Does malaria suffer from lack of memory?

It is widely perceived that immunity to malaria is, to an extent, defective and that one component of this defective immune response is the inability to induce or maintain long-term memory responses. If true, this is likely to pose problems for development of an effective vaccine against malaria. In this article, we critically review and challenge this interpretation of the epidemiological and experimental evidence. While evasion and modulation of host immune responses clearly occurs and naturally acquired immunity is far from optimal, mechanisms to control blood-stage parasites are acquired and maintained by individuals living in endemic areas, allowing parasite density to be kept below the threshold for induction of acute disease. Furthermore, protective immunity to severe pathology is achieved relatively rapidly and is maintained in the absence of boosting by re-infection. Nevertheless, there are significant challenges to overcome. The need for multiple infections to acquire immunity means that young children remain at risk of infection for far too long. Persistent or frequent exposure to antigen seems to be required to maintain anti-parasite immunity (premunition). Lastly, pre-erythrocytic and sexual stages of the life cycle are poorly immunogenic, and there is little evidence of effective pre-erythrocytic or transmission-blocking immunity at the population level. While these problems might theoretically be due to defective immunological memory, we suggest alternative explanations. Moreover, we question the extent to which these problems are malaria-specific rather than generic (i.e. result from inherent limitations of the vertebrate immune system).