COMMENTARY MALARIOLOGY Malaria
parasites go ape
previously identified P vivax CS proteins, but identical to the CS protein of another Toque monkey parasite, P simiovale? Is it really a new species? Why is the CS protein difference so important? The CS protein is the major surface protein of the sporozoite (the stage of the parasite inoculated by the mosquito) and has been studied extensively as a potential source of malaria vaccine antigens. The B-cell epitope consists of series of nine aminoacid repeats interspersed with polymorphic T-cell determinants. Until now two P vivax parasite types have been described on the basis of different CS repeat sequences,7,8 but there is no evidence yet that these CS protein differences have any functional significance. Geneticists will want to know more
There are four species of human malaria parasites in the genus Plasmodium.1 The potentially lethal P (Laverania) falciparum is thought to be a relatively recent evolutionary aquisition (perhaps within the past 10 000 years). It is genetically closest to the malarias of birds whereas the other about the ribosomal RNA genes of the different P vivax three human parasites-P vivax, P ovale, and P MMarKM— lie close to the simian malarias on the evolutionary tree.2 In types and P simiovale (ie, how close are these parasites fact P brasilianum, a common malaria of New World genetically?); taxonomists and parasitologists will need is P malariae after a few information on morphology and biology; and clinicians will hundred monkeys, probably years of simian adaptation. P malariae in turn may have originated ask whether there are any important clinical differences from a malaria of West African chimpanzees. In terms of between infections with the three P vivax types. P vivax small subunit ribosomal RNA gene sequence homology, from the island of New Guinea has long been known to be P vivax is closer to the Toque monkey parasite Pfragile than relatively primaquine resistant, and more recently has it is to P malariae or P ovale.2 These malaria parasites developed chloroquine resistance in some areas. Are these probably evolved alongside their primate hosts, with the drug sensitivity patterns related to CS protein type? Until tertian parasites originating some 30 million years ago when these questions are answered, all we have is a different the main simian groups separated.3 The tropical frequentprotein, and a close relation between one type of P vivax and P simiovale. Conclusion? There is considerable genotypic relapse strains of P vivax are thought to have originated in the forests of South-East Asia, possibly when our hominid and phenotypic variation within the P vivax species, but we do not have a fifth species of human malaria-yet. ancestors began to invade the forest environment and there acquired the parasites from other arboreal primates. Several N. J. White species of monkey malaria parasites can infect man and zoonoses may occur where man lives in proximity with 1. Garnham PCC. Malaria parasites and other haemosporidia. Oxford: monkeys1 (although they are unlikely to be diagnosed Blackwell, 1966. 2. Waters The Kra P knowlesi was once AP, Higgins DG, McCutchan T. Plasmodium falciparum appears monkey parasite correctly). to have arisen as a result of lateral transfer between avian and human used for the malariatherapy of neurosyphilis until repeated hosts. Proc Natl Acad Sci USA 1991; 88: 3140-44. passage made the strain so virulent it was abandoned. 3. Bruce-Chwatt LJ. History of malaria from prehistory to eradication. In: When, in 1917, the Viennese psychiatrist von WagnerWemsdorfer W, McGregor I, eds. Malaria: principles and practice of malariology. Edinburgh: Churchill Livingstone, 1988: 1-59. Jauregg began treating general paralysis of the insane by 4. von Wagner-Jauregg J. The treatment of general paresis by inoculation of he later won the Nobel malaria4 which (for Prize), inducing malaria. J Nerv Mental Dis 1922; 55: 369-75. malaria was common in North America, Europe, and across 5. Shute PG. Latency and long term relapses in benign tertian malaria. Russia.3 The predominant parasite in these cooler areas was Trans R Soc Trop Med Hyg 1946; 40: 189-200. 6. Kitchen SF. Vivax malaria. In: Boyd MF, ed. Malariology. Philadelphia: P vzvax, which can develop in the female anopheline Saunders, 1949. mosquito (sporogony) at temperatures down to 16°C, by 7. Arnot DE, Barnwell JW, Tam JP, Nussensweig V, Nussensweig R, Enea contrast, P falciparum prefers more tropical climates V. Circumsporozoite protein of Plasmodium vivax: gene cloning and (>20°C). The P vivax (hibemans) subspecies that caused characterization of the immunodominant epitope. Science 1985; 230: 815-16. these infections was splendidly adapted to cold climates; it 8. Hall T, Rosenberg R, Wirtz RZ, et al. Circumsporozoite protein of 9 had an incubation and a similar months, usually period heterogeneity in the human malaria parasite Plasmodium vivax. Science duration between relapses to coincide with the short 1989; 245: 973-76. summer mosquito-breeding seasons.l.6 At the other extreme lie the tropical (Chesson) strains of P vivax, in which about half the sporozoites inoculated by the feeding female anopheline mosquito develop immediately in the IMMUNOLOGY liver (incubation period 2 weeks to disease), and the other half lie dormant (hypnozoites), but awaken frequently such Immunosenescence and mucosal immunity that relapses occur at intervals of several months or less. The extensive malariatherapy experience also showed that there The immune system is probably the best understood of all were other differences between malaria parasites of the same bodily systems, both mechanistically and in terms of species but different geographic origins. Some strains age-related changes. The "immunogerontology" database of published work is immense and cluttered with conflicting required much higher doses of quinine to attenuate or cure the infections. Some were more virulent than others5.6 (the results. A common source of such cbnflict, especially in studies in man, has been the poor characterisation of normal European strains of P falciparum were notorious). Thus, there is considerable phenotypic variety within the species of subjects. Consequently, a group of European researchers human malaria parasites. proposed a set of inclusion criteria that are sufficiently So, what should we make of the report in this issue (p 780) stringent to eliminate the effects of disease and, at least in from Papua New Guinea of a "P vivax-like" human parasite theory, permit conclusions to be drawn about the effects of that is common and widely distributed with a ageing.1 These SENIEUR criteria have now been adopted circumsporozoite (CS) protein which is unlike the two widely.