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Transcriptomic Profiling of Blood-Stage Plasmodium falciparum in Children with Severe Malarial Anemia

ABSTRACT: Malaria is a major global health threat, with millions of cases and hundreds of thousands of deaths reported annually, primarily in sub-Saharan Africa. Children under five years of age residing in holoendemic Plasmodium falciparum transmission regions are the most vulnerable to malaria, accounting for vast majority of cases and mortality. The major clinical manifestation of severe malaria in these children is severe malarial anemia [SMA, hemoglobin (Hb)<6.0 g/dL]. The molecular mechanisms underlying SMA pathogenesis, particularly the contribution to this disease process of P. falciparum gene activities at transcriptomic levels, remain largely unexplored. As such, the overall objective of the study was to profile the blood-stage Plasmodium falciparum transcriptome in children with SMA. To achieve this goal, we performed RNAseq on total RNA from peripheral blood samples of 60 pediatric malaria patients (3-36 months) with non-SMA (Hb≥6.0 g/dL, n=40) and SMA (n=20) at enrollment. The RNA reads were mapped to the P. falciparum reference genome (PfKE01). Diffentially expressed genes (DEGs) in SMA relative to non-SMA and relevant biological pathways in P. falciparum were identified. In addition, the performance of the expressed parasite genes in predicting SMA was assesed. These findings promote the identification of potential parasite-derived biomarkers and therapeutic targets for improving SMA management.

ORGANISM(S): Plasmodium falciparum

PROVIDER: GSE316842 | GEO | 2026/06/07

REPOSITORIES: GEO

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Project description:Malaria represents a major public health problem in Africa [1]. In the East African highlands, even in high-altitude areas previously considered too cold to support vector population and parasite transmission [2], frequent malaria epidemics have been reported since the 1980M-bM-^@M-^Ys [3]. Plasmodium falciparum infections have been detected in areas as high as 1,600-2,400m above sea level in Africa [4], albeit there is a marked gradient of parasite prevalence along the altitude transect [5-7]. Both the historical absence of malaria in the African highlands and now the intensive malaria control efforts put in place after the recent outbreaks have reduced malaria prevalence and incidence [8], rendering the East African highlands particularly prone to epidemic malaria due to the lack of the protective immunity, and causing significant human mortality amongst all age groups [9]. Therefore, malaria transmission monitoring in the East African highlands becomes a particularly important public health issue.Despite the overall lower immunity of the population in these historically malaria-free areas, the many successive outbreaks since the 1980M-bM-^@M-^Ys may have generated some level of immunity against P. falciparum amongst highland residents. The antibody response to Plasmodium is cumulative and long lasting, developing after repeated exposures to the parasite and persisting for months or years after infection was resolved. The antibody response to Plasmodium varies amongst individuals of different age groups (i.e. toddlers, children and adults) as well as amongst individuals of same age groups from areas of different parasite prevalence [10]. The repertoire of targets of the antibody response also expands after multiple infections, with the number of recognized antigens being correlated to parasite prevalence, age and immunity to clinical malaria [11,12]. Serological studies bring forth indirect evidence of human exposure to the parasite, and can reliably assess its prevalence and transmission intensity in an endemic area [13-15]. However, the vast majority of serological studies of malaria have been, hereto, limited to a small number of the parasiteM-bM-^@M-^Ys antigens. The work we present here is an expansion of the study published by Badu et al. [16], in which the antibody response to the 19kDa fragment of merozoite surface protein 1 (MSP-119) was examined in populations from two endemic areas in the western Kenyan highlands. There, the tremendous variations of malaria transmission intensity in a small spatial scale are caused by substantial differences in altitude, topography and other environmental conditions [6,7,17,18]. We now expand our antibody profiling survey to include 854 P. falciparum proteins by using high-throughput proteomic microarray technology. Protein microarrays have been used to explore the humoral response to P. falciparum in other African settings [19-24], but this is the broadest characterization of the antibody responses of the population of western Kenyan highlands to date. In the present study we: i) determined the serological reactivity against P. falciparum (Pf) in subjects residing in a low transmission area, and detected hotspots of transmission; ii) examined the dynamics of antibody response to hundreds of Pf proteins generated by sera from toddlers, older children and adults residing in two endemic areas differing in transmission intensities, during two distinct malaria seasons, and compared the intensity, breadth and antigenic targets of these responses; and iii) identified candidate Pf antigenic markers that could provide more sensitive serological surveillance to detect micro-geographic variations in malaria transmission levels and differentiate hotspots of infection in low endemic areas. (references provided in the 'readme.txt') Antibody profiling was performed on sera from residents of western Kenyan highlands against Plasmodium falciparum. One-hundred and ten age-stratified serum samples collected during the dry and the wet seasons, from residents of two locations with differing parasite transmission levels (uphill and valley bottom), and 10 unexposed USA controls were probed on a protein microarray displaying 854 unique proteins of P. falciparum.

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Transcriptomic Profiling of Blood-Stage Plasmodium falciparum in Children with Severe Malarial Anemia

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