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Pharmaceutical Development and... Mar 2024The aim of this study was to evaluate the suitability of a non-disruptive Raman spectroscopic method to quantify drug concentrations below 5 w% within a polymer matrix...
The aim of this study was to evaluate the suitability of a non-disruptive Raman spectroscopic method to quantify drug concentrations below 5 w% within a polymer matrix produced by hot-melt extrusion (HME). For calibration, praziquantel (PZQ)-polyvinylpyrrolidone-vinylacetat-copolymer (PVP-VA) mixtures were extruded. By focusing the laser light of the Raman probe to a diameter of 1 mm and implementing a self-constructed filament holder, the signal-to-noise (S/N) ratio could be reduced considerably. The obtained Raman spectra show quite high fluorescence, which is likely to be caused by dissolved pharmaceutical active ingredient (API) in the polymer matrix. For content determination, HPLC analysis was conducted as a reference method using the same filament segments. A partial least squares (PLS) model, regressing the PZQ concentrations from HPLC method analysis versus the off-line collected Raman spectra, was developed. The linear correlation for a suitable extrusion run for the production of low-dosed filaments (extrusion 1, two kneading zones) is acceptable (R = 0.9915) while the correlation for a extrusion set-up with low miscibility (extrusion 2; without kneading zone) is unacceptable (R = 0.5349). The predictive performance of the calibration model from extrusion 1 is rated by the root mean square error of estimation (RMSEE), which was 0.08%. This calibration can now be used to validate the content of low-dosed filaments during HME.
Topics: Spectrum Analysis, Raman; Povidone; Polymers; Hot Melt Extrusion Technology; Drug Compounding; Hot Temperature
PubMed: 38407128
DOI: 10.1080/10837450.2024.2323622 -
Parasites & Vectors Feb 2024Cystic echinococcosis (CE), caused by the larval stage of Echinococcus granulosus sensu lato, is a zoonotic parasitic disease of economic and public health importance...
BACKGROUND
Cystic echinococcosis (CE), caused by the larval stage of Echinococcus granulosus sensu lato, is a zoonotic parasitic disease of economic and public health importance worldwide, especially in the Mediterranean area. Canids are the main definitive hosts of the adult cestode contaminating the environment with parasite eggs released with feces. In rural and peri-urban areas, the risk of transmission to livestock as well as humans is high because of the free-roaming behavior of owned/not owned dogs. Collecting data on animal movements and behavior using GPS dataloggers could be a milestone to contain the spread of this parasitosis. Thus, this study aims to develop a comprehensive control strategy, focused on deworming a dog population in a pilot area of southern Italy (Campania region) highly endemic for CE.
METHODS
Accordingly, five sheep farms, tested to be positive for CE, were selected. In each sheep farm, all shepherd dogs present were treated every 2 months with praziquantel. Furthermore, 15 GPS dataloggers were applied to sheep and dogs, and their movements were tracked for 1 month; the distances that they traveled and their respective home ranges were determined using minimum convex polygon (MCP) analysis with a convex hull geometry as output.
RESULTS
The results showed that the mean daily walking distances traveled by sheep and dogs did not significantly differ. Over 90% of the point locations collected by GPS fell within 1500 mt of the farm, and the longest distances were traveled between 10:00 and 17:00. In all the sheep farms monitored, the area traversed by the animals during their daily activities showed an extension of < 250 hectares. Based on the home range of the animals, the area with the highest risk of access from canids (minimum safe convex polygon) was estimated around the centroid of each farm, and a potential scheme for the delivery of praziquantel-laced baits for the treatment of not owned dogs gravitating around the grazing area was designed.
CONCLUSIONS
This study documents the usefulness of geospatial technology in supporting parasite control strategies to reduce disease transmission.
Topics: Humans; Adult; Animals; Dogs; Sheep; Praziquantel; Dog Diseases; Echinococcosis; Echinococcus granulosus; Zoonoses
PubMed: 38395867
DOI: 10.1186/s13071-024-06184-x -
Experimental Parasitology Mar 2024Helminth infections pose a significant economic threat to livestock production, causing productivity declines and, in severe cases, mortality. Conventional...
