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European Urology May 2021The African continent is unique in terms of its epidemiological evidence, causes, and possible future trends for bladder cancer (BCa). Factors include smoking rates and...
The African continent is unique in terms of its epidemiological evidence, causes, and possible future trends for bladder cancer (BCa). Factors include smoking rates and parasitic infection with Schistosoma haematobium. These issues in Africa could be addressed by increasing cultural awareness of BCa causes and symptoms via social media, banning smoking in public places, and ensuring that praziquantel is readily available in areas at high risk of schistosomiasis.
Topics: Animals; Anthelmintics; Humans; Praziquantel; Schistosoma haematobium; Schistosomiasis; Urinary Bladder Neoplasms
PubMed: 33280932
DOI: 10.1016/j.eururo.2020.11.041 -
Expert Review of Clinical Pharmacology 2016Schistosomiasis is a debilitating neglected tropical disease caused by schistosome worms. Global efforts to control schistosomiasis rely predominantly on mass drug...
Schistosomiasis is a debilitating neglected tropical disease caused by schistosome worms. Global efforts to control schistosomiasis rely predominantly on mass drug administration of the drug praziquantel to populations at risk of infection. We review the history of schistosome drug development and the current position of schistosome drug research. We conclude that with no additional candidates currently in the anti-schistosome drug clinical trial pipeline, a practical and necessary approach is to optimise the health benefits from praziquantel. We offer suggestions of where and how this can be achieved. We also highlight knowledge gaps in the utility of praziquantel particularly in the treatment of chronic schistosomiasis, which includes fibrosis, organomegaly and cervical lesions associated with female genital schistosomiasis.
Topics: Animals; Drug Design; Female; Humans; Neglected Diseases; Praziquantel; Schistosoma; Schistosomiasis; Schistosomicides; Tropical Climate
PubMed: 26508363
DOI: 10.1586/17512433.2015.1102051 -
Parasites & Vectors Jan 2017Children carry most of the schistosomiasis burden. While school-aged children are the principal target group of preventive chemotherapy with praziquantel, limited... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Children carry most of the schistosomiasis burden. While school-aged children are the principal target group of preventive chemotherapy with praziquantel, limited information on efficacy and safety exists for preschool-aged children.
METHODS
Here, we conducted a meta-analysis of clinical trials of praziquantel for treating children with any form of schistosomiasis. Efficacy was reported as cure rate (CR) and egg reduction rates (ERR); statistical corrections were applied based on methodological disparities across trials to derive the predicted geometrical mean ERR (pERRgm). Safety was reported as frequencies of adverse events.
RESULTS
Forty-seven comparative and non-comparative studies were identified, enrolling 15,549 children of whom 14,340 (92%) were assessed between 3 and 8 weeks post-treatment with praziquantel 40 mg/kg (the WHO-recommended treatment, n = 8,380, 56%) or comparators (n = 5,960, 44%). The median age was 10 years (range 1-19), 11% (n = 1,694) were preschool-aged. The CR and pERRgm with praziquantel 40 mg/kg were respectively: S. haematobium, 73.6% (95% CI: 63.5-81.40, 25 study arms) and 94.7% (95% CI: 92.7-96.4); S. mansoni, 76.4% (95% CI: 71.5-81.0, 34 arms) and 95.3% (95% CI: 94.2-96.2); S. mansoni/S. haematobium, 67.6% (95% CI: 54.1-80.7, 5 arms) and 93.4% (95% CI: 89.9-96.2); S. japonicum, 94.7% (95% CI: 92.2-98.0) and 98.7% (95% CI: 98.3-99.2). Mixed-effect multivariate analysis found no significant difference between preschool- and school-aged children for CR or pERRgm in S. haematobium (P = 0.309 and P = 0.490, respectively) or S. mansoni (P = 0.982 and P = 0.895) after controlling for time of assessment, formulation, intensity of infection and detection method. Praziquantel was reportedly safe at all ages, with only mild reported adverse events which cleared rapidly after treatment.
CONCLUSIONS
Praziquantel 40 mg/kg was effective at reducing infection intensity in all Schistosoma species without differences between preschool- and school-aged children. However, conclusions should be tempered because of the limited number of preschool-aged children enrolled, disparities in study procedures and limited information made available in publications, as well as the current imperfect test-of-cure. Also, although reportedly well-tolerated, safety was inconsistently assessed. Studies in target groups, individual-data meta-analysis and standardised methodologies are needed for more robust evidence-base.
