Artemether and artesunate show the highest efficacies in rescuing mice with late-stage cerebral malaria and rapidly...

Area of Science:

• * Parasitology
• * Neuroscience
• * Pharmacology

Background:

• * The murine model of experimental cerebral malaria (ECM) is crucial for understanding pathogenesis and developing therapeutics for human cerebral malaria.
• * Limited research has explored adjunctive therapies for ECM, necessitating the establishment of effective treatment protocols.
• * Defining rescue treatments for mice with late-stage ECM is a critical first step.

Purpose of the Study:

• * To evaluate the efficacy of artemisinin derivatives (artemether, artesunate) and quinine in treating Plasmodium berghei ANKA (PbA)-infected mice with moderate parasitemia and late-stage ECM.
• * To establish objective criteria for defining ECM in mice, including clinical signs, hypothermia, and motor behavior.
• * To provide a framework for future studies on adjunctive therapies for cerebral malaria.

Main Methods:

• * Assessed antimalarial efficacy of artemisinin, artemether, artesunate, and quinine, alone and with mefloquine, in suppressing PbA infection.
• * Evaluated rescue efficacy of artemether, artesunate, and quinine in PbA-infected mice with ECM, using strict clinical and neurological criteria.
• * Measured parasite clearance, survival rates, and brain leukocyte accumulation post-treatment.

Main Results:

• * Artemether demonstrated the fastest parasite killing (24h) and prevented recrudescence in a 5-day protocol.
• * Artemether (46% survival) and artesunate (43% survival) were effective in rescuing mice with late-stage ECM, while quinine showed poor efficacy (12.5% survival).
• * Artemether treatment significantly reduced brain leukocyte accumulation within 24 hours.

Conclusions:

• * Artemether and artesunate are effective rescue treatments for experimental cerebral malaria, improving survival rates.
• * These drugs also mitigate brain inflammation associated with ECM.
• * The established treatment protocols and clinical evaluation criteria facilitate future research into adjunctive therapies for cerebral malaria.