An integrated environmental improvement of marshlands:impact on control and elimination of schistosomiasis in marshland regions along the Yangtze River,China

Background:Schistosomiasis is a global snail-transmitted infectious disease of poverty.Transmission control had been achieved in China in 2015 after the control efforts for over 60 years.Currently,the remaining core regions endemic for Schistosoma japonicum are mainly located in the marshland and lake regions along the Yangtze River basin.Methods:During the period from 2001 through 2015,an integrated environmental improvement of the marshlands was carried out through the implementation of industrial,agricultural and resources development projects in Yizheng County along the Yangtze River.S.japonicum infection in humans,livestock and snails was estimated by serology,stool examination,hatching technique and microscopy during the 15-year study period to evaluate the effect of the integrated environmental improvement on control and elimination of schistosomiasis.Results:A 0.05%overall rate of S.japonicum infection was observed in snails during the 15-year study period,and no infected snails were detected since 2012.The overall prevalence of S.japonicum infection was 0.09%in humans during the study period,and no human infection was found since 2012.In addition,only 13 bovines were identified with S.japonicum infection in 2003 during the 15-year study period,and since 2004,no infection was found in livestock.Conclusion:The results of the present study demonstrate that the implementation of industrial,agricultural and water resources development projects,not only alters snail habitats in marshland regions,and promotes local economic development,which appears a win-to-win strategy to block the transmission of S.japonicum and accelerate socio-economic development along the Yangtze River.

Challenges in and lessons learned during the implementation of the 1-3-7 malaria surveillance and response strategy in China: a qualitative study

Background:China has made great progress in malaria control over the last century and now aims to eliminate malaria by 2020.In 2012,the country launched its 1-3-7 surveillance and response strategy for malaria elimination.The strategy involves to case reporting within 1 day,case investigation within 3 days,and focus investigation and public health actions within 7 days.The aim of this study was to evaluate the challenges in and lessons learned during the implementation of the 1-3-7 strategy in China so far.Methods:This qualitative study was conducted in two provinces in China:Gansu province(northwestern China)and Jiangsu province(southeastern China)in 2014.Key informant interviews(n=6)and in-depth interviews(n=36)about the implementation aspects of the 1-3-7 strategy were conducted with malaria experts,health staff,laboratory practitioners,and village doctors at the provincial,city,county,township,and village levels.Results:Broad themes related to the challenges in and lessons learned during the implementation of the 1-3-7 strategy were identified according to:case reporting within 1 day,case investigation within 3 days,focus investigation within 7 days,and the overall strategy.The major challenges outlined were related to respecting the timeline of surveillance procedures,the absence of or difficulties in following guidelines on conducting focus investigations,diagnostics,and the increasing number of returning migrant workers from malaria-endemic countries.Important lessons learned revolve around the importance of continuous capacity building,supervision and motivation,quality control,information technology support,applied research,governmental commitment,and intersectoral collaboration.Conclusions:Surveillance is a key intervention in malaria elimination programs.The Chinese 1-3-7 strategy has already proven to be successful but still needs to be improved.In particular,dealing appropriately with imported malaria cases through the screening of migrant workers from malaria-endemic countries is essential for achieving and sustaining malaria elimination in China.China has perfect preconditions for successful malaria elimination provided political commitment and financial investment are guaranteed.The 1-3-7 strategy may also be considered as a model for other countries.

Development and application of a new random walk model to simulate the transport of degradable pollutants

To simulate the pollutant transport with seif-purification in inland waters,the widely used random walk model(RWM)is modified to include a source term for the degradation and to consider the impact of land boundaries.The source term for the degradation is derived from the assumption of the first-order reaction kinetics.Parameters for the new model are determined by a comparison to the analytical results.The proposed model is then applied to simulate and analyze the transport of a test pollutant and its spatial distribution in a large reservoir in northeast China.Reasonable results are obtained,and the effects of the runoff,the flow structure,and the wind on the pollutant transport are analyzed.The results may help the risk assessment and the management of the water pollution in inland waters.

