Materiały źródłowe

• #1

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8404698/

  Giardia duodenalis is a noninvasive pathogen of the small intestine and produces a wide range of clinical presentations, including chronic diarrhea with weight loss, postinfectious complications of irritable bowel and chronic fatigue, growth stunting, and asymptomatic infections. […] Recent in-depth reviews of these advances are also available. The trophozoites adhere tightly to the small intestinal mucosa, leaving a detectable imprint when they detach from the intestinal epithelium, so the possibility of direct pathogenesis from the mechanical attachment has been raised. However, there is currently no evidence to support this possibility. Rather, current data suggest that a combination of secreted proteases and other Giardia factors, the host immune response, and the interaction of these factors with the intestinal microbiota contribute to the various manifestations.

• #1

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8404698/

  The role of excretory secretory products (ESPs), most notably the cysteine proteases, has received substantial attention over the last decade. Although serine proteases are also present in the ESP, the major portion of the protease activity is from the cysteine proteases. It may be that the primary role of these proteases is to control encystation and excystation, but they also play roles in the interaction between the trophozoite and the host intestinal epithelium. […] Trophozoites interfere with the intestinal tight junction by a number of mechanisms that include the cysteine proteases. A study of the effect of CP2 (called giardipain 1 in this study) on an intestinal epithelial cell line (IEC-6) monolayer demonstrated damage to the cell junctions that was prevented by the protease inhibitor E-64. In addition, CP2 induces apoptosis and damages the villi by its interaction with villin.

• #1

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8404698/

  The intestinal mucus layer is a key component of innate defense against pathogens and, as such, it is notable that the cysteine proteases have a complex effect on the mucus. MUC2 (human mucus protein) is degraded in vitro, and MUC2 gene expression in goblet-like cells is increased, leading to the hypothesis that the Giardia cysteine proteases may deplete the normal intestinal mucus reserve.

• #2 Giardiasis: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/176718-overview

  Infection with Giardia intestinalis most often results from fecal-oral transmission or ingestion of contaminated water. Contaminated food is a less common etiology. Person-to-person spread is common, with 30% of family members with infected children themselves becoming infected. […] The mechanisms by which Giardia causes diarrhea and intestinal malabsorption are probably multifactorial and not yet fully elucidated. Postulated mechanisms include damage to the endothelial brush border, enterotoxins, immunologic reactions, and altered gut motility and fluid hypersecretion via increased adenylate cyclase activity. […] Adhesion of trophozoites to the epithelium has been demonstrated to cause increased epithelial permeability. Giardia-induced loss of intestinal brush border surface area, villus flattening, inhibition of disaccharidase activities, and eventual overgrowth of enteric bacterial flora appear to be involved in the pathophysiology of giardiasis but have yet to be causatively linked to the disease’s clinical manifestations.

• #2 Giardiasis: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/176718-overview

  Giardia can also prevent the formation of nitric oxide, a compound known to inhibit giardial growth, by consuming local arginine, which effectively removes the substrate needed by enterocytes to produce nitric oxide. This mechanism may contribute to Giardia-induced enterocyte apoptosis, because arginine starvation in these cells is known to result in programmed cell death. […] G intestinalis is genetically heterogeneous with eight genetically distinct genotypes or assemblages, designated A-H; assemblages A and B can infect humans. Genotypes vary within group A and B, which could explain why the role of animals in the epidemiology of human infection remains poorly understood. Some strains appear more biologically suitable than other strains. This feature is potentially important in giardiasis pathogenesis.

• #3

  https://link.springer.com/article/10.1007/s40475-015-0049-8

  Giardiasis impairs weight gain and is responsible for a variety of extra-intestinal and post-infectious complications, including post-infectious irritable bowel syndrome, chronic fatigue, failure to thrive, and cognitive impairment. […] Giardiasis occurs in the absence of invasion of the intestinal tissues by the trophozoites and in the absence of any overt inflammatory cell infiltration, with the exception of a modest increase in intraepithelial lymphocytes and mast cells. […] No known toxin has yet been directly implicated in the pathophysiology of giardiasis. […] The pathophysiology of acute diarrhea in giardiasis implicates increased rates of enterocyte apoptosis, a disruption of the intestinal barrier function, activation of host lymphocytes, CD8+ lymphocyte-mediated shortening of brush border microvilli with or without coinciding villous atrophy, disaccharidase deficiencies, small intestinal malabsorption, anion hypersecretion, and increased intestinal transit rates.

