The molecular basis of paediatric malarial disease

  • Ian A. Clark
  • Michael J. Griffiths
Part of the Birkhäuser Advances in Infectious Diseases book series (BAID)


Severe falciparum malaria is an acute systemic disease that can affect multiple organs, including those in which few parasites are found. The acute disease bears many similarities both clinically and, potentially, mechanistically, to the systemic diseases caused by bacteria, rickettsia, and viruses. Traditionally the morbidity and mortality associated with severe malarial disease has been explained in terms of mechanical obstruction to vascular flow by adherence to endothelium (termed sequestration) of erythrocytes containing mature-stage parasites. However, over the past few decades an alternative ‘cytokine theory of disease’ has also evolved, where malarial pathology is explained in terms of a balance between the pro- and anti-inflammatory cytokines. The final common pathway for this pro-inflammatory imbalance is believed to be a limitation in the supply and mitochondrial utilisation of energy to cells. Different patterns of ensuing energy depletion (both temporal and spatial) throughout the cells in the body present as different clinical syndromes. This chapter draws attention to the over-arching position that inflammatory cytokines are beginning to occupy in the pathogenesis of acute malaria and other acute infections. The influence of inflammatory cytokines on cellular function offers a molecular framework to explain the multiple clinical syndromes that are observed during acute malarial illness, and provides a fresh avenue of investigation for adjunct therapies to ameliorate the malarial disease process.


Falciparum Malaria Severe Malaria Cerebral Malaria Ethyl Pyruvate Plasmodium Falciparum Malaria 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Birkhäuser Verlag Basel/Switzerland 2007

Authors and Affiliations

  • Ian A. Clark
    • 1
  • Michael J. Griffiths
    • 2
  1. 1.School of Biochemistry and Molecular BiologyAustralian National UniversityCanberraAustralia
  2. 2.Department of PaediatricsNewcastle General HospitalNewcastle upon TyneUK

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