RESUMEN
Genomic replication is a critical, regulated process that ensures accurate genetic information duplication. In eukaryotic cells, strategies have evolved to prevent conflicts between replication and transcription. Giardia lamblia, a binucleated protozoan, alternates between tetraploid and octaploid genomes during its cell cycle. Using single-molecule techniques like DNA combing and nanopore-based sequencing, we investigated the spatio-temporal organization of DNA replication, replication fork progression and potential head-on replication-transcription collisions in Giardia trophozoites. Our findings indicate that Giardia chromosomes are replicated from only a few active origins, which are widely spaced and exhibit faster replication rates compared to those in other protozoan parasites. Immunofluorescence assays revealed that â¼20% of trophozoites show asynchronous replication between nuclei. Forksense and gene ontology analyses disclosed that genes in regions with potential head-on collisions are linked to chromatin dynamics, cell cycle regulation and DNA replication/repair pathways, possibly explaining the observed asynchronous replication in part of the population. This study offers the first comprehensive view of replication dynamics in Giardia, which is the pathogen that causes giardiasis, a diarrheal disease impacting millions worldwide.
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Giardia lamblia , Giardiasis , Humanos , Giardia lamblia/genética , Giardiasis/parasitología , Ciclo Celular/genética , Núcleo Celular , Replicación del ADN/genéticaRESUMEN
Giardia intestinalis is a non-invasive, protozoan parasite infecting the upper small intestine of most mammals. Symptomatic infections cause the diarrhoeal disease giardiasis in humans and animals, but at least half of the infections are asymptomatic. However, the molecular underpinnings of these different outcomes of the infection are still poorly defined. Here, we studied the early transcriptional response to G. intestinalis trophozoites, the disease-causing life-cycle stage, in human enteroid-derived, 2-dimensional intestinal epithelial cell (IEC) monolayers. Trophozoites preconditioned in media that maximise parasite fitness triggered only neglectable inflammatory transcription in the IECs during the first hours of co-incubation. By sharp contrast, "non-fit" or lysed trophozoites induced a vigorous IEC transcriptional response, including high up-regulation of many inflammatory cytokines and chemokines. Furthermore, "fit" trophozoites could even suppress the stimulatory effect of lysed trophozoites in mixed infections, suggesting active G. intestinalis suppression of the IEC response. By dual-species RNA-sequencing, we defined the IEC and G. intestinalis gene expression programs associated with these differential outcomes of the infection. Taken together, our results inform on how G. intestinalis infection can lead to such highly variable effects on the host, and pinpoints trophozoite fitness as a key determinant of the IEC response to this common parasite.
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Giardia lamblia , Giardiasis , Animales , Humanos , Giardiasis/metabolismo , Trofozoítos/metabolismo , Intestinos , Giardia lamblia/metabolismo , Células Epiteliales/metabolismo , MamíferosRESUMEN
Giardia lamblia is an important protozoan cause of diarrheal disease worldwide, delayed development and cognitive impairment in children in low- and middle-income countries, and protracted post-infectious syndromes in developed regions. G. lamblia resides in the lumen and at the epithelial surface of the proximal small intestine but is not mucosa invasive. The protozoan parasite is genetically diverse with significant genome differences across strains and assemblages. Animal models, particularly murine models, have been instrumental in defining mechanisms of host defense against G. lamblia, but mice cannot be readily infected with most human pathogenic strains. Antibiotic pretreatment can increase susceptibility, suggesting that the normal microbiota plays a role in controlling G. lamblia infection in mice, but the broader implications on susceptibility to diverse strains are not known. Here, we have used gnotobiotic mice to demonstrate that robust intestinal infection can be achieved for a broad set of human-pathogenic strains of the genetic assemblages A and B. Furthermore, gnotobiotic mice were able to eradicate infection with a similar kinetics to conventional mice after trophozoite challenge. Germ-free mice could also be effectively immunized by the mucosal route with a protective antigen, α1-giardin, in a manner dependent on CD4 T cells. These results indicate that the gnotobiotic mouse model is powerful for investigating acquired host defenses in giardiasis, as the mice are broadly susceptible to diverse G. lamblia strains yet display no apparent defects in mucosal immunity needed for controlling and eradicating this lumen-dwelling pathogen.
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Modelos Animales de Enfermedad , Vida Libre de Gérmenes , Giardia lamblia , Giardiasis , Animales , Giardiasis/inmunología , Giardiasis/parasitología , Giardia lamblia/inmunología , Giardia lamblia/genética , Ratones , Vacunas Antiprotozoos/inmunología , Vacunación , Mucosa Intestinal/inmunología , Mucosa Intestinal/microbiología , Mucosa Intestinal/parasitología , Humanos , FemeninoRESUMEN
The intestinal parasites Giardia lamblia and Entamoeba histolytica are major causes of morbidity and mortality associated with diarrheal diseases. Metronidazole is the most common drug used to treat giardiasis and amebiasis. Despite its efficacy, treatment failures in giardiasis occur in up to 5%-40% of cases. Potential resistance of E. histolytica to metronidazole is an increasing concern. Therefore, it is critical to search for more effective drugs to treat giardiasis and amebiasis. We identified antigiardial and antiamebic activities of the rediscovered nitroimidazole compound, fexinidazole, and its sulfone and sulfoxide metabolites. Fexinidazole is equally active against E. histolytica and G. lamblia trophozoites, and both metabolites were 3- to 18-fold more active than the parent drug. Fexinidazole and its metabolites were also active against a metronidazole-resistant strain of G. lamblia. G. lamblia and E. histolytica cell extracts exhibited decreased residual nitroreductase activity when metabolites were used as substrates, indicating nitroreductase may be central to the mechanism of action of fexinidazole. In a cell invasion model, fexinidazole and its metabolites significantly reduced the invasiveness of E. histolytica trophozoites through basement membrane matrix. A q.d. oral dose of fexinidazole and its metabolites at 10 mg/kg for 3 days reduced G. lamblia infection significantly in mice compared to control. The newly discovered antigiardial and antiamebic activities of fexinidazole, combined with its FDA-approval and inclusion in the WHO Model List of Essential Medicines for the treatment of human African trypanosomiasis, offer decreased risk and a shortened development timeline toward clinical use of fexinidazole for treatment of giardiasis or amebiasis.
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Amebiasis , Entamoeba histolytica , Giardia lamblia , Giardiasis , Nitroimidazoles , Ratones , Animales , Humanos , Giardiasis/tratamiento farmacológico , Giardiasis/parasitología , Metronidazol/farmacología , Metronidazol/uso terapéutico , Nitroimidazoles/farmacología , NitrorreductasasRESUMEN
The deep-branching eukaryote Giardia lamblia is an extracellular parasite that attaches to the host intestine via a microtubule-based structure called the ventral disc. Control of attachment is mediated in part by the movement of two regions of the ventral disc that either permit or exclude the passage of fluid under the disc. Several known disc-associated proteins (DAPs) contribute to disc structure and function, but no force-generating protein has been identified among them. We recently identified several Giardia actin (GlActin) interacting proteins at the ventral disc, which could potentially employ actin polymerization for force generation and disc conformational changes. One of these proteins, Disc and Actin Associated Protein 1 (DAAP1), is highly enriched at the two regions of the disc previously shown to be important for fluid flow during attachment. In this study, we investigate the role of both GlActin and DAAP1 in ventral disc morphology and function. We confirmed interaction between GlActin and DAAP1 through coimmunoprecipitation, and used immunofluorescence to localize both proteins throughout the cell cycle and during trophozoite attachment. Similar to other DAPs, the association of DAAP1 with the disc is stable, except during cell division when the disc disassembles. Depletion of GlActin by translation-blocking antisense morpholinos resulted in both impaired attachment and defects in the ventral disc, indicating that GlActin contributes to disc-mediated attachment. Depletion of DAAP1 through CRISPR interference resulted in intact discs but impaired attachment, gating, and flow under the disc. As attachment is essential for infection, elucidation of these and other molecular mediators is a promising area for development of new therapeutics against a ubiquitous parasite.
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Giardia lamblia , Giardiasis , Proteínas de Microfilamentos , Parásitos , Animales , Actinas/metabolismo , Giardia lamblia/genética , Giardia lamblia/metabolismo , Giardiasis/parasitología , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/metabolismo , Parásitos/metabolismo , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismoRESUMEN
Attachment to the intestinal epithelium is critical to the lifestyle of the ubiquitous parasite Giardia lamblia. The ventrolateral flange is a sheet-like membrane protrusion at the interface between parasites and attached surfaces. This structure has been implicated in attachment, but its role has been poorly defined. Here, we identified a novel actin associated protein with putative WH2-like actin binding domains we named Flangin. Flangin complexes with Giardia actin (GlActin) and is enriched in the ventrolateral flange making it a valuable marker for studying the flanges' role in Giardia biology. Live imaging revealed that the flange grows to around 1 µm in width after cytokinesis, then remains uniform in size during interphase, grows in mitosis, and is resorbed during cytokinesis. A flangin truncation mutant stabilizes the flange and blocks cytokinesis, indicating that flange disassembly is necessary for rapid myosin-independent cytokinesis in Giardia. Rho family GTPases are important regulators of membrane protrusions and GlRac, the sole Rho family GTPase in Giardia, was localized to the flange. Knockdown of Flangin, GlActin, and GlRac result in flange formation defects. This indicates a conserved role for GlRac and GlActin in forming membrane protrusions, despite the absence of canonical actin binding proteins that link Rho GTPase signaling to lamellipodia formation. Flangin-depleted parasites had reduced surface contact and when challenged with fluid shear force in flow chambers they had a reduced ability to remain attached, confirming a role for the flange in attachment. This secondary attachment mechanism complements the microtubule based adhesive ventral disc, a feature that may be particularly important during mitosis when the parental ventral disc disassembles in preparation for cytokinesis. This work supports the emerging view that Giardia's unconventional actin cytoskeleton has an important role in supporting parasite attachment.
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Giardia lamblia , Giardiasis , Parásitos , Actinas/metabolismo , Animales , Giardia/metabolismo , Giardia lamblia/genética , Giardia lamblia/metabolismo , Giardiasis/parasitología , Parásitos/metabolismo , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismoRESUMEN
BACKGROUND: Diarrhoeal diseases are common among children in low- and middle-income countries and are major causes of morbidity and mortality. Cryptosporidium and Giardia are considered to be the main parasitic causes of diarrhoea in children. The aim of the present study was to determine the prevalence and associated factors of Cryptosporidium and Giardia infection in children under five years of age presenting at two health centres (Ndirande and Limbe) in Blantyre, Malawi. METHODS: This cross-sectional study was performed from February to July 2019 and included 972 children under 5 years of age with diarrhoea. Stool samples were immediately tested after collection at enrolment with a rapid diagnostic test for Cryptosporidium and Giardia infection. Descriptive statistics were used to assess the prevalence of these protozoan parasitic infections, and differences in the basic demographic and anthroponotic variables (between children with diarrhoea and parasite infection, being either Cryptosporidium and Giardia or both versus children with diarrhoea but no RDT confirmed parasite infection) were assessed. Their association with Cryptosporidium and Giardia infection was analysed using simple logistic regressions. RESULTS: Of the children recruited, 88 (9.1%) tested positive for Cryptosporidium and 184 (18.9%) for Giardia. Children with only a Giardia infection or a coinfection (of both parasites) were significantly older (mean age 24-26 months) compared to children with only a Cryptosporidium infection (mean age 13 months) or no parasitic infection (mean age 14 months). No significant differences were found with respect to gender, body temperature, stunting or wasting between the different groups of children with moderate to severe diarrhoea. Children attending the Ndirande health centre had almost two times higher odds of testing positive for both infections than those attending Limbe health centre. CONCLUSION: Cryptosporidium and Giardia infections are highly prevalent in children < 5 years with moderate to severe diarrhoea attending the Limbe and Ndirande health centres in Blantyre, Malawi.
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Criptosporidiosis , Cryptosporidium , Giardiasis , Niño , Humanos , Preescolar , Lactante , Giardiasis/complicaciones , Giardiasis/epidemiología , Prevalencia , Criptosporidiosis/epidemiología , Malaui/epidemiología , Estudios Transversales , Diarrea/epidemiologíaRESUMEN
BACKGROUND: Giardia duodenalis is an important intestinal parasitic protozoan that infects several vertebrates, including humans. Cattle are considered the major source of giardiasis outbreak in humans. This study aimed to investigate the prevalence and multilocus genotype (MLG) of G. duodenalis in Shanxi, and lay the foundation for the prevention and control of Giardiosis. METHODS AND RESULTS: DNA extraction, nested polymerase chain reaction, sequence analysis, MLG analysis, and statistical analysis were performed using 858 bovine fecal samples from Shanxi based on three gene loci: ß-giardin (bg), glutamate dehydrogenase (gdh), and triosephosphate isomerase (tpi). The overall prevalence of G. duodenalis was 28.3%, while its prevalence in Yingxian and Lingqiu was 28.1% and 28.5%, respectively. The overall prevalence of G. duodenalis in dairy cattle and beef cattle was 28.0% and 28.5%, respectively. G. duodenalis infection was detected in all age groups evaluated in this study. The overall prevalence of G. duodenalis in diarrhea and nondiarrhea samples was 32.4% and 27.5%, respectively, whereas that in intensively farmed and free-range cattle was 35.0% and 19.9%, respectively. We obtained 83, 53, and 59 sequences of bg, gdh, and tpi in G. duodenalis, respectively. Moreover, assemblage A (n = 2) and assemblage E (n = 81) by bg, assemblage A (n = 1) and assemblage E (n = 52) by gdh, and assemblage A (n = 2) and assemblage E (n = 57) by tpi were identified. Multilocus genotyping yielded 29 assemblage E MLGs, which formed 10 subgroups. CONCLUSIONS: To the best of our knowledge, this is the first study to report cattle infected with G. duodenalis in Shanxi, China. Livestock-specific G. duodenalis assemblage E was the dominant assemblage genotype, and zoonotic sub-assemblage AI was also detected in this region.
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Giardia lamblia , Giardiasis , Humanos , Bovinos , Animales , Giardia lamblia/genética , Tipificación de Secuencias Multilocus , Proteínas Protozoarias/genética , Giardiasis/epidemiología , Giardiasis/veterinaria , Giardiasis/parasitología , Genotipo , China/epidemiología , Prevalencia , Heces/parasitología , Triosa-Fosfato Isomerasa/genética , Glutamato Deshidrogenasa/genética , FilogeniaRESUMEN
Cryptosporidium spp., Giardia intestinalis and microsporidia are unicellular opportunistic pathogens that can cause gastrointestinal infections in both animals and humans. Since companion animals may serve as a source of infection, the aim of the present screening study was to analyse the prevalence of these intestinal protists in fecal samples collected from dogs living in 10 animal shelters in central Europe (101 dogs from Poland and 86 from the Czech Republic), combined with molecular subtyping of the detected organisms in order to assess their genetic diversity. Genus-specific polymerase chain reactions were performed to detect DNA of the tested species and to conduct molecular subtyping in collected samples, followed by statistical evaluation of the data obtained (using χ2 or Fisher's tests). The observed prevalence was 15.5, 10.2, 1 and 1% for G. intestinalis, Enterocytozoon bieneusi, Cryptosporidium spp. and Encephalitozoon cuniculi, respectively. Molecular evaluation has revealed the predominance of dog-specific genotypes (Cryptosporidium canis XXe1 subtype; G. intestinalis assemblages C and D; E. cuniculi genotype II; E. bieneusi genotypes D and PtEbIX), suggesting that shelter dogs do not pose a high risk of human transmission. Interestingly, the percentage distribution of the detected pathogens differed between both countries and individual shelters, suggesting that the risk of infection may be associated with conditions typical of a given location.
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Criptosporidiosis , Cryptosporidium , Enfermedades de los Perros , Enterocytozoon , Heces , Giardiasis , Microsporidiosis , Animales , Perros , Enfermedades de los Perros/parasitología , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/microbiología , Enterocytozoon/genética , Enterocytozoon/aislamiento & purificación , Enterocytozoon/clasificación , Cryptosporidium/genética , Cryptosporidium/aislamiento & purificación , Cryptosporidium/clasificación , Microsporidiosis/veterinaria , Microsporidiosis/epidemiología , Polonia/epidemiología , Criptosporidiosis/epidemiología , Criptosporidiosis/parasitología , Heces/parasitología , Heces/microbiología , República Checa/epidemiología , Giardiasis/veterinaria , Giardiasis/epidemiología , Giardiasis/parasitología , Prevalencia , Giardia/genética , Giardia/aislamiento & purificación , Giardia/clasificación , Genotipo , Giardia lamblia/genética , Giardia lamblia/aislamiento & purificación , Giardia lamblia/clasificación , Especificidad del HuéspedRESUMEN
BACKGROUND: We reported a rare case of combined Giardiasis, sepsis, and DIC in a Tibetan Chinese male in this study. METHODS: Multiple fecal routine examinations, blood routine examination, blood culture, coagulation screening, and biochemical tests were done after August 1st, 2022. RESULTS: The child had intermittent diarrhea. Giardia cysts were found in his stool mounts. Sepsis, disseminated intravascular coagulation, fever with blood routine decreasing, low proteinemia, hyperlactemia and hypocalcemia were also found in this case. CONCLUSIONS: It is suggested that improving the resistance, immunity, and personal hygiene is particularly important for children from remote ethnic minority areas of China.
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Giardiasis , Sepsis , Niño , Humanos , Masculino , Giardiasis/complicaciones , Giardiasis/diagnóstico , Tibet , Etnicidad , Grupos Minoritarios , China/epidemiología , Sepsis/diagnósticoRESUMEN
Giardiasis is a common waterborne zoonotic disease caused by Giardia intestinalis. Upon infection, Giardia releases excretory and secretory products (ESPs) including secreted proteins (SPs) and extracellular vesicles (EVs). Although the interplay between ESPs and intestinal epithelial cells (IECs) has been previously described, the functions of EVs in these interactions and their differences from those of SPs require further exploration. In the present study, EVs and EV-depleted SPs were isolated from Giardia ESPs. Proteomic analyses of isolated SPs and EVs showed 146 and 91 proteins, respectively. Certain unique and enriched proteins have been identified in SPs and EVs. Transcriptome analysis of Caco-2 cells exposed to EVs showed 96 differentially expressed genes (DEGs), with 56 upregulated and 40 downregulated genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) indicated that Caco-2 genes related to metabolic processes, the HIF-1 signaling pathway, and the cAMP signaling pathway were affected. This study provides new insights into host-parasite interactions, highlighting the potential significance of EVs on IECs during infections.
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Vesículas Extracelulares , Giardia lamblia , Mucosa Intestinal , Humanos , Células CACO-2 , Giardia lamblia/genética , Giardia lamblia/metabolismo , Vesículas Extracelulares/metabolismo , Mucosa Intestinal/parasitología , Mucosa Intestinal/metabolismo , Perfilación de la Expresión Génica , Células Epiteliales/parasitología , Células Epiteliales/metabolismo , Proteómica , Interacciones Huésped-Parásitos , Expresión Génica , Transcriptoma , Giardiasis/parasitologíaRESUMEN
Giardiasis is a disease caused by the protist Giardia lamblia. As no human vaccines have been approved so far against it, and resistance to current drugs is spreading, new strategies for combating giardiasis need to be developed. The G. lamblia ribosome may provide a promising therapeutic target due to its distinct sequence differences from ribosomes of most eukaryotes and prokaryotes. Here, we report the cryo-electron microscopy structure of the G. lamblia (WB strain) ribosome determined at 2.75 Å resolution. The ribosomal RNA is the shortest known among eukaryotes, and lacks nearly all the eukaryote-specific ribosomal RNA expansion segments. In contrast, the ribosomal proteins are typically eukaryotic with some species-specific insertions/extensions. Most typical inter-subunit bridges are maintained except for one missing contact site. Unique structural features are located mainly at the ribosome's periphery. These may be exploited as target sites for the design of new compounds that inhibit selectively the parasite's ribosomal activity.
