Molluscicide screening and identification of novel targets against Pomacea canaliculata.

BACKGROUND: Owing to the nonavailability of any clear targets for molluscicides against Pomacea canaliculata, target-based screening strategy cannot be employed. In this study, the molluscicidal effects of typical pesticides on P. canaliculata were evaluated to obtain the molluscicide target. A series of arylpyrrole compounds were synthesized based on the discovered target, and their structure-activity relationships explored. A preliminary strategy for screening molluscicides based on specific targets was also developed. RESULTS: A laboratory colony of P. canaliculata was developed, which showed no difference in sensitivity to niclosamide compared with the wild group, while exhibiting a higher stability against pesticide response. Mitochondrial adenosine triphosphate (ATP) synthase inhibitors and mitochondrial membrane potential uncouplers were identified and validated as potential targets for molluscicide screening against P. canaliculata. A series of arylpyrrole compounds were designed and synthesized. The median lethal concentration of 4-bromo-2-(4-chlorophenyl)-5-(trifluoromethyl)-1H-pyrrole-3-carbonitrile (Compound 102) was 10-fold lower than that of niclosamide. CONCLUSION: New molluscicide targets were discovered and validated, and preliminary strategies were explored for pesticide screening based on these targets. Compound 102 exhibited a high molluscicidal activity and had a great potential value for exploring a molluscicide to control P. canaliculata. © 2024 Society of Chemical Industry.

A configurational analysis on career success of scientific and technological innovation talents in universities.

Introduction: Increasing the career success of scientific and technological innovation talents has become an important means of keeping and using talents in countries around the world. However, the problem has not been solved effectively. Methods: Thirty-five cases were chosen in this study. The combined effects of human capital, psychological capital, micro-social capital, team social capital, and macro-social capital on the career success of scientific and technological innovation talents, as well as relevant influencing mechanisms, were discussed using qualitative comparative analysis (QCA). Results: Results demonstrate that: (a) while a single factor cannot be the only condition for the high career success of scientific and technological innovation talents in universities, increasing macro-social capital plays a relatively universal role in a high career success rate. (b) There are three paths driving the high career success of scientific and technological innovation talents in universities. (c) There are two paths driving the non-high career success of scientific and technological innovation. Both have characteristics of absent psychological capital and micro-social capital. Moreover, the driving mechanism of high career success has an asymmetrical causal relationship. Discussion: Research conclusions are not only conducive to expanding the research perspectives of social capital theory and career success, but also provide valuable insight into how to stimulate the career success of scientific and technological innovation talents in universities.

In vivo efficiency of praziquantel treatment of single-sex Schistosoma japonicum aged three months old in mice.

Schistosomiasis is a major neglected tropical disease mainly caused by Schistosoma haematobium, S. japonicum and S. mansoni, and results in the greatest disease burden. Mass drug administration (MDA) with praziquantel (PZQ), a single drug only available for the disease, has played a vital role in schistosomiasis control. Therefore, any possibility of selection of the parasites for PZQ resistance or low sensitivity may hamper the 2030's target of global disease elimination. We had experimentally demonstrated the long-term survival and reproductive potential of single-sex (of either sex) S. japonicum infections in definitive hosts mice. What has not yet been adequately addressed is whether the long live single-sex schistosomes remain sensitive to PZQ, and what reproduction potential for those schistosomes surviving treatment may have. We therefore performed experimental mice studies to explore the treatment effectiveness of PZQ (at total doses of 200 or 400 mg/kg, corresponding to the sub-standard or standard treatment doses in humans) for single-sex S. japonicum aged three months old. The results showed that no treatment efficiency was observed on female schistosomes, whereas on male schistosomes only at PZQ 400 mg/kg a significant higher efficiency in reducing worm burdens was observed. Moreover, either schistosome males or females surviving PZQ treatment remained their reproduction potential as normal. The results indicate that long (i.e., three months) live single-sex S. japonicum can easily survive the current treatment strategy, and moreover, any schistosomes, if with PZQ resistance or low sensitivity, could be easily transmitted in nature. Therefore, in order to realize the target for the national and the global schistosomiasis elimination, there is undoubtedly a great need for refining PZQ administration and dosage, looking for alternative therapies, and/or developing vaccines against schistosome.

Evaluation of the molluscicidal activities of arylpyrrole on Oncomelania hupensis, the intermediate host of Schistosoma japonicum.

The snail Oncomelania hupensis is the only intermediate host of the highly invasive parasite Schistosoma japonicum. Molluscicide is often used to curb transmission of S. japonicum. Niclosamide, the only World Health Organization (WHO) recognized molluscicide, presents major drawbacks, including high cost and toxicity towards aquatic animals. In the present study, a number of aryl pyrrole derivatives (ADs) were synthesized to serve as potential molluscicides and were tested on O. hupensis. To uncover the underlying mechanisms, adenosine triphosphate (ATP) and adenosine diphosphate (ADP) levels were assessed in the soft body of ADs-exposed O. hupensis, using high performance liquid chromatography (HPLC). The effect of C6 on key points of energy metabolism (the activities of complexes I, III, IV and the membrane potential) was determined. We demonstrated that the Compound 6 (C6, 4-bromo-1-(bromomethyl)-2-(4-chlorophenyl)-5-(trifluoromethyl)-1H-pyrrole-3-carbonitrile) exerted the strongest molluscicidal activity against adult O. hupensis at LC50 of 0.27, 0.19, and 0.13 mg/L for 24, 48, and 72 h respectively. Moreover, we found that the bromide on the pyrrole ring of C6 was essential for molluscicidal activity. Furthermore, the ATP content reduced from 194.46 to 139.75 µg/g after exposure to 1/2 LC50, and reduced to 93.06 µg/g after exposure to LC50. ADP, on the other hand, remained the same level before and after C6 exposure. We found that C6, at 1/2 LC50, reduced the membrane potential of O. hupensis, while no significant changes were observed in the activities of complexes I, III, and IV. C6 was identified with excellent activities on O. hupensis. The obtained structure-activity relationship and action mechanism study results should be useful for further compound design and development.

Discovery and Validation of a Novel Target of Molluscicides against Oncomelania hupensis, the Intermediate Host of Schistosoma japonicum.

In this study, 196 strains of actinomycetes isolated from marshland soil samples were tested for molluscicidal activity against Oncomelania hupensis. Five strains demonstrated molluscicidal activity, of which the molluscicidal efficiency of Actinomycetes strain A183 was the maximum. After the fermentation supernatant of actinomycetes A183 was extracted with ethyl acetate (EWEA), the LC50 of the EWEA after leaching for 48 h and 72 h were 0.2688 and 0.2195 mg/L, respectively. The effect of EWEA on the key points of energy metabolism was determined. We noted that 1 mg/L of EWEA (A813) significantly reduced the activity of mitochondrial respiratory chain complex I (P < 0.05), while no significant changes were observed in the activities of complexes II, III, and IV. In addition, EWEA (A813) could decrease the membrane potential of O. hupensis purified mitochondria in vitro. The LC50 of the 3 uncoupler (FCCP, DNP, and Tyrphostin A9) after immersion for 24 h were 0.065, 0.135, and 0.110 mg/L, respectively; LC50 after 48 h treatment was 0.064, 0.124, and 0.082 mg/L, respectively; LC50 after 72 h treatment was 0.063, 0.129, and 0.061 mg/L, respectively, and all uncoupler showed strong molluscicidal activities, demonstrating that the mitochondrial membrane potential uncoupling is a potential target for molluscicides against O. hupensis. Moreover, the molluscicidal active substance of strain A183 needs to be further isolated, purified, and structurally characterized considering its promising potential applications.

GWC1 is essential for high grain quality in rice.

