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/ 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:

Davenport, Gregory C. ^[1]; Hittner, James B.  ^[2];

• Search DOE PAGES for author "Hittner, James B."
• Search DOE PAGES for ORCID "0000-0002-5766-9763"

Otieno, Vincent  ^[3];

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• Search DOE PAGES for ORCID "0000-0001-9805-3394"

Karim, Zachary  ^[4];

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• Search DOE PAGES for ORCID "0000-0002-8681-2872"

Mukundan, Harshini ^[5]; Fenimore, Paul W. ^[6]; Hengartner, Nicolas W. ^[6]; McMahon, Benjamin H. ^[6]; Kempaiah, Prakasha  ^[4];

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• Search DOE PAGES for ORCID "0000-0002-2901-0339"

Ong’echa, John M. ^[3]; Perkins, Douglas J.  ^[7]

• Search DOE PAGES for author "Perkins, Douglas J."
• Search DOE PAGES for ORCID "0000-0001-9390-6255"

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+ Show Author Affiliations

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:

Fri Jan 01 00:00:00 EST 2016

Research Org.:

Los Alamos National Lab (LANL), Los Alamos, NM (United States)

Sponsoring Org.:

USDOE National Nuclear Security Administration (NNSA); National Institutes of Health (NIH)

OSTI Identifier:

1259191

Alternate Identifier(s):

OSTI ID: 1626230

Grant/Contract Number:  

AC52-06NA25396; R01AI051305; D43TW005884

Resource Type:

Published Article

Journal Name:

Mediators of Inflammation

Additional Journal Information:

Journal Name: Mediators of Inflammation Journal Volume: 2016; Journal ID: ISSN 0962-9351

Publisher:

Hindawi Publishing Corporation

Country of Publication:

Country unknown/Code not available

Language:

English

Subject:

Cell Biology; Immunology