title: A high-throughput screen targeting malaria transmission stages opens new avenues for drug development.
abstract: A major goal of the worldwide malaria eradication program is the reduction and eventual elimination of malaria transmission. All currently available antimalarial compounds were discovered on the basis of their activity against the asexually reproducing red blood cell stages of the parasite, which are responsible for the morbidity and mortality of human malaria. Resistance against these compounds is widespread, and there is an urgent need for novel approaches to reduce the emergence of resistance to new antimalarials as they are introduced. We have established and validated the first high-throughput assay targeting the red blood cell parasite stage required for transmission, the sexually reproducing gametocyte. This assay will permit identification of compounds specifically targeting the transmission stages in addition to the asexual stage parasites. Such stage-specific compounds may be used in a combination therapy, reducing the emergence of resistance by blocking transmission of resistant parasites that may be selected in a patient.
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Buchholz
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Burke
authors.forename: Kim C
authors.initials: KC
authors.lastname: Williamson
authors.forename: Roger C
authors.initials: RC
authors.lastname: Wiegand
authors.forename: Dyann F
authors.initials: DF
authors.lastname: Wirth
authors.forename: Matthias
authors.initials: M
authors.lastname: Marti
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004912:Erythrocytes; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology / Q000517:prevention & control / Q000635:transmission; D030781:Organisms, Genetically Modified; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D015203:Reproducibility of Results
chemical_list: D000962:Antimalarials