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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 -
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 -
Nature Medicine Jan 2024Schistosomiasis treatment entirely relies on a single drug, praziquantel, prompting research into alternative therapeutics. Here we evaluated the efficacy and safety of... (Randomized Controlled Trial)
Randomized Controlled Trial
Schistosomiasis treatment entirely relies on a single drug, praziquantel, prompting research into alternative therapeutics. Here we evaluated the efficacy and safety of the antimalarial combination artesunate-mefloquine for the treatment of schistosomiasis in a proof-of-concept, pragmatic, open-label, randomized controlled trial in primary schools of six villages endemic for schistosomiasis in northern Senegal. Children (6-14 years) were eligible if Schistosoma eggs were detected by microscopy in urine and/or stool. In total, 726 children were randomized 1:1 to praziquantel (standard care: 40 mg kg single dose; n = 364) or to artesunate-mefloquine (antimalarial dosage: artesunate 4 mg kg and mefloquine 8 mg kg daily for three consecutive days; n = 362). Eight children not meeting the inclusion criteria were excluded from efficacy analysis. Median age of the remaining 718 participants was 9 years; 399 (55.6%) were male, and 319 (44.4%) female; 99.3% were infected with Schistosoma haematobium and 15.2% with S. mansoni. Primary outcomes were cure rate, assessed by microscopy, and frequency of drug-related adverse effects of artesunate-mefloquine versus praziquantel at 4 weeks after treatment. Cure rate was 59.6% (208/349) in the artesunate-mefloquine arm versus 62.1% (211/340) in the praziquantel arm. The difference of -2.5% (95% confidence interval (CI) -9.8 to 4.8) met the predefined criteria of noninferiority (margin set at 10%). All drug-related adverse events were mild or moderate, and reported in 28/361 children receiving artesunate-mefloquine (7.8%; 95% CI 5.4 to 11.0) versus 8/363 (2.2%; 95% CI 1.1 to 4.3) receiving praziquantel (P < 0.001). Artesunate-mefloquine at antimalarial dosage was moderately safe and noninferior to standard-care praziquantel for the treatment of schistosomiasis, predominantly due to S. haematobium. Multicentric trials in different populations and epidemiological settings are needed to confirm these findings. ClinicalTrials.gov identifier: NCT03893097 .
Topics: Child; Female; Humans; Male; Antimalarials; Artesunate; Mefloquine; Praziquantel; Schistosomiasis; Treatment Outcome; Adolescent
PubMed: 38177851
DOI: 10.1038/s41591-023-02719-4 -
Journal of Parasitology Research 2023Anaemia is common in sub-Saharan Africa, and parasitic infections could worsen its burden during pregnancy. Moreover, women become susceptible to malaria during...
BACKGROUND
Anaemia is common in sub-Saharan Africa, and parasitic infections could worsen its burden during pregnancy. Moreover, women become susceptible to malaria during pregnancy. We investigated () and () infections and determined their association with anaemia during pregnancy.
METHODS
A cross-sectional study involving 707 pregnant women attending antenatal care visits (ANC) and 446 at delivery was conducted in Battor and Adidome hospitals. Pregnant women were screened by microscopy and qPCR for and infections. Haemoglobin (Hb) levels were determined, and most participants received intermittent preventive treatment during pregnancy (IPTp) during ANC till delivery. Regression analyses were performed for associations between parasite infection and anaemia.
RESULTS
microscopy prevalence at ANC and delivery was 8% and 2%, respectively, and by PCR 24% at ANC and 12% at delivery. Anaemia prevalence at ANC was 52% and 49% at delivery. There was an increased risk of anaemia with infection (aOR = 1.92; = 0.04). IPTp ( = 0.003) and age ( = 0.004) were associated with increased Hb levels at delivery. prevalence by microscopy was 4% at ANC and 2% at delivery. No significant correlation between and Hb levels was observed (coef. = -0.62 g/dl; = 0.07).
CONCLUSION
High anaemia prevalence was observed during pregnancy, and infection was associated with anaemia at ANC. Low prevalence could be attributed to previous praziquantel treatment during mass drug administration. Routine diagnosis and treatment of infections in endemic areas could be initiated to reduce schistosomiasis during pregnancy.
PubMed: 37808169
DOI: 10.1155/2023/7500676 -
Cureus Aug 2023A 25-year-old man with no medical history presented with a seizure one month after taking a self-administered dose of albendazole. Magnetic resonance imaging (MRI) of...
A 25-year-old man with no medical history presented with a seizure one month after taking a self-administered dose of albendazole. Magnetic resonance imaging (MRI) of the brain revealed multiple ring-enhancing lesions, and the workup confirmed neurocysticercosis (NCC). Treatment with antiparasitics was delayed due to concern for worsening symptoms from the presence of cysts in the midbrain and hippocampus. The balance between treating NCC and limiting cerebral inflammation is delicate and relies on judgment from a multispecialty clinical team. In this case, corticosteroids and antiepileptics alone prevented additional seizures but failed to reduce the overall inflammation of cysts and the progression of the disease. Evidence of new cysts on MRI at week 13 from the onset of symptoms was evidence of an acute, evolving infectious process. Treatment with albendazole and praziquantel was initiated at 13 weeks from the onset of symptoms, and by 31 weeks, nearly all cysts had resolved with minimal residual inflammation.
