Longitudinal proteomics and single-cell transcriptomic data of P. falciparum malaria-infected travellers
https://doi.org/10.48723/cmgs-aj72
Comprehensive plasma proteomics and targeted single‑cell multi‑omics were generated from a longitudinal cohort of returning travelers treated for Plasmodium falciparum malaria. Plasma and peripheral blood mononuclear cells (PBMCs) were collected from symptomatic patients at Karolinska University Hospital after informed consent and followed with repeated sampling from acute disease up to one year post‑treatment in the absence of reinfection. Plasma protein profiling was performed in collaboration with the Human Protein Atlas using next‑generation affinity proteomics based on Proximity Extension Assay with NGS readout (Olink Explore 1536). Protein abundance was reported as Normalized Protein eXpression (NPX, log2 scale) after bridge normalization across batches. Proteins below the limit of detection in more than 70% of samples were excluded, resulting in a final dataset of 1,427 plasma proteins.
To infer potential cellular sources and targets of circulating proteins, targeted single‑cell multi‑omics profiling was performed on PBMCs from a subset of donors with overlapping time points. Gene expression of 399 immune‑related genes and 29 cell‑surface proteins was assessed using BD Rhapsody with AbSeq. Libraries were sequenced on a NovaSeq 6000 platform and processed using the BD Targeted Analysis Pipeline, and downstream analyses were conducted in R using Seurat. In addition, a publicly available scRNA‑seq dataset from an independent malaria cohort was reanalyzed to validate and extend the findings. Integrated proteomic and single‑cell analyses were used to stratify patients into subgroups associated with malaria disease severity.
The dataset consists of two data modalities:
Plasma proteomics: Olink NPX values for 132 samples across 1,427 proteins
PBMC single‑cell multi‑omics: targeted gene expression and AbSeq protein data from 12 samples
Parts of the plasma proteomics data are available in aggregated form through the Human Protein Atlas Disease Atlas. An interactive Shiny application accompanies the associated publication (Lautenbach et al., Immunity, 2025) to enable exploratory data analysis.
The dataset consists of 2 files:
Part1: Plasma proteomics (Olink PEA with NGS readout - Explore 1536)
File: Plasma_proteomics/Explore1536_tidy_long.rds (709 kB)
Part2: Targeted single-cell transcriptomics data (BD Rhapsody scRNA‑seq + AbSeq)
- Seurat object
File: MalariaTraveler_RhapsodyAbSeq_Cell_Calling_qc_cca_wnn_clustering_annotated_clean.rds (507.2 MB)
Documentation files
Documentation files
Citation and access
Citation and access
Data access level:
Creator/Principal investigator(s):
Research principal:
Data contains personal data:
Yes
Type of personal data:
Health data
Code key exists:
Yes
Sensitive personal data:
Yes
Citation:
Language:
Method and outcome
Method and outcome
Unit of analysis:
Population:
The Malaria Immunology Traveler Cohort is an ongoing, prospective study of adults diagnosed with acute Plasmodium falciparum malaria after returning from travel to malaria‑endemic regions. Participants are enrolled at the time of diagnosis and followed longitudinally, with repeated sampling from the acute phase through up to one year of recovery.
In the present analysis, 72 returning travelers were included; this group represents a substantial subset of the larger, continuously expanding cohort.
Time method:
Study design:
- Cohort study: Prospective
- Cohort study
- Observational study
Description of study design:
Adults diagnosed with acute Plasmodium falciparum malaria at Karolinska University Hospital (Stockholm, Sweden) between 2011 and 2021 were enrolled in a prospective cohort study and followed with repeated sampling for one year. Plasma proteomic profiling was performed during the acute episode (Acute, n = 72) and, in subsets of participants, approximately 10 days after treatment (Day 10, n = 27) and 12 months later (Month 12, n = 33). Targeted single‑cell transcriptomics was performed on PBMCs from four participants (two primary infected and two previously exposed) at all three time points (Acute, Day 10, Month 12).
Time period(s) investigated:
Number of individuals/objects:
72
Samples/material - Existing from scientific collection/biobank
Samples/material - Existing from scientific collection/biobank
Name:
Stockholms medicinska biobank (biobank no. 914) - Provsamlingen "Immune activation in malaria and other infections” (Bbk2024)
Type(s) of sample:
Peripheral blood (blood plasma, peripheral blood mononuclear cells (PBMCs), packed cells)
Data collection - Measurements and tests
Data collection - Measurements and tests
Mode of collection:
Measurements and tests
Source of the data:
- Biological samples
Geographic coverage
Geographic coverage
Geographic location:
Administrative information
Administrative information
Responsible department/unit:
Department of Medicine, Solna [K2]
Ethical Review
Ethical Review
Reviewer:
- Stockholm Ethical Review Board
Registration number:
2006/893-31/4, 2013/550-32, 2015/2200-32, 2016/1940/32, 2018/2354-32, 2019-03436, 2020-00859, 2020-04147, 2024-00374-02
Ethical review information:
The prospective studies were conducted at the Karolinska University Hospital in Stockholm, Sweden, with ethical approval from the Ethical Review Board in Stockholm and the Swedish Ethical Review Authority (Malaria immunology cohort: Dnr 2006/893-31/4, 2013/550-32, 2015/2200-32, 2016/1940/32, 2018/2354-32, 2019-03436, 2020-00859, 2020-04147, 2024-00374-02. All participants gave written informed consent.
Funding
Funding
Funding agency:
- Swedish Research Council
Opens a new window at ror.org.
ROR
Award number:
2024-06343_VR
Award title:
Malaria treatment outcomes in travelers- addressing emerging drug resistance
Funding information:
Malaria is a potentially severe and fatal disease. Artemisinin combination therapy (ACT) is the first line therapy for malaria. Alarming emergence of resistance to artemisinin and partner drugs is now reported from Sub-Saharan Africa. Understanding treatment outcomes and identifying drug resistant markers could guide management and development of new treatment strategies. The purpose of this preparatory study is to plan: 1) a nationwide prospective treatment efficacy study using a new standardized follow-up protocol for all malaria patients in Sweden for detecting treatment failures, and 2) to plan a comprehensive prospective study in adults treated for Plasmodium falciparum malaria with more extensive sampling to assess parasite clearance time in relation to antimalarial drug concentrations, host immunity and parasite genomics. Within the preparatory study, we will assess current practice of diagnostics and management of malaria across Sweden. Moreover, we will perform a retrospective review of treatment outcomes since ACT was introduced, and also perform a pilot analysis of resistance mutations in available archived samples. The project involves experts in infectious diseases, pediatrics, microbiology and pharmacology; and the aim is to establish a nationwide collaborative network including all treating clinics. The findings from this project will lead to improved management and monitoring of malaria in travelers, and could also inform treatment strategies in endemic areas.
Topic and keywords
Topic and keywords
CESSDA topic classification:
Swedish Standard Classification of Research Subjects 2025:
Relations
Relations
Is supplemented by:
Is supplement to:
Publications
Publications
Citation:
Lautenbach, M. J., Wyss, K., Yman, V., Foroogh, F., Satarvandi, D., Mousavian, Z., Sondén, K., Wang, J., Alvez, M. B., Bergström, S., Nilsson, P., Edfors, F., Brodin, P., Uhlén, M., Sundling, C., & Färnert, A. (2025). Systems analysis of clinical malaria reveals proteomic perturbation and innate-adaptive crosstalk linked to disease severity. In Immunity. https://doi.org/10.1016/j.immuni.2025.06.014
SwePub:
Metadata
Metadata
Version 1
