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Scientific Reports Jan 2024Schistosomiasis is caused by parasites of the genus Schistosoma, which infect more than 200 million people. Praziquantel (PZQ) has been the main drug for controlling...
Schistosomiasis is caused by parasites of the genus Schistosoma, which infect more than 200 million people. Praziquantel (PZQ) has been the main drug for controlling schistosomiasis for over four decades, but despite that it is ineffective against juvenile worms and size and taste issues with its pharmaceutical forms impose challenges for treating school-aged children. It is also important to note that PZQ resistant strains can be generated in laboratory conditions and observed in the field, hence its extensive use in mass drug administration programs raises concerns about resistance, highlighting the need to search for new schistosomicidal drugs. Schistosomes survival relies on the redox enzyme thioredoxin glutathione reductase (TGR), a validated target for the development of new anti-schistosomal drugs. Here we report a high-throughput fragment screening campaign of 768 compounds against S. mansoni TGR (SmTGR) using X-ray crystallography. We observed 49 binding events involving 35 distinct molecular fragments which were found to be distributed across 16 binding sites. Most sites are described for the first time within SmTGR, a noteworthy exception being the "doorstop pocket" near the NADPH binding site. We have compared results from hotspots and pocket druggability analysis of SmTGR with the experimental binding sites found in this work, with our results indicating only limited coincidence between experimental and computational results. Finally, we discuss that binding sites at the doorstop/NADPH binding site and in the SmTGR dimer interface, should be prioritized for developing SmTGR inhibitors as new antischistosomal drugs.
Topics: Animals; Child; Humans; Schistosoma mansoni; Crystallography, X-Ray; NADP; Schistosomiasis; Binding Sites; Schistosomiasis mansoni; Multienzyme Complexes; NADH, NADPH Oxidoreductases
PubMed: 38238498
DOI: 10.1038/s41598-024-52018-2 -
Child's Nervous System : ChNS :... Feb 2024Spinal cord schistosomiasis is a rare and severe form of schistosomiasis. The prognosis is largely conditioned by early diagnosis and treatment. The authors present a...
Spinal cord schistosomiasis is a rare and severe form of schistosomiasis. The prognosis is largely conditioned by early diagnosis and treatment. The authors present a case of spinal cord schistosomiasis complicated by spinal cord compression syndrome. This is the case of a 6-year-old patient who presented with febrile gastroenteritis followed by complete paralysis of both lower limbs of sudden onset following a brief stay in a village setting with notion of multiple baths at a stream. Spinal cord MRI revealed an enlarged spinal cord spanning D10 to D12 with heterogeneous contrast enhancement and a syrinx cavity above the lesion. Biological workup revealed an inflammatory syndrome. Treatment consisted of decompressive laminectomy with biopsy of the lesion and a syringo-subarachnoid shunt. Pathological analysis revealed fragments of central nervous system tissues with an infiltrate composed of lymphocytes, plasmocytes, and macrophages producing granulomatous foci lined with areas of necrosis in addition to a large contingent of polynuclear eosinophils, agglutinating around or covering in some places elongated ovoid structures, with relatively thick eosinophilic shells and presenting a terminal spur. Adjuvant treatment consisted of praziquantel and corticotherapy for 1 month. The evolution showed marked improvement in the neurological deficits. She now walks unassisted and has good sphincter control. Spinal cord schistosomiasis is rare in our context; its diagnosis is difficult. The treatment is both medical and surgical.
Topics: Child; Female; Humans; Spinal Cord; Schistosomiasis; Spinal Cord Compression; Syringomyelia; Praziquantel
PubMed: 38224362
DOI: 10.1007/s00381-024-06282-2 -
Journal of Infection and Chemotherapy :... Jul 2024Paragonimiasis is a parasitic disease primarily contracted through consumption of undercooked freshwater crustaceans or wild boar meat. Large-scale nationwide...
