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Journal of Parasitic Diseases :... Jun 2024Echinochasmidae are considered one of the digenean intestinal parasites of carnivorous mammals and humans. Some larvicidal medications, such as praziquantel and...
Echinochasmidae are considered one of the digenean intestinal parasites of carnivorous mammals and humans. Some larvicidal medications, such as praziquantel and albendazole, were employed to interrupt the life cycle of Echinochasmidae, which may cause harmful and serious effects on the domestic fish, ducks, and humans in our ecosystem. Cercariae of sp. (gymnocephalus type) were harvested by exposing snails to strong artificial illumination. The emerging cercariae were exposed in vitro to different concentrations of praziquantel and albendazole at the same period of incubation 12 h. Using probit analysis in SPSS version 25, the lethal concentrations 50 and 95% were determined. They were 0.036 and 0.82 ppm, respectively, for praziquantel and 5.3 and 9.2 ppm, respectively, for albendazole. The ultrastructural changes using scanning electron microscope on the tegumental surface of the treated cercariae with the two drugs were compared to the untreated cercariae. The untreated cercariae have a pear-shaped body with a long tail. The oral sucker is armed with a spiny collar and decorated with ciliated and unciliated sensory papillae. The cardinal ventral sucker has a thick, muscular wall. The cercarial tail is decorated with parallel longitudinal tegumental processes and spherical, unciliated papillae. In comparisons, cercariae treated with both drugs lost all healthy morphological features, but in varying degrees and effects between the two drugs. Our findings suggest that the use of both drugs can be recommended during the design of control strategies to combat this type of intestinal parasite.
PubMed: 38840870
DOI: 10.1007/s12639-024-01670-6 -
Journal of Microbiology, Immunology,... May 2024Co-therapy with albendazole and steroid is commonly used in patients with eosinophilic meningoencephalitis caused by Angiostrongylus cantonensis infections. However,...
Curative effects and mechanisms of AG1296 and LY294002 co-therapy in Angiostrongylus cantonensis-induced neurovascular unit dysfunction and eosinophilic meningoencephalitis.
BACKGROUND
Co-therapy with albendazole and steroid is commonly used in patients with eosinophilic meningoencephalitis caused by Angiostrongylus cantonensis infections. However, anthelminthics often worsen symptoms, possibly due to the inflammatory reaction to antigens released by dying worms. Therefore, the present study was to investigate the curative effects and probable mechanisms of the platelet-derived growth factor receptor-beta (PDGFR-β) inhibitor AG1296 (AG) and the phosphoinositide 3-kinase inhibitor (PI3K) LY294002 (LY) in A. cantonensis-induced neurovascular unit dysfunction and eosinophilic meningoencephalitis.
METHODS
Western blots were used to detect matrix protein degradation and the expressions of PDGFR-β/PI3K signaling pathway. The co-localization of PDGFR-β and vascular smooth muscle cells (VSMCs), and metalloproteinase-9 (MMP-9) and VSMCs on the blood vessels were measured by confocal laser scanning immunofluorescence microscopy. Sandwich enzyme-linked immunosorbent assays were used to test S100B, interleukin (IL)-6, and transforming growth factor beta in the cerebrospinal fluid to determine their possible roles in mouse resistance to A. cantonensis.
RESULTS
The results showed that AG and LY cotherapy decreased the MMP-9 activity and inflammatory reaction. Furthermore, S100B, IL-6 and eosinophil counts were reduced by inhibitor treatment. The localization of PDGFR-β and MMP-9 was observed in VSMCs. Furthermore, we showed that the degradation of the neurovascular matrix and blood-brain barrier permeability were reduced in the mouse brain.
CONCLUSIONS
These findings demonstrate the potential of PDGFR-β inhibitor AG and PI3K inhibitor LY co-therapy as anti-A. cantonensis drug candidates through improved neurovascular unit dysfunction and reduced inflammatory response.
PubMed: 38839542
DOI: 10.1016/j.jmii.2024.05.012 -
Molecular Therapy. Oncology Jun 2024The immune response plays a crucial role in the functionality of oncolytic viruses. In this study, Albendazole, an antihelminthic drug known to modulate the immune...
