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

Cox-Singh J, Hiu J, Lucas SB, Divis PC, Zulkarnaen M, Chandran P, Wong KT, Adem P, Zaki SR, Singh B, Krishna S - Malar. J. (2010)

Bottom Line: 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.There were important differences including the absence of coma despite petechial haemorrhages and parasite sequestration in the brain.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Cellular and Molecular Medicine, Centre For Infection, St George's University of London, London SW17 0RE, UK. coxsingh@gmail.com

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.

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Related in: MedlinePlus

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.
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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.

Mentions: Although sections from the spleen showed some autolysis, expansion of the red pulp and atrophy of the white pulp was noted. Germinal centers were not observed. Abundant pigment-containing macrophages and some haemophaghocytosis was evident in the red pulp and parasitized red cells were plentiful (Figure 5a). There was no necrosis or fibrin deposition in the spleen.


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

Cox-Singh J, Hiu J, Lucas SB, Divis PC, Zulkarnaen M, Chandran P, Wong KT, Adem P, Zaki SR, Singh B, Krishna S - Malar. J. (2010)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2818646&req=5

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.
Mentions: Although sections from the spleen showed some autolysis, expansion of the red pulp and atrophy of the white pulp was noted. Germinal centers were not observed. Abundant pigment-containing macrophages and some haemophaghocytosis was evident in the red pulp and parasitized red cells were plentiful (Figure 5a). There was no necrosis or fibrin deposition in the spleen.

Bottom Line: 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.There were important differences including the absence of coma despite petechial haemorrhages and parasite sequestration in the brain.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Cellular and Molecular Medicine, Centre For Infection, St George's University of London, London SW17 0RE, UK. coxsingh@gmail.com

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.

Show MeSH
Related in: MedlinePlus