BACKGROUND
Paragonimiasis is a parasitic disease primarily contracted through consumption of undercooked freshwater crustaceans or wild boar meat. Large-scale nationwide epidemiological data on paragonimiasis are lacking. In this study, we aimed to investigate the nationwide epidemiology of hospitalized patients with paragonimiasis in Japan using a comprehensive nationwide Japanese administrative database.
METHODS
We evaluated the Japanese Diagnosis Procedure Combination (DPC) data of patients diagnosed with pulmonary paragonimiasis between April 1, 2012 and March 30, 2020. The patients' address and information, including age, sex, treatment (medication: praziquantel; surgery: open thoracotomy or intracranial mass extirpation), Japan coma scale, comorbidities, and length of hospital stay, were extracted.
RESULTS
Of the 49.6 million hospitalized patients, data were extracted on 73 patients with paragonimiasis, of whom 36 were male and 37 were female. The mean age was 49.7 years and the mean length of stay was 12.5 days. The most frequent comorbidity was pleural effusion (31.5 %), followed by pneumothorax (13.7 %). The sites of ectopic paragonimiasis in organs other than the lung included the liver (5.5 %), skin (4.1 %), and brain (2.7 %). Geographically, most patients were from the Kyushu region (54.8 %), followed by the Kanto region (22.0 %). Fukuoka Prefecture had the highest number of patients (22.0 %) by prefecture. During the study period, an average of 9.1 patients/year were hospitalized with lung paragonimiasis in Japan.
CONCLUSION
Paragonimiasis has not completely disappeared in Japan; thus, physicians should be aware of paragonimiasis in the Kyushu region, especially in the Fukuoka Prefecture.
Topics: Humans; Paragonimiasis; Japan; Male; Female; Middle Aged; Adult; Databases, Factual; Aged; Length of Stay; Lung Diseases, Parasitic; Young Adult; Hospitalization; Praziquantel; Adolescent; Animals; Comorbidity; East Asian People
PubMed: 38219980
DOI: 10.1016/j.jiac.2024.01.005 -
Beilstein Journal of Nanotechnology 2024Schistosomiasis causes over 200,000 deaths annually. The current treatment option, praziquantel, presents limitations, including low bioavailability and resistance. In... (Review)
Review
Schistosomiasis causes over 200,000 deaths annually. The current treatment option, praziquantel, presents limitations, including low bioavailability and resistance. In this context, nanoparticles have emerged as a promising option for improving schistosomiasis treatment. Several narrative reviews have been published on this topic. Unfortunately, the lack of clear methodologies presented in these reviews leads to the exclusion of many important studies without apparent justification. This integrative review aims to examine works published in this area with a precise and reproducible method. To achieve this, three databases (i.e., Pubmed, Web of Science, and Scopus) were searched from March 31, 2022, to March 31, 2023. The search results included only original research articles that used nanoparticles smaller than 1 µm in the treatment context. Additionally, a search was conducted in the references of the identified articles to retrieve works that could not be found solely using the original search formula. As a result, 65 articles that met the established criteria were identified. Inorganic and polymeric nanoparticles were the most prevalent nanosystems used. Gold was the primary material used to produce inorganic nanoparticles, while poly(lactic--glycolic acid) and chitosan were commonly used to produce polymeric nanoparticles. None of these identified works presented results in the clinical phase. Finally, based on our findings, the outlook appears favorable, as there is a significant diversity of new substances with schistosomicidal potential. However, financial efforts are required to advance these nanoformulations.
PubMed: 38213572
DOI: 10.3762/bjnano.15.2 -
Brain Pathology (Zurich, Switzerland) Jan 2024Despite being a leading cause of acquired seizures in endemic regions, the pathological mechanisms of neurocysticercosis are still poorly understood. This study aims to...
