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Malaria Journal Nov 2023The overlap in the epidemiology of malaria and helminths has been identified as a potential area to exploit for the development of an integrated control strategy that... (Randomized Controlled Trial)
Randomized Controlled Trial
Feasibility and safety of integrating mass drug administration for helminth control with seasonal malaria chemoprevention among Senegalese children: a randomized controlled, observer-blind trial.
BACKGROUND
The overlap in the epidemiology of malaria and helminths has been identified as a potential area to exploit for the development of an integrated control strategy that may help to achieve elimination of malaria and helminths. A randomized, controlled, observer-blind trial was conducted to assess the feasibility and safety of combining mass drug administration (MDA) for schistosomiasis and soil transmitted helminths (STH) with seasonal malaria chemoprevention (SMC) among children living in Senegal.
METHODS
Female and male children aged 1-14 years were randomized 1:1:1, to receive Vitamin A and Zinc on Day 0, followed by SMC drugs (sulfadoxine-pyrimethamine and amodiaquine) on Days 1-3 (control group); or praziquantel and Vitamin A on Day 0, followed by SMC drugs on Days 1-3 (treatment group 1); or albendazole and praziquantel on Day 0, followed by SMC drugs on Days 1-3 (treatment group 2). Safety assessment was performed by collecting adverse events from all children for six subsequent days following administration of the study drugs. Pre- and post-intervention, blood samples were collected for determination of haemoglobin concentration, malaria microscopy, and PCR assays. Stool samples were analyzed using Kato-Katz, Merthiolate-iodine-formalin and PCR methods. Urine filtration, PCR and circulating cathodic antigen tests were also performed.
RESULTS
From 9 to 22 June 2022, 627 children aged 1-14 years were randomized into the three groups described above. Mild, transient vomiting was observed in 12.6% (26/206) of children in treatment group 2, in 10.6% (22/207) in group 1, and in 4.2% (9/214) in the control group (p = 0.005). Pre-intervention, the geometric mean value of Plasmodium falciparum parasite density was highest among children who received albendazole, praziquantel with SMC drugs. Post-intervention, the parasite density was highest among children who received SMC drugs only. Children who received praziquantel and SMC drugs had a lower risk of developing severe anaemia than their counterparts who received SMC drugs alone (OR = 0.81, 95% CI 0.13-5.00, p = 0.63).
CONCLUSIONS
Integration of MDA for helminths with SMC drugs was safe and feasible among Senegalese children. These findings support further evaluation of the integrated control model.
TRIAL REGISTRATION
The study is registered at Clinical Trial.gov NCT05354258.
Topics: Animals; Humans; Child; Male; Female; Antimalarials; Praziquantel; Albendazole; Mass Drug Administration; Seasons; Feasibility Studies; Vitamin A; Malaria; Helminths; Chemoprevention
PubMed: 37957702
DOI: 10.1186/s12936-023-04784-z -
Cureus May 2024Cerebellar hydatid cysts are uncommon lesions, with limited cases reported in the literature. This systematic review aimed to summarize current diagnostic and management... (Review)
Review
Cerebellar hydatid cysts are uncommon lesions, with limited cases reported in the literature. This systematic review aimed to summarize current diagnostic and management approaches, given the low suspicion index of hydatid cysts in the cerebellum. The review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42023437853. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-P) reporting guidelines. Two independent researchers searched PubMed, Scopus, and Google Scholar databases on June 27, 2023. We included 15 studies published between 1965 and 2022, comprising 12 case reports and three case series. A pooled analysis of reported cases (nine females and seven males) with cerebellar hydatid cysts revealed a mean age of 24 ± 20 years. Most of the cases were reported in Turkish hospitals ( = 8). The prominent signs and symptoms observed were headaches (10, 62.5%), ataxic gait (9, 56.25%), and visual disturbances (9, 56.25%). The time from symptom onset to hospital visit varied, with most patients seeking medical attention within the first three months. The left cerebellar hemisphere was the most common location of the cysts (6, 37.5%), and compression of the fourth ventricle was frequently observed. Computed tomography (CT) and magnetic resonance imaging (MRI) were the primary diagnostic tools used in three-fourths of cases, and surgical intervention was the primary treatment approach. Albendazole and praziquantel were commonly prescribed postoperatively, and two patients underwent preoperative needle decompression. This systematic review contributes to a better understanding of cerebellar hydatid cysts and guides future research and clinical management of this entity.
