Treatment Of Giardiasis Research Articles

Current state of infection and prevalence of giardiasis in Malaysia: a review of 20 years of research.

BackgroundGiardiasis is a neglected parasitic zoonotic disease caused by Giardia duodenalis that is often overlooked despite the damage inflicted upon humans and domestic/wild animals. Lack of surveillance studies, low sensitivity of diagnostic tools, and resistance to giardiasis treatment add to the challenge in managing giardiasis, leaving a gap that continues to render giardiasis a silent threat to public health worldwide. This situation is not much different in Malaysia, where giardiasis remains a public health problem, especially in the indigenous communities. Realizing the existence of gaps in the literature and information on giardiasis in Malaysia, this review aims to revisit and update the situation of giardiasis in Malaysia based on articles published in 20 years from 2000 to 2020, providing estimates on the incidence of giardiasis in humans, animals, and the environment, which may inform efforts to prevent and control the impact of giardiasis in the country.MethodologyWe searched PubMed, Science Direct, and Scopus using MeSH terms and text keywords “Giardia duodenalis OR Giardia intestinalis OR Giardia lamblia OR intestinal protozoa AND Malaysia”. Information was collected from all giardiasis reports published between 2000 and 2020.ResultsGiardiasis in Malaysia is more prevalent among the poorest segments of the population, namely the indigenous communities and people living in densely populated areas such as slums and prisons, due to low standard of personal hygiene, unsafe water resources, and improper sanitation. While the prevalence data is hugely dependent on microscopic fecal examination in epidemiological studies of giardiasis, current studies mostly focused on species identification and genotype distribution by multilocus genotyping. Thus far, the outbreak of giardiasis has not been reported in the country, but the disease was found to be significantly associated with stunting, wasting, and malnutrition among children of the indigenous communities. Surveillance studies also discovered the simultaneous presence of Giardia in the animal-environments, including wild animals, ruminants, and treated and untreated water. The data collected here will be a useful addition to the literature body on giardiasis in Malaysia, which can be exploited in efforts to prevent and control the impact of giardiasis in the country.ConclusionsThe last 10 years have shown that the overall mean rate of giardiasis in Malaysia is quite encouraging at 13.7%. While this figure appears to be declining, there has been a slight increase in the prevalence of underweight, stunting, and wasting among rural children in 2019. The fact that giardiasis is linked to long-term childhood developmental problems, indicates that addressing and providing better disease control against giardiasis should be a priority in supporting the national agenda to achieve Malaysia Global Nutrition Targets by 2025.

On some new aspects of the diagnosis and treatment of giardiasis

The past 103 years since the detailed description of lamblia has not led to a unanimity of views on the nature and degree of their influence on the body.

Clinic and treatment of hepatic giardiasis in children

In recent years, interest in studying the role of lamblia in the etiology of diseases of the gastrointestinal tract has increased significantly.

APPLYING NANOPARTICLES FOR TREATING GIARDIA INFECTION: A SYSTEMATIC REVIEW

At present, chemotherapy with some drugs such as nitroimidazoes derivatives is the preferred treatment for giardiasis. However, these agents are associated with adverse side effects ranging from nausea to possible genotoxicity. The present investigation was designed to systematically review the in vitro, in vivo, and clinical studies about the efficacy of nanoparticles against giardiasis. The study was carried out based on the 06-PRISMA guideline and registered in the CAMARADES-NC3Rs Preclinical Systematic Review and Meta-analysis Facility (SyRF) database. The search was performed in five English databases, including Scopus, PubMed, Web of Science, EMBASE, and Google Scholar, without time limitation for publications around the world about anti-Giardia effects of all organic and inorganic nanoparticles without date limitation in order to identify all the published articles. The searched words and terms were “Giardiasis”, “Giardia lamblia”, “Giardia intestinalis”, “Giardia duodenalis”, “nanoparticles”, “nanomedicine”, “in vitro”, in vivo”, and “clinical trial”. Out of 312 papers, 10 papers, including 4 in vitro (40.0%), 5 in vivo (50.0%), and 1 in vitro/in vivo (10.0%) up to 2021 met the inclusion criteria for discussion in this systematic review. The most common type of nanoparticles was metal nanoparticles (5 studies, 50.0%) such as silver, gold, etc., followed by organic nanoparticles such as chitosan nanoparticles (4 studies, 40.0%). The results of this review study showed the high efficacy of a wide range of organic and non-organic NPs against giardiasis, indicating that nanoparticles could be considered as an alternative and complementary resource for treating giardiasis, since they have no significant toxicity. However, more studies are required to elucidate this conclusion, especially in clinical systems.

