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PLoS Neglected Tropical Diseases Mar 2016In 2012 the World Health Assembly adopted resolution WHA65.21 on elimination of schistosomiasis, calling for increased investment in schistosomiasis control and support... (Review)
Review
Schistosomiasis Prevalence and Intensity of Infection in Latin America and the Caribbean Countries, 1942-2014: A Systematic Review in the Context of a Regional Elimination Goal.
BACKGROUND
In 2012 the World Health Assembly adopted resolution WHA65.21 on elimination of schistosomiasis, calling for increased investment in schistosomiasis control and support for countries to initiate elimination programs. This study aims to analyze prevalence and intensity of Schistosoma mansoni infection in children in Latin America and the Caribbean countries and territories (LAC), at the second administrative level or lower.
METHODOLOGY
A systematic review of schistosomiasis prevalence and intensity of infection was conducted by searching at PubMed, LILACS and EMBASE. Experts on the topic were informally consulted and institutional web pages were reviewed (PAHO/WHO, Ministries of Health). Only SCH infection among children was registered because it can be a 'proxi-indicator' of recent transmission by the time the study is conducted.
PRINCIPAL FINDINGS
One hundred thirty two full-text articles met the inclusion criteria and provided 1,242 prevalence and 199 intensity of infection data points. Most of them were from Brazil (69.7%). Only Brazil published studies after 2001, showing several 'hot spots' with high prevalence. Brazil, Venezuela, Suriname and Saint Lucia need to update the epidemiological status of schistosomiasis to re-design their national programs and target the elimination of Schistosoma mansoni transmission by 2020. In Antigua and Barbuda, Dominican Republic, Guadeloupe, Martinique, Montserrat and Puerto Rico schistosomiasis transmission may be interrupted. However the compilation of an elimination dossier and follow-up surveys, per WHO recommendations, are needed to verify that status. Hence, the burden of subtle SCH chronic infection may be still present and even high in countries that may have eliminated transmission. Heterogeneity in the methodologies used for monitoring and evaluating the progress of the schistosomiasis programs was found, making cross-national and chronological comparisons difficult.
CONCLUSIONS
There is a need for updating the schistosomiasis status in the historically endemic countries and territories in LAC to address the required public health interventions for control and elimination programs or to verify the elimination of transmission of Schistosoma mansoni. Improved reporting and standardization of the monitoring and evaluation methodologies used are recommended, while using available WHO guidelines. Meeting a regional elimination goal will require additional and improved epidemiological data by age group and sex.
Topics: Anthelmintics; Disease Eradication; Humans; Latin America; Praziquantel; Schistosomiasis
PubMed: 27007193
DOI: 10.1371/journal.pntd.0004493 -
Scientific Reports Sep 2021Praziquantel pharmacokinetics studies in schistosomiasis infected children are scarce partly due to the challenges/complexity of intensive blood sampling in the target...
Praziquantel pharmacokinetics studies in schistosomiasis infected children are scarce partly due to the challenges/complexity of intensive blood sampling in the target population. This study was aimed to investigate the optimal single sampling time-point for monitoring praziquantel exposure. This was intensive pharmacokinetic study conducted among 32 Schistosoma mansoni infected children treated with an oral standard single-dose 40 mg/kg praziquantel. Plasma samples were collected at 0, 1, 2, 4, 6 and 8 h post-praziquantel administration. Quantification of praziquantel and its enantiomers (R- and S-praziquantel) concentrations was done by Liquid chromatography-tandem mass spectrometer (LC-MS/MS). The correlation between area under the plasma concentration-time curve from 0 to 8 h (AUC) and plasma concentrations at each specific sampling time-point was determined by Pearson's correlation coefficient (r). The median age (range) of the study population was 12.5 years (10-17). The study participants were 17 males and 15 females. Both total praziquantel and its enantiomers (R- and S-praziquantel) displayed a wide inter-individual pharmacokinetic variability. Regression analysis indicated that, plasma concentrations collected at 4 h post-dose had a significantly highest correlation with the AUC for both total praziquantel (r = 0.81, p < 0.001) and S-praziquantel (r = 0.84, p < 0.001) than any other sampling time-point; while for R-praziquantel, plasma concentrations collected at 6 h sampling time-point had a significantly highest correlation with the AUC (r = 0.79, p < 0.001) than any other sampling time-point. Four hours sampling time-point post-praziquantel administration is ideal optimal single sampling time-point for therapeutic monitoring of total praziquantel exposure while 6 h sampling time-point is suitable for monitoring of a pharmacologically active R-praziquantel enantiomer.
Topics: Administration, Oral; Adolescent; Animals; Anthelmintics; Biological Availability; Blood Specimen Collection; Child; Chromatography, Liquid; Drug Monitoring; Feces; Female; Humans; Isomerism; Male; Praziquantel; Schistosoma mansoni; Schistosomiasis mansoni; Tandem Mass Spectrometry
PubMed: 34504222
DOI: 10.1038/s41598-021-97409-x -
The American Journal of Tropical... Jan 2021Spinal sparganosis of the cauda equina has been rarely reported. A 54-year-old man presented at the hospital after having experienced lower back pain for 10 months,... (Review)
Review
Spinal sparganosis of the cauda equina has been rarely reported. A 54-year-old man presented at the hospital after having experienced lower back pain for 10 months, progressive weakness and numbness of the left leg for 4 months, and urinary incontinence for 3 weeks. Magnetic resonance imaging of the lumbosacral spine revealed a heterogeneous enhancing mass at the T12-S1 level. Spinal sparganosis was diagnosed by histological examination and molecular identification of the parasite in the tissue section. The patient was treated with a high dose of praziquantel because the parasitic mass was only partially removed and symptoms worsened following surgery.
Topics: Anthelmintics; Anti-Ulcer Agents; Cauda Equina; Cimetidine; Humans; Male; Middle Aged; Polyradiculopathy; Praziquantel; Sparganosis
PubMed: 33124542
DOI: 10.4269/ajtmh.20-0712 -
Journal of Pharmacokinetics and... Jun 2022Racemic praziquantel (PZQ) is the standard treatment for schistosomiasis and liver fluke infections (opisthorchiasis and clonorchiasis). The development of an optimal...
R-praziquantel integrated population pharmacokinetics in preschool- and school-aged African children infected with Schistosoma mansoni and S. haematobium and Lao adults infected with Opisthorchis viverrini.
Racemic praziquantel (PZQ) is the standard treatment for schistosomiasis and liver fluke infections (opisthorchiasis and clonorchiasis). The development of an optimal pediatric formulation and dose selection would benefit from a population pharmacokinetic (popPK) model. A popPK model was developed for R-PZQ, the active enantiomer of PZQ, in 664 subjects, 493 African children (2-15 years) infected with Schistosoma mansoni and S. haematobium, and 171 Lao adults (15-78 years) infected with Opisthorchis viverrini. Racemate tablets were administered as single doses of 20, 40 and 60 mg/kg in children and 30, 40 and 50 mg/kg in 129 adults, and as 3 × 25 mg/kg apart in 42 adults. Samples collected by the dried-blood-spot technique were assayed by LC-MS/MS. A two-compartment disposition model, with allometric scaling and dual first-order and transit absorption, was developed using Phoenix™ software. Inversely parallel functions of age described the apparent oral bioavailability (BA) and clearance maturation in children and ageing in adults. BA decreased slightly in children with dose increase, and by 35% in adults with multiple dosing. Crushing tablets for preschool-aged children increased the first-order absorption rate by 64%. The mean transit absorption time was 70% higher in children. A popPK model for R-PZQ integrated African children over 2 years of age with schistosomiasis and Lao adults with opisthorchiasis, and should be useful to support dose optimization in children. In vitro hepatic and intestinal metabolism data would help refining and validating the model in younger children as well as in target ethnic pediatric and adult groups.
Topics: Adult; Animals; Anthelmintics; Child; Child, Preschool; Chromatography, Liquid; Humans; Laos; Opisthorchiasis; Opisthorchis; Praziquantel; Schistosoma mansoni; Schistosomiasis; Tandem Mass Spectrometry
PubMed: 35024995
DOI: 10.1007/s10928-021-09791-8 -
Systematic Reviews Oct 2022The early childhood development of millions of children in some low- and medium-income countries may be compromised by schistosomiasis infections contracted at the age...
BACKGROUND
The early childhood development of millions of children in some low- and medium-income countries may be compromised by schistosomiasis infections contracted at the age of 5 years and below. Currently, there are no standard guidelines for treating schistosomiasis in children that are 5 years and younger using praziquantel (PZQ), the only drug that the World Health Organization (WHO) recommends for treating schistosomiasis. The review is on processes and resources involved in the treatment of schistosomiasis in children aged 5 years and below.
METHODS
An electronic search for peer-reviewed articles published in the period from January 2011 to August 2021 was done in the Academic Search Complete, CINAHL with Full Text, Health Source: Nursing/Academic Edition, and MEDLINE databases via EBSCOHost and Google Scholar databases. The search targeted journals that described the treatment of schistosomiasis in children 5 years and below using praziquantel.
RESULTS
Thirteen studies met the inclusion criteria. The patient journey for treating schistosomiasis in children aged 5 years old and below using PZQ included the following activities: enrolment of the children into the treatment program; clinical examination; diagnosis; taking anthropometric measurements; feeding the children, making the PZQ palatable to the children; administration of PZQ; and monitoring of side effects. There was also a variation in the resources used to treat children aged 5 and below for schistosomiasis.
CONCLUSIONS
A PZQ mass drug administration program for children aged 5 years old and below in endemic areas should exclude the diagnosis of schistosomiasis before treatment. The resources required in the treatment process should be affordable, and should not require skills and maintenance resources that are beyond those that are available at the primary healthcare level.
Topics: Child; Child, Preschool; Humans; Praziquantel; Mass Drug Administration; Anthelmintics; Schistosomiasis; Drug-Related Side Effects and Adverse Reactions
PubMed: 36271455
DOI: 10.1186/s13643-022-02087-z -
PLoS Neglected Tropical Diseases Sep 2020Schistosomiasis control is heavily reliant on the drug praziquantel (PZQ), which is used as preventive chemotherapy as part of national helminth control strategies.... (Review)
Review
Schistosomiasis control is heavily reliant on the drug praziquantel (PZQ), which is used as preventive chemotherapy as part of national helminth control strategies. Given the heavy reliance on PZQ for mass drug administration, there has been considerable research on the potential of parasites developing resistance to the drug, resulting in decreased drug efficacy. However, there have been comparatively fewer studies of other factors that can potentially alter PZQ efficacy. Here, we investigate whether host PZQ metabolism contributes towards variable cure rates. We evaluate factors that can influence the metabolism of PZQ and the resultant effect on the efficacy of PZQ treatment to determine factors that potentially influence an individual's response to the drug. The literature search was directed at published studies from three online databases: Web of Science, PubMed, and EMBASE. The search terms for the review comprised of ([praziquantel OR PZQ] AND [schistosom* OR bilharzia] AND [pharmaco*]) and included studies evaluating PZQ metabolism. Publications were categorised into pharmacokinetics, drug-drug interactions, pharmacogenetics, and metabolite analysis. Forty publications describing human and experimental studies fitted the inclusion criteria and were subjected to data extraction and analysis. The analyses showed that variable exposure to PZQ was associated with alterations in the liver's capacity to metabolise PZQ and observed drug-drug interactions. Other factors influencing the efficacy of PZQ were brand, formulation, and co-administered food. Although some work has been performed on metabolite identification, there was minimal information on PZQ's metabolic pathway, and no pharmacogenetics studies were identified. The study indicated that in both human and experimental studies alterations in the liver's capacity to metabolise PZQ as well as drug-drug interactions affected systemic levels of PZQ that could result in variable cure rates. The study confirmed previous findings of higher antischistosomal activity of (R)-PZQ enantiomer when administered alone compared to the racemate at the same dose as well as improved efficacy when the drug is administered with food. The study also highlighted the need for more comprehensive studies of the PZQ metabolic pathway and PZQ pharmacogenetic studies in humans.
