A ll the manifestations of malarial illness are caused by the infection of the red blood cells by the asexual forms of the malaria parasite and the involvement of the red cells makes malaria a potentially multisystem disease, as every organ of the body is reached by the blood. A greater appreciation of the pfemp1 molecules important for the development of protective immunity and immunopathology is a prerequisite for the rational discovery and development of a safe and protective anti. Malaria caused by plasmodium species threatens 40% of worlds population. Here, although cerebral malaria, hypoglycaemia, and anemia form part of the picture, severe malaria is more commonly a multisystem disorder often with marked renal and hepatic dysfunction which are rare in children. This may be relevant to the etiology of burkitts lymphoma. The ins and outs of cerebral malaria pathogenesis ncbi. Immunopathogenesis of cerebral malaria sciencedirect. Pdf immunopathogenesis of cerebral malaria researchgate. Dba2j mice similarly inoculated developed a nonfatal cerebral malaria, with mild temporary cerebral symptoms, and died between days 15 and 22 from other malariarelated complications.
In contrast, il10 is regarded as necessary for suppressing severe pathology during plasmodium infection. Severe malarial anemia arises because of destruction of infected and uninfected erythrocytes and inappropriate erythropoiesis. Role of cytokines and adhesion molecules in malaria. Evolution of virulence in malaria journal of biology. Cerebral malaria is the most severe pathology caused by the malaria parasite, plasmodium falciparum. Cerebral malaria is a severe neuropathological complication of plasmodium falciparum infection. Clinical features and pathogenesis of severe malaria. Immunological processes in malaria pathogenesis nature. Because of the prevalence and severity of cerebral malaria, a better understanding of the underlying molecular mechanisms of its. Its principal feature is endothelial damage associated with the sequestration of plasmodium falciparum schizonts within the microvasculature of the brain. This contrasts with the more classical model with p. Beeson2 and kevin marsh1 1centre for geographic medicine research coast, kenya medical research institute wellcome trust collaborative programme, kili. Immunopathology of cerebral malaria infection and immunity. While they cannot provide protection against bloodstage parasites, they can cause immunopathology, thus leading to the severe manifestation of cerebral malaria.
The neuropathology of fatal cerebral malaria in malawian children. Pdl1 fusion protein protects against experimental cerebral. Cerebral malaria is one of a number of clinical syndromes associated with infection by human malaria parasites of the genus. Pdf specific depletion of ly6chi inflammatory monocytes. As many of the surface antigens of malaria parasites and the parasite proteins inserted into the plasma membrane of the infected red blood cell are polymorphic or exhibit clonal antigenic variation, it has been proposed that one may need to develop a diverse repertoire of antibodies capable of blocking parasite. The pathogenesis of cerebral malaria is poorly defined and progress in understanding the condition is severely hampered by the inability to study in detail, antemortem, the parasitological and immunological events within the brain that lead to the onset of clinical symptoms. Plasmodium berghei anka was tested for its usefulness as a model for cerebral malaria in inbred mouse strains a, a2g, aj, c57l, sjlj and swr. The pathogenic mechanisms leading to cerebral malaria are still poorly defined as studies have.
Cerebral malaria cm, mainly caused by plasmodium falciparum p. The war between the malaria parasite and the immune system. Cerebral malaria cm is a complex of syndromes relating to the presence of plasmodium falciparuminfected erythrocytes sequestering in the brain. This item appears in the following collections academic publications 177027 academic output radboud university. Immunopathology, extracellular vesicles, immunometabolism, and trained immunity article pdf available in. Pdf malaria is one of the most important global health problems, potentially affecting more than one third of the worlds population. Sequestration of plasmodiuminfected red blood cells irbcs in brain microvessels is a hallmark of cm pathology. Tissuespecific immunopathology during malaria infection. Parasite sequestration in murine brain microvasculature. The role of the spleen in the immunology of parasitic diseases, p. Morphological evidence of parasite sequestration in murine brain. Human cerebral malaria cm is a serious neurological condition that can lead to coma and death. Malaria is one of the most important global health problems, potentially affecting more than one third of the worlds population. We developed a novel model of maards with many similarities to human maards and without cerebral complications.
Cerebral malaria is a lifethreatening complication of malaria infection. It is clear that host immunopathology plays a central role, and a recent paper in bmc evolutionary biology suggests that the ability of the parasite to stimulate interleukin10 production is a major factor and speculates on its impact on the coevolution of host and parasite. There are two theories that seek to explain the pathogenesis of cerebral malaria, the mechanical obstruction hypothesis and the immunopathology hypothesis. The neuropathology of fatal cerebral malaria in malawian. Interleukin il 10, antiinflammatory cytokine, is known to inhibit the protective immune responses against malaria parasites and to be involved in exacerbating parasitemia during plasmodium infection.
