Isothermal microcalorimetry, a new tool to monitor drug action against <em>Trypanosoma brucei</em> and <em>Plasmodium falciparum</em> (Publications)
and Plasmodium falciparum. Heat flow signals obtained for these pathogens allowed us to monitor parasite growth on a real-time basis as the signals correlated with the number of viable cells. To showcase [...] drugs, chloroquine, artemether and dihydroartemisinin, each at two concentrations on the respective parasite. With the real time measurement, inhibition was observed immediately by a reduced heat flow compared [...] control samples. The onset of drug action, the degree of inhibition and...
Whipworm and roundworm infections (Publications)
species elicit type 2 anti-parasite immunity. Diagnosis is typically based on clinical presentation (gastrointestinal symptoms and inflammation) and the detection of eggs or parasite DNA in the faeces. Prevention [...] nematodes Trichuris trichiura (a whipworm) and Ascaris lumbricoides (a roundworm), respectively. Both parasites are staggeringly prevalent, particularly in tropical and subtropical areas, and are associated with [...] c drugs are needed, together with vaccine development and tools...
Discovery of 4-((1-(1<em>H</em>-imidazol-2-yl)alkoxy)methyl)pyridines as a new class of <em>Trypanosoma cruzi </em>growth inhibitors (Publications)
described. In vitro screening of a subset of compounds from our in-house compound collection against the parasite led to the identification of hit compound 1 with low micromolar inhibition of T. cruzi growth. SAR [...] SAR exploration on the hit compound led to the identification of compounds that show nanomolar parasite growth inhibition (T. cruzi EC50 50 muM). Further investigation identified CYP51 inhibition (compound [...] (compound 11 CYP51 IC50 52 nM) as a possible mechanism of action of...
Synthesis and biological evaluation of phosphate prodrugs of 4-phospho-d -erythronohydroxamic acid, an Inhibitor of 6-phosphogluconate dehydrogenase (Publications)
stability and activity against the intact parasites. Most prodrugs caused inhibition of the growth of the parasites. The activity of the prodrugs against the parasites appeared to be related to their stability
Synthesis and biological evaluation of phosphate prodrugs of 4-phospho-d -erythronohydroxamic acid, an Inhibitor of 6-phosphogluconate dehydrogenase (Publications)
stability and activity against the intact parasites. Most prodrugs caused inhibition of the growth of the parasites. The activity of the prodrugs against the parasites appeared to be related to their stability
Discovery of 4-((1-(1<em>H</em>-imidazol-2-yl)alkoxy)methyl)pyridines as a new class of <em>Trypanosoma cruzi </em>growth inhibitors (Publications)
described. In vitro screening of a subset of compounds from our in-house compound collection against the parasite led to the identification of hit compound 1 with low micromolar inhibition of T. cruzi growth. SAR [...] SAR exploration on the hit compound led to the identification of compounds that show nanomolar parasite growth inhibition (T. cruzi EC50 50 muM). Further investigation identified CYP51 inhibition (compound [...] (compound 11 CYP51 IC50 52 nM) as a possible mechanism of action of...
Changes in metabolic phenotypes of <em>Plasmodium falciparum</em> <em>in vitro</em> cultures during gametocyte development (Publications)
differences between parasite and sham cultures were assessed via principal component analyses and partial-least squares analyses, and univariate statistical methods. RESULTS: Clear parasite-associated changes [...] culture period, revealing differences between asexual parasites and gametocyte stages. With culture progression and development of gametocytes, parasitic release of the glycolytic end products lactate, pyruvate [...] CONCLUSIONS: This study uniquely presents an initial...
Changes in metabolic phenotypes of <em>Plasmodium falciparum</em> <em>in vitro</em> cultures during gametocyte development (Publications)
differences between parasite and sham cultures were assessed via principal component analyses and partial-least squares analyses, and univariate statistical methods. RESULTS: Clear parasite-associated changes [...] culture period, revealing differences between asexual parasites and gametocyte stages. With culture progression and development of gametocytes, parasitic release of the glycolytic end products lactate, pyruvate [...] CONCLUSIONS: This study uniquely presents an initial...
<em>Plasmodium vivax </em>molecular diagnostics in community surveys: pitfalls and solutions (Publications)
A distinctive feature of Plasmodium vivax infections is the overall low parasite density in peripheral blood. Thus, identifying asymptomatic infected individuals in endemic communities requires diagnostic [...] improved more than tenfold, compared to standard 18S rRNA targets, thereby allowing detection of lower parasite densities. In a very low transmission area in Brazil, application of a mitochondrial DNA-based assay [...] however, is the challenge of demonstrating test accuracy and quality...
The influence of biological, epidemiological, and treatment factors on the establishment and spread of drug-resistant <em>Plasmodium falciparum</em> (Publications)
Spread of partial artemisinin resistance was slowed with prolonged parasite exposure to artemisinin derivatives and accelerated when the parasite was also resistant to the partner drug. Thus, to slow the spread [...] the lower levels of (i) immunity and (ii) within-host competition between genotypes. Spread of parasites resistant to artemisinin partner drugs depended on the period of low drug concentration (known as [...] . Furthermore, implementing more sustainable artemisinin-based therapies...
