Studies on Malignant Malaria in Macedonia

Gaskell, J. F.; Millar, W. L.

doi:10.1093/qjmed/os-13.52.381

Cited by 36 publications

(14 citation statements)

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“…125 Hemorrhages. Brain hemorrhages have long been observed in CM, 123,[127][128][129][130][131][132] and are described as petechial, punctuate, and most specifically, as ring hemorrhages. These are hemorrhages composed of extravasated red blood cells (usually not PRBCs) surrounding an occluded, or possibly thrombosed vessel.…”

Section: Pathophysiology Of Fatal Malariamentioning

confidence: 99%

Pathophysiology of fatal falciparum malaria in African children.

Newton¹,

Taylor²,

Whitten³

1998

Am J Trop Med Hyg

122

121

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Abstract. Children living in sub-Saharan Africa bear the brunt of the mortality from falciparum malaria, yet there is a dearth of relevant post-mortem data. Clinical studies from centers in Africa suggest that the pathophysiology of severe malaria is different in children and adults. Three overlapping clinical syndromes, metabolic acidosis manifesting as hyperpnea, cerebral malaria, and severe anemia, are responsible for nearly all the deaths in African children. Despite improvements in antimalarial treatment, there has not been a significant reduction in mortality. We review the pathology and pathophysiology of fatal falciparum malaria in African children. Many questions remain, the answers to which would facilitate the development and evaluation of new approaches to the management of this disease.Severe and complicated Plasmodium falciparum infections continue to threaten the survival of young children in sub-Saharan Africa: one in 15 children on the Kenyan coast will have experienced an episode of severe malaria before the age of five, 1 and 1% of Gambian children less than five years of age will die of malaria. 2 The annual death toll is estimated to be one million children across the continent; 90% of the annual worldwide malaria mortality. 3 Although most children die in the community, on the Kenyan coast it is estimated that more than 40% die in a hospital (Marsh K, unpublished data) and one-third of pediatric hospital admissions and one-third of pediatric hospital deaths in Malawi can be attributed to malaria. 4

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Section: Pathophysiology Of Fatal Malariamentioning

confidence: 99%

Pathophysiology of fatal falciparum malaria in African children.

Newton¹,

Taylor²,

Whitten³

1998

Am J Trop Med Hyg

122

121

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“…6 Studies in vivo and histopathological observations in fatal P. falciparum malaria and also in the lethal sequestering animal malarias suggest that the red cells containing more mature parasites are sequestered in the brain and other organs from the middle of the parasite life cycle until schizont rupture. [7][8][9][10][11][12][13][14][15][16] The next generation of motile daughter merozoites is then released and invades more red cells to continue the blood stage infection. In most patients with falciparum malaria relatively few P. falciparum trophozoites and schizonts are seen in the peripheral blood, while these more mature parasites are abundant in the capillaries and venules of vital organs (particularly the brain).…”

mentioning

confidence: 99%

“…Others have reported that all stages of parasite development are represented. 7,8,11 The aims of this study were to describe the microvasculature pattern and distribution of parasite developmental stages in the brain in fatal cases of severe falciparum malaria.…”

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confidence: 99%

A Quantitative Analysis of the Microvascular Sequestration of Malaria Parasites in the Human Brain

Silamut

Phu

Whitty

et al. 1999

The American Journal of Pathology

344

332

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Microvascular sequestration was assessed in the brains of 50 Thai and Vietnamese patients who died from severe malaria (Plasmodium falciparum, 49; P. vivax, 1). Malaria parasites were sequestered in 46 cases; in 3 intravascular malaria pigment but no parasites were evident; and in the P. vivax case there was no sequestration. Cerebrovascular endothelial expression of the putative cytoadherence receptors ICAM-1 , VCAM-1 , E-selectin , and chondroitin sulfate and also HLA class II was increased. The median (range) ratio of cerebral to peripheral blood parasitemia was 40 (1.8 to 1500). Within the same brain different vessels had discrete but different populations of parasites, indicating that the adhesion characteristics of cerebrovascular endothelium change asynchronously during malaria and also that significant recirculation of parasitized erythrocytes following sequestration is unlikely. The median (range) ratio of schizonts to trophozoites (0.15:1; 0.0 to 11.7) was significantly lower than predicted from the parasite life cycle (P < 0.001). Antimalarial treatment arrests development at the trophozoite stages which remain sequestered in the brain. There were significantly more ring form parasites (age < 26 hours) in the cerebral microvasculature (median range: 19%; 0 -90%) than expected from free mixing of these cells in the systemic circulation (median range ring parasitemia: 1.8%; 0 -36.2%). All developmental stages of P. falciparum are sequestered in the brain in severe malaria. (Am J Pathol 1999, 155:395-410)Severe falciparum malaria remains one of the most important causes of death in the tropics. Cerebral malaria is the major lethal manifestation of this infection. The sequestration of red blood cells containing mature forms of Plasmodium falciparum in the cerebral microvasculature is considered to be the essential underlying pathological process, although how this leads to coma and death remains unresolved.

