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Introduction: Cutaneous Leishmaniasis (CL) is a significant public health concern worldwide. Iran is among the most CL-affected countries, being one of the six most endemic countries in the world. This study aimed to provide a spatio-temporal visualisation of CL cases in an endemic urban area in north-eastern Iran identifying high-risk and low-risk areas during the period 2016-2019., Methods: This ecological study was conducted in the city of Mashhad, north-eastern Iran. All cases (n=2425) were diagnosed based on clinical findings and parasitological tests. The patient data were aggregated at the census tract level (the highest resolution available). CL incidence rates were subjected to Empirical Bayesian smoothing across the census tracts followed by spatial autocorrelation analysis to identify clusters and outliers. Spatial scan statistic was used to explore the purely temporal, purely spatial and spatio-temporal trend of the disease. In all instances, the null hypothesis of no clusters was rejected at p ≤0.05., Results: The overall crude incidence rate decreased from 34.6 per 100,000 individuals in 2016 to 19.9 per 100,000 in 2019. Cluster analysis identified high-risk areas in south-western Mashhad and low-risk areas in the north-eastern areas. Purely time scan statistics identified March to July as the time period with highest risk for CL occurrence. One most likely purely high-risk spatial cluster and six secondary purely high-risk spatial clusters were identified. Further, two spatio-temporal high-risk clusters, one in the north of the city from April to August and a second in the south-western part from March to September were observed., Conclusions: Significant spatial, temporal and spatio-temporal patterns of CL distribution were observed in the study area, which should be considered when designing tailored interventions, such as effective resource allocation models, informed control plans and implementation of efficient surveillance systems. Furthermore, this study generated new hypotheses to test potential relationships between socio-economic and environmental risk factors and incidence of CL in high-risk areas., (Copyright © 2021. Published by Elsevier B.V.)

Echinococcoses are serious zoonotic diseases in China's vast, western and north-western pastoral areas that has one of the highest prevalence in the world. The two most common forms, cystic echinococcosis (CE) and alveolar echinococcosis (AE), are co-epidemic in some areas causing a grave threat to people's health and economic development. Echinococcus spp. are transmitted through domestic, sylvatic and mixed cycles involving many kinds of host. Successful transmission requires a favourable environment for the growth of the parasites and survival of their eggs, while the unique customs and religious beliefs in the endemic areas pose a challenge to the prevention and control of these parasites. Based on previous epidemiological studies, this paper reviews the particular factors affecting the transmission of Echinococcus parasites in China, with a focus on biological (parasite genotype and the species, age, sex and density of hosts), environmental (landscape and climate) and social (age, gender, ethnicity, education, occupation, life style, cultural customs, living conditions and hygiene practices of humans in the endemic areas). These three factors interact with each other and jointly determine the parasites' transmission intensity, the study of which supports the formulation of the strategies and measures that are significant for control of these infections., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Soil-transmitted helminthiases (STHs) are caused by a group of intestinal nematode infections due to poor hygiene and environments, and clonorchiasis is a food-borne trematode (FBT) infection caused by ingestion of raw freshwater fish. Both are endemic in the People's Republic of China. To explore a suitable control strategy, integrated interventions were applied between 2007 and 2009 in ten pilot counties (eight for the STHs and two for clonorchiasis). Drug administration was used for treatment and complementary efforts to improve the situation based on health education, provision of clean water and sanitation were carried out. Significant achievements were gained as reflected by a drastic decrease in prevalence these infections were demonstrated. The overall prevalence of STHs and clonorchiasis decreased from 35.9% to 7.8% and from 41.4% to 7.0%, respectively. The reduction of prevalence and high cost-effectiveness were documented supporting large-scale application of this integrated intervention in China and elsewhere., (Copyright © 2020. Published by Elsevier B.V.)

