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TropicalMed
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Antiparasitic Treatment and Experimental Pharmacotherapy of Echinococcosis
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Antiparasitic Treatment and Experimental Pharmacotherapy of Echinococcosis

A special issue of Tropical Medicine and Infectious Disease (ISSN 2414-6366).

Deadline for manuscript submissions: closed (11 December 2023) | Viewed by 16171

Special Issue Editors

Dr. María Celina Elissondo

E-Mail Website
Guest Editor
Instituto de Investigaciones en Producción Sanidad y Ambiente (IIPROSAM CONICET-UNMdP), Facultad de Ciencias Exactas y Naturales–Universidad Nacional de Mar del Plata, Centro Científico Tecnológico Mar del Plata–CONICET, Mar del Plata, Argentina
Interests: echinococcosis; Echinococcus spp.; experimental pharmacological treatment; murine models of echinococcosis; albendazole; neurocysticercosis; essential oils; plant extracts
Dr. Andrew Hemphill

E-Mail Website
Guest Editor
Institute of Parasitology, Faculties of Veterinary Medicine and Medicine, University of Berne, Länggass-Strasse 122, 3012 Berne, Switzerland
Interests: apicomplexan parasites; toxoplasma; neospora; besnoitia
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to invite you to contribute to a Special Issue of Tropical Medicine and Infectious Disease entitled, “Antiparasitic treatment and Experimental Pharmacotherapy of echinococcosis”.

Echinococcosis is a parasitic disease caused by cestodes of the genus Echinococcus. They cause a variety of diseases in humans, including cystic echinococcosis, alveolar echinococcosis, and neotropical echinococcosis. The World Health Organization has recognized them as “Neglected Tropical Diseases”.

Echinococcus spp. has an indirect, two-host life cycle where the definitive host is always a carnivore. Numerous species of intermediate hosts (herbivorous or omnivorous) are susceptible to infection with the metacestode following accidental ingestion of the eggs.

Pharmacological treatment of echinococcosis is applicable to the various stages of Echinococcus spp.-related infections, in the intermediate host (including humans) and in the definitive host (domestic or wild animals). Anti-parasitic drugs can kill or delay the development of the stages of Echinococcus spp. However, the type of drugs or treatment schedules may be different for the various stages and the various diseases.

In this Special Issue, we welcome the submission of full articles and review articles presenting novel concepts regarding the pharmacological treatment of echinococcosis, including human and animal anti-parasitic treatment, in vitro and in vivo drug screening, experimental animal models of echinococcosis, pharmacotechnical strategies to improve the efficacy of albendazole, drug discovery and potential drug targets, natural products, and phytomedicine.

I look forward to receiving your contributions.

Dr. María Celina Elissondo
Dr. Andrew Hemphill
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Tropical Medicine and Infectious Disease is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • echinococcosis
  • Echinococcus spp.
  • albendazole
  • pharmacological treatment
  • pharmacotechnical strategies

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Published Papers (7 papers)