• #3

  https://link.springer.com/article/10.1007/s40475-015-0049-8

  The reduction in intestinal barrier function induced by giardiasis implicates disruptions of F-actin, zonula occludens 1 (ZO-1), claudin-1 and claudin-4, occludin, and -actinin, the latter being a component of the actomyosin ring that regulates paracellular flow. […] Loss of epithelial barrier integrity is mediated by activation of epithelial myosin light chain kinase. […] Disruptions of epithelial tight junctional proteins by Giardia are caspase-3-dependent, similarly to other enteric disorders. […] Recent findings also point to a direct role for cysteine proteases released by the parasite in the proteolytic disruption of epithelial villin, an important constituent of brush border microvilli. […] Overall, Giardia-induced diffuse shortening of brush border microvilli causes small intestinal malabsorption due to impaired absorption of water, glucose, and electrolytes.

• #3

  https://link.springer.com/article/10.1007/s40475-015-0049-8

  Recent findings indicate that the pathogenic effects of Giardia may be further compounded by degradation of local mucins by the parasite, which may in turn contribute to the translocation of commensal bacteria through the epithelium. […] A true Giardia enterotoxin has yet to be identified, and attempts to ascribe symptom variability to Giardia genotypes have remained inconclusive. […] Cathepsin-like cysteine proteases are key components of the pathogenesis of several protozoan parasitic disorders, and the Giardia genome contains genes for 23 of those proteases. […] Recent observations have established that the parasite can cause post-infectious visceral hypersensitivity, adding Giardia duodenalis to the list of enteropathogens known to be responsible for post-infectious irritable bowel syndrome.

• #4 Giardia duodenalis: New Research Developments in Pathophysiology, Pathogenesis, and Virulence Factors

  https://prism.ucalgary.ca/items/118da49d-0d2c-4326-95df-1884167c0b59

  Giardia duodenalis is a very common, ubiquitous, intestinal protozoan parasite infecting animals and humans. […] Giardiasis occurs in the absence of invasion of the intestinal tissues by the trophozoites and in the absence of any overt inflammatory cell infiltration, with the exception of a modest increase in intraepithelial lymphocytes and mast cells. […] Recent observations have demonstrated that this effect may be due to a direct immuno-modulating effect of the parasite via its cathepsin B cysteine protease which cleaves pro-inflammatory CXCL8. […] No known toxin has yet been directly implicated in the pathophysiology of giardiasis. […] Findings from ongoing research indicate that the post-infectious effects of giardiasis may be due to microbiota dysbiosis induced by the parasite during the acute phase of infection.

• #5 CDC – DPDx – Giardiasis

  https://www.cdc.gov/dpdx/giardiasis/index.html

  Giardia duodenalis is a protozoan flagellate (Diplomonadida). […] Cysts are resistant forms and are responsible for transmission of giardiasis. Both cysts and trophozoites can be found in the feces (diagnostic stages). […] Infection occurs by the ingestion of cysts in contaminated water, food, or by the fecal-oral route (hands or fomites). […] In the small intestine, excystation releases trophozoites (each cyst produces two trophozoites). […] Trophozoites multiply by longitudinal binary fission, remaining in the lumen of the proximal small bowel where they can be free or attached to the mucosa by a ventral sucking disk. […] Encystation occurs as the parasites transit toward the colon. […] Giardiasis is diagnosed by the identification of cysts or trophozoites in the feces, using direct mounts as well as concentration procedures.

• #6

  https://link.springer.com/article/10.1007/s40588-015-0026-y

  The ventral disc, a spiral microtubule array, mediates trophozoite attachment via an as-yet-unknown mechanism. […] Giardia trophozoites have eight flagella that are organized into four laterally bisymmetric pairs. […] Parasite motility is a crucial process for initiating and maintaining infection in the gut, permitting the parasite to avoid peristaltic flow, and consequently search for suitable sites to attach to the intestinal lumen. […] The contribution of flagellar motility in the trophozoite transition to cysts and subsequent excystation is not entirely clear. […] The ventral disc is a large microtubule-based structure that is unique to Giardia and facilitates the attachment of the parasite to surfaces. […] The mechanism by which attachment is achieved remains unclear: however, this mechanism permits the parasite to attach to the microvilli of a wide range of mammalian hosts as well as to inert surfaces such as glass or plastic.

• #7

  https://byjus.com/biology/giardia-life-cycle/

  Giardia is a single-celled parasite that causes diarrheal disease known as Giardiasis. This infection occurs when contaminated water, food or fecal matter is ingested by human beings. Excystation is the stage in which the parasite escapes from the cyst and emerges as a trophozoite. In the small intestine, the process of excystation begins where each cyst releases two trophozoites. These trophozoites multiply through binary fission, remaining in the small bowel. Encystation is the process of forming a cyst or to become enclosed in a capsule. Encystation occurs when the parasite migrates to the colon. The cyst stage is most commonly found in non diarrheal feces. Owing to the infectious nature of cysts, shortly after passing stool, it can spread from one person to another. This parasite causes the disease giardiasis. The symptoms of giardiasis can range from zero to chronic diarrhea.

• #8 BugBitten Giardiasis from Proteomics to Pathogenesis

  https://blogs.biomedcentral.com/bugbitten/2018/03/23/giardiasis-from-proteomics-to-pathogenesis/

  To win the fight against parasitic diahorreal disease, the molecular detail of pathogenesis must be understood. […] Giardia is transmitted via the ingestion of cysts from contaminated water or raw food and is responsible for over 280 million symptomatic cases of parasitic diarrhoea worldwide every year. After passing through the stomach, trophozoites emerge in the small intestine and colonise its upper part. Trophozoites are responsible for giardiasis, which can take the form of a watery diarrhoea explosive and foul-smelling. […] The established narrative of pathogenesis is trophozoite attachment to the duodenal epithelium via a ventral disc which sometimes (but not always) causes villus atrophication by apoptosis (programmed cell death) of surrounding cells, initiating inflammation and disrupting intestinal barrier function.

• #8 BugBitten Giardiasis from Proteomics to Pathogenesis

  https://blogs.biomedcentral.com/bugbitten/2018/03/23/giardiasis-from-proteomics-to-pathogenesis/

  Localized damage cannot be the sole cause of the profound diarrhoea that can affect the intestinal absorption over a much wider area of the digestive tract than the site of colonization suggesting a role for soluble, secreted, virulence factors. […] Most of the proteins highlighted as secreted and up-regulated by trophozoites belong to three major group of proteins: Giardia tenascins, cathepsin B precursors (GCATBs) and high cysteine membrane proteins (HCMPs). […] A novel mechanism of early pathogenesis has been proposed: Pyridoxamine 5phosphate oxidase (PNPO), secreted by Giardia, produces a reducing environment favouring the growth of Giardia trophozoites. […] Giardia extracellular nuclease degrades the outer layer of the intestinal mucus granting better access to the mucus layer to GCATBs.

• #8 BugBitten Giardiasis from Proteomics to Pathogenesis

  https://blogs.biomedcentral.com/bugbitten/2018/03/23/giardiasis-from-proteomics-to-pathogenesis/

  Further degradation of the protective intestinal mucus barrier may be caused by GCATBs as well as subsequent disruption of the intestinal intracellular junctions. […] Tenascins are likely to be responsible for reducing adhesion between epithelial cells and thereby maintaining intestinal cell separation. […] Giardia mediated dismantling of the barriers provided by the mucosal membranes and modulation of the environment leaves the intestinal epithelia prone to secondary infections by opportunist microbes residing in the intestinal lumen and sensitive to irritation by allergens in foodstuffs.

• #9 Giardiasis in Animals – Digestive System – Merck Veterinary Manual

  https://www.merckvetmanual.com/digestive-system/giardiasis-giardia/giardiasis-in-animals

  Giardiasis is an intestinal infection with the protozoan flagellate parasite Giardia spp. […] Giardia infections cause an increase in epithelial permeability, increased numbers of intraepithelial lymphocytes, and activation of T lymphocytes. Trophozoite toxins and T-cell activation initiate a diffuse shortening of brush border microvilli and decreased activity of the small-intestinal brush border enzymes, especially lipase, some proteases, and disaccharidases. The diffuse microvillus shortening leads to a decrease in overall absorptive area in the small intestine and thus an impaired intake of water, electrolytes, and nutrients. In addition, the proteins secreted by Giardia trophozoites contribute to degrading the intestinal mucous barriers and disrupting the intestinal intracellular junctions. The combined effect of decreased resorption, brush-border enzyme deficiencies, and a lack of integrity between cells of the intestine results in dysregulation of the absorption and barrier functions of the intestinal epithelium, resulting in malabsorptive diarrhea. […] The reduced activity of lipase and the increased production of mucin by goblet cells may explain the steatorrhea and mucous diarrhea that has frequently been described in symptomatic giardiasis.

