title: Relationship between inflammatory mediator patterns and anemia in HIV-1 positive and exposed children with Plasmodium falciparum malaria.
abstract: Anemia is the primary hematological manifestation of both Plasmodium falciparum malaria and HIV-1 in pediatric populations in sub-Saharan Africa. We have previously shown that HIV-1 positive and exposed children have greater risk of developing severe anemia (hemoglobin, Hb <6.0 g dL⁻¹) during acute malaria. However, enhanced severity of anemia was unrelated to either erythropoietic suppression or parasite-driven red blood cell hemolysis. To further explore mechanisms of anemia, circulating inflammatory mediators (IMs) were determined using a 25-plex bead array in P. falciparum-infected (Pf[+]) children (3-36 month, n = 194) stratified into three groups: HIV-1 negative (HIV-1[-]/Pf[+]); HIV-1 exposed (HIV-1[exp]/Pf[+]); and HIV-1 infected (HIV-1[+]/Pf[+]). IL-12, MIG/CXCL9, eotaxin/CCL11, and GM-CSF differed significantly and progressively increased across the groups (HIV-1[-]→HIV-1[exp]→HIV-1[+]). To further explore the relationship between the inflammatory milieu (i.e., cytokines, chemokines, and growth factors) and HIV-1 status, the large panel of IMs was reduced into discrete groups by principal component factor analysis. Of the six principal components that emerged, three components were significantly higher in the HIV-1 [+]/pf[+] and HIV[exp]/Pf[+] groups, demonstrating that inflammatory profiles differ according to HIV-1 status. Additional analyses exploring the relationship between the components and anemia revealed significant positive correlations between Hb and Component 3 (IL-1Ra, IL-7, IL-17, IFN-α, IFN-γ, MIG/CXCL9) in the HIV-1[-]/Pf[+] group, and Component 4 (IL-4, IL-5, IL-12, Eotaxin/CCL11) in HIV-1[+]/Pf[+] children. Further analyses of the HIV-1[+]/Pf[+] group revealed that IL-12 had the strongest association with anemia. Results presented here demonstrate that there are unique relationships between the inflammatory environment and anemia in HIV-1 positive and exposed children with malaria.
authors.affiliation: Center for Global Health, Department of Internal Medicine, University of New Mexico, Albuquerque, NM 87131-0001, USA.
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Davenport
authors.forename: James B
authors.initials: JB
authors.lastname: Hittner
authors.forename: Tom
authors.initials: T
authors.lastname: Were
authors.forename: John M
authors.initials: JM
authors.lastname: Ong'echa
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Perkins
mesh_terms: D000740:Anemia / Q000097:blood / Q000209:etiology / Q000276:immunology* / Q000503:physiopathology; D054413:Chemokine CCL11 / Q000097:blood; D054370:Chemokine CXCL9 / Q000097:blood; D002675:Child, Preschool; D015331:Cohort Studies; D060085:Coinfection / Q000276:immunology / Q000469:parasitology / Q000503:physiopathology / Q000821:virology; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D015658:HIV Infections / Q000150:complications / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D006679:HIV Seropositivity / Q000150:complications / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D018664:Interleukin-12 / Q000097:blood; D007630:Kenya; D016778:Malaria, Falciparum / Q000150:complications / Q000276:immunology* / Q000469:parasitology / Q000503:physiopathology; D008297:Male; D010963:Plasmodium falciparum / Q000276:immunology* / Q000302:isolation & purification; D012720:Severity of Illness Index
chemical_list: C515456:CCL11 protein, human; C080810:CXCL9 protein, human; D054413:Chemokine CCL11; D054370:Chemokine CXCL9; D016207:Cytokines; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor