Community effectiveness of intermittent preventive treatment for infants (IPTi) in rural southern Tanzania (Publications)
Intermittent preventive treatment of malaria in infants (IPTi) with sulphadoxine-pyrimethamine shows evidence of efficacy in individually randomized, controlled trials. In a large-scale effectiveness study [...] selected divisions out of 24 in 6 districts of rural southern Tanzania. Coverage and effects on malaria and anemia were estimated through a representative survey in 2006 with 600 children aged 2-11 months [...] implemented on a large scale by existing health service staff, with a...
Design, synthesis, and biological and crystallographic evaluation of novel inhibitors of <em>Plasmodium falciparum</em> enoyl-ACP-reductase... (Publications)
Malaria, a disease of worldwide significance, is responsible for over one million deaths annually. The liver-stage of Plasmodium's life cycle is the first, obligatory, but clinically silent step in malaria [...] development and has been regarded as a potential antimalarial target for the development of drugs for malaria prophylaxis and liver-stage eradication. In this paper, new coumarin-based triclosan analogues are
An assay to probe <em>Plasmodium falciparum</em> growth, transmission stage formation and early gametocyte development (Publications)
proliferation to sexual differentiation initiates the production of the gametocyte, which is the malaria parasite stage required for human-to-mosquito transmission. This protocol describes an assay designed [...] s on asexual replication, sexual conversion and early gametocyte development in the major human malaria parasite Plasmodium falciparum. Synchronized asexually replicating parasites are induced for gametocyte [...] transmission-blocking compounds and to further investigate the mechanism...
Preclinical characterization and target validation of the antimalarial pantothenamide MMV693183 (Publications)
Drug resistance and a dire lack of transmission-blocking antimalarials hamper malaria elimination. Here, we present the pantothenamide MMV693183 as a first-in-class acetyl-CoA synthetase (AcAS) inhibitor [...] Pharmacokinetic-pharmacodynamic modelling predict that a single 30 mg oral dose is sufficient to cure a malaria infection in humans. Toxicology studies in rats indicate a > 30-fold safety margin in relation to [...] promising candidate for further (pre)clinical development with a novel...
Antimalarial pantothenamide metabolites target acetyl-coenzyme A biosynthesis in <em>Plasmodium falciparum</em> (Publications)
enzymes in the sensitivity of the malaria parasites to pantothenamides. These pantothenamide compounds with a new mode of action may have potential as drugs against malaria parasites. [...] Malaria eradication is critically dependent on new therapeutics that target resistant Plasmodium parasites and block transmission of the disease. Here, we report that pantothenamide bioisosteres were active
The temporal dynamics and infectiousness of subpatent <em>Plasmodium falciparum</em> infections in relation to parasite density (Publications)
transmission and whether they need to be detected and targeted to achieve malaria elimination. In this study we analyse a range of malaria datasets to quantify the density, detectability, course of infection [...] Malaria infections occurring below the limit of detection of standard diagnostics are common in all endemic settings. However, key questions remain surrounding their contribution to sustaining transmission
Discovery and structure-activity relationships of quinazolinone-2-carboxamide derivatives as novel orally efficacious antimalarials (Publications)
against laboratory-resistant strains of malaria. Profiling of 19f suggested a fast in vitro killing profile. In vivo activity in a murine model of human malaria in a dose-dependent manner constitutes a
Discovery and structure-activity relationships of quinazolinone-2-carboxamide derivatives as novel orally efficacious antimalarials (Publications)
against laboratory-resistant strains of malaria. Profiling of 19f suggested a fast in vitro killing profile. In vivo activity in a murine model of human malaria in a dose-dependent manner constitutes a
Health information given by Swiss travel agencies (Publications)
agents mentioned preventive measures against malaria, but only 69% indicated the need for vaccinations against other diseases. Spontaneous advice on malaria risk and vaccinations was better than advice [...] through travel agencies every year. These agencies are thus an important source of information about malaria and other important health risks and little is known about the appropriate health information provided [...] advice given upon prompting. One fifth of all travel agents neither...
Indigenous emergence and spread of <em>kelch13</em> C469Y artemisinin-resistant <em>Plasmodium falciparum</em> in Uganda (Publications)
As part of the Community Access to Rectal Artesunate for Malaria project, we collected blood samples from 697 children with signs of severe malaria in northern Uganda between 2018 and 2020, before and after [...] Artemisinin-based combination therapies (ACTs) were introduced as the standard of care for uncomplicated malaria in Africa almost two decades ago. Recent studies in East Africa have reported a gradual increase [...] geographic origin of k13 mutations. Of the 697 children, 540 were...