Helminth infections, many of them listed as neglected tropical diseases by the World Health Organization, remain a public health issue in many parts of the world. The People's Republic of China (P.R. China) stands out due to impressive progress in the control and local elimination of helminth infections. An important contextual factor is P.R. China's sustained social and economic development that allowed implementation of health-related poverty alleviation, improving water, sanitation and hygiene, enhancing information, education and communication, coupled with major engineering and infrastructure development and intersectoral collaboration. Nonetheless, food-borne trematodiases, soil-transmitted helminthiases, echinococcosis, cysticercosis/taeniasis and schistosomiasis still exert a considerable burden in P.R. China, even though the numbers of infected people have decreased substantially since the new millennium. This special issue of Acta Tropica provides a comprehensive update of the current knowledge of the main helminth infections in P.R. China, summarises progress in research and discusses future prospects for gaining and sustaining control towards the final goal of breaking transmission and hence, eliminating helminthiases. It consists of 34 articles with a wide coverage that can be grouped into six domains: (i) epidemiological assessment and disease burden estimates; (ii) diagnostics and antigen characterisation; (iii) drug and vaccine development; (iv) host-parasite interactions and snail genetics; (v) surveillance and public health response; and (vi) capacity building and international cooperation. The control and elimination of helminthiases not only furthers the health and wellbeing of the Chinese people, but also provides innovative approaches, tools and strategies, which can be adopted and applied in other countries and regions of the world where helminthiases still prevail., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Epidemiological mapping and risk profiling build on the idea that diseases are tied to social-ecological systems that govern the distribution and abundance of transmissible pathogens, vectors and hosts. This is the heart of the emerging field of ecohealth, which examines how biological, cultural, demographic, economic, physical, political and social environments change and how these changes affect the health and wellbeing of humans, animals and ecosystems and the services they provide. This paper is an overview of a special issue of Acta Tropica, whose 15 publications reflect a geographically and epidemiologically diverse landscape of ecohealth. Nowhere is an ecohealth approach better suited than in Africa and its myriad of landscapes that include contexts varying from profuse expanses of tropical rain forests to the world's greatest desert. The publication of African ecohealth-related projects displays a biological, cultural and social diversity in health system contexts and a wide variety of contributions pertaining to different, often neglected, tropical diseases, including brucellosis, Buruli ulcer, fascioliasis, malaria, Q fever, rabies, Rift Valley fever and schistosomiasis. Pursuing an ecohealth approach provides a platform that brings together community members, decision makers, scientists and other stakeholders with a view to understand how ecosystem changes affect health conditions. Taken together, the presentation of this variety of papers dealing with environmental variables associated with health inaugurates the vital concept of ecohealth. By emphasizing that all organisms are part of social-ecological systems, the long-term wellbeing of both people and animals depending on healthy and productive ecosystems is highlighted., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The downward trend in prevalence and intensity of Schistosoma japonicum infection in the People's Republic of China (P.R. China) has reached a level where accurate methods are required for monitoring the national schistosomiasis control programme and to verify whether transmission has been interrupted. We have assessed the prevalence of active S. japonicum infection by use of an up-converting phosphor lateral-flow (UCP-LF) assay for determination of circulating anodic antigens (CAA) in urine and serum, and compared the findings with those of the Kato-Katz technique for egg detection in stool and an immunohaemagglutination assay (IHA) for specific antibodies in serum. The study was carried out in three villages located in a remaining S. japonicum-endemic area in P.R. China. Overall, 423 individuals were investigated by Kato-Katz, 395 by IHA, 371 with the UCP-LF CAA assay adapted for urine and 178 with the UCP-LF CAA assay applied on serum. The IHA showed the highest number of positive results (n=107, 27.1%). The UCP-LF CAA urine assay detected 36 CAA positives (9.7%) and the serum-based CAA assay 21 positives (11.8%). The Kato-Katz technique revealed only six positive stool samples (1.4%). Among those 166 individuals with complete data records, sensitivities of the different assays were determined versus a combined 'gold' standard, showing the highest sensitivity for the urine CAA assay (93%), followed by the serum CAA (73%) and IHA (53%), whilst triplicate Kato-Katz thick smears had a very low sensitivity (13%). Serum CAA concentrations were about 10-fold higher than in urine and were significantly correlated. Highest prevalences as determined by CAA were found in older age groups (>40 years). Half of the CAA- or egg-positive cases were negative for antibodies by IHA, thereby revealing an important obstacle for the effectiveness of the current schistosomiasis control and elimination efforts. The significantly higher prevalence of active schistosome infections as shown by the urine and serum UCP-LF CAA assays has implications for the national control and elimination programme in P.R. China, particularly in respect to case-finding and intervention strategies., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The presentation of the World Health Organization (WHO)'s roadmap for neglected tropical diseases (NTDs) in January 2012 raised optimism that many NTDs can indeed be eliminated. To make this happen, the endemic, often low-income countries with still heavy NTD burdens must substantially strengthen their health systems. In particular, they need not only to apply validated, highly sensitive diagnostic tools and sustainable effective control approaches for treatment and transmission control, but also to participate in the development and use of surveillance-response schemes to ensure that progress made also is consolidated and sustained. Surveillance followed-up by public health actions consisting of response packages tailored to interruption of transmission in different settings will help to effectively achieve the disease control/elimination goals by 2020, as anticipated by the WHO roadmap. Risk-mapping geared at detection of transmission hotspots by means of geospatial and other dynamic approaches facilitates decision-making at the technical as well as the political level. Surveillance should thus be conceived and developed as an intervention approach and at the same time function as an early warning system for the potential re-emergence of endemic infections as well as for new, rapidly spread epidemics and pandemics., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Schistosomiasis remains of considerable public health concern in many tropical and subtropical regions of the world, including the People's Republic of China (P.R. China). The effectiveness of schistosomiasis control interventions are, among other factors, governed by the social-ecological context. However, eco-social determinants of schistosomiasis are poorly understood, particularly at the household or village levels. In the current study, residents in 26 villages of Eryuan county, Yunnan province, P.R. China, were screened for Schistosoma japonicum infection with a serological assay that was followed by stool examination for sero-positive individuals. Bayesian multilevel models with spatial random effects were employed to profile the S. japonicum infection risk based on known transmission sites of S. japonicum that are scattered across individual land parcels in this part of the country. The key risk factors identified with this approach were the absence of a sanitary stall house for livestock and presence of living and infected intermediate host snails in close proximity. We conclude that a spatially explicit Bayesian multilevel approach can deepen our understanding of eco-social determinants that govern schistosomiasis transmission at a small geographical scale., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Modelling is an important tool for the exploration of Schistosoma japonicum transmission patterns. It provides a general theoretical framework for decision-makers and lends itself specifically to assessing the progress of the national control programme by following the outcome of surveys. The challenge of keeping up with the many changes of social, ecological and environmental factors involved in control activities is greatly facilitated by modelling that can also indicate which activities are critical and which are less important. This review examines the application of modelling tools in the epidemiological study of schistosomiasis japonica during the last 20 years and explores the application of enhanced models for surveillance and response. Updated and timely information for decision-makers in the national elimination programme is provided but, in spite of the new modelling techniques introduced, many questions remain. Issues on application of modelling are discussed with the view to improve the current situation with respect to schistosomiasis japonica., (Copyright © 2014 Elsevier B.V. All rights reserved.)

