Cerebral malaria: of mice and men

Chamarika J Weerasekera1,2, Nicholas J White2,3

  • 1Department of Parasitology, Faculty of Medical Sciences, University of Sri Jayewardenepura, Gangodawila, Nugegoda, Sri Lanka.

Abstract

Insights

The murine model for cerebral malaria poorly predicts effective treatments for humans. Most studies in mice do not follow guidelines, leading to unreliable results for human cerebral malaria therapies.

Area of Science:

  • * Malariology and tropical diseases research.
  • * Preclinical models for infectious diseases.

Background:

  • * Cerebral malaria is a severe complication of Plasmodium infection, causing significant mortality in endemic regions.
  • * The C57BL/6 mouse model infected with Plasmodium berghei ANKA is widely used but shows significant differences from human cerebral malaria.
  • * Guidelines recommend testing interventions in mice alongside antimalarials and after syndrome onset to better reflect human disease.

Purpose of the Study:

  • * To evaluate the utility of the murine model in predicting effective adjuvant therapies for human cerebral malaria.
  • * To assess adherence to 2012 consensus guidelines for murine cerebral malaria research.

Main Methods:

  • * Systematic review of publications on human and murine cerebral malaria research from 2010 onwards.
  • * Analysis of intervention testing methodologies in the murine model, including timing and concomitant treatments.

Main Results:

  • * Clinical research on human cerebral malaria has slowed, with no adjuvant interventions proving effective.
  • * 149 interventions evaluated in the mouse model since 2010 reported high success rates (95%).
  • * A significant majority of murine studies (74%) did not adhere to guidelines, with only 26% testing interventions after syndrome onset and 65% omitting concurrent antimalarial drugs.

Conclusions:

  • * The murine model for cerebral malaria has very limited predictive value for identifying successful adjuvant therapeutic interventions in humans.
  • * Non-adherence to established guidelines in murine studies contributes to the poor translation of findings to human cerebral malaria treatment.