10 Jun 04

Researchers in Zoology have discovered more about how malaria manages to stay in the body for so long – and paradoxically, the key is the body's own immune response, according to their paper in Nature.

An antigen is a substance which elicits a specific immune response. When an individual is infected with malaria, their blood is flooded with malaria parasites, and each of these parasites gives away its presence by displaying certain 'flags' on the infected red blood cell – the antigen – which alerts the host to infection and activates the immune response.

It has long been known that antigenic variation – changing these flags over the time course of an infection – plays a part in how malaria manages to avoid being eliminated by the immune response. Antigenic variation is a survival mechanism which involves the pathogen having a large variety of antigens, so that homing in on one alone is not enough for the immune system to halt the disease.

Malaria has about 50 antigen variants, and one variant is dominant at any one time. The fact that the variants 'show themselves' one by one, rather than all at the same time, greatly prolongs malaria infection. The puzzle was how the trillions of pathogens which invade the body of a malaria patient manage to co-ordinate, so that they all display one variant at any one time.

Now, Sunetra Gupta and Mario Recker believe they have worked out the answer using mathematical modelling. Any one variant has a number of component parts, some of which will be shared by other variants, and the immune system responses to each component individually. Any variants that share one or more of the component parts of the first variant will hence be suppressed as well. A variant with none of those component parts can thus rise up without opposition. The immune system responds to this new variant, and any other variants which share component parts with it; in turn another variant which shares none of those parts will rise, and so on. This sequential, rather than simultaneous, rising up of the variants greatly prolongs the duration of malaria.

Dr Recker said: 'It is interesting that the immune response itself provides this orchestration which allows the pathogen to stay in the body for so long. It means that, ironically, individuals with stronger cross-reactive immune responses are more likely to become chronically infected – though they are less likely to die from the disease.'