Aminoguanidines: New leads for treatment of Giardia duodenalis infection.
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ABSTRACT:
SUBMITTER: Abraham RJ
PROVIDER: S-EPMC6479099 | biostudies-literature | 2019 Aug
REPOSITORIES: biostudies-literature
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Aminoguanidines: New leads for treatment of Giardia duodenalis infection.
Abraham Rebecca J RJ Abraham Sam S Stevens Andrew J AJ Page Stephen W SW McCluskey Adam A Trott Darren J DJ O'Handley Ryan M RM
International journal for parasitology. Drugs and drug resistance 20190408
Giardia duodenalis is an ubiquitous parasitic pathogen that causes significant morbidity and mortality worldwide. Failures in drug therapy are commonly due to poor patient compliance as a result of the need for repeated administration, off target drug effects and increasing parasite drug resistance. In this study the in vitro efficacy and selectivity of the aminoguanidine compound robenidine and 2 structural analogues against Giardia were determined. After 5 h exposure to each compound the IC<su ...[more]
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Project description:BACKGROUND:The zoonotic parasite, Giardia duodenalis (syns. G. lamblia and G. intestinalis), has been widely reported in humans and animals, including rodents. The bamboo rat, a rodent species belonged to the subfamily Rhizomyinae, is farmed in China because of its medicinal and edible values. However, no information of G. duodenalis infection was available in bamboo rats prior to the present study. Here, the prevalence and genetic diversity of G. duodenalis in bamboo rats from Hunan Province of China were investigated. RESULTS:Of 480 faecal samples collected from six farms located in four cities (Wugang, Chenzhou, Huaihua and Jishou) of Hunan Province, 52 (10.8%) were positive for G. duodenalis infection by using a nested PCR approach targeting the beta giardin (bg) gene. Significant differences (P < 0.01) in prevalence were found among different age groups and geographical localities, and among different farms in Wugang city. Sequence analysis revealed existence of the zoonotic assemblage B and genetic diversity of G. duodenalis in these animals. Multilocus genotyping analysis also indicated broad genetic diversity of assemblage B isolates in these bamboo rats. CONCLUSIONS:This is the first report of the infection and genetic variations of G. duodenalis in bamboo rats. These findings will provide basic data for implementing effective strategies to control giardiasis in bamboo rats.
| S-EPMC6149208 | biostudies-literature
Project description:Giardia duodenalis has linear chromosomes capped with typical eukaryotic repeats [(TAGGG)n], subtelomeric rRNA genes, and telomere gene units. The absence of two closely associated NotI sites in the large-subunit rRNA gene was used as an indicator in hybridizations of one- and two-dimensional NotI-cleaved Giardia chromosome separations that some chromosomes carry only rearranged and, by deduction, nonfunctional rRNA genes.
| S-EPMC549325 | biostudies-other
Project description:BackgroundThe aim of this study was to assess potential associations between Giardia duodenalis infection in dogs, as determined by three diagnostic tests, and dog's group of origin, fecal consistency, age, sex, neuter status, and co-infections with other gastrointestinal parasites.MethodsFecal samples from 1291 dogs from four groups (household, shelter, hunting and clinical dogs) were tested with qPCR, rapid enzyme immunochromatographic assay (IDEXX SNAP® Giardia), and direct immunofluorescence (DFA, Merifluor) for presence of G. duodenalis. Moreover, fecal samples were tested with centrifugation sedimentation flotation (CSF) coproscopical analysis for presence of gastrointestinal parasites. Associations were expressed as odds ratios (ORs).ResultsSeveral significant associations were found, of which a few were consistent for all three tests and Giardia positivity in general (positive with at least one of these tests). Dogs older than one year were significantly less likely to test positive for Giardia than younger dogs. Group-housed dogs, especially hunting dogs, were significantly more likely to test positive for Giardia compared to household and clinical dogs. A consistently significant association with Trichuris appeared to be driven by the high prevalence in hunting dogs. Although there was no significant association between loose stool and Giardia infection in the overall population, household dogs were significantly more likely to test Giardia-positive when having loose stool. Overall, Giardia-positive dogs with loose stool shed significantly more cysts, both determined semi-quantitatively with CSF and quantitatively by qPCR, than positive dogs with no loose stool. When other gastrointestinal parasites were present, significantly fewer cysts were detected with CSF, but this was not confirmed with qPCR.ConclusionGiardia is the most common gastrointestinal parasite in Dutch dogs, except for hunting dogs, in which Trichuris and strongyle-type eggs (hookworms) prevailed. Giardia infection was not significantly associated with loose stool, except for household dogs. Young dogs and group-housed dogs were significantly more often Giardia-positive. These associations were consistent across diagnostic tests. Young dogs, clinical dogs and dogs with loose stool shed Giardia cysts in the highest numbers. If another gastrointestinal parasite was present lower numbers of cysts were observed by microscope (CSF), but not with a molecular method (qPCR).
| S-EPMC6873540 | biostudies-literature
Project description:Giardia duodenalis, originally regarded as a commensal organism, is the etiologic agent of giardiasis, a gastrointestinal disease of humans and animals. Giardiasis causes major public and veterinary health concerns worldwide. Transmission is either direct, through the faecal-oral route, or indirect, through ingestion of contaminated water or food. Genetic characterization of G. duodenalis isolates has revealed the existence of seven groups (assemblages A to G) which differ in their host distribution. Assemblages A and B are found in humans and in many other mammals, but the role of animals in the epidemiology of human infection is still unclear, despite the fact that the zoonotic potential of Giardia was recognised by the WHO some 30 years ago. Here, we performed an extensive genetic characterization of 978 human and 1440 animal isolates, which together comprise 3886 sequences from 4 genetic loci. The data were assembled into a molecular epidemiological database developed by a European network of public and veterinary health Institutions. Genotyping was performed at different levels of resolution (single and multiple loci on the same dataset). The zoonotic potential of both assemblages A and B is evident when studied at the level of assemblages, sub-assemblages, and even at each single locus. However, when genotypes are defined using a multi-locus sequence typing scheme, only 2 multi-locus genotypes (MLG) of assemblage A and none of assemblage B appear to have a zoonotic potential. Surprisingly, mixtures of genotypes in individual isolates were repeatedly observed. Possible explanations are the uptake of genetically different Giardia cysts by a host, or subsequent infection of an already infected host, likely without overt symptoms, with a different Giardia species, which may cause disease. Other explanations for mixed genotypes, particularly for assemblage B, are substantial allelic sequence heterogeneity and/or genetic recombination. Although the zoonotic potential of G. duodenalis is evident, evidence on the contribution and frequency is (still) lacking. This newly developed molecular database has the potential to tackle intricate epidemiological questions concerning protozoan diseases.
| S-EPMC2777335 | biostudies-literature
Project description:Italy is the only European country where the crested porcupine (Hystrix cristata) lives. A parasitological investigation was performed on faecal samples, aimed to evaluate Giardia and other parasites in a free-ranging crested porcupine population in Central Italy. Samples were collected from captured and road-killed individuals as well as from feeding areas and pathways. Collected faecal samples were examined by the Mini-FLOTAC technique and a rapid immunoassay for the search of Giardia and Cryptosporidium spp. faecal antigens. For the identification of Giardia species and genotypes, molecular analysis was performed on Giardia-positive samples, by using PCR protocols able to amplify glutamate dehydrogenase, triosephosphate isomerase and a fragment of the small subunit ribosomal RNA genes. A total of 52 crested porcupine faecal samples were collected and analysed. At microscopical examination, 39 out of 52 samples were found positive for at least a single parasite species and six different parasite taxa were identified. Forty-eight percent (25/52) of faecal samples were positive for Giardia spp. and 1.9% (1/52) for Cryptosporidium spp. at the immunoassay. Among 12 faecal samples belonging to different individuals, 33.3% (4/12) were positive for Giardia spp. By using the Mini-FLOTAC technique, positivity for Trichuris spp. (32.7%, 17/52), gastrointestinal strongyles (32.7%, 17/52), capillariid eggs (3.8%, 2/52) and coccidian oocysts (1.9%; 1/52) was also evidenced. Molecular analysis was performed on 17 out of 25 Giardia-positive isolates. At the SSU rDNA locus, expected bands were achieved for 12 out of 17 isolates and all samples were assigned to Giardia duodenalis assemblage B. Sequencing at tpi locus revealed potentially zoonotic G. duodenalis assemblage AII (two isolates) and assemblage BIV (one isolate). The present study provides the first report of G. duodenalis infection in H. cristata. More in depth studies are needed on the impact and epidemiology of G. duodenalis and other identified parasites in crested porcupines.
