THE INTENSIVE TREATMENT OF SYPHILIS

develop a fatal Plasmodium kntnolesi infection on inoculation with that plasmodium. By protection tests which showed prolongation of the usually fatal infections or transferenceinto a chronic form without the aid of chemotherapy, Coggeshall and Kumm showed that protective antibodies could be demonstratedregularly in the serum of rhesus monkeys with chronic Plasmodium kno..wlesi· infection. This has been confirmed by other observers. Cog-geshallhas utilized the discovery of Knowles and Das Gupta who produced active malarial infections following inoculations with Plasmodiu In knoiclesi. He inoculated patientssuffering from generalparalysiswith Plasmodium knouilcsi for its therapeuticeffl'ct and he took samplesof serum from these patients at various intervals during their malarial infection and used them in protection experiments with the rhesus monkey. The results, Coggeshall states, show that man, like the laboratory animal, acquiresprotectivesubstancesin his serum during the courseof a knowlesi malarial infection. "That these substancesare acquired as a result of the infection is shown by the fact that they are not present until the chronic stage of the infection has been reached." An interesting observation is recorded which Coggeshall thinks will probably explain failures in previous attempts to demonstratepassive immunity. An effort was made to determine quantitatively the relationship between the amount of immune serum and number of viable parasites in the inoculum. It was found by titration that a definite relationship existed and it was possible to obscure completely the protective effect of a potent immune serum if the number of parasiteswas not kept to a minimum. Becauseprotective antibodies are hard to detect, it does not meanthat they are presentin extremely low dilutions. Coggeshall presumes that the malarial parasite has a Protective covering in the red cell membranewhich prevents an optimal union between the organism and the antibody. According to this idea antibodies might be present in appreciableconcentrationsand yet be unable to exert their maximal I'ffect on the parasite. Coggeshall's conclusion on this aspect of the subject is that the accumulateddata furnish defin ite proof of the existence of the humoral factor in malarial immunity. "Its importance in the defensemechanismhas yet to be evaluated, but the fact that man 01' animal only retainsan immunity to the strainswith which they have had actual experience must mean that some factor or factors in addition to a highly efficient cellular defense mechanismis responsible for the marked degree of specificity encountered with malarial infections." Cog-geshall proceedsfrom the conclusion just stated to show that the concentrationof protective antibodies in a chronic malarial infection is constantly shifting as it respondsto the rate of multiplication of the parasite. He shows that in Plasmodium ktunolesi infections in the rhesus monkey it is possible to produce a hyperimmune serum of high potency with repeatedinoculations of massive numbers of living parasites. This is an indication that the host is responding,although there is no change in the numbers of circulating parasites. In nature, Coggeshallpoints out, the sameresult is probably obtained through the constantexposureof individuals to the bites of infected mosquitoeswhich may serve as a stimulus to maintain a high level of immunity. Referencehas already been made to people living in the tropics, obviously not ill, but harbouring in the blood stream considerable numbers of parasites. Although the exact role of theprotectiveantibody has not been demonstrated,Coggeshall refers to experimental evidence which suggeststhat theantibody acts as an opsonin and alters or sensitizesthe' parasite so that it becomes more susceptible to phagocytosis. According to this view "the effective functioning of the defensiveefforts of the host does not dependsolely upon a cellular or humoral basis,but upon the cooperative' efforts of both". Two aspectsremain to be mentioned. The first has to' do with the duration of immunity. In this regard it must be rememberedthat there is no way of showing whether" the host is resistant becauseof a residual immunity following the complete disappearanceof an infection or because of the presence of an undetectable infection. Coggeshall gives three main reasons why it is almost impossible to know the statusor duration of immunity.