Pharmacological and immunological effects of praziquantel against Schistosoma japonicum: a scoping review of experimental studies.

BACKGROUND: Chemotherapy for schistosomiasis has been around for 100 years. During the past century, great efforts have been made to develop new antischistosomal drugs from antimonials to nonantimonials, and some of these have been used extensively in clinical treatment. With the exception of a few drugs, such as oxamniquine and metrifonate, most of the antischistosomals developed in the pre-praziquantel period have variable limitations with respect to safety and efficacy. Although oxamniquine and metrifonate have been used for schistosomiasis control, they are only effective against Schistosoma mansoni and S. haematobium, respectively. Currently, praziquantel is the only drug used for treatment of all five species of human schistosomes. In this review, the pharmacological and immunological effects of praziquantel against S. japonicum are summarized and discussed. MAIN TEXT: From the end of the 1970s until the 2000s, scientists have conducted a series of experimental studies on the effects of praziquantel against S. japonicum. These have included examining its unique pharmacological action on schistosomes, the characteristics in susceptibility of the different developmental stages of schistosomes to the drug, the relationship between plasma concentration of the drug and efficacy, the impact of host factors on cidal action of the drug, prevention and early treatment of schistosomal infection, as well as praziquantel-resistant schistosomiasis. CONCLUSION: The effects of praziquantel against S. japonicum, as elucidated by the experimental studies that are reviewed in this paper, may have some reference significance for the development of new antischistosomals.

Silencing Rab14 represses the proliferation and migration of oral squamous cell carcinoma, and enhances cisplatin sensitivity.

Oral squamous cell carcinoma (OSCC) is a subtype of head and neck cancer with a relatively poor prognosis. The mechanisms underlying the initiation and progression of OSCC are complex and not yet fully understood; however, this information is critical for developing novel therapeutic targets and improving patient outcome. Rab14, a Ras related protein, has been implicated in multiple forms of cancer. In the present study, we confirmed that Rab14 is overexpression in human OSCC tissue, compared with normal oral mucosa samples. In addition, knockdown of Rab14 exerted potent anti-tumor effects by repressing the proliferation and migration of OSCC cell lines. Moreover, knockdown of Rab14 reduced the expression of Cyclin D1 and CXCR4, at the level of protein and mRNA, both in vitro and in vivo. Additionally, abrogation of Rab14 enhanced cisplatin sensitivity in OSCC cells in vitro and in vivo. Taken together, our data provides evidence for Rab14 as a potential therapeutic target in OSCC treatment.

Spatial pattern of spontaneous retinal waves instructs retinotopic map refinement more than activity frequency.

Spontaneous activity during early development is necessary for the formation of precise neural connections, but it remains uncertain whether activity plays an instructive or permissive role in brain wiring. In the visual system, retinal ganglion cell (RGC) projections to the brain form two prominent sensory maps, one reflecting eye of origin and the other retinotopic location. Recent studies provide compelling evidence supporting an instructive role for spontaneous retinal activity in the development of eye-specific projections, but evidence for a similarly instructive role in the development of retinotopy is more equivocal. Here, we report on experiments in which we knocked down the expression of ß2-containing nicotinic acetylcholine receptors (ß2-nAChRs) specifically in the retina through a Cre-loxP recombination strategy. Overall levels of spontaneous retinal activity in retina-specific ß2-nAChR mutant mice (Rx-ß2cKO), examined in vitro and in vivo, were reduced to a degree comparable to that observed in whole animal ß2-nAChR mouse mutants (ß2KO). However, many residual spontaneous waves in Rx-ß2cKO mice displayed local propagating features with strong correlations between nearby but not distant RGCs typical of waves observed in wild-type (WT) but not ß2KO mice. We further observed that eye-specific segregation was disrupted in Rx-ß2cKO mice, but retinotopy was spared in a competition-dependent manner. These results suggest that propagating patterns of spontaneous retinal waves are essential for normal development of the retinotopic map, even while overall activity levels are significantly reduced, and support an instructive role for spontaneous retinal activity in both eye-specific segregation and retinotopic refinement.

Assessment of morbidity due to Schistosoma japonicum infection in China.

