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, >1...

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Main Authors: Gregory C. Davenport, James B. Hittner, Vincent Otieno, Zachary Karim, Harshini Mukundan, Paul W. Fenimore, Nicolas W. Hengartner, Benjamin H. McMahon, Prakasha Kempaiah, John M. Ong’echa, Douglas J. Perkins
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2016/4286576
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author Gregory C. Davenport
James B. Hittner
Vincent Otieno
Zachary Karim
Harshini Mukundan
Paul W. Fenimore
Nicolas W. Hengartner
Benjamin H. McMahon
Prakasha Kempaiah
John M. Ong’echa
Douglas J. Perkins
author_facet Gregory C. Davenport
James B. Hittner
Vincent Otieno
Zachary Karim
Harshini Mukundan
Paul W. Fenimore
Nicolas W. Hengartner
Benjamin H. McMahon
Prakasha Kempaiah
John M. Ong’echa
Douglas J. Perkins
author_sort Gregory C. Davenport
collection DOAJ
description 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.
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spelling doaj-art-ea5dde96b7d34d9da89cc09e5348c31a2025-08-20T02:21:54ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/42865764286576Reduced Parasite Burden in Children with Falciparum Malaria and Bacteremia Coinfections: Role of Mediators of InflammationGregory C. Davenport0James B. Hittner1Vincent Otieno2Zachary Karim3Harshini Mukundan4Paul W. Fenimore5Nicolas W. Hengartner6Benjamin H. McMahon7Prakasha Kempaiah8John M. Ong’echa9Douglas J. Perkins10Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USADepartment of Psychology, College of Charleston, Charleston, SC, USAUniversity of New Mexico/KEMRI Laboratories of Parasitic and Viral Diseases, Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, KenyaCenter for Global Health, Department of Internal Medicine, Division of Infectious Diseases, School of Medicine, University of New Mexico, Albuquerque, NM 87131, USAChemistry Division, Los Alamos National Laboratory, Los Alamos, NM, USATheoretical Biology Group, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM, USATheoretical Biology Group, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM, USATheoretical Biology Group, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM, USACenter for Global Health, Department of Internal Medicine, Division of Infectious Diseases, School of Medicine, University of New Mexico, Albuquerque, NM 87131, USAUniversity of New Mexico/KEMRI Laboratories of Parasitic and Viral Diseases, Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, KenyaCenter for Global Health, Department of Internal Medicine, Division of Infectious Diseases, School of Medicine, University of New Mexico, Albuquerque, NM 87131, USABacteremia 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.http://dx.doi.org/10.1155/2016/4286576
spellingShingle Gregory C. Davenport
James B. Hittner
Vincent Otieno
Zachary Karim
Harshini Mukundan
Paul W. Fenimore
Nicolas W. Hengartner
Benjamin H. McMahon
Prakasha Kempaiah
John M. Ong’echa
Douglas J. Perkins
Reduced Parasite Burden in Children with Falciparum Malaria and Bacteremia Coinfections: Role of Mediators of Inflammation
Mediators of Inflammation
title Reduced Parasite Burden in Children with Falciparum Malaria and Bacteremia Coinfections: Role of Mediators of Inflammation
title_full Reduced Parasite Burden in Children with Falciparum Malaria and Bacteremia Coinfections: Role of Mediators of Inflammation
title_fullStr Reduced Parasite Burden in Children with Falciparum Malaria and Bacteremia Coinfections: Role of Mediators of Inflammation
title_full_unstemmed Reduced Parasite Burden in Children with Falciparum Malaria and Bacteremia Coinfections: Role of Mediators of Inflammation
title_short Reduced Parasite Burden in Children with Falciparum Malaria and Bacteremia Coinfections: Role of Mediators of Inflammation
title_sort reduced parasite burden in children with falciparum malaria and bacteremia coinfections role of mediators of inflammation
url http://dx.doi.org/10.1155/2016/4286576
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