Disseminated Intravascular Coagulation Complicated by Peripheral Gangrene in a Rhesus Macaque (Macaca Mulatta) Experimentally Infected With Plasmodium Coatneyi

Abstract

We report the first case of disseminated intravascular coagulation (DIC) complicated by peripheral gangrene induced by Plasmodium coatneyi in rhesus monkeys. Ten days after experimental challenge, numerous petechiae were noted over the trunk and extremities, with polychromasia, severe anemia, thrombocytopenia, and moderate parasitemia. These changes were accompanied by elevated serum activity of blood urea nitrogen, creatinine, transaminases, and creatinine phosphokinase. The animal received intravenous fluid support, artemether, and blood transfusion. Three days after treatment, the platelet counts returned to normal, and parasitemia was abated. However, several areas of skin discoloration with gangrenous tissue in the hands and the tail were observed. Coagulation profile showed elevated D-dimers and elevated levels of fibrinogen/fibrin degradation products with low levels of protein S functional activity. DIC with peripheral gangrene is very rare in Plasmodium-infected individuals. Our results indicate that the experimental model of P. coatneyi infection of rhesus monkeys is important for studies of malarial anemia and coagulopathy.

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

“…Two animals developed severe anemia by day 11 with hemoglobin levels lower than 5 g/dl. In one of these subjects, the severe anemia was associated with thrombocytopenia and coagulopathy, complications that ultimately led to disseminated intravascular coagulation and peripheral gangrene (25). The mean hemoglobin levels increased after subcurative antimalaria treatment but reached only 40 to 60% of the baseline hemoglobin levels.…”

“…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). Similar capillary samples were also taken and monitored from uninfected control animals.…”

A Review of Plasmodium coatneyi–Macaque Models of Severe Malaria

“…This resulted in dermal infarction of the digits and the tail due to thrombosis of the superficial vasculature. 78 A similar unpublished case occurred in Thailand in a rhesus macaque also experimentally infected with P. coatneyi. In that instance, the animal developed a necrotizing rhinitis and cheilitis that progressed to erosion and ulceration.…”

“…24 In addition to the necrosis, mononuclear hepatitis was frequently noted, accompanied by a marked accumulation of birefringent malaria pigment observed within Küpffer cells. 60,78 It is significant that while increases in inducible liver enzymes are a common feature of severe malaria in adult humans, there are only rare reports of centrilobular hepatic necrosis. 20,24 Kidney.…”

“…41,52 The thrombocytopenia may result from splenic sequestration, peroxidation of the platelet lipid membranes, or platelet consumption from formation of systemic microthrombi. 78 Metabolic disturbances were evaluated in the rhesus macaque model. 19 Animals infected with P. coatneyi demonstrated variably increased serum and cerebrospinal fluid glucose levels, as well as elevated lactate that increased with parasitemia.…”