National Institute for Parasitic Diseases

Schistosoma japonicum is a parasitic flatworm that causes human schistosomiasis, which is a significant cause of morbidity in China and the Philippines. Here we present a draft genomic sequence for the worm. The genome provides a global insight into the molecular architecture and host interaction of this complex metazoan pathogen, revealing that it can exploit host nutrients, neuroendocrine hormones and signalling pathways for growth, development and maturation. Having a complex nervous system and a well-developed sensory system, S. japonicum can accept stimulation of the corresponding ligands as a physiological response to different environments, such as fresh water or the tissues of its intermediate and mammalian hosts. Numerous proteases, including cercarial elastase, are implicated in mammalian skin penetration and haemoglobin degradation. The genomic information will serve as a valuable platform to facilitate development of new interventions for schistosomiasis control. Two international consortia this week report the whole genome sequences of the blood flukes Schistosoma mansoni and Schistosoma japonicum, two of the three major pathogens that cause schistosomiasis, also called bilharzia. Schistosomiasis is a 'neglected' tropical disease affecting more than 200 million people in 76 countries. Analyses of the new genome sequences provide insights into the molecular architecture and host interactions of these pathogens, as well as avenues for future development of targeted interventions for this disease. These are the first two flatworm genomes to be sequenced, so they offer new angles on the early events in animal evolution, in particular the determination of body pattern and the development of tissues into organs. Schistosoma mansoni and Schistosoma japonicum are the pathogenic agents that cause the tropical disease schistosomiasis. Here, and in an accompanying paper, the genomes of these two flatworms are sequenced and analysed. The results provide insights into the molecular architecture and host interactions of the flatworms, as well as avenues for future development of targeted interventions for schistosomiasis.

ookworm infection in humans is caused by an infection with the helminth nematode parasites Necator americanus and Ancylostoma duodenale and is transmitted through contact with contaminated soil. It is one of the most common chronic infections, with an estimated 740 million cases in areas of rural poverty in the tropics and subtropics. 1 Because hookworm infection occurs predominantly among the world's most impoverished people, 1 it holds a unique place in modern history. For example, the reputation of pre-1949 China as the "sick man of Asia" was partly a result of the high prevalence and intensity of infection with hookworm. 2 Mohandas Gandhi had hookworm infection in the last years of his life. 3 Hookworm was also a contributing factor in the slowing of economic development during the early part of the 20th century in the southern United States. 4 Today, hookworm infection is among the most important tropical diseases in humans; the use of disability-adjusted life years as a quantitative measure of the burden of disease reveals that this infection outranks African trypanosomiasis, dengue, Chagas' disease, schistosomiasis, and leprosy. he greatest number of hookworm cases occur in Asia, followed by sub-Saharan Africa. In contrast to these major anthropophilic species, three species of zoonotic hookworm are minor causes of disease in humans. A. ceylanicum infects dogs and cats and can also infect humans but is not considered an important pathogen. The dog hookworm A. caninum causes human eosinophilic enteritis in northeastern Australia, 6 and A. braziliense causes cutaneous larva migrans.

Soil-transmitted helminths of the genus Strongyloides (S. fuelleborni and the more prevalent S. stercoralis) are currently believed to infect an estimated 30-100 million people worldwide. The health consequences of S. stercoralis infections range from asymptomatic light infections to chronic symptomatic strongyloidiasis. Uncontrolled multiplication of the parasite (hyperinfection) and potentially life-threatening dissemination of larvae to all internal organs is found among individuals with compromised immune system functions. This paper provides an overview of the current state of the art in relation to diagnostic methods for detecting the infection, the morbidity caused by the infection and the recommended treatment. It further discusses some of the reasons why this infection is so neglected and the consequence of this for the estimated global prevalence. The paper finally points to the gaps in our knowledge and future research needs related to this infection. As Strongyloides infections have the potential to develop into severe disease in certain population subgroups, untreated infections could cause serious problems in the community. Therefore, we need to carefully investigate this parasite in order to develop and implement effective control programmes.

