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PLoS Neglected Tropical Diseases Sep 2011Praziquantel remains the drug of choice for the worldwide treatment and control of schistosomiasis. The drug is synthesized and administered as a racemate. Use of the...
BACKGROUND
Praziquantel remains the drug of choice for the worldwide treatment and control of schistosomiasis. The drug is synthesized and administered as a racemate. Use of the pure active enantiomer would be desirable since the inactive enantiomer is associated with side effects and is responsible for the extremely bitter taste of the pill.
METHODOLOGY/PRINCIPAL FINDINGS
We have identified two resolution approaches toward the production of praziquantel as a single enantiomer. One approach starts with commercially available praziquantel and involves a hydrolysis to an intermediate amine, which is resolved with a derivative of tartaric acid. This method was discovered through an open collaboration on the internet. The second method, identified by a contract research organisation, employs a different intermediate that may be resolved with tartaric acid itself.
CONCLUSIONS/SIGNIFICANCE
Both resolution procedures identified show promise for the large-scale, economically viable production of praziquantel as a single enantiomer for a low price. Additionally, they may be employed by laboratories for the production of smaller amounts of enantiopure drug for research purposes that should be useful in, for example, elucidation of the drug's mechanism of action.
Topics: Anthelmintics; Chemistry, Pharmaceutical; Humans; International Cooperation; Praziquantel; Schistosomiasis; Stereoisomerism; Technology, Pharmaceutical
PubMed: 21949890
DOI: 10.1371/journal.pntd.0001260 -
International Journal of Infectious... Jan 2017Mass drug administration utilising a single oral dose of 40mg/kg of praziquantel (PZQ) has been endorsed and advocated by the World Health Organisation (WHO) for the...
Mass drug administration utilising a single oral dose of 40mg/kg of praziquantel (PZQ) has been endorsed and advocated by the World Health Organisation (WHO) for the global control and elimination of schistosomiasis. However, this strategy is failing primarily because the drugs are not getting to the people who need them the most. The current global coverage is 20%, the drug compliance rate is less than 50%, and the drug efficacy is approximately 50%. Thus in reality, only about 5% of the reservoir human population is actually receiving intermittent chemotherapy. Despite claims that more of the drug will soon be made available the current strategy is inherently flawed and will not lead to disease elimination. We discuss the many practical issues related to this global strategy, and advocate for an integrated control strategy targeting the life cycle and the most at-risk. Moreover, we discuss how an integrated control package for schistosomiasis should fit within a larger integrated health package for rural and remote villages in the developing world. A holistic health system approach is required to achieve sustainable control and ultimately disease elimination.
Topics: Anthelmintics; Global Health; Humans; Infection Control; Population Groups; Praziquantel; Rural Population; Schistosomiasis
PubMed: 27939558
DOI: 10.1016/j.ijid.2016.09.023 -
The National Medical Journal of India 1997Neurocysticercosis, the most common parasitic disease of the central nervous system, was treated surgically for a long time. Praziquantel (an isoquinolone) and... (Review)
Review
Neurocysticercosis, the most common parasitic disease of the central nervous system, was treated surgically for a long time. Praziquantel (an isoquinolone) and albendazole (an imidazole) are anticysticercal drugs that are currently being used for the treatment of neurocysticercosis. Both have been reported to eliminate or markedly reduce the number and size of cysticerci. Albendazole is less expensive than praziquantel, and is as effective when given for 8 days as compared to longer periods. In a small number of comparative trials, albendazole appeared to be slightly more effective than praziquantel for the treatment of parenchymal cysticercosis. Albendazole has also been found effective in ventricular, subarachnoidal and racemose forms of the disease. However, the response to treatment is not universal. Treatment with these drugs has been associated with a high frequency of adverse reactions, probably due to the host's inflammatory reaction to the dying parasites. Headache, nausea and seizures are common but usually transient. Steroids appear to ameliorate these effects and their concomitant administration has been advocated. However, no data are available to support this view. The rationale of medical therapy in spinal cysticercosis is presently based on the reported efficacy of anticysticercal drugs in cerebral cysticercosis. A marked improvement in an associated seizure disorder following anticysticercal therapy has been observed. Though seizure control is better, the total duration of anti-epileptic drug therapy has not been determined. Some single enhancing computed tomography lesions in patients of epilepsy may be benign forms of neurocysticercosis. The spontaneous resolution of a majority of these lesions has led to doubts of them being merely infective in aetiology. Also, a controlled trial could not demonstrate any beneficial effect of albendazole on such lesions. Hence, most authors recommend that these patients should be treated with anti-epileptic drugs only. Doubts persist about the efficacy of anticysticercal drugs in altering the natural course of the disease and the reported tendency of cysticercus lesions to resolve.
