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Giardia lamblia is an important protozoan cause of diarrheal disease worldwide, delayed development and cognitive impairment in children in low- and middle-income countries, and protracted post-infectious syndromes in developed regions. G. lamblia resides in the lumen and at the epithelial surface of the proximal small intestine but is not mucosa invasive. The protozoan parasite is genetically diverse with significant genome differences across strains and assemblages. Animal models, particularly murine models, have been instrumental in defining mechanisms of host defense against G. lamblia, but mice cannot be readily infected with most human pathogenic strains. Antibiotic pretreatment can increase susceptibility, suggesting that the normal microbiota plays a role in controlling G. lamblia infection in mice, but the broader implications on susceptibility to diverse strains are not known. Here, we have used gnotobiotic mice to demonstrate that robust intestinal infection can be achieved for a broad set of human-pathogenic strains of the genetic assemblages A and B. Furthermore, gnotobiotic mice were able to eradicate infection with a similar kinetics to conventional mice after trophozoite challenge. Germ-free mice could also be effectively immunized by the mucosal route with a protective antigen, α1-giardin, in a manner dependent on CD4 T cells. These results indicate that the gnotobiotic mouse model is powerful for investigating acquired host defenses in giardiasis, as the mice are broadly susceptible to diverse G. lamblia strains yet display no apparent defects in mucosal immunity needed for controlling and eradicating this lumen-dwelling pathogen.

Giardia is a prevalent single-celled microaerophilic intestinal parasite causing diarrheal disease and significantly impacting global health. Double diploid (essentially tetraploid) Giardia trophozoites have presented a formidable challenge to the development of molecular genetic tools to interrogate gene function. High sequence divergence and the high percentage of hypothetical proteins lacking homology to proteins in other eukaryotes have limited our understanding of Giardia protein function, slowing drug target validation and development. For more than 25 years, Giardia A and B assemblages have been readily amenable to transfection with plasmids or linear DNA templates. Here, we highlight the utility and power of genetic approaches developed to assess protein function in Giardia, with particular emphasis on the more recent clustered regularly interspaced palindromic repeats/Cas9-based methods for knockdowns and knockouts. Robust and reliable molecular genetic approaches are fundamental toward the interrogation of Giardia protein function and evaluation of druggable targets. New genetic approaches tailored for the double diploid Giardia are imperative for understanding Giardia's unique biology and pathogenesis.

The intestinal parasites Giardia lamblia and Entamoeba histolytica are major causes of morbidity and mortality associated with diarrheal diseases. Metronidazole is the most common drug used to treat giardiasis and amebiasis. Despite its efficacy, treatment failures in giardiasis occur in up to 5%-40% of cases. Potential resistance of E. histolytica to metronidazole is an increasing concern. Therefore, it is critical to search for more effective drugs to treat giardiasis and amebiasis. We identified antigiardial and antiamebic activities of the rediscovered nitroimidazole compound, fexinidazole, and its sulfone and sulfoxide metabolites. Fexinidazole is equally active against E. histolytica and G. lamblia trophozoites, and both metabolites were 3- to 18-fold more active than the parent drug. Fexinidazole and its metabolites were also active against a metronidazole-resistant strain of G. lamblia. G. lamblia and E. histolytica cell extracts exhibited decreased residual nitroreductase activity when metabolites were used as substrates, indicating nitroreductase may be central to the mechanism of action of fexinidazole. In a cell invasion model, fexinidazole and its metabolites significantly reduced the invasiveness of E. histolytica trophozoites through basement membrane matrix. A q.d. oral dose of fexinidazole and its metabolites at 10 mg/kg for 3 days reduced G. lamblia infection significantly in mice compared to control. The newly discovered antigiardial and antiamebic activities of fexinidazole, combined with its FDA-approval and inclusion in the WHO Model List of Essential Medicines for the treatment of human African trypanosomiasis, offer decreased risk and a shortened development timeline toward clinical use of fexinidazole for treatment of giardiasis or amebiasis.

BACKGROUND: Giardia duodenalis (Gd) causes intestinal parasitosis. The involvement of the intestinal microbiome in determining the infections clinical phenotype is unknown. OBJECTIVE: Investigate the fecal microbiome features in dogs with giardiasis. ANIMALS AND METHODS: Cross-sectional study, including fecal samples of kenneled dogs with Gd diagnosed by fecal Giardia antigen dot ELISA. The fecal microbial compositional characteristics and dysbiosis index (DI) were compared between diarrheic and nondiarrheic dogs. RESULTS: Fecal samples of 38 Gd-infected dogs (diarrheic, 21; nondiarrheic, 17) were included. No differences were found in Faiths phylogenic diversity and beta diversity (weighted UniFrac distances) and in specific taxa abundances at the phylum, genus, and species levels, as well as in alpha and beta diversities between diarrheic and nondiarrheic dogs, and also when divided by sex or age. Among diarrheic dogs, alpha diversity was higher in males than in females (pairwise Kruskal-Wallis, q = 0.01). Among males, fecal abundances of the genus Clostridium (W = 19) and Clostridium spiroforme species (W = 33) were higher in diarrheic compared to nondiarrheic dogs. In diarrheic dog fecal samples, Proteobacteria were more prevalent (W = 1), whereas Verrucomicrobia were less prevalent in dogs

Background: The ubiquitous protozoan parasite Giardia duodenalis is a major contributor to the global burden of diarrhoea, particularly in young children living in poor-resource regions. Although rarely mortal, giardiasis is associated with growth retardation and cognitive impairment in early childhood. Here we investigate the epidemiology of human giardiasis in Iranshahr (south-eastern Iran), a region where this information was previously lacking. Methods: Stool samples were collected from 17,455 outpatients and inpatients attended at three major hospital settings during April 2020 and March 2022. Microscopy was used as a screening method for the presence of Giardia cysts, and the identification of G. duodenalis assemblages was carried out using PCR and Sanger sequencing. Results: The overall prevalence of giardiasis was 1.87 (326/17,455; 95% CI: 1.7–2.1). Being female was positively associated with higher odds of giardiasis (p = 0.014). Individuals without diarrhoea were less likely to have giardiasis (p = 0.022). Individuals attending the Iran Hospital were more likely to harbour G. duodenalis infections compared to those attending at the Khatam Hospital and the Clinical Reference Laboratory (p = 0.001). Our sequence analyses revealed the presence of assemblages A (56.5%, 13/23), B (39.1%, 9/23), and A + B (4.4%, 1/23). No association was observed between the occurrence of a given assemblage and the occurrence of diarhroea. Conclusions: Giardia infections were found at relatively low prevalence rates in both symptomatic and asymptomatic individuals seeking medical attention. Being female, having diarrhoea, and being sampled during 2020–21 were predictors of giardiasis. Although limited, our molecular data indicate that some Giardia infections may be zoonotic in nature. These data should be corroborated and expanded in future epidemiological studies targeting simultaneously human, animal, and environmental (water) samples to improve our understanding of the epidemiology of giardiasis in Iran. [ABSTRACT FROM AUTHOR]

