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PLoS Neglected Tropical Diseases May 2024Despite several years of LF-MDA implementation, Ghana still has some districts with mf prevalence >1%, partly due to poor treatment coverage levels resulting from...
BACKGROUND
Despite several years of LF-MDA implementation, Ghana still has some districts with mf prevalence >1%, partly due to poor treatment coverage levels resulting from non-participation in MDA. To address the challenges, we implemented Engage & Treat (E&T) and Test & Treat (T&T) strategies for individuals who miss or refuse MDA respectively, in a hotspot district, enabling us to reach many of those who seldom, or never, take part in MDA. This financial cost study was undertaken to analyse data on the LF-MDA, E&T and T&T implementation in 2021 and the financial cost to inform the rollout of the E&T and T&T as mop-up strategies in future LF-MDAs.
METHODS
This costing study analysed cost data from the 2021 LF-MDA implementation activities carried out by the Neglected Tropical Diseases (NTD) programme of the Ghana Health Service and the SENTINEL study, carried out in Ahanta West district for the two interventions (i.e., E&T and T&T). The 2021 Ghana Population and Housing Census data was used to estimate the LF-MDA-eligible population. The financial cost per person treated was estimated and these costs were applied to the projected population to obtain the financial cost for subsequent years.
RESULTS
Implementing MDA mop-up strategies either through the E&T or T&T to improve coverage comes at an additional cost to the elimination goals. For example, in 2024 the projected cost per person treated by the routine LF-MDA is estimated at US$0.83. The cost using the integrated LF-MDA and the E&T, T&T led by the NTD programme or T&T integrated into the health system was estimated at US$1.62, US$2.88, and US$2.33, respectively, for the same year. Despite the increased cost, the proposed combined LF-MDA and mop-up strategies will have a higher estimated population treated for 2024 (i.e., 1,392,211) compared to the routine LF-MDA approach (i.e., 988,470) for the same year.
CONCLUSION
Combining LF-MDA with E&T/T&T mop-up strategies, despite their high costs, may provide NTD Programmes with the options of improving treatment coverage and reaching the LF elimination target sooner, given that the routine LF-MDA alone approach has been implemented for many years with some districts yet to reach the elimination targets.
Topics: Ghana; Humans; Elephantiasis, Filarial; Disease Eradication; Mass Drug Administration; Filaricides; Prevalence
PubMed: 38787898
DOI: 10.1371/journal.pntd.0012213 -
Pathogens (Basel, Switzerland) May 2024Deer are susceptible to infection with parasitic helminths, including species which are of increasing economic concern to the livestock industry due to anthelmintic drug... (Review)
Review
Deer are susceptible to infection with parasitic helminths, including species which are of increasing economic concern to the livestock industry due to anthelmintic drug resistance. This paper systematically collates helminth prevalence data from deer across Europe and explores patterns in relation to host and parasite species, as well as landscape factors. A livestock pasture contact index (LPCI) is developed to predict epidemiological overlap between deer and livestock, and hence to examine deer helminth fauna in the context of their surrounding environment. Fifty-eight studies comprising fallow (), red (), roe () and sika () deer were identified. Deer populations in "likely" contact with livestock pasture had a higher mean prevalence of the abomasal nematodes , , and ( = 0.01), which are common in livestock and not primarily associated with deer. Roe deer populations had a higher prevalence of ( = 0.02) and ( = 0.01) than fallow deer and a higher prevalence of than both red ( = 0.01) and fallow deer ( = 0.02). Liver fluke and lungworm species were present sporadically at low prevalence, while the abomasal nematode occurred locally at high prevalence. Insights from this research suggest that deer helminth fauna is reflective of their surrounding environment, including the livestock species which inhabit areas of shared grazing. This is explored from an epidemiological perspective, and the prospect of helminth transmission between wild and domestic hosts is discussed, including drug-resistant strains, alongside the role of helminths as indicators relevant to the transmission of other pathogens at the wildlife-livestock interface.