Apropos:critical analysis of molluscicide application in schistosomiasis control programs in Brazil

Schistosomiasis is a snail-transmitted infectious disease affecting over 200 million people worldwide.Snail control has been recognized as an effective approach to interrupt the transmission of schistosomiasis,since the geographic distribution of this neglected tropical disease is determined by the presence of the intermediate host snails.In a recent Scoping Review published in Infectious Diseases of Poverty,Coelho and Caldeira performed a critical review of using molluscicides in the national schistosomiasis control programs in Brazil.They also described some chemical and plant-derived molluscicides used in China.In addition to the molluscicides described by Coelho and Caldeira,a large number of chemicals,plant extracts and microorganisms have been screened and tested for molluscicidal actions against Oncomelania hupensis,the intermediate host of Schistosoma japonicum in China.Here,we presented the currently commercial molluscicides available in China,including 26%suspension concentrate of metaldehyde and niclosamide(MNSC),25%suspension concentrate of niclosamide ethanolamine salt(SCNE),50%niclosamide ethanolamine salt wettable powder(WPN),4%niclosamide ethanolamine salt dustable powder(NESP),5%niclosamide ethanolamine salt granule(NESG)and the plant-derived molluscicide“Luowei”.These molluscicides have been proved to be active against O.hupensis in both laboratory and endemic fields,playing an important role in the national schistosomiasis control program of China.Currently,China is transferring its successful experiences on schistosomiasis control to African countries.The introduction of Chinese commercial molluscicides to Africa,with adaptation to local conditions,may facilitate the progress towards the elimination of schisosomiasis in Africa.

RIP3 deficiency attenuated hepatic stellate cell activation and liver fibrosis in schistosomiasis through JNK-cJUN/Egr1 downregulation

Dear Editor,Activated hepatic stellate cells(HSCs)synthesizing a large amount of extracellular matrix(ECM)are the key events to hepatic fibrosis.1 However,there are no effective drugs for curing liver fibrosis in the clinic.1 Therefore,clarifying the formation mechanism of liver fibrosis is of great importance for finding anti-liver fibrosis drug targets.Recently,an increasing amount of research has shown that necroptosis regulated by receptor-interacting protein kinase 3(RIP3)plays an important role in inflammatory disease injury and could be used as a drug target.2 We found that RIP3 was highly expressed in liver tissues of wildtype(WT)mice infected with Schistosoma japonicum(S.japonicum),mainly at 6 w(weeks)and 8 w post-infection(Fig.1a)。

Approaches being used in the national schistosomiasis elimination programme in China:a review

Schistosomiasis japonica,caused by the human blood fluke Schistosoma japonicum,remains a major public health problem in China,although great success has been achieved.The control efforts during the past half-decade,notably the wide implementation of the new integrated strategy with emphasis on control of the source of S.japonicum infection across the country since 2004,has greatly reduced S.japonicum in humans,livestock,and intermediate host Oncomelania hupensis snails,and transmission control of schistosomiasis was achieved in China in 2015.A two-stage roadmap was therefore proposed for schistosomiasis elimination in 2015,with aims to achieve transmission interruption by 2020 and achieve disease elimination by 2025 in the country.During the last two decades,a variety of approaches,which target the epidemiological factors of schistosomiasis japonica have been developed,in order to block the transmission cycle of the parasite.These approaches have been employed in the national or local schistosomiasis control activities,and facilitated,at least in part,the progress of the schistosomiasis elimination programs.Here,we present an approach to control the source of S.japonicum infection,three new tools for snail control,three approaches for detecting and monitoring S.japonicum infection,and a novel model for health education.These approaches are considered to play a great role in the stage moving towards transmission interruption and elimination of schistosomiasis in China.

A multidisciplinary,integrated approach for the elimination of schistosomiasis:a longitudinal study in a historically hyperendemic region in the lower reaches of the Yangtze River,China from 2005 to 2014

