Major Parasites Research Articles

Analysis of the Major Gastrointestinal Parasites Community in Yili Horses in Zhaosu of Xinjiang, Western China

Analysis of the Major Gastrointestinal Parasites Community in Yili Horses in Zhaosu of Xinjiang, Western China

Molecular surveillance for operationally relevant genetic polymorphisms in Plasmodium falciparum in Southern Chad, 2016\u20132017

BackgroundResistance to anti-malarials is a serious threat to the efforts to control and eliminate malaria. Surveillance based on simple field protocols with centralized testing to detect molecular markers associated with anti-malarial drug resistance can be used to identify locations where further investigations are needed.MethodsDried blood spots were collected from 398 patients (age range 5–59 years, 99% male) with Plasmodium falciparum infections detected using rapid diagnostic tests over two rounds of sample collection conducted in 2016 and 2017 in Komé, South-West Chad. Specimens were genotyped using amplicon sequencing or qPCR for validated markers of anti-malarial resistance including partner drugs used in artemisinin-based combination therapy (ACT).ResultsNo mutations in the pfk13 gene known to be associated with artemisinin resistance were found but a high proportion of parasites carried other mutations, specifically K189T (190/349, 54.4%, 95%CI 49.0–59.8%). Of 331 specimens successfully genotyped for pfmdr1 and pfcrt, 52% (95%CI 46.4–57.5%) carried the NFD-K haplotype, known to be associated with reduced susceptibility to lumefantrine. Only 20 of 336 (6.0%, 95%CI 3.7–9.0%) had parasites with the pfmdr1-N86Y polymorphism associated with increased treatment failures with amodiaquine. Nearly all parasites carried at least one mutation in pfdhfr and/or pfdhps genes but ‘sextuple’ mutations in pfdhfr—pfdhps including pfdhps -A581G were rare (8/336 overall, 2.4%, 95%CI 1.2–4.6%). Only one specimen containing parasites with pfmdr1 gene amplification was detected.ConclusionsThese results provide information on the likely high efficacy of artemisinin-based combinations commonly used in Chad, but suggest decreasing levels of sensitivity to lumefantrine and high levels of resistance to sulfadoxine-pyrimethamine used for seasonal malaria chemoprevention and intermittent preventive therapy in pregnancy. A majority of parasites had mutations in the pfk13 gene, none of which are known to be associated with artemisinin resistance. A therapeutic efficacy study needs to be conducted to confirm the efficacy of artemether-lumefantrine.

Epidemiological Risk Factors and Progression of Gastrointestinal Parasitic Infestation among Food Animals of Bangladesh: A Systematic Review and Meta-analysis

The gastrointestinal parasitic infestation seems to have a substantial economic impact on the entire livestock production industry. Because of the parasites' environmental appropriateness, numerous domestic animals in Bangladesh are particularly susceptible to the infestation; however, the extent to which people are aware of the potential risk factors is debatable. Therefore, the current meta-analysis' objective is to determine the precise understanding of potential risk variables and the impact of climatological variations on five important gastrointestinal parasites: Paramphistomum species, Strongyloides species, Trichuris species, Schistosoma species, and Moneizia species. Four globally recognized databases, including Web of Science, Scopus, PubMed, and Google Scholar were screened to choose the studies published in English language from 2000 to 2020. Finally, 29 studies were selected for further analysis and recorded the maximum prevalence in Paramphistomum species (26%; 95% CI: 19-33), followed by Strongyloides species (9%, 95% CI: 5-12), Trichuris species (10%, 95% CI: 4-17), Schistosoma species (19%, 95% CI: 7-31), and Moneizia species (8%, 95% CI: 5-10); besides the overall prevalence was noted as 15% (95% CI: 11-18). Furthermore, subgroup analysis revealed that parasite infestation was most prevalent in females (21%) and the elderly animal population (14%) and the summer season (26%). To sum up, the current meta-analysis visualized the epidemiological risk factors with the overall incidence of five major parasite infestations in livestock animals in Bangladesh; hence, the government and shareholders may employ it as proof before launching any control programs or improving farmers' awareness.

