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1.
J Transl Med ; 22(1): 910, 2024 Oct 07.
Article in English | MEDLINE | ID: mdl-39375691

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic and lethal lung disorder for which effective treatments remain limited. Recent investigations revealed a potential link between altered glucose metabolism and the activation of fibroblasts, the key cells responsible for generating and depositing extracellular matrix proteins within the lung interstitium during IPF development. METHOD: In this study, we aimed to investigate the potential therapeutic impact of albendazole on fibroblast to myofibroblast transition in IPF. We assess albendazole's effectiveness in attenuating the activation of fibroblasts. We focused on elucidating the mechanism underlying albendazole's impact on TGF-ß1-induced aerobic glycolysis in both lung tissues and fibroblasts obtained from patients with IPF and other lung fibrosis types. Furthermore, the antifibrotic effects of oral administration of albendazole were investigated in mouse models of pulmonary fibrosis induced by BLM or SiO2. Human precision-cut lung slices were employed to evaluate the impact of albendazole following TGF-ß1 stimulation. RESULT: In this work, we demonstrated that albendazole, a first-line broad-spectrum anthelmintic drug, effectively attenuated fibroblast to myofibroblast transition through alleviating TGF-ß1-induced aerobic glycolysis dependent on the LRRN3/PFKFB3 signaling pathway. Additionally, LRRN3 expression was downregulated in both lung tissues and fibroblasts from patients with IPF and other types of lung fibrosis. Importantly, the levels of LRRN3 correlated with the progression of the disease. Notably, oral administration of albendazole exerted potent antifibrotic effects in mouse models of pulmonary fibrosis induced by BLM or SiO2, and in human precision-cut lung slices after TGF-ß1 stimulation, as evidenced by improvements in lung morphology, reduced myofibroblast formation, and downregulation of α-SMA, collagen type 1 and Fibronectin expression in the lungs. CONCLUSION: Our study implies that albendazole can act as a potent agonist of LRRN3 during fibroblast to myofibroblast differentiation and its oral administration shows potential as a viable therapeutic approach for managing IPF.


Subject(s)
Albendazole , Glycolysis , Myofibroblasts , Pulmonary Fibrosis , Transforming Growth Factor beta1 , Animals , Albendazole/pharmacology , Albendazole/therapeutic use , Humans , Myofibroblasts/drug effects , Myofibroblasts/metabolism , Myofibroblasts/pathology , Glycolysis/drug effects , Transforming Growth Factor beta1/metabolism , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/pathology , Pulmonary Fibrosis/metabolism , Mice, Inbred C57BL , Lung/pathology , Lung/drug effects , Male , Mice , Signal Transduction/drug effects , Disease Models, Animal , Bleomycin , Female
2.
Infect Dis Poverty ; 13(1): 72, 2024 Oct 08.
Article in English | MEDLINE | ID: mdl-39380086

ABSTRACT

BACKGROUND: Soil-transmitted helminths (STH) affect approximately 1.5 billion people globally. The current STH control strategy is annual or twice-annual preventive chemotherapy, typically school-based deworming targeting children and women of reproductive age. Mathematical modeling suggests that it may be possible to interrupt STH transmission through high-coverage community-wide mass drug administration (cMDA). DeWorm3 is a cluster randomized trial testing cMDA for prevalence reduction and transmission interruption. The purpose of this study is to describe coverage of cMDA in study clusters over time and correlates of coverage at individual and cluster levels. METHODS: From 2018-2020, DeWorm3 delivered six rounds of cMDA with 400 mg albendazole at sites in Benin, India, and Malawi. We report coverage, treatment uptake, and directly observed therapy across all rounds. Factors associated with coverage at the cluster level were identified using binomial generalized estimating equations, while factors associated with non-treatment at the individual level were identified using binomial mixed-effects models. RESULTS: Coverage was high across all clusters and rounds, exceeding the WHO target of 75% in all sites and across all rounds (78% to 95%); cluster-level coverage tended to increase over time. Younger, unmarried, and migratory adults were more likely to be untreated at all sites; adult males were more likely to be untreated in Benin and Malawi. Among children, girls were more likely to be untreated, as were non-school-attending and migratory children. Higher adult education was associated with greater odds of non-treatment among adults, but lower odds among children in the household. Belonging to a less wealthy or minority language-speaking household was associated with non-treatment among both adults and children. CONCLUSIONS: It is possible to deliver community-wide MDA with high coverage. Unique individual and community-level factors influence treatment across settings, and these may be addressed through targeted programming. TRIAL REGISTRATION: Field Studies on the Feasibility of Interrupting the Transmission of Soil-transmitted Helminths (STH), NCT03014167.


Subject(s)
Albendazole , Anthelmintics , Helminthiasis , Mass Drug Administration , Soil , Humans , Malawi/epidemiology , Mass Drug Administration/statistics & numerical data , Mass Drug Administration/methods , Female , Helminthiasis/drug therapy , Helminthiasis/prevention & control , Helminthiasis/epidemiology , Helminthiasis/transmission , Male , Soil/parasitology , Benin/epidemiology , India/epidemiology , Child , Adolescent , Adult , Albendazole/therapeutic use , Albendazole/administration & dosage , Anthelmintics/therapeutic use , Anthelmintics/administration & dosage , Young Adult , Child, Preschool , Helminths/drug effects , Middle Aged , Prevalence
3.
Turkiye Parazitol Derg ; 48(3): 191-194, 2024 10 07.
Article in English | MEDLINE | ID: mdl-39373595

ABSTRACT

Cystic echinococcosis is a parasitic disease with significant importance for public health in endemic regions. Spinal cystic echinococcosis, however, is a rare form that may lead to severe complications due to its localization. In this manuscript, we presented a 16-year-old male patient who admitted with abdominal and back edema for 2 months, evaluated with preliminary diagnoses of Pott's abscess and malignant mass, subsequently diagnosed with spinal cystic echinococcosis. It was concluded that cystic echinococcosis should be considered in differential diagnosis of large cystic masses and percutaneous aspiration, injection, reaspiration method might be a safe and effective treatment option particularly for cases of complicated spinal cystic echinococcosis.