Background:Although great success has been achieved,schistosomiasis remains a major public health concern in China,and the remaining core endemic regions are concentrated along the middle and lower reaches of the Yangtze River.In this longitudinal study,we evaluated the effectiveness of a multidisciplinary,integrated approach for schistosomiasis elimination in a historically hyper-endemic region in the lower reaches of the Yangtze River,China over the 10-year period from 2005 through 2014.Methods:A three-step roadmap for schistosomiasis elimination was designed in the study site,and multidisciplinary,integrated interventions were implemented by the health,agriculture,water resources development,land and resources,and forestry sectors from 2005 to 2014,including chemotherapy for infected individuals,health education,management of the source of Schistosoma japonicum infection,and intermediate host snail control.The annual number of schistosomiasis patients,S.japonicum infection in humans,bovines and Oncomelania hupensis snails,and water infectivity were observed to assess the effectiveness of the multidisciplinary,integrated approach for the elimination of schistosomiasis.Results:There was a tendency towards a gradual decline in both the number of schistosomiasis cases and the prevalence of S.japonicum human infection across the study period from 2005 through 2014.No S.japonicum human infection was detected since 2012,and no acute infection was seen since 2006.During the study period,no infection was found in bovines,and a 0.03%overall infection rate was observed in O.hupensis snails.Since 2009,no infected snails were identified,and the area of both snail habitats and infected snail habitats appeared a reduction over the study period.Following the 3-year multidisciplinary,integrated control,infection control was achieved,and transmission control was achieved after 6-year implementation,with all infected snails and water infectivity eliminated;in addition,the 10-year implementation resulted in interruption of schistosomiasis transmission in the study site in 2014.Conclusions:The results of the present 10-year longitudinal study demonstrate that the multidisciplinary,integrated approach is effective for the elimination of schistosomiasis as a public health problem in the lower reaches of the Yangtze River,China.

Estimation of disability weight for paragonimiasis:a systematic analysis

Background:Paragonimiasis,caused by helminths of the genus Paragonimus spp.,is a neglected tropical disease.Human suffering from paragonimiasis is often misunderstood and its quantification by the disability weight of the disability-adjusted life years largely varies in different global burden of disease(GBD)estimates.This paper is to systematically review clinical paragonimiasis cases and requantify the disability weight of human paragonimiasis.Methods:A systematic analysis was conducted using articles from the following databases:PubMed,Institute for Scientific Information Web of Science,China National Knowledge Infrastructure,the Chinese scientific journal databases Wanfang Data and CQVIP,Africa Journal Online,and the System for Information on Grey Literature in Europe.Search terms were the combination of“paragonim*”with“clinical”or“infection”.Only articles fulfilling the following conditions were recruited for this study:the occurrence of clinical signs and symptoms of paragonimiasis in human beings were reported;diagnosis was confirmed;no comorbidities were reported;the reviewed clinical cases or epidemiological findings were not already included in any other articles.The information and frequencies of paragonimiasis outcomes from included articles using predefined data fields were extracted two times by two separate individuals.Outcome disability weights were selected mainly from the GBD 2004 and GBD 2013 datasets.Frequencies and disability weights of paragonimiasis outcomes were modelled into a decision tree using the additive approach and multiplicative approach,respectively.Monte Carlo simulations were run 5000 times for an uncertainty analysis.Results:The disability weight estimates of paragonimiasis were simulated with 5302 clinical cases from 80 general articles.The overall disability weight was estimated at 0.1927(median 0.1956)with a 95%uncertainty interval(UI)of 0.1632-0.2378 using the additive approach,and 0.1791(median 0.1816)with a 95%UI of 0.1530-0.2182 using the multiplicative approach.The simulated disability weights of Paragonimus westermani cases were higher than that of P.skrjabini cases.Lung outcomes and headache were the top two contributors to disability weight for both species.Conclusions:The use of paragonimiasis disability weight needs to be reconsidered with regard to availability of morbidity data and species variation.Calculating the disease burden of paragonimiasis requires further modification and thus has considerable implications for public health prioritization in research,monitoring,and control.

ReishiMax inhibits mTORC1/2 by activating AMPK and inhibiting IGFR/PI3K/Rheb in tumor cells

Ganoderma lucidum(G.lucidum)extracts,as dietary supplements,have been found to exert potent anticancer activity,which is attributed to the presence of polysaccharides and triterpenes.However,the molecular mechanism underlying the anticancer action of G.lucidum extracts remains to be investigated.Here,we show that ReishiMax GLp,containing G.lucidum polysaccharides and triterpenes(GLPT),inhibited cell proliferation and induced cell death in human lung cancer cells(A549 and A427)and simultaneously suppressed the signaling pathways of mammalian target of rapamycin complexes 1 and 2(mTORC1 and mTORC2),respectively.Mechanistically,GLPT downregulated the phosphorylation and protein levels of insulin-like growth factor 1 receptor(IGFR)and phosphoinositide 3-kinase(PI3K)as well as the protein level of RAS homolog enriched in brain(Rheb).In addition,GLPT also activated the AMP-activated protein kinase(AMPK)network.This was evidenced by observations that GLPT increased the phosphorylation of AMPKα(T172)and its substrates tuberous sclerosis complex 2(TSC2,S1387)and regulatory-associated protein of mTOR(raptor,S792).Ectopic expression of dominant-negative AMPKαpartially mitigated the inhibitory effect of GLPT on mTORC1,indicating that GLPT inhibits mTORC1 partly by activating AMPK.The results suggest that G.lucidum extracts exert anticancer action at least partly by suppressing mTORC1/2 signaling via activation of AMPK and inhibition of IGFR/PI3K/Rheb in tumor cells.