Topics: Animals; Anthelmintics; Disease Models, Animal; Humans; Praziquantel; Schistosoma mansoni; Schistosomiasis
PubMed: 32976496
DOI: 10.1371/journal.pntd.0008649 -
International Journal For Parasitology.... Aug 2023Ancylostoma caninum is the most common and important gastrointestinal nematode of dogs in the United States. Despite recent reports of A. caninum isolates resistant to...
Ancylostoma caninum is the most common and important gastrointestinal nematode of dogs in the United States. Despite recent reports of A. caninum isolates resistant to all classes of anthelmintics, little is known about the frequency and extent of this anthelmintic resistance. The study aim was to evaluate the efficacy of three commercial anthelmintic products in the treatment of foxhound dogs with a history of persistent A. caninum infections. In the first phase of this study, 35 foxhounds were randomly divided into three treatment groups: moxidectin/imidacloprid (MI), pyrantel pamoate/febantel/praziquantel (PFP), and emodepside/praziquantel (EP). Fecal samples were collected on day 0, 11, and 33 post-treatment (PT), and hookworm eggs were quantified using the mini-FLOTAC technique with a multiplication factor of 5 eggs per gram (EPG). The fecal egg count reduction (FECR) on day 11 PT was 65% (95% CI: 62%-68%) for MI, 69% (95% CI: 66%-72%) for PFP, and 96% (95% CI: 94%-97%) for EP. On day 33 PT, the FEC in the MI and PFP groups returned to almost the same values as on day 0, while in the EP group, the FEC remained low. Since MI and PFP proved ineffective, 32 animals were randomly divided into two groups in the second phase. They were treated either with a combination of MI/PFP or EP. The FECR at day 13 PT for the combination MI/PFP was 89% (95% CI: 87%-91%) and 99% (95% CI: 98%-99%) for EP. These results suggest that this A. caninum population is resistant to multiple anthelmintics. Although the combination of MI/PFP improved the anthelmintic efficacy, the FECR remained below 90%. Future studies are indicated to evaluate further the epidemiology of persistent hookworm infections in dogs in the US and to identify more effective treatment protocols as they pose a significant health risk to canine and human health.
Topics: Animals; Dogs; Ancylostoma; Ancylostomatoidea; Anthelmintics; Dog Diseases; Feces; Hookworm Infections; Nematoda; Parasite Egg Count; Praziquantel
PubMed: 37481894
DOI: 10.1016/j.ijpddr.2023.07.001 -
PLoS Neglected Tropical Diseases Aug 2014Both tribendimidine and mebendazole are broad-spectrum drugs for anti-intestinal nematodes. We aim to assess the efficacy and safety of tribendimidine and mebendazole in... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Both tribendimidine and mebendazole are broad-spectrum drugs for anti-intestinal nematodes. We aim to assess the efficacy and safety of tribendimidine and mebendazole in patients with co-infection of Clonorchis sinensis and other helminths.
METHOD
We performed a randomized open-label trial in Qiyang, People's Republic of China. Eligible participants were randomly assigned to one of four groups: (i) a single dose of 400 mg tribendimidine, (ii) 200 mg tribendimidine twice daily, (iii) 75 mg/kg praziquantel divided in four doses within 2 days, and (iv) a single dose of 400 mg mebendazole. Cure rates and egg reduction rates were assessed, and adverse events were monitored after treatments. Uncured patients accepted the second treatment with the same drugs after the first treatment.
RESULTS
156 patients were eligible for the study. Results from the first treatment showed that the cure rates of single-dose tribendimidine and praziquantel against C. sinensis were 50% and 56.8%, respectively; the single-dose tribendimidine achieved the cure rate of 77.8% in the treatment for hookworm, which was significantly higher than that of praziquantel; Low cure rates were obtained in the treatment of single-dose tribendimidine against Ascaris lumbricoides and Trichuris trichiura (28.6% and 23.1%). Results of the second treatment illustrated the cure rates of tribendimidine and praziquantel against C. sinensis were 78.1% and 75%, respectively. Most adverse events were mild and transient. Adverse events caused by tribendimidine were significantly less than praziquantel.
