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Background: Cystic echinococcosis (CE), a widespread helminthic disease caused by the larval stage of the dog tapeworm Echinococcus granulosus represents a public health concern in humans. Albendazole (ABZ) is the first -line treatment for CE; however therapeutic failure of ABZ against CE occurs because of size and location of formed cysts as well its low aqueous solubility and consequently its erratic bioavailability in plasma. Serious adverse effects have also been observed following the long-term use of ABZ in vivo.Methods: We evaluated the apoptotic effects of ABZ-loaded 13-cyclodextrin (ABZ-13-CD) against protoscoleces (PSCs) versus ABZ alone. After 15 h of exposure, Caspase-3 enzymatic activity was determined by fluorometric assay in PSCs treated with ABZ and ABZ-13-CD groups. To assess the treatment efficacy of ABZ-13-CD against PSCs, mRNA expression of Arginase (EgArg) and Thioredoxin peroxidase (EgTPx) were quantified by Real-time PCR.Results: A significant scolicidal activity of ABZ was observed only at a concentration of 800 mu g/mL (100% PSCs mortality rate after 4 days of exposure), while the 200 and 400 mu g/mL ABZ reached 100% PSCs mortality rate after 9 sequential days. The 400 mu g/mL ABZ-13-CD had 100% scolicidal rate after 5 days of exposure. Morpho-logical alterations using scanning electron microscopy in treated PSCs revealed that 400 mu g/mL ABZ-13-CD induced higher Caspase-3 activity than their controls, indicating a more potent apoptotic outcome on the PSCs. Also, we showed that the 400 mu g/mL ABZ-13-CD can down-regulate the mRNA expression of EgArg and EgTPx , indicating more potent interference with growth and antioxidant properties of PSCs.Conclusions: In the present study, a significant scolicidal rate, apoptosis intensity and treatment efficacy was observed in PSCs treated with 400 mu g/mL ABZ-13-CD compared to ABZ alone. This provides new insights into the use of nanostructured 13 -CD carriers with ABZ as a promising candidate to improve the treatment of CE in in vivo models., Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; [59631], Funding This study was financially supported by Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran (Grant no. 59631) .

Helminth infection represents a major health problem causing approximately 5 million disability-adjusted life years worldwide. Concerns that repeated anti-helminthic treatment may lead to drug resistance render it important that vaccines are developed but will require increased understanding of the immune-mediated cellular and antibody responses to helminth infection. IL-4 or antibody-activated murine macrophages are known to immobilize parasitic nematode larvae, but few studies have addressed whether this is translatable to human macrophages. In the current study, we investigated the capacity of human macrophages to recognize and attack larval stages of Ascaris suum, a natural porcine parasite that is genetically similar to the human helminth Ascaris lumbricoides. Human macrophages were able to adhere to and trap A suum larvae in the presence of either human or pig serum containing Ascaris-specific antibodies and other factors. Gene expression analysis of serum-activated macrophages revealed that CCL24, a potent eosinophil attractant, was the most upregulated gene following culture with A suum larvae in vitro, and human eosinophils displayed even greater ability to adhere to, and trap, A suum larvae. These data suggest that immune serum-activated macrophages can recruit eosinophils to the site of infection, where they act in concert to immobilize tissue-migrating Ascaris larvae.

Cestodiases are common parasitic diseases of animals and humans. As cestodes have complex lifecycles, hexacanth larvae, metacestodes (including cysticercoids), and adults produce proteins allowing them to establish invasion and to survive in the hostile environment of the host. Hymenolepis diminuta is the most commonly used model cestode in experimental parasitology. The aims of the present study were to perform a comparative proteomic analysis of two consecutive developmental stages of H. diminuta (cysticercoid and adult) and to distinguish proteins which might be characteristic for each of the stages from those shared by both stages. Somatic proteins of H. diminuta were isolated from 6-week-old cysticercoids and adult tapeworms. Cysticercoids were obtained from experimentally infected beetles, Tenebrio molitor, whereas adult worms were collected from experimentally infected rats. Proteins were separated by GeLC-MS/MS (one dimensional gel electrophoresis coupled with liquid chromatography and tandem mass spectrometry). Additionally protein samples were digested in-liquid and identified by LC-MS/MS. The identified proteins were classified according to molecular function, cellular components and biological processes. Our study showed a number of differences and similarities in the protein profiles of cysticercoids and adults; 233 cysticercoid and 182 adult proteins were identified. From these proteins, 131 were present only in the cysticercoid and 80 only in the adult stage samples. Both developmental stages shared 102 proteins; among which six represented immunomodulators and one is a potential drug target. In-liquid digestion and LC-MS/MS complemented and confirmed some of the GeLC-MS/MS identifications. Possible roles and functions of proteins identified with both proteomic approaches are discussed.

