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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 -
The New England Journal of Medicine Dec 2019
Topics: Africa, Southern; Animals; Female; Genital Diseases, Female; HIV Infections; Humans; Life Cycle Stages; Praziquantel; Reproductive Health; Schistosoma haematobium; Schistosomiasis haematobia; Schistosomicides; Sexually Transmitted Diseases
PubMed: 31881137
DOI: 10.1056/NEJMp1914709 -
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 -
The Cochrane Database of Systematic... Jun 2021Neurocysticercosis is a parasitic infection of the central nervous system by the larval stage of the pork tapeworm and is a common cause of seizures and epilepsy in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Neurocysticercosis is a parasitic infection of the central nervous system by the larval stage of the pork tapeworm and is a common cause of seizures and epilepsy in endemic areas. Anthelmintics (albendazole or praziquantel) may be given alongside supportive treatment (antiepileptics/analgesia) with the aim of killing these larvae (cysticerci), with or without corticosteroid treatment. However, there are potential adverse effects of these drugs, and the cysticerci may eventually die without directed anthelminthic treatment.
OBJECTIVES
To assess the effects of anthelmintics on people with neurocysticercosis.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, the WHO ICTRP, and ClinicalTrials.gov, up to 21 October 2020.
SELECTION CRITERIA
Randomized controlled trials comparing anthelmintics and supportive treatment (+/- corticosteroids) with supportive treatment alone (+/- corticosteroids) for people with neurocysticercosis.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the title and abstract of all articles identified by the search. We obtained full-text articles to confirm the eligibility of all studies that passed screening. One review author extracted data, which a second review author checked. Two review authors assessed the risk of bias of each trial and performed GRADE assessments. In cases of disagreement at consensus discussion stage between review authors, we consulted a third review author. We calculated risk ratios (RR) for dichotomous variables, with 95% confidence intervals (CIs) for pooled data from studies with similar interventions and outcomes.
MAIN RESULTS
We included 16 studies in the review. Only two studies investigated praziquantel and did not report data in a format that could contribute to meta-analysis. Most results in this review are therefore applicable to albendazole versus placebo or no anthelmintic. The aggregate analysis across all participants with neurocysticercosis did not demonstrate a difference between groups in seizure recurrence, but heterogeneity was marked (RR 0.94, 95% CI 0.78 to 1.14; 10 trials, 1054 participants; I = 67%; low-certainty evidence). When stratified by participants with a single cyst or multiple cysts, pooled analysis suggests that albendazole probably improves seizure recurrence for participants with a single cyst (RR 0.61, 95% CI 0.4 to 0.91; 5 trials, 396 participants; moderate-certainty evidence). All studies contributing to this analysis recruited participants with non-viable, intraparenchymal cysts only, and most participants were children. We are uncertain whether or not albendazole reduces seizure recurrence in participants with multiple cysts, as the certainty of the evidence is very low, although the direction of effect is towards albendazole causing harm (RR 2.05, 95% CI 1.28 to 3.31; 2 trials, 321 participants; very low-certainty evidence). This analysis included a large study containing a highly heterogeneous population that received an assessment of unclear risk for multiple 'Risk of bias' domains. Regarding radiological outcomes, albendazole probably slightly improves the complete radiological clearance of lesions (RR 1.22, 95% CI 1.07 to 1.39; 13 trials, 1324 participants; moderate-certainty evidence) and the evolution of cysts (RR 1.27, 95% CI 1.10 to 1.47; 6 trials, 434 participants; moderate-certainty evidence). More adverse events appeared to be observed in participants treated with either albendazole or praziquantel compared to those receiving placebo or no anthelmintic. The most commonly reported side effects were headache, abdominal pain, and nausea/vomiting.
AUTHORS' CONCLUSIONS
For participants with a single cyst, there was less seizure recurrence in the albendazole group compared to the placebo/no anthelmintic group. The studies contributing to this evidence only recruited participants with a non-viable intraparenchymal cyst. We are uncertain whether albendazole reduces seizure recurrence for participants with multiple cysts. We also found that albendazole probably increases radiological clearance and evolution of lesions. There were very few studies reporting praziquantel outcomes, and these findings apply to albendazole only.
Topics: Adult; Albendazole; Anticestodal Agents; Bias; Brain Diseases; Child; Humans; Neurocysticercosis; Placebos; Praziquantel; Randomized Controlled Trials as Topic; Seizures
PubMed: 34060667
DOI: 10.1002/14651858.CD000215.pub5 -
The American Journal of Tropical... Jan 2020Subarachnoid neurocysticercosis (SUBNCC) is usually caused by an aberrant proliferative form of causing mass effect and arachnoiditis. Thirty of 34 SUBNCC patients were...
Subarachnoid neurocysticercosis (SUBNCC) is usually caused by an aberrant proliferative form of causing mass effect and arachnoiditis. Thirty of 34 SUBNCC patients were treated with extended cysticidal and anti-inflammatory regimens and followed up a median of 4.2 years posttreatment (range: 15 for ≥ 4 years, 20 ≥ 2 years, 26 > 1 year, and 3 < 1 year). The median ages at the time of first symptom, diagnosis, and enrollment were 29.7, 35.6, and 37.9 years, respectively; 58.8% were male and 82.4% were Hispanic. The median time from immigration to symptoms (minimum incubation) was 10 years and the estimated true incubation period considerably greater. Fifty percent also had other forms of NCC. Common complications were hydrocephalus (56%), shunt placement (41%), infarcts (18%), and symptomatic spinal disease (15%). Thirty patients (88.2%) required prolonged treatment with albendazole (88.2%, median 0.55 year) and/or praziquantel (61.8%; median 0.96 year), corticosteroids (88.2%, median 1.09 years), methotrexate (50%, median 1.37 years), and etanercept (34.2%, median 0.81 year), which led to sustained inactive disease in 29/30 (96.7%) patients. Three were treated successfully for recurrences and one has continuing infection. Normalization of cerebral spinal fluid parameters and cestode antigen levels guided treatment decisions. All 15 patients with undetectable cestode antigen values have sustained inactive disease. There were no deaths and moderate morbidity posttreatment. Corticosteroid-related side effects were common, avascular necrosis of joints being the most serious (8/33, 24.2%). Prolonged cysticidal treatment and effective control of inflammation led to good clinical outcomes and sustained inactive disease which is likely curative.
Topics: Adolescent; Adult; Albendazole; Animals; Anthelmintics; Anti-Inflammatory Agents; Antigens, Helminth; Child; Female; Humans; Male; Middle Aged; Neurocysticercosis; Praziquantel; Subarachnoid Space; Taenia solium; Young Adult
PubMed: 31642423
DOI: 10.4269/ajtmh.19-0436 -
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 -
Zoonoses and Public Health Dec 2019Cystic echinococcosis (CE), caused by Echinococcus granulosus, is a chronic and debilitating zoonotic larval cestode infection in humans, which is principally... (Review)
Review
Cystic echinococcosis (CE), caused by Echinococcus granulosus, is a chronic and debilitating zoonotic larval cestode infection in humans, which is principally transmitted between dogs and domestic livestock, particularly sheep. Human CE occurs in almost all pastoral communities and rangeland areas of the underdeveloped and developed world. Control programmes against CE have been implemented in several endemic countries to reduce or eliminate the disease. New Zealand and Tasmania are examples of some of the first programmes to be undertaken (in insular territories) and which were very successful in the elimination of CE. The advent and proven effectiveness of praziquantel, plus the experience of insular models, produced high expectations for rapid advances in a second generation of control programmes undertaken in continental areas (Argentina, Uruguay and Chile). Nevertheless, only moderate gains in CE control have been made and the impact on prevalence among humans has been slight. A major impediment to the adoption of procedures that were successful in New Zealand and Tasmania has been the requirement to administer praziquantel to dogs in rural areas eight times per year over numerous years. In addition, there have been clear technological improvements made in the diagnosis of canine echinococcosis for surveillance, the genetic characterization of parasite strains and in vaccination against CE infection in livestock. In order to establish new paradigms and appropriate combinations of control strategies, we have carried out a review and discussion of the available control tools and control models. Control strategies must be suitable and sustainable to benefit the Echinococcosis-endemic areas primarily, which at the same time are the poorest regions of the world.
Topics: Animals; Anthelmintics; Argentina; Chile; Dog Diseases; Dogs; Echinococcosis; Echinococcus granulosus; Humans; Livestock; Praziquantel; Prevalence; Sheep; Sheep Diseases; Uruguay; Zoonoses
PubMed: 31529690
DOI: 10.1111/zph.12649 -
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 -
World Neurosurgery Apr 2024Pseudotumoral encephalic schistosomiasis (PES) is the chronic form of cerebral neuroschistosomiasis, and is rarely encountered in clinical practice. Clinically, PES... (Review)
Review
Pseudotumoral encephalic schistosomiasis (PES) is the chronic form of cerebral neuroschistosomiasis, and is rarely encountered in clinical practice. Clinically, PES closely resembles other intracranial space-occupying lesions including brain tumors. Laboratory investigations are usually inconclusive, and neuroradiologic findings are frequently reported as non-specific. Such diagnostic difficulties may result in delayed diagnosis and treatment. Across the literature, there is a paucity of information about and controversy over many aspects of the disease. Particularly, inconsistent magnetic resonance imaging (MRI) findings, a wide variation of medical treatment protocols, lacking consensus regarding the indications of surgery, and undetermined information regarding the impact of the extent of resection on prognosis. We herein review the pertinent literature with the aim of providing focused information regarding the pathogenesis of PES, its currently identified more distinctive neuroimaging features, and the indications and extent of surgery in light of the state-of-the-art operative neurosurgical practice. A distinctive multinodular arborizing pattern of PES lesions can often be observed on MRI in patients with PES. Praziquantel is considered by many authors to be the drug of choice in all cases, and seems to be effective at variable dose regimens. Although lesion excision utilizing current technology is generally safe, the indications and extent of surgery are still undetermined and should be decided on a case-by-case basis. Multicenter collaborative research is further needed to fill the existing gaps in the current knowledge on PES.
Topics: Humans; Brain; Praziquantel; Neuroschistosomiasis; Prognosis; Multicenter Studies as Topic
PubMed: 38159601
DOI: 10.1016/j.wneu.2023.12.134 -
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