Intra-Specific Diversity of Leishmania major Isolates: A Key Determinant of Tunisian Zoonotic Cutaneous Leishmaniasis Clinical Polymorphism.

The clinical expression of zoonotic cutaneous leishmaniasis (ZCL) caused by Leishmania (L.) major parasites has a broad spectrum ranging from asymptomatic infection to self-limited cutaneous sores or severe disease. In concert with the host immune responses, the vector variability and the number of bites, genetic variation between L. major isolates might impact on the clinical output of the disease. We investigated herein the intra-specific variability of L. major field isolates independently of host or vector factors and then tried to correlate parasite variability to ZCL severity in corresponding patients. Several assays were applied, i.e., in vivo pathogenicity of promastigotes in a BALB/c mice model, resistance/sensibility to complement lysis, in vitro growth kinetics, and expression of different lectins on the promastigote surface. Combining all these parameters allowed us to conclude that the resistance to complement lysis and PNA/Jacalin lectins binding to parasite surfaces are important markers of parasite virulence. These factors correlate significantly with clinic polymorphism of ZCL and modestly with genetic micro-heterogeneity, a characteristic we previously revealed with a MLMT profile.

Comparative transcriptomic analysis of the malaria parasites Plasmodium falciparum and Plasmodium vivax sensitive and resistant strains

Introduction. Malaria is the sixth leading cause of death worldwide. According to a WHO survey (2019-2020), the total number of malaria deaths is estimated to be 409000. Plasmodium falciparum and Plasmodium vivax are major malaria parasites, particularly in subtropical areas.Materials and methods. In the present study, we used a transcriptome analysis of raw RNA sequence data to identify and characterize the differentially expressed genes in Plasmodium falciparum chloroquine-sensitive and chloroquine-resistant strains, as well as Plasmodium vivax primaquine sensitive and primaquine resistant strains. The raw RNA sequence data were obtained from the NCBI SRA database using the Accession IDs PRJNA308455, SRR14191963, and SRR332573.Results and discussion. The sequence of raw RNA was quantified, mapped, and annotated. The total number of reads mapped to the reference genome for Plasmodium falciparum was found to be 45474448 and for Plasmodium vivax was 38226870. The Cufflinks-Cuffdiff tool was used to identify differentially expressed genes in Plasmodium falciparum and Plasmodium vivax sensitive and resistant strains. This differentially expressed gene was further annotated and plotted using the "Limma" package of Bioconductor. The PPI network was constructed in String Database and Cytoscape software. Pathway enrichment analysis of list differentially expressed gene performed using KEGG and GO tool.Conclusion. In sensitive and resistant strains, comparative transcriptome analysis revealed differentially regulated gene expression patterns.

Synthesis, Characterization and Pharmacological Evaluation of Chalcones and Its Derivatives for Antileishmanial Activity

Medicinal chemistry is almost always geared toward drug discovery and development. The focus on development of new synthetic drug compounds has resulted in the incorporation of many other disciplines, such as biochemistry, combinatorial chemistry, chemical biology, phytochemistry, pharmacology, enzymology, pharmacognosy, statistics, physical chemistry and molecular biology into medicinal chemistry. In this view medicinal chemists are also trying to speed up drug discovery process for finding the lead molecule [1]. The compounds with chalcone as backbone have been reported to possess varied biological and pharmacological activities, including antimicrobial, anti-inflammatory, analgesic, cytotoxic, antitumor, antimalarial, antitubercular, antiviral, anti-HIV, antiulcerative, antileishmanial activities. Leishmaniasis is a vector-borne disease caused by protozoan parasites of the genus Leishmania. It is transmitted through the bite of female phlebotomine sandflies and can range from mild self-healing cutaneous lesions to lethal visceral leishmaniasis. Lic A (1), efficiently inhibited the proliferation of Leishmania donovani and Leishmania major promastigotes and amastigotes in vitro by inhibiting fumarate reductase (Chen et al. 1993), a selective target present in the parasite mitochondria. The Lic C (113) inhibited the growth of the L. major parasite to the same extent as Lic A (1) (Nielson et al. 1995).

