title: Reduced Parasite Burden in Children with Falciparum Malaria and Bacteremia Coinfections: Role of Mediators of Inflammation.
abstract: 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/μL), 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-1β 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.affiliation: 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.
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Davenport
authors.affiliation: Department of Psychology, College of Charleston, Charleston, SC, USA.
authors.forename: James B
authors.identifier: 0000-0002-5766-9763
authors.initials: JB
authors.lastname: Hittner
authors.affiliation: University of New Mexico/KEMRI Laboratories of Parasitic and Viral Diseases, Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya.
authors.forename: Vincent
authors.identifier: 0000-0001-9805-3394
authors.initials: V
authors.lastname: Otieno
authors.affiliation: Center for Global Health, Department of Internal Medicine, Division of Infectious Diseases, School of Medicine, University of New Mexico, Albuquerque, NM 87131, USA.
authors.forename: Zachary
authors.identifier: 0000-0002-8681-2872
authors.initials: Z
authors.lastname: Karim
authors.affiliation: Chemistry Division, Los Alamos National Laboratory, Los Alamos, NM, USA.
authors.forename: Harshini
authors.initials: H
authors.lastname: Mukundan
authors.affiliation: Theoretical Biology Group, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM, USA.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Fenimore
authors.affiliation: Theoretical Biology Group, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM, USA.
authors.forename: Nicolas W
authors.initials: NW
authors.lastname: Hengartner
authors.affiliation: Theoretical Biology Group, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM, USA.
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: McMahon
authors.affiliation: Center for Global Health, Department of Internal Medicine, Division of Infectious Diseases, School of Medicine, University of New Mexico, Albuquerque, NM 87131, USA.
authors.forename: Prakasha
authors.identifier: 0000-0002-2901-0339
authors.initials: P
authors.lastname: Kempaiah
authors.affiliation: University of New Mexico/KEMRI Laboratories of Parasitic and Viral Diseases, Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya.
authors.forename: John M
authors.initials: JM
authors.lastname: Ong'echa
authors.affiliation: 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.
authors.forename: Douglas J
authors.identifier: 0000-0001-9390-6255
authors.initials: DJ
authors.lastname: Perkins
mesh_terms: D016470:Bacteremia / Q000097:blood / Q000382:microbiology* / Q000469:parasitology*; D002675:Child, Preschool; D060085:Coinfection / Q000097:blood* / Q000382:microbiology* / Q000469:parasitology*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007249:Inflammation / Q000097:blood / Q000382:microbiology / Q000469:parasitology; D016898:Interferon-alpha / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D019409:Interleukin-15 / Q000097:blood; D020381:Interleukin-17 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D015848:Interleukin-5 / Q000097:blood; D015851:Interleukin-7 / Q000097:blood; D016778:Malaria, Falciparum / Q000097:blood / Q000382:microbiology* / Q000469:parasitology*; D008297:Male; D012475:Salmonella / Q000472:pathogenicity; D013211:Staphylococcus aureus / Q000472:pathogenicity; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D016898:Interferon-alpha; D019409:Interleukin-15; D020381:Interleukin-17; D015848:Interleukin-5; D015851:Interleukin-7; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma