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1.
Infect Immun ; 92(6): e0006524, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38722167

RESUMEN

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.


Asunto(s)
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 , Femenino
2.
Exp Parasitol ; 262: 108773, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38723845

RESUMEN

Giardiasis is a prevalent parasitic diarrheal disease caused by Giardia lamblia, affecting people worldwide. Recently, the availability of several drugs for its treatment has highlighted issues such as multidrug resistance, limited effectiveness and undesirable side effects. Therefore, it is necessary to develop alternative new drugs and treatment strategies that can enhance therapeutic outcomes and effectively treat giardiasis. Natural compounds show promise in the search for more potent anti-giardial agents. Our investigation focused on the effect of Andrographolide (ADG), an active compound of the Andrographis paniculata plant, on Giardia lamblia, assessing trophozoite growth, morphological changes, cell cycle arrest, DNA damage and inhibition of gene expression associated with pathogenic factors. ADG demonstrated anti-Giardia activity almost equivalent to the reference drug metronidazole, with an IC50 value of 4.99 µM after 24 h of incubation. In cytotoxicity assessments and morphological examinations, it showed significant alterations in trophozoite shape and size and effectively hindered the adhesion of trophozoites. It also caused excessive ROS generation, DNA damage, cell cycle arrest and inhibited the gene expression related to pathogenesis. Our findings have revealed the anti-giardial efficacy of ADG, suggesting its potential as an agent against Giardia infections. This could offer a natural and low-risk treatment option for giardiasis, reducing the risk of side effects and drug resistance.


Asunto(s)
Antiprotozoarios , Puntos de Control del Ciclo Celular , Daño del ADN , Diterpenos , Giardia lamblia , Concentración 50 Inhibidora , Especies Reactivas de Oxígeno , Trofozoítos , Diterpenos/farmacología , Giardia lamblia/efectos de los fármacos , Giardia lamblia/crecimiento & desarrollo , Giardia lamblia/genética , Trofozoítos/efectos de los fármacos , Trofozoítos/crecimiento & desarrollo , Puntos de Control del Ciclo Celular/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Daño del ADN/efectos de los fármacos , Antiprotozoarios/farmacología , Humanos , Animales , Expresión Génica/efectos de los fármacos , Metronidazol/farmacología
3.
Euro Surveill ; 29(20)2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38757286

RESUMEN

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 (< 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.


Asunto(s)
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 Años
4.
Przegl Epidemiol ; 77(4): 520-530, 2024 May 20.
Artículo en Inglés, Polaco | MEDLINE | ID: mdl-38783661

RESUMEN

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 Sexo
5.
Gastroenterology ; 162(3): 844-858, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34822802

RESUMEN

BACKGROUND & AIMS: The protozoa Giardia duodenalis is a major cause of gastrointestinal illness worldwide, but underlying pathophysiological mechanisms remain obscure, partly due to the absence of adequate cellular models. We aimed at overcoming these limitations and recapitulating the authentic series of pathogenic events in the primary human duodenal tissue by using the human organoid system. METHODS: We established a compartmentalized cellular transwell system with electrophysiological and barrier properties akin to duodenal mucosa and dissected the events leading to G. duodenalis-induced barrier breakdown by functional analysis of transcriptional, electrophysiological, and tight junction components. RESULTS: Organoid-derived cell layers of different donors showed a time- and parasite load-dependent leak flux indicated by collapse of the epithelial barrier upon G. duodenalis infection. Gene set enrichment analysis suggested major expression changes, including gene sets contributing to ion transport and tight junction structure. Solute carrier family 12 member 2 and cystic fibrosis transmembrane conductance regulator-dependent chloride secretion was reduced early after infection, while changes in the tight junction composition, localization, and structural organization occurred later as revealed by immunofluorescence analysis and freeze fracture electron microscopy. Functionally, barrier loss was linked to the adenosine 3',5'-cyclic monophosphate (cAMP)/protein kinase A-cAMP response element-binding protein signaling pathway. CONCLUSIONS: Data suggest a previously unknown sequence of events culminating in intestinal barrier dysfunction upon G. duodenalis infection during which alterations of cellular ion transport were followed by breakdown of the tight junctional complex and loss of epithelial integrity, events involving a cAMP/protein kinase A-cAMP response element-binding protein mechanism. These findings and the newly established organoid-derived model to study G. duodenalis infection may help to explore new options for intervening with disease and infection, in particular relevant for chronic cases of giardiasis.


Asunto(s)
Giardiasis/fisiopatología , Mucosa Intestinal/fisiopatología , Transporte Iónico , Transducción de Señal , Uniones Estrechas/fisiología , Apoptosis , Células CACO-2 , Cloruros/metabolismo , AMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Duodeno , Impedancia Eléctrica , Giardia lamblia , Giardiasis/genética , Giardiasis/inmunología , Humanos , Interleucina-1/genética , Transporte Iónico/genética , FN-kappa B/genética , Organoides , Carga de Parásitos , Miembro 2 de la Familia de Transportadores de Soluto 12/genética , Uniones Estrechas/genética , Uniones Estrechas/patología , Uniones Estrechas/ultraestructura , Transcriptoma , Factor de Necrosis Tumoral alfa/genética
6.
Parasitology ; 150(12): 1096-1104, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37655745

RESUMEN

From the safety inside vehicles, Knowsley Safari offers visitors a close-up encounter with captive olive baboons. As exiting vehicles may be contaminated with baboon stool, a comprehensive coprological inspection was conducted to address public health concerns. Baboon stools were obtained from vehicles, and sleeping areas, inclusive of video analysis of baboon­vehicle interactions. A purposely selected 4-day sampling period enabled comparative inspections of 2662 vehicles, with a total of 669 baboon stools examined (371 from vehicles and 298 from sleeping areas). As informed by our pilot study, front-line diagnostic methods were: QUIK-CHEK rapid diagnostic test (RDT) (Giardia and Cryptosporidium), Kato­Katz coproscopy (Trichuris) and charcoal culture (Strongyloides). Some 13.9% of vehicles were contaminated with baboon stool. Prevalence of giardiasis was 37.4% while cryptosporidiosis was <0.01%, however, an absence of faecal cysts by quality control coproscopy, alongside lower than the expected levels of Giardia-specific DNA, judged RDT results as misleading, grossly overestimating prevalence. Prevalence of trichuriasis was 48.0% and strongyloidiasis was 13.7%, a first report of Strongyloides fuelleborni in UK. We advise regular blanket administration(s) of anthelminthics to the colony, exploring pour-on formulations, thereafter, smaller-scale indicator surveys would be adequate.


Asunto(s)
Criptosporidiosis , Cryptosporidium , Giardiasis , Parasitosis Intestinales , Parásitos , Animales , Humanos , Papio anubis , Criptosporidiosis/parasitología , Proyectos Piloto , Parasitosis Intestinales/epidemiología , Parasitosis Intestinales/veterinaria , Giardiasis/epidemiología , Papio/parasitología , Giardia , Strongyloides , Heces/parasitología , Reino Unido
7.
Parasitology ; 150(8): 693-699, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37231841

RESUMEN

The aim of this study was to determine if the protozoa that cause dysentery might have been present in Jerusalem, the capital of the Kingdom of Judah, during the Iron Age. Sediments from 2 latrines pertaining to this time period were obtained, 1 dating from the 7th century BCE and another from the 7th to early 6th century BCE. Microscopic investigations have previously shown that the users were infected by whipworm (Trichuris trichiura), roundworm (Ascaris lumbricoides), Taenia sp. tapeworm and pinworm (Enterobius vermicularis). However, the protozoa that cause dysentery are fragile and do not survive well in ancient samples in a form recognizable using light microscopy. Enzyme-linked immunosorbent assay kits designed to detect the antigens of Entamoeba histolytica, Cryptosporidium sp. and Giardia duodenalis were used. Results for Entamoeba and Cryptosporidium were negative, while Giardia was positive for both latrine sediments when the analysis was repeated three times. This provides our first microbiological evidence for infective diarrhoeal illnesses that would have affected the populations of the ancient near east. When we integrate descriptions from 2nd and 1st millennium BCE Mesopotamian medical texts, it seems likely that outbreaks of dysentery due to giardiasis may have caused ill health throughout early towns across the region.


