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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 -
Journal of Medicinal Chemistry Dec 2023Schistosomiasis is a disease affecting >200 million people worldwide, but its treatment relies on a single agent, praziquantel. To investigate new avenues for...
Schistosomiasis is a disease affecting >200 million people worldwide, but its treatment relies on a single agent, praziquantel. To investigate new avenues for schistosomiasis control, we have conducted the first systematic analysis of bromodomain-containing proteins (BCPs) in a causative species, . Having identified 29 putative bromodomains (BRDs) in 22 proteins, we selected BRD3, a tandem BRD-containing BCP that shows high similarity to the human bromodomain and extra terminal domain (BET) family, for further studies. Screening 697 small molecules identified the human BET BRD inhibitor I-BET726 as a ligand for BRD3. An X-ray crystal structure of I-BET726 bound to the second BRD of BRD3 [BRD3(2)] enabled rational design of a quinoline-based ligand () with an ITC = 364 ± 26.3 nM for BRD3(2). The ethyl ester pro-drug of compound (compound ) shows substantial effects on sexually immature larval schistosomula, sexually mature adult worms, and snail-infective miracidia in assays.
Topics: Animals; Female; Humans; Schistosoma mansoni; Oviposition; Ligands; Schistosomiasis; Schistosomiasis mansoni
PubMed: 38048437
DOI: 10.1021/acs.jmedchem.3c01321 -
Microbiology Spectrum Jan 2024Schistosomes cause schistosomiasis, one of the neglected tropical diseases as defined by the WHO. For decades, the treatment of schistosomiasis relies on a single drug,...
Schistosomes cause schistosomiasis, one of the neglected tropical diseases as defined by the WHO. For decades, the treatment of schistosomiasis relies on a single drug, praziquantel. Due to its wide use, there is justified fear of resistance against this drug, and a vaccine is not available. Besides its biological relevance in signal transduction processes, the class of G protein-coupled receptors (GPCRs) is also well suited for drug design. Against this background, we characterized one GPCR of , GPCR20, at the molecular and functional level. We identified two potential neuropeptides (NPPs) as ligands, NPP26 and NPP40, and unraveled their roles, in combination with GPCR20, in neuronal processes controlling egg production, oogenesis, and growth of females. Since eggs are closely associated with the pathogenesis of schistosomiasis, our results contribute to the understanding of processes leading to egg production in schistosomes, which is under the control of pairing in this exceptional parasite.
Topics: Animals; Female; Schistosoma mansoni; Schistosomiasis mansoni; Rhodopsin; Sex Differentiation; Schistosomiasis
PubMed: 38047698
DOI: 10.1128/spectrum.02193-23 -
The Journal of Biological Chemistry Jan 2024Parasitic flatworms cause various clinical and veterinary infections that impart a huge burden worldwide. The most clinically impactful infection is schistosomiasis, a...
Parasitic flatworms cause various clinical and veterinary infections that impart a huge burden worldwide. The most clinically impactful infection is schistosomiasis, a neglected tropical disease caused by parasitic blood flukes. Schistosomiasis is treated with praziquantel (PZQ), an old drug introduced over 40 years ago. New drugs are urgently needed, as while PZQ is broadly effective it suffers from several limitations including poor efficacy against juvenile worms, which may prevent it from being completely curative. An old compound that retains efficacy against juvenile worms is the benzodiazepine meclonazepam (MCLZ). However, host side effects caused by benzodiazepines preclude development of MCLZ as a drug and MCLZ lacks an identified parasite target to catalyze rational drug design for engineering out human host activity. Here, we identify a transient receptor potential ion channel of the melastatin subfamily, named TRPM, as a parasite target of MCLZ. MCLZ potently activates Schistosoma mansoni TRPM through engagement of a binding pocket within the voltage-sensor-like domain of the ion channel to cause worm paralysis, tissue depolarization, and surface damage. TRPM reproduces all known features of MCLZ action on schistosomes, including a lower activity versus Schistosoma japonicum, which is explained by a polymorphism within this voltage-sensor-like domain-binding pocket. TRPM is distinct from the TRP channel targeted by PZQ (TRPM), with both anthelmintic chemotypes targeting unique parasite TRPM paralogs. This advances TRPM as a novel druggable target that could circumvent any target-based resistance emerging in response to current mass drug administration campaigns centered on PZQ.
