- The establishment of in vitro culture and drug screening systems for a newly isolated strain of Trypanosoma equiperdum. [Journal Article]
- IJInt J Parasitol Drugs Drug Resist 2017 Apr 13; 7(2):200-205
- Dourine is caused by Trypanosoma equiperdum via coitus with an infected horse. Although dourine is distributed in Equidae worldwide and is listed as an internationally important animal disease by the...
Dourine is caused by Trypanosoma equiperdum via coitus with an infected horse. Although dourine is distributed in Equidae worldwide and is listed as an internationally important animal disease by the World Organization for Animal Health (OIE), no effective treatment strategies have been established. In addition, there are no reports on drug discovery, because no drug screening system exists for this parasite. A new T. equiperdum strain was recently isolated from the genital organ of a stallion that showed typical symptoms of dourine. In the present study, we adapted T. equiperdum IVM-t1 from soft agarose media to HMI-9 liquid media to develop a drug screening assay for T. equiperdum. An intracellular ATP-based luciferase assay using CellTiter-Glo reagent and an intracellular dehydrogenase activity-based colorimetric assay using WTS-8 tetrazolium salt (CCK-8 reagent) were used in order to examine the trypanocidal effects of each compound. In addition, the IC50 values of 4 reference trypanocidal compounds (pentamidine, diminazene, suramin and melarsomine) were evaluated and compared using established assays. The IC50 values of these reference compounds corresponded well to previous studies involving other strains of T. equiperdum. The luciferase assay would be suitable for the mass screening of chemical libraries against T. equiperdum because it allows for the simple and rapid-evaluation of the trypanocidal activities of test compounds, while a simple, inexpensive colorimetric assay will be applicable in developing countries for the evaluation of the drug sensitivity of epidemic trypanosome strains.
- Corrigendum to "Therapeutic effect of ursolic acid in experimental visceral leishmaniasis" [Int. J. Parasitol. Drugs Drug Resist. 7 (2017) 1-11]. [Published Erratum]
- IJInt J Parasitol Drugs Drug Resist 2017 Apr 04
- Epigenetic landscapes underlining global patterns of gene expression in the human malaria parasite, Plasmodium falciparum. [Review]
- IJInt J Parasitol 2017 Apr 13
- The dynamic chromatin landscape displaying combinatorial complexity of the epigenome impacts gene expression that underlies many events of differentiation and cell cycle progression. In the past few ...
The dynamic chromatin landscape displaying combinatorial complexity of the epigenome impacts gene expression that underlies many events of differentiation and cell cycle progression. In the past few years, epigenetic mechanisms have emerged as important processes involved in the tight gene regulation in malaria parasites, Plasmodium spp. Focusing predominantly on Plasmodium falciparum, the species associated with the most severe form of the disease, many advances have been made in our understanding of the interaction between transcriptional regulation and epigenetic mechanisms as the pivotal processes in regulating life cycle progression, host parasite interactions and parasite adaptation to the host environment. This review focuses on the epigenome and its effect on transcriptional regulation in P. falciparum, highlighting its unique, evolutionary diverse features.
- The unhealthy attraction of Plasmodium vivax to reticulocytes expressing transferrin receptor 1 (CD71). [Review]
- IJInt J Parasitol 2017 Apr 13
- The majority of malaria parasite species prefer to invade reticulocytes, the most infamous being Plasmodium vivax. While the absence of an in vitro continuous culture method has hampered the study of...
The majority of malaria parasite species prefer to invade reticulocytes, the most infamous being Plasmodium vivax. While the absence of an in vitro continuous culture method has hampered the study of P. vivax invasion biology, studies utilising primate models and ex vivo assays have provided some important insights. Most importantly, P. vivax merozoites have a strong preference for a subset of immature erythrocytes characterised by the expression of the transferrin receptor (CD71). This current opinion piece on P. vivax merozoite invasion highlights important gaps in our understanding of how this parasite recognises and enters reticulocytes, and discusses some recent conceptual advances in P. vivax invasion biology.
- Pufferfish nests vs. parasite hooks: A bizarre resemblance. [Journal Article]
- IJInt J Parasitol Parasites Wildl 2017; 6(2):69
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- Novel carbazole aminoalcohols as inhibitors of β-hematin formation: Antiplasmodial and antischistosomal activities. [Journal Article]
- IJInt J Parasitol Drugs Drug Resist 2017 Apr 02; 7(2):191-199
- Malaria and schistosomiasis are two of the most socioeconomically devastating parasitic diseases in tropical and subtropical countries. Since current chemotherapeutic options are limited and defectiv...
Malaria and schistosomiasis are two of the most socioeconomically devastating parasitic diseases in tropical and subtropical countries. Since current chemotherapeutic options are limited and defective, there is an urgent need to develop novel antiplasmodials and antischistosomals. Hemozoin is a disposal product formed from the hemoglobin digestion by some blood-feeding parasites. Hemozoin formation is an essential process for the parasites to detoxify free heme, which is a reliable therapeutic target for identifying novel antiparasitic agents. A series of novel carbazole aminoalcohols were designed and synthesized as potential antiplasmodial and antischistosomal agents, and several compounds showed potent in vitro activities against Plasmodium falciparum 3D7 and Dd2 strains and adult and juvenile Schistosoma japonicum. Investigations on the dual antiparasitic mechanisms showed the correlation between inhibitory activity of β-hematin formation and antiparasitic activity. Inhibiting hemozoin formation was identified as one of the mechanisms of action of carbazole aminoalcohols. Compound 7 displayed potent antiplasmodial (Pf3D7 IC50 = 0.248 μM, PfDd2 IC50 = 0.091 μM) and antischistosomal activities (100% mortality of adult and juvenile schistosomes at 5 and 10 μg/mL, respectively) and exhibited low cytotoxicity (CC50 = 7.931 μM), which could be considered as a promising lead for further investigation. Stoichiometry determination and molecular docking studies were also performed to explain the mode of action of compound 7.
