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International Maritime Health 2024Schistosomiasis, caused by Schistosoma trematode worms, represents a significant global health challenge. This review offers a thorough examination of the disease's... (Review)
Review
Schistosomiasis, caused by Schistosoma trematode worms, represents a significant global health challenge. This review offers a thorough examination of the disease's epidemiology, transmission dynamics, diagnostic modalities, and treatment options. Diagnostic techniques encompass direct parasitological methods, immunological assays, DNA/RNA detection, and biomarker utilization, each with distinct advantages and limitations. There is an urgent need for improved diagnostic tools with enhanced sensitivity and specificity. Praziquantel remains the cornerstone of treatment, exhibiting efficacy against all Schistosoma species, while the potential of artemisin derivatives in combination therapy is also explored. In this review, we focus on the importance of praziquantel administration as the central aspect of schistosomiasis treatment, highlighting ongoing efforts to optimize its utilization for improved patient outcomes.
Topics: Praziquantel; Humans; Schistosomiasis; Anthelmintics; Animals; Schistosoma
PubMed: 38647059
DOI: 10.5603/imh.99453 -
Ugeskrift For Laeger May 2024
Topics: Humans; Male; Testicular Diseases; Schistosomiasis; Anthelmintics; Praziquantel; Adult
PubMed: 38808760
DOI: 10.61409/V72026 -
Helminthologia Sep 2023Conservative treatment of human hydatidosis (cystic echinococcosis) with albendazole has improved significantly the prognosis of the disease. But its therapeutic...
Conservative treatment of human hydatidosis (cystic echinococcosis) with albendazole has improved significantly the prognosis of the disease. But its therapeutic effectiveness is 30 - 70 %. There is some evidence that the effectiveness of albendazole can be enhanced by praziquantel but there is no strict recommendation for the use of praziquantel as part of long-term drug therapy for hydatidosis. The aim of the study was to evaluate the effectiveness of the combination of albendazole and praziquantel in patients with hepatic and/or pulmonary hydatidosis. A total of 20 patients (aged 12 - 70 years old) were included in the study for a 5-year period. Fourteen patients (70 %) were with hepatic hydatidosis, 4 (20 %) with pulmonary and 2 (10 %) with hepatic and pulmonary hydatidosis. They were treated with albendazole (15 mg/kg/day) and praziquantel (40 mg/kg/weekly) for 2 - 9 one-month courses. The result of the therapy was followed using imaging (abdominal ultrasound, lung radiography, computed tomography) and serology. Seventeen (85 %) out of 20 patients showed evidence of response on imaging defined as improvement or cure of hydatid cysts. Seven (35 %) of the patients with multiple cystic echinococcosis took praziquantel once a week for 6 months. Only 3 patients (15 %) with multiple hydatidosis (2 with liver and 1 with pulmonary hydatidosis) failed to respond to the therapy with both drugs. No side effects have been reported by the patients. The combination of albendazole and praziquantel seems to be an option to improve the therapeutic effectiveness of the conservative treatment of cystic echinococcosis.
PubMed: 38152469
DOI: 10.2478/helm-2023-0028 -
Current Opinion in Infectious Diseases Oct 2023Cystic echinococcosis is a neglected zoonosis for which humans are dead end hosts. It is not only widely distributed in sheep rearing areas of low-income and... (Review)
Review
PURPOSE OF REVIEW
Cystic echinococcosis is a neglected zoonosis for which humans are dead end hosts. It is not only widely distributed in sheep rearing areas of low-income and middle-income countries but also has a significant presence in wealthy countries, for example, in Europe. It results in considerable morbidity, and its current management is far from optimal. Medical management is with a benzimidazole, with the addition of praziquantel under some circumstances.
RECENT FINDINGS
Interest in mebendazole as an anticancer drug has stimulated research into new drug formulations to improve bioavailability and possibly reduce inter-individual variability in in-vivo drug levels, which may help its activity against cystic echinococcosis. Further evidence to support administration of albendazole with a fatty meal has been provided. GlaxoSmithKilne (GSK) has agreed to extend its albendazole donation programme to include echinococcosis. The search for new drugs has focussed on natural products, such as essential oils and on repurposing of existing drugs licensed for human use against other conditions.
SUMMARY
The medical treatment of cystic echinococcosis remains sorely neglected, with no new drugs for almost 40 years. We need a better understanding of how to use the drugs we do have, whilst seeking new ones. Drug repurposing may be the best pathway.