Topics: Adrenal Cortex Hormones; Albendazole; Anthelmintics; Antiplatyhelmintic Agents; Central Nervous System Diseases; Cysticercosis; Drug Interactions; Humans; Praziquantel
PubMed: 9325640
DOI: No ID Found -
Clinical Medicine (London, England) Oct 2011
Topics: Animals; Anthelmintics; Endemic Diseases; Humans; Life Cycle Stages; Praziquantel; Schistosoma; Schistosomiasis; Travel
PubMed: 22034712
DOI: 10.7861/clinmedicine.11-5-479 -
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 -
Asian Pacific Journal of Cancer... 2013The liver fluke, Opisthorchis viverrini, and the associated incidence of subsequent cholangiocarcinoma (CCA) are still a public health problem in Thailand, and... (Review)
Review
BACKGROUND
The liver fluke, Opisthorchis viverrini, and the associated incidence of subsequent cholangiocarcinoma (CCA) are still a public health problem in Thailand, and praziquantel (PZQ) remains the antihelminthic drug of choice for treatment. Evidence in hamsters shows that repeated infection and PZQ treatments could increase the risk of CCA. However, the existing evidence in humans is inconclusive regarding increased risk of CCA with frequency of PZQ intake.
OBJECTIVES
To investigate the relationship between number of repeated PZQ treatments and CCA in patients with O viverrini infection.
MATERIALS AND METHODS
The reviewed studies were searched in EMBASE, MEDLINE, ProQuest, PubMed and SCOPUS from inception to October, 2012 using prespecified keywords. The risk of bias (ROB) of included studies was independently assessed by two reviewers using a quality scale from the Newcastle-Ottawa Scale (NOS). Risk effect of PZQ was estimated as a pooled odds ratio (OR) with its 95% confidence interval (95%CI) in the random-effects model using DerSimonian and Laird's estimator.
RESULTS
Three studies involving 637 patients were included. Based on the random effects model performed in two included studies of 237 patients, the association between PZQ treatments and CCA was not statistical significant with a pooled OR of 1.8 (95%CI; 0.81 to 4.16).
CONCLUSIONS
The present systematic review and meta-analysis provides inconclusive evidence of risk effect of PZQ on increasing the risk of CCA and significant methodological limitations. Further research is urgently needed to address the shortcomings found in this review, especially the requirement for histological confirmation.
Topics: Animals; Anthelmintics; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Humans; Opisthorchiasis; Opisthorchis; Praziquantel; Prognosis
PubMed: 24377641
DOI: 10.7314/apjcp.2013.14.11.7011 -
PLoS Neglected Tropical Diseases 2014Extensive use of praziquantel for treatment and control of schistosomiasis requires a comprehensive understanding of efficacy and safety of various doses for different... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Extensive use of praziquantel for treatment and control of schistosomiasis requires a comprehensive understanding of efficacy and safety of various doses for different Schistosoma species.
