The challenge of effective surveillance in moving from low transmission to elimination of schistosomiasis in China

Until recently, intensified efforts in China to suppress the transmission of Schistosoma japonicum relied principally on routine praziquantel treatment, extensive use of molluscicides and health education programs. These efforts, now supplemented by a broader range of control measures, have been quite successful in reducing the prevalence and intensity of human infection to very low levels. However, re-emergent transmission has occurred in formerly endemic areas of several provinces, signalling the need for more locally effective, integrated control strategies. We argue that these low but persistent levels of transmission also require important changes in both the tactics and strategy of disease surveillance to move forward towards elimination. Here we present recent data exemplifying the low transmission environment which suggests that we are reaching limits of detection of current diagnostic techniques used for human infection surveillance in these communities. However, both epidemiological data and theoretical results indicate that (i) transmission in the human population can persist at very low infection intensities even in the presence of routine control activities; (ii) the parasite can be reintroduced into parasite-free environments by very modest external inputs; and (iii) transmission at these low infection intensities exhibits very slow inter-year dynamics. These observations motivate the need for new, sensitive tools to identify low-level infections in mammalian or snail hosts, or the presence of S. japonicum in environmental media. Environmental monitoring offers an alternative, and perhaps more efficient, approach to large-scale surveillance of human infections in low transmission regions.     

Comparison between schistosomiasis transmission modelings considering acquired immunity and age-structured contact pattern with infested water

In order to analyze the effects of acquired immunity and the contact pattern with infested water on the overall transmission of schistosomiasis, a semi-stochastic model is proposed. The model's assumptions are the simplest possible to enhance the differences between two hypotheses. With respect to the human host, it is assumed the mounting of an immune response after elapsing a fixed period of time L from the first infection, which is partially effective and never lost. With respect to the contact pattern with infested water, it is assumed a decreasing age-related function. Both models are compared to a purely random model, which is taken as the basic model.     

Expression, purification, and human antibody response to a 67 kDa vaccine candidate for schistosomiasis japonica

Schistosomiasis remains a leading cause of morbidity and mortality in the developing tropical world, and vaccines to prevent these infections remain a scientific and public health priority. Sj67 is a 67 kDa Schistosoma japonicum surface membrane protein homologous to a family of actin-binding proteins. Sj67 is recognized by a mouse monoclonal antibody (mAb 6) that confers resistance to challenge infection in passive transfer experiments. These data support Sj67 as a potential vaccine candidate for schistosomiasis japonica. In the present study, we report the ligation-independent cloning of a cDNA encoding thioredoxin/elastin-like polypeptide (ELP)/rSj67 into a pET-32 Xa/LIC vector. Soluble recombinant fusion protein (Thio-ELP-rSj67) was expressed and purified using anion-exchange and size exclusion chromatography. rSj67 was cleaved from the Thio-ELP fusion partner by digestion with Factor Xa protease and purified using hydroxyapatite column chromatography. Endotoxin was reduced by absorption to a polymyxin support. Purified rSj67 had a molecular weight of 67 kDa and N-terminal sequencing confirmed that the first five amino acids of the recombinant protein matched the predicted sequence for the Sj67 gene. In Western blot analysis, rSj67 was recognized by the Sj67 specific mAb 6 antibody. IgG antibodies in sera from schistosomiasis infected volunteers living in an endemic area of the Philippines (n = 13) recognized rSj67 with 4.7-fold greater median fluorescence compared to uninfected North American controls (n = 5) (p < 0.009). Together, these data confirm the expression and purification of recombinant Sj67 and its immuno-reactivity with sera from S. japonicum infected humans.     

Snail control strategies for reduction of schistosomiasis transmission

As intermediate hosts, molluscs play a major role in the transmission of schistosomes; they are the sites of an intense multiplication of parasites. Thus, snail control strategies are considered a priority for the reduction of schistosomiasis transmission. Here, Vinca Lardans and Colette Dissous review the efficacy of environmental management and the use of molluscicides and biological agents to control snail populations. They then describe the development of diagnostic tests, based on the detection of parasite antigens or specific parasite DNA sequences in snail tissues, to detect the early infection of snails. Finally, they discuss progress in studying the molecular basis of susceptibility and resistance phenotypes, and the possible application of the genetic manipulation of molluscs.     

