Resistance to Artemisinin Combination Therapies (ACTs): do not forget the partner drug! (Publications)
remaining parasites after a standard 3-day ACT regimen. When introduced, ACTs were highly efficacious and contributed to the steep decrease of malaria over the last decades. However, parasites with decreased [...] discovered. However, resistance to partner drugs is critical, as ACTs can still be effective against parasites with decreased susceptibility to artemisinins, when the latter are combined with a highly efficacious
Genetic validation of <em>Pf</em>FKBP35 as an antimalarial drug target (Publications)
Plasmodium falciparum accounts for the majority of over 600,000 malaria-associated deaths annually. Parasites resistant to nearly all antimalarials have emerged and the need for drugs with alternative modes [...] small molecules, a genetic validation of this factor as a drug target is missing and its function in parasite biology remains elusive. Here, we show that limiting PfFKBP35 levels are lethal to P. falciparum [...] with major implications for the development of FK506-derived molecules...
Global metabolic responses of NMRI mice to an experimental <em>Plasmodium berghei</em> infection (Publications)
disturbance of the gut microbial community caused by the parasite. Although several of the observed metabolic changes are also associated with other parasitic infections, the combination of metabolic changes and [...] Twelve female NMRI mice were infected intravenously with approximately 20 million P. berghei-parasitized erythrocytes. Urine and plasma samples were collected 4-6 h before infection, and at days 1, 2
2-Octadecynoic acid as a dual life stage inhibitor of <em>Plasmodium</em> infections and plasmodial FAS-II enzymes (Publications)
The malaria parasite Plasmodium goes through two life stages in the human host, a non-symptomatic liver stage (LS) followed by a blood stage with all clinical manifestation of the disease. In this study [...] stages. 2-Octadecynoic acid (2-ODA) was identified as the best inhibitor of Plasmodium berghei parasites with ten times higher potency (IC50=0.34µg/ml) than the control drug. In target determination studies [...] study identifies 2-ODA as the most promising antiparasitic 2-AFA, particularly...
A <em>var</em> gene promoter controls allelic exclusion of virulence genes in <em>Plasmodium falciparum</em> malaria (Publications)
used by many organisms to mediate phenotypic variation of surface proteins. In the apicomplexan parasite Plasmodium falciparum, responsible for the severe form of malaria in humans, this is exemplified [...] represents a major virulence factor due to its central role in immune evasion and intravascular parasite sequestration. Mutually exclusive expression of PfEMP1 is controlled by epigenetic mechanisms involving [...] for our understanding of antigenic variation in P. falciparum. Furthermore,...
Multiparasitism: a neglected reality on global, regional and local scale (Publications)
communities, particularly in tropical and subtropical areas. Intestinal parasites are the most numerous group, but an array of parasites is located elsewhere than in the human gastrointestinal tract. Although [...] villages highlight the significance of its evaluation for the design of locally adapted and sustainable parasite control and poverty alleviation programmes. We conclude by listing a set of research needs for future
Deoxyuridine triphosphate nucleotidohydrolase as a potential antiparasitic drug target (Publications)
small-molecule inhibitors of the enzyme deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) from parasitic protozoa. The successful synthesis of a variety of analogues of dUMP is described in which the [...] enzyme to give a measure of selectivity. The compounds were also tested in vitro against the intact parasites P. falciparum and L. donovani. A number of potent and selective inhibitors of the P. falciparum [...] determined. The correlation observed between the inhibition of the...
Assessment of dual life stage antiplasmodial activity of British seaweeds (Publications)
collected from the south coast of England against blood stage (BS) and liver stage (LS) Plasmodium parasites. The majority (14) of the extracts were active against BS of P. falciparum, with brown seaweeds [...] generally had high selectivity indices (> 10). Eight seaweed extracts inhibited the growth of LS parasites of P. berghei without any obvious effect on the viability of the human hepatoma (Huh7) cells, and [...] incurvus, all LS-active extracts showed dual activity versus both malarial...
High-throughput <em>Plasmodium falciparum hrp2</em> and <em>hrp3 </em>gene deletion typing by digital PCR to monitor malaria rapid diagnostic test... (Publications)
limit of detection was 0.33 parasites/microL. The deletion was reliably detected in mixed infections with wild-type and hrp2-deleted parasites at a density of > 100 parasites/reaction. For a side-by-side
Analysis of <em>Plasmodium falciparum</em> infections in a village community in Northern Nigeria: determination of msp2 genotypes and parasitespecific... (Publications)
sm (RFLP). 94.2% of all samples were parasite positive by PCR and over 80% of those had multiple infections. The age distribution of the average number of parasite clones present in P. falciparum infections [...] Mean multiplicity in those 8-10-year-old children was 5.4 clones per carrier. Peak multiplicity and parasite diversity in Nigerian individuals is compared to findings from other study sites in Africa and PNG