Innate lymphoid cells (ILCs) play an important role in regulating immune responses at mucosal surfaces. The transcription factor T-bet is crucial for the function of ILC1s and NCR+ ILC3s and constitutive deletion of T-bet prevents the development of these subsets. Lack of T-bet in the absence of an adaptive immune system causes microbiota-dependent colitis to occur due to aberrant ILC3 responses. Thus, T-bet expression in the innate immune system has been considered to dampen pathogenic immune responses. Here, we show that T-bet plays an unexpected role in negatively regulating innate type 2 responses, in the context of an otherwise intact immune system. Selective loss of T-bet in ILCs leads to the expansion and increased activity of ILC2s, which has a functionally important impact on mucosal immunity, including enhanced protection from Trichinella spiralis infection and inflammatory colitis. Mechanistically, we show that T-bet controls the intestinal ILC pool through regulation of IL-7 receptor signalling. These data demonstrate that T-bet expression in ILCs acts as the key transcriptional checkpoint in regulating pathogenic vs. protective mucosal immune responses, which has significant implications for the understanding of the pathogenesis of inflammatory bowel diseases and intestinal infections.

Foodborne parasites are a source of human parasitic infection. Zoonotic infections of humans arise from a variety of domestic and wild animals, including sheep, goats, cattle, camels, horses, pigs, boars, bears, felines, canids, amphibians, reptiles, poultry, and aquatic animals such as fishes and shrimp. Therefore, the implementation of efficient, accessible, and controllable inspection policies for livestock, fisheries, slaughterhouses, and meat processing and packaging companies is highly recommended. In addition, more attention should be paid to the education of auditors from the quality control (QC) and assurance sectors, livestock breeders, the fishery sector, and meat inspection veterinarians in developing countries with high incidence of zoonotic parasitic infections. Furthermore, both the diagnosis of zoonotic parasitic infections by inexpensive, accessible, and reliable identification methods and the organization of effective control systems with sufficient supervision of product quality are other areas to which more attention should be paid. In this review, we present some examples of successful inspection policies and recent updates on present conventional, serologic, and molecular diagnostic methods for zoonotic foodborne parasites from both human infection and animal-derived foods.

Background A wide range of molecules are used by tapeworm metacestodes to establish successful infection in the hostile environment of the host. Reports indicating the proteins in the cestode-host interactions are limited predominantly to taeniids, with no previous data available for non-taeniid species. A non-taeniid, Hymenolepis diminuta, represents one of the most important model species in cestode biology and exhibits an exceptional developmental plasticity in its life-cycle, which involves two phylogenetically distant hosts, arthropod and vertebrate. Results We identified H. diminuta cysticercoid proteins that were recognized by sera of H. diminuta-infected rats using two-dimensional gel electrophoresis (2DE), 2D-immunoblotting, and LC-MS/MS mass spectrometry. Proteomic analysis of 42 antigenic spots revealed 70 proteins. The largest number belonged to structural proteins and to the heat-shock protein (HSP) family. These results show a number of the antigenic proteins of the cysticercoid stage, which were present already in the insect host prior to contact with the mammal host. These are the first parasite antigens that the mammal host encounters after the infection, therefore they may represent some of the molecules important in host-parasite interactions at the early stage of infection. Conclusions These results could help in understanding how H. diminuta and other cestodes adapt to their diverse and complex parasitic life-cycles and show universal molecules used among diverse groups of cestodes to escape the host response to infection. Electronic supplementary material The online version of this article (10.1186/s13071-017-2519-4) contains supplementary material, which is available to authorized users.

Parasitic infections are ubiquitous in wildlife, livestock and human populations, and healthy ecosystems are often parasite rich. Yet, their negative impacts can be extreme. Understanding how both anticipated and cryptic changes in a system might affect parasite transmission at an individual, local and global level is critical for sustainable control in humans and livestock. Here we highlight and synthesize evidence regarding potential effects of ‘system changes’ (both climatic and anthropogenic) on parasite transmission from wild host–parasite systems. Such information could inform more efficient and sustainable parasite control programmes in domestic animals or humans. Many examples from diverse terrestrial and aquatic natural systems show how abiotic and biotic factors affected by system changes can interact additively, multiplicatively or antagonistically to influence parasite transmission, including through altered habitat structure, biodiversity, host demographics and evolution. Despite this, few studies of managed systems explicitly consider these higher-order interactions, or the subsequent effects of parasite evolution, which can conceal or exaggerate measured impacts of control actions. We call for a more integrated approach to investigating transmission dynamics, which recognizes these complexities and makes use of new technologies for data capture and monitoring, and to support robust predictions of altered parasite dynamics in a rapidly changing world. This article is part of the themed issue ‘Opening the black box: re-examining the ecology and evolution of parasite transmission’.