Thiosugar naphthalene diimide conjugates: G-quadruplex ligands with antiparasitic and anticancer activity

Glycosyl conjugation to drugs is a strategy being used to take advantage of glucose transporters (GLUT) overexpression in cancer cells in comparison with non-cancerous cells. Its extension to the conjugation of drugs to thiosugars tries to exploit their higher biostability when compared to O-glycosides. Here, we have synthesized a series of thiosugar naphthalene diimide conjugates as G-quadruplex ligands and have explored modifications of the amino sidechain comparing dimethyl amino and morpholino groups. Then, we studied their antiproliferative activity in colon cancer cells, and their antiparasitic activity in T. brucei and L. major parasites, together with their ability to bind quadruplexes and their cellular uptake and location. We observed higher toxicity for the sugar-NDI-NMe2 derivatives than for the sugar-NDI-morph compounds, both in mammalian cells and in parasites. Our experiments indicate that a less efficient binding to quadruplexes and a worse cellular uptake of the carb-NDI-morph derivatives could be the reasons for these differences. We found small variations in cytotoxicity between O-carb-NDIs and S-carb-NDIs, except against non-cancerous human fibroblasts MRC-5, where thiosugar-NDIs tend to be less toxic. This leads to a notable selectivity for β-thiomaltosyl-NDI-NMe212 (9.8 fold), with an IC50 of 0.3 μM against HT-29 cells. Finally, the antiparasitic activity observed for the carb-NDI-NMe2 derivatives against T. brucei was in the nanomolar range with a good selectivity index in the range of 30- to 69- fold.

First Molecular Identification of Caligus clemensi on Cultured Crimson Snapper Lutjanus erythropterus on Jerejak Island, Penang, Peninsular Malaysia.

Fish parasites such as Caligus clemensi are a serious concern for cultured fish in many regions of the world, including Malaysia. This study was designed to elucidate the parasites’ prevalence and intensity coupled with the morphology and molecular identification of C. clemensi on cultured Lutjanus erythropterus in Jerejak Island, Penang, Peninsular Malaysia. The study was carried out on 200 fish specimens of cultured L. erythropterus obtained from the GST group aquaculture farm. Parasites were collected from the infested part of L. erythropterus fish, and their prevalence and intensity were determined. The parasites were identified morphologically using a field emission scanning electron microscope. Molecular studies were performed through PCR amplification and sequencing. MEGA 5 was used to construct a phylogenetic tree using the pairwise distance method. The results showed that only the C. clemensi parasite was found prevalent on L. erythropterus fish with a prevalence and mean intensity (S.D) of 198 (99%) and 36.4 ± 12.2, respectively. The prevalence varied significantly with respect to fish length (p < 0.05). The nucleotide BLAST sequence for 18S ribosomal RNA partial sequences showed 97% with 100% query similarity, E-value 0 with C. clemensi with the accession number DQ123833.1. Conclusively, C. clemensi remains a major parasite of L. erythropterus in the study area.

Effect of topical berberine in murine cutaneous leishmaniasis lesions.

ObjectivesMore effective topical treatments remain an unmet need for the localized forms of cutaneous leishmaniasis (CL). The aim of this study was to evaluate the efficacy and safety of a topical berberine cream in BALB/c mice infected with Leishmania major parasites.MethodsA cream containing 0.5% berberine-β-glycerophosphate salt and 2.5% menthol was prepared. Its physicochemical and stability properties were determined. The cream was evaluated for its capacity to reduce lesion size and parasitic load as well as to promote wound healing after twice-a-day administration for 35 days. Clinical biochemical profile was used for estimating off-target effects. In vitro time-to-kill curves in L. major-infected macrophages and skin and plasma pharmacokinetics were determined, aiming to establish pharmacokinetic/pharmacodynamic relationships.ResultsThe cream was stable at 40°C for 3 months and at 4°C for at least 8 months. It was able to halt lesion progression in all treated mice. At the end of treatment, parasite load in the skin was reduced by 99.9% (4 log) and genes involved in the wound healing process were up-regulated compared with untreated mice.The observed effects were higher than expected from in vitro time-to-kill kinetic and plasma berberine concentrations, which ranged between 0.07 and 0.22 μM.ConclusionsThe twice-a-day administration of a topical berberine cream was safe, able to stop parasite progression and improved the appearance of skin CL lesions. The relationship between drug plasma levels and in vivo effect was unclear.

