The importance of strict patient definitions in studies of malaria pathogenesis [1]

Abstract

Most clinical studies of malariapathogenesis in humans are performed ascross-sectional studies comparing differentpatient categories. We have looked atstudies of similar clinical manifestations ofmalaria and found wide variation in theirconclusions. The differences could presenttrue geographical variation caused eitherby transmission pattern or by host andparasite genetics, or both. Anotherimportant reason for the variation is,however, ill-defined patient groups thathave not been designed specifically toaddress the questions raised by the studies.The bulk of evidence suggests that thedifferent complications of malaria differ inpathogenesis, management and prognosis.Malarial anaemia and cerebral malariaaffect different age groups of childrenexposed to different levels of malariatransmission1and are associated withdifferent cytokine profiles2. In fact,probably both malarial anaemia andcerebral malaria should be furthersubdivided into distinct entities3,4(B.A. Astrup et al., unpublished). We thuspropose that severe malaria should not bestudied as one disease entity, and thatcareful and uniform case definitions arecrucial for studies of malaria pathogenesis.It is also problematic to use so-called ‘mild’malaria as controls.