Appearance quality is an important determinant of rice quality. Many genes that affect grain appearance quality have been identified, but the regulatory mechanisms that contribute to this trait remain unclear. Here, two grains with chalkiness (gwc1) mutants, gwc1-1 and gwc1-2, were identified from an EMS-mutagenized population of indica rice cultivar Shuhui498 (R498). The gwc1 mutants had poor grain appearance quality consistent with the measured values for the percentage of grains with chalkiness, square of chalky endosperm, the total starch, amylose and sucrose contents. Milling quality and grain size were also affected in the gwc1 mutants. The gwc1-1 and gwc1-2 were found to be loss-of-function allelic mutants. GWC1 was mapped to the long arm of rice chromosome 8 using the MutMap strategy and incorrectly annotated in the reference genome for Nipponbare (MSU). The GWC1 gene corresponds to the WTG1/OsOTUB1 gene, which encodes an otubain-like protease with deubiquitinating activity that is homologous to human OTUB1. GWC1 transcripts accumulated to high levels in early endosperm after fertilization and developing inflorescences, and GWC1-green fluorescent protein (GFP) signal was detected in the nucleus and cytoplasm. GWC1 is likely to regulate grain appearance quality through genes involved in sucrose metabolism and starch biosynthesis. Overall, the present findings reveal that GWC1 is important for grain quality and yield due to its effects on grain chalkiness and size.

Evaluation of protective efficacy induced by different heterologous prime-boost strategies encoding triosephosphate isomerase against Schistosoma japonicum in mice.

BACKGROUND: In China, schistosomiasis japonica is a predominant zoonotic disease, and animal reservoir hosts in the environment largely sustain infections. The development of transmission-blocking veterinary vaccines is urgently needed for the prevention and efficient control of schistosomiasis. Heterologous prime-boost strategy is more effective than traditional vaccination and homologous prime-boost strategies against multiple pathogens infection. In the present study, to further improve protective efficacy, we immunized mice with three types of heterologous prime-boost combinations based on our previously constructed vaccines that encode triosphate isomerase of Schistosoma japonicum, tested the specific immune responses, and evaluated the protective efficacy through challenge infection in mice. METHODS: DNA vaccine (pcDNA3.1-SjTPI.opt), adenoviral vectored vaccine (rAdV-SjTPI.opt), and recombinant protein vaccine (rSjTPI) were prepared and three types of heterologous prime-boost combinations, including DNA i.m. priming-rAdV i.m. boosting, rAdV i.m. priming-rAdV s.c. boosting, and rAdV i.m. priming-rSjTPI boosting strategies, were carried out. The specific immune responses and protective efficacies were evaluated in BALB/c mice RESULTS: Results show that different immune profiles and various levels of protective efficacy were elicited by using different heterologous prime-boost combinations. A synergistic effect was observed using the DNA i.m. priming-rAdV i.m. boosting strategy; however, its protective efficacy was similar to that of rAdV i.m. immunization. Conversely, an antagonistic effect was generated by using the rAd i.m. priming-s.c. boosting strategy. However, the strategy, with rAdV i.m. priming- rSjTPI s.c. boosting, generated the most optimal protective efficacy and worm or egg reduction rate reaching up to 70% in a mouse model. CONCLUSIONS: A suitable immunization strategy, rAdV i.m. priming-rSjTPI boosting strategy, was developed, which elicits a high level of protective efficacy against Schistosoma japonicum infection in mice.

Evaluating the risk of Schistosoma mansoni transmission in mainland China.

Biomphalaria straminea, an intermediate host of Schistosoma mansoni, is predominantly distributed in the South Americas and Caribbean; however, this snail, as an invasive species, was introduced to Shenzhen, southern China, in 1981, and recent epidemiologic surveys demonstrate that the distribution of B. straminea has expanded across the Zhujiang River Basin, South China. In the presence of continuous importation of S. mansoni-infected cases, there is a growing concern about the transmission of S. mansoni in China. To evaluate the risk of S. mansoni transmission in China, we tested the compatibility of B. straminea captured from the snail habitats in southern China with S. mansoni in laboratory. We detected no S. mansoni infections in B. straminea following exposure to the parasite larvae at snail/miracidium ratios of 1:5, 1:10, 1:20, 1:40, and 1:80, while 6.7 to 66.7 % infections occurred in the control Biomphalaria glabrata depending on the ratio. The results of the present study demonstrate that the invasive B. straminea snails seem to be incompatible with S. mansoni, suggesting a low risk of S. mansoni transmission in mainland China.

Resistance to niclosamide in Oncomelania hupensis, the intermediate host of Schistosoma japonicum: should we be worried?

