-
The American Journal of Tropical... Apr 2024Unlike praziquantel, artemisinin derivatives are effective against juvenile schistosome worms. We assessed the efficacy and safety of a single oral dose of artesunate...
Efficacy of a Single Oral Dose of Artesunate plus Sulfalene-Pyrimethamineversus Praziquantel in the Treatment of Schistosoma mansoni in Kenyan Children: An Open-Label, Randomized, Exploratory Trial.
Unlike praziquantel, artemisinin derivatives are effective against juvenile schistosome worms. We assessed the efficacy and safety of a single oral dose of artesunate plus sulfalene-pyrimethamine versus praziquantel in the treatment of Schistosoma mansoni. Seventy-three schoolchildren (aged 9-15 years) with confirmed S. mansoni infection in Rarieda, western Kenya, were randomly assigned to receive either a single oral dose of artesunate plus sulfalene-pyrimethamine (n = 39) or a single dose of praziquantel (n = 34). The cure and egg reduction rates at 4 weeks posttreatment were 69.4% (25/36) versus 80.6% (25/31) (P = 0.297) and 99.1% versus 97.5% (P = 0.607) in the artesunate plus sulfalene-pyrimethamine group versus praziquantel group, respectively. Fourteen children developed adverse events, and there were no serious adverse events. A single oral dose of artesunate plus sulfalene-pyrimethamine has efficacy comparable to that of praziquantel in the treatment of S. mansoni, but these results should be confirmed in larger randomized controlled trials.
Topics: Adolescent; Animals; Child; Humans; Anthelmintics; Artemisinins; Artesunate; Drug Therapy, Combination; East African People; Kenya; Praziquantel; Pyrimethamine; Schistosoma mansoni; Schistosomiasis mansoni; Sulfalene; Treatment Outcome
PubMed: 38460198
DOI: 10.4269/ajtmh.23-0337 -
Frontiers in Epidemiology 2023The burden of schistosomiasis in Zambia has remained high over the years. The World Health Assembly recommended adequate mass drug administration coverage for...
The burden of schistosomiasis in Zambia has remained high over the years. The World Health Assembly recommended adequate mass drug administration coverage for schistosomiasis using Praziquantel chemotherapy for school-aged children and all at-risks adults. We aimed at investigating the coverage and the factors associated to the uptake for MDA for schistosomiasis in Ng'ombe township of Lusaka, Zambia. A cross-sectional survey was conducted in May and June 2021 phone calls to the residents of Ng'ombe township. Commcare software was used in the conduct of the survey. Pearson's Chi-square test and multiple logistic regression were conducted using the STATA version 15.0. 769 study participants were randomly selected using systematic sampling, of which 76.3% were younger than 40 years, 64.9% were female, 64.4% were married, 56.3% had reached the secondary educational level and 51.9% were employed. Coverage for MDA for schistosomiasis in Ng'ombe township in 2018 was found to be 49.8% (95% CI: 46.2%-53.4%). Positive predictors of the MDA were prior knowledge of the occurrence of the MDA in 2018 (aOR: 2.892, < 0.001) and believing that the provision of incentives like snacks was important during the MDA with PZQ in Ng'ombe township (aOR: 1.926, = 0.001), whereas age (aOR:0.979, = 0.009), marital status (aOR:0.620, = 0.006), employment status (aOR:0.587, = 0.001) were negative predictors of the MDA. Elimination of the burden of schistosomiasis in endemic settings needs the attainment of an optimum coverage and uptake during MDA with PZQ. Therefore, prior knowledge about an impending intervention and the provision of incentives like snacks during the intervention should be prioritized by MDA implementers, while background characteristics such as age, marital status, and employment status need to be taken into consideration when planning and promoting uptake in future MDAs.
PubMed: 38455938
DOI: 10.3389/fepid.2023.1168282 -
Parasitology International Aug 2024A case description of a rare occurrence of female genital schistosomiasis affecting the upper genital tract that presented with features mimicking an ovarian neoplasm.
OBJECTIVE
A case description of a rare occurrence of female genital schistosomiasis affecting the upper genital tract that presented with features mimicking an ovarian neoplasm.