PubMed: 37727167
DOI: 10.7759/cureus.43746 -
Malaria Journal Nov 2023The overlap in the epidemiology of malaria and helminths has been identified as a potential area to exploit for the development of an integrated control strategy that... (Randomized Controlled Trial)
Randomized Controlled Trial
Feasibility and safety of integrating mass drug administration for helminth control with seasonal malaria chemoprevention among Senegalese children: a randomized controlled, observer-blind trial.
BACKGROUND
The overlap in the epidemiology of malaria and helminths has been identified as a potential area to exploit for the development of an integrated control strategy that may help to achieve elimination of malaria and helminths. A randomized, controlled, observer-blind trial was conducted to assess the feasibility and safety of combining mass drug administration (MDA) for schistosomiasis and soil transmitted helminths (STH) with seasonal malaria chemoprevention (SMC) among children living in Senegal.
METHODS
Female and male children aged 1-14 years were randomized 1:1:1, to receive Vitamin A and Zinc on Day 0, followed by SMC drugs (sulfadoxine-pyrimethamine and amodiaquine) on Days 1-3 (control group); or praziquantel and Vitamin A on Day 0, followed by SMC drugs on Days 1-3 (treatment group 1); or albendazole and praziquantel on Day 0, followed by SMC drugs on Days 1-3 (treatment group 2). Safety assessment was performed by collecting adverse events from all children for six subsequent days following administration of the study drugs. Pre- and post-intervention, blood samples were collected for determination of haemoglobin concentration, malaria microscopy, and PCR assays. Stool samples were analyzed using Kato-Katz, Merthiolate-iodine-formalin and PCR methods. Urine filtration, PCR and circulating cathodic antigen tests were also performed.
RESULTS
From 9 to 22 June 2022, 627 children aged 1-14 years were randomized into the three groups described above. Mild, transient vomiting was observed in 12.6% (26/206) of children in treatment group 2, in 10.6% (22/207) in group 1, and in 4.2% (9/214) in the control group (p = 0.005). Pre-intervention, the geometric mean value of Plasmodium falciparum parasite density was highest among children who received albendazole, praziquantel with SMC drugs. Post-intervention, the parasite density was highest among children who received SMC drugs only. Children who received praziquantel and SMC drugs had a lower risk of developing severe anaemia than their counterparts who received SMC drugs alone (OR = 0.81, 95% CI 0.13-5.00, p = 0.63).
CONCLUSIONS
Integration of MDA for helminths with SMC drugs was safe and feasible among Senegalese children. These findings support further evaluation of the integrated control model.
TRIAL REGISTRATION
The study is registered at Clinical Trial.gov NCT05354258.
Topics: Animals; Humans; Child; Male; Female; Antimalarials; Praziquantel; Albendazole; Mass Drug Administration; Seasons; Feasibility Studies; Vitamin A; Malaria; Helminths; Chemoprevention
PubMed: 37957702
DOI: 10.1186/s12936-023-04784-z -
Cureus May 2024Cerebellar hydatid cysts are uncommon lesions, with limited cases reported in the literature. This systematic review aimed to summarize current diagnostic and management... (Review)
Review
Cerebellar hydatid cysts are uncommon lesions, with limited cases reported in the literature. This systematic review aimed to summarize current diagnostic and management approaches, given the low suspicion index of hydatid cysts in the cerebellum. The review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42023437853. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-P) reporting guidelines. Two independent researchers searched PubMed, Scopus, and Google Scholar databases on June 27, 2023. We included 15 studies published between 1965 and 2022, comprising 12 case reports and three case series. A pooled analysis of reported cases (nine females and seven males) with cerebellar hydatid cysts revealed a mean age of 24 ± 20 years. Most of the cases were reported in Turkish hospitals ( = 8). The prominent signs and symptoms observed were headaches (10, 62.5%), ataxic gait (9, 56.25%), and visual disturbances (9, 56.25%). The time from symptom onset to hospital visit varied, with most patients seeking medical attention within the first three months. The left cerebellar hemisphere was the most common location of the cysts (6, 37.5%), and compression of the fourth ventricle was frequently observed. Computed tomography (CT) and magnetic resonance imaging (MRI) were the primary diagnostic tools used in three-fourths of cases, and surgical intervention was the primary treatment approach. Albendazole and praziquantel were commonly prescribed postoperatively, and two patients underwent preoperative needle decompression. This systematic review contributes to a better understanding of cerebellar hydatid cysts and guides future research and clinical management of this entity.
PubMed: 38841019
DOI: 10.7759/cureus.59706 -
BioRxiv : the Preprint Server For... Sep 2023Diseases caused by parasitic flatworms impart a considerable healthcare burden worldwide. Many of these diseases - for example, the parasitic blood fluke infection,...