In Asia, Schistosoma japonicum is the predominant schistosome species, while Schistosoma mekongi is confined to limited foci in Cambodia and Lao People's Democratic Republic. While the People's Republic of China has been successful in controlling schistosomiasis, the disease remains a major public health issue in other areas. In order to prioritise intervention areas, not only accurate diagnosis is important but also other factors, such as practicality, time-efficiency and cost-effectiveness, since they strongly influence the success of control programmes. To evaluate the highly specific urine-based assays for the schistosome circulating cathodic antigen (CCA) and the circulating anodic antigen (CAA), banked urine samples from Cambodia (n=106) and the Philippines (n=43) were examined by the upconverted phosphor lateral flow (UCP-LF) CAA assay and the point-of-care (POC)-CCA urine assay. Based on 250 μl urine samples, UCP-LF CAA sensitivity outcomes surpassed a single stool examination by the Kato-Katz technique. The banked urine samples in the current study did not allow the evaluation of larger volumes, which conceivably should deliver considerably higher readings. The sensitivity of a single urine POC-CCA was in the same order as that of a single Kato-Katz thick smear examination, while the sensitivity approached that of triplicate Kato-Katz when a combination of both CAA and CCA assays was used. The promising results from the current proof-of-concept study call for larger investigations that will determine the accuracy of the urine-based CCA and CAA assays for S. mekongi and S. japonicum diagnosis., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Schistosomiasis japonica was endemic in 12 provinces (including municipalities and autonomous regions) in the People's Republic of China (PR China). Despite the tremendous decrease of schistosomiasis incidence after almost 60 years of control, the distribution of snail-breeding sites has not been reduced significantly. In order to verify current transmission risks and identify the potential establishment of new foci of schistosomiasis driven by environmental changes, we conducted surveillance in selected risk areas of three provinces: Jiangsu, Anhui and Shandong from 2008 to 2010 in addition to routine snail surveillance. We investigated populations and possible reservoirs in sentinel sites and report that the total number of new acute cases did not diminish further in spite of ongoing control activities. In Anhui Province the local count compared to the national count was 43% (19/44) in 2008, 33% (25/75) in 2009 and 40% (17/42) in 2010. In all, 31.58 km(2) areas of snail breeding sites were newly detected nationwide through the year 2008-2010, of which the proportion of Anhui was 42% (5.03/11.98) in 2008, 95% (8.39/8.79) in 2009 and 79% (8.52/10.81) in 2010. Sentinel surveillance showed eight, nine and five confirmed cases of acute schistosomiasis in mobile populations (fishermen, migrant workers) in 2008, 2009 and 2010, respectively. All these cases were detected in Chaohu County, which must therefore be deemed an area at risk. We conclude that continuous surveillance with an emphasis on snails must be enhanced in potential risk areas in PR China., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The overall aim of the Regional Network for Asian Schistosomiasis and other Helminth Zoonoses (RNAS(+)) is to strengthen collaboration between control authorities in the regional, endemic countries. The network has provided critical research input during its 12 years of existence developing gradually from a small forum for information exchange. RNAS(+) now provides advice on regional strategies regularly and contributes to the mobilization of resources with respect to multi-country projects on several parasitic diseases in Southeast Asia, primarily schistosomiasis but also other helminth infections including polyparasitism. To make progress towards these goals, RNAS(+) has focused on platform design and technical standardization aiming at fostering research capacity and the development of networking capacities with easy access to information databases. This administrative body is largely virtual connecting RNAS(+) members via the Internet, providing database and administrative back-up. This strategy, aiming at boosting research on the target diseases, strongly emphasizes ways and means to alleviate the spectre of disease and poverty from the endemic areas., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The 4-year (2006-2010) alliance to optimize schistosomiasis control and transmission surveillance in sub-Saharan Africa (CONTRAST), funded by the European Commission, stands out as a 'game-changer' by successfully harnessing and combining new as well as previously available capabilities for schistosomiasis control in selected African countries. By establishing an African research network and promoting an interactive agenda that operates simultaneously at the molecular, biological, spatial and social levels, a navigable avenue for validation and application of tools complementary to preventive chemotherapy has been opened., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The dipstick dye immunoassay (DDIA), developed in China for the detection of antibodies against Schistosoma japonicum, relies on soluble egg antigen (SEA) labelled with a colloidal dye. This assay is not only rapid, simple and inexpensive, but also particularly useful for screening in the field. In order to determine whether S. japonicum antigens are sufficiently cross-reactive to make the assay applicable for the diagnosis also of S. mekongi a DDIA approach based on the S. japonicum SEA was tried in cohorts of healthy and infected people living in areas non-endemic and endemic with regard to schistosomiasis mekongi in Cambodia and Laos. A sensitivity of 97.1% was recorded when testing Cambodian subjects, correctly diagnosing 33 out of 34 infected people. When the assay was applied in Laos, a sensitivity of 98.6% (69/70) was found. None of 114 residents living in a non-endemic area in Cambodia tested positive. A cross-reaction of 18.3% was found in patients infected with Opisthorchis viverrini. The results support the notion that the DDIA using S. japonicum SEA antigens can safely be implemented for the diagnosis of schistosomiasis mekongi, but care is needed in the interpretation of results obtained from areas that are co-endemic for O. viverrini.