Helminth infections pose a significant economic threat to livestock production, causing productivity declines and, in severe cases, mortality. Conventional anthelmintics, exemplified by fenbendazole, face challenges related to low solubility and the necessity for high doses. This study explores the potential of supramolecular complexes, created through mechanochemical modifications, to address these limitations. The study focuses on two key anthelmintics, praziquantel (PZQ) and fenbendazole (FBZ), employing mechanochemical techniques to enhance their solubility and efficacy. Solid dispersions (SD) of PZQ with polymers and dioctyl sulfosuccine sodium (DSS) and fenbendazole with licorice extract (ES) and DSS were prepared. The helminthicidal activity of these complexes was assessed through helminthological dissections of sheep infected with Schistosoma turkestanicum, moniesiasis, and parabronemosis. In the assessment of supramolecular complex of FBZ (SMCF) at doses ranging from 1.0 to 3.0 mg/kg for the active substance (AS), optimal efficacy was observed with the fenbendazole formulation containing arabinogalactan and polyvinylpyrrolidone at a 3.0 mg/kg dosage. At this concentration, the formulation demonstrated a remarkable 100% efficacy in treating spontaneous monieziosis in sheep, caused by Moniezia expansa (Rudolphi, 1810) and M. benedenii (Moniez, 1879). Furthermore, the SMCF, administered at doses of 1.0, 2.0, and 3.0 mg/kg, exhibited efficacy rates of 42.8%, 85.7%, and 100%, respectively, against the causative agent of parabronemosis (Parabronema skrjabini Rassowska, 1924). Mechanochemical modifications, yielding supramolecular complexes of PZQ and FBZ, present a breakthrough in anthelmintic development. These complexes address solubility issues and significantly reduce required doses, offering a practical solution for combating helminth infections in livestock. The study underscores the potential of supramolecular formulations for revolutionizing helminthiasis management, thereby enhancing the overall health and productivity of livestock.
Topics: Animals; Sheep; Fenbendazole; Anthelmintics; Praziquantel; Schistosomiasis; Cestode Infections
PubMed: 38367946
DOI: 10.1016/j.exppara.2024.108714 -
PLoS Neglected Tropical Diseases Feb 2024The drug praziquantel (PZQ) has served as the long-standing drug therapy for treatment of infections caused by parasitic flatworms. These encompass diseases caused by... (Review)
Review
The drug praziquantel (PZQ) has served as the long-standing drug therapy for treatment of infections caused by parasitic flatworms. These encompass diseases caused by parasitic blood, lung, and liver flukes, as well as various tapeworm infections. Despite a history of clinical usage spanning over 4 decades, the parasite target of PZQ has long resisted identification. However, a flatworm transient receptor potential ion channel from the melastatin subfamily (TRPMPZQ) was recently identified as a target for PZQ action. Here, recent experimental progress interrogating TRPMPZQ is evaluated, encompassing biochemical, pharmacological, genetic, and comparative phylogenetic data that highlight the properties of this ion channel. Various lines of evidence that support TRPMPZQ being the therapeutic target of PZQ are presented, together with additional priorities for further research into the mechanism of action of this important clinical drug.
Topics: Praziquantel; Anthelmintics; Phylogeny; Transient Receptor Potential Channels
PubMed: 38358948
DOI: 10.1371/journal.pntd.0011929 -
Tropical Medicine & International... Apr 2024Schistosomiasis is persistent in Lake Albert, Uganda, but local data are limited. This study aims to describe the local burden of moderate-to-heavy infection and...
OBJECTIVES
Schistosomiasis is persistent in Lake Albert, Uganda, but local data are limited. This study aims to describe the local burden of moderate-to-heavy infection and associated morbidity in all ages and identify factors associated with these outcomes to guide further research.
METHODS
This cross-sectional pilot study was conducted in July-August, 2022 in four village sites (Walukuba, Rwentale, Kyabarangwa and Runga) of the Praziquantel in Preschoolers (PIP) trial. Residents (approximately four per household) of any age of households of PIP participants were eligible, but individuals <10 years were only enrolled if no older individuals were available. Socio-demographic information, household location, single stool Kato-Katz and hepatic ultrasound results were obtained for a convenience sampled subset of trial households. The primary outcome, moderate-to-heavy infection (≥100 eggs per gram of faeces), was analysed using mixed-effects logistic regression, with a household random effect. Univariate analyses were used for the secondary outcome, periportal fibrosis (Niamey protocol ultrasound image pattern C-F).
RESULTS
Of 243 participants with a median age of 22 (interquartile range 12-33) years from 66 households, 49.8% (103/207 with a Kato-Katz result) had moderate-to-heavy infection and 11.2% (25/224 with ultrasound data) had periportal fibrosis. Moderate-to-heavy infection clustered by household (intraclass correlation coefficient = 0.11) and, in multivariable analysis, varied by village (Walukuba vs. Kyabarangwa adjusted odds ratio [aOR] 0.11, 95% CI 0.02-0.71), was highest in participants aged 10-15 years (vs. 5-9 years aOR 6.14, 95% CI 1.61-23.38) and lower in those reporting praziquantel treatment in the past year (aOR 0.39, 95% CI 0.18-0.88).