Nationwide prospective surveillance of all-age patients with acute respiratory infections was conducted in China between 2009‒2019. Here we report the etiological and epidemiological features of the 231,107 eligible patients enrolled in this analysis. Children <5 years old and school-age children have the highest viral positivity rate (46.9%) and bacterial positivity rate (30.9%). Influenza virus, respiratory syncytial virus and human rhinovirus are the three leading viral pathogens with proportions of 28.5%, 16.8% and 16.7%, and Streptococcus pneumoniae, Mycoplasma pneumoniae and Klebsiella pneumoniae are the three leading bacterial pathogens (29.9%, 18.6% and 15.8%). Negative interactions between viruses and positive interactions between viral and bacterial pathogens are common. A Join-Point analysis reveals the age-specific positivity rate and how this varied for individual pathogens. These data indicate that differential priorities for diagnosis, prevention and control should be highlighted in terms of acute respiratory tract infection patients' demography, geographic locations and season of illness in China.

BACKGROUND: Soil-transmitted helminth (STH) infections (i.e., Ascaris lumbricoides, hookworm, and Trichuris trichiura) affect more than a billion people. Preventive chemotherapy (i.e., repeated administration of anthelmintic drugs to at-risk populations), is the mainstay of control. This strategy, however, does not prevent reinfection. We performed a systematic review and meta-analysis to assess patterns and dynamics of STH reinfection after drug treatment. METHODOLOGY: We systematically searched PubMed, ISI Web of Science, EMBASE, Cochrane Database of Systematic Reviews, China National Knowledge Infrastructure, WanFang Database, Chinese Scientific Journal Database, and Google Scholar. Information on study year, country, sample size, age of participants, diagnostic method, drug administration strategy, prevalence and intensity of infection pre- and posttreatment, cure and egg reduction rate, evaluation period posttreatment, and adherence was extracted. Pooled risk ratios from random-effects models were used to assess the risk of STH reinfection after treatment. Our protocol is available on PROSPERO, registration number: CRD42011001678. PRINCIPAL FINDINGS: From 154 studies identified, 51 were included and 24 provided STH infection rates pre- and posttreatment, whereas 42 reported determinants of predisposition to reinfection. At 3, 6, and 12 months posttreatment, A. lumbricoides prevalence reached 26% (95% confidence interval (CI): 16-43%), 68% (95% CI: 60-76%) and 94% (95% CI: 88-100%) of pretreatment levels, respectively. For T. trichiura, respective reinfection prevalence were 36% (95% CI: 28-47%), 67% (95% CI: 42-100%), and 82% (95% CI: 62-100%), and for hookworm, 30% (95% CI: 26-34%), 55% (95% CI: 34-87%), and 57% (95% CI: 49-67%). Prevalence and intensity of reinfection were positively correlated with pretreatment infection status. CONCLUSION: STH reinfections occur rapidly after treatment, particularly for A. lumbricoides and T. trichiura. Hence, there is a need for frequent anthelmintic drug administrations to maximize the benefit of preventive chemotherapy. Integrated control approaches emphasizing health education and environmental sanitation are needed to interrupt transmission of STH.

BACKGROUND: Soil-transmitted helminth infections are common throughout the tropics and subtropics and they disproportionately affect the poorest of the poor. In view of a growing global commitment to control soil-transmitted helminthiasis, there is a need to elucidate the effect of repeated stool sampling and the use of different diagnostic methods in areas targeted for preventive chemotherapy that are characterized by low-infection intensities. In this study, we focused on schoolchildren on Unguja Island, Zanzibar, an area where anthelminthic drugs have been repeatedly administered over the past decade. METHODOLOGY/PRINCIPAL FINDINGS: Three serial stool samples from each of 342 schoolchildren were examined using the Kato-Katz (K-K), Koga agar plate (KAP), and Baermann (BM) techniques. These methods were used individually or in combination for the diagnosis of Ascaris lumbricoides (K-K), Trichuris trichiura (K-K), hookworm (K-K and KAP), and Strongyloides stercoralis (KAP and BM). The examination of multiple stool samples instead of a single one resulted in an increase of the observed prevalence; e.g., an increase of 161% for hookworm using the K-K method. The diagnostic sensitivity of single stool sampling ranged between 20.7% for BM to detect S. stercoralis and 84.2% for K-K to diagnose A. lumbricoides. Highest sensitivities were observed when different diagnostic approaches were combined. The observed prevalences for T. trichiura, hookworm, A. lumbricoides, and S. stercoralis were 47.9%, 22.5%, 16.5%, and 10.8% after examining 3 stool samples. These values are close to the 'true' prevalences predicted by a mathematical model. CONCLUSION/SIGNIFICANCE: Rigorous epidemiologic surveillance of soil-transmitted helminthiasis in the era of preventive chemotherapy is facilitated by multiple stool sampling bolstered by different diagnostic techniques.