This paper presents a historical assessment of morbidity due to the Schistosoma japonicum infection in China. Due to the socio-economic situation, which did not allow for a control program to be implemented until the early 1950s, morbidity was serious and mortality was high before this. Based on a few investigations and published papers, it can be said that the disease caused millions of deaths, and destroyed numerous families and villages. Since the 1950s, there has been a national control program, intensive control and prevention work has been carried out, and consequently the disease is being controlled. At present, both the prevalence and the morbidity of the disease have been decreasing substantially. The morbidity of the three phases of the disease is outlined in this paper. Comparatively higher morbidity is seen in the acute and advanced phases of the disease. The four major forms of advanced schistosomiasis i.e., ascites, megalosplenia, dwarfism, and colonic tumoroid proliferation, are outlined with their characteristic clinical presentations; their proportions are different during various periods of the national control program. Ectopic schistosomiasis and the relationship between the S. japonicum infection and colorectal cancer are also discussed. Post-transmission schistosomiasis is briefly discussed (which can happen even if the disease reaches the criteria of elimination, and the infection and transmission have stopped, but yet it still develops). The problem of mammalian reservoir hosts of S. japonicum makes the epidemiology and control of schistosomiasis in China even more complicated and arduous, and the control progress in animal reservoirs is briefly presented.

Research and development of antischistosomal drugs in the People's Republic of China a 60-year review.

A comprehensive 60-year review of antischistosomal drug discovery and development research in the People's Republic of China (P.R. China) is presented. In the 1950s, three antimonials were developed, which, compared to potassium antimony tartrate-the treatment of choice against schistosomiasis at the time-showed equal efficacy but lower toxicity when administered orally or intramuscularly. Activity of furapromidum against Schistosoma japonicum was reported in the early 1960s, and this drug became the first non-antimonial used in clinical treatment of schistosomiasis japonica. Subsequently, two additional nitrofuran derivatives (furadiamine and fuvinazole) were investigated in the laboratory and clinically. In the late 1960s, niridazole and amoscanate were developed by western scientists, which encouraged Chinese researchers to synthesise and further modify the chemical structures of these compounds. However, the modified compounds were less efficacious but similarly toxic, which impeded their further development. The advent of the safe, highly efficacious broad-spectrum antischistosomal drug praziquantel, in the mid-1970s, eventually resulted in a change of the global schistosomiasis control strategy from a multi-pronged transmission control approach to drug-based morbidity control. Numerous studies were carried out in P.R. China to further the understanding of efficacy, mechanism of action and safety of praziquantel against S. japonicum. Efforts have also been made to develop antischistosomal drugs from Chinese traditional medicine, and research with cucurbitin (an amino acid isolated from pumpkin seeds), among other products, showed interesting in vitro and in vivo activities against S. japonicum. In the 1990s, the artemisinins-originally reserved for malaria treatment-were developed as 'chemoprophylactic' agents against S. japonicum, which in turn led to a series of new developments of artemisinins and related compounds as broad-spectrum antischistosomal and anthelminthic therapies.

Epidemiology of schistosomiasis in the People's Republic of China, 2004.

Results from the third nationwide cluster sampling survey on the epidemiology of schistosomiasis in the People's Republic of China, conducted by the Ministry of Health in 2004, are presented. A stratified cluster random sampling technique was used, and 239 villages were selected in 7 provinces where Schistosoma japonicum remains endemic. A total of 250,987 residents 6-65 years of age were included in the survey. Estimated prevalence rates in the provinces of Hunan, Hubei, Jiangxi, Anhui, Yunnan, Sichuan, and Jiangsu were 4.2%, 3.8%, 3.1%, 2.2%, 1.7%, 0.9%, and 0.3%, respectively. The highest prevalence rates were in the lake and marshland region (3.8%) and the lowest rates were in the plain region with waterway networks (0.06%). Extrapolation to all residents in schistosome-endemic areas indicated 726,112 infections. This indicates a reduction of 16.1% compared with a nationwide survey conducted in 1995. However, human infection rates increased by 3.9% in settings where transmission is ongoing.

Conquering schistosomiasis in China: the long march.