The potential of artemether for the control of schistosomiasis

Schistosomiasis continues to rank – following malaria – at the second position of the world's parasitic diseases in terms of the extent of endemic areas and the number of infected people. There is yet no vaccine available and the current mainstay of control is chemotherapy with praziquantel used as the drug of choice. In view of concern about the development of tolerance and/or resistance to praziquantel, there is a need for research and development of novel drugs for the prevention and cure of schistosomiasis. Interestingly, derivatives of artemisinin, which are already effectively used in the treatment of malaria, also exhibit antischistosomal properties. Significant advances have been made with artemether, the methyl ether derivative of artemisinin. We review the discovery of the antischistosomal activity of artemether by Chinese scientists two decades ago; the detailed laboratory studies of the susceptibility of, and effect on, the different developmental stages of Schistosoma japonicum, Schistosoma mansoni and Schistosoma haematobium to artemether; the possible mechanism of action and the potential long-term toxicity. Finally, we look at the effect of combined treatment with artemether and praziquantel; and clinical findings thus far obtained from randomised controlled trials with oral artemether for the prevention of patent infections and morbidity. The review intends to create a forum for strategic discussion of how these laboratory and clinical findings could be translated into public health actions. We conclude that artemether – as part of integrated current control measures and adapted to specific socio-ecological and epidemiological settings – has considerable potential to significantly reduce the current burden of schistosomiasis in many parts of the world.     

Assessment of the national schistosomiasis control program in a typical region along the Yangtze River,China

Schistosomiasis remains a major public health problem in eastern China, particularly along the Yangtze River Basin. The latest national schistosomiasis control program (NSCP) was implemented in 2005 with the main goal of reducing the rate of infection to less than 5% by 2008 and 1% by 2015. To assess the progress, we applied a Bayesian spatio-temporal model to describe dynamics of schistosomiasis in Guichi, Anhui Province, China, using annual parasitological and environmental data collected within 41 sample villages for the period 2005–2011. Predictive maps of schistosomiasis showed that the disease prevalence remains constant and low. Results of uncertainty analysis, in the form of probability contour maps (PCMs), indicated that the first goal of “infection rate less than 5% by 2008” was fully achieved in the study area. More longitudinal data for schistosomiasis are needed for the assessment of the second goal of “infection rate less than 1% by 2015”. Compared with the traditional way of mapping uncertainty (e.g., variance or mean-square error), our PCMs provide more realistic information for schistosomiasis control.     

Haemostatic abnormalities in hepatosplenic schistosomiasis mansoni

Hepatosplenic schistosomiasis is a complex immuno-regulatory disease and is major health problem in endemic countries. Acute bleeding is one of its most serious complications and often life-threatening. Clinical studies have demonstrated that the patients with hepatosplenic schistosomiasis are prone to develop complex haemostatic abnormalities that may be linked to the potential risk of bleeding from ruptured esophageal varices in these patients. The deficit in haemostatic parameters is more pronounced with the advancement of the disease and is maximal in the patients with experience of haematomesis. Evidences of enhanced generation of thrombin and plasmin indicate the presence of low-grade DIC in advanced hepatosplenic schistosomiasis, which is considered as a principal cause of haemostatic abnormalities in this endemic disease. Demonstration of procoagulant expression in peripheral blood monocytes of the patients and in the livers, spleens and intestines of S. mansoni-infected mice suggest their possible implication in the causation of DIC in S. mansoni infections. Moreover, because in vitro analysis indicates a participation of immune mechanisms in the localized procoagulant expression, it seems likely that the immune responses to schstosomes play a major role in the pathogenic mechanisms of haemostatic abnormalities in hepatosplenic schistosomiasis.     

Recent advances in proteomic applications for schistosomiasis research: potential clinical impact

Introduction: Schistosomiasis is a neglected tropical disease affecting hundreds of millions of people worldwide. Recent advances in the field of proteomics and the development of new and highly sensitive mass spectrometers and quantitative techniques have provided new tools for advancing the molecular biology, cell biology, diagnosis and vaccine development for public health threats such as schistosomiasis.

Areas covered: In this review we describe the latest advances in research that utilizes proteomics-based tools to address some of the key challenges to developing effective interventions against schistosomiasis. We also provide information about the potential of extracellular vesicles to advance the fight against this devastating disease.

Expert commentary: Different proteins are already being tested as vaccines against schistosomiasis with promising results. The re-analysis of the Schistosoma spp. proteomes using new and more sensitive mass spectrometers as well as better separation approaches will help identify more vaccine targets in a rational and informed manner. In addition, the recent development of new proteome microarrays will facilitate characterisation of novel markers of infection as well as new vaccine and diagnostic candidate antigens.     

