Snail-Related Contributions from the Schistosomiasis Consortium for Operational Research and Evaluation Program Including Xenomonitoring, Focal Mollusciciding, Biological Control, and Modeling.

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was created in 2008 to answer questions of importance to program managers working to reduce the burden of schistosomiasis in Africa. In the past, intermediate host snail monitoring and control was an important part of integrated schistosomiasis control. However, in Africa, efforts to control snails have declined dramatically over the last 30 years. A resurgence of interest in the control of snails has been prompted by the realization, backed by a World Health Assembly resolution (WHA65.21), that mass drug administration alone may be insufficient to achieve schistosomiasis elimination. SCORE has supported work on snail identification and mapping and investigated how xenomonitoring techniques can aid in the identification of infected snails and thereby identify potential transmission areas. Focal mollusciciding with niclosamide was undertaken in Zanzibar and Côte d'Ivoire as a part of elimination studies. Two studies involving biological control of snails were conducted: one explored the association of freshwater riverine prawns and snail hosts in Côte d'Ivoire and the other assessed the current distribution of Procambarus clarkii, the invasive Louisiana red swamp crayfish, in Kenya and its association with snail hosts and schistosomiasis transmission. SCORE also supported modeling studies on the importance of snail control in achieving elimination and a meta-analysis of the impact of molluscicide-based snail control programs on human schistosomiasis prevalence and incidence. SCORE's snail control studies contributed to increased investment in building capacity, and specimens collected during SCORE research deposited in the Schistosomiasis Collections at the Natural History Museum (SCAN) will provide a valuable resource for the years to come.

Recent advances in Schistosoma mekongi ecology, transcriptomics and proteomics of relevance to snail control.

Mekong schistosomiasis caused by Schistosoma mekongi is a public health problem that occurs along the border between southern Laos and northern Cambodia. Given its restricted distribution and low prevalence, eventual eradication via an effective control program can be expected to be successful. To achieve this goal detailed knowledge of its basic biology, molecular biology, biochemistry, and pathology is urgently required. In this regard, recent studies on transcriptome analysis of adult male and female S. mekongi worms, and proteome analysis of developmental stages have been reported and are discussed here. The biology, habitat, and distribution of the snail intermediate host Neotricula aperta, which are factors in disease transmission, are discussed in this review. These have initiated renewed interest in S. mekongi research and contributed promising data that will be utilized in the generation of effective control and prevention strategies.

Helminth-microbiota cross-talk - A journey through the vertebrate digestive system.

The gastrointestinal (GI) tract of vertebrates is inhabited by a vast array of organisms, i.e., the microbiota and macrobiota. The former is composed largely of commensal microorganisms, which play vital roles in host nutrition and maintenance of energy balance, in addition to supporting the development and function of the vertebrate immune system. By contrast, the macrobiota includes parasitic helminths, which are mostly considered detrimental to host health via a range of pathogenic effects that depend on parasite size, location in the GI tract, burden of infection, metabolic activity, and interactions with the host immune system. Sharing the same environment within the vertebrate host, the GI microbiota and parasitic helminths interact with each other, and the results of such interactions may impact, directly or indirectly, on host health and homeostasis. The complex relationships occurring between parasitic helminths and microbiota have long been neglected; however, recent studies point towards a role for these interactions in the overall pathophysiology of helminth disease, as well as in parasite-mediated suppression of inflammation. Whilst several discrepancies in qualitative and quantitative modifications in gut microbiota composition have been described based on host and helminth species under investigation, we argue that attention should be paid to the systems biology of the gut compartment under consideration, as variations in the abundances of the same population of bacteria inhabiting different niches of the GI tract may result in varying functional consequences for host physiology.

Sympatric versus allopatric evolutionary contexts shape differential immune response in Biomphalaria / Schistosoma interaction.

Selective pressures between hosts and their parasites can result in reciprocal evolution or adaptation of specific life history traits. Local adaptation of resident hosts and parasites should lead to increase parasite infectivity/virulence (higher compatibility) when infecting hosts from the same location (in sympatry) than from a foreign location (in allopatry). Analysis of geographic variations in compatibility phenotypes is the most common proxy used to infer local adaptation. However, in some cases, allopatric host-parasite systems demonstrate similar or greater compatibility than in sympatry. In such cases, the potential for local adaptation remains unclear. Here, we study the interaction between Schistosoma and its vector snail Biomphalaria in which such discrepancy in local versus foreign compatibility phenotype has been reported. Herein, we aim at bridging this gap of knowledge by comparing life history traits (immune cellular response, host mortality, and parasite growth) and molecular responses in highly compatible sympatric and allopatric Schistosoma/Biomphalaria interactions originating from different geographic localities (Brazil, Venezuela and Burundi). We found that despite displaying similar prevalence phenotypes, sympatric schistosomes triggered a rapid immune suppression (dual-RNAseq analyses) in the snails within 24h post infection, whereas infection by allopatric schistosomes (regardless of the species) was associated with immune cell proliferation and triggered a non-specific generalized immune response after 96h. We observed that, sympatric schistosomes grow more rapidly. Finally, we identify miRNAs differentially expressed by Schistosoma mansoni that target host immune genes and could be responsible for hijacking the host immune response during the sympatric interaction. We show that despite having similar prevalence phenotypes, sympatric and allopatric snail-Schistosoma interactions displayed strong differences in their immunobiological molecular dialogue. Understanding the mechanisms allowing parasites to adapt rapidly and efficiently to new hosts is critical to control disease emergence and risks of Schistosomiasis outbreaks.

