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Giardia is a leading but treatable cause of infectious gastroenteritis worldwide, with a reported prevalence of 2-7% in high income countries and 2-30% in low income countries.1 Giardiasis is included in the World Health Organization Neglected Diseases Initiative owing to its burden and association with poverty.2 Its incidence in the United Kingdom is underestimated because of the lack of diagnostic sensitivity of traditional faecal microscopy3 and the mistaken belief that it is mostly acquired abroad, so often only people reporting foreign travel are tested. This update discusses the epidemiology, clinical presentation, diagnosis, and management of giardiasis specifically in high income countries. References

Key Points Giardia intestinalis is recognized as a major worldwide contributor to diarrhoeal disease in humans and other mammals, but the disease mechanisms have been poorly understood until recently. Giardia spp. are some of the most divergent eukaryotes examined to date and provide unique opportunities for gaining basic insights into key pathways that characterize eukaryotic cells and also for identifying new molecular mechanisms. Cell differentiation in Giardia spp. involves two major developmental transitions: from the ingested, dormant cyst via the excyzoite to trophozoites, in a process known as excystation, and from the motile, replicating trophozoite back to the infective cyst, in a process known as encystation. Mitosomes in Giardia spp. are elongated, double-membraned organelles that are related to mitochondria, and their only known function is in the assembly of Fe–S clusters. Giardia spp., like all diplomonads, have two nuclei. These nuclei have been shown to be equivalent in size and in the amount of DNA that they contain, and both are transcriptionally active. Analyses of Giardia spp. genomes indicate that these organisms encode rudimentary forms of many cellular processes, with fewer subunits present in simplified cellular machineries, and have a limited metabolic repertoire with many bacterial-like enzymes that were introduced by horizontal gene transfer. The adhesive disc and the four flagella of the pathogen, together with differentiation and antigenic variation of the variant-specific surface proteins (VSPs), are the major virulence factors identified to date for Giardia spp. Epigenetic mechanisms, microRNAs and RNA interference have been shown to be important in the regulation of vsp gene expression. Several mechanisms (including epithelial-barrier dysfunction, apoptosis, diffuse shortening of microvilli, hypersecretion of Cl − and inhibition of brush-border enzymes) have been proposed to be important for the induction of symptoms during giardial infection, and the cause of giardiasis is probably multifactorial. In addition to being a major worldwide contributor to diarrhoeal disease, Giardia intestinalis is a useful model system for studying basic eukaryotic cellular processes owing to its reduced complexity. Here, Svärd and colleagues review the recent advances in our understanding of giardial cell biology and pathogenesis. The eukaryotic intestinal parasite Giardia intestinalis was first described in 1681, when Antonie van Leeuwenhoek undertook a microscopic examination of his own diarrhoeal stool. Nowadays, although G. intestinalis is recognized as a major worldwide contributor to diarrhoeal disease in humans and other mammals, the disease mechanisms are still poorly understood. Owing to its reduced complexity and proposed early evolutionary divergence, G. intestinalis is used as a model eukaryotic system for studying many basic cellular processes. In this Review we discuss recent discoveries in the molecular cell biology and pathogenesis of G. intestinalis .

Giardia intestinalis is a non-invasive protozoan parasite that causes giardiasis in humans, the most common form of parasite-induced diarrhea. Disease mechanisms are not completely defined and very few virulence factors are known. To identify putative virulence factors and elucidate mechanistic pathways leading to disease, we have used proteomics to identify the major excretory-secretory products (ESPs) when Giardia trophozoites of WB and GS isolates (assemblages A and B, respectively) interact with intestinal epithelial cells (IECs) in vitro. The main parts of the IEC and parasite secretomes are constitutively released proteins, the majority of which are associated with metabolism but several proteins are released in response to their interaction (87 and 41 WB and GS proteins, respectively, 76 and 45 human proteins in response to the respective isolates). In parasitized IECs, the secretome profile indicated effects on the cell actin cytoskeleton and the induction of immune responses whereas that of Giardia showed anti-oxidation, proteolysis (protease-associated) and induction of encystation responses. The Giardia secretome also contained immunodominant and glycosylated proteins as well as new candidate virulence factors and assemblage-specific differences were identified. A minor part of Giardia ESPs had signal peptides (29% for both isolates) and extracellular vesicles were detected in the ESPs fractions, suggesting alternative secretory pathways. Microscopic analyses showed ESPs binding to IECs and partial internalization. Parasite ESPs reduced ERK1/2 and P38 phosphorylation and NF-κB nuclear translocation. Giardia ESPs altered gene expression in IECs, with a transcriptional profile indicating recruitment of immune cells via chemokines, disturbances in glucose homeostasis, cholesterol and lipid metabolism, cell cycle and induction of apoptosis. This is the first study identifying Giardia ESPs and evaluating their effects on IECs. It highlights the importance of host and parasite ESPs during interactions and reveals the intricate cellular responses that can explain disease mechanisms and attenuated inflammatory responses during giardiasis.

