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Title: Reduced Parasite Burden in Children with Falciparum Malaria and Bacteremia Coinfections: Role of Mediators of Inflammation

Bacteremia and malaria coinfection is a common and life-threatening condition in children residing in sub-Saharan Africa. We previously showed that coinfection with Gram negative (G[−]) enteric Bacilli and Plasmodium falciparum ( Pf [+]) was associated with reduced high-density parasitemia (HDP, >10,000 parasites/ μ L), enhanced respiratory distress, and severe anemia. Since inflammatory mediators are largely unexplored in such coinfections, circulating cytokines were determined in four groups of children ( n = 206 , aged <3 yrs): healthy; Pf [+] alone; G[−] coinfected; and G[+] coinfected. Staphylococcus aureus and non-Typhi Salmonella were the most frequently isolated G[+] and G[−] organisms, respectively. Coinfected children, particularly those with G[−] pathogens, had lower parasite burden (peripheral and geometric mean parasitemia and HDP). In addition, both coinfected groups had increased IL-4, IL-5, IL-7, IL-12, IL-15, IL-17, IFN- γ , and IFN- α and decreased TNF- α relative to malaria alone. Children with G[−] coinfection had higher IL-1 β and IL-1Ra and lower IL-10 than the Pf [+] group and higher IFN- γ than the G[+] group. To determine how the immune response to malaria regulates parasitemia, cytokine production was investigated with a multiple mediation model. Cytokines with the greatest mediational impact on parasitemia were IL-4, IL-10, IL-12, and IFN- γ . Results here suggest that enhanced immune activation, especially in G[−] coinfected children, acts to reduce malaria parasite burden.
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [5] ;  [6] ;  [6] ;  [6] ;  [4] ;  [3] ;  [7]
  1. Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA, Center for Global Health, Department of Internal Medicine, Division of Infectious Diseases, School of Medicine, University of New Mexico, Albuquerque, NM 87131, USA
  2. Department of Psychology, College of Charleston, Charleston, SC, USA
  3. University of New Mexico/KEMRI Laboratories of Parasitic and Viral Diseases, Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya
  4. Center for Global Health, Department of Internal Medicine, Division of Infectious Diseases, School of Medicine, University of New Mexico, Albuquerque, NM 87131, USA
  5. Chemistry Division, Los Alamos National Laboratory, Los Alamos, NM, USA
  6. Theoretical Biology Group, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM, USA
  7. Center for Global Health, Department of Internal Medicine, Division of Infectious Diseases, School of Medicine, University of New Mexico, Albuquerque, NM 87131, USA, University of New Mexico/KEMRI Laboratories of Parasitic and Viral Diseases, Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya
Publication Date:
OSTI Identifier:
1259191
Type:
Published Article
Journal Name:
Mediators of Inflammation
Additional Journal Information:
Journal Volume: 2016; Related Information: CHORUS Timestamp: 2016-08-18 14:25:35; Journal ID: ISSN 0962-9351
Publisher:
Hindawi Publishing Corporation
Sponsoring Org:
USDOE
Country of Publication:
Country unknown/Code not available
Language:
English