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PLoS Neglected Tropical Diseases Jul 2014Treatment and morbidity control of schistosomiasis relies on a single drug, praziquantel. Hence, there is a pressing need to develop additional therapeutics against... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Treatment and morbidity control of schistosomiasis relies on a single drug, praziquantel. Hence, there is a pressing need to develop additional therapeutics against schistosomiasis. The antimalarial drug mefloquine shows antischistosomal activity in animal models and clinical trials, which calls for further investigations.
METHODOLOGY
We comparatively assessed the efficacy and tolerability of the following treatments against Schistosoma haematobium in school-aged children in Côte d'Ivoire: (i) praziquantel (40 mg/kg; standard treatment); (ii) mefloquine (25 mg/kg) combined with praziquantel (40 mg/kg); and (iii) mefloquine-artesunate (3× (100 mg artesunate +250 mg mefloquine)) combined with praziquantel (40 mg/kg) (treatments administered on subsequent days). Two urine samples were collected before, and on days 21-22 and 78-79 after the first dosing.
PRINCIPAL FINDINGS
Sixty-one children were present on all examination time points and had complete datasets. No difference in efficacy was observed between the three treatment groups on either follow-up. On the 21-22 day posttreatment follow-up, based on available case analysis, cure rates of 33% (95% confidence interval (CI) 11-55%), 29% (95% CI 8-50%), and 26% (95% CI 5-48%) were observed for praziquantel, mefloquine-artesunate-praziquantel, and mefloquine-praziquantel, respectively. The corresponding egg reduction rates were 94% and above. On the second follow-up, observed cure rates ranged from 19% (praziquantel) to 33% (mefloquine-artesunate-praziquantel), and egg reduction rates were above 90%. Praziquantel monotherapy was the best tolerated treatment. In the mefloquine-artesunate-praziquantel group, adverse events were reported by 91% of the participants, and in the mefloquine-praziquantel group, 95% experienced adverse events. With the exception of abdominal pain at moderate severity, adverse events were mild.
CONCLUSIONS/SIGNIFICANCE
The addition of mefloquine or mefloquine-artesunate does not increase the efficacy of praziquantel against chronic S. haematobium infection. Additional studies are necessary to elucidate the effect of the combinations against acute schistosomiasis.
Topics: Adolescent; Animals; Anthelmintics; Artemisinins; Artesunate; Child; Cote d'Ivoire; Drug Therapy, Combination; Female; Humans; Male; Mefloquine; Praziquantel; Schistosoma haematobium; Schistosomiasis haematobia
PubMed: 25033291
DOI: 10.1371/journal.pntd.0002975 -
International Journal For Parasitology.... Apr 2022Parasitic diseases are major constraints in fish mariculture. The anthelmintic praziquantel (PZQ) can effectively treat a range of flatworm parasites in a variety of... (Review)
Review
Parasitic diseases are major constraints in fish mariculture. The anthelmintic praziquantel (PZQ) can effectively treat a range of flatworm parasites in a variety of fish species and has potential for broader application than its current use in the global aquaculture industry. In this review we report on PZQ's current use in the aquaculture industry and discuss its efficacy against various flatworm parasites of fish. Routes of PZQ administration are evaluated, along with issues related to palatability, pharmacokinetics and toxicity in fish, while PZQ's effects on non-target species, environmental impacts, and the development of drug-resistance are discussed.
Topics: Animals; Anthelmintics; Aquaculture; Platyhelminths; Praziquantel
PubMed: 35220160
DOI: 10.1016/j.ijpddr.2022.02.001 -
Infectious Diseases of Poverty Feb 2018Chemotherapy for schistosomiasis has been around for 100 years. During the past century, great efforts have been made to develop new antischistosomal drugs from... (Review)
Review
BACKGROUND
Chemotherapy for schistosomiasis has been around for 100 years. During the past century, great efforts have been made to develop new antischistosomal drugs from antimonials to nonantimonials, and some of these have been used extensively in clinical treatment. With the exception of a few drugs, such as oxamniquine and metrifonate, most of the antischistosomals developed in the pre-praziquantel period have variable limitations with respect to safety and efficacy. Although oxamniquine and metrifonate have been used for schistosomiasis control, they are only effective against Schistosoma mansoni and S. haematobium, respectively. Currently, praziquantel is the only drug used for treatment of all five species of human schistosomes. In this review, the pharmacological and immunological effects of praziquantel against S. japonicum are summarized and discussed.
MAIN TEXT
From the end of the 1970s until the 2000s, scientists have conducted a series of experimental studies on the effects of praziquantel against S. japonicum. These have included examining its unique pharmacological action on schistosomes, the characteristics in susceptibility of the different developmental stages of schistosomes to the drug, the relationship between plasma concentration of the drug and efficacy, the impact of host factors on cidal action of the drug, prevention and early treatment of schistosomal infection, as well as praziquantel-resistant schistosomiasis.
CONCLUSION
The effects of praziquantel against S. japonicum, as elucidated by the experimental studies that are reviewed in this paper, may have some reference significance for the development of new antischistosomals.
Topics: Animals; Drug Resistance; Humans; Life Cycle Stages; Mice; Praziquantel; Schistosoma japonicum; Schistosoma mansoni; Schistosomiasis; Schistosomicides
PubMed: 29409536
DOI: 10.1186/s40249-018-0391-x -
Parasites & Vectors Oct 2011Praziquantel has been used as first-line drug for chemotherapy of schistosomiasis since 1984. Besides praziquantel, artemether and artesunate have also been used for the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Praziquantel has been used as first-line drug for chemotherapy of schistosomiasis since 1984. Besides praziquantel, artemether and artesunate have also been used for the control of this infectious disease since late 1990s. In this article, we conducted a systematic review and meta-analysis to evaluate the antischistosomal efficacy of different medication strategies including monotherapy or combination therapies of these drugs.
RESULTS
A number of 52 trials from 38 articles published in peer-reviewed journals before July 2011 were selected for analysis after searching the following literature databases: the Cochrane Library, PubMed/Medline, ISI Web of Science, Chinese Biomedicine Literature Database, and China National Knowledge Infrastructure. Our meta-analyses showed that a dosage of 30-60 mg/kg praziquantel compared with placebo produced a protection rate of about 76% (95% CI: 67%-83%) for treating human schistosomiasis, which varied from 70% to 76% with no significant differences among the subspecies S. haematobium, S. japonicum or S. mansoni. Protection rates were higher when praziquantel doses were elevated, as concluded from the nRCTs results: the protection rate of praziquantel at 40 mg/kg was 52% (95% CI: 49%-55%), and it increased to 91% (95% CI: 88%-92%) when the dosages were elevated to 60/80/100 mg/kg divided two or more doses. Multiple doses of artemether or artesunate over 1- or 2-week intervals resulted in protection rates of 65% to 97% for preventing schistosomiasis, and increased doses and shorter medication intervals improved their efficacies. Praziquantel and artemisinin derivatives (artemether or artesunate) in combination resulted in a higher protection rate of 84% (95% CI: 64%-91%) than praziquantel monotherapy for treatment. praziquantel and artesunate in combination had a great protection rate of 96% (95% CI: 78%-99%) for preventing schistosomes infection.
CONCLUSIONS
According to the results, praziquantel remains effective in schistosomiasis treatment, and multiple doses would improve its efficacy; meanwhile, praziquantel is also a good drug for preventing acute schistosomiasis morbidity. It's better to use multiple doses of artemether or artesunate with 1- or 2-week intervals for prevention against schistosome infection. Praziquantel and artemether or artesunate in combination perform better in treatment than praziquantel monotherapy, and they are especially suitable for treating the patients with repeated exposure to infected water.
Topics: Animals; Artemisinins; Dose-Response Relationship, Drug; Humans; Praziquantel; Randomized Controlled Trials as Topic; Schistosoma; Schistosomiasis; Schistosomicides
PubMed: 22004571
DOI: 10.1186/1756-3305-4-201 -
Scientific Reports Oct 2022This study aimed to assess the toxicity of praziquantel (anthelmintic drug) in different developmental stages of common carp (Cyprinus carpio) based on mortality, early...
This study aimed to assess the toxicity of praziquantel (anthelmintic drug) in different developmental stages of common carp (Cyprinus carpio) based on mortality, early ontogeny, growth, oxidative stress, antioxidant enzymes, histology and behaviour. Praziquantel at all tested concentrations ranging from 1 to 4 mg/L showed no significant adverse effects on mortality, the early ontogeny and behaviour locomotory (activity, moved distance and velocity) of carp after 35-day exposure. Concentrations of 3 and 4 mg/L caused significantly (P < 0.01) lower growth, total superoxide dismutase and catalase activities compared with controls. Praziquantel is safe for the early life of carp in concentrations ≤ 2 mg/L.
