Cross-species Immunity in Malaria

Abstract

In their interesting paper on apparent interactions between Plasmodium vivax and P. falciparum, Maitland et al.[1xMaitland, K.A. et al. Parasitol. Today. 1997; 13: 227–231Abstract | Full Text PDF | PubMed | Scopus (93)See all References][1] refer to the possibility of cross-immunity between species, but, in my view, fail to distinguish clearly between the involvement of non-specific and specific factors. The consequences of infection by more than one species of malaria on mosquito transmission were also not mentioned, but may be important in understanding these parasite–parasite interactions.While the authors point out that antitoxic (antidisease) immunity is not species specific, there is also evidence for non-specific antiparasite resistance to blood-stages, generated during infection. For example, sera from acutely infected mice will inhibit P. falciparum growth in vitro[2xButcher, G.A. and Clark, I.A. Parasitology. 1990; 98: 321–326CrossrefSee all References][2], and high infective doses of P. knowlesi were shown to damage P. cynomolgi parasites in vivo[3xButcher, G.A. et al. Immunology. 1978; 34: 77–86PubMedSee all References][3]. While these rather dramatic effects may be short-lived, it is conceivable that some longer-term subtle non-specific inhibition by blood-stage parasites of liver-stage development of a second parasite might occur. The presence of parasites in even asymptomatic carriers is associated with raised CRP levels[4xNaik, P. and Voller, A. Trans. R. Soc. Trop. Med. Hyg. 1984; 78: 812–813PubMed | Scopus (28)See all References][4] (indicating non-specific factors are operating), for example. Furthermore, a more prolonged non-specific resistance may result from splenic enlargement caused by one parasite inhibiting replication of a second parasite[5xRichie, T.L. Parasitology. 1988; 96: 607–639Crossref | PubMedSee all References][5]. This antiparasite resistance has, of course, to be balanced against the possible immunosuppressive effects of a chronic infection.With regard to long-term acquired (antibody-mediated) immunity to blood-stage malaria, although this seems to be largely strain- and even variant-specific, it would not be surprising to find common antigens and therefore a degree of crossresistance between different strains of parasites such as P. cynomolgi bastianelli and P. cynomolgi cynomolgi, as mentioned by Maitland et al.[1xMaitland, K.A. et al. Parasitol. Today. 1997; 13: 227–231Abstract | Full Text PDF | PubMed | Scopus (93)See all References][1] However, heterologous immunity between species infecting a common host is generally not observed[5xRichie, T.L. Parasitology. 1988; 96: 607–639Crossref | PubMedSee all References][5]. As Richie has argued convincingly[5xRichie, T.L. Parasitology. 1988; 96: 607–639Crossref | PubMedSee all References][5], it is unlikely that parasites sharing the same host would share common protective antigens, as the acquisition of immunity to one would hazard the survival of subsequent infecting species. Parasites inhabiting a common host thus probably tend to diverge antigenically and long-term immunity is largely species specific.Nevertheless, there are many observations showing that infection by more than one parasite is not uncommon and that different Plasmodium species may `take it in turns', by whatever mechanisms, to predominate in the blood of the host[5xRichie, T.L. Parasitology. 1988; 96: 607–639Crossref | PubMedSee all References][5]. It is tempting to speculate that they have evolved to take advantage of this situation through enhanced transmission. Increased infectivity of one parasite caused by the presence of a preceding infection of another parasite has been shown in simian malaria[6xCollins, W.E. et al. J. Parasitol. 1975; 61: 718–721Crossref | PubMedSee all References, 7xArrada-Meyer, M.de et al. Am. J. Hyg. Trop. Med. 1979; 28: 627–633PubMedSee all References] and with P. vivax and P. falciparum in Aotus monkeys[7xArrada-Meyer, M.de et al. Am. J. Hyg. Trop. Med. 1979; 28: 627–633PubMedSee all References][7]. A further consideration is that recrudescent parasites (following subcurative treatment) appear to generate greater numbers of gametocytes than first infections[8xShute, P.G. and Maryon, M. Trans. R. Soc. Trop. Med. Hyg. 1951; 44: 421–438PubMed | Scopus (35)See all References, 9xBuckling, A.G.L. Proc. R. Soc. London Ser. B. 1997; 264: 553–559Crossref | PubMedSee all References]. Thus, interactions between different parasites, in which suppression alternates with recrudescence, may, for a limited period, provide conditions in which each parasite has an opportunity to generate new waves of gametocytes. It is almost as if each parasite species temporarily (until immunity causes it to decline) inhibits others, rather in the manner that plant species in the same habitat generate toxins for other competing species, but both have their chances of transmission enhanced by the other.More study of natural infections in non-human hosts, as I have suggested elsewhere[10xButcher, G.A. Parasitol. Today. 1996; 12: 378–382Abstract | Full Text PDF | PubMed | Scopus (13)See all References][10], might help us to find the answer to these intriguing questions.