Volume 13 Supplement 1

Challenges in malaria research: Core science and innovation

Open Access

Co-infection with Schistosoma haematobium modulates the gene expression profile of malaria infection in schoolchildren in Gabon

  • Katie Ewer1,
  • Julius Muller1,
  • Marielle Haks2,
  • Marguerite Massinga Loembe3,
  • Maria Yazdanbakhsh3,
  • Magali Matsumiya1,
  • Edwin Quinten2,
  • Tom Ottenhoff2,
  • Peter Kremsner4,
  • Adrian Hill1,
  • Hermelijn Smits2 and
  • Akim Adegnika3
Malaria Journal201413(Suppl 1):P30

https://doi.org/10.1186/1475-2875-13-S1-P30

Published: 22 September 2014

Background

Helminths and malaria parasites inhabit the same geo graphical areas and coinfection is frequently observed. The immunological interaction between helminth and malaria infections is highly relevant to disease control and elimination, yet is poorly understood and understudied. Chronic helminth infection causes immune hyporesponsiveness and stimulates anti-inflammatory cytokine production, which in turn modulates the host immune response to malaria. In epidemiological studies, many data are conflicting with some reporting protective effects against malaria for Ascaris lumbricoides and Schistosoma haematobium while infection with hookworm or S. mansoni may increase the incidence of malaria and worsen pathology.

Materials and methods

We undertook a prospective study of schoolchildren aged 5-16 in an area endemic for schistosomiasis near Lambaréné in Gabon. 425 children were recruited and demographic data was collected. Laboratory analysis for P. falciparum malaria infection (thick blood smear and rapid test) and S. haematobium infection (urine microscopy) was performed and treatment was provided to infected children. Children were followed up locally for malaria-like symptoms, actively for two months and passively for a further 2 years. At recruitment, whole blood was collected into Paxgene tubes from a subset of children for transcriptional profiling among uninfected (n = 12), S. haematobium infected (n = 16), malaria infected (asymptomatic, n = 8) or coinfected (n = 13) children. RNA was extracted, amplified and hybridized to Illumina HT12v4 microarrays.

Results

In the full cohort age, gender and schistosomiasis were not associated with malaria and malaria incidence among these schoolchildren was 0.4 episodes per person per year. Analysis of the microarray data revealed monoinfection with either S. haematobium or malaria resulted in relatively insignificant changes to the transcriptome relative to healthy controls at the 10% false discovery level. There was also no difference in gene expression profile between healthy controls and coinfected children. However, between malaria infected and coinfected children there were 240 differentially expressed genes with 180 genes upregulated and 60 downregulated in the coinfected group. Specific genes of relevance to malaria infection, including CD8a, were significantly downregulated in malaria-infected compared to coinfected children. Pathway analysis revealed substantial modulation of gene expression in defence and immune responses and in particular modulation of genes in the Fcγ-receptor-mediated phagocytosis pathway.

Conclusions

Confirmatory experiments are underway to confirm these intriguing insights into the immunomodulatory effect of S. haematobium on P. falciparum malaria in a key population for public health intervention.

Declarations

Acknowledgements

This work was funded by the IDEA project, the European Commission 7th Framework Program.

Authors’ Affiliations

(1)
The Jenner Institute, University of Oxford
(2)
Leiden University Medical Centre
(3)
Centre de Recherches Médicale de Lambaréné, Fondation Internationale de l’Hôpital Albert Schweitzer
(4)
Institut für Tropenmedizin

Copyright

© Ewer et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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