The immune response plays a crucial role in the functionality of oncolytic viruses. In this study, Albendazole, an antihelminthic drug known to modulate the immune checkpoint PD-L1, was combined with the oncolytic virus M1 (OVM1) to treat mice with either prostate cancer (RM-1) or glioma (GL261) tumors. This combination therapy enhanced anti-tumor effects in immunocompetent mice, but not in immunodeficient ones, without increasing OVM1 replication. Instead, it led to an increase in the number of CD8 T cells within the tumor, downregulated the expression of PD1 on CD8 T cells, and upregulated activation markers such as Ki67, CD44, and CD69 and the secretion of cytotoxic factors including interferon (IFN)-γ, granzyme B, and tumor necrosis factor (TNF)-α. Consistently, it enhanced the tumor-killing activity of lymphocytes from tumor-draining lymph nodes or spleens. The synergistic effect of Albendazole on OVM1 was abolished by depleting CD8 T cells, suggesting a CD8 T cell-dependent mechanism. In addition, Albendazole and OVM1 therapy increased CTLA4 expression in the spleen, and the addition of CTLA4 antibodies further enhanced the anti-tumor efficacy . In summary, Albendazole can act synergistically with oncolytic viruses via CD8 T cell activation, and the Albendazole/OVM1 combination can overcome resistance to CTLA4-based immune checkpoint blockade therapy.
PubMed: 38817541
DOI: 10.1016/j.omton.2024.200813 -
International Journal For Parasitology May 2024Xenobiotic biotransformation is an important modulator of anthelmintic drug potency and a potential mechanism of anthelmintic resistance. Both the free-living nematode...
Xenobiotic biotransformation is an important modulator of anthelmintic drug potency and a potential mechanism of anthelmintic resistance. Both the free-living nematode Caenorhabditis elegans and the ruminant parasite Haemonchus contortus biotransform benzimidazole drugs by glucose conjugation, likely catalysed by UDP-glycosyltransferase (UGT) enzymes. To identify C. elegans genes involved in benzimidazole drug detoxification, we first used a comparative phylogenetic analysis of UGTs from humans, C. elegans and H. contortus, combined with available RNAseq datasets to identify which of the 63 C. elegans ugt genes are most likely to be involved in benzimidazole drug biotransformation. RNA interference knockdown of 15 prioritized C. elegans genes identified those that sensitized animals to the benzimidazole derivative albendazole (ABZ). Genetic mutations subsequently revealed that loss of ugt-9 and ugt-11 had the strongest effects. The "ugt-9 cluster" includes these genes, together with six other closely related ugts. A CRISPR-Cas-9 deletion that removed seven of the eight ugt-9 cluster genes had greater ABZ sensitivity than the single largest-effect mutation. Furthermore, a double mutant of ugt-22 (which is not a member of the ugt-9 cluster) with the ugt-9 cluster deletion further increased ABZ sensitivity. This additivity of mutant phenotypes suggest that ugt genes act in parallel, which could have several, not mutually exclusive, explanations. ugt mutations have different effects with different benzimidazole derivatives, suggesting that enzymes with different specificities could together more efficiently detoxify drugs. Expression patterns of ugt-9, ugt-11 and ugt-22 gfp reporters differ and so likely act in different tissues which may, at least in part, explain their additive effects on drug potency. Overexpression of ugt-9 alone was sufficient to confer partial ABZ resistance, indicating increasing total UGT activity protects animals. In summary, our results suggest that the multiple UGT enzymes have overlapping but not completely redundant functions in benzimidazole drug detoxification and may represent "druggable" targets to improve benzimidazole drug potency.
PubMed: 38806068
DOI: 10.1016/j.ijpara.2024.05.003 -
The American Journal of Tropical... May 2024In countries where soil-transmitted helminth (STH) infections are endemic, deworming programs are recommended to reduce morbidity; however, increasing levels of...
In countries where soil-transmitted helminth (STH) infections are endemic, deworming programs are recommended to reduce morbidity; however, increasing levels of resistance to benzimidazoles are of concern. In an observational study in Peru, we studied the clinical efficacy of 400 mg of albendazole 20 days after treatment among children aged 2-11 years. Of 426 participants who provided samples, 52.3% were infected with a STH, 144 (33.8%) were positive for Ascaris (41.8% light, 50.8% moderate, and 7.4% heavy infections), 147 (34.5%) were positive for Trichuris (75.2% light, 22.5% moderate, and 2.3% heavy infections), and 1.1% were positive for hookworm species (100% light infections). Additional stool samples were examined at 20, 90, and 130 days after the initial treatment. At 20 days post-administration of albendazole, the cure rate (CR) of Ascaris infection was 80.1% (95% CI: 73.5-86.7), and the egg reduction rate (ERR) was 70.8% (95% CI: 57.8-88.7); the CR for Trichuris infection was 27.1% (95% CI: 20.0-34.3), and the ERR was 29.8% (95% CI: -1.40 to 57.5). Among participants with persistent or recurrent infections with Trichuris, the combined therapy of albendazole (400 mg) and ivermectin at 600 µg/dose increased overall CR for Trichuris infection to 75.2% (95% CI: 67.3-83.2%) with an ERR of 84.2% (95% CI: 61.3-93.8%). Albendazole administration alone for the control of STH was associated with high rates of treatment failure, especially for Trichuris. Combined single doses of albendazole and ivermectin was observed to have improved efficacy.