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.

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.

Few studies comparing schistosomiasis vaccine candidate antigens between laboratories have been carried out and published. Generally, only the investigators who discovered the molecules have evaluated them in either experimental animal models or in human correlate studies. In an attempt to identify responses against specific antigens and investigate their association with resistance versus susceptibility to re-infection, we studied the serological reactions and the cytokine responses stimulated by a panel of 10 candidate vaccine molecules in 225 long-term residents of an area endemic for Schistosoma mansoni in Egypt. The panel consisted of four recombinant antigens (Sm62-Irv5, Sm37-G3PDH, Sm28-GST and Sm14-FABP), one full-length native protein (Sm97-paramyosin), two synthetic peptides (MAP3 and MAP4) and three unpublished antigens (PR52-filamin, PL45-phosphoglycerate kinase, PN18-cyclophilin). Two different study designs, one based on retrospective and the other on prospective parasitological data were applied in the evaluation of the immune responses. Using historical data collected over the previous 5 years, correlations between frequency of re-infection and antigen-specific immune responses were investigated. In the prospective arm of the study, the subjects were followed over time after treatment with praziquantel with periodic immunological tests and stool examinations. Thus, highly specific humoral and cellular immune reactions in response to the 10 antigens described above could be correlated, both prospectively and retrospectively, with detailed epidemiological data covering a 66-month period. The immune response profiles produced were unique to each antigen but no clear "winner" or "winners" were identified. However, markers for both resistance and susceptibility to re-infection were identified for each molecule indicating which types of responses to aim for in vaccination and which ones to avoid. The insights gained from this approach should be useful for antigen selection and ultimately for vaccine formulation prior to Phase I/II trials in humans.