Topics: Anthelmintics; Child; Child, Preschool; Female; Humans; Male; Praziquantel; Schistosomiasis
PubMed: 28126024
DOI: 10.1186/s13071-016-1958-7 -
Current Topics in Medicinal Chemistry 2018Despite being one of the most commonly used drugs, the molecular mechanism of action of the anthelmintic praziquantel remains unknown. There are some unusual features of... (Review)
Review
Despite being one of the most commonly used drugs, the molecular mechanism of action of the anthelmintic praziquantel remains unknown. There are some unusual features of this drug. Critically, widespread resistance to praziquantel has not developed despite decades of use. Here, we set out some challenges in praziquantel research and propose some provocative hypotheses to address these. We suggest that praziquantel may have multiple pharmacologically relevant targets and the effects on these may synergise to produce an overall, detrimental effect on the parasite. Praziquantel also acts on a number of host proteins and we propose that these actions are important in the drug's overall mechanism. Although the drug is largely used in the treatment of human and domestic animal worm infections, there is a considerable "grey literature" along with some academic studies which may have been overlooked. It appears that praziquantel may be effective against hydra. It may also be effective against some unicellular parasites such as Giardia spp. Further, scientific work on these understudied areas may be useful in understanding the molecular mechanism in Trematoda. The lack of widespread resistance suggests that praziquantel may act, at least in part, on a protein-protein interaction. Altered drug metabolism or enhanced drug efflux are the most likely ways resistance may arise. There is a critical need to understand the biochemical pharmacology of this drug in order to inform the discovery of the next generation of anthelmintic drugs.
Topics: Animals; Anthelmintics; Giardia lamblia; Humans; Parasitic Sensitivity Tests; Praziquantel; Trematoda
PubMed: 30370849
DOI: 10.2174/1568026618666181029143214 -
British Journal of Pharmacology Dec 2021The anthelmintic drug praziquantel has been used as a standard treatment for schistosomiasis for over 40 years. This study aimed to repurpose praziquantel to treat...
BACKGROUND AND PURPOSE
The anthelmintic drug praziquantel has been used as a standard treatment for schistosomiasis for over 40 years. This study aimed to repurpose praziquantel to treat psoriasis.
EXPERIMENTAL APPROACH
Psoriasis-like skin inflammation was induced in mice (C57 and Balb/C) by topical application of imiquimod or intradermal injection of recombinant IL-23. Praziquantel was either orally or topically administered during the psoriasis induction period.
KEY RESULTS
Mice treated with either oral or topical praziquantel exhibited markedly improved psoriasiform skin symptoms when compared with control mice, as judged by disease severity score, epidermal thickening, inflammatory cell infiltration and spleen size. Flow cytometric analysis of infiltrating immune cells from mouse skin displayed reduced infiltration of Th17 cells. In vitro experiments revealed that praziquantel inhibited STAT3 phosphorylation and RORγt expression in splenic CD4 T-cells. Praziquantel also decreased STAT3 phosphorylation in HEK-A/F cells. Down-regulation of STAT3 phosphorylation in these cells accounts for the decreased number of Th17 cells and keratinocytes.
CONCLUSION AND IMPLICATIONS
These results provide the first preclinical evidence that praziquantel may effectively treat psoriasis, and suggest that praziquantel alleviates symptoms in mice by inhibiting STAT3 phosphorylation, thereby suppressing Th17 immune responses.
Topics: Animals; Anthelmintics; Disease Models, Animal; Drug Repositioning; Mice; Mice, Inbred BALB C; Praziquantel; Psoriasis; Skin; Th17 Cells
PubMed: 34363611
DOI: 10.1111/bph.15652 -
Acta Tropica Dec 2019China was once a country plagued by parasitic diseases. At the beginning of the founding of the People's Republic of China, nearly 80% of the population suffered from... (Review)
Review
China was once a country plagued by parasitic diseases. At the beginning of the founding of the People's Republic of China, nearly 80% of the population suffered from parasitic diseases because of poverty and poor sanitary conditions. After nearly 70 years of development, China has made remarkable achievements in the prevention and control of parasitic diseases, and the prevalence of parasitic diseases has been greatly reduced. In addition to organizational leadership from the government and various preventive measures, drug treatment and drug research & development are important and irreplaceable links in prevention and control work. Since the 1950s, China has begun to introduce, produce and imitate antiparasitic drugs from abroad, such as santonin, benzimidazole, and praziquantel. Chinese scientists have also contributed to the optimization of production techniques, improvements in drug formulation, the application in the clinic and the mechanisms of actions of generic drugs. At the same time, China has independently developed tribendimidine (TrBD, a broad spectrum anthelminthic), and its anthelminthic spectrum has been comprehensively studied. It is active against almost 20 parasites, is especially superior to benzimidazoles against Necator americanus, and surpasses the effectiveness of praziquantel against Clonorchis sinensis. In the treatment of tapeworm disease, the traditional Chinese medicines pumpkin seeds and betel nuts have good curative effects for taeniasis. Chinese scientists have explored the action modes and clinical administration methods of pumpkin seeds and betel nuts, which is still the main clinical regimen for the disease. This paper reviews the history and progress of the study of anthelmintics in intestinal helminth infections since the founding of the People's Republic of China and aiming to support clinicians and drug researchers in China and other countries.
