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Trichomonas vaginalis is the most common non-viral sexually transmitted infection. 5-Nitroimidazoles [metronidazole (MTZ) and tinidazole (TDZ)] are FDA-approved treatments. To better understand treatment failure, we conducted a systematic review on mechanisms of 5-nitroimidazole resistance.
PubMed, ScienceDirect and EMBASE databases were searched using keywords Trichomonas vaginalis, trichomoniasis, 5-nitroimidazole, metronidazole, tinidazole and drug resistance. Non-English language articles and articles on other treatments were excluded.
The search yielded 606 articles, of which 550 were excluded, leaving 58 articles. Trichomonas vaginalis resistance varies and is higher with MTZ (2.2–9.6%) than TDZ (0–2%). Resistance can be aerobic or anaerobic and is relative rather than absolute. Differential expression of enzymes involved in trichomonad energy production and antioxidant defenses affects 5-nitroimidazole drug activation; reduced expression of pyruvate:ferredoxin oxidoreductase, ferredoxin, nitroreductase, hydrogenase, thioredoxin reductase and flavin reductase are implicated in drug resistance. Trichomonas vaginalis infection with Mycoplasma hominis or T. vaginalis virus has also been associated with resistance. Trichomonas vaginalis has two genotypes, with greater resistance seen in type 2 (vs type 1) populations.
5-Nitroimidazole resistance results from differential expression of enzymes involved in energy production or antioxidant defenses, along with genetic mutations in the T. vaginalis genome. Alternative treatments outside of the 5-nitroimidazole class are needed.
This systematic review investigated the evidence for the therapeutic potential of essential oils (EOs) against Leishmania amazonensis. We searched available scientific publications from 2005 to 2019 in the PubMed and Web of Science electronic databases, according to PRISMA statement. The search strategy utilized descriptors and free terms. The EOs effect of 35 species of plants identified in this systematic review study, 45.7% had half of the maximal inhibitory concentration (IC50) 10 < IC50 ⩽ 50 μg mL−1 and 14.3% had a 10 < IC50μg mL−1 for promastigote forms of L. amazonensis. EOs from Cymbopogon citratus species had the lowest IC50 (1.7 μg mL−1). Among the plant species analyzed for activity against intracellular amastigote forms of L. amazonensis, 39.4% had an IC50 10 < IC50 ⩽ 50 μg mL−1, and 33.3% had an IC50 10 < IC50μg mL−1. Aloysia gratissima EO showed the lowest IC50 (0.16 μg mL−1) for intracellular amastigotes. EOs of Chenopodium ambrosioides, Copaifera martii and Carapa guianensis, administered by the oral route, were effective in reducing parasitic load and lesion volume in L. amazonensis-infected BALB/c mice. EOs of Bixa orellana and C. ambrosioides were effective when administered intraperitoneally. Most of the studies analyzed in vitro and in vivo for the risk of bias showed moderate methodological quality. These results indicate a stimulus for the development of new phytotherapy drugs for leishmaniasis treatment.
Echinococcus multilocularis causes alveolar echinococcosis which is a chronic, progressive zoonotic disease that mainly affects the liver. Hepatic alveolar echinococcosis is insidious and the patients are asymptomatic most of the time. Generally, it is incidentally found on imaging studies performed for other reasons. Specific symptoms may evolve if the vascular and biliary structures of the liver are affected. Hepatic alveolar echinococcosis shows a similar pattern to malignancies in terms of radiologic and clinical features. For this reason, oncological surgical principles should be applied during the resection of hepatic alveolar echinococcosis. The gold standard surgical treatment is resection with negative surgical margin. However, in patients whose radical resection is not possible other therapeutic options include palliative resection which has no benefit to the patient, and other curative major surgical options such as ex vivo liver resection, and autotransplantation and ultimately liver transplantation. The remnant liver volume has paramount importance if resection is going to be performed. For this reason, occasionally, remnant liver volume hypertrophy is induced by employing either two-stage hepatectomy or associating liver partition and portal vein ligation for staged hepatectomy.
Equine piroplasmosis (EP) is a tick-borne disease of economic importance, relevant in the international movement of equids. The causative agents are at least two apicomplexan protozoan parasites Babesia caballi and Theileria equi. To date, there is no study that estimates global and regional exposure of equids to EP. We therefore conducted a systematic review and meta-analysis to estimate the pooled prevalence and heterogeneity of EP using random-effects model. Six electronic databases were searched for publications on EP and assessed according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A total of 66 eligible studies published between 1990 and 2019 and representing 24 041 equids were included. The overall pooled prevalence estimates (PPEs) of B. caballi was 22.3% (95% CI 21.7–22.8), while the overall PPE for T. equi was 29.4% (95% CI 28.7–30.0). The overall pooled prevalence due to co-infection with both parasites was 11.8% (95% CI 11.32–12.32). Also, subgroup analysis according to sex, age, diagnostic technique, equid species, region and publication years showed a substantial degree of heterogeneity across studies computed for both B. caballi and T. equi infections in equids. Awareness of the current status of EP globally will alert the relevant authorities and stakeholders where necessary on the need for better preventive and control strategies against the disease.
In this study, we evaluated the efficacy, expressed as a mean weight decrease of the whole echinococcal cyst mass, of novel benzimidazole salt formulations in a murine Echinococcus granulosus infection model. BALB/c mice were intraperitoneally infected with protoscoleces of E. granulosus (genotype G1). At 9 months post-infection, treatment with albendazole (ABZ), ricobendazole (RBZ) salt formulations, and RBZ enantiomer salts (R)-(+)-RBZ-Na and (S)-(−)-RBZ-Na formulations were initiated. Drugs were orally applied by gavage at 10 mg kg−1 body weight per day during 30 days. Experimental treatments with benzimidazole sodium salts resulted in a significant reduction of the weight of cysts compared to conventional ABZ treatment, except for the (S)-(−)-RBZ-Na enantiomer formulation. Scanning electron microscopy and histological inspection revealed that treatments impacted not only the structural integrity of the parasite tissue in the germinal layer, but also induced alterations in the laminated layer. Overall, these results demonstrate the improved efficacy of benzimidazole salt formulations compared to conventional ABZ treatment in experimental murine cystic echinococcosis.
Toxoplasma gondii rhoptry protein TgROP18 is a polymorphic virulence effector that targets immunity-related GTPases (IRGs) in rodents. Given that IRGs are uniquely diversified in rodents and not in other T. gondii intermediate hosts, the role of TgROP18 in manipulating non-rodent cells is unclear. Here we show that in human cells TgROP18I interacts with the interferon-gamma-inducible protein N-myc and STAT interactor (NMI) and that this is a property that is unique to the type I TgROP18 allele. Specifically, when expressed ectopically in mammalian cells only TgROP18I co-immunoprecipitates with NMI in IFN-γ-treated cells, while TgROP18II does not. In parasites expressing TgROP18I or TgROP18II, NMI only co-immunoprecipitates with TgROP18I and this is associated with allele-specific immunolocalization of NMI on the parasitophorous vacuolar membrane (PVM). We also found that TgROP18I reduces NMI association with IFN-γ-activated sequences (GAS) in the IRF1 gene promoter. Finally, we determined that polymorphisms in the C-terminal kinase domain of TgROP18I are required for allele-specific effects on NMI. Together, these data further define new host pathway targeted by TgROP18I and provide the first function driven by allelic differences in the highly polymorphic ROP18 locus.
The aim of this study is to determine the species of parasite that infected the population of Brussels during the Medieval and Renaissance periods, and determine if there was notable variation between different households within the city. We compared multiple sediment layers from cesspits beneath three different latrines dating from the 14th–17th centuries. Helminths and protozoa were detected using microscopy and enzyme-linked immunosorbent assay (ELISA). We identified Ascaris sp., Capillaria sp., Dicrocoelium dendriticum, Entamoeba histolytica, Fasciola hepatica, Giardia duodenalis, Taenia sp. and Trichuris sp. in Medieval samples, and continuing presence of Ascaris sp., D. dendriticum, F. hepatica, G. duodenalis and Trichuris sp. into the Renaissance. While some variation existed between households, there was a broadly consistent pattern with the domination of species spread by fecal contamination of food and drink (whipworm, roundworm and protozoa that cause dysentery). These data allow us to explore diet and hygiene, together with routes for the spread of fecal–oral parasites. Key factors explaining our findings are manuring practices with human excrement in market gardens, and flooding of the polluted River Senne during the 14th–17th centuries.