BACKGROUND: Schistosoma japonicum causes an infection involving humans, livestock, and snails and is a significant cause of morbidity in China. METHODS: We evaluated a comprehensive control strategy in two intervention villages and two control villages along Poyang Lake in the southeastern province of Jiangxi, where annual synchronous chemotherapy is routinely used. New interventions, implemented from 2005 through 2007, included removing cattle from snail-infested grasslands, providing farmers with mechanized farm equipment, improving sanitation by supplying tap water and building lavatories and latrines, providing boats with fecal-matter containers, and implementing an intensive health-education program. During the intervention period, we observed changes in S. japonicum infection in humans, measured the rate of infection in snails, and tested the infectivity of lake water in mice. RESULTS: After three transmission seasons, the rate of infection in humans decreased to less than 1.0% in the intervention villages, from 11.3% to 0.7% in one village and from 4.0% to 0.9% in the other (P<0.001 for both comparisons). The rate of infection in humans in control villages fluctuated but remained at baseline levels. In intervention villages, the percentage of sampling sites with infected snails decreased from 2.2% to 0.1% in one grassland area and from 0.3% to no infection in the other (P<0.001 for both comparisons). The rate of infection in mice after exposure to lake water decreased from 79% to no infection (P<0.001). CONCLUSIONS: A comprehensive control strategy based on interventions to reduce the rate of transmission of S. japonicum infection from cattle and humans to snails was highly effective. These interventions have been adopted as the national strategy to control schistosomiasis in China.

BACKGROUND: Neglected tropical diseases (NTDs) have long been overlooked in the global health agenda. They are intimately related to poverty, cause important local burdens of disease, but individually do not represent global priorities. Yet, NTDs were estimated to affect close to 2 billion people at the turn of the millennium, with a collective burden equivalent to HIV/AIDS, tuberculosis, or malaria. A global response was therefore warranted. MAIN TEXT: The World Health Organization (WHO) conceived an innovative strategy in the early 2000s to combat NTDs as a group of diseases, based on a combination of five public health interventions. Access to essential NTD medicines has hugely improved thanks to strong public-private partnership involving the pharmaceutical sector. The combination of a WHO NTD roadmap with clear targets to be achieved by 2020 and game-changing partner commitments endorsed in the London Declaration on Neglected Tropical Diseases, have led to unprecedented progress in the implementation of large-scale preventive treatment, case management and care of NTDs. The coming decade will see as challenges the mainstreaming of these NTD interventions into Universal Health Coverage and the coordination with other sectors to get to the roots of poverty and scale up transmission-breaking interventions. Chinese expertise with the elimination of multiple NTDs, together with poverty reduction and intersectoral action piloted by municipalities and local governments, can serve as a model for the latter. The international community will also need to keep a specific focus on NTDs in order to further steer this global response, manage the scaling up and sustainment of NTD interventions globally, and develop novel products and implementation strategies for NTDs that are still lagging behind. CONCLUSIONS: The year 2020 will be crucial for the future of the global response to NTDs. Progress against the 2020 roadmap targets will be assessed, a new 2021-2030 NTD roadmap will be launched, and the London Declaration commitments will need to be renewed. It is hoped that during the coming decade the global response will be able to further build on today's successes, align with the new global health and development frameworks, but also keep focused attention on NTDs and mobilize enough resources to see the effort effectively through to 2030.

Schistosomiasis japonica is a serious communicable disease and a major disease risk for more than 30 million people living in the tropical and subtropical zones of China. Infection remains a major public health concern despite 45 years of intensive control efforts. It is estimated that 865,000 people and 100,250 bovines are today infected in the provinces where the disease is endemic, and its transmission continues. Unlike the other schistosome species known to infect humans, the oriental schistosome, Schistosoma japonicum, is a true zoonotic organism, with a range of mammalian reservoirs, making control efforts extremely difficult. Clinical features of schistosomiasis range from fever, headache, and lethargy to severe fibro-obstructive pathology leading to portal hypertension, ascites, and hepatosplenomegaly, which can cause premature death. Infected children are stunted and have cognitive defects impairing memory and learning ability. Current control programs are heavily based on community chemotherapy with a single dose of the drug praziquantel, but vaccines (for use in bovines and humans) in combination with other control strategies are needed to make elimination of the disease possible. In this article, we provide an overview of the biology, epidemiology, clinical features, and prospects for control of oriental schistosomiasis in the People's Republic of China.