Subject(s)
Echinococcosis , Humans , Male , Adolescent , Spinal Diseases/parasitology , Diagnosis, Differential , Suction , Albendazole/therapeutic use , Albendazole/administration & dosage , Magnetic Resonance Imaging
4.
Sci Rep ; 14(1): 23543, 2024 10 09.
Article in English | MEDLINE | ID: mdl-39384803

ABSTRACT

Trichuris trichiura is one of four soil-transmitted helminth species that, collectively, are responsible for a considerable public health burden. The World Health Organization recommends preventive chemotherapy as the main intervention to eliminate soil-transmitted helminthiasis as a public health problem. Clinical trials estimated the efficacy of different drugs and treatment regimen against T. trichiura and other soil-transmitted helminth species, whilst meta-analyses and modeling efforts were conducted to determine the most efficacious drugs and drug combinations. Of note, the diagnostic error was often neglected, and hence, cure rates (CRs) might be overestimated. We developed a Bayesian model, which estimates drug efficacy against T. trichiura, taking into account the transmission mechanism and the diagnostic error. The model was fitted to individual-level egg count data from an ensemble of seven trials with 29 treatments. We estimated the 'true' CRs, which were consistently lower than those reported in the literature. In our analysis, the treatment with the highest CR was combination therapy of albendazole plus pyrantel pamoate plus oxantel pamoate with a CR of 79% and an egg reduction rate (ERR) of 91%. Albendazole plus oxantel pamoate showed the highest ERR of 97% and a CR of 69%. Additionally, we estimated the intensity-dependent sensitivity of the Kato-Katz technique. For 24 eggs per gram of stool, the sensitivity was around 50% for a single Kato-Katz thick smear and increased to almost 70% for duplicate Kato-Katz thick smears. Combination therapies against soil-transmitted helminthiasis should be considered and the evaluation of infection intensity in low transmission settings via multiple Kato-Katz thick smears is recommended.


Subject(s)
Bayes Theorem , Drug Therapy, Combination , Trichuriasis , Trichuris , Trichuris/drug effects , Trichuriasis/drug therapy , Animals , Humans , Anthelmintics/therapeutic use , Anthelmintics/administration & dosage , Treatment Outcome , Albendazole/therapeutic use , Albendazole/administration & dosage , Parasite Egg Count , Pyrantel Pamoate/therapeutic use , Pyrantel Pamoate/analogs & derivatives , Soil/parasitology
5.
Parasite ; 31: 56, 2024.
Article in English | MEDLINE | ID: mdl-39311470

ABSTRACT

Alveolar echinococcosis (AE) is a severe liver disease due to infection with the Echinococcus multilocularis larval stage, called the metacestode. Management of AE is based on benzimidazole chemotherapy (albendazole or mebendazole), associated with surgery when possible. Benzimidazoles are the only compounds recommended for the treatment of AE; however, these are parasitostatic, which means that the parasite can resume growth when treatment is interrupted. Also, benzimidazoles can cause liver dysfunction which may prevent their use. Numerous drugs have been reported to have in vitro activity against E. multilocularis, but few had satisfactory in vivo activity, and none were clearly more effective than benzimidazoles. These drugs belong to various therapeutic categories including anti-infective agents (e.g. amphotericin B, mefloquine, pentamidine derivatives), anti-neoplastic compounds (e.g. imatinib, nilotinib, bortezomib), plant-extracted compounds (e.g. thymol, crocin, carvacrol) and others (e.g. metformin, verapamil, thiaclopride). These treatments are generally of limited interest due to their toxicity, their unfavorable pharmacokinetics, or the scarcity of studies involving humans. Apart from benzimidazoles, only amphotericin B, mefloquine and nitazoxanide have been reported to be used for human AE treatment, with unsatisfactory results. Few studies have aimed at developing innovative strategies for AE drug therapy, such as vectorization of drugs using nanoparticles. Altogether, this review emphasizes the urgent need for new therapeutic strategies in AE management, for which there is currently no curative chemotherapy.


