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Biomedicines Aug 2023Schistosomiasis, a potentially fatal chronic disease whose etiological agents are blood trematode worms of the genus spp., is one of the most prevalent and debilitating...
Schistosomiasis, a potentially fatal chronic disease whose etiological agents are blood trematode worms of the genus spp., is one of the most prevalent and debilitating neglected diseases. The treatment of schistosomiasis depends exclusively on praziquantel (PZQ), a drug that has been used since the 1970s and that already has reports of reduced therapeutic efficacy, related with the development of -resistant or -tolerant strains. Therefore, the search for new therapeutic alternatives is an urgent need. Plumbagin (PLUM), a naphthoquinone isolated from the roots of plants of the genus , has aroused interest in research due to its antiparasitic properties against protozoa and helminths. Here, we evaluated the in vivo schistosomicidal potential of PLUM against and the in silico pharmacokinetic parameters. ADMET parameters and oral bioavailability were evaluated using the PkCSM and SwissADME platforms, respectively. The study was carried out with five groups of infected mice and divided as follows: an untreated control group, a control group treated with PZQ, and three groups treated orally with 8, 16, or 32 mg/kg of PLUM. After treatment, the Kato-Katz technique was performed to evaluate a quantity of eggs in the feces (EPG). The animals were euthanized for worm recovery, intestine samples were collected to evaluate the oviposition pattern, the load of eggs was determined on the hepatic and intestinal tissues and for the histopathological and histomorphometric evaluation of tissue and hepatic granulomas. PLUM reduced EPG by 65.27, 70.52, and 82.49%, reduced the total worm load by 46.7, 55.25, and 72.4%, and the female worm load by 44.01, 52.76, and 71.16%, for doses of 8, 16, and 32 mg/kg, respectively. PLUM also significantly reduced the number of immature eggs and increased the number of dead eggs in the oogram. A reduction of 36.11, 46.46, and 64.14% in eggs in the hepatic tissue, and 57.22, 65.18, and 80.5% in the intestinal tissue were also observed at doses of 8, 16, and 32 mg/kg, respectively. At all doses, PLUM demonstrated an effect on the histopathological and histomorphometric parameters of the hepatic granuloma, with a reduction of 41.11, 48.47, and 70.55% in the numerical density of the granulomas and 49.56, 57.63, and 71.21% in the volume, respectively. PLUM presented itself as a promising in vivo antiparasitic candidate against , acting not only on parasitological parameters but also on hepatic granuloma. Furthermore, in silico, PLUM showed good predictive pharmacokinetic profiles by ADMET.
PubMed: 37760782
DOI: 10.3390/biomedicines11092340 -
Journal of Veterinary Diagnostic... Nov 2023infections in dogs and cats are underestimated because of a lack of proglottid observations and poor recovery of parasite elements by centrifugal flotation. We...
infections in dogs and cats are underestimated because of a lack of proglottid observations and poor recovery of parasite elements by centrifugal flotation. We developed an immunoassay that employs a pair of monoclonal antibodies to capture specific coproantigen in fecal extracts from dogs and cats. Real-time PCR for DNA in perianal swabs and observation of proglottids were used as reference methods. In 6 experimentally infected dogs, parasite DNA, coproantigen, and proglottid segments were first detected at 22, 23, and 26 d post-infection, respectively. Praziquantel treatment of 3 experimentally infected dogs resulted in the elimination of both coproantigen and proglottid shedding within 1-5 d post-treatment; however, parasite DNA persisted for 14 d. Immunohistochemistry on immature and mature tapeworm segments using an antibody against the coproantigen supports the premise that the antigen is produced in mature segments. We assessed the performance of our coproantigen test in natural infections in 78 dogs from a flea-endemic area. Of the 12 antigen-positive samples, 11 were confirmed with a positive PCR test and/or proglottid observation. Finally, we evaluated a convenience sample set of 730 canine and 163 feline fecal samples obtained from a commercial diagnostic laboratory; antigen was detected in 4.1% of the canine and 12.9% of the feline samples, whereas parasite elements were observed in only 0.028% of samples. Our coproantigen immunoassay provides a sensitive method for the detection of infection in dogs and cats.
