SciCombinator

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Journal: International journal for parasitology

54

Plasmodium falciparum and Plasmodium vivax account for more than 95% of all human malaria infections, and thus pose a serious public health challenge. To control and potentially eliminate these pathogens, it is important to understand their origins and evolutionary history. Until recently, it was widely believed that P. falciparum had co-evolved with humans (and our ancestors) over millions of years, while P. vivax was assumed to have emerged in southeastern Asia following the cross-species transmission of a parasite from a macaque. However, the discovery of a multitude of Plasmodium spp. in chimpanzees and gorillas has refuted these theories and instead revealed that both P. falciparum and P. vivax evolved from parasites infecting wild-living African apes. It is now clear that P. falciparum resulted from a recent cross-species transmission of a parasite from a gorilla, while P. vivax emerged from an ancestral stock of parasites that infected chimpanzees, gorillas and humans in Africa, until the spread of the protective Duffy-negative mutation eliminated P. vivax from human populations there. Although many questions remain concerning the biology and zoonotic potential of the P. falciparum- and P. vivax-like parasites infecting apes, comparative genomics, coupled with functional parasite and vector studies, are likely to yield new insights into ape Plasmodium transmission and pathogenesis that are relevant to the treatment and prevention of human malaria.

Concepts: Immune system, Malaria, Plasmodium falciparum, Plasmodium, Plasmodium vivax, Hominidae, Chimpanzee, Gorilla

29

Herein we show for the first time that S. mansoni adult worms secrete exosome-like extracellular vesicles (EVs) ranging from 50-130 nm in size. EVs were collected from the excretory/secretory products of cultured adult flukes and purified by Optiprep density gradient, resulting in highly pure EV preparations as confirmed by transmission electron microscopy and Nanosight tracking analysis. EV proteomic analysis showed numerous known vaccine candidates, potential virulence factors and molecules implicated in feeding. These findings provide new avenues for the exploration of host-schistosome interactions and offer a potential mechanism by which some vaccine antigens exert their protective efficacy.

Concepts: Protein, Electron, Microbiology, Schistosoma mansoni, Schistosoma

29

We recently completed clinical trials in people with diet-treated celiac disease who were purposefully infected with the ubiquitous human hookworm, Necator americanus. Hookworm infection elicited not only parasite-specific immunity but also modified the host’s immune response to gluten. After infection, mucosal IL-1β and IL-22 responses were enhanced, but IFNγ and IL-17A levels and circulating regulatory T cells following gluten challenge were suppressed, and the adaptive response to gluten acquired a helper T cell type-2 profile. In this review, we briefly, (i) highlight the utility celiac disease offers autoimmune research, (ii) discuss safety and personal experience with N. americanus, (iii) summarise the direct and bystander impact that hookworm infection has on mucosal immunity to the parasite and gluten, respectively, and (iv) speculate why this hookworm’s success depends on healing its host and how this might impact on a propensity to autoimmunity.

Concepts: Immune system, Infection, Immunology, Major histocompatibility complex, Autoimmunity, Coeliac disease, Hookworm, Necator

28

We believe this study is the first attempt to address molecular prospecting for species diversity of Diplostomum (Digenea: Diplostomidae) in Europe. A database linking sequences from the barcode region of the cytochrome c oxidase subunit 1 (cox1) mitochondrial gene and from the internal transcribed spacer cluster (ITS1-5.8S-ITS2) of the rRNA gene was generated for larval and adult parasites of snails, fish and gulls from central Europe. Analyses of the novel cox1 dataset revealed the presence of six genetically distinct Diplostomum lineages in the snail and fish populations studied in the River Ruhr drainage (Germany). ITS1-5.8S-ITS2 sequences from a representative subset of isolates supported the delineation detected by cox1. Molecular elucidation of the life-cycles of Diplostomum spathaceum and Diplostomum pseudospathaceum in central Europe was achieved by matching multiple sequences for isolates from natural infections in snails, fish and birds identified on the basis of the morphology of all life-cycle stages. Comparative analyses restricted to the ITS1 rDNA region and incorporating sequences for six European and seven North American Diplostomum spp. retrieved from GenBank, corroborated the results of the molecular prospecting based on the cox1 dataset. Taken together, these analyses depicted 20 molecularly characterised species and lineages of Diplostomum including three complexes of genetically distinct lineages i.e. ‘Diplostomum mergi’, ‘Diplostomum baeri’ and ‘Diplostomum huronense’, that require further appraisal with the application of molecular, morphological and experimental approaches. Two of the species and 10 of the lineages (arguably species) delineated in the datasets studied originate from central and northern Europe thus indicating a substantial unrecognized genetic diversity inferred from molecular evidence on Diplostomum spp. in Europe.

