of transmission, and can assist public health officials in limiting the geographic spread of infection.
Targeting the cellular Ca(2+) channels and pumps that underpin parasite Ca(2+) homeostasis may realize novel antihelmintic agents. Indeed, the antischistosomal drug praziquantel (PZQ) is a key clinical agent that has been proposed to work in this manner. Heterologous expression data has implicated an action of PZQ on voltage-operated Ca(2+) channels, although the relevant in vivo target of this drug has remained undefined over three decades of clinical use. The purpose of this review is to bring new perspective to this issue by discussing the potential utility of free-living planarian flatworms for providing new insight into the mechanism of PZQ action. First, we discuss in vivo functional genetic data from the planarian system that broadly supports the molecular data collected in heterologous systems and the ‘Ca(2+) hypothesis’ of PZQ action. On the basis of these similarities we highlight our current knowledge of platyhelminth voltage operated Ca(2+) channels, their unique molecular pharmacology and the downstream functional PZQ interactome engaged by dysregulation of Ca(2+) influx that has potential to yield novel antischistosomal targets. Overall the broad dataset underscore a common theme of PZQ-evoked disruptions of Ca(2+) homeostasis in trematodes, cestodes and turbellarians, and showcase the utility of the planarian model for deriving insight into drug action and targets in parasitic flatworms.
Bioavailability and in vivo efficacy of a praziquantel-polyvinylpyrrolidone solid dispersion in Schistosoma mansoni-infected mice.
- European journal of drug metabolism and pharmacokinetics
- Published about 6 years ago
One of the problems of praziquantel (PZQ) is its very low aqueous solubility. Moreover, its dissolution rate is considered the limiting factor for its bioavailability. This work correlates the physical properties and the dissolution behavior of PZQ-polyvinylpyrrolidone (PVP) solid dispersion (SD) at the ratios of 1:1 and 3:7 with its oral bioavailability and its in vivo efficacy against Schistosoma mansoni (S. mansoni). The PZQ and PZQ-PVP SD were characterized by infrared spectroscopy, differential scanning calorimetry, scanning electron microscopy (SEM) and solubility test. Results showed a decrease in crystallinity, possible interaction between PZQ and PVP, greater increase in dissolution rate and appreciable reduction in particle size. S. mansoni-infected mice treated orally with either pure PZQ or PZQ-PVP at a single dose of 500 mg/kg showed a higher increase in AUC((0-8h)), C (max), K (a) and t (1/2e) with a significant decrease in k (el) versus the corresponding uninfected mice. Moreover, uninfected and infected mice treated with PZQ-PVP SD showed 2.3-, 1.6- and 1.3-, 1.25-fold increase, respectively, in AUC((0-8h)) and C (max), with a decrease in k (el) and increase in t (1/2e) by twofold versus the corresponding pure PZQ-treated groups. Percentage worm reduction at all administered doses (62.5, 125, 250, 500 and 1,000 mg/kg) was significantly higher (1- to 1.5-fold) in mice treated with PZQ-PVP SD (ED(50) = 40.92) versus those treated with pure PZQ (ED(50) = 99.29). In addition, a significant reduction in total tissue egg load concomitant with a significant decrease in total immature and mature eggs and an increase in dead eggs in PZQ-PVP SD-treated groups versus their corresponding pure PZQ-treated groups was recorded. Solid dispersion of PZQ with PVP could lead to a further improvement in the effectiveness of PZQ therapy especially with the appearance of some PZQ-tolerant S. mansoni isolates.
One approach to fight against schistosomiasis is to develop an efficient vaccine. Schistosoma mansoni tetraspanning orphan receptor (SmTOR) might be a vaccine candidate, as it is a tegument membrane protein expressed most highly in cercariae. In this study we characterized the recombinant first extracellular domain of SmTOR (rSmTORed1) as having the expected property to bind C2 of complement similarly to a smaller peptide of the same domain, and to produce specific and high-titre antibodies in BALB/c mice immunized using complete Freund’s adjuvant/incomplete Freund’s adjuvant (CFA/IFA). Immunization was protective against parasite infection, as demonstrated by a significant decrease in worm burden in immunized BALB/c mice versus the control groups over two independent trials [64 and 45% reduction for mean adult worm burden in immunized versus phosphate-bufferd saline (PBS) injected mice]. Interestingly, infection by itself did not lead to the generation of anti-rSmTORed1 antibodies, corresponding to the low frequency of specific anti-rSmTORed1 antibodies detected in the sera of patients infected with S. mansoni (2/20; 10%). These data suggest that, as opposed to the natural infection during which SmTOR induces antibodies only rarely, immunization with its smaller first extracellular domain might be more efficient.