Background: Giardia duodenalis is a common enteric protozoan parasite that is categorized into eight assemblages (A–H). In particular, assemblages A and B are zoonotic, capable of infecting both humans and animals worldwide, resulting in significant economic losses and public health challenges in epidemic regions. Thus, the development of rapid, accurate and non-laboratory-based diagnostic methods for infected animals is crucial for the effective prevention and control of giardiasis. Recent advancements in clustered, regularly interspaced, short palindromic repeats (CRISPR) and CRISPR-associated (Cas) protein (Cas12a) systems allow promising avenues for nucleic acid detection, characterized by their high flexibility, sensitivity and specificity. Methods: Combined recombinase polymerase amplification and CRISPR/Cas12a systems were combined and used as end-point diagnostic methods (termed REPORT) to detect G. duodenalis assemblage A and B. The diagnostic results can be observed by fluorescence readouts with the naked eye under blue light or colorimetric signals using a lateral flow strip (LFS). Results: The limit of detection (LOD) of the REPORT‑based G. duodenalis assemblage A detection was 2.04 CFU/ml and 10 trophozoites per gram (TPG), and the LOD of assemblage B was 1.1 CFU/ml and 10 cysts per gram (CPG). The REPORT‑based G. duodenalis assemblage A and assemblage B detection methods have strong specificity and no cross-reactivity with other assemblages of G. duodenalis or common enteric parasitic protozoa and have excellent performance in clinical sample detection. Conclusions: This study presents a novel strategy for the direct identification of G. duodenalis assemblages A and B, requiring neither highly trained personnel nor costly specialized equipment. [ABSTRACT FROM AUTHOR]

Giardia duodenalis, an important zoonotic protozoan parasite, adheres to host intestinal epithelial cells (IECs) via the ventral disc and causes giardiasis characterized mainly by diarrhea. To date, it remains elusive how excretory-secretory products (ESPs) of Giardia enter IECs and how the cells respond to the entry. Herein, we initially demonstrated that ESPs evoked IEC endocytosis in vitro. We indicated that ESPs contributed vitally in triggering intrinsic apoptosis, pro-inflammatory responses, tight junction (TJ) protein expressional changes, and autophagy in IECs. Endocytosis was further proven to be implicated in those ESPs-triggered IEC responses. Ten predicted virulent excretory-secretory proteins of G. duodenalis were investigated for their capability to activate clathrin/caveolin-mediated endocytosis (CME/CavME) in IECs. Pyridoxamine 5'-phosphate oxidase (PNPO) was confirmed to be an important contributor. PNPO was subsequently verified as a vital promoter in the induction of giardiasis-related IEC apoptosis, inflammation, and TJ protein downregulation. Most importantly, this process seemed to be involved majorly in PNPO-evoked CME pathway, rather than CavME. Collectively, this study identified Giardia ESPs, notably PNPO, as potentially important pathogenic factors during noninvasive infection. It was also noteworthy that ESPs-evoked endocytosis might play a role in triggering giardiasis-inducing cellular regulation. These findings would deepen our understanding about the role of ESPs, notably PNPO, in the pathogenesis of giardiasis and the potential attributed endocytosis mechanism. [ABSTRACT FROM AUTHOR]

Aim: Helicobacter pylori and infections due to intestinal parasites are quite common in developing countries around the world, in societies with low socioeconomic levels, and in regions with inadequate and unhealthy drinking water and food. Our study aimed to reveal the association Helicobacter pylori positivity and intestinal parasites (IP) in the stool patients who came to the hospital due to dyspeptic complaints. Materials and Methods: Between 01.2018 and 04.2024, 953 patients admitted to the hospital with dyspepsia and whose stool samples were taken were examined. The data of patients for whom stool Helicobacter pylori rapid antigen test, IP test and demographic variables were requested were evaluated retrospectively. Results: Of the 953 patients, 396 (41.6%) were male and 557 (58.4%) were female. Patient ages ranged from 18 to 85 years and the average was 38.65± 15,15.64 years. The patients were divided into two age groups. There were 882 (92.5%) patients between the ages of 18-65, and 71 (7.5%) patients between the ages of 66-85. Entamoeba histolytica (E. histolytica)/Entamoeba dispar (E. dispar) in 12 (1.3%) of the patients, Giardia intestinalis (G. intestinalis) in 24 (2.5%), Blastocystis hominis (B. Hominis) in 3 (0.3%) and H. pylori was detected in 128 (13.4%). The relationship between H. pylori and IP was found to be statistically significant. IP was detected in 20.3% of cases in which H. pylori was detected. No relationship was found between gender and H. pylori and IP. No relationship was found between age groups and H. pylori and IP. Conclusion: H. pylori and IP are found quite frequently in the world. To better understand the association between them, more comprehensive multi-center studies are needed, in which high-sensitivity methods are used and data can be compared with healthy control groups. [ABSTRACT FROM AUTHOR]

Giardia duodenalis is the causative agent of the neglected diarrhoeal disease giardiasis. While often self-limiting, giardiasis is ubiquitous and impacts hundreds of millions of people annually. It is also a common gastro-intestinal disease of domestic pets, wildlife, and livestock animals. However, despite this impact, there is no vaccine for Giardia currently available. In addition, treatment relies on chemotherapies that are associated with increasing failure rates. To identify new treatment options for giardiasis we recently screened the Compounds Australia Scaffold Library for new chemotypes with selective anti-Giardia activity, identifying three compounds with sub-μM activity and promising selectivity. Here we extended these studies by examining the anti-Giardia activity of series CL9569 compounds. This compound series was of interest given the promising activity (IC50 1.2 μM) and selectivity demonstrated by representative compound, SN00798525 (1). Data from this work has identified an additional three thieno [3,2-b]pyrrole 5-carboxamides with anti-Giardia activity, including 2 which displayed potent cytocidal (IC50 ≤ 10 nM) and selective activity against multiple Giardia strains, including representatives from both human-infecting assemblages and metronidazole resistant parasites. Preclinical studies in mice also demonstrated that 2 is well-tolerated, does not impact the normal gut microbiota and can reduce Giardia parasite burden in these animals.

Giardia doudenalis (lamblia, intestinalis) is a protozoan parasite that inhabits the lumen of the upper small intestine of vertebrates, causing chronic abdominal pains and severe diarrhea, symptoms of giardiasis, a persistent and recurrent infection. This characteristic is mainly due to the presence of membrane variant-specific surface proteins (VSPs) that give this parasite the ability to successively infect the host through antigenic variation. Using high-resolution scanning microscopy (HR-SM), we observed the presence, formation, and extension of tunneling-nanotube-like surface structures in Giardia, especially following parasite challenges with VSP antibodies. They were seen all over the parasite surface, both in vitro and in vivo, showing that G. duodenalis nanotube formation occurs in complex environments such as the gut. In addition, we also observed that some of these nanotubes displayed a periodic strangulation that produces 100 nm vesicles that seemed to be released in a process similar to that previously observed in Trypanosoma brucei. The presence of nanotube-like structures in G. duodenalis highlights yet another strategy of cellular communication utilized by these parasites, whether between themselves or with the host cell. [ABSTRACT FROM AUTHOR]

Toxoplasmosis has a major public health significance because of its social and economic influence on the public. A protozoan parasite causes gastrointestinal problems characterised by acute or chronic diarrhoea, commonly known as giardiasis. The occurrence of giardiasis in dogs and cats has consequences for clinical and public health. Instead of being a potential threat to public health, no study has been planned to detect the occurrence of these important zoonotic parasites in pets of Faisalabad or Pakistan. Therefore, keeping in mind the importance, the current study was planned with the objectives of finding the occurrence of Toxoplasma gondii and Giardia in owned dogs and cats of Faisalabad and to find information about how much the owners know and are concerned about zoonosis. For this purpose, 150 (each for dogs and cats) faecal and blood samples were collected from 150 dogs and cats from pets that were presented to different veterinary clinics. Direct microscopy was used to screen for Giardia, while Toxoplasma was detected using the Toxoplasmosis Latex Kit (ANTEC Diagnostic®, UK). A questionnaire was completed to reveal the associated risk factors and awareness of zoonosis. The generated data were analysed using the chi-squared test. In dogs, an overall prevalence of 42% for Giardia and 37% for Toxoplasma gondii was found. The corresponding values for cats were 36% and 39.33%, respectively. These findings indicated a statistically non-significant (P>0.05) difference in the prevalence of these parasites in both species. Moreover, the findings of the study clearly illustrate that cats and dogs being kept as pet animals pose a serious threat to human beings, and owners are not aware of this alarming situation. [ABSTRACT FROM AUTHOR]