PubMed: 38806041
DOI: 10.4269/ajtmh.23-0497 -
International Journal of Surgery Case... Jul 2024Hydatidosis, caused by Echinococcus granulosus, is endemic in regions where cattle rearing is prevalent. While liver and lung involvement are common, isolated splenic...
INTRODUCTION
Hydatidosis, caused by Echinococcus granulosus, is endemic in regions where cattle rearing is prevalent. While liver and lung involvement are common, isolated splenic hydatid cysts are rare, particularly among adolescents. We present a rare case of a 14-year-old female with an isolated giant splenic hydatid cyst.
CASE PRESENTATION
A 14-year-old female presented with left upper quadrant pain. Imaging revealed a large splenic cyst without evidence of liver or lung involvement. A total splenectomy was performed, and a histological examination confirmed the diagnosis of a hydatid cyst. The patient underwent postoperative albendazole therapy and remained asymptomatic during follow-up.
CLINICAL DISCUSSION
Isolated splenic hydatid cysts are rare in the pediatric population. Imaging techniques such as ultrasound and CT play a crucial role in diagnosis. Surgical resection and Puncture-aspiration-injection-reaspiration remain the choice of treatment, supplemented by anti-parasitic therapy. Postoperative follow-up is essential to monitor for recurrence.
CONCLUSION
Isolated splenic hydatid cysts are exceptionally rare in pediatric patients. Prompt diagnosis, surgical intervention, and postoperative surveillance are crucial for successful management and prevention of recurrence.
PubMed: 38805842
DOI: 10.1016/j.ijscr.2024.109768 -
PloS One 2024Despite integrated prevention and control measures, the prevalence of hookworm is still high in Ethiopia. The re-infection rates and predictors are poorly addressed....
BACKGROUND
Despite integrated prevention and control measures, the prevalence of hookworm is still high in Ethiopia. The re-infection rates and predictors are poorly addressed. Therefore, this study aimed to determine the patterns of hookworm re-infection rates and predictors among schoolchildren in northwest Ethiopia.
METHODS
A prospective follow-up study was conducted among 86 schoolchildren from May to December 2022. Data on predictors was collected using a questionnaire. Stool samples were collected and processed via Kato-Katz, McMaster, and spontaneous tube sedimentation techniques. All hookworm-infected children were treated with albendazole and followed for six months. The re-infection rates of hookworm were checked in the 4th and 6th months. Data was entered into Epi-data version 3.1 and analysed using SPSS version 25. Descriptive statistics were used to compute the re-infection rate. The associations of predictors with hookworm re-infection rates were calculated by logistic regression. Variables with a p-value < 0.05 were considered statistically significant.
RESULTS
Of the 86, 81 schoolchildren completed the study. The prevalence of hookworm re-infection in the 4th and 6th months was 23.5% and 33.3%, respectively. Living with family members greater than five (p = .017), poor utilization of latrine (p = .008), infrequent shoe wear (p = .039), and participating in irrigation (p = .020) were the predictors significantly associated with hookworm re-infections.
CONCLUSIONS
The re-infection rate was high during the fourth and sixth months. Participating in irrigation, infrequent shoe wear, and poor latrine utilization were predictors of hookworm re-infection. Therefore, mass drug administration, regular shoe wearing, and health education should be advocated.
