Schistosomiasis Chemotherapy

After malaria, schistosomiasis (or bilharzia) is the second most prevalent disease in Africa, and is occurring in over 70 countries in tropical and subtropical regions. It is estimated that 600 million people are at risk of infection, 200 million people are infected, and at least 200 000 deaths per year are associated with the disease. All schistosome species are transmitted through contact with fresh water that is infested with free‐swimming forms of the parasite, which is known as cercariae and produced by snails. When located in the blood vessels of the host, larval and adult schistosomes digest red cells to acquire amino acids for growth and development. Vaccine candidates have been unsuccessful up to now. Against such devastating parasitic disease, the antischistosomal arsenal is currently limited to a single drug, praziquantel, which has been used for more than 35 years. Because the question of the reduction of the activity of praziquantel was raised recently, it is thus urgent to create new and safe antischistosomal drugs that should be combined with praziquantel to develop efficient bitherapies.     

初中学生血吸虫病检查结果与影响因素分析

目的调查和分析江西南昌地区血吸虫病流行区初中学生血吸虫病情况,及相关影响因素。方法 2015年8月至2016年8月,将江西南昌地区血吸虫病流行区中的19个重点县分为血吸虫病传播控制区和血吸虫病疫情控制区,其中传播控制区调查人数1 569名,疫情控制区调查人数1 723名,对所有的学生均采取问卷调查措施。结果疫情控制区初中学生血吸虫病检查率明显高于传播控制区初中学生血吸虫病检查率,数据比较差异具有统计学意义(P0.05);血防知识知晓及格率越高,检查率越高;学校血防教育频次越高,检查率越高;血防部分教育频次及格率越高,检查率越高,数据比较差异均具有统计学意义(P0.05)。结论江西南昌地区血吸虫病流行区初中学生血吸虫病检查率较低,需要加强对初中学生的健康教育,实现提高初中学生血吸虫病检查率的目的。     

A schistosomiasis compartment model with incubation and its optimal control

A new mathematical model included an exposed compartment is established in consideration of incubation period of schistosoma in human body. The basic reproduction number is calculated to illustrate the threshold of disease outbreak. The existence of the disease free equilibrium and the endemic equilibrium are proved. Studies about stability behaviors of the model are exploited. Moreover, control measure assessments are investigated in order to seek out effective control interventions for anti‐schistosomiasis. Then, the corresponding optimal control problem according to the model is presented and solved. Theoretical analyses and numerical simulations induce several prevention and control strategies for anti‐schistosomiasis. At last, a discussion is provided about our results and further work. Copyright © 2017 John Wiley & Sons, Ltd.     

Albatrellus confluens (Alb. & Schwein.) Kotl. & Pouz.: Natural Fungal Compounds and Synthetic Derivatives with In Vitro Anthelmintic Activities and Antiproliferative Effects against Two Human Cancer Cell Lines

Neglected tropical diseases affect the world’s poorest populations with soil-transmitted helminthiasis and schistosomiasis being among the most prevalent ones. Mass drug administration is currently the most important control measure, but the use of the few available drugs is giving rise to increased resistance of the parasites to the drugs. Different approaches are needed to come up with new therapeutic agents against these helminths. Fungi are a source of secondary metabolites, but most fungi remain largely uninvestigated as anthelmintics. In this report, the anthelmintic activity of Albatrellus confluens against Caenorhabditis elegans was investigated using bio-assay guided isolation. Grifolin (1) and neogrifolin (2) were identified as responsible for the anthelmintic activity. Derivatives 4–6 were synthesized to investigate the effect of varying the prenyl chain length on anthelmintic activity. The isolated compounds 1 and 2 and synthetic derivatives 4–6, as well as their educts 7–10, were tested against Schistosoma mansoni (adult and newly transformed schistosomula), Strongyloides ratti, Heligmosomoides polygyrus, Necator americanus, and Ancylostoma ceylanicum. Prenyl-2-orcinol (4) and geranylgeranyl-2-orcinol (6) showed promising activity against newly transformed schistosomula. The compounds 1, 2, 4, 5, and 6 were also screened for antiproliferative or cytotoxic activity against two human cancer lines, viz. prostate adenocarcinoma cells (PC-3) and colorectal adenocarcinoma cells (HT-29). Compound 6 was determined to be the most effective against both cell lines with IC₅₀ values of 16.1 µM in PC-3 prostate cells and 33.7 µM in HT-29 colorectal cells.     

