The proposed research is designed to determine if excessive activity of the T helper lymphocyte type 1 (Th-1) immune response and decreased activity of the Th-2 immune response are involved in the pathogenesis of severe anemia in children with Plasmodium falciparum malaria. Severe malarial anemia (hemoglobin <5g/dL in a patient with a positive malaria smear) accounts for almost 10 percent of pediatric hospital admissions in southern Zambia and has a mortality of 9 percent despite aggressive therapy with blood transfusion and anti-malaria therapy. Th-1 cytokines suppress erythroid precursors, divert iron from hemoglobin synthesis to stores, and lead to moderate to severe anemia. MIF, produces by macrophages upon ingestion of P. falciparum-infected erythrocytes, is an immune modulator hat has a suppressive effect on erythropoiesis. This study hypothesizes that severe malarial anemia develops in a patient with an abnormal immune response pattern characterized by 1) the persistence or resurgence of a prominent Th-1 response in the presence of chronic malaria and 2) 2xcessive release of MIF. The proposed research will examine the Th-1 and Th-2 responses and MIF production in Zambian children with uncomplicated malaria. The nutritional status, underlying parasitic infections, and genotypes and numbers of infecting P. falciparum strains will also be characterized.
|Thuma, Philip E; van Dijk, Janneke; Bucala, Rick et al. (2011) Distinct clinical and immunologic profiles in severe malarial anemia and cerebral malaria in Zambia. J Infect Dis 203:211-9|
|Kassim, Olakunle O; Loyevsky, Mark; Elliott, Biaffra et al. (2005) Effects of root extracts of Fagara zanthoxyloides on the in vitro growth and stage distribution of Plasmodium falciparum. Antimicrob Agents Chemother 49:264-8|
|Geall, Andrew J; Baugh, John A; Loyevsky, Mark et al. (2004) Targeting malaria with polyamines. Bioconjug Chem 15:1161-5|
|Walcourt, Asikiya; Loyevsky, Mark; Lovejoy, David B et al. (2004) Novel aroylhydrazone and thiosemicarbazone iron chelators with anti-malarial activity against chloroquine-resistant and -sensitive parasites. Int J Biochem Cell Biol 36:401-7|
|Loyevsky, M; LaVaute, T; Allerson, C R et al. (2001) An IRP-like protein from Plasmodium falciparum binds to a mammalian iron-responsive element. Blood 98:2555-62|