PubMed: 38787230
DOI: 10.3390/pathogens13050378 -
Metabolites Apr 2024Phytochemical profiling followed by antimicrobial and anthelmintic activity evaluation of the Australian plant known for its customary use in Indigenous Australian...
Phytochemical profiling followed by antimicrobial and anthelmintic activity evaluation of the Australian plant known for its customary use in Indigenous Australian ceremonies and bush medicine, was performed. In the present study, seven previously reported compounds were isolated including auraptene, 6'-dehydromarmin, geiparvarin, marmin acetonide, flindersine, and two flindersine derivatives from the bark and leaves, together with a new compound, chlorogeiparvarin, formed as an artefact during the isolation procedure and isolated as a mixture with geiparvarin. Chemical profiling allowed for a qualitative and quantitative comparison of the compounds in the leaves, bark, flowers, and fruit of this plant. Subsequently, a subset of these compounds as well as crude extracts from the plant were evaluated for their antimicrobial and anthelmintic activities. Anthelmintic activity assays showed that two of the isolated compounds, auraptene and flindersine, as well as the dichloromethane and methanol crude extracts of , displayed significant activity against a parasitic nematode (). This is the first report of the anthelmintic activity associated with these compounds and indicates the importance of such fundamental explorations for the discovery of bioactive phytochemicals for therapeutic application(s).
PubMed: 38786736
DOI: 10.3390/metabo14050259 -
Biomolecules May 2024Excitotoxicity is a common pathological process in neurological diseases caused by excess glutamate. The purpose of this study was to evaluate the effect of gypenoside...
Excitotoxicity is a common pathological process in neurological diseases caused by excess glutamate. The purpose of this study was to evaluate the effect of gypenoside XVII (GP-17), a gypenoside monomer, on the glutamatergic system. In vitro, in rat cortical nerve terminals (synaptosomes), GP-17 dose-dependently decreased glutamate release with an IC value of 16 μM. The removal of extracellular Ca or blockade of N-and P/Q-type Ca channels and protein kinase A (PKA) abolished the inhibitory effect of GP-17 on glutamate release from cortical synaptosomes. GP-17 also significantly reduced the phosphorylation of PKA, SNAP-25, and synapsin I in cortical synaptosomes. In an in vivo rat model of glutamate excitotoxicity induced by kainic acid (KA), GP-17 pretreatment significantly prevented seizures and rescued neuronal cell injury and glutamate elevation in the cortex. GP-17 pretreatment decreased the expression levels of sodium-coupled neutral amino acid transporter 1, glutamate synthesis enzyme glutaminase and vesicular glutamate transporter 1 but increased the expression level of glutamate metabolism enzyme glutamate dehydrogenase in the cortex of KA-treated rats. In addition, the KA-induced alterations in the N-methyl-D-aspartate receptor subunits GluN2A and GluN2B in the cortex were prevented by GP-17 pretreatment. GP-17 also prevented the KA-induced decrease in cerebral blood flow and arginase II expression. These results suggest that (i) GP-17, through the suppression of N- and P/Q-type Ca channels and consequent PKA-mediated SNAP-25 and synapsin I phosphorylation, reduces glutamate exocytosis from cortical synaptosomes; and (ii) GP-17 has a neuroprotective effect on KA-induced glutamate excitotoxicity in rats through regulating synaptic glutamate release and cerebral blood flow.