Topics: Animals; Humans; Anthelmintics; Benzodiazepines; Benzodiazepinones; Clonazepam; Praziquantel; Schistosoma mansoni; Schistosomiasis mansoni; TRPM Cation Channels
PubMed: 38043794
DOI: 10.1016/j.jbc.2023.105528 -
Microbiology Resource Announcements Jan 2024Here, we describe the fecal microbiome of laboratory beagles in a non-invasive experiment designed to contrast versus bioequivalence in response to antiparasitic drug...
Here, we describe the fecal microbiome of laboratory beagles in a non-invasive experiment designed to contrast versus bioequivalence in response to antiparasitic drug administration. The experiment provided a unique opportunity to evaluate metagenomic profiles of canine feces before and after anti-parasitic drug exposure.
PubMed: 38018965
DOI: 10.1128/MRA.00860-23 -
Trials Nov 2023Schistosomiasis control relies on praziquantel for preventive chemotherapy. Alternative drugs are needed for the treatment and control of schistosomiasis. Praziquantel...
SCHISTOACT: a protocol for an open-label, five-arm, non-inferiority, individually randomized controlled trial of the efficacy and safety of praziquantel plus artemisinin-based combinations in the treatment of Schistosoma mansoni infection.
BACKGROUND
Schistosomiasis control relies on praziquantel for preventive chemotherapy. Alternative drugs are needed for the treatment and control of schistosomiasis. Praziquantel is effective against adult schistosome worms but ineffective against larval stages of the parasite and cannot prevent re-infection or interrupt the transmission of infection. Continued reliance on praziquantel for wide-scale schistosomiasis control will likely accelerate the emergence of drug resistance. Artemisinin derivatives are effective against the juvenile stages but ineffective against adult worms. The SCHISTOACT study aimed to evaluate the efficacy and safety of praziquantel plus one of four artemisinin-based combinations in treating Schistosoma mansoni infection in Kenya.
METHODS
The SCHISTOACT study is an open-label, head-to-head, five-arm, proof-of-concept, non-inferiority, individually randomized controlled trial with a follow-up of 12 weeks. A total of 540 primary school-aged children from the Mwea area, Kirinyaga County in central Kenya, diagnosed with S. mansoni infection (by Kato-Katz method) are randomly allocated (1:1:1:1:1) to a single dose of praziquantel plus a 3-day course of artesunate-sulfalene/pyrimethamine, or artesunate-amodiaquine, or artesunate plus mefloquine, or dihydroartemisinin-piperaquine, or praziquantel control arm. The primary endpoints are efficacy (cure rate, assessed by microscopy) and safety (adverse events) of each study arm 6 weeks after treatment. Secondary endpoints include cumulative cure rate, egg reduction rate, and re-infection 12 weeks after treatment. The non-inferiority margin is set at - 10 for the risk difference in cure rates between praziquantel and the combined treatment.
DISCUSSION
This study assesses a strategy for repurposing artemisinin-based combination therapies (ACTs) for treating schistosomiasis. It adopts a head-to-head comparison of four different ACTs to test a non-inferiority hypothesis and to strengthen local capacity to conduct clinical trials for interventions against neglected tropical diseases.
TRIAL REGISTRATION
Pan-African Clinical Trials Registry PACTR202001919442161 . Retrospectively registered on 6 January 2020.
Topics: Adult; Animals; Child; Humans; Anthelmintics; Artemisinins; Artesunate; Drug Therapy, Combination; Praziquantel; Randomized Controlled Trials as Topic; Reinfection; Schistosoma mansoni; Schistosomiasis; Schistosomiasis mansoni; Treatment Outcome; Equivalence Trials as Topic
PubMed: 38012787
DOI: 10.1186/s13063-023-07790-3 -
Infectious Diseases of Poverty Nov 2023Over the past two decades, preventive chemotherapy (PC) with praziquantel (PZQ) is the major strategy for controlling schistosomiasis in Senegal. The objective of this...
BACKGROUND
Over the past two decades, preventive chemotherapy (PC) with praziquantel (PZQ) is the major strategy for controlling schistosomiasis in Senegal. The objective of this analysis was to update the endemicity of schistosomiasis at community level for better targeting mass treatment with PZQ in Senegal.
