Genetic differentiation of Plasmodium vivax duffy binding protein in Ethiopia and comparison with other geographical isolates.

BACKGROUND: Plasmodium vivax Duffy binding protein (PvDBP) is a merozoite surface protein located in the micronemes of P. vivax. The invasion of human reticulocytes by P. vivax merozoites depends on the parasite DBP binding domain engaging Duffy Antigen Receptor for Chemokine (DARC) on these red blood cells (RBCs). PvDBPII shows high genetic diversity which is a major challenge to its use in the development of a vaccine against vivax malaria. METHODS: A cross-sectional study was conducted from February 2021 to September 2022 in five study sites across Ethiopia. A total of 58 blood samples confirmed positive for P. vivax by polymerase chain reaction (PCR) were included in the study to determine PvDBPII genetic diversity. PvDBPII were amplified using primers designed from reference sequence of P. vivax Sal I strain. Assembling of sequences was done using Geneious Prime version 2023.2.1. Alignment and phylogenetic tree constructions using MEGA version 10.1.1. Nucleotide diversity and haplotype diversity were analysed using DnaSP version 6.12.03, and haplotype network was generated with PopART version 1.7. RESULTS: The mean age of the participants was 25 years, 5 (8.6%) participants were Duffy negatives. From the 58 PvDBPII sequences, seven haplotypes based on nucleotide differences at 8 positions were identified. Nucleotide diversity and haplotype diversity were 0.00267 ± 0.00023 and 0.731 ± 0.036, respectively. Among the five study sites, the highest numbers of haplotypes were identified in Arbaminch with six different haplotypes while only two haplotypes were identified in Gambella. The phylogenetic tree based on PvDBPII revealed that parasites of different study sites shared similar genetic clusters with few exceptions. Globally, a total of 39 haplotypes were identified from 223 PvDBPII sequences representing different geographical isolates obtained from NCBI archive. The nucleotide and haplotype diversity were 0.00373 and 0.845 ± 0.015, respectively. The haplotype prevalence ranged from 0.45% to 27.3%. Two haplotypes were shared among isolates from all geographical areas of the globe. CONCLUSIONS: PvDBPII of the Ethiopian P. vivax isolates showed low nucleotide but high haplotype diversity, this pattern of genetic variability suggests that the population may have undergone a recent expansion. Among the Ethiopian P. vivax isolates, almost half of the sequences were identical to the Sal-I reference sequence. However, there were unique haplotypes observed in the Ethiopian isolates, which does not share with isolates from other geographical areas. There were two haplotypes that were common among populations across the globe. Categorizing population haplotype frequency can help to determine common haplotypes for designing an effective blood-stage vaccine which will have a significant role for the control and elimination of P. vivax.

Abnormal uterine bleeding and associated factors among reproductive age women in Jimma town, Oromia Region, Southwest Ethiopia.

INTRODUCTION: Abnormal uterine bleeding is any bleeding that deviates from normal menstruations. It differs in terms of frequency of bleeding, duration, and the pattern of bleeding during menstrual cycle or menopause. It is a major gynecological problem for medical visits among women in the reproductive aged group. However, data on abnormal uterine bleeding in Ethiopia are limited. Therefore, this study aimed to assess the abnormal uterine bleeding and associated factors among reproductive age women in Jimma town, Southwest Ethiopia. METHODS: Community-based cross-sectional study was employed from 1 January to 30 April 2020. Six hundred sixty women were selected by using systematic random sampling. Data were collected by using semi-structured questionnaires. Data were entered into EPI data version 3.1 and analyzed by using SPSS version 25 software. All predictor's variables with p value <0.25 in bivariable analysis were entered into multivariable logistic regression analysis. Variables with a p value of less than 0.05 in the multivariable analysis were taken as statistically significant predictors of abnormal uterine bleeding. RESULTS: Out of 660 participants, 225 (34.1%) had abnormal uterine bleeding. From women with abnormal uterine bleeding, the prevalence of metrorrhagia, heavy periods, oligomenorrhea, inter-menstrual bleeding, polymenorrhea, and amenorrhea was 59 (26.2%), 54 (24%), 53 (23.5%), 46 (20.4%), 35 (15.5%), and 25 (11.1%), respectively. History of abortion (adjusted odds ratio = 1.5, 95% confidence interval: 1.02-2.41), history of uterine fibroids (adjusted odds ratio = 3.83, 95% confidence interval: 1.85-7.94), history of sexually transmitted infection (adjusted odds ratio = 2.2, 95% confidence interval: 1.33-3.66), and the history of intrauterine device (adjusted odds ratio = 2.1, 95% confidence interval: 1.39-2.97) were significantly associated with abnormal uterine bleeding. CONCLUSION: The prevalence of abnormal uterine bleeding was higher in Jimma town.

Genomic analysis reveals independent evolution of Plasmodium falciparum populations in Ethiopia.

BACKGROUND: Plasmodium falciparum parasite populations in Ethiopia have been experiencing local selective pressures from drugs and immunity, leading to evolutionary adaptation. However, there was a paucity of data on genomic characterization and evolutionary adaptations of P. falciparum isolates from the central area of Ethiopia. METHODS: Whole-genome analysis of 25 P. falciparum isolates from central Ethiopia, specifically from West Arsi, were studied to determine their genetic diversity, population structures, and signatures of selection in known drug resistance alleles against global isolates from Cambodia, Thailand, DR Congo, and Malawi. RESULTS: A total of 18,517 high-quality single-nucleotide polymorphisms (SNPs) were identified in Ethiopian P. falciparum isolates. About 84% of the Ethiopian P. falciparum isolates had a FWS value > 0.95 showing a dominant single genotype infection in most isolates at the time of collection with little potential for out-crossing as expected in areas with low transmission intensity. Within-host diversity of Ethiopian infections was significantly different from East African (p < 0.001), but not Southeast Asian infections (P > 0.05). A significant population structure has been observed by PCA and population differentiation between Ethiopian parasites and East African (Fst ~ 10%) and Southeast Asian populations (Fst ~ 18%), suggesting limited gene flow and the independent evolution of the Ethiopian parasite population. Moreover, a total of 125 genes under balancing selection was found that include ama1, trap, eba175, and lsa3, previously identified as targets of human host immunity. Recent directional selection analysis using integrated standardized haplotype score (IHS) did not detect any selection signatures in the Pfcrt, Pfdhfr, Pfdhps, Pfmdr1, and PfK13 genes. However, known drug resistance-conferring mutations analysis showed that at least one SNP marker was fixed in these genes, but not in Pfdhps and PfK13. CONCLUSION: Plasmodium falciparum populations in the central region of Ethiopia was structurally diverged from both Southeast Asian and other East African populations. Malaria infections in Ethiopia had low within-host diversity, and parasites carry fixed chloroquine resistance markers despite the withdrawal of this drug for the treatment of P. falciparum.