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PLoS Neglected Tropical Diseases Apr 2020Praziquantel has been in use by helminthiasis and schistosomiasis control programs for about 30 years. Although deemed to be safe with regard to its adverse drug...
INTRODUCTION
Praziquantel has been in use by helminthiasis and schistosomiasis control programs for about 30 years. Although deemed to be safe with regard to its adverse drug reaction profile in reference to the product information of Biltricide, the Eritrean Pharmacovigilance Center received reports of visual abnormalities related to the drug. This is a case series assessment of unusual cases of visual abnormalities associated with praziquantel.
METHODS
Search was made in VigiBase by setting praziquantel as a drug substance, Eritrea as the reporting country and all eye disorders, high level term (HLT) to capture all visual disorders associated with Praziquantel. The retrieved dataset was exported into an Excel spreadsheet for descriptive analysis and causality was assessed using Austin Bradford-Hill criteria.
RESULTS
There are a total of 2579 Individual Case Safety Reports (ICSRs) of various Adverse Drug Reactions (ADRs) of praziquantel reported from Eritrea in VigiBase. The 61 reports of visual abnormalities that arose within the first 24 hours of praziquantel administration are of note. With a strong association as evidenced by the positive IC025 value, the association of praziquantel and blurred vision was consistently reported from different health facilities over a period of three years. It is a specific association in terms of both the exposure (only praziquantel) and the outcome (blurred vision) as reported in majority of the cases. However, experimental evidences for the association are lacking, the underweight profile of the Eritrean population suggests overdosing as a possible risk factor for the occurrence of these reactions.
CONCLUSION
The strength, temporal plausibility, consistency and specificity of the association are suggestive of a causal association between praziquantel and visual disorders.
Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aged; Anthelmintics; Child; Databases, Factual; Eritrea; Female; Helminthiasis; Humans; Male; Middle Aged; Pharmacovigilance; Praziquantel; Risk Factors; Vision Disorders; Young Adult
PubMed: 32294081
DOI: 10.1371/journal.pntd.0008198 -
Infectious Diseases of Poverty Mar 2017The current approach of morbidity control of schistosomiasis, a helminth disease of poverty with considerable public health and socioeconomic impact, is based on... (Review)
Review
The current approach of morbidity control of schistosomiasis, a helminth disease of poverty with considerable public health and socioeconomic impact, is based on preventive chemotherapy with praziquantel. There is a pressing need for new drugs against this disease whose control entirely depends on this single drug that has been widely used over the past 40 years. We argue that a broader anthelminthic approach supplementing praziquantel with new antischistosomals targeting different parasite development stages would not only increase efficacy but also reduce the risk for drug resistance. Repositioning drugs already approved for other diseases provides a shortcut to clinical trials, as it is expected that such drugs rapidly pass the regulatory authorities. The antischistosomal properties of antimalarial drugs (e.g., semisynthetic artemisinins, synthetic trioxolanes, trioxaquines and mefloquine) and of drugs being developed or registered for other purposes (e.g., moxidectin and miltefosin), administered alone or in combination with praziquantel, have been tested in the laboratory and clinical trials. Another avenue to follow is the continued search for new antischistosomal properties in plants. Here, we summarise recent progress made in schistosomiasis chemotherapy, placing particular emphasis on repositioning of existing drugs against schistosomiasis.
Topics: Animals; Anthelmintics; Antimalarials; Drug Repositioning; Drug Resistance; Drug Therapy, Combination; Humans; Praziquantel; Public Health; Schistosoma; Schistosomiasis
PubMed: 28351414
DOI: 10.1186/s40249-017-0286-2 -
Parasitology Research Apr 2024Because of recent reports of praziquantel resistance in schistosome infections, there have been suggestions to employ ivermectin as a possible alternative, especially as...
