Treatment failure after multiple courses of triclabendazole in a Portuguese patient with fascioliasis

2020 ◽  
Vol 13 (3) ◽  
pp. e232299 ◽  
Author(s):  
Elsa Alves Branco ◽  
Rogerio Ruas ◽  
João Nuak ◽  
António Sarmento
Keyword(s):  
The Netherlands ◽  
Treatment Failure ◽  
Effective Treatment ◽  
Fasciola Hepatica ◽  
Contaminated Water ◽  
Cure Rate ◽  
Multiple Treatment ◽  
Emergence Of Resistance ◽  
First Time ◽  
Livestock Rearing

Fascioliasis is a trematode flatworm infection caused by Fasciola hepatica. Humans are incidental hosts, and the infection is most often acquired by eating watercress grown in contaminated water in livestock-rearing areas. Triclabendazole is the only highly effective treatment, with a reported cure rate of >90%. Treatment failure may be due to several factors, though resistance is rare in humans and scarcely reported, most probably a reflection of the widespread use of anthelmintics in livestock. There are three papers describing cases of treatment failure, possibly due to resistance, in the Netherlands, Chile and Peru. We document for the first time one case of failure after multiple treatment courses with triclabendazole in Portugal, probably due to resistance to the anthelmintic. Our aim is to alert for the emergence of resistance across continents, with consequent predictable difficulties in the management of the disease and encourage more investigation in the field.

Structure-Reactivity Relationships on Substrates and Inhibitors of the Lysine Deacylase Sirtuin 2 from Schistosoma Mansoni (SmSirt2)

2019 ◽  
Author(s):  
Daria Monaldi ◽  
Dante Rotili ◽  
Julien Lancelot ◽  
Martin Marek ◽  
Nathalie Wössner ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Human Cancer ◽  
Egg Laying ◽  
Human Cancer Cells ◽  
Parasite Survival ◽  
Survival And Reproduction ◽  
Emergence Of Resistance ◽  
First Time ◽  
Parasitic Life Cycle

The only drug for treatment of Schistosomiasis is Praziquantel, and the possible emergence of resistance makes research on novel therapeutic agents necessary. Targeting of Schistosoma mansoni epigenetic enzymes, which regulate the parasitic life cycle, emerged as promising approach. Due to the strong effects of human Sirtuin inhibitors on parasite survival and reproduction, Schistosoma sirtuins were postulated as therapeutic targets. In vitro testing of synthetic substrates of S. mansoni Sirtuin 2 (SmSirt2) and kinetic experiments on a myristoylated peptide demonstrated lysine long chain deacylation as an intrinsic SmSirt2 activity for the first time. Focused in vitro screening of the GSK Kinetobox library and structure-activity relationships (SAR) of identified hits, led to the first SmSirt2 inhibitors with activity in the low micromolar range. Several SmSirt2 inhibitors showed potency against both larval schistosomes (viability) and adult worms (pairing, egg laying) in culture without general toxicity to human cancer cells.<br>

scholarly journals Recognition Pattern of the Fasciola hepatica Excretome/Secretome during the Course of an Experimental Infection in Sheep by 2D Immunoproteomics

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 725
Author(s):  
David Becerro-Recio ◽  
Javier González-Miguel ◽  
Alberto Ucero ◽  
Javier Sotillo ◽  
Álvaro Martínez-Moreno ◽  
...  
Keyword(s):  
Experimental Infection ◽  
Fasciola Hepatica ◽  
Cathepsin L ◽  
Helminth Parasites ◽  
Glutathione S Transferase ◽  
Serum Samples ◽  
Secretory Products ◽  
Immunogenic Proteins ◽  
Host Parasite ◽  
First Time

Excretory/secretory products released by helminth parasites have been widely studied for their diagnostic utility, immunomodulatory properties, as well as for their use as vaccines. Due to their location at the host/parasite interface, the characterization of parasite secretions is important to unravel the molecular interactions governing the relationships between helminth parasites and their hosts. In this study, the excretory/secretory products from adult worms of the trematode Fasciola hepatica (FhES) were employed in a combination of two-dimensional electrophoresis, immunoblot and mass spectrometry, to analyze the immune response elicited in sheep during the course of an experimental infection. Ten different immunogenic proteins from FhES recognized by serum samples from infected sheep at 4, 8, and/or 12 weeks post-infection were identified. Among these, different isoforms of cathepsin L and B, peroxiredoxin, calmodulin, or glutathione S-transferase were recognized from the beginning to the end of the experimental infection, suggesting their potential role as immunomodulatory antigens. Furthermore, four FhES proteins (C2H2-type domain-containing protein, ferritin, superoxide dismutase, and globin-3) were identified for the first time as non-immunogenic proteins. These results may help to further understand host/parasite relationships in fasciolosis, and to identify potential diagnostic molecules and drug target candidates of F. hepatica.

