Metabolic disturbances in Plasmodium coatneyi-infected rhesus monkeys.
To investigate metabolic disturbances in an animal model of human malaria, four rhesus monkeys (Macaca mulatta) were infected with Plasmodium coatneyi, a parasite which induces cytoadherence of infected erythrocytes. When moribund or the parasitaemia had plateaued, the monkeys were sacrificed (3 animals) or treated with chloroquine (1 animal). Blood and cerebrospinal fluid (CSF) were sampled at intervals between inoculation and sacrifice or treatment. Arterial and CSF glucose and lactate rose during infection, indicating evolving insulin resistance. The arteriovenous difference in glucose concentration also increased, consistent with increased glucose consumption by parasitised tissues. Arterial plasma lactate rose but a positive arteriovenous concentration difference suggested tissue lactate uptake. The animal with the highest plasma lactate at sacrifice remained hyperglycaemic but also had the highest CSF lactate, the greatest cerebral sequestration and neurological depression, and biochemical and histological evidence of severe hepatic pathology. Serum cholesterol and corrected serum calcium fell consistently during infection; serum phosphate was also reduced in animals without renal impairment. These preliminary results indicate that lactic acidosis is a late complication of severe malaria and, by implication from this and other studies, hypoglycaemia occurs even later; other metabolic changes during P. coatneyi infection in rhesus monkeys also parallel those of severe falciparum malaria in humans. The model could be used in further studies of malaria-associated metabolic dysfunction and its management.
Davis
T M
TM
University of Western Australia, Department of Medicine, Fremantle Hospital.
Brown
A E
AE
Smith
C D
CD
D000818:Animals; D001344:Autopsy; D001786:Blood Glucose / Q000032:analysis; D005947:Glucose / Q000134:cerebrospinal fluid / Q000378:metabolism*; D006943:Hyperglycemia / Q000097:blood; D007773:Lactates / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D008074:Lipoproteins / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D008253:Macaca mulatta; D008288:Malaria / Q000378:metabolism*; D008903:Minerals / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*
D001786:Blood Glucose; D007773:Lactates; D008074:Lipoproteins; D008903:Minerals; D005947:Glucose