Title: Chimiothérapie de l'échinococcose alvéolaire : où en sommes-nous ? Abstract: L'échinococcose alvéolaire (EA) est une maladie sévère du foie due à l'infection par la forme larvaire d'Echinococcus multilocularis, appelée métacestode. La prise en charge de l'EA repose sur la chimiothérapie par benzimidazolés (albendazole ou mébendazole), si possible associée à la chirurgie. Les benzimidazolés sont les seules molécules recommandées dans le traitement de l'EA, toutefois, ceux-ci sont parasitostatiques, ce qui signifie que le parasite peut reprendre sa croissance lors d'une interruption du traitement. Également, les benzimidazolés peuvent causer une dysfonction hépatique qui peut empêcher leur utilisation. De nombreux médicaments ont été rapportés comme ayant une activité in vitro contre E. multilocularis, mais peu d'entre eux avaient une activité in vivo satisfaisante et aucun n'était clairement plus efficace que les benzimidazolés. Ces médicaments appartiennent à diverses catégories, notamment les agents anti-infectieux (par exemple l'amphotéricine B, la méfloquine, des dérivés de la pentamidine), les composés antinéoplasiques (par exemple l'imatinib, le nilotinib, le bortézomib), les composés extraits de plantes (par exemple le thymol, la crocine, le carvacrol) et d'autres (par exemple metformine, vérapamil, thiaclopride). Ces traitements présentent généralement un intérêt limité en raison de leur toxicité, de leur pharmacocinétique défavorable ou de la rareté des études menées chez l'homme. Outre les benzimidazolés, seules l'amphotéricine B, la méfloquine et la nitazoxanide ont été utilisées dans le traitement de l'EA humaine, avec des résultats insatisfaisants. Peu d'études se sont intéressées à développer des stratégies médicamenteuses innovantes contre l'EA, comme la vectorisation de médicaments à l'aide de nanoparticules. Cette revue souligne le besoin urgent de nouvelles stratégies thérapeutiques dans la prise en charge de l'EA, pour lesquelles il n'existe pas de chimiothérapie curative.


Subject(s)
Echinococcosis , Echinococcus multilocularis , Humans , Animals , Echinococcosis/drug therapy , Echinococcus multilocularis/drug effects , Anthelmintics/therapeutic use , Benzimidazoles/therapeutic use , Echinococcosis, Hepatic/drug therapy , Albendazole/therapeutic use , Antineoplastic Agents/therapeutic use , Anti-Infective Agents/therapeutic use
6.
BMJ Case Rep ; 17(9)2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39242125

ABSTRACT

A complex liver lesion presents a significant challenge in terms of diagnosis and management. This case is an illustrative example, highlighting the steps involved in managing such complex scenarios. This patient, in her early 20s, presented with a fever associated with worsening abdominal pain, as well as a background history of chronic abdominal pain, anorexia, vomiting, constipation and weight loss. The radiology revealed an irregular complex cyst in the liver with biliary and vascular invasion, raising concerns about hepatocellular carcinoma. The diagnosis was changed to alveolar echinococcosis after the infectious diseases consultant gave helpful advice, and echinococcosis antibodies were found. We subsequently started the patient on albendazole therapy. Following prudent advice from hepatobiliary surgeons and given the complexity of the hepatic lesion, a liver transplant was considered the best management option due to the extensive involvement of the biliary and venous systems. The combined approach of albendazole and a liver transplant marked a transformative phase for this patient, putting an end to her prolonged suffering.


Subject(s)
Albendazole , Carcinoma, Hepatocellular , Echinococcosis, Hepatic , Liver Neoplasms , Liver Transplantation , Humans , Echinococcosis, Hepatic/diagnosis , Echinococcosis, Hepatic/diagnostic imaging , Carcinoma, Hepatocellular/diagnosis , Female , Liver Neoplasms/diagnosis , Diagnosis, Differential , Albendazole/therapeutic use , Young Adult , Anthelmintics/therapeutic use , Tomography, X-Ray Computed
7.
Sci Rep ; 14(1): 21970, 2024 09 20.
Article in English | MEDLINE | ID: mdl-39304661

ABSTRACT

Soil-transmitted helminths (STH) are neglected parasites more prevalent in the tropics. Periodic mass distribution of albendazole, is one key strategy to control STHI in endemic areas. However, benzimidazoles have low efficacy against STHI, and there is a lack of information on the magnitude of the problem in Ethiopia. Articles were searched from PubMed using MeSH words, Google Scholar, Web of science, EMBASE and Scopus database to retrieve the data published and available until December 30, 2022. Totally, 107 published articles were retrieved. Only studies conducted in English that reported the efficacy of albendazole against STHI in any year and studies with more than fifty positive cases were included in the present study. The efficacy of albendazole was estimated by its cure rate and egg reduction rate. Excel software was used to extract the name of the authors, the total sample size, number of cured participants, treatment assessment time, STH parasite involved, the study area, and the year of publication. The pooled efficacy of albendazole against STHs was analyzed using comprehensive meta-analysis version 2.2 software. A total of 14 studies (13 for hookworm, 12 for Ascaris lumbricoides, and 12 for Trichuris trichiura) fulfilled the inclusion criteria for the present systematic review and meta-analysis. The total positives for hookworm, A. lumbricoides, and T. trichiura were 1253 (24.9%), 1570 (29.5%), and 1647 (30.6%), respectively. The overall pooled efficacy of albendazole was 92.2% (95% CI 86.2-98.9%) against hookworm, 97.7% (95% CI 96.3-98.6%) against A. lumbricoides, and 38.6% (95% CI 31.0-46.9%) against T. trichiura. In subgroup analysis, the efficacy of albendazole against hookworm was 93.4% (95% CI 85.1-97.2%) in Oromia, 96.7% (95% CI 93.8-98.2%) in Sidama, and 77.2% (95% CI 64.4-86.4%) in Amhara region. Its heterogeneity was high (I2 = 89.418). The efficacy of albendazole against A. lumbricoides was 98.3% (95% CI 97.0-99.0%) in Oromia and 96.63% (95% CI 93.2-98.3%) in Sidama region. Its heterogeneity was moderate (I2 = 41.5%). Albendazole efficacy against T. trichiura was 39.0% (95% CI 30.4-48.5%) in Oromia and 37.8% (95% CI 21.8-56.9%) in Sidama region with high heterogeneity (I2 = 90.6%). In the present review, albendazole is effective against hookworm and A. lumbricoides but less effective against T. trichiura. Albendazole should therefore be used as a treatment option in hookworm and A. lumbricoides endemic areas. However, alternative drugs should be sought for T. trichiura.


Subject(s)
Albendazole , Anthelmintics , Helminthiasis , Soil , Albendazole/therapeutic use , Albendazole/pharmacology , Ethiopia/epidemiology , Humans , Soil/parasitology , Helminthiasis/drug therapy , Helminthiasis/epidemiology , Helminthiasis/parasitology , Anthelmintics/therapeutic use , Anthelmintics/pharmacology , Animals , Ascaris lumbricoides/drug effects , Treatment Outcome , Ascariasis/drug therapy , Ascariasis/parasitology , Ascariasis/epidemiology , Trichuris/drug effects , Trichuriasis/drug therapy , Trichuriasis/epidemiology
8.
Parasit Vectors ; 17(1): 387, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39267171

ABSTRACT

Soil-transmitted helminth (STH) infections account for a significant global health burden, necessitating mass drug administration with benzimidazole-class anthelmintics, such as albendazole (ALB), for morbidity control. However, ALB efficacy shows substantial variability, presenting challenges for achieving consistent treatment outcomes. We have explored the potential impact of the baseline gut microbiota on ALB efficacy in hookworm-infected individuals through microbiota profiling and machine learning (ML) techniques. Our investigation included 89 stool samples collected from hookworm-infected individuals that were analyzed by microscopy and quantitative PCR (qPCR). Of these, 44 were negative by microscopy for STH infection using the Kato-Katz method and qPCR 21 days after treatment, which entails a cure rate of 49.4%. Microbiota characterization was based on amplicon sequencing of the V3-V4 16S ribosomal RNA gene region. Alpha and beta diversity analyses revealed no significant differences between participants who were cured and those who were not cured, suggesting that baseline microbiota diversity does not influence ALB treatment outcomes. Furthermore, differential abundance analysis at the phylum, family and genus levels yielded no statistically significant associations between bacterial communities and ALB efficacy. Utilizing supervised ML models failed to predict treatment response accurately. Our investigation did not provide conclusive insights into the relationship between gut microbiota and ALB efficacy. However, the results highlight the need for future research to incorporate longitudinal studies that monitor changes in the gut microbiota related to the infection and the cure with ALB, as well as functional metagenomics to better understand the interaction of the microbiome with the drug, and its role, if there is any, in modulating anthelmintic treatment outcomes in STH infections. Interdisciplinary approaches integrating microbiology, pharmacology, genetics and data science will be pivotal in advancing our understanding of STH infections and optimizing treatment strategies globally.


Subject(s)
Albendazole , Anthelmintics , Feces , Gastrointestinal Microbiome , Hookworm Infections , Albendazole/therapeutic use , Albendazole/pharmacology , Albendazole/administration & dosage , Humans , Gastrointestinal Microbiome/drug effects , Gastrointestinal Microbiome/genetics , Anthelmintics/therapeutic use , Anthelmintics/administration & dosage , Hookworm Infections/drug therapy , Feces/parasitology , Feces/microbiology , Female , Male , RNA, Ribosomal, 16S/genetics , Adult , Treatment Outcome , Animals , Young Adult , Middle Aged , Ancylostomatoidea/drug effects , Ancylostomatoidea/genetics , Adolescent , Child
9.
BMJ Case Rep ; 17(9)2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39266042

ABSTRACT

Neurocysticercosis (NCC) is the most common parasitic infection of the central nervous system, caused by the pork tapeworm, Taenia solium Common presenting features are seizures, headaches and focal neurodeficits. The present report details the anecdote of a middle-aged Asian man, who presented with subacute onset of persistent nausea, vomiting and hiccups. Following unsuccessful trials with numerous prokinetic, antipsychotic, muscle relaxant and anticonvulsant medications, as well as an uneventful battery of gastrointestinal tests, he was referred for neurological evaluation. The constellation of symptoms was congruent with the diagnosis of area postrema syndrome. Although initial CT scan of brain was normal, MRI with contrast evaluation revealed a circumscribed, ring-enhancing lesion of the dorsal medulla oblongata, reminiscent of colloid vesicular stage of NCC. The patient was successfully treated with steroids and albendazole. The association of refractory singultus, nausea and vomiting and NCC is thus far, not reported in the literature.


Subject(s)
Albendazole , Area Postrema , Neurocysticercosis , Vomiting , Humans , Neurocysticercosis/complications , Neurocysticercosis/drug therapy , Neurocysticercosis/diagnosis , Neurocysticercosis/diagnostic imaging , Male , Albendazole/therapeutic use , Area Postrema/diagnostic imaging , Vomiting/etiology , Vomiting/parasitology , Nausea/etiology , Middle Aged , Magnetic Resonance Imaging , Hiccup/etiology , Hiccup/drug therapy , Syndrome , Anthelmintics/therapeutic use
10.
Medicine (Baltimore) ; 103(39): e39714, 2024 Sep 27.
Article in English | MEDLINE | ID: mdl-39331943