Effects of Tinidazole on Food Intake in Chinchillas (Chinchilla lanigera).

Tinidazole is a second-generation nitroimidazole compound that is used as an antimicrobial to treat anaerobic bacterial and protozoal infections in humans and, less frequently, in veterinary medicine. However, metronidazole, another secondgeneration nitroimidazole, is more commonly used. Nonetheless, tinidazole has proven to be a superior therapy for parasitic infections in humans, particularly in the treatment of giardiasis. Furthermore, in chinchillas, metronidazole has been shown to cause a clinically relevant reduction in food intake after oral administration at published dosages. This study's objective was to evaluate the effect of orally administered tinidazole on food intake in healthy chinchillas. In 2 randomized, placebocontrolled, blinded, crossover studies, tinidazole was evaluated at 2 single high doses (100 mg/kg and 200 mg/kg PO, n = 9) and a repeated dosing schedule at a lower dose (20 mg/kg PO q12h for 10 doses, n = 12). Food intake was measured over 24-h periods before and after drug administration. The single-dose treatment groups both displayed significantly reduced food intake (200 mg/kg: -26 ± 21%; 100 mg/kg: -9 ± 21%, P < 0.01) as compared with the control group during the first 24 h after drug administration. Food intake returned to pretreatment values within 4-5 d. Repeated administration at 20 mg/kg q12h was not associated with any significant changes in food intake. No other adverse effects were noted during this study. Tinidazole administration at single higher doses resulted in an acute self-limiting reduction in food intake. In comparison, repeated administration of lower doses (20 mg/kg PO q12h) had no significant effects on food intake in healthy chinchillas. Therefore, tinidazole may be a more suitable drug for treating Giardia and anaerobic bacterial infections in this species than the more commonly used metronidazole.

Multilevel Approach for the Treatment of Giardiasis by Targeting Arginine Deiminase.

Giardiasis represents a latent problem in public health due to the exceptionally pathogenic strategies of the parasite Giardia lamblia for evading the human immune system. Strains resistant to first-line drugs are also a challenge. Therefore, new antigiardial therapies are urgently needed. Here, we tested giardial arginine deiminase (GlADI) as a target against giardiasis. GlADI belongs to an essential pathway in Giardia for the synthesis of ATP, which is absent in humans. In silico docking with six thiol-reactive compounds was performed; four of which are approved drugs for humans. Recombinant GlADI was used in enzyme inhibition assays, and computational in silico predictions and spectroscopic studies were applied to follow the enzyme’s structural disturbance and identify possible effective drugs. Inhibition by modification of cysteines was corroborated using Ellman’s method. The efficacy of these drugs on parasite viability was assayed on Giardia trophozoites, along with the inhibition of the endogenous GlADI. The most potent drug against GlADI was assayed on Giardia encystment. The tested drugs inhibited the recombinant GlADI by modifying its cysteines and, potentially, by altering its 3D structure. Only rabeprazole and omeprazole decreased trophozoite survival by inhibiting endogenous GlADI, while rabeprazole also decreased the Giardia encystment rate. These findings demonstrate the potential of GlADI as a target against giardiasis.

Treatment strategies for nitroimidazole-refractory giardiasis: a systematic review.