Topics: Animals; Glutamic Acid; Rats; Male; Gynostemma; Cyclic AMP-Dependent Protein Kinases; Rats, Sprague-Dawley; Synaptosomes; Neuroprotective Agents; Kainic Acid; Seizures; Synapses; Synaptosomal-Associated Protein 25; Synapsins; Phosphorylation; Calcium; Plant Extracts
PubMed: 38785996
DOI: 10.3390/biom14050589 -
Heliyon May 2024Natural plant-based medicines have gained in popularity, replacing artificial models and chemicals as a result of new pharmacological discoveries. The increased... (Review)
Review
Natural plant-based medicines have gained in popularity, replacing artificial models and chemicals as a result of new pharmacological discoveries. The increased popularity and acceptability of herbal medications such as arose from the assumption that all-natural products are safe, readily available, and inexpensive. The genus (Commelinaceae), which has over 200 species, has long been utilized as a treatment for a variety of ailments and conditions around the world. However, to the authors' knowledge, there are no Comprehensive scientific reports of many medicinally important species of the genus under one roof. The current narrative review aims to present an updated overview of the various species of focusing on its morphology; geographical distribution; traditional medicinal use (species type, parts of the plant used, the mode of action, ailments treated, and countries practicing); phytochemical constituents; and pharmacological properties. The data search approach was carried out utilizing English-language electronic databases such as PubMed, Web of Science, Scopus, Science Direct, Research Gates, Ethnobotany Research and Applications, and Google Scholar. Using key terms such as "medicinal plant," "genus ," "traditional medicinal usage of species," "photochemistry of species," and "pharmacological (biologic) activities of species" numerous searches and in-depth discussions are conducted. It was found that many species contain bioactive-phytochemicals (secondary metabolites) with a variety of structural kinds, including alkaloids, phenolics, flavonoids, glycosides, tannins, saponins, sterols, anthocyanins, and others which are presumed for their pharmacological activities. According to the invitro and preclinical reports, the species have shown anti-diabetic, antioxidant, anti-microbial, analgesic, anti-inflammatory, anti-cancer, hepato-protective, diuretic, fertility-inducing, anti-diarrheal, and anthelmintic activity, sedative, and anxiolytic activities. Although standardized extracts and phytochemicals derived from numerous species are presumed to provide safer alternatives for treating a variety of human ailments, the phytochemistry and pharmacology of the genus' plants have yet to be thoroughly investigated, both in preclinical studies with various animal models and in large-scale clinical trials. The authors also advocate for future collaboration among scientists, pharmaceutical firm owners, and other interested parties to develop novel drugs.
PubMed: 38784558
DOI: 10.1016/j.heliyon.2024.e30945 -
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 -
Veterinary Parasitology Jul 2024Previous reports of macrocyclic lactone (ML) resistance in Dirofilaria immitis, the parasitic nematode which causes heartworm disease, have mainly been from the southern...
Investigating Dirofilaria immitis isolates infecting domestic canines and their susceptibility/resistance patterns to macrocyclic lactones in the northern region of the Mississippi Delta area (southeast Missouri).
Previous reports of macrocyclic lactone (ML) resistance in Dirofilaria immitis, the parasitic nematode which causes heartworm disease, have mainly been from the southern Mississippi Delta region. Southeast Missouri (SEMO), forming the northern boundary of this region, has not previously been well studied. The area is an ideal propagation region for heartworm infection and possibly for the spread of ML resistance. To assess whether D. immitis isolates infecting domestic canines in SEMO exhibit evidence of resistance to MLs, domestic canines, presented to veterinary facilities testing positive for heartworms through antigen and microfilariae (MF) examination, were utilized in the study. Using a descriptive epidemiological cross-sectional study, from March 2021 through February 2022, blood sample collection from 96 canines living in SEMO testing positive for heartworms were analyzed. MiSeq technology was utilized to sequence specific genetic markers associated with susceptibility/resistance for MLs in D. immitis isolates. Genomic data revealed most D. immitis isolates had genotypic profiles consistent with resistance to MLs. Of the 96 samples tested, 91 (94.8%) had a resistant genotype, 4 (4.2%) had a mixed genotype, and 1 sample (1%) genotyped as susceptible. While detailed and reliable medical histories were not available for most canines, detailed medical history from 2 canines indicated evidence of phenotypic resistance that was consistent with their genotypes. However, in vivo preventive tests are needed to confirm a high frequency of phenotypic ML resistance in D. immitis from this region. Increasing resistance patterns to MLs indicate the approach to heartworm prevention/treatment protocol should be reconsidered. New measures may be required to stop heartworm disease.
Topics: Animals; Dirofilaria immitis; Dirofilariasis; Dogs; Dog Diseases; Missouri; Drug Resistance; Cross-Sectional Studies; Female; Lactones; Male; Filaricides; Genotype
PubMed: 38781830
DOI: 10.1016/j.vetpar.2024.110199 -
Scientific Reports May 2024Metabolism of praziquantel (PZQ), a racemic mixture and the only drug approved to treat S. mansoni infection, is mediated by genetically polymorphic enzymes. Periodic...
Metabolism of praziquantel (PZQ), a racemic mixture and the only drug approved to treat S. mansoni infection, is mediated by genetically polymorphic enzymes. Periodic school-based mass drug administration (MDA) with PZQ is the core intervention to control schistosomiasis. However data on the impact of pharmacogenetic variation, nutrition, and infection status on plasma PZQ exposure is scarce. We investigated genetic and non-genetic factors influencing PZQ plasma concentration and its metabolic ratios (trans-4-OH-PZQ/PZQ and cis-4-OH-PZQ/PZQ). Four hundred forty-six school children aged 7-15 years from four primary schools in southern Ethiopia who received albendazole and PZQ preventive chemotherapy through MDA campaign were enrolled. Genotyping for common functional variants of CYP3A4 (*1B), CYP3A5 (*3, *6), CYP2C19 (*2, *3, *17), CYP2C9 (*2, *3), and CYP2J2*7 was performed. Plasma concentrations of PZQ, trans-4-OH-PZQ, and cis-4-OH-PZQ were quantified using UPLCMS/MS. Carriers of CYP2C19 defective variant alleles (*2 and *3) had significantly higher mean PZQ plasma concentration than CYP2C19*1/*1 or *17 carriers (p = 0.005). CYP2C19*1/*1 and CYP2C19*17 carriers had higher trans-4-OH-PZQ/PZQ and cis-4-OH-PZQ/PZQ metabolic ratios compared with CYP2C19*2 or *3 carriers (p < 0.001). CYP2J2*7 carriers had lower mean PZQ plasma concentration (p = 0.05) and higher trans-4-OH-PZQ/PZQ and cis-4-OH-PZQ/PZQ metabolic ratios. Male participants had significantly higher PZQ concentration (p = 0.006) and lower metabolic ratios (p = 0.001) than females. There was no significant effect of stunting, wasting, S. mansoni or soil-transmitted helminth infections, CYP3A4, CYP3A5, or CYP2C9 genotypes on plasma PZQ or its metabolic ratios. In conclusion, sex, CYP2C19 and CYP2J2 genotypes significantly predict PZQ plasma exposure among Ethiopian children. The impact of CYP2C19 and CYP2J2 genotypes on praziquantel treatment outcomes requires further investigation.
Topics: Humans; Praziquantel; Child; Male; Female; Ethiopia; Adolescent; Cytochrome P-450 CYP2C19; Genotype; Cytochrome P-450 Enzyme System; Anthelmintics; Schistosomiasis mansoni
PubMed: 38778126
DOI: 10.1038/s41598-024-62669-w -
European Journal of Medical Research May 2024Artesunate (ART), an effective antimalarial semisynthetic derivative of artemisinin, exhibits antitumour properties, but the mechanism(s) involved remain elusive. In...
