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1.
BMC Vet Res ; 20(1): 240, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831389

RESUMO

BACKGROUND: Trichuris spp. (whipworms) are soil-transmitted helminths distributed worldwide, parasitizing several mammalian hosts such as ruminants, primates, and rodents. Trichuris spp. is one of the most common intestinal parasites affecting both humans and animals, and it can spread directly through the fecal-oral route, resulting in severe illness and financial loss. So, this work aims to detect the frequency of Trichuris spp. in camels in Beheira Governorate, Egypt, and to identify Trichuris spp. through morphometrical studies, molecular analysis, and phylogenetic analysis. RESULTS: A total of 35 dromedaries out of 127 investigated had Trichuris spp. infection, meaning that the overall prevalence was 27.56%. The age of the camel affected the infection rate, older animals (> 5 years) having a higher prevalence of infection (24%) than animals of ages (< 3 years) (20%) than animals of ages (3-5 years) (19.14%). According to season: Trichuris spp. showed a unique pattern in camels in different seasons: summer (31.25%) > autumn (28.13%) > spring (25.8%) > winter (25%) indicating year-round infection. T. globulosa was identified morphometrically from camels in Beheira Governorate, Egypt. The BLAST analysis revealed the presence of T. globulosa isolate from camels using the Genbank database depending on nuclear small subunit ribosomal RNA (18s) and cytochrome b (Cytb) genes. CONCLUSION: A high prevalence of T. globulosa was found in camels in Beheira Governorate, Egypt. This is the first report to confirm the identification of T. globulosa from camel based on morphometrical studies and molecular and phylogenetic analysis in Egypt. More thorough studies on the incidence, molecular, and genetic analysis of Trichuris spp. in Egypt are required in addition to camel control programs.


Assuntos
Camelus , Filogenia , Tricuríase , Trichuris , Animais , Camelus/parasitologia , Egito/epidemiologia , Tricuríase/veterinária , Tricuríase/epidemiologia , Tricuríase/parasitologia , Trichuris/genética , Trichuris/isolamento & purificação , Trichuris/classificação , Prevalência , Masculino , Feminino , Estações do Ano
2.
J Investig Med High Impact Case Rep ; 12: 23247096231224328, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38193443

RESUMO

Trichuriasis is a neglected tropical disease caused by Trichuris trichiura that spreads through the ingestion of embryonated eggs in contaminated soil, water, or food. In nonendemic areas, T trichiura infestation is very rare and sporadic and is often diagnosed in immigrants from endemic countries such as the Philippines. Whipworms feed on human blood and also erode the colonic mucosa, thereby evoking an inflammatory response. In milder forms, trichuriasis can be asymptomatic and often an incidental diagnosis on screening colonoscopy. Heavily infested patients usually present with abdominal pain, nausea, vomiting, tenesmus, chronic diarrhea, iron deficiency anemia, or stunted growth. T trichiura worms can be removed with biopsy forceps during a colonoscopy; however, most patients require a course of albendazole, mebendazole, or ivermectin. We describe a unique case of T trichiura as an incidental finding during a screening colonoscopy. The whipworms were retrieved using biopsy forceps and the patient was treated with albendazole. At the time of the colonoscopy, the patient did not exhibit any specific symptoms related to the worm infestation.


Assuntos
Tricuríase , Trichuris , Humanos , Animais , Tricuríase/diagnóstico , Tricuríase/tratamento farmacológico , Albendazol/uso terapêutico , Achados Incidentais , Colonoscopia
3.
Adv Parasitol ; 121: 1-63, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37474238