CASE REPORT
Female genital schistosomiasis is a neglected clinical manifestation of the water-born parasitic disease which occurs due to the presence of schistosome eggs in the genitalia of women. A 23-year-old nulliparous woman presented with progressive abdominal distension. An abdominopelvic CT scan revealed a multilobulated right adnexal mass with gross ascites. Diagnosis of schistosomiasis was made by histology of biopsied specimens following laparotomy. Cervical colposcopic findings were consistent with female genital schistosomiasis. She was successfully treated with praziquantel.
CONCLUSION
Female genital schistosomiasis of the upper genital tract can mimic an ovarian malignancy. Hence there is a need for its consideration as a differential diagnosis in patients with non-classical presentations of pelvic tumours in schistosomiasis-endemic areas.
Topics: Female; Humans; Ovarian Neoplasms; Praziquantel; Diagnosis, Differential; Young Adult; Anthelmintics; Schistosomiasis haematobia; Schistosomiasis; Animals
PubMed: 38452972
DOI: 10.1016/j.parint.2024.102878 -
Journal of Taibah University Medical... Apr 2024Schistosomiasis, a neglected tropical disease, is a leading cause of mortality in affected geographic areas. Currently, because no vaccine for schistosomiasis is...
OBJECTIVES
Schistosomiasis, a neglected tropical disease, is a leading cause of mortality in affected geographic areas. Currently, because no vaccine for schistosomiasis is available, control measures rely on widespread administration of the drug praziquantel (PZQ). The mass administration of PZQ has prompted concerns regarding the emergence of drug resistance. Therefore, new therapeutic targets and potential compounds are necessary to combat schistosomiasis.
METHODS
Twenty-four potent derivatives of PZQ were optimized via density functional theory (DFT) at the B3LYP/6-31G∗ level. Quantitative structureactivity relationship (QSAR) models were generated and statistically validated, and a lead candidate was selected to develop therapeutic options with improved efficacy against schistosomiasis. The biological and binding energies of the designed compounds were evaluated. In addition, molecular dynamics; drug-likeness; absorption, distribution, metabolism, excretion, and toxicity (ADMET); and DFT studies were performed on the newly designed compounds.
RESULTS
Five QSAR models were generated, among which model 1 had favorable validation parameters (R: 0.957, R: 0.941, LOF: 0.101, Qcv: 0.906, and R: 0.783) and was chosen to identify a lead candidate. Other statistical parameters for the chosen model included variance inflation factor values ranging from 1.242 to 1.678, and a Y-scrambling coefficient (cRp) of 0.747. Five new compounds were designed with improved predicted activity (ranging from 5.081 to 7.022) surpassing those of both the lead compound and PZQ (predicted pEC of 5.545). Molecular dynamics simulation revealed high binding affinity of the proposed compounds toward the target receptor. ADMET and drug-likeness assessments indicated adherence to Lipinski's rule of five criteria, thereby suggesting pharmacological and oral safety. In addition, DFT analysis indicated resistance to electronic alteration during chemical reactions.
CONCLUSION
The proposed compounds exhibited potential drug characteristics, thus indicating their suitability for further investigation to enhance schistosomiasis treatment options.
PubMed: 38440085
DOI: 10.1016/j.jtumed.2024.02.003 -
Travel Medicine and Infectious Disease 2024
Topics: Humans; Schistosomiasis haematobia; Cystoscopy; Animals; Schistosoma haematobium; Urinary Tract Infections; Recurrence; Anthelmintics; Male; Female; Praziquantel; Adult
PubMed: 38423232
DOI: 10.1016/j.tmaid.2024.102702 -
PLoS Neglected Tropical Diseases Feb 2024Schistosomiasis is a major neglected parasitic disease that affects more than 240 million people worldwide caused by Platyhelminthes of the genus Schistosoma. The...
