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Background: Duffy Binding Protein (PvDBP) binding to the Duffy antigen receptor for chemokine (DARC) is essential for Plasmodium vivax invasion of human reticulocytes. PvDBP copy number variation (CNV) might increase parasite invasion and thus parasitemia. We examined the spatial distribution of PvDBP CNVs and DARC genotypes and their association with parasitemia in P. vivax endemic settings in Ethiopia. Methodology/Principal findings: P. vivax isolates (n = 435) collected from five P. vivax endemic settings in Ethiopia were genotyped by amplifying the GATA1 transcription factor-binding site of the Duffy blood group and the CNV of PvDBP was quantified. Parasitemia was determined using 18S-based qPCR. The majority of participants were Duffy positive (96.8%, 421/435). Of the few Duffy negative individuals, most (n = 8) were detected from one site (Gondar). Multiple copies of PvDBP were detected in 83% (363/435) isolates with significant differences between sites (range 60%-94%). Both heterozygous (p = 0.005) and homozygous (p = 0.006) patients were more likely to have been infected by parasites with multiple PvDBP copies than Duffy negatives. Parasitemia was higher among the Duffy positives (median 17,218 parasites/µL; interquartile range [IQR] 2,895–104,489) than Duffy negatives (170; 78–24,132, p = 0.004) as well as in infections with 2 to 3 PvDBP copies (20,468; 3,649–110,632, p = 0.001) and more than 3 PvDBP copies (17,139; 2,831–95,946, p = 0.004) than single copy (5,673; 249–76,605). Conclusions/Significance: A high proportion of P. vivax infection was observed in Duffy positives in this study, yet few Duffy negatives were found infected with P. vivax. The significant prevalence of multi-copy PvDBP observed among Ethiopian P. vivax isolates explains the high prevalence and parasitemia observed in clinical cases. This suggests that vivax malaria is a public health concern in the country where the Duffy positive population predominates. Investigating the relative contribution to the maintenance of the infectious reservoir of infections with different genotyping backgrounds (both host and parasite) might be required. Author summary: P. vivax establishes infection in humans using its DBP which binds to the DARC receptor on host erythrocytes. A single point mutation in the DARC promoter region results in Duffy negative phenotype. This phenotype results in lower infection success of P. vivax and can explain the heterogeneity in the global geographic distribution of P. vivax. Here, we investigated the association between Duffy genotypes, CNV of PvDBP, and level of parasitemia using 435 P. vivax isolates from five different endemicities in Ethiopia. The results revealed that the majority of P. vivax infections do occur in Duffy positive individuals. This explains the high prevalence of P. vivax in Ethiopia. The high prevalence of multi-copy PvDBP along with the high rate of Duffy positivity explains the transmission success of P. vivax in the country, where the majority of the population are Duffy positive. The lower parasitemia levels among the Duffy-negatives, despite small samples, may signify an "undetected silent reservoir". [ABSTRACT FROM AUTHOR]

Background: Shigellosis is an acute gastroenteritis infection and one of Ethiopia's most common causes of morbidity and mortality, especially in children under five. Antimicrobial resistance (AMR) has spread quickly among Shigella species due to inappropriate antibiotic use, inadequacies of diagnostic facilities, and unhygienic conditions. This study aimed to characterize Shigella sonnei (S. sonnei) using whole genome sequence (WGS) analysis in Addis Ababa, Ethiopia. Methods: The raw reads were quality-filtered and trimmed, and a minimum length of 50bp was retained and taxonomically classified using MiniKraken version 1. The whole genome data were aligned with Antibiotic Resistance Gene (ARG) sequences of the Comprehensive Antibiotic Resistance Database (CARD) by Resistance Gene Identifier (RGI). Plasmids were analyzed using the PlasmidFinder tool version 2.1. Additionally, AMR and virulence genes were screened at the Centre for Genomic Epidemiology (CGE) web-based server. Results: All isolates in our investigation contained genes encoding blaEC-8 and blaZEG-1. Here, 60.7% of the isolates were phenotypically sensitive to cefoxitin among the blaEC-8 genes detected in the genotyping analysis, whereas all isolates were completely resistant to amoxicillin and erythromycin phenotypically. The study also identified genes that conferred resistance to trimethoprim (dfrA). Plasmid Col156 and Col (BS512) types were found in all isolates, while IncFII and Col (MG828) plasmids were only identified in one isolate. Conclusion: This study found that many resistant genes were present, confirming the high variety in S. sonnei strains and hence a divergence in phylogenetic relationships. Thus, combining WGS methods for AMR prediction and strain identification into active surveillance may be beneficial for monitoring the spread of AMR in S. sonnei and detecting the potential emergence of novel variations. [ABSTRACT FROM AUTHOR]