Because of recent reports of praziquantel resistance in schistosome infections, there have been suggestions to employ ivermectin as a possible alternative, especially as its chemical composition is different from that of praziquantel, so cross-resistance is not expected. In order to ascertain possible damage and elimination of worms, we used ivermectin by oral gavage in infected mice, at a high dose (30.1 mg/kg, bordering toxicity). We also tested the efficacy of the drug at various times postinfection (PI), to check on possible effect on young and mature stages of the parasites. Thus, we treated mice on days 21 and 22 or on days 41 and 42 and even on days 21, 22, 41, and 42 PI. None of the treatment regimens resulted in cure rates or signs of lessened pathology in the mice. We also compared the effect of ivermectin to that of artemisone, an artemisinin derivative which had served us in the past as an effective anti-schistosome drug, and there was a stark difference in the artemisone's efficacy compared to that of ivermectin; while ivermectin was not effective, artemisone eliminated most of the worms, prevented egg production and granulomatous inflammatory response. We assume that the reported lack of activity of ivermectin, in comparison with praziquantel and artemisinins, originates from the difference in their mode of action. In wake of our results, we suggest that ivermectin is not a suitable drug for treatment of schistosomiasis.
Topics: Animals; Mice; Praziquantel; Ivermectin; Schistosomiasis; Artemisinins; Schistosomatidae
PubMed: 38592544
DOI: 10.1007/s00436-024-08178-1 -
Acta Tropica Apr 2022Schistosomiasis is a public health issue of concern in Gabon, with the disease being reported from all regions of the country. The topic has been of interest for the... (Review)
Review
INTRODUCTION
Schistosomiasis is a public health issue of concern in Gabon, with the disease being reported from all regions of the country. The topic has been of interest for the local researchers and physicians for over two decades. The objective of this narrative review was to provide an overview of the research activities in the area from 2000 to early 2021.
METHODS
We performed a narrative literature review. The search strategy was designed to get a broad overview of the different research topics on schistosomiasis and the national control programme, and included grey literature.
RESULTS
A total of 159 articles was screened, and 42 were included into the review in addition to the grey literature. During the past two decades, the work on schistosomiasis originated from five out of the nine provinces of the country, with diverse aspects of the disease investigated; including immunology, epidemiology, diagnosis and treatment. Several studies investigated various aspects of schistosomiasis-related morbidity in the respective study populations. The body of work demonstrates that much effort was made to understand the details of the host immune response to schistosomiasis, and the immune profile changes induced in patients treated with praziquantel. Although some MDA campaigns were conducted in the country; little, however, is known on the epidemiological situation of the disease, particularly of its distribution within the population, as well as co-infections with other parasitic diseases also endemic in the area.
CONCLUSION
Progress has been made over the past two decades in the understanding of schistosomiasis in the country, including disease-related morbidity and its interaction with other parasitic infections, and the immunology and epidemiology of the disease. However, for optimising control of the disease, there is a need to fine-tune these findings with detailed local epidemiological and malacological data. We call for such studies to accomplish the knowledge of schistosomiasis in the country, particularly in areas of moderate or high endemicity, and recommend this approach to comparable schistosomiasis-endemic areas elsewhere.
Topics: Coinfection; Gabon; Humans; Morbidity; Praziquantel; Schistosomiasis
PubMed: 35051384
DOI: 10.1016/j.actatropica.2022.106317 -
Parasites & Vectors Oct 2023Schistosomiasis, also known as bilharzia, is a devastating parasitic disease. This progressive and debilitating helminth disease is often associated with poverty and can...
BACKGROUND
Schistosomiasis, also known as bilharzia, is a devastating parasitic disease. This progressive and debilitating helminth disease is often associated with poverty and can lead to chronic poor health. Despite ongoing research, there is currently no effective vaccine for schistosomiasis, and praziquantel remains the only available treatment option. According to the progression of schistosomiasis, infections caused by schistosomes are classified into three distinct clinical phases: acute, chronic and advanced schistosomiasis. However, the underlying immune mechanism involved in the progression of schistosomiasis remains poorly understood.
METHODS
We employed single-cell RNA sequencing (scRNA-seq) to profile the immune landscape of Schistosomiasis japonica infection based on peripheral blood mononuclear cells (PBMCs) from a healthy control group (n = 4), chronic schistosomiasis group (n = 4) and advanced schistosomiasis group (n = 2).
RESULTS
Of 89,896 cells, 24 major cell clusters were ultimately included in our analysis. Neutrophils and NK/T cells accounted for the major proportion in the chronic group and the healthy group, and monocytes dominated in the advanced group. A preliminary study showed that NKT cells were increased in patients with schistosomiasis and that CXCR2 + NKT cells were proinflammatory cells. Plasma cells also accounted for a large proportion of B cells in the advanced group. MHC molecules in monocytes were notably lower in the advanced group than in the chronic group or the healthy control group. However, monocytes in the advanced group exhibited high expression of FOLR3 and CCR2.