METHODS
Demographic and epidemiological data from 1610 community health areas were analyzed using the schistosomiasis community data analysis tool of Expanded Special Project for Elimination of Neglected Tropical Diseases which developed by World Health Organization/Africa Office (WHO/AFRO). The tool uses a WHO/AFRO decision tree for areas without epidemiological data to determine whether mass treatment should be continued at community level. Descriptive analysis was performed.
RESULTS
Overall, the endemicity of 1610 community health areas were updated based on the data from the district endemicity (33.5%) and the form of Join request for selected PC medicine (40.5%). Up to 282 (17.5%) and 398 (24.7%) of community health areas were classified as moderate and high endemicity. 41.1% of communities were non endemic. High endemicity was more important in Tambacounda, Saint Louis, Matam, Louga and Kedougou. A change in endemicity category was observed when data was disagregted from district level to community level. Implementation units classified non endemic were more important at community level (n = 666) compared to district level (n = 324). Among 540 areas previously classified high endemic at district level, 392 (72.6%) remained high prevalence category, while 92 (17.0%) became moderate, 43 (8.0%) low and 13 (2.4%) non-endemics at community level. Number of implementation units requiring PC was more important at district level (1286) compared to community level (944). Number of school aged children requiring treatment was also more important at district level compared to community level.
CONCLUSIONS
The analysis to disaggregate data from district level to community level using the WHO/AFRO schistosomiasis sub-district data optimization tool provide an update of schistosomiasis endemicity at community level. This study has allowed to better target schistosomiasis interventions, optimize use of available PZQ and exposed data gaps.
Topics: Child; Humans; Praziquantel; Senegal; Schistosomiasis; Chemoprevention; Prevalence; Anthelmintics
PubMed: 38008772
DOI: 10.1186/s40249-023-01155-3 -
Infectious Diseases of Poverty Nov 2023Screening for opisthorchiasis, a parasitic worm infection affecting many millions of people in Southeast Asia, has traditionally relied on faecal egg examination such as...
BACKGROUND
Screening for opisthorchiasis, a parasitic worm infection affecting many millions of people in Southeast Asia, has traditionally relied on faecal egg examination such as the formalin-ethyl acetate concentration technique (FECT) and Kato-Katz method. Although the urinary enzyme-linked immunosorbent assay (ELISA) has been used more recently, we developed a urinary antigen-based rapid diagnostic test (RDT) to simplify diagnosis and as a point-of-care testing (POCT) and field applications for surveillance and control of opisthorchiasis.
METHODS
A urinary Opisthorchis viverrini (OV)-RDT was developed using immunochromatographic methodology with a specific monoclonal antibody against OV. The diagnostic performance of the urinary OV-RDT was compared to that of quantitative faecal FECT and urinary antigen ELISA (n = 493). Cross-reactivities of urinary OV-RDT with other helminthiases coexisted with O. viverrini were determined (n = 96). A field trial in the application of urinary OV-RDT was compared with urinary antigen ELISA at baseline screening and assessment of drug treatment outcomes in opisthorchiasis (n = 1629). The McNemar chi-square, Kruskal-Wallis and Cohen's kappa coefficient (κ-value) tests were used for statistical analyses.
RESULTS
Urinary OV-RDT had sensitivity of 94.2% and specificity of 93.2%, compared to faecal FECT. Urinary OV-RDT had high diagnostic agreement (Kappa = 0.842-0.874, P < 0.001) and quantitative correlation with urinary antigen ELISA (Kruskal-Wallis tests = 316.2, P < 0.0001) and faecal FECT (Kruskal-Wallis tests = 362.3, P < 0.0001). The positive rates by OV-RDT, ELISA and FECT were 48.9%, 52.5% and 49.3%, respectively. Cross-reactions of urinary OV-RDT with other helminthiases were few (2%). Field trials of urinary OV-RDT yielded comparable prevalence of O. viverrini between urinary OV-RDT (53.2%) and urinary antigen ELISA (54.0%). OV screening showed high diagnostic agreement (kappa > 0.8, P < 0.0001) between urinary OV-RDT and urinary antigen ELISA. The cure rates of opisthorchiasis at 1 month post-praziquantel treatment determined by urinary OV-RDT (86.6%) and urinary antigen ELISA (80.5%) were similar (P > 0.05).