SUMMARY Miracidia are short-lived, non-feeding (lecithotrophic) free-living stages of trematodes, whose survival is potentially influenced by temperature. Climate change may result in elevated temperatures affecting trematode transmission. Therefore understanding their thermobiology forms an important step in determining the future dynamics of parasite populations. An empirical relationship exists between the mean expected life span of lecithotrophic larvae and the half life of their population (t 0·5 ) and therefore t 0·5 is a good indicator of glycogen utilization. In this study experimental data on the effects of temperature on miracidial survival were compiled from the scientific literature and evaluated in terms of metabolism using Q 10 and Arrhenius activation energy (E* or μ). Temperature poorly influenced survival/metabolism with all miracidia having distinct zone(s) of thermostability. Overall there were few differences in Q 10 and E* values between most species temperature ranges whilst there were only limited strain-specific variations in thermal responses of laboratory-maintained Schistosoma mansoni. Miracidia demonstrated a trend of greater thermal resistance than cercariae. In particular, comparative studies on 4 strains of the same species of miracidia and cercariae showed little correlation in thermal biology between the 2 life-history stages. The importance of these results for trematode transmission under global climate change is discussed.
The aim of this study was to assess the efficacy and safety of two closely spaced doses of praziquantel (PZQ) against Schistosoma haematobium and S. mansoni infection in school-aged children, and to characterise re-infection patterns over a 12-month period. The study was carried out in five villages in western Niger: Falmado, Seberi and Libore (single S. haematobium infection foci), and Diambala and Namarigoungou (mixed S. haematobium-S. mansoni infection foci). Parasitological examinations consisted of triplicate urine filtrations and triplicate Kato-Katz thick smears at each visit. Two 40mg/kg oral doses of PZQ were administered 3 weeks apart. Adverse events were monitored within 4h after dosing by the survey team and 24h after treatment using a questionnaire. Our final study cohort comprised 877 children who were infected with either S. haematobium, or S. mansoni, or both species concurrently and received both doses of PZQ. Follow-up visits were conducted 6 weeks, 6 months and 12 months after the first dose of PZQ. At baseline, the geometric mean (GM) infection intensity of S. haematobium ranged from 3.6 (Diambala) to 30.3eggs/10ml of urine (Falmado). The GM infection intensity of S. mansoni ranged from 86.7 (Diambala) to 151.4eggs/g of stool (Namarigoungou). Adverse events were reported by 33.0% and 1.5% of the children after the first and second doses of PZQ, respectively. We found cure rates (CRs) in S. haematobium-infected children 3 weeks after the second dose of PZQ ranging between 49.2% (Falmado) and 98.4% (Namarigoungou) and moderate-to-high egg reduction rates (ERRs) (71.4-100%). Regarding S. mansoni, only moderate CRs and ERRs were found (51.7-58.8% in Diambala, 55.2-60.2% in Namarigoungou). Twelve months post-treatment, prevalence rates approached pre-treatment levels, but infection intensities remained low. In conclusion, PZQ, given in two closely spaced doses, is efficacious against S. haematobium, but the low ERR observed against S. mansoni raises concern about mounting PZQ tolerance.
Herein we show for the first time that S. mansoni adult worms secrete exosome-like extracellular vesicles (EVs) ranging from 50-130 nm in size. EVs were collected from the excretory/secretory products of cultured adult flukes and purified by Optiprep density gradient, resulting in highly pure EV preparations as confirmed by transmission electron microscopy and Nanosight tracking analysis. EV proteomic analysis showed numerous known vaccine candidates, potential virulence factors and molecules implicated in feeding. These findings provide new avenues for the exploration of host-schistosome interactions and offer a potential mechanism by which some vaccine antigens exert their protective efficacy.