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Giardia lamblia , Giardiasis , Parásitos , Animales , Microscopía por Crioelectrón , Eucariontes/genética , Giardia lamblia/genética , Giardiasis/metabolismo , Humanos , Parásitos/genética , ARN Ribosómico/metabolismo , Ribosomas/metabolismoRESUMEN
Giardiasis is a common intestinal infection caused by Giardia duodenalis, which is a major economic and health burden for humans and livestock. Currently, a convenient and effective detection method is urgently needed. CRISPR/Cas12a-based diagnostic methods have been widely used for nucleic acid-based detection of pathogens due to their high efficiency and sensitivity. In this study, a technique combining CRISPR/Cas12a and RPA was established that allows the detection of G. duodenalis in faecal samples by the naked eye with high sensitivity (10-1 copies/µL) and specificity (no cross-reactivity with nine common pathogens). In clinical evaluations, the RPA-CRISPR/Cas12a-based detection assay detected Giardia positivity in 2% (1/50) of human faecal samples and 47% (33/70) of cattle faecal samples, respectively, which was consistent with the results of nested PCR. Our study demonstrated that the RPA-CRISPR/Cas12a technique for G. duodenalis is stable, efficient, sensitive, specific and has low equipment requirements. This technique offers new opportunities for on-site detection in remote and poor areas.
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Giardia lamblia , Giardiasis , Humanos , Animales , Bovinos , Giardia lamblia/genética , Sistemas CRISPR-Cas , Giardiasis/diagnóstico , Giardiasis/veterinaria , Giardia/genética , BioensayoRESUMEN
Giardia duodenalis is an intestinal protozoan that can infect both humans and animals, leading to public health issues and economic losses in the livestock industry. G. duodenalis has been reported to infect dairy cattle, but there is limited information available on large-scale dairy farms in Xinjiang, China. The study collected 749 fresh faecal samples from five large-scale cattle farms in Xinjiang, China. The study used a nested PCR assay of the small subunit ribosomal RNA (SSU rRNA*) gene to determine the presence of G. duodenalis. The results showed that 24.0% (180/749) of dairy cattle were positive for G. duodenalis, with the highest infection rate observed in pre-weaned calves (45.1%, 69/153). Among the 180 G. duodenalis positive samples, three assemblages were identified: assemblage E (n = 176), assemblage A (n = 3) and assemblage B (n = 1). Sixty-nine, 67 and 49 sequences were obtained for the beta-giardin (bg*) gene, the glutamate dehydrogenase (gdh*) gene and the triose phosphate isomerase (tpi*) gene, respectively. Thirteen novel sequences of assemblage E were identified, including five sequences from the bg* gene, four sequences from the gdh* gene and four sequences from the tpi* gene. This study found that 32 G. duodenalis assemblage E isolates formed 26 MLGs, indicating genetic variation and geographic isolation-based differentiation in bovine-derived G. duodenalis assemblage E. These findings provide fundamental insights into the genetic diversity of G. duodenalis in dairy cattle and can aid in the prevention and control of its occurrence in large-scale dairy cattle farms.
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Enfermedades de los Bovinos , Giardia lamblia , Giardiasis , Humanos , Bovinos , Animales , Giardia lamblia/genética , Giardiasis/epidemiología , Giardiasis/veterinaria , Granjas , Tipificación de Secuencias Multilocus/veterinaria , Genotipo , Enfermedades de los Bovinos/epidemiología , Prevalencia , China/epidemiología , HecesRESUMEN
Marsupials, inhabiting diverse ecosystems, including urban and peri-urban regions in Australasia and the Americas, intersect with human activities, leading to zoonotic spill-over and anthroponotic spill-back of pathogens, including Cryptosporidium and Giardia. This review assesses the current knowledge on the diversity of Cryptosporidium and Giardia species in marsupials, focusing on the potential zoonotic risks. Cryptosporidium fayeri and C. macropodum are the dominant species in marsupials, while in possums, the host-specific possum genotype dominates. Of these three species/genotypes, only C. fayeri has been identified in two humans and the zoonotic risk is considered low. Generally, oocyst shedding in marsupials is low, further supporting a low transmission risk. However, there is some evidence of spill-back of C. hominis into kangaroo populations, which requires continued monitoring. Although C. hominis does not appear to be established in small marsupials like possums, comprehensive screening and analysis are essential for a better understanding of the prevalence and potential establishment of zoonotic Cryptosporidium species in small marsupials. Both host-specific and zoonotic Giardia species have been identified in marsupials. The dominance of zoonotic G. duodenalis assemblages A and B in marsupials may result from spill-back from livestock and humans and it is not yet understood if these are transient or established infections. Future studies using multilocus typing tools and whole-genome sequencing are required for a better understanding of the zoonotic risk from Giardia infections in marsupials. Moreover, much more extensive screening of a wider range of marsupial species, particularly in peri-urban areas, is required to provide a clearer understanding of the zoonotic risk of Cryptosporidium and Giardia in marsupials.