Parasite species richness and host range are not spatially conserved

AbstractAimInteractor richness in host–parasite networks, corresponding to either parasite species richness for host species or host range for parasite species, can be a function of taxonomic or trait constraints. Species appearing in multiple networks can have similar interactor richness in each network owing to these taxonomic and trait constraints, resulting in a spatially conserved mean interactor richness and lower variation in interaction richness relative to a null expectation. Here, we used a global database of host–helminth interactions to examine the variability in interactor richness across a spatially explicit collection of 299 host–helminth networks.LocationGlobal.Time period1800–2003.Major taxa studiedHelminth parasite species and their host species.MethodsWe used randomization tests to examine spatial conservation of species interactions for both host and helminth species.ResultsWe failed to detect a signal of interactor richness conservation for &gt; 95% of host and helminth parasite species relative to a set of three null models, where both the mean number of interactions per species and the variation in the number of interactions per species did not differ from a random draw. Furthermore, we detected a significant taxonomic signal in divergence in parasite species richness from a null model for host species, indicating that slight departures from null expectations are related to host phylogenetic relationships.Main conclusionsOverall, this indicates that interactor richness can vary widely for the same species and that host and helminth parasite species can play very different functional roles in interaction networks across spatial or environmental gradients.

PARASITES OF AN ENDANGERED HARVEST MOUSE (REITHRODONTOMYS RAVIVENTRIS HALICOETES) IN A NORTHERN CALIFORNIA MARSH.

Disease may limit recovery of endangered species. We surveyed parasites in the federally endangered salt marsh harvest mouse (SMHM; Reithrodontomys raviventris halicoetes) and sympatric rodents in Suisun Marsh (Solano County, California, USA) from April 2018 through March 2019. We investigated individual SMHM risk factors (age, sex, reproductive status, and body condition) for infection and relationships among the estimated parasite prevalence and season and habitat management (natural tidal habitats versus diked, nontidal habitats). We captured 625 individual rodents, including 439 SMHM, and tested these for infection with Bartonella spp., Borrelia spp., Rickettsia spp., Francisella tularensis, Leptospira spp., Cryptosporidium spp., Giardia spp., and Toxoplasma gondii by PCR. Over one-third (34.6%, confidence interval [CI], 30.2-39.3%) of SMHM tested positive for at least one parasite. Four percent (CI, 2.8-6.3%) of SMHM were infected with F. tularensis holarctica, a virulent bacterium that causes mortality in rodents shortly after infection. Additionally, we detected three species of Bartonella (B. henselae, B. rochalimae, B. vinsonii arupensis), Leptospira borgpetersenii serovar Ballum, Cryptosporidium sp. (deer mouse [Peromyscus maniculatus] genotype), Cryptosporidium parvum, Giardia intestinalis, and an unidentified Borrelia sp. The only parasite that was associated with habitat management was Bartonella spp., which was more prevalent in diked than tidal areas. Male SMHM were more likely to be parasitized than females, and individuals in modestly poor body condition were most likely to be infected with Bartonella spp. The estimated sample prevalence of multiple parasites varied by season and by host species. This is the first major parasite assessment in a long-endangered species, and these results will assist managers to incorporate parasitic disease into recovery planning and provide a critical baseline for future investigations, including how climatically induced habitat and species composition changes could alter disease dynamics.

Plasmodium vivax in the Elimination Phase - China, 2013-2020.

What is already known about this topic?Plasmodium vivax (P. vivax) was the most widely distributed and major human malaria parasite in China, considered the last parasite to be eliminated. What is added by this report?The last domestic P. vivax case was reported in 2016, while hundreds of imported cases were reported annually from 2013–2020, predominantly from Southeast Asia. What are the implications for public health practice?In the post-elimination phase, adaptive and practical strategies focusing on imported P. vivax cases should be updated and adopted to prevent malaria resurgence.

Efficacy of two endectoparasiticide products combining fipronil and (S)-methoprene or esafoxolaner with eprinomectin and praziquantel against fleas and intestinal helminths in cats naturally infested in Brazil.