Giardiasis is one of the most common human protozoal infections worldwide. First-line therapy of giardiasis includes nitroimidazole antibiotics. However, treatment failure with nitroimidazoles is increasingly reported, with up to 45% of patients not responding to initial treatment. There is no clear consensus on the approach to the management of nitroimidazole-refractory giardiasis. This systematic review aims to summarize the literature on pharmacotherapy for nitroimidazole-refractory giardiasis. We conducted a systematic review of the literature to determine the optimal management strategies for nitroimidazole-refractory giardiasis. We searched Pubmed/MEDLINE, Embase and Cochrane library using the following search terms 'Giardia' AND 'treatment failure' OR 'refractory giardia' OR 'resistant giardia' with date limits of 1 January 1970 to 30 June 2021. We included all reports on humans, which described clinical outcomes of individuals with treatment refractory giardiasis, including case series and case reports. A descriptive synthesis of the data was conducted with pooling of data for interventions. Included in this review were five prospective studies, three retrospective studies, seven case series and nine case reports. Across these reports, a wide heterogeneity of treatment regimens was employed, including retreatment with an alternative nitroimidazole, combination therapy with a nitroimidazole and another agent and monotherapy with non-nitroimidazole regimens, including quinacrine, paromomycin and nitazoxanide. Retreatment with a nitroimidazole was not an effective therapy for refractory giardiasis. However, treatment with a nitroimidazole in combination with albendazole had a cure rate of 66.9%. In the included studies, quinacrine monotherapy was administered to a total of 179 patients, with a clinical cure rate of 88.8%. Overall, quinacrine was fairly well tolerated. Reports on the treatment of nitroimidazole-refractory giardiasis demonstrate a heterogeneous approach to treatment. Of these, quinacrine appeared to be highly effective, though more data on its safety are needed.

Evaluation of the role of combined prebiotic and probiotic supplements as prophylactic and therapeutic agents against experimental giardiasis

Background: Giardiasis is considered as one of the most prevalent gastrointestinal parasitic infectionsworldwide. Most of the used anti-Giardia drugs may cause side effects and are often associated withclinical failure and drug resistance. Prebiotic and probiotic therapy has been posited as potential naturaltherapeutic agent for many parasitic diseases.Objective: To evaluate the effect of combined prebiotic and probiotic therapy as a natural supplement andafter addition to nitazoxanide (NTZ) in treatment of giardiasis in murine model.Material and Methods: Ninety-six laboratory bred Swiss albino male mice were used. Mice were dividedinto three main groups that included 16 subgroups (6 mice each). Control group (A1-7) included controlnegative (non-infected non-treated), control positive (infected non-treated), and another five controlsubgroups (SGs) that received natural prebiotic and probiotic supplements and NTZ. Prophylactic group (B)included three SGs in which infected mice received prebiotic and probiotic separately and in combinationfor one week before infection and continued till the end of experiment. Infected treated group (C1-6)composed of six infected SGs that received treatment by prebiotic and probiotic separately, and combinedprebiotic/probiotic, NTZ alone (full dose), and after addition of combined supplement to NTZ (half orfull dose). Evaluation was achieved using parasitological, histopathological, immunohistochemical, andimmunological parameters.Results: There was significant reduction of Giardia cyst shedding in all prophylactic and infected treatedSGs. The highest mean cyst reduction was observed in group C after addition of combined supplementto NTZ post infection (PI) and in group B receiving prophylactic combined supplement. Remarkableimprovement of histopathological findings was observed especially in group C after receiving combinedsupplement in addition to NTZ, followed by other prophylactic and infected treated SGs. The resultsof immunohistochemical caspase 3 expression revealed that combined supplement was effective inpreventing apoptotic cell death of intestinal cells that is induced by giardiasis especially after addition ofcombined supplement to NTZ in group C. Immunological assessment of interleukin-6 (IL-6) level showedsignificant increase in all treated SGs with boosted elevation in combined supplement after addition toNTZ in group C.Conclusion: Combined prebiotic and probiotic products can be considered as good prophylactic andtherapeutic agents when added to NTZ against giardiasis.

Probiotics in the management of Giardia duodenalis: an update on potential mechanisms and outcomes.

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

Quinacrine Treatment of Nitroimidazole-Refractory Giardiasis.

BackgroundLimited evidence exists on efficacy and tolerability of quinacrine for nitroimidazole-refractory giardiasis.MethodsNitroimidazole-refractory giardiasis cases, defined as microbiologically (microscopy and/or PCR) confirmed treatment failure after 2 courses, during 2008–2020, were retrospectively identified.ResultsOf 87 patients, 54 (62%) had visited India. Quinacrine was used in 54 (62%); 51 received monotherapy and 3 combined with metronidazole. Only 3 had positive stool samples with persisting symptoms after quinacrine treatment (94% parasitological efficacy) and all were cured after a second treatment. One (1.9%) had mild adverse effects recorded.ConclusionsQuinacrine is an effective treatment for nitroimidazole-refractory giardiasis with good tolerability.

