Lyman P. Frick

Schistosoma mansoni infections in Cercopithecus sabaeus monkeys.

Cercopithecus sabaeus (green) monkeys discharged eggs up to 3.5 years after initial exposure and for a comparable period after reexposure. The number and development of worms from challenge infections were similar to initial infections, but excretion of eggs was delayed after challenge. Monkeys exposed repeatedly to moderate or small numbers of cercariae tolerated a burden of worms that would have been lethal as a single initial infection. There was evidence that worms lived for 5 years, and without regression in size. Large accumulations of eggs still occurred in the liver and intestine after 5 years, and the relative numbers of immature, mature, and degenerate eggs were similar to early stages of first infections. The response of the green monkey to S. mansoni is in marked contrast to that of Macaca mulatta, which suppresses excretion of eggs after 6 to 9 months and quickly acquires strong resistance to challenge infections. The longer output of eggs by the green monkey is more like what occurs in man. A corresponding comparison of acquired resistance is not possible because too little is known about resistance imposed against schistosomes in the human host. The rhesus and the green monkeys may provide a valuable experimental model for investigating the immune mechanism against schistosomes. The green monkey may be useful in the evaluation of schistosomicidal drugs. The need for experimental hosts of human schistosomes that react to the infections more like man than the commonly used Macaca mulatta (rhesus) monkey was emphasized by Sadun et al. (1966a). Their studies and those of Sadun and Bruce (1964) on the biology and pathology of schistosomiasis in 10 species of primates showed that worm recovery rates were highest in three species of Macaca, but self-cure occurred within a few months. The baboon and chimpanzee discharged eggs for much longer periods, but worm recovery was relatively low. For other species, the infections were abortive from the beginning. Only the chimpanzee developed pipe-stem fibrosis of the liver. The need for information on other primate hosts was noted by the above authors. Information on acquired resistance among primate hosts is essentially limited to the rhesus monkey. For man, too little is known to recognize a suitable model. The current study is concerned with another primate, Cercopithecus sabaeus, the green Received for publication 22 May 1967. * Assigned to Walter Reed Army Institute of Research, Washington, D. C. (20012), with duty station at the Department of Preventive and Social Medicine, University of Ibadan, Ibadan, Nigeria. t Present address: Tropical Disease Section, Ecological Investigations Program, Communicable Disease Center, U. S. Public Health Service, San Juan, Puerto Rico. monkey, and includes observations on the length of the prepatent period, duration and pattern of egg discharge, life-span of the infection, distribution and condition of eggs in tissues, and acquired resistance. These objectives were not all completed as originally planned, due to closing of this laboratory. A number of investigators have exposed the green monkey to human schistosomes for limited objectives, and only a few animals were involved, or the infections were of short duration (Archibald, 1923; Black, 1932; Vogel and Minning, 1953; Kuntz, 1955; Vogel, 1962; Hsii and Hsii, 1962; Meisenhelder and Thompson, 1963; and Ritchie et al., 1964). The green monkey was found to discharge eggs for relatively long periods. In contrast to M. mulatta, challenge infections developed to maturity in animals that had been infected

Enhancement of acquired resistance against Schistosoma mansoni in albino mice by intraperitoneal immunizing exposures.

Immunization of albino mice against Schistosoma mansoni by multiple, low-grade cercarial exposures resulted in earlier and higher levels of resistance when exposures were administered intraperitoneally (ip) than when the percutaneous (pc) route was used. Mice which received a course of ten weekly ip injections of ten cercariae each had significantly fewer worms than their controls. This did not occur when the exposures were made percutaneously. Both courses elicited strong resistance against challenge, although the level of this resistance was higher following ip immunization. With pc immunization resistance apparently was directly related to the maturation of immunizing infections and accumulation of eggs. This was not the case with ip immunization since significant resistance against challenge was evident only 7 days after the last of five weekly ip exposures. In ip immunization the basis for resistance may be the prolonged immunologic stimulation of lungs and liver resulting from the delayed escape of young worms from the peritoneal cavity, and the tendency of worms that remain in the peritoneal cavity to persist as schistosomular stages for extended periods. Lurie and DeMeillon (1957) have reported that a series of intraperitoneal injections with small numbers of cercariae elicited strong, rapidly developing resistance against Schistosoma mansoni in mice. Essentially complete resistance was achieved with all of several schedules, suggesting that even those worms which must have developed before resistance became effective had been eliminated relatively soon thereafter. Other investigators working with the more conventional plan of immunization followed by challenge usually have not observed such remarkable levels of resistance (see reviews by Kagan, 1958; Stirewalt, 1963). The percutaneous route of exposure has been used almost invariably, and to the limited extent that single and multiple immunizing exposures have been compared, it has not been shown conclusively that either procedure is superior to the other. The study reported herein was undertaken to compare the intraperitoneal and percuReceived for publication 10 July 1964. * Presented in part at Annual Meeting, American Society of Parasitologists, November 1963. taneous routes of immunization against S. mansoni in mice, using a series of low-grade cercarial exposures. The occurrence of important differences between mean worm burdens and response to challenge infection following exposures by one route as compared with the other, indicate that the route by which an immunizing infection was acquired may be an important factor in the development of resistance. MATERIALS AND METHODS Bagg strain albino female mice with an initial weight of 18 to 22 g were used exclusively. Cercariae of a stock laboratory strain of Puerto Rican S. mansoni were used for immunization and challenge. The several cercarial pools necessary for each experiment were always obtained from groups of 30 to 50 laboratory-reared and infected Australorbis glabratus. Immunization consisted of a series of ten (or in one case only five) percutaneous or intraperitoneal exposures performed by conventional methods. In Experiments 1 and 3, on the occasion of each immunizing exposure, a new group of five mice were exposed in parallel in order to assay cercarial infectivity. The cumulative mean from these groups provided a basis for determining the resistance that mice acquired during the course of multiple exposures. In Experiment 2, however, five to ten

Effect of pH on molluscicidal activity of Bayer 73 vS. Australorbis glabratus of Puerto Rico under laboratory conditions.

Abstract : A Laboratory strain of Australorbis glabratus of Puerto Rico when exposed for 24 hours in Bayer 73, 5-chlorosalicylic acid (2-chloro, 4-nitro) anilide, at 0.2 parts per million in aerated tap water (pH 7.0-8.2) invariably succumbs, 100% of the snails being killed. However, in test waters of high acidity (pH 4 and pH 5) and high alkalinity (pH 9.3-9.9) 4 to 8 times as much molluscicide or 0.8 to 1.6 ppm may be necessary to effect 100% mortality. Different kinds of water such as distilled, chlorinated tap, aerated tap, and the like, give markedly different mortality results in toxicological experiments in various laboratories throughout the world. This may be partly explained by the different qualities of the water, of which an important one is the pH. (Author)

Effect of the duration of Schistosoma mansoni infections on the degree of protection against subsequent exposures

Abstract Prolongation of initial infection with S. mansoni in rodents results in decreased levels of acquired resistance despite continued presence of adult worms. In the albino rat a significant decrease in resistance occurs between 32 and 64 weeks after primary exposure, although resistance is still at a significant level at the latter time. In hamsters acquired resistance is lost sometime after 12 weeks and before 32 weeks. The mechanism of acquired resistance in the rat develops independently from the mechanism responsible for innate resistance in this host; is presumably unrelated to the latter; and has characteristics similar to the same mechanism in the highly susceptible mouse and hamster.