A5066714087- Research on Leishmaniasis Studies
- Trypanosoma species research and implications
- Parasites and Host Interactions
- Synthesis and Biological Evaluation
- Viral Infections and Vectors
- Neonatal Health and Biochemistry
- Metabolism and Genetic Disorders
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Insect and Pesticide Research
- Eicosanoids and Hypertension Pharmacology
- Insect Pest Control Strategies
- Inflammatory mediators and NSAID effects
- Pharmacological Effects of Natural Compounds
- Family and Patient Care in Intensive Care Units
- Cardiac Arrest and Resuscitation
- Advanced Drug Delivery Systems
- bioluminescence and chemiluminescence research
- Anorectal Disease Treatments and Outcomes
- Essential Oils and Antimicrobial Activity
- Viral gastroenteritis research and epidemiology
- Digital and Traditional Archives Management
- ICT in Developing Communities
- Paraoxonase enzyme and polymorphisms
- Electrolyte and hormonal disorders
- Calcium signaling and nucleotide metabolism
University of Antwerp
2015-2024
KU Leuven
2012-2018
Institute of Biomedical Science
2016
Fairfax Neonatal Associates
2012
During the last decade miltefosine (MIL) has been used as first-line treatment for visceral leishmaniasis in endemic areas with antimonial resistance, but a decline clinical effectiveness is now being reported. While only two MIL-resistant Leishmania infantum strains from HIV co-infected patients have documented, phenotypic MIL-resistance L. donovani not yet identified laboratory. Hence, better understanding of factors contributing to increased MIL-treatment failure necessary. Given paucity...
Leishmaniasis is a tropical infectious disease caused by the protozoan Leishmania parasite. The transmitted female sand flies and, depending on infecting parasite species, causes either cutaneous (stigmatizing skin lesions), mucocutaneous (destruction of mucous membranes nose, mouth and throat) or visceral (a potentially fatal infection liver, spleen bone marrow). Although more than 1 million new cases occur annually, chemotherapeutic options are limited their efficacy jeopardized increasing...
Abstract Approximately 20% of sleeping sickness patients exhibit respiratory complications, however, with a largely unknown role the parasite. Here we show that tsetse fly-transmitted Trypanosoma brucei parasites rapidly and permanently colonize lungs occupy extravascular spaces surrounding blood vessels alveoli bronchi. They are present as nests multiplying exhibiting close interactions collagen active secretion extracellular vesicles. The local immune response shows substantial increase...
Although miltefosine and paromomycin were only recently introduced to treat visceral leishmaniasis, increasing numbers of treatment failures occasional primary resistance both drugs have been reported. Understanding alterations in parasite behaviour linked drug is essential assess the propensity for emergence spread resistant strains, particularly since a positive effect on fitness has reported antimony-resistant parasites. This laboratory study compared drug-susceptible parent WT clinical...
Three new chemical series (bicyclic nitroimidazoles, aminopyrazoles and oxaboroles) were selected by Drugs for Neglected Diseases initiative as potential drug leads leishmaniasis. Pharmacodynamics studies included both in vitro vivo efficacy, cross-resistance profiling against the current antileishmanial reference drugs evaluation of their cidal activity potential. Efficacy laboratory strains Leishmania infantum (MHOM/MA(BE)/67/ITMAP263) L. donovani (MHOM/ET/67/L82) was evaluated on...
Abstract Given the discontinuation of various first-line drugs for visceral leishmaniasis (VL), large-scale in vivo drug screening, establishment a relapse model rodents, immunophenotyping, and transcriptomics were combined to study persistent infections therapeutic failure. Double bioluminescent/fluorescent Leishmania infantum L. donovani reporter lines enabled identification long-term hematopoietic stem cells (LT-HSC) as niche bone marrow with remarkably high parasite burdens, feature...
New drugs for visceral leishmaniasis that are safe, low cost, and adapted to the field urgently required. Despite concerted efforts over last several years, number of new chemical entities suitable clinical development treatment Leishmania remains low. Here, we describe discovery preclinical DNDI-6174, an inhibitor cytochrome bc 1 complex activity originated from a phenotypically identified pyrrolopyrimidine series. This compound fulfills all target candidate profile criteria required...
Paromomycin (PMM) has recently been introduced for treatment of visceral leishmaniasis in India. Although no clinical resistance yet reported, proactive vigilance should be warranted. The present vitro study compared the outcome and stability experimental PMM-resistance induction on promastigotes intracellular amastigotes. Cloned antimony-resistant L. donovani field isolates from India Nepal were exposed to stepwise increasing concentrations PMM (up 500 µM), either as or One resulting...
Since miltefosine monotherapy against visceral leishmaniasis (VL) caused by Leishmania donovani has been discontinued in the Indian subcontinent due to an increase number of treatment failures, single dose liposomal amphotericin B is now advocated as a option choice. Paromomycin-miltefosine combination therapy can be used substitute first-line regions without cold-chain potential. Previous laboratory studies closely related species infantum have demonstrated that paromomycin fairly rapidly...
ABSTRACT In 2002 and 2006, respectively, miltefosine (MIL) paromomycin (PMM) were licensed in the Indian subcontinent for treatment of visceral leishmaniasis; however, their future routine use might become jeopardized by development drug resistance. Although experimental selection resistant strains vitro has repeatedly been reported using less relevant promastigote vector stage, outcome resistance on intracellular amastigotes was to be protocol species dependent. To corroborate these...
Abstract Background Since the introduction of miltefosine (MIL) as first-line therapy in kala-azar elimination programme Indian subcontinent, treatment failure rates have been increasing. parasite infectivity and virulence may become altered upon relapse, this laboratory study assessed phenotypic effects repeated vitro vivo MIL exposure. Methods Syngeneic Leishmania donovani lines either or not exposed to were compared for drug susceptibility, rate promastigote multiplication...
Animal trypanosomiasis (AT) is a parasitic disease with high socio-economic impact. Given the limited therapeutic options and problems of toxicity drug resistance, this study assessed redirecting our previously identified antitrypanosomal nucleosides for treatment AT. Promising hits were excellent in vitro activity across all important animal trypanosome species. Compound 7, an inosine analogue, described lead compound, 3'-deoxytubercidin (8), showed broad spectrum anti-AT activity,...
Addressing the challenges of quiescence and post-treatment relapse is utmost importance in microbiology field. This study shows that Leishmania infantum L. donovani parasites rapidly enter into after an estimated 2–3 divisions both human mouse bone marrow stem cells. Interestingly, this behavior not observed macrophages, which are primary host cells parasite. Transcriptional comparison quiescent non-quiescent metabolic states confirmed overall decrease gene expression as a hallmark...
Background: Nepal is very rich in biodiversity, and no extensive effort has yet been carried out to screen plants that are used by traditional healers against parasitic diseases.The aim of this study was evaluate the vitro antileishmanial antimalarial activity crude methanolic or ethanolic extracts 29 plant species currently local people for treating different ailments.Methods: Crude leaves, twigs, aerial parts, and/or roots selected were evaluated inhibitory intracellular amastigotes...
Background: The importance of early cardiopulmonary resuscitation (CPR) during an out-of-hospital cardiac arrest (OHCA) cannot be emphasized enough and has a major impact on survival. Unfortunately, CPR education in schools is often inadequate or non-existing due to lack educators financial resources. introduction application-based teaching could facilitate as no instructor needed. aim present study compare app-based self-teaching (intervention group) with traditional instructor-led course...
Background Miltefosine (MIL) is currently the only oral drug available to treat visceral leishmaniasis but its use as first-line monotherapy has been compromised by an increasing treatment failure. Despite scarce number of resistant clinical isolates, MIL-resistance mutations in a single aminophospholipid transporter gene can easily be selected laboratory environment. These result reduced survival mammalian host, which partially restored exposure MIL, suggesting kind drug-dependency....
The alkylphospholipid oleylphosphocholine (OlPC) is a structural analogue of miltefosine and may represent potential therapeutic backup for the treatment visceral leishmaniasis (VL). This laboratory study compared in vitro vivo activity profile both OlPC miltefosine. potency was with that miltefosine, amphotericin B, paromomycin pentavalent antimony (SbV) using intracellular amastigote assay on different Old World New Leishmania species. efficacy dose titrated infantum hamster model after...
Paromomycin has recently been introduced for the treatment of visceral leishmaniasis and emergence drug resistance can only be appropriately judged upon its long term routine use in field. Understanding alterations parasite behavior linked to paromomycin-resistance may essential assess propensity spread resistant strains. A standardized integrated laboratory approach was adopted define fitness both promastigotes amastigotes using an experimentally induced paromomycin-resistant Leishmania...
Despite a continued search for novel antileishmanial drugs, treatment options remain restricted to few standard e.g. antimonials, miltefosine, amphotericin B and paromomycin. Although these drugs have now been used several decades, their mechanism of action still remains partly hypothetical dynamics cidal time-to-kill are poorly documented. An in vitro assay on intracellular amastigotes the laboratory reference strains Leishmania donovani (MHOM/ET/67/L82) infantum [MHOM/MA(BE)/67/ITMAP263]...
Miltefosine is currently the only oral drug for visceral leishmaniasis, and although deficiency in an aminophospholipid/miltefosine transporter (MT) sufficient to elicit resistance, very few naturally miltefosine-resistant (MIL-R) strains have yet been isolated. This study aimed make a detailed analysis of impact acquired miltefosine resistance treatment on vivo infection.Bioluminescent versions MIL-R strain its syngeneic parental line were generated by integration red-shifted firefly...
This study evaluated the implications of clinically acquired miltefosine resistance (MIL-R) by assessing virulence in mice and sand flies to reveal potential MIL-R strains circulate. Experimental infections with clinical Leishmania infantum isolate MHOM/FR/2005/LEM5159, having a defect LiROS3 subunit MIL-transporter, its syngeneic experimentally reconstituted MIL-S counterpart (LEM5159LiROS3) were performed BALB/c Lutzomyia longipalpis Phlebotomus perniciosus flies. In mice, amastigote...