title: Fosmidomycin, a novel chemotherapeutic agent for malaria.
abstract: In previous studies, fosmidomycin has been shown to possess activity against Plasmodium falciparum in vitro and in the mouse model. It has a novel mode of action through inhibition of 1-deoxy-D-xylulose 5-phosphate reductoisomerase, an enzyme of the nonmevalonate pathway of isoprenoid biosynthesis, which is absent in humans. In this open-label, uncontrolled trial, the efficacy and safety of fosmidomycin, in an oral dose of 1,200 mg every 8 h for 7 days, were evaluated in the treatment of acute uncomplicated Plasmodium falciparum malaria in 20 adult subjects in Gabon and Thailand. Clinical assessments were performed and thick blood smears were evaluated every 8 h until parasite clearance and resolution of symptoms were achieved; assessments continued at weekly intervals thereafter for the duration of the 28-day followup period. All subjects were clinically and parasitologically cured on day 7 (primary end point). Parasite and fever clearance were rapid, with means of 44 and 41 h, respectively. On day 28, seven out of nine subjects (78%) were cured in Gabon and two out of nine subjects (22%) were cured in Thailand. The drug was well tolerated, although mild gastrointestinal side effects were recorded for five subjects. Analysis of hematological and biochemical parameters showed no clinically significant changes throughout the study. Fosmidomycin is an effective and safe antimalarial drug, although its use as a single agent is restricted by the occurrence of recrudescent infections. However, its role in combination therapy should be explored.
authors.affiliation: Department of Parasitology, Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Lell
authors.forename: Ronnatrai
authors.initials: R
authors.lastname: Ruangweerayut
authors.forename: Jochen
authors.initials: J
authors.lastname: Wiesner
authors.forename: Michel Anoumou
authors.initials: MA
authors.lastname: Missinou
authors.forename: Andreas
authors.initials: A
authors.lastname: Schindler
authors.forename: Thomas
authors.initials: T
authors.lastname: Baranek
authors.forename: Martin
authors.initials: M
authors.lastname: Hintz
authors.forename: David
authors.initials: D
authors.lastname: Hutchinson
authors.forename: Hassan
authors.initials: H
authors.lastname: Jomaa
authors.forename: Peter Gottfried
authors.initials: PG
authors.lastname: Kremsner
mesh_terms: D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D023381:Endpoint Determination; D005260:Female; D005578:Fosfomycin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D005681:Gabon; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D010963:Plasmodium falciparum / Q000187:drug effects*; D013785:Thailand
chemical_list: D000962:Antimalarials; D005578:Fosfomycin; C024640:fosmidomycin