We have investigated the expression of a strain-specific malarial antigen on the surface of erythrocytes infected with knobless (K-) variants of knob-positive (K+) strains of Plasmodium falciparum. Aotus blood infected with K+ or K- parasites derived from two independent geographical isolates (Malayan camp and Santa Lucia) was surface iodinated by the lactoperoxidase method. Infected and uninfected erythrocytes were then separated by a new procedure involving equilibrium density sedimentation on a Percoll gradient containing sorbitol. Strain-specific antigens were readily identified on the surface of erythrocytes infected with either of the K+ strains by their characteristic size and detergent solubility. These proteins were not detected on the surface of erythrocytes infected with either of the K- variants nor on uninfected erythrocytes isolated from K+- or K- -infected blood. These results are consistent with a role for the strain-specific surface antigen in cytoadherence of P. falciparum-infected erythrocytes. Our findings represent the second biochemical difference (with the knob-associated histidine-rich protein) between K+ and K- P. falciparum.
Three persons were experimentally inoculated with malaria by means of Anopheles ludlowi reared from larvae and infected with a pure strain of subtertian plasmodium (Plasmodium falciparum), thus proving that there exists no mechanical impediment or obstacle to the free exit of sporozoites from the salivary ducts or proboscis. In the dissection of infected mosquitoes there were no evidences of degenerated zygotes. Sporozoites appeared promptly in the salivary glands (9 to 12 days). Inoculation occurred with ease either in an interrupted feeding or after mosquitoes had been fed twice previously. The period of incubation was 14 and 18 days. The clinical manifestations were more severe in the subject that had never been infected with malaria previously, while the splenic enlargement was most pronounced in the subject infected after a long interval of freedom from malaria. In a third subject already suffering from tertian malaria there was only the slightest evidence of physical illness elicited by the superimposed subtertian infection; his temperature, however, became duly elevated. The type of febrile reaction in the two uncomplicated cases was at first tertian, becoming quotidian later, and this phenomenon in a pure strain leads strongly to the supposition that Plasmodium falciparum possesses inherently both tertian (or subtertian) and quotidian tendencies, as well as its well known tendencies to cause fever of the irregularly remittent or continued type. The creation of a specific plasmodium to account for clinical forms of aestivo-autumnal or subtertian malaria having a quotidian periodidty is probably unwarranted. In consideration of the facility with which this species can be infected and man inoculated experimentally, the occurrence of naturally infected wild specimens, and the positive epidemiological evidence, there should no longer exist in the minds of sanitarians any doubt as to its being a malarial carrier. Operations against this species can therefore be recommended without reservation and should be carried out without delay.
Purified schizonts (6--10 nuclei) and membranes of schizont-infected erythrocytes from the Malaysian and Philippine strain of Plasmodium knowlesi are analyzed immunochemically using immunoglobulin of rhesus monkey hyperimmune sera against schizonts and of sera from naturally immune monkeys. The anti-schizont Ig identifies less than 20 immune components in Triton X-100-solubilized schizonts and membranes of infected cells. Of these antigens, 9 (component 1, 3, 4, 5, 6, 10, 11, 18, and 20) are common to parasites and membranes of infected erythrocytes, and 12 (2A,B, 6, 8, 9, 12, 13p, 14, 16A,B, 19 A,Bp, 21, 22p, and 23) are predominantly found in the parasite; 4 components (13i, 19A,Bi, 22A, B, and 24) are unique to the membrane of infected erythrocytes. Only three parasite-specific components (1, 13, and 19) are exposed on the surface of parasitized erythrocytes as revealed by both lactoperoxidase-catalyzed radioiodination and extensive absorption of anti-schizont Ig using intact infected erythrocytes. Two plasmodium-specific antigens (1 and 13) on the surface of infected erythrocytes are recognized by sera of rhesus monkeys rendered naturally immune against P. knowlesi infections and, therefore, represent antigens in vivo. Analyses of schizonts and membranes of parasitized erythrocytes of the two different strains of P. knowlesi yields only some minor quantitative, but no qualitative differences when analyzed with both types of antisera. Importantly, components 1 and 13 appear identical in both strains.