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Journal of Child Neurology Apr 2022To compare the efficacy of combined albendazole and praziquantel therapy vs albendazole monotherapy in a placebo-controlled, double-blinded, randomized trial in children... (Randomized Controlled Trial)
Randomized Controlled Trial
AIM
To compare the efficacy of combined albendazole and praziquantel therapy vs albendazole monotherapy in a placebo-controlled, double-blinded, randomized trial in children with persisting neurocysticercosis.
METHODS
Children with persistent neurocysticercosis were randomized into 3 groups-albendazole (n = 19), albendazole and praziquantel (n = 21), and placebo (n = 20)-for 30 days and followed up at 3 and 6 months for resolution and recurrence of seizures.
RESULTS
Mean age of children was 9.3 ± 2.9 years (range 3-14). At baseline, the majority of lesions were ring-enhancing (70%), colloidal (97%), with scolex (68%) and perilesional-edema (45%), and located in the parietal (58%) lobe. One case each in albendazole and placebo groups had a recurrence of seizure in the first month of treatment. The majority (62%) of children in the combination therapy group showed complete resolution of the persisting lesion at the end of 6 months compared to the albendazole alone group (26.3%, = .02). Percentage reduction in the lesion's mean area at 6 months was highest in the combination group compared with other groups ( = .006). Rate of calcification was identical in all 3 groups (10%). None of the patients required interruption of therapy.
CONCLUSION
Our study demonstrates the safety and efficacy of albendazole and praziquantel in combination for complete radiologic resolution in children with persistent neurocysticercosis when compared with albendazole monotherapy or placebo. The combination therapy did not result in increased seizure recurrence or adverse drug reaction compared with albendazole monotherapy.
Topics: Adolescent; Albendazole; Anthelmintics; Child; Child, Preschool; Drug Therapy, Combination; Humans; Neurocysticercosis; Praziquantel; Seizures
PubMed: 35213246
DOI: 10.1177/08830738221077762 -
Frontiers in Immunology 2019Like soil-transmitted helminth infections, schistosomiasis is an important neglected tropical disease (NTD) related to poverty with a major impact on public health in... (Review)
Review
The Advances in Molecular and New Point-of-Care (POC) Diagnosis of Schistosomiasis Pre- and Post-praziquantel Use: In the Pursuit of More Reliable Approaches for Low Endemic and Non-endemic Areas.
Like soil-transmitted helminth infections, schistosomiasis is an important neglected tropical disease (NTD) related to poverty with a major impact on public health in developing countries. Diagnosis of active infection is crucial for surveillance of controlled or post-elimination schistosomiasis areas. In addition, the use of conventional diagnostic tools in non-exposed populations (such as travelers) results in misdiagnoses in the prepatent period of infection. Also, the accuracy of standard tests applied in low-endemicity areas (LEAs) decreases after several rounds of treatment. We aimed to determine whether it would be necessary to replace schistosomiasis conventional diagnostic tests such as parasitological methods in LEAs. Also, we evaluate the use of new tools in non-endemic areas. Reliable, cheap and easy-to-use diagnostic tools are needed to respond to the demands of a new era of elimination and eradication of schistosomiasis. To this end, molecular diagnosis-including nucleic acid-based assays (loop-mediated isothermal amplification, polymerase chain reaction) and circulating cathodic and anodic antigen detection tests have become promising strategies. In this review, we attempt to address the use of alternative diagnostic tests for active infection detection and drug-monitoring after specific schistosomiasis treatment.
Topics: Anthelmintics; Antigens, Helminth; Humans; Neglected Diseases; Point-of-Care Systems; Praziquantel; Schistosomiasis
PubMed: 31191512
DOI: 10.3389/fimmu.2019.00858 -
Journal of Proteome Research Jun 2018Schistosomiasis is a widespread chronic neglected tropical disease prevalent mostly in children in under-resourced rural areas. Its pathological effects have been...