CONCLUSIONS
In this setting, schistosome infection and morbidity are pervasive in all age groups. More intensive interventions are needed, for example more frequent praziquantel treatment, under investigation in the PIP trial and improved water and sanitation. More research is needed to understand local treatment barriers and optimal control strategies.
Topics: Adolescent; Adult; Animals; Child; Humans; Young Adult; Cross-Sectional Studies; Feces; Lakes; Liver Cirrhosis; Morbidity; Pilot Projects; Praziquantel; Prevalence; Schistosoma mansoni; Schistosomiasis mansoni; Uganda; Clinical Trials as Topic
PubMed: 38356464
DOI: 10.1111/tmi.13978 -
BMC Pharmacology & Toxicology Feb 2024Pulmonary fibrosis is a chronic progressive disease with complex pathogenesis, short median survival time, and high mortality. There are few effective drugs approved for...
BACKGROUND
Pulmonary fibrosis is a chronic progressive disease with complex pathogenesis, short median survival time, and high mortality. There are few effective drugs approved for pulmonary fibrosis treatment. This study aimed to evaluate the effect of praziquantel (PZQ) on bleomycin (BLM)-induced pulmonary fibrosis.
METHODS
In this study, we investigated the role and mechanisms of PZQ in pulmonary fibrosis in a murine model induced by BLM. Parameters investigated included survival rate, lung histopathology, pulmonary collagen deposition, mRNA expression of key genes involved in pulmonary fibrosis pathogenesis, the activity of fibroblast, and M2/M1 macrophage ratio.
RESULTS
We found that PZQ improved the survival rate of mice and reduced the body weight loss induced by BLM. Histological examination showed that PZQ significantly inhibited the infiltration of inflammatory cells, collagen deposition, and hydroxyproline content in BLM-induced mice. Besides, PZQ reduced the expression of TGF-β and MMP-12 in vivo and inhibited the proliferation of fibroblast induced by TGF-β in vitro. Furthermore, PZQ affected the balance of M2/M1 macrophages.
CONCLUSIONS
Our study demonstrated that PZQ could ameliorate BLM-induced pulmonary fibrosis in mice by affecting the balance of M2/M1 macrophages and suppressing the expression of TGF-β and MMP-12. These findings suggest that PZQ may act as an effective anti-fibrotic agent for preventing the progression of pulmonary fibrosis.
Topics: Animals; Mice; Pulmonary Fibrosis; Bleomycin; Praziquantel; Matrix Metalloproteinase 12; Lung; Fibrosis; Transforming Growth Factor beta; Collagen; Mice, Inbred C57BL
PubMed: 38355586
DOI: 10.1186/s40360-024-00737-7 -
BioRxiv : the Preprint Server For... Jan 2024The neglected tropical disease schistosomiasis infects over 200 million people worldwide and is treated with just one broad spectrum antiparasitic drug (praziquantel)....
The neglected tropical disease schistosomiasis infects over 200 million people worldwide and is treated with just one broad spectrum antiparasitic drug (praziquantel). Alternative drugs are needed in the event of emerging praziquantel resistance or treatment failure. One promising lead that has shown efficacy in animal models and a human clinical trial is the benzodiazepine meclonazepam, discovered by Roche in the 1970's. Meclonazepam was not brought to market because of dose-limiting sedative side effects. However, the human target of meclonazepam that causes sedation (GABARs) are not orthologous to the parasite targets that cause worm death. Therefore, we were interested in whether the structure of meclonazepam could be modified to produce antiparasitic benzodiazepines that do not cause host sedation. We synthesized 18 meclonazepam derivatives with modifications at different positions on the benzodiazepine ring system and tested them for antiparasitic activity. This identified five compounds that progressed to screening in a murine model, two of which cured parasite infections with comparable potency to meclonazepam. When these two compounds were administered to mice that were run on the rotarod test, both were less sedating than meclonazepam. These findings demonstrate the proof of concept that meclonazepam analogs can be designed with an improved therapeutic index, and point to the C3 position of the benzodiazepine ring system as a logical site for further structure-activity exploration to further optimize this chemical series.
PubMed: 38352313
DOI: 10.1101/2024.01.26.577323 -
Clinical Case Reports Feb 2024In the evaluation of acute flaccid paralysis, particularly in pediatric populations within endemic areas for schistosomiasis infection, clinicians must maintain a high...