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Research

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13 pages, 4724 KiB  
Article
Anthelmintic Effect of Cannabidiol against Echinococcus granulosus sensu stricto
by Clara María Albani, Giselle Fuentes, Cristina Lujan Ramírez, Patricia Eugenia Pensel, Florencia Gatti, Adriana Albanese, Diego Nutter, Matías Ezequiel Aguirre, Yésica Dolores Di Iorio and María Celina Elissondo
Trop. Med. Infect. Dis. 2024, 9(2), 35; https://doi.org/10.3390/tropicalmed9020035 - 31 Jan 2024
Cited by 1 | Viewed by 2184
Abstract
Cystic echinococcosis is a global parasitic zoonosis caused by infection with the larval stage of Echinococcus granulosus sensu lato. Cystic echinococcosis affects more than 1 million people worldwide, causing important economic costs in terms of management and livestock associated losses. Albendazole is the [...] Read more.
Cystic echinococcosis is a global parasitic zoonosis caused by infection with the larval stage of Echinococcus granulosus sensu lato. Cystic echinococcosis affects more than 1 million people worldwide, causing important economic costs in terms of management and livestock associated losses. Albendazole is the main drug used in treating human cystic echinococcosis. In spite of this, its low aqueous solubility, poor absorption, and consequently erratic bioavailability are the cause of its chemotherapeutic failures. Based on the described problem, new treatment alternatives urgently need to be developed. The aim of the present research was to study the in vitro and in vivo efficacy of cannabidiol (CBD), the second most abundant component of the Cannabis sativa plant, was demonstrated against E. granulosus sensu stricto. CBD (50 µg/mL) caused a decrease in protoscoleces viability of 80 % after 24 h of treatment which was consistent with the observed tegumental alterations. Detachment of the germinal layer was observed in 50 ± 10% of cysts treated with 50 µg/mL of CBD during 24 h. In the clinical efficacy study, all treatments reduced the weight of cysts recovered from mice compared with the control group. However, this reduction was only significant with ABZ suspension and the CBD + ABZ combination. As we could observe by the SEM study, the co-administration of CBD with ABZ suspension caused greater ultrastructural alteration of the germinal layer in comparison with that provoked with the monotherapy. Further in vivo research will be conducted by changing the dose and frequency of CBD and CBD + ABZ treatments and new available CBD delivery systems will also be assayed to improve bioavailability in vivo. Full article
(This article belongs to the Special Issue Antiparasitic Treatment and Experimental Pharmacotherapy of Echinococcosis)
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13 pages, 2108 KiB  
Article
In Vitro Activities of Dithiocarbamate Derivatives against Echinococcus multilocularis Metacestode Vesicles
by Marc Kaethner, Georg Rennar, Tom Gallinger, Tobias Kämpfer, Andrew Hemphill, Patrick Mäder, Ana Luque-Gómez, Martin Schlitzer and Britta Lundström-Stadelmann
Trop. Med. Infect. Dis. 2023, 8(12), 517; https://doi.org/10.3390/tropicalmed8120517 - 12 Dec 2023
Cited by 1 | Viewed by 2147
Abstract
The metacestode stage of the fox tapeworm Echinococcus multilocularis causes the severe zoonotic disease alveolar echinococcosis. New treatment options are urgently needed. Disulfiram and dithiocarbamates were previously shown to exhibit activity against the trematode Schistosoma mansoni. As both parasites belong to the platyhelminths, [...] Read more.
The metacestode stage of the fox tapeworm Echinococcus multilocularis causes the severe zoonotic disease alveolar echinococcosis. New treatment options are urgently needed. Disulfiram and dithiocarbamates were previously shown to exhibit activity against the trematode Schistosoma mansoni. As both parasites belong to the platyhelminths, here we investigated whether these compounds were also active against E. multilocularis metacestode vesicles in vitro. We used an in vitro drug-screening cascade for the identification of novel compounds against E. multilocularis metacestode vesicles with disulfiram and 51 dithiocarbamates. Five compounds showed activity against E. multilocularis metacestode vesicles after five days of drug incubation in a damage marker release assay. Structure–activity relationship analyses revealed that a S-2-hydroxy-5-nitro benzyl moiety was necessary for anti-echinococcal activity, as derivatives without this group had no effect on E. multilocularis metacestode vesicles. The five active compounds were further tested for potential cytotoxicity in mammalian cells. For two compounds with low toxicity (Schl-32.315 and Schl-33.652), IC50 values in metacestode vesicles and IC50 values in germinal layer cells were calculated. The compounds were not highly active on isolated GL cells with IC50 values of 27.0 ± 4.2 µM for Schl-32.315 and 24.7 ± 11.5 µM for Schl-33.652, respectively. Against metacestode vesicles, Schl-32.315 was not very active either with an IC50 value of 41.6 ± 3.2 µM, while Schl-33.652 showed a low IC50 of 4.3 ± 1 µM and should be further investigated in the future for its activity against alveolar echinococcosis. Full article