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Criptosporidiosis , Cryptosporidium , Giardiasis , Humanos , Animales , Giardia/genética , Giardiasis/epidemiología , Giardiasis/veterinaria , Cryptosporidium/genética , Criptosporidiosis/epidemiología , Ecosistema , MacropodidaeRESUMEN
Giardia duodenalis, the protozoan responsible for giardiasis, is a significant contributor to millions of diarrheal diseases worldwide. Despite the availability of treatments for this parasitic infection, therapeutic failures are alarmingly frequent. Thus, there is a clear need to identify new therapeutic targets. Giardia telomeres were previously identified, but our understanding of these structures and the critical role played by Giardia telomerase in maintaining genomic stability and its influence on cellular processes remains limited. In this regard, it is known that all Giardia chromosomes are capped by small telomeres, organized and protected by specific proteins that regulate their functions. To counteract natural telomere shortening and maintain high proliferation, Giardia exhibits constant telomerase activity and employs additional mechanisms, such as the formation of G-quadruplex structures and the involvement of transposable elements linked to telomeric repeats. Thus, this study aims to address the existing knowledge gap by compiling the available information (until 2023) about Giardia telomeres and telomerase, focusing on highlighting the distinctive features within this parasite. Furthermore, the potential feasibility of targeting Giardia telomeres and/or telomerase as an innovative therapeutic strategy is discussed.
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Giardia lamblia , Giardiasis , Telomerasa , Humanos , Telomerasa/genética , Telomerasa/metabolismo , Giardiasis/parasitología , Giardia/genética , Telómero/genética , Giardia lamblia/genética , Giardia lamblia/metabolismoRESUMEN
BackgroundGiardia duodenalis is a major cause of gastroenteritis globally, and is the most common food- and waterborne parasitic infection in Europe.AimTo describe the epidemiology of reported acute giardiasis cases in Germany and compare demographic and clinical characteristics between imported and autochthonous cases.MethodsWe conducted a descriptive analysis of giardiasis cases that fulfilled the national case definition and were reported between January 2002 and December 2021. We defined an imported case as having at least one place of exposure abroad in the 3-25 days before symptom onset. We analysed case numbers and incidence by age, sex, month reported and geographic region, both overall and stratified by autochthonous and imported cases.ResultsFrom 2002 to 2021, 72,318 giardiasis cases were reported in Germany, corresponding to a mean annual incidence of 4.4 per 100,000 population. Annual incidence gradually decreased since 2013, declining sharply during the COVID-19 pandemic in 2020-21. Of 69,345 cases reported between 2002 and 2019, 35% were imported. Incidence of autochthonous cases (overall yearly mean: 3.1/100,000) was highest in males and young children (<â¯5 years); imported cases were predominantly adults aged 20-39 years. We identified seasonal patterns for imported and autochthonous cases.ConclusionsGiardiasis in Germany is typically assumed to be imported. Our data, however, underline the importance of autochthonous giardiasis. Travel advice might reduce imported infections, but prevention strategies for autochthonous infections are less clear. Dietary, behavioural and environmental risk factors need to be further investigated to enhance infection prevention measures for autochthonous giardiasis.
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Giardiasis , Humanos , Giardiasis/epidemiología , Alemania/epidemiología , Adulto , Masculino , Femenino , Incidencia , Persona de Mediana Edad , Adolescente , Niño , Adulto Joven , Anciano , Preescolar , Lactante , Viaje , COVID-19/epidemiología , Vigilancia de la Población , SARS-CoV-2 , Distribución por Edad , Gastroenteritis/epidemiología , Gastroenteritis/parasitología , Enfermedades Transmisibles Importadas/epidemiología , Distribución por Sexo , Estaciones del Año , Anciano de 80 o más AñosRESUMEN
Parasitic diseases, predominantly prevalent in developing countries, are increasingly spreading to high-income nations due to shifting migration patterns. The World Health Organization (WHO) estimates approximately 300 million annual cases of giardiasis. The emergence of drug resistance and associated side effects necessitates urgent research to address this growing health concern. In this study, we evaluated over eleven thousand pharmacological compounds sourced from the FDA database to assess their impact on the TATA-binding protein (TBP) of the early diverging protist Giardia lamblia, which holds medical significance. We identified a selection of potential pharmacological compounds for combating this parasitic disease through in silico analysis, employing molecular modeling techniques such as homology modeling, molecular docking, and molecular dynamics simulations. Notably, our findings highlight compounds DB07352 and DB08399 as promising candidates for inhibiting the TBP of Giardia lamblia. Also, these compounds and DB15584 demonstrated high efficacy against trophozoites in vitro. In summary, this study identifies compounds with the potential to combat giardiasis, offering the prospect of specific therapies and providing a robust foundation for future research.