Human schistosomiasis in the post mass drug administration era.

Profound changes are occurring in the epidemiology of schistosomiasis, a neglected tropical disease caused by a chronic infection with parasitic helminths of the genus Schistosoma. Schistosomiasis currently affects 240 million people worldwide, mostly in sub-Saharan Africa. The advent and proliferation of mass drug administration (MDA) programmes using the drug praziquantel is resulting in substantial increases in the number of people, mainly children aged 6-14 years, being effectively treated, approaching the point where most people in endemic areas will receive one or more treatments during their lifetimes. Praziquantel treatment not only cures infection but also frees the host from the powerful immunomodulatory action of the parasites. The treatment simultaneously enhances exposure to key parasite antigens, accelerating the development of protective acquired immunity, which would take many years to develop naturally. At a population level, these changes constitute a substantial alteration to schistosome ecology in that the parasites are more likely to be exposed not only to praziquantel directly but also to hosts with altered immune phenotypes. Here, we consider the consequences of this for schistosome biology, immunoepidemiology, and public health. We anticipate that there could be substantial effects on chronic pathology, natural immunity, vaccine development strategies, immune disorders, and drug efficacy. This makes for a complex picture that will only become apparent over decades. We recommend careful monitoring and assessment to accompany the roll-out of MDA programmes to ensure that the considerable health benefits to populations are achieved and sustained.

Cerebral and spinal schistosomiasis.

Cerebral schistosomiasis and spinal schistosomiasis are severe underrecognized complications of Schistosoma sp. infection, and can occur at any time during the parasitic infection. Neuroschistosomiasis has been increasingly reported not only in endemic areas but also in Western countries owing to immigration and international travel. Immunogenic interaction between schistosome egg deposition and the delayed hypersensitivity reaction of the host are the main neuropathogenic mechanisms involved. Eggs induce a periovular granulomatous reaction in the tissues. In some cases, schistosome adult worms may aberrantly migrate to the central nervous system via the vertebral venous plexus and place the ova at an ectopic site. Headache and seizures are common in cerebral schistosomiasis, and intracranial hypertension and hydrocephalus may occur in tumour-like and cerebellar schistosomiasis. Spinal schistosomiasis may manifest itself as acute myelitis and/or myeloradiculopathy. Recognition of neuroschistosomiasis is important so that early treatment with praziquantel and steroids can be started in an attempt to prevent severe disability.

[Effects of Schistosoma 22.6 kDa/26 GST molecule mixed with Sepharose 4B beads on induction of CD4+CD25+ regulatory T cells].

OBJECTIVE: To study the responses of regulatory T cells induced by Sepharose 4B beads mixed antigen. METHODS: Mice were immunized with different dosages of antigens, and the proportions of regulatory T cells were examined by flow cytometry. The 3H-thymidin incorporation method was used to detect the inhibitory function of Tregs. In vitro, dendritic cells were pulsed with different antigens. The expressions of MHC II, CD40, CD80/86 molecules on dendritic cells and the proportions of regulatory T cells were examined by flow cytometry. The 3H-thymidin incorporation method was used for the determination of Tregs function. RESULTS: Compared with control groups, the proportion of regulatory T cells in mice immunized with Sepharose 4B beads mixed antigen was(11.48 +/- 4.12)%, and the difference was significant (P < 0.05). The inhibition of regulatory T cells in mice immunized with Sepharose 4B beads mixed antigen showed a stronger potential (cpm was 720 +/- 180.4). Meanwhile, the proportions of regulatory T cells were (17.0 +/- 80.57)% and (30.14 +/- 3.62)% when the CD4+ T cells were co-cultured with dendritic cells pulsed with Sepharose 4B beads mixed rSj22.6/26GST and OVA, respectively. CONCLUSION: Sepharose 4B beads mixed antigen could induce the regulatory T cells in vivo and in vitro.