Giardia lamblia, the cause of giardiasis, significantly impacts patients with metabolic disorders related to insulin resistance (IR). Both giardiasis and metabolic disorders share elements such as chronic inflammation and intestinal dysbiosis, which substantially affect the metabolic and cytokine profiles of patients. This review discusses the mechanisms of virulence of G. lamblia, its influence on the immune system, and its association with metabolic disorders. The review aims to show how G. lamblia invasion acts on the immune system and the glucose and lipid metabolism. Key findings reveal that G. lamblia infection, by disrupting intestinal permeability, alters microbiota composition and immune responses, potentially impairing metabolic status. Future research should focus on elucidating the specific mechanisms by which G. lamblia influences the metabolism, exploring the long-term consequences of chronic infection, and developing targeted therapeutic strategies that include both parasitic and metabolic aspects. These insights underscore the need for a multidisciplinary approach to the treatment of giardiasis in patients with metabolic disorders. [ABSTRACT FROM AUTHOR]

The current study aimed to detect Giardia lamblia subtypes that infect children under 13 years and determine the association of subtype infection with some risk factors as age, gender, and residence. Triosephosphate isomerase gene from the positive microscopic samples was isolated. To confirm infection and the sensitivity of this gene, DNA in one negative and some positive samples were confirmed when amplified using β-giardin gene primers. From the 66 samples positive by microscopy, 65 tested positive by molecular assay of the triosephosphate isomerase gene with 98.4% sensitivity. While 37/65 (56.9%) represented subtype B, 23/65 (35.4%) represented subtype A, 5 (7.6%) represented A+B, while there was no E subtype. A subtype A in asymptomatic children exceeded 10/25 (40%) compared to 13/40 (32.5%) in symptomatic children. The proportion of B subtype among symptomatic children was higher than that of asymptomatic children (57.5% and 56% respectively). There was no significant difference between the subtype presence and gender, age or residence. Subtype A was higher in the watery diarrhoea samples than in the steatorrhea samples. On the contrary, B subtype was higher in the steatorrhea samples than in watery diarrhoea. Use of the gene triosephosphate isomerase showed a high sensitivity for molecular detection of Giardia spp. Children could be infected with both groups A and B subtypes. The study did not record any presence of subtype E. No significant difference between genders, age groups or place of residence was recorded. Symptoms and diarrhoea were insignificantly associated with subtype B. [ABSTRACT FROM AUTHOR]

Giardiasis is among the most prevalent protozoan infections around the globe infecting various species of mammals, birds, reptiles, amphibians, and humans. Among all the species of Giardia, only Giardia lamblia (assemblages A and B) have high zoonotic importance. It is an enteric disease marked by dysentery, abdominal cramps, perfused diarrhea, and anorexia. The giardiasis is majorly controlled by metronidazole, which plays a primary role in the control. The reports of resistance, ecotoxicity, and side effects of this drug necessitate the need for an alternative for the control of this disease; among all the alternatives, phytochemicals are the most promising substance to be used for future anti-giardiasis drug development. Plant preparations containing simple phenolics, alkaloids, saponins, flavonoids, and vitamins have been recently used by researchers. These drugs have been proven effective because of several direct and indirect mechanisms. Simple phenolics easily penetrate the cell of Giardia and disturb energy synthesis, flavonoids destroy the enzymatic process, and alkaloids disturb glycolysis. The vitamins alter the cell energy primarily. Because of these actions, they can be used for control of giardiasis. However, their pharmacological interactions and clinical toxicity studies are needed for their future use. [ABSTRACT FROM AUTHOR]

Giardiasis is a parasitic disease caused by Giardia lamblia (G. lamblia) that affects people worldwide. Still, few studies report on the immunoregulatory effects of the biomolecules of colostrum during interactions with G. lamblia. This study aimed to assess the concentrations of melatonin and cortisol hormones, the percentage of Treg cells, and the levels of cytokines IL-10 and TGF-β in colostrum from mothers who tested positive for the parasite. This cross-sectional study analyzed colostrum samples from 25 puerperal. The samples were tested using an ELISA to determine if they were seropositive for G. lamblia and the type of antibody present (IgM and IgG). Based on the results, the samples were divided into three groups: a control group (N = 10) with no reaction to either IgM or IgG, a group seropositive for IgG (IgG+/IgM−; N = 8), and a group seropositive for IgM (IgM+/IgG−; N = 7). The concentrations of melatonin and cortisol were measured using the ELISA method. Additionally, cytokines IL-10 and TGF-β and immunophenotyping were analyzed using flow cytometry. In the group that tested positive for IgM anti-G. lamblia, the concentration of melatonin was lower. However, in the colostrum from mothers who tested positive for IgG anti-G. lamblia, the level of this hormone had increased. The cortisol levels were similar between the groups, regardless of seropositivity. There was a higher percentage of Treg cells in the colostrum from mothers who tested positive for IgM anti-G. lamblia. TGF-β levels also increased in the colostrum of mothers who tested positive for IgM anti-G. lamblia. In the seronegative group for G. lamblia, there was a positive correlation between melatonin concentration and the percentage of Treg cells. These data suggest that the increase in regulatory cells and cytokines and the reduction in melatonin in colostrum from mothers with recent giardia infection may contribute to the evolution and manifestation of the disease. [ABSTRACT FROM AUTHOR]

Background: Giardiasis and zinc deficiency have been identified as serious health problems worldwide. Although Zn depletion is known to occur in giardiasis, no work has investigated whether changes occur in brain structures. Methods: Three groups of gerbils were used: control (1), orogastrically inoculated on day 3 after birth with trophozoites of two isolates of Giardia intestinalis (HGINV/WB) group (2 and 3). Estimates were made at five ages covering: establishment of infection, Giardia population growth, natural parasite clearance and a post-infection age. QuantiChrome zinc assay kit, cresyl violet staining and TUNEL technique were used. Results: A significant decrease (p<0.01) in tissue zinc was observed and persisted after infection. Cytoarchitectural changes were observed in 75% of gerbils in the HGINV or WB groups. Ectopic pyramidal neurons were found in the cornus ammonis (CA1-CA3). At 60 and 90 days of age loss of lamination was clearly visible in CA1. In the dentate gyrus (DG), thinning of the dorsal lamina and abnormal thickening of the ventral lamina were observed from 30 days of age. In the cerebellum, we found an increase (p<0.01) in the thickness of the external granular layer (EGL) at 14 days of age that persisted until day 21 (C 3 ± 0.3 μm; HGINV 37 ± 5 μm; WB 28 ± 3 μm); Purkinje cell population estimation showed a significant decrease; a large number of apoptotic somas were observed scattered in the molecular layer; in 60 and 90 days old gerbils we found granular cell heterotopia and Purkinje cell ectopia. The pattern of apoptosis was different in the cerebellum and hippocampus of parasitized gerbils. Conclusion: The morphological changes found suggest that neuronal migration is affected by zinc depletion caused by giardiasis in early postnatal life; for the first time, the link between giardiasis-zinc depletion and damaged brain structures is shown. This damage may explain the psychomotor/cognitive delay associated with giardiasis. These findings are alarming. Alterations in zinc metabolism and signalling are known to be involved in many brain disorders, including autism. Author summary: Giardia intestinalis (Syn. G. duodenalis or G. lamblia), is a protozoan flagellate that parasitizes humans and animals and is transmitted by the ingestion of food or water contaminated with cysts or via person-to-person contact. Causes diarrhoea. Affects children and adults worldwide. Giardiasis is known to have long-term effects. When giardiasis occurs in the first two years of a child's life, it is associated with stunted growth and psychomotor and cognitive retardation. Giardiasis and zinc deficiency have been identified as serious health problems worldwide. Although Zn depletion is known to occur in giardiasis, no work has investigated whether changes occur in brain structures. We modelled Giardia infection in gerbils in the first days of postnatal life and found morphological changes that suggest neuronal migration is affected by zinc depletion caused by giardiasis in early postnatal life. For the first time, the link between giardiasis-zinc depletion and damaged brain structures is shown. This damage may explain the psychomotor-cognitive delay associated with giardiasis. Alterations in zinc metabolism and signalling are known to be involved in many brain disorders, including autism. [ABSTRACT FROM AUTHOR]