- Temporal and demographic blood parasite dynamics in two free-ranging neotropical primates. [Journal Article]
- IJInt J Parasitol Parasites Wildl 2017; 6(2):59-68
- Parasite-host relationships are influenced by several factors intrinsic to hosts, such as social standing, group membership, sex, and age. However, in wild populations, temporal variation in parasite...
Parasite-host relationships are influenced by several factors intrinsic to hosts, such as social standing, group membership, sex, and age. However, in wild populations, temporal variation in parasite distributions and concomitant infections can alter these patterns. We used microscropy and molecular methods to screen for naturally occurring haemoparasitic infections in two Neotropical primate host populations, the saddleback (Leontocebus weddelli) and emperor (Saguinus imperator) tamarin, in the lowland tropical rainforests of southeastern Peru. Repeat sampling was conducted from known individuals over a three-year period to test for parasite-host and parasite-parasite associations. Three parasites were detected in L. weddelli including Trypanosoma minasense, Mansonella mariae, and Dipetalonema spp., while S. imperator only hosted the latter two. Temporal variation in prevalence was observed in T. minasense and Dipetalonema spp., confirming the necessity of a multi-year study to evaluate parasite-host relationships in this system. Although callitrichids display a distinct reproductive dominance hierarchy, characterized by single breeding females that typically mate polyandrously and can suppress the reproduction of subdominant females, logistic models did not identify sex or breeding status as determining factors in the presence of these parasites. However, age class had a positive effect on infection with M. mariae and T. minasense, and adults demonstrated higher parasite species richness than juveniles or sub-adults across both species. Body weight had a positive effect on the presence of Dipetalonema spp. The inclusion of co-infection variables in statistical models of parasite presence/absence data improved model fit for two of three parasites. This study verifies the importance and need for broad spectrum and long-term screening of parasite assemblages of natural host populations.
- Schistosome-induced pulmonary B cells inhibit allergic airway inflammation and display a reduced Th2-driving function. [Journal Article]
- IJInt J Parasitol 2017 Apr 04
- Chronic schistosome infections protect against allergic airway inflammation (AAI) via the induction of IL-10-producing splenic regulatory B (Breg) cells. Previous experiments have demonstrated that s...
Chronic schistosome infections protect against allergic airway inflammation (AAI) via the induction of IL-10-producing splenic regulatory B (Breg) cells. Previous experiments have demonstrated that schistosome-induced pulmonary B cells can also reduce AAI, but act independently of IL-10. We have now further characterized the phenotype and inhibitory activity of these protective pulmonary B cells. We excluded a role for regulatory T (Treg) cell induction as putative AAI-protective mechanisms. Schistosome-induced B cells showed increased CD86 expression and reduced cytokine expression in response to Toll-like receptor (TLR) ligands compared with control B cells. To investigate the consequences for T cell activation we cultured ovalbumin (OVA)-pulsed, schistosome-induced B cells with OVA-specific transgenic T cells and observed less Th2 cytokine expression and T cell proliferation compared with control conditions. This suppressive effect was preserved even under optimal T cell stimulation by anti-CD3/28. Blocking of the inhibitory cytokines IL-10 or TGF-β only marginally restored Th2 cytokine induction. These data suggest that schistosome-induced pulmonary B cells are impaired in their capacity to produce cytokines to TLR ligands and to induce Th2 cytokine responses independent of their antigen-presenting function. These findings underline the presence of distinct B cell subsets with different stimulatory or inhibitory properties even if induced by the same type of helminth.
- The Vivax Surveyor: Online mapping database for Plasmodium vivax clinical trials. [Review]
- IJInt J Parasitol Drugs Drug Resist 2017 Mar 24; 7(2):181-190
- CONCLUSIONS: Over the last 20 years there has been a substantial increase in clinical research on the treatment of P. vivax, which has generated a greater awareness of the global extent of chloroquine resistance. The WWARN open access, online interactive map provides up to date information of areas where drug resistant P. vivax is emerging.
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- Two new species of Syndesmis (Platyhelminthes, Rhabdocoela, Umagillidae) from the sea urchin Pseudechinus magellanicus (Echinodermata, Echinoidea) in the Southwestern Atlantic Ocean. [Journal Article]
- IJInt J Parasitol Parasites Wildl 2017; 6(2):54-58
- In this paper, we describe two new species of Syndesmis living in Pseudechinus magellanicus in the Southwest Atlantic Ocean. The new species have a long stylet in the male reproductive system, which ...
In this paper, we describe two new species of Syndesmis living in Pseudechinus magellanicus in the Southwest Atlantic Ocean. The new species have a long stylet in the male reproductive system, which is different from that of the known species of the genus. Specimens of Syndesmis selknami n. sp. have a ∼220-μm-long stylet (∼1/3 of the body length, 0.69 mm). This ratio is unique because only four species (Syndesmis echinorum, Syndesmis rubida, Syndesmis inconspicua and Syndesmis echiniacuti) have similar stylet lengths but are larger in body sizes (3-5 mm). Specimens of Syndesmis aonikenki n. sp. have a ∼148-μm-long stylet (∼1/10 of the body length, 1.11 mm). Syndesmis pallida has a similar ratio but the uterus is located posteriorly, and the filament glands are very small and located in the posterior region of the body. These are the first flatworms reported parasitizing Pseudechinus magellanicus.