Effect of gold nanoparticles on mice splenomegaly induced by schistosomiasis mansoni

Schistosomiasis is still one of the main parasitic diseases that affect human health in tropical regions. Whilst praziquantel (PZQ) is the main classic antischistosomal drug, the need for new drugs is still a must due to the low effectiveness of the drug on the schistosome young worms, and the evolving of PZQ resistant strains. Nanotechnology is one of the most important recent and current methods used to treat human diseases including parasitic ones. Therefore, the present study aimed to examine the curative role of gold nanoparticles (GNPs) on splenic tissue of mice infected with Schistosoma mansoni Sambon, 1907. High-resolution transmission electron microscopy was used for characterization of nanoparticles (NP). GNPs of 1 mg/kg mice body weight were inoculated into mice infected with S. mansoni. The parasite caused deteriorations in histological architecture of the spleen tissue, and splenomegaly. Additionally, the parasite induced a significant reduction in splenic tissue glutathione levels; however, the concentrations of nitric oxide and malondialdehyde were significantly increased. Treatment of mice with GNPs reduced the extent of histological impairment and oxidative stress in spleen tissue. Therefore, our results demonstrate the protective role of GNPs against splenic damage in mice infected with S. mansoni.     

History of Katayama disease: schistosomiasis japonica in Katayama district, Hiroshima, Japan

Historical account of Katayama disease is presented as a centenary record since the discovery of Schistosoma japonicum in Japan in 1904. The ever unknown endemic disease was called Katayama disease. Katayama district, Hiroshima Prefecture is one of endemic areas of schistosomiasis japonica in Japan. The causative parasite was first discovered in a human case in Katayama district. After the discovery of the parasite, life history, diagnosis, treatment, control measures and even eradication have been worked out, attempted and succeeded in Katayama district together with other endemic areas in Japan. Hiroshima Prefecture declared safety from the disease in 1980.     

Chitosan-colloidal gold complexes as polycationic probes for the detection of anionic sites by transmission and scanning electron microscopy

A new cationic colloidal gold complex has been developed for ultrastructural localization of cell surface anionic sites by transmission and scanning electron microscopy. The marker is prepared by labelling gold particles of suitable sizes (6 to 70 nm in diameter) with chitosan, a polymer of beta (1----4)-linked D-glucosamine. Using human red blood cells as a model, chitosan-gold complexes were shown to be specific for anionic sites and at pH 2 for sialic acid residues. The binding capacity of complexes of different sizes with carboxymethyl and phosphorylated celluloses was examined as a function of pH and ionic strength. The results indicated that these complexes can be used under acidic conditions as well as in physiological buffers. The complexes were further tested by transmission and scanning electron microscopy in detecting anionic sites on cells of various origins such as Escherichia coli, Lactobacillus maltaromicus, Lactobacillus reuteri, Saccharomyces cerevisiae, Saccharomyces rouxii, Schizosaccharomyces pombe, Fusarium oxysporum, Catharantus roseus.     

Chitosan-colloidal gold complexes as polycationic probes for the detection of anionic sites by transmission and scanning electron microscopy

Summary A new cationic colloidal gold complex has been developed for ultrastructural localization of cell surface anionic sites by transmission and scanning electron microscopy. The marker is prepared by labelling gold particles of suitable sizes (6 to 70 nm in diameter) with chitosan, a polymer of (14)-linked d-glucosamine. Using human red blood cells as a model, chitosan-gold complexes were shown to be specific for anionic sites and at pH 2 for sialic acid residues. The binding capacity of complexes of different sizes with carboxymethyl and phosphorylated celluloses was examined as a function of pH and ionic strength. The results indicated that these complexes can be used under acidic conditions as well as in physiological buffers. The complexes were further tested by transmission and scanning electron microscopy in detecting anionic sites on cells of various origins such as Escherichia coli, Lactobacillus maltaromicus, Lactobacillus reuteri, Saccharomyces cerevisiae, Saccharomyces rouxii, Schizosaccharomyces pombe, Fusarium oxysporum, Catharantus roseus.     

Praziquantel pharmacotherapy reduces systemic osteopontin levels and liver collagen content in murine schistosomiasis mansoni

The pathogenesis of schistosomiasis and the mechanism of disease regression after Praziquantel pharmacotherapy are not fully elucidated. Schistosoma mansoni egg antigens directly stimulate the expression of the profibrogenic molecule osteopontin (OPN), and systemic OPN levels strongly correlate with disease severity, suggesting its use as a potential morbidity biomarker. In this study, we investigated the impact of Praziquantel use on systemic OPN levels and on liver collagen deposition in chronic murine schistosomiasis. Praziquantel treatment significantly reduced systemic OPN levels and liver collagen deposition, indicating that OPN could be a reliable tool for monitoring PZQ efficacy and fibrosis regression in murine schistosomiasis.     

