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Acta Tropica Aug 2024The World Health Organization calls for schistosomiasis endemic countries to regularly monitor the efficacy of Praziquantel (PZQ) drug, the only antischistosomal drug...
Efficacy of praziquantel drug against Schistosoma haematobium and performance of urine reagent strips among pre-and-school aged children during the high transmission season in North-Western Tanzania.
The World Health Organization calls for schistosomiasis endemic countries to regularly monitor the efficacy of Praziquantel (PZQ) drug, the only antischistosomal drug used for four decades in Tanzania. In response to that call, the current study investigated the efficacy of single dose of PZQ against Schistosoma haematobium during the high transmission season and further assessed, the sensitivity and specificity of urine reagent strips before and after treatment. The study recruited a total of 2,498 -children aged (4 -17 years old) who provided a single urine sample that was visually examined for macro-haematuria, then using urine dipstick and urine filtration technique for microhaematuria and the presence of S. haematobium eggs. The baseline prevalence of S. haematobium eggs positive based on urine filtration test was 29.2 % (95 %CI:27.5-31.0) and that of microhaematuria was 43.1 % (95 %CI:41.1-45.0). Of the infected participants, 40.9 % (95 %CI:37.4-44.6) had a heavy intensity of infection and the geometrical mean intensity (GMI) of infection was 33.7 eggs/10mls of urine. A single dose of PZQ reduced the prevalence of infection to 16.2 %, the GMI of infection to 18.8eggs/10mls of urine and that of microhaematuria to 27.9 %. Cure rate and egg reduction rates (ERR) were 83.8 % and 44.3 % respectively. At baseline, the sensitivity and specificity of the urine reagent strips were 59.7 % and 93.8 %, whereas at post-treatment they were 16.7 % and 93.6 %. When PZQ drug is administered during the high transmission season, its efficacy in term of ERR is poor. The urine reagent strips had low sensitivity but high specificity at pre-and-post PZQ treatment.
Topics: Praziquantel; Tanzania; Humans; Schistosomiasis haematobia; Child; Animals; Child, Preschool; Female; Male; Sensitivity and Specificity; Anthelmintics; Schistosoma haematobium; Adolescent; Reagent Strips; Prevalence; Urine; Treatment Outcome; Parasite Egg Count
PubMed: 38729329
DOI: 10.1016/j.actatropica.2024.107232 -
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 -
Orvosi Hetilap Dec 2023
Topics: Humans; Urinary Bladder; Schistosomiasis; Anthelmintics
PubMed: 38043096
DOI: 10.1556/650.2023.32902 -
Pediatric Nephrology (Berlin, Germany) Jun 2024Schistosomiasis affects approximately 230 million people worldwide. There is an increased incidence of schistosomiasis cases in France acquired from outside the country....
BACKGROUND
Schistosomiasis affects approximately 230 million people worldwide. There is an increased incidence of schistosomiasis cases in France acquired from outside the country. This increases the risk of schistosomiasis outbreaks as observed in Corsica. Clinicians from non-endemic regions are not accustomed to diagnosing and managing this pathology. The objective of this study is to provide a better description of the clinical and paraclinical characteristics and disease evolution of affected children.
METHODS
Through the French Pediatric Nephrology Society and the Pediatric Infectious Pathology Group, we contacted all French pediatric centers that may have treated children with urinary schistosomiasis between 2013 and 2019. Age, sex, comorbidities, and clinical, biological, and radiological data (at discovery and follow-up) were collected retrospectively.
RESULTS
A total of 122 patients from 10 different centers were included. The median age was 14 years and the sex ratio M/F was 4:1. Hematuria was present in 82% of the patients while urinary tract abnormality was found in 36% of them. Fourteen patients (11%) displayed complicated forms of urinary schistosomiasis including 10 patients with chronic kidney disease. A total of 110 patients received treatment with praziquantel, which was well-tolerated and led to clinical resolution of symptoms in 98% of cases.