Schistosomiasis is a widespread chronic neglected tropical disease prevalent mostly in children in under-resourced rural areas. Its pathological effects have been clinically characterized, yet the molecular-level effects are understudied. In this study, the biochemical effects of Schistosoma mansoni infection and praziquantel treatment were studied in 130 preschool aged and 159 school aged infected children and 11 noninfected children in Azaguié, Côte d'Ivoire. Urine samples were collected prior to receiving 20, 40, or 60 mg/kg of praziquantel or a placebo, as well as 24 h post-treatment, and at the 3-week follow up. Urinary metabolic phenotypes were measured using H NMR spectroscopy, and metabolic variation associated with S. mansoni infection and praziquantel administration was identified using multivariate statistical techniques. Discriminatory metabolic signatures were detected between heavily infected and noninfected children at baseline as well as according to the dose of praziquantel administered 24 h post treatment. These signatures were primarily associated with the metabolic activity of the gut microbiota, gut health and growth biomarkers and energy and liver metabolism. These analyses provide insights into the metabolic phenotype of schistosomiasis and treatment with praziquantel in two important demographics.
Topics: Case-Control Studies; Child; Child, Preschool; Dose-Response Relationship, Drug; Humans; Metabolome; Praziquantel; Proton Magnetic Resonance Spectroscopy; Schistosomiasis mansoni
PubMed: 29701975
DOI: 10.1021/acs.jproteome.7b00910 -
PLoS Neglected Tropical Diseases Jan 2021Even though the international combat against Neglected Tropical Diseases such as schistosomiasis or soil-transmitted helminthiases depends on reliable therapeutics,...
BACKGROUND
Even though the international combat against Neglected Tropical Diseases such as schistosomiasis or soil-transmitted helminthiases depends on reliable therapeutics, anthelminthic pharmacovigilance has been neglected on many national African drug markets. Therefore, quality and composition of Albendazole, Mebendazole and Praziquantel locally collected in Burkina Faso, Côte d'Ivoire, Ghana and Tanzania were analysed.
METHODS
Samples of 88 different batches were obtained from randomly selected facilities. Sampling took place in Northwest Tanzania, Western Burkina Faso, Southeast Côte d'Ivoire and Southwest Ghana. Visual examination of both packaging and samples was performed according to the WHO 'Be Aware' tool. Products were then screened with the GPHF Minilab, consisting of tests of mass uniformity, disintegration times and thin-layer chromatography (TLC). Confirmatory tests were performed according to international pharmacopoeiae, applying assays for dissolution profiles and high-performance liquid chromatography (HPLC).
FINDINGS
Despite minor irregularities, appearance of the products did not hint at falsified medicines. However, 19.6% of the brands collected in Ghana and Tanzania were not officially licensed for sale. Mass uniformity was confirmed in 53 out of 58 brands of tablets. 41 out of 56 products passed disintegration times; 10 out of the 15 failing products did not disintegrate at all. Evaluating TLC results, only 4 out of 83 batches narrowly missed specification limits, 18 batches slightly exceeded them. Not more than 46.3% (31 / 67) of the tablets assayed passed the respective pharmaceutical criteria for dissolution. HPLC findings confirmed TLC results despite shifted specification limits: 10 out of 83 tested batches contained less than 90%, none exceeded 110%.
CONCLUSION
In the four study countries, no falsified anthelminthic medicine was encountered. The active pharmaceutical ingredient was not found to either exceed or fall below specification limits. Galenic characteristics however, especially dissolution profiles, revealed great deficits.
