Short-course regimens of artesunate-fosmidomycin in treatment of uncomplicated Plasmodium falciparum malaria.
Fosmidomycin is effective against malaria, but it needs to be given for > or =4 days when used alone. We conducted a study of 50 children with Plasmodium falciparum malaria to evaluate the safety and efficacy of consecutively shortened regimens of artesunate-fosmidomycin (1 to 2 mg/kg of body weight and 30 mg/kg of body weight, respectively; doses given every 12 hours). All dosing regimens were well tolerated. Artesunate-fosmidomycin acted rapidly, resulting in consolidated geometric mean parasite and fever clearance times of 24 h and 15 h, respectively. Treatment regimens of > or =2 days led to cure ratios of 100% by day 14 (39/39; 95% confidence interval [95% CI], 91% to 100%). Most importantly, the 3-day regimen achieved 100% cure on day 28 (10/10; 95% CI, 69% to 100%). Treatment with artesunate-fosmidomycin was associated with transient grade I or II neutropenia (absolute neutrophil counts of 750 to 1,200/microl and 400 to 749/microl, respectively) in six or two patients, respectively. Artesunate-fosmidomycin demonstrates the feasibility and potential value of short-course artemisinin-based combination chemotherapy with rapidly eliminated combination partners.
Borrmann
Steffen
S
Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon.
Adegnika
Ayola A
AA
Moussavou
Félicien
F
Oyakhirome
Sunny
S
Esser
Gilbert
G
Matsiegui
Pierre-Blaise
PB
Ramharter
Michael
M
Lundgren
Ingrid
I
Kombila
Maryvonne
M
Issifou
Saadou
S
Hutchinson
David
D
Wiesner
Jochen
J
Jomaa
Hassan
H
Kremsner
Peter G
PG
D000962:Antimalarials / Q000009:adverse effects / Q000627:therapeutic use*; D037621:Artemisinins / Q000009:adverse effects / Q000627:therapeutic use*; D000077332:Artesunate; D002626:Chemistry, Pharmaceutical; D002648:Child; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D023381:Endpoint Determination; D005260:Female; D005578:Fosfomycin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012717:Sesquiterpenes / Q000009:adverse effects / Q000627:therapeutic use*
D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D012717:Sesquiterpenes; D005578:Fosfomycin; C024640:fosmidomycin; D000077332:Artesunate