Biology subjects

Rumaseb, A.

Publications and source records attributed to Rumaseb, A..

3 recordsLinked to original sources

bioRxiv2026

Plasmodium vivax relapse reservoirs in Ethiopia: microhaplotype sequencing informs recurrent infection origins

Determining the origin of recurrent Plasmodium vivax infections is critical for quantifying the public health burden of the hypnozoite reservoir, understanding transmission potential, and evaluating anti-relapse antimalarial efficacy. In Ethiopia, P. vivax is a major contributor to malaria burden, but the relative contribution of relapse to recurrent infections remains poorly quantified. We performed microhaplotype genotyping using a panel of 93 genome-wide markers and applied a probabilistic recurrence classification framework to recurrent P. vivax samples collected in two Ethiopian radical cure trials (IMPROV and OPRA). Genotyping was conducted on parasite isolates collected at enrolment and subsequent recurrences, with participants monitored over a 12-month follow-up period (IMPROV: 604 samples from 444 participants; OPRA: 621 samples from 342 participants). Recurrent infections were classified using a Bayesian hierarchical model implemented in Pv3Rs, which estimated marginal posterior probabilities of relapse, reinfection, or recrudescence based on genotyping data and background population dynamics. Priors were structured across biologically motivated time windows reflecting the natural history of P. vivax infection in Ethiopia and anticipated drug efficacy. Recurrences with a probability of relapse (p(L)) [≥] 0.75 were classified as relapses. In the absence of primaquine, probable relapse was the dominant classification for primary recurrent infections in both trials (75.5%; 102/135) and for consecutive recurrent infections within individuals (75.2%; 204/271). Primaquine substantially reduced the proportion of participants experiencing recurrent infections attributable to probable relapse, from 57.3% to 1.7% in IMPROV and from 60.2% to 9.5% in OPRA. Polyclonal infection at enrolment was independently associated with increased odds of recurrence and a higher rate of probable relapse in OPRA, with a consistent but non-significant trend observed in IMPROV. These findings provide direct molecular evidence that the hypnozoite reservoir is the dominant driver of recurrent P. vivax infections in Ethiopia in the absence of radical cure. The marked reduction in probable relapse following primaquine treatment highlights the critical importance of expanding access to safe and effective radical cure strategies in Ethiopia and other comparable high-transmission settings.

genetics↗

bioRxiv2026

Decoding Ethiopia's unique and structurally divergent Plasmodium falciparum populations using genomics

Previous genome-wide studies suggest that Ethiopian Plasmodium falciparum parasites are unique and structurally divergent from sub-Saharan African populations but were limited by small sample sizes. The emergence of molecular markers associated with reduced artemisinin susceptibility in northern Ethiopia, and the drug pressures created by sympatric P. falciparum and P. vivax, may have fostered a distinct and permissive genetic background for the emergence and spread of multidrug resistant parasites. To characterise parasite population structure and evolutionary dynamics in this setting, we generated whole-genome sequencing data for 163 P. falciparum isolates from southern Ethiopia (2017-2021) and integrated these with 854 isolates from across sub-Saharan Africa. Ethiopian parasites exhibited markedly reduced diversity, highly conserved genomes, and distinct admixture ancestry. Near-fixation of chloroquine and antifolate associated resistance markers, potentially driven by P. vivax co-circulation, suggests persistent drug-related selection pressures. We identified a previously undescribed deletion in the pfmdr1 5' UTR that is common in Ethiopia and potentially widespread across African populations. Although clinically relevant pfk13 variants have emerged in northern Ethiopia, these were not detected in southern Ethiopia. However, strong genetic connectivity between regions indicates the potential for rapid spread of resistance and is therefore important for public health policy and practice.

genomics↗

bioRxiv2025

Rapid detection of G6PD deficiency SNPs using a novel amplicon-based MinION Sequencing Assay

Plasmodium vivax malaria remains a significant global health challenge, complicated by the parasites ability to form dormant liver stages (hypnozoites) that cause relapses. Radical cure of P. vivax malaria requires administration of a hypnozoitocidal drug, such as primaquine or tafenoquine. However, these drugs can cause severe haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD deficiency is caused by more than 230 different variants at the gene level that confer different degrees of deficiency phenotypically. Understanding the distribution of different G6PD variants in affected populations is essential to inform safer antimalarial treatment strategies. This study aimed to develop a cost-effective sequencing assay targeting key regions of the G6PD gene, suitable for field deployment. A novel assay based on Nanopore technology was designed to amplify two amplicons covering exon 3 to exon 13, focusing on known variants associated with enzyme deficiency. A total of 79 samples from individuals in Cambodia, Vietnam, Afghanistan, and China were sequenced, and a bioinformatics pipeline was created for the targeted variant calling of 192 G6PD SNP mutations. The assay demonstrated reliable detection of known variants, with high concordance between runs, within runs, and with Sanger sequencing. The Nanopore MinION long-amplicon sequencing assay offers a robust and portable solution for large-scale G6PD genotyping in low-resource settings, that will improve malaria control and elimination strategies by enabling safer antimalarial treatment.

microbiology↗