Artesunate (ART), an effective antimalarial semisynthetic derivative of artemisinin, exhibits antitumour properties, but the mechanism(s) involved remain elusive. In this study, we investigated the antitumour effects of ART on human oesophageal squamous cell carcinoma (ESCC) cell lines. Treatment of ESCC cell lines with ART resulted in the production of excessive reactive oxygen species (ROS) that induced DNA damage, reduced cell proliferation and inhibited clonogenicity via G1-S cell cycle arrest and/or apoptosis in vitro. The administration of ART to nude mice with ESCC cell xenografts inhibited tumour formation in vivo. However, the cytotoxicity of ART strongly differed among the ESCC cell lines tested. Transcriptomic profiling revealed that although the expression of large numbers of genes in ESCC cell lines was affected by ART treatment, these genes could be functionally clustered into pathways involved in regulating cell cycle progression, DNA metabolism and apoptosis. We revealed that p53 and Cdk4/6-p16-Rb cell cycle checkpoint controls were critical determinants required for mediating ART cytotoxicity in ESCC cell lines. Specifically, KYSE30 cells with p53/p16 were the most sensitive to ART, KYSE150 and KYSE180 cells with p53/p16 exhibited intermediate responses to ART, and Eca109 cells with p53/p16 exhibited the most resistance to ATR. Consistently, perturbation of p53 expression using RNA interference (RNAi) and/or Cdk4/6 activity using the inhibitor palbociclib altered ART cytotoxicity in KYSE30 cells. Given that the p53 and Cdk4/6-cyclin D1-p16-Rb genes are commonly mutated in ESCC, our results potentially shed new light on neoadjuvant chemotherapy strategies for ESCC.
Topics: Humans; Artesunate; Esophageal Neoplasms; Animals; Esophageal Squamous Cell Carcinoma; Mice; Cell Line, Tumor; Cell Cycle Checkpoints; Cell Proliferation; Apoptosis; Mice, Nude; Carcinoma, Squamous Cell; DNA Damage; Xenograft Model Antitumor Assays; Artemisinins; Reactive Oxygen Species; Antineoplastic Agents
PubMed: 38773551
DOI: 10.1186/s40001-024-01882-9 -
Scientific Reports May 2024Artemisia cina (Ac) is a plant with anthelmintic compounds such as 3'-demethoxy-6-O-demethylisoguaiacin (D) and norisoguaiacin (N). Three major objectives were proposed:...
Artemisia cina (Ac) is a plant with anthelmintic compounds such as 3'-demethoxy-6-O-demethylisoguaiacin (D) and norisoguaiacin (N). Three major objectives were proposed: (1) To evaluate biochemical parameters in blood (2) to determine the tissue oxidative stress by biomarkers as TBARS and glutathione peroxidase activity, and (3) to evaluate anatomopathological changes in organs such as the brain, liver, kidney, and lung after oral administration of n-hexane extract of Ac and D and N. D and N were administrated following the OECD guides for acute oral toxicity evaluation (Guide 420). Fifty Wistar rats were distributed into ten groups as follows: Group 1 (G1): 4 mg/Kg; G2: 40 mg/Kg; G3: 240 mg/Kg; G4: 1600 mg/Kg of n-hexane extract of Ac. G5: 2 mg/Kg; G6: 20 mg/Kg; G7: 120 mg/Kg; G8: 800 mg/Kg of D and N, G9: water and G10: polyvinylpyrrolidone at 2000 mg/Kg. At 14 days, the rats were euthanized, and the blood, liver, brain, kidney, and lung were taken for biochemical analysis, anatomopathological changes, and TBARS and GSH evaluation. Glucose, cholesterol, and phosphorus were altered. Histopathological analysis showed multifocal neuronal degeneration in the brain (G2). The kidney and lungs had changes in G7. The GSH and TBARS increased in G6 and G7. The TBARS activity was higher in G1 and G2. In conclusion, extract and D and N of Ac did not have damage at therapeutic doses. D, N, and n-hexane extract of A. cina do not cause histopathological damage at pharmaceutical doses. Still, the brain, kidney, and liver are related to biochemical parameters at higher doses. However, compounds are proposed as antioxidant agents.
Topics: Animals; Oxidative Stress; Rats, Wistar; Biomarkers; Rats; Plant Extracts; Male; Kidney; Brain; Liver; Glutathione Peroxidase; Thiobarbituric Acid Reactive Substances
PubMed: 38773157
DOI: 10.1038/s41598-024-61903-9