PubMed: 38841019
DOI: 10.7759/cureus.59706 -
BioRxiv : the Preprint Server For... Sep 2023Diseases caused by parasitic flatworms impart a considerable healthcare burden worldwide. Many of these diseases - for example, the parasitic blood fluke infection,...
Diseases caused by parasitic flatworms impart a considerable healthcare burden worldwide. Many of these diseases - for example, the parasitic blood fluke infection, schistosomiasis - are treated with the drug praziquantel (PZQ). However, PZQ is ineffective against disease caused by liver flukes from the genus . This is due to a single amino acid change within the target of PZQ, a transient receptor potential ion channel (TRPM), in species. Here we identify benzamidoquinazolinone analogs that are active against TRPM. Structure-activity studies define an optimized ligand (BZQ) that caused protracted paralysis and damage to the protective tegument of these liver flukes. BZQ also retained activity against comparable to PZQ and was active against TRPM orthologs in all profiled species of parasitic fluke. This broad spectrum activity was manifest as BZQ adopts a pose within the binding pocket of TRPM dependent on a ubiquitously conserved residue. BZQ therefore acts as a universal activator of trematode TRPM and a first-in-class, broad spectrum flukicide.
PubMed: 37790347
DOI: 10.1101/2023.09.22.559026 -
Frontiers in Veterinary Science 2023Milbemycin oxime (MBO) and praziquantel (PZQ) have a broad spectrum of biological activity and are commonly used to treat the parasitic infection in the veterinary...
Development and validation of an LC-MS/MS method for the simultaneous quantification of milbemycin oxime and praziquantel in plasma: application to a pharmacokinetic study in cats.
INTRODUCTION
Milbemycin oxime (MBO) and praziquantel (PZQ) have a broad spectrum of biological activity and are commonly used to treat the parasitic infection in the veterinary clinic. In this study, a fast and efficient LC-MS/MS method was established and validated for the simultaneous determination of MBO, PZQ, cis-4-hydroxylated-PZQ (C-4-OH-PZQ) and trans-4-hydroxylated-PZQ (T-4-OH-PZQ) and in cat plasma.
METHODS
Extraction of analytes and internal standards from cat plasma by acetonitrile protein precipitation, allows rapid processing of large batches of samples. MBO, PZQ, C-4-OH-PZQ, T-4-OH-PZQ, and internal standard (IS) were eluted for 13.5 min on a C column with a 0.1% formic acid water/acetonitrile mixture as the mobile phase.
RESULTS
Results showed that the method had good precision, accuracy, recovery, and linearity. The linearity range was 2.5-250 ng/mL for MBO, and 10-1000 ng/mL for PZQ, C-4-OH-PZQ, and T-4-OH-PZQ. The intra-day and inter-day precision CV values of the tested components were within 15%. The extraction recoveries of the four components ranged from 98.09% to 107.46%. The analytes in plasma remained stable for 6 h at room temperature, 26 h in the autosampler (4 °C), after freeze-thaw (-20°C) cycles, and 60 days in a -20°C freezer. Method sensitivity sufficed for assessing pharmacokinetic parameters of MBO, PZQ, C-4-OH-PZQ, and T-4-OH-PZQ in plasma samples with LLOQ of 2.5 ng/mL for MBO and 10 ng/mL for PZQ, C-4-OH-PZQ, and T-4-OH-PZQ.
CONCLUSION
In this study, a selective and sensitive LC-MS/MS method for the simultaneous quantification of MBO, PZQ, C-4-OH-PZQ, and T-4-OH-PZQ in cat plasma was developed and validated.This method had been successfully applied to evaluate the pharmacokinetics of MBO, PZQ, C-4-OH-PZQ, and T-4-OH-PZQ after a single oral administration of 8 mg MBO and 20 mg PZQ in cats.
PubMed: 37964913
DOI: 10.3389/fvets.2023.1285932 -
Current Research in Parasitology &... 2023The miticide efficacy of a single treatment with Felpreva® (tigolaner, emodepside and praziquantel) spot-on solution for cats was evaluated in two European field...
Field efficacy and safety of Felpreva® (tigolaner, emodepside and praziquantel) spot-on for the treatment of natural ear mite infestations () and notoedric mange () in cats.
