title: Fosmidomycin as an antimalarial drug: a meta-analysis of clinical trials.
abstract: With first indications of resistance against artemisinin compounds, the development of novel alternative antimalarials remains an urgent need. One candidate is fosmidomycin (Fos), a phosphonic acid derivative. This PRISMA guideline-adhering and PROSPERO-registered systematic review and meta-analysis provides an overview of the state-of-the-art of the clinical development of Fos as an antimalarial. Pooling six clinical trials of Fos against uncomplicated malaria in African children yielded an overall day 28 cure rate of 85% (95% CI: 71-98%); a parasite clearance time of 39 h; and a fever clearance time of 30 h. In four adult cohorts, the corresponding values were 70% (95% CI: 40-100%), 49 and 42 h, respectively. Data suggest that besides the partner drug, formulation determines efficacy. We advocate further clinical development of Fos-combinations. PROSPERO registration number: CRD42014013688.
authors.affiliation: Institut für Tropenmedizin, University of Tübingen, Wilhelmstraße 27, D-72074 Tübingen, Germany.|Centre de Recherches Médicales de Lambaréné (CERMEL), Albert Schweitzer Hospital, BP 118 Lambaréné, Gabon.|Center of Tropical Medicine & Travel Medicine, Department of Infectious Diseases, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Jose Francisco
authors.initials: JF
authors.lastname: Fernandes
authors.affiliation: Institut für Tropenmedizin, University of Tübingen, Wilhelmstraße 27, D-72074 Tübingen, Germany.|Centre de Recherches Médicales de Lambaréné (CERMEL), Albert Schweitzer Hospital, BP 118 Lambaréné, Gabon.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Lell
authors.affiliation: Institut für Tropenmedizin, University of Tübingen, Wilhelmstraße 27, D-72074 Tübingen, Germany.|Centre de Recherches Médicales de Lambaréné (CERMEL), Albert Schweitzer Hospital, BP 118 Lambaréné, Gabon.
authors.forename: Selidji Todagbe
authors.initials: ST
authors.lastname: Agnandji
authors.affiliation: Centre de Recherches Médicales de Lambaréné (CERMEL), Albert Schweitzer Hospital, BP 118 Lambaréné, Gabon.
authors.forename: Regis Maurin
authors.initials: RM
authors.lastname: Obiang
authors.affiliation: Barcelona Center for International Health Research (CRESIB, Hospital Clíníc-Universitat de Barcelona), Barcelona, Spain.|Centro de investigação em saúde de Manhiça (CISM), Maputo, Mozambique.
authors.forename: Quique
authors.initials: Q
authors.lastname: Bassat
authors.affiliation: Institut für Tropenmedizin, University of Tübingen, Wilhelmstraße 27, D-72074 Tübingen, Germany.|Centre de Recherches Médicales de Lambaréné (CERMEL), Albert Schweitzer Hospital, BP 118 Lambaréné, Gabon.
authors.forename: Peter Gottfried
authors.initials: PG
authors.lastname: Kremsner
authors.affiliation: Institut für Tropenmedizin, University of Tübingen, Wilhelmstraße 27, D-72074 Tübingen, Germany.|Centre de Recherches Médicales de Lambaréné (CERMEL), Albert Schweitzer Hospital, BP 118 Lambaréné, Gabon.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Mordmüller
authors.affiliation: Institut für Tropenmedizin, University of Tübingen, Wilhelmstraße 27, D-72074 Tübingen, Germany.|Centre de Recherches Médicales de Lambaréné (CERMEL), Albert Schweitzer Hospital, BP 118 Lambaréné, Gabon.|Center of Tropical Medicine & Travel Medicine, Department of Infectious Diseases, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Martin Peter
authors.initials: MP
authors.lastname: Grobusch
mesh_terms: D000328:Adult; D000962:Antimalarials / Q000494:pharmacology / Q000592:standards / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D005578:Fosfomycin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects
chemical_list: D000962:Antimalarials; D005578:Fosfomycin; C024640:fosmidomycin
keywords: DOXP reducto-isomerase; antimalarial drug; clinical studies; drug development; fosmidomycin; fosmidomycin-clindamycin; malaria