scholarly journals AB0243 CONSIDERING THE COMBINATION OF TWO BIOLOGICS IN CASE OF FAILURE OF THE MONOTHERAPY IN JUVENILE ONSET RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1147.1-1147
Author(s):  
A. Haddouche ◽  
K. Ait Bellabas ◽  
W. F. Hamrani ◽  
S. Sahraoui ◽  
R. Fatma ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Alternative Therapy ◽  
Biologic Therapies ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Juvenile Onset ◽  
Multiple Treatment ◽  
Tnf Blocker ◽  
Different Types ◽  
First Time

Background:The management of rheumatoid arthritis refractory to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) is currently well codified and includes different types of biologics and even targeted sDMARDs. A rotation of biologic therapies is recommended in order to better control the disease.Methods:We report the case of a 20-year-old patient followed in our hospital for the management of a deforming and erosive seropositive rheumatoid arthritis (FR +, ACPA +) with a juvenile onset at the age of 8 years. The diagnosis of an immunopositive polyarticular form of JIA was retained in 2010 (9 years old); the patient was treated with methotrexate (MTX) at a dose of 10 mg per week and methylprednisolone at doses varying between 4 and 10 mg per day. Following the failure of MTX, etanercept was introduced for 6 months without success, followed by tocilizumab in 2012 at a dose of 8mg/kg/month for a year, without good response. In 2014, a course of rituximab (RTX) at a dose of 2 shots of 500mg, 2 weeks apart was prescribed followed 9 months later by etanercept at a dose of 50 mg a week for 3 years then by adalimumab (40mg/ week) because of the multiple treatment failures.In 2018, the repetition of RTX at a dose of 1g, renewed 15 days later, improved the patient for only 3 months. Then, a combination of two biologics, namely RTX (2 x 1g, 15 days apart) and adalimumab 1 month later (40mg / week) was received by the patient with a good response at 3 months. The latter was maintained for 7 months even after stopping the adalimumab following confinement for COVID-19. In September 2020, flares occurred and the adalimumab (ADA) has been delivered but without success during 3 months, stopped later for a benign form of COVID-19 (15 months after RTX). In January 2021, the association RTX + ADA was given again and we hope that it will be as effective as the first prescription.Results:The clinical and biological severity of our patient’s rheumatoid arthritis led us to give a combination of two biological treatments. Indeed, we do not have other therapeutic classes to deliver to her, that encouraged us to rotate between all the available biological therapies in our country. The combination of a CD20 inhibitor (RTX) with a TNF blocker (ADA) was safe and made possible, for the first time, the achievement of clinical and biological remission during 7 months, even after stopping the TNF blocker. Greenwald et al. reported the safety of the combination of RTX + TNF inhibitors in a randomized clinical trial in 51 patients. Its efficacy, a secondary goal of the study, was suggested at 24 weeks by the percentage of ACR 20 and ACR 50 responses that was greater than in the RTX placebo group.Conclusion:The combination of RTX with a TNF blocker can be a real alternative therapy in rheumatoid arthritis with failure to a biological monotherapy.Disclosure of Interests:None declared

scholarly journals A Meningo-Leucoencephalomyelitis Resembling Visna in Dutch Zwoeger Sheep

1966 ◽  
Vol 3 (5) ◽  
pp. 401-411 ◽  
Author(s):  
A. A. Ressang ◽  
F. C. Stam ◽  
G. F. De Boer
Keyword(s):  
White Matter ◽  
The Netherlands ◽  
Final Stage ◽  
Chronic Condition ◽  
Cerebral Lesions ◽  
Terminal Stage ◽  
Icelandic Sheep ◽  
Close Relationship ◽  
Secondary Demyelination ◽  
First Time

Zwoegerziekte is a disease in Dutch sheep which morphologically closely resembles an Icelandic sheep disease, Maedi2. Chronic lung affection and emaciation are the principal symptoms of both diseases. Visna is another chronic condition in Icelandic sheep affecting mainly the C.N.S. A virus has been isolated from sheep affected with Maedi or Visna and a close relationship in properties has been found between both viruses. In two Dutch sheep autopsied in the final stage of Zwoegerziekte, lesions were present in the C.N.S., which histologically resembled those in Visna. Another sheep slaughtered at the municipal abattoir, with lung lesions characteristic for the terminal stage of Zwoegerziekte, exhibited early cerebral lesions resembling Visna. The lesions in the C.N.S. of these three sheep were meningitis and severe encephalomyelitis of the glial type affecting the white matter. Secondary demyelination was striking. Though Zwoegerziekte has been known for several decades in the Netherlands, the accompanying C.N.S. lesions are described for the first time.

scholarly journals Frequent Emergence of Resistance in Clostridium difficile during Treatment of C. difficile-Associated Diarrhea with Fusidic Acid

2006 ◽  
Vol 50 (9) ◽  
pp. 3028-3032 ◽  
Author(s):  
T. Norén ◽  
M. Wullt ◽  
Thomas Åkerlund ◽  
E. Bäck ◽  
I. Odenholt ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Treatment Failure ◽  
Fusidic Acid ◽  
Negative Impact ◽  
Acid Resistance ◽  
Clinical Recurrence ◽  
Acid Therapy ◽  
Emergence Of Resistance ◽  
Culture Positive

ABSTRACT Samples from patients with Clostridium difficile-associated diarrhea (CDAD) that were randomized to fusidic acid (n = 59) or metronidazole (n = 55) therapy for 7 days were cultured for Clostridium difficile in feces on days 1, 8 to 13, and 35 to 40. Of the patients who were culture positive only before treatment, 77% (36/47) were permanently cured (no treatment failure and no clinical recurrence), compared to 54% (22/41) of those with persistence of C. difficile at one or both follow-ups (P = 0.03). A similar association between bacterial persistence and a worse outcome of therapy was seen in both treatment groups. Resistance to fusidic acid was found in 1 of 88 pretherapy isolates available, plus in at least 1 subsequent isolate from 55% (11/20) of patients who remained culture-positive after fusidic acid therapy. In 10 of these 11 patients, the resistant follow-up isolate(s) belonged to the same PCR ribotype as the susceptible day 1 isolate, confirming frequent emergence of resistance to fusidic acid during treatment. Despite this, 5 of these 11 patients were permanently cured with fusidic acid, relative to 5 of 9 patients with susceptible C. difficile at follow-up (P = 1.0). None of the 36 PCR ribotypes of C. difficile identified was associated with any particular clinical outcome or emergence of fusidic acid resistance. In conclusion, culture positivity for C. difficile was common after both fusidic acid and metronidazole therapy and was associated with treatment failure or recurrence of CDAD. Development of resistance in C. difficile was frequent in patients given fusidic acid, but it was without apparent negative impact on therapeutic efficacy in the actual CDAD episode.

De windmolen

2020 ◽  
Vol 5 (1) ◽  
pp. 17-32
Author(s):  
JOS BAZELMANS
Keyword(s):  
The Netherlands ◽  
19Th Century ◽  
Turn Of The Century ◽  
The 19Th Century ◽  
First Time ◽  
At Home

The windmill. The origins of a Dutch icon The windmill is an icon of the Netherlands. But when did this instrument acquire this symbolic role at home and abroad? After all, mills are also common outside of the Netherlands. In this essay, it is argued that during the second half of the 19th century, foreigners systematically identified the Netherlands and the windmill for the first time. More than in other countries, there was a varied use of mills in the Netherlands, large and robust mills and clusters of industrial mills. Within the Netherlands itself, development towards an iconic position is only visible around the turn of the century when the mill turned out to be a plus in tourist recruitment abroad and when mills were slowly disappearing from the landscape.

scholarly journals Predictors of multiple treatment failure of antipsychotics in early-onset psychosis

2016 ◽  
Vol 26 ◽  
pp. S539-S540
Author(s):  
L. Pina-Camacho ◽  
H. Dean ◽  
S. Lechler ◽  
N. Sears ◽  
R. Patel ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Early Onset ◽  
Multiple Treatment ◽  
Early Onset Psychosis

scholarly journals Exploratory Analysis into the in vitro and in silico Activity of E. fusca Lour. (Fabaceae) Elucidates Substantial Antiplasmodial Activity of the Plant

2021 ◽  
Author(s):  
Saiful Arefeen Sazed ◽  
Ohedul Islam ◽  
Sarah L. Bliese ◽  
Muhammad Riadul Haque Hossainey ◽  
Jakaria Shawon ◽  
...  
Keyword(s):  
Antimalarial Drug ◽  
Simulation Analysis ◽  
Antimalarial Activity ◽  
Dynamics Simulation ◽  
Drug Candidate ◽  
Phytochemical Investigation ◽  
High Degree ◽  
Emergence Of Resistance ◽  
First Time

The exploration of alternative antimalarial therapeutics is a requisite for the emergence of resistance against Artemisinin. Considering the required cost and time length of classical small molecule drug discovery process, phytochemical screening of traditionally used medicinal plant which are repertoire of active compounds with antimalarial activity has become popular. To investigate the antimalarial property of traditionally used medicinal plants, a number of Erythrina spp have been reviewed systematically where less studied E. fusca has been selected for further analysis. Phytochemical investigation yielded five compounds namely; Phaseolin, Phytol, &beta;-amyrin, Lupeol, and Stigmasterol. In-vitro antimalarial drug sensitivity HRP-II ELISA was carried out against chloroquine (CQ) sensitive 3D7 and CQ-resistant Dd2 strains. Extracts showed significant antimalarial activity against 3D7 and Dd2 strains (IC50 4.94 &ndash; 22 &micro;g/mL) and these compounds have been reported here for the first time. Molecular docking analysis showed high binding energy (&minus;9.0 &plusmn; 0.32 kcal/mole) indicating high degree of interaction between Phaseolin and 14 clinically important Plasmodium falciparum proteins at the active site. Stable interaction was also observed between ligand and protein from molecular dynamics simulation analysis with high free energy (&minus;75.156 &plusmn; 11.459) that substantiates the potential of Phaseolin as an antimalarial drug candidate.

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