The miticide efficacy of a single treatment with Felpreva® (tigolaner, emodepside and praziquantel) spot-on solution for cats was evaluated in two European field studies. One study was conducted in cats naturally infested with . The other study was conducted in cats naturally infested with . In both studies, the presence of viable mites was confirmed prior to treatment (Day -1/Day 0) and re-evaluated on Day 14 ( study) and on Day 28 (both studies). Efficacy was calculated based on the number of viable mites found after treatment. In the study, the primary criterion was the percentage of mite-free cats after treatment with Felpreva® compared to a sarolaner/selamectin combination (Stronghold® Plus, Zoetis) as a positive control. In the study, the primary criterion was the difference between arithmetic mean mite counts of cats treated with Felpreva® and cats treated with a placebo formulation (solketal). Secondary criteria in both studies were changes in clinical lesion scores after treatment. In both studies, all Felpreva®-treated cats were mite-free (100% parasitological cure) on Day 28, 4 weeks after treatment. Signs of mange on Day 28 were clinically improved in all -infested cats (100%) and clinically cured in all -infested cats (100%). There were no records of any adverse events or application site reactions in Felpreva®-treated cats.
PubMed: 37954512
DOI: 10.1016/j.crpvbd.2023.100146 -
Journal of Medical Case Reports Jun 2024Schistosomiasis is one of the endemic parasitic diseases in many developing countries. Despite this, appendicitis secondary to schistosomiasis is an uncommon condition...
BACKGROUND
Schistosomiasis is one of the endemic parasitic diseases in many developing countries. Despite this, appendicitis secondary to schistosomiasis is an uncommon condition even in some endemic areas. Schistosomal appendicitis, an incidentally discovered appendicitis associated with schistosomiasis histological findings, affects young males predominantly. Timely diagnosis and treatment, including appendectomy and anti-helminthic therapy, are crucial.
CASE REPORT
A 24-year-old Sudanese male patient presented with abdominal pain. Diagnosed with acute appendicitis, he underwent appendectomy, revealing appendix inflammation with Schistosoma ova in histopathology. Abdominal ultrasound detected no complications. Weakly positive Schistosoma serology was noted, but stool and urine analysis showed no infection evidence. Prescribed praziquantel, patient had 3-year post-op follow-up without complications.
CONCLUSIONS
This case report underscores the significance of including schistosomiasis in the differential diagnosis of appendicitis, particularly in regions where the disease is endemic. It underscores the necessity of histopathological evaluations for accurate diagnosis, emphasizing the potential implications for clinical practice in similar settings.
Topics: Humans; Appendicitis; Male; Young Adult; Praziquantel; Appendectomy; Anthelmintics; Schistosomiasis; Diagnosis, Differential; Abdominal Pain; Ultrasonography; Animals; Treatment Outcome; Appendix
PubMed: 38890741
DOI: 10.1186/s13256-024-04610-3 -
Frontiers in Immunology 2023The World Health Organization (WHO) recognizes schistosomiasis as one of the Neglected Tropical Diseases targeted for global elimination in the 2030 Agenda of the... (Review)
Review
The World Health Organization (WHO) recognizes schistosomiasis as one of the Neglected Tropical Diseases targeted for global elimination in the 2030 Agenda of the Sustainable Development Goals. In Brazil, schistosomiasis mansoni is considered a public health problem, particularly prevalent among vulnerable populations living in areas with poor environmental and sanitary conditions. In 2022, the WHO published a Guideline encompassing recommendations to assist national programs in endemic countries in achieving morbidity control, eliminating schistosomiasis as a public health problem, and advancing towards interrupting transmission. The perspectives presented here, collectively prepared by members of the Oswaldo Cruz Foundation's (Fiocruz) Schistosomiasis Translational Program (FioSchisto), along with invited experts, examine the feasibility of the WHO recommendations for the Brazilian settings, providing appropriate recommendations for public health policies applicable to the epidemiological reality of Brazil, and suggests future research to address relevant issues. In Brazil, the provision of safe water and sanitation should be the key action to achieve schistosomiasis elimination goals. The agencies involved in measures implementation should act together with the Primary Care teams for planning, executing, monitoring, and evaluating actions in priority municipalities based on their epidemiological indicators. Host snails control should prioritize judicious ecological interventions at breeding sites. The Information, Education, and Communication (IEC) strategy should be associated with water and sanitation and other control actions, actively involving school community. To identify infected carriers, FioSchisto recommends a two-stage approach of immunological and molecular tests to verify transmission interruption during the intervention and beyond. Praziquantel administration should be done under medical supervision at the Primary Care level. MDA should be considered in exceptional settings, as a measure of initial attack strategy in locations presenting high endemicity, always integrated with water and sanitation, IEC, and snail control. To assist decision-making, as well as the monitoring and evaluation of strategic actions, there is a need for an Information System. FioSchisto considers this systematization essential to make investments in strategic research to support the improvement of schistosomiasis control actions. Efforts toward schistosomiasis elimination in Brazil will succeed with a paradigm shift from the vertical prescriptive framework to a community-centered approach involving intersectoral and interdisciplinary collaboration.