Topics: Humans; Animals; Sheep; Albendazole; Echinococcosis; Zoonoses; Europe; Mebendazole
PubMed: 37593991
DOI: 10.1097/QCO.0000000000000947 -
Pharmaceutics Dec 2023This review discusses the entire progress made on the anthelmintic drug praziquantel, focusing on the solid state and, therefore, on anhydrous crystalline polymorphs,... (Review)
Review
This review discusses the entire progress made on the anthelmintic drug praziquantel, focusing on the solid state and, therefore, on anhydrous crystalline polymorphs, amorphous forms, and multicomponent systems (i.e., hydrates, solvates, and cocrystals). Despite having been extensively studied over the last 50 years, new polymorphs and the greater part of their cocrystals have only been identified in the past decade. Progress in crystal engineering science (e.g., the use of mechanochemistry as a solid form screening tool and more strategic structure-based methods), along with the development of analytical techniques, including Synchrotron X-ray analyses, spectroscopy, and microscopy, have furthered the identification of unknown crystal structures of the drug. Also, computational modeling has significantly contributed to the prediction and design of new cocrystals by considering structural conformations and interactions energy. Whilst the insights on praziquantel polymorphs discussed in the present review will give a significant contribution to controlling their formation during manufacturing and drug formulation, the detailed multicomponent forms will help in designing and implementing future praziquantel-based functional materials. The latter will hopefully overcome praziquantel's numerous drawbacks and exploit its potential in the field of neglected tropical diseases.
PubMed: 38258039
DOI: 10.3390/pharmaceutics16010027 -
World Neurosurgery Apr 2024Pseudotumoral encephalic schistosomiasis (PES) is the chronic form of cerebral neuroschistosomiasis, and is rarely encountered in clinical practice. Clinically, PES... (Review)
Review
Pseudotumoral encephalic schistosomiasis (PES) is the chronic form of cerebral neuroschistosomiasis, and is rarely encountered in clinical practice. Clinically, PES closely resembles other intracranial space-occupying lesions including brain tumors. Laboratory investigations are usually inconclusive, and neuroradiologic findings are frequently reported as non-specific. Such diagnostic difficulties may result in delayed diagnosis and treatment. Across the literature, there is a paucity of information about and controversy over many aspects of the disease. Particularly, inconsistent magnetic resonance imaging (MRI) findings, a wide variation of medical treatment protocols, lacking consensus regarding the indications of surgery, and undetermined information regarding the impact of the extent of resection on prognosis. We herein review the pertinent literature with the aim of providing focused information regarding the pathogenesis of PES, its currently identified more distinctive neuroimaging features, and the indications and extent of surgery in light of the state-of-the-art operative neurosurgical practice. A distinctive multinodular arborizing pattern of PES lesions can often be observed on MRI in patients with PES. Praziquantel is considered by many authors to be the drug of choice in all cases, and seems to be effective at variable dose regimens. Although lesion excision utilizing current technology is generally safe, the indications and extent of surgery are still undetermined and should be decided on a case-by-case basis. Multicenter collaborative research is further needed to fill the existing gaps in the current knowledge on PES.
Topics: Humans; Brain; Praziquantel; Neuroschistosomiasis; Prognosis; Multicenter Studies as Topic
PubMed: 38159601
DOI: 10.1016/j.wneu.2023.12.134 -
BioRxiv : the Preprint Server For... Aug 2023The bad bitter taste of some medicines is a barrier to overcoming non-compliance with medication use, especially life-saving drugs given to children and the elderly....
PURPOSE
The bad bitter taste of some medicines is a barrier to overcoming non-compliance with medication use, especially life-saving drugs given to children and the elderly. Here we evaluated a new class of bitter blockers (thiazolidinediones; TZDs).
METHODS
In this study, two TZDs were tested, rosiglitazone (ROSI) and a simpler form of TZD, using a high-potency sweetener as a positive control (neohesperidin dihydrochalcone, NHDC). We tested bitter-blocking effects using the bitter drugs tenofovir alafenamide fumarate (TAF), a treatment for HIV and hepatitis B infection, and praziquantel (PRAZ), a treatment for schistosomiasis, by conducting taste testing with two separate taste panels: a general panel (N=97, 20-23 yrs, 82.5% female, all Eastern European) and a genetically informative panel (N=158, including 68 twin pairs, 18-82 yrs, 76% female, 87% European ancestry). Participants rated the bitterness intensity of the solutions on a 100-point generalized visual analog scale.
FINDINGS
Participants in both taste panels rated the bitter drugs TAF and PRAZ as less bitter on average when mixed with NHDC than when sampled alone. ROSI partially suppressed the bitterness of TAF and PRAZ, but effectiveness differed between the two panels: bitterness was significantly reduced for PRAZ but not TAF in the general panel and for TAF but not PRAZ in the genetically informative panel. ROSI was a more effective blocker than the other TZD.
IMPLICATIONS
These results suggest that TZDs are partially effective bitter blockers, suggesting other TZDs should be designed and tested with more drugs and on diverse populations to define which ones work best with which drugs and for whom. The discovery of bitter receptor blockers can improve compliance with medication use.