RESUMO

The mouse whipworm, Trichuris muris, has been used for over 60 years as a tractable model for human trichuriasis, caused by the related whipworm species, T. trichiura. The history of T. muris research, from the discovery of the parasite in 1761 to understanding the lifecycle and outcome of infection with different doses (high versus low dose infection), as well as the immune mechanisms associated with parasite expulsion and chronic infection have been detailed in an earlier review published in 2013. Here, we review recent advances in our understanding of whipworm biology, host-parasite interactions and basic immunology brought about using the T. muris mouse model, focussing on developments from the last decade. In addition to the traditional high/low dose infection models that have formed the mainstay of T. muris research to date, novel models involving trickle (repeated low dose) infection in laboratory mice or infection in wild or semi-wild mice have led to important insights into how immunity develops in situ in a multivariate environment, while the use of novel techniques such as the development of caecal organoids (enabling the study of larval development ex vivo) promise to deliver important insights into host-parasite interactions. In addition, the genome and transcriptome analyses of T. muris and T. trichiura have proven to be invaluable tools, particularly in the context of vaccine development and identification of secreted products including proteins, extracellular vesicles and micro-RNAs, shedding further light on how these parasites communicate with their host and modulate the immune response to promote their own survival.


Assuntos
Tricuríase , Trichuris , Camundongos , Humanos , Animais , Trichuris/genética , Estágios do Ciclo de Vida , Interações Hospedeiro-Parasita
5.
Clin Case Rep ; 11(4): e7250, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37102100

RESUMO

Trichuris trichiura parasitizes only humans through fecal-oral transmission. In non-endemic areas, the frequency of endoscopic identification has been increasing due to the increasing number of immigrants from endemic countries. To prevent infection, it is important to pay attention to sanitary conditions such as soil and water sources.

6.
J Infect Dis ; 227(12): 1428-1432, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-36932044

RESUMO

Infection with intestinal whipworms (Trichuris spp.) causes widespread morbidity and may alter responses to enteric and extraintestinal coinfections. Here, we show that Trichuris muris infection in mice increases coinfection with 2 evolutionary divergent enteric pathogens, the bacterium Citrobacter rodentium and the helminth Heligmosomoides polygyrus. Coinfection caused reduced weight gain and promoted type 1-biased inflammation. In contrast, T. muris-infected mice were more resistant to migrating Ascaris suum larvae in the lungs. Our results highlight the divergent nature of pathogen interactions and suggest that whipworm infection is a risk factor for coinfections with other pathogens within the gastrointestinal tract.


Assuntos
Coinfecção , Tricuríase , Animais , Camundongos , Ascaris , Intestinos , Trichuris , Pulmão
7.
Int J Paleopathol ; 41: 43-49, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36947954

RESUMO

OBJECTIVE: To characterize patterns in the taxonomic diversity of parasites infecting the population of Aalst, Belgium, between the 12th and 17th centuries. MATERIALS: 14 sediment samples from seven cesspits dated 1100-1700 CE. METHODS: Digital light microscopy and Enzyme-linked immunosorbent assay (ELISA). RESULTS: We identified eggs of four species of helminths: whipworm (Trichuris trichiura), roundworm (Ascaris lumbricoides), Echinostoma fluke and Dicrocoelium fluke. ELISA results for protozoal parasites were negative. CONCLUSIONS: Taxonomic diversity of parasite infections remained constant from the 12th to the 17th centuries. Roundworm and whipworm, spread by poor sanitation, were dominant. Two species of zoonotic parasites were also identified, including for the first time ever in the Low Countries the Echinostoma fluke, which may have been spread by eating uncooked freshwater animal foods. SIGNIFICANCE: Analysis of sediment samples spanning such a broad chronology (six centuries) from a single city offers the opportunity to track diachronic change, which is rare in paleoparasitological studies. LIMITATIONS: We were unable to acquire samples from cesspits dating to the 14th century. SUGGESTIONS FOR FURTHER RESEARCH: Additional data from other Low Countries towns may strengthen the patterns identified in this paper. A similar approach can be used to investigate towns in different regions of the world.


