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. Am. J. Hematol. 87:652–658, 2012. © 2012 Wiley Periodicals, Inc.

Enhanced T cell activation in Plasmodium falciparum malaria-infected human immunodeficiency virus-1 patients from Mozambique

“…Co-expression of CD38/HLA-DR on T cell subsets has previously been studied in both HIV-1/AIDS or malaria alone (Hunt et al 2003, Eggena et al 2006, Naniche et al 2011) and immune activation was considered a predictor of treatment failure in malaria patients (Eggena et al 2006). Malaria infection can present with a pro-inflammatory response and cytokine imbalance (Ayimba et al 2011, Davenport et al 2012. In this study, Pf/HIV co-infected patients exhibited the highest percentages of HLA-DR and CD38 on the CD3 + and CD8 + T lymphocytes, respectively.…”

“…The release of pro-inflammatory cytokines due to increased T cell activation during acute malaria has been implicated in the clinical complications and contributes to a disruption in the balance of effector/regulatory immune state (Ayimba et al 2011, Davenport et al 2012). In HIV-1/AIDS, it is well established that the VL is directly associated with CD8 + T cell activation (Benito et al 2004).…”

Coinfection HIV and Malaria in Department of Paediatrics of the University Hospital Souro Sanou

“…3. Antiretroviral therapy would promote the control of malaria infections, firstly, by restoring the antimalarial immune response and on the other, by the effect of certain molecules that could have an antimalarial effect in vitro, so protease inhibitors such as ritonavir and saquinavir inhibit parasite growth in vitro at clinically effective concentrations [24,25]. ARV treatment also by non-nucleoside reverse transcriptase inhibitors is associated with a decrease in the incidence of malarial attacks without ruling out the involvement of the effects of immune restoration.…”

Suppressed circulating bicyclo-PGE2 levels and leukocyte COX-2 transcripts in children co-infected with P. falciparum malaria and HIV-1 or bacteremia

“…Our laboratory has identified clinical predictors associated with enhanced pathogenesis of SMA [8] and inflammatory biomarkers of pediatric severe anemia [9]. Additional investigations revealed unique hematological predictors and inflammatory mediator patterns associated with the worsening anemia observed in children co-infected with falciparum malaria and HIV-1 [10,11]. Among the various effector molecules implicated in pathogenesis of severe malaria is cyclooxygenase (COX)-2-derived prostaglandin E 2 (PGE 2 ), a potential biomarker that is inversely associated with disease severity in cerebral malaria, malarial anemia, and malaria during pregnancy [12–14].…”