METHODOLOGY/PRINCIPAL FINDINGS
A systematic review and meta-analysis of comparative and non-comparative trials of praziquantel at any dose for any Schistosoma species assessed within two months post-treatment. Of 273 studies identified, 55 were eligible (19,499 subjects treated with praziquantel, control treatment or placebo). Most studied were in school-aged children (64%), S. mansoni (58%), and the 40 mg/kg dose (56%); 68% of subjects were in Africa. Efficacy was assessed as cure rate (CR, n=17,017) and egg reduction rate (ERR, n=13,007); safety as adverse events (AE) incidence. The WHO-recommended dose of praziquantel 40 mg/kg achieved CRs of 94.7% (95%CI 92.2-98.0) for S. japonicum, 77.1% (68.4-85.1) for S. haematobium, 76.7% (95%CI 71.9-81.2) for S. mansoni, and 63.5% (95%CI 48.2-77.0) for mixed S. haematobium/S. mansoni infections. Using a random-effect meta-analysis regression model, a dose-effect for CR was found up to 40 mg/kg for S. mansoni and 30 mg/kg for S. haematobium. The mean ERR was 95% for S. japonicum, 94.1% for S. haematobium, and 86.3% for S. mansoni. No significant relationship between dose and ERR was detected. Tolerability was assessed in 40 studies (12,435 subjects). On average, 56.9% (95%CI 47.4-67.9) of the subjects receiving praziquantel 40 mg/kg experienced an AE. The incidence of AEs ranged from 2.3% for urticaria to 31.1% for abdominal pain.
CONCLUSIONS/SIGNIFICANCE
The large number of subjects allows generalizable conclusions despite the inherent limitations of aggregated-data meta-analyses. The choice of praziquantel dose of 40 mg/kg is justified as a reasonable compromise for all species and ages, although in a proportion of sites efficacy may be lower than expected and age effects could not be fully explored.
Topics: Africa; Animals; Anthelmintics; Feces; Humans; Incidence; Intestines; Praziquantel; Schistosoma haematobium; Schistosomiasis haematobia; Schistosomiasis mansoni; Treatment Outcome
PubMed: 25412105
DOI: 10.1371/journal.pntd.0003286 -
Journal of Veterinary Internal Medicine May 2021Established treatment protocols for schistosomiasis (Heterobilharzia americana) in dogs are expensive. Anecdotal reports suggest that lower doses of praziquantel,...
BACKGROUND
Established treatment protocols for schistosomiasis (Heterobilharzia americana) in dogs are expensive. Anecdotal reports suggest that lower doses of praziquantel, combined with fenbendazole, may eliminate asymptomatic infections.
OBJECTIVES
Evaluate the efficacy of a low-dose praziquantel and fenbendazole protocol to manage asymptomatic schistosomiasis in dogs and compare fecal saline sedimentation (FSS) and fecal PCR (FPCR) for therapeutic monitoring.
ANIMALS
Twelve asymptomatic dogs with positive FPCR and FSS results for schistosomiasis.
METHODS
Prospective observational study. On day 0, dogs received praziquantel at a median dose of 5 mg/kg PO q8h for 2 days, with fenbendazole at 24 mg/kg PO q24h for 7 days. Fecal PCR and FSS were repeated in all dogs on days 30, 60, and 90.
RESULTS
By day 30, 10 of 12 dogs were negative by FSS, but only 3 of 12 were negative by FPCR. By day 60, all 12 dogs were negative by FSS, and 8 of 12 had become negative by FPCR. By day 90, all 12 dogs remained negative by FSS, but 5 of 12 were positive by FPCR (including 2 that were negative by FPCR on day 60). Three dogs that were positive by FPCR on day 60 were re-treated and subsequently became both FPCR and FSS negative. One FPCR-positive dog developed a mild increase in serum ALP activity, another developed mild hypercalcemia, and a third developed diarrhea.
CONCLUSIONS AND CLINICAL IMPORTANCE
A low-dose praziquantel/fenbendazole protocol may be effective for asymptomatic schistosomiasis in some dogs, but monitoring to ensure treatment success is recommended. Fecal saline sedimentation and FPCR may demonstrate discrepant results, with FPCR being positive more frequently.
