Relapse Mechanisms in Malaria: Emergence of Variant Strains of Plasmodium lophurae from Serum Antigen-Immunized Ducks

Abstract

By passing Plasmodium lophurae in serum antigen (SA)-immunized ducks and selecting the infections for subsequent passage that resisted the established immunity as indicated by rapidly rising parasitemia, a strain of P. lophurae was derived that was immunity resistant (IR). Selection of infections that had responded to immunity as indicated by low parasitemia and survival produced a strain that was immunity susceptible (IS). In nonimmunized ducks parasitemia and time of death indicated that the IR and IS strains were equally virulent, and that neither differed in virulence from the parent strain of P. lophurae. It would therefore appear that the IR and IS strains differed only in their response to serum antigen-induced immunity. The selection of the IR strain of P. lophurae may be indicative of the mechanisms whereby malaria may relapse from latent infection. Some of the outstanding features of the immunity to malaria are the frequent failure of an established immunity to protect all immunized animals from challenge, the failure of the immunity to prevent recrudescences of infection, and often the failure of immunity established by infection with one strain to afford protection against challenge with a different strain of the same species. Cox (1957, 1958) found that while mice with druginduced latent Plasmodium berghei infections were quite resistant to challenge with P. berghei, relapses of the latent infection were frequent, often as late as 3 or 4 months after the mice had recovered from the initial onset. Sadun et al. (1966) reported that serum globulins of Africans from areas of endemic Plasmodium falciparum infections protected chimpanzees from a West African strain of P. falciparum but did not protect them from a strain from Southeast Asia; and the reverse, human globulin of Southeast Asia afforded protection against Asian P. falciparum, but not against the African strain. Thus it would Received for publication 25 November 1969. * Research Associate, Australian Meat Research Committee, Sydney, Australia. This research was supported in part by Grant No. AI08508-01 from NIAID, NIH, by Contract No. DADA-17-67-C-0031 from the U. S. Army Medical Research and Development Command, and by grants from the Michigan Agricultural Experiment Station. This manuscript is contribution No. 730 in the U. S. Army Malaria Research Program and Article No. 4894 for the Michigan Agricultural Experiment Station. appear that in addition to being poorly immunogenic, Plasmodium parasites mediate immunity that is speciesand strain-specific. In contrast, reports on immunity in experimental malaria indicate a nonspecific immunity to reinfection. Nussenweig et al. (1966) found that in mice recovering from Plasmodium chabaudi infection, resistance was conferred to challenge with Plasmodium vinckei. The lack of specificity in mice immunized with P. chabaudi infection was confirmed, and extended when it was found that this immunity was effective against challenge of Babesia rodhaini (Cox and Milar, 1968). The interspecies and intergeneric nature of immunity established by acute hemosporidian infections was confirmed by F.E.G. Cox (1968). It has since been established that this nonspecific immunity is undoubtedly mediated by antigens which are present in the serum of animals with acute hemosporidian infections (Corwin et al., 1965; Cox, 1966; Sibinovic et al., 1967a, b, 1969; Ferris et al., 1968; Cox et al., 1968; Corwin and Cox, 1969). In experiments of Corwin and Cox (1969), a proportion of the ducklings given serum antigens (SA) from ducks with acute Plasmodium lophurae or Plasmodium spartani,' SA from hens with acute Plasmodium gallinaceum or SA from rats with acute B. rodhaini infections did not survive challenge with P. lophurae. Parasitemia and time of death after challenge in the nonsurviving immunized ducks 1Plasmodium spartani was previously described by Corwin and Cox (1969).