BACKGROUND: For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and locations, while reflecting on the remaining post-COVID-19 challenges to achieving our collective global health ambitions. METHODS: The GBD 2023 combined analysis estimated years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 375 diseases and injuries, and risk-attributable burden associated with 88 modifiable risk factors. Of the more than 310 000 total data sources used for all GBD 2023 (about 30% of which were new to this estimation round), more than 120 000 sources were used for estimation of disease and injury burden and 59 000 for risk factor estimation, and included vital registration systems, surveys, disease registries, and published scientific literature. Data were analysed using previously established modelling approaches, such as disease modelling meta-regression version 2.1 (DisMod-MR 2.1) and comparative risk assessment methods. Diseases and injuries were categorised into four levels on the basis of the established GBD cause hierarchy, as were risk factors using the GBD risk hierarchy. Estimates stratified by age, sex, location, and year from 1990 to 2023 were focused on disease-specific time trends over the 2010-23 period and presented as counts (to three significant figures) and age-standardised rates per 100 000 person-years (to one decimal place). For each measure, 95% uncertainty intervals [UIs] were calculated with the 2·5th and 97·5th percentile ordered values from a 250-draw distribution. FINDINGS: Total numbers of global DALYs grew 6·1% (95% UI 4·0-8·1), from 2·64 billion (2·46-2·86) in 2010 to 2·80 billion (2·57-3·08) in 2023, but age-standardised DALY rates, which account for population growth and ageing, decreased by 12·6% (11·0-14·1), revealing large long-term health improvements. Non-communicable diseases (NCDs) contributed 1·45 billion (1·31-1·61) global DALYs in 2010, increasing to 1·80 billion (1·63-2·03) in 2023, alongside a concurrent 4·1% (1·9-6·3) reduction in age-standardised rates. Based on DALY counts, the leading level 3 NCDs in 2023 were ischaemic heart disease (193 million [176-209] DALYs), stroke (157 million [141-172]), and diabetes (90·2 million [75·2-107]), with the largest increases in age-standardised rates since 2010 occurring for anxiety disorders (62·8% [34·0-107·5]), depressive disorders (26·3% [11·6-42·9]), and diabetes (14·9% [7·5-25·6]). Remarkable health gains were made for communicable, maternal, neonatal, and nutritional (CMNN) diseases, with DALYs falling from 874 million (837-917) in 2010 to 681 million (642-736) in 2023, and a 25·8% (22·6-28·7) reduction in age-standardised DALY rates. During the COVID-19 pandemic, DALYs due to CMNN diseases rose but returned to pre-pandemic levels by 2023. From 2010 to 2023, decreases in age-standardised rates for CMNN diseases were led by rate decreases of 49·1% (32·7-61·0) for diarrhoeal diseases, 42·9% (38·0-48·0) for HIV/AIDS, and 42·2% (23·6-56·6) for tuberculosis. Neonatal disorders and lower respiratory infections remained the leading level 3 CMNN causes globally in 2023, although both showed notable rate decreases from 2010, declining by 16·5% (10·6-22·0) and 24·8% (7·4-36·7), respectively. Injury-related age-standardised DALY rates decreased by 15·6% (10·7-19·8) over the same period. Differences in burden due to NCDs, CMNN diseases, and injuries persisted across age, sex, time, and location. Based on our risk analysis, nearly 50% (1·27 billion [1·18-1·38]) of the roughly 2·80 billion total global DALYs in 2023 were attributable to the 88 risk factors analysed in GBD. Globally, the five level 3 risk factors contributing the highest proportion of risk-attributable DALYs were high systolic blood pressure (SBP), particulate matter pollution, high fasting plasma glucose (FPG), smoking, and low birthweight and short gestation-with high SBP accounting for 8·4% (6·9-10·0) of total DALYs. Of the three overarching level 1 GBD risk factor categories-behavioural, metabolic, and environmental and occupational-risk-attributable DALYs rose between 2010 and 2023 only for metabolic risks, increasing by 30·7% (24·8-37·3); however, age-standardised DALY rates attributable to metabolic risks decreased by 6·7% (2·0-11·0) over the same period. For all but three of the 25 leading level 3 risk factors, age-standardised rates dropped between 2010 and 2023-eg, declining by 54·4% (38·7-65·3) for unsafe sanitation, 50·5% (33·3-63·1) for unsafe water source, and 45·2% (25·6-72·0) for no access to handwashing facility, and by 44·9% (37·3-53·5) for child growth failure. The three leading level 3 risk factors for which age-standardised attributable DALY rates rose were high BMI (10·5% [0·1 to 20·9]), drug use (8·4% [2·6 to 15·3]), and high FPG (6·2% [-2·7 to 15·6]; non-significant). INTERPRETATION: Our findings underscore the complex and dynamic nature of global health challenges. Since 2010, there have been large decreases in burden due to CMNN diseases and many environmental and behavioural risk factors, juxtaposed with sizeable increases in DALYs attributable to metabolic risk factors and NCDs in growing and ageing populations. This long-observed consequence of the global epidemiological transition was only temporarily interrupted by the COVID-19 pandemic. The substantially decreasing CMNN disease burden, despite the 2008 global financial crisis and pandemic-related disruptions, is one of the greatest collective public health successes known. However, these achievements are at risk of being reversed due to major cuts to development assistance for health globally, the effects of which will hit low-income countries with high burden the hardest. Without sustained investment in evidence-based interventions and policies, progress could stall or reverse, leading to widespread human costs and geopolitical instability. Moreover, the rising NCD burden necessitates intensified efforts to mitigate exposure to leading risk factors-eg, air pollution, smoking, and metabolic risks, such as high SBP, BMI, and FPG-including policies that promote food security, healthier diets, physical activity, and equitable and expanded access to potential treatments, such as GLP-1 receptor agonists. Decisive, coordinated action is needed to address long-standing yet growing health challenges, including depressive and anxiety disorders. Yet this can be only part of the solution. Our response to the NCD syndemic-the complex interaction of multiple health risks, social determinants, and systemic challenges-will define the future landscape of global health. To ensure human wellbeing, economic stability, and social equity, global action to sustain and advance health gains must prioritise reducing disparities by addressing socioeconomic and demographic determinants, ensuring equitable health-care access, tackling malnutrition, strengthening health systems, and improving vaccination coverage. We live in times of great opportunity. FUNDING: Gates Foundation and Bloomberg Philanthropies.