KEY CLINICAL MESSAGE
In the evaluation of acute flaccid paralysis, particularly in pediatric populations within endemic areas for schistosomiasis infection, clinicians must maintain a high index of suspicion for neuroschistosomiasis. Prompt identification is imperative to mitigate the risk of irreversible neurological sequelae.
ABSTRACT
Spinal cord involvement in neuroschistosomiasis (NS) is considerably rare, with even fewer reported cases affecting the conus medullaris in children. While NS's neurological sequelae are typically thought to be reversible, delayed diagnosis and treatment can lead to permanent deficits. We report a case of a 9-year-old boy who presented with 3 weeks of progressive bilateral lower extremity weakness. A spinal MRI showed patchy gadolinium enhancement in an expanded conus medullaris, leading to a presumed diagnosis of Guillain-Barre syndrome, and the patient was treated with intravenous immunoglobulin. However, the lack of improvement necessitated surgical laminectomy. The post-operative histopathological examination confirmed the presence of a schistosomal parasite. Despite initiating therapy with corticosteroid and praziquantel, the patient did not exhibit clinical improvement, resulting in persistent flaccid paralysis, bladder, and bowel incontinence. In conclusion, spinal NS should be considered in patients presenting with myeloradicular symptoms in regions endemic for schistosomal infection, as delayed recognition can result in irreversible outcomes.
PubMed: 38344355
DOI: 10.1002/ccr3.8475 -
Acta Tropica Apr 2024The impact of diet composition and energy content on schistosomiasis evolution and treatment efficacy is still controversial. This study compared the impact of...
The impact of diet composition and energy content on schistosomiasis evolution and treatment efficacy is still controversial. This study compared the impact of sucrose-rich diet and intermittent fasting on Schistosoma mansoni infection and praziquantel (PZQ)-based chemotherapy response in mice. BALB/c mice were infected with S. mansoni and followed for 15 weeks. The animals were randomized into nine groups receiving high glycemic load (high-sucrose diet - HSD), low caloric load (standard chow alternate-day fasting - ADF), and standard chow ad libitum (AL). Eight weeks after S. mansoni infection, these groups remained untreated or were treated with PZQ (300 mg/kg/day) for 3 days. Our results indicated that parasite load (S. mansoni eggs and parasite DNA levels), granulomatous inflammation (granulomas number and size), and liver microstructural damage (reduction in hepatocytes number, increase in nucleus-cytoplasm ratio, connective stroma expansion and fibrosis) were increased in ADF-treated animals. These animals also showed decreased eggs retention, granulomatous inflammation and collagen accumulation in the small intestine. Conversely, HSD diet and PZQ treatment attenuated all these parameters and stimulated hepatic regenerative response. PZQ also stimulated fibrosis resolution in HSD-treated mice, effect that was limited ADF-exposed mice. Our findings indicate that dietary glycemic and energy load can modulate schistosomiasis progression and the severity of hepatic and intestinal granulomatous inflammation in untreated and PZQ-treated mice. Thus, lower intestinal eggs retention may potentially be linked to worsening liver disease in ADF, while attenuation of hepatic and intestinal granulomatous inflammation is consistent with reduced parasite load in HSD- and PZQ-treated animals.
Topics: Animals; Mice; Schistosoma mansoni; Antiparasitic Agents; Praziquantel; Schistosomiasis mansoni; Liver; Liver Diseases; Schistosomiasis; Inflammation; Fibrosis; Diet; Sucrose; Anthelmintics
PubMed: 38342286
DOI: 10.1016/j.actatropica.2024.107141 -
Annals of Medicine and Surgery (2012) Feb 2024Schistosomiasis is the second most common parasite disease after malaria and a rare cause of appendicitis. It has been well-documented in the literature that...
INTRODUCTION
Schistosomiasis is the second most common parasite disease after malaria and a rare cause of appendicitis. It has been well-documented in the literature that schistosomiasis infection can have several multisystem effects. The unusual condition known as schistosomal appendicitis was initially described by Turner.
CASE PRESENTATION
We present a 48-year-old man with perforated appendicitis and schistosomiasis-like radiological findings. An appendectomy was performed, and schistosomiasis was confirmed by a histological study of the excised appendix. Praziquantel was administered in a single dosage.
CONCLUSION
Although schistosomiasis is a rare cause of appendicitis and is very prevalent in developing nations, it should be considered when managing the condition. Anti-shistosoma drugs, which are not frequently used in post-appendectomy cases, should also be considered in the management.
PubMed: 38333312
DOI: 10.1097/MS9.0000000000001480