• #10

  https://drpress.org/ojs/index.php/HSET/article/view/1387

  Giardia intestinalis infection leads to intestinal cell damage and loss of the brush border of the intestinal epithelium, resulting in shortened microvilli and impaired epithelial barrier function. […] Watery diarrhoea, diarrhoea, nausea, abdominal pain, vomiting, and weight loss are all symptoms of this pathological alteration. […] Malnutrition absorption is the most common symptom of Giardia intestinalis infection. […] In recent years, its pathogenesis, including structural proteins and excretion of Giardia intestinalis, surface antigen variants, and the role of Giardia intestinalis in the small intestine, has been extensively studied. […] This article discusses this issue and lists the risks of Giardia intestinalis to the human intestine and the various diseases it can cause.

• #11 Giardiasis – Wikipedia

  https://en.wikipedia.org/wiki/Giardiasis

  Giardiasis is caused by the protozoan Giardia duodenalis. The infection occurs in many animals, including beavers, other rodents, cows, and sheep. Animals are believed to play a role in keeping infections present in an environment. […] Infection with Giardia results in decreased expression of brush border enzymes, morphological changes to the microvillus, increased intestinal permeability, and programmed cell death of small intestinal epithelial cells. Both trophozoites and cysts are contained within the gastrointestinal tract and do not invade beyond it. […] The attachment of trophozoites causes villous flattening and inhibition of enzymes that break down disaccharide sugars in the intestines. Ultimately, the community of microorganisms that lives in the intestine may overgrow and may be the cause of further symptoms, though this idea has not been fully investigated. The alteration of the villi leads to an inability of nutrient and water absorption from the intestine, resulting in diarrhoea, one of the predominant symptoms.

• #11 Giardiasis – Wikipedia

  https://en.wikipedia.org/wiki/Giardiasis

  There appears to be a further increase in programmed enterocyte cell death by Giardia intestinalis, which further damages the intestinal barrier and increases permeability. There is significant upregulation of the programmed cell death cascade by the parasite, and substantial downregulation of the anti-apoptotic protein Bcl-2 and upregulation of the proapoptotic protein Bax. These connections suggest a role of caspase-dependent apoptosis in the pathogenesis of giardiasis.

• #12 High-fat diet increases the severity of Giardia infection in association with low-grade inflammation and gut microbiota dysbiosis | Scientific Reports

  https://www.nature.com/articles/s41598-021-98262-8

  Exogenous factors that may influence the pathophysiology of Giardia infection remain incompletely understood. We have investigated the role of dietary fat in the pathogenesis of Giardia infection. In infected animals, the trophozoite burden was higher in HF+Giardia mice compared to the LF+Giardia group at day 7 post infection. Fatty acids exerted direct pro-growth effects on Giardia trophozoites. Analysis of disease parameters showed that HF+Giardia mice exhibited more mucosal infiltration by inflammatory cells, decreased villus/crypt ratios, goblet cell hyperplasia, mucus disruption, increased gut motility, and elevated fecal water content compared with LF+Giardia. HF diet-dependent exacerbation of Giardia-induced goblet cell hyperplasia was associated with elevated Atoh1 and Muc2 gene expression.

• #12 High-fat diet increases the severity of Giardia infection in association with low-grade inflammation and gut microbiota dysbiosis | Scientific Reports