ABSTRACT

RATIONALE: Strongyloides stercoralis, a rare human intestinal parasite, poses a significant health risk, capable of causing lifelong infection and even mortality due to its atypical manifestation of symptoms. In this case report, we reported a case of a patient diagnosed with S. stercoralis infection of the residual stomach and meticulously detail its treatment process, offering valuable insights and a reference point for clinicians. PATIENT CONCERNS: we report a case of infection caused by S. stercoralis after subtotal gastrectomy (Billroth type II) in a 47-year-old middle-aged man. It presents with recurrent nausea and vomiting, accompanied by intermittent food residue vomiting and constipation. DIAGNOSES: Upon endoscopic examination, we observed mucosal swelling and erosion in the anastomosis and output ring of stomach, while pathological analysis confirmed the presence of Strongyloides stercoralis eggs. Subsequently, the administration of albendazole for anti-infection treatment proved to be effective, thereby reinforcing the diagnosis of S. stercoralis infection. INTERVENSIONS: The patient underwent aggressive management including fasting, fluid replacement, anti-infection therapy, albumin supplementation, and albendazole treatment at a dose of 300 mg/kg/day for 3 days to eliminate the parasite. OUTCOMES: After treatment, the patient's symptoms of nausea, vomiting, and constipation were alleviated and returned to normal upon discharge. Over the subsequent 3 years, the patient reported no instances of vomiting and experienced a recovery of digestive function compared to their discharge status. LESSONS: S. stercoralis infection is relatively rare in the remnant stomach, endoscopic and pathological examination may be one of the important methods to diagnose S. stercoralis infection, and it is effective to treat albendazole according to the course of treatment.


Subject(s)
Gastritis , Strongyloides stercoralis , Strongyloidiasis , Humans , Strongyloidiasis/diagnosis , Strongyloidiasis/complications , Strongyloidiasis/drug therapy , Strongyloides stercoralis/isolation & purification , Middle Aged , Male , Animals , Gastritis/parasitology , Gastritis/diagnosis , Gastritis/drug therapy , Gastritis/complications , Albendazole/therapeutic use , Gastrectomy , Anthelmintics/therapeutic use
11.
Biomed Pharmacother ; 179: 117400, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39243427

ABSTRACT

PURPOSE: To improve the oral bioavailability of albendazole (ABZ), a series of albendazole-bile acid conjugates (ABCs) were synthesized. ABC's transmembrane transport mechanism and in vivo pharmacokinetic properties were preliminarily studied. METHODS: The transmembrane transport mechanism of ABCs was studied using the Caco-2 monolayer cell model and intestinal perfusion model. The concentration of ABCs and ABZ were evaluated using High-Performance Liquid Chromatography (HPLC) and HPLC-Mass Spectrometry (HPLC-MS/MS). RESULTS: Compared to ABZ, better permeability was observed for different types and concentrations of ABCs using the Caco-2 monolayer cell model, with ABC-C8 showing the highest permeability. The transmembrane transport of ABCs was affected by ASBT inhibitors, indicating an ASBT-mediated active transport mechanism. Additionally, introducing cholic acid resulted in ABZ no longer being a substrate for P-gp, MRP2, and BCRP, effectively reversing ABZ efflux. In vivo unidirectional intestinal perfusion results in rats showed that ABCs altered the absorption site of ABZ from the jejunum to the ileum. The absorption efficiency of ABCs in each intestinal segment was higher than that of ABZ, and the transmembrane transport efficiency decreased with increasing concentrations of ASBT inhibitors. This further confirmed the presence of both passive diffusion and ASBT-mediated active transport mechanisms in the transport of ABCs. The solubility of ABCs in gastric juice and pharmacokinetics in rats showed that ABZ-C4 exhibited enhanced solubility. Moreover, ABCs significantly increased oral bioavailability compared to ABZ, with ABC-C4 showing an approximately 31-fold increase in bioavailability. CONCLUSION: The transmembrane transport mechanism of ABCs involves a combination of ASBT-mediated active transport and passive diffusion. Moreover, the incorporation of BAs successfully reverses the efflux of ABZ by efflux proteins. Among the synthesized conjugates, ABC-C4 demonstrated superior dissolution behavior both in vitro and in vivo.


Subject(s)
Albendazole , Bile Acids and Salts , Intestinal Absorption , Rats, Sprague-Dawley , Caco-2 Cells , Animals , Albendazole/pharmacokinetics , Albendazole/chemistry , Albendazole/pharmacology , Albendazole/administration & dosage , Humans , Male , Intestinal Absorption/drug effects , Rats , Bile Acids and Salts/metabolism , Bile Acids and Salts/chemistry , Biological Availability , Biological Transport , Administration, Oral
12.
Tidsskr Nor Laegeforen ; 144(10)2024 Sep 10.
Article in English, Norwegian | MEDLINE | ID: mdl-39254012

ABSTRACT

Alveolar echinococcosis is a much-feared parasitic zoonosis caused by the larval stage of Echinococcus multilocularis. Mainland Norway is free from infection, but alveolar echinococcosis is, on rare occasions, imported from endemic regions. Those infected develop slow-growing, multicystic tumours that are clinically and radiologically reminiscent of malignant disease. The disease mainly attacks the liver. Treatment often consists of extensive surgical resection in combination with prolonged use of albendazole. In this clinical review article we summarise the life cycle, clinical findings, diagnosis, treatment and epidemiology of alveolar echinococcosis, and provide examples of the disease course with two patient case reports.