Topics: Animals; Cats; Dogs; Cat Diseases; Dog Diseases; Cestoda; Cestode Infections; Immunoassay; Feces; DNA
PubMed: 37491878
DOI: 10.1177/10406387231189193 -
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 -
Life (Basel, Switzerland) Sep 2023The existing treatment strategy for Schistosomiasis centers on praziquantel, a single drug, but its effectiveness is limited due to resistance and lack of preventive...
The existing treatment strategy for Schistosomiasis centers on praziquantel, a single drug, but its effectiveness is limited due to resistance and lack of preventive benefits. Thus, there is an urgent need for novel antischistosomal agents. glutathione S-transferase (GST) is an essential parasite enzyme, with a high potential for targeted drug discovery. In this study, we conducted a screening of compounds possessing antihelminth properties, focusing on their interaction with the glutathione S-transferase (GST) protein. We demonstrated the unique nature of GST in comparison to human GST. Evolutionary analysis indicated its close relationship with other parasitic worms, setting it apart from free-living worms such as . Through an assessment of binding pockets and subsequent protein-ligand docking, we identified Scutiaquinone A and Scutiaquinone B, both naturally derived Perylenequinones, as robust binders to GST. These compounds have exhibited effectiveness against similar parasites and offer promising potential as antischistosomal agents.
PubMed: 37895339
DOI: 10.3390/life13101957 -
Bioinformatics and Biology Insights 2024Schistosomiasis, otherwise known as bilharzia or snail fever, is a disease that usually affects poor people and people exposed to poor sanitation. The disease affects...
Schistosomiasis, otherwise known as bilharzia or snail fever, is a disease that usually affects poor people and people exposed to poor sanitation. The disease affects over 200 million people worldwide annually. Schistosomiasis has been treated using a single drug, praziquantel, since the 1970s and this is resulting in schistosomes becoming resistant. Therefore, there is an urgent need to develop new antischistosoma drugs and vaccines. This study focuses on identifying potential antischistosomal compounds from the plant . We virtually screened a library of 163 compounds by docking against sulfotransferase (SULT) using the PyRx software. Docking scores ranged from -4.7 to -9.3 kcal/mol. Compounds with binding affinity of -7.6 or stronger were subjected to drug-likeness assessments using the DataWarrior software. We also employed the PAINS removal tool to filter off false-positive results. Twelve compounds passed the drug-likeness screen, and these were subjected to in silico toxicity predictions to determine their mutagenic, tumorigenic and reproductive potential. Seven compounds were predicted to be nontoxic. After considering the toxicity analysis results and drug scores of the compounds, we identified rosmarinic acid and hispidulin as qualifying for further evaluation as potential drugs against schistosomiasis. Free energy calculations using the fastDRH webserver and molecular dynamics simulations using CABS-flex showed that the receptor-ligand complexes for the 2 lead compounds are stable under physiological conditions. We recommend that rosmarinic acid and hispidulin be used as hit compounds for the development of potential antischistosomal drugs.
PubMed: 38550337
DOI: 10.1177/11779322241240651 -
Parasite Epidemiology and Control Nov 2023World Health Organization (WHO) recommends periodic praziquantel Mass Drug Administration (MDA) to vulnerable populations, especially school-aged children, to reduce the...
BACKGROUND
World Health Organization (WHO) recommends periodic praziquantel Mass Drug Administration (MDA) to vulnerable populations, especially school-aged children, to reduce the risk of transmission. In the endemic Lindi region, on the southeastern coast of Tanzania, praziquantel has been distributed for more than a decade (12 rounds) in schools. However, there is a paucity of data on the current burden and factors perpetuating ongoing urogenital schistosomiasis among SAC. The study investigated the prevalence and factors associated with the ongoing transmission of among school-age children (SAC) after 12 rounds of praziquantel in Nachingwea, Southern Tanzania.