Eprinomectin and praziquantel, nematodicide and cestodicide compounds, are both combined with the insecticide and acaricide compounds fipronil and (S)-methoprene in Frontline® Protect/Broadline®, or esafoxolaner in NexGard® Combo. These topical feline endectoparasiticide products were tested for efficacy against fleas and intestinal helminths in a field trial in Brazil. Flea- and/or helminth-infested domestic cats were treated twice at a monthly interval following label instructions: 160 cats with Frontline® Protect/Broadline® and 165 cats with NexGard® Combo. The flea and intestinal helminth infestations were evaluated using comb counts and copromicroscopy, respectively before first treatment for baseline value, then 9 and 30 days after each treatment for fleas, and 9 days after each treatment for helminths. Multiparasitism was very frequent at baseline, as amongst the 325 included cats, 295, 280, 86 and 93 cats were at least infested with Ctenocephalides fleas, Ancylostoma, Toxocara and Dipylidium caninum, respectively. Efficacies were calculated by comparing the geometric means at baseline and at post-treatment timepoints for each parasite genus/species. Inclusive of both products and of all evaluation timepoints, the Ctenocephalides, Ancylostoma, Toxocara and D. caninum efficacies were at least 98.3%, 99.8%, 99.8% and 96.3%, respectively. No adverse reactions were observed, except for a few instances of mild, transient, and self-resolving hypersalivation occurring on the day of treatment in both groups. This field trial demonstrated high-level efficacy of Frontline® Protect/Broadline® and NexGard® Combo against major parasites of cats in Brazil.

In vitro and in vivo effects of natural honey on Leishmania major.

Leishmaniosis is an insect-borne disease whose clinical manifestations range from skin ulcer to visceral disease. Antimony compounds are currently known to be the main treatment for leishmaniosis, but there are limitations to their use. This study was performed to determine the in vitro and in vivo efficiency of honey on a standard strain of Leishmania major parasite in comparison with glucantime and amphotericin as the first line treatment. Leishmania major was exposed to different concentrations of honey extract at 400, 200, 100, 50, 25, 12.5, 6.25 μg/ml. The effectiveness of honey concentrations was determined by counting the parasite by Neubauer's chamber. Then, using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) colorimetric method, for promastigotes and macrophages then IC50 was calculated. A flow cytometry test was performed and necrosis and apoptosis diagrams were drawn. Next, the effect of the honey on the amastigotes inside macrophage cells was investigated. Finally, for the in vivo experimentation, the parasite was injected in the base of BALB/c mice tails and the resulting wounds were treated with honey. The results of all tests showed that the honey extract at 400 μg/ml concentration had the best effects on all stages. The honey has lethal effects on Leishmania parasite in vitro as well as therapeutic effects on wounds caused by the parasite. Further experiments are recommended to evaluate the performance of the extract on the parasite in volunteer human models.

Scanning electron microscopy of Quilonia renniei from Asian elephants revealing variation in coronal leaflet number.

Although parasitic nematodes in the genera Murshidia and Quilonia (family Strongylidae) are recognized as major gastrointestinal parasites in Asian elephants, they have been poorly studied. Recently, light micrographs of these parasites in Myanmar have been presented, almost 100 years after the original drawings. However, the number of coronal leaflets, a key taxonomic feature of Quilonia species, has not been precisely determined based on light microscopy. The current study aimed to determine the exact number of coronal leaflets in Quilonia renniei specimens from Asian elephants in Myanmar. On the basis of scanning electron micrographs, leaflet number in females (19–20, average 19.7, n = 9) was significantly higher (P < 0.005) than that in males (16–19, average 18.1, n = 8). This compares with 18 coronal leaflets indicated in the original species description. Specimens bearing 19 coronal leaflets were most numerous, followed by those with 20 leaflets. Median-joining network analysis of mitochondrial cytochrome c oxidase subunit I gene sequences with 16 haplotypes from 19 individuals revealed no clear association between parasite populations and the number of coronal leaflets. These results highlight the importance of determining the number of coronal leaflets in the taxonomy of Q. renniei and other related Quilonia species infecting Asian elephants.