Inadequate rodent control is considered to play a role in Toxoplasma gondii infection of pigs. This issue was addressed in the current study by combining a 4-month rodent control campaign and a 7-month longitudinal analysis of T. gondii seroprevalence in slaughter pigs. Three organic pig farms with known rodent infestation were included in the study. On these farms, presence of T. gondii in trapped rodents was evaluated by real-time PCR. All rodent species and shrews investigated had T. gondii DNA in brain or heart tissue. Prevalence was 10.3% in Rattus norvegicus, 6.5% in Mus musculus, 14.3% in Apodemus sylvaticus and 13.6% in Crocidura russula. Initial T. gondii seroprevalence in the slaughter pigs ranged between 8% and 17% and dropped on the three farms during the rodent control campaign to 0¿10%, respectively. After 4 months of rodent control, T. gondii infection was absent from pigs from two of the three farms investigated and appeared again in one of those two farms after the rodent control campaign had stopped. This study emphasizes the role of rodents and shrews in the transmission of T. gondii to pigs and the importance of rodent control towards production of T. gondii-free pig meat. Keywords: T. gondii; Rodent control; Pigs; Parasite reservoir; Rattus norvegicus; Mus musculus; Apodemus sylvaticus; Crocidura russula

Anti-helminth immunity involves CD4(+) T cells, yet the precise effector mechanisms responsible for parasite killing or expulsion remain elusive. We now report an essential role for antibodies in mediating immunity against the enteric helminth Heligmosomoides polygyrus (Hp), a natural murine parasite that establishes chronic infection. Polyclonal IgG antibodies, present in naive mice and produced following Hp infection, functioned to limit egg production by adult parasites. Comparatively, affinity-matured parasite-specific IgG and IgA antibodies that developed only after multiple infections were required to prevent adult worm development. These data reveal complementary roles for polyclonal and affinity-matured parasite-specific antibodies in preventing enteric helminth infection by limiting parasite fecundity and providing immune protection against reinfection, respectively. We propose that parasite-induced polyclonal antibodies play a dual role, whereby the parasite is allowed to establish chronicity, while parasite load and spread are limited, likely reflecting the long coevolution of helminth parasites with their hosts.

One-third of the human world population is infected with the protozoan parasite Toxoplasma gondii. Recent calculations of the disease burden of toxoplasmosis rank this foodborne disease at the same level as salmonellosis or campylobacteriosis. The high disease burden in combination with disappointing results of the currently available treatment options have led to a plea for more effective prevention. In this review we describe Toxoplasma as a hazard associated with the consumption of undercooked meat or meat products and provide an analysis of the various options to control the risk of human toxoplasmosis via this source. Monitoring and surveillance programs may be implemented for pre-harvest control of Toxoplasma infection of farm animals, with the reduction of environmental oocyst load as the most important milestone. Alternatively, Toxoplasma safe meat can be obtained through simple post-harvest decontamination procedures, whereby freezing the meat may currently be the best option, although new technologies using irradiation or high-pressure treatment may offer promising alternatives. Influence of culture, religion and food handling customs may predispose a certain type of meat as an important source of infection, indicating that prevention needs to be tailored according to social habits in different regions in the world. The rationale for more stringent control measures to prevent toxoplasmosis both from disease and economic points of view is emphasized.

Upregulation of CGRP-immunoreactive (IR) primary afferent nerve fibers accompanied by mastocytosis is characteristic for the Schistosoma mansoni-infected murine ileum. These mucosal mast cells (MMC) and CGRP-IR fibers, which originate from dorsal root (DRG) and nodose ganglia, are found in close apposition. We examined interactions between primary cultured MMC and CGRP-IR DRG neurons in vitro by confocal recording of intracellular Ca2+concentration ([Ca2+]i). The degranulatory EC50for the mast cell secretagogue compound 48/80 (C48/80; 10 μg/ml) and the neuropeptides CGRP (2.10−8M) and substance P (SP; 3.10−8M) were determined by measurement of extracellular release of the granule chymase, mouse mast cell protease-1. Application of C48/80 (10 μg/ml) and CGRP and SP (both 10−7M) to Fluo-4-loaded MMC induced a transient rise in [Ca2+]iafter a lag time, indicative of mast cell degranulation and/or secretion. The CGRP response could be completely blocked by pertussis toxin (2 μg/ml), indicating involvement of Giproteins. Application of MMC juice, obtained by C48/80 degranulation of MMC, to Fluo-4-loaded DRG neurons induced in all neurons a rise in [Ca2+]i, indicative of activation. Degranulation of MMC by C48/80 in culture dishes containing Fluo-4-loaded DRG neurons also caused activation of the DRG neurons. In conclusion, these results demonstrate a bidirectional cross-talk between cultured MMC and CGRP-IR DRG neurons in vitro. This indicates that such a communication may be the functional relevance for the close apposition between MMC and CGRP-IR nerve fibers in vivo.

