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1.
J Parasitol ; 108(1): 1-9, 2022 01 01.
Article in English | MEDLINE | ID: mdl-34995352

ABSTRACT

Giardia duodenalis genotypes A and B have been reported in Colombia. The population consisted of 235 schoolchildren whose ages ranged from 2 to 10 yr of age from the municipalities of Soledad and Galapa in the department of Atlántico, Colombia. Fecal samples were obtained and then analyzed in triplicate using the sedimentation in formalin-ether (Ritchie's method) and direct examination techniques. Of the 235 fecal samples, 35 samples were positive for G. duodenalis; positive samples were concentrated in a sucrose gradient and sonicated for 3 cycles of 20 sec. DNA extraction was performed, and the parasites were genotyped by conventional PCR amplifying a region of the ß-giardin gene. A general prevalence of G. duodenalis of 13.2% was found, and of these genotyped samples, 13 (56.7%) and 7 (20%) corresponded to genotype A, 1 (4.3%), and 3 (25%) corresponded to genotype B, and 9 (39.1%) and 2 (16.7%) were not defined, in the municipalities Soledad and Galapa, respectively. Additionally, 23 children were diagnosed with symptomatologic giardiasis, and 12 were asymptomatic; the most relevant symptoms were abdominal pain (7, 20%) and diarrhea (13, 56.7%). The nutritional status of children with Giardia genotypes A and B were as follows: 3 in a state of malnutrition (10%), 10 normal (33.3%), and 6 overweight and obese (20%) with genotype A, and 1 in a state of malnutrition (3.3%) and 3 normal (10%) with genotype B. The genotypes found in G. duodenalis did not show an association with nutritional status or with the clinical manifestations evaluated in schoolchildren.


Subject(s)
Giardia lamblia/classification , Giardiasis/parasitology , Malnutrition/complications , Nutritional Status/physiology , Child , Child, Preschool , Colombia , Genotype , Genotyping Techniques , Giardia lamblia/genetics , Giardiasis/complications , Giardiasis/physiopathology , Humans , Malnutrition/parasitology
2.
Gastroenterology ; 162(3): 844-858, 2022 03.
Article in English | MEDLINE | ID: mdl-34822802

ABSTRACT

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.


Subject(s)
Giardiasis/physiopathology , Intestinal Mucosa/physiopathology , Ion Transport , Signal Transduction , Tight Junctions/physiology , Apoptosis , Caco-2 Cells , Chlorides/metabolism , Cyclic AMP/metabolism , Cyclic AMP-Dependent Protein Kinases/metabolism , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Duodenum , Electric Impedance , Giardia lamblia , Giardiasis/genetics , Giardiasis/immunology , Humans , Interleukin-1/genetics , Ion Transport/genetics , NF-kappa B/genetics , Organoids , Parasite Load , Solute Carrier Family 12, Member 2/genetics , Tight Junctions/genetics , Tight Junctions/pathology , Tight Junctions/ultrastructure , Transcriptome , Tumor Necrosis Factor-alpha/genetics
3.
Naunyn Schmiedebergs Arch Pharmacol ; 394(9): 1869-1878, 2021 09.
Article in English | MEDLINE | ID: mdl-34324017

ABSTRACT

Giardia duodenalis is a common cause of infection in children and travelers. The most frequent symptom is diarrhea in these patients. G. duodenalis trophozoites use a highly specialized adhesive disc to attach the host intestinal epithelium to induce intestinal damages. Pathological features of the small intestine following giardiasis include villous atrophy; infiltration of granulocytes, lymphocytes, and plasma cells into the lamina propria; and nodular lymphoid hyperplasia. The disturbed intestinal microbiota has been observed in patients with giardiasis. Therefore, a growing body of evidence has emphasized restoring the gut microbiome by probiotics in giardiasis. This study aimed to review the literature to find the pathologic features of giardiasis and its relationship with imbalanced microbiota. Then, benefits of probiotics in giardiasis and their potential molecular mechanisms were discussed. It has been illustrated that using probiotics (e.g., Lactobacillus and Saccharomyces) can reduce the time of gastrointestinal symptoms and repair the damages, particularly in giardiasis. Probiotics' capability in restoring the composition of commensal microbiota may lead to therapeutic outcomes. According to preclinical and clinical studies, probiotics can protect against parasite-induced mucosal damages via increasing the antioxidant capacity, suppressing oxidative products, and regulating the systemic and mucosal immune responses. In addition, they can reduce the proportion of G. duodenalis load by directly targeting the parasite. They can destroy the cellular architecture of parasites and suppress the proliferation and growth of trophozoites via the production of some factors with anti-giardial features. Further researches are required to find suitable probiotics for the prevention and treatment of giardiasis.