Topics: Albendazole; Anthelmintics; Burkina Faso; Cote d'Ivoire; Ghana; Helminthiasis; Humans; Mebendazole; Praziquantel; Schistosomiasis; Tablets; Tanzania
PubMed: 33493211
DOI: 10.1371/journal.pntd.0009038 -
Zhongguo Xue Xi Chong Bing Fang Zhi Za... Jul 2017To investigate the pharmacokinetics and relative bioavailability of praziquantel injection in buffaloes in contrast to praziquantel tablet. A single oral... (Comparative Study)
Comparative Study
To investigate the pharmacokinetics and relative bioavailability of praziquantel injection in buffaloes in contrast to praziquantel tablet. A single oral administration of praziquantel tablet at a dose of 20 mg/kg or intramuscular administration of praziquantel injection at a dose of 10 mg/kg was performed in six healthy adult buffalos according to a twoperiod crossover design. The praziquantel concentration in plasma was determined by a high performance liquid chromatography (HPLC) method. The pharmacokinetic parameters were calculated by non-compartmental analysis. The main pharmacokinetic parameters of praziquantel tablet were as follows: = (0.60±0.29)h, = (0.57±0.37)μg/ml, = (0.70±0.42)h, = (0.80±0.70) (μg/ml)·h. The main pharmacokinetic parameters of praziquantel injection were as follows: = (0.65± 0.49)h, = (3.82±1.17)μg/ml, = (1.00±0.73)h, = (1.61±0.89) (μg/ml)·h. The relative bioavailability of praziquantel injection was 402.5% in contrast to praziquantel tablet. The praziquantel injection has pharmacokinetic characteristics of rapid absorption, high bioavailability and extensive distribution, and the clinical recommended dosage of praziquantel injection is 10 mg/kg.
Topics: Administration, Oral; Animals; Biological Availability; Buffaloes; Cross-Over Studies; Injections, Intramuscular; Praziquantel; Tablets
PubMed: 29508574
DOI: 10.16250/j.32.1374.2017032 -
Frontiers in Immunology 2021Beyond transient control of the infection, additional benefits of mass drug administration of praziquantel in endemic communities have been suggested in communities but...
Beyond transient control of the infection, additional benefits of mass drug administration of praziquantel in endemic communities have been suggested in communities but not mechanistically investigated experimentally. The present study sought to evaluate the additional and hitherto unreported benefits of repeated mass drug administration of praziquantel. We used a tractable mouse model of infection to assess the effects of repeated infection-treatment cycles on the host susceptibility to reinfection. Parasitaemia was assessed by quantification of Schistosoma egg burden in liver tissues and morbidity was followed up by histological observation of liver lesions by microscopy and using biochemical measurement of liver transaminases. Immune responses were further determined by serum probing of schistosoma-specific antibodies, cytokines and quantification of liver cellular and soluble mediator responses by flow cytometry and ELISA, respectively. At similar ages and comparable gender distribution, groups of mice undergoing higher number of infections treatment cycles over a longer period, remained susceptible to reinfection by the parasite, as judged by the presence of eggs and the associated increasing pathology in the liver tissues. However, notably, there was a clear and significantly higher propensity to lower egg burden upon reinfection when compared to counterparts undergoing a lower number of infection-treatment cycles. This relative reduction of susceptibility to infection was paralleled by a more robust humoral response against parasite antigens, elevated serum IL-4 and liver cytokines. Of note, praziquantel treatment of infected mice left them at a higher baseline of serum IL-4, IgE and liver cytokines but lower CD4+ T cell -derived cytokines when compared to infected non-treated mice supporting an immunological treatment-induced advantage of previously infected mice over naïve mice and infected/not treated mice. Notably, repeated infection-treatment cycles did not preclude the infection-driven aggravation of collagen deposition in the livers over time and was corroborated by a more robust local production of inflammatory cytokines in the most exposed livers. Taken together, our data reveal that treatment of -infected hosts with praziquantel rewires the immune system to a conformation less permissive to subsequent reinfection in mice. Provided the data are translatable from mouse to human, our findings may provide mechanistic support to the potential benefits of more frequent MDAs in high transmission areas to allow rapid acquisition of protective immunity against reinfection.
Topics: Administration, Oral; Animals; Anthelmintics; Flow Cytometry; Mice; Mice, Inbred Strains; Parasitic Sensitivity Tests; Praziquantel; Schistosoma mansoni; Schistosomiasis mansoni
PubMed: 34956183
DOI: 10.3389/fimmu.2021.748387 -
International Journal For Parasitology May 2021The pathogenesis of schistosomiasis and the mechanism of disease regression after Praziquantel pharmacotherapy are not fully elucidated. Schistosoma mansoni egg antigens...