Giardia duodenalis (syn. G. intestinalis, G. lamblia) is a widespread gastrointestinal protozoan parasite with debated taxonomic status. Currently, eight distinct genetic sub-groups, termed assemblages A-H, are defined based on a few genetic markers. Assemblages A and B may represent distinct species and are both of human public health relevance. Genomic studies are scarce and the few reference genomes available, in particular for assemblage B, are insufficient for adequate comparative genomics. Here, by combining long- and short-read sequences generated by PacBio and Illumina sequencing technologies, we provide nine annotated genome sequences for reference from new clinical isolates (four assemblage A and five assemblage B parasite isolates). Isolates chosen represent the currently accepted classification of sub-assemblages AI, AII, BIII and BIV. Synteny over the whole genome was generally high, but we report chromosome-level translocations as a feature that distinguishes assemblage A from B parasites. Orthologue gene group analysis was used to define gene content differences between assemblage A and B and to contribute a gene-set-based operational definition of respective taxonomic units. Giardia is tetraploid, and high allelic sequence heterogeneity (ASH) for assemblage B vs. assemblage A has been observed so far. Noteworthy, here we report an extremely low ASH (0.002%) for one of the assemblage B isolates (a value even lower than the reference assemblage A isolate WB-C6). This challenges the view of low ASH being a notable feature that distinguishes assemblage A from B parasites, and low ASH allowed assembly of the most contiguous assemblage B genome currently available for reference. In conclusion, the description of nine highly contiguous genome assemblies of new isolates of G. duodenalis assemblage A and B adds to our understanding of the genomics and species population structure of this widespread zoonotic parasite.

Parasitic diseases, predominantly prevalent in developing countries, are increasingly spreading to high-income nations due to shifting migration patterns. The World Health Organization (WHO) estimates approximately 300 million annual cases of giardiasis. The emergence of drug resistance and associated side effects necessitates urgent research to address this growing health concern. In this study, we evaluated over eleven thousand pharmacological compounds sourced from the FDA database to assess their impact on the TATA-binding protein (TBP) of the early diverging protist Giardia lamblia, which holds medical significance. We identified a selection of potential pharmacological compounds for combating this parasitic disease through in silico analysis, employing molecular modeling techniques such as homology modeling, molecular docking, and molecular dynamics simulations. Notably, our findings highlight compounds DB07352 and DB08399 as promising candidates for inhibiting the TBP of Giardia lamblia. Also, these compounds and DB15584 demonstrated high efficacy against trophozoites in vitro. In summary, this study identifies compounds with the potential to combat giardiasis, offering the prospect of specific therapies and providing a robust foundation for future research. [ABSTRACT FROM AUTHOR]

Background Prolonged diarrhoea is common amongst returning travellers and is often caused by intestinal protozoa. However, the epidemiology of travel-associated illness caused by protozoal pathogens is not well described. Methods We analysed records of returning international travellers with illness caused by Giardia duodenalis , Cryptosporidium spp. Cyclospora cayetanensis or Cystoisospora belli , reported to the GeoSentinel Network during January 2007–December 2019. We excluded records of travellers migrating, with an unascertainable exposure country, or from GeoSentinel sites that were not located in high-income countries. Results There were 2517 cases, 82.3% giardiasis (n  = 2072), 11.4% cryptosporidiosis (n  = 287), 6.0% cyclosporiasis (n  = 150) and 0.3% cystoisosporiasis (n  = 8). Overall, most travellers were tourists (64.4%) on long trips (median durations: 18–30 days). Cryptosporidiosis more frequently affected people < 18 years (13.9%) and cyclosporiasis affected people ≥ 40 years (59.4%). Giardiasis was most frequently acquired in South Central Asia (45.8%) and sub-Saharan Africa (22.6%), cryptosporidiosis in sub-Saharan Africa (24.7%) and South-Central Asia (19.5%), cyclosporiasis in South East Asia (31.3%) and Central America (27.3%), and cystoisosporiasis in sub-Saharan Africa (62.5%). Cyclosporiasis cases were reported from countries of uncertain endemicity (e.g. Cambodia) or in countries with no previous evidence of this parasite (e.g. French Guiana). The time from symptom onset to presentation at a GeoSentinel site was the longest amongst travellers with giardiasis (median: 30 days). Over 14% of travellers with cryptosporidiosis were hospitalized. Conclusions This analysis provides new insights into the epidemiology and clinical significance of four intestinal protozoa that can cause morbidity in international travellers. These data might help optimize pretravel advice and post-travel management of patients with travel-associated prolonged gastrointestinal illnesses. This analysis reinforces the importance of international travel-related surveillance to identify sentinel cases and areas where protozoal infections might be undetected or underreported. [ABSTRACT FROM AUTHOR]

This study demonstrates the capability of Raman microscopy for detecting structural differences in Giardia cells exposed to different drugs and incubation times. While metronidazole (MTZ) visibly affects the cells by inducing extracellular vesicle releases of toxic iron intermediates and modified triple-bond moieties, oseltamivir (OSM) alters the phenylalanine and lipid structures. Modifications in the heme protein environment and the transformation of iron from ferric to ferrous observed for both drug treatments are more notable for MTZ. Different contents and amounts of vesicle excretion are detected for 24 h or 48 h with MTZ incubation. At a shorter drug exposure, releases of altered proteins, glycogen, and phospholipids dominate. Agglomerates of transformed iron complexes from heme proteins and multiple-bond moieties prevail at 48 h of treatment. No such vesicle releases are present in the case of OSM usage. Drug incorporations into the cells and their impact on the plasma membrane and the dynamics of lipid raft confirmed by confocal fluorescence microscopy reveal a more destructive extent by OSM, corroborating the Raman results. Raman microscopy provides a broader understanding of the multifaceted factors and mechanisms responsible for giardiasis treatment or drug resistance by enabling a label-free, simultaneous monitoring of structural changes at the cellular and molecular levels. [ABSTRACT FROM AUTHOR]

On an annual basis the flagellate protozoan, Giardia duodenalis, is responsible for an estimated one billion human infections of which approximately two hundred million cause disease. However, the treatment of Giardia infections is reliant on a small group of chemotherapeutic classes that have a broad spectrum of antimicrobial activity and increasing treatment failure rates. To improve this situation, we need new drugs. In this study we screened the Compounds Australia Scaffolds Library for compounds with potent and selective activity against these parasites. Unlike previous drug discovery efforts that have focused on drug repurposing, this library is comprised of commercially available synthetic compounds arranged into lead-like scaffolds to facilitate structure activity relationship assessments and de novo drug discovery. A screen of 2451 compounds in this library identified 40 hits (>50% inhibitory activity at 10 µM, over 48 h). Secondary testing identified three compounds with IC50 values 50-fold selectivity for parasites over mammalian cells and a hit series, CL9406, comprising compounds with potent (lowest IC50 180 nM) and selective activity for Giardia parasites. The most promising compound in this series, SN00797640, displayed selective activity against assemblage A, B, and metronidazole resistant parasites which was parasiticidal (minimum lethal concentration 625 nM) and synergistic with albendazole. SN00797640 was well-tolerated when administered to mice at doses of 50 mg/kg daily for three days paving the way for pre-clinical in vivo activity assessment.

