Plasma proteomic profiling identifies country-specific diversity in visceral leishmaniasis patients across East Africa
- 1University of York
Abstract
BackgroundVisceral leishmaniasis (VL) is the most severe form of leishmaniasis and is caused by parasites from the Leishmania donovani complex. VL is endemic in 54 countries, with East Africa (EA) accounting for [~]70% of the global burden. Therefore, there is a pressing need to prioritize VL research in EA. Transcriptomics analysis in rodent models and patients following treatment have shown that immune homeostasis is not restored by the end of treatment. However, comprehensive proteomic studies in VL remain scarce, and the few available studies were conducted outside EA.
Methodology/Principal FindingsAs a part of ImmStat@cure consortium, we used the Olink Reveal proximity extension assay to profile circulating proteins in VL patients from Ethiopia, Kenya and Sudan. By comparing patients at admission and 17 days after treatment with SSG-PM, we have identified a systemic Th1-cytotoxic inflammatory profile at admission, characterized by high abundance of IFN{gamma}, IL-1B, IL-6, and the granzymes A and B. Chemokines with high abundance included CXCL8/10/11, CCL3, CCL4, CCL8, CXCL8 and CCL20, consistent with the recruitment of monocytes, macrophages, T cells, and NK cells. There were also evidence of immune regulation/exhaustion, with high levels of PD1, PD-L2, IDO1 and KYNU. Although the immune profiles were similar at admission, country specific differences were observed after treatment. Kenyan patients exhibited a sustained inflammatory profile and signatures of myeloid recruitment, characterized by high levels of IL-1B, IL-6 , IL-12A, CXCL8, CCL2, CCL3, CCL4 ,CCL7 and CEBPB. Sudanese patients showed signatures associated with lymphocyte activation and immune regulation.
Conclusions/SignificanceThese results highlight the complexity of the immune changes associated with VL, identifying both core conserved profiles at admission and country-specific profiles after treatment. The data provided here will provide a valuable resource for future comparative studies across more diverse different geographic regions, for linkage studies that assess the impact of parasite genotype on immune / metabolic response and for use during the evaluation of new therapies against VL.
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BibTeX
@misc{cunha2026plasma,
title = {{Plasma proteomic profiling identifies country-specific diversity in visceral leishmaniasis patients across East Africa}},
author = {J. Cunha and A. Addisu and D. Matano and B. Younis and A. Bayiyana and R. Kumar and R. Tiwari and J. Engel and K. Hogg and R. Wiggins and W. Biwott and F. Osuna and C. Ichugu and A. J. Zeleke and E. Ayele and O. J. Sande and E. A. G. Khalil and H. M. H. Ibrahim and M. A. Mahmoud and A. I. B. Zakaria and B. Adiko and The Immstat@Cure Consortium and P. O'Toole and F. D'Alessio and C. J. N. Lacey and C. R. Engwerda and S. Sundar and J. Mbui and A. Hailu and M. Mbuchi and A. Musa and J. Olobo and P. M. Kaye},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.16.26365713},
url = {https://www.medrxiv.org/content/10.64898/2026.10.16.26365713v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Plasma proteomic profiling identifies country-specific diversity in visceral leishmaniasis patients across East Africa
AU - J. Cunha
AU - A. Addisu
AU - D. Matano
AU - B. Younis
AU - A. Bayiyana
AU - R. Kumar
AU - R. Tiwari
AU - J. Engel
AU - K. Hogg
AU - R. Wiggins
AU - W. Biwott
AU - F. Osuna
AU - C. Ichugu
AU - A. J. Zeleke
AU - E. Ayele
AU - O. J. Sande
AU - E. A. G. Khalil
AU - H. M. H. Ibrahim
AU - M. A. Mahmoud
AU - A. I. B. Zakaria
AU - B. Adiko
AU - The Immstat@Cure Consortium
AU - P. O'Toole
AU - F. D'Alessio
AU - C. J. N. Lacey
AU - C. R. Engwerda
AU - S. Sundar
AU - J. Mbui
AU - A. Hailu
AU - M. Mbuchi
AU - A. Musa
AU - J. Olobo
AU - P. M. Kaye
PY - 2026
DA - 2026/10/16
PB - medRxiv
DO - 10.64898/2026.10.16.26365713
UR - https://www.medrxiv.org/content/10.64898/2026.10.16.26365713v1
AB - BackgroundVisceral leishmaniasis (VL) is the most severe form of leishmaniasis and is caused by parasites from the Leishmania donovani complex. VL is endemic in 54 countries, with East Africa (EA) accounting for [~]70% of the global burden. Therefore, there is a pressing need to prioritize VL research in EA. Transcriptomics analysis in rodent models and patients following treatment have shown that immune homeostasis is not restored by the end of treatment. However, comprehensive proteomic studies in VL remain scarce, and the few available studies were conducted outside EA. Methodology/Principal FindingsAs a part of ImmStat@cure consortium, we used the Olink Reveal proximity extension assay to profile circulating proteins in VL patients from Ethiopia, Kenya and Sudan. By comparing patients at admission and 17 days after treatment with SSG-PM, we have identified a systemic Th1-cytotoxic inflammatory profile at admission, characterized by high abundance of IFN{gamma}, IL-1B, IL-6, and the granzymes A and B. Chemokines with high abundance included CXCL8/10/11, CCL3, CCL4, CCL8, CXCL8 and CCL20, consistent with the recruitment of monocytes, macrophages, T cells, and NK cells. There were also evidence of immune regulation/exhaustion, with high levels of PD1, PD-L2, IDO1 and KYNU. Although the immune profiles were similar at admission, country specific differences were observed after treatment. Kenyan patients exhibited a sustained inflammatory profile and signatures of myeloid recruitment, characterized by high levels of IL-1B, IL-6 , IL-12A, CXCL8, CCL2, CCL3, CCL4 ,CCL7 and CEBPB. Sudanese patients showed signatures associated with lymphocyte activation and immune regulation. Conclusions/SignificanceThese results highlight the complexity of the immune changes associated with VL, identifying both core conserved profiles at admission and country-specific profiles after treatment. The data provided here will provide a valuable resource for future comparative studies across more diverse different geographic regions, for linkage studies that assess the impact of parasite genotype on immune / metabolic response and for use during the evaluation of new therapies against VL.
ER -