Despite the great interest to quantify the structure of host–parasite interaction networks, the real influence of some factors such as taxonomy, host body size and ecological opportunity remains poorly understood. In this paper, we investigate the general patterns of organization and structure of interactions in two anuran–parasite networks in the Brazilian Pantanal (seasonally flooded environment) and Atlantic Forest (non-flooded forest). We present theoretical models to test whether the structures of these host–parasite interaction networks are influenced by neutrality, host taxonomy and host body size. Subsequently, we calculated metrics of connectance, nestedness and modularity to characterize the network structure. We demonstrated the structure networks were influenced mainly by body size and taxonomy of the host. Moreover, our results showed that the seasonally flooded environment present networks with higher connectance/nestedness and lower modularity compared to the other environment. The results also suggest that seasonal floods may promote ecological opportunities for new species associations.
In this study, a microsporidian pathogen of the date moth (Apomyelois (Ectomyelois) ceratoniae, Zeller, 1839) also known as the carob moth, is described based on light microscopy, ultrastructural characteristics and comparative molecular analysis. The pathogen infects the gut and hemolymph of A. ceratoniae. All development stages are in direct contact with the host cell cytoplasm. Fresh spores with nuclei arranged in a diplokaryon are oval and measured 3.29 ± 0.23 μm (4.18–3.03 μm, n = 200) in length and 1.91 ± 0.23 μm (2.98–1.66 μm, n = 200) in width. Spores stained with Giemsa's stain measured 3.11 ± 0.31 μm (3.72–2.41 μm, n = 150) in length and 1.76 ± 0.23 μm (2.16–1.25 μm, n = 150) in width. Spores have an isofilar polar filament with 10-12 coils. An 1110 bp long alignment of the current microsporidium showed an SSU rRNA gene difference of only 0.0009, corresponding to >99.91% sequence similarity with Nosema fumiferanae, while RPB1 gene sequences were 98.03% similar within an alignment of 969 bp. All morphological, ultrastructural and molecular features indicate that the microsporidian pathogen of A. ceratoniae is the new isolate of the N. fumiferanae and is named here as Nosema fumiferanae TY61.
Mature worms of Stephanoprora amurensis sp. nov. were obtained in an experimental study of its life cycle. In the Russian southern Far East, this trematode circulates using freshwater snails Parajuga subtegulata, freshwater fish and birds as the first, second intermediate and final hosts, respectively. Stephanoprora amurensis sp. nov. differs from the well-known representatives of Stephanoprora in a number of morphometric indicators of the developmental stages. The validity of the species was also confirmed by nuclear and mitochondrial DNA markers. In addition, new genetic data were obtained for Echinochasmus suifunensis and Echinochasmus milvi. An analysis of phylogenetic relationships within Echinochasmidae based on the 28S rRNA gene and ITS2 region identified two clusters, one of which combines species of Echinochasmus with 20–22 collar spines and short-tailed cercariae, and the other which includes Stephanoprora spp. and a number of representatives of Echinochasmus with 24 collar spines and long-tailed cercariae. The results of phylogenetic analysis based on ITS2 data show interfamily level of differences between the two clusters and intergeneric differentiation between the three subclusters uniting the species of Stephanoprora and Echinochasmus.
The gastrointestinal nematode Heligmosomoides polygyrus bakeri shows enhanced survival in mice with colitis. As the antibody response plays an important role in antiparasitic immunity, antibodies against male and female L4 H. polygyrus were examined in mice with and without colitis. Levels of specific antibodies in the mucosa and serum were determined by enzyme-linked immunosorbent assay and immunogenic proteins of male and female parasites were identified using 2D electrophoresis and mass spectrometry. The function of identified proteins was explored with Blast2Go. Nematodes in mice with colitis induced higher levels of specific immunoglobulin G (IgG1) and IgA, a lower level of IgE in the small intestine and a higher level of IgE in serum against female L4. Infected mice with colitis recognized 12 proteins in male L4 and 10 in female L4. Most of the recognized proteins from male L4 were intermediate filament proteins, whereas the proteins from female L4 were primarily actins and galectins. Nematodes from mice with colitis were immunogenically different from nematodes from control mice. This phenomenon gives new insights into helminth therapy as well as host–parasite interactions.