As the currently only available molluscicide, niclosamide has been widely used for snail control for over 2 decades in China. There is therefore a concern about the emergence of niclosamide-resistant snail populations following repeated, extensive use of the chemical. The purpose of this study was to investigate the likelihood of niclosamide resistance in Oncomelania hupensis in China. Active adult O. hupensis snails derived from 20 counties of 10 schistosomiasis-endemic provinces of China, of 10 snails in each drug concentration, were immersed in solutions of 1, 0.5, 0.25, 0.125, 0.063, 0.032, 0.016 and 0.008 mg L-1 of a 50% wettable powder of niclosamide ethanolamine salt (WPN) for 24 and 48 h at 25 °C, and the median lethal concentration (LC50) was estimated. Then, the 24- and 48-h WPN LC50 values were compared with those determined in the same sampling sites in 2002. The results indicated that the 24- and 48-h WPN LC50 values for O. hupensis were not significantly different from those determined in 2002 (P = 0.202 and 0.796, respectively). It is concluded that the current sensitivity of O. hupensis to niclosamide has not changed after more than 2 decades of repeated, extensive application in the main endemic foci of China, and there is no evidence of resistance to niclosamide detected in O. hupensis.

[Cloning and expression of Schistosoma japonicum VCP gene and its mRNA expression levels in different stages].

OBJECTIVE: To prokaryotically express the valosin-containing protein (VCP) of Schistosoma japonicum, and analyze its VCP mRNA expressions in the cercaria, schistosomulum, adult worm (female and male worms) and egg. METHODS: RNA of S. japonicum eggs were extracted, and reversely transcribed into cDNA. The VCP gene of S. japonicum was amplified by using polymerase chain reaction (PCR), and subcloned into the prokaryotically expressed vector pET15b. The recombined plasmid was transformed into BL21 cells, and the expression of the target gene was induced with isopropyl-beta-D-thiogalactopyranoside (IPTG). The recombinant protein was yielded through the purification of inclusion body, and identified by using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The RNA (s) of cercaria, schistosomulum, female adult worm, male adult worm, and egg of S. japonicum were extracted, digested with DNase, purified, and reversely transcribed into cDNA. The mRNA expressions of the VCP gene in various developmental stages of S. japonicum were determined by using fluorescence-based quantitative real-time PCR. RESULTS: The VCP gene of S. japonicum was yielded by PCR amplification, and the recombinant protein was obtained through recombinant plasmid expression and purification of inclusion body. The highest VCP mRNA expression in S. japonicum cercaria was detected by the fluorescence-based quantitative real-time PCR, while low expressions were found in the schistosomulum, egg, female and male adult worms. CONCLUSION: The recombinant protein encoded by the VCP gene of S. japonicum is successfully obtained, and the VCP mRNA expression is determined in various developmental stages of S. japonicum.

Sensitivity of Oncomelania hupensis to niclosamide: a nation-wide survey in China.

Schistosomiasis japonica, transmitted by the intermediate host snail Oncomelania hupensis of the causative agent Schistosoma japonicum, remains a major public-health concern in China, and control of this snail is one of the major approaches used in attempts to interrupt the transmission of this neglected tropical disease. Niclosamide is currently the only commercial molluscicide available for the control of O. hupensis snails in China. The purpose of this study was to evaluate the current sensitivity of O. hupensis to niclosamide in China. O. hupensis snails derived from 17 sampling sites from eight schistosomiasis-endemic provinces of China were used for the molluscicidal tests. Active adult snails (10 for each drug concentration), were immersed in solutions of 1, 0.5, 0.25, 0.125, 0.063, 0.032, 0.016 and 0.008 mg/L of 50% wettable powder of niclosamide ethanolamine salt (WPN) for 24 and 48 h at 25°C, and then the snail mortality was estimated and LC50 values were calculated. All field-derived O. hupensis snails were dead following immersion in 0.5 and 1 mg/L WPN for 24 h, whereas no death was observed after immersion in 0.008 mg/L WPN for 24 h. Immersion in 0.5, 0.25, 0.125, 0.063, 0.032 and 0.016 mg/L WPN for 24 h resulted in 80%-100%, 63.33%-100%, 0%-85%, 0%-50%, 0%-15%, and 0%-5% snail mortalities, respectively. The 24 h WPN LC50 values for the O. hupensis snails derived from the 17 sampling sites in China ranged from 0.0743 to 0.2285 mg/L, and no significant difference was detected by the Kolmogorov-Smirnov test (p = 0.2). The results indicate that there is no regional variation in the current susceptibility to niclosamide in O. hupensis populations in China. It is suggested that the current sensitivity of niclosamide against O. hupensis remains high and has not changed after more than two decades of repeated, extensive application for snail control in the main endemic areas of China.