We present the first mathematical model on the transmission dynamics of Schistosoma japonicum. The work extends Barbour's classic model of schistosome transmission. It allows for the mammalian host heterogeneity characteristic of the S. japonicum life cycle, and solves the problem of under-specification of Barbour's model by the use of Chinese data we are collecting on human-bovine transmission in the Poyang Lake area of Jiangxi Province in China. The model predicts that in the lake/marshland areas of the Yangtze River basin: (1) once-yearly mass chemotherapy of humans is little better than twice-yearly mass chemotherapy in reducing human prevalence. Depending on the heterogeneity of prevalence within the population, targeted treatment of high prevalence groups, with lower overall coverage, can be more effective than mass treatment with higher overall coverage. Treatment confers a short term benefit only, with prevalence rising to endemic levels once chemotherapy programs are stopped; (2) depending on the relative contributions of bovines and humans, bovine treatment can benefit humans almost as much as human treatment. Like human treatment, bovine treatment confers a short-term benefit. A combination of human and bovine treatment will dramatically reduce human prevalence and maintains the reduction for a longer period of time than treatment of a single host, although human prevalence rises once treatment ceases; (3) assuming 75% coverage of bovines, a bovine vaccine which acts on worm fecundity must have about 75% efficacy to reduce the reproduction rate below one and ensure mid-term reduction and long-term elimination of the parasite. Such a vaccination program should be accompanied by an initial period of human treatment to instigate a short-term reduction in prevalence, following which the reduction is enhanced by vaccine effects; (4) if the bovine vaccine is only 45% efficacious (the level of current prototype vaccines) it will lower the endemic prevalence, but will not result in elimination. If it is accompanied by an initial period of human treatment and by a 45% improvement in human sanitation or a 30% reduction in contaminated water contact by humans, elimination is then possible.

A number of different schistosome antigens are capable of partially protecting experimental animals from challenge infection. More than 100 such antigens have been identified, about 15% of which are strongly protective and deemed promising though they do not reach the level close to sterile immunity seen after vaccination with irradiated cercariae. Studies of human correlate reactions, i.e. serological reactions and cytokine responses to schistosomiasis antigens, in individuals living in areas endemic for schistosomiasis have shown associations between certain antigen-specific immune responses and lack of re-infection over time. This approach was applied in Brazil and Egypt where it was possible to epidemiologically follow cohorts of individuals in endemic areas for extended periods of time correlating infection status with immune responses against a panel of well-researched, highly purified vaccine candidates. The immune correlates found were unique to each antigen and could be either positive or negative, i.e. associated with resistance or with susceptibility to re-infection. However, few antigens were clear-cut in this respect, i.e. the majority of them induced ambiguous responses. For example, a single antigen might have a significant positive correlation when antigen-driven interferon (INF)-gamma production is measured but also show a significant negative correlation with respect to the IgG1 titre induced. These observations suggest that there are desirable, antigen-specific immune responses that would be valuable in a vaccine but they also indicate that there are responses that must be avoided. The insights gained should be useful not only for antigen selection but also for vaccine formulation prior to Phase I/II trials in humans. It would be of great value if similar independent, long-term human correlate studies could also be undertaken in areas endemic for Schistosoma japonicum.

Two decades ago, a group of Chinese scientists discovered the antischistosomal properties of artemether, a derivative of the antimalarial drug artemisinin. However, it was only recently that the importance of this finding was recognized internationally, following a collaborative effort between Chinese, European and African scientists, who investigated the effects of artemether against the major human schistosome species. Laboratory studies revealed that artemether exhibits the highest activity against juvenile stages of the parasites, while adult worms are significantly less susceptible. There was no indication of neurotoxicity following repeated high doses of artemether given fortnightly for up to 5 months. Randomized controlled clinical trials confirmed that artemether, orally administered at a dose of 6 mg/kg once every 2-3 weeks, results in no drug-related adverse effects, and significantly reduces the incidence and intensity of schistosome infections. The risk that these treatment regimens might select for resistance, particularly for resistant-plasmodia, appears to be low. Combined treatment with artemether and praziquantel, given to animals harbouring juvenile and adult schistosome worms, resulted in significantly higher worm burden reductions than each drug administered singly. In conclusion, artemether-integrated with other control strategies-has considerable potential for reducing the current burden of schistosomiasis in different epidemiological settings.