Asunto(s)
Disentería , Giardia lamblia , Giardiasis , Humanos , Disentería/historia , Disentería/parasitología , Heces/parasitología , Giardiasis/diagnóstico , Historia Antigua , Ensayo de Inmunoadsorción Enzimática , Antígenos Helmínticos/análisis , Israel
8.
Int J Mol Sci ; 24(2)2023 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-36675151

RESUMEN

Apicomplexan infections, such as giardiasis and cryptosporidiosis, negatively impact a considerable proportion of human and commercial livestock populations. Despite this, the molecular mechanisms of disease, particularly the effect on the body beyond the gastrointestinal tract, are still poorly understood. To highlight host-parasite-microbiome biochemical interactions, we utilised integrated metabolomics-16S rRNA genomics and metabolomics-proteomics approaches in a C57BL/6J mouse model of giardiasis and compared these to Cryptosporidium and uropathogenic Escherichia coli (UPEC) infections. Comprehensive samples (faeces, blood, liver, and luminal contents from duodenum, jejunum, ileum, caecum and colon) were collected 10 days post infection and subjected to proteome and metabolome analysis by liquid and gas chromatography-mass spectrometry, respectively. Microbial populations in faeces and luminal washes were examined using 16S rRNA metagenomics. Proteome-metabolome analyses indicated that 12 and 16 key pathways were significantly altered in the gut and liver, respectively, during giardiasis with respect to other infections. Energy pathways including glycolysis and supporting pathways of glyoxylate and dicarboxylate metabolism, and the redox pathway of glutathione metabolism, were upregulated in small intestinal luminal contents and the liver during giardiasis. Metabolomics-16S rRNA genetics integration indicated that populations of three bacterial families-Autopobiaceae (Up), Desulfovibrionaceae (Up), and Akkermanasiaceae (Down)-were most significantly affected across the gut during giardiasis, causing upregulated glycolysis and short-chained fatty acid (SCFA) metabolism. In particular, the perturbed Akkermanasiaceae population seemed to cause oxidative stress responses along the gut-liver axis. Overall, the systems biology approach applied in this study highlighted that the effects of host-parasite-microbiome biochemical interactions extended beyond the gut ecosystem to the gut-liver axis. These findings form the first steps in a comprehensive comparison to ascertain the major molecular and biochemical contributors of host-parasite interactions and contribute towards the development of biomarker discovery and precision health solutions for apicomplexan infections.


Asunto(s)
Criptosporidiosis , Cryptosporidium , Microbioma Gastrointestinal , Giardiasis , Microbiota , Ratones , Animales , Humanos , ARN Ribosómico 16S/genética , ARN Ribosómico 16S/metabolismo , Regulación hacia Arriba , Proteoma/metabolismo , Criptosporidiosis/metabolismo , Ratones Endogámicos C57BL , Cryptosporidium/metabolismo , Metabolómica , Metaboloma , Hígado/metabolismo , Oxidación-Reducción
9.
Chimia (Aarau) ; 77(9): 574-576, 2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-38047832

RESUMEN

Quinacrine, the main antimalarial drug during World War II, has had a chequered history that included the successful repurposing as an intrapleural sclerosant for the treatment of malignant pleural effusions, a non-surgical method of female sterilisation, and the use as an immunomodulatory drug in lupus erythematosus. While no longer used for these former indications, quinacrine (re)emerged as an indispensable second-line drug for the treatment of nitroimidazole-refractory Giardia duodenalis infections, and thus depicts an indispensable "orphan drug".


Asunto(s)
Antiinfecciosos , Antimaláricos , Nitroimidazoles , Femenino , Humanos , Antimaláricos/farmacología , Quinacrina/farmacología , Antiparasitarios/farmacología
10.
Clin Microbiol Rev ; 34(4): e0002419, 2021 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-34378955