PAMAM-Lys, a novel vaccine delivery vector, enhances the protective effects of the SjC23 DNA vaccine against Schistosoma japonicum infection.

BACKGROUND: Schistosomiasis japonica remains a major public-health concern in China. Praziquantel-based chemotherapy effectively reduces both infections and intensity; however, it can not prevent re-infection. Furthermore, there is an increasing concern about praziquantel resistance following long-term repeated use of the drug in endemic areas. Therefore, development of a schistosomiasis vaccine, as a strategy to prevent and control schistosomiasis japonica, has been given high priority. The present study was conducted to develop PAMAM dendrimers as a novel vaccine delivery vector for a schistosomiasis japonica DNA vaccine and evaluate its ability to enhance protective effects against Schistosoma japonicum infection. METHODOLOGY/PRINCIPAL FINDINGS: Lysine was used to modify 4.0G PAMAM, and the modified product PAMAM-Lys was synthesized. PAMAM-Lys showed both high transfection and low cytotocity for gene delivery in vitro. DNA vaccines combined with PAMAM-Lys produced higher level of protection compare with naked DNA vaccines against S. japonicum infection in a mouse model. Futhermore,antibodies from mice immunized with PAMAM-Lys combined DNA vaccines were significantly higher than those of mice immunized with the naked DNA vaccines. The PAMAM-Lys vector elicited a predominantly IgG2a antibody response and a tremendously increase in the production of IL-2 and IFN-γ. CONCLUSION/SIGNIFICANCE: Lysine-modified PAMAM-Lys is an excellent vector. PAMAM-Lys may enhance the immunoreactivity of DNA vaccine and increase the protective effect of the SjC23 DNA vaccine against S. japonicum infection.

Efficacy of artemether and artesunate in mice infected with praziquantel non-susceptible isolate of Schistosoma japonicum.

Praziquantel is currently the only drug of choice for the treatment of human Schistosoma japonicum infections, and praziquantel-based chemotherapy has been proved to be generally effective to control the morbidity and reduce the prevalence and intensity of S. japonicum infections. However, the potential emergence of praziquantel resistance in S. japonicum seriously threatens the elimination of this neglected tropical disease in China. The purpose of this study was designed, in mouse animals, to evaluate the in vivo efficacy of artemether and artesunate against praziquantel non-susceptible S. japonicum. Mice infected with a praziquantel non-susceptible isolate and a praziquantel-susceptible isolate of S. japonicum were treated with artemether and artesunate at a single oral dose of 300 mg/kg given once on each of days 7-8 and 35-36 post-infection to assess the efficacy against juvenile and adult worms. Administration with artemether and artesunate at a single oral dose of 300 mg/kg on each of days 7-8 post-infection resulted in total worm burden reductions of 72.8 and 73.5% in mice infected with praziquantel-susceptible S. japonicum, and 77.9 and 74.1% in mice infected with the non-susceptible isolate (both P values >0.05), while the same treatments given on days 35-36 post-infection reduced total worm burdens by 71.4 and 69.6% in mice infected with the susceptible isolate, and 75.3 and 69.6% in mice infected with the non-susceptible parasite (both P values >0.05). It is concluded that there is no evidence for reduced susceptibility of artemether and artesunate in praziquantel non-susceptible S. japonicum.

Is there a reduced sensitivity of dihydroartemisinin against praziquantel-resistant Schistosoma japonicum?

Praziquantel is currently the only drug of choice for the treatment of human schistosomiases. However, it has been proved that Schistosoma japonicum subjected to drug pressure may develop resistance to praziquantel. To evaluate the efficacy of dihydroartemisinin against praziquantel-resistant S. japonicum, mice infected with a praziquantel-resistant isolate and a praziquantel-susceptible isolate of S. japonicum were treated with dihydroartemisinin at a single oral dose of 300 mg/kg given once on each of 35-36 post-infection days, while infected but untreated mice served as controls. All mice were sacrificed 50 days post-infection, and the worm burden reductions were estimated. Administration of dihydroartemisinin at a single oral dose of 300 mg/kg on each of 35-36 post-infection days reduced total worm burdens of 69.8% and female worm burdens of 86% in mice infected with the praziquantel-susceptible isolate, and total worm burdens of 66.1% and female worm burdens of 85.1% in mice infected with the praziquantel-resistant isolate (both P values > 0.05). It is concluded that the sensitivity of artemisinin derivative dihydroartemisinin does not reduce in praziquantel-resistant S. japonicum.

[Surveillance and forecast system of schistosomiasis in Jiangsu Province. VI. Detection technology of water infectivity based on enrichment of Schistosoma japonicum cercariae on water surface].

OBJECTIVE: To explore the enrichment technique of Schistosoma japonicum cercariae on the water surface, so as to establish a new method combined with the existing technology to detect the cercarial infested water body quickly and sensitively. METHODS: Soybean oil, gasoline, kerosene and isophorone were screened as expanding agents. The cercariae were enriched by the thrust of the expanding agents when diffusing on the water surface, and PE adsorption film and C-6 film were applied to seize them so as to determine the infectivity of the water quickly. The relationship between the dose of expanding agents and diffusion radius were explored. RESULTS: Gasoline, kerosene and isophorone were suitable expanding agents, and the diffusion effect of isophorone was the best. After the enrichment by the expanding agents, the detection rate of cercariae of the method seizing cercariae with the film significantly improved in the water. CONCLUSION: This new method could effectively improve the detection rate of the cercarial infested water and is suitable for the low-degree infested water.

In vivo activity of dihydroartemisinin against Schistosoma mansoni schistosomula in mice.

Dihydroartemisinin, an anti-malarial agent, has been shown to exhibit activity against Schistosoma japonicum and S. mansoni. The purpose of the present study was to investigate the in vivo activity of dihydroartemisinin against juvenile S. mansoni and the changes to the genital system among worms surviving drug treatment. Mice were infected with 200 S. mansoni cercariae each and randomly assigned to groups. Dihydroartemisinin at a single oral dose of 300 mg/kg was given to mice on Days 14 or 16, 18, 20, 21, 22, 24, 26 or 28 post-infection, to assess the efficacy of dihydroartemisinin against juvenile S. mansoni. Mice were treated with dihydroartemisinin using various protocols with the total drug dose of 900 mg/kg, to investigate the efficacy of dihydroartemisinin against the schistosomula of S. mansoni. In addition, changes to the genital system among worms surviving dihydroartemisinin treatment, were recorded. An oral dose of dihydroartemisinin of 300 mg/kg was given to mice on Days 14, 16, 18, 20, 21, 22, 24, 26 or 28 days post-infection; this resulted in a 65.0-82.4% reduction in total worm burden and a 70.9-83.0% female worm burden. Better results were seen when treatment was given 20-24 days post-infection. Administration of multiple-dose and low-oral-dose dihydroarteminisinin (at doses of 90, 180, 300 and 450 mg/kg) at different times, reduced total worm burdens by 88.7-99.1% and female worm burdens by 93.2-99.5%. The egg tubercles in mice livers were significantly reduced following treatment; in some mice no egg tubercles were found. These findings indicate dihydroartemisinin exhibits high in vivo activity against the schistosomula of S. mansoni. It causes damage to the genital system of worms, influences the development of of S. mansoni worms, reduces the oviposition of surviving worms and enhances the formation of granulomas around tissue-trapped eggs, thereby reducing damage to the infected mammalian host.

[Preparation and molluscicidal effect of 5% niclosamide ethanolamine granules].

OBJECTIVE: To explore the preparation of 5% niclosamide ethanolamine granules and evaluate its molluscicidal effect. METHODS: The optimal formula was obtained by the selection of wetting agents, dispersants, adhesives and carriers. The molluscicidal effect of 5% niclosamide ethanolamine granules was measured by the spray methods in the laboratory and field. RESULTS: The mixed 5% niclosamide ethanolamine, 0.2% sodium lauryl sulfate, and 1% alkylphenol sulfonic polyxyethylene ether sulfonate were crushed by gas flow, and then mixed with 93.7% quartz sand and 0.1% polyvinyl alcohol water solution, drying to 5% niclosamide ethanolamine granules. The density, bulk density, and moisture of 5% niclosamide ethanolamine granules were 1.4 g/ml, 1.3 g/ml, and 2.4%, respectively, and the hot storage stability was qualified. Under the lab condition, the death rates of Oncomelania hupensis snails sprayed with 0.5 g/m2 (7 d) or 1.0 g/m2 (1 d) of 5% niclosamide ethanolamine granules were higher than 95%. In the field, the death rates of the snails sprayed with 0.5 g/m2 (7 d) or 1.0 g/m2 (1 d) were higher than 85%. CONCLUSION: There is a high molluscicidal effect of 5% niclosamide ethanolamine granules and it is suitable for field application.

[Distribution of niclosamide spreading oil on water surface and its efficacy against cercariae of Schistosoma japonicum].

OBJECTIVE: To investigate the distribution and spreading speed of niclosamide spreading oil, as well as its effect against cercariae of Schistosoma japonicum. METHODS: The foamed plastic with a diameter of 4 mm served as a buoyage, which was placed at the center of the still water surface. The niclosamide spreading oil was dropped at 0.5 cm from the buoyage, the floating distance of the buoyage was observed, and the spreading speed and area of the niclosamide spreading oil were measured. A cylindrical bucket (at a diameter of 40 cm and height of 50 cm) was filled with de-chlorinated water at a temperature of 25 +/- 1 degrees C, and then 60 microl of the spreading oil was dropped at the center of the water surface. At 10 cm and 20 cm from the center, 1 ml water was sampled at water depths of 10, 20, 30, 40 cm and 50 cm, respectively, and the niclosamide concentrations were determined by using high-performance liquid chromatography in each sample. The niclosamide spreading oil was diluted into solutions at effective concentrations of 1.25 mg/L and 0.63 mg/L with ethanol, and then 10 microl of each solution was added to 24-well plates which contained S. japonicum cercariae to yield the niclosamide concentration of 6.25 x 10(-3) mg/L and 3.13 x 10(-3) mg/L per well, respectively. The survival of the cercariae was observed at different time. RESULTS: The spreading speeds and areas were 59, 55, 71, 90, 111, 122 cm/s and 153 cm/s, and 5.31, 5.89, 7.07, 10.06, 12.56, 15.20 m2 and 16.61 m2, respectively, while dropping 20, 30, 40, 50, 60, 70 microl and 80 microl of the niclosamide spreading oil on water surface. The spreading showed an accelerating trend with the increasing dropping volume, and there was a good linear relationship observed between them. In addition, the spreading area also enlarged with the increase in the dropping volume. After dropping 60 microl of the niclosamide spreading oil on water surface, the peak concentration of niclosamide reached 1.27 mg/L on water surface, and remained more than 0.07 mg/L 2 h later. However, the concentration of niclosamide was all lower than 0.04 mg/L at 10 cm under surface or more. Following the treatment with 6.25 x 10(-3) mg/L of niclosamide spreading oil for 1 min, all the cercariae were dead, while the mortality rates of the cercariae were 0, 1.39%, 13.89%, 19.44%, 43.06%, 69.44% and 79.17% at 1, 2, 3, 5, 10, 20 min and 30 min, respectively, after the treatment with 3.13 x 10(-3) mg/L of the drug. CONCLUSIONS: The niclosamide spreading oil is fast to spread and is kept retention for a long time on water surface, and exhibits high activity against S. japonicum cercariae, and it can be used for killing the cercariae on water surface and interrupting the transmission of schistosomiasis in the endemic field.

[Studies on standardization of methods for screening molluscicides in laboratory IV sensitivity of Oncomelania snails from different months to niclosamide].