Abstract 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. Male 3 to 4-week-old C57BL/6 mice were fed either a low fat (LF) or a high fat (HF) diet for 12 days and challenged with G. duodenalis . 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. Gut microbiota analysis revealed that the HF diet alone induces a taxonomic shift. HF + Giardia mice exhibited microbiota dysbiosis characterized by an increase of Firmicutes and a decrease of Bacteroidetes and significant changes in α- and β-diversity metrics. Taken together, the findings suggest that a HF diet exacerbates the outcome of Giardia infection. The data demonstrate that elevated dietary fat represents an important exogenous factor promoting the pathophysiology of giardiasis.

Giardia duodenalis is the most common intestinal parasite of humans in the USA, but the risk factors for sporadic (non-outbreak) giardiasis are not well described. The Centers for Disease Control and Prevention and the Colorado and Minnesota public health departments conducted a case-control study to assess risk factors for sporadic giardiasis in the USA. Cases (N = 199) were patients with non-outbreak-associated laboratory-confirmed Giardia infection in Colorado and Minnesota, and controls (N = 381) were matched by age and site. Identified risk factors included international travel (aOR = 13.9; 95% CI 4.9–39.8), drinking water from a river, lake, stream, or spring (aOR = 6.5; 95% CI 2.0–20.6), swimming in a natural body of water (aOR = 3.3; 95% CI 1.5–7.0), male–male sexual behaviour (aOR = 45.7; 95% CI 5.8–362.0), having contact with children in diapers (aOR = 1.6; 95% CI 1.01–2.6), taking antibiotics (aOR = 2.5; 95% CI 1.2–5.0) and having a chronic gastrointestinal condition (aOR = 1.8; 95% CI 1.1–3.0). Eating raw produce was inversely associated with infection (aOR = 0.2; 95% CI 0.1–0.7). Our results highlight the diversity of risk factors for sporadic giardiasis and the importance of non-international-travel-associated risk factors, particularly those involving person-to-person transmission. Prevention measures should focus on reducing risks associated with diaper handling, sexual contact, swimming in untreated water, and drinking untreated water.

Giardia duodenalis is a significant cause of waterborne and foodborne infections, day-care center outbreaks, and traveler’s diarrhea worldwide. In protozoa such as Trichomonas vaginalis and Entamoeba histolytica, iron affects the growth, pathogenicity mechanisms, and expression of virulence genes. One of the proposed iron regulatory mechanisms is at the post-transcriptional level through an IRE/IRP-like (iron responsive element/iron regulatory protein) system. Recently, the expression of many putative giardial virulence factors in the free-iron levels has been reported in subsequent RNAseq experiments; however, the iron regulatory mechanism remains unknown. Thus, this work aimed to determine the effects of iron on the growth, gene expression, and presence of IRE-like structures in G. duodenalis. First, the parasite’s growth kinetics at different iron concentrations were studied, and the cell viability was determined. It was observed that the parasite can adapt to an iron range from 7.7 to 500 µM; however, in conditions without iron, it is unable to survive in the culture medium. Additionally, the iron modulation of three genes was determined by RT-PCR assays. The results suggested that Actin, glucosamine-6-phosphate deaminase, and cytochrome b5 mRNA were down-regulated by iron. To investigate the presence of IRE-like structures, in silico analyses were performed for different mRNAs from the Giardia genome database. The Zuker mfold v2.4 web server and theoretical analysis were used to predict the secondary structures of the 91 mRNAs analyzed. Interestingly, the iron-induced downregulation of the genes analyzed corresponds to the location of the stem–loop structures found in their UTR regions. In conclusion, iron modulates the growth and expression of specific genes, likely due to the presence of IRE-like structures in G. duodenalis mRNAs.