RESUMEN

Giardia duodenalis captured the attention of Leeuwenhoek in 1681 while he was examining his own diarrheal stool, but, ironically, it did not really gain attention as a human pathogen until the 1960s, when outbreaks were reported. Key technological advances, including in vitro cultivation, genomic and proteomic databases, and advances in microscopic and molecular approaches, have led to an understanding that this is a eukaryotic organism with a reduced genome rather than a truly premitochondriate eukaryote. This has included the discovery of mitosomes (vestiges of mitochondria), a transport system with many of the features of the Golgi apparatus, and even evidence for a sexual or parasexual cycle. Cell biology approaches have led to a better understanding of how Giardia survives with two nuclei and how it goes through its life cycle as a noninvasive organism in the hostile environment of the lumen of the host intestine. Studies of its immunology and pathogenesis have moved past the general understanding of the importance of the antibody response in controlling infection to determining the key role of the Th17 response. This work has led to understanding of the requirement for a balanced host immune response that avoids the extremes of an excessive response with collateral damage or one that is unable to clear the organism. This understanding is especially important in view of the remarkable ranges of early manifestations, which range from asymptomatic to persistent diarrhea and weight loss, and longer-term sequelae that include growth stunting in children who had no obvious symptoms and a high frequency of postinfectious irritable bowel syndrome (IBS).


Asunto(s)
Giardia lamblia , Giardiasis , Síndrome del Colon Irritable , Diarrea , Humanos , Masculino , Proteómica
11.
J Infect Dis ; 226(2): 319-323, 2022 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-35262728

RESUMEN

The protozoan pathogen Giardia lamblia is an important worldwide cause of diarrheal disease and malabsorption. Infection is managed with antimicrobials, although drug resistance and treatment failures are a clinical challenge. Prior infection provides significant protection, yet a human vaccine has not been realized. Individual antigens can elicit partial protection in experimental models, but protection is weaker than after prior infection. Here, we developed a multivalent nanovaccine by coating membranes derived from the parasite onto uniform and stable polymeric nanoparticles loaded with a mucosal adjuvant. Intranasal immunization with the nanovaccine induced adaptive immunity and effectively protected mice from G. lamblia infection.


Asunto(s)
Giardia lamblia , Giardiasis , Nanopartículas , Parásitos , Adyuvantes Inmunológicos , Animales , Giardiasis/parasitología , Giardiasis/prevención & control , Humanos , Inmunidad Mucosa , Ratones
12.
J Infect Dis ; 225(10): 1773-1776, 2022 05 16.
Artículo en Inglés | MEDLINE | ID: mdl-34036328

RESUMEN

BACKGROUND: Limited evidence exists on efficacy and tolerability of quinacrine for nitroimidazole-refractory giardiasis. METHODS: Nitroimidazole-refractory giardiasis cases, defined as microbiologically (microscopy and/or PCR) confirmed treatment failure after 2 courses, during 2008-2020, were retrospectively identified. RESULTS: Of 87 patients, 54 (62%) had visited India. Quinacrine was used in 54 (62%); 51 received monotherapy and 3 combined with metronidazole. Only 3 had positive stool samples with persisting symptoms after quinacrine treatment (94% parasitological efficacy) and all were cured after a second treatment. One (1.9%) had mild adverse effects recorded. CONCLUSIONS: Quinacrine is an effective treatment for nitroimidazole-refractory giardiasis with good tolerability.


Asunto(s)
Antiprotozoarios , Giardiasis , Nitroimidazoles , Giardiasis/tratamiento farmacológico , Humanos , Metronidazol/uso terapéutico , Nitroimidazoles/uso terapéutico , Quinacrina/efectos adversos , Quinacrina/uso terapéutico , Estudios Retrospectivos
13.
Eur J Clin Microbiol Infect Dis ; 41(5): 835-839, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35243573

RESUMEN

Cryptosporidiosis has been a notifiable infection in Norway since 2012 and giardiasis since 1977. For both infections, there has been an increase in notified cases. We used a questionnaire to explore whether this may be associated with implementation of molecular diagnostic methods. We received responses from 14 of 16 laboratories, most of which had implemented molecular diagnostic methods for these parasites. Algorithms for testing had also been modified, and several laboratories now test more faecal samples than previously for both parasites. The increase in reported cases may reflect not only higher sensitivity of diagnostic methods, but also more sample testing.