PubMed: 37609224
DOI: 10.1101/2023.08.08.552460 -
Frontiers in Pharmacology 2024Schistosomiasis is a parasitic disease that endangers human health and social development. The granulomatous reaction of Schistosoma eggs in the liver is the main cause... (Review)
Review
Schistosomiasis is a parasitic disease that endangers human health and social development. The granulomatous reaction of Schistosoma eggs in the liver is the main cause of hepatosplenomegaly and fibrotic lesions. Anti liver fibrosis therapy is crucial for patients with chronic schistosomiasis. Although Praziquantel is the only clinical drug used, it is limited in insecticide treatment and has a long-term large-scale use, which is forcing the search for cost-effective alternatives. Previous research has demonstrated that plant metabolites and extracts have effective therapeutic effects on liver fibrosis associated with schistosomiasis. This paper summarizes the mechanisms of action of metabolites and some plant extracts in alleviating schistosomiasis-associated liver fibrosis. The analysis was conducted using databases such as PubMed, Google Scholar, and China National Knowledge Infrastructure (CNKI) databases. Some plant metabolites and extracts ameliorate liver fibrosis by targeting multiple signaling pathways, including reducing inflammatory infiltration, oxidative stress, inhibiting alternate macrophage activation, suppressing hepatic stellate cell activation, and reducing worm egg load. Natural products improve liver fibrosis associated with schistosomiasis, but further research is needed to elucidate the effectiveness of natural products in treating liver fibrosis caused by schistosomiasis, as there is no reported data from clinical trials in the literature.
PubMed: 38770001
DOI: 10.3389/fphar.2024.1332027 -
PLoS Pathogens Jul 2023Schistosomiasis, a severe parasitic disease, is primarily caused by Schistosoma mansoni, Schistosoma japonicum, or Schistosoma haematobium. Currently, praziquantel is... (Review)
Review
Schistosomiasis, a severe parasitic disease, is primarily caused by Schistosoma mansoni, Schistosoma japonicum, or Schistosoma haematobium. Currently, praziquantel is the only recommended drug for human schistosome infection. However, the lack of efficacy of praziquantel against juvenile worms and concerns about the emergence of drug resistance are driving forces behind the research for an alternative medication. Schistosomes are obligatory parasites that survive on nutrients obtained from their host. The ability of nutrient uptake depends on their physiological structure. In short, the formation and maintenance of the structure and nutrient supply are mutually reinforcing and interdependent. In this review, we focus on the structural features of the tegument, esophagus, and intestine of schistosomes and their roles in nutrient acquisition. Moreover, we introduce the significance and modes of glucose, lipids, proteins, and amino acids intake in schistosomes. We linked the schistosome structure and nutrient supply, introduced the currently emerging targets, and analyzed the current bottlenecks in the research and development of drugs and vaccines, in the hope of providing new strategies for the prevention and control of schistosomiasis.
Topics: Animals; Humans; Praziquantel; Schistosomiasis; Schistosoma japonicum; Schistosoma haematobium; Schistosoma mansoni; Eating
PubMed: 37498810
DOI: 10.1371/journal.ppat.1011498 -
International Journal of Pharmaceutics Sep 2023In this paper we report a successful example of combining drugs through cocrystallization. Specifically, the novel solid is formed by two anthelminthic drugs, namely...
In this paper we report a successful example of combining drugs through cocrystallization. Specifically, the novel solid is formed by two anthelminthic drugs, namely praziquantel (PZQ) and niclosamide (NCM) in a 1:3 molar ratio, and it can be obtained through a sustainable one-step mechanochemical process in the presence of micromolar amounts of methanol. The novel solid phase crystallizes in the monoclinic space group of P2/c, showing one PZQ and three NCM molecules linked through homo- and heteromolecular hydrogen bonds in the asymmetric unit, as also attested by SSNMR and FT-IR results. A plate-like habitus is evident from scanning electron microscopy analysis with a melting point of 202.89 °C, which is intermediate to those of the parent compounds. The supramolecular interactions confer favorable properties to the cocrystal, preventing NCM transformation into the insoluble monohydrate both in the solid state and in aqueous solution. Remarkably, the PZQ - NCM cocrystal exhibits higher anthelmintic activity against in vitro S. mansoni models than corresponding physical mixture of the APIs. Finally, due to in vitro promising results, in vivo preliminary tests on mice were also performed through the administration of minicapsules size M.
Topics: Animals; Mice; Praziquantel; Niclosamide; Antiparasitic Agents; Pharmaceutical Preparations; Spectroscopy, Fourier Transform Infrared; Anthelmintics; Schistosoma mansoni
PubMed: 37579827
DOI: 10.1016/j.ijpharm.2023.123315