Seroprevalence of Toxoplasma gondii among HIV Positive Patients under Surveillance in Greek Infectious Disease Units: A Screening Study with Comparative Evaluation of Serological Methods.

This study aims to screen for IgG antibodies against Toxoplasma gondii (T. gondii) in the sera of 155 newly diagnosed Human Immunodeficiency Virus (HIV) positive patients under surveillance in Greek Infectious Disease Units. Additionally, risk factors based on patient demographics were examined, and a comparative evaluation of commercially available serological methods was conducted. Three methods were employed to detect IgG antibodies against T. gondii: Enzyme-Linked Immunosorbent Assay (ELISA), Indirect Immunofluorescence Antibody Test (IFAT), and Western Blot (WB), which was used as a reference here. Forty-nine sera samples were true-positive for IgG antibodies against T. gondii, resulting in a 31.61% positivity rate, and the immunoassay test statistical reliability analysis resulted in higher IFAT accuracy (90.97%) compared to ELISA (76.26%). Furthermore, statistical analysis of demographic and immunological data included in the study placed female and foreign/non-Greek individuals at 2.24 (p = 0.0009) and 2.34 (p = 0.0006) times higher risk of positive T. gondii IgG testing compared to their male and Greek counterparts, respectively. Our findings on positivity rates and comparative serology underscore the importance of early and suitable screening measures for newly diagnosed HIV+ patients to mitigate the life-threatening outcomes that may arise from a potential subsequent T. gondii activation.

Malaria Vaccines: From the Past towards the mRNA Vaccine Era.

Plasmodium spp. is the etiological agent of malaria, a life-threatening parasitic disease transmitted by infected mosquitoes. Malaria remains a major global health challenge, particularly in endemic regions. Over the years, various vaccine candidates targeting different stages of Plasmodium parasite life-cycle have been explored, including subunit vaccines, vectored vaccines, and whole organism vaccines with Mosquirix, a vaccine based on a recombinant protein, as the only currently approved vaccine for Plasmodium falciparum malaria. Despite the aforementioned notable progress, challenges such as antigenic diversity, limited efficacy, resistant parasites escaping protective immunity and the need for multiple doses have hindered the development of a highly efficacious malaria vaccine. The recent success of mRNA-based vaccines against SARS-CoV-2 has sparked renewed interest in mRNA vaccine platforms. The unique mRNA vaccine features, including their potential for rapid development, scalability, and flexibility in antigen design, make them a promising avenue for malaria vaccine development. This review provides an overview of the malaria vaccines' evolution from the past towards the mRNA vaccine era and highlights their advantages in overcoming the limitations of previous malaria vaccine candidates.

Climate Changes Exacerbate the Spread of Ixodes ricinus and the Occurrence of Lyme Borreliosis and Tick-Borne Encephalitis in Europe-How Climate Models Are Used as a Risk Assessment Approach for Tick-Borne Diseases.

Climate change has influenced the transmission of a wide range of vector-borne diseases in Europe, which is a pressing public health challenge for the coming decades. Numerous theories have been developed in order to explain how tick-borne diseases are associated with climate change. These theories include higher proliferation rates, extended transmission season, changes in ecological balances, and climate-related migration of vectors, reservoir hosts, or human populations. Changes of the epidemiological pattern have potentially catastrophic consequences, resulting in increasing prevalence of tick-borne diseases. Thus, investigation of the relationship between climate change and tick-borne diseases is critical. In this regard, climate models that predict the ticks' geographical distribution changes can be used as a predicting tool. The aim of this review is to provide the current evidence regarding the contribution of the climatic changes to Lyme borreliosis (LB) disease and tick-borne encephalitis (TBE) and to present how computational models will advance our understanding of the relationship between climate change and tick-borne diseases in Europe.

The incidence of recurrent cardiovascular events among acute coronary syndrome patients treated with generic or original clopidogrel in relation to their sociodemographic and clinical characteristics. The Aegean study.

INTRODUCTION: The use of generic drugs is continuously growing; however, there are limited epidemiological data regarding the therapeutic equivalence of each original drug formulation with its generic counterparts. We evaluated the 12-month composite endpoint of recurrent acute myocardial infarction, ischaemic stroke, cardiac deaths, or hospitalisation due to a major bleeding in acute coronary syndrome (ACS) patients treated with original clopidogrel or a generic clopidogrel formulation, in relation to sociodemographic and clinical characteristics. MATERIAL AND METHODS: Consecutive Greek ACS patients (n = 1194) hospitalised in the Aegean islands and the Attica region were enrolled. Clopidogrel treatment was recorded either as original clopidogrel hydrogen sulphate (Plavix®/Iscover®) or as a generic clopidogrel besylate formulation (Clovelen®). The composite endpoint was recorded at 12-month follow-up. RESULTS: The 12-month composite endpoint was 3.9% (4.6% in the Aegean islands and 3.5% in the Attica area, p > 0.05). The respective incidence in men was 4.0% and in women 3.8% (p > 0.05). Overall, generic and original clopidogrel use was 87% and 13% of patients, respectively. No significant differences were observed between original and generic clopidogrel use and 12-month composite endpoint incidence. Subgroup analysis with gender, region of residence, and clinical and lifestyle factors as strata did not reveal any significant outcomes. Haemorrhage incidence did not exceed 1% in the total sample. CONCLUSIONS: The use of a generic clopidogrel besylate formulation was quite high in both urban and insular areas of Greece and had similar efficacy and safety profile with the original clopidogrel salt, supporting the routine use of this low-cost generic clopidogrel in the management of cardiovascular disease patients.

Comparison of the Level of Awareness about the Transmission of Echinococcosis and Toxocariasis between Pet Owners and Non-Pet Owners in Greece.

Ζoonotic parasitic diseases that can occur through animal contact pose risks to pets, their owners and to their bond. This study aims to assess the level of knowledge about zoonoses, specifically echinococcosis and toxocariasis, among cat/dog owners and non-pet owners in Greece. Multiple-choice questionnaires were designed to obtain data regarding the knowledge of pet and non-pet owners on echinococcosis and toxocariasis, including signs and symptoms of these zoonoses, ways of transmission and precautions that need to be taken into account in order to avoid it. A total of 185 questionnaires were retrieved and data was expressed as absolute (Ν) and relative frequencies (%). Associations between pet ownership, residence and outcome variables were evaluated using the Fisher exact test and Chi-squared test, respectively. Multifactorial linear regression analysis was used to investigate the cross-sectional association between demographic characteristics and the awareness of helminthic zoonoses. All tests were two-sided and statistical significance was set at p < 0.05. Our study revealed a disturbing lack of awareness of echinococcosis and toxocariasis (mean zoonotic knowledge score 8.11 ± 3.18) independently of pet ownership. Surprisingly, in some cases the ignorance of pet owners exceeded that of non-pet owners. Given the progressive impact of toxocariasis in public health and the high prevalence of echinococcosis in the Mediterranean region, measures should be taken to inform people about zoonoses and eliminate their putative transmission.

Circulating progenitor cells and their interaction with platelets in patients with an acute coronary syndrome.