Concepts: DNA, Biodiversity, Mitochondrion, Europe, Eastern Europe, Western Europe, Cytochrome c, Central Europe

28

Modern hygienic lifestyles are associated with the emergence of inflammatory bowel disease (IBD) which now afflicts millions of people in highly-developed countries. Meticulous hygiene interrupts conduits of transmission required for ubiquitous exposure to parasitic worms (helminths). We proposed that loss of exposure to helminths permits development of IBD. Early clinical trials suggested that exposure to helminths such as Trichuris suis or Necator americanus can improve IBD. Over the last several years, processes to “medicinalize"T. suis have been developed and use of this helminth is now being studied in large multi-center clinical trials. Concurrently, we and others have identified some of the immune regulatory mechanisms elicited by helminth exposure that suppress inappropriate intestinal inflammation. These efforts could soon result in new therapies for patients with IBD.

Concepts: Immune system, Inflammation, Intestinal parasite, Ulcerative colitis, Gastroenterology, Inflammatory bowel disease, Helminthic therapy, Hookworm

28

Trichinella spiralis is a tissue-dwelling nematode parasite. A loop-mediated isothermal amplification (LAMP) assay was developed and validated for the sensitive and rapid detection of T. spiralis larvae in muscle samples. Sixteen sets of primers were designed to recognise distinct sequences of a conserved gene, a 1.6kb repetitive element of the Trichinella genome. One set of primers was selected as the most appropriate for rapid detection. The specificity and sensitivity of the primers in LAMP reactions for T. spiralis larvae and muscle samples of mice infected with T. spiralis were determined. Another 10 heterologous parasites were selected for specificity assays. The results showed that target DNA was amplified and visualised by monitoring turbidity and adding calcein detection methods within 70min at an isothermal temperature of 63°C. The sensitivity of LAMP with the detection limit of 362fg/μl was >10 times higher than that for PCR. The designed primers had a good specificity. No cross-reactivity was found with the DNA of any other parasites. The assay was able to detect T. spiralis in all mouse muscle samples infected with 10 T. spiralis larvae on day 20 p.i. We believe this is the first report regarding the application of the LAMP assay for detection of T. spiralis larvae in muscle samples from experimentally infected mice. This method demonstrates a potentially valuable means for the direct detection of T. spiralis larvae in meat inspection.

Concepts: Gene, Parasites, Sensitivity and specificity, Trichinella spiralis, Trichinella, Trichinosis

28

Costs of parasitism are predicted to be higher with greater parasite intensities and higher inter-parasite competition (diversity). We tested whether greater helminth intensities and diversity were associated with poorer body composition (whole-body fat, protein, mineral and true body mass) in lesser snow geese, Chen caerulescens caerulescens. As part of a larger study on nutritional ecology, 828 wintering or migrating geese were shot between January and May 1983 in 27 different date-locations (samples) during their northward migration through mid-continental North America. A large proportion of overall variation in body composition and parasite communities was among samples, so we analyzed data within each of the 27 samples, controlling for structural body size (the first principal component of 10 body size measurements), sex and the age of geese. There was no compelling evidence that cestodes, trematodes or helminth diversity were associated with variation in body composition but nematodes had several negative associations with fat reserves. However, negative associations between fat reserves and nematodes occurred most often in geese collected between March and May when nematode prevalences and intensities were relatively low. This suggests several possibilities: that the most common nematodes (Heterakis dispar and Trichostrongylus tenuis) were more virulent at this time, that infected individuals had been chronically infected and suffered cumulative nutrient deficits that lasted until late in the spring migration, or that geese became more vulnerable to the effects of parasites at this time of year, possibly because they redirected resources away from immunity toward fat storage in preparation for reproduction.

Concepts: Intestinal parasite, Parasitism, Anser, Chen, Snow Goose

28

In this work, evidence for a critical role of Trichomonas vaginalis protein phosphatase 1 gamma (TvPP1γ) in proliferation and attachment of the parasite to the mammalian cell is provided. Firstly, proliferation and attachment of T. vaginalis parasites to HeLa cells was blocked by calyculin A (CA), a potent PP1 inhibitor. Secondly, it was demonstrated that the enzyme activity of native and recombinant TvPP1γ proteins was inhibited by CA. Thirdly, reverse genetic studies confirmed that antisense oligonucleotides targeted to PP1γ but not PP1α or β inhibited proliferation and attachment of trichomonads CA-treated parasites underwent cytoskeletal modifications, including a lack of axostyle typical labelling, suggesting that cytoskeletal phosphorylation could be regulated by a CA-sensitive phosphatase where the role of PP1γ could not be ruled out. Analysis of subcellular distribution of TvPP1γ by cell fractionation and electron microscopy demonstrated the association between TvPP1γ and the cytoskeleton. The expression of adhesins, AP120 and AP65, at the cell surface was also inhibited by CA. The concomitant inhibition of expression of adhesins and changes in the cytoskeleton in CA-treated parasites suggest a specific role for PP1γ -dependent dephosphorylation in the early stages of the host-parasite interaction. Molecular modelling of TvPP1γ showed the conservation of residues critical for maintaining proper folding into the gross structure common to PP1 proteins. Taken together, these results suggest that TvPP1γ could be considered a potential novel drug target for treatment of trichomoniasis.