Topics: Animals; Dog Diseases; Dogs; Fenbendazole; Praziquantel; Schistosomatidae; Schistosomiasis
PubMed: 33955589
DOI: 10.1111/jvim.16142 -
International Journal For Parasitology.... Aug 2023Anoplocephalid tapeworms are commonly occurring in grazing horses around the world. Two currently available anthelmintics have documented high efficacy against...
Anoplocephalid tapeworms are commonly occurring in grazing horses around the world. Two currently available anthelmintics have documented high efficacy against Anoplocephala perfoliata; praziquantel in various dosages ranging from 1.0 to 2.5 mg/kg and pyrantel pamoate administered at 13.2 mg base/kg. Anthelmintic resistance has not been reported in A. perfoliata, but anecdotal reports made during 2022 have suggested a possible loss of efficacy for both actives. This paper reports fecal egg count data from a Thoroughbred operation in Central Kentucky in 2023. Fifty-six yearlings were first dewormed with a combination of ivermectin (200 μg/kg) and praziquantel (1.5 mg/kg) and subsequently treated with pyrantel pamoate (13.2 mg base/kg). Fecal egg counts were determined at the day of treatment and again 14 days post-treatment. Two groups of mares (n = 39 and 45) were also treated with ivermectin/praziquantel and examined pre- and post-treatment. Low efficacy of ivermectin and pyrantel pamoate was demonstrated against strongylid parasites in the yearlings with mean Fecal Egg Count Reductions (FECRs) at 75.6% or below and upper 95% credible interval (CI) limits below 90% in all cases. Overall anti-cestodal FECR levels in the yearlings were 23.5% (95% CI: 11.2-48.0) for praziquantel and 50.9% (20.5-72.0) for pyrantel pamoate. Praziquantel eliminated anoplocephalid eggs from three of 17 yearlings, but another 5 yearlings went from negative to positive status following treatment. Pyrantel pamoate failed to eliminate anoplocephalid eggs from any of 14 treated tapeworm-positive yearlings. Nine of 84 mares tested positive for anoplocephalid eggs, and seven of these were still positive post praziquantel treatment. These findings sharply contrast data from historic field efficacy studies conducted for both actives and raise concern about anthelmintic resistance having possibly developed. This emphasizes the need for developing and refining antemortem methodologies for evaluating anti-cestodal treatment efficacy and for searching for possible alternative treatment options.
Topics: Animals; Horses; Female; Pyrantel Pamoate; Praziquantel; Ivermectin; Horse Diseases; Anthelmintics; Cestoda; Treatment Failure; Feces; Treatment Outcome; Parasite Egg Count
PubMed: 37354849
DOI: 10.1016/j.ijpddr.2023.06.002 -
Ui Sahak Aug 2021The Korean parasite control program is regarded as one of the most successful examples of health care movement in Korea. This 'Parasite Eradication Program' which was...
The Korean parasite control program is regarded as one of the most successful examples of health care movement in Korea. This 'Parasite Eradication Program' which was conducted from 1969 to 1995, involved testing and treating of 300 million people. In cooperation with Japan, parasitologists and activists who participated in the parasite control program formed a common system called the 'Mass Testing, Mass Treatment.' This study focuses on the localization process of Praziquantel, Clonorchiasis treatment production and its application in Clonorchiasis control program. Parasitologists rapidly introduced newly developed Praziquantel, and Korean chemists quickly reverse engineered the compound to evade patent issues. This allowed for the mass production of Praziquantel at a lower price, which in turn enabled a nationwide Clonorchiasis control program. At the same time, low price and stable supply opened the private market for Praziquantel. However, acceptance and understanding of the Praziquantel differed significantly among the stakeholders. For the government, it was a means for policy propaganda, and for the health agencies, it was a means for mass scale control program, while for the public, it was a means for maintaining conventional eating habits without risk of infection. This study reveals how the material end of a disease control policy is accepted and interpreted by different actors.
Topics: Animals; Clonorchiasis; Clonorchis sinensis; Humans; Japan; Praziquantel; Republic of Korea
PubMed: 34663774
DOI: 10.13081/kjmh.2021.30.317