CONCLUSION
Patients with schistosomiasis present frequent kidney, urinary, or genital involvement. Systematic screening of patients returning from endemic areas is therefore recommended, especially since treatment with antiparasitic drugs is effective and well-tolerated. Enhancing medical knowledge of this pathology among all practitioners is essential to improve care and outcomes.
Topics: Humans; Child; Adolescent; Animals; Schistosomiasis haematobia; Retrospective Studies; Praziquantel; Hematuria; France; Schistosoma haematobium
PubMed: 38212419
DOI: 10.1007/s00467-023-06260-x -
Trends in Parasitology May 2024Highlighting recent literature, we review the epidemiological and clinical importance of male genital schistosomiasis (MGS) in Malawi. We then discuss why individual...
Highlighting recent literature, we review the epidemiological and clinical importance of male genital schistosomiasis (MGS) in Malawi. We then discuss why individual disease management is an unmet public health challenge and outline how future interventions should be better set within routine services of HIV and men's sexual and reproductive health clinics.
PubMed: 38821840
DOI: 10.1016/j.pt.2024.05.003 -
PLoS Pathogens Jul 2023Human schistosomiasis is a neglected tropical disease caused by Schistosoma mansoni, S. haematobium, and S. japonicum. Praziquantel (PZQ) is the method of choice for...
Human schistosomiasis is a neglected tropical disease caused by Schistosoma mansoni, S. haematobium, and S. japonicum. Praziquantel (PZQ) is the method of choice for treatment. Due to constant selection pressure, there is an urgent need for new therapies for schistosomiasis. Previous treatment of S. mansoni included the use of oxamniquine (OXA), a drug that is activated by a schistosome sulfotransferase (SULT). Guided by data from X-ray crystallography and Schistosoma killing assays more than 350 OXA derivatives were designed, synthesized, and tested. We were able to identify CIDD-0150610 and CIDD-0150303 as potent derivatives in vitro that kill (100%) of all three Schistosoma species at a final concentration of 71.5 μM. We evaluated the efficacy of the best OXA derivates in an in vivo model after treatment with a single dose of 100 mg/kg by oral gavage. The highest rate of worm burden reduction was achieved by CIDD -150303 (81.8%) against S. mansoni, CIDD-0149830 (80.2%) against S. haematobium and CIDD-066790 (86.7%) against S. japonicum. We have also evaluated the ability of the derivatives to kill immature stages since PZQ does not kill immature schistosomes. CIDD-0150303 demonstrated (100%) killing for all life stages at a final concentration of 143 μM in vitro and effective reduction in worm burden in vivo against S. mansoni. To understand how OXA derivatives fit in the SULT binding pocket, X-ray crystal structures of CIDD-0150303 and CIDD-0150610 demonstrate that the SULT active site will accommodate further modifications to our most active compounds as we fine tune them to increase favorable pharmacokinetic properties. Treatment with a single dose of 100 mg/kg by oral gavage with co-dose of PZQ + CIDD-0150303 reduced the worm burden of PZQ resistant parasites in an animal model by 90.8%. Therefore, we conclude that CIDD-0150303, CIDD-0149830 and CIDD-066790 are novel drugs that overcome some of PZQ limitations, and CIDD-0150303 can be used with PZQ in combination therapy.
Topics: Animals; Humans; Praziquantel; Oxamniquine; Schistosomiasis; Schistosoma mansoni; Combined Modality Therapy; Neglected Diseases; Schistosomiasis mansoni; Anthelmintics
PubMed: 37428793
DOI: 10.1371/journal.ppat.1011018 -
Scientific Reports Dec 2023This research aims to study the anthelmintic properties of selected five (5) tropical plant extracts, ascertained margin of fish host safety in reference with...
This research aims to study the anthelmintic properties of selected five (5) tropical plant extracts, ascertained margin of fish host safety in reference with praziquantel, a commonly used chemo-therapeutics. Qualitative and quantitative analysis of Alligator pepper seeds (Aframomum melegueta), Moringa leaves (Moringa oleifera), Neem leaves (Azadirachta indica), Ginger bulbs (Zingiber officinale) and Garlic (Allium sativum) and their potencies in reference to praziquantel against Clarias gariepinus and different classes of helminth parasites were investigated. The results obtained show that the 70% ethanol extract had 80 to 100% presence of the phytochemical content, compared with the 100% aqueous and 100% ethanol extracts with 50 to 80% and 50 to 90%, respectively. Among the five tropical plants, the richest in saponin and flavonoids are alligator pepper and neem with alkaloids, tannin, flavonoid and saponin in ratios 1:1:3:9 and 1:1:4:3 respectively. While, moringa, garlic and ginger are rich in alkaloids with alkaloids, tannin, flavonoid and saponin in ratios, 8:1:10:1, 6:2:1:4 and 6:3:2:1, respectively. Aframomum melegueta and praziquantel showed above 70% potency (at 96 h LC) against all the classes of parasites; Wenyonia spp (cestode), Procamallanus spp (nematode), Tenuisentis spp (acanthocephalan), and Electrotaenia sp (cestode) as compared to the other plant extracts that showed above 70% potency (at 96 h LC) only against Electrotaenia spp. Sub-lethal Concentrations (96 h LC) of praziquantel and Aframomum melegueta on the juvenile fish host (12.36 mg/l and 9.9 mg/l respectively) were found to be 90.9% and 93.5% effective against adult Electrotaenia spp after 8 to 10 min of exposure. These concentrations were 78 to 85.7% and 89.7 to 88.4%, respectively, effective against the other classes of parasites after 18 to 25 min and 15 to 21 min of exposure. These concentrations were tested on the post juvenile of the fish to determine behavioral changes; there were no significant behavioral responses after 24 h of exposure. The effective concentrations indicate the widest margin of safety for the fish host.
Topics: Animals; Parasites; Tannins; Praziquantel; Anthelmintics; Plant Extracts; Alkaloids; Zingiber officinale; Zingiberaceae; Ethanol; Garlic; Fishes; Phytochemicals; Flavonoids; Saponins
PubMed: 38123590
DOI: 10.1038/s41598-023-48164-8 -
Tropical Medicine and Health Dec 2023Preventive chemotherapy with a single dose of praziquantel given to an all-at-risk population through mass drug administration is the cornerstone intervention to control...
BACKGROUND
Preventive chemotherapy with a single dose of praziquantel given to an all-at-risk population through mass drug administration is the cornerstone intervention to control and eliminate schistosomiasis as a public health problem. This intervention mainly targets school age children, and pre-school age children (pre-SAC) are excluded from receiving preventive chemotherapy, partly due to scarcity of data on praziquantel treatment outcomes.
METHODS
We conducted active efficacy and safety surveillance of praziquantel treatment among 240 Schistosoma mansoni-infected pre-SAC who received a single dose of praziquantel (40 mg/kg) in southern Ethiopia. The study outcomes were egg reduction rates (ERR) and cure rates (CRs) four weeks after treatment using the Kato-Katz technique and treatment-associated adverse events (AEs) that occurred within 8 days post-treatment.
RESULTS
The overall ERR was 93.3% (WHO reference threshold ≥ 90%), while the CR was 85.2% (95% CI = 80.0-89.5%). Baseline S. mansoni infection intensity was significantly associated with CRs, 100% among light infected than moderate (83.4%) or heavy (29.4%) infected children. An increase of 100 in baseline S. mansoni egg count per gram of stool resulted in a 26% (95% CI: 17%, 34%) reduction in the odds of cure. The incidence of experiencing at least one type of AE was 23.1% (95% CI: 18.0%, 29.0%). Stomachache, diarrhea, and nausea were the most common AEs. AEs were mild-to-moderate grade and transient. Pre-treatment moderate (ARR = 3.2, 95% CI: 1.69, 6.14) or heavy infection intensity (ARR = 6.5, 95% CI: 3.62, 11.52) was a significant predictor of AEs (p < 0.001). Sex, age, or soil-transmitted helminth coinfections were not significant predictors of CR or AEs.