CD34+ cells expressing KDR (CD34+/KDR+) represent a small proportion of circulating progenitor cells that have the capacity to interact with platelets and to differentiate into mature endothelial cells, thus contributing to vascular homeostasis and regeneration as well as to re-endothelialization. We investigated the levels of CD34+ and CD34+/KDR+ progenitor cells as well as their interaction with platelets in acute coronary syndrome (ACS) patients before the initiation (baseline) of their treatment with a P2Y12 receptor antagonist, and at 5-days post-treatment (follow-up). Sixty-seven consecutive ACS patients and thirty healthy subjects (controls) participated in the study. On admission, all patients received 325 mg aspirin, followed by 100 mg/day and then were loaded either with 600 mg clopidogrel or 180 mg ticagrelor, followed by 75 mg/day (n = 36) or 90 mg × 2/day (n = 31), respectively. The levels of circulating CD34+ and CD34+/KDR+ progenitor cells, as well as their interaction with platelets, were determined by flow cytometry, before and after activation with ADP, in vitro. The circulating levels of CD34+ and CD34+/KDR+ cells in both patient groups at baseline were lower compared with controls while they were significantly increased at 5-days of follow-up in both groups, this increase being more pronounced in the ticagrelor group. The platelet/CD34+ (CD61+/CD34+) conjugates were higher at baseline and reduced at follow-up while the platelet/KDR+ (CD61+/KDR+) conjugates were lower at baseline and increased at follow-up, both changes being more pronounced in the ticagrelor group. ADP activation of control samples significantly increased the KDR expression by CD34+ cells and the CD61+/KDR+ conjugates, these parameters being unaffected in patients at baseline but increased at follow-up. Short-term dual antiplatelet therapy in ACS patients restores the low platelet/KDR+ conjugates and CD34+ cell levels and improves the low membrane expression levels of KDR in these cells, an effect being more pronounced in ticagrelor-treated patients. This may represent a pleiotropic effect of antiplatelet therapy towards vascular endothelial regeneration.

Comparison of Triflusal with Aspirin in the Secondary Prevention of Atherothrombotic Events; Α Randomised Clinical Trial.

BACKGROUND: Triflusal has demonstrated an efficacy similar to aspirin in the prevention of vascular events in patients with acute myocardial infarction (ΜΙ) and ischaemic stroke but with less bleeding events. OBJECTIVE: We performed a randomised, multicentre, phase 4 clinical trial to compare the clinical efficacy and safety of triflusal versus aspirin, administered for 12 months in patients eligible to receive a cyclooxygenase-1 (COX-1) inhibitor. METHODS: Patients with stable coronary artery disease or with a history of non-cardioembolic ischaemic stroke were randomly assigned to receive either triflusal 300 mg twice or 600 mg once daily or aspirin 100 mg once daily for 12 months. The primary efficacy endpoint was the composite of: (a) ΜΙ, (b) stroke (ischaemic or haemorrhagic), or, (c) death from vascular causes for the entire follow-up period. The primary safety endpoints were the rate of bleeding events as defined by Bleeding Academic Research Consortium (BARC) criteria. RESULTS: At 12-month follow-up, an equivalent result was revealed between the triflusal (n=559) and aspirin (n=560) in primary efficacy endpoint. Specifically, the combined efficacy outcome rate (i.e. MI, stroke or death from vascular causes) difference was equal to -1.3% (95% confidence interval -1.1 to 3.5) and lied within the a-priori defined equivalence interval (p<0.001). Regarding the primary safety endpoints, patients on triflusal treatment were 50% less likely to develop bleeding events according to the BARC criteria, and especially any clinically overt sign of haemorrhage that requires diagnostic studies, hospitalisation or special treatment (BARC type 2). CONCLUSION: The efficacy of triflusal in the secondary prevention of vascular events is similar to aspirin when administered for 12 months. Importantly, triflusal significantly reduced the incidence of ΜΙ and showed a better safety profile compared with aspirin. (ASpirin versus Triflusal for Event Reduction In Atherothrombosis Secondary prevention, ASTERIAS trial; Clinical Trials.gov Identifier: NCT02616497).

Antiplatelet Agents and Anticoagulants: From Pharmacology to Clinical Practice.

Thrombosis is the formation of potentially deadly blood clots in the artery (arterial thrombosis) or vein (venous thrombosis). Since thrombosis is one of the main causes of death worldwide, the development of antithrombotic agents is a global medical priority. They are subdivided into antiplatelet agents and anticoagulants. Antiplatelet agents inhibit clot formation by preventing platelet activation and aggregation, while anticoagulants primarily inhibit the coagulation cascade and fibrin formation. Therapeutics within each category differs with respect to the mechanism of action, time to onset, duration of effect and route of administration. In this review, we critically discuss their main pharmacodynamic and pharmacokinetic characteristics as well as recent advances in daily clinical practice.