Assuntos
Enteropatias Parasitárias , Animais , Bélgica , Enteropatias Parasitárias/história , Ascaris lumbricoides , Trichuris
8.
Vet Parasitol ; 315: 109886, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36724679

RESUMO

With a global population of around 35 million in 47 countries, camels play a crucial role in the economy of many marginal and desert areas of the world where they survive in harsh conditions. Nonetheless, there is insufficient knowledge regarding camels' parasite fauna which can reduce their milk and meat production. A molecular study for the Trichuris population of Camelus bactrianus from Spain is presented based on sequences of mitochondrial (cox1, cob, rrnL) and ribosomal (ITS1 and ITS2) DNA regions. Bayesian Inference and Maximum Likelihood methods were used to infer phylogenies for (i) each gene separately, (ii) the combined mitochondrial data, and (iii) the combined mitochondrial and ribosomal dataset. Molecular analyses revealed the existence of two different genetic lineages in the Trichuris parasites populations of C. bactrianus. Future studies should focus on whether there is a coevolution process corresponding to the wild or domestic character of C. bactrianus and Camelus dromedarius. Furthermore, it is necessary to increase integrative taxonomic studies on Trichuris spp. based on morphological, biometric, and molecular data, which will inevitably contribute to our knowledge of the etiology of trichuriasis.


Assuntos
Camelus , Parasitos , Animais , Camelus/parasitologia , Trichuris/genética , Teorema de Bayes , Filogenia , Mitocôndrias
9.
Parasitol Res ; 121(12): 3381-3392, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36258094

RESUMO

Beyond participating in the oxygen transport by red blood cells, iron is an essential micronutrient and contributes to different physiological pathways and processes, such as cell proliferation, DNA repair, and other homeostatic functions. Iron deficiency affects millions of people, especially children and pregnant women. The consequences of iron deficiency are diverse, including inadequate child development, impaired cognition, and reduced productivity. Several factors contribute to iron deficiency, such as iron-poor diet, genetic factors, and infection with soil-transmitted helminths (STHs), especially roundworms (Ascaris lumbricoides), hookworms (Necator americanus and Ancylostoma duodenale), and whipworms (Trichuris trichiura). This review updates and summarizes the role of STHs as drivers of iron deficiency. Also, the poorly explored connections between STH infection, geophagia (a pica manifestation), immune response, and iron deficiency are discussed, highlighting how iron deficiency may act as a risk factor for infections by STHs, in addition to being a consequence of intestinal parasitic infections. Finally, strategies for control and management of iron deficiency and STH infection are described.


Assuntos
Helmintíase , Helmintos , Deficiências de Ferro , Gravidez , Criança , Animais , Feminino , Humanos , Solo/parasitologia , Helmintíase/complicações , Helmintíase/parasitologia , Ascaris lumbricoides , Trichuris , Ferro , Prevalência , Fezes/parasitologia
10.
Parasit Vectors ; 15(1): 348, 2022 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-36175934

RESUMO

Whipworm (Trichuris) is a genus of roundworms that causes gastrointestinal infections in humans and animals. Of particular interest are T. trichiura, the causative agent of human trichuriasis, a neglected tropical disease that affects 477 million people worldwide, and T. suis, the pig whipworm species, responsible for growth stunting and economic losses within the agricultural industry. The naturally occurring mouse whipworm, T. muris, has been used for decades as a model for trichuriasis, yielding knowledge on the biology of these parasites and the host response to infection. Ex vivo culture of T. muris (and to some extent, T. suis) has provided insight into the composition of the excretory/secretory (E/S) products released by worms, which include a myriad of proteins, RNAs, lipids, glycans, metabolites and extracellular vesicles. T. muris E/S has formed the basis of the search for whipworm vaccine candidates, while the immunomodulatory potential of T. suis and T. muris secretions has been investigated with the aim of improving our understanding of how these parasites modulate host immunity, as well as identifying immunomodulatory candidates with therapeutic potential in the context of inflammatory diseases. This article will review the various components found within Trichuris E/S, their potential as vaccine candidates and their immunomodulatory properties.