Asunto(s)
Antiprotozoarios , Giardia lamblia , Giardiasis , Simulación del Acoplamiento Molecular , United States Food and Drug Administration , Giardiasis/tratamiento farmacológico , Giardia lamblia/efectos de los fármacos , Antiprotozoarios/farmacología , Antiprotozoarios/química , Estados Unidos , Humanos , Proteínas Protozoarias/química , Proteínas Protozoarias/metabolismo , Proteínas Protozoarias/antagonistas & inhibidores , Simulación de Dinámica MolecularRESUMEN
INTRODUCTION: Giardiosis is a parasitic disease caused by the protozoa Giardia lamblia (also known as Giardia intestinalis and Giardia duodenalis), which causes gastrointestinal symptoms. Infection usually occurs through the ingestion of contaminated water/food or through contact with an infected person. In Poland, giardiasis is notifiable disease, acoording to the EU deffinition implement in the polish surveillance system. AIM OF THE STUDY: The aim of this study is to asses epidemiological situation of giardiasis in Poland in 2021 and compare it to the previous years. MATERIALS AND METHODS: The assessment of the epidemiological situation of giardiasis in Poland in 2021 was performed on the basis of data from the annual bulletins "Infectious diseases and poisoning in Poland" for the years 2008-2021, data on individual cases collected for the purposes of epidemiological surveillance in the EpiBaza system and data from food-born outbreak investigations recorded in the Registry of Epidemic Outbreaks (ROE). RESULTS: In 2021, 559 cases of giardiasis were reported in Poland (558 confirmed case, 1 probable case). There was an increase in the number of reported cases in comparision to 2020 by 56% and decrease to 2019 by 29%. Cases of giardiasis were reported in all voivodeships, with the highest incidence rate in Podlaskie voivodeship (9.1/100 000), incidence rate for Poland was 1.5/100 000. Giardiasis was diagnosed in patiens in all age group, the largest group of patiens were children (age groups 0-4 and 5-9). The hospitalization rate of patients diagnosed with giardiasis was 9.7% and was lower than in 2020, when it was 12.4%. As in previous years, no deaths from giardiasis were reported. CONCLUSIONS: The number of cases of giardiasis has increased compared to 2020, but has not reached pre-pandemic levels. As in previous years, differences in the incidence by age and sex of people with the disease were noted when comparing data reported from Poland and EU/EEA countries.
Asunto(s)
Giardiasis , Polonia/epidemiología , Humanos , Giardiasis/epidemiología , Niño , Preescolar , Lactante , Masculino , Adolescente , Femenino , Adulto , Incidencia , Persona de Mediana Edad , Recién Nacido , Adulto Joven , Sistema de Registros , Giardia lamblia/aislamiento & purificación , Anciano , Distribución por Edad , Brotes de Enfermedades/estadística & datos numéricos , Población Rural/estadística & datos numéricos , Población Urbana/estadística & datos numéricos , Distribución por SexoRESUMEN
This report describes a case of giardiasis detected through stool smear analysis of postoperative stool fluid collected from a high output stoma for obstructive colorectal cancer. The patient, a 67-year-old male, underwent right hemicolectomy with ileostomy for obstructive colorectal cancer. The persistent excessive excretion of postoperative stool fluid from the stoma prompted a stool smear test. The findings revealed the presence of Giardia intestinalis. Fecal output decreased when metronidazole was administered orally. The study strongly recommends that patients with prolonged gastrointestinal symptoms need to undergo stool smear tests.