arteflene and Malaria--Falciparum

Arteflene is a synthetic peroxide recently developed from an indication of antimalarial activity found in the Chinese plant Artabotrys uncinatus. The new antimalarial was compared against mefloquine in a phase 3, open-labeled, randomized trial in children with uncomplicated Plasmodium falciparum malaria in Gabon. Patients received single oral doses of either 25 mg/kg of arteflene suspension or 15 mg/kg of mefloquine tablets. High-grade (RII and RIII) resistance was observed in eight (40%) of the 20 patients receiving the single dose of arteflene, but in none of the 21 mefloquine-treated patients (P < 0.005). At day 28, only one patient in the arteflene group, compared with all 21 patients in the mefloquine group, was cured (P < 0.001). Arteflene cleared fever slightly but not significantly faster than mefloquine and the 50% and 90% parasite clearance times were comparable in both treatment groups. In vitro results in the arteflene group suggest an increase of arteflene resistance when comparing sensitivity of paired parasite isolates before treatment and at recrudescence. Both treatment regimens were well-tolerated. In conclusion, single dose monotherapy with arteflene was not effective in curing children suffering from uncomplicated P. falciparum malaria in Gabon, while mefloquine proved to be highly effective for this purpose.

Topics: Adolescent; Antimalarials; Artemisinins; Bridged Bicyclo Compounds, Heterocyclic; Child; Humans; Malaria, Falciparum; Mefloquine; Styrenes

An open, non-comparative clinical trial was carried out in Nigeria and Burkina Faso to investigate the safety and efficacy of the novel antimalarial arteflene in patients with mild malaria. Patients were males aged 12 to 16 years, with a Plasmodium falciparum count of 10(4) to 10(5) parasites/microliters and a body temperature of 37.5 to 38.5 degrees C. Twenty-three patients received a single dose of Ro 42-1611 (arteflene), corresponding to 25 +/- 2.5 mg/kg bodyweight. Nineteen patients were evaluable for standard efficacy. Efficacy was assessed at 6, 9, 12, 24, 36, 48 and 72 hours, and at seven days, by: reduction in parasitaemia and time to parasite clearance; resolution of fever; and clinical cure (defined as the absence of signs and symptoms of malaria). Adverse events were reported at each assessment point, and laboratory tests were carried out at baseline and at 2 and 7 days. The parasite count was reduced by 50% or more in 89.5% of patients after 48 hours, and 52.6% were completely free of parasites at the same time. Normal temperature was achieved in 89.5% of patients and clinical cure in 75%, after 48 hours. One patient reported mild vertigo and mild pruritus. The lower than expected effect was thought to be due to inadequate storage of the arteflene suspension. There were no withdrawals due to adverse events and no deaths. A single dose of 25 mg/kg arteflene was found to be an effective and well-tolerated treatment for mild P. falciparum malaria.

Topics: Adolescent; Antimalarials; Artemisinins; Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Burkina Faso; Child; Humans; Malaria, Falciparum; Male; Nigeria; Styrenes; Time Factors

The novel antimalarial Ro 42-1611 (arteflene) was evaluated for safety and efficacy in an open, non-comparative study of patients with mild malaria in the south of Cameroon. Thirty male patients aged 12 to 42 years, with an initial Plasmodium falciparum count of > 5000 (mean: 21,406) parasites/microliters and a body temperature of 37.7% to 39.8 degrees C, were selected to receive a single dose of arteflene, corresponding to 25 +/- 2.5 mg/kg bodyweight. Efficacy was assessed at 6, 9, 12, 24, 36, 48 and 72 hours, and at seven days by: reduction in parasitaemia and time to parasite clearance; resolution of fever and clinical cure (defined as the absence of signs and symptoms of malaria). Adverse events were reported at baseline and at each assessment point, and laboratory tests were carried out at 2 and 7 days. The mean number of parasites/microliter fell from 21,406 at baseline to 157 after 48 hours, at which point 80% of patients were completely free of parasites. Mean body temperature was reduced from 38.9 degrees C at baseline to 37.3 degrees C 12 hours after arteflene administration, and by this time 80% of patients had a normal temperature. Clinical cure rates were also high, with 70% of patients free of all signs and symptoms after 24 hours. However, by day 7, 6/30 (20%) presented with smears positive for P. falciparum. There were no adverse events considered to be related to treatment. A single dose of 25 mg/kg arteflene was found to be an effective and well-tolerated treatment for mild P. falciparum malaria.

Topics: Adolescent; Adult; Antimalarials; Artemisinins; Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Cameroon; Child; Fever; Humans; Malaria, Falciparum; Male; Styrenes; Time Factors

The purpose of this study was to investigate the ability of the antimalarial drug, Ro 42-1611 to block parasite mediated cytokine induction in vitro as well as cytoadherence of infected erythrocytes to melanoma cells in vitro. The biological activity of Ro 42-1611 was confirmed as it blocked Plasmodium falciparum growth in cultures. Ro 42-1611, had no major effect on TNF, IL-alpha or IL-6 cytokine release from mononuclear cells stimulated with malaria antigens or lipopolysaccharide and it did not affect cell viability. Ro 42-1611 only slightly suppressed cytoadherence of infected erythrocytes to melanoma cells. The therapeutic effect of To 42-1611 appears to be confined to its parasite killing activity.

Topics: Adult; Animals; Antigens, Protozoan; Antimalarials; Artemisinins; Bridged Bicyclo Compounds, Heterocyclic; Cell Adhesion; Cell Survival; Chloroquine; Cytokines; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Erythrocytes; Humans; Immunoglobulin G; Interleukin-1; Interleukin-6; Lipopolysaccharides; Lymphocytes; Malaria, Falciparum; Mefloquine; Melanoma; Plasmodium falciparum; Styrenes; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha