title: Inadequate efficacy of a new formulation of fosmidomycin-clindamycin combination in Mozambican children less than three years old with uncomplicated Plasmodium falciparum malaria.
abstract: The combination of fosmidomycin and clindamycin (F/C) is effective in adults and older children for the treatment of malaria and could be an important alternative to existing artemisinin-based combinations (ACTs) if proven to work in younger children. We conducted an open-label clinical trial to assess the efficacy, safety, and tolerability of F/C for the treatment of uncomplicated P. falciparum malaria in Mozambican children <3 years of age. Aqueous solutions of the drugs were given for 3 days, and the children were followed up for 28 days. The primary outcome was the PCR-corrected adequate clinical and parasitological response at day 28. Secondary outcomes included day 7 and 28 uncorrected cure rates and fever (FCT) and parasite (PCT) clearance times. Fifty-two children were recruited, but only 37 patients were evaluable for the primary outcome. Day 7 cure rates were high (94.6%; 35/37), but the day 28 PCR-corrected cure rate was 45.9% (17/37). The FCT was short (median, 12 h), but the PCT was longer (median, 72 h) than in previous studies. Tolerability was good, and most common adverse events were related to the recurrence of malaria. The poor efficacy observed for the F/C combination may be a consequence of the new formulations used, differential bioavailability in younger children, naturally occurring variations in parasite sensitivity to the drugs, or an insufficient enhancement of their effects by naturally acquired immunity in young children. Additional studies should be conducted to respond to the many uncertainties arising from this trial, which should not discourage further evaluation of this promising combination.
authors.affiliation: Barcelona Centre for International Health Research, CRESIB, Hospital Clínic Universitat de Barcelona, Barcelona, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Lanaspa
authors.forename: Cinta
authors.initials: C
authors.lastname: Moraleda
authors.forename: Sónia
authors.initials: S
authors.lastname: Machevo
authors.forename: Raquel
authors.initials: R
authors.lastname: González
authors.forename: Beatriz
authors.initials: B
authors.lastname: Serrano
authors.forename: Eusebio
authors.initials: E
authors.lastname: Macete
authors.forename: Pau
authors.initials: P
authors.lastname: Cisteró
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mayor
authors.forename: David
authors.initials: D
authors.lastname: Hutchinson
authors.forename: Peter G
authors.initials: PG
authors.lastname: Kremsner
authors.forename: Pedro
authors.initials: P
authors.lastname: Alonso
authors.forename: Clara
authors.initials: C
authors.lastname: Menéndez
authors.forename: Quique
authors.initials: Q
authors.lastname: Bassat
mesh_terms: D000962:Antimalarials / Q000008:administration & dosage / Q000627:therapeutic use*; D002675:Child, Preschool; D002981:Clindamycin / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000379:methods*; D005578:Fosfomycin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016778:Malaria, Falciparum / Q000188:drug therapy*
chemical_list: D000962:Antimalarials; D005578:Fosfomycin; D002981:Clindamycin; C024640:fosmidomycin