Schistosomiasis is a major neglected parasitic disease that affects more than 240 million people worldwide caused by Platyhelminthes of the genus Schistosoma. The treatment of schistosomiasis relies on the long-term application of a single safe drug, praziquantel (PZQ). Unfortunately, PZQ is very effective on adult parasites and poorly on larval stage and immature juvenile worms; this can partially explain the re-infection in endemic areas where patients are likely to host parasites at different developmental stages concurrently. Moreover, the risk of development of drug resistance because of the widespread use of a single drug in a large population is nowadays a serious threat. Hence, research aimed at identifying novel drugs to be used alone or in combination with PZQ is needed. Schistosomes display morphologically distinct stages during their life cycle and epigenetic mechanisms are known to play important roles in parasite growth, survival, and development. Histone deacetylase (HDAC) enzymes, particularly HDAC8, are considered valuable for therapeutic intervention for the treatment of schistosomiasis. Herein, we report the phenotypic screening on both larvae and adult Schistosoma mansoni stages of structurally different HDAC inhibitors selected from the in-house Siena library. All molecules have previously shown inhibition profiles on human HDAC6 and/or HDAC8 enzymes. Among them we identified a quinolone-based HDAC inhibitor, NF2839, that impacts larval and adult parasites as well as egg viability and maturation in vitro. Importantly, this quinolone-based compound also increases histone and tubulin acetylation in S. mansoni parasites, thus representing a leading candidate for the development of new generation anti-Schistosoma chemotherapeutics.
Topics: Animals; Humans; Anthelmintics; Histone Deacetylase 6; Larva; Praziquantel; Quinolones; Repressor Proteins; Schistosoma mansoni; Schistosomiasis; Schistosomiasis mansoni; Histone Deacetylase Inhibitors
PubMed: 38416775
DOI: 10.1371/journal.pntd.0011992 -
Parasite (Paris, France) 2024This clinical study assessed the efficacy of a topical combination of esafoxolaner, eprinomectin and praziquantel (NexGard Combo) in treating cats naturally infected...
This clinical study assessed the efficacy of a topical combination of esafoxolaner, eprinomectin and praziquantel (NexGard Combo) in treating cats naturally infected with the eyeworm Thelazia callipaeda (Nematoda, Thelaziidae). On Study Day (SD) 0, sixteen client-owned cats with eyeworm infection were allocated to an untreated control group (G1, 8 cats) or to a NexGard Combo treated group (G2, 8 cats) and subjected to ocular examination. Cats in G2 received the treatment as per label recommendations. On SD 7 and 14 (±1), cats were examined for the presence of eyeworms and clinical signs. On SD 14, eyeworms were collected and counted. On SD 7 and 14, all cats in G1 were still infected with eyeworms, while G2 cats were free from eyeworms on SD 7 and 14, demonstrating 100% efficacy (p < 0.0001). All collected eyeworms were morphologically and molecularly confirmed to be T. callipaeda. On SD 0, fifteen out of the sixteen cats (7 in G1 and 8 in G2) displayed inflammatory ocular signs. On SD 7, all eight untreated cats and seven treated cats displayed inflammatory ocular signs. On SD 14, five out of eight G2 treated cats had recovered, while the eight untreated cats still displayed inflammatory ocular signs. The treatment significantly reduced lacrimation and conjunctivitis (p = 0.0001). No adverse reactions occurred. This clinical study provides evidence that NexGard Combo is highly safe and effective for the treatment of T. callipaeda infection in cats under field conditions.
Topics: Humans; Cats; Animals; Praziquantel; Ivermectin; Thelazioidea; Isoxazoles; Naphthalenes
PubMed: 38415717
DOI: 10.1051/parasite/2024008 -
World Journal of Clinical Cases Feb 2024Ankylosing spondylitis (AS) is a chronic immune-mediated inflammatory disease. The prevailing theory links AS onset to infections in susceptible individuals....
BACKGROUND
Ankylosing spondylitis (AS) is a chronic immune-mediated inflammatory disease. The prevailing theory links AS onset to infections in susceptible individuals. Furthermore, infections may impair the immune responses. Numerous studies have investigated links between AS and various infections-bacterial, viral, fungal, and other microorganism infections. However, limited attention has been given to the association between AS and () infection.
CASE SUMMARY
A 27-year-old male with a 10-yr history of AS presented to our hospital with inflammatory lower back pain as the primary manifestation. Ten years ago, the patient had achieved a stable condition after treatment with biological agents. However, he experienced a recurrence of lumbosacral pain with an unexplained cause 10 d before hospital admission. A lumbosacral magnetic resonance imaging (MRI) scan revealed bone marrow edema in the left sacroiliac joint, and laboratory indicators were elevated. Moreover, the presence of eggs was detected in the stool. The patient was prescribed praziquantel, resulting in the disappearance of eggs in subsequent routine stool tests and relief from lumbosacral pain. A follow-up MRI scan performed after 4 months revealed a reduction in bone marrow edema around the left sacroiliac joint.