Dynamic platelet adhesion in patients with an acute coronary syndrome: The effect of antiplatelet therapy.

Platelet adhesion and aggregation are key functions leading to thrombus formation. The effect of aspirin, clopidogrel, and ticagrelor on platelet aggregation has been well established, however, there is limited data on the effect of these drugs on platelet adhesion. We therefore evaluated the effect of these drugs on platelet adhesion in acute coronary syndrome (ACS) patients. Citrated blood was collected from 50 ACS patients loaded with 325 mg of aspirin (baseline) and at 5 days after the administration of aspirin 100 mg/day and clopidogrel (600 mg loading dose, 75 mg/day) (n = 26) or ticagrelor (180 mg loading dose, 90 mg × 2/day) (n = 24). High on-treatment platelet reactivity (HTPR) to clopidogrel was estimated by vasodilator stimulated phosphoprotein (VASP) phosphorylation assay. Platelet adhesion to collagen was studied for 6 min under high shear stress and was evaluated using the time to platelet recruitment (TPR), the perimeter and average area of each adherent object, number of adherent objects, and the total percent of surface coverage (SC%). Six ACS patients exhibited HTPR to clopidogrel and excluded from the platelet adhesion assays. TPR and SC% values were similar among patient groups at baseline and controls. However, all other adhesion parameters were different in ACS patients, indicating the formation of more aggregates in regard to controls. At 5 days post-treatment with either clopidogrel or ticagrelor, the TPR values were increased and the SC% values were reduced to a similar extent compared with baseline. However, significant differences were observed in the ticagrelor group in the perimeter, number of adherent objects, and the average area of each adherent object indicating a more potent inhibition of adherence-induced platelet aggregation than clopidogrel. In conclusion, aspirin does not affect platelet adherence to collagen, whereas clopidogrel and ticagrelor inhibit to a similar extent dynamic platelet adhesion at 5 days post-treatment in ACS patients. However, ticagrelor exhibits a greater inhibitory effect on reducing adhesion-induced platelet aggregation.

Deconvoluting the Dual Antiplatelet Activity of a Plant Extract.

A thorough evaluation of the antiplatelet activity profile of hexane olive leaf extract in human platelets indicated a potent activity accomplished through a two axis inhibition of platelet activation triggered both by ADP and thrombin. To delineate the extract components responsible for this dual activity, an NMR based method was established to determine and quantify the triterpenoid content leading to the characterization of uvaol, erythrodiol, and oleanolic acid. The antiplatelet profile of the total extract and of the 3 determined triterpenoids was evaluated against in vitro platelet aggregation induced by several platelet agonists as also on PAC-1 binding and P-selectin membrane expression both in healthy volunteers and in platelets from patients with an acute coronary syndrome receiving dual antiplatelet therapy with aspirin and ticagrelor. The extract was identified to inhibit ADP-induced platelet activation due to its erythrodiol content and TRAP-induced platelet activation due to the activity of uvaol and oleanolic acid.

Salts of Clopidogrel: Investigation to Ensure Clinical Equivalence: A 12-Month Randomized Clinical Trial.