(This article belongs to the Special Issue Antiparasitic Treatment and Experimental Pharmacotherapy of Echinococcosis)
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18 pages, 6425 KiB  
Article
Resveratrol against Echinococcus sp.: Discrepancies between In Vitro and In Vivo Responses
by Julia A. Loos, Micaela Franco, Maia Chop, Christian Rodriguez Rodrigues and Andrea C. Cumino
Trop. Med. Infect. Dis. 2023, 8(10), 460; https://doi.org/10.3390/tropicalmed8100460 - 26 Sep 2023
Cited by 1 | Viewed by 1740
Abstract
In an attempt to find new anti-echinococcal drugs, resveratrol (Rsv) effectiveness against the larval stages of Echinococcus granulosus and E. multilocularis was evaluated. The in vitro effect of Rsv on parasites was assessed via optical and electron microscopy, RT-qPCR and immunohistochemistry. In vivo [...] Read more.
In an attempt to find new anti-echinococcal drugs, resveratrol (Rsv) effectiveness against the larval stages of Echinococcus granulosus and E. multilocularis was evaluated. The in vitro effect of Rsv on parasites was assessed via optical and electron microscopy, RT-qPCR and immunohistochemistry. In vivo efficacy was evaluated in murine models of cystic (CE) and alveolar echinococcosis (AE). The impact of infection and drug treatment on the mouse bone marrow hematopoietic stem cell (HSC) population and its differentiation into dendritic cells (BMDCs) was investigated via flow cytometry and RT-qPCR. In vitro treatment with Rsv reduced E. granulosus metacestode and protoscolex viability in a concentration-dependent manner, caused ultrastructural damage, increased autophagy gene transcription, and raised Eg-Atg8 expression while suppressing Eg-TOR. However, the intraperitoneal administration of Rsv was not only ineffective, but also promoted parasite development in mice with CE and AE. In the early infection model of AE treated with Rsv, an expansion of HSCs was observed followed by their differentiation towards BMCDs. The latter showed an anti-inflammatory phenotype and reduced LPS-stimulated activation compared to control BMDCs. We suggest that Rsv ineffectiveness could have been caused by the low intracystic concentration achieved in vivo and the drug’s hormetic effect, with opposite anti-parasitic and immunomodulatory responses in different doses. Full article
(This article belongs to the Special Issue Antiparasitic Treatment and Experimental Pharmacotherapy of Echinococcosis)
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11 pages, 2297 KiB  
Article
Propofol Induces the Expression of Nrf2 and HO-1 in Echinococcus granulosus via the JNK and p38 Pathway In Vitro
by Guangyi Luo, Bin Ma, Yufeng Jiang and Hailong Lv
Trop. Med. Infect. Dis. 2023, 8(6), 306; https://doi.org/10.3390/tropicalmed8060306 - 3 Jun 2023
Cited by 1 | Viewed by 1884
Abstract
The purpose of this study was to establish the relationship between mitogen-activated protein kinase (MAPK) and Nrf2 signaling pathways in Echinococcus granulosus (E. granulosus). E. granulosus protoscoleces (PSCs) cultured in vitro were divided into different groups: a control group, PSCs were [...] Read more.
The purpose of this study was to establish the relationship between mitogen-activated protein kinase (MAPK) and Nrf2 signaling pathways in Echinococcus granulosus (E. granulosus). E. granulosus protoscoleces (PSCs) cultured in vitro were divided into different groups: a control group, PSCs were pretreated with various concentrations of propofol followed by exposure to hydrogen peroxide (H2O2), and PSCs were pretreated with MAPK inhibitors, then co-treated with propofol and incubated in the presence of H2O2. PSCs activity was observed under an inverted microscope and survival rate was calculated. Reactive oxygen species (ROS) was detected by fluorescence microscopy, western blotting was used to detect the expression of Nrf2, Bcl-2, and heme oxygenase 1 (HO-1) in the PSCs among different groups. Pretreatment of PSCs with 0–1 mM propofol for 8 h prevented PSCs death after exposure to 0.5 mM H2O2. PSCs were pretreated with PD98059, SB202190, or SP600125 for 2 h, co-treated with propofol for an additional 8 h, and then exposed to 0.5 mM H2O2 for 6 h. On day 6, the PSCs viability was 42% and 39% in the p38 and JNK inhibitor groups, respectively. Additionally, pretreatment with propofol significantly attenuated the generation of ROS following H2O2 treatment. Propofol increased the expression of Nrf2, HO-1, and BCL2 compared with that of the control group. Pretreatment PSCs with SP600125 or SB202190, co-incubation with propofol and H2O2, can reduce the expression of Nrf2, HO-1, and BCL2 (p < 0.05). These results suggest that propofol induces an upregulated expression of HO-1 and Nrf2 by activation of the JNK and p38 MAPK signaling pathways. This study highlights the cross role of metabolic regulation of ROS signaling and targeting signalling pathways that may provide a promising strategy for the treatment of E. granulosus disease. Full article