Efficacy of Capparis spinosa Linn Leaf and Fruit Extracts on Giardia Lambia Cysts In vitro

Aims: Giardia lamblia (G. lamblia) is one of the most common intestinal parasites worldwide. There are some side effects and the reports of parasite resistance to metronidazole as the first line treatment of giardiasis. Therefore, it is essential to discover an effect and safe drug to treat giardiasis.&#x0D; Methodology: In this study, the anti-parasitic activity of hydroalcoholic extracts of Capparis spinosa Linn (C. spinosa) leaves and fruits with different concentrations (4 to 0.125 mg/ml) was assessed against human isolates of the G. lamblia cysts and incubated at 37℃. After staining Giardia cysts with 0.1% eosin, the lethal percentage and 50% lethal concentration (LC50) of fruit and leave C. spinosa L extracts and metronidazole on G. lamblia cysts were calculated after 3, 6, 24 and 48 hours.&#x0D; Results: Anti-giardia activity of fruit and leaf extracts of C. spinosa was different between concentrations and time points (p&lt;0.005). The lethal effect of both C. spinosa L extracts and metronidazole increased significantly in a concentration - and time–dependent response (P&lt;0.0001). The highest lethal percentage of G. lamblia cysts was observed a concentration of 4 mg / ml of fruit (100%) and leaf (44%) extracts of C. spinosa L after 48 hours, respectively. LC50 values were 0.38 ± 0.02mg/ml for fruit extract, 2.32 ± 0.1 mg/ml for leaf extract and 0.53 ± 0.03 µg/ml for metronidazole after 48hours.&#x0D; Conclusion: C. spinosa can be effective in eliminating Giardia cyst of contaminated environments and water.

High resolution mass spectrometric analysis reveals that Giardia cysts are metabolically active and generates membrane lipids with long chain fatty acyl moieties

Giardia lamblia, the causative agent of “giardiasis” affects people throughout the world. Metronidazole (Mtz, Flagyl®), a nitroimidazole group of compounds is the commonly prescribed treatment for giardiasis. However, Mtz is a genotoxic agent and a potential carcinogen. Therefore, it is imperative to identify new and specific targets in Giardia that could be exploited to develop non-Mtz classes of drugs to treat giardiasis. Because of its limited lipid synthetic ability, Giardia was proposed to scavenge phospholipids, sterols and free fatty acids from the hosts or its environment for membrane and organelle biogenesis. In the current study, we utilized a quantitative lipidomic and proteomic approach to further elucidate the lipid metabolic pathways in Giardia. Vegetative and encysting trophozoites as well as osmotically resistant cysts were cultured in the laboratory, collected, and subjected to lipid extraction or tryptic digestion followed by the high-resolution mass spectrometric analysis (Q Exactive Plus Hybrid Quadrupole-Orbitrap mass spectrometer equipped with a heated electrospray (HESI-II) or a Nanospray Flex Ion source, Thermo Fisher). Lipid identification and confirmation was performed on open-source software MS-DIAL and LipidMatch flow. Proteomic analysis was performed on a licensed version of Proteome Discoverer. Lipidomic analysis revealed the dynamic changes of overall lipid and fatty acid (mostly C16, C18 moieties) profiles throughout the life stages of Giardia. Lipid classes that were found in cysts included LPC, P- and O-LPC, LPE, DG, TG, CE, PC, P-PC (Plasmalogen), and ceramides. Lipids, such as SM, PG, BMP were present mostly in encysting trophozoites rather than cysts. Ether linked PC species revealed to be most abundant in trophozoites. Proteomic analysis identified increased levels of several enzymes from lipid elongation pathway i.e., acyl-CoA ligases, long-chain fatty acid elongase, oxidoreductase and enoyl-CoA reductase in cysts.These studies suggest that although limited, Giardia maintains an active and robust lipid metabolism in all stages including the water-resistant non-motile cysts. It is possible that active lipid metabolism in cysts is required for the successful excystation to produce infective membranous trophozoites.