BACKGROUND: In the present clinical trial, we compared the efficacy and safety of the generic clopidogrel besylate (CB) with the innovator clopidogrel hydrogen sulfate (CHS) salt in patients eligible to receive clopidogrel. METHODS: A prospective 2-arm, multicenter, open-label, phase 4 clinical trial. Consecutive patients (n = 1864) were screened and 1800 were enrolled in the trial and randomized to CHS or CB. Primary efficacy end point was the composite of myocardial infarction, stroke, or death from vascular causes, and primary safety end point was rate of bleeding events as defined by Bleeding Academic Research Consortium criteria. RESULTS: At 12-month follow-up, no differences were observed between CB (n = 759) and CHS (n = 798) in primary efficacy and safety end points (age, sex, history of percutaneous coronary intervention adjusted odds ratio [OR], 0.70; 95% confidence interval [CI], 0.41-1.21 and OR, 0.81; 95% CI, 0.51-1.29, respectively) between CHS and CB. Analyses of efficacy and safety in subgroups that were defined according to the qualifying diagnosis revealed that there was no difference between CHS and CB. CONCLUSION: The efficacy and safety of CB administered for 12 months for the secondary prevention of atherothrombotic events are similar to that of CHS. (Salts of Clopidogrel: Investigation to ENsure Clinical Equivalence, SCIENCE trial; ClinicalTrials.gov Identifier:NCT02126982).

Generic Clopidogrel Besylate in the Secondary Prevention of Atherothrombotic Events: A 6-month Follow-up of a Randomised Clinical Trial.

BACKGROUND: The aim of the present interim analysis was to compare the clinical efficacy and safety of the generic clopidogrel besylate (CB) with the innovator clopidogrel hydrogen sulphate (CHS) salt in patient groups eligible to receive clopidogrel. METHODS: A 2-arm, multicenter, open-label, phase 4 clinical trial. Consecutive patients (n=1,864) were screened and 1,800 were enrolled in the trial and randomized to CHS (n=759) or CB (n=798). Primary efficacy end point was the composite of myocardial infarction, stroke or death from vascular causes, and primary safety end point was rate of bleeding events as defined by Bleeding Academic Research Consortium (BARC) criteria. RESULTS: At 6-months follow-up no differences were observed between CB and CHS in primary efficacy end point (OR, 0.80; 95% CI, 0.37 to 1.71; p=0.57). Rates of BARC-1,-2,-3a and -5b bleeding were similar between the two study groups whereas no bleeding events according to BARC-3b, -3c, -4 and -5a were observed in either CHS or CB group. CONCLUSION: The clinical efficacy and safety of the generic CB is similar to that of the innovator CHS salt, thus, it can be routinely used in the secondary prevention of atherothrombotic events for a period of at least 6 months. (Salts of Clopidogrel: Investigation to ENsure Clinical Equivalence, SCIENCE study Clinical Trials.gov Identifier: NCT02126982).

Clopidogrel generic formulations in the era of new antiplatelets: a systematic review.

Clopidogrel is a thienopyridine that selectively and irreversibly inhibits the ADP purinergic receptor P2Y12 and the subsequent ADP-mediated platelet activation. Clopidogrel has been approved for clinical use as clopidogrel hydrogen sulfate (bisulfate) salt. The clinical usefulness of clopidogrel bisulfate salt has been proved in a wide variety of large scale clinical trials, thus clopidogrel bisulfate has been extensively used in a large spectrum of patients been under thrombotic risk. Recently, several generic clopidogrel formulations have been approved for clinical use. Consequently, clopidogrel is currently a cost-effective antiplatelet agent. Only small studies have compared the pharmacokinetic and pharmacodynamic properties of various clopidogrel generic salt formulations with the innovator bisulfate salt. In addition few data are available concerning the clinical efficacy and safety of these generic clopidogrel formulations in order to guide clinicians in deciding when generic substitution is appropriate. The aim of this review is to summarize the physicochemical properties as well as the pharmacokinetic and pharmacodynamic characteristics of the generic clopidogrel salts. We also critically present existing data on the clinical efficacy and safety of the generic clopidogrel formulations compared with the innovator clopidogrel bisulfate salt in patients with cardiovascular disease.

Pharmacodynamic properties of antiplatelet agents: current knowledge and future perspectives.