The article presents a clinical case of the treatment of H. pylori infection and giardiasis in a 27-year-old female patient who had been suffering from spastic pain in the epigastrium, umbilical region, nausea and severity in the epigastrium after eating, decreased appetite, unstable stools for three years. An eradication regimen was prescribed with nifuratel, which has indications for the treatment of H. pylori infection and giardiasis in the instructions for use. The following drugs were recommended to the patient for 14 days: esomeprazole 20 mg 2 times a day 30 minutes before meals + nifuratel 400 mg 2 times a day after meals + аmoxicillin 1000 mg 2 times a day 15 minutes after taking nifuratel + bismuth tricalium dicitrate 240 mg 2 times 60 minutes before meals. Negative results of three-fold analysis of feces for giardia and feces for H. pylori antigen by ELISA confirmed the patient's convalescence, which proved the effectiveness of this treatment regimen.

Even when asymptomatic, intestinal parasitosis can have a significant impact on the health of children. Materials and methods. An analysis of the medical documentation of the children's clinic for 2016—2023 was carried out. Results. It has been established that enterobiasis dominates in children living in St. Petersburg (87.8%—98.8%), the proportion of ascariasis and giardiasis in different years did not exceed 5.2% and 10.0%, respectively. The maximum proportion of those affected by E. vermicularis (50.6%—66.8%) and Giardia (67.3%) was in the age group of 7—14 years, while ascariasis most often affected children 3—6 years old (51.7%). Enterobiasis was more often recorded during annual preventive examinations (September-November) (52.0%—65.9%), ascariasis was detected at a later date — November-January (41.5%), the largest number of episodes of giardiasis was observed in the spring months (53.9%). If helminthic infestations in all cases were asymptomatic and were discovered by chance during a microscopic examination of feces, then in the case of giardiasis, 46.2% of those infected complained of abdominal pain (42.3%), discomfort after eating (25.0%), diarrhea/constipation (21.2%), bloating (19.2%), frequent belching of air (13.5%). Thus, a single microscopic examination of feces is not very informative. Knowledge of the clinical and epidemiological features of parasitic infestations will allow the pediatrician to conduct an in-depth examination of the child to decide on antiparasitic treatment

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

Giardia duodenalis is one of the major causes of diarrhea among children. We performed a systematic review and meta-analysis to assess the prevalence of G. duodenalis and associated risk factors among Asian children. We searched online databases (PubMed, Scopus and Web of Science) and Google Scholar search engine for studies published from 1 January 2000 to 15 March 2022 that measured the prevalence of G. duodenalis among Asian children. Accordingly, the pooled prevalence and 95% CIs were estimated using a random-effects meta-analysis model for the included studies. A total of 182 articles from 22 Asian countries met the inclusion criteria. The pooled prevalence of G. duodenalis infection among Asian children was estimated as 15.1% (95% CI 14.1 to 16%). The highest and lowest pooled prevalence values of G. duodenalis infection were estimated for Tajikistan and China as 26.4% (95% CI 22.9 to 30%) and 0.6% (95% CI 0.001 to 1.02%), respectively. The infection had a higher prevalence in males than in females (OR=1.24; 95% CI 1.16 to 1.31; p<0.001), which was statistically significant. Giardiasis is common among Asian children, hence, a prevention and control scheme of this protozoan in children should be considered by health officials and health policymakers, especially in Asian countries where the prevalence is highest. [ABSTRACT FROM AUTHOR]

Giardiasis is a parasitosis caused by Giardia lamblia with significant epidemiological and clinical importance due to its high prevalence and pathogenicity. The lack of optimal therapies for treating this parasite makes the development of new effective chemical entities an urgent need. In the search for new inhibitors of the adenylyl cyclase gNC1 obtained from G. lamblia, 14 extracts from Argentinian native plants were screened. Lepechinia floribunda and L. meyenii extracts exhibited the highest gNC1 inhibitory activity, with IC50 values of 9 and 31 µg/mL, respectively. In silico studies showed rosmarinic acid, a hydroxycinnamic acid present in both mentioned species, to be a promising anti-gNC1 compound. This result was confirmed experimentally, with rosmarinic acid showing an IC50 value of 10.1 µM. Theoretical and experimental findings elucidate the molecular-level mechanism of rosmarinic acid, pinpointing the key interactions stabilizing the compound–enzyme complex and the binding site. These results strongly support that rosmarinic acid is a promising scaffold for developing novel compounds with inhibitory activity against gNC1, which could serve as potential therapeutic agents to treat giardiasis. [ABSTRACT FROM AUTHOR]

Background and Objective: Giardia is a parasitic hard protozoan that causes a variety of parasitological and pathological changes in gastrointestinal epithelial cells and is resistant to a variety of disinfectants and treatments. This study used experimental animals infected with Giardia Lamblia to assess the potential therapeutic effect of Lactobacillus casei, Lactobacillus bulgaricus (Lactobacillus in yoghurt) and curcumin in comparison to one of the commonly used drugs (metronidazole). Methods: The study included 54 Syrian hamsters (Mesocricetus auratus) that ranged in weight from 80 to 100 g and were divided into six groups: The effect of the used preparations was assessed in terms of parasitological and histopathological aspects in Group I non-infected healthy control, Group II infected non-treated, Group III infected treated with metronidazole MTZ, Group IV infected treated with Lactobacillus casei, Group V infected treated with curcumin, and Group VI infected treated with, Lactobacillus bulgaricus (Lactobacillus in yoghurt). The number of G. lamblia cysts per gram of stool was counted during the parasitological examination. Results: The difference between the infected non-treated group and all the treated groups was statistically significant (P0.05). When compared to the infected untreated group, Lactobacillus casei and, Lactobacillus bulgaricus (Lactobacillus in yoghurt) produced a 100% reduction in G. lamblia cyst shedding, curcumin produced an 87.80% reduction in number of cysts, and metronidazole produced a 78.4% reduction in number of cysts. Conclusion: Our results highlight the potentially effective therapeutic effect of different preparations of probiotics and curcumin against Giardiasis. [ABSTRACT FROM AUTHOR]

Giardiasis, caused by the protozoan Giardia intestinalis, affects around 400 million people worldwide, emphasizing the critical need for accurate diagnosis to enhance human health, especially in children. Prolonged giardiasis in childhood can lead to intellectual deficits and other complications. A variety of diagnostic tools, including microscopic, immunological, and molecular methods, are available for detecting G. intestinalis infection. Choosing the most suitable method can be challenging due to the abundance of options. This systematic review assesses the reliability and applicability of these diagnostic modalities. Utilizing the Dimensions and Wordart platforms for data analysis, we focus on relevant literature addressing diagnostic methods for human giardiasis. Microscopic techniques, particularly Ritchie's method, emerge as the primary choice, followed by enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR). PCR's limited use is attributed to its high cost and infrastructure challenges in developing nations. In conclusion, our analysis supports microscopic methods as the gold standard for giardiasis diagnosis. However, in cases where symptoms persist despite a negative diagnosis, employing more sensitive diagnostic approaches is advisable. [ABSTRACT FROM AUTHOR]