Assuntos
Tricuríase , Vacinas , Animais , Interações Hospedeiro-Parasita , Humanos , Lipídeos , Camundongos , Suínos , Tricuríase/parasitologia , Trichuris
11.
Parasit Vectors ; 15(1): 311, 2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36057606

RESUMO

BACKGROUND: Intestinal parasite contamination from infected dogs can place other dogs and humans at risk. A study was initiated to estimate the prevalence of canine intestinal parasitism by collecting fecal samples in cities across Western Europe. METHODS: Fresh fecal samples were collected from 2469 dogs visiting 164 parks in 33 cities across 12 countries. Each owner responded to a questionnaire focusing on their dog's signalment and recent anthelmintic treatment history. The collected samples were examined for hookworms, whipworms, ascarids and Giardia using a coproantigen diagnostic immunoassay and microscopy following centrifugal flotation. RESULTS: Nematodes or Giardia were detected in at least one sample from 100% of cities and in 93.3% of parks. Nematodes were detected in 57% of parks. Overall, 22.8% of dogs tested positive for an intestinal parasite, with Giardia being the most commonly identified parasites (17.3% of dogs, 83.5% of parks). For nematode infection, 7.6% of all dogs tested positive, with 9.9% of dogs aged < 1 year infected, 7.7% of those aged 1-3 years, 7.3% of those aged 4-6 years and 6.6% of those aged ≥ 7 years. Among the nematodes detected, ascarids were the most prevalent (3.6% of dogs, parks, 28.7% of parks), being most common in dogs aged < 1 year but also present in older dogs, including those aged ≥ 7 years. Hookworms and whipworms were detected in 3.2% and 2.3% of dogs of all ages, respectively, and in 37.2% and 17.7% of parks, respectively. A larger proportion of fecal samples tested positive with the coproantigen immunoassay than with centrifugal flotation. Positive test results for Giardia were sevenfold higher when both diagnostic tests were used than when centrifugal flotation alone was used, and there were 60% more positive test results for nematodes when both tests were used than when flotation alone was used. Overall, 77.2% of owners reported previous anthelmintic treatment, among whom at least 62.7% failed to follow recommended treatment frequency. Dogs receiving anthelmintic within the previous month had a lower percentage of nematode infection than those in which > 1 month had passed since the previous dose. CONCLUSIONS: The prevalence estimates of intestinal parasite infections in dogs reported here highlight the need for owner education concerning guidelines for regular testing and treatment, even in older dogs. Failure to adhere to guidelines can result in ongoing transmission of these infections, including those with zoonotic potential. Combining coproantigen immunoassay with centrifugal flotation for diagnostic testing and regular anthelmintic treatment are important measures for ensuring optimal intestinal parasite control.


Assuntos
Anti-Helmínticos , Doenças do Cão , Giardíase , Helmintos , Enteropatias Parasitárias , Nematoides , Infecções por Nematoides , Parasitos , Tricuríase , Animais , Doenças do Cão/diagnóstico , Doenças do Cão/epidemiologia , Doenças do Cão/parasitologia , Cães , Fezes/parasitologia , Giardia , Giardíase/diagnóstico , Giardíase/epidemiologia , Giardíase/veterinária , Humanos , Enteropatias Parasitárias/epidemiologia , Prevalência , Trichuris
12.
Int J Paleopathol ; 39: 115-121, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35989173

RESUMO

OBJECTIVE: To investigate how lifestyle may have impacted the risk of contracting intestinal parasites in medieval England . Regular clergy (such as those living in monasteries) and the lay population form interesting groups for comparison as diet and lifestyle varied significantly. Monasteries were built with latrine blocks and hand washing facilities, unlike houses of the poor. MATERIALS: Sediment samples from the pelvis, along with control samples from feet and skull, of 19 burials of Augustinian Friars (13th-16th century), and 25 burials from All Saints by the Castle parish cemetery (10th-14th century), Cambridge. METHODS: We analysed the sediment using micro-sieving and digital light microscopy to identify the eggs of intestinal parasites. RESULTS: Parasite prevalence (roundworm and whipworm) in the Augustinian friars was 58%, and in the All Saints by the Castle parishioners just 32% (Barnards Test score statistic 1.7176, p-value 0.092). CONCLUSIONS: It is interesting that the friars had nearly double the infection rate of parasites spread by poor hygiene, compared with the general population. We consider options that might explain this difference, and discuss descriptions and treatment of intestinal worms in medical texts circulating in Cambridge during the medieval period. SIGNIFICANCE: This is the first study to compare prevalence of parasite infection between groups with different socioeconomic status from the same location. LIMITATIONS: Quality of egg preservation was suboptimal, so our data may under-represent the true prevalence. SUGGESTIONS FOR FURTHER RESEARCH: Larger studies with greater statistical power, covering different time periods and regions.