Subject(s)
Giardia lamblia/isolation & purification , Giardiasis/therapy , Probiotics/administration & dosage , Animals , Child , Diarrhea/parasitology , Diarrhea/therapy , Gastrointestinal Microbiome , Giardiasis/physiopathology , Humans , Intestine, Small/parasitology , Lactobacillus , Saccharomyces
4.
J Med Chem ; 63(22): 13330-13354, 2020 11 25.
Article in English | MEDLINE | ID: mdl-32869995

ABSTRACT

Giardia parasites are ubiquitous protozoans of global importance that impact a wide range of animals including humans. They are the most common enteric pathogen of cats and dogs in developed countries and infect ∼1 billion people worldwide. While Giardia infections can be asymptomatic, they often result in severe and chronic diseases. There is also mounting evidence that they are linked to postinfection disorders. Despite growing evidence of the widespread morbidity associated with Giardia infections, current treatment options are limited to compound classes with broad antimicrobial activity. Frontline anti-Giardia drugs are also associated with increasing drug resistance and treatment failures. To improve the health and well-being of millions, new selective anti-Giardia drugs are needed alongside improved health education initiatives. Here we discuss current treatment options together with recent advances and gaps in drug discovery. We also propose criteria to guide the discovery of new anti-Giardia compounds.


Subject(s)
Antiprotozoal Agents/administration & dosage , Drug Discovery/trends , Gastrointestinal Tract/drug effects , Gastrointestinal Tract/parasitology , Giardia/drug effects , Giardiasis/drug therapy , Animals , Antiprotozoal Agents/chemistry , Benzimidazoles/administration & dosage , Benzimidazoles/chemistry , Drug Delivery Systems/methods , Drug Delivery Systems/trends , Drug Discovery/methods , Drug Therapy, Combination , Giardia/physiology , Giardiasis/physiopathology , Humans , Nitroimidazoles/administration & dosage , Nitroimidazoles/chemistry , Nitroimidazoles/therapeutic use
5.
Adv Parasitol ; 106: 129-169, 2019.
Article in English | MEDLINE | ID: mdl-31630757

ABSTRACT

During the course of giardiasis in humans and experimental models, G. duodenalis trophozoites express and secrete several proteins (ESPs) affecting structural, cellular and soluble components of the host intestinal milieu. These include the toxin-like molecules CRP136 and ESP58 that induce intestinal hyper-peristalsis. After the completion of the Giardia genome database and using up-to date transcriptomic and proteomic approaches, secreted 'virulence factors' have also been identified and experimentally characterized. This repertoire includes arginine deiminase (ADI) that competes for arginine, an important energy source for trophozoites, some high-cysteine membrane proteins (HCMPs) and VSP88, a versatile variant surface protein (VSP) that functions as an extracellular protease. Another giardial protein, enolase, moonlights as a metabolic enzyme that interacts with the fibrinolytic system and damages host epithelial cells. Other putative Giardia virulence factors are cysteine proteases that degrade multiple host components including mucin, villin, tight junction proteins, immunoglobulins, defensins and cytokines. One of these proteases, named giardipain-1, decreases transepithelial electrical resistance and induces apoptosis in epithelial cells. A putative role for tenascins, present in the Giardia's secretome, is interfering with the host epidermal growth factor. Based on the roles that these molecules play, drugs may be designed to interfere with their functions. This review presents a comprehensive description of secreted Giardia virulence factors. It further describes their cytotoxic mechanisms and roles in the pathophysiology of giardiasis, and then assesses their potential as targets for drug development.