MDR1 protein (ABC-C1) Over Expression in Giardia Intestinalis Incubated with Albendazole and Nitazoxanide

Giardia intestinalis is a worldwide parasite. Drugs used for the treatment of giardiasis are metronidazole, albendazole and nitazoxanide. The development of drug resistance is an obstacle to the effective treatment. Resistance mechanisms in some parasites involve the participation of ATP-binding cassette (ABC) transporter superfamily. To find if the ATP-binding cassette genes are overexpressed in trophozoites treated with albendazole or nitazoxanide. A search for ATP-binding cassette genes in Giardia sequence database (GiardiaDB) was done and six genes were selected. Trophozoites treated with albendazole or nitazoxanide and the expression of these six ABC genes was quantitated by real-time RT-PCR. The ABC-C1 gene was selected, and a fragment cloned. The ABC-C1 protein was expressed, and polyclonal antibodies were elicited in mice to detect the protein in treated trophozoites, finally a docking analysis was performed for ABC-C1 and tizoxanide interaction. Bioinformatics analysis showed that the ATP-binding cassette (ABC) topology is present in the six proteins. The qRT-PCR revealed that the ABC-C1 gene was overexpressed in cells incubated with nitazoxanide or albendazole. Confocal analysis showed that ABC-C1 protein levels increased in trophozoites with both treatments but was higher with nitazoxanide. The mark was detected heavily in the periphery of the cells. Using a docking analysis, it was found that the nitazoxanide metabolite, tizoxanide was docked close to the ATP-binding region as well as in the exit tunnel, located in the transmembrane region. These findings in Giardia intestinalis, support the possible role of ABC-C1 in drug efflux.

Preventive role of probiotic bacteria against gastrointestinal diseases in mice caused by Giardia lamblia.

Giardiasis is one of the most prevalent gastrointestinal diseases in the world. It is caused by Giardia, Giardia lamblia, a common and opportunistic zoonotic parasite. The aim of our work is to find a natural and safe alternative treatment for giardiasis, specifically, to determine if probiotic bacteria (Lactobacillus acidophilus, Bifidobacterium bifidum, and Lactobacillus helveticus) can contribute to treatment, and act as preventives. Sixty weanling albino mice, Mus musculus, were divided into control and experimental, probiotic-fed groups. We determined infection intensity, and cure and prevention rates of giardiasis through ELISA (enzyme-linked immunosorbent assay) of stool samples and histopathological comparison of intestinal tissue. In experimental groups, there was a significant reduction in infection intensity (P<0.001) on days 10, 15, and 20, while cure rate reached 87.5%. The control group showed no signs of reduced infection or cure and only the group treated with probiotics prior to infection showed significant prevention rates. In the experimental groups, intestinal changes due to giardiasis appeared 7 days post-infection. However, almost all of these changes disappeared by the 25th day. Our results suggest a beneficial and significant effect of probiotics in the prevention and treatment of giardiasis in mice.

Saccharomyces boulardii as therapeutic alternative in experimental giardiasis.

The objective of this study was to evaluate the effect of treatment with the probiotic Saccharomyces boulardii with or without metronidazole in experimental giardiasis. The effect of treatment with S. boulardii with or without metronidazole on the intestinal mucosa, the antioxidant defence system and the parasitic load was determined in experimental giardiasis. Eight groups of animals with infection and/or treatment with the probiotic and/or drugs for 1week after infection with Giardia lamblia were used. A reduction of approximately 90% in the parasitic load was observed in all the treated groups. Saccharomyces boulardii attenuated the damage caused by infection in the intestinal mucosa preserving its architecture and inhibiting the oxidative stress induced by parasite and metronidazole. Saccharomyces boulardii was effective alone or in combination with metronidazole in resolving already established G. lamblia infection. These results suggest the use of S. boulardii as an alternative treatment for giardiasis mainly in cases of resistance or intolerance to conventional treatment.

Assessment of the Therapeutic Effect of Probiotic Lactobacilli Alone and in Combination with Metronidazole in Murine Giardiasis