Assuntos
Enteropatias Parasitárias , Monges , Humanos , Enteropatias Parasitárias/epidemiologia , Sepultamento , Cemitérios , Reino Unido
13.
Parasit Vectors ; 15(1): 294, 2022 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-35996178

RESUMO

BACKGROUND: Canine intestinal parasite prevalence may be influenced by geographical region, age, and health status of the dog. Behaviors such as predation, scavenging, or roaming as well as routine administration of anthelmintics also play a role. The purpose of this study was to evaluate fecal test results using zinc sulfate flotation by centrifugation combined with coproantigen testing directed at protein antigens excreted or secreted by hookworms (Ancylostoma spp. Uncinaria stenocephala), ascarids (Toxocara canis, Toxascaris spp. Baylisascaris spp.), whipworms (Trichuris vulpis), and Giardia spp. during active infection in owned dogs visiting dog parks in Western Canada. METHODS: A total of 774 participants were recruited from Edmonton, Alberta, Canada. Canine fecal samples were collected from seven dedicated off-leash dog parks. Participating dog owners responded to a questionnaire regarding their dogs' signalment, previous veterinary history, and use of parasite-preventive products. Fecal samples were tested using zinc sulfate centrifugation combined with coproantigen testing. RESULTS: The overall prevalence of canine intestinal parasites in client-owned dogs was similar to previous studies conducted in the US. Mean age of dogs tested was 4 years, with puppies and older dogs having higher rates of infection than the mean. Fecal flotation centrifugation found 3.2% hookworm, ascarid, whipworm, and Giardia spp.-positive infections. Coproantigen testing identified 5.8% positive infections, including all of the above that were detected using fecal flotation centrifugation. CONCLUSIONS: Coproantigen testing detected more hookworm, ascarid, whipworm, and Giardia spp.-positive samples in addition to detecting all positive results found using fecal flotation centrifugation. Fecal flotation centrifugation combined with coproantigen testing improves sensitivity over flotation alone and may detect pre-patent or sub-clinical infections in dogs visiting public dog parks.


Assuntos
Doenças do Cão , Giardíase , Enteropatias Parasitárias , Nematoides , Tricuríase , Alberta/epidemiologia , Animais , Doenças do Cão/diagnóstico , Doenças do Cão/epidemiologia , Doenças do Cão/parasitologia , Cães , Fezes/parasitologia , Giardia , Giardíase/epidemiologia , Giardíase/veterinária , Humanos , Enteropatias Parasitárias/epidemiologia , Prevalência , Trichuris , Sulfato de Zinco
14.
Microorganisms ; 10(5)2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35630469

RESUMO

Anaemia is an important cause of morbidity and mortality globally. Among infectious agents responsible for anaemia, helminthic infections are often neglected, particularly in non-endemic countries. However, they should not be neglected in this setting, as international travel and migration are on the rise. In this narrative review, we aimed to describe soil-transmitted helminths as a cause of or contributing factor to anaemia, focusing on hookworms (Necator americanus and Ancylostoma duodenale), the whipworm (Trichuris trichiura), the roundworm (Ascaris lumbricoides), and the threadworm (Strongyloides stercoralis). A general review on the epidemiology, lifecycle, and clinical spectrum of anaemia is proposed, with a special focus on helminthic infections' association with anaemia as well as the diagnostic approach, which are both particularly important in non-endemic settings.

15.
Parasitol Res ; 121(3): 1047-1051, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35106651

RESUMO

Whipworms are soil-transmitted helminths that can infect a variety of animals. A Chinese serow possibly infected by whipworms was found during a wildlife disease surveillance project in Baima Snow Mountain National Nature Reserve, Yunnan, China, in 2021. As convergent evolution is common in coinhabiting parasites, a mitochondrial gene sequence (cox1) and ribosomal gene sequence (ITS1) were used to identify species similar to Trichuris from Chinese serow. The phylogenetic trees and genetic distances of ten Trichuris samples from a Chinese serow together with other Trichuris spp. that have been previously reported were analysed based on the cox1 and ITS1 sequences. The combined results of the phylogenetic tree and genetic distances based on cox1 gene showed that the whipworms in Chinese serow are T. skrjabini. However, the whipworms in the present study were divided into two apparent clades in the phylogenic trees constructed by the cox1 sequences (Clades A and B) and the ITS1 sequences (Clades C and D). In addition, the Fst and Nm values were 0.82 and 0.23 between Clade A and Clade B for the cox1 gene, and 0.30 and 0.45 between Clade C and Clade D for the ITS1 sequences; both indicators showed low gene flow among the clades. Therefore, the genetic population structure of T. skrjabini was illustrated.


Assuntos
Tricuríase , Trichuris , Animais , Sequência de Bases , China/epidemiologia , Filogenia , Análise de Sequência de DNA , Tricuríase/epidemiologia , Tricuríase/veterinária
16.
Int J Parasitol ; 51(13-14): 1243-1253, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34774540

RESUMO

The major soil-transmitted helminths that infect humans are the roundworms, whipworms and hookworms. Soil-transmitted helminth infections rank among the most important neglected tropical diseases in terms of morbidity, and almost one billion people are still infected with at least one species. While anthelmintic drugs are available, they do not offer long term protection against reinfection, precipitating the need for vaccines that provide long-term immunologic defense. Vaccine discovery and development is in advanced clinical development for hookworm infection, with a bivalent human hookworm vaccine in clinical trials in Brazil and Africa, but is in its infancy for both roundworm (ascariasis) and whipworm (trichuriasis) infections. One of the greatest hurdles to developing soil-transmitted helminth vaccines is the potent immunoregulatory properties of these helminths, creating a barrier to the induction of meaningful long-term protective immunity. While challenging for vaccinologists, this phenomenon presents unique opportunities to develop an entirely new class of anti-inflammatory drugs that capitalise on these immunomodulatory strategies. Epidemiologic studies and clinical trials employing experimental soil-transmitted helminth challenge models, when coupled with findings from animal models, show that at least some soil-transmitted helminth-derived molecules can protect against the onset of autoimmune, allergic and metabolic disorders, and several natural products with the desired bioactivity have been isolated and tested in pre-clinical settings. The yin and yang of soil-transmitted helminth infections reflect both the urgency for effective vaccines and the potential for new immunoregulatory molecules from parasite products.


Assuntos
Ascaríase , Helmintíase , Helmintos , Infecções por Uncinaria , Nematoides , Tricuríase , Vacinas , Ancylostomatoidea , Animais , Helmintíase/tratamento farmacológico , Helmintíase/prevenção & controle , Infecções por Uncinaria/tratamento farmacológico , Infecções por Uncinaria/prevenção & controle , Humanos , Prevalência , Solo/parasitologia , Trichuris
17.
Methods Mol Biol ; 2369: 319-332, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34313996

RESUMO

The identification, detection, and use of small RNA species have rapidly gained interest-especially to study parasite-host interactions. Parasite-to-host communication is contributed by small secreted extracellular vesicle (EV)-derived nucleic acid species. In particular, microRNAs (miRNAs) and small interfering RNAs can regulate the host response by targeting cells at both transcriptional and posttranscriptional levels. Here, modified protocols for density gradient purification of EVs from nematodes and the subsequent extraction of EV-derived small RNAs using commercially available reagents and kits are provided with a special focus on basic background information. Further, considerations for Next-Generation Sequencing using the Illumina NextSeq500 sequencing technology (kit-based library preparation, small RNA sequencing, and miRNA sequence analysis pipelines using the miRDeep2 package) are introduced.