Platelets play an important role in atherothrombotic disease. The currently available antiplatelet drugs target key steps of platelet activation including thromboxane A(2) synthesis, ADP-mediated signaling, and glycoprotein IIb/IIIa-mediated platelet aggregation. The improvement of our understanding on the pharmacokinetic and pharmacodynamic characteristics of these drugs enables the tailoring of the most appropriate anti-thrombotic therapy to the individual patient and risk situation in the daily clinical practice. However, current antiplatelet therapies are associated with increased bleeding risk. Thus, further research on platelet functions may give rise to numerous new antiplatelet agents with high anti-thrombotic efficiency and low adverse hemorrhagic side effects.

Platelet-mediated inflammation in cardiovascular disease. Potential role of platelet-endothelium interactions.

Inflammation of the vascular wall is considered as the principal underlying mechanism in the development of atherosclerosis. Besides their specific functions in haemostasis via thrombus formation after an endothelial injury, a growing body of evidence indicates that platelets play an important role in the inflammatory reactions occurring in the vascular wall as well as in the subsequent tissue repair mechanisms. Platelets interact with activated endothelium as well as with circulating leukocytes and progenitor cells. These interactions, involve direct cell-to-cell interactions as well as autocrine and paracrine pathways, which lead to activation of platelets and their respective cellular counterpart. An increasing body of evidence suggests that antiplatelet therapy may reduce vascular inflammation primarily by inhibiting platelet activation. The aim of the present review is to highlight the molecular basis of platelet-mediated inflammatory response, focusing on the mechanisms underlying the platelet-endothelial cell interaction. The anti-inflammatory effects of current antiplatelet therapies will be also discussed.

Effect of clopidogrel besylate on platelet reactivity in patients with acute coronary syndromes. Comparison with clopidogrel hydrogen sulfate.

OBJECTIVE: The efficacy of clopidogrel therapy in patients with an acute coronary syndrome (ACS) has been established using the clopidogrel hydrogen sulfate (CHS) formulation. In this study we compared the antiplatelet effectiveness of a generic clopidogrel salt, clopidogrel besylate (CB), with the original CHS in patients with an ACS. RESEARCH DESIGN AND METHODS: Ninety-six ACS patients were randomized to receive a 600-mg loading dose of either CHS (n = 45) or CB (n = 51), followed by 75 mg/day. Sixty-eight patients underwent a percutaneous coronary intervention (PCI), whereas 28 were treated conservatively. Platelet aggregatory response, vasodilator-stimulated phosphoprotein (VASP) phosphorylation, P-selectin expression and platelet-leucocyte conjugates were determined before clopidogrel loading (baseline), as well as at 5 days and at 1 month afterwards. RESULTS: No difference in the clopidogrel response variability was observed between patients receiving CHS or CB either at 5 days or at 1 month of follow-up. Similarly, no difference in the inhibition of platelet aggregation, P-selectin expression or in the platelet-leucocyte conjugates was observed between CHS and CB group during the follow-up. CONCLUSIONS: There is no overall significant difference in the antiplatelet efficacy between CB and CHS during their administration in ACS patients for up to 1 month after the episode.

Antiplatelet efficacy of long-term treatment with clopidogrel besylate in patients with a history of acute coronary syndrome: comparison with clopidogrel hydrogen sulfate.

The efficacy of clopidogrel therapy in patients with an acute coronary syndrome (ACS) has been established using the clopidogrel hydrogen sulfate (CHS) formulation. We compared the antiplatelet effectiveness of long-term administration of the original CHS with a generic clopidogrel besylate (CB) salt formulation in 86 patients with a history of an ACS. At 1 month after the episode, patients receiving 75 mg/d CHS were randomized to continue with CHS (n = 41) or to switch to 75 mg/d CB (n = 45). Platelet aggregation, vasodilator-stimulated phosphoprotein (VASP) phosphorylation, P-selectin expression, and platelet-leucocyte conjugates were determined before randomization and at 6 months afterward. No difference in any platelet parameter studied was observed between the 2 groups either before randomization or after 6 months of treatment with CHS or CB. We conclude that there is no difference in the antiplatelet efficacy between CB and CHS during long-term administration in patients with a history of an ACS.