Studies on Human Malaria in Aotus Monkeys. V. Blood-Induced Infections of Plasmodium vivax

Abstract

Blood-induced infections of Plasmodiulw vivax in splenectomized Aotus trivirgatus monkeys produce peaks in the parasitemia an average of once every 42 days. Associated with these peaks are infections in Anopheles freeborni mlosquitoes which are highest in the 4 days before and including the peak in the parasitemia. Higher levels of mosquito infection and higher numbers of oocysts per gut were obtained in mosquitoes fed on monkeys splenectomized after a short period of parasitemia than in those splenectomized prior to inoculation. Intact monkeys infected mosquitoes at a very low level only. The Aotus trivirgatus monkey has been shown to be a useful host for studies of Plasmodiumn vivax (Young et al., 1966; Porter and Young, 1966). Of necessity, most of our early studies have been with animals infected by the inoculation of parasitized blood; these have been studied for the course of the parasitemia, both in intact and splenectomized animals, and for the infection of mosquitoes. Reported here are the results of some of our observations on blood-induced infections in these animals. MATERIALS AND METHODS A total of 70 monkeys infected with 14 different strains of P. vivax were examined. Twenty monkeys were infected with strains from Southeast Asia, 10 with Chesson strain (from New Guinea), and 40 with strains from Central and South America. The results were pooled since there appeared to be as much variation in parasitemia and infectivity between different monkeys as was seen between the different strains. All monkeys were the A. trivirgatus griseimnemibra subspecies originally from Colombia. Prior parasitologic and serologic examination indicated that they were free of natural malarial infection. All monkeys were infected by the intravenous inoculation of either fresh or frozen heparinized parasitized blood. During the early course of the infection, thick and thin blood films were made daily and stained with Giemsa for microscopic examination. Later, especially during periods of latency, smears were made at less frequent intervals. Whenever mosquitoes were fed, gametocyte counts were made on a daily basis. Anopheles freeborni mosquitoes were fed on the restrained animals between 0800 and 1200 hr. Incubation was at 25 C and 10% Karo syrup soluReceived for publication 4 December 1973. * Center for Disease Control, Tropical Disease Program, 1600 Clifton Road, Atlanta, Georgia 30333. tion was provided daily. Dissections of the guts were made between the 7th and 10th days after feeding and the total number of oocysts present on each gut was recorded. Splenectomy of monkeys was made according to the technique of Sodeman et al. (1970). RESULTS The monkeys can be divided into three groups: (1) intact animals, (2) monkeys splenectomized prior to infection, and (3) monkeys splenectomized after the appearance of parasites. Intact monkeys Twenty-eight monkeys were inoculated. The peak in the parasitemia was obtained between the 6th and 29th days after infection (mean 15.4 days). The peak parasitemia ranged from 20 to 720,000 per mm3 with a mean of 41,400 per mm3. Since the parasitemias thereafter usually fell to very low levels, most of the monkeys were splenectomized soon after the primary peak. Only one animal had a second peak in the parasitemia and this occurred on day 42. Presplenectomized monkeys A total of 42 monkeys were inoculated from 1 to 332 days after splenectomy (mean 62 days). The recrudescences in the parasitemia which could be identified by distinct peaks in the parasitemia are presented in Table I. Three of the animals had seven recrudescences, the longest interval between inoculation and final peak parasitemia being 319 days. The mean peak parasitemia was highest during the primary attack and continued to drop with each succeeding recrudescence. It is important to note that the reason some animals did not