Studies on sporozoite-induced and chronic infections with Plasmodium fragile in Macaca mulatta and New World monkeys

Plasmodium fragile continues to be investigated because of its biologic similarities to the human malaria parasite, Plasmodium falciparum. Two strains of P. fragile are available for study; one strain is able to infect mosquitoes, whereas the other strain is transmissible only by blood inoculation. The Sri Lanka strain of P. fragile was transmitted to Macaca mulatta, Macaca fascicularis, Aotus lemurinus griseimembra, Aotus nancymaae, Aotus vociferans, and Saimiri boliviensis monkeys via sporozoites that developed to maturity only in Anopheles dirus mosquitoes. The prepatent periods ranged from 12 to 35 days for macaques and from 15 to 30 days for New World monkeys after intravenous injection of sporozoites. Eight rhesus monkeys were infected with the Nilgiri strain and followed for 482 days. Parasitemia in 6 animals persisted at relatively high density through the period of observation. Erythrocyte, hematocrit, and hemoglobin values reached their lowest levels 3 wk after infection and slowly recovered; however, the values did not approach preinfection levels as long as parasitemia persisted in the monkeys. The mean corpuscular volume and corpuscular hemoglobin concentration reached their peak and lowest values, respectively, at day 38 and then returned to the preinfection level. The mean corpuscular hemoglobin value decreased to its lowest level at day 87 and then returned to preinfection level.     

The development of exoerythrocytic stages of Plasmodium inui shortti in New World monkeys

Attempts are being made to adapt Old World monkey malarial parasites to New World monkeys for vaccine and molecular studies. Several of these (Plasmodium cynomolgi Berok, Plasmodium fragile, and Plasmodium knowlesi) grow readily but have failed to produce infective gametocytes. Plasmodium gonderi and Plasmodium fieldi develop in the liver after sporozoite inoculation but have failed to establish infection in the erythrocyte. Anopheles dirus mosquitoes infected with Plasmodium inui shortti by feeding on infected macaques transmitted the infection to Saimiri boliviensis monkeys. Infective gametocytes were produced, and sporozoite transmission from Saimiri to Saimiri monkey was obtained. Exoerythrocytic stages have also been observed in the liver tissue of Saimiri monkeys. The availability of the complete transmission cycle provides an additional resource for immunologic and vaccine studies.     

Parturition in rhesus monkeys (Macaca mulatta)

During five years of birth season fieldwork, we observed two births and three peri-birth instances of behavior of free-ranging rhesus living in Kathmandu, Nepal. These constitute the first two recorded free-ranging rhesus births, and we compare them to the behavior which has been observed in captivity and expected in the wild. The free-ranging parturition behavior was characterized by a general lack of contact with other troop members and by overall inconspicuousness. In the first birth we observed, the troop moved about 70 m up the hill, leaving the laboring female behind on an open hillside. Two males, a female and a juvenile returned and rested about 20 m from the delivering female. During the second delivery, the female stayed with the troop and seemed to participate normally in most troop interactions, although she avoided physical contact with other troop members. We propose that this near-normal behavior may help to assure successful parturition by allowing the female the needed social isolation and inconspicuousness without any loss of troop protection. It may also partly explain why births have not been observed during previous studies. Observations of rhesus parturition behavior reported from studies of captive monkeys and reports from other free-ranging primate studies are compared with our data.     

Plasmodium fallax: phagocytosis of exoerythrocytic stages in tissue culture

Wandering phagocytes in tissue cultures were attracted to the exoerythrocytic stages, both intracellular and extracellular, of Plasmodium fallax. They phagocytized free merozoites or schizonts that had been freed from host cells. They attempted to phagocytize large intracellular parasites.     

Plasmodium lophurae: the ultrastructure of the exoerythrocytic stages

The fine structure of the exoerythrocytic stages of Plasmodium lophurae was studied. in specimens grown in tissue cultures of avian cells. Specimens were prepared for sectioning by a method which minimizes disturbance and permits precise selection and orientation specimens.Plasmodium lophurae is similar in many aspects to P. fallax. Merozoites are highly specialized and differentiated. Analysis of their ultrastructure revealed the polar complex to be a specialization of the pellicular envelope and its associated underlying microtubules. The polar rings may simply be a modification of the inner membrane of the pellicle and not discrete structures as previously reported. The electron-dense polar organelles are separated on morphological grounds into three groups: the large paired organelles and the small dense bodies which are both linked to microducts, and the transitional bodies, a third organelle being reported for the first time. Transitional bodies are without microducts, occur in fully mature merozoites and persist only for a short period. All three of these organelles appear to be related to and possibly even derived from internal membrane systems and ribosomes. The apolar end of the merozoite contains the mitochondrion and its associated spherical body. Detailed study of the latter shows it to be cylindrical.Upon entering the host cell, the parasite adds a third membrane at the interface between it and the cell. The merozoite becomes spherical and undergoes transformation into a trophozoite. During this reorganization phase, dedifferentiation occurs and is followed by a rapid growth phase. The end of the growth phase is signaled by the appearance of germinal clefts and nuclear division. The entire process of schizogony culminates in a highly synchronized formation of merozoites.Processes of the limiting membrane forming the host parasite interface were observed extending deply into the cytoplasm of the host cell and often appeared to form bridges between two or more parasites. The significance of this new observation is not yet established.