Giardiasis, which is caused by Giardia duodenalis, has clinical symptoms such as steatorrhea and can be very dangerous in children. In addition, some documents reported that this parasite is present inside the tissue of patients with cancer. In this study, we analyzed the gene expression profiles of some main genes important to apoptosis and anti-apoptosis in humans. Expression profile arrays of Genomic Spatial Event (GSE) 113666, GSE113667, and GSE113679 obtained from Gene Expression Omnibus were used for meta-analysis using R commands. Cytoscape and STRING databases used the protein–protein Interaction network. Then, the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis was performed. Similar genes in Homo sapiens were identified using Basic Local Alignment Search Tool analysis. The validation was performed on eight people using real-time Polymerase chain reaction. In addition to the candidate genes, the gene expression of some other genes, including Serine/Threonine Kinase 1 (AKT1), Cyclin Dependent Kinase Inhibitor 2A (CDKN2A), Kirsten Rat Sarcoma (KRAS), and Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA) were also examined. Analysis of the expression of serum amyloid A1 (SAA1), Regenerating Islet-Derived 3 Gamma (REG3G), and REG3A genes did not show any difference between the two groups of healthy and diseased people. Examining the mean expression of the four genes AKT1, CDKN2A, KRAS, and PIK3CA showed that three genes of AKT1, CDKN2A, and KRAS had increased expression in people with a history of giardiasis compared to healthy people. We showed that the gene expression pattern differs in apoptosis and anti-apoptosis signaling in people with a history of giardiasis. Giardia duodenalis seems to induce post-non-infectious symptoms with stimulation of human gene expression. [ABSTRACT FROM AUTHOR]

Background: We aimed to determine the prevalence of Giardia intestinalis and Cryptosporidium spp. in patients who admitted hospital with diarrhea and to gain information about the transmission of these parasites in Ağrı, Türkiye. Methods: This study included 184 patients who applied to Ağrı-Diyadin State Hospital, Türkiye in 2022. The immunochromatographic card test was used for detection of the G. intestinalis and Cryptosporidium spp. Nested PCR-RFLP analysis of the COWP gene and sequence analysis of the gp60 gene were used to genotype and subtype Cryptosporidium spp., whereas Nested PCR and sequence analyses of ß-giardin gene were used genotype G. intestinalis. Results: Of the 184 stool specimens examined, 12 (14.29%) and 7 (3.80%) were positive for G. intestinalis and Cryptosporidium spp., respectively. The Cryptosporidium species were identified as C. parvum belonging to the IId subtype family. The G. intestinalis were identified assemblages A. Conclusion: Assemblage A, which is associated with diarrhea, is responsible for giardiasis and C. parvum IId subtype, often found in sheep, goats and cattle, is responsible for cryptosporidiosis in Ağrı, Türkiye. [ABSTRACT FROM AUTHOR]

Background: Giardia intestinalis is an intestinal protozoan which commonly causes parasitic gastroenteritis globally. It is a species complex consisting of at least eight assemblages (genotypes). In India, Giardia is mostly underreported and missed in asymptomatic cases. Aim: The aim of this study was to genotype the G. intestinalis isolates from stool samples of patients at a tertiary care center in Rajasthan, India, and to clinically correlate it. Methods: This prospective pilot cross-sectional study was conducted from 2019 to 2021 in a tertiary care center in western India. Patients who were microscopically positive for giardiasis were enrolled. DNA was extracted from their stool samples and amplified by polymerase chain reaction (PCR) using 4E1-HP as the target sequence. Anthropometric measurements and analysis were done for children by using Anthrocal application. Results: A total of 50 patients were enrolled. Diarrhea was present in 18 patients (36%). Among these, 6 were immunocompromised and had different comorbidities. Among the children <12 years of age, 55.17% (n = 16/29) were stunted (<-2 S.D.), and among <5 years, 44.4% (n = 4/9) showed wasting (<-2 S.D.). A PCR product corresponding to assemblage B of G. intestinalis was amplified in 47 stool specimens. Only three stool samples were negative for both assemblages A and B and posed an interesting enigma. Conclusion: In this study, a predominance of assemblage B of G. intestinalis was detected in 94% of the isolates. Furthermore, the possibility of zoonotic transmission could not be ruled out. [ABSTRACT FROM AUTHOR]

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The current experimental study is designed to examine the in vitro and in vivo effects of green synthesized silver nanoparticles (AgNPs) against Giardia lamblia, a major cause of parasitic diarrhea. The precipitation method was employed for the green synthesis of AgNPs by Astragalus ecbatanus aqueous extract. In the, in vitro, Giardia lamblia cysts and trophozoites were exposed to AgNPs at 10, 20, and 40 mg/mL for 10–360 min. The effects of AgNPs on trophozoite plasma membrane and their cytotoxic effects on normal and colon cancer cells were evaluated using Sytox green and MTT assay for cell viability. The in vivo assay included BALB/c mice, infected by Giardia, treated with AgNPs at 10, 15, and 20 mg/kg/day for one week. On the 8th day post-infection, stool examination was conducted to assess the presence of Giardia cysts and the reduction rate. The size distribution of AgNPs ranged between 5 and 80 nm, with the maximum particle size observed at 40–60 nm. AgNPs significantly (P<0.001) increased the mortality of Giardia lamblia trophozoites in a dosedependent manner. Specifically, AgNPs at concentrations of 200 and 300 μg/mL destroyed Giardia lamblia cysts after 4 and 2 h, respectively. Trophozoites of Giardia lamblia showed more sensitivity to AgNPs compared to cysts. At concentrations of 100, 200, and 300 μg/mL, AgNPs eliminated all trophozoites after 4, 2, and 1 h of treatment, respectively. AgNPs dose-dependently reduced (P<0.001) the parasite load and viability of Giardia lamblia cysts. Exposure of Giardia lamblia trophozoites to AgNPs dose-dependently increased the plasma membrane permeability as indicated by rise in the exposed fluorescence. The CC50 value AgNPs for colon cancer and normal cell lines was 402.3 μg/mL and 819.6 μg/mL, respectively. The selectivity value greater than 2 (2.04), suggests that these AgNPs are safe for normal cells in comparison with cancer cells. This experimental study showed that AgNPs green synthesized by Astragalus ecbatanus exhibited significant in vitro and in vivo anti-Giardia activity, positioning them as potential candidates for Giardia infection treatment. Nevertheless, further research on the precise mechanisms of action and comprehensive exploration of all toxicity aspects associated with this type of AgNPs need to be considered. [ABSTRACT FROM AUTHOR]