Helminth Infections in Cattle and Goats in Kanchanaburi, Thailand, with Focus on Strongyle Nematode Infections.

Gastrointestinal helminths are major enteric parasites affecting the health of important livestock ruminants, such as cattle and goats. It is important to routinely survey these animals for helminth infections to allow effective management and control programs to be implemented. A cross-sectional helminth survey carried out in Kanchanaburi Province, Thailand, revealed the infection rate of gastrointestinal helminths in cattle (n = 157) and goats (n = 117) to be 35.7% and 88%, respectively, by microscopic fecal examination, and a 100% herd prevalence was observed in goats. Eggs of strongyle nematodes, Strongyloides spp., Trichuris spp., Capillaria spp., Paramphistomum spp., and Moniezia spp. were detected, with a relatively high rate of strongyle nematode infection in both cattle (28.7%) and goats (86.3%). Mixed infections were observed in 14.3% and 35.9% of egg-positive samples from cattle and goats, respectively. Risk factor analysis showed that dairy cattle were 5.1 times more likely to be infected with strongyles than meat cattle. In contrast, meat goats were 9.3 times more likely to be infected with strongyles than dairy goats. The inverse findings in cattle and goats are discussed. Female gender was associated with a higher risk of strongyle infection in goats. DNA sequencing and in-house semi-nested PCR with primers specific to a region in the internal transcribed spacer 2 (ITS2) were successfully used to identify strongyle genera in randomly selected egg-positive cattle (n = 24) and goat (n = 24) samples. Four strongyle genera, i.e., Cooperia spp., Haemonchus spp., Oesophagostomum spp., and Trichostrongylus spp. were identified by DNA sequencing. By semi-nested PCR, Cooperia spp. were detected as a major parasite of cattle (70.8%), whereas Haemonchus spp. were abundant in goats (100%). The majority of samples from cattle (58.3%) and goats (95.8%) were found to coinfect with at least two strongyle genera, suggesting that coinfection with multiple strongyle genera was more common than single infection in these animals.

CPD article: Felid lungworms: from complete strangers to major parasites

The parasitic nematodes Aelurostrongylus abstrusus, Troglostrongylus brevior and Capillaria aerophila affect the respiratory system of cats and are a primary cause of respiratory disease in cats in many countries. While they have been underestimated for a long time, in recent years academics and veterinarians have become more aware of their importance, and now felid lungworms are recognised as primary agents of respiratory disease. Therefore, timely diagnosis and treatment, and efficacious prevention methods are a priority in feline clinical practice. Recent data have unveiled many features of diseases caused by these nematodes, and this article reviews and discusses practical and clinical knowledge, as well as recent updates on clinical management of aelurostrongylosis, troglostrongylosis and capillariosis in cats.

Evaluation of Antileishmania Effect of Methanolic Extract of Dandelion Root (Taraxacum Officinale) on Leishmanaia Major Promastigotes in Vitro Techniques

Background and Objectives: Cutaneous leishmaniasis is one of the common diseases between humans and animals that is considered a health problem in Iran and many countries around the world. Currently, glucantime is used to treat cutaneous leishmaniasis. Due to its high side effects and resistance, the use of alternative therapies, especially plants and natural compounds, has been highly recommended by researchers. The aim of this study is to investigate the effect of the methanolic extract of dandelion root (Taraxacum officinale) on Leishmania major in vitro techniques. Methods: In this experimental study, the extract was prepared by the Soxhlet method and to evaluate the effect of methanolic extract of dandelion root on L. major parasite at concentrations of 300-1200 mg/ml. Amphotericin B and distilled water were considered as positive and negative controls, respectively. Then, 106 live parasites were added to all tubes, and all groups were kept at 25 ±1 °C. At 24, 48, and 72 hours, the number of live parasites was counted by Trypan Blue using a neobar slide and light microscope (Hemocytometer method). Then Half-maximal inhibitory concentration (IC50) value for the above extract was calculated using SigmaPlot™ 13 software. All steps of the experiment were done in triplicate and the results were considered as average. Results: The IC50 content of methanolic extract of dandelion roots after 24, 48, and 72 hours on L. major were calculated to be 1.04, 0.9, and 0.68 µg/ml. The highest growth inhibition (100%) was observed at a concentration of 1200 μg/ml after 72 hours of exposure. There was a significant difference between the IC50 extract and amphotericin B drug after 24, 48 and 72 hours (P&lt;0.05). Conclusion: Methanolic extract of dandelion root in different concentrations has an inhibitory effect on the growth of L. major and it is suggested that more and more complete studies be performed on the components of this plant and the lethal effect of the parasite in vivo.