Diseases caused by parasitic flatworms impart a considerable healthcare burden worldwide. Many of these diseases - for example, the parasitic blood fluke infection, schistosomiasis - are treated with the drug praziquantel (PZQ). However, PZQ is ineffective against disease caused by liver flukes from the genus . This is due to a single amino acid change within the target of PZQ, a transient receptor potential ion channel (TRPM), in species. Here we identify benzamidoquinazolinone analogs that are active against TRPM. Structure-activity studies define an optimized ligand (BZQ) that caused protracted paralysis and damage to the protective tegument of these liver flukes. BZQ also retained activity against comparable to PZQ and was active against TRPM orthologs in all profiled species of parasitic fluke. This broad spectrum activity was manifest as BZQ adopts a pose within the binding pocket of TRPM dependent on a ubiquitously conserved residue. BZQ therefore acts as a universal activator of trematode TRPM and a first-in-class, broad spectrum flukicide.
PubMed: 37790347
DOI: 10.1101/2023.09.22.559026 -
Frontiers in Veterinary Science 2023Milbemycin oxime (MBO) and praziquantel (PZQ) have a broad spectrum of biological activity and are commonly used to treat the parasitic infection in the veterinary...
Development and validation of an LC-MS/MS method for the simultaneous quantification of milbemycin oxime and praziquantel in plasma: application to a pharmacokinetic study in cats.
INTRODUCTION
Milbemycin oxime (MBO) and praziquantel (PZQ) have a broad spectrum of biological activity and are commonly used to treat the parasitic infection in the veterinary clinic. In this study, a fast and efficient LC-MS/MS method was established and validated for the simultaneous determination of MBO, PZQ, cis-4-hydroxylated-PZQ (C-4-OH-PZQ) and trans-4-hydroxylated-PZQ (T-4-OH-PZQ) and in cat plasma.
METHODS
Extraction of analytes and internal standards from cat plasma by acetonitrile protein precipitation, allows rapid processing of large batches of samples. MBO, PZQ, C-4-OH-PZQ, T-4-OH-PZQ, and internal standard (IS) were eluted for 13.5 min on a C column with a 0.1% formic acid water/acetonitrile mixture as the mobile phase.
RESULTS
Results showed that the method had good precision, accuracy, recovery, and linearity. The linearity range was 2.5-250 ng/mL for MBO, and 10-1000 ng/mL for PZQ, C-4-OH-PZQ, and T-4-OH-PZQ. The intra-day and inter-day precision CV values of the tested components were within 15%. The extraction recoveries of the four components ranged from 98.09% to 107.46%. The analytes in plasma remained stable for 6 h at room temperature, 26 h in the autosampler (4 °C), after freeze-thaw (-20°C) cycles, and 60 days in a -20°C freezer. Method sensitivity sufficed for assessing pharmacokinetic parameters of MBO, PZQ, C-4-OH-PZQ, and T-4-OH-PZQ in plasma samples with LLOQ of 2.5 ng/mL for MBO and 10 ng/mL for PZQ, C-4-OH-PZQ, and T-4-OH-PZQ.
CONCLUSION
In this study, a selective and sensitive LC-MS/MS method for the simultaneous quantification of MBO, PZQ, C-4-OH-PZQ, and T-4-OH-PZQ in cat plasma was developed and validated.This method had been successfully applied to evaluate the pharmacokinetics of MBO, PZQ, C-4-OH-PZQ, and T-4-OH-PZQ after a single oral administration of 8 mg MBO and 20 mg PZQ in cats.
PubMed: 37964913
DOI: 10.3389/fvets.2023.1285932 -
ACS Infectious Diseases May 2024The term "zoonosis" denotes diseases transmissible among vertebrate animals and humans. These diseases constitute a significant public health challenge, comprising 61%... (Review)
Review
The term "zoonosis" denotes diseases transmissible among vertebrate animals and humans. These diseases constitute a significant public health challenge, comprising 61% of human pathogens and causing an estimated 2.7 million deaths annually. Zoonoses not only affect human health but also impact animal welfare and economic stability, particularly in low- and middle-income nations. Leishmaniasis and schistosomiasis are two important neglected tropical diseases with a high prevalence in tropical and subtropical areas, imposing significant burdens on affected regions. Schistosomiasis, particularly rampant in sub-Saharan Africa, lacks alternative treatments to praziquantel, prompting concerns regarding parasite resistance. Similarly, leishmaniasis poses challenges with unsatisfactory treatments, urging the development of novel therapeutic strategies. Effective prevention demands a One Health approach, integrating diverse disciplines to enhance diagnostics and develop safer drugs. Metalloenzymes, involved in parasite biology and critical in different biological pathways, emerged in the last few years as useful drug targets for the treatment of human diseases. Herein we have reviewed recent reports on the discovery of inhibitors of metalloenzymes associated with zoonotic diseases like histone deacetylases (HDACs), carbonic anhydrase (CA), arginase, and heme-dependent enzymes.
Topics: Animals; Humans; Leishmaniasis; Schistosoma; Zoonoses; Schistosomiasis; Leishmania; Carbonic Anhydrases; Histone Deacetylases; Enzyme Inhibitors
PubMed: 38669567
DOI: 10.1021/acsinfecdis.4c00163