Correlação interobservador das alterações morfológicas das vias biliares em pacientes com esquistossomose mansoni pela colangiorressonância magnética / Evaluation of morphological changes of the biliary tree by magnetic resonance cholangiography in patients with schistosomiasis mansoni: interobserver agreement

OBJETIVO: Descrever as alterações das vias biliares pela colangiografia por ressonância magnética (CPRM) na esquistossomose hepatoesplênica e avaliar a concordância interobservador da CPRM na detecção de colangiopatia esquistossomótica. MATERIAIS E MÉTODOS: Estudo prospectivo e transversal em 24 pacientes com a forma hepatoesplênica da esquistossomose mansoni e em 6 pacientes sadios, como grupo controle, com avaliação da via biliar pela CPRM. As alterações da via biliar consideradas foram: distorção, afilamento, estenose, dilatação e irregularidade. Foi calculada a concordância interobsevador para alteração da via biliar com o teste de McNemar e o índice kappa (κ). RESULTADOS: A concordância interobservador na caracterização de distorção e afilamento da via biliar foi quase perfeita (κ = 0,867; intervalo de confiança [IC] 95 por cento [0,512-1,0] e κ = 0,865; IC 95 por cento [0,51-1,0], respectivamente). A concordância foi substancial para a estenose (κ = 0,78; IC 95 por cento [0,424-1,0]), moderada para dilatação (κ = 0,595; IC 95 por cento [0,247-0,942]) e regular para afilamento (κ = 0,229; IC 95 por cento [0,095-0,552]). CONCLUSÃO: As alterações observadas nas vias biliares foram, em ordem decrescente de ocorrência: distorção, afilamento, estenose, dilatação e irregularidade. A concordância interobservador para sinais de colangiopatia esquistossomótica foi quase perfeita para distorção e afilamento e substancial para estenose.

OBJECTIVE: To describe changes of the biliary tree demonstrated by magnetic resonance cholangiography (MRC) in patients with the hepatosplenic presentation of schistosomiasis mansoni, and evaluating the interobserver agreement in the detection of schistosomal cholangiopathy. MATERIALS AND METHODS: Prospective, cross-sectional study involving 24 patients with hepatosplenic schistosomiasis and 6 healthy patients (control group) submitted to biliary tree evaluation by MRC. The following changes of the biliary tree were considered: distortion, thinning, stenosis, dilation and irregularity. The interobserver agreement in the detection of biliary tree changes was calculated with the McNemar's test and the kappa index of agreement (κ). RESULTS: The interobserver agreement in the detection of distortion and thinning of the biliary tree was almost perfect (κ = 0.867; confidence interval [CI] 95 percent [0.512-1.0] and κ = 0.865; CI 95 percent [0.51-1.0], respectively). There was a substantial agreement for stenosis (κ = 0.78; CI 95 percent [0.424-1.0]), moderate agreement for dilation (κ = 0.595; CI 95 percent [0.247-0.942]) and mild agreement for thinning (κ = 0.229; CI 95 percent [0.095-0.552]). CONCLUSION: In a decreasing order of frequency, the changes of the biliary tree were observed: distortion, thinning, stenosis, dilation and irregularity. The interobserver agreement for signs of schistosomal cholangiopathy was almost perfect for distortion and thinning, and substantial for stenosis.

Community acceptability of the use of low-dose niclosamide (Bayluscide), as a molluscicide in the control of human schistosomiasis in Sahelian Cameroon.

Although field trials of the application of molluscicides for the control of human schistosomiasis have been conducted in several settings, the acceptability of molluscide use at the community level has been poorly documented. The death and putrefaction of aquatic organisms in water treated with niclosamide (Bayluscide), for example, and the yellowish colouration of such water, may decrease the molluscide's acceptability. It may be possible, however, to use doses of a molluscicide that are only just high enough to kill the target snails but not high enough to kill non-target fish and frogs, thereby reducing the application's impact on water quality and colour and improving its acceptability to local communities. In a study in northern Cameroon, Bayluscide WP70 was applied to ponds at concentrations of 0, 0.25, 0.5 or 1 g/m(3). Changes in human contact with the water in the ponds were explored both by direct observation and by in-depth interviews with key informants from the local community. Although all applications of niclosamide greatly decreased human use of the treated ponds for a few days, most informants (99%) were in favour of niclosamide application and only 6% of the interviewees gave change in water colour or bad smell as a reason for not using a particular water body. Over the few days post-application, use of ponds treated with 0.25 or 0.5 g Bayluscide WP70/m(3) was higher than that of the ponds treated with 1 g/m(3), indicating that relatively low-dose applications, if effective in controlling snails, may be more acceptable to local communities than applications at higher doses.