Background and Aim: According to the World Health Organization, close to 21% of India's population may be affected by intestinal parasites, accounting for 39 million disability-adjusted life years, which may likely be due to substandard sanitation practices and insufficient personal hygiene standards. This research was conducted with the aim of determining the prevalence of helminthic infections among school-aged children in the South Canara district of India. Materials and Methods: We conducted a cross-sectional study involving school children from nursery to the 8th Grade in the South Canara district of Karnataka, India. The presence of various intestinal parasites in different age groups was determined by performing routine stool microscopy. Modified acid-fast staining was performed for stool samples collected from children <5 years of age for the detection of intestinal coccidian parasites. Statistical analysis was carried out to analyze age-related trends in relation to the prevalence of commonly detected intestinal parasites. Results: Intestinal parasites were identified in 10 of the 253 students (3.9%), with the highest incidence observed in the age group of 7-10 years (1.9%). The most prevalent parasite identified was the cysts of Giardia lamblia, with a prevalence of 7.54%, followed by Ascaris lumbricoides and hookworm, each having a prevalence of 5.66%. Of the 253 students, 92.2% practiced handwashing with soap after defecation, while 7.8% did not use soap. The handwashing practices did not significantly vary across different age groups. Clinically, pallor was observed in 64.2% of the individuals. Conclusion: Giardiasis was the most common parasitic infection, followed by soil-transmitted helminths such as Ascariasis and hookworm. The level of hygiene practices among children exceeded the prevailing national and state standards. [ABSTRACT FROM AUTHOR]

Background: We reported a rare case of combined Giardiasis, sepsis, and DIC in a Tibetan Chinese male in this study. Methods: Multiple fecal routine examinations, blood routine examination, blood culture, coagulation screening, and biochemical tests were done after August 1st, 2022. Results: The child had intermittent diarrhea. Giardia cysts were found in his stool mounts. Sepsis, disseminated intravascular coagulation, fever with blood routine decreasing, low proteinemia, hyperlactemia and hypocalcemia were also found in this case. Conclusions: It is suggested that improving the resistance, immunity, and personal hygiene is particularly important for children from remote ethnic minority areas of China. [ABSTRACT FROM AUTHOR]

Background: Giardiasis is an important cause of diarrheal disease and is associated with morbidity in children and adults worldwide. We aimed to study the prevalence of Giardiasis, its clinical presentations, seasonal trends in detection, and coinfection with other intestinal parasites along with comparison of fecal antigen and microscopy for the detection of Giardiasis. Materials and Methods: It is a retrospective study conducted from Jan. 2017 to Dec. 2021 at our university hospital. Iodine and normal saline mounts and enzyme-linked immunosorbent assay (ELISA) were used for the detection of Giardiasis in stool samples. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of tests were computed. Results: Of 8364 patients, 432 (5.2%) had Giardiasis by microscopy and/or ELISA. Giardiasis was more common in males compared to females (318/5613 [5.6%] vs. 114/2751 [4.1%]; P = 0.003) and among those ≤10 y compared to older individuals (102/560 [18.2%] vs. 330/7804 [4.2%]; P

From the safety inside vehicles, Knowsley Safari offers visitors a close-up encounter with captive olive baboons. As exiting vehicles may be contaminated with baboon stool, a comprehensive coprological inspection was conducted to address public health concerns. Baboon stools were obtained from vehicles, and sleeping areas, inclusive of video analysis of baboon–vehicle interactions. A purposely selected 4-day sampling period enabled comparative inspections of 2662 vehicles, with a total of 669 baboon stools examined (371 from vehicles and 298 from sleeping areas). As informed by our pilot study, front-line diagnostic methods were: QUIK-CHEK rapid diagnostic test (RDT) (Giardia and Cryptosporidium), Kato–Katz coproscopy (Trichuris) and charcoal culture (Strongyloides). Some 13.9% of vehicles were contaminated with baboon stool. Prevalence of giardiasis was 37.4% while cryptosporidiosis was

A screen for compounds with antigiardial activity in the Compounds Australia Scaffolds library identified SN00797640 (supplied structure being 8-acylaminodibenzoxazepinone 1) as a hit compound with potent anti-parasitic activity (concentration for 50% growth inhibition of Giardia duodenalis, IC50 0.18 μM). To further explore the structure–activity relationships in this series, compound 1 and analogues, including its 7-acylaminodibenzoxazepinone regioisomer (2), were synthesized and assessed for anti-Giardia activity. While regioisomer 2 demonstrated antigiardial activity, resynthesized 1 and other 8-acylaminodibenzoxazepinone analogues were inactive. Comparison of spectroscopic and physical properties demonstrated the correct structure of SN00797640 to be 7-acylamino regioisomer 2. These results highlight the importance of independent synthesis in verifying the structure and activity of screening hits.

Giardia lamblia is a leading protozoal cause of diarrheal disease worldwide. Infection is associated with abdominal pain, malabsorption and weight loss, and protracted post-infectious syndromes. A human vaccine is not available against G. lamblia. Prior studies with human and murine immune sera have identified several parasite antigens, including surface proteins and metabolic enzymes with intracellular functions. While surface proteins have demonstrated vaccine potential, they can exhibit significant variation between G. lamblia strains. By comparison, metabolic enzymes show greater conservation but their vaccine potential has not been established. To determine whether such proteins can serve as vaccine candidates, we focused on two enzymes, α-enolase (ENO) and ornithine carbamoyl transferase (OCT), which are involved in glycolysis and arginine metabolism, respectively. We show in a cohort of patients with confirmed giardiasis that both enzymes are immunogenic. Intranasal immunization with either enzyme antigen in mice induced strong systemic IgG1 and IgG2b responses and modest mucosal IgA responses, and a marked 100- to 1,000-fold reduction in peak trophozoite load upon oral G. lamblia challenge. ENO immunization also reduced the extent and duration of cyst excretion. Examination of 44 cytokines showed only minimal intestinal changes in immunized mice, although a modest increase of CCL22 was observed in ENO-immunized mice. Spectral flow cytometry revealed increased numbers and activation state of CD4 T cells in the small intestine and an increase in α4β7-expressing CD4 T cells in mesenteric lymph nodes of ENO-immunized mice. Consistent with a key role of CD4 T cells, immunization of CD4-deficient and Rag-2 deficient mice failed to induce protection, whereas mice lacking IgA were fully protected by immunization, indicating that immunity was CD4 T cell-dependent but IgA-independent. These results demonstrate that conserved metabolic enzymes can be effective vaccine antigens for protection against G. lamblia infection, thereby expanding the repertoire of candidate antigens beyond primary surface proteins.

The MORDOR trial in Niger, Malawi, and Tanzania found that biannual mass distribution of azithromycin to children younger than 5 years led to a 13.5% reduction in all-cause mortality (NCT02048007). To help elucidate the mechanism for mortality reduction, we report IgG responses to 11 malaria, bacterial, and protozoan pathogens using a multiplex bead assay in pre-specified substudy of 30 communities in the rural Niger placebo-controlled trial over a three-year period (n = 5642 blood specimens, n = 3814 children ages 1-59 months). Mass azithromycin reduces Campylobacter spp. force of infection by 29% (hazard ratio = 0.71, 95% CI: 0.56, 0.89; P = 0.004) but serological measures show no significant differences between groups for other pathogens against a backdrop of high transmission. Results align with a recent microbiome study in the communities. Given significant sequelae of Campylobacter infection among preschool aged children, our results support an important mechanism through which biannual mass distribution of azithromycin likely reduces mortality in Niger.

Giardiasis is a protozoan disease that affects the health of animals, as well as other humans all over the world. Based on its host spectrum and genetic variability, Giardia duodenalis is classified into 8 assemblages (A–H). The present study was aimed at comparing the efficiency of the three most frequently used methods (the flotation method, the SNAP test and the ELISA assay) for the detection of giardiasis in carnivores in terms of the applicability thereof for the scientific purposes and the practicality of their application in the veterinary clinical practice. In the period from March 2020 to February 2022, a total of 173 faecal samples (141 samples collected from shelter dogs; 28 samples from pet dogs; and 6 samples from working dogs) were examined by applying the flotation method. The prevalence of Giardia duodenalis identified by the flotation method was 25 %. The SNAP test conducted with the fresh faecal samples revealed the high-level efficiency of 96 %, whereas the enzyme-linked immunosorbent assay (ELISA) achieved the efficiency of 65 %. By applying the nested PCR method, five samples were positively tested for assemblages C and D (G. canis) by the amplification of the bg and tpi loci. The dogs from shelters which were positive for G. duodenalis were also presented with a coinfection caused by other intestinal parasites, such as Trichuris vulpis (28.0 %) and parasites from the Ancylostomatidae family (8.0 %).

