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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI044857-01A2
Application #
6194662
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Program Officer
James, Stephanie
Project Start
2000-09-01
Project End
2005-08-31
Budget Start
2000-09-01
Budget End
2001-08-31
Support Year
1
Fiscal Year
2000
Total Cost
$325,880
Indirect Cost
Name
Howard University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
056282296
City
Washington
State
DC
Country
United States
Zip Code
20059
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