The Distribution and Intensity of Parasite Sequestration in Comatose Malawian Children
1Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; 2College of Osteopathic Medicine, Michigan State University, East Lansing; 3The Brigham and Women’s Hospital, Boston, Massachusetts; 4Department of Histopathology, 5Malawi‐Liverpool‐Wellcome Trust Clinical Research Programme, and 6Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi; 7School of Tropical Medicine, University of Liverpool, United Kingdom
Background.
The sequestration of Plasmodium falciparum–infected erythrocytes in capillary beds is a characteristic feature of severe malaria and is believed to be central to disease pathogenesis. Sequestration occurs in all P. falciparum infections, including those in asymptomatic individuals. Therefore, sequestration cannot be the sole determinant of severe disease; the intensity or distribution of infected erythrocytes may also contribute. Discerning the relationship between sequestration and well‐defined clinical syndromes may enhance understanding of disease mechanisms.
Methods.We measured the concentration of parasite‐derived lactate dehydrogenase (pLDH) in tissue samples obtained at autopsy from patients with clinically defined cerebral malaria. On the basis of the autopsy findings, patients were divided into 2 groups: those with an identifiable, nonmalarial cause of death and those without, who were presumed to have died of cerebral malaria. The concentration of pLDH, as determined by enzyme‐linked immunosorbent assay, was used to estimate parasite load in different organs.
Results.When pLDH could be detected, the parasite load was higher in patients with presumed cerebral malaria than in parasitemic patients with assumed cerebral malaria with a nonmalaria cause of death identified at autopsy (
for brain, intestine, and skin).
Conclusions.These findings suggest that sequestration in patients with fatal cerebral malaria occurs in multiple organs and does not reflect a predilection in the parasite for the cerebral vasculature.
Received 31 October 2005; accepted 3 February 2006; electronically published 13 June 2006.
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Presented in part: American Society of Tropical Medicine and Hygiene annual meeting, Miami, Florida, 7–11 November 2004 (abstract 2023).
Potential conflicts of interest: none reported.
Financial support: US National Institutes of Health (grant RO1 AI34969); Wellcome Trust, UK (grant 042390/Z/94); National Institute of Allergy and Infectious Diseases intramural research funds.