Malaria, erythrocytic infection, and anemia.
Malaria is a major world health problem. It results from infection of parasites belonging to the genus Plasmodium. Plasmodium falciparum and Plasmodium vivax cause the major human malarias, with P falciparum being the more virulent. During their blood stages of infection, both P falciparum and P vivax induce anemia. Severe malarial anemia caused by P falciparum is responsible for approximately a third of the deaths associated with disease. Malarial anemia appears to be multi-factorial. It involves increased removal of circulating erythrocytes as well as decreased production of erythrocytes in the bone marrow. The molecular mechanisms underlying malarial anemia are largely unknown. Over the last five years, malaria parasite ligands have been investigated for their remodeling of erythrocytes and possible roles in destruction of mature erythrocytes. Polymorphisms in cytokines have been associated with susceptibility to severe malarial anemia: these cytokines and malaria "toxins" likely function by perturbing erythropoiesis. Finally a number of co-infections increase susceptibility to malarial anemia, likely because they exacerbate inflammation caused by malaria. Because of the complexities involved, the study of severe malarial anemia may need a "systems approach" to yield comprehensive understanding of defects in both erythropoiesis and immunity associated with disease. New and emerging tools such as (i) mathematical modeling of the dynamics of host control of malarial infection, (ii) ex vivo perfusion of human spleen to measure both infected and uninfected erythrocyte retention, and (iii) in vitro development of erythroid progenitors to dissect responsiveness to cytokine imbalance or malaria toxins, may be especially useful to develop integrated mechanistic insights and therapies to control this major and fatal disease pathology.
Haldar
Kasturi
K
Center for Rare and Neglected Diseases, University of Notre Dame, South Bend, IN, USA. khaldar@nd.edu
Mohandas
Narla
N
D000740:Anemia / Q000209:etiology*; D000818:Animals; D002648:Child; D016207:Cytokines / Q000378:metabolism; D004912:Erythrocytes / Q000469:parasitology*; D004920:Erythropoiesis; D006790:Host-Parasite Interactions; D006801:Humans; D007249:Inflammation; D008288:Malaria / Q000097:blood* / Q000150:complications / Q000276:immunology / Q000469:parasitology; D044342:Malnutrition / Q000097:blood / Q000150:complications; D051379:Mice; D018512:Parasitemia / Q000097:blood* / Q000150:complications / Q000276:immunology; D010274:Parasitology / Q000379:methods; D010961:Plasmodium / Q000276:immunology / Q000502:physiology; D015800:Protozoan Proteins / Q000097:blood / Q000276:immunology / Q000502:physiology; D013154:Spleen / Q000503:physiopathology
D016207:Cytokines; D015800:Protozoan Proteins