Amplification of cytoadherence in cerebral malaria: towards a more rational explanation of disease pathophysiology

Hommel, M.

doi:10.1080/00034983.1993.11812821

Cited by 33 publications

(19 citation statements)

References 42 publications

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“…Adults living in malaria endemic areas have normally been exposed to repeated infections with Plasmodium falciparum and are, therefore, clinically immune to the disease [1,2]. However, this is not true in the case of pregnant women and the disease is more pronounced in primigravid women than in multigravidas.…”

Section: Introductionmentioning

confidence: 99%

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Khattab

Reinhardt

Staalsøe

et al. 2004

Malar J

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Background: Pregnancy-associated malaria (PAM) is caused by Plasmodium falciparum-infected erythrocytes that can sequester in placental intervillous space by expressing particular variant surface antigens (VSA) that can mediate adhesion to chondroitin sulfate A (CSA) in vitro. IgG antibodies with specificity for the VSA expressed by these parasites (VSA PAM ) are associated with protection from maternal anaemia, prematurity and low birth weight, which is the greatest risk factor for death in the first month of life.

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Section: Introductionmentioning

confidence: 99%

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Khattab

Reinhardt

Staalsøe

et al. 2004

Malar J

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“…During the past decade, a number of studies have shown that IRBC sequestration is mediated by the binding of P. falciparum erythrocyte membrane protein 1, an antigenic var gene family protein expressed on the surface of IRBC, to the host endothelial cell adhesion molecules (23,25). It is thought that adherence of IRBC results in capillary obstruction and induction of proinflammatory cytokines locally in response to toxic parasite factors, resulting in tissue damage and clinical manifestations (10,15,21,23,25,26). Adults in areas where malaria is endemic, however, have natural immunity against developing severe malaria, which is acquired in response to repeated infections with P. falciparum (3,10,30).…”

mentioning

confidence: 99%

“…It is thought that adherence of IRBC results in capillary obstruction and induction of proinflammatory cytokines locally in response to toxic parasite factors, resulting in tissue damage and clinical manifestations (10,15,21,23,25,26). Adults in areas where malaria is endemic, however, have natural immunity against developing severe malaria, which is acquired in response to repeated infections with P. falciparum (3,10,30). A significant component of the protective immunity appears to be due to the anti-IRBC adhesion antibody response, which can limit IRBC sequestration to microvascular endothelia.…”

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confidence: 99%

Gravidity-Dependent Production of Antibodies That Inhibit Binding ofPlasmodium falciparum-Infected Erythrocytes to Placental Chondroitin Sulfate Proteoglycan during Pregnancy

et al. 2001

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During pregnancy, Plasmodium falciparum-infected erythrocytes sequester in the placenta by adhering to chondroitin 4-sulfate, creating a risk factor for both the mother and the fetus. The primigravidae are at higher risk for placental malaria than the multigravidae. This difference in susceptibility has been attributed to the lack of antibodies that block the adhesion of infected erythrocytes to placental chondroitin 4-sulfate in primigravid women. However, recent results show that many primigravidae at term have antibody levels similar to those of multigravidae, and thus the significance of antiadhesion antibodies in providing protection against malaria during pregnancy remains unclear. In this study, we analyzed plasma samples from women of various gravidities at different gestational stages for antiadhesion antibodies. The majority of women, regardless of gravidity, had similar levels of antibodies at term. Most primigravidae had low levels of or no antiadhesion antibodies prior to ϳ20 weeks of pregnancy and then produced antibodies. Multigravidae also lacked antibodies until ϳ12 weeks of pregnancy, but thereafter they efficiently produced antibodies. In pregnant women who had placental infection at term, higher levels of antiadhesion antibodies correlated with lower levels of placental parasitemia. The difference in kinetics of antibody production between primigravidae and multigravidae correlated with the prevalence of malaria in these groups, suggesting that antibodies are produced during pregnancy in response to placental infection. The early onset of efficient antibody response in multigravidae and the delayed production to antibodies in primigravidae appear to account for the graviditydependent differential susceptibilities of pregnant women to placental malaria.

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“…Thus, sequestration depends also on the susceptibility of the host to endotoxins, the subsequent regulation of adhesion molecules, and the host's level of immunity (4). A key role is played by TNF.…”

Section: Discussionmentioning

confidence: 99%

In vivo sequestration of Plasmodium falciparum-infected human erythrocytes: a severe combined immunodeficiency mouse model for cerebral malaria.

Willimann

Matile

Weiss

et al. 1995

The Journal of Experimental Medicine

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SummaryCerebral malaria is a fatal complication of infection by Plasmodiumfakiparum in man. The neurological symptoms that characterize this form of malarial disease are accompanied by the adhesion of infected erythrocytes to the vasculature of the brain. To study this phenomenon in vivo, an acute phase severe combined immunodeficiency (SCID) mouse model was developed in which sequestration of P.fakiparum-infected human erythrocytes took place. During acute cerebral malaria in humans, the expression of intercellular adhesion molecule-1 (ICAM-1) is induced in vascular endothelium by inflammatory reactions. Acute phase ICAM-1 expression can also be obtained in SCID mice. The endothelium of the midbrain region was the most responsive to such inflammatory stimulus. It is noteworthy that the reticular formation in the midbrain controls the level of consciousness, and loss of consciousness is a symptom of cerebral malaria. We found that infected human erythrocytes were retained 24 times more than normal erythrocytes in ICAM-1-positive mouse brain. Sequestration to the brain was reduced by anti-ICAM-1 antibodies. These in vivo results were confirmed by the binding of P. fakiparum-infected erythrocytes to the ICAM-l-positive endothelium in tissue sections of mouse brain. We conclude that the SCID mouse serves as a versatile in vivo model that allows the study ofP.fakiparum-infected erythrocyte adhesion as it occurs in human cerebral malaria. Upregulation of ICAM-1 expression in the region of the midbrain correlates with increased retention of malaria-infected erythrocytes and with the symptoms of cerebral malaria.p , lasmodium falciparum, one of the four plasmodium spedes that infect man, produces a fulminant disease that can lead to severe cerebral symptoms. Every year, this parasite causes about 250 million clinical cases of malaria (1). Approximately 2 million individuals, mainly children under 5 years of age, die from the main complications, which are cerebral malaria and severe anemia. A special feature of P. falciparum pathology is the absence of mature intraerythrocytic stages of the parasite in the circulating blood. Mature forms are found attached to the lining of microvessels in peripheral organs. This adhesion of infected erythrocytes to the vascular endothelium is called sequestration. Clinically severe neurological symptoms correlate with a much higher frequency of sequestered parasitized erythrocytes in the brain vasculature compared to other organs (2).Sequestration is thought to depend on differences between P.fakiparum strains leading to the expression of different erythrocyte surface molecules mediating adhesion to endothelia, as well as variation in the production of endotoxins eliciting a TNF-ot response by host macrophages (3). Thus, sequestration depends also on the susceptibility of the host to endotoxins, the subsequent regulation of adhesion molecules, and the host's level of immunity (4). A key role is played by TNF. Its plasma concentration levels are elevated in patients with fatal cerebral m...

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Amplification of cytoadherence in cerebral malaria: towards a more rational explanation of disease pathophysiology

Cited by 33 publications

References 42 publications

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Gravidity-Dependent Production of Antibodies That Inhibit Binding ofPlasmodium falciparum-Infected Erythrocytes to Placental Chondroitin Sulfate Proteoglycan during Pregnancy

In vivo sequestration of Plasmodium falciparum-infected human erythrocytes: a severe combined immunodeficiency mouse model for cerebral malaria.

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