CONCLUSION
Single-dose tribendimidine showed similar efficacy against C. sinensis as praziquantel with less adverse events, and achieved significantly higher cure rate in the treatment for hookworm than those of praziquantel and mebendazole. Low cure rates, which were still higher than other drugs, were obtained in the treatment of single-dose tribendimidine against Ascaris lumbricoides and Trichuris trichiura.
TRIAL REGISTRATION
Controlled-Trials.com ISRCTN55086560.
Topics: Adult; Animals; Anthelmintics; Ascariasis; Clonorchiasis; Coinfection; Female; Helminthiasis; Humans; Male; Mebendazole; Middle Aged; Phenylenediamines; Praziquantel
PubMed: 25122121
DOI: 10.1371/journal.pntd.0003046 -
ACS Infectious Diseases May 2023In September 2022, the Drug Discovery Unit at the University of Dundee, UK, organised an international meeting at the Wellcome Collection in London to explore the... (Review)
Review
In September 2022, the Drug Discovery Unit at the University of Dundee, UK, organised an international meeting at the Wellcome Collection in London to explore the current clinical situation and challenges associated with treating schistosomiasis. The aim of this meeting was to discuss the need for new treatments in view of the clinical situation and to ascertain what the key requirements would be for any potential new anti-schistosomals. This information will be essential to inform ongoing drug discovery efforts for schistosomiasis. We also discussed the potential drug discovery pathway and associated criteria for progressing compounds to the clinic. To date, praziquantel (PZQ) is the only drug available to treat all species causing schistosomiasis, but it is often unable to completely clear parasites from an infected patient, partially due to its inactivity against juvenile worms. PZQ-mediated mass drug administration campaigns conducted in endemic areas (e.g., sub-Saharan Africa, where schistosomiasis is primarily prevalent) have contributed to reducing the burden of disease but will not eliminate the disease as a public health problem. The potential for to develop resistance towards PZQ, as the sole treatment available, could become a concern. Consequently, new anthelmintic medications are urgently needed, and this Perspective aims to capture some of the learnings from our discussions on the key criteria for new treatments.
Topics: Animals; London; Schistosomiasis; Praziquantel; Anthelmintics; Schistosoma
PubMed: 37083395
DOI: 10.1021/acsinfecdis.3c00081 -
Journal of Fish Diseases Apr 2018This study evaluated efficacy and toxicity of the pyrazinoisoquinoline anthelmintic praziquantel (PZQ) in barbel infected with metacercariae of Diplostomum spathaceum...
This study evaluated efficacy and toxicity of the pyrazinoisoquinoline anthelmintic praziquantel (PZQ) in barbel infected with metacercariae of Diplostomum spathaceum and adult Pomphorhynchus laevis, and assessed antioxidant biomarkers and the lipid peroxidation response in juvenile barbel post-treatment. The estimated 96-hr LC50 of PZQ was 28.6 mg/L. For evaluation of efficacy, barbel naturally infected with D. spathaceum were exposed to a 10 and 20 mg/L PZQ 4-day bath treatment. Both concentrations were 100% effective against D. spathaceum and significantly (p < .01) affected the activity of catalase, superoxide dismutase, glutathione reductase and glutathione-S-transferase as well as levels of reduced glutathione in liver and muscle. The efficacy of orally administered PZQ was assessed in adult barbel naturally infected with P. laevis. Fish were administered 10, 30 and 50 mg/kg of body weight and examined via gut dissection after 6 days. The 50 mg/kg dose significantly decreased the intensity of infection. Praziquantel is a feasible bath treatment for barbel infected with D. spathaceum and has potential for oral treatment of broodfish infected with P. laevis.
Topics: Acanthocephala; Animals; Anthelmintics; Antioxidants; Cyprinidae; Dose-Response Relationship, Drug; Female; Fish Diseases; Helminthiasis, Animal; Oxidative Stress; Praziquantel; Random Allocation; Trematoda; Trematode Infections
PubMed: 29349797
DOI: 10.1111/jfd.12764