Severe malaria - a case of fatal Plasmodium knowlesi infection with post-mortem findings: a case report

Abstract

Background: Zoonotic malaria caused by Plasmodium knowlesi is an important, but newly recognized, human pathogen. For the first time, post-mortem findings from a fatal case of knowlesi malaria are reported here.

Case presentation: A formerly healthy 40 year-old male became symptomatic 10 days after spending time in the jungle of North Borneo. Four days later, he presented to hospital in a state of collapse and died within two hours. He was hyponatraemic and had elevated blood urea, potassium, lactate dehydrogenase and amino transferase values; he was also thrombocytopenic and eosinophilic. Dengue haemorrhagic shock was suspected and a post-mortem examination performed. Investigations for dengue virus were negative. Blood for malaria parasites indicated hyperparasitaemia and single species P. knowlesi infection was confirmed by nested-PCR. Macroscopic pathology of the brain and endocardium showed multiple petechial haemorrhages, the liver and spleen were enlarged and lungs had features consistent with ARDS. Microscopic pathology showed sequestration of pigmented parasitized red blood cells in the vessels of the cerebrum, cerebellum, heart and kidney without evidence of chronic inflammatory reaction in the brain or any other organ examined. Brain sections were negative for intracellular adhesion molecule-1. The spleen and liver had abundant pigment containing macrophages and parasitized red blood cells. The kidney had evidence of acute tubular necrosis and endothelial cells in heart sections were prominent.

Conclusions: The overall picture in this case was one of systemic malaria infection that fit the WHO classification for severe malaria. Post-mortem findings in this case were unexpectedly similar to those that define fatal falciparum malaria, including cerebral pathology. There were important differences including the absence of coma despite petechial haemorrhages and parasite sequestration in the brain. These results suggest that further study of knowlesi malaria will aid the interpretation of, often conflicting, information on malaria pathophysiology in humans.

Figure 1

Thin blood film showing mostly late trophozoites of P. knowlesi in poorly defined erythrocytes (1a) and heavily pigmented monocyte (1b). Note that the blood film was prepared 24 hours post mortem and shows red cell ghosts, particularly among parasite infected red blood cells.

Figure 2

Gross appearance of the brain. The outer surface appears dusky with petechial haemorrhages seen on the outer surface of the cerebellum (2a). Cut section of the cerebellum with multiple petechial haemorrhages seen within the cerebellar grey matter (2b).

Figure 3

Plasmodium-specific anti-aldolase immunohistochemistry stained sections from the brain. Parasites appear red.

Figure 4

Haematoxylin and eosin stained sections of the cerebellum (a, b, c, e, f) and cerebrum (d). Low power view showing haemorrhages in the grey and white matter × 20 (4a). Haemorrhage in the cerebellar molecular layer × 40 (4b). 4c × 400 and 4d both × 200 show capillaries with sequestered parasitized red blood cells. There was no perivascular inflammation nor intravascular thrombosis. Venule with parasitized red blood cells × 200 (4e) and haemorrhage showing mixture of parasitized and non-parasitized red blood cells × 400 (4f).

Figure 5

Haematoxylin and eosin stained extra cerebral tissues. (5a) spleen × 400 showing red pulp macrophages containing much haemozoin pigment as well as phagocytozed red blood cells. (5b) liver × 400 showing macrovesicular steatosis of hepatocytes without parenchymal inflammation. The sinusoids have abundant parasitized red blood cells as well as Kupffer cells containing haemozoin. (5c) kidney × 200 showing acute tubular necrosis and intratubular casts. Intravascular parasitized red blood cells also visible. The myofibres of the left ventricle of the heart are normal (5d × 200). Small veins and capillaries contain abundant parasitized red blood cells and endothelial cells are prominent.