Introduction

The relationship between virulence and transmissibility is an important theme in analysis of host-parasite interactions in natural populations (Anderson and May 1991). However, there are few studies of the effects of parasite virulence on the population dynamics of major infectious diseases of humans. Data from the era of malaria therapy (James 1932, Covell 1951) and recent molecular studies (reviewed by Marsh 1992) indicate that there may be considerable variation in virulence within the Plasmodium falciparum parasite, which causes over 1 million malaria deaths each year. In this paper we explore the population dynamic and genetic implications of such proposed parasite diversity to ask whether they may explain some of the now well-defined epidemiological features of malarial disease.

In African children, amongst whom the great majority of malaria deaths occur, Plasmodium falciparum malaria can be clinically resolved into ‘mild’ and ‘severe’ types. This distinction describes a clear, and readily recognisable, clinical differentiation of malaria into a majority (about 99%) of uncomplicated cases with a very low mortality (« 1%), and a small number of severe cases with a mortality of 10-20% under treatment (Brewster 1990). Furthermore, severe malarial disease manifests as either severe malarial anaemia or cerebral malaria, both pathologically distinct from mild malaria. Hence, this classification is not just an arbitrary division of a continuum of disease severity, but reflects a clear bimodality in the severity of malarial disease.

There is strong evidence that host genetic susceptibility influences the clinical outcome of malarial infection; the immunological, nutritional and sociological status of the host may also be of varying degrees of importance (reviewed by Greenwood et al. (1991)).