Topics: Humans; Ethiopia; Child; Male; Female; Hookworm Infections; Prospective Studies; Albendazole; Prevalence; Reinfection; Adolescent; Feces; Follow-Up Studies; Anthelmintics; Ancylostomatoidea; Schools; Animals
PubMed: 38805475
DOI: 10.1371/journal.pone.0303502 -
Cureus Apr 2024is an uncommon parasitic disease contracted through the consumption of undercooked pork. We report the case of a 59-year-old man with a history of bicuspid aortic valve...
is an uncommon parasitic disease contracted through the consumption of undercooked pork. We report the case of a 59-year-old man with a history of bicuspid aortic valve with recent travel to the Philippines and consumption of raw pork presenting with progressive myalgia and hypereosinophilia (nadir 12,940/uL) in profound cardiogenic shock in the setting of critical aortic stenosis. He underwent emergent balloon valvuloplasty, which was complicated by aortic insufficiency. This necessitated a transcatheter aortic valve replacement. However, despite hemodynamic stabilization, he developed catastrophic eosinophilic myocarditis, complicated by cardiac arrest from ventricular tachycardia. A rectus femoris muscle biopsy confirmed the diagnosis, showing a parasite and significant eosinophilic infiltration. Empiric treatment with albendazole, ivermectin, and methylprednisolone resulted in the significant resolution of symptoms and the liberalization of critical illness. This case highlights the challenges of diagnosing the underlying etiologies of hypereosinophilia and/or eosinophilic myocarditis, underscoring the importance of considering parasitic etiologies, particularly in endemic regions or in patients who have a significant travel history to such areas. Prompt diagnosis and treatment are essential to prevent morbidity and mortality.
PubMed: 38800259
DOI: 10.7759/cureus.58946 -
BioRxiv : the Preprint Server For... May 2024Tumors frequently harbor isogenic yet epigenetically distinct subpopulations of multi-potent cells with high tumor-initiating potential-often called Cancer Stem-Like...
Tumors frequently harbor isogenic yet epigenetically distinct subpopulations of multi-potent cells with high tumor-initiating potential-often called Cancer Stem-Like Cells (CSLCs). These can display preferential resistance to standard-of-care chemotherapy. Single-cell analyses can help elucidate Master Regulator (MR) proteins responsible for governing the transcriptional state of these cells, thus revealing complementary dependencies that may be leveraged via combination therapy. Interrogation of single-cell RNA sequencing profiles from seven metastatic breast cancer patients, using perturbational profiles of clinically relevant drugs, identified drugs predicted to invert the activity of MR proteins governing the transcriptional state of chemoresistant CSLCs, which were then validated by CROP-seq assays. The top drug, the anthelmintic albendazole, depleted this subpopulation without noticeable cytotoxicity Moreover, sequential cycles of albendazole and paclitaxel-a commonly used chemotherapeutic -displayed significant synergy in a patient-derived xenograft (PDX) from a TNBC patient, suggesting that network-based approaches can help develop mechanism-based combinatorial therapies targeting complementary subpopulations.
PubMed: 38798673
DOI: 10.1101/2023.11.08.562798 -
International Journal of Surgery Case... Jun 2024Hydatid disease, caused by Echinococcus granulosus, is a zoonotic infection prevalent in specific regions, including Tunisia. Complications are rare but potentially...
INTRODUCTION AND IMPORTANCE
Hydatid disease, caused by Echinococcus granulosus, is a zoonotic infection prevalent in specific regions, including Tunisia. Complications are rare but potentially life-threatening. This case report highlights the significance of early diagnosis and intervention in a unique case where anaphylaxis resulted from minor abdominal trauma in a 17-year-old male with an undiagnosed hydatid cyst.
CASE REPORT
The patient arrived at the emergency department with syncope and hypotension after a classroom accident. Physical examination showed an urticarial rash and abdominal tenderness. Anaphylactic shock was diagnosed and promptly treated. A computed tomography scan confirmed a ruptured liver hydatid cyst. The patient received anthelmintic treatment and underwent conservative surgical management. Intraoperatively, a second anaphylactic shock occurred and was promptly treated. The post-operative course was uneventful, and histopathological analysis identified Echinococcus granulosus.
CLINICAL DISCUSSION
This case emphasizes the importance of recognizing hydatid disease as a potential cause of anaphylaxis post-trauma, even in asymptomatic patients. Early diagnosis through imaging is crucial for prompt intervention. Surgical management should be considered, with conservative approaches favored in acute cases. Post-surgical albendazole treatment is essential to prevent recurrence.
CONCLUSION
This report serves as a valuable reference for healthcare professionals, highlighting the need for heightened clinical suspicion in cases like this. It underscores the significance of considering hydatid cyst rupture in the differential diagnosis of anaphylaxis following blunt trauma. Awareness among pediatricians, emergency physicians, and primary care providers can lead to early diagnosis and better patient outcomes, preventing severe complications or fatalities associated with this rare condition.
PubMed: 38781844
DOI: 10.1016/j.ijscr.2024.109779