Asunto(s)
Criptosporidiosis , Cryptosporidium , Giardiasis , Algoritmos , Criptosporidiosis/diagnóstico , Criptosporidiosis/parasitología , Cryptosporidium/genética , Atención a la Salud , Heces/parasitología , Giardiasis/diagnóstico , Giardiasis/parasitología , Humanos , Reacción en Cadena de la Polimerasa
14.
Exp Parasitol ; 240: 108329, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35868574

RESUMEN

Intestinal epithelial cells (IECs) reside in a highly anaerobic environment that is subject to daily fluctuations in partial oxygen pressure (pO2), depending on intestinal tissue perfusion. This condition, known as physiological hypoxia, has a major impact on the maintenance of gut homeostasis, such as effects on the integrity and function of the intestinal epithelial barrier. Giardia lamblia is a microaerophilic protozoan parasite that infects and colonizes the small intestine of its host, causing watery diarrhea. The disease, known as giardiasis, is associated with enhanced intestinal permeability and disruption or reorganization of tight junction (TJ) proteins between IECs. Given the central role of oxygen in gut homeostasis, in this study, we aimed to evaluate whether pO2 affects intestinal permeability (flux of ions and macromolecules) and TJ protein expression in human IECs during G. lamblia infection. Using human cell lines HuTu-80 and Caco-2 as models of "loose" (low resistance) and "tight" (high resistance) intestines, respectively, we elucidated that low pO2 drives intestinal barrier dysfunction in IECs infected with trophozoites through dephosphorylation of protein kinase C (PKC α/ß II). Additionally, we demonstrated that IECs infected with trophozoites in the presence of a pharmacological PKC activator (phorbol 12-myristate 13-acetate) partially restored the barrier function, which was correlated with increased protein expression levels of zonula occludens (ZO)-2 and occludin. Collectively, these results support the emerging theory that molecular oxygen impacts gut homeostasis during Giardia infection via direct host signaling pathways. These findings further our knowledge regarding Giardia-host interactions and the pathophysiological mechanisms of human giardiasis.


Asunto(s)
Giardia lamblia , Giardiasis , Células CACO-2 , Células Epiteliales/parasitología , Giardia lamblia/metabolismo , Giardiasis/parasitología , Humanos , Mucosa Intestinal/parasitología , Oxígeno/metabolismo , Permeabilidad , Uniones Estrechas/metabolismo , Proteína de la Zonula Occludens-1/metabolismo
15.
Ann Diagn Pathol ; 61: 152031, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36055006

RESUMEN

OBJECTIVE: To measure the villous height, the crypt depth, and the number of intraepithelial lymphocytes/100 enterocytes of the small intestinal mucosa of children and adolescents with celiac disease; and to classify these findings according to Q- Marsh and Q-histology scales. METHODS: Retrospective study of a database from the Department of Pathology of biopsies from the second portion of the duodenum of pediatric patients. According to the histological report, three groups were established: celiac disease at diagnosis (n = 50), controls (n = 26), giardiasis (n = 10). In each biopsy, software (cellSens and Image J) evaluated 5 villous heights, 5 crypt depth and the number of intraepithelial lymphocytes/100 enterocytes. RESULTS: The celiac group had the lowest mean villous height (197.83 µm) of all three groups (control = 477.70 µm; giardiasis = 397.04 µm. The celiac group's villous:crypt ratio (0.78) was significantly lower than the control group (1.89). The number of intraepithelial lymphocytes ≥25 was exclusive to the celiac group, with a sensitivity and specificity of 100 %. Only celiac patients were included in types 2 and 3 of the Q-histology classification. CONCLUSION: Celiac disease patients showed shorter villous height than other groups, and the number of intraepithelial lymphocytes ≥25 was the best parameter to differentiate celiac from controls and giardiasis groups. Intraepithelial lymphocytes ≥25/100 enterocytes associated with any degree of villous atrophy, the classic Marsh 3 type, set the histological parameters of celiac disease. Quantitative histology is a valuable tool for diagnosing celiac disease, enabling histological changes in a short time, and the Q-histology scale appears to be more suitable than the Q-Marsh scale.