  https://www.nature.com/articles/s41598-021-98262-8

  The pathophysiology of giardiasis is multifactorial and remains incompletely understood. Giardia cysteine proteases disrupt the intestinal tissue barrier, the mucus layers, and the gut microbiota, both at the site of infection and beyond. These effects facilitate bacterial translocation. Giardia infection is responsible for maldigestion, and nutrient and water malabsorption. Finally, increasing evidence suggests that the gut microbiota plays a key role in regulating both the colonization of trophozoites and the outcome of Giardia infection. Indeed, Giardia fragments the microbiota biofilm and promotes the release of pathobionts that in turn trigger an inflammatory response. […] The results demonstrate that a HF diet significantly increases parasite burden, exacerbates villus/crypt injury, and enhances mucosal infiltration of mixed inflammatory cells in giardiasis. These changes were associated with elevated levels of pro-inflammatory cytokines and chemokines in infected mice given a high fat diet (Il-6, Tnf-). Saturated (i.e., palmitic acid) and monounsaturated (i.e., oleic acid) fatty acids, which are more abundant in this HF diet formulation, significantly increased trophozoite metabolic activity and disrupted epithelial claudin-1 and claudin-4 in epithelial cells exposed to the parasite. The HF diet also exacerbated small intestinal goblet cell hyperplasia in association with elevated expression of the Atoh1 gene, which regulates intestinal secretory cell proliferation, while in the colon it worsened the mucus granule depletion induced by the infection. The results also showed that consumption of either HF or LF diets induces significant shifts in the bacterial community of the gut. Microbiota dysbiosis induced by giardiasis was more pronounced in the mice given a HF diet, with significant increases in bacterial richness and evenness (-diversity) and elevated representation of Firmicutes concurrent with reduced levels of Bacteroidetes. […] The results suggest that Giardia-induced alterations in gastrointestinal motility and stool water contents are exacerbated by a HF diet.

• #13 Extra-intestinal and long term consequences of Giardia duodenalis infections

  https://www.wjgnet.com/1007-9327/full/v19/i47/8974.htm

  As it is the case with other enteropathogens, induction of apoptosis in enterocytes by Giardia represents a key component in the pathogenesis of the infection. Enterocytes apoptosis during giardiasis is caspase-3 and -9 dependent. While both host and parasite factors may modulate intestinal epithelial cell apoptosis, the products responsible for its activation during giardiasis have yet to be identified. In addition to promoting increased rates of enterocyte apoptosis, Giardia trophozoites may also halt enterocyte cell-cycle progression via consumption of arginine, and up-regulation of cell-cycle inhibitory genes. […] Findings from studies on giardiasis in vivo demonstrate that the most severe intestinal permeability and macromolecular uptake coincides with the peak of trophozoites colonization. The effects of the infection on gut barrier function following host parasite clearance require further investigation. Giardia-mediated increases in intestinal permeability result from alterations to the apical tight junctional complexes, including disruption of F-actin, zonula-occludens-1, claudin-1 and alpha-actinin, a component of the actomyosin ring that regulates paracellular flow. The role of Giardia proteinases in these effects is a topic of ongoing research.

• #13 Extra-intestinal and long term consequences of Giardia duodenalis infections

  https://www.wjgnet.com/1007-9327/full/v19/i47/8974.htm

  Giardia-induced diffuse shortening of epithelial brush border microvilli represents a key factor in the production of diarrheal disease via malabsorption and maldigestion. Whether or not the diffuse loss of microvillous border surface area associated with giardiasis is related to the release of a toxin by the parasite, a phenomenon similar to the release of proteases in the bacterial overgrowth syndrome, remains poorly understood. Regardless, G. duodenalis infection causes microvillous shortening in a lymphocyte-mediated manner which in turns impairs activities of disaccharidases. […] Giardia infections tend to be self-limiting in individuals with competent immune systems. A recent study in Brazilian children suggests that symptoms are less severe during re-infection, consistent with the hypothesis that if previous exposure does not always protect against future infections, it does at least reduce the severity of pathology. Patients with common variable immunodeficiency and Brutons X-linked agammaglobulinemia are prone to chronic giardiasis, which underscores the necessity of antibodies to fully control giardiasis.

• #13 Extra-intestinal and long term consequences of Giardia duodenalis infections

  https://www.wjgnet.com/1007-9327/full/v19/i47/8974.htm

  Central features of the pathophysiology of giardiasis are briefly outlined below, as these mechanisms may be key to our understanding of the complications discussed further. While the Giardia genotype has been proposed to play a role in the induction of symptoms, there is currently no consensus concerning the connection between genotype and virulence. […] After cyst ingestion in contaminated water or food, excystation occurs liberating two or four trophozoites, which adhere to the epithelial surface of the intestine via a ventral adhesive disk. This tight attachment between Giardia trophozoites and intestinal epithelial cells, as well as the production of yet incompletely characterized parasitic products, culminate in the production of diarrhea. Pathophysiology is believed to involve heightened rates of enterocytes apoptosis, intestinal barrier dysfunction, activation of host lymphocytes, shortening of brush border microvilli with or without coinciding villous atrophy, disaccharidase deficiencies, small intestinal malabsorption, anion hypersecretion and increased intestinal transit rates.

