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Journal of Chromatographic Science Nov 2023The topical product with three active pharmaceutical ingredients (APIs), namely, esafoxolaner, eprinomectin and praziquantel has demonstrated its efficacy in the...
Simultaneous Determination of Esafoxolaner, Eprinomectin, Praziquantel, BHT and Their Related Substances in a Topical Finished Product by a Single Reversed-Phase High-Performance Liquid Chromatography Method.
The topical product with three active pharmaceutical ingredients (APIs), namely, esafoxolaner, eprinomectin and praziquantel has demonstrated its efficacy in the treatment of cats with mixed infections with ectoparasites and nematodes and cestodes. A reversed-phase high-performance liquid chromatography (RP-HPLC) method has been developed and validated for assay and determination of related substances peaks of three APIs including the assay of antioxidant butylated hydroxytoluene (BHT) in the finished product. Analytes were separated on a short Zorbax SB-C18 column (50 × 4.6 mm I.D., 5 μm particle size, pore size: 80 Å) with gradient elution at 40 °C column temperature. Analytes were detected at 245 nm for praziquantel, esafoxolaner, eprinomectin and their degradation products. BHT and eprinomectin degradation product 8a-oxo-B1a were detected at 280 nm. All analytes of interest were adequately separated within 40 min. The assay for praziquantel, esafoxolaner, eprinomectin and BHT was conducted against their corresponding external reference standards. The related substances peaks of each API were determined by peak area and relative response factor against total peak area of their corresponding API peak in sample solution. This method has been demonstrated to be accurate, robust, specific and stability indicating.
Topics: Praziquantel; Chromatography, High Pressure Liquid; Ivermectin; Pesticides
PubMed: 36151056
DOI: 10.1093/chromsci/bmac078 -
Nature Structural & Molecular Biology May 2024Diseases 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 Fasciola because of a single amino acid change within the target of PZQ, a transient receptor potential ion channel in the melastatin family (TRPM), in Fasciola species. Here, we identify benzamidoquinazolinone analogs that are active against Fasciola TRPM. Structure-activity studies define an optimized ligand (BZQ) that caused protracted paralysis and tegumental damage to these liver flukes. BZQ also retained activity against Schistosoma mansoni comparable to PZQ and was active against TRPM orthologs in all profiled species of parasitic fluke. This broad-spectrum activity manifests as BZQ adopts a pose within the binding pocket of TRPM that is 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: 38714890
DOI: 10.1038/s41594-024-01298-3 -
Parasites & Vectors Jun 2024Reliance on praziquantel for the treatment and control of schistosomiasis is likely to facilitate the emergence of drug resistance. Combination therapy targeting adult... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of single-dose artesunate plus sulfalene/pyrimethamine combined with praziquantel for the treatment of children with Schistosoma mansoni or Schistosoma haematobium in western Kenya: a randomised, open-label controlled trial.
BACKGROUND
Reliance on praziquantel for the treatment and control of schistosomiasis is likely to facilitate the emergence of drug resistance. Combination therapy targeting adult and juvenile schistosome worms is urgently needed to improve praziquantel efficacy and delay the potential development of drug resistance. We assessed the efficacy and safety of single-dose praziquantel combined with single-dose artesunate plus sulfalene-pyrimethamine in the treatment of Kenyan children with schistosomiasis.
METHODS
This was an open-label, randomised clinical trial involving 426 school-aged children (7-15 years old) diagnosed with Schistosoma mansoni (by Kato-Katz) or S. haematobium (by urine filtration). They were randomly assigned (1:1:1) to receive a single dose of praziquantel (40 mg/kg), a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate) or combination therapy using a single dose of praziquantel (40 mg/kg) combined with a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate). The primary outcome was cure and egg reduction rates at 6 weeks post-treatment in the available case population. Adverse events were assessed within 3 h after treatment.
RESULTS
Of the 426 children enrolled, 135 received praziquantel, 150 received artesunate plus sulfalene-pyrimethamine, and 141 received combination therapy. Outcome data were available for 348 (81.7%) children. For S. mansoni-infected children (n = 335), the cure rates were 75.6%, 60.7%, and 77.8%, and the egg reduction rates were 80.1%, 85.0%, and 88.4% for praziquantel, artesunate plus sulfalene-pyrimethamine, and combination therapy, respectively. For S. haematobium-infected children (n = 145), the corresponding cure rates were 81.4%, 71.1%, and 82.2%, and the egg reduction rates were 95.6%, 97.1%, and 97.7%, respectively. Seventy-one (16.7%) children reported mild-intensity adverse events. The drugs were well tolerated and no serious adverse events were reported.
CONCLUSIONS
A single oral dose of praziquantel combined with artesunate plus sulfalene-pyrimethamine cured a high proportion of children with S. haematobium but did not significantly improve the treatment efficacy for either urinary or intestinal schistosomiasis. Sequential administration of praziquantel and artesunate plus sulfalene-pyrimethamine may enhance the efficacy and safety outcomes.
Topics: Humans; Child; Praziquantel; Pyrimethamine; Animals; Adolescent; Artesunate; Female; Male; Schistosomiasis mansoni; Schistosoma haematobium; Schistosomiasis haematobia; Schistosoma mansoni; Drug Therapy, Combination; Kenya; Artemisinins; Treatment Outcome; Anthelmintics; Sulfalene; Drug Combinations; Parasite Egg Count
PubMed: 38943214
DOI: 10.1186/s13071-024-06359-6 -
Cureus Sep 2023Neuroschistosomiasis is a rare manifestation of schistosomal infections presenting with cerebral and spinal cord involvement. We reported a case of a 31-year-old woman...
Neuroschistosomiasis is a rare manifestation of schistosomal infections presenting with cerebral and spinal cord involvement. We reported a case of a 31-year-old woman who presented with a history of headache, dizziness, and nausea. Brain MRI with contrast showed features suggestive of brain lesion with edema, and a serology test for Schistosoma was positive. She was diagnosed with neuroschistosomiasis and treated with intravenous steroids followed by praziquantel resulting in a significant regression of the brain mass. Cerebral neuroschistosomiasis is a rare complication of Schistosoma infection, and clinicians should consider it among the differential diagnosis of unexplained brain lesions.
PubMed: 37854757
DOI: 10.7759/cureus.45418 -
Parasitology Research Dec 2023Schistosomiasis is a neglected tropical disease caused by a parasitic, trematode blood fluke of the genus Schistosoma. With 20 million people infected, mostly due to... (Review)
Review
Schistosomiasis is a neglected tropical disease caused by a parasitic, trematode blood fluke of the genus Schistosoma. With 20 million people infected, mostly due to Schistosoma haematobium, Nigeria has the highest burden of schistosomiasis in the world. We review the status of human schistosomiasis in Nigeria regarding its distribution, prevalence, diagnosis, prevention, orthodox and traditional treatments, as well as snail control strategies. Of the country's 36 states, the highest disease prevalence is found in Lagos State, but at a geo-political zonal level, the northwest is the most endemic. The predominantly used diagnostic techniques are based on microscopy. Other methods such as antibody-based serological assays and DNA detection methods are rarely employed. Possible biomarkers of disease have been identified in fecal and blood samples from patients. With respect to preventive chemotherapy, mass drug administration with praziquantel as well as individual studies with artemisinin or albendazole have been reported in 11 out of the 36 states with cure rates between 51.1 and 100%. Also, Nigerian medicinal plants have been traditionally used as anti-schistosomal agents or molluscicides, of which Tetrapleura tetraptera (Oshosho, aridan, Aidan fruit), Carica papaya (Gwanda, Ìbẹ́pẹ, Pawpaw), Borreria verticillata (Karya garma, Irawo-ile, African borreria), and Calliandra portoricensis (Tude, Oga, corpse awakener) are most common in the scientific literature. We conclude that the high endemicity of the disease in Nigeria is associated with the limited application of various diagnostic tools and preventive chemotherapy efforts as well as poor knowledge, attitudes, and practices (KAP). Nonetheless, the country could serve as a scientific base in the discovery of biomarkers, as well as novel plant-derived schistosomicides and molluscicides.
Topics: Animals; Humans; Plants, Medicinal; Nigeria; Schistosomiasis; Schistosoma haematobium; Plant Extracts; Biomarkers; Schistosomiasis haematobia
PubMed: 37851179
DOI: 10.1007/s00436-023-07993-2 -
Acta Tropica Jun 2024The drug of choice for the treatment of opisthorchiasis caused by trematodes Opisthorchis viverrini and O. felineus is praziquantel (PZQ), but there is a constant search... (Comparative Study)
Comparative Study
BACKGROUND
The drug of choice for the treatment of opisthorchiasis caused by trematodes Opisthorchis viverrini and O. felineus is praziquantel (PZQ), but there is a constant search for new anthelmintics, including those of plant origin. Positive results on the use of artemisinin derivatives against O. viverrini opisthorchiasis have been shown previously, but the effect of these compounds on O. felineus has not been studied. Therefore, here, a comparative analysis of anthelmintic properties of artemisinin derivatives (artesunate [AS], artemether [AM], and dihydroartemisinin [DHA]) was carried out in vitro in relation to PZQ. Experiments were performed on newly excysted metacercariae (NEMs) and adult flukes of O. felineus.
RESULTS
Dose- and time-dependent effects of artemisinin derivatives and of PZQ were assessed in terms of motility and mortality of both NEMs and adult flukes. The most pronounced anthelmintic action was exerted by DHA, whose half-maximal inhibitory concentrations (IC) of 1.9 (NEMs) and 2.02 µg/mL (adult flukes) were lower than those of PZQ (0.56 and 0.25 µg/mL, respectively). In contrast to PZQ, the effects of DHA and AS were similar when we compared the two developmental stages of O. felineus (NEMs and adult flukes). In addition, AM, AS, and especially DHA at doses of 100 µg/mL disrupted tegument integrity in adult flukes, which was not observed with PZQ.
CONCLUSIONS
Artemisinin derivatives (AS, AM, and DHA) have good anthelmintic efficacy against the trematode O. felineus, and the action of these substances is comparable to (and sometimes better than) the effects of PZQ.
Topics: Animals; Artemisinins; Opisthorchis; Anthelmintics; Inhibitory Concentration 50; Praziquantel; Survival Analysis; Artemether; Artesunate; Dose-Response Relationship, Drug
PubMed: 38521124
DOI: 10.1016/j.actatropica.2024.107196 -
EBioMedicine Nov 2023A controlled human infection model for schistosomiasis (CHI-S) can speed up vaccine development and provides insight into early immune responses following schistosome...
BACKGROUND
A controlled human infection model for schistosomiasis (CHI-S) can speed up vaccine development and provides insight into early immune responses following schistosome exposure. Recently, we established CHI-S model using single-sex male-only Schistosoma mansoni (Sm) cercariae in Schistosoma-naïve individuals. Given important differences in antigenic profile and human immune responses to schistosomes of different sex, we pioneered a single-sex female-only CHI-S model for future use in vaccine development.
METHODS
We exposed 13 healthy, Schistosoma-naïve adult participants to 10 (n = 3) or 20 (n = 10) female cercariae and followed for 20 weeks, receiving treatment with praziquantel (PZQ) 60 mg/kg at week 8 and 12 after exposure.