Despite being a leading cause of acquired seizures in endemic regions, the pathological mechanisms of neurocysticercosis are still poorly understood. This study aims to investigate the impact of anthelmintic treatment on neuropathological features in a rat model of neurocysticercosis. Rats were intracranially infected with Taenia solium oncospheres and treated with albendazole + praziquantel (ABZ), oxfendazole + praziquantel (OXF), or untreated placebo (UT) for 7 days. Following the last dose of treatment, brain tissues were evaluated at 24 h and 2 months. We performed neuropathological assessment for cyst damage, perilesional brain inflammation, presence of axonal spheroids, and spongy changes. Both treatments showed comparable efficacy in cyst damage and inflammation. The presence of spongy change correlated with spheroids counts and were not affected by anthelmintic treatment. Compared to white matter, gray matter showed greater spongy change (91.7% vs. 21.4%, p < 0.0001), higher spheroids count (45.2 vs. 0.2, p = 0.0001), and increased inflammation (72.0% vs. 21.4%, p = 0.003). In this rat model, anthelmintic treatment destroyed brain parasitic cysts at the cost of local inflammation similar to what is described in human neurocysticercosis. Axonal spheroids and spongy changes as markers of damage were topographically correlated, and not affected by anthelmintic treatment.
PubMed: 38212958
DOI: 10.1111/bpa.13237 -
Parasitology Research Jan 2024The aim of this study was to evaluate the efficacy of a topical combination of moxidectin 3.5%, imidacloprid 10% and praziquantel 10% for the prevention of Dirofilaria...
The aim of this study was to evaluate the efficacy of a topical combination of moxidectin 3.5%, imidacloprid 10% and praziquantel 10% for the prevention of Dirofilaria immitis (Leidy, 1856) infection in dogs. For this purpose, a randomized and controlled clinical trial was conducted between August 2021 and October 2022, in the municipality of Goiana, state of Pernambuco, north-eastern Brazil, where heartworm is highly prevalent. Of the 213 dogs initially sampled (baseline), 68 (31.9%) were positive for adult antigens (SNAP 4Dx Plus, Idexx) and/or microfilariae (modified Knott's test). On day 0, 140 negative dogs were randomly included in the treatment and control groups, 70 animals each. During the study, 60 dogs (34 treated and 26 untreated) were removed for different reasons. At the end of the study (day 360 ± 2), 36 treated and 44 untreated were sampled and included in the efficacy calculation. The efficacy against the development of adults and microfilariae was 84.7%, with only one treated dog being positive for adult antigens but negative for microfilariae. On the other hand, eight untreated dogs were positive for adult antigens and/or microfilariae, resulting in a significant difference in the number of positives between groups (Chi-square test = 4.706, df = 1, P = 0.0301). Remarkably, the efficacy against the appearance of D. immitis microfilariae was 100% (i.e., all treated dogs negative) and three untreated dogs were positive for microfilariae. The topical combination of moxidectin 3.5%, imidacloprid 10% and praziquantel 10% significantly reduced the risk of D. immitis infection in treated dogs as compared with untreated dogs, in a highly endemic area in north-eastern Brazil.
Topics: Animals; Dogs; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Drug Therapy, Combination; Macrolides; Microfilariae; Neonicotinoids; Nitro Compounds; Praziquantel
PubMed: 38212547
DOI: 10.1007/s00436-023-08112-x -
Pediatric Nephrology (Berlin, Germany) Jun 2024Schistosomiasis affects approximately 230 million people worldwide. There is an increased incidence of schistosomiasis cases in France acquired from outside the country....
BACKGROUND
Schistosomiasis affects approximately 230 million people worldwide. There is an increased incidence of schistosomiasis cases in France acquired from outside the country. This increases the risk of schistosomiasis outbreaks as observed in Corsica. Clinicians from non-endemic regions are not accustomed to diagnosing and managing this pathology. The objective of this study is to provide a better description of the clinical and paraclinical characteristics and disease evolution of affected children.
METHODS
Through the French Pediatric Nephrology Society and the Pediatric Infectious Pathology Group, we contacted all French pediatric centers that may have treated children with urinary schistosomiasis between 2013 and 2019. Age, sex, comorbidities, and clinical, biological, and radiological data (at discovery and follow-up) were collected retrospectively.
