Anemia is a common and serious complication of malaria due to Plasmodium falciparum infection, a major health problem in tropical areas. Herein, the relation was investigated between the levels of circulating erythropoietin (EPO) and immunomodulatory cytokines in response to chloroquine treatment. Thirty-seven healthy control subjects and 40 patients with acute P. falciparum infection were included in the study. All subjects were adult male Sudanese. Blood samples were collected before chloroquine administration (25 mg/kg body weight, orally on three consecutive days) and 3 and 30 days after start of the therapy. Measurements included routine hematological parameters and the concentrations of immunoreactive EPO, tumor necrosis factor-alpha (TNF-alpha), interleukin 1alpha (IL-1), IL-6, and interferon gamma (INF-gamma). Chloroquine treatment led to a decrease in EPO levels in the control subjects but an increase in malaria patients at day 30. The latter was likely due to the anti-inflammatory action of the drug because INF-gamma, IL-1, and IL-6 concentrations declined on chloroquine treatment. Based on these findings, the authors propose that an impaired EPO production in association with a prolonged elevation of certain inflammatory cytokines can contribute to the anemia in some malaria patients which can be reversed by chloroquine therapy.

Ferroquine (FQ or SR97193) is a novel antimalarial drug candidate, currently in development at Sanofi-Aventis. In contrast to conventional drugs, FQ is the first organometallic drug: a ferrocenyl group covalently flanked by a 4-aminoquinoline and a basic alkylamine. FQ is able to overcome the CQ resistance problem, an important limit to the control of Plasmodium falciparum, the principal causative agent of malaria. After fifteen years of effort, it is now possible to propose a multifactorial mechanism of action of FQ by its capacity to target lipids, to inhibit the formation of hemozoin and to generate reactive oxygen species.