The murine model of cerebral malaria (ECM) caused by Plasmodium berghei ANKA (PbA) infection in susceptible mice has been extensively used for studies of pathogenesis and identification of potential targets for human CM therapeutics. However, the model has been seldom explored to evaluate adjunctive therapies for this malaria complication. A first step toward this goal is to define a treatment protocol with an effective antimalarial drug able to rescue mice presenting late-stage ECM. We evaluated the efficacy of artemisinin, artemether, artesunate, and quinine given intraperitoneally once a day, and combinations with mefloquine, in suppressing PbA infection in mice with moderate parasitemia. Artemether, artesunate, and quinine were then evaluated for efficacy in rescuing PbA-infected mice with ECM, strictly defined by using objective criteria based on the presentation of clinical signs of neurological involvement, degree of hypothermia, and performance in a set of six motor behavior tests. Artemether at 25 mg/kg presented the fastest parasite killing ability in 24 h and fully avoided recrudescence in a 5-day treatment protocol. Artemether and artesunate were equally effective in rescuing mice with late-stage ECM (46 and 43% survival, respectively), whereas quinine had a poor performance (12.5% survival). Artemether caused a marked decrease in brain leukocyte accumulation 24 h after the first dose. In conclusion, artemether and artesunate are effective in rescuing mice with late-stage ECM and decrease brain inflammation. In addition, the described protocols for more strict clinical evaluation and for rescue treatment provide a framework for studies of CM adjunctive therapies using this mouse model.

Over 20 species of Angiostrongylus have been described from around the world, but only Angiostrongylus cantonensis has been confirmed to cause central nervous system disease in humans. A neurotropic parasite that matures in the pulmonary arteries of rats, A. cantonensis is the most common cause of eosinophilic meningitis in southern Asia and the Pacific and Caribbean islands. The parasite can also cause encephalitis/encephalomyelitis and rarely ocular angiostrongyliasis. The present paper reviews the life cycle, epidemiology, pathogenesis, clinical features, diagnosis, treatment, prevention and prognosis of A. cantonesis infection. Emphasis is given on the spectrum of central nervous system manifestations and disease pathogenesis.