MATERIAL AND METHODS
A quantitative cross-sectional study was conducted between May and June 2022 among 483 SAC in the Nachingwea district. Macrohematuria, microhaematuria, and eggs were assessed in the collected urine sample for each participant, using macroscopic observation, urine dipstick, and urine filtration techniques, respectively. Infection intensity was quantified for positive urine samples. Knowledge and attitudes towards schistosomiasis were assessed among participants through an interview-administered questionnaire, and water contact practices were registered through an observation checklist. Data were summarized using descriptive statistics, the Chi-square test, and logistic regression.
RESULTS
The prevalence of infection was 10.6%, with 0.6% (3/51) prevalence of heavy infection. The factors associated with persistence transmission were a habit of visiting the water bodies (AOR = 1.62, 95% CI: 0.40-1.96), swimming in the visited water bodies (AOR = 4.58, 95% CI: 1.72-12.19), using water from the river source (AOR = 3.79, 95% CI: 1.51-9.51) and attending Mkumba Primary School (17.4%; AOR = 6.12, 95% CI: 1.64-22.85).
CONCLUSIONS
Findings suggest ongoing transmission of urogenital schistosomiasis in the Nachingwea District despite 12 rounds of praziquantel treatment, with a low prevalence of heavy infection (0.6%). Praziquantel distribution should be complemented with health education, especially on the cause and transmission of urogenital schistosomiasis to increase knowledge that will improve a good attitude towards schistosomiasis prevention. An adequate water supply is to be considered to reduce infections due to the visit to water sources for daily use.
PubMed: 37692460
DOI: 10.1016/j.parepi.2023.e00323 -
Pathogens (Basel, Switzerland) Dec 2023Aporocotylid blood flukes and are an ongoing health concern for the Southern Bluefin Tuna (, SBT) industry, where infections can lead to morbidity and mortality in...
Aporocotylid blood flukes and are an ongoing health concern for the Southern Bluefin Tuna (, SBT) industry, where infections can lead to morbidity and mortality in ranched SBT populations. This study compared blood fluke infection in SBT from two companies during the 2021 ranching season. Both companies administered the same dosage of praziquantel approximately 5 weeks after transfer, feeding with frozen baitfish daily; the only difference in the company's practices was that the pontoons were located 2.5 km apart. Infection severity was measured as prevalence and intensity by quantifying adult in SBT heart and copy numbers of and ITS-2 DNA in SBT heart and gills. Data from the 2018 and 2019 harvests of SBT were used to make comparisons with 2021 harvest data. was detected at transfer and no longer detected after treatment with praziquantel. spp. were present in 83% of sampled SBT in 2021. Both companies demonstrated similar patterns of infection, and Company A had higher prevalence and intensity of spp. infection. Based on ITS-2 DNA, infection intensity at harvest was significantly greater for both companies in 2021 when compared to 2018 and 2019. Continued monitoring of spp. in SBT and improvements in diagnostics contribute to our understanding of spp. epizootiology and the detection of changes in treatment efficacy.
PubMed: 38133326
DOI: 10.3390/pathogens12121443 -
Saudi Medical Journal Apr 2024Echinococcosis is a parasitic infection that is distributed worldwide. Its clinical presentation depends on the size and location of the cyst. A 7-year-old was found...
Echinococcosis is a parasitic infection that is distributed worldwide. Its clinical presentation depends on the size and location of the cyst. A 7-year-old was found with a superimposed infected pulmonary hydatid cyst that was initially misdiagnosed as complicated pneumonia. Our case underscores the challenges of diagnosing and managing echinococcosis, emphasizes the need for a high index of suspicion, and describes the disease's ability to mimic other clinical entities.
Topics: Humans; Echinococcosis, Pulmonary; Child; Male; Diagnosis, Differential; Tomography, X-Ray Computed
PubMed: 38657978
DOI: 10.15537/smj.2024.45.4.20230078 -
Memorias Do Instituto Oswaldo Cruz 2023Schistosomiasis is a neglected tropical disease caused by trematodes of the genus Schistosoma, with a limited treatment, mainly based on the use of praziquantel (PZQ)....