CONCLUSIONS
Single-dose praziquantel is tolerable and effective against S. mansoni infection among pre-SAC, and associated AEs are mostly mild-to-moderate and transient. However, the reduced CR in heavily infected and AEs in one-fourth of S. mansoni-infected pre-SAC underscores the need for safety and efficacy monitoring, especially in moderate-to-high infection settings. Integrating pre-SACs in the national deworming programs is recommended to accelerate the elimination of schistosomiasis as a public health problem.
PubMed: 38124206
DOI: 10.1186/s41182-023-00562-4 -
Pharmacogenomics and Personalized... 2023This study aimed to discern the association between PLP2 expression, its biological significance, and the extent of immune infiltration in human GBM.
OBJECTIVE
This study aimed to discern the association between PLP2 expression, its biological significance, and the extent of immune infiltration in human GBM.
METHODS
Utilizing the GEPIA2 and TCGA databases, we contrasted the expression levels of PLP2 in GBM against normal tissue. We utilized GEPIA2 and LinkedOmics for survival analysis, recognized genes co-expressed with PLP2 via cBioPortal and GEPIA2, and implemented GO and KEGG analyses. The STRING database facilitated the construction of protein-protein interaction networks. We evaluated the relationship of PLP2 with tumor immune infiltrates using ssGSEA and the TIMER 2.0 database. An IHC assay assessed PLP2 and PDL-1 expression in GBM tissue, and the Drugbank database aided in identifying potential PLP2-targeting compounds. Molecular docking was accomplished using Autodock Vina 1.2.2.
RESULTS
PLP2 expression was markedly higher in GBM tissues in comparison to normal tissues. High PLP2 expression correlated with a decrease in overall survival across two databases. Functional analyses highlighted a focus of PLP2 functions within leukocyte. Discrepancies in PLP2 expression were evident in immune infiltration, impacting CD4+ T cells, neutrophils, myeloid dendritic cells, and macrophages. There was a concomitant increase in PLP2 and PD-L1 expression in GBM tissues, revealing a link between the two. Molecular docking with ethosuximide and praziquantel yielded scores of -7.441 and -4.295 kcal/mol, correspondingly.
CONCLUSION
PLP2's upregulation in GBM may adversely influence the lifespan of GBM patients. The involvement of PLP2 in pathways linked to leukocyte function is suggested. The positive correlation between PLP2 and PD-L1 could provide insights into PLP2's role in glioma modulation. Our research hints at PLP2's potential as a therapeutic target for GBM, with ethosuximide and praziquantel emerging as potential treatment candidates, especially emphasizing the potential of these compounds in GBM treatment targeting PLP2.
PubMed: 37964785
DOI: 10.2147/PGPM.S425251 -
Tierarztliche Praxis. Ausgabe K,... Oct 2023A 4-year-old, spayed female mixed breed dog was presented with large crater-like, well-demarcated, erosive and ulcerative necrotic lesions of the skin, elevated body...
A 4-year-old, spayed female mixed breed dog was presented with large crater-like, well-demarcated, erosive and ulcerative necrotic lesions of the skin, elevated body temperature and lethargy, that began 14 days after vaccination and treatment with fluralaner and milbemycin/praziquantel. Cytology revealed severe pyogranulomatous inflammation with moderate numbers of extracellular microorganisms. Histopathologic examination showed severe multifocal pyogranulomatous dermatitis and panniculitis with severe dermal edema and severe neutrophilic exocytosis with band-like infiltration of the lower portion of the epidermis consistent with pyoderma gangrenosum. Despite intensive immunosuppressive and antimicrobial therapy and intensive inpatient care, the dog was euthanized 16 days after admission due to complications with clinical signs of sepsis, acute dyspnea and thoracic effusion.
Topics: Dogs; Female; Animals; Pyoderma Gangrenosum; Immunosuppressive Agents; Anti-Infective Agents; Skin; Dog Diseases
PubMed: 37956667
DOI: 10.1055/a-2174-6948