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https://www.arca.fiocruz.br/handle/icict/36881
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ArticleCopyright
Open access
Embargo date
2020-11-06
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- INI - Artigos de Periódicos [3488]
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ARTEMETHER AND ARTESUNATE SHOW THE HIGHEST EFFICACIES IN RESCUING MICE WITH LATE-STAGE CEREBRAL MALARIA AND RAPIDLY DECREASE LEUKOCYTE ACCUMULATION IN THE BRAIN
Affilliation
La Jolla Bioengineering Institute. San Diego, CA, USA.
La Jolla Bioengineering Institute. San Diego, CA, USA.
La Jolla Bioengineering Institute. San Diego, CA, USA / Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.
La Jolla Bioengineering Institute. San Diego, CA, USA.
La Jolla Bioengineering Institute. San Diego, CA, USA.
La Jolla Bioengineering Institute. San Diego, CA, USA.
La Jolla Bioengineering Institute. San Diego, CA, USA / Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.
La Jolla Bioengineering Institute. San Diego, CA, USA.
La Jolla Bioengineering Institute. San Diego, CA, USA.
Abstract
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.
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