| S-EPMC6994745 | biostudies-literature
Project description:BackgroundGiardia duodenalis is one of the most common enteric parasites in domestic animals including dogs. Young animals are more prone to the infection, with clinical manifestations ranging from asymptomatic to acute or chronic diarrhoea. Dogs are primarily infected by canine-specific (C-D) assemblages of G. duodenalis. However, zoonotic assemblages A and B have been increasingly documented in canine isolates, raising the question of whether and to which extent dogs can act as natural reservoirs of human giardiosis.MethodsIn this cross-sectional epidemiological survey we assessed the molecular diversity of G. duodenalis in dogs in the province of Castellón, Eastern Spain. A total of 348 individual faecal samples from sheltered (n = 218), breeding (n = 24), hunting (n = 68), shepherd (n = 24), and pet (n = 14) dogs were collected between 2014 and 2016. Detection of G. duodenalis cysts in faecal material was carried out by direct fluorescence microscopy as a screening test, whereas a qPCR targeting the small subunit ribosomal RNA gene of the parasite was subsequently used as a confirmatory method.ResultsGiardia duodenalis was detected in 36.5% (95% CI: 31.6-41.7%) of dogs. No significant differences in prevalence rates could be demonstrated among dogs according to their sex and geographical origin, but breeding (45.8%; 95% CI: 27.9-64.9%) and sheltered (40.4%; 95% CI: 34.1-47.0%) dogs harboured significantly higher proportions of G. duodenalis. Multi-locus sequence-based genotyping of the glutamate dehydrogenase and β-giardin genes of G. duodenalis allowed the characterization of 35 canine isolates that were unambiguously assigned to assemblages A (14.3%), B (22.9%), C (5.7%), and D (37.1%). A number of inter-assemblage mixed infections including A + B (11.4%), A + D (2.9%), and A + B + D (5.7%) were also identified.ConclusionsData presented here are strongly indicative of high infection pressures in kennelled animals. Zoonotic sub-assemblages AII, BIII, and BIV were responsible for a considerable proportion of the G. duodenalis infections detected, but very few of the genotypes identified have been previously documented in Spanish human populations. Although possible, zoonotic transmission between dogs and humans seems an infrequent event in this Spanish region.
| S-EPMC5778629 | biostudies-literature
Project description:BackgroundApplication of chemotherapeutics in cancer patients may provide an immunosuppressive milieu, favourable for parasitic infections. Giardia duodenalis is an important zoonotic intestinal parasite responsible for diarrhoea in humans worldwide.MethodsThe present systematic review and meta-analysis was conducted to estimate the prevalence of G. duodenalis and respective odds ratios (ORs) in cancer patients around the globe. Four online databases-PubMed, Scopus, Web of Science and Google Scholar-were carefully explored for relevant literature without time limitation until 28 November 2020. Meta-analysis was done based on a random effects model to pool the estimations and define 95% confidence intervals (CIs).ResultsThe overall weighted prevalence of G. duodenalis infection in cancer patients was calculated to be 6.9% (95% CI 0.5 to 9.3) globally, based on data from 32 studies. Although not statistically significant, eight case-control studies revealed that cancer patients were 1.24 times (95% CI 0.66 to 2.31; p=0.501) more exposed to G. duodenalis infection than healthy controls. Moreover, the prevalence of infection was not significantly associated with quantitative variables, including publication year (regression coefficient -0.0135, p=0.578), sample size (regression coefficient -0.0007, p=0.074) and human development index (regression coefficient -1.6263, p=0.419). Also, subgroup analysis of the pooled G. duodenalis infection was performed for publication year, World Health Organization regions, countries, continents, cancer types and country income.ConclusionsAltogether, the epidemiology of G. duodenalis infection and its associated risk factors in immunocompromised individuals, especially cancer patients, is still open to question and deserves comprehensive investigations.