Appraisal of the present and future impact of climate change and climate variability on the transmission of infectious diseases is a complex but pressing public health issue. We developed a biology-driven model to assess the potential impact of rising temperature on the transmission of schistosomiasis in China. We found a temperature threshold of 15.4 degrees C for development of Schistosoma japonicum within the intermediate host snail (i.e., Oncomelania hupensis), and a temperature of 5.8 degrees C at which half the snail sample investigated was in hibernation. Historical data suggest that the occurrence of O. hupensis is restricted to areas where the mean January temperature is above 0 degrees C. The combination of these temperature thresholds, together with our own predicted temperature increases in China of 0.9 degrees C in 2030 and 1.6 degrees C in 2050 facilitated predictive risk mapping. We forecast an expansion of schistosomiasis transmission into currently non-endemic areas in the north, with an additional risk area of 783,883 km(2) by 2050, translating to 8.1% of the surface area of China. Our results call for rigorous monitoring and surveillance of schistosomiasis in a future warmer China.

BACKGROUND: Infections with schistosomes and soil-transmitted helminths exert a considerable yet underappreciated economic and public health burden on afflicted populations. Accurate diagnosis is crucial for patient management, drug efficacy evaluations, and monitoring of large-scale community-based control programs. METHODS/PRINCIPAL FINDINGS: The diagnostic accuracy of four copromicroscopic techniques (i.e., Kato-Katz, Koga agar plate, ether-concentration, and FLOTAC) for the detection of Schistosoma mansoni and soil-transmitted helminth eggs was compared using stool samples from 112 school children in Côte d'Ivoire. Combined results of all four methods served as a diagnostic 'gold' standard and revealed prevalences of S. mansoni, hookworm, Trichuris trichiura, Strongyloides stercoralis and Ascaris lumbricoides of 83.0%, 55.4%, 40.2%, 33.9% and 28.6%, respectively. A single FLOTAC from stool samples preserved in sodium acetate-acetic acid-formalin for 30 or 83 days showed a higher sensitivity for S. mansoni diagnosis (91.4%) than the ether-concentration method on stool samples preserved for 40 days (85.0%) or triplicate Kato-Katz using fresh stool samples (77.4%). Moreover, a single FLOTAC detected hookworm, A. lumbricoides and T. trichiura infections with a higher sensitivity than any of the other methods used, but resulted in lower egg counts. The Koga agar plate method was the most accurate diagnostic assay for S. stercoralis. CONCLUSION/SIGNIFICANCE: We have shown that the FLOTAC method holds promise for the diagnosis of S. mansoni. Moreover, our study confirms that FLOTAC is a sensitive technique for detection of common soil-transmitted helminths. For the diagnosis of S. stercoralis, the Koga agar plate method remains the method of choice.