The pathogenesis of schistosomiasis and the mechanism of disease regression after Praziquantel pharmacotherapy are not fully elucidated. Schistosoma mansoni egg antigens directly stimulate the expression of the profibrogenic molecule osteopontin (OPN), and systemic OPN levels strongly correlate with disease severity, suggesting its use as a potential morbidity biomarker. In this study, we investigated the impact of Praziquantel use on systemic OPN levels and on liver collagen deposition in chronic murine schistosomiasis. Praziquantel treatment significantly reduced systemic OPN levels and liver collagen deposition, indicating that OPN could be a reliable tool for monitoring PZQ efficacy and fibrosis regression in murine schistosomiasis.
Topics: Animals; Anthelmintics; Collagen; Liver; Mice; Osteopontin; Praziquantel; Schistosoma mansoni; Schistosomiasis mansoni
PubMed: 33493521
DOI: 10.1016/j.ijpara.2020.11.002 -
Molecules (Basel, Switzerland) Jul 2023Malaria and schistosomiasis are two of the neglected tropical diseases that persistently wreak havoc worldwide. Although many antimalarial drugs such as chloroquine are...
Malaria and schistosomiasis are two of the neglected tropical diseases that persistently wreak havoc worldwide. Although many antimalarial drugs such as chloroquine are readily available, the emergence of drug resistance necessitates the development of new therapies to combat this disease. Conversely, Praziquantel (PZQ) remains the sole effective drug against schistosomiasis, but its extensive use raises concerns about the potential for drug resistance to develop. In this project, the concept of molecular hybridization was used as a strategy to design the synthesis of new molecular hybrids with potential antimalarial and antischistosomal activity. A total of seventeen molecular hybrids and two PZQ analogues were prepared by coupling 6-alkylpraziquanamines with cinnamic acids and cyclohexane carboxylic acid, respectively. The synthesised compounds were evaluated for their antimalarial and antischistosomal activity; while all of the above compounds were inactive against (IC > 6 µM), many were active against schistosomiasis with four particular compounds exhibiting up to 100% activity against newly transformed schistosomula and adult worms at 50 µM. Compared to PZQ, the reference drug, the activity of which is 91.7% at 1 µM, one particular molecular hybrid, compound , which bears a para-isopropyl group on the cinnamic acid moiety, exhibited a notable activity at 10 µM (78.2% activity). This compound has emerged as the front runner candidate that might, after further optimization, hold promise as a potential lead compound in the fight against schistosomiasis.
Topics: Animals; Praziquantel; Antimalarials; Schistosoma mansoni; Schistosomicides; Schistosomiasis
PubMed: 37446846
DOI: 10.3390/molecules28135184 -
Journal of Veterinary Internal Medicine May 2021The trematode Heterobilharzia americana (HA) causes granulomatous gastrointestinal and hepatic disease in dogs. Before 2008, diagnosis relied on saline fecal...
BACKGROUND
The trematode Heterobilharzia americana (HA) causes granulomatous gastrointestinal and hepatic disease in dogs. Before 2008, diagnosis relied on saline fecal sedimentation or histopathology, and earlier reports primarily described dogs with advanced disease or cases diagnosed incidentally at necropsy. The advent of a fecal PCR test has facilitated the diagnosis of HA and provided insights into manifestations and response to treatment.
OBJECTIVES
Describe the clinical findings, response to treatment, and outcome for dogs infected with HA.
ANIMALS
Sixty dogs diagnosed with HA between 2010 and 2019.
METHODS
Retrospective study. Medical records were searched for dogs diagnosed with HA by fecal PCR testing, identification of ova in feces, or histopathology.