(This article belongs to the Special Issue Antiparasitic Treatment and Experimental Pharmacotherapy of Echinococcosis)
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13 pages, 2142 KiB  
Article
Effect of Temperature and Ionic Substitutions on the Tegumental Potentials of Protoscoleces of Echinococcus granulosus
by Mónica Patricia Antonella Carabajal, María José Fernández Salom, Santiago Olivera and Horacio F. Cantiello
Trop. Med. Infect. Dis. 2023, 8(6), 303; https://doi.org/10.3390/tropicalmed8060303 - 2 Jun 2023
Viewed by 1720
Abstract
The protoscolex (PSC) is generated by asexual reproduction at the larval stage of taeniid Echinococcus granulosus that causes cystic echinococcosis or hydatidosis, a worldwide zoonosis. The PSC is enveloped by a complex cellular syncytial tegument responsible for ionic movements and the hydroelectrolytic balance [...] Read more.
The protoscolex (PSC) is generated by asexual reproduction at the larval stage of taeniid Echinococcus granulosus that causes cystic echinococcosis or hydatidosis, a worldwide zoonosis. The PSC is enveloped by a complex cellular syncytial tegument responsible for ionic movements and the hydroelectrolytic balance of the parasite. We recently reported on two electrical potentials in bovine lung protoscoleces (PSCs) that reflect differences in ionic movements between the parasite’s invaginated and evaginated developmental stages. Here, we explored the effect of temperature and ionic substitutions on the tegumental potentials of bovine lung PSCs of Echinococcus granulosus by microelectrode impalements. We observed that the transient peak potential was temperature-dependent, consistent with an active transport component in the invaginated state only. Further changes in the electrical potentials by high K+ depolarization, low external Ca2+, and addition of the diuretic amiloride are in agreement with the presence of a Ca2+-sensitive cation-selective electrodiffusional pathway in the outer surface of the parasite. Variations in electrical potential differences through the tegument provide an accessible and valuable parameter for studying ionic transport mechanisms and, therefore, potential targets for developing novel antiparasitic drugs. Full article
(This article belongs to the Special Issue Antiparasitic Treatment and Experimental Pharmacotherapy of Echinococcosis)
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20 pages, 4622 KiB  
Article
Eugenol Essential Oil and Nanoemulsion as Antihydatic Agents with Antifibrotic and Immunomodulatory Effects in Cystic Echinococcosis
by Alzahraa Abdelraouf Ahmad, Maria Naged Maurice, Mohamed El-Salahy M. Monib, Mahmoud Soliman, Sultan S. Al-Thagfan and Enas Abdelhameed Mahmoud Huseein
Trop. Med. Infect. Dis. 2023, 8(5), 253; https://doi.org/10.3390/tropicalmed8050253 - 27 Apr 2023
Cited by 1 | Viewed by 2021
Abstract
Conventional scolicidal agents are still unsatisfactory in combating hydatid disease due to their low efficacy and increased drug side effects. Therefore, novel scolicides are required. This study aimed to evaluate the antihydatic and immunomodulatory effects of eugenol essential oil (Eug) and its nanoemulsion [...] Read more.
Conventional scolicidal agents are still unsatisfactory in combating hydatid disease due to their low efficacy and increased drug side effects. Therefore, novel scolicides are required. This study aimed to evaluate the antihydatic and immunomodulatory effects of eugenol essential oil (Eug) and its nanoemulsion (Eug-NE) in cystic echinococcosis (CE). Eug and Eug-NE were administered orally to CE-infected rats and compared to albendazole (ABZ). Hydatid cyst development was assessed based on organ weight and hypertrophy indicators of the infected organs, along with a histopathological and histochemical evaluation of collagen content. The immunomodulatory effects of treatment on CE were evaluated by serum cytokine levels measurement of interferon-γ (IFN-γ) and interleukin (IL)-4 and immunohistochemical (IHC) analysis of signal transducer and activator of transcription 4 (STAT4) and GATA-binding protein 3 (GATA3) markers. Eug-NE was the most effective in reducing the cyst weights, organ weights, and hypertrophy indicators and improving histopathological lesions with reduced collagen content. Eug and Eug-NE significantly increased the IFN-γ levels and decreased the IL-4 levels, while IHC analysis demonstrated a significant reduction in STAT4 and GATA3 expression in all treated groups. Eug and Eug-NE demonstrated antihydatic and preventative effects, with a substantial decrease in liver fibrosis compared to that of ABZ. Besides their promising immunomodulatory effects, their good treatment response suggests their use as alternatives or complementary scolicidal agents in hydatid cyst treatment. Full article
(This article belongs to the Special Issue Antiparasitic Treatment and Experimental Pharmacotherapy of Echinococcosis)
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Review