Schistosomiasis remains a serious public health problem with an estimated 200 million people infected in 76 countries. Here we isolated ~ 8,400 potential protein-encoding cDNA contigs from Schistosoma japonicum after sequencing circa 84,000 expressed sequence tags. In tandem, we undertook a high-throughput proteomics approach to characterize the protein expression profiles of a number of developmental stages (cercariae, hepatic schistosomula, female and male adults, eggs, and miracidia) and tissues at the host-parasite interface (eggshell and tegument) by interrogating the protein database deduced from the contigs. Comparative analysis of these transcriptomic and proteomic data, the latter including 3,260 proteins with putative identities, revealed differential expression of genes among the various developmental stages and sexes of S. japonicum and localization of putative secretory and membrane antigens, enzymes, and other gene products on the adult tegument and eggshell, many of which displayed genetic polymorphisms. Numerous S. japonicum genes exhibited high levels of identity with those of their mammalian hosts, whereas many others appeared to be conserved only across the genus Schistosoma or Phylum Platyhelminthes. These findings are expected to provide new insights into the pathophysiology of schistosomiasis and for the development of improved interventions for disease control and will facilitate a more fundamental understanding of schistosome biology, evolution, and the host-parasite interplay.

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.

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The potential impact of the Three Gorges Dam (TGD) on schistosomiasis transmission in China has invoked considerable global concern. The TGD will result in changes in the water level and silt deposition downstream, favoring the reproduction of Oncomelania snails. Combined with blockages of the Yangtze River's tributaries, these changes will increase the schistosomiasis transmission season within the marshlands along the middle and lower reaches of the Yangtze River. The changing schistosome transmission dynamics necessitate a comprehensive strategy to control schistosomiasis. This review discusses aspects of the epidemiology and transmission of Schistosoma japonicum in China and considers the pathology, clinical outcomes, diagnosis, treatment, immunobiology, and genetics of schistosomiasis japonica together with an overview of current progress in vaccine development, all of which will have an impact on future control efforts. The use of synchronous praziquantel (PZQ) chemotherapy for humans and domestic animals is only temporarily effective, as schistosome reinfection occurs rapidly. Drug delivery requires a substantial infrastructure to regularly cover all parts of an area of endemicity. This makes chemotherapy expensive and, as compliance is often low, a less than satisfactory control option. There is increasing disquiet about the possibility that PZQ-resistant schistosomes will develop. Consequently, as mathematical modeling predicts, vaccine strategies represent an essential component in the future control of schistosomiasis in China. With the inclusion of focal mollusciciding, improvements in sanitation, and health education into the control scenario, China's target of reducing the level of schistosome infection to less than 1% by 2015 may be achievable.

BACKGROUND: Eosinophilic meningitis (angiostrongyliasis) caused by Angiostrongylus cantonensis is emerging in mainland China. However, the distribution of A. cantonensis and its intermediate host snails, and the role of two invasive snail species in the emergence of angiostrongyliasis, are not well understood. METHODOLOGY/PRINCIPAL FINDINGS: A national survey pertaining to A. cantonensis was carried out using a grid sampling approach (spatial resolution: 40x40 km). One village per grid cell was randomly selected from a 5% random sample of grid cells located in areas where the presence of the intermediate host snail Pomacea canaliculata had been predicted based on a degree-day model. Potential intermediate hosts of A. cantonensis were collected in the field, restaurants, markets and snail farms, and examined for infection. The infection prevalence among intermediate host snails was estimated, and the prevalence of A. cantonensis within P. canaliculata was displayed on a map, and predicted for non-sampled locations. It was confirmed that P. canaliculata and Achatina fulica were the predominant intermediate hosts of A. cantonensis in China, and these snails were found to be well established in 11 and six provinces, respectively. Infected snails of either species were found in seven provinces, closely matching the endemic area of A. cantonensis. Infected snails were also found in markets and restaurants. Two clusters of A. cantonensis-infected P. canaliculata were predicted in Fujian and Guangxi provinces. CONCLUSIONS/SIGNIFICANCE: The first national survey in China revealed a wide distribution of A. cantonensis and two invasive snail species, indicating that a considerable number of people are at risk of angiostrongyliasis. Health education, rigorous food inspection and surveillance are all needed to prevent recurrent angiostrongyliasis outbreaks.

