Claire M. Dunican (United Kingdom)

Imperial College London Medicine
I am a third year PhD student and Bioinformatician at Imperial College London whose primary research interests are in prognosis and outcome prediction in patients with a variety of infectious diseases using whole blood transcriptomic analysis. My research is also interested in Malaria specifically especially regarding the transcriptomics behind the different manifestations of this disease, particularly asymptomatic Plasmodium falciparum infections. My background is in Biology, later specialising in Bioinformatics during my Masters degree.

Presenter of 1 Presentation

 Conference Calendar

PARASITES UNDER THE RADAR: ASYMPTOMATIC INFECTION WITH PLASMODIUM FALCIPARUM ELICITS NO TRANSCRIPTOMIC HOST-RESPONSE (ID 174)

Session Name
2550 - PARALLEL SYMPOSIUM 13 : CONTROLLING ARTHROPOD TROPICAL INFECTIONS (ID 95)
Lecture Time
12:59 - 13:06
Room
Hall 02
Presenter

Abstract

Background

Naturally acquired immunity to malaria, which follows many previous infections, eventually allows individuals in endemic countries to tolerate infection without symptoms. However, asymptomatic infections do act as an undetected reservoir sustaining malaria transmission. Therefore, understanding the mechanisms enabling the asymptomatic state, and identifying biomarkers of asymptomatic infection could contribute to malaria elimination. This study analysed whole blood transcriptomes of Ghanaian children without malaria, with asymptomatic Plasmodium falciparum infection, and with symptomatic P. falciparum malaria to investigate the host response.

Methods

Children (n=37) were recruited in Obom, a high transmission peri-urban region in Ghana, frequency-matched for age and sex between groups. Illumina RNA-sequencing was undertaken from Paxgene whole blood samples. Differential gene expression analysis was conducted using DESeq2, with adjustment for variation in major leukocyte populations measured by flow-cytometry analysis (false discovery rate ≤ 5%).

Results

Comparison of symptomatic (n=9) vs uninfected (n=7) children revealed 735 differentially expressed genes, enriched in immune response pathways. In contrast, comparison of asymptomatic (n=21) vs uninfected (n=7) children showed no differentially expressed genes. We replicated these results by reanalysis of a published microarray dataset (Gene Expression Omnibus database ID: GSE1124).

Conclusions

These findings suggest that the asymptomatic state in P. falciparum infection is not the result of a suppressive response acting on-, or orchestrated by circulating blood cells. Parasites instead appear to be “under the radar”, not triggering any immune response at all. This suggests that host-response biomarkers of asymptomatic infection will not be successful and alternative mechanisms enabling and maintaining the asymptomatic state, including epigenetic modifications, should be investigated.

Clinical Trial Registration

My trial/study does not report the results of a controlled trial.

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