Trichinellosis is a zoonotic parasitic disease with a worldwide distribution. The aim of this work was to describe the epidemiological and clinical data of five outbreaks of trichinellosis, which affected ethnic minorities living in remote mountainous areas of northwestern Vietnam from 1970 to 2012. Trichinellosis was diagnosed in 126 patients, of which 11 (8.7%) were hospitalized and 8 (6.3%) died. All infected people had consumed raw pork from backyard and roaming pigs or wild boar at wedding, funeral, or New Year parties. The short incubation period (average of 9.5 days), the severity of the symptoms, which were characterized by diarrhea, abdominal pain, fever, myalgia, edema, weight loss, itch, and lisping, and the high mortality, suggest that patients had ingested a high number of larvae. The larval burden in pigs examined in one of the outbreaks ranged from 70 to 879 larvae/g. These larvae and those collected from a muscle biopsy taken from a patient from the 2012 outbreak were identified as Trichinella spiralis. Data presented in this work show that the northern regions of Vietnam are endemic areas for Trichinella infections in domestic pigs and humans.

High pressure processing (HPP) has been shown to be an effective non-thermal method of eliminating non-spore forming bacteria from a variety of food products. The shelf-life of the products is extended and the sensory features of the food are not or only minimally effected by HPP. The present study examined the effects of HPP using a commercial scale unit on the viability of Toxoplasma gondii oocysts. Oocysts were exposed from 100 to 550 MPa for I min in the HPP unit and then HPP treated oocysts were orally fed to groups of mice. Oocysts treated with 550 MPa or less did not develop structural alterations when viewed with light microscopy. Oocysts treated with 550 MPa, 480 MPa, 400 Mpa, or 340 MPa were tendered noninfectious for mice. Mice fed oocysts treated with no or 100 to 270 MPa became infected and most developed acute toxoplasmosis and were killed or died 7 to 10 days after infection. These results suggest that HPP technology may be useful in the removal of T. gondii oocysts from food products. NOAA Office of Sea Grant U.S. Department of Commerce, under Grant No. NA56RG0141 Virginia Graduate Marine Science Consortium Virginia Sea Grant College Program

▪ Abstract Parasitic nematodes that infect humans, animals, and plants cause serious diseases that are deleterious to human health and agricultural productivity. Chemical and biological control methods have reduced the impact of these parasites. However, surviving environmental stages lead to persistent reinfection of host species. In addition, development of resistance to nematicides and anthelmintics by these parasites and reduced availability of some nematicides, for environmental protection, pose significant obstacles for current and future prospects of effective parasite control. Due to marked differences in host species, research on animal and plant parasitic nematodes often proceeds independently. Despite the differences between animals and plants, basic cellular properties are shared among these host organisms. Some common properties may be important for mechanisms [homologous or convergent (homoplastic)] by which nematodes successfully infect these diverse hosts or by which animal and plant hosts resist infections by these pathogens. Here we compare host/parasite interactions between plant parasitic nematodes (PPN) and animal parasitic nematodes, with an emphasis on mammalian hosts (MPN). Similarities and differences are considered in the context of progress on molecular dissection of these interactions. A comprehensive coverage is not possible in the space allotted. Instead, an illustrative approach is used to establish examples that, it is hoped, exemplify the value of the comparative approach.

We evaluated industrially prepared Western blot strips designed to avoid the cross-reactions observed with indirect immunofluorescence and enzyme-linked immunosorbent assays used for the serodiagnosis of trichinellosis. The antigen preparations were crude extracts of Trichinella spiralis . The Western blot profile characteristic of trichinellosis was characterized by comparing 60 sera from patients infected by Trichinella to 11 sera from healthy subjects, 51 sera from patients with other proven parasitic diseases (cysticercosis, schistosomiasis, strongyloidosis, fascioliasis, toxocariasis, liver amebiasis, anisakiasis, filariasis, toxoplasmosis, hydatidosis, or malaria), and 23 sera from patients with autoantibodies. Specific 43- to 44-kDa and 64-kDa bands were obtained with all of the sera from 51 patients with acute trichinellosis, in 4 out of 9 patients at the early stages of the disease, and in only 1 control patient, who had suspected anisakiasis and in whom trichinellosis could not be ruled out by muscle biopsy.