Historical view of schistosomiasis japonica in Japan: implementation and evaluation of disease-control strategies in Yamanashi Prefecture

We summarized historical aspects of disease control activities targeting schistosomiasis japonica in Kofu basin, Yamanashi Prefecture, Japan. Kofu Basin was one of the biggest endemic foci of schistosomiasis japonica in Japan, and the last place where transmission of Schistosoma japonicum was confirmed in Japan. Because of the most severe endemic situations in Yamanashi, intensive control measures had been implemented by the central as well as the local government. The last human case in Japan was in 1977, which is just before praziquantel being available. Therefore, the main efforts were focused on snail control. Mass examination and mass chemotherapy were implemented, however, the compliance was not so good because of the severe side effects due to the available therapeutics, Stibnal. Along with socioeconomic development after World War II, big changes in land use, life style, and farming led drastic reduction in the disease prevalence in Kofu Basin in the 1960s. A large amount of budget was also used for disease control. Cementing water canals covered more than 95% of paddy fields in Kofu Basin, and this resulted in ecological changes. After elimination of schistosomiasis, environmental repair is the urgent subject in Kofu Basin. Our experiences in Yamanashi contain both good influences and also a lot of reflection. It is important to evaluate each activity in our history before we give intensive cooperation with countries where endemic foci is still present.     

Schistosomiasis: Evaluation of the indirect fluorescent antibody,complement fixation,and slide flocculation tests in screening for schistosomiasis

Foreign Service personnel undergo pertinent parasitologic examinations upon return from foreign duty posts. Under this program, 2800 sera have been evaluated for schistosomiasis in this laboratory. The majority of individuals tested were considered to have limited exposure to schistosomiasis, although a few indigenous people from endemic areas also were screened. Nonindigenous populations usually gave stronger serological reactions than did indigenous populations. A comparison was made between those having protozoan and helminthic infections and those that were negative parasitologically. A number of subjects with tissue-phase helminths were evaluated and consistently gave strong reactions in the indirect fluorescent antibody (IFA) tests. On the other hand, there was no characteristic pattern observed in individuals with low serum titers. The IFA test proved to be highly sensitive and sufficiently specific for screening, provided that low background reactions were disregarded (i.e., when +/? and 1+ reactions were ignored at low serum dilutions). Thus, the IFA test was the method of choice for screening. Recourse to the complement fixation (CF) and slide flocculation (SF) tests, however, was necessary for definitive diagnosis. In view of the differences in the antigens and the serodiagnostic technics used in this survey, absolute correlation of test results could not be expected. Nevertheless, the three procedures (IFA, CF, and SF) showed excellent correlation in proven cases of schistosomiasis.     

Evolution in a multi-host parasite: Chronobiological circadian rhythm and population genetics of Schistosoma japonicum cercariae indicates contrasting definitive host reservoirs by habitat

Schistosomiasis japonica is a disease of profound medical and veterinary importance which has remained endemic in many regions and has re-emerged where previously controlled in China. Although over 40 mammalian species are suspected as reservoirs for Schistosoma japonicum, their relative roles, particularly wildlife, remain to be ascertained. As cercarial emergence is a heritable trait shaped by the definitive hosts’ behaviour, three chronobiological trials of cercarial emergence from field-collected snails from two contrasting ecological regions within China were performed, followed by genetic analyses of the parasites. Two distinct modes were identified, with late afternoon emergence mainly found in the hill region, compatible with a nocturnal rodent reservoir, and early emergence within the marshland consistent with a diurnal cattle reservoir. Furthermore, genetic analyses pointed to a clear separation between cercariae with different biological traits. The phenotypic and genotypic differentiation of the parasites identified here between and within two regions may indicate a strain complex. Such parasite diversity could, in turn, provide an explanation for the different infection scenarios observed between the two regions, and hence have important applied implications in terms of targeted control of key reservoirs.     

Road to the elimination of schistosomiasis from Asia: the journey is far from over

Schistosomiasis is a neglected tropical disease with a very long endemic history in Asia. Great strides have been made to control the disease in China and the Philippines but the road to elimination is far from over, given the zoonotic nature of the schistosome parasites in both countries.     

Polyserositis in a patient with acute paracoccidioidomycosis and hepatosplenic schistosomiasis

A severe case of juvenile paracoccidioidomycosis (PCM), manifested as cholestatic jaundice, lymphnode enlargement and an unusual form of polyserositis, associated with portal hypertension secondary to schistosomiasis, as well as bactermias caused byE. coli andS. aureus and post-transfusional hepatitis C is reported. Temporary unresponsiveness of in vivo and in vitro cellular immune responses toP. brasiliensis were registered. The authors discuss the possible interference of either agent in the host immune response, thus explaining the severity of PCM in the present case.