Asunto(s)
Enfermedad Celíaca , Giardiasis , Humanos , Niño , Adolescente , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/patología , Giardiasis/diagnóstico , Giardiasis/patología , Estudios Retrospectivos , Duodeno/patología , Mucosa Intestinal/patología , Biopsia
16.
Int J Mol Sci ; 23(22)2022 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-36430836

RESUMEN

Treatments to combat giardiasis have been reported to have several drawbacks, partly due to the drug resistance and toxicity of current antiparasitic agents. These constraints have prompted many researchers to investigate new drugs that act against protozoan parasites. Enzyme inhibition is an important means of regulating pathogen metabolism and has recently been identified as a significant alternative target in the search for new treatments. Glucose-6-phosphate dehydrogenase and 6-phosphogluconolactonase (G6PD::6PGL) is a bifunctional enzyme involved in the pentose phosphate pathway (PPP) in Giardia lamblia (G. lamblia). The G. lamblia enzyme is unusual since, unlike the human enzyme, it is a fused enzyme. Here, we show, through inhibition assays, that an in-house chemical library of 120 compounds and four target compounds, named CNZ-7, CNZ-8, CMC-1, and FLP-2, are potent inhibitors of the G. lamblia G6PD::6PGL fused enzyme. With a constant (k2) of 2.3, 3.2, and 2.8 M−1 s−1, respectively, they provoke alterations in the secondary and tertiary protein structure and global stability. As a novel approach, target compounds show antigiardial activity, with IC50 values of 8.7, 15.2, 15.3, and 24.1 µM in trophozoites from G. lamblia. Moreover, these compounds show selectivity against G. lamblia, since, through counter-screening in Caco-2 and HT29 human cells, they were found to have low toxicity. This finding positions these compounds as a potential and attractive starting point for new antigiardial drugs.


Asunto(s)
Giardia lamblia , Giardiasis , Animales , Humanos , Giardiasis/tratamiento farmacológico , Giardiasis/parasitología , Trofozoítos/metabolismo , Glucosafosfato Deshidrogenasa/metabolismo , Células CACO-2
17.
Int J Mol Sci ; 23(21)2022 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-36362435

RESUMEN

In giardiasis, diarrhoea, dehydration, malabsorption, weight loss and/or chronic inflammation are indicative of epithelial barrier dysfunction. However, the pathogenesis of giardiasis is still enigmatic in many aspects. Here, we show evidence that a cysteine protease of Giardia duodenalis called giardipain-1, contributes to the pathogenesis of giardiasis induced by trophozoites of the WB strain. In an experimental system, we demonstrate that purified giardipain-1 induces apoptosis and extrusion of epithelial cells at the tips of the villi in infected jirds (Meriones unguiculatus). Moreover, jird infection with trophozoites expressing giardipain-1 resulted in intestinal epithelial damage, cellular infiltration, crypt hyperplasia, goblet cell hypertrophy and oedema. Pathological alterations were more pronounced when jirds were infected intragastrically with Giardia trophozoites that stably overexpress giardipain-1. Furthermore, Giardia colonization in jirds results in a chronic inflammation that could relate to the dysbiosis triggered by the protist. Taken together, these results reveal that giardipain-1 plays a key role in the pathogenesis of giardiasis.


Asunto(s)
Proteasas de Cisteína , Giardia lamblia , Giardiasis , Animales , Proteasas de Cisteína/genética , Gerbillinae , Giardia , Trofozoítos , Mucosa Intestinal/patología , Homeostasis , Inflamación
18.
Int J Mol Sci ; 23(19)2022 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-36232855

RESUMEN

Beyond the problem in public health that protist-generated diseases represent, understanding the variety of mechanisms used by these parasites to interact with the human immune system is of biological and medical relevance. Giardia lamblia is an early divergent eukaryotic microorganism showing remarkable pathogenic strategies for evading the immune system of vertebrates. Among various multifunctional proteins in Giardia, arginine deiminase is considered an enzyme that plays multiple regulatory roles during the life cycle of this parasite. One of its most important roles is the crosstalk between the parasite and host. Such a molecular "chat" is mediated in human cells by membrane receptors called Toll-like receptors (TLRs). Here, we studied the importance of the 3D structure of giardial arginine deiminase (GlADI) to immunomodulate the human immune response through TLRs. We demonstrated the direct effect of GlADI on human TLR signaling. We predicted its mode of interaction with TLRs two and four by using the AlphaFold-predicted structure of GlADI and molecular docking. Furthermore, we showed that the immunomodulatory capacity of this virulent factor of Giardia depends on the maintenance of its 3D structure. Finally, we also showed the influence of this enzyme to exert specific responses on infant-like dendritic cells.