FINDINGS
The majority (11/13) participants reported rash and/or itch at the site of exposure, 5/13 had transient symptoms of acute schistosomiasis. Exposure to 20 cercariae led to detectable infection, defined as serum circulating anodic antigen levels >1.0 pg/mL, in 6/10 participants. Despite two rounds of PZQ treatment, 4/13 participants showed signs of persistent infection. Additional one- or three-day PZQ treatment (1 × 60 mg/kg and 3 × 60 mg/kg) or artemether did not result in cure, but over time three participants self-cured. Antibody, cellular, and cytokine responses peaked at week 4 post infection, with a mixed Th1, Th2, and regulatory profile. Cellular responses were (most) discriminative for symptoms.
INTERPRETATION
Female-only infections exhibit similar clinical and immunological profiles as male-only infections but are more resistant to PZQ treatment. This limits future use of this model and may have important implications for disease control programs.
FUNDING
European Union's Horizon 2020 (grant no. 81564).
Topics: Adult; Animals; Humans; Male; Female; Schistosomiasis mansoni; Healthy Volunteers; Schistosoma mansoni; Praziquantel; Cytokines; Anthelmintics
PubMed: 37837930
DOI: 10.1016/j.ebiom.2023.104832 -
Frontiers in Public Health 2024Baseline mapping showed that schistosomiasis was highly/moderately endemic in nine districts in Sierra Leone. Mass drug administration (MDA) with praziquantel started in...
BACKGROUND
Baseline mapping showed that schistosomiasis was highly/moderately endemic in nine districts in Sierra Leone. Mass drug administration (MDA) with praziquantel started in 2009, and after multiple rounds of treatment, an impact assessment was conducted in 2016 followed by a second re-assessment in 2022 using cluster sampling to provide more granular data for refining chiefdom (sub-district) treatment strategies.
METHODS
On average, 20 rural villages were systematically selected per district by probability proportional to population size across the nine districts. Surveys were conducted in schools, and 24 school children aged between 5 and 14 years were randomly selected, with an equal number of boys and girls. One stool sample and one urine sample were collected per child. Two Kato-Katz slides were examined per stool for infection. Hemastix strips were used as a proxy for infection with urine filtration used for egg counts on hematuria-positive samples.
RESULTS
In total, 4,736 stool samples and 4,618 urine samples were examined across 200 schools in 125 chiefdoms. Overall, the prevalence of was 16.3% (95% CI: 15.3-17.4%), while the overall prevalence of was 2.0% (95% CI: 1.6-2.4%) by hematuria. The prevalence of heavy infections for and was 1.5% (95% CI: 1.1-1.9%) and 0.02% (95% CI: 0.0-0.14%), respectively. Among 125 chiefdoms surveyed, the overall schistosomiasis prevalence was <10% in 65 chiefdoms, 10-49.9% in 47 chiefdoms, and ≥ 50% in 13 chiefdoms. There was a mixed relationship between schistosomiasis in school children and WASH access in schools.
CONCLUSION
Sierra Leone has made significant progress in reducing schistosomiasis prevalence across the country after a decade of MDA intervention. However, high prevalence remains in some hotspot chiefdoms. The next steps are for the national program to investigate and address any potential issues such as low coverage or poor knowledge of schistosomiasis risk behaviors and, where appropriate, consider broadening to community-wide treatment in hotspot chiefdoms or communities.
Topics: Humans; Sierra Leone; Child; Female; Male; Adolescent; Child, Preschool; Praziquantel; Feces; Animals; Mass Drug Administration; Prevalence; Anthelmintics; Schistosomiasis; Schistosoma mansoni; Schistosomiasis mansoni; Rural Population; Endemic Diseases; Cluster Analysis; Schistosoma haematobium
PubMed: 38932788
DOI: 10.3389/fpubh.2024.1415486 -
Cureus Jul 2023Neurological involvement in schistosomiasis presents a significant and serious complication. While the disease is generally considered treatable during the early stages,...
BACKGROUND
Neurological involvement in schistosomiasis presents a significant and serious complication. While the disease is generally considered treatable during the early stages, the rarity of this condition often leads to delays in diagnosis and treatment. This study aims to report the clinical characteristics of pediatric patients with spinal neuroschistosomiasis (NS) in an endemic area to the disease.
