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BMC Medicine
Published in: BMC Medicine 1/2019

Open Access 01-12-2019 | Malaria | Research article

Repeated clinical malaria episodes are associated with modification of the immune system in children

Authors: Yaw Bediako, Rhys Adams, Adam J. Reid, John Joseph Valletta, Francis M. Ndungu, Jan Sodenkamp, Jedidah Mwacharo, Joyce Mwongeli Ngoi, Domtila Kimani, Oscar Kai, Juliana Wambua, George Nyangweso, Etienne P. de Villiers, Mandy Sanders, Magda Ewa Lotkowska, Jing-Wen Lin, Sarah Manni, John W. G. Addy, Mario Recker, Chris Newbold, Matthew Berriman, Philip Bejon, Kevin Marsh, Jean Langhorne

Published in: BMC Medicine | Issue 1/2019

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Abstract

Background

There are over 200 million reported cases of malaria each year, and most children living in endemic areas will experience multiple episodes of clinical disease before puberty. We set out to understand how frequent clinical malaria, which elicits a strong inflammatory response, affects the immune system and whether these modifications are observable in the absence of detectable parasitaemia.

Methods

We used a multi-dimensional approach comprising whole blood transcriptomic, cellular and plasma cytokine analyses on a cohort of children living with endemic malaria, but uninfected at sampling, who had been under active surveillance for malaria for 8 years. Children were categorised into two groups depending on the cumulative number of episodes experienced: high (≥ 8) or low (< 5).

Results

We observe that multiple episodes of malaria are associated with modification of the immune system. Children who had experienced a large number of episodes demonstrated upregulation of interferon-inducible genes, a clear increase in circulating levels of the immunoregulatory cytokine IL-10 and enhanced activation of neutrophils, B cells and CD8+ T cells.

Conclusion

Transcriptomic analysis together with cytokine and immune cell profiling of peripheral blood can robustly detect immune differences between children with different numbers of prior malaria episodes. Multiple episodes of malaria are associated with modification of the immune system in children. Such immune modifications may have implications for the initiation of subsequent immune responses and the induction of vaccine-mediated protection.
Appendix
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Metadata
Title
Repeated clinical malaria episodes are associated with modification of the immune system in children
Authors
Yaw Bediako
Rhys Adams
Adam J. Reid
John Joseph Valletta
Francis M. Ndungu
Jan Sodenkamp
Jedidah Mwacharo
Joyce Mwongeli Ngoi
Domtila Kimani
Oscar Kai
Juliana Wambua
George Nyangweso
Etienne P. de Villiers
Mandy Sanders
Magda Ewa Lotkowska
Jing-Wen Lin
Sarah Manni
John W. G. Addy
Mario Recker
Chris Newbold
Matthew Berriman
Philip Bejon
Kevin Marsh
Jean Langhorne
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2019
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-019-1292-y

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