Plasmodium coatneyi: observations on periodicity, mosquito infection, and transmission to Macaca mulatta monkeys.

Abstract

Abstract. Plasmodium coatneyi has adapted well to experimental studies with Macaca mulatta monkeys and Anopheles dirus mosquitoes. Studies were made to determine 1) the course of asexual parasitemia, 2) periods when infective gametocytes were produced, 3) the laboratory-reared mosquitoes susceptible to infection, 4) the mosquito most capable of transmitting the infection to monkeys via bite, 5) the pattern of recrudescence, and 6) the prepatent periods following the bites of infected An. dirus mosquitoes. The period when infective gametocytes are produced is concentrated primarily in the first week when parasitemia exceeds 1,000/l. Mosquitoes were more heavily infected on days when the asexual parasite counts were highest. Gametocyte counts were generally low. Mature forms of the parasite markedly sequestered giving a pattern of high-low periodicity. Anopheles dirus and An. freeborni mosquitoes were nearly equal in terms of their ability to support oocyst development. Other species (An. stephensi, An. maculatus, and An. gambiae,) were less supportive. High sporozoite densities in the salivary glands were frequently produced in An. dirus and sporozoite transmission was obtained via the bites of these mosquitoes after 12-18 days of extrinsic incubation. Prepatent periods ranged from 10 to 15 days. The presence of frequent parasitic recrudescences suggests mechanisms similar to that seen in human infections with P. falciparum. It is proposed that P. coatneyi in M. mulatta monkeys can be a suitable model for studies on cerebral pathology, vaccine efficacy, and the testing of antimalarial drugs.

Plasmodium coatneyi in Rhesus Macaques Replicates the Multisystemic Dysfunction of Severe Malaria in Humans

“…Suppression of erythropoiesis with bone marrow hyperplasia accompanied by dyserythropoiesis and inefficient reticulocyte production index has been described in patients with severe malarial anemia (53)(54)(55). Acquired immunity in P. coatneyi-infected rhesus monkeys is not sterilizing and can be used to mimic chronic infections that reproduce what is seen in children in areas of high stable transmission (21). Taken together, the data support the use of P. coatneyi in rhesus macaques to study the molecular mechanisms involved in severe malarial anemia.…”

“…1). Parasitemia in the five monkeys followed the expected pattern of peaks on alternating days followed by a sharp drop in parasite levels, coinciding with the maturation and sequestration of the parasites, comparable to that of P. falciparum (21); presumably via predicted variant antigens analogous to the var gene-encoded erythrocyte membrane protein-1 (PfEMP1) and SICA antigens of P. knowlesi (references 26 and 27 and unpublished data). Parasite increases were recorded on days 3, 5, and 7 or 9 after experimental infection.…”

“…The animals were experimentally challenged intravenously with 1 ϫ 10 4 P. coatneyiinfected erythrocytes/kg of body weight obtained from an active infection in a donor monkey. To ensure that these infections mimicked the natural course of P. coatneyi infections in rhesus macaques as originally described (20,21), parasites were inoculated from the original line of P. coatneyi (24), archived as cryopreserved stocks at the CDC and confirmed to have no history of experimental passage in splenectomized animals. Parasitemias, hemoglobin levels, and reticulocyte counts were determined daily from peripheral blood capillary samples as described previously (25).…”

“…Procedures used were approved by Emory University's Institutional Animal Care and Use Committee and followed accordingly. The Hackeri strain of P. coatneyi used in these studies came from archived stocks maintained by cryopreservation at the Centers for Disease Control and Prevention (21). Twenty animals were randomized into four groups of 5 animals; and two of these groups were exposed to P. coatneyi at two different time points.…”

The Role of Soluble Tumor Necrosis Factor Receptor Types I and II and Tumor Necrosis Factor–α in Malaria during Pregnancy

“…The frozen inoculum, obtained from a simian-retrovirus-uninfected free monkey infected with P. coatneyi, contained˜10 6 parasites/mL and was thawed in 37ЊC water before intravenous administration. Because P. coatneyi sequesters and produces serious clinical malaria with recrudescence in rhesus monkeys [35], this model has been used to study cerebral malaria [36] and malaria during pregnancy [13].…”