RESULTS
Mean age was 7.5 (±4.1) years and weight was 23.2 (±10.18) kg. Clinical signs included diarrhea (55.8%), vomiting (46.2%), and weight loss with or without anorexia (15.4%). Laboratory abnormalities included hyperglobulinemia (42.6%) and increased liver enzyme activities (30%). More than 40% of dogs had an eosinophil count >500/μL. Hypercalcemia attributable to HA was identified in only 4 dogs. Pinpoint hyperechoic foci were noted in intestines, liver, or mesenteric lymph nodes during transabdominal ultrasonography in 64.4% of dogs. Survival data was available for 34 dogs, of which 73.5% (25) were alive 6 months after diagnosis.
CONCLUSIONS AND CLINICAL IMPORTANCE
Hyperglobulinemia, high eosinophil count, and ultrasonographic evidence of visceral mineralization were suggestive of infection. Hypercalcemia was uncommon. Combination treatment with praziquantel and fenbendazole was variably effective, and 17.6% of treated dogs with known outcome died as a result of HA infection.
Topics: Animals; Dog Diseases; Dogs; Praziquantel; Retrospective Studies; Schistosomatidae; Trematode Infections
PubMed: 33934409
DOI: 10.1111/jvim.16127 -
BMC Medicine Jun 2018Despite decades of experience with praziquantel treatment in school-aged children (SAC) and adults, we still face considerable knowledge gaps relevant to the successful... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of ascending doses of praziquantel against Schistosoma haematobium infection in preschool-aged and school-aged children: a single-blind randomised controlled trial.
BACKGROUND
Despite decades of experience with praziquantel treatment in school-aged children (SAC) and adults, we still face considerable knowledge gaps relevant to the successful treatment of preschool-aged children (PSAC). This study aimed to assess the efficacy and safety of escalating praziquantel dosages in PSAC infected with Schistosoma haematobium.
METHODS
We conducted a randomised, dose-finding trial in PSAC (2-5 years) and as comparator a cohort of SAC (6-15 years) infected with S. haematobium in Côte d'Ivoire. A total of 186 PSAC and 195 SAC were randomly assigned to 20, 40 or 60 mg/kg praziquantel or placebo. The nature of the dose-response relationship in terms of cure rate (CR) was the primary objective. Egg reduction rate (ERR) and tolerability were secondary outcomes. CRs and ERRs were assessed using triplicate urine filtration over 3 consecutive days. Available-case analysis was performed including all participants with primary endpoint data.
RESULTS
A total of 170 PSAC and 174 SAC received treatment. Almost 90% of PSAC and three quarters of SAC were lightly infected with S. haematobium. Follow-up data were available for 157 PSAC and 166 SAC. In PSAC, CRs of praziquantel were 85.7% (30/35), 78.0% (32/41) and 68.3% (28/41) at 20, 40 and 60 mg/kg and 47.5% (19/40) for placebo. In SAC, CRs were 10.8% for placebo (4/37), 55.6% for 20 mg/kg (25/45), 68.3% for 40 mg/kg (28/41) and 60.5% for 60 mg/kg (26/43). ERRs based on geometric means ranged between 96.5% (60 mg/kg) and 98.3% (20 mg/kg) in PSAC and between 97.6% (20 mg/kg and 60 mg/kg) and 98.6% (40 mg/kg) in SAC. Adverse events were mild and transient.
CONCLUSIONS
Praziquantel revealed dose-independent efficacy against light infections of S. haematobium. Over the dose range tested, praziquantel displayed a ceiling effect with the highest response for 20 mg/kg in PSAC. In SAC maximum efficacy was obtained with 40 mg/kg praziquantel. Further investigations are required in children with moderate to heavy infections.
TRIAL REGISTRATION
This trial is registered with International Standard Randomised Controlled Trial Number ISRCTN15280205 .
Topics: Adolescent; Animals; Anthelmintics; Child; Child, Preschool; Cohort Studies; Female; Humans; Male; Praziquantel; Schistosoma haematobium; Schistosomiasis haematobia; Single-Blind Method; Treatment Outcome
PubMed: 29855373
DOI: 10.1186/s12916-018-1066-y