CONCLUSION
infections could potentially trigger the exacerbation of AS. Clinicians should pay attention to investigating the presence of infections.
PubMed: 38414593
DOI: 10.12998/wjcc.v12.i5.1018 -
Parasitology Research Feb 2024The objective of the study was to evaluate the in vitro and in vivo schistosomicidal activity of sanguinarine (SA) on Schistosoma mansoni and its in silico...
Sanguinarine: an alkaloid with promising in vitro and in vivo antiparasitic activity against different developmental stages of Schistosoma mansoni and in silico pharmacokinetic properties (ADMET).
The objective of the study was to evaluate the in vitro and in vivo schistosomicidal activity of sanguinarine (SA) on Schistosoma mansoni and its in silico pharmacokinetic parameters. ADMET parameters and oral bioavailability were evaluated using the PkCSM and SwissADME platforms, respectively. The activity of SA in vitro, at the concentrations of 1.0-25 µM, was analyzed through the parameters of motility, mortality, and cell viability of the worms at intervals of 3-24 h. Mice were infected with cercariae and treated by gavage with SA (5 mg/kg/day, in a single dose or two doses of 2.5 mg/kg every 12 h for 5 consecutive days) on the 1st (skin schistosomula), 14th (pulmonary schistosomula), 28th (young worms), and 45th (adult worms) days after infection. In vitro and in vivo praziquantel was the control. In vitro, SA showed schistosomicidal activity against schistosomula, young worms, and couples; with total mortality and reduced cell viability at low concentrations and incubation time. In a single dose of 5 mg/kg/day, SA reduces the total worm load by 47.6%, 54%, 55.2%, and 27.1%, and female worms at 52.0%, 39.1%, 52.7%, and 20.2%, respectively, results which are similar to the 2.5 mg/kg/day dose. SA reduced the load of eggs in the liver, and in histopathological and histomorphometric analyses, there was a reduction in the number and volume of hepatic granulomas, which exhibited less inflammatory infiltrate. SA has promising in vitro and in vivo schistosomicidal activity against different developmental stages of S. mansoni, in addition to reducing granulomatous liver lesions. Furthermore, in silico, SA showed good predictive pharmacokinetic ADMET profiles.
Topics: Female; Animals; Mice; Antiparasitic Agents; Schistosoma mansoni; Benzophenanthridines; Alkaloids; Anti-Infective Agents; Schistosomicides; Isoquinolines
PubMed: 38407619
DOI: 10.1007/s00436-024-08153-w -
Pharmaceutical Development and... Mar 2024The aim of this study was to evaluate the suitability of a non-disruptive Raman spectroscopic method to quantify drug concentrations below 5 w% within a polymer matrix...
The aim of this study was to evaluate the suitability of a non-disruptive Raman spectroscopic method to quantify drug concentrations below 5 w% within a polymer matrix produced by hot-melt extrusion (HME). For calibration, praziquantel (PZQ)-polyvinylpyrrolidone-vinylacetat-copolymer (PVP-VA) mixtures were extruded. By focusing the laser light of the Raman probe to a diameter of 1 mm and implementing a self-constructed filament holder, the signal-to-noise (S/N) ratio could be reduced considerably. The obtained Raman spectra show quite high fluorescence, which is likely to be caused by dissolved pharmaceutical active ingredient (API) in the polymer matrix. For content determination, HPLC analysis was conducted as a reference method using the same filament segments. A partial least squares (PLS) model, regressing the PZQ concentrations from HPLC method analysis versus the off-line collected Raman spectra, was developed. The linear correlation for a suitable extrusion run for the production of low-dosed filaments (extrusion 1, two kneading zones) is acceptable (R = 0.9915) while the correlation for a extrusion set-up with low miscibility (extrusion 2; without kneading zone) is unacceptable (R = 0.5349). The predictive performance of the calibration model from extrusion 1 is rated by the root mean square error of estimation (RMSEE), which was 0.08%. This calibration can now be used to validate the content of low-dosed filaments during HME.
Topics: Spectrum Analysis, Raman; Povidone; Polymers; Hot Melt Extrusion Technology; Drug Compounding; Hot Temperature
PubMed: 38407128
DOI: 10.1080/10837450.2024.2323622