Subject(s)
Albendazole , Echinococcosis, Hepatic , Echinococcosis , Echinococcus multilocularis , Humans , Echinococcus multilocularis/isolation & purification , Echinococcosis, Hepatic/diagnostic imaging , Albendazole/therapeutic use , Animals , Echinococcosis/diagnosis , Echinococcosis/drug therapy , Echinococcosis/diagnostic imaging , Norway , Male , Tomography, X-Ray Computed , Adult , Female , Middle Aged , Anthelmintics/therapeutic use , Life Cycle Stages
13.
PLoS Negl Trop Dis ; 18(9): e0012526, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39348380

ABSTRACT

Human angiostrongyliasis, caused by consuming the larva stage of Angiostrongylus cantonensis, is an infectious disease involving the central nervous system (CNS) and ophthalmic system. Current treatment of angiostrongyliasis involves albendazole accompanied by analgesics and corticosteroids. However, long-term use of corticosteroids may lead to significant adverse effects. In the current study, we screened through different potentially effective flavonoid compounds and identified quercetin as an effective anti-inflammatory agent in an angiostrongyliasis mouse model. Our results identified that quercetin may reverse the neurological defects in mice with angiostrongyliasis. The brain pathology and inflammatory status were also improved by albendazole-quercetin co-therapy. Further analysis showed that albendazole-quercetin co-therapy had a better therapeutic effect than albendazole or quercetin monotherapy. This therapeutic effect was achieved by inhibiting the brain inflammasome activation and apoptosis. Albendazole-quercetin co-therapy also leads to the inhibition of brain IL-5, possibly leading to improved pathology. Our results here proved that quercetin may serve as a potential adjuvant drug in treating human angiostrongyliasis.


Subject(s)
Albendazole , Angiostrongylus cantonensis , Quercetin , Strongylida Infections , Albendazole/therapeutic use , Albendazole/pharmacology , Animals , Quercetin/pharmacology , Quercetin/therapeutic use , Strongylida Infections/drug therapy , Strongylida Infections/parasitology , Mice , Angiostrongylus cantonensis/drug effects , Disease Models, Animal , Brain/parasitology , Brain/pathology , Brain/drug effects , Anthelmintics/therapeutic use , Female , Flavonoids/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Apoptosis/drug effects , Drug Therapy, Combination , Inflammasomes/drug effects , Inflammasomes/metabolism , Humans
14.
PLoS Negl Trop Dis ; 18(9): e0012511, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39325836

ABSTRACT

Genomics, transcriptomics, and proteomics have significantly advanced our understanding of obligately host-associated microbes, where interrogation of the biology is often limited by the complexity of the biological system and limited tools. This includes the causative agents of many neglected tropical diseases, including filarial nematodes. Therefore, numerous transcriptomics studies have been undertaken on filarial nematodes. Most of these transcriptomics studies focus on Brugia malayi, which causes lymphatic filariasis and is a laboratory model for human filarial disease. Here, we undertook a meta-analysis of the publicly available B. malayi transcriptomics data enabling the direct cross comparison of samples from almost a dozen studies. This reanalysis highlights the consistency of transcriptomics results across many different studies and experimental designs from across the globe for over a decade of research, across many different generations of a sequencing technology, library preparation protocols, and differential expression tools. Males and microfilariae across samples had similar expression profiles. However, female samples were clustered into two differential expression patterns that were significantly different from one another. Largely, we confirm previous results for all studies reanalyzed including tissue-specific gene expression and anti-Wolbachia doxycycline treatment of microfilaria. However, we did not detect previously reported differential expression upon in vitro or in vivo treatment with ivermectin, albendazole, and DEC, instead identifying a consistent lack of transcriptomic change upon exposure to these anthelminthic drugs. Updated annotation has been provided that denotes poorly supported genes including those overlapping rRNAs.


Subject(s)
Brugia malayi , Gene Expression Profiling , Transcriptome , Brugia malayi/genetics , Brugia malayi/drug effects , Female , Animals , Male , Elephantiasis, Filarial/parasitology , Elephantiasis, Filarial/genetics , Microfilariae/genetics , Humans , Albendazole/pharmacology , Molecular Sequence Annotation
15.
Parasitol Int ; 103: 102940, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39094680

ABSTRACT

The use of medicinal plants as a means of combating parasites is becoming increasingly popular due to general resistance to synthetic anthelmintics. Goats typically respond less well to anthelminthic treatments, which may increase their resistance to nematodes. For this purpose, the anthelmintic effect of Pelargonium quercetorum Agnew (P. quercetorum) extract was tested in an in vivo study against gastrointestinal parasites of goats. A total of 40 goats naturally infected with mixed gastrointestinal nematode species were divided into four groups: the first group was treated with albendazole (7.5 mg/kg), the second group received a single dose of closantel (7.5 mg/kg), the third group received plant extract (7.5 mg/kg), and the fourth group served as an untreated control. Fecal egg counts (FEC) were carried out on day 14, as well as day 0, which was prior to the first treatment dose. According to the results, maximum reduction in FEC percentage was observed in P. quercetorum treated group (63.41%). Furthermore, nematode parasites responded poorly to synthetic drugs, although there was a 4.72% and 45.54% decrease in FEC in the albendazole and closantel-treated groups, respectively. Although no significant difference was found between the treatment groups, the P. quercetorum treated group showed a significant reduction in fecal egg count after treatment. Based on findings, a P. quercetorum based anthelmintic could be a sustainable alternative to combat parasite infestation. Therefore, further studies are needed to determine the optimal dose rate and frequency of doses required for effective control of gastrointestinal parasites in goats.


