Therapeutic efficacy of nanocompounds in the treatment of cystic and alveolar echinococcoses: challenges and future prospects

Bakhtiar, Nayer Mehdizad; Akbarzadeh, Abolfazl; Casulli, Adriano; Mahami-Oskouei, Mahmoud; Ahmadpour, Ehsan; Nami, Sanam; Rostami, Ali; Spotin, Adel

doi:10.1007/s00436-019-06416-5

Cited by 15 publications

(16 citation statements)

References 56 publications

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“…However, to date only the (i) BMZ were shown to be active also against human AE. More recent studies suggest to improve the absorption and oral bioavailability of these drugs by developing new formulations such as BMZ salt formulations ( Cirilli et al, 2017 ) or nanocrystals ( Pensel et al, 2018 ; Bakhtiar et al, 2019 ; Ullio Gamboa et al, 2019 ). Two other drugs that reached clinical application against AE over the last years are (ii) the broad-spectrum anti-parasitic nitazoxanide and (iii) the anti-fungal agent amphotericin B.…”

Section: Identification Of Novel Drugs Against Alveolar Echinococcosimentioning

confidence: 99%

Drug repurposing applied: Activity of the anti-malarial mefloquine against Echinococcus multilocularis

Lundström‐Stadelmann

Rufener

Hemphill

2020

International Journal for Parasitology: Drugs and Drug Resistan

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The current chemotherapeutical treatment against alveolar echinococcosis relies exclusively on benzimidazoles, which are not parasiticidal and can induce severe toxicity. There are no alternative treatment options. To identify novel drugs with activity against Echinococcus multilocularis metacestodes, researchers have studied potentially interesting drug targets (e.g. the parasite's energy metabolism), and/or adopted drug repurposing approaches by undertaking whole organism screenings. We here focus on drug screening approaches, which utilize an in vitro screening cascade that includes assessment of the drug-induced physical damage of metacestodes, the impact on metacestode viability and the viability of isolated parasite stem cells, structure-activity relationship (SAR) analysis of compound derivatives, and the mode of action. Finally, once in vitro data are indicative for a therapeutic window, the efficacy of selected compounds is assessed in experimentally infected mice. Using this screening cascade, we found that the anti-malarial mefloquine was active against E. multilocularis metacestodes in vitro and in vivo . To shed more light into the mode of action of mefloquine, SAR analysis on mefloquine analogues was performed. E. multilocularis ferritin was identified as a mefloquine-binding protein, but its precise role as a drug target remains to be elucidated. In mice that were infected either intraperitoneally with metacestodes or orally with eggs, oral treatment with mefloquine led to a significant reduction of parasite growth compared to the standard treatment with albendazole. However, mefloquine was not acting parasiticidally. Assessment of mefloquine plasma concentrations in treated mice showed that levels were reached which are close to serum concentrations that are achieved in humans during long-term malaria prophylaxis. Mefloquine might be applied in human AE patients as a salvage treatment. Future studies should focus on other repurposed anti-infective compounds (MMV665807, niclosamide, atovaquone), which showed stronger in vitro activity against E. multilocularis than mefloquine.

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Section: Identification Of Novel Drugs Against Alveolar Echinococcosimentioning

confidence: 99%

Drug repurposing applied: Activity of the anti-malarial mefloquine against Echinococcus multilocularis

Lundström‐Stadelmann

Rufener

Hemphill

2020

International Journal for Parasitology: Drugs and Drug Resistan

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“…The only choice of treatment for patients who are not candidates for radical resection surgery and those undergoing palliative resection involves antihydatid therapy with drugs such as albendazole [ 3 ]. However, there is no well-defined treatment period for HAE, which leads to long-term medication-associated complications in patients [ 4 , 5 ]. Theoretically, the critical indicator for medication termination involves the absence of biological activity of HAE lesions; however, this criterion is not clinically feasible.…”

Section: Introductionmentioning

confidence: 99%

Hepatic Alveolar Echinococcosis: Predictive Biological Activity Based on Radiomics of MRI

Ren

Wang

Miao

et al. 2021

BioMed Research International

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Background. To evaluate the role of radiomics based on magnetic resonance imaging (MRI) in the biological activity of hepatic alveolar echinococcosis (HAE). Methods. In this study, 90 active and 46 inactive cases of HAE patients were analyzed retrospectively. All the subjects underwent MRI and positron emission tomography computed tomography (PET-CT) before surgery. A total of 1409 three-dimensional radiomics features were extracted from the T2-weighted MR images (T2WI). The inactive group in the training cohort was balanced via the synthetic minority oversampling technique (SMOTE) method. The least absolute shrinkage and selection operator (LASSO) regression method was used for feature selection. The machine learning (ML) classifiers were logistic regression (LR), multilayer perceptron (MLP), and support vector machine (SVM). We used a fivefold cross-validation strategy in the training cohorts. The classification performance of the radiomics signature was evaluated using receiver operating characteristic curve (ROC) analysis in the training and test cohorts. Results. The radiomics features were significantly associated with the biological activity, and 10 features were selected to construct the radiomics model. The best performance of the radiomics model for the biological activity prediction was obtained by MLP ( AUC = 0.830 ± 0.053 ; accuracy = 0.817 ; sensitivity = 0.822 ; specificity = 0.811 ). Conclusions. We developed and validated a radiomics model as an adjunct tool to predict the HAE biological activity by combining T2WI images, which achieved results nearly equal to the PET-CT findings.

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“…To improve chemotherapy there is a need for new formulations of benzimidazoles (BMZs) that would have better and more stable bioavailability features [31]. In the future electromagnetically produced nanodrugs and newly structured entities with nanoparticles might be an alternative treatment for this neglected infection.…”

Section: Discussionmentioning

confidence: 99%

Alveolar Echinococcosis in Children

Jonaitytė

Judickas

Tamulevičienė

et al. 2020

Case Reports in Pediatrics

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Alveolar echinococcosis (AE) is an infectious zoonotic disease that is caused by Echinococcus multilocularis. The disease is generally identified accidentally because of the long asymptomatic period, has a malignant behaviour, and mainly occurs in the liver. Usually it is diagnosed in adults and is very rare in pediatric patients. We report two cases of AE and 1 differential case between AE and cystic echinococcosis (CE) in children: two of them had lesions in the liver and one had rare extrahepatic presentation of a cyst in the spleen. All our patients received chemotherapy with albendazole because surgical treatment was not recommended. The children were followed-up from 10 to 30 months and no significant improvement was seen. In this report we discuss the difficulties we faced in the treatment and follow-up of these patients. We also review the main clinical manifestations, general diagnostic methods, and treatment options of AE according to the current literature.

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Therapeutic efficacy of nanocompounds in the treatment of cystic and alveolar echinococcoses: challenges and future prospects

Cited by 15 publications

References 56 publications

Drug repurposing applied: Activity of the anti-malarial mefloquine against Echinococcus multilocularis

Drug repurposing applied: Activity of the anti-malarial mefloquine against Echinococcus multilocularis

Hepatic Alveolar Echinococcosis: Predictive Biological Activity Based on Radiomics of MRI

Alveolar Echinococcosis in Children

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