• #14 The Influence of the Protozoan Giardia lamblia on the Modulation of the Immune System and Alterations in Host Glucose and Lipid Metabolism

  https://www.mdpi.com/1422-0067/25/16/8627

  G. lamblia secretes various proteases, including cathepsin B-like cysteine proteases and giardipain-1, which degrade host proteins, disrupt the epithelial barrier, induce apoptosis in intestinal epithelial cells, and modulate host immune responses. […] Studies conducted on in vivo and in vitro models have shown that G. lamblia causes disturbances in the absorption of glucose, sodium, and water, and reduces disaccharidase activity by reducing the absorptive surface area of the epithelium. […] G. lamblia affects intestinal motility by limiting the movements of intestinal villi and muscle contractions, disrupting the coordination of villi movements and disturbing the balance of gut microbiota. […] The combined effects of Giardia’s virulence factors on intestinal motility and microbiota composition interact to induce intestinal inflammation and disturb the absorption of lipids, carbohydrates, and other essential nutrients.

• #14 The Influence of the Protozoan Giardia lamblia on the Modulation of the Immune System and Alterations in Host Glucose and Lipid Metabolism

  https://www.mdpi.com/1422-0067/25/16/8627

  Giardia infections result in several changes to the intestinal microbiota, such as disruption of microbial biofilm structure, altered virulence in commensal species, and changes in species abundance and diversity, which influence Giardia pathogenesis by affecting colonization resistance, immune responses, and brush border defects. […] The overall impact of these mechanisms contributes to the complex clinical presentation of giardiasis, including both gastrointestinal symptoms as potential systemic effects. […] The gut microbiota plays a crucial role in metabolic disorders like obesity, dyslipidemia, dysglycemia, and type 2 diabetes. […] Research indicates that intestinal parasites can induce metabolic changes, including dysregulation of glucose and insulin metabolism. […] Infection with the G. lamblia parasite can activate the AKT pathway, affecting glucose and insulin levels in the host’s body. […] Increasing evidence suggests that giardiasis may significantly impact carbohydrate, lipid, and hormonal metabolism in the body.

• #15 SciELO Brazil – Effect of probiotics on giardiasis. Where are we? Effect of probiotics on giardiasis. Where are we?

  https://www.scielo.br/j/bjps/a/Br3dCGL7d8Ws4Sqdp6hJz8B/

  Giardiasis, an intestinal infection caused by the protozoan Giardia lamblia, is considered the most common human intestinal parasitosis in the world. It is frequent in both developed and developing countries, and is estimated to inflict 280 million symptomatic human infections annually. In most cases, infection is asymptomatic, and when symptoms occur, the most common manifestations are fatigue, anorexia, belching, vomiting, flatulence, abdominal pain and distension, and steatorrhea. Such clinical conditions establish an intestinal malabsorption syndrome that can lead to significant weight loss and nutritional deficiencies of the host and, when present in children, may lead to severe growth and cognitive deficits. […] The pathophysiology of acute diarrhea in giardiasis implicates increased rates of enterocyte apoptosis, disruption of the intestinal barrier function, activation of host lymphocytes, CD8+ lymphocyte-mediated shortening of brush border microvilli with or without coinciding villous atrophy, crypt hyperplasia, deficiency of disaccharidases, intestinal malabsorption, anion hypersecretion, and increased intestinal transit. Both innate and adaptive immunity mechanisms are essential for the elimination of the parasite from the intestine.

• #16 Immunological aspects of Giardia infections | Parasite

  https://www.parasite-journal.org/articles/parasite/full_html/2014/01/parasite140090/parasite140090.html

  Studies of Giardia infections in rodents have implicated interleukin-6 (IL-6) in anti-Giardia immunity. IL-6-deficient mice have a diminished ability to clear infection caused by G. intestinalis. The findings suggest that IL-6 contributes to clearance of Giardia infection in mice (albeit by an unknown mechanism that appears not to involve IgA). Recent work has identified dendritic cells (of bone marrow origin) as a source of IL-6 that promotes clearance of G. intestinalis infection in mice. […] There is evidence that intestinal nitric oxide (NO) contributes to host clearance of Giardia trophozoites. In view of the fact that arginine is a substrate for generation of NO, it is interesting that Giardia trophozoites appear to compete with the host for arginine. Giardia trophozoites are able to metabolise arginine.