Topics: Animals; Anthelmintics; Cestode Infections; China; Clonorchis sinensis; Helminthiasis; History, 20th Century; History, 21st Century; Humans; Intestinal Diseases, Parasitic; Parasitic Diseases; Phenylenediamines; Praziquantel; Taeniasis
PubMed: 31542370
DOI: 10.1016/j.actatropica.2019.105181 -
British Medical Bulletin Sep 2017In endemic areas, schistosomiasis causes both overt and subclinical disease in young children and their mothers, as well as in returned travellers. (Review)
Review
BACKGROUND
In endemic areas, schistosomiasis causes both overt and subclinical disease in young children and their mothers, as well as in returned travellers.
SOURCES OF DATA
Key recently published literature.
AREAS OF AGREEMENT
An action plan for paediatric schistosomiasis and female genital schistosomiasis (FGS) is needed with expanded access to praziquantel (PZQ) treatment required.
AREAS OF CONTROVERSY
Schistosomiasis-related morbidity is underappreciated. Present and future demand for PZQ treatment is bottlenecked, imbalanced and inequitable. Current dosing, treatment algorithms and access plans are suboptimal with treatment stalled during pregnancy.
GROWING POINTS
Raised dosing of PZQ (>40 mg/kg) is being explored in young children. Surveillance of female genital schistosomiasis FGS is increasing. Use of PZQ in pregnancy is safe and preventive chemotherapy guidelines are being revised in morbidity- and transmission-control settings.
AREAS TIMELY FOR DEVELOPING RESEARCH
Shifting focus of population-level control to individual-case management. Detection and prevention of FGS within general health services and integration of PZQ treatment for women and children in antenatal clinics. Feasibility studies assessing alternative and expanded access to PZQ treatment to at-risk children and mothers and pregnant women.
Topics: Anthelmintics; Child; Communicable Diseases, Imported; Female; Humans; Praziquantel; Pregnancy; Pregnancy Complications, Parasitic; Schistosomiasis
PubMed: 28910994
DOI: 10.1093/bmb/ldx028 -
Trends in Parasitology Jan 2022Schistosomiasis is a debilitating helminthiasis which commonly establishes as a chronic infection in people from endemic areas. As a potent modulator of the host immune... (Review)
Review
Schistosomiasis is a debilitating helminthiasis which commonly establishes as a chronic infection in people from endemic areas. As a potent modulator of the host immune response, the Schistosoma parasite and its associated products can directly interfere with its host's ability to mount adequate immune responses to unrelated antigens. As a result, increased attention is gathering on studies assessing the influence of helminths, particularly the causal agent of schistosomiasis, on host responsiveness to vaccines. However, to date, no consensus has been drawn regarding the influence of schistosomiasis on host vaccine responses. Here, we review available evidence on the influence of transgenerational and direct Schistosoma parasite exposure on host immune responses to unrelated vaccines. In addition, we evaluate the potential of praziquantel (PZQ) treatment in restoring schistosomiasis-impacted vaccine responses.
Topics: Animals; Anthelmintics; Humans; Immunity; Praziquantel; Schistosoma; Schistosomiasis; Vaccines
PubMed: 34389214
DOI: 10.1016/j.pt.2021.07.009 -
Future Medicinal Chemistry Jan 2018Praziquantel has remained the drug of choice for schistosomiasis chemotherapy for almost 40 years. The pressing need to develop a new antischistosomal drug may... (Review)
Review
Praziquantel has remained the drug of choice for schistosomiasis chemotherapy for almost 40 years. The pressing need to develop a new antischistosomal drug may necessitate exploring and filtering chemotherapeutic history to search for the most promising ones. In this context, this review attempts to summarize all progress made in schistosomiasis chemotherapy from the early 20th century (mid-1910s) to 2016. We gathered almost 100 compounds providing information on therapeutic action, specifically covering at least first in vivo studies in animal model and in vitro. Pharmacokinetic and toxicity profiles of antischistosomal agents were also described. Preclinical studies indicate a handful of promising future candidates.
Topics: Animals; Anthelmintics; Humans; Parasitic Sensitivity Tests; Praziquantel; Schistosoma; Schistosomiasis
PubMed: 29235368
DOI: 10.4155/fmc-2017-0112 -
Advances in Parasitology 2022Schistosomiasis is a poverty-associated tropical disease caused by blood dwelling trematodes that threaten approximately 10% of the world population. Praziquantel, the... (Review)
Review
Schistosomiasis is a poverty-associated tropical disease caused by blood dwelling trematodes that threaten approximately 10% of the world population. Praziquantel, the sole drug currently available for treatment, is insufficient to eliminate the disease and the clinical drug development pipeline is empty. Here, we review the characteristics of the patent Schistosoma mansoni mouse model used for in vivo antischistosomal drug discovery, highlighting differences in the experimental set-up across research groups and their potential influence on experimental results. We explore the pharmacokinetic/pharmacodynamic relationship of selected drug candidates, showcasing opportunities to improve the drug profile to accelerate the transition from the early drug discovery phase to new clinical candidates.
Topics: Animals; Drug Discovery; Mice; Praziquantel; Schistosoma mansoni; Schistosomiasis; Schistosomiasis mansoni; Schistosomicides
PubMed: 35878949
DOI: 10.1016/bs.apar.2022.05.002