Whole-genome characterization of Plasmodium falciparum population structure and drug resistance across Uganda and neighboring countries
- 1Department of Immunology and Molecular Biology, Makerere University College of Health Sciences, Kampala, Uganda
Abstract
Uganda has one of the world's highest malaria burdens, but parasite population structure and connectivity have not been characterized nationally with whole-genome data. We analyzed 249 monoclonal Plasmodium falciparum genomes from 26 sentinel sites across Uganda in 2023 and compared them with publicly available genomes from five neighboring countries. Genetic diversity was high and differentiation low in Uganda, but identity-by-descent detected limited structure. This was most pronounced in the low-transmission southwest, where parasites shared ancestry and recent relatedness with isolates from western Tanzania. Selection scans identified signals at loci associated with resistance to artemisinins and their partner drugs, and to chloroquine and antifolates. The strongest signal was at PfPX1 where the PIN haplotype (L1222P, M1701I, D1705N) reached 70% prevalence nationwide, but selection was carried by PIN haplotypes that had additionally acquired D384A, largely confined to northern and eastern Uganda. A second substitution at the same codon, D384Y, formed a haplotype shared across the Tanzanian border. PfKelch13 variants were partitioned across multiple backgrounds, consistent with repeated independent emergence, and C469Y was enriched on the PfPX1 D384A-PIN background. These genomes provide a 2023 baseline for tracking potential mediators of drug resistance and support coordinated genomic surveillance across Uganda and its neighbors.
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BibTeX
@misc{kiyaga2026wholegenome,
title = {{Whole-genome characterization of Plasmodium falciparum population structure and drug resistance across Uganda and neighboring countries}},
author = {S. Kiyaga and M. Mbabazi and T. Katairo and V. Asua and F. D. Semakuba and B. Nsengimaana and S. Tukwasibwe and I. Wiringilimaana and J. Nakasaanyaa and J. Mulondoa and E. Watyekele and C. S. Maiteki and D. P. Katete and J. N. Nabende and D. Jjingo and G. Mboowa and C. Batte and N. Sam and M. R. Kamya and B. B. Agaba and I. Ssewanyana and A. Aranda-Diazi and F. V. Ajogbasile and M. Davlieva and G. Dorsey and P. J. Rosenthal and M. D. Conrad and B. Greenhouse and N. J. Hathaway and J. Briggs},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.27.754784},
url = {https://www.biorxiv.org/content/10.64898/2026.09.27.754784v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Whole-genome characterization of Plasmodium falciparum population structure and drug resistance across Uganda and neighboring countries
AU - S. Kiyaga
AU - M. Mbabazi
AU - T. Katairo
AU - V. Asua
AU - F. D. Semakuba
AU - B. Nsengimaana
AU - S. Tukwasibwe
AU - I. Wiringilimaana
AU - J. Nakasaanyaa
AU - J. Mulondoa
AU - E. Watyekele
AU - C. S. Maiteki
AU - D. P. Katete
AU - J. N. Nabende
AU - D. Jjingo
AU - G. Mboowa
AU - C. Batte
AU - N. Sam
AU - M. R. Kamya
AU - B. B. Agaba
AU - I. Ssewanyana
AU - A. Aranda-Diazi
AU - F. V. Ajogbasile
AU - M. Davlieva
AU - G. Dorsey
AU - P. J. Rosenthal
AU - M. D. Conrad
AU - B. Greenhouse
AU - N. J. Hathaway
AU - J. Briggs
PY - 2026
DA - 2026/09/27
PB - bioRxiv
DO - 10.64898/2026.09.27.754784
UR - https://www.biorxiv.org/content/10.64898/2026.09.27.754784v1
AB - Uganda has one of the world's highest malaria burdens, but parasite population structure and connectivity have not been characterized nationally with whole-genome data. We analyzed 249 monoclonal Plasmodium falciparum genomes from 26 sentinel sites across Uganda in 2023 and compared them with publicly available genomes from five neighboring countries. Genetic diversity was high and differentiation low in Uganda, but identity-by-descent detected limited structure. This was most pronounced in the low-transmission southwest, where parasites shared ancestry and recent relatedness with isolates from western Tanzania. Selection scans identified signals at loci associated with resistance to artemisinins and their partner drugs, and to chloroquine and antifolates. The strongest signal was at PfPX1 where the PIN haplotype (L1222P, M1701I, D1705N) reached 70% prevalence nationwide, but selection was carried by PIN haplotypes that had additionally acquired D384A, largely confined to northern and eastern Uganda. A second substitution at the same codon, D384Y, formed a haplotype shared across the Tanzanian border. PfKelch13 variants were partitioned across multiple backgrounds, consistent with repeated independent emergence, and C469Y was enriched on the PfPX1 D384A-PIN background. These genomes provide a 2023 baseline for tracking potential mediators of drug resistance and support coordinated genomic surveillance across Uganda and its neighbors.
ER -