• #16 Immunological aspects of Giardia infections | Parasite

  https://www.parasite-journal.org/articles/parasite/full_html/2014/01/parasite140090/parasite140090.html

  Immunodeficiency, particularly antibody deficiency, predisposes to increased intensity and persistence of Giardia infections. Giardia-infected immunocompetent hosts produce serum and intestinal antibodies against Giardia trophozoites. The number of Giardia muris trophozoites, in mice with G. muris infection, is reduced by intra-duodenal administration of anti-G. muris antibody. Giardia intestinalis antigens that are recognised by human anti-trophozoite antibodies include variable (variant-specific) and invariant proteins. Nitric oxide (NO) appears to contribute to host clearance of Giardia trophozoites. Arginine is a precursor of NO and is metabolised by Giardia trophozoites, possibly reducing its availability for generation of NO by the host. Work with mice suggests that T lymphocytes and interleukin-6 (IL-6) contribute to clearance of Giardia infection via mechanisms independent of antibodies.

• #16 Immunological aspects of Giardia infections | Parasite

  https://www.parasite-journal.org/articles/parasite/full_html/2014/01/parasite140090/parasite140090.html

  Giardia infections are increased in intensity and/or duration in human or non-human mammalian hosts with various forms of immunodeficiency, in comparison with their immunocompetent counterparts. This situation indicates that host immunological responses limit the intensity and/or duration of these infections. The extant literature suggests that impaired production of anti-Giardia antibodies is the main reason why immunodeficiency states predispose to severe/prolonged Giardia infections. […] A plausible mechanism for presumed antibody-mediated clearance of Giardia infections would involve prevention (by antibodies) of trophozoite attachment to the host intestinal epithelium followed by peristaltic expulsion of these organisms from the intestine. […] Experimental work with mice has suggested that T lymphocytes can contribute directly (i.e., in the absence of antibodies) to clearance of infection with a clone of G. intestinalis (GS/M-H7). The mechanism(s) involved in this putative T-cell-mediated clearance of Giardia infection does not appear to be known.

• #17 SciELO Brazil – Effect of probiotics on giardiasis. Where are we? Effect of probiotics on giardiasis. Where are we?

  https://www.scielo.br/j/bjps/a/Br3dCGL7d8Ws4Sqdp6hJz8B/?lang=en

  T cell participation is associated with disease progression, since the depletion of CD4+ T cells in animals resulted in chronic giardiasis, whereas CD8+ T cells are more related to intestinal mucosa tissue damage resulting from giardiasis than with controlling the infection. […] Probiotics have been studied as an alternative treatment for giardiasis. […] Probiotics are considered non-pathogenic microorganisms (bacteria or yeasts) that, when consumed in adequate amounts, produce beneficial effects on the health and well-being of the host. […] Probiotics are defined as live microorganisms that, when administered in suitable amounts, confer a health benefit to the host. […] Probiotics have a beneficial effect on the modulation of giardiasis. […] Probiotics are considered non-pathogenic microorganisms (bacteria or yeasts) that, when consumed in adequate amounts, produce beneficial effects on the health and well-being of the host. […] Probiotics have been shown to modulate the mucosal immune response in Giardia-infected mice. […] Probiotics offer a safe and effective mode to prevent and treat Giardia infection.

• #18

  https://www.jci.org/articles/view/69932

  What determines whether Giardia is a harmless commensal or a devastating pathogen? The difference may relate in part to the virulence of various Giardia strains, and more studies are needed to define these differences between Giardia strains and assemblages. […] In this issue of the JCI, Bartelt et al. describe a novel animal model of giardiasis in which malnourished, weaned mice developed epithelial apoptosis and crypt hyperplasia associated with a Th2-mediated inflammatory response, persistent shedding of the infecting strain, and growth retardation secondary to Giardia infection. […] The model allows a characterization of mucosal histopathological response to Giardia infection mimicking that seen in humans, characterized by apoptosis of epithelium with intraepithelial eosinophils, decreased height of villi, alteration of crypt depth and cellularity, and a Th2-based immune response.