Asunto(s)
Giardia , Giardiasis , Animales , Humanos , Hidrolasas , Inmunidad , Inmunomodulación , Simulación del Acoplamiento Molecular , Receptores Toll-Like
19.
Medicina (Kaunas) ; 58(4)2022 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-35454310

RESUMEN

Background and Objectives: Protozoan parasites-Cryptosporidium and Giardia-are important causes of diarrhea with an underestimated short-term burden on childhood growth and wellbeing in children under five years of age. The main transmission routes for both parasites are food and drinking water; transmission from person to person; and, due to their zoonotic nature, from domestic or wild animals to humans. The aims of the present study were to summarize the officially reported human cases of cryptosporidiosis and giardiasis in Latvia and to assess the occurrence of Cryptosporidium and Giardia in children within a prospective prevalence study. Materials and Methods: The number of officially reported cases of cryptosporidiosis and giardiasis in the time period of 2000-2020 was collected from the Centre for Disease Prevention and Control of Latvia. Data from a clinical diagnostic laboratory were included in the study in the period from 1 January 2008 to 31 December 2018. Additionally, a prospective study was performed, and fecal samples were collected from unique 0-17-year-old patients from January to February 2021 and tested using fluorescent microscopy. Results: Overall, during the 20-year period, 71 cases (mean per year = 9) of cryptosporidiosis and 1020 (mean per year = 34) cases of giardiasis were officially reported in Latvia. Meanwhile, within the prospective study, we found 35 (6.0%; 95%CI 4.3-8.1) Cryptosporidium and 42 (7.2%; 95%CI 5.3-9.6) Giardia cases. Conclusions: Here, we provide clear proof that both Cryptosporidium and Giardia are underdiagnosed in Latvia, which could also be true for neighboring Baltic and European countries, where a low number of cases are officially reported. Therefore, we highlight the hypothesis that the actual number of cryptosporidiosis and giardiasis human cases in the Baltic states is higher than that officially reported, including in Latvia.


Asunto(s)
Criptosporidiosis , Cryptosporidium , Giardiasis , Animales , Niño , Preescolar , Criptosporidiosis/diagnóstico , Criptosporidiosis/epidemiología , Criptosporidiosis/parasitología , Giardia , Giardiasis/diagnóstico , Giardiasis/epidemiología , Giardiasis/parasitología , Humanos , Letonia/epidemiología , Prevalencia , Estudios Prospectivos
20.
Internist (Berl) ; 63(4): 379-387, 2022 Apr.
Artículo en Alemán | MEDLINE | ID: mdl-35244737

RESUMEN

Gastrointestinal infections are among the most frequent imported diseases diagnosed in Germany in travelers or migrants from the tropics. Acute traveler's diarrhea is the most frequent illness in long-distance travelers and in high-risk areas (e.g. India, Mexico) around one third of all travelers suffer from diarrhea. Chronic diarrhea plays a role especially after longer stays abroad (> 4 weeks) and in migrants and is often caused by protozoa. Helminths are less frequently the causative agent of gastrointestinal complaints (diarrhea, nausea, abdominal pain). A worm infestation of the large and small intestines is often present but helminths can also affect the liver or lead to generalized symptoms of illness when larvae migrate. In principle, in the case of gastrointestinal complaints after exposure to the tropics, the possibility of an imported tropical endemic infectious disease must be considered and appropriate diagnostics initiated. For travelers returning from tropical countries other, sometimes life-threatening diseases, such as malaria, typhoid fever, rickettsiosis and viral hemorrhagic fever (VHF) can present with gastrointestinal symptoms and should never be overlooked.


Asunto(s)
Enfermedades Transmisibles , Migrantes , Enfermedades Transmisibles/epidemiología , Diarrea/diagnóstico , Diarrea/epidemiología , Diarrea/etiología , Alemania , Humanos , Viaje
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