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“…[1][2][3] The current theories about the mechanisms leading to the development of cerebral and other forms of severe malaria are based on the fact that parasitized red blood cells (PRBC) sequester in the deep microvasculature of many organs and that excessive sequestration leads to vaso-occlusion, a histologic finding also seen at autopsy in the affected organs. [4][5][6][7][8][9] Two forms of adhesive capacity have been identified that underlie the sequestration: cyto-adhesion to the vascular endothelium, [10][11][12] and rosette formation, the binding of uninfected red blood cells (RBC) to PRBC. [13][14][15][16] An in vitro correlation has been found between binding of PRBC to CD36-expressing cells and pulmonary disease, 17 and several studies have shown a strong association between the capacity in vitro to form rosettes and the severe forms of malaria.…”

mentioning

confidence: 99%

The time course of cytoadhesion, immunoglobulin binding, rosette formation, and serum-induced agglutination of Plasmodium falciparum-infected erythrocytes.

Treutiger¹,

Carlson²,

Scholander³

et al. 1998

The American Journal of Tropical Medicine and Hygiene

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Abstract. We describe morphologic characteristics of acridine orange-stained Plasmodium falciparum-infected erythrocytes and the sequential expression of several adhesion phenomena. In particular, we have studied when the adhesive and antigenic modifications appear on the infected erythrocyte surface that mediate binding to C32 melanoma cells (cytoadherence) or to erythrocytes (rosette formation) during a complete 48-hr life cycle of the parasite. The C32 melanoma cell binding started at about 12 hr and was seen during the whole life cycle with a peak around 28 hr (650 infected erythrocytes/100 C32 melanoma cells). Rosettes started to appear and immunoglobulin was found bound to the parasitized red blood cell (PRBC) somewhat later (16-20 hr). These adhesive events culminated at the mid-trophozoite/schizont stage (24-36 hr) with rosette formation and an immunoglobulin binding rate of about 50%, which decreased to about half of the peak values at the end of the life cycle. Serum-induced agglutination of the infected erythrocytes was also most extensive at 24-36 hr, but agglutination was seen with all late stage parasites, i.e., both trophozoites and schizonts at 24-48 hr of age. Taken together, adhesion to C32 melanoma cells starts prior to that of rosette formation, immunoglobulin binding, or serum-induced agglutination.The incidence of Plasmodium falciparum malaria has been estimated to be 100 million new infections each year with 90% seen in tropical Africa.1 Estimates of malaria mortality vary from 1.5 to 2.7 million deaths annually affecting mainly children, with the two main causes of death being cerebral malaria and severe anemia.1-3 The current theories about the mechanisms leading to the development of cerebral and other forms of severe malaria are based on the fact that parasitized red blood cells (PRBC) sequester in the deep microvasculature of many organs and that excessive sequestration leads to vaso-occlusion, a histologic finding also seen at autopsy in the affected organs.4-9 Two forms of adhesive capacity have been identified that underlie the sequestration: cyto-adhesion to the vascular endothelium, 10-12 and rosette formation, the binding of uninfected red blood cells (RBC) to PRBC. [13][14][15][16] An in vitro correlation has been found between binding of PRBC to CD36-expressing cells and pulmonary disease, 17 and several studies have shown a strong association between the capacity in vitro to form rosettes and the severe forms of malaria. [18][19][20][21] Antibodies that block cytoadherence or disrupt rosettes seem important for development of the immunity that protects against severe disease. 18, 19 Taken together, it appears that the causation of severe malaria is at least partly due to various adhesive events that are modulated by anti-adhesive antibodies.In this study, two in vitro propagated strains of P. falciparum (FCR3S1 and TM284), selected either for rosette formation or cytoadherence to C32 melanoma cells, were investigated for their time course of adhesion. The parasites in culture...

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Studies on Malignant Malaria in Macedonia

Cited by 36 publications

References 0 publications

Pathophysiology of fatal falciparum malaria in African children.

Pathophysiology of fatal falciparum malaria in African children.

A Quantitative Analysis of the Microvascular Sequestration of Malaria Parasites in the Human Brain

The time course of cytoadhesion, immunoglobulin binding, rosette formation, and serum-induced agglutination of Plasmodium falciparum-infected erythrocytes.

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