OBJECTIVE: To understand the sensitivity of Oncomelania snails collected from different months to niclosamide, so as to provide the scientific evidence for the standardization of methods for molluscicide screening and efficacy evaluation in laboratory. METHODS: The snails collected from the marshland of Zhenjiang City, Jiangsu Province month by month from June 2010 to May 2011. After being raised in laboratory for 24 h, the snails were randomly grouped, and then immersed in different concentrations of 50% wettable powder formulation of niclosamide ethanolamine salt at (25 +/- 1) degrees C with a humidity of 60%. The dead snails were identified and counted, and the mortality rate of snails and median lethal concentration (LC50) were calculated. RESULTS: When the snails were immersed in the solutions of niclosamide at concentrations of more than 0.5 mg/L for 24 h, all the snails collected from different months were dead, while 60%-100% of the snail mortality was achieved for 0.250 mg/L niclosamide, 3%-27% for 0.125 mg/L niclosamide, and 3%-20% for 0.062 5 mg/L niclosamide. When the concentration was lower than 0.032 mg/L, the niclosamide was not toxic to the snails within 24 h. The LC50 value was 0.140-0.209 mg/L for 24 h. When the snails were immersed in the solutions of niclosamide at concentrations of more than 0.5 mg/L for 48 h, all the snails collected from different months were dead, while 90%-100% of the snail mortality was achieved for 0.250 mg/L niclosamide, 3%-57% for 0.125 mg/L niclosamide, 3%-13% for 0.062 5 mg/L niclosamide, and 0-10% for 0.032 mg/L niclosamide. When the concentration was lower than 0.016 mg/L, the niclosamide was not toxic to the snails within 48 h. The LC50 value was 0.112-0.170 mg/L for 48 h. There were no significant differences in the mortality of snails caused by niclosamide treatment observed at 24 and 48 h (P values = 0.374 and 0.267, respectively). CONCLUSIONS: There are little changes in the sensitivity of snails collected from different months to niclosamide, with minor fluctuations in LC50 values. Such a finding indicates that the snails collected from different months have few effects on screening of molluscicides and efficacy evaluation.

Immunodiagnostic efficacy of detection of Schistosoma japonicum human infections in China: a meta analysis.

OBJECTIVE: To assess the diagnostic efficacy of the currently most widely used indirect hemagglutination assay (IHA) and enzyme-linked immunosorbent assay (ELISA) for detection of Schistosoma japonicum human infections. METHODS: A comprehensive search was undertaken from China National Knowledge Infrastructure, Wanfang Database, VIP Database, PubMed, Cochrane Library, Science Citation Index Expanded, Proquest, and the inclusion and exclusion criteria were strictly settled. The funnel plot was used to assess the publication bias, Cochran's Q test was employed to measure the homogeneity between studies, a summary receiver operating characteristic (SROC) curve was used to compare the diagnostic accuracy between the IHA and ELISA qualitatively by means of the Weighted Least Square method, the Ordinary Least Square method and the Robust regression method, and the diagnostic odds ratio (DOR) was drawn to compare the accuracy quantitatively. RESULTS: Out of 785 publications, 19 papers were eventually selected for analysis. Literature quality assessment indicated that minor publication bias existed in studies pertaining IHA test, but no bias was found in literatures regarding ELISA test. The heterogeneity test showed a heterogeneity between studies was present (χ(2)=466.07 and 34.67, both P values<0.0001). The areas under the SROC curves of IHA were all higher than that of ELISA test using the three methods (Weighted Least Square method: 0.766 vs. 0.695, Ordinary Least Square method: 0.826 vs. 0.741, Robust regression: 0.815 vs. 0.715). The TPR* values for IHA and ELISA were 0.710, 0.759, 0.749, and 0.650, 0.686 and 0.666, respectively, and OR values were 5.997, 9.937, 8.893, and 3.432, 4.784 and 3.959, respectively. The DOR of IHA was 9.41 (95% CI: 4.88-18.18), and 4.78 (95% CI: 3.21-7.13) for ELISA. CONCLUSIONS: All above results revealed that the diagnostic performance of IHA is better than that of ELISA. However, taking into account their unsatisfactory diagnostic value in areas with low infection intensity, a search for a better diagnostic test that can be applied in field situations in China should be given high priority.