We determined the dengue virus (DENV) serotypes and genotypes in archived serum samples that were collected during the 2014–2016 and 2021 dengue outbreaks in Dire Dawa City and the Somali region in Ethiopia. DENV serotype 1 (DENV-1) was predominant followed by DENV serotype 2 (DENV-2). Thirteen of the DENV-1 strains were assigned to Genotype-I, while the remaining two were found to be Genotype-III. All three DENV-2 strains were assigned the Cosmopolitan Genotype. The DENV strains responsible for the outbreaks are genetically closely related to the DENV strains that circulated in neighboring and Asian countries. The findings also showed continued local transmission of a monophyletic lineage and a co-circulation of DENV-1 and DENV-2 during the outbreaks. There is a need to strengthen DENV genomic surveillance capacity for the early detection of circulating serotypes, and prevent devastating consequences of future outbreaks due to the co-circulation of different serotypes. [ABSTRACT FROM AUTHOR]

Purpose: In Ethiopia, most people rely heavily on traditional therapeutic plants that have been used for years. The practice of traditional medicines use to treat hepatitis is currently gaining popularity due to the limited availability and affordability of modern drugs. The aim of this study was, therefore, to assess the traditional medicinal plants use to treat viral hepatitis among communities of Central region of Ethiopia. Methods: Data was collected from November 2018 to December 2021 in Central Ethiopia. An open-ended semi-structured interview was used among purposively selected herbalists, traditional medicine entrepreneurs, village heads, and patients visiting traditional healers for hepatitis treatments. A 5 mL blood sample was collected from patients who visited a traditional healers' clinic for hepatitis treatment and tested for HBsAg and HCV-antibody by using ELISA. Among HBsAg-positives, further nucleic acid test for HBV-DNA load was assessed to measure the effects of prescribed medicinal plants. Results: Herbalists cited 24 plants that were used for hepatitis treatment; of which Rumex nepalensis, Vangueria apiculata, and Solanum incanum were the most frequently cited plants. Remedies were commonly prepared by crushing or powdering, mixing them with water, and taken orally. Forty-two individuals were diagnosed and treated as hepatitis patients by herbalists, of which eight of them were HBsAg-positive but no positives for anti-HCV ELISA. At the third and sixth months of viral load assessment among HBsAg-positive, serum HBV-DNA suppression was observed in three individuals treated with different combinations of frequently cited plants. Conclusion: In this study, traditional healers used various plants to treat hepatitis. HBV-DNA suppressive activity was detected in three NAT-positive individuals who were treated by using a mixture of these frequently cited and highest preference-ranked plants. This suggests that these plants have antiviral properties and serve as a basis for more pharmacological research in the quest for new antiviral agents. [ABSTRACT FROM AUTHOR]

Background: Polymorphisms in glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) can cause an entire gene deletion. The current methodology can accurately identify GSTM1 and GSTT1 copy number variants (CNVs), which may shed light on the true contribution of each gene copy to the cellular detoxification process and disease risk. Because liver cirrhosis is becoming a critical worldwide health issue, this study determined the CNVs of GSTM1 and GSTT1 and their relationship to the risk of liver cirrhosis.Methods: In this study, we compared 106 patients with liver cirrhosis to 104 healthy controls. Real-time PCR was used to identify the CNVs of GSTM1 and GSTT1. Logistic and linear regression models were used to estimate the relationship between liver cirrhosis and clinical chemistry variables with the CNVs, respectively.Results: In 3.3% of the study participants, > 2 copies of the GSTM1 or GSTT1 genes were detected. GSTT1 carriers had a significantly lower risk of liver cirrhosis (p< 0.05) compared with individuals who had homozygous deletion (adjusted odds ratio (AOR) = 0.47; 95% CI: 0.25, 0.86). This risk reduction was significant (p< 0.05) in patients with a single copy of the GSTT1 gene (AOR = 0.48; 95% CI: 0.25, 0.91). Those with ≥ 2 copies of combined GSTM1 and GSTT1 also had a significantly (p< 0.05) lower risk of developing liver cirrhosis compared with double null genotypes (AOR = 0.38; 95% CI: 0.16, 0.91, p trend < 0.001). Moreover, ≥ 2 copies of combined GSTM1 and GSTT1 genes were associated with a substantial decrease in alanine amino transferase (ALT) and aspartate aminotransferase (AST) levels, respectively.Conclusion: A single copy number of GSTT1, and ≥ 2 copies of combined GSTM1 and GSTT1 genes were associated with a reduced risk of liver cirrhosis in Ethiopians. These findings underscore the importance of gene–environment interactions in the multifactorial development of liver cirrhosis. [ABSTRACT FROM AUTHOR]

The ubiquitin‐proteasome system plays a crucial role in cell cycle progression. A previous study suggested that Spo12, a component of the Cdc14 early anaphase release (FEAR) network, is targeted for degradation by the APC/CCdh1 complex in G1 phase. In the present study, we demonstrate that the Hect‐type ubiquitin ligase Tom1 contributes to the turnover of Spo12 in G2/M phase. Coimmunoprecipitation analysis confirmed that Tom1 and Spo12 interact. Overexpression of Spo12 is cytotoxic in the absence of Tom1. Notably, Spo12 is degraded in S phase even in the absence of Tom1 and Cdh1, suggesting that an additional E3 ligase(s) also mediates Spo12 degradation. Together, we propose that several distinct degradation pathways control the level of Spo12 during the cell cycle. [ABSTRACT FROM AUTHOR]