Repurposing the Trypanosomatidic GSK Kinetobox for the Inhibition of Parasitic Pteridine and Dihydrofolate Reductases.

Three open-source anti-kinetoplastid chemical boxes derived from a whole-cell phenotypic screening by GlaxoSmithKline (Tres Cantos Anti-Kinetoplastid Screening, TCAKS) were exploited for the discovery of a novel core structure inspiring new treatments of parasitic diseases targeting the trypansosmatidic pteridine reductase 1 (PTR1) and dihydrofolate reductase (DHFR) enzymes. In total, 592 compounds were tested through medium-throughput screening assays. A subset of 14 compounds successfully inhibited the enzyme activity in the low micromolar range of at least one of the enzymes from both Trypanosoma brucei and Lesihmania major parasites (pan-inhibitors), or from both PTR1 and DHFR-TS of the same parasite (dual inhibitors). Molecular docking studies of the protein–ligand interaction focused on new scaffolds not reproducing the well-known antifolate core clearly explaining the experimental data. TCMDC-143249, classified as a benzenesulfonamide derivative by the QikProp descriptor tool, showed selective inhibition of PTR1 and growth inhibition of the kinetoplastid parasites in the 5 μM range. In our work, we enlarged the biological profile of the GSK Kinetobox and identified new core structures inhibiting selectively PTR1, effective against the kinetoplastid infectious protozoans. In perspective, we foresee the development of selective PTR1 and DHFR inhibitors for studies of drug combinations.

Soil-transmitted helminths, intestinal protozoa and Clonorchis sinensis infections in southeast China

BackgroundExtensive parasitic diseases epidemiology in Zhejiang province has not been carried out since the second national survey in 2004. Therefore, dynamics in prevalence and infection pattern of the major intestinal parasites should be explored.MethodsThe distribution of three parasites including soil-transmitted helminths (STH), intestinal protozoa and C. sinensis in Zhejiang from 2014 to 2015 were explored. Kato-Katz technique was used for STH and C. sinensis detection, whereas transparent adhesive paper anal swab was used for pinworm detection, and iodine smear was used for protozoa detection. A questionnaire survey on alimentary habits and sanitary behaviors was conducted in half of the studied counties.ResultsThis study recruited 23,552 participants: 19,935 from rural and 3617 from urban area. Overall prevalence of intestinal helminth infections was 1.80%. In this study, seven helminth species were identified including A. duodenale, N. americanus, Trichuris trichiura, Ascaris lumbricoides, C. sinensis, Fasciolopsis buski and pinworm. The average prevalence of STH infection was 1.71%: 1.94% in rural and 0.44% in urban area. Hookworm was the most prevalent infection at 1.58%: 1.79% in rural and 0.44% in urban area. Prevalence varied considerably in the studied counties. Prevalence was highest in Yongkang county at 10.25%. Only 2.79% of children from rural area were infected with pinworm. A proportion of 0.40% of rural participants were infected with protozoa, whereas Endolimax nana was the most prevalent at 0.23%. C. sinensis showed infection only in one man. Awareness on C. sinensis was 24.47% in rural and 45.96% in urban area, respectively.ConclusionsPrevalence of STH and protozoa infections declined considerably whereas C. sinensis infections remained few in Zhejiang province compared with the prevalence reported in previous large scale surveys (19.56% for national STH infection in 2004, 18.66% and 4.57% for provincial STH and protozoa infection, respectively in 1999). The findings of this study showed that hookworm, mainly N. americanus remained a parasitic threat to population health, mainly in the central and western Zhejiang. Therefore, more health education regarding fertilization and farming habits is necessary in rural areas. The awareness concerning hookworm infection should be reinforced.