Parasitic central nervous system infections: echinococcus and schistosoma.

Central nervous system (CNS) manifestations of Echinococcus and Schistosoma infections occur throughout the world, with incidence increasing in developed regions. A detailed literature review generated a current summary on epidemiology, parasitology, pathology, clinical manifestations, imaging studies, diagnosis, and treatment of neuroechinococcosis and neuroschistosomiasis. Recent advancements have been made in diagnosis, treatment, and prevention of these parasitic CNS infections. Ongoing advancements in neuroimaging and diagnostic studies, as well as efforts to better understand the parasite genome and host-parasite relationships, will likely continue to improve patient management.

DNA therapy for asthma.

Asthma therapy, like other therapies, has been moving towards a molecular basis for several years. This year, there have been several preclinical studies published which utilize attributes or facets of DNA to address asthma therapeutics. These include antisense oligonucleotides (against the nuclear transcription factor GATA-3 and the mast cell chemotactic agent, stem cell factor), gene transfer (of interleukin-18, both by plasmid and viral vectors), and CpG oligodeoxynucleotides (which suppress Th2 and stimulate Th1 responses). No clinical experience has yet been reported for any of these areas of research in asthma, but clinical trials are ongoing utilizing CpG oligonucleotides.

Worms take the 'phyto' out of 'phytochelatins'.

Phytochelatin synthase is the enzyme responsible for the synthesis of heavy-metal-binding peptides (phytochelatins) from glutathione and related thiols. It has recently been determined that it is not only restricted to plants and some fungi, as was once thought, but also has an essential role in heavy-metal detoxification in the model nematode Caenorhabditis elegans. These findings and others that demonstrate phytochelatin synthase-coding sequences in the genomes of several other invertebrates, including pathogenic nematodes, schistosomes and roundworms, herald a new era in phytochelatin research, in which these novel post-translationally synthesized peptides will not only be investigated in the context of phytoremediation but also from a clinical parasitological standpoint.

Transient expression of DNA and RNA in parasitic helminths by using particle bombardment.

Parasitic helminths (worms belonging to several metazoan phyla) cause considerable morbidity and mortality in humans. They are an important veterinary problem, and they result in significant economic losses in animal grazing and agriculture. Experimental studies on parasitic helminths have been limited by a lack of parasite cell lines and methods for molecular genetic analyses. We evaluated particle bombardment (biolistics) as a strategy to introduce and express nucleic acids in these multicellular parasites. By using embryos of the parasitic nematode Ascaris as a model, we developed methods to introduce and express both DNA and RNA during several stages of Ascaris embryogenesis. Biolistic transfection will facilitate experimental strategies in Ascaris embryos complementing other biochemical tools available (e.g., in vitro whole-cell embryo extracts for transcription, RNA processing, and translation). Transfection experiments with adult schistosomes further suggest that the biolistic strategy should be applicable to a variety of other parasitic helminths. The development of these methods provides molecular genetic tools to study gene expression and the biology of a variety of types and developmental stages of important helminth parasites.

Estudo da resposta linfoproliferativa de pacientes com diferentes formas clínicas de esquistossomose mansônica / Study of proliferative response of patients with different clinical forms of schistosomiasis mansoni

O objetivo deste trabalho foi avaliar a resposta linfoproliferativa "in vitro" de células do baço e do sangue periférico de pacientes infectados com ::"chistosoma mansoni com diferentes formas clínicas e/ou intensidade de infecção aos seguintes antígenos: antígeno ovular solúvel (SEA), triose fosfato isomerase recombinante (rTPI), peptídeo sintético P4 derivado do rTPI, derivado protéico purificado (PPO) e mitógeno fitohemaglutinina. Os pacientes foram classificados em três grupos: 1- Hepatoíntestinal, 2- Hepatoesplênico e 3- Tratados e Curados. A resposta linfoproliferativa a estes antígenos foi testada em células mononucleares do sangue periférico de pacientes com as três formas clínicas. Também foi avaliada a resposta linfoproliferativa de células povenientes do baço de pacientes com a forma hepatoesplênica e que haviam sido submetidos a esplenectomia terapêutica. As células mononucleares do sangue periférico dos pacientes com a forma hepatointestinal e dos pacientes tratados e curados responderam ao antígeno SEA, sendo maior o nível de resposta observado neste último grupo. As células mononucleares do sangue periférico e do baço de pacientes com a forma hepatoespiênica mostraram uma resposta linfoproliferativa ao antígeno SEA inferior às células dos pacientes dos demais grupos. Não foi observada resposta linfoproliferativa estatisticamente significante aos antígenos P4 e rTPl em nenhum dos grupos estudados.