Giardia lamblia is considered one of the most common intestinal parasites that infect human. It is the causative agent of giardiasis, a major cause of diarrheal illness. Current recommended treatment usually accomplished using one of several drugs. However, resistance is increasing, and new alternatives are being sought. Currently the interest in alternative biotherapeutic strategies which have included natural interventions such as probiotic Lactobacillus bacteria which displays antiprotozoal effect is required. The present study was conducted on 57 laboratory bred Swiss albino mice provided by animal house in Theodor Bilharz Research Institute to evaluate the effect of Lactobacillus casei on Giardia lamblia versus the commercially used drug metronidazole in experimentally infected mice. The mice were divided into two main groups: group (A) which included normal non infected mice and group (B) which included infected mice. Each group was subsequently divided into 4 subgroups (control, treated with metronidazole, treated with L. casei and treated with both metronidazole & L. casei) in addition to prophylactic subgroup in group (B) (received L.casei seven days before and 10 days after infection directly then for ten days after approval of infection by Giardia cysts). The mice were infected with Giardia cysts in a dose of 104±10 cysts/mouse. Parasitological, histopathological and immunohistochemical assessments of the drug effect were done. The obtained results of infected treated group were plotted in comparison to healthy control, non-infected treated mice and infected control. Parasitological assessment was done through counting of cysts output of infected mice 7 and 10 days after starting treatment. Histopathological and immunohistochemical assessments were done by examining sections of the duodenum. There was a significant reduction of the excreted cysts count in infected treated subgroups. The highest cyst reduction was in prophylactic and treated with both L.casei & metronidazole subgroups compared to metronidazole treated and infected control. Histopathological examination of infected control revealed profound effect on the structure of the intestinal mucosa with diffuse loss of brush border of intestinal villi. After treatment there was remarkable improvement of these histopathological findings especially in prophylactic subgroup compared to metronidazole treated and infected control. Immunohistochemical staining revealed marked increase in IgA secretory plasma cells in prophylactic and treated with both L.casei & metronidazole subgroups compared to infected control and metronidazole treated mice. The results achieved that probiotics have a promise in the treatment of giardiasis. The protective response of probiotic in mice is better when Lactobacilli were administered for many days before infection.

Psidium guajava Linn leaf ethanolic extract: In vivo giardicidal potential with ultrastructural damage, anti-inflammatory and antioxidant effects.

Considering the magnitude of giardiasis problem, the side-effects of the used anti-giardia drugs and the resistance posed against them, the current study aimed to evaluate the in-vivo giardicidal effect of Psidium guajava leaf extract (PGLE). For fulfilling this aim, five Swiss-albino mice groups were included; GI: non-infected, GII: Giardia-infected and non-treated, GIII: Giardia-infected and metronidazole-treated, GIV: Giardia-infected and PGLE-treated, and GV: Giardia-infected and treated with both metronidazole and PGLE. Treatment efficacy was assessed via; Giardia cyst viability and trophozoite count, trophozoite electron microscopic ultrastructure, duodenal histopathological scoring, immunohistochemistry for TNF-α and duodenal scanning electron microscopy. Moreover, mice serum liver enzymes, total bilirubin, albumin, lipid profile including; total cholesterol, HDL, LDL and triglycerides were assessed. Additionally, hepatic oxidative stress markers including; malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH) and superoxide dismutase (SOD) were measured. Results showed that PGLE whether alone or combined with metronidazole has induced significant trophozoite count reduction and major architectural changes. Duodenal histological improvement, and local protective anti-inflammatory effect were confirmed. PGLE has also helped in healing of Giardia-induced gut atrophy. Thus, offered a comprehensive therapy for both the pathogen and the resultant pathological sequalae. Serum markers showed favorable hepatoprotective effect. Total cholesterol, LDL and triglycerides levels were less in PGLE-treated group than in metronidazole-treated group. Hepatic oxidative stress markers revealed the promising extract antioxidant effect. This study highlights, the promising in-vivo giardicidal PGLE activity, that was comparable to metronidazole, thus, the extract would be an ideal strongly recommended treatment for giardiasis. When combined with metronidazole, the extract potentiated its therapeutic effect. Besides, having hepatoprotective, anti-inflammatory, and antioxidant properties, the extract can combat the major side effects of metronidazole therapy.

Discovery and Preclinical Development of Antigiardiasis Fumagillol Derivatives.