RESULTS
A total of 122 patients from 10 different centers were included. The median age was 14 years and the sex ratio M/F was 4:1. Hematuria was present in 82% of the patients while urinary tract abnormality was found in 36% of them. Fourteen patients (11%) displayed complicated forms of urinary schistosomiasis including 10 patients with chronic kidney disease. A total of 110 patients received treatment with praziquantel, which was well-tolerated and led to clinical resolution of symptoms in 98% of cases.
CONCLUSION
Patients with schistosomiasis present frequent kidney, urinary, or genital involvement. Systematic screening of patients returning from endemic areas is therefore recommended, especially since treatment with antiparasitic drugs is effective and well-tolerated. Enhancing medical knowledge of this pathology among all practitioners is essential to improve care and outcomes.
Topics: Humans; Child; Adolescent; Animals; Schistosomiasis haematobia; Retrospective Studies; Praziquantel; Hematuria; France; Schistosoma haematobium
PubMed: 38212419
DOI: 10.1007/s00467-023-06260-x -
Revista Espanola de Enfermedades... Jan 2024A 23-year-old male from Brazil presented with bright red hematochezia. Proctological examination revealed grade II internal hemorrhoids, but flexible sigmoidoscopy...
A 23-year-old male from Brazil presented with bright red hematochezia. Proctological examination revealed grade II internal hemorrhoids, but flexible sigmoidoscopy uncovered a 6 mm-pedunculated polyp in the sigmoid colon, which was found to result from inflammatory reaction to Schistosoma mansoni egg deposition. The patient had no signs of portal hypertension and was successfully treated with praziquantel. This case underscores a rare presentation of chronic intestinal schistosomiasis and emphasizes the role of early diagnosis in preventing severe hepatic sequelae of chronic Schistosoma infection.
PubMed: 38205695
DOI: 10.17235/reed.2024.10155/2023 -
Female Genital Schistosomiasis Lesion Resolution Post-Treatment with Praziquantel in Zambian Adults.The American Journal of Tropical... Feb 2024We evaluated changes in female genital schistosomiasis (FGS) 6 to 12 months after praziquantel treatment among 43 adult Zambian women. Most women (60%) experienced...
We evaluated changes in female genital schistosomiasis (FGS) 6 to 12 months after praziquantel treatment among 43 adult Zambian women. Most women (60%) experienced decreased FGS severity and 23% experienced complete lesion resolution. This is the first study to demonstrate a meaningful effect of praziquantel treatment of FGS in adult women.
Topics: Adult; Female; Humans; Praziquantel; Zambia; Schistosomiasis; Genitalia, Female; Schistosomiasis haematobia; Genital Diseases, Female
PubMed: 38190749
DOI: 10.4269/ajtmh.23-0552 -
Analytical Methods : Advancing Methods... Feb 2024Two new techniques for analyzing praziquantel (PZQ), an effective antiparasitic drug used in fresh and saltwater aquariums, were optimized and compared. One method was...
Two new techniques for analyzing praziquantel (PZQ), an effective antiparasitic drug used in fresh and saltwater aquariums, were optimized and compared. One method was based on voltammetry and the other method used gas chromatography combined with mass spectrometry (GC-MS), although both procedures utilized the same sample pretreatment strategy which involved the PZQ being quantitatively transferred into acetonitrile using solid phase extraction. GC-MS analysis led to lower limits of detection (0.32 μM, 0.10 ppm) and quantification (0.72 μM, 0.22 ppm) compared to voltammetry, although both methods gave acceptable quantification for levels of PZQ > 25 μM (7.8 ppm). GC-MS is preferred for the most accurate determination, but voltammetry may provide a cost-effective alternative for detecting PZQ where on site testing is required.
Topics: Praziquantel; Gas Chromatography-Mass Spectrometry; Tandem Mass Spectrometry; Fresh Water
PubMed: 38189186
DOI: 10.1039/d3ay01905e