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22 pages, 2944 KiB  
Review
Challenges and Prospective of Enhancing Hydatid Cyst Chemotherapy by Nanotechnology and the Future of Nanobiosensors for Diagnosis
by Soheil Sadr, Narges Lotfalizadeh, Amir Mohammad Abbasi, Nooshinmehr Soleymani, Ashkan Hajjafari, Elahe Roohbaksh Amooli Moghadam and Hassan Borji
Trop. Med. Infect. Dis. 2023, 8(11), 494; https://doi.org/10.3390/tropicalmed8110494 - 6 Nov 2023
Cited by 12 | Viewed by 3299
Abstract
Hydatid cysts have been widely recognized for decades as a common medical problem that affects millions of people. A revolution in medical treatment may be on the prospect of nanotechnology enhancing chemotherapy against hydatid cysts. An overview of nanotechnology’s impact on chemotherapeutics is [...] Read more.
Hydatid cysts have been widely recognized for decades as a common medical problem that affects millions of people. A revolution in medical treatment may be on the prospect of nanotechnology enhancing chemotherapy against hydatid cysts. An overview of nanotechnology’s impact on chemotherapeutics is presented in the current review. It discusses some of the challenges as well as some of the opportunities. The application of nanotechnology to enhance chemotherapy against hydatid cysts is what this review will explore. Nanotechnology is a critical component of delivering therapeutic agents with greater precision and efficiency and targeting hydatid cysts with better efficacy, and minimizing interference with surrounding tissue. However, there are biodistribution challenges, toxicity, and resistance problems associated with nanotherapeutics. Additionally, nanobiosensors are being investigated to enable the early diagnosis of hydatid cysts. A nanobiosensor can detect hydatid cysts by catching them early, non-invasively, rapidly, and accurately. The sensitivity and specificity of diagnostic tests can be enhanced with nanobiosensors because they take advantage of the unique properties of nanomaterials. By providing more precise and customized treatment options for hydatid cysts, nanotechnology may improve therapeutic options and strategies for diagnosing the disease. In conclusion, treatment with nanotechnology to treat hydatid cysts is potentially effective but presents many obstacles. Furthermore, nanobiosensors are being integrated into diagnostic techniques, as well as helping to diagnose patients earlier and more accurately. Full article
(This article belongs to the Special Issue Antiparasitic Treatment and Experimental Pharmacotherapy of Echinococcosis)
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