Giardiasis, caused by the intestinal parasite Giardia lamblia, is a severe diarrheal disease, endemic in poverty-stricken regions of the world, and also a common infection in developed countries. The available therapeutic options are associated with adverse effects, and G. lamblia resistance to the standard-of-care drugs is spreading. Fumagillin, an antimicrosporidiosis drug, is a therapeutic agent with potential for the treatment of giardiasis. However, it exhibits considerable, albeit reversible, toxicity when used to treat immunocompromised microsporidiosis patients. Fumagillin is also a highly unstable compound. To address these liabilities, we designed and synthesized stable fumagillol derivatives with lower levels of permeation across polarized epithelial Caco-2 cells and better potency against G. lamblia trophozoites than fumagillin. Metronidazole-resistant G. lamblia strains were also susceptible to the new fumagillol derivatives. In addition, these compounds were more potent against the amebiasis-causing parasite Entamoeba histolytica than fumagillin. Two compounds exhibited better thermal and acid stability than fumagillin, which should prolong the drug shelf life and reduce compound degradation in the stomach. Studies with a mouse model of giardiasis with the most stable compound, 4-(((((3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl)oxy)carbonyl)amino)benzoic acid (compound 9), revealed that it had better efficacy (effective dose [ED]) than fumagillin at both the fully curative dose (the 100% ED) of 6.6 mg/kg of body weight and a 50% ED of 0.064 mg/kg. Plasma pharmacokinetics revealed the slow absorption of compound 9 through the gut, consistent with the in vitro characterization in Caco-2 cells. An acute-dose study yielded a maximum tolerated dose (MTD) of 1,500 mg/kg, 227-fold higher than the fully curative dose. Thus, along with improved stability, compound 9 also exhibited an excellent therapeutic window.

Giardiasis treatment: an update with a focus on refractory disease.

Giardiasis remains a common cause of diarrhea and intestinal enteropathy globally. Here we give an overview of clinical treatment studies and discuss potential mechanisms and molecular targets for in-vitro testing of drug resistance. Giardia is a cause of disease both in diarrheal and nondiarrheal cases. The prevalence of treatment refractory giardiasis is increasing. Recent studies reveal 5-nitroimidazole refractory infection occurs in up to 50% of cases. Mechanisms of drug resistance are not known. Placebo controlled studies of drug efficacy, taking the self-limiting course of giardiasis into account, has not been reported. No randomized controlled trials of treatment of refractory infection have been performed the last 25 years. Based on the clinical studies reported, combination treatment with a 5-nitroimidazole and a benzimidazole is more effective than repeated courses of 5-nitroimidazole or monotherapies in refractory cases. Quinacrine is effective in refractory cases, but potentially severe side effects limit its use. A combination of a 5-nitroimidazole and albendazole or mebendazole, and quinacrine monotherapy, are rational choices in nitroimidazole refractory infections, but randomized controlled studies are needed. Further research into more recent clinical isolates is necessary to uncover mechanisms for the increase in metronidazole refractory giardiasis observed during the last decade.

The uses of gold nanoparticles and Citrullus colocynthis L. nanoparticles against Giardia lambliain vivo

BackgroundThe herbs have been used to prevent and treat many diseases, because of their safe and available. With unique properties of gold nanoparticles, and its accurate ability to deliver medicines, making it a suitable for chemotherapy. ObjectiveCitrullus colocynthis and gold nanoparticles were used in the treatment of Giardia lamblia in vitro, but not in vivo. Materials and methodsExperimental animals were divided into three groups, control non-treated group (sub divided into infected and non-infected), group B (treated and non-infected), and group C (infected and treated). All infected groups inoculated with 2 × 104 cysts and all treated groups received an aqueous extract of fruits and nanoparticles of C. colocynthis as well as gold nanoparticles Once as single and twice as combination therapy. Mean of cysts in the stool (from the third day of infection) and remaining trophozoites in the intestines (after the eighth day of treatment) were counted, compered the effect of single or combine agents use among infected (treated and non-treated) groups. Some hematological and chemical parameters in the non-infected (treated and non-treated) groups Were compared and the toxicity of that nanoparticles was estimated. ResultsThe current study revealed that combination therapy is better than a single treatment, and that treatment with gold plus C. colocynthis nanoparticles is better than treatment with gold nanoparticles and native C. colocynthis. The study did not record significant effect of all compounds in hematological and chemical parameters, although it recorded variations in the levels and concentrations of these parameters. ConclusionUses of C. colocynthis nanoparticles combined with gold nanoparticles has the Highest efficiency in Giardiasis treatment in vivo, but with an incomplete cure. Biological parameters may be considered in some safety when using this type of nanoparticle.