• #19 Giardiasis: What It Is, Symptoms, Treatments & Medications

  https://my.clevelandclinic.org/health/diseases/15238-giardiasis

  Giardia infection doesn’t always cause noticeable symptoms, but it can. Some symptoms are due to the parasite itself, and others are due to your body activating to remove the parasite. For example, the parasite feeding off your nutrients might sap your energy, making you feel increasingly tired. Diarrhea, swelling and skin reactions are symptoms of inflammation, part of your immune system’s response. […] If giardiasis lasts a long time, or keeps coming back, it can do more long-term damage. This might happen if you have a weaker immune system, possibly from a preexisting health condition. In developing countries, malnutrition and lower health status can make people more vulnerable to complications from giardiasis. […] If giardiasis lasts a long time, it can damage the lining of your small intestine. This can cause chronic gastrointestinal symptoms and trigger irritable bowel syndrome. It can also damage your intestines’ ability to absorb the nutrients in your food. You could develop nutritional deficiencies. This could affect growth and development in children.

• #19 Giardiasis: What It Is, Symptoms, Treatments & Medications

  https://my.clevelandclinic.org/health/diseases/15238-giardiasis

  In some people with severe and/or chronic giardiasis, long-term inflammation triggers an autoimmune response. This means that part of your immune response to the infection becomes hyperactive and automatic, continuing even after the infection is gone. Some people have developed reactive arthritis, chronic fatigue syndrome or new food allergies.

• #20 Giardiasis – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/intestinal-protozoa-and-microsporidia/giardiasis

  For symptomatic giardiasis, tinidazole, metronidazole, secnidazole, or nitazoxanide are used. Treatment failures and resistance can occur with any of them. […] Even after parasitologic cure, patients may experience lactose intolerance, irritable bowel syndrome, or fatigue that last for weeks to months.

• #21 Giardia – Wikipedia

  https://en.wikipedia.org/wiki/Giardia

  Giardia is a genus of anaerobic flagellated protozoan parasites of the phylum Metamonada that colonise and reproduce in the small intestines of several vertebrates, causing the disease giardiasis. Their life cycle alternates between a swimming trophozoite and an infective, resistant cyst. […] The symptoms of Giardia, which may begin to appear 2 days after infection, can include mild to violent diarrhoea, excess gas, stomach or abdominal cramps, upset stomach, and nausea. Resulting dehydration and nutritional loss may need immediate treatment. A typical infection can be slight, resolve without treatment, and last between 2 and 6 weeks, although it can sometimes last longer and/or be more severe. Coexistence with the parasite is possible (symptoms fade), but an infected individual can remain a carrier and transmit it to others. Medication containing tinidazole or metronidazole decreases symptoms and time to resolution. Albendazole is also used, and has an anthelmintic (anti-worm) property as well, ideal for certain compounded issues when a general vermicidal agent is preferred. Giardia causes a disease called giardiasis, which causes the villi of the small intestine to atrophy and flatten, resulting in malabsorption in the intestine. Lactose intolerance can persist after the eradication of Giardia from the digestive tract.

• #22 Giardiasis: Causes, Symptoms, and Treatment

  https://www.healthline.com/health/giardiasis

  Giardiasis is an infection in your small intestine. Its caused by a microscopic parasite called Giardia lamblia. […] G. lamblia are found in animal and human feces. These parasites also thrive in contaminated food, water, and soil, and can survive outside a host for long periods of time. Accidentally consuming these parasites can lead to an infection. […] The most common way to get giardiasis is to drink water that contain G. lamblia. Contaminated water can be in swimming pools, spas, and bodies of water, such as lakes. […] Giardiasis can lead to complications such as weight loss and dehydration from diarrhea. The infection can also cause lactose intolerance in some people. […] Giardiasis infections usually last about six to eight weeks, but problems such as lactose intolerance can persist after the infection clears up.

• #23 Treatment-refractory giardiasis: challenges and solutions | IDR

  https://www.dovepress.com/treatment-refractory-giardiasis-challenges-and-solutions-peer-reviewed-fulltext-article-IDR

  Clinical MTZ resistance has been attributed to increased MTZ tolerance in Giardia isolated from patients who failed treatment therapy. […] Our knowledge about resistance mechanisms in Giardia is limited and fragmented. […] Most studies on resistance mechanisms in Giardia have focused mainly on MTZ, but resistance mechanisms against nitazoxanide, ABZ, furazolidone, and quinacrine were also investigated. […] The increasing resistance observed especially in travelers returning from Asia is indicative of a heritable genetic trait in Giardia. […] The main challenge in treatment-refractory giardiasis is understanding of its mechanisms of resistance and an evidence base for its clinical management.

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