Plasmodium knowlesi Malaria in the Rhesus Monkey

Abstract

Abstract. Twelve Rhesus monkeys were inoculated intravenously with about 500 000 malaria parasites, Plas~nodiwn kriowlesi. Acute hemolysis occurred 5 days later, and all animals died on the 6th or 7th day after inoculation. All organs were gray-green to graybrown because of deposition of hemoglobin and malaria pigments. This deposition was particularly striking in the lung, brain, abdominal fat and serous surfaces. Microscopic changes indicative of acute hypoxia were found in the liver (centrilobular necrosis) and kidneys (acute tubular necrosis). Terminal intravascular coagulopathy was evidenced by widely distributed, recently formed, fibrin thrombi.Plasmodium knowlesi, a simian parasite o f quotidian periodicity, is indigenous to the jungle and swamp forests of Malaysia. Its range extends from the East Indian Archipelago to the Philippines. where Macaca fascicularis is the natural host and the Anopheline mosquito is the primary vector (4, 6, IS]. Contact with the vector can result in human infection 141. Experimentally induced infections in the Rhesus monkey (Macaca mulatta) are rapidly and uniformly fatal and have been used as a model for the human disease.The parasite has a life cycle similar to that of other malarial organisms. During the asexual (intraerythrocytic) phase, the outer membrane of the trophozoite acquires a digestive function, which results in the degradation of hemoglobin to hematin (hemozoin or "malaria pigment") [6]. The distribution of this compound is responsible for the gray-brown discoloration of affected organs and serous membranes.Reports on the pathology of simian malaria have appeared sporadically in the literature [6. 16, 20, 221. These studies included a number of different malarial parasites and primate species and in general, concentrate on the description of a single organ system. As a result, documented discussion of pathological features of the disease is fragmentary. The pathology of P. falciparum malaria in owl monkeys has been reported recently 191, but pathological changes were sparse.This report describes and documents the range of pathological changes in 12 Rhesus monkeys inoculated experimentally with P. knowlesi. 83

Intravascular haemolysis in severe Plasmodium knowlesi malaria: association with endothelial activation, microvascular dysfunction, and acute kidney injury

“…Massive destruction of RBCs has been previously reported in P. knowlesi -infected rhesus macaques ( Macaca mulatta ), another unnatural host for this parasite. As well as the red cell agglutination and sludging reported in these early studies 32 , haemolytic phenomena such as haemoglobinuria, renal tubular acidosis and haemoglobin casts within tubular lumens were frequently noted as pre-terminal events 33 , 34 . The marked haemolysis associated with P. knowlesi makes this parasite an ideal model to study the pathophysiological consequences of haemolysis in severe human malaria.…”

A Review of Plasmodium coatneyi–Macaque Models of Severe Malaria

“…This is evidenced by the incompatibility of P. knowlesi and the rhesus macaque to cohabitate the same range of forest because P. knowlesi causes a rapidly fatal course of disease in this monkey, making malaria persistence impossible. 92,106 This degree of pathogenicity may be the result of recent evolutionary collision between the host and pathogen in which the malaria parasite maintained a high level of virulence due to insufficient evolutionary time to adapt to the host. This particular point is potentially important in selection and interpretation of a model, as differing species of macaques from diverse geographic origins may display differing susceptibility to various plasmodia.…”

REVIEW PAPER: Emerging and Reemerging Infectious Diseases of Nonhuman Primates in the Laboratory Setting

“…Hematopoietic cells accumulate in the congested vasa recta. 126 Species that cause infected erythrocytes to adhere to vessel walls result in plugs of parasitized erythrocytes lodged in small capillaries. 104 Diagnosis.…”