CONCLUSIONS
Overall, this study enhances our understanding of the immune mechanisms involved in schistosomiasis. It provides a transcriptional atlas of peripheral immune cells that may contribute to elimination of the disease. This preliminary study suggests that the increased presence of CCR2 + monocyte and CXCR2 + NKT cells might participate in the progression of schistosomiasis.
Topics: Humans; Schistosomiasis japonica; Schistosomiasis; Praziquantel; Natural Killer T-Cells; Sequence Analysis, RNA
PubMed: 37817226
DOI: 10.1186/s13071-023-05975-y -
Infectious Diseases of Poverty Apr 2017Despite increased international efforts to control schistosomiasis using preventive chemotherapy, several challenges still exist in reaching the target populations.... (Review)
Review
Despite increased international efforts to control schistosomiasis using preventive chemotherapy, several challenges still exist in reaching the target populations. Until recently, preschool-aged children had been excluded from the recommended target population for mass drug administration, i.e. primary school children aged 6-15 years. Our studies and those of others provided the evidence base for the need to treat preschool-aged children that led to recommendations by the World Health Organization to include preschool-aged children in treatment programmes in 2010. The major challenge now lies in the unavailability of a child-size formulation of the appropriate anthelmintic drug, praziquantel.The currently available formulation of praziquantel presents several problems. First, it is a large tablet, making it difficult for young children and infants to swallow it and thus requires its breaking/crushing to allow for safe uptake. Second, it is bitter so it is often mixed with a sweetener to make it palatable for young children. Third, the current formulation of 600 mg does not allow for flexible dose adjustments for this age group. Thus, there is a need to formulate a child-appropriate praziquantel tablet.This paper discusses the target product profile for paediatric praziquantel, as well as knowledge gaps pertinent to the successful control of schistosome infection and disease in preschool-aged children.
Topics: Adolescent; Anthelmintics; Chemoprevention; Child; Child, Preschool; Drug Compounding; Humans; Practice Guidelines as Topic; Praziquantel; Schistosomiasis; World Health Organization
PubMed: 28388940
DOI: 10.1186/s40249-017-0300-8 -
Future Medicinal Chemistry 2015In the recent years, there has been a growing interest in the use of novel approaches for the treatment of parasitic diseases such as schistosomiasis. Among the... (Review)
Review
In the recent years, there has been a growing interest in the use of novel approaches for the treatment of parasitic diseases such as schistosomiasis. Among the different approaches used, organometallic compounds were found to offer unique opportunities in the design of antiparasitic drug candidates. A ferrocenyl derivative, namely ferroquine, has even entered clinical trials as a novel antimalarial. In this short review, we report on the studies describing the use of organometallic compounds against schistosomiasis.
Topics: Animals; Antifungal Agents; Antimalarials; Drug Discovery; Drug Repositioning; Humans; Organometallic Compounds; Praziquantel; Schistosoma; Schistosomiasis; Schistosomicides
PubMed: 25996072
DOI: 10.4155/fmc.15.22 -
Pharmacology Research & Perspectives Aug 2020Racemic praziquantel (PZQ) is the drug of choice for the treatment of schistosomiasis. R-Praziquantel (R-PZQ) has been shown as the therapeutic form, whereas S-PZQ is... (Randomized Controlled Trial)
Randomized Controlled Trial
Racemic praziquantel (PZQ) is the drug of choice for the treatment of schistosomiasis. R-Praziquantel (R-PZQ) has been shown as the therapeutic form, whereas S-PZQ is less efficacious and responsible for the bitter taste of the tablet. This study aimed at investigating the metabolism of R- and S-PZQ as this could have implications on efficacy and safety of racemate and R-PZQ specific formulations under development. In vitro CYP reaction phenotyping assay using 10 recombinant CYP (rCYP) isoenzymes showed hepatic CYP1A2, 2C19, 2D6, 3A4, and 3A5 were the major enzymes involved in metabolism of PZQ. Enzyme kinetic studies were performed by substrate depletion and metabolite formation methods, by incubating PZQ and its R- or S-enantiomers in human liver microsomes (HLM) and the rCYP enzymes. The effect of selective CYP inhibitors on PZQ metabolism was assessed in HLM. CYP1A2, 2C19, and 3A4 exhibited different catalytic activity toward PZQ, R- and S-enantiomers. Metabolism of R-PZQ was mainly catalyzed by CYP1A2 and CYP2C19, whereas metabolism of S-PZQ was mainly by CYP2C19 and CYP3A4. Based on metabolic CL obtained through formation of hydroxylated metabolites, CYP3A4 was estimated to contribute 89.88% to metabolism of S-PZQ using SIMCYP IVIVE prediction. Reanalysis of samples from a human PZQ-ketoconazole (KTZ) drug-drug interaction pharmacokinetic study confirmed these findings in that KTZ, a potent inhibitor of CYP3A, selectively increased area under the curve of S-PZQ by 68% and that of R-PZQ by just 9%. Knowledge of enantioselective metabolism will enable better understanding of variable efficacy of PZQ in patients and the R-PZQ formulation under development.