Giardia lamblia (also known as Giardia intestinalis and Giardia duodenalis) is the most frequent intestinal parasite responsible for chronic diarrhea and malnutrition. Giardia infections commonly cause nausea, abdominal cramping, bloating, and foul-smelling diarrhea in patients. Usually, Giardiasis causes a self-limiting illness, but it can progress to a severe disease in immunocompromised individuals and cause dehydration, malnutrition, and failure to thrive. As a result, early diagnosis and treatment are required to control the infection and prevent complications. Infectious Disease Society of America diagnostic guidelines recommend obtaining stool studies to diagnose Giardiasis. When stool tests are negative, but suspicion persists, a duodenal biopsy is a gold standard for diagnosis. We present the case of a patient diagnosed with Giardia by an incidental duodenal biopsy specimen obtained during a workup for malnutrition and chronic diarrhea, despite a normal stool examination. A few cases of Giardiasis have been diagnosed and reported in the literature using a duodenal biopsy. Some studies addressed the same issue, and we believe that duodenal biopsy can be a good strategy for diagnosing Giardiasis with high sensitivity and specificity.

Abstract Background The mechanisms underlying the clinical outcome disparity during human infection with Giardia duodenalis are still unclear. In recent years, evidence has pointed to the roles of host factors as well as parasite’s genetic heterogeneity as major contributing factors in the development of symptomatic human giardiasis. However, it remains contested as to how only a small fraction of individuals infected with G. duodenalis develop clinical gastrointestinal manifestations, whereas the majority of infected individuals remain asymptomatic. Here, we demonstrate that diversity in the fecal microbiome correlates with the clinical outcome of human giardiasis. Methods The genetic heterogeneity of G. duodenalis clinical isolates from human subjects with asymptomatic and symptomatic giardiasis was determined using a multilocus analysis approach. We also assessed the genetic proximity of G. duodenalis isolates by constructing phylogenetic trees using the maximum likelihood. Total genomic DNA (gDNA) from fecal specimens was utilized to construct DNA libraries, followed by performing paired-end sequencing using the HiSeq X platform. The Kraken2-generated, filtered FASTQ files were assigned to microbial metabolic pathways and functions using HUMAnN 3.04 and the UniRef90 diamond annotated full reference database (version 201901b). Results from HUMAnN for each sample were evaluated for differences among the biological groups using the Kruskal–Wallis non-parametric test with a post hoc Dunn test. Results We found that a total of 8/11 (72.73%) human subjects were infected with assemblage A (sub-assemblage AII) of G. duodenalis, whereas 3/11 (27.27%) human subjects in the current study were infected with assemblage B of the parasite. We also found that the parasite’s genetic diversity was not associated with the clinical outcome of the infection. Further phylogenetic analysis based on the tpi and gdh loci indicated that those clinical isolates belonging to assemblage A of G. duodenalis subjects clustered compactly together in a monophyletic clade despite being isolated from human subjects with asymptomatic and symptomatic human giardiasis. Using a metagenomic shotgun sequencing approach, we observed that infected individuals with asymptomatic and symptomatic giardiasis represented distinctive microbial diversity profiles, and that both were distinguishable from the profiles of healthy volunteers. Conclusions These findings identify a potential association between host microbiome disparity with the development of clinical disease during human giardiasis, and may provide insights into the mechanisms by which the parasite induces pathological changes in the gut. These observations may also lead to the development of novel selective therapeutic targets for preventing human enteric microbial infections. Graphical Abstract

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

Giardiasis is among the ignored zoonotic illnesses accorded by the World Health Organization that is caused by Giardia duodenalis. The disease is ignored regardless of the harm it causes to people and other creatures. In this paper, a mathematical model for giardiasis illness transmission is formed, which considers sickness carriers and control measures such as screening, treatment, and sanitation of the environment around people. In the assessment, the basic reproduction number, R 0 , which is used for analyzing the local stability of the equilibria is determined using the state-of-the-art next-generation matrix, while the Metzler constancy speculation is used to show the overall adequacy of the global stability of the equilibrium point free from the disease. In addition, a Lyapunov function has been used to study the stability of the endemic equilibrium point. The assessment of parameters is performed to explore the limits that significantly influence the transmission components of the disease disorders using the normalizing sensitivity index method. The result revealed that the recruitment rate is the most sensitive limit to the reproduction number. The environment-human interaction parameter is the second influential factor in the transmission of giardiasis in the community. In the same manner, the outcomes recommend that carriers assume an expected part in the rate of giardiasis subsequently; disregarding them could risk endeavors to control the pestilence. Besides, the mathematical recreation of the model shows that a mix of each of the three interventions fundamentally affects the control of giardiasis. In this way, we advise implementing the strategies simultaneously in endemic areas to effectively stop the spread of the giardiasis disease in humans. [ABSTRACT FROM AUTHOR]

Giardia lamblia (G. lamblia) is one of the most common protozoal infections and a key cause of malabsorption, some cases of mental developmental issues in children, and reduced body weight. The known antiparasitic medications, which are the standard drugs used for parasitic treatment, have several side effects and sometimes exhibit low efficacy. Therefore, the current study aimed to evaluate the treatment with quercetin (QC) or chitosan (CH), either alone or in combination, as possible alternative therapeutic agents that may alleviate the side effects of G. lamblia infections and restore the normal architecture of the intestinal muscles. They are investigated as alternatives to other routinely administered drugs that may gradually lose their efficacy due to human resistance to therapeutic agents. This study was carried out on 50 male albino rats that were divided into five groups with 10 rats in each group: the control group (Group I), the infected non-treated group (Group II), the infected group treated with QC (Group III), the infected treated group with CH (Group IV), and the infected group treated with a combination of QC and CH (Group V). The effect was first evaluated by counting the G. lamblia fecal cysts in the stool, examining histopathological sections of the intestine with the appearance of trophozoites in the infected group, and conducting a transmission electron microscopic examination of the tissues of the small intestine. Alterations in the biochemical parameters of liver and kidney function and the antioxidant enzymes in the liver tissues of SOD, CAT, and GSH, and non-enzymatic markers of lipid peroxidation (MDA) were evaluated. The results showed a significant decline in the number of parasites in the stool samples, with a marked elevation in the number of trophozoites in the intestinal sections of the infected non-treated group as compared to the infected treated groups. The last group, which was treated with a combination of QC and CH, showed the best results in terms of a decline in the infection rate of G. lamblia in stool samples, with a marked and clear improvement in the intestinal mucosa, regular muscles with normal enteric ganglions, and reduced rates of intestinal injuries caused by G. lamblia trophozoites. Both QC and CH had non-toxic effects on the biochemical parameters of the liver and kidneys, as well as pronounced antioxidant activities due to the elevation of SOD, CAT, and GSH in conjunction with a decline in the levels of MDA. A combination of QC and CH can be considered a potent antiparasitic, anti-hepatotoxic, and antioxidant therapeutic agent; it could constitute a promising alternative treatment agent against G. lamblia infection. [ABSTRACT FROM AUTHOR]