Cerebral malaria, characterized by neurological symptoms, is a lifethreatening complication of malaria affecting over 500,000 young children in africa every year. New methods are needed to protect the host from injury. Clinical features and pathogenesis of severe malaria claire l. The serology of tropical splenomegaly syndrome and its relationship to malaria. The immunopathology of falciparum malaria has been linked to cyto. Malaria symptoms, treatment, causes, types, contagious. Here, we summarize the role of il10 during murine malaria infection, focusing. Immunology research and training centre, department of pathology, university of geneva, geneva, switzerland. Pathology of fatal and resolving plasmodium berghei. Pdf irgm3 contributes to immunopathology and is required. Malaria can affect the humoral immune response to unrelated antigens and infectious agents. American journal of respiratory and critical care medicine.
Morphological evidence of parasite sequestration in murine brain microvasculature article pdf available in infection and immunity 689. Immunopathology and dexamethasone therapy in a new model for malariaassociated acute respiratory distress syndrome philippe e. As our understanding of pathogenic responses to plasmodium parasites gathers momentum, the chance of a. Cerebral malaria pathogenesis is complex and incompletely under stood. Thus, some combination of these concepts seems necessary to explain the very complex pattern of changes seen. A suitable model was obtained in a or aj strain mice.
Mortality was 100% after five to eight days with brain haemorrhages occurring terminally. Cbat6 and balbc mice inoculated with plasmodium berghei anka strain pba died from cerebral malaria 68 days postinoculation. The main complications are severe malarial anemia, cerebral malaria cm, malariaassociated acute lung injury ali and its more severe form, malariaassociated acute respiratory distress syndrome maards. Evidence consistent with both ideas has accumulated from studies of the human disease and experimental models. During pregnancy there is some loss of acquired immunity to p. Pdf the ins and outs of cerebral malaria pathogenesis.
Cerebral malaria cm is the most common cause of death in severe malaria. To further probe a potential connection between tgf. The pathogenesis of severe malarial disease is not yet fully understood. Cerebral malaria cm is a deadly complication of plasmodium falciparum infection, yet its pathogenesis remains incompletely understood. R12 january 1998 with 118 reads how we measure reads. Cerebral malaria cm is a neurological complication of malarial infection and a large contributor to malarial fatalities, with a similar. A murine model that closely resembles human cerebral malaria is presented, in which characteristic features of parasite sequestration and inflammation in the brain are clearly demonstrable. Plasmodium berghei anka pba infection of c57bl6 mice leads to experimental cerebral malaria ecm that is commonly associated with serious t cell mediated damage. In other parasitic infection models, inflammatory monocytes have been shown to. Immunopathology of malaria europe pmc article europe pmc. The cerebralmalaria and severemalarialanaemia syndromes, in particular, seem to involve dysregulation of immune responses.
Morphological evidence of parasite sequestration in murine brain microvasculature jocelyn hearn,1 neil rayment,1 david n. In other parasitic infection models, inflammatory monocytes have been shown to regulate th1 responses but their role in ecm remains poorly defined, whereas neutrophils are reported to contribute to ecm immune pathology. Immunopathology and dexamethasone therapy in a new. Immunopathology of cerebral malaria article pdf available in memorias do instituto oswaldo cruz 87. Cerebral malaria cm is a lifethreatening neurological syndrome caused by plasmodium falciparum infection afflicting mainly children in africa. Pathophysiology, clinical presentation and treatment of. C57bl6f1 mice infected with plasmodium berghei anka developed typical neurological symptoms 7 to 8 days later and then died, although their parasitemias were below 20%. Although the mechanisms of this neurologic complication remain poorly understood, studies in an experimental model of cm suggest that a natural body protein seems to be a major cause of this deadliest complication of malaria, a finding that could point towards new. Specific depletion of ly6chi inflammatory monocytes. Current pathogenesis models implicate parasite and hostderived factors in impairing brain vascular endothelium bve integrity.
838 1498 695 20 956 1123 755 1203 1496 1483 1080 1648 503 1385 731 815 1412 1088 454 394 1518 543 634 1268 1114 925 1403 1431 1402 249 484 737 1306 942 1328 1378 930 773 972 1439 958 27 504 1010