Mapping the molecular epidemiology of drug resistance markers and genetic diversity in Plasmodium falciparum across varying malaria transmission intensities in Ethiopia

PhD candidate: Bacha Mekonen Tafa
Institution: University of Barcelona, ISGlobal, in collaboration with Ethiopian Public Health Institute (EPHI) and Aklilu Lemma Institute of Health Research, Addis Ababa University (ALIHR, AAU).
Supervisors: Prof. Lemu Golassa; Prof. Alfredo Mayor; Dr Lauren Fromont

Malaria remains a major public health challenge in Ethiopia, despite substantial progress toward control and elimination. In recent years, however, the country has experienced a concerning resurgence driven by a combination of biological and operational factors. Plasmodium falciparum, the dominant malaria parasite (~70%), is currently treated with artemisinin-based combination therapies (ACTs), the cornerstone of malaria case management since 2004. Emerging and spreading mutations in the pfkelch13 gene, associated with reduced drug susceptibility and delayed parasite clearance, are raising concerns about the long-term effectiveness of these treatments.

Within the EpiGen Ethiopia initiative, aimed at “Building Scalable Pathogen Genomic Epidemiology in Ethiopia”, this PhD project investigation focuses on generating high-resolution molecular evidence to better understand malaria dynamics across Ethiopia’s diverse transmission settings. Specifically, the study investigates the distribution of anti-malarial drug resistance markers and the genetic diversity of Plasmodium falciparum, which remain insufficiently characterized across diverse malaria transmission strata.

Methodologically, the study employs a cross-sectional, multi-stage cluster design across ten health facilities representing diverse ecological and transmission contexts. A minimum of 530 microscopy-confirmed Plasmodium falciparum cases will be enrolled. Clinical, demographic, and geospatial data will be collected using digital tools (KoboToolbox), alongside dried blood spot (DBS) samples for molecular analysis. Genomic DNA extracted from DBS samples will be analyzed using multiplexed targeted amplicon sequencing on the Illumina MiSeq platform, following the MAD4HatTeR protocol. Bioinformatics analyses will be conducted using standardized pipelines to characterize drug resistance mutations and parasite genetic diversity.

Overall, by integrating field epidemiology, next-generation sequencing laboratory methods, and bioinformatics genomic data analysis, this project will provide critical insights into the molecular epidemiology of malaria in Ethiopia. The findings will support evidence-based decision-making, strengthen national molecular surveillance systems, and contribute to the broader goal of malaria elimination and pathogen genomics surveillance.