Abstract
To evaluate whether recovery from complicated malaria follows a common trajectory in terms of immunological mechanism or, rather, is highly individualized for each patient, we performed longitudinal gene expression profiling of whole blood. RNA sequencing (RNAseq) was performed on blood samples obtained from eight patients on four consecutive days between hospital admission and discharge. Six patients were infected with Plasmodium falciparum, and two with Plasmodium vivax; one patient was a pregnant woman infected with P. falciparum, who was hospitalized for several weeks. The characterization of blood transcript modules (BTM) and blood informative transcripts (BIT) revealed that patients’ responses showed little commonality, being dominated by the balance of gene activity relating to lymphocyte function, inflammation, and interferon responses specific to each patient. Only weak correlations with specific complicated malaria symptoms such as jaundice, thrombocytopenia, or anemia were observed. The differential expression of individual genes, including transcripts derived from the human leukocyte antigen (HLA) complex, generally reflected differences in the underlying immune processes. Although the results of this pilot study do not point to any single process that might provide a target for complicated malaria treatment or prevention or personalized medical strategies, larger patient series and more extensive blood sampling may allow the classification of patients according to their type of response in order to develop novel therapeutic approaches.
Highlights
Malaria is the most prevalent parasitic disease worldwide with over 200 million clinical cases and about 445,000 deaths reported globally every year [1]
Chaussabel and colleagues [23] found 28 modules that are conserved across datasets but characteristic of 11 different immune diseases. We reduced these to nine super-modules, or “blood informative transcript” (BIT) axes [24], after recognizing that there is a very high correlation between the PC1 scores in multiple cohorts of healthy people
In order to refine the contributions of natural killer (NK) cells, T-helper cells, and T-cytotoxic cells, we identified the top 10 genes differentially expressed between these three cell types in the single-cell RNA sequencing (RNAseq) dataset reported in reference [21]
Summary
Malaria is the most prevalent parasitic disease worldwide with over 200 million clinical cases and about 445,000 deaths reported globally every year [1]. While most clinical cases are characterized by classical signs and symptoms such as fever, chills, headache, and malaise that rapidly disappear upon early diagnosis and prompt treatment, failure to recover quickly can lead to a more severe and complicated disease that usually requires hospitalized management [2,3,4,5]. In these cases, multiple organs can suffer irreversible damage, leading to multi-systemic failure and eventually to death [6].
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