The last half-century of schistosomiasis control activities in China have brought down the overall prevalence of human infection with Schistosoma japonicum to less than 10% of the level initially documented in the mid 1950s. Importantly, this reduction is not only, or even mainly, due to the advent of praziquantel in the 1970s and its subsequent dramatic fall in price. Instead, it is the result of a sustained, multifaceted national strategy, adapted to different eco-epidemiological settings, which has been versatile enough to permit subtle adjustments over time as the nature of the challenge changed. Consequently, prevalence has been falling relatively smoothly over the whole period rather than suddenly dropping when mass chemotherapy became feasible. Thus, early recognition of the huge public health and economic significance of the disease, and the corresponding political will to do something about it,underpinned this success. In addition, intersectoral collaboration and community participation played important roles in forming a sustained commitment to a working control strategy based on local resources. The unfolding story is presented from the early years' strong focus on snail control, by means of environmental management, to the last period of praziquantel-based morbidity control carried out under the 10-year World Bank Loan Project (WBLP). An important legacy of the WBLP is the understanding that a research component would sustain control measures and enable future progress. We are now witnessing the payoffs of this forward thinking in the form of a new promising class of drugs, improved diagnostics, and budding vaccine development in addition to novel ways of disease risk prediction and transmission control using satellite-based remote sensing. Different aspects of social and economic approaches are also covered and the importance of health promotion and education is emphasized. Issuing from the review is a set of recommendations, which might further consolidate current control activities, with the ultimate aim to eliminate schistosomiasis from the Chinese mainland.

Surveillance of schistosomiasis in five provinces of China which have reached the national criteria for elimination of the disease.

Surveillance of schistosomiasis consists mainly of surveys carried out in formerly endemic areas to observe infection and re-infection of resident and mobile human populations, and domestic animals (e.g. bovines) plus snail monitoring. Here, we focus on the schistosomiasis situation in the five Chinese provinces which have reached the national criteria for elimination of the disease, i.e. Fujian, Guangdong, Guangxi, Shanghai and Zhejiang. With the exception of three newly infected persons in Guangdong province, detected in 1992, repeated surveys in these provinces have not detected any new locally infected case in either humans or bovines. When the newly infected persons were discovered in Guangdong, residual snail habitats including Schistosoma japonicum-infected snails were found in the neighbourhood. These were destroyed and the infected persons treated before further spread could take place. The surveillance system in place has thus been successful in consolidating the results of the control effort. We conclude that rigorous surveillance for and control of schistosomiasis is the way to prevent resurgence of infection and disease in areas which have reached the national criteria for elimination or transmission interruption.

A geographic information and remote sensing based model for prediction of Oncomelania hupensis habitats in the Poyang Lake area, China.

A model was developed using remote sensing and geographic information system technologies for habitat identification of Oncomelania hupensis, the intermediate host snail of Schistosoma japonicum, in the Poyang Lake area, China. In a first step, two multi-temporal Landsat TM 5 satellite images, one from the wet and the second from the dry season, were visually classified into different land-use types. Next, the normalized difference vegetation index was extracted from the images and the tasseled-cap transformation was employed to derive the wetness feature. Our model predicted an estimated 709 km2 of the marshlands in Poyang Lake as potential habitats for O. hupensis. Near-ground temperature measurements in April and August yielded a range of 22.8-24.2 degrees C, and pH values of 6.0-8.5 were derived from existing records. Both climatic features represent suitable breeding conditions for the snails. Preliminary validation of the model at 10 sites around Poyang Lake revealed an excellent accuracy for predicting the presence of O. hupensis. We used the predicted snail habitats as centroids and established buffer zones around them. Villages with an overall prevalence of S. japonicum below 3% were located more than 1200m away from the centroids. Furthermore, a gradient of high-to-low prevalence was observed with increasing distance from the centroids. In conclusion, the model holds promise for identifying high risk areas of schistosomiasis japonica and may become an important tool for the ongoing national schistosomiasis control programme. The model is of particular relevance for schistosome-affected regions that lack accurate surveillance capabilities and are large enough to be detected at most commercially available remote sensing scales.

An economic evaluation of the national schistosomiasis control programme in China from 1992 to 2000.