On 6 December 2010 a fire in Hemiksem, Belgium, was extinguished by the fire brigade with both river water and tap water. Local physicians were asked to report all cases of gastroenteritis. We conducted a retrospective cohort study among 1000 randomly selected households. We performed a statistical and geospatial analysis. Human stool samples, tap water and river water were tested for pathogens. Of the 1185 persons living in the 528 responding households, 222 (18·7%) reported symptoms of gastroenteritis during the time period 6–13 December. Drinking tap water was significantly associated with an increased risk for gastroenteritis (relative risk 3·67, 95% confidence interval 2·86–4·70) as was place of residence. Campylobacter sp. (2/56), norovirus GI and GII (11/56), rotavirus (1/56) and Giardia lamblia (3/56) were detected in stool samples. Tap water samples tested positive for faecal indicator bacteria and protozoa. The results support the hypothesis that a point-source contamination of the tap water with river water was the cause of the multi-pathogen waterborne outbreak.

Infections with Giardia are among the most common causes of food and water-borne diarrheal disease worldwide. Here, we investigated Th17, Treg and IgA responses, and alterations in gut microbiota in two mouse lines with varying susceptibility to Giardia muris infection. Infected BALB/c mice shed significantly more cysts compared with C57BL/6 mice. Impaired control of infection in BALB/c mice was associated with lower Th17 activity and lower IgA levels compared with C57BL/6 mice. The limited metabolic activity, proliferation and cytokine production of Th17 cells in BALB/c mice was associated with higher proportions of intestinal Foxp3 + RORγt + regulatory T cells and BALB/c mice developed increased RORγt + Treg:Th17 ratios in response to G. muris infection. Furthermore, G. muris colonization led to a significantly reduced evenness in the gut microbial communities of BALB/c mice. Our data indicate that differential susceptibility to Giardia infections may be related to RORγt + Treg controlling Th17 activity and that changes in the microbiota composition upon Giardia infection partially depend on the host background.

The purpose of this study was to determine the intestinal parasite distributions in patients who applied to the Parasitology Laboratory of Istanbul University-Cerrahpaşa, Cerrahpaşa Medical Faculty, by evaluating the parasites retrospectively. Normal saline and stool lugol were applied for direct examination of stool samples that were sent for parasite examination; cellophane band samples were evaluated microscopically. The samples suspected to have protozoa were evaluated using modified acid fast and trichrome staining methods. We evaluated the parasitological examination results of patients who applied to our laboratory between January 2012 and December 2018. A total of 2.96% of the 20,948 patients who applied had parasites in their faeces. spp. was detected at the highest rate (63.23%), followed by (17.26%), (12.58%), (2.42%), spp. (1.94%) and (1.45%). Although the prevalence of intestinal parasitic infections has decreased when compared to previous years, it still remains important. For this reason, solving infrastructure problems, providing information on personal hygiene and sanitation rules are among the most important tasks needed to reduce the prevalence of intestinal parasites.

Intestinal Parasitic Infections (IPIs) are a major public health problem worldwide, especially among children with a need for periodical evaluation of prevalence and risk factors to adopt an appropriate prevention strategy. This cross-sectional prospective study was conducted to identify prevalence, risk factors, characteristics, and impact of IPIs on school children in different regions of Jeddah, Saudi Arabia. Children were recruited from randomly selected schools. Questionnaires were distributed to students and filled by their parents to collect relevant information about sociodemographic, environmental, and hygienic living conditions. Stool samples and anthropometric measurements as indicators of nutritional status were collected from students who agreed to participate in the study. Fecal samples were examined by direct smear and formol-ether concentration method. Out of 581 collected stool samples, only 31 (5.3%) samples were positive for IPIs especially Blastocystis hominis (10 samples) and Giardia lamblia (six samples). The only two significant risk factors associated with IPIs were drinking water from tanks [odds ratio (OR): 3.35, 95% confidence interval (CI): 1.60–6.99, p = 0.001] and washing hands with only water (OR: 2.63, 95% CI: 1.17–5.93, p = 0.03). There was no significant impact of IPIs on growth parameters or level of children’s academic performance.