BACKGROUND
Schistosomiasis is a neglected tropical disease caused by trematodes of the genus Schistosoma, with a limited treatment, mainly based on the use of praziquantel (PZQ). Currently, several aspartic proteases genes have already been identified within the genome of Schistosoma species. At least one enzyme encoded from this gene family (SmAP), named SmCD1, has been validated for the development of schistosomicidal drugs, since it has a key role in haemoglobin digestion by worms.
OBJECTIVE
In this work, we integrated a structure-based virtual screening campaign, enzymatic assays and adult worms ex vivo experiments aiming to discover the first classes of SmCD1 inhibitors.
METHODS
Initially, the 3D-structures of SmCD1, SmCD2 and SmCD3 were generated using homology modelling approach. Using these models, we prioritised 50 compounds from 20,000 compounds from ChemBridge database for further testing in adult worm aqueous extract (AWAE) and recombinant SmCD1 using enzymatic assays.
FINDINGS
Seven compounds were confirmed as hits and among them, two compounds representing new chemical scaffolds, named 5 and 19, had IC50 values against SmCD1 close to 100 μM while presenting binding efficiency indexes comparable to or even higher than pepstatin, a classical tight-binding peptide inhibitor of aspartyl proteases. Upon activity comparison against mammalian enzymes, compound 50 was selective and the most potent against the AWAE aspartic protease activity (IC50 = 77.7 μM). Combination of computational and experimental results indicate that compound 50 is a selective inhibitor of SmCD2. Compounds 5, 19 and 50 tested at low concentrations (10 uM) were neither cytotoxic against WSS-1 cells (48 h) nor could kill adult worms ex-vivo, although compounds 5 and 50 presented a slight decrease on female worms motility on late incubations times (48 or 72 h).
MAIN CONCLUSION
Overall, the inhibitors identified in this work represent promising hits for further hit-to-lead optimisation.
Topics: Female; Animals; Schistosoma mansoni; Protease Inhibitors; Mammals
PubMed: 37672425
DOI: 10.1590/0074-02760230031 -
Radiology Case Reports Sep 2023Hydatid disease is still endemic in several regions worldwide including Morocco, and is caused in most cases by the larval form of 2 species of the tapeworm...
Hydatid disease is still endemic in several regions worldwide including Morocco, and is caused in most cases by the larval form of 2 species of the tapeworm Echinococcus: E. granulosus and E. multilocularis. Primary hydatid disease of the bone without systemic involvement is rare. The disease has a silent clinical evolution until it reaches complicated stages. Complications may include pathological fracture, neural deficit, infection, and fistulization of the abscess. Preoperative diagnosis is based on clinical history, imaging findings, and serological tests, which lack high sensitivity and specificity. Although the interpretation of imaging studies can prove to be very confusing because the bone changes evolve with time, and the nonspecificity of these findings often leads to a mistaken diagnosis. The diagnosis requires a high index of suspicion, especially in patients who reside in or travel to sheep-raising areas where hydatid disease is endemic. A high index of suspicion is necessary for the diagnosis, especially in patients that live in or travel to sheep-raising areas where hydatid disease is endemic. The treatment of choice remains surgical, following the principles of a locally malignant lesion. Chemotherapy (albendazole alone or in combination with praziquantel) is indicated when surgery is not possible or as an adjuvant treatment. The prognosis is often poor. We report the case of a 28-year-old woman with long-standing pain in the left hip joint in which the imaging findings were thought of as being either tuberculous or neoplastic. The result of a CT-guided biopsy concurred with an unexpected diagnosis of a hydatid cyst. This case highlights that in the absence of a high index of suspicion for echinococcal infection, the semblance of imaging findings of hydatid disease in the bone to those of other skeletal pathologies can lead to misinterpretation.
PubMed: 37409101
DOI: 10.1016/j.radcr.2023.06.022