In many infectious diseases, there are clinically important distinctions to be made between different manifestations associated with the same underlying pathogen and malaria clinical syndromes are a clear case in point. The pathogenesis of malaria due to its erythrocytic cycle occurs in the cardiovascular system and it is plausible that proteome changes in organs such as brain, spleen, kidney and bone marrow can be reflected in the plasma proteome. Our study confirms that there are proteome changes characteristic of the clinical malarial syndromes with different level of accuracy. Furthermore, host modulation by the pathogen is likely to generate changing patterns of protein expression associated with the progression of severe malaria syndromes and our current studies are designed to address such changes.