Assuntos
Vesículas Extracelulares , Animais , MicroRNAs/genética , Nippostrongylus , Análise de Sequência de RNA , Trichuris
18.
Parasitology ; : 1-7, 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34075864

RESUMO

Trichuris, whipworm nematode infections are prevalent in humans, domestic livestock and mammals. All share an epithelial dwelling niche and similar life cycle with the chronic infections that follow implying that immune evasion mechanisms are operating. Nematode excretory secretory (ES) products have been shown to be a rich source of immunomodulatory molecules for many species. The Trichuris muris model is a natural parasite of mice and has been used extensively to study host­parasite interactions and provides a tractable platform for investigation of the immunoregulatory capacity of whipworm ES. The present review details progress in identification of the composition of T. muris ES, immunomodulatory components and their potential mechanisms of action. The adult T. muris secretome is dominated by one protein with modulatory capacity although remains to be completely characterized. In addition, the secretome contains multiple other proteins and small molecules that have immunomodulatory potential, certainly by comparison to other Trichuris species. Moreover, T. muris-derived exosomes/exosome-like vesicles contain both protein and multiple miRNAs providing an alternate delivery process for molecules with the potential to modulate host immunity.

19.
ACS Infect Dis ; 7(5): 1260-1274, 2021 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-33797218

RESUMO

Nine hundred million people are infected with the soil-transmitted helminths Ascaris lumbricoides (roundworm), hookworm, and Trichuris trichiura (whipworm). However, low single-dose cure rates of the benzimidazole drugs, the mainstay of preventative chemotherapy for whipworm, together with parasite drug resistance, mean that current approaches may not be able to eliminate morbidity from trichuriasis. We are seeking to develop new anthelmintic drugs specifically with activity against whipworm as a priority and previously identified a hit series of dihydrobenzoxazepinone (DHB) compounds that block motility of ex vivo Trichuris muris. Here, we report a systematic investigation of the structure-activity relationship of the anthelmintic activity of DHB compounds. We synthesized 47 analogues, which allowed us to define features of the molecules essential for anthelmintic action as well as broadening the chemotype by identification of dihydrobenzoquinolinones (DBQs) with anthelmintic activity. We investigated the activity of these compounds against other parasitic nematodes, identifying DHB compounds with activity against Brugia malayi and Heligmosomoides polygyrus. We also demonstrated activity of DHB compounds against the trematode Schistosoma mansoni, a parasite that causes schistosomiasis. These results demonstrate the potential of DHB and DBQ compounds for further development as broad-spectrum anthelmintics.


Assuntos
Anti-Helmínticos , Brugia Malayi , Nematospiroides dubius , Parasitos , Animais , Anti-Helmínticos/farmacologia , Humanos , Schistosoma mansoni , Trichuris
20.
Front Cell Infect Microbiol ; 11: 637570, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33777847

RESUMO

The human whipworm Trichuris trichiura infects 289 million people worldwide, resulting in substantial morbidity. Whipworm infections are difficult to treat due to low cure rates and high reinfection rates. Interactions between whipworm and its host's intestinal microbiome present a potential novel target for infection control or prevention but are very complicated and are identified using inconsistent methodology and sample types across the literature, limiting their potential usefulness. Here, we used a combined 16S rRNA gene OTU analysis approach (QIIME2) for samples from humans and mice infected with whipworm (T. trichiura and T. muris, respectively) to identify for the first time, bacterial taxa that were consistently associated with whipworm infection spanning host species and infection status using four independent comparisons (baseline infected vs uninfected and before vs after deworming for both humans and mice). Using these four comparisons, we identified significant positive associations for seven taxa including Escherichia, which has been identified to induce whipworm egg hatching, and Bacteroides, which has previously been identified as a major component of the whipworm internal microbiome. We additionally identified significant negative associations for five taxa including four members of the order Clostridiales, two from the family Lachnospiraceae, including Blautia which was previously identified as positively associated with whipworm in independent human and mouse studies. Using this approach, bacterial taxa of interest for future association and mechanistic studies were identified, and several were validated by RT-qPCR. We demonstrate the applicability of a mouse animal model for comparison to human whipworm infections with respect to whipworm-induced intestinal microbiome disruption and subsequent restoration following deworming. Overall, the novel cross-species analysis approach utilized here provides a valuable research tool for studies of the interaction between whipworm infection and the host intestinal microbiome.


Assuntos
Microbioma Gastrointestinal , Microbiota , Tricuríase , Animais , Humanos , Camundongos , RNA Ribossômico 16S , Trichuris/genética
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