The World Bank Loan Project, by far the largest effort in China for schistosomiasis control since control activities were initiated in the mid 1950s, was carried out for a 9-year period commencing in 1992 in the 8 provinces where Schistosoma japonicum remained endemic when the project started. To evaluate its impact, a retrospective economic evaluation was done in 2001. Six representative counties, i.e. Huarong in Hunan province, Qianjiang in Hubei province, Yugan in Jiangxi province, Tongling in Anhui province, Xichang in Sichuan province and Dali in Yunnan province, were selected for the study. The total financial input in these counties from 1992 to 2000 was RMB Yuan 90.334 million with the World Bank loan accounting for 40.9%. Control efforts resulted in reduction of human prevalence rates in the six counties from 0.7-9.0% in 1992 to 0.1-2.7% in 2000. With regard to S. japonicum infection in bovines, a high reduction was observed in Qianjiang, and smaller decreases were noted in four counties, while there was an increase in Dali. In general, the areas infested by the intermediate host snail fluctuated around the initial level. The net benefit-cost ratio was 6.20, which means that this project gained US$ 6.20 for every dollar spent. The correlation coefficients of the net benefit-cost ratio to the human and bovine infection rates at the beginning of the project were 0.55 and 0.66, respectively. It is conceivable that further progress in schistosomiasis control is an important feature for sustained growth of the local economy, particularly in areas where control of the disease has been most challenging.

Use of praziquantel for clinical treatment and morbidity control of schistosomiasis japonica in China: a review of 30 years' experience.

Chemotherapy is widely acknowledged as the most important, rapid and cost-effective method of reducing morbidity due to schistosome infections. The discovery of praziquantel in the 1970s has been a breakthrough for treatment of patients infected with schistosomes, including Schistosoma japonicum in China, and entire communities at risk of schistosomiasis. Praziquantel is usually administered in a single oral dose and has no or only mild and transient side effects. The drug is highly efficacious against S. japonicum, both in patients with acute and chronic stages of the infection, among subjects with extensive hepatosplenic involvement, and in patients with other complicated diseases. The cost of praziquantel has been reduced significantly over the past years. Hence, praziquantel has become the backbone of the national schistosomiasis control programme in China and in other countries where the disease remains endemic, most notably in sub-Saharan Africa. Chemotherapy with praziquantel also plays a role in transmission control of schistosomiasis, although transmission interruption cannot be reached by chemotherapy alone. Here, I review 30 years' of experiences gained with the use of praziquantel for clinical treatment and larger-scale control of schistosomiasis japonica in China.

The public health significance and control of schistosomiasis in China--then and now.

The description of schistosomiasis in China dates back more than two millennia. The disease caused social and economic hardship, and the rates of morbidity and mortality were high. In the mid 1950s, when China's population was approximately 600 million, an estimated 11.6 million people were infected with Schistosoma japonicum. Hence, a national control programme was launched, with an emphasis on intermediate host snail control by means of environmental management. Over the past 50 years, the national control programme has made great progress and praziquantel-based morbidity control became the mainstay of control. In 2000, the number of infected people had been reduced to an estimated 694,788, the snail-infested area has been abridged by over 75%, and the disease had been eliminated in five of the 12 previously endemic provinces. Between the mid 1980s and 2003, the criteria of transmission interruption have been reached in 260 counties (60.0%), transmission control has been achieved in 63 counties (14.5%), but the disease was still endemic in the remaining 110 counties (25.4%). Comparison between the number of cases in 2000 and 2003 suggests that schistosomiasis has re-emerged; an estimated 843,011 people were infected with S. japonicum in 2003. Here, we provide a short historical account of the pubic health significance of schistosomiasis in China, highlight the progress made to date with the national control programme, and place particular emphasis on the most recent trends. Finally, we discuss remaining challenges for schistosomiasis control with the ultimate goal of disease elimination.

The National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention: a new administrative structure for schistosomiasis control.