Multidisciplinary Preclinical Investigations on Three Oxamniquine Analogues as New Drug Candidates for Schistosomiasis**

Schistosomiasis is a disease of poverty affecting millions of people. Praziquantel (PZQ), with its strengths and weaknesses, is the only treatment available. We previously reported findings on three lead compounds derived from oxamniquine (OXA), an old antischistosomal drug: ferrocene-containing (Fc-CH₂-OXA), ruthenocene-containing (Rc-CH₂-OXA) and benzene-containing (Ph-CH₂-OXA) OXA derivatives. These derivatives showed excellent in vitro activity against both Schistosoma mansoni larvae and adult worms and S. haematobium adult worms, and were also active in vivo against adult S. mansoni. Encouraged by these promising results, we conducted additional in-depth preclinical studies and report in this investigation on metabolic stability studies, in vivo studies on S. haematobium and juvenile S. mansoni, computational simulations, and formulation development. Molecular dynamics simulations supported the in vitro results on the target protein. Though all three compounds were poorly stable within an acidic environment, they were only slightly cleared in the in vitro liver model. This is likely the reason why the promising in vitro activity did not translate into in vivo activity on S. haematobium. This limitation could not be overcome by the formulation of lipid nanocapsules as a way to improve the in vivo activity. Further studies should focus on increasing the compound's bioavailability, to reach an active concentration in the microenvironment of the parasite.     

Microencapsulation of astiban acid for the treatment ofSchistosomiasis mansoni

Schistosomiasis is among the top five diseases in the world in terms of morbidity, affecting perhaps 200 million people in tropical and subtropical countries. Antischistosomal drugs are toxic and rapidly metabolized. Hence, they must be given in a number of spaced doses. In spite of this there are severe side effects leading to poor patient compliance. This is an ideal situation for the application of sustained drug release to avoid the toxic peak concentration of drug. This study was carried out using Astiban acid, an antimonial drug that is effective againstS. mansoni. Unfortunately, the drug is sufficiently soluble that 50 mg will dissolve in 100 mL water in less than a minute. To permit sustained release of intramuscularly injected drug, microcapsules of astiban acid in poly(d,l-lactic acid) were formed by coacervation. Release studies show that an appreciable fraction of the drug is available at the surface for rapid solution. After this surface drug dissolves, the remaining drug is released slowly with half-times of many hours. After the initial burst, the release of drug follows Higuchi’s equation up to approximately 80% release, with exponentially decreasing release rates thereafter.     

Thermoanalytical characterization of potentially schistosomicide polymeric derivatives

Oxamniquine (OXA) is a schistosomicide agent that causes some adverse effects in central nervous system. Intending to improve OXA therapeutic properties, a polymeric prodrug was designed. Currently, there is an increasing interest of thermal analytical techniques in the pharmaceutical area, so differential thermal analysis (DTA) and thermogravimetry (TG) were carried out to evaluate the thermal behavior of OXA, polymethacrylic acid (PMA), [poly(methacrylic-co-oxamniquine methacrylate)acid] (PMOXA) and physical mixture (OXA+PMA). The thermoanalytical profile of the physical mixture showed characteristic events of the thermal decomposition of OXA and PMA. Distinctly, PMOXA DTA curve did not show an endothermic peak at 148.5°C indicating that the drug was incorporated into the polymeric system. These results were corroborated by the IR spectroscopy and X-ray diffraction data. This revised version was published online in August 2006 with corrections to the Cover Date.     

Drug Repurposing and De Novo Drug Discovery of Protein Kinase Inhibitors as New Drugs against Schistosomiasis

Schistosomiasis is a neglected tropical disease affecting more than 200 million people worldwide. Chemotherapy relies on one single drug, praziquantel, which is safe but ineffective at killing larval stages of this parasite. Furthermore, concerns have been expressed about the rise in resistance against this drug. In the absence of an antischistosomal vaccine, it is, therefore, necessary to develop new drugs against the different species of schistosomes. Protein kinases are important molecules involved in key cellular processes such as signaling, growth, and differentiation. The kinome of schistosomes has been studied and the suitability of schistosomal protein kinases as targets demonstrated by RNA interference studies. Although protein kinase inhibitors are mostly used in cancer therapy, e.g., for the treatment of chronic myeloid leukemia or melanoma, they are now being increasingly explored for the treatment of non-oncological conditions, including schistosomiasis. Here, we discuss the various approaches including screening of natural and synthetic compounds, de novo drug development, and drug repurposing in the context of the search for protein kinase inhibitors against schistosomiasis. We discuss the status quo of the development of kinase inhibitors against schistosomal serine/threonine kinases such as polo-like kinases (PLKs) and mitogen-activated protein kinases (MAP kinases), as well as protein tyrosine kinases (PTKs).     

THE ROLLING DEVELOPMENT MODEL OF ECOLOGICAL ECONOMY COMBINED WATER CONSERVANCY CONSTRUCTION WITH SCHISTOSOMIASIS CONTROL

Abstract. On the basis of classification of geographical properties a rolling development goal programming model is formulated in correspondence with the ecopattern group in Four-Lake Area. In this model, the control of schistosomiasis and strengthen-Lug of the drainage-storage function are both regarded as ecological measures during the process of multi-year(r0) ecological economic rolling development to make the ecoagrlcultural system in this area into a stably operating, ordered, and good cyclicsystem under the support of some controllable factors.