Topics: Anthelmintics; Area Under Curve; Cross-Over Studies; Cytochrome P-450 Enzyme System; Drug Interactions; Humans; Isoenzymes; Ketoconazole; Male; Microsomes, Liver; Praziquantel; Stereoisomerism
PubMed: 32700798
DOI: 10.1002/prp2.618 -
Pathogens and Global Health Oct 2023Praziquantel (PZQ) has been extensively used as the drug of choice for the treatment of schistosomiasis on account of its safety and effectiveness against all major...
Praziquantel (PZQ) has been extensively used as the drug of choice for the treatment of schistosomiasis on account of its safety and effectiveness against all major forms of schistosomiasis. However, low cure rate, reduced susceptibility of to PZQ and treatment failures in . infections have been reported, raising concerns about its efficacy. Using the search terms, 'praziquantel efficacy, schistosomiasis, school children, reinfection' as well as defined inclusion criteria, and guided by the PRISMA guidelines, articles from 2001 to 2022 were selected from the PubMed and Google Scholar databases and reviewed to assess their importance to the research question. This review assessed the efficacy of PZQ against schistosomiasis and reinfection rates following treatment of infections in children. Majority of both intestinal and urinary schistosomiasis studies reported comparable egg reduction rates (ERRs) of 94.2% to 99.9% and 91.9% to 98%, respectively. However, ERRs suggestive of sub-optimal PZQ efficacy as well as generally high and comparable cure rates for intestinal (81.2%-99.1%) and urinary (79%-93.7%) schistosomiasis studies were reported. Schistosomiasis reinfection rates varied widely for urinary (8.1%-39.6%) and intestinal (13.9%-63.4%) studies within eight to 28 weeks following PZQ treatment. Praziquantel treatment of urinary and intestinal schistosomiasis should be accompanied by the provision of potable water, toilet, and recreational facilities to reduce reinfection and egg reduction rates and increase cure rate to expedite schistosomiasis elimination.
Topics: Child; Humans; Praziquantel; Schistosomiasis mansoni; Anthelmintics; Reinfection; Treatment Outcome; Schistosomiasis haematobia
PubMed: 36394218
DOI: 10.1080/20477724.2022.2145070 -
ACS Infectious Diseases Jul 2020Schistosomiasis is a neglected tropical disease of considerable public health burden. We recently discovered a micromolar activity of several cardenolides against newly...
Schistosomiasis is a neglected tropical disease of considerable public health burden. We recently discovered a micromolar activity of several cardenolides against newly transformed schistosomula (NTS) of the parasitic flatworm in a small compound screen including different substance classes of both natural products as well as synthetic molecules. In further experiments, a focused library of naturally occurring and synthetic steroids was explored against NTS and adult , revealing seven cardenolides with comparable activities as known anthelminthics such as praziquantel. Of these, gomphoside monoacetate and uscharin showed suitable therapeutic indices. In a first study, at a dose of 10 mg/kg, only minor activity in mice harboring a chronic infection could be shown, which will be further investigated by structure-activity relationship studies as well as pharmacodynamic and pharmacokinetic approaches.
Topics: Animals; Anthelmintics; Cardenolides; Mice; Praziquantel; Schistosoma mansoni; Structure-Activity Relationship
PubMed: 32364372
DOI: 10.1021/acsinfecdis.0c00175