Praziquantel (PZQ) is the drug of choice for schistosomiasis. The potential drug resistance necessitates the search for adjunct or alternative therapies to PZQ. Previous functional genomics has shown that RNAi inhibition of Ca2+/calmodulin-dependent protein kinase II (CaMKII) gene in Schistosoma adult worms significantly improved the effectiveness of PZQ. Here we tested the in vitro efficacy of 15 selective and non-selective CaMK inhibitors against Schistosoma mansoni and showed that PZQ efficacy was improved against refractory juvenile parasites when combined with these CaMK inhibitors. By measuring CaMK activity and the mobility of adult S. mansoni, we identified two non-selective CaMK inhibitors, Staurosporine (STSP) and 1Naphthyl PP1 (1NAPP1), as promising candidates for further study. The impact of STSP and 1NAPP1 was investigated in mice infected with S. mansoni in the presence or absence of a sub-lethal dose of PZQ against 2- and 7-day-old schistosomula and adults. Treatment with STSP/PZQ induced a significant (47–68%) liver egg burden reduction compared with mice treated with PZQ alone. The findings indicate that the combination of STSP and PZQ dosages significantly improved anti-schistosomal activity compared to PZQ alone, demonstrating the potential of selective and non-selective CaMK/kinase inhibitors as a combination therapy with PZQ in treating schistosomiasis.
Acanthocephalans are obligate parasites of vertebrates, mostly of fish. There is limited knowledge about the diversity of fish-parasitizing Acanthocephala in Austria. Seven determined species and an undetermined species are recorded for Austrian waters. Morphological identification of acanthocephalans remains challenging due to their sparse morphological characters and their high intraspecific variations. DNA barcoding is an effective tool for taxonomic assignment at the species level. In this study, we provide new DNA barcoding data for three genera of Acanthocephala (Pomphorhynchus Monticelli, 1905, Echinorhynchus Zoega in Müller, 1776 and Acanthocephalus Koelreuter, 1771) obtained from different fish species in Austria and provide an important contribution to acanthocephalan taxonomy and distribution in Austrian fish. Nevertheless, the taxonomic assignment of one species must remain open. We found indications for cryptic species within Echinorhynchus cinctulus Porta, 1905. Our study underlines the difficulties in processing reliable DNA barcodes and highlights the importance of the establishment of such DNA barcodes to overcome these. To achieve this goal, it is necessary to collect and compare material across Europe allowing a comprehensive revision of the phylum in Europe.
Parabronema skrjabini is one of the most harmful nematodes to camels and is responsible for economic losses in animal husbandry industry. There is an urgent need for in-depth studies of potential vectors of the nematode due to its scant regarding information. As previous studies indicated that flies may be the vectors of P. skrjabini, we captured flies in the main camel-producing areas of Inner Mongolia. After autopsy of the specimens of two species of horn flies, we observed the morphology of the suspected nematode larvae found in them. Internal transcribed spacer ribosomal-DNA gene sequences were considered the best candidate to confirm the species of the larvae found. Our results showed that the homology compared with P. skrjabini was 99.5% in GenBank. Subsequently, we preliminarily identified two species of horn flies through morphological observation and then sequenced the mitochondrial-DNA-gene cytochrome oxidase subunit I obtained from two species of horn flies, with 100 and 99.2% similarity to sequences deposited in GenBank, respectively. Thus, we identified Haematobia titillans and Haematobia irritans and provided evidence for their potential role as vectors of parabronemosis. Our study provides reference for future research on the life history of the nematode and the vectors of parabronemosis.
The study of priority effects with respect to coinfections is still in its infancy. Moreover, existing coinfection studies typically focus on infection outcomes associated with exposure to distinct sets of parasite species, despite that functionally and morphologically similar parasite species commonly coexist in nature. Therefore, it is important to understand how interactions between similar parasites influence infection outcomes. Surveys at seven ponds in northwest Pennsylvania found that multiple species of echinostomes commonly co-occur. Using a larval anuran host (Rana pipiens) and the two most commonly identified echinostome species from our field surveys (Echinostoma trivolvis and Echinoparyphium lineage 3), we examined how species composition and timing of exposure affect patterns of infection. When tadpoles were exposed to both parasites simultaneously, infection loads were higher than when exposed to Echinoparyphium alone but similar to being exposed to Echinostoma alone. When tadpoles were sequentially exposed to the parasite species, tadpoles first exposed to Echinoparyphium had 23% lower infection loads than tadpoles first exposed to Echinostoma. These findings demonstrate that exposure timing and order, even with similar parasites, can influence coinfection outcomes, and emphasize the importance of using molecular methods to identify parasites for ecological studies.
Monocytes and macrophages are involved in a wide range of biological processes and parasitic diseases. The characterization of the molecular mechanisms governing such processes usually requires precise control of the expression of genes of interest. We implemented a tetracycline-controlled gene expression system in the U937 cell line, one of the most used in vitro models for the research of human monocytes and macrophages. Here we characterized U937-derived cell lines in terms of phenotypic (morphology and marker expression) and functional (capacity for phagocytosis and for Leishmania parasite hosting) changes induced by phorbol-12-myristate-13-acetate (PMA). Finally, we provide evidence of tetracycline-inducible and reversible Lamin-A gene silencing of the PMA-differentiated U937-derived cells.
Parasites sometimes expand their host range and cause new disease aetiologies. Genetic changes can then occur due to host-specific adaptive alterations, particularly when parasites cross between evolutionarily distant hosts. Characterizing genetic variation in Cryptosporidium from humans and other animals may have important implications for understanding disease dynamics and transmission. We analyse sequences from four loci (gp60, HSP-70, COWP and actin) representing multiple Cryptosporidium species reported in humans. We predicted low genetic diversity in species that present unusual human infections due to founder events and bottlenecks. High genetic diversity was observed in isolates from humans of Cryptosporidium meleagridis, Cryptosporidium cuniculus, Cryptosporidium hominis and Cryptosporidium parvum. A deviation of expected values of neutrality using Tajima's D was observed in C. cuniculus and C. meleagridis. The high genetic diversity in C. meleagridis and C. cuniculus did not match our expectations but deviations from neutrality indicate a recent decrease in genetic variability through a population bottleneck after an expansion event. Cryptosporidium hominis was also found with a significant Tajima's D positive value likely caused by recent population expansion of unusual genotypes in humans. These insights indicate that changes in genetic diversity can help us to understand host-parasite adaptation and evolution.
Contracaecum sp. nematodes are important parasites of fish eating birds that can cause animal health problems. In the present study, specimens of Contracaecum rudolphii sensu lato, from the great cormorant Phalacrocorax carbo sinensis from Sardinia, were characterized based on morphological and molecular data. The morphological analysis allowed to identify all the fourth stage larvae (n = 1918) as Contracaecum sp., and adults, male (n = 5845) and female (n = 8312), as C. rudolphii sensu lato. Population genetics and phylogenetic relationships were inferred based on mitochondrial and nuclear markers. Multiple sequence alignment of the ribosomal internal transcribed spacer showed the coexistence of C. rudolphii A (n = 157), C. rudolphii B (n = 22) and a rare heterozygote of these species. Moreover, mitochondrial markers, namely NADH dehydrogenase subunits I (nad1), cytochrome c oxidase subunit (cox1 and cox2) and small subunit of rRNA (rrnS), showed that the studied C. rudolphii A populations had undergone bottleneck, or founder effect event, subsequent to a rapid population growth and expansion. The observed heterozygote is with a mitochondrial pattern of C. rudolphii B. Although, both Contracaecum species showed high genetic diversity, no genetic structure between localities was detected. Phylogenetic reconstructions supported the paraphyly of the avian Contracaecum species including C. ogmorhini (parasite of otariids).
Chagas disease (CD) is a neglected disease and endemic in Brazil. In the Brazilian Northeast Region, it affects millions of people. Therefore, it is necessary to identify the spatiotemporal trends of CD mortality in the Northeast of Brazil. This ecological study was designed, in which the unit of analysis was the municipality of the Brazilian northeast. The data source was the Information System of Mortality. It was calculated relative risk from socioeconomic characteristics. Mortality rates were smoothed by the Local Empirical Bayes method. Spatial dependency was analysed by the Global and Local Moran Index. Scan spatial statistics were also used. A total of 11 287 deaths by CD were notified in the study. An expressive parcel of this number was observed among 70-year-olds or more (n = 4381; 38.8%), no schooling (n = 4381; 38.8%), mixed-race (n = 4381; 62.3%), male (n = 6875; 60.9%). It was observed positive spatial autocorrelation, mostly in municipalities of the state of Bahia, Piauí (with high-high clusters), and Maranhão (with low-low clusters). The spatial scan statistics has presented a risk of mortality in 24 purely spatial clusters (P < 0.05). The study has identified the spatial pattern of CD mortality mostly in Bahia and Piauí, highlighting priority areas in planning and control strategies of the health services.