CONCLUSIONS
The urinary OV-RDT test has high potential as a new tool for screening and evaluating treatment outcomes in opisthorchiasis. The ease of sample collection and simplicity of urinary OV-RDT may facilitate mass screening, control and elimination of opisthorchiasis, thereby contributing to a reduction in the disease burden in Southeast Asia.
Topics: Animals; Humans; Opisthorchiasis; Rapid Diagnostic Tests; Sensitivity and Specificity; Opisthorchis; Praziquantel; Thailand
PubMed: 37990282
DOI: 10.1186/s40249-023-01162-4 -
Revista Espanola de Enfermedades... Nov 2023Schistosomiasis is a parasitic infection caused by trematode species of the genus Schistosoma. It is prevalent in tropical regions of Africa, Asia and South America,...
Schistosomiasis is a parasitic infection caused by trematode species of the genus Schistosoma. It is prevalent in tropical regions of Africa, Asia and South America, being rare in Europe, where it is usually diagnosed in immigrants and tourists from endemic areas. It has different clinical forms of presentation. Hepatosplenic schistosomiasis produces periportal fibrosis, which can progress to presinusoidal portal hypertension, with all its associated complications. We present the case of a 43-year-old female patient from the Philippines who was referred to gastroenterology consultation due to liver enzyme alteration with a predominantly cholestatic pattern. An aetiological study was performed, with negative results. An abdominal ultrasound revealed signs of chronic liver disease, with transient elastography of 9.5 kPa. A percutaneous liver biopsy was performed, with histological findings consistent with infestation by schistosome eggs, receiving treatment with praziquantel and subsequently verifying its eradication with a stool test.
PubMed: 37982557
DOI: 10.17235/reed.2023.10036/2023 -
Veterinary Parasitology Dec 2023Intestinal parasites, including cestodes like Dipylidium caninum, are common in dogs in the United States of America (USA), but fecal flotation consistently, and, at...
Intestinal parasites, including cestodes like Dipylidium caninum, are common in dogs in the United States of America (USA), but fecal flotation consistently, and, at times, dramatically, fails to identify many of these infections. To determine the extent to which including coproantigen testing for D. caninum would improve the identification of dogs infected with this cestode, we evaluated fecal samples from 877 dogs (589 pet and 288 from municipal shelters) from six USA states using zinc sulfate (specific gravity 1.24) fecal flotation with centrifugation along with coproantigen detection for Giardia sp., hookworms, ascarids, and Trichuris vulpis. For D. caninum, PCR of perianal swabs was included. Intestinal parasite infections were identified, using centrifugal fecal flotation or coproantigen, in 265 dogs (13.2 % pet, 64.9 % shelter). Dipylidium caninum infection was detected in 5.6 % of dogs with the combination of coproantigen and centrifugal fecal flotation, and 7.3 % of dogs when perianal swab results were included; prevalence varied by diagnostic method, population, and geographic region. In pet dogs, D. caninum infection was identified by fecal flotation (0), coproantigen (2.2 %), or perianal swabs (1.2 %). The same methods revealed infection in 0.3 %, 12.5 %, and 11.1 % of shelter dogs, respectively. Frequent use of praziquantel in shelter dogs (116/288; 40.3 %) may have reduced prevalence. Positive and negative agreement of D. caninum coproantigen with perianal swab PCR in pet dogs was 85.7 % and 98.8 %, respectively. Multiple logistic regression analysis accounting for region, population, and age found D. caninum infection to be more common in shelter dogs relative to pet (adjusted OR 4.91 [2.48, 10.24]) and in the Southcentral and Southeast regions relative to North (adjusted OR 9.59 [1.92, 174.13] and 17.69 [3.67, 318.09] respectively). Coproantigen testing also enhanced the detection of other intestinal parasites over fecal flotation alone, including Giardia sp. (14.7 % vs 3.3 %), hookworms (13.8 % vs 8.4 %), ascarids (2.9 % vs 2.2 %), and T. vulpis (2.9 % vs 1.4 %). Together, these data indicate that the coproantigen assay employed increases detection of D. caninum infections several fold, supporting the use of this test in clinical practice, and add to a growing body of research documenting enhanced diagnosis through implementation of multiple laboratory-based methods.
Topics: Animals; Dogs; Parasites; Intestinal Diseases, Parasitic; Cestode Infections; Trichuris; Giardia; Feces; Prevalence; Dog Diseases
PubMed: 37976897
DOI: 10.1016/j.vetpar.2023.110073