Research gaps for three main tropical diseases in the People’s Republic of China

This scoping review analyzes the research gaps of three diseases:schistosomiasis japonica,malaria and echinococcosis.Based on available data in the P.R.China,we highlight the gaps between control capacity and prevalence levels,and between diagnostic/drug development and population need for treatment at different stages of the national control programme.After reviewing the literature from 848 original studies and consultations with experts in the field,the gaps were identified as follows.Firstly,the malaria research gaps include(i)deficiency of active testing in the public community and no appropriate technique to evaluate elimination,(ii)lack of sensitive diagnostic tools for asymptomatic patients,(iii)lack of safe drugs for mass administration.Secondly,gaps in research of schistosomiasis include(i)incongruent policy in the implementation of integrated control strategy for schistosomiasis,(ii)lack of effective tools for Oncomelania sp.snail control,(iii)lack of a more sensitive and cheaper diagnostic test for large population samples,(iv)lack of new drugs in addition to praziquantel.Thirdly,gaps in research of echinococcosis include(i)low capacity in field epidemiology studies,(ii)lack of sanitation improvement studies in epidemic areas,(iii)lack of a sensitivity test for early diagnosis,(iv)lack of more effective drugs for short-term treatment.We believe these three diseases can eventually be eliminated in China's Mainland if all the research gaps are abridged in a short period of time.

Slow-release praziquantel for dogs:presentation of a new formulation for echinococcosis control

Background:Echinococcosis is a serious,zoonotic,parasitic disease with worldwide distribution.According to a epidemiological survey in 2012 in China,there are 20,000 infected patients and more than 50 million people at the risk.As the dog is the main,definitive host,the Government of China encourages monthly praziquantel treatment of every dog.However,this is difficult to achieve in geographically challenging areas,such as the Tibetan plateau,where there are also many dogs without owners.To overcome these problems,we investigated the transmission blocking capacity of a slow-release formulation of praziquantel administered by subcutaneous injection.Methods:The impact of a slow-release preparation of two pharmacokinetically stereoselective praziquantel enantiomers,i.e.,R-(−)-praziquantel(R-PZQ)and S-(+)-praziquantel(S-PZQ)absorbed into a biodegradable polymer was studied in beagle dogs(N=6).The preparation was given by subcutaneous injection using a single dose of 100 mg/kg.Chiral-selective,high-performance liquid chromatography(HPLC)and high-resolution mass spectrometry(HRMS)were applied to measure the praziquantel enantiomers in the plasma of the dogs.The lower limit for estimating plasma concentrations accurately for R-PZQ was 4 ng/ml and for S-PZQ 20 ng/ml.The pharmacokinetic parameters were calculated by a noncompartmental analysis model using Drug Analyze System(DAS)software 2.0.The SPSS 19.0 software was used for statistical analysis,and the statistical comparison between enantiomers was assessed using the two-tailed t-test.Results:Two hours after administration,peak concentrations of R-PZQ and S-PZQ:321±26 and 719±263 ng/ml,respectively,were achieved.After 180 days,the average plasma concentration of R-PZQ in the six dogs had decreased to 13 ng/ml.The average concentration value of S-PZQ was higher than that of R-PZQ in the first 90-day period but fell afterwards and could not be accurately estimated when dropping below 20 ng/ml(the lower methodological limit for this enantiomer).Taking all the dogs into account,the average maximum concentration(Cmax)of S-PZQ in plasma over the first 3 months was higher than that of R-PZQ by 114.0%(P<0.05),while the average mean retention time(MRT)of R-PZQ in plasma was higher than that of S-PZQ by 96.3%(P<0.05).Conclusions:Praziquantel given as an in situ slow-release formulation by subcutaneous injection resulted in concentrations of the active principle in beagle dogs,which should be capable of resisting new Echinococcus infections for at least 6 months.The new formulation of praziquantel represents a potential,alternative way of presenting medication against tapeworm infections in dogs.

Synthesis of 2,5-disubstitued benzimidazole using SnCl_2-catalyzed reduction system at room temperature

Stannous chloride dihydrate is used as an efficient catalyst in reductive cyclization of 2-nitro-5- substituted aniline Schiff base leading to stable 2,5-disubstitued benzimidazole derivatives in excellent yields with good purity. It provides a novel method of synthesis of 2,5-disubstitued benzimidazole under reductive system at room temperature.