Subject(s)
Epithelial Cells/parasitology , Giardia/metabolism , Giardiasis/physiopathology , Protozoan Proteins/metabolism , Virulence Factors/metabolism , Animals , Humans
6.
Parasitol Res ; 118(12): 3509-3517, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31624910

ABSTRACT

Cryptosporidium spp. and Giardia duodenalis are protozoan parasites that cause diarrhea in humans and animals. Molecular data on Cryptosporidium spp. and G. duodenalis in calves in the Republic of Korea (ROK) is limited; thus, we investigated the prevalence of Cryptosporidium and Giardia in pre-weaned calves, analyzed the association between these parasites and diarrhea, and identified their zoonotic potential for human infection. Fecal samples were collected from 315 pre-weaned calves aged 1-60 days from 10 different regions in the ROK and screened for Cryptosporidium spp. and G. duodenalis using PCR. Overall prevalence of Cryptosporidium spp. and G. duodenalis was 4.4% (n = 14) and 12.7% (n = 40), respectively. Co-infection was not detected. All Cryptosporidium-positive samples were identified as C. parvum after sequence analysis of a small subunit rRNA fragment and further subtyped into zoonotic IIaA15G2R1 (n = 13) and IIaA18G3R1 (n = 1) by DNA sequencing of the 60-kDa glycoprotein gene. To our knowledge, this is the first report of C. parvum IIaA15G2R1 subtype in calves in the ROK. Based on ß-giardin (bg) gene, G. duodenalis-positive samples belonged to assemblages E (n = 36) and A (n = 4), with the latter belonging to subtype A1, the zoonotic genotype. Six subtypes of assemblage E were identified at the bg locus: E1 (n = 6), E2 (n = 3), E3 (n = 13), E5 (n = 1), E8 (n = 1), and E11 (n = 1). The occurrence of C. parvum and G. duodenalis was not associated with diarrhea in pre-weaned Korean native calves. The present results suggest that the prevalence of C. parvum is not related to calf age; in contrast, the prevalence of G. duodenalis was significantly higher in 41-50-day-old calves (odds ratio = 9.90, 95% confidence interval 2.37-41.34; P = 0.001) than in 1-10-day-old calves. Therefore, calves are a potential source of zoonotic transmission, which may have significant public health implications.


Subject(s)
Cattle Diseases/parasitology , Cryptosporidiosis/parasitology , Cryptosporidium/genetics , Cryptosporidium/isolation & purification , Giardia/genetics , Giardiasis/veterinary , Animals , Cattle , Cattle Diseases/epidemiology , Cattle Diseases/physiopathology , Cryptosporidiosis/epidemiology , Cryptosporidiosis/physiopathology , Cryptosporidium/classification , Feces/parasitology , Female , Genotype , Giardia/classification , Giardia/isolation & purification , Giardiasis/epidemiology , Giardiasis/parasitology , Giardiasis/physiopathology , Male , Polymerase Chain Reaction , Prevalence , Republic of Korea/epidemiology , Weaning
7.
Infect Immun ; 85(6)2017 06.
Article in English | MEDLINE | ID: mdl-28396324

ABSTRACT

Giardia lamblia is the most frequently identified protozoan cause of intestinal infection. Over 200 million people are estimated to have acute or chronic giardiasis, with infection rates approaching 90% in areas where Giardia is endemic. Despite its significance in global health, the mechanisms of pathogenesis associated with giardiasis remain unclear, as the parasite neither produces a known toxin nor induces a robust inflammatory response. Giardia colonization and proliferation in the small intestine of the host may, however, disrupt the ecological homeostasis of gastrointestinal commensal microbes and contribute to diarrheal disease associated with giardiasis. To evaluate the impact of Giardia infection on the host microbiota, we used culture-independent methods to quantify shifts in the diversity of commensal microbes throughout the gastrointestinal tract in mice infected with Giardia We discovered that Giardia's colonization of the small intestine causes a systemic dysbiosis of aerobic and anaerobic commensal bacteria. Specifically, Giardia colonization is typified by both expansions in aerobic Proteobacteria and decreases in anaerobic Firmicutes and Melainabacteria in the murine foregut and hindgut. Based on these shifts, we created a quantitative index of murine Giardia-induced microbial dysbiosis. This index increased at all gut regions during the duration of infection, including both the proximal small intestine and the colon. Giardiasis could be an ecological disease, and the observed dysbiosis may be mediated directly via the parasite's unique anaerobic fermentative metabolism or indirectly via parasite induction of gut inflammation. This systemic alteration of murine gut commensal diversity may be the cause or the consequence of inflammatory and metabolic changes throughout the gut. Shifts in the commensal microbiota may explain observed variations in giardiasis between hosts with respect to host pathology, degree of parasite colonization, infection initiation, and eventual clearance.