Subject(s)
Albendazole , Anthelmintics , Feces , Goat Diseases , Goats , Nematoda , Nematode Infections , Parasite Egg Count , Pelargonium , Plant Extracts , Animals , Goat Diseases/parasitology , Goat Diseases/drug therapy , Parasite Egg Count/veterinary , Nematode Infections/veterinary , Nematode Infections/drug therapy , Nematode Infections/parasitology , Nematode Infections/prevention & control , Feces/parasitology , Anthelmintics/therapeutic use , Anthelmintics/pharmacology , Anthelmintics/administration & dosage , Pelargonium/chemistry , Nematoda/drug effects , Albendazole/therapeutic use , Albendazole/pharmacology , Albendazole/administration & dosage , Plant Extracts/pharmacology , Gastrointestinal Diseases/parasitology , Gastrointestinal Diseases/veterinary , Gastrointestinal Diseases/drug therapy , Salicylanilides/pharmacology , Salicylanilides/administration & dosage , Intestinal Diseases, Parasitic/veterinary , Intestinal Diseases, Parasitic/drug therapy , Intestinal Diseases, Parasitic/parasitology
16.
J Med Case Rep ; 18(1): 399, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39210392

ABSTRACT

BACKGROUND: Hydatid disease, also known as echinococcosis, is a zoonotic parasitic infection caused by the larvae of the Echinococcus tapeworm. It is endemic in various regions worldwide, particularly in rural areas of countries in southern South America, Central Asia, China, parts of Africa, the Mediterranean, and parts of the Middle East. The disease primarily affects the liver (60-70% of cases) and the lungs (10-25% of cases), but it can involve any organ, including the brain, bones, and rarely the pelvic region, as seen in our case report. Hydatid disease typically follows an asymptomatic course in the early stages of the primary infection and may remain so potentially for years or even permanently. If symptoms occur, they depend on various factors, such as the number, size, and location among other factors. Typically, hydatid disease presents with nonspecific symptoms. Common symptoms include abdominal pain, hepatomegaly, as well as anaphylaxis in case of cyst rupture. Extrahepatic intra-abdominal isolated hydatic cyst is a rare finding (6-11%). CASE PRESENTATION: In our case, a 70 year-old Asian white male presented with right thigh pain radiating to the lower leg, which is an atypical presentation for an extrahepatic intraabdominal hydatid cyst. Primary intraabdominal hydatid cysts involving the pelvic region are relatively rare, and such cases pose diagnostic and management challenges. CONCLUSION: This case report underscores the challenges in diagnosing and managing extrahepatic intraabdominal hydatid cysts, particularly in atypical presentations. A combination of clinical evaluation, serological studies, and imaging techniques facilitates accurate diagnosis.


Subject(s)
Echinococcosis , Humans , Male , Echinococcosis/diagnosis , Echinococcosis/diagnostic imaging , Echinococcosis/surgery , Aged , Tomography, X-Ray Computed , Albendazole/therapeutic use , Treatment Outcome , Animals , Anthelmintics/therapeutic use
17.
Int J Pharm ; 663: 124586, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39147249

ABSTRACT

This study demonstrates the application of Langmuir and Langmuir-Blodgett films as biomimetic drug reservoirs and delivery systems to investigate the effect of an anthelmintic on cancer cell culture. The repurposing of benzimidazole anthelmintics for cancer therapy due to their microtubule-inhibiting properties has gained attention, showing promising anticancer effects and tumor-suppressive properties. Although widely used in medicine, the low aqueous solubility of benzimidazole compounds poses challenges for studying their effects on cancer cells, requiring incorporation into various formulations. Our study demonstrates that incorporating albendazole into stable Palmitic Acid Langmuir monolayers, forming Langmuir-Blodgett films, significantly affects the proliferation of liver carcinoma cells. This report presents the initial findings of the effect of an antitumoral drug on cancer cell culture using a simple and repeatable methodology.


Subject(s)
Albendazole , Antineoplastic Agents , Cell Proliferation , Drug Delivery Systems , Albendazole/chemistry , Albendazole/administration & dosage , Albendazole/pharmacology , Humans , Drug Delivery Systems/methods , Antineoplastic Agents/chemistry , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacology , Cell Proliferation/drug effects , Hep G2 Cells , Cell Line, Tumor , Anthelmintics/chemistry , Anthelmintics/administration & dosage , Anthelmintics/pharmacology , Solubility , Surface Properties
18.
Rev Bras Parasitol Vet ; 33(3): e004924, 2024.
Article in English | MEDLINE | ID: mdl-39194144

ABSTRACT

In aquaculture worldwide, most of the chemotherapeutic agents used for disease control and treatment are unregulated chemical products derived from agriculture. In this study, we investigated the efficacy of therapeutic baths with albendazole against the monogeneans Anacanthorus spathulatus, Notozothecium janauachensis and Mymarothecium boegeri, which infest the gills of Colossoma macropomum, and the hematological and histopathological effects of this anthelmintic agent on these fish. Albendazole at a concentration of 500 mg/L was used in three baths of 24 hours each, with intervals of 24 hours between these baths. Three replications of this treatment were used, and the control group consisted of water from the cultivation tank. Afterwards, hematological, histopathological and parasitological analyses were conducted. We found that the therapeutic baths with albendazole at 500 mg/L presented high efficacy (94.9%) against monogeneans de C. macropomum and caused few physiological or histopathological alterations. Therefore, baths with albendazole at 500 mg/L, as used in this strategy, can be recommended for controlling and treating infections by monogeneans in C. macropomum.