Concepts: DNA, Protein, Protein structure, Genetics, Bacteria, Enzyme, Cytoplasm, Trichomonas vaginalis

28

Trichinellosis is a zoonotic disease caused by parasites of the genus Trichinella, which have a cosmopolitan distribution. For diagnostic purposes, a confirmatory test for ELISA-positive human and pig sera such as Western blotting is required, due to the high number of ELISA false positive sera. The objective of this study was to identify the Trichinella-specific antigens most frequently recognized by sera from Trichinella-infected humans and pigs, so as to define a distinctive pattern of Trichinella infection in sera from infected hosts using Western blots which allow false positive sera to be distinguished from true positive sera. Using excretory/secretory antigens, 450 human sera were tested by Western blotting: 150 from persons with a confirmed diagnosis of trichinellosis and 300 from persons who did not have trichinellosis but who tested positive by ELISA (i.e., false positives). We also tested 210 pig sera: (i) 30 from pigs experimentally infected with Trichinella spiralis; (ii) 90 from naturally T. spiralis-infected pigs; and (iii) 90 from pigs not infected with Trichinella, as shown after artificial digestion of the diaphragm pillars, yet which tested positive by ELISA (i.e., false positives). All true positive sera (i.e., sera from persons with confirmed trichinellosis as well as sera from naturally and experimentally infected pigs), reacted with a three-band pattern ranging in size from 48-72kDa. A distinctive pattern for recognizing Trichinella spp. infections in humans and pigs by Western blots is defined; it shows a sensitivity of 100% and it allows sera from Trichinella-infected humans and pigs to be distinguished from sera from persons and pigs that were not infected with Trichinella spp. (100% specificity).

Concepts: Antibody, Molecular biology, Infection, Type I and type II errors, Sensitivity and specificity, Western blot, Trichinella spiralis, Southern blot

28

Myxobolus cerebralis is a microscopic metazoan parasite (Phylum Myxozoa: Myxosporea) associated with salmonid whirling disease. There are currently no vaccines to minimise the serious negative economical and ecological impacts of whirling disease among populations of salmonid fish worldwide. UV irradiation has been shown to effectively inactivate the waterborne infective stages or triactinomyxons of M. cerbralis in experimental and hatchery settings but the mechanisms by which the parasite is compromised are unknown. Treatments of triactinomyxons with UV irradiation at doses from 10 to 80 mJ/cm(2) either prevented (20-80 mJ/cm(2)) or significantly inhibited (10 mJ/cm(2)) completion of the parasite life cycle in experimentally exposed juvenile rainbow trout (Oncorhynchus mykiss). However, even the highest doses of UV irradiation examined (80 mJ/cm(2)) did not prevent key steps in the initiation of parasite infection, including attachment and penetration of the epidermis of juvenile rainbow trout as demonstrated by scanning electron and light microscopy. Furthermore, replication of UV-treated parasites within the first 24h following invasion of the caudal fin was suggested by the detection of concentrations of parasite DNA by quantitative PCR comparable to that among fish exposed to an equal concentration of untreated triactinomyxons. Subsequent development of parasites treated with an 80 mJ/cm(2) dose of UV irradiation however, was impaired as demonstrated by the decline and then lack of detection of parasite DNA; a trend beginning at 10 days and continuing thereafter until the end of the study at 46 days post parasite exposure. Treatments of triactinomyxons with a lower dose of UV irradiation (20 mJ/cm(2)) resulted in a more prolonged survival with parasite DNA detected, although at very low concentrations, in fish up to 49 days post parasite exposure. The successful invasion but only short-term survival of parasites treated with UV in rainbow trout resulted in a protective response to challenges with fully infective triactinomyxons. Prior treatments of juvenile rainbow trout with UV-treated triactinomyxons (10 and 20 mJ/cm(2)) resulted in a reduced prevalence of infection and significantly lower concentrations of cranial myxospores (two direct measures of the severity of whirling disease) compared with trout receiving no prior treatments when assessed 5 months post parasite exposure to fully infective triactinomyxons.

Concepts: Salmon, Oncorhynchus, Salmonidae, Rainbow trout, Cutthroat trout, Myxozoa, Myxobolus cerebralis, Myxosporea