Topics: Animals; Antioxidants; Carps; Catalase; Embryo, Nonmammalian; Larva; Praziquantel; Superoxide Dismutase; Water Pollutants, Chemical
PubMed: 36241766
DOI: 10.1038/s41598-022-21679-2 -
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 -
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 -
Antimicrobial Agents and Chemotherapy Aug 2018There is a growing consensus to include preschool-aged children in preventive chemotherapy programs with praziquantel to improve schistosomiasis control. However,...
There is a growing consensus to include preschool-aged children in preventive chemotherapy programs with praziquantel to improve schistosomiasis control. However, pharmacokinetic data, crucial to establish a safe and effective dose for this age group, are sparse. The objective of this study was to establish and compare the pharmacokinetic parameters of praziquantel in preschool- and school-aged children with schistosomiasis. Two pharmacokinetic trials in school- and preschool-aged children infected with or were conducted in Côte d'Ivoire. Dried blood spot samples were taken from 492 children at 10 time points following a single oral dose of 20, 40, or 60 mg/kg of body weight of praziquantel and analyzed using liquid chromatography-mass spectrometry. Noncompartmental analysis (NCA) was performed to obtain the pharmacokinetic parameters of -praziquantel (RPZQ), -praziquantel (SPZQ), and -4-hydroxy-praziquantel. No significant differences in pharmacokinetic parameters between species-specific infections were observed. While pharmacokinetic parameters differed significantly between age groups for , this trend was not observed with Neither the area under the curve (AUC) nor the maximal blood concentration () presented clear dose proportionality for R- and SPZQ. Logistic regression indicated a relationship between the RPZQ AUC and and the probability of cure. Praziquantel is subject to complex metabolic processes following erratic absorption. While the results of NCA are a very informative base for a better understanding of the drug, a more targeted approach in the form of population modeling is needed to quantify the factors influencing metabolic processes and draw conclusions.
Topics: Adolescent; Animals; Child; Child, Preschool; Chromatography, Liquid; Humans; Praziquantel; Schistosoma haematobium; Schistosoma mansoni; Schistosomiasis mansoni; Tandem Mass Spectrometry
PubMed: 29866859
DOI: 10.1128/AAC.02253-17 -
BioMed Research International 2021Soil-transmitted helminths (STHs) and are the main causes of morbidity among schoolchildren in the tropics. A school-based deworming program was launched to control and...
BACKGROUND
Soil-transmitted helminths (STHs) and are the main causes of morbidity among schoolchildren in the tropics. A school-based deworming program was launched to control and eliminate the infection in endemic countries including Ethiopia. Although periodic deworming is conducted in endemic areas, the prevalence of the infection is high in the country. In addition, periodic evaluation of the efficacy of the anthelminthic drug is limited.
OBJECTIVE
This study is aimed at checking the efficacy of mebendazole and praziquantel with the respective STHs and parasites.
METHODS
A longitudinal study was conducted from February to March 2018 among 422 schoolchildren. Stool samples were collected at baseline and at 2 and 4 weeks posttreatment and were processed using the Kato-Katz technique. Schoolchildren positive for STHs were treated with mebendazole and those positive for with praziquantel. After two weeks, a second round of stool was collected and examined, and then, single-dose redosing was given to each positive child. Lastly, the third stool sample was collected two weeks after the initiation of the redosing and checked for STHs and parasites. A close follow-up of students who were treated was done. All the data were entered and analyzed using SPSS version 20 for analysis. Descriptive statistics was used to compute the cure rate and egg reduction rate of mebendazole and praziquantel.
RESULTS
Among 422 participants, the prevalence of STHs, hookworm, , and was 44.7%, 35.1%, 21.1%, and 13.9%, respectively. The cure rate of mebendazole against increased from 60% in the single dose to 100% in redosing after two weeks. The cure rate of mebendazole against hookworm also increased from 32.4% in the single dose to 91.0% in the redosing. The cure rate of praziquantel against -infected children was 91.5% in the first round and 100% in the redosing phase. There was a 98.6-100% egg reduction rate in the redosing regimen of both drugs.
CONCLUSION
The cure and egg reduction rates of single-dose mebendazole in the treatment of hookworm and are lower at week two than at redosing, while cure and egg reduction rates of single-dose praziquantel are satisfactory to treat . Therefore, single-dose praziquantel to and redosing of single-dose mebendazole to and hookworm infections can be used for treatment purposes.
Topics: Adolescent; Animals; Child; Ethiopia; Female; Geography; Helminthiasis; Helminths; Humans; Male; Mebendazole; Ovum; Praziquantel; Schistosoma mansoni; Schistosomiasis mansoni; Schools; Soil; Students; Treatment Outcome
PubMed: 34327236
DOI: 10.1155/2021/6682418 -
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