Priorities of China’s participation in global malaria elimination:the perspective of malaria endemic countries

Background:Malaria is one of the major diseases afecting global health,while progress in malaria control and elimination has stagnated in some endemic countries.China has been certifcated malaria free by World Health Organization in 2021,and will get more involved on global malaria elimination.Further discussion is needed on how to collaborate with the malaria endemic countries and provide efective help.This study was to investigate the perceptions of malaria endemic countries on China’s contribution to global malaria elimination and to lay a foundation for further action.Methods:Semi-structured interviews were conducted with key informants including national malaria project managers and technicians from malaria endemic countries.Thematic framework approach was used to analyze the data.Results:Malaria endemic countries now face challenges in insufcient funds,technique,products,public health systems and inadequacy of international assistance.They hold a positive attitude towards cooperation with China and identifed experience and technique exchange,personnel training,system building and scientifc research cooperation as prioritized areas.Conclusions:China could make full use of its own advantages in technique transfer,health system improvement,information system construction,and health human resource training and take an active part in global malaria elimination.

Infectious Diseases of Poverty,the first five years

Although the focus in the area of health research may be shifting from infectious to non-communicable diseases,the infectious diseases of poverty remain a major burden of disease of global health concern.A global platform to communicate and share the research on these diseases is needed to facilitate the translation of knowledge into effective approaches and tools for their elimination.Based on the“One health,One world”mission,a new,openaccess journal,Infectious Diseases of Poverty(IDP),was launched by BioMed Central in partnership with the National Institute of Parasitic Diseases(NIPD),Chinese Center for Disease Control and Prevention(China CDC)on October 25,2012.Its aim is to identify and assess research and information gaps that hinder progress towards new interventions for a particular public health problem in the developing world.From the inaugural IDP issue of October 25,2012,a total of 256 manuscripts have been published over the following five years.Apart from a small number of editorials,opinions,commentaries and letters to the editor,the predominant types of publications are research articles(69.5%)and scoping reviews(21.5%).A total of 1081 contributing authors divided between 323 affiliations across 68 countries,territories and regions produced these 256 publications.The journal is indexed in major international biomedical databases,including Web of Science,PubMed,Scopus and Embase.In 2015,it was assigned its first impact factor(4.11),which is now 2.13.During the past five years,IDP has received manuscripts from 90 countries,territories and regions across six continents with an annual acceptance rate of all contributions maintained at less than 40%.Content analysis shows that neglected tropical diseases(NTDs),followed by the“Big Three”(HIV/AIDS,malaria and tuberculosis)and infectious diseases in general comprise 88%of all publications.In addition,a series of 10 thematic issues,covering 118 publications in all,was published as separate parts of the first five volumes.These publications were cited 975 times,which equals an average of 8.3 times per publication.The current challenge is to identify cutting-edge research topics and attract and to publish first-rate publications leading to increasing importance and impact of the journal in its field.

Decoquinate derivatives:A new class of potent antischistosomal agents against Schistosoma japonicum

Decoquinate（1）, an old and inexpensive coccidiostat, exhibited potent antimalarial activity, however, its antischistosomal activity against Schistosoma japonicum has not yet been evaluated. Based on decoquinate, a series of decoquinate derivatives was designed, synthesized, evaluated as a new class of antischistosomal agents against S. japonicum adult worms in vitro. Among them, compound 15 killed 100% of adult S. japonicum in 72 h at the concentration of 10 mmol/L in vitro, exhibited stronger wormkilling activity than PZQ in vitro and could serve as a promising lead compound to develop new antischistosomal agents.