| S-EPMC8769951 | biostudies-literature
Project description:BackgroundGiardia duodenalis is highly endemic in East Africa but its effects on child health, particularly of submicroscopic infections, i.e., those below the threshold of microscopy, and of genetic subgroups (assemblages), are not well understood. We aimed at addressing these questions and at examining epidemiological characteristics of G. duodenalis in southern highland Rwanda.Methodology/principal findingsIn 583 children <5 years of age from communities and health facilities, intestinal parasites were assessed by triplicate light microscopy and by PCR assays, and G. duodenalis assemblages were genotyped. Cluster effects of villages were taken into account in statistical analysis. The prevalence of G. duodenalis as detected by microscopy was 19.8% but 60.1% including PCR results. Prevalence differed with residence, increased with age, and was reduced by breastfeeding. In 492 community children without, with submicroscopic and with microscopic infection, underweight (weight-for-age z-score <-2 standard deviations) was observed in 19.7%, 22.1%, and 33.1%, respectively, and clinically assessed severe malnutrition in 4.5%, 9.5%, and 16.7%. Multivariate analysis identified microscopically detectable G. duodenalis infection as an independent predictor of underweight and clinically assessed severe malnutrition. Submicroscopic infection showed respective trends. Overall, G. duodenalis was not associated with gastrointestinal symptoms but assemblages A parasites (proportion, 13%) were increased among children with vomiting and abdominal pain.Conclusions/significanceThe prevalence of G. duodenalis in high-endemicity areas may be greatly underestimated by light microscopy, particularly when only single stool samples are analysed. Children with submicroscopic infections show limited overt manifestation, but constitute unrecognized reservoirs of transmission. The predominance of assemblage B in Rwanda may be involved in the seemingly unimposing manifestation of G. duodenalis infection. However, the association with impaired child growth points to its actual relevance. Longitudinal studies considering abundant submicroscopic infections are needed to clarify the actual contribution of G. duodenalis to morbidity in areas of high endemicity.
| S-EPMC3373622 | biostudies-literature
Project description:Giardia duodenalis is the most common intestinal protozoan in humans and animals worldwide, including eight morphologically identical assemblages, infecting pets, livestock, wildlife and human beings. Assemblages A and B are those with the higher zoonotic potential, and they have been detected in several mammals other than humans; the others (C to H) show a higher host specificity. Cats can harbour both the specific Assemblage F and the zoonotic ones A and B. Several studies have been carried out on G. duodenalis genotypes in cats; however, the role of this species in the epidemiology of giardiasis is still poorly understood. In this scenario, the present study carried out the detection and genetic characterization at sub-assemblage level of G. duodenalis from colony stray cats in central Italy. In the period 2018-2019, 133 cat faecal samples were analysed for the presence of G. duodenalis cysts by a direct immunofluorescence assay. Positive samples were subsequently subjected to molecular analyses for assemblage/sub-assemblage identification. Forty-seven samples (35.3%) were positive for G. duodenalis cysts by immunofluorescence. G. duodenalis DNA was amplified at SSU-rDNA locus from 39 isolates: 37 were positive for zoonotic Assemblage A and 2 showed a mixed infection (A + B). Positive results for the β-giardin gene were achieved for 25 isolates. Sequence analysis revealed 16 isolates belonging to Sub-assemblage AII and 8 to Sub-assemblage AIII. One isolate resulted as ambiguous AI/AIII. Large sequence variability at the sub-assemblage level was detected, with several double peaks and mutations, making complex a proper isolate allocation. When compared with previous studies, the 35.3% prevalence of G. duodenalis in cats reported in the present article was surprisingly high. Moreover, all positive cats resulted to be infected with zoonotic assemblages/sub-assemblages, thus indicating stray cats as a possible source of human giardiasis and highlighting the sanitary relevance of cat colonies in the study area.
| S-EPMC9290339 | biostudies-literature
Project description:C57BL/6 mice were infected with the GS strain of G. duodenalis and total RNA prepared from the duodenum on day 10. Age matched controls were compared using Affy chips to determine changes in gene expression induced by infection. The majority of induced transcripts are invlved in antibody production. Genes exhibiting the greatest increase in expression are all mast cell transcripts.
2013-10-21 | GSE23372 | GEO