Proper dynamic regulation of the spindle is essential for successful cell division. However, the molecular mechanisms that regulate spindle dynamics in mitosis are not fully understood. In this study, we show that Cullin 5--interacting suppressor of cytokine signaling box protein ASB7 ubiquitinates DDA3, a regulator of spindle dynamics, thereby targeting it for proteasomal degradation. The presence of microtubules (MTs) prevented the ASB7--DDA3 interaction, thus stabilizing DDA3. Knockdown of ASB7 decreased MT polymerization and increased the proportion of cells with unaligned chromosomes, and this phenotype was rescued by deletion of DDA3. Collectively, these data indicate that ASB7 plays a crucial role in regulating spindle dynamics and genome integrity by controlling the expression of DDA3. [ABSTRACT FROM AUTHOR]

Globally, drug-resistant tuberculosis (DR-TB) is responsible for 13% of mortality attributable to antimicrobial resistance. In Ethiopia, extrapulmonary tuberculosis (EPTB) is a significant public health challenge, and drug resistance (DR) in EPTB is often overlooked. In a cross-sectional study conducted between August 2022 and October 2023, we aimed to explore the magnitude of phenotypic drug resistance and identify genetic mutations linked to resistance using 189 Mycobacterium tuberculosis (MTB) isolates cultured from extrapulmonary clinical specimens. Additionally, we assessed the agreement of the phenotypic and whole genome sequencing (WGS) based genotypic drug resistance detection. We performed phenotypic drug sensitivity testing (pDST) using liquid culture BD BACTECTM MGITTM 960 system and WGS using Illumina NextSeq500/550. The genomic data analysis pipelines MTBSeq and TBProfiler were used to predict drug resistance-conferring mutations. The agreement between the pDST and WGS was analyzed using SPSS version 29.0 software. Our result demonstrated phenotypic resistance to at least one anti-TB drug was detected in 16.9% (32/189) of the study participants. Isoniazid-resistant rifampicin-susceptible-TB (Hr-TB) and multi-drug-resistant TB (MDR-TB) phenotypes accounted for 2.6% (5/189) and 4.2% (8/189) respectively. Prevalence of MDR-TB was 2.4% (4/170) among newly diagnosed and 21.1% (4/19) among previously treated cases. WGS identified more (14/160, 8.75%) rifampicin-resistant genotypes (RR-TB) compared to pDST (8/189, 4.2%). We have identified a putative compensatory mutation for rifampicin (rpoBSer450Leu, rpoCAsp747Ala) for the first time from an EPTB clinical specimen in Ethiopia. Overall, there was a 3.75% rifampicin mono-resistant-TB(RMR-TB) genotype, which remains undetected using the conventional pDST and represented 42.9% (6/14) of the identified RR-TB genotypes. Mutations conferring rifampicin resistance-interim (rpoB.Ser450Ala) represented the majority (83.3%) of RMR-TB. Changes in ethA genes associated with ethionamide resistance were the most common resistance (n=7, 87.5%) in MDR-TB cases. There was a strong agreement between the pDST and WGS-TB Profiler pipeline to detect RR-TB (kappa=0.8) compared to the MTBSeq pipeline (k=0.58). In conclusion, MDR-TB, Hr-TB, and interim-RMR-TB are equally important public health challenges in the realm of EPTB in Ethiopia. The role of WGS is tremendous in detecting borderline/interim RMR-TB, which will help for tailored, personalized treatment strategies.

Background: Newcastle disease (ND) is a highly infectious poultry disease that causes major economic losses worldwide. The disease is caused by Newcastle Disease Virus (NDV) and early detection and identification of the viral strain is essential. Having knowledge of the NDV strain genotype that circulates in some regions would help in designing an effective vaccine to control the disease. In this regard, there is little information on NDV strain in chickens in mid Rift Valley and the central part of Ethiopia. Therefore, the purpose of this study was to detect and characterize NDV strain genotype from chickens in mid-Rift Valley and the central part of Ethiopia and test whether this NDV strain genotype matches the vaccine strain currently used in the study area., Methods: A total of 98 samples: 78 (tracheal and cloacal) swabs from chicken pools of five and 20 tissue samples were collected. To detect NDV strain, conserved region of the virus Matrix (M) gene was amplified by qRT-PCR. To characterize NDV strain genotypes, M-gene positive samples were specifically re-amplified by conventional PCR targeting the Fusion (F) gene region and sequenced by Sanger method., Results: 13.26% of tested samples were positive for NDV strain in the study area with statistically significant difference (P<0.05) among the study sites. Further characterization of the F genes from NDV strain isolates by phylogenetic analysis indicated that one field isolate clustered with genotype VII whereas three of the isolates clustered to genotype I, II, and III. The isolate of the current NDV strain vaccine in use in the study area clustered with genotype II., Conclusion: The current study indicates the existence of different NDV strain genotype from that of the vaccine strain currently used. Even though large-scale characterization of several isolates is required at national level, the current study laid baseline information for the existence of variations between field NDV strain genotype and vaccine strain currently used against ND in the country., Competing Interests: The authors declared that they have no competing interests in this work, (© 2024 Alemu et al.)