Subject(s)
Albendazole , Anthelmintics , Fish Diseases , Animals , Fish Diseases/drug therapy , Fish Diseases/parasitology , Albendazole/therapeutic use , Albendazole/pharmacology , Anthelmintics/therapeutic use , Anthelmintics/pharmacology , Characiformes/parasitology , Trematode Infections/drug therapy , Trematode Infections/veterinary , Trematode Infections/parasitology , Trematoda/drug effects , Platyhelminths/drug effects
19.
Lancet ; 404(10453): 683-691, 2024 Aug 17.
Article in English | MEDLINE | ID: mdl-39153818

ABSTRACT

BACKGROUND: Human hookworm is a cause of enormous global morbidity. Current treatments have insufficient efficacy and their extensive and indiscriminate distribution could also result in drug resistance. Therefore, we tested the efficacy and safety of emodepside, a strong anthelmintic candidate that is currently undergoing clinical development for onchocerciasis and soil-transmitted helminth infections. METHODS: We conducted a double-blind, superiority, phase 2b, randomised controlled clinical trial comparing emodepside and albendazole. Participants in the emodepside group received six 5 mg tablets of emodepside (totalling 30 mg) and one placebo; participants in the albendazole group received one 400 mg tablet of albendazole and six placebos. Participants were recruited from four endemic villages and three secondary schools in Pemba Island, Tanzania. Participants aged 12-60 years were eligible for treatment if they were positive for hookworm infection, and they had 48 or more eggs per gram from four Kato-Katz thick smears and at least two slides had more than one hookworm egg present. Participants' treatment allocation was stratified by infection intensity and efficacy was measured by cure rate: participants who were hookworm positive and became hookworm negative after treatment. Adverse events were reported at 3 h, 24 h, 48 h, and 14-21 days post-treatment. The trial is registered at ClinicalTrials.gov, NCT05538767. FINDINGS: From Sept 15 to Nov 8, 2022, and from Feb 15 to March 15, 2023, 1609 individuals were screened for hookworm. Of these, 293 individuals were treated: 147 with albendazole and 146 with emodepside. Emodepside demonstrated superiority, with an observed cure rate against hookworm of 96·6%, which was significantly higher compared with albendazole (cure rate 81·2%, odds ratio 0·14, 95% CI 0·04-0·35; p=0·0001). The most common adverse event in the emodepside treatment group was vision blur at 3 h after treatment (57 [39%] of 146). Other common adverse events were vision blur at 24 h after treatment (55 [38%]), and headache and dizziness at 3 h after treatment (55 [38%] for headache and 43 [30%] for dizziness). In the emodepside treatment group, 298 (93%) of the 319 adverse events were mild. The most commonly reported adverse events in the albendazole treatment group were headache and dizziness at 3 h after treatment (27 [18%] of 147 for headache and 14 [10%] for dizziness). No serious adverse events were reported. INTERPRETATION: This phase 2b clinical trial confirms the high efficacy of emodepside against hookworm infections, solidifying emodepside as a promising anthelmintic candidate. However, although the observed safety events were generally mild in severity, considerations must be made to balance the strong efficacy outcomes with the increased frequency of adverse events compared with albendazole. FUNDING: European Research Council.


Subject(s)
Albendazole , Anthelmintics , Depsipeptides , Hookworm Infections , Adolescent , Adult , Child , Female , Humans , Male , Middle Aged , Young Adult , Albendazole/therapeutic use , Albendazole/adverse effects , Anthelmintics/adverse effects , Anthelmintics/therapeutic use , Depsipeptides/adverse effects , Depsipeptides/therapeutic use , Double-Blind Method , Hookworm Infections/drug therapy , Tanzania , Treatment Outcome
20.
BMC Infect Dis ; 24(1): 778, 2024 Aug 03.
Article in English | MEDLINE | ID: mdl-39097707

ABSTRACT

BACKGROUND: Albendazole (ABZ) and atovaquone (ATO) achieve killing efficacy on Echinococcus granulosus (Egs) by inhibiting energy metabolism, but their utilization rate is low. This study aims to analyze the killing efficacy of ABZ-ATO loading nanoparticles (ABZ-ATO NPs) on Egs. METHODS: Physicochemical properties of NPs were evaluated by ultraviolet spectroscopy and nanoparticle size potentiometer. In vitro experiments exmianed the efficacy of ATO, ABZ, or ATO-ABZ NPs on protoscolex activity, drug toxicity on liver cell LO2, ROS production, and energy metabolism indexes (lactic dehydrogenase, lactic acid, pyruvic acid, and ATP). In vivo of Egs-infected mouse model exmianed the efficacy of ATO, ABZ, or ATO-ABZ NPs on vesicle growth and organ toxicity. RESULTS: Drug NPs are characterized by uniform particle size, stability, high drug loading, and - 21.6mV of zeta potential. ABZ or ATO NPs are more potent than free drugs in inhibiting protoscolex activity. The protoscolex-killing effect of ATO-ABZ NPs was stronger than that of free drugs. In vivo Egs-infected mice experiment showed that ATO-ABZ NPs reduced vesicle size and could protect various organs. The results of energy metabolism showed that ATO-ABZ NPs significantly increased the ROS level and pyruvic acid content, and decreased lactate dehydrogenase, lactic acid content, and ATP production in the larvae. In addition, ATO-ABZ NPs promoted a decrease in DHODH protein expression in protoscolexes. CONCLUSION: ATO-ABZ NPs exhibits anti-CE in vitro and in vivo, possibly by inhibiting energy production and promoting pyruvic acid aggregation.


Subject(s)
Albendazole , Atovaquone , Echinococcosis , Echinococcus granulosus , Energy Metabolism , Nanoparticles , Animals , Albendazole/pharmacology , Albendazole/chemistry , Albendazole/administration & dosage , Mice , Energy Metabolism/drug effects , Echinococcus granulosus/drug effects , Nanoparticles/chemistry , Echinococcosis/drug therapy , Echinococcosis/parasitology , Atovaquone/pharmacology , Anthelmintics/pharmacology , Anthelmintics/administration & dosage , Humans , Particle Size , Disease Models, Animal , Female
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