Schistosomiasis is a chronic and debilitating disease that is caused by parasitic trematode worms (schistosomes). It continues to threaten millions of people, particularly the rural poor in the developing world ([11][1], [24][2]). Of the estimated 200 million infected people, more than half have

BACKGROUND: Malaria was once one of the most serious public health problems in China. However, the disease burden has sharply declined and epidemic areas have shrunk after the implementation of an integrated malaria control and elimination strategy, especially since 2000. In this review, the lessons were distilled from the Chinese national malaria elimination programme and further efforts to mitigate the challenges of malaria resurgence are being discussed. METHODS: A retrospective evaluation was performed to assess the changes in malaria epidemic patterns from 1950 to 2017 at national level. The malaria data before 2004 were collected from paper-based annual reports. After 2004, each of the different cases from the Infectious Diseases Information Reporting Management System (IDIRMS) was closely examined and scrutinized. An additional documenting system, the National Information Management System for Malaria, established in 2012 to document the interventions of three parasitic diseases, was also examined to complete the missing data from IDIRMS. RESULTS: From 1950 to 2017, the occurrence of indigenous malaria has been steeply reduced, and malaria-epidemic regions have substantially shrunk, especially after the launch of the national malaria elimination programme. There were approximately 30 million malaria cases annually before 1949 with a mortality rate of 1%. A total of 5999 indigenous cases were documented from 2010 to 2016, with a drastic reduction of 99% over the 6 years (2010, n = 4262; 2016, n = 3). There were indigenous cases reported in 303 counties from 18 provinces in 2010, but only 3 indigenous cases were reported in 2 provinces nationwide in 2016. While in 2017, for the first time, zero indigenous case was reported in China, and only 7 of imported cases were in individuals who died of Plasmodium falciparum infection. CONCLUSION: Malaria elimination in China is a country-led and country-owned endeavour. The country-own efforts were a clear national elimination strategy, supported by two systems, namely a case-based surveillance and response system and reference laboratory system. The country-led efforts were regional and inter-sectoral collaboration as well as sustained monitoring and evaluation. However, there are still some challenges, such as the maintenance of non-transmission status, the implementation of a qualified verification and assessment system, and the management of imported cases in border areas, through regional cooperation. The findings from this review can probably help improving malaria surveillance systems in China, but also in other elimination countries.

BACKGROUND: The treatment and control of schistosomiasis, an often neglected tropical disease that exacerbates poverty, depends on a single drug, praziquantel. The large-scale use of praziquantel might select for drug-resistant parasites, hence there is a need to develop new antischistosomal compounds. Here, we report that the antimalarial drug mefloquine possesses promising antischistosomal properties in mice. METHODOLOGY/PRINCIPAL FINDINGS: A single dose of mefloquine (200 or 400 mg/kg) administered orally to mice infected with adult Schistosoma mansoni or adult S. japonicum resulted in high or complete total and female worm burden reductions (72.3%-100%). Importantly, high worm burden reductions were also observed for young developing stages of S. mansoni and S. japonicum harbored in the mouse. Both mefloquine erythro-enantiomers resulted in high and comparable total and female worm burden reductions when given to mice with either a sub-patent or patent S. mansoni infection. CONCLUSIONS/SIGNIFICANCE: Our findings hold promise for the development of a novel antischistosomal drug based on an aminoalcohol functionality. Further in vitro and in vivo studies have been launched to elucidate the possible mechanism of action and to study the effect of mefloquine on S. haematobium and other trematodes. It will be interesting to investigate whether mefloquine, which is widely and effectively used for the treatment of malaria, has an impact on schistosomiasis in areas where both malaria and schistosomiasis co-exist.