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.

Short report: evaluation of a simple and inexpensive photometric device for the measurement of hemoglobin.

We have evaluated the accuracy of a simple and inexpensive photometric device (DHT) for the estimation of the blood concentration of hemoglobin by comparison with an automated, high-resolution, flow cytometry-based hematology analyzer (CellDyn 3000) and a centrifugal quantitative buffy coat hematology system (QBC I). We have analyzed the hemoglobin values of 163 individual blood samples. Bland-Altman analysis showed that the methods agreed only poorly: mean differences were 1.0 g/dL with limits of agreement (LOA) of -1.2 g/dL to 3.2 g/dL for the comparison of DHT and CellDyn measurements, 0.5 g/dL with LOA of -2.0 g/dL to 3.0 g/dL for the comparison of DHT with QBC measurements, and 0.5 g/dL with LOA of -1.1 g/dL to 2.1 g/dL for the comparison of QBC with CellDyn measurements. We conclude that the poor agreement of the DHT with the CellDyn does not permit the use of the DHT for critical hemoglobin measurements, particularly in transfusion services.

Fosmidomycin-clindamycin for the treatment of Plasmodium falciparum malaria.

It has been demonstrated that fosmidomycin has good tolerability and rapid onset of action, but late recrudescences preclude its use alone; in vitro, clindamycin has been shown to act synergistically with fosmidomycin against Plasmodium falciparum. We conducted a study in pediatric outpatients with P. falciparum malaria in Gabon to evaluate the efficacy and safety of an oral combination of fosmidomycin-clindamycin of 30 mg/kg and 10 mg/kg of body weight, respectively, every 12 h. Patients 7-14 years old were recruited in cohorts of 10. The first 10 patients were treated for 5 days. The duration of treatment was then incrementally shortened in intervals of 1 day if >85% of the patients in a cohort were cured by day 14. All dosing regimens were well tolerated, and no serious adverse events occurred. Asexual parasites and fever rapidly cleared in all patients. Cure ratios of 100% on day 14 were achieved with treatment durations of 5 (10/10 patients), 4 (10/10 patients), 3 (10/10 patients), and 2 days (10/10 patients); 1 day of treatment led to a cure ratio of 50% (5/10 patients). Fosmidomycin-clindamycin is safe and well tolerated, and short-course regimens achieved high efficacy in children with P. falciparum malaria. Fosmidomycin-clindamycin is a promising novel treatment option for malaria.