Blood signatures for second stage Human African Trypanosomiasis: A transcriptomic approach.

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Abstract Background Rhodesiense sleeping sickness is caused by infection with T. b rhodesiense parasites resulting in an acute disease that is fatal if not treated in time. The global impact of active T. b rhodesiense infection on the patient’s immune response in the early and late stages of the disease is not known. Results We previously described the transcriptomes of T. b rhodesiense from infected early stage blood (n=3) and late stage CSF (n=3) samples from Eastern Uganda. We here identify human transcripts that were differentially expressed (padj < 0.05) in the early stage blood versus healthy controls (n=3) and early stage blood versus late stage CSF. Differential expression in infected blood showed an enrichment of innate immune response genes whereas that of the CSF showed enrichment for anti-inflammatory and neuro-degeneration signalling pathways. We also identified genes (C1QC, MARCO, IGHD3-10) that were up-regulated (log 2 FC > 2.5) in both the blood and CSF. Conclusion The data yields insights into the host’s response to T. b rhodesiense parasites in the blood and central nervous system. We identified key pathways and signalling molecules for the predominant innate immune response in the early stage infection; and anti-inflammatory and neuro-degeneration pathways associated with sleep disorders in second stage infection. We further identified potential blood biomarkers that can be used for diagnosis of late stage disease without the need for lumbar puncture.

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