Topics: Humans; Brazil; Schistosomiasis; Praziquantel; World Health Organization; Water
PubMed: 38143743
DOI: 10.3389/fimmu.2023.1268998 -
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 -
Pharmaceutics Jul 2023To date, the treatment for cysticercosis and neurocysticercosis consists of a single oral intake of praziquantel (5-10 mg/kg), which since it is only available as...
To date, the treatment for cysticercosis and neurocysticercosis consists of a single oral intake of praziquantel (5-10 mg/kg), which since it is only available as tablets, hinders its administration to pediatric patients. Praziquantel is a poorly water-soluble drug which represents a challenge for its formulation in solution, particularly for the pediatric population. Thus, this study aimed to develop a palatable solution for praziquantel using pharmaceutical-accepted co-solvent systems. A design of experiments approach was applied to identify the optimal conditions for achieving a suitable amount of praziquantel in solution using co-solvent mixtures. Thus, praziquantel solubility increased from 0.38 up to 43.50 mg/mL in the optimized system. A taste masking assay in healthy human volunteers confirmed a successful reduction of drug bitterness after the addition of selected flavors and a sweetener. Stability studies were also conducted at different temperatures (4, 25, and 40 °C) for 12 months Even though the presence of the three known impurities of praziquantel was observed, their amounts never exceeded the acceptance criteria of the USP. Thus, this novel approach should be considered a valuable alternative for further preclinical studies considering the high prevalence of this infection worldwide.
PubMed: 37631264
DOI: 10.3390/pharmaceutics15082050 -
PloS One 2023Anthelmintic drugs are used to treat parasitic roundworm and flatworm infections in humans and other animals. Caenorhabditis elegans is an established model to...
Anthelmintic drugs are used to treat parasitic roundworm and flatworm infections in humans and other animals. Caenorhabditis elegans is an established model to investigate anthelmintics used to treat roundworms. In this study, we use C. elegans to examine the mode of action and the mechanisms of resistance against the flatworm anthelmintic drug praziquantel (PZQ), used to treat trematode and cestode infections. We found that PZQ inhibited development and that this developmental delay varies by genetic background. Interestingly, both enantiomers of PZQ are equally effective against C. elegans, but the right-handed PZQ (R-PZQ) is most effective against schistosome infections. We conducted a genome-wide association mapping with 74 wild C. elegans strains to identify a region on chromosome IV that is correlated with differential PZQ susceptibility. Five candidate genes in this region: cct-8, znf-782, Y104H12D.4, Y104H12D.2, and cox-18, might underlie this variation. The gene cct-8, a subunit of the protein folding complex TRiC, has variation that causes a putative protein coding change (G226V), which is correlated with reduced developmental delay. Gene expression analysis suggests that this variant correlates with slightly increased expression of both cct-8 and hsp-70. Acute exposure to PZQ caused increased expression of hsp-70, indicating that altered TRiC function might be involved in PZQ responses. To test if this variant affects development upon exposure to PZQ, we used CRISPR-Cas9 genome editing to introduce the V226 allele into the N2 genetic background (G226) and the G226 allele into the JU775 genetic background (V226). These experiments revealed that this variant was not sufficient to explain the effects of PZQ on development. Nevertheless, this study shows that C. elegans can be used to study PZQ mode of action and resistance mechanisms. Additionally, we show that the TRiC complex requires further evaluation for PZQ responses in C. elegans.
Topics: Animals; Humans; Praziquantel; Caenorhabditis elegans; Genome-Wide Association Study; Anthelmintics; Schistosoma
PubMed: 37561720
DOI: 10.1371/journal.pone.0286473