METHODS
A retrospective cross-sectional review was conducted at Althora General Hospital in Ibb, Yemen, from January 2016 to January 2021. The study examined confirmed pediatric cases of spinal NS, analyzing their clinical characteristics, laboratory and radiological data, treatment approaches, and complications.
RESULTS
The study identified 10 cases of spinal NS with a mean age of 10.1± 3.2 years. The majority (90%) were male and from rural areas, all with a history of freshwater exposure, a known risk factor for schistosomiasis. The average time from presentation to treatment was 33.4± 45.6 days (7-150 days). Common symptoms observed in all patients were bladder dysfunction and paresthesia (100%). Intestinal dysfunction was prevalent in 90% of cases, while 80% exhibited limb weakness or inability to walk. The diagnosis was confirmed through cerebrospinal fluid (CSF) serology in 80% of cases, and stool and urine exams yielded positive results in 90% and 30% of cases, respectively. Magnetic Resonance Imaging findings revealed medullary lesions in 50% of cases, cauda equina lesions in 20%, and multiple lesions in 30%. All patients received oral praziquantel and high-dose steroids for at least three days as part of their initial treatment. During the average follow-up period of 5.6±1.7 months, one patient experienced lower extremity paraplegia, while two cases (20%) showed partial improvement with residual deficits including urinary and fecal incontinence. Complete resolution of symptoms was achieved in seven cases (70%).
CONCLUSION
Schistosomiasis should be considered in pediatric patients with myeloradicular manifestations, especially in endemic areas. Early identification can be achieved through history, prompt imaging, and CSF serology. In the absence of immediate test results, expert-guided presumptive therapy should be considered to minimize neurological complications.
PubMed: 37575694
DOI: 10.7759/cureus.41758 -
The American Journal of Tropical... Nov 2023Integration of vertical programs for the control of malaria, schistosomiasis, and soil-transmitted helminthiasis has been recommended to achieve elimination of malaria... (Randomized Controlled Trial)
Randomized Controlled Trial
Integration of vertical programs for the control of malaria, schistosomiasis, and soil-transmitted helminthiasis has been recommended to achieve elimination of malaria and neglected tropical diseases (NTD) by 2030. This qualitative study was conducted within the context of a randomized controlled trial to explore the perceptions and views of parents/caregivers of at-risk children and healthcare providers to determine their acceptability of the integrated malaria-helminth treatment approach. Randomly selected parents/caregivers of children enrolled in the trial, healthcare providers, trial staff, malaria, and NTD program managers were interviewed using purpose-designed topic guides. Transcripts obtained from the interviews were coded and common themes identified using content analysis were triangulated. Fifty-seven study participants comprising 26 parents/caregivers, 10 study children aged ≥ 10 years, 15 trial staff, four healthcare providers, and two managers from the Senegal Ministry of Health were interviewed. Thirty-eight of the participants (66.7%) were males, and their ages ranged from 10 to 65 years. Overall, the integrated malaria-helminth treatment approach was considered acceptable, but the study participants expressed concerns about the taste, smell, and side effects associated with amodiaquine and praziquantel in the combination package. Reluctance to accept the medications was also observed among children aged 10 to 14 years due to peer influence and gender-sensitive cultural beliefs. Addressing concerns about the taste and smell of amodiaquine and praziquantel is needed to optimize the uptake of the integrated treatment program. Also, culturally appropriate strategies need to be put in place to cater for the inclusion of children aged 10 to 14 years in this approach.
Topics: Child; Male; Animals; Humans; Adolescent; Young Adult; Adult; Middle Aged; Aged; Female; Praziquantel; Amodiaquine; Senegal; Helminthiasis; Helminths; Malaria
PubMed: 37722662
DOI: 10.4269/ajtmh.23-0113