Since more than 5 decades, the overall responsibility for the national programme on schistosomiasis control in China resides at the government level, i.e. Ministry of Health. Day-to-day activities are carried out by independent provincial parasitic institutes situated in the endemic areas. Along with the general economic development and the steady progress in the medical sciences, successful developments in control and research of the parasitic diseases in the country were achieved. This necessitated a corresponding reorganization of the administrative structures which has taken place at several levels. In January 2002, the Chinese Centre for Disease Control and Prevention was reorganized and the Institute of Parasitic Diseases in Shanghai became part of this new organization under the name of the National Institute of Parasitic Diseases to better reflect its new role. By assigning all administrative tasks regarding research and control of parasitic diseases under the umbrella of one administrative central laboratory, the new task force for epidemiological surveys and direction of parasitic control programmes is well suited to respond to the daunting challenges of the future. The new institution has only existed for a few years but has already become a well-functioning force with a broad contact net of national and international experts on research and control of parasitic diseases.

DNA sequences of Paragonimus skrjabini populations from five provinces in China.

BACKGROUND: To study differences among Paragonimus skrjabini (P. skrjabini) populations from five provinces in China (Guangdong, Fujian, Yunnan, Hubei, and Sichuan) and Paragonimus szechuanensis. METHODS: DNA sequences were obtained from the ITS2 and CO1 genes and phylogenetic trees were constructed from the results. Sequences were also obtained from several other species of Paragonimus for comparative purposes. RESULTS: Although differences existed in the DNA sequence among P. skrjabini populations from five provinces, the differences were very small. There was also some resemblance between P. miyazakii from Japan and Fujian strains of P. skrjabini. CONCLUSION: All studied populations can be regarded as different strains of P. skrjabini; P. szechuanensis is not a separate species but may be a geographical strain of P. skrjabini. We also found that P. miyazakii may be synonymous with P. skrjabini.

[Taxonomic status in DNA sequences of five species of genus Paragonimus].

OBJECTIVE: To analyze the taxonomic status of Paragonimus hokuoensis, P. paishuihoensis, P. menglaensis, P. bangkokensis and P. xiangshanensis in Genus Paragonimus Braun, 1899. METHODS: DNA sequences were obtained from the ITS2 and CO I genes and phylogenetic trees were built from these. RESULTS: There are some DNA sequence differences among P. paishuihoensis, P. menglaensis, P. bangkokensis and P. xiangshanensis, but the differences are small. P. hokuoensis and P. skrjabini are similar in DNA sequence. CONCLUSION: P. paishuihoensis, P. menglaensis, P. bangkokensis and P. xiangshanensis are closer in the genetic relationship. Their taxonomic status lies between P. skrjabini and P. westermani. The genetic relationship between P. hokuoensis and P. skrjabini is very close.

[Study on DNA sequences of Paragonimus skrjabini populations from five provinces in China].

OBJECTIVE: To study differences among Paragonimus skrjabini populations from five provinces (Guangdong, Fujian, Yunnan, Hubei, Sichuan) and Paragonimus szechuanensis and to analyze the taxonomic status of P. heterotremus and P. veocularis in the Genus Paragonimus Braun, 1899. METHODS: DNA sequences were obtained from the ITS2 and CO1 genes and phylogenetic trees were built. RESULTS: Difference of the DNA sequences among P. skrjabini populations from five provinces were minor. P. veocularis and P. skrjabini were similar in DNA sequences. There were also some resemblances between P. miyazakii from Japan and the Fujian isolates of P. skrjabin. In addition, P. heterotremus was found to be closer to P. skrjabini and quite a distance from P. westermani in the phylogenetic tree. CONCLUSION: All studied populations can be regarded as different strains of P. skrjabini; P. szechuanensis is not a separate species, but possibly a geographical strain of P. skrjabini. Also found was that P. veocularis and P. miyazakii may be the synonyms of P. skrjabini. As a separate species, P. heterotremus was found to be closer to P. skrjabini and quite a distance from P. westermani in the genetic relationship.

[Improvement in the preparation of Paragonimus westermani chromosome for karyotype analysis].

OBJECTIVE: To improve Paragonimus westermani chromosome preparation technique. METHODS: After being exposed to colchicine, the gonadal cells of P. westermani were treated by the following procedures: hypotonicity, fixation, dropping onto a slide and staining. RESULTS: The chromosome number of P. westermani is 22, and the karyotype is 2m + 6Sm + 14t chromosome. CONCLUSION: The improved technique of chromosome preparation is feasible to operate and the chromosome is clear enough for karyotype analysis.