Subject(s)
Dysbiosis/parasitology , Gastrointestinal Microbiome , Giardiasis/physiopathology , Intestine, Small/parasitology , Animals , Female , Giardia lamblia , Host-Pathogen Interactions , Intestine, Small/microbiology , Mice , Mice, Inbred C57BL , Parasite Load
8.
Trends Parasitol ; 33(7): 561-576, 2017 07.
Article in English | MEDLINE | ID: mdl-28336217

ABSTRACT

Intestinal protozoa are important etiological agents of diarrhea, particularly in children, yet the public health risk they pose is often neglected. Results from the Global Enteric Multicenter Study (GEMS) showed that Cryptosporidium is among the leading causes of moderate to severe diarrhea in children under 2 years. Likewise, Giardia infects approximately 200 million individuals worldwide, and causes acute diarrhea in children under 5 years. Despite this recognized role as pathogens, the question is why and how these parasites cause disease in some individuals but not in others. This review focuses on known pathogenic mechanisms of Cryptosporidium and Giardia, and infection progress towards disease.


Subject(s)
Cryptosporidiosis/physiopathology , Giardiasis/physiopathology , Age Factors , Cryptosporidiosis/parasitology , Cryptosporidium/pathogenicity , Giardia/pathogenicity , Giardiasis/parasitology , Humans
9.
Parasitol Res ; 116(3): 939-944, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28039497

ABSTRACT

In this study were proposed different protocols for the treatment of mice naturally infected with Giardia muris. Male Swiss mice were divided into seven groups, with five animals each, in a blind, controlled, randomized by drawing lots and once-repeated experiment. Parasite detection and cure control were performed using the Faust method and search by trophozoites in the intestinal mucosa. Clinical parameters (weight, water and feed consumption, elimination of excreta, aspect of the fur and feces) were also evaluated. All animals were treated with metronidazole (M), fenbendazole (F), and probiotics (P), administered intragastrically, during 7 days. M1, FM1, and F1 groups were treated 1×/day; M3, FM3, and PM3 groups 3×/day; and ST (control group) received only water. After the 5th and 7th days of treatment, the animals in FM1/FM3 and PM3/M3 groups presented, respectively, negative results and remained negative in the following 10 days. Animals in F1 group consumed less water (p = 0.00010) compared with FM1/FM3/PM3. The animals in M1 group compared with FM3/M3, F1 compared with M3, and ST compared with FM1/FM3/M3/PM3 consumed a larger amount of feed (p = 0.00001). The animals in F1 group compared with FM3/M1/M3/PM3, FM1 compared with FM3, and ST compared with FM3/M1/M3/PM3 eliminated lower volume of excreta (p = 0.00001). The results show that the association between F and M potentiates the effects, indicating a synergistic action of these two drugs, and FM1 is the best protocol due to early negativity in the animals, lower concentrations of the drugs, lower risk of toxicity and stress, and less alterations in clinical parameters.


Subject(s)
Antiprotozoal Agents/administration & dosage , Fenbendazole/administration & dosage , Giardia/drug effects , Giardiasis/drug therapy , Metronidazole/administration & dosage , Animals , Body Weight/drug effects , Drug Synergism , Feces/parasitology , Female , Giardia/physiology , Giardiasis/parasitology , Giardiasis/physiopathology , Humans , Intestinal Mucosa/parasitology , Male , Mice , Trophozoites/drug effects , Trophozoites/physiology
10.
Antimicrob Agents Chemother ; 59(11): 6749-54, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26282413

ABSTRACT

Enteric protozoan parasites, which are spread by the fecal-oral route, are important causes of diarrhea (Giardia duodenalis) and amebic dysentery (Entamoeba histolytica). Cyst walls of Giardia and Entamoeba have a single layer composed of fibrils of ß-1,3-linked GalNAc and ß-1,4-linked GlcNAc (chitin), respectively. The goal here was to determine whether hand sanitizers that contain ethanol or isopropanol as the active microbicide might reduce transmission of these parasites. We found that treatment with these alcohols with or without drying in a rotary evaporator (to model rapid evaporation of sanitizers on hands) kills 85 to 100% of cysts of G. duodenalis and 90 to 100% of cysts of Entamoeba invadens (a nonpathogenic model for E. histolytica), as shown by nuclear labeling with propidium iodide and failure to excyst in vitro. Alcohols with or without drying collapsed the cyst walls of Giardia but did not collapse the cyst walls of Entamoeba. To validate the in vitro results, we showed that treatment with alcohols eliminated oral infection of gerbils by 1,000 G. duodenalis cysts, while a commercial hand sanitizer (Purell) killed E. invadens cysts that were directly applied to the hands. These results suggest that expanded use of alcohol-based hand sanitizers might reduce the transmission of Giardia and Entamoeba.


Subject(s)
Entamoeba/pathogenicity , Giardia/pathogenicity , Hand Sanitizers/therapeutic use , 2-Propanol/pharmacokinetics , 2-Propanol/therapeutic use , Animals , Entamoeba/drug effects , Ethanol/pharmacology , Ethanol/therapeutic use , Female , Gerbillinae , Giardia/drug effects , Giardiasis/drug therapy , Giardiasis/physiopathology , Hand Sanitizers/pharmacology
11.
Georgian Med News ; (236): 55-61, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25541827

ABSTRACT

Giardia is the most common causes of protozoan diarrhea that lead to significant morbidity and mortality worldwide. Giardiasis can be cause of disturbance of host immune response. The treatment of Giardiasis is unsuccessful in some cases. The purpose of this study was to determine the clinical features and the content of secretory immunoglobulin A (sIgA) among adults and to evaluate efficiency of new plant preparation "Sausalin". The clinical studies were conducted in Karaganda Regional Infection Hospital (Kazakhstan). 250 patients with giardiasis were randomly assigned to receive sausalin at a dose 720 mg/day or ornidazole at 1500 mg/day. Clinical symptoms of giardisis and efficiency of treatment were evaluated. Protozoal clearance rate and clinical symptoms were assessed. Stool samples were collected from 40 patients and examined the content of sIgA. Our study found the prevalence of abdominal pain, dyspeptic syndrome and the symptoms of intoxication in patients with giardiasis. The increase the level of sIgA was detected, especially in females (88 mg/l). Sausalin was more effectiveness than ornidazole. After the treatment, the clearance rate of giardia (85.71% vs. 42.19%; P<0.05) and the clinical efficacy were significantly higher in the sausalin-treated group than in the ornidazole-treated group. The features of clinic manifestations of giardiasis were identified in population of Kazakhstan. Our data suggest the higher level of sIgA was significantly associated with features of clinic manifestations that the participant had. Treatment with sausalin was more effective than treatment with ornidazole. Further research is needed to explain the existence relationship between Giardia infection and host immune response.


Subject(s)
Abdominal Pain/drug therapy , Giardiasis/drug therapy , Giardiasis/physiopathology , Metronidazole/administration & dosage , Ornidazole/administration & dosage , Abdominal Pain/diagnosis , Abdominal Pain/parasitology , Abdominal Pain/physiopathology , Adolescent , Adult , Female , Giardiasis/diagnosis , Giardiasis/parasitology , Humans , Kazakhstan , Male , Middle Aged , Prevalence
12.
Georgian Med News ; (234): 74-8, 2014 Sep.
Article in Russian | MEDLINE | ID: mdl-25341243

ABSTRACT

Giardia is the most common causes of protozoan diarrhea that leads to significant morbidity and mortality worldwide. The purpose of this study was to determine the clinical efficiency of different scheme of therapy giardiasis with new original plant preparation "Sausalin" (Kazakhstan). We conducted open clinical trial with participation of 93 patients with giardiasis. According the method of treatment the patients were divided into three groups.  Group I - Sausalin at the dose 300 mg/day; group II - Metronidazole at 750 mg/ day; group III - combination of Sausalin 300 mg/day and Metronidazole 750 mg/ day. The treatment was conducted during 10 days. The protozoal clearance rate and clinical symptoms were assessed. There were no significant differences in the efficiency of treatments in group I and group II. The protozoal clearance rate was 68% in group I (Sausalin); in group II -  42,1% (metronidazole). In group III - 83,2% (combination therapy) (р=0.001; 95% CI 54,6-89,7). There was no negative effect on clinical and biochemical blood analysis. We detected statistically significant differences in the dynamics of clinical symptoms (defecation disorders, dyspepsia, abdominal pain, asthenia) of giardiasis in a group of patients receiving Sausalin.The scheme with new drug Sausalin can be used as alternative treatment of Giardiasis. Moreover, the use of the Sausalin is improved the clinical symptoms and safety of therapy.


Subject(s)
Drug Combinations , Giardiasis/drug therapy , Metronidazole/administration & dosage , Abdominal Pain/drug therapy , Abdominal Pain/epidemiology , Abdominal Pain/physiopathology , Adult , Aged , Female , Giardiasis/epidemiology , Giardiasis/physiopathology , Humans , Kazakhstan , Male , Metronidazole/adverse effects , Middle Aged , Treatment Outcome
13.
Rio de Janeiro; s.n; 2014. xiii,96 p. ilus, graf, tab, mapas.
Thesis in Portuguese | LILACS | ID: lil-746878

ABSTRACT

Giardia intestinalis (G. intestinalis) é o parasita gastrointestinal mais comum que coloniza o trato intestinal humano onde permanece extracelular e aderido às células intestinais. O parasita tem uma distribuição mundial, causando um número estimado de 2.8x108 casos por ano e recentemente a doença foi incluída como parte da Iniciativa das Doenças Negligenciadas da Organização Mundial de Saúde. As manifestações clínicas da giardíase são variáveis, e vão desde a ausência de sintomas até diarreias agudas ou crônicas. Adicionalmente, estudos recentes indicam que distúrbios gastrintestinais funcionais, tais como a síndrome do intestino irritável, e o déficit de crescimento em crianças podem ser associados com a infecção por G. intestinalis. Apesar da alta prevalência e das consequências desta doença, os mecanismos fisiopatológicos subjacentes na giardíase ainda permanecem incompreendidos. Os trofozoítos causam a doença sem penetrar no epitélio intestinal, nem entrar na corrente sanguínea e sem secretar nenhuma toxina conhecida. Nos últimos anos, tem sido descrito que as vesículas extracelulares podem participar na interação parasita-célula hospedeira. As vesículas extracelulares podem ser: microvesículas (MVs) e derivadas da membrana plasmática; exosomos, pequenas vesículas originadas a partir de membranas de endossomos; e corpos apoptóticos contendo material do núcleo celular. As MVs têm sido mostradas como importantes fatores na interação parasita-célula hospedeiraNo presente trabalho, foi utilizada uma combinação de metodologias, incluindo citometria de fluxo, microscopia de fluorescência, proliferação celular, análises de proteoma e ensaios de aderência celular para investigar o papel das microvesículas liberadas por trofozoítos de G. intestinalis nas propriedades patogênicas deste parasita.


Demonstramos que G. intestinalis produz e secreta microvesículas com exposição superficial de fosfatidilserina. Além disso, o processo de liberação de MVs é dependente do tempo e da concentração de cálcio, envolve microdomínios de membrana e as microvesículas contêm RNA de baixo peso molecular. Observamos também que os microdomínios de membrana estão envolvidos na adesão do parasita à células Caco-2. Nossa análise proteômica preliminar sugere presença de componentes do citoesqueleto, alfa giardinas, enzimas metabólicas e proteínas variáveis de xi superfície (VSP) nas MVs isoladas de G. intestinalis. Foi demonstrado também que as MVs de G. intestinalis interagem com as células do hospedeiro aumentando a proliferação destas e incrementado também o número de trofozóitos aderidas à estas células. O presente estudo é o primeiro a sugerir um papel potencial para as microvesículas de G. intestinalis na colonização do hospedeiro. Uma melhor compreensão do papel das MVs liberadas pelo parasita na interação com a célula hospedeira poderá fornecer novas perspectivas sobre patogênese e possivelmente novas ferramentas para o diagnóstico e a terapia da doença.


Giardia intestinalis (G. intestinalis) is the most common gastrointestinal parasite thatcolonizes the human intestinal tract where it remains extracellular and adheres to intestinalcells. The parasite has a global distribution causing an estimated 2.8x108cases per year andthe illness was recently included in the World Health Organization Neglected DiseaseInitiative. Clinical manifestations of giardiasis are quite variable, and range from the absenceof symptoms to acute or chronic diarrhea. Aditionally, recent studies indicate that functionalgastrointestinal disorders, such as irritable bowel syndrome, and failure of children to thrivecan be associated with G. intestinalis infection. Even though the high prevalence andconsequences of this disease, pathophysiological mechanisms underlying symptomaticgiardiasis remain incompletely understood. Trophozoites cause disease without penetratingthe intestinal epithelium, entering the bloodstream or secreting toxins. In recent years it hasbeen described that extracellular vesicles could participate in parasite-host cell interaction.The extracellular vesicles may be: microvesicles (MVs) and derived from the plasmamembrane; exosomes, small vesicles originated from endosomal limiting membrane; andapoptotic bodies containing nuclear material. MVs have been shown to be important factors inthe parasite-host cell interaction. Here, we used a combination of methodologies includingflow cytometry, fluorescence microscopy, cell proliferation, proteomics analysis and celladherence assays to investigate the role of released microvesicles from G. intestinalistrophozoites on the pathogenic properties of this parasite.


We have found that G. intestinalisproduces and secretes microvesicles with superficial exposition of phosphatidilserine.Additionally, the shedding process was calcium and time-dependent, involves membranemicrodomains and the microvesicles contain low-molecular weight RNA. We also observedthat membrane microdomains are involved in parasite attachment to Caco-2 cells. Ourpreliminary proteomic analysis suggested the presence of cytoskeleton components, alphagiardins, metabolic enzymes and variant-specific surface protein (VSP) in the isolated MVsfrom G. intestinalis. We demonstrate that G. intestinalis microvesicles interact with host cellsxiiiincreasing their proliferation and augmenting the number of trophozoites adhered to thesecells. The present study is the first to suggest a potential role for G. intestinalis microvesiclesin host cell colonization. A better understanding of the role of the released microvesicles bythe parasite on the host-cell interaction will provide insights into pathogenesis and possiblynew tools for diagnosis and therapy.


Subject(s)
Giardia lamblia/microbiology , Giardiasis/diagnosis , Giardiasis/epidemiology , Giardiasis/physiopathology , Host-Parasite Interactions
14.
World J Gastroenterol ; 19(47): 8974-85, 2013 Dec 21.
Article in English | MEDLINE | ID: mdl-24379622

ABSTRACT

Giardiasis is the most common waterborne parasitic infection of the human intestine worldwide. The etiological agent, Giardia duodenalis (syn. G. intestinalis, G. lamblia), is a flagellated, binucleated protozoan parasite which infects a wide array of mammalian hosts. Human giardiasis is a true cosmopolitan pathogen, with highest prevalence in developing countries. Giardiasis can present with a broad range of clinical manifestations from asymptomatic, to acute or chronic diarrheal disease associated with abdominal pain and nausea. Most infections are self-limiting, although re-infection and chronic infection can occur. Recent evidence indicating that Giardia may cause chronic post-infectious gastrointestinal complications have made it a topic of intense research. The causes of the post-infectious clinical manifestations due to Giardia, even after complete elimination of the parasite, remain obscure. This review offers a state-of-the-art discussion on the long-term consequences of Giardia infections, from extra-intestinal manifestations, growth and cognitive deficiencies, to post-infectious irritable bowel syndrome. The discussion also sheds light on some of the novel mechanisms recently implicated in the production of these post-infectious manifestations.


Subject(s)
Giardia lamblia/pathogenicity , Giardiasis/parasitology , Antiprotozoal Agents/therapeutic use , Cognition Disorders/parasitology , Failure to Thrive/parasitology , Giardia lamblia/drug effects , Giardiasis/complications , Giardiasis/diagnosis , Giardiasis/drug therapy , Giardiasis/physiopathology , Growth Disorders/parasitology , Humans , Irritable Bowel Syndrome/parasitology , Nutritional Status , Time Factors , Treatment Outcome
15.
16.
Mediciego ; 16(supl 2)dic. 2010.
Article in Spanish | LILACS | ID: lil-616679

ABSTRACT

Se realizó un estudio experimental en los consultorios 15, 16, 17 y 18 correspondientes al área de salud del Policlínico Gaspar con el objetivo de evaluar la respuesta a diferentes regímenes terapéuticos en el período comprendido desde junio del 2007 al 2008. La muestra estuvo comprendida por 200 pacientes con edades comprendidas entre 0 y 14 años con complementarios de heces fecales directos o seriados positivos de giardiasis y sin tratamiento anterior. Los pacientes fueron distribuidos de forma aleatoria a cada uno de los grupos de tratamiento garantizando la homogeneidad de la muestra. Al finalizar el tratamiento se realizó la evaluación final en relación con los síntomas clínicos y los resultados de heces fecales. El grupo de edades comprendida entre 10 a 14 años y el sexo femenino predominaron en el universo de pacientes estudiados, el dolor abdominal y las diarreas fueron los síntomas más frecuentemente encontrados, estos desaparecieron en más de la mitad de los niños que fueron tratados con tinidazol y metronidazol. Los mejores resultados en el análisis de las heces fecales después de culminado el tratamiento correspondieron a los grupos tratados con estos dos medicamentos.


An experimental study was conducted in 15, 16, 17 and 18 clinics for the health area of Gaspar Polyclinic in order to evaluate the response to different treatment regimens from June 2007 to 2008. The sample consisted of 200 patients aged between 0 and 14 years with fecal specimens or positive serial of giardiasis and without prior treatment. Patients were randomly assigned to each of the treatment groups by ensuring the homogeneity sample. After treatment the final evaluation was conducted in relation to clinical symptoms and fecal specimens’ results. The age group between 10 and 14 years and female predominance in the studied group of patients, abdominal pain and diarrhea were the most frequently found symptoms; they disappeared in more than half of children who were treated with tinidazole and metronidazole. The best results in the analysis of feces after the treatment completion corresponded to the groups treated with these two drugs.


Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Giardiasis/drug therapy , Giardiasis/epidemiology , Giardiasis/physiopathology
17.
Mediciego ; 16(supl 2)dic 16, 2010.
Article in Spanish | CUMED | ID: cum-45727

ABSTRACT

Se realizó un estudio experimental en los consultorios 15, 16, 17 y 18 correspondientes al área de salud del Policlínico Gaspar con el objetivo de evaluar la respuesta a diferentes regímenes terapéuticos en el período comprendido desde junio del 2007 al 2008. La muestra estuvo comprendida por 200 pacientes con edades comprendidas entre 0 y 14 años con complementarios de heces fecales directos o seriados positivos de giardiasis y sin tratamiento anterior. Los pacientes fueron distribuidos de forma aleatoria a cada uno de los grupos de tratamiento garantizando la homogeneidad de la muestra. Al finalizar el tratamiento se realizó la evaluación final en relación con los síntomas clínicos y los resultados de heces fecales. El grupo de edades comprendida entre 10 a 14 años y el sexo femenino predominaron en el universo de pacientes estudiados, el dolor abdominal y las diarreas fueron los síntomas más frecuentemente encontrados, estos desaparecieron en más de la mitad de los niños que fueron tratados con tinidazol y metronidazol. Los mejores resultados en el análisis de las heces fecales después de culminado el tratamiento correspondieron a los grupos tratados con estos dos medicamentos(AU)


An experimental study was conducted in 15, 16, 17 and 18 clinics for the health area of Gaspar Polyclinic in order to evaluate the response to different treatment regimens from June 2007 to 2008. The sample consisted of 200 patients aged between 0 and 14 years with fecal specimens or positive serial of giardiasis and without prior treatment. Patients were randomly assigned to each of the treatment groups by ensuring the homogeneity sample. After treatment the final evaluation was conducted in relation to clinical symptoms and fecal specimens results. The age group between 10 and 14 years and female predominance in the studied group of patients, abdominal pain and diarrhea were the most frequently found symptoms; they disappeared in more than half of children who were treated with tinidazole and metronidazole. The best results in the analysis of feces after the treatment completion corresponded to the groups treated with these two drugs(AU)


Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Giardiasis/drug therapy , Giardiasis/epidemiology , Giardiasis/physiopathology
19.
Allergol Immunopathol (Madr) ; 38(6): 343-5, 2010.
Article in English | MEDLINE | ID: mdl-20554104
20.
Pak J Biol Sci ; 13(5): 229-34, 2010 Mar 01.
Article in English | MEDLINE | ID: mdl-20464945

ABSTRACT

In order to determine the association between Giardia infection and nutritional status, a cross-sectional study was performed on twenty randomly selected primary schools from two regions of Ardabil province in 2005. Anthropometric factors including height, weight and midarm muscle circumference (MAC) were measured for 813 children (413 males, 400 females). The food intake was estimated for energy and other nutrients by 24 h recall method for three days in week. Determination of Giardia infection was done by using direct wet mount and formalin-ether sedimentation concentration. 10.9% of boys and 17.2% of girls were infected with Giardia infection. Weight and MAC in none infected girls and boys (only 7 and 11 years old) were higher than in infected groups. The average values for weight, height and MAC for both genders were lower than those of NCHS values. Vitamin E and phosphorous intake in non infected boys (in 7-10 years old) were less than infected boys. Calorie, protein, vitamins (B3, B5, B6, E and folacin) and minerals (copper, magnesium, phosphorous, potassium and selenium) intake of infected girls were less than non infected girls in 11-12 years old category. Based on the results found in this study, we conclude that Giardia infection may affect on some of anthropometric factors as well as the calorie and other nutrients intake in some of age groups.


Subject(s)
Giardiasis/physiopathology , Nutritional Status , Anthropometry , Child